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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Heart rate variability and target organ damage in hypertensive patients</title><author><name sortKey="Melillo, Paolo" sort="Melillo, Paolo" uniqKey="Melillo P" first="Paolo" last="Melillo">Paolo Melillo</name><affiliation><nlm:aff id="I1">Multidisciplinary Department of Medical Sciences, Second University of Naples, Via Pansini, 5, Naples, Italy</nlm:aff></affiliation></author><author><name sortKey="Izzo, Raffaele" sort="Izzo, Raffaele" uniqKey="Izzo R" first="Raffaele" last="Izzo">Raffaele Izzo</name><affiliation><nlm:aff id="I2">Departments of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University Hospital, Via Pansini, 5, Naples, Italy</nlm:aff></affiliation></author><author><name sortKey="De Luca, Nicola" sort="De Luca, Nicola" uniqKey="De Luca N" first="Nicola" last="De Luca">Nicola De Luca</name><affiliation><nlm:aff id="I2">Departments of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University Hospital, Via Pansini, 5, Naples, Italy</nlm:aff></affiliation></author><author><name sortKey="Pecchia, Leandro" sort="Pecchia, Leandro" uniqKey="Pecchia L" first="Leandro" last="Pecchia">Leandro Pecchia</name><affiliation><nlm:aff id="I3">Electrical Systems and optics research division, Faculty of Engineering, University of Nottingham, University Park, Nottingham, NG7 2RD, UK</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23153340</idno><idno type="pmc">3536621</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536621</idno><idno type="RBID">PMC:3536621</idno><idno type="doi">10.1186/1471-2261-12-105</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000329</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000329</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Heart rate variability and target organ damage in hypertensive patients</title><author><name sortKey="Melillo, Paolo" sort="Melillo, Paolo" uniqKey="Melillo P" first="Paolo" last="Melillo">Paolo Melillo</name><affiliation><nlm:aff id="I1">Multidisciplinary Department of Medical Sciences, Second University of Naples, Via Pansini, 5, Naples, Italy</nlm:aff></affiliation></author><author><name sortKey="Izzo, Raffaele" sort="Izzo, Raffaele" uniqKey="Izzo R" first="Raffaele" last="Izzo">Raffaele Izzo</name><affiliation><nlm:aff id="I2">Departments of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University Hospital, Via Pansini, 5, Naples, Italy</nlm:aff></affiliation></author><author><name sortKey="De Luca, Nicola" sort="De Luca, Nicola" uniqKey="De Luca N" first="Nicola" last="De Luca">Nicola De Luca</name><affiliation><nlm:aff id="I2">Departments of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University Hospital, Via Pansini, 5, Naples, Italy</nlm:aff></affiliation></author><author><name sortKey="Pecchia, Leandro" sort="Pecchia, Leandro" uniqKey="Pecchia L" first="Leandro" last="Pecchia">Leandro Pecchia</name><affiliation><nlm:aff id="I3">Electrical Systems and optics research division, Faculty of Engineering, University of Nottingham, University Park, Nottingham, NG7 2RD, UK</nlm:aff></affiliation></author></analytic><series><title level="j">BMC Cardiovascular Disorders</title><idno type="eISSN">1471-2261</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD).</p></sec><sec><title>Methods</title><p>A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index.</p></sec><sec><title>Results</title><p>Significantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors.</p></sec><sec><title>Conclusions</title><p>Depressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Yusuf, S" uniqKey="Yusuf S">S Yusuf</name></author><author><name sortKey="Reddy, S" uniqKey="Reddy S">S Reddy</name></author><author><name sortKey="Ounpuu, S" uniqKey="Ounpuu S">S Ounpuu</name></author><author><name sortKey="Anand, S" uniqKey="Anand S">S Anand</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chambless, Le" uniqKey="Chambless L">LE Chambless</name></author><author><name sortKey="Folsom, Ar" uniqKey="Folsom A">AR Folsom</name></author><author><name sortKey="Clegg, Lx" uniqKey="Clegg L">LX Clegg</name></author><author><name sortKey="Sharrett, Ar" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Cardiovasc Disord</journal-id><journal-id journal-id-type="iso-abbrev">BMC Cardiovasc Disord</journal-id><journal-title-group><journal-title>BMC Cardiovascular Disorders</journal-title></journal-title-group><issn pub-type="epub">1471-2261</issn><publisher><publisher-name>BioMed Central</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23153340</article-id><article-id pub-id-type="pmc">3536621</article-id><article-id pub-id-type="publisher-id">1471-2261-12-105</article-id><article-id pub-id-type="doi">10.1186/1471-2261-12-105</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Heart rate variability and target organ damage in hypertensive patients</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes" id="A1"><name><surname>Melillo</surname><given-names>Paolo</given-names></name><xref ref-type="aff" rid="I1">1</xref><email>paolo.melillo@unina2.it</email></contrib><contrib contrib-type="author" id="A2"><name><surname>Izzo</surname><given-names>Raffaele</given-names></name><xref ref-type="aff" rid="I2">2</xref><email>rafizzo@unina.it</email></contrib><contrib contrib-type="author" id="A3"><name><surname>De Luca</surname><given-names>Nicola</given-names></name><xref ref-type="aff" rid="I2">2</xref><email>nideluca@unina.it</email></contrib><contrib contrib-type="author" id="A4"><name><surname>Pecchia</surname><given-names>Leandro</given-names></name><xref ref-type="aff" rid="I3">3</xref><email>Leandro.Pecchia@nottingham.ac.uk</email></contrib></contrib-group><aff id="I1"><label>1</label>Multidisciplinary Department of Medical Sciences, Second University of Naples, Via Pansini, 5, Naples, Italy</aff><aff id="I2"><label>2</label>Departments of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University Hospital, Via Pansini, 5, Naples, Italy</aff><aff id="I3"><label>3</label>Electrical Systems and optics research division, Faculty of Engineering, University of Nottingham, University Park, Nottingham, NG7 2RD, UK</aff><pub-date pub-type="collection"><year>2012</year></pub-date><pub-date pub-type="epub"><day>15</day><month>11</month><year>2012</year></pub-date><volume>12</volume><fpage>105</fpage><lpage>105</lpage><history><date date-type="received"><day>23</day><month>8</month><year>2012</year></date><date date-type="accepted"><day>8</day><month>11</month><year>2012</year></date></history><permissions><copyright-statement>Copyright ©2012 Melillo et al.; licensee BioMed Central Ltd.</copyright-statement><copyright-year>2012</copyright-year><copyright-holder>Melillo et al.; licensee BioMed Central Ltd.</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><self-uri xlink:href="http://www.biomedcentral.com/1471-2261/12/105"></self-uri><abstract><sec><title>Background</title><p>We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD).</p></sec><sec><title>Methods</title><p>A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index.</p></sec><sec><title>Results</title><p>Significantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors.</p></sec><sec><title>Conclusions</title><p>Depressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD.</p></sec></abstract><kwd-group><kwd>Heart Rate Variability</kwd><kwd>Target organ damage</kwd><kwd>Hypertension</kwd></kwd-group></article-meta></front><body><sec><title>Background</title><p>Cardiovascular (CV) diseases are one of the most leading causes of morbidity and mortality in high developed countries [<xref ref-type="bibr" rid="B1">1</xref>]. A number of prospective population or cohort studies, such as the Atherosclerosis Risk in Communities Study [<xref ref-type="bibr" rid="B2">2</xref>], the Rotterdam Study [<xref ref-type="bibr" rid="B3">3</xref>], the Cardiovascular Health Study [<xref ref-type="bibr" rid="B4">4</xref>], and the Carotid Atherosclerosis Progression Study [<xref ref-type="bibr" rid="B5">5</xref>], have shown that asymptomatic organ damage is significantly related to incident CV events. If CV involvement is early detected by physicians, it is possible to influence the progression or regression of the disease by the therapy [<xref ref-type="bibr" rid="B6">6</xref>]. Although there is still a little information on the specific causes of these pathologies, a recent review by Thayer suggested that autonomic imbalance may be a final common pathway to increased morbidity and mortality from a host of conditions and pathologies, including CV diseases [<xref ref-type="bibr" rid="B7">7</xref>]. Analysis of heart rate variability (HRV) on the basis of routine 24-hour Holter recordings has been shown to provide a sensitive measurement of cardiac control by the autonomous nervous system (ANS) [<xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref>]. HRV is a non-invasive measure reflecting the variation over time of the period between consecutive heartbeats (RR intervals) [<xref ref-type="bibr" rid="B8">8</xref>]. In fact, heart rate (HR), which continuously fluctuates over time, is under the influence of control mechanisms aimed at maintaining a dynamic stability called homoeostasis [<xref ref-type="bibr" rid="B10">10</xref>]. In this equilibrium, the sympathetic stimulation causes acceleration in HR by increasing the firing rate of pacemaker cells in the heart’s sino-atrial node, while the parasympathetic system causes deceleration in HR by decreasing of the firing rate of pacemaker cells [<xref ref-type="bibr" rid="B8">8</xref>]. Clinical studies have shown reduced HRV in patients with congestive heart failure [<xref ref-type="bibr" rid="B11">11</xref>-<xref ref-type="bibr" rid="B16">16</xref>], diabetes [<xref ref-type="bibr" rid="B17">17</xref>], and white coat hypertension [<xref ref-type="bibr" rid="B18">18</xref>]. Moreover, decreased HRV measures have been shown to be a risk factor for mortality in chronic haemodialysis patients [<xref ref-type="bibr" rid="B19">19</xref>] and for progression to end-stage renal disease [<xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B21">21</xref>]. Furthermore, several studies have shown that incidence of CV events can be reduced by therapeutic correction of any modifiable risk factors, such as hypertension, abnormal cholesterol, diabetes, smoking habit or physical inactivity. As noted and shown in the review by Thayer [<xref ref-type="bibr" rid="B7">7</xref>], there is at least some data to suggest that each of these risk factors is associated with decreased HRV. Regarding hypertensive patients a sympatho-vagal imbalance as evaluated by HRV with increased sympathetic activity and reduced vagal tone has been reported [<xref ref-type="bibr" rid="B22">22</xref>] and a recent paper by Garcia-Garcia [<xref ref-type="bibr" rid="B23">23</xref>] investigate the correlation between heart rate and the parameters that assess vascular, renal and cardiac target organ damage (TOD). However, only two HRV measures were selected in the study by Garcia-Garcia [<xref ref-type="bibr" rid="B23">23</xref>]. The aim of the current study was to evaluate the association between linear standard HRV measures with the vascular, renal and cardiac TOD in hypertensive patients registered in the Campania Salute network. The Campania Salute network is an open registry collecting information from a network of general practitioners and community hospitals networked with the centre, and providing a centralised database including demographics and clinical information of the patients.</p></sec><sec sec-type="methods"><title>Methods</title><sec><title>Population study</title><p>For the present study, among the initial cohort of 12,000 patients registered in the database of the Campania Salute Network, we selected all the hypertensive subjects who underwent at least one visit in the Outpatient Hypertension Clinic of the University of Naples “Federico II” from 2000 to 2010 and were evaluated by a cardiac and carotid ultrasonography and by a 24h Holter ECG. The ECG Holter was performed after a one-month antihypertensive therapy wash-out. Details on this cohort have been previously reported [<xref ref-type="bibr" rid="B24">24</xref>,<xref ref-type="bibr" rid="B25">25</xref>]. Exclusion criteria for the present analysis were: diagnosis of secondary resistant and/or uncontrolled hypertension, prevalent CV disease, clinical history of cancer, liver cirrhosis and/or failure, narcotics abuse, lifestyle changes in the last 12 months. Moreover, patients with atrial fibrillation and frequent ectopic beats as assessed by Holter were excluded. Prevalent CV disease was defined as history of previous myocardial infarction or angina or procedures of coronary revascularization, stroke or transitory ischemic attack, congestive heart failure, chronic kidney disease more than grade 3 (eGFR by MDRD < 30mL/min/1.73m<sup>2</sup>) at the time of the first examination in the outpatient clinic. Prevalent CV disease was excluded by an ad-hoc committee in the Hypertension Centre, based on patients’ history, contact with the referring general practitioner and clinical records documenting the occurrence of disease. In the sub-cohort of 10254 patients with arterial hypertension, 4257 patients were excluded for diagnosis of secondary resistant and/or uncontrolled hypertension, prevalent CV disease, clinical history of cancer, liver cirrhosis and/or failure, narcotics abuse, lifestyle changes in the last 12 months; 1814 for chronic kidney disease more than grade 3 (eGFR by MDRD < 30mL/min/1.73m<sup>2</sup>); 2556 for missing data (i.e. ultrasonography, holter ECG); 942 for atrial fibrillation and 485 for frequent ectopic beats.</p></sec><sec><title>Ethical issues</title><p>All the data of the patients (i.e. medical history, physical examination, routine laboratory tests and other diagnostic procedures) were stored in the computerised database of Campania Salute Network. The database generation of the Campania Salute Network was approved by the Federico II University Hospital Ethic Committee. All the participants signed informed consent to use data for scientific purposes.</p></sec><sec><title>Protocol</title><p>At the first visit all patients were given a detailed questionnaire inquiring about specifics lifestyle behaviours and smoking habit. In the current study they were categorised as non-smokers, ex-smokers or smokers. During the visits, blood pressure (BP), lipid and glucose profiles were measured for each patient by standard methods. Diagnosis and stratification of essential hypertension was performed according to the criteria established by the Guidelines for the Management of Arterial Hypertension [<xref ref-type="bibr" rid="B26">26</xref>]: systolic and diastolic BP were measured by a standard aneroid sphygmomanometer after 5 min rest in the supine position, according to the current guidelines [<xref ref-type="bibr" rid="B26">26</xref>]. Three BP measurements were obtained at 2-min intervals. The averages of these measurements were used for the analysis. Glomerular filtration rate (eGFR) was estimated by the Modification of Diet in Renal Disease (MDRD) formula [<xref ref-type="bibr" rid="B27">27</xref>]. Diabetes was defined as a fasting blood glucose ≥126 mg/dL or active glucose-lowering therapy [<xref ref-type="bibr" rid="B28">28</xref>].</p></sec><sec><title>Echocardiography</title><p>Two-dimensional-guided M-mode echocardiograms were performed using a dedicated ultrasound machine (SONOS 5500, Philips) with an ultrasound transducer of 2.5 MHz. The examinations were recorded on a digital recorder and analysed by three independent, trained and experienced physicians. The parameters relative to the left ventricle (LV) were measured in the parasternal long-axis view and obtained, according to the criteria of the American Society of Echocardiography [<xref ref-type="bibr" rid="B29">29</xref>], as an average of at least three measurements, as also performed in previous studies [<xref ref-type="bibr" rid="B30">30</xref>,<xref ref-type="bibr" rid="B31">31</xref>]. LV mass was determined by using the formula developed by Devereux [<xref ref-type="bibr" rid="B32">32</xref>] as recommend by American Society of Echocardiography (ASE) [<xref ref-type="bibr" rid="B33">33</xref>] and divided by the body surface area to calculate LV mass index (LVMi, g/m<sup>2</sup>). Intraoperator and interassay variability were 5% and 6%, respectively [<xref ref-type="bibr" rid="B34">34</xref>].</p></sec><sec><title>Carotid ultrasound</title><p>B-mode ultrasonography of carotid arteries was performed with patients in the supine position with the neck extended in mild rotation. The scanning protocol was performed with an ultrasound device (SONOS 5500, Philips) equipped with a 7.5-MHz high-resolution transducer with an axial resolution of 0.1 nm. Examinations were recorded on S-VHS videotapes. All measurement were analysed by three different trained experienced physicians. An average of two readings was considered for subsequent calculations. The accuracy of determinations was evaluated as previously described by Lembo et al. [<xref ref-type="bibr" rid="B35">35</xref>]: the variability of measurements to evaluate intrasonographer and intersonographer reproducibility was 0.01 and 0.03 mm, respectively. The maximum arterial intima media thickness (IMT) in up to 12 arterial walls, including the right and the left, near and far distal common carotid (1 cm), bifurcation, and proximal internal carotid artery was estimated offline with an image processing workstation with the software COMPACS (Rev. 10.5.8, Medimatic, Genoa, Italy).</p></sec><sec><title>Assessment of TOD</title><p>Cardiac Involvement was evaluated as Left Ventricular Hypertrophy (LVH) which was diagnosed if LVMi exceeded 110 g/m<sup>2</sup> in female and 125 g/m<sup>2</sup> in male [<xref ref-type="bibr" rid="B36">36</xref>]. Vascular involvement was assessed as carotid artery atherosclerosis shown by increased IMT in B-mode ultrasonography. IMT values between 1.0 and 1.3 mm were defined as "thickening" and those higher than 1.3 mm as “plaque”. Chronic kidney disease was assessed by eGFR and involvement was quantified as follows:</p><p>1. group 1: increased or normal eGFR (eGFR ≥ 90 mL/min/1.73 m<sup>2</sup>)</p><p>2. group 2: mild eGFR (60 < eGFR < 90 mL/min/1.73 m<sup>2</sup>)</p><p>3. group 3: moderate eGFR (eGFR ≤ 60 mL/min/1.73 m<sup>2</sup>) [<xref ref-type="bibr" rid="B37">37</xref>]</p></sec><sec><title>Processing 24-hour holter recordings</title><p>On 2 consecutive days, patients underwent a 24-hour ECG Holter recording. The recorders were applied between 9 and 11 AM on a working day, and the patients were asked to follow as closely as possible their usual daily activities during each monitoring session. They were asked to stay in bed from 11 PM to 7 AM, and all reported to have slept normally during the nights they were monitored. The series of normal to normal (NN) beat intervals were obtained from ECG recordings using OSAS, an open-source software for QRS detection and beat classification [<xref ref-type="bibr" rid="B38">38</xref>]. Standard long-term HRV analysis on nominal 24-h recordings according to International Guidelines was performed [<xref ref-type="bibr" rid="B8">8</xref>]. The HRV analysis was performed using PhysioNet's HRV Toolkit [<xref ref-type="bibr" rid="B39">39</xref>]. We chose this toolkit as it is an open source and a rigorously validated package. All the computed basic time- and frequency-domain HRV measures were widely used in the literature [<xref ref-type="bibr" rid="B8">8</xref>]. A number of standard statistical time-domain HRV measures are calculated: Average of all NN intervals (AVNN), standard deviation of all NN intervals (SDNN), standard deviation of the averages of NN intervals in all 5-min segments of a 24-h recording (SDANN), mean of the standard deviations of NN intervals in all 5-min segments of a 24-h recording (SDNN IDX), square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD), percentage of differences between adjacent NN intervals that are longer than 50 ms (pNN50). The frequency-domain HRV measures rely on the estimation of power spectral density (PSD) computed, in this work, by Lomb-Scamble periodogram [<xref ref-type="bibr" rid="B40">40</xref>]. After PSD estimation, six standard frequency-domain HRV measures were calculated: total spectral power of all NN intervals up to 0.4 Hz (TOTPWR), between 0 and 0.003 Hz (ULF), between 0.003 and 0.04 Hz (VLF), between 0.04 and 0.15 Hz (LF), and between 0.15 and 0.4 Hz (HF), ratio of low to high frequency power (LF/HF).</p></sec><sec><title>Statistical analysis</title><p>Data were analysed by the use of PASW Statistics 18 software (Release 18.0; SPSS IBM, Chicago, IL, USA). Univariate differences were analysed using Kruskal-Wallis and Wilcoxon test for HRV measures, ANOVA and t-test for the other continuous variables (for instance age, IMT, etc.) and χ<sup>2</sup> test for the categorical variables (for instance sex, smoking). For each HRV measure, which differs significantly among the three groups, an adjusted model was proposed by performing a binary or multinomial logistic regression, as appropriate. For each factor or covariate, the coefficient of the estimated regression model (β), the corresponding statistical significance (p), the odds ratio (OR) and the confidence interval for OR at 95% are presented. A p-value less than 5% was considered statistically significant.</p></sec></sec><sec sec-type="results"><title>Results</title><p>200 patients were analysed (127 male and 73 female). Demographic, clinical and laboratory characteristics of the study sample are shown in Table <xref ref-type="table" rid="T1">1</xref>. Table <xref ref-type="table" rid="T2">2</xref> shows the characteristic of the study sample of patients categorised by eGFR. The moderate eGFR group is significantly older than the others and has a significantly higher proportion of patients taking diuretics. Systolic BP and Pulse Pressure values were significantly higher in mild decreased eGFR group (compared to normal eGFR group), where IMT values were significantly lower in normal eGFR group (compared to moderate decreased eGFR group). Table <xref ref-type="table" rid="T3">3</xref> shows the descriptive statistics of HRV measures in the groups stratified by eGFR. The three groups differed significantly in LF/HF. Table <xref ref-type="table" rid="T4">4</xref> shows the characteristic of the study sample of patients categorised by IMT. The Plaque group is significantly older than the others. LVMi values were significantly lower in the normal group compared to the Plaque group and the proportion of patients with LVH was significantly lower. A significantly higher proportion of patients with family history of hypertension was assessed in the Thickening group. A significant difference in the proportion of patients taking beta-blockers was observed. Table <xref ref-type="table" rid="T5">5</xref> shows the descriptive statistics of HRV measures in the three groups according to IMT. The three groups differed significantly in SDNN, SDANN, SDNN IDX TOTPWR, LF, and LF/HF. Table <xref ref-type="table" rid="T6">6</xref> shows the characteristic of the study sample of patients categorised by LVH. The LVH group is significantly older than the group without LVH. IMT values were significantly higher in the LVH group and the proportion of patients with vascular abnormalities was significantly higher. A significantly higher proportion of patients taking diuretics was assessed in LVH group. The values of Systolic BP and Pulse Pressure were significantly higher in the LVH group. Table <xref ref-type="table" rid="T7">7</xref> shows the comparison of HRV measures in the patients with and without LVH. The two groups differed significantly in LF/HF. Most differences persisted even in the adjusted models, which are reported in Table <xref ref-type="table" rid="T8">8</xref>. As concerns renal TOD, the multinomial logistic regression selected age, family history of hypertension and systolic BP. Higher values of LF/HF are associated with an increased probability that a subject belongs to normal or mild eGFR groups rather than to moderate group (OR 2.718 and 2.637, respectively). Older age is associated with a decreased probability of being in normal or mild decreased eGFR groups (OR 0.897 and 0.943, respectively). The absence of family history of hypertension is associated with an increased probability of belonging to normal eGFR group (OR 2.951). Elevated systolic BP seems to be associated with a slightly increased probability of belonging to mild decreased eGFR group (OR 1.024). As regards vascular TOD, the adjusted models confirmed the differences in the values of SDNN and SDANN. In fact, higher values of SDNN and SDANN are associated with an increased probability that a subject had no vascular alterations rather than plaque. Moreover, this model confirms that older age is associated with vascular alterations. As regards cardiac TOD, the binomial logistic regression did not confirm the difference in LF/HF and showed that other variables are associated with LVH such as age, systolic BP, cholesterol, and diuretics.</p><table-wrap position="float" id="T1"><label>Table 1</label><caption><p>Characteristics of the study sample of patients</p></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="left"></col></colgroup><thead valign="top"><tr><th align="left"><bold>Characteristic</bold></th><th align="left"><bold>Value</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="bottom">Age (years)<hr></hr></td><td align="left" valign="bottom">62.5 ± 12.1<hr></hr></td></tr><tr><td align="left" valign="bottom">Sex (male/female, %)<hr></hr></td><td align="left" valign="bottom">63.5/36.5<hr></hr></td></tr><tr><td align="left" valign="bottom">Family history of hypertension (yes/no, %)<hr></hr></td><td align="left" valign="bottom">56.5/43.5<hr></hr></td></tr><tr><td align="left" valign="bottom">Family history of stroke (yes/no, %)<hr></hr></td><td align="left" valign="bottom">19.5/80.5<hr></hr></td></tr><tr><td align="left" valign="bottom">Smokers (yes/ex/no, %)<hr></hr></td><td align="left" valign="bottom">17.5/21/61.5<hr></hr></td></tr><tr><td align="left" valign="bottom">Diabetes (yes/no, %)<hr></hr></td><td align="left" valign="bottom">10/90<hr></hr></td></tr><tr><td align="left" valign="bottom">Diastolic BP (mmHg)<hr></hr></td><td align="left" valign="bottom">75.6 ± 12.0<hr></hr></td></tr><tr><td align="left" valign="bottom">Systolic BP (mmHg)<hr></hr></td><td align="left" valign="bottom">133.2 ± 22.6<hr></hr></td></tr><tr><td align="left" valign="bottom">Pulse pressure (mmHg)<hr></hr></td><td align="left" valign="bottom">57.6 ± 17.8<hr></hr></td></tr><tr><td align="left" valign="bottom">Fasting blood glucose (mmHg)<hr></hr></td><td align="left" valign="bottom">102.7 ± 24.1<hr></hr></td></tr><tr><td align="left" valign="bottom">Total Cholesterol (mg/dl)<hr></hr></td><td align="left" valign="bottom">185.8 ± 40.6<hr></hr></td></tr><tr><td align="left" valign="bottom">BMI (kg/m<sup>2</sup>)<hr></hr></td><td align="left" valign="bottom">27.7 ± 4.6<hr></hr></td></tr><tr><td align="left" valign="bottom">Beta-blockers (yes/no, %)<hr></hr></td><td align="left" valign="bottom">33.5/66.5<hr></hr></td></tr><tr><td align="left" valign="bottom">Alphabeta-blockers (yes/no, %)<hr></hr></td><td align="left" valign="bottom">10.5/89.5<hr></hr></td></tr><tr><td align="left" valign="bottom">Alpha-blockers (yes/no, %)<hr></hr></td><td align="left" valign="bottom">8/92<hr></hr></td></tr><tr><td align="left" valign="bottom">Diuretics (yes/no, %)<hr></hr></td><td align="left" valign="bottom">43.5/56.5<hr></hr></td></tr><tr><td align="left" valign="bottom">ACE inhibitor (yes/no, %)<hr></hr></td><td align="left" valign="bottom">37.5/62.5<hr></hr></td></tr><tr><td align="left" valign="bottom">Dihydropyridine (yes/no, %)<hr></hr></td><td align="left" valign="bottom">26/74<hr></hr></td></tr><tr><td align="left" valign="bottom">eGFR (mL/min/1.73 m<sup>2</sup>)<hr></hr></td><td align="left" valign="bottom">77.0 ± 18.9<hr></hr></td></tr><tr><td align="left" valign="bottom">Kidney Involvement (group 1/ 2 /3 %)<hr></hr></td><td align="left" valign="bottom">24/59.5/16.5<hr></hr></td></tr><tr><td align="left" valign="bottom">IMT (mm)<hr></hr></td><td align="left" valign="bottom">2.24 ± 1.56<hr></hr></td></tr><tr><td align="left" valign="bottom">Vascular abnormalities (no/ thickening/plaque, %)<hr></hr></td><td align="left" valign="bottom">13/11/78<hr></hr></td></tr><tr><td align="left" valign="bottom">LVMi g/m<sup>2</sup><hr></hr></td><td align="left" valign="bottom">130.5 ± 31.0<hr></hr></td></tr><tr><td align="left">Left Ventricular hypertrophy (no/yes, %)</td><td align="left">40/60</td></tr></tbody></table><table-wrap-foot><p>Data are expressed as mean and standard deviation for continuous variables (i.e. age) and as percentage of patients per each group for categorical variables (i.e. gender).</p></table-wrap-foot></table-wrap><table-wrap position="float" id="T2"><label>Table 2</label><caption><p>Characteristics of the study sample of patients stratified according to the eGFR</p></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="top"><tr><th align="left" valign="bottom"> <hr></hr></th><th align="center" valign="bottom"><bold>Normal eGFR (group 1)</bold><hr></hr></th><th align="center" valign="bottom"><bold>Mild decreased eGFR (group 2)</bold><hr></hr></th><th align="center" valign="bottom"><bold>Moderate decreased eGFR (group 3)</bold><hr></hr></th><th colspan="4" align="center" valign="bottom"><bold>P Values</bold><hr></hr></th></tr><tr><th align="left"> </th><th align="center"> </th><th align="center"> </th><th align="center"> </th><th align="center"><bold>ANOVA or χ</bold><sup><bold>2</bold></sup></th><th align="center"><bold>group 1 vs group 2</bold></th><th align="center"><bold>group 1 vs group 3</bold></th><th align="center"><bold>group 2 vs group 3</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="bottom">Age (years)<hr></hr></td><td align="center" valign="bottom">56 ± 11.5<hr></hr></td><td align="center" valign="bottom">63,0 ± 11.7<hr></hr></td><td align="center" valign="bottom">70.0 ± 9.4<hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td><td align="center" valign="bottom"><bold>0.001</bold><hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td><td align="center" valign="bottom"><bold>0.05</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">Gender (male/female)<hr></hr></td><td align="center" valign="bottom">31/17<hr></hr></td><td align="center" valign="bottom">76/43<hr></hr></td><td align="center" valign="bottom">20/13<hr></hr></td><td align="center" valign="bottom">0.928<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Family history of hypertension (yes/no)<hr></hr></td><td align="center" valign="bottom">25/23<hr></hr></td><td align="center" valign="bottom">69/50<hr></hr></td><td align="center" valign="bottom">19/14<hr></hr></td><td align="center" valign="bottom">0.778<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Family history of stroke (yes/no)<hr></hr></td><td align="center" valign="bottom">11/37<hr></hr></td><td align="center" valign="bottom">22/97<hr></hr></td><td align="center" valign="bottom">6/27<hr></hr></td><td align="center" valign="bottom">0.790<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Smokers (yes/ex/no)<hr></hr></td><td align="center" valign="bottom">13/8/27<hr></hr></td><td align="center" valign="bottom">8/27/7<hr></hr></td><td align="center" valign="bottom">27/75/21<hr></hr></td><td align="center" valign="bottom">0.379<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Diabetes (yes/no)<hr></hr></td><td align="center" valign="bottom">5/43<hr></hr></td><td align="center" valign="bottom">11/108<hr></hr></td><td align="center" valign="bottom">4/29<hr></hr></td><td align="center" valign="bottom">0.883<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Diastolic BP (mmHg)<hr></hr></td><td align="center" valign="bottom">73.2 ± 14.0<hr></hr></td><td align="center" valign="bottom">77.3 ± 11.5<hr></hr></td><td align="center" valign="bottom">73.0 ± 9.8<hr></hr></td><td align="center" valign="bottom">0.048<hr></hr></td><td align="center" valign="bottom">0.129<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">0.185<hr></hr></td></tr><tr><td align="left" valign="bottom">Systolic BP (mmHg)<hr></hr></td><td align="center" valign="bottom">124.5 ± 23.3<hr></hr></td><td align="center" valign="bottom">137.5 ± 20.0<hr></hr></td><td align="center" valign="bottom">130.2 ± 27.3<hr></hr></td><td align="center" valign="bottom"><bold>0.002</bold><hr></hr></td><td align="center" valign="bottom"><bold>0.002</bold><hr></hr></td><td align="center" valign="bottom">0.754<hr></hr></td><td align="center" valign="bottom">0.286<hr></hr></td></tr><tr><td align="left" valign="bottom">Pulse pressure (mmHg)<hr></hr></td><td align="center" valign="bottom">51.3 ± 14.1<hr></hr></td><td align="center" valign="bottom">60.1 ± 16.9<hr></hr></td><td align="center" valign="bottom">57.3 ± 23.3<hr></hr></td><td align="center" valign="bottom"><bold>0.014</bold><hr></hr></td><td align="center" valign="bottom"><bold>0.010</bold><hr></hr></td><td align="center" valign="bottom">0.396<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td></tr><tr><td align="left" valign="bottom">Fasting blood glucose (mmHg)<hr></hr></td><td align="center" valign="bottom">99.7 ± 32.2<hr></hr></td><td align="center" valign="bottom">102.8 ± 20.0<hr></hr></td><td align="center" valign="bottom">106.7 ± 23.9<hr></hr></td><td align="center" valign="bottom">0.432<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">0.589<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td></tr><tr><td align="left" valign="bottom">Total Cholesterol (mg/dl)<hr></hr></td><td align="center" valign="bottom">178.9 ± 36.4<hr></hr></td><td align="center" valign="bottom">187.7 ± 40.8<hr></hr></td><td align="center" valign="bottom">189.0 ± 45.8<hr></hr></td><td align="center" valign="bottom">0.395<hr></hr></td><td align="center" valign="bottom">0.610<hr></hr></td><td align="center" valign="bottom">0.817<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td></tr><tr><td align="left" valign="bottom">BMI (kg/m<sup>2</sup>)<hr></hr></td><td align="center" valign="bottom">27.4 ± 5.2<hr></hr></td><td align="center" valign="bottom">28.1 ± 4.6<hr></hr></td><td align="center" valign="bottom">26.7 ± 3.5<hr></hr></td><td align="center" valign="bottom">0.261<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">0.379<hr></hr></td></tr><tr><td align="left" valign="bottom">Beta-blockers (yes/no)<hr></hr></td><td align="center" valign="bottom">15/33<hr></hr></td><td align="center" valign="bottom">41/78<hr></hr></td><td align="center" valign="bottom">11/22<hr></hr></td><td align="center" valign="bottom">0.924<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Alphabeta-blockers (yes/no)<hr></hr></td><td align="center" valign="bottom">5/43<hr></hr></td><td align="center" valign="bottom">14/105<hr></hr></td><td align="center" valign="bottom">2/31<hr></hr></td><td align="center" valign="bottom">0.639<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Alpha-blockers (yes/no)<hr></hr></td><td align="center" valign="bottom">3/45<hr></hr></td><td align="center" valign="bottom">8/111<hr></hr></td><td align="center" valign="bottom">5/28<hr></hr></td><td align="center" valign="bottom">0.252<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Diuretics (yes/no)<hr></hr></td><td align="center" valign="bottom">17/31<hr></hr></td><td align="center" valign="bottom">49/70<hr></hr></td><td align="center" valign="bottom">21/12<hr></hr></td><td align="center" valign="bottom"><bold>0.03</bold><hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">ACE inhibitor (yes/no)<hr></hr></td><td align="center" valign="bottom">16/32<hr></hr></td><td align="center" valign="bottom">48/71<hr></hr></td><td align="center" valign="bottom">11/22<hr></hr></td><td align="center" valign="bottom">0.604<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Dihydropyridine (yes/no)<hr></hr></td><td align="center" valign="bottom">12/36<hr></hr></td><td align="center" valign="bottom">30/89<hr></hr></td><td align="center" valign="bottom">10/23<hr></hr></td><td align="center" valign="bottom">0.826<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">eGFR (mL/min/1.73 m<sup>2</sup>)<hr></hr></td><td align="center" valign="bottom">101.9 ± 12.0<hr></hr></td><td align="center" valign="bottom">74.3 ± 8.8<hr></hr></td><td align="center" valign="bottom">50.6 ± 8.0<hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">IMT (mm)<hr></hr></td><td align="center" valign="bottom">1.8 ± 0.76<hr></hr></td><td align="center" valign="bottom">2.23 ± 1.21<hr></hr></td><td align="center" valign="bottom">2.91 ± 2.85<hr></hr></td><td align="center" valign="bottom"><bold>0.007</bold><hr></hr></td><td align="center" valign="bottom">0.282<hr></hr></td><td align="center" valign="bottom"><bold>0.005</bold><hr></hr></td><td align="center" valign="bottom">0.81<hr></hr></td></tr><tr><td align="left" valign="bottom">Vascular abnormalities (no/ thickening/plaque)<hr></hr></td><td align="center" valign="bottom">33/6/9<hr></hr></td><td align="center" valign="bottom">91/13/15<hr></hr></td><td align="center" valign="bottom">28/3/2<hr></hr></td><td align="center" valign="bottom">0.502<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">LVMi g/m<sup>2</sup><hr></hr></td><td align="center" valign="bottom">124.3 ± 26. 2<hr></hr></td><td align="center" valign="bottom">133.0 ± 32.3<hr></hr></td><td align="center" valign="bottom">130.4 ± 32.1<hr></hr></td><td align="center" valign="bottom">0.258<hr></hr></td><td align="center" valign="bottom">0.301<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td></tr><tr><td align="left">Left Ventricular hypertrophy (no/yes)</td><td align="center">24/24</td><td align="center">44/75</td><td align="center">12/21</td><td align="center">0.268</td><td align="center"> </td><td align="center"> </td><td align="center"> </td></tr></tbody></table><table-wrap-foot><p>Data are expressed as mean and standard deviation for continuous variables (i.e. age) and as number of patients per each group for categorical variables (i.e. gender).</p><p>The p-values refer to ANOVA and post-hoc comparisons with Bonferroni corrections for continuous variables, to χ<sup>2</sup> for categorical variables.</p></table-wrap-foot></table-wrap><table-wrap position="float" id="T3"><label>Table 3</label><caption><p>Comparisons of HRV measurement in patients stratified by eGFR</p></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="top"><tr><th align="left" valign="bottom"> <hr></hr></th><th colspan="5" align="center" valign="bottom"><bold>Normal eGFR (group 1)</bold><hr></hr></th><th colspan="5" align="center" valign="bottom"><bold>Mild decreased eGFR (group 2)</bold><hr></hr></th><th colspan="5" align="center" valign="bottom"><bold>Moderate decreased eGFR (group 3)</bold><hr></hr></th><th align="center" valign="bottom"><bold>P-values</bold><hr></hr></th></tr><tr><th align="left" valign="bottom"> <hr></hr></th><th align="center" valign="bottom"><bold>Mean</bold><hr></hr></th><th align="center" valign="bottom"><bold>St. Dev.</bold><hr></hr></th><th colspan="3" align="center" valign="bottom"><bold>Quartiles</bold><hr></hr></th><th align="center" valign="bottom"><bold>Mean</bold><hr></hr></th><th align="center" valign="bottom"><bold>St. Dev.</bold><hr></hr></th><th colspan="3" align="center" valign="bottom"><bold>Quartiles</bold><hr></hr></th><th align="center" valign="bottom"><bold>Mean</bold><hr></hr></th><th align="center" valign="bottom"><bold>St. Dev.</bold><hr></hr></th><th colspan="3" align="center" valign="bottom"><bold>Quartiles</bold><hr></hr></th><th align="center" valign="bottom"> <hr></hr></th></tr><tr><th align="left"> </th><th align="center"> </th><th align="center"> </th><th align="center"><bold>1</bold><sup><bold>st</bold></sup></th><th align="center"><bold>2</bold><sup><bold>nd</bold></sup></th><th align="center"><bold>3</bold><sup><bold>rd</bold></sup></th><th align="center"> </th><th align="center"> </th><th align="center"><bold>1</bold><sup><bold>st</bold></sup></th><th align="center"><bold>2</bold><sup><bold>nd</bold></sup></th><th align="center"><bold>3</bold><sup><bold>rd</bold></sup></th><th align="center"> </th><th align="center"> </th><th align="center"><bold>1</bold><sup><bold>st</bold></sup></th><th align="center"><bold>2</bold><sup><bold>nd</bold></sup></th><th align="center"><bold>3</bold><sup><bold>rd</bold></sup></th><th align="center"> </th></tr></thead><tbody valign="top"><tr><td align="left" valign="bottom">AVNN<hr></hr></td><td align="center" valign="bottom">859.7<hr></hr></td><td align="center" valign="bottom">109.4<hr></hr></td><td align="center" valign="bottom">784.1<hr></hr></td><td align="center" valign="bottom">848.9<hr></hr></td><td align="center" valign="bottom">916.8<hr></hr></td><td align="center" valign="bottom">867.8<hr></hr></td><td align="center" valign="bottom">136.4<hr></hr></td><td align="center" valign="bottom">774.9<hr></hr></td><td align="center" valign="bottom">853.5<hr></hr></td><td align="center" valign="bottom">954.4<hr></hr></td><td align="center" valign="bottom">884.4<hr></hr></td><td align="center" valign="bottom">119.0<hr></hr></td><td align="center" valign="bottom">793.6<hr></hr></td><td align="center" valign="bottom">875.4<hr></hr></td><td align="center" valign="bottom">963.4<hr></hr></td><td align="center" valign="bottom">0.525<hr></hr></td></tr><tr><td align="left" valign="bottom">SDNN<hr></hr></td><td align="center" valign="bottom">125.7<hr></hr></td><td align="center" valign="bottom">30.2<hr></hr></td><td align="center" valign="bottom">101.9<hr></hr></td><td align="center" valign="bottom">119.5<hr></hr></td><td align="center" valign="bottom">146.1<hr></hr></td><td align="center" valign="bottom">119.4<hr></hr></td><td align="center" valign="bottom">38.8<hr></hr></td><td align="center" valign="bottom">92.2<hr></hr></td><td align="center" valign="bottom">111.1<hr></hr></td><td align="center" valign="bottom">140.1<hr></hr></td><td align="center" valign="bottom">116.6<hr></hr></td><td align="center" valign="bottom">36.1<hr></hr></td><td align="center" valign="bottom">94.7<hr></hr></td><td align="center" valign="bottom">113.6<hr></hr></td><td align="center" valign="bottom">141.1<hr></hr></td><td align="center" valign="bottom">0.280<hr></hr></td></tr><tr><td align="left" valign="bottom">SDANN<hr></hr></td><td align="center" valign="bottom">113.4<hr></hr></td><td align="center" valign="bottom">32.5<hr></hr></td><td align="center" valign="bottom">90.1<hr></hr></td><td align="center" valign="bottom">108.6<hr></hr></td><td align="center" valign="bottom">137.0<hr></hr></td><td align="center" valign="bottom">106.6<hr></hr></td><td align="center" valign="bottom">38.7<hr></hr></td><td align="center" valign="bottom">78.0<hr></hr></td><td align="center" valign="bottom">99.4<hr></hr></td><td align="center" valign="bottom">129.1<hr></hr></td><td align="center" valign="bottom">105.2<hr></hr></td><td align="center" valign="bottom">36.1<hr></hr></td><td align="center" valign="bottom">81.2<hr></hr></td><td align="center" valign="bottom">104.0<hr></hr></td><td align="center" valign="bottom">132.4<hr></hr></td><td align="center" valign="bottom">0.308<hr></hr></td></tr><tr><td align="left" valign="bottom">SDNN IDX<hr></hr></td><td align="center" valign="bottom">51.9<hr></hr></td><td align="center" valign="bottom">11.8<hr></hr></td><td align="center" valign="bottom">43.2<hr></hr></td><td align="center" valign="bottom">51.4<hr></hr></td><td align="center" valign="bottom">58.9<hr></hr></td><td align="center" valign="bottom">51.2<hr></hr></td><td align="center" valign="bottom">16.5<hr></hr></td><td align="center" valign="bottom">40.7<hr></hr></td><td align="center" valign="bottom">47.4<hr></hr></td><td align="center" valign="bottom">61.1<hr></hr></td><td align="center" valign="bottom">45.4<hr></hr></td><td align="center" valign="bottom">13.7<hr></hr></td><td align="center" valign="bottom">36.2<hr></hr></td><td align="center" valign="bottom">44.3<hr></hr></td><td align="center" valign="bottom">58.3<hr></hr></td><td align="center" valign="bottom">0.168<hr></hr></td></tr><tr><td align="left" valign="bottom">RMSSD<hr></hr></td><td align="center" valign="bottom">32.6<hr></hr></td><td align="center" valign="bottom">12.5<hr></hr></td><td align="center" valign="bottom">24.4<hr></hr></td><td align="center" valign="bottom">30.1<hr></hr></td><td align="center" valign="bottom">38.1<hr></hr></td><td align="center" valign="bottom">35.7<hr></hr></td><td align="center" valign="bottom">18.9<hr></hr></td><td align="center" valign="bottom">22.6<hr></hr></td><td align="center" valign="bottom">30.7<hr></hr></td><td align="center" valign="bottom">42.3<hr></hr></td><td align="center" valign="bottom">35.6<hr></hr></td><td align="center" valign="bottom">14.3<hr></hr></td><td align="center" valign="bottom">24.4<hr></hr></td><td align="center" valign="bottom">33.5<hr></hr></td><td align="center" valign="bottom">42.1<hr></hr></td><td align="center" valign="bottom">0.602<hr></hr></td></tr><tr><td align="left" valign="bottom">pNN50<hr></hr></td><td align="center" valign="bottom">8.8<hr></hr></td><td align="center" valign="bottom">6.6<hr></hr></td><td align="center" valign="bottom">3.8<hr></hr></td><td align="center" valign="bottom">7.7<hr></hr></td><td align="center" valign="bottom">11.9<hr></hr></td><td align="center" valign="bottom">11.2<hr></hr></td><td align="center" valign="bottom">10.4<hr></hr></td><td align="center" valign="bottom">2.8<hr></hr></td><td align="center" valign="bottom">7.9<hr></hr></td><td align="center" valign="bottom">17.8<hr></hr></td><td align="center" valign="bottom">11.5<hr></hr></td><td align="center" valign="bottom">11.0<hr></hr></td><td align="center" valign="bottom">4.1<hr></hr></td><td align="center" valign="bottom">9.7<hr></hr></td><td align="center" valign="bottom">12.9<hr></hr></td><td align="center" valign="bottom">0.714<hr></hr></td></tr><tr><td align="left" valign="bottom">TOTPWR<hr></hr></td><td align="center" valign="bottom">18224<hr></hr></td><td align="center" valign="bottom">8902<hr></hr></td><td align="center" valign="bottom">11002<hr></hr></td><td align="center" valign="bottom">16124<hr></hr></td><td align="center" valign="bottom">23743<hr></hr></td><td align="center" valign="bottom">17498<hr></hr></td><td align="center" valign="bottom">12477<hr></hr></td><td align="center" valign="bottom">8919<hr></hr></td><td align="center" valign="bottom">13736<hr></hr></td><td align="center" valign="bottom">21744<hr></hr></td><td align="center" valign="bottom">17099<hr></hr></td><td align="center" valign="bottom">10273<hr></hr></td><td align="center" valign="bottom">9648<hr></hr></td><td align="center" valign="bottom">14338<hr></hr></td><td align="center" valign="bottom">24713<hr></hr></td><td align="center" valign="bottom">0.354<hr></hr></td></tr><tr><td align="left" valign="bottom">ULF<hr></hr></td><td align="center" valign="bottom">14919<hr></hr></td><td align="center" valign="bottom">8093<hr></hr></td><td align="center" valign="bottom">8797<hr></hr></td><td align="center" valign="bottom">12379<hr></hr></td><td align="center" valign="bottom">18709<hr></hr></td><td align="center" valign="bottom">14098<hr></hr></td><td align="center" valign="bottom">10139<hr></hr></td><td align="center" valign="bottom">7083<hr></hr></td><td align="center" valign="bottom">10675<hr></hr></td><td align="center" valign="bottom">18458<hr></hr></td><td align="center" valign="bottom">14311<hr></hr></td><td align="center" valign="bottom">8999<hr></hr></td><td align="center" valign="bottom">7867<hr></hr></td><td align="center" valign="bottom">11539<hr></hr></td><td align="center" valign="bottom">20217<hr></hr></td><td align="center" valign="bottom">0.368<hr></hr></td></tr><tr><td align="left" valign="bottom">VLF<hr></hr></td><td align="center" valign="bottom">1815<hr></hr></td><td align="center" valign="bottom">843<hr></hr></td><td align="center" valign="bottom">1184<hr></hr></td><td align="center" valign="bottom">1592<hr></hr></td><td align="center" valign="bottom">2384<hr></hr></td><td align="center" valign="bottom">1872<hr></hr></td><td align="center" valign="bottom">1417<hr></hr></td><td align="center" valign="bottom">961<hr></hr></td><td align="center" valign="bottom">1471<hr></hr></td><td align="center" valign="bottom">2416<hr></hr></td><td align="center" valign="bottom">1368<hr></hr></td><td align="center" valign="bottom">835<hr></hr></td><td align="center" valign="bottom">780<hr></hr></td><td align="center" valign="bottom">1254<hr></hr></td><td align="center" valign="bottom">1959<hr></hr></td><td align="center" valign="bottom">0.071<hr></hr></td></tr><tr><td align="left" valign="bottom">LF<hr></hr></td><td align="center" valign="bottom">861<hr></hr></td><td align="center" valign="bottom">522<hr></hr></td><td align="center" valign="bottom">481<hr></hr></td><td align="center" valign="bottom">711<hr></hr></td><td align="center" valign="bottom">1108<hr></hr></td><td align="center" valign="bottom">823<hr></hr></td><td align="center" valign="bottom">795<hr></hr></td><td align="center" valign="bottom">368<hr></hr></td><td align="center" valign="bottom">601<hr></hr></td><td align="center" valign="bottom">922<hr></hr></td><td align="center" valign="bottom">660<hr></hr></td><td align="center" valign="bottom">460<hr></hr></td><td align="center" valign="bottom">344<hr></hr></td><td align="center" valign="bottom">543<hr></hr></td><td align="center" valign="bottom">925<hr></hr></td><td align="center" valign="bottom">0.123<hr></hr></td></tr><tr><td align="left" valign="bottom">HF<hr></hr></td><td align="center" valign="bottom">629<hr></hr></td><td align="center" valign="bottom">502<hr></hr></td><td align="center" valign="bottom">293<hr></hr></td><td align="center" valign="bottom">471<hr></hr></td><td align="center" valign="bottom">743<hr></hr></td><td align="center" valign="bottom">705<hr></hr></td><td align="center" valign="bottom">715<hr></hr></td><td align="center" valign="bottom">205<hr></hr></td><td align="center" valign="bottom">496<hr></hr></td><td align="center" valign="bottom">815<hr></hr></td><td align="center" valign="bottom">760<hr></hr></td><td align="center" valign="bottom">602<hr></hr></td><td align="center" valign="bottom">251<hr></hr></td><td align="center" valign="bottom">527<hr></hr></td><td align="center" valign="bottom">1230<hr></hr></td><td align="center" valign="bottom">0.626<hr></hr></td></tr><tr><td align="left">LF/HF</td><td align="center">1.74</td><td align="center">0.92</td><td align="center">1.17</td><td align="center">1.44</td><td align="center">2.11</td><td align="center">1.48</td><td align="center">0.90</td><td align="center">0.91</td><td align="center">1.25</td><td align="center">1.75</td><td align="center">1.00</td><td align="center">0.47</td><td align="center">0.71</td><td align="center">0.85</td><td align="center">1.25</td><td align="center"><bold><0.001</bold></td></tr></tbody></table><table-wrap-foot><p>St. Dev. standard deviation.</p><p>The p-values refer to Kruskal-Wallis test.</p></table-wrap-foot></table-wrap><table-wrap position="float" id="T4"><label>Table 4</label><caption><p>Characteristics of the study sample of patients stratified according to IMT</p></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="top"><tr><th align="left" valign="bottom"> <hr></hr></th><th align="center" valign="bottom"><bold>Normal</bold><hr></hr></th><th align="center" valign="bottom"><bold>Thickening</bold><hr></hr></th><th align="center" valign="bottom"><bold>Plaque</bold><hr></hr></th><th colspan="4" align="center" valign="bottom"><bold>P Values</bold><hr></hr></th></tr><tr><th align="left"> </th><th align="center"> </th><th align="center"> </th><th align="center"> </th><th align="center"><bold>ANOVA or χ</bold><sup><bold>2</bold></sup></th><th align="center"><bold>Normal vs Thickening</bold></th><th align="center"><bold>Normal vs Plaque</bold></th><th align="center"><bold>Thickening vs Plaque</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="bottom">Age (years)<hr></hr></td><td align="center" valign="bottom">47.3 ± 13.3<hr></hr></td><td align="center" valign="bottom">57.0 ± 9.6<hr></hr></td><td align="center" valign="bottom">65.9 ± 9.8<hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td><td align="center" valign="bottom"><bold>0.004</bold><hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td><td align="center" valign="bottom"><bold>0.001</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">Sex (male/female)<hr></hr></td><td align="center" valign="bottom">16/10<hr></hr></td><td align="center" valign="bottom">10/12<hr></hr></td><td align="center" valign="bottom">101/51<hr></hr></td><td align="center" valign="bottom">0.157<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Family history of hypertension (yes/no)<hr></hr></td><td align="center" valign="bottom">16/10<hr></hr></td><td align="center" valign="bottom">18/4<hr></hr></td><td align="center" valign="bottom">79/73<hr></hr></td><td align="center" valign="bottom"><bold>0.026</bold><hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Family history of stroke (yes/no)<hr></hr></td><td align="center" valign="bottom">4/22<hr></hr></td><td align="center" valign="bottom">6/16<hr></hr></td><td align="center" valign="bottom">29/123<hr></hr></td><td align="center" valign="bottom">0.564<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Smokers (yes/ex/no)<hr></hr></td><td align="center" valign="bottom">4/3/19<hr></hr></td><td align="center" valign="bottom">6/2/14<hr></hr></td><td align="center" valign="bottom">25/37/90<hr></hr></td><td align="center" valign="bottom">0.242<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Diabetes (yes/no)<hr></hr></td><td align="center" valign="bottom">2/24<hr></hr></td><td align="center" valign="bottom">1/21<hr></hr></td><td align="center" valign="bottom">17/135<hr></hr></td><td align="center" valign="bottom">0.572<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Diastolic BP (mmHg)<hr></hr></td><td align="center" valign="bottom">76.5 ± 10.8<hr></hr></td><td align="center" valign="bottom">73.4 ± 18.6<hr></hr></td><td align="center" valign="bottom">75.8 ± 11.1<hr></hr></td><td align="center" valign="bottom">0.643<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td></tr><tr><td align="left" valign="bottom">Systolic BP (mmHg)<hr></hr></td><td align="center" valign="bottom">131.5 ± 19.2<hr></hr></td><td align="center" valign="bottom">124.1 ± 33.2<hr></hr></td><td align="center" valign="bottom">134.8 ± 21.1<hr></hr></td><td align="center" valign="bottom">0.106<hr></hr></td><td align="center" valign="bottom">0.768<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">0.113<hr></hr></td></tr><tr><td align="left" valign="bottom">Pulse pressure (mmHg)<hr></hr></td><td align="center" valign="bottom">55.0 ± 14.9<hr></hr></td><td align="center" valign="bottom">50.6 ± 19.9<hr></hr></td><td align="center" valign="bottom">59.0 ± 17.8<hr></hr></td><td align="center" valign="bottom">0.086<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">0.856<hr></hr></td><td align="center" valign="bottom">0.117<hr></hr></td></tr><tr><td align="left" valign="bottom">Fasting blood glucose (mmHg)<hr></hr></td><td align="center" valign="bottom">98.0 ± 20.7<hr></hr></td><td align="center" valign="bottom">95.7 ± 22.0<hr></hr></td><td align="center" valign="bottom">104.5 ± 24.7<hr></hr></td><td align="center" valign="bottom">0.154<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">0.601<hr></hr></td><td align="center" valign="bottom">0.321<hr></hr></td></tr><tr><td align="left" valign="bottom">Total Cholesterol (mg/dl)<hr></hr></td><td align="center" valign="bottom">182.0 ± 38.0<hr></hr></td><td align="center" valign="bottom">192.0 ± 39.1<hr></hr></td><td align="center" valign="bottom">185.6 ± 41.4<hr></hr></td><td align="center" valign="bottom">0.687<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td></tr><tr><td align="left" valign="bottom">BMI (kg/m<sup>2</sup>)<hr></hr></td><td align="center" valign="bottom">28.8 ± 5.4<hr></hr></td><td align="center" valign="bottom">27.3 ± 3.7<hr></hr></td><td align="center" valign="bottom">27.6 ± 4.6<hr></hr></td><td align="center" valign="bottom">0.395<hr></hr></td><td align="center" valign="bottom">0.747<hr></hr></td><td align="center" valign="bottom">0.596<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td></tr><tr><td align="left" valign="bottom">Beta-blockers (yes/no)<hr></hr></td><td align="center" valign="bottom">15/11<hr></hr></td><td align="center" valign="bottom">6/16<hr></hr></td><td align="center" valign="bottom">46/106<hr></hr></td><td align="center" valign="bottom"><bold>0.019</bold><hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Alphabeta-blockers (yes/no)<hr></hr></td><td align="center" valign="bottom">1/25<hr></hr></td><td align="center" valign="bottom">3/19<hr></hr></td><td align="center" valign="bottom">17/135<hr></hr></td><td align="center" valign="bottom">0.465<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Alpha-blockers (yes/no)<hr></hr></td><td align="center" valign="bottom">1/25<hr></hr></td><td align="center" valign="bottom">2/20<hr></hr></td><td align="center" valign="bottom">13/139<hr></hr></td><td align="center" valign="bottom">0.702<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Diuretics (yes/no)<hr></hr></td><td align="center" valign="bottom">9/17<hr></hr></td><td align="center" valign="bottom">8/14<hr></hr></td><td align="center" valign="bottom">70/82<hr></hr></td><td align="center" valign="bottom">0.429<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">ACE inhibitor (yes/no)<hr></hr></td><td align="center" valign="bottom">10/16<hr></hr></td><td align="center" valign="bottom">8/14<hr></hr></td><td align="center" valign="bottom">57/95<hr></hr></td><td align="center" valign="bottom">0.989<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">Dihydropyridine (yes/no)<hr></hr></td><td align="center" valign="bottom">7/19<hr></hr></td><td align="center" valign="bottom">4/18<hr></hr></td><td align="center" valign="bottom">41/111<hr></hr></td><td align="center" valign="bottom">0.675<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">eGFR (mL/min/1.73 m<sup>2</sup>)<hr></hr></td><td align="center" valign="bottom">84.1 ± 17.5<hr></hr></td><td align="center" valign="bottom">81.2 ± 17.8<hr></hr></td><td align="center" valign="bottom">75.2 ± 19.1<hr></hr></td><td align="center" valign="bottom">0.045<hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom">0.077<hr></hr></td><td align="center" valign="bottom">0.479<hr></hr></td></tr><tr><td align="left" valign="bottom">Renal involvement<hr></hr></td><td align="center" valign="bottom">9/15/2<hr></hr></td><td align="center" valign="bottom">6/13/3<hr></hr></td><td align="center" valign="bottom">33/91/28<hr></hr></td><td align="center" valign="bottom">0.502<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom">IMT (mm)<hr></hr></td><td align="center" valign="bottom">0.89 ± 0.11<hr></hr></td><td align="center" valign="bottom">1.19 ± 0.08<hr></hr></td><td align="center" valign="bottom">2.62 ± 1.61<hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td><td align="center" valign="bottom">1<hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">LVMi g/m<sup>2</sup><hr></hr></td><td align="center" valign="bottom">109.6 ± 19.0<hr></hr></td><td align="center" valign="bottom">126.7 ± 33.2<hr></hr></td><td align="center" valign="bottom">134.6 ± 30.9<hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td><td align="center" valign="bottom">0.149<hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td><td align="center" valign="bottom">0.744<hr></hr></td></tr><tr><td align="left">Left Ventricular hypertrophy (no/yes)</td><td align="center">20/6</td><td align="center">11/11</td><td align="center">49/103</td><td align="center"><bold><0.001</bold></td><td align="center"> </td><td align="center"> </td><td align="center"> </td></tr></tbody></table><table-wrap-foot><p>Data are expressed as mean and standard deviation for continuous variables (i.e. age) and as number of patients per each group for categorical variable (i.e. gender).</p><p>The p-value refers to ANOVA and post-hoc comparison with Bonferroni corrections for continuous variables and to χ<sup>2</sup> for categorical variables.</p></table-wrap-foot></table-wrap><table-wrap position="float" id="T5"><label>Table 5</label><caption><p>Comparisons of HRV measurement in the group of patients stratified by IMT</p></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="top"><tr><th align="left" valign="bottom"> <hr></hr></th><th colspan="5" align="center" valign="bottom"><bold>Normal IMT</bold><hr></hr></th><th colspan="5" align="center" valign="bottom"><bold>Thickening</bold><hr></hr></th><th colspan="5" align="center" valign="bottom"><bold>Plaque</bold><hr></hr></th><th align="center" valign="bottom"><bold>P-value</bold><hr></hr></th></tr><tr><th align="left" valign="bottom"> <hr></hr></th><th align="center" valign="bottom"><bold>Mean</bold><hr></hr></th><th align="center" valign="bottom"><bold>St. Dev.</bold><hr></hr></th><th colspan="3" align="center" valign="bottom"><bold>Quartiles</bold><hr></hr></th><th align="center" valign="bottom"><bold>Mean</bold><hr></hr></th><th align="center" valign="bottom"><bold>St. Dev.</bold><hr></hr></th><th colspan="3" align="center" valign="bottom"><bold>Quartiles</bold><hr></hr></th><th align="center" valign="bottom"><bold>Mean</bold><hr></hr></th><th align="center" valign="bottom"><bold>St. Dev.</bold><hr></hr></th><th colspan="3" align="center" valign="bottom"><bold>Quartiles</bold><hr></hr></th><th align="center" valign="bottom"> <hr></hr></th></tr><tr><th align="left"> </th><th align="center"> </th><th align="center"> </th><th align="center"><bold>1</bold><sup><bold>st</bold></sup></th><th align="center"><bold>2</bold><sup><bold>nd</bold></sup></th><th align="center"><bold>3</bold><sup><bold>rd</bold></sup></th><th align="center"> </th><th align="center"> </th><th align="center"><bold>1</bold><sup><bold>st</bold></sup></th><th align="center"><bold>2</bold><sup><bold>nd</bold></sup></th><th align="center"><bold>3</bold><sup><bold>rd</bold></sup></th><th align="center"> </th><th align="center"> </th><th align="center"><bold>1</bold><sup><bold>st</bold></sup></th><th align="center"><bold>2</bold><sup><bold>nd</bold></sup></th><th align="center"><bold>3</bold><sup><bold>rd</bold></sup></th><th align="center"> </th></tr></thead><tbody valign="top"><tr><td align="left" valign="bottom">AVNN<hr></hr></td><td align="center" valign="bottom">830.0<hr></hr></td><td align="center" valign="bottom">123.5<hr></hr></td><td align="center" valign="bottom">749.2<hr></hr></td><td align="center" valign="bottom">821.6<hr></hr></td><td align="center" valign="bottom">916.2<hr></hr></td><td align="center" valign="bottom">842.3<hr></hr></td><td align="center" valign="bottom">141.8<hr></hr></td><td align="center" valign="bottom">746.7<hr></hr></td><td align="center" valign="bottom">820.5<hr></hr></td><td align="center" valign="bottom">957.3<hr></hr></td><td align="center" valign="bottom">879.0<hr></hr></td><td align="center" valign="bottom">124.7<hr></hr></td><td align="center" valign="bottom">797.1<hr></hr></td><td align="center" valign="bottom">864.8<hr></hr></td><td align="center" valign="bottom">952.0<hr></hr></td><td align="center" valign="bottom">0.116<hr></hr></td></tr><tr><td align="left" valign="bottom">SDNN<hr></hr></td><td align="center" valign="bottom">140.1<hr></hr></td><td align="center" valign="bottom">48.8<hr></hr></td><td align="center" valign="bottom">105.3<hr></hr></td><td align="center" valign="bottom">132.3<hr></hr></td><td align="center" valign="bottom">171.3<hr></hr></td><td align="center" valign="bottom">121.7<hr></hr></td><td align="center" valign="bottom">34.3<hr></hr></td><td align="center" valign="bottom">94.2<hr></hr></td><td align="center" valign="bottom">115.3<hr></hr></td><td align="center" valign="bottom">147.2<hr></hr></td><td align="center" valign="bottom">116.9<hr></hr></td><td align="center" valign="bottom">33.3<hr></hr></td><td align="center" valign="bottom">93.3<hr></hr></td><td align="center" valign="bottom">111.6<hr></hr></td><td align="center" valign="bottom">136.9<hr></hr></td><td align="center" valign="bottom"><bold>0.049</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">SDANN<hr></hr></td><td align="center" valign="bottom">128.4<hr></hr></td><td align="center" valign="bottom">49.7<hr></hr></td><td align="center" valign="bottom">88.2<hr></hr></td><td align="center" valign="bottom">124.8<hr></hr></td><td align="center" valign="bottom">157.9<hr></hr></td><td align="center" valign="bottom">110.8<hr></hr></td><td align="center" valign="bottom">34.7<hr></hr></td><td align="center" valign="bottom">81.0<hr></hr></td><td align="center" valign="bottom">102.2<hr></hr></td><td align="center" valign="bottom">138.3<hr></hr></td><td align="center" valign="bottom">104.1<hr></hr></td><td align="center" valign="bottom">33.5<hr></hr></td><td align="center" valign="bottom">80.3<hr></hr></td><td align="center" valign="bottom">98.5<hr></hr></td><td align="center" valign="bottom">124.1<hr></hr></td><td align="center" valign="bottom"><bold>0.046</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">SDNN IDX<hr></hr></td><td align="center" valign="bottom">58.9<hr></hr></td><td align="center" valign="bottom">19.0<hr></hr></td><td align="center" valign="bottom">44.4<hr></hr></td><td align="center" valign="bottom">55.2<hr></hr></td><td align="center" valign="bottom">73.1<hr></hr></td><td align="center" valign="bottom">50.7<hr></hr></td><td align="center" valign="bottom">13.8<hr></hr></td><td align="center" valign="bottom">43.0<hr></hr></td><td align="center" valign="bottom">48.9<hr></hr></td><td align="center" valign="bottom">56.5<hr></hr></td><td align="center" valign="bottom">49.0<hr></hr></td><td align="center" valign="bottom">14.2<hr></hr></td><td align="center" valign="bottom">38.8<hr></hr></td><td align="center" valign="bottom">47.4<hr></hr></td><td align="center" valign="bottom">59.5<hr></hr></td><td align="center" valign="bottom"><bold>0.042</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">RMSSD<hr></hr></td><td align="center" valign="bottom">36.9<hr></hr></td><td align="center" valign="bottom">13.5<hr></hr></td><td align="center" valign="bottom">26.8<hr></hr></td><td align="center" valign="bottom">32.2<hr></hr></td><td align="center" valign="bottom">42.6<hr></hr></td><td align="center" valign="bottom">30.7<hr></hr></td><td align="center" valign="bottom">11.7<hr></hr></td><td align="center" valign="bottom">22.1<hr></hr></td><td align="center" valign="bottom">29.7<hr></hr></td><td align="center" valign="bottom">34.0<hr></hr></td><td align="center" valign="bottom">35.2<hr></hr></td><td align="center" valign="bottom">17.9<hr></hr></td><td align="center" valign="bottom">22.7<hr></hr></td><td align="center" valign="bottom">30.5<hr></hr></td><td align="center" valign="bottom">41.7<hr></hr></td><td align="center" valign="bottom">0.216<hr></hr></td></tr><tr><td align="left" valign="bottom">pNN50<hr></hr></td><td align="center" valign="bottom">12.5<hr></hr></td><td align="center" valign="bottom">9.1<hr></hr></td><td align="center" valign="bottom">5.9<hr></hr></td><td align="center" valign="bottom">8.2<hr></hr></td><td align="center" valign="bottom">16.5<hr></hr></td><td align="center" valign="bottom">9.2<hr></hr></td><td align="center" valign="bottom">9.1<hr></hr></td><td align="center" valign="bottom">2.8<hr></hr></td><td align="center" valign="bottom">6.1<hr></hr></td><td align="center" valign="bottom">11.3<hr></hr></td><td align="center" valign="bottom">10.6<hr></hr></td><td align="center" valign="bottom">10.0<hr></hr></td><td align="center" valign="bottom">3.1<hr></hr></td><td align="center" valign="bottom">8.3<hr></hr></td><td align="center" valign="bottom">15.5<hr></hr></td><td align="center" valign="bottom">0.195<hr></hr></td></tr><tr><td align="left" valign="bottom">TOTPWR<hr></hr></td><td align="center" valign="bottom">24209<hr></hr></td><td align="center" valign="bottom">16727<hr></hr></td><td align="center" valign="bottom">12113<hr></hr></td><td align="center" valign="bottom">19664<hr></hr></td><td align="center" valign="bottom">31647<hr></hr></td><td align="center" valign="bottom">17583<hr></hr></td><td align="center" valign="bottom">10891<hr></hr></td><td align="center" valign="bottom">9798<hr></hr></td><td align="center" valign="bottom">14497<hr></hr></td><td align="center" valign="bottom">22534<hr></hr></td><td align="center" valign="bottom">16480<hr></hr></td><td align="center" valign="bottom">9863<hr></hr></td><td align="center" valign="bottom">9300<hr></hr></td><td align="center" valign="bottom">13860<hr></hr></td><td align="center" valign="bottom">21255<hr></hr></td><td align="center" valign="bottom"><bold>0.049</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">ULF<hr></hr></td><td align="center" valign="bottom">19550<hr></hr></td><td align="center" valign="bottom">13805<hr></hr></td><td align="center" valign="bottom">9436<hr></hr></td><td align="center" valign="bottom">16075<hr></hr></td><td align="center" valign="bottom">25947<hr></hr></td><td align="center" valign="bottom">14453<hr></hr></td><td align="center" valign="bottom">9137<hr></hr></td><td align="center" valign="bottom">7958<hr></hr></td><td align="center" valign="bottom">11822<hr></hr></td><td align="center" valign="bottom">18562<hr></hr></td><td align="center" valign="bottom">13420<hr></hr></td><td align="center" valign="bottom">8327<hr></hr></td><td align="center" valign="bottom">7216<hr></hr></td><td align="center" valign="bottom">10942<hr></hr></td><td align="center" valign="bottom">17851<hr></hr></td><td align="center" valign="bottom">0.092<hr></hr></td></tr><tr><td align="left" valign="bottom">VLF<hr></hr></td><td align="center" valign="bottom">2590<hr></hr></td><td align="center" valign="bottom">1944<hr></hr></td><td align="center" valign="bottom">1113<hr></hr></td><td align="center" valign="bottom">2117<hr></hr></td><td align="center" valign="bottom">3172<hr></hr></td><td align="center" valign="bottom">1746<hr></hr></td><td align="center" valign="bottom">1101<hr></hr></td><td align="center" valign="bottom">1091<hr></hr></td><td align="center" valign="bottom">1514<hr></hr></td><td align="center" valign="bottom">1862<hr></hr></td><td align="center" valign="bottom">1640<hr></hr></td><td align="center" valign="bottom">1027<hr></hr></td><td align="center" valign="bottom">960<hr></hr></td><td align="center" valign="bottom">1325<hr></hr></td><td align="center" valign="bottom">2251<hr></hr></td><td align="center" valign="bottom">0.052<hr></hr></td></tr><tr><td align="left" valign="bottom">LF<hr></hr></td><td align="center" valign="bottom">1255<hr></hr></td><td align="center" valign="bottom">1040<hr></hr></td><td align="center" valign="bottom">471<hr></hr></td><td align="center" valign="bottom">1006<hr></hr></td><td align="center" valign="bottom">1863<hr></hr></td><td align="center" valign="bottom">819<hr></hr></td><td align="center" valign="bottom">627<hr></hr></td><td align="center" valign="bottom">493<hr></hr></td><td align="center" valign="bottom">688<hr></hr></td><td align="center" valign="bottom">934<hr></hr></td><td align="center" valign="bottom">726<hr></hr></td><td align="center" valign="bottom">595<hr></hr></td><td align="center" valign="bottom">357<hr></hr></td><td align="center" valign="bottom">568<hr></hr></td><td align="center" valign="bottom">934<hr></hr></td><td align="center" valign="bottom"><bold>0.009</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">HF<hr></hr></td><td align="center" valign="bottom">813<hr></hr></td><td align="center" valign="bottom">685<hr></hr></td><td align="center" valign="bottom">305<hr></hr></td><td align="center" valign="bottom">542<hr></hr></td><td align="center" valign="bottom">1299<hr></hr></td><td align="center" valign="bottom">566<hr></hr></td><td align="center" valign="bottom">517<hr></hr></td><td align="center" valign="bottom">178<hr></hr></td><td align="center" valign="bottom">499<hr></hr></td><td align="center" valign="bottom">617<hr></hr></td><td align="center" valign="bottom">694<hr></hr></td><td align="center" valign="bottom">661<hr></hr></td><td align="center" valign="bottom">229<hr></hr></td><td align="center" valign="bottom">477<hr></hr></td><td align="center" valign="bottom">914<hr></hr></td><td align="center" valign="bottom">0.376<hr></hr></td></tr><tr><td align="left">LF/HF</td><td align="center">1.78</td><td align="center">0.98</td><td align="center">1.05</td><td align="center">1.53</td><td align="center">2.25</td><td align="center">2.02</td><td align="center">1.25</td><td align="center">1.14</td><td align="center">1.55</td><td align="center">2.71</td><td align="center">1.33</td><td align="center">0.75</td><td align="center">0.82</td><td align="center">1.13</td><td align="center">1.68</td><td align="center"><bold>0.002</bold></td></tr></tbody></table><table-wrap-foot><p>St. Dev. standard deviation.</p><p>The p-values refer to Kruskal-Wallis test.</p></table-wrap-foot></table-wrap><table-wrap position="float" id="T6"><label>Table 6</label><caption><p>Characteristics of the study sample of patients with and without LVH</p></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="top"><tr><th align="left" valign="bottom"> <hr></hr></th><th colspan="2" align="center" valign="bottom"><bold>LVH</bold><hr></hr></th><th align="center" valign="bottom"><bold>P values</bold><hr></hr></th></tr><tr><th align="left"> </th><th align="center"><bold>Patient Group with LVH</bold></th><th align="center"><bold>Patient group without LVH</bold></th><th align="center"> </th></tr></thead><tbody valign="top"><tr><td align="left" valign="bottom">Age (years)<hr></hr></td><td align="center" valign="bottom">56.8 ± 12.1<hr></hr></td><td align="center" valign="bottom">66.3 ± 10.6<hr></hr></td><td align="center" valign="bottom"><bold>0.001</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">Sex (male/female)<hr></hr></td><td align="center" valign="bottom">49/31<hr></hr></td><td align="center" valign="bottom">78/42<hr></hr></td><td align="center" valign="bottom">0.589<hr></hr></td></tr><tr><td align="left" valign="bottom">Family history of hypertension (yes/no)<hr></hr></td><td align="center" valign="bottom">48/32<hr></hr></td><td align="center" valign="bottom">65/55<hr></hr></td><td align="center" valign="bottom">0.415<hr></hr></td></tr><tr><td align="left" valign="bottom">Family history of stroke (yes/no)<hr></hr></td><td align="center" valign="bottom">15/65<hr></hr></td><td align="center" valign="bottom">24/96<hr></hr></td><td align="center" valign="bottom">0.827<hr></hr></td></tr><tr><td align="left" valign="bottom">Smokers (yes/ex/no)<hr></hr></td><td align="center" valign="bottom">17/18/45<hr></hr></td><td align="center" valign="bottom">18/24/78<hr></hr></td><td align="center" valign="bottom">0.404<hr></hr></td></tr><tr><td align="left" valign="bottom">Diabetes (yes/no)<hr></hr></td><td align="center" valign="bottom">2/78<hr></hr></td><td align="center" valign="bottom">18/102<hr></hr></td><td align="center" valign="bottom"><bold>0.004</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">Diastolic BP (mmHg)<hr></hr></td><td align="center" valign="bottom">73.8 ± 12.1<hr></hr></td><td align="center" valign="bottom">76.8 ± 11.8<hr></hr></td><td align="center" valign="bottom">0.094<hr></hr></td></tr><tr><td align="left" valign="bottom">Systolic BP (mmHg)<hr></hr></td><td align="center" valign="bottom">126.1 ± 25.3<hr></hr></td><td align="center" valign="bottom">137.9 ± 19.4<hr></hr></td><td align="center" valign="bottom"><bold>0.001</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">Pulse pressure (mmHg)<hr></hr></td><td align="center" valign="bottom">52.3 ± 18.0<hr></hr></td><td align="center" valign="bottom">61.1 ± 16.8<hr></hr></td><td align="center" valign="bottom"><bold>0.001</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">Fasting blood glucose (mmHg)<hr></hr></td><td align="center" valign="bottom">99.8 ± 23.6<hr></hr></td><td align="center" valign="bottom">104.7 ± 24.3<hr></hr></td><td align="center" valign="bottom">0.161<hr></hr></td></tr><tr><td align="left" valign="bottom">Total Cholesterol (mg/dl)<hr></hr></td><td align="center" valign="bottom">191.0 ± 38.6<hr></hr></td><td align="center" valign="bottom">182.3 ± 41.7<hr></hr></td><td align="center" valign="bottom">0.132<hr></hr></td></tr><tr><td align="left" valign="bottom">BMI (kg/m<sup>2</sup>)<hr></hr></td><td align="center" valign="bottom">27.2 ± 4.3<hr></hr></td><td align="center" valign="bottom">28.0 ± 4.8<hr></hr></td><td align="center" valign="bottom">0.235<hr></hr></td></tr><tr><td align="left" valign="bottom">Beta-blockers (yes/no)<hr></hr></td><td align="center" valign="bottom">31/49<hr></hr></td><td align="center" valign="bottom">36/84<hr></hr></td><td align="center" valign="bottom">0.199<hr></hr></td></tr><tr><td align="left" valign="bottom">Alphabeta-blockers (yes/no)<hr></hr></td><td align="center" valign="bottom">7/73<hr></hr></td><td align="center" valign="bottom">14/106<hr></hr></td><td align="center" valign="bottom">0.510<hr></hr></td></tr><tr><td align="left" valign="bottom">Alpha-blockers (yes/no)<hr></hr></td><td align="center" valign="bottom">5/75<hr></hr></td><td align="center" valign="bottom">11/109<hr></hr></td><td align="center" valign="bottom">0.456<hr></hr></td></tr><tr><td align="left" valign="bottom">Diuretics (yes/no)<hr></hr></td><td align="center" valign="bottom">25/55<hr></hr></td><td align="center" valign="bottom">62/58<hr></hr></td><td align="center" valign="bottom"><bold>0.004</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">ACE inhibitor (yes/no)<hr></hr></td><td align="center" valign="bottom">25/55<hr></hr></td><td align="center" valign="bottom">50/70<hr></hr></td><td align="center" valign="bottom">0.136<hr></hr></td></tr><tr><td align="left" valign="bottom">Dihydropyridine (yes/no)<hr></hr></td><td align="center" valign="bottom">17/63<hr></hr></td><td align="center" valign="bottom">35/85<hr></hr></td><td align="center" valign="bottom">0.211<hr></hr></td></tr><tr><td align="left" valign="bottom">eGFR (mL/min/1.73 m<sup>2</sup>)<hr></hr></td><td align="center" valign="bottom">79.9 ± 17.9<hr></hr></td><td align="center" valign="bottom">75.1 ± 19.5<hr></hr></td><td align="center" valign="bottom">0.071<hr></hr></td></tr><tr><td align="left" valign="bottom">Kidney Involvement (1/2 /3)<hr></hr></td><td align="center" valign="bottom">24/44/12<hr></hr></td><td align="center" valign="bottom">24/75/21<hr></hr></td><td align="center" valign="bottom">0.268<hr></hr></td></tr><tr><td align="left" valign="bottom">IMT (mm)<hr></hr></td><td align="center" valign="bottom">1.82 ± 0.93<hr></hr></td><td align="center" valign="bottom">2.52 ± 1.82<hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td></tr><tr><td align="left" valign="bottom">Vascular abnormalities (no/ thickening/plaque)<hr></hr></td><td align="center" valign="bottom">20/11/49<hr></hr></td><td align="center" valign="bottom">6/11/103<hr></hr></td><td align="center" valign="bottom"><bold><0.001</bold><hr></hr></td></tr><tr><td align="left">LVMi g/m<sup>2</sup></td><td align="center">105.0 ± 13.8</td><td align="center">147.5 ± 27.3</td><td align="center"><bold><0.001</bold></td></tr></tbody></table><table-wrap-foot><p>Data are expressed as mean and standard deviation for continuous variables (i.e. age) and as number of patients per each group for categorical variable (i.e. gender).</p><p>The p-values refer to t-test for continuous variables and χ<sup>2</sup> for categorical variables.</p></table-wrap-foot></table-wrap><table-wrap position="float" id="T7"><label>Table 7</label><caption><p>Comparisons of HRV measurement in the group of patients with and without LVH</p></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="top"><tr><th align="left" valign="bottom"> <hr></hr></th><th colspan="5" align="center" valign="bottom"><bold>Patients with LVH</bold><hr></hr></th><th colspan="5" align="center" valign="bottom"><bold>Patients without LVH</bold><hr></hr></th><th align="center" valign="bottom"><bold>P values</bold><hr></hr></th></tr><tr><th align="left" valign="bottom"> <hr></hr></th><th align="center" valign="bottom"><bold>Mean</bold><hr></hr></th><th align="center" valign="bottom"><bold>St. Dev.</bold><hr></hr></th><th colspan="3" align="center" valign="bottom"><bold>Quartiles</bold><hr></hr></th><th align="center" valign="bottom"><bold>Mean</bold><hr></hr></th><th align="center" valign="bottom"><bold>St. Dev.</bold><hr></hr></th><th colspan="3" align="center" valign="bottom"><bold>Quartiles</bold><hr></hr></th><th align="center" valign="bottom"> <hr></hr></th></tr><tr><th align="left"> </th><th align="center"> </th><th align="center"> </th><th align="center"><bold>1</bold><sup><bold>st</bold></sup></th><th align="center"><bold>2</bold><sup><bold>nd</bold></sup></th><th align="center"><bold>3</bold><sup><bold>rd</bold></sup></th><th align="center"> </th><th align="center"> </th><th align="center"><bold>1</bold><sup><bold>st</bold></sup></th><th align="center"><bold>2</bold><sup><bold>nd</bold></sup></th><th align="center"><bold>3</bold><sup><bold>rd</bold></sup></th><th align="center"> </th></tr></thead><tbody><tr><td align="left" valign="bottom">AVNN<hr></hr></td><td align="center" valign="bottom">846.9<hr></hr></td><td align="center" valign="bottom">121.8<hr></hr></td><td align="center" valign="bottom">772.6<hr></hr></td><td align="center" valign="bottom">829.5<hr></hr></td><td align="center" valign="bottom">916.8<hr></hr></td><td align="center" valign="bottom">883.1<hr></hr></td><td align="center" valign="bottom">129.2<hr></hr></td><td align="center" valign="bottom">789.9<hr></hr></td><td align="center" valign="bottom">863.7<hr></hr></td><td align="center" valign="bottom">963.8<hr></hr></td><td align="center" valign="bottom">0.071<hr></hr></td></tr><tr><td align="left" valign="bottom">SDNN<hr></hr></td><td align="center" valign="bottom">123.5<hr></hr></td><td align="center" valign="bottom">37.0<hr></hr></td><td align="center" valign="bottom">101.5<hr></hr></td><td align="center" valign="bottom">118.3<hr></hr></td><td align="center" valign="bottom">142.3<hr></hr></td><td align="center" valign="bottom">118.4<hr></hr></td><td align="center" valign="bottom">36.0<hr></hr></td><td align="center" valign="bottom">91.8<hr></hr></td><td align="center" valign="bottom">112.7<hr></hr></td><td align="center" valign="bottom">142.4<hr></hr></td><td align="center" valign="bottom">0.247<hr></hr></td></tr><tr><td align="left" valign="bottom">SDANN<hr></hr></td><td align="center" valign="bottom">111.2<hr></hr></td><td align="center" valign="bottom">37.6<hr></hr></td><td align="center" valign="bottom">88.0<hr></hr></td><td align="center" valign="bottom">106.7<hr></hr></td><td align="center" valign="bottom">128.7<hr></hr></td><td align="center" valign="bottom">105.9<hr></hr></td><td align="center" valign="bottom">36.3<hr></hr></td><td align="center" valign="bottom">79.4<hr></hr></td><td align="center" valign="bottom">99.0<hr></hr></td><td align="center" valign="bottom">129.5<hr></hr></td><td align="center" valign="bottom">0.304<hr></hr></td></tr><tr><td align="left" valign="bottom">SDNN IDX<hr></hr></td><td align="center" valign="bottom">51.9<hr></hr></td><td align="center" valign="bottom">15.0<hr></hr></td><td align="center" valign="bottom">42.7<hr></hr></td><td align="center" valign="bottom">49.5<hr></hr></td><td align="center" valign="bottom">60.8<hr></hr></td><td align="center" valign="bottom">49.5<hr></hr></td><td align="center" valign="bottom">15.2<hr></hr></td><td align="center" valign="bottom">38.5<hr></hr></td><td align="center" valign="bottom">47.8<hr></hr></td><td align="center" valign="bottom">58.4<hr></hr></td><td align="center" valign="bottom">0.127<hr></hr></td></tr><tr><td align="left" valign="bottom">RMSSD<hr></hr></td><td align="center" valign="bottom">32.8<hr></hr></td><td align="center" valign="bottom">14.5<hr></hr></td><td align="center" valign="bottom">22.9<hr></hr></td><td align="center" valign="bottom">29.2<hr></hr></td><td align="center" valign="bottom">36.4<hr></hr></td><td align="center" valign="bottom">36.4<hr></hr></td><td align="center" valign="bottom">18.1<hr></hr></td><td align="center" valign="bottom">23.1<hr></hr></td><td align="center" valign="bottom">32.4<hr></hr></td><td align="center" valign="bottom">42.3<hr></hr></td><td align="center" valign="bottom">0.123<hr></hr></td></tr><tr><td align="left" valign="bottom">pNN50<hr></hr></td><td align="center" valign="bottom">9.9<hr></hr></td><td align="center" valign="bottom">10.3<hr></hr></td><td align="center" valign="bottom">3.2<hr></hr></td><td align="center" valign="bottom">7.1<hr></hr></td><td align="center" valign="bottom">11.9<hr></hr></td><td align="center" valign="bottom">11.2<hr></hr></td><td align="center" valign="bottom">9.4<hr></hr></td><td align="center" valign="bottom">3.4<hr></hr></td><td align="center" valign="bottom">9.2<hr></hr></td><td align="center" valign="bottom">17.0<hr></hr></td><td align="center" valign="bottom">0.163<hr></hr></td></tr><tr><td align="left" valign="bottom">TOTPWR<hr></hr></td><td align="center" valign="bottom">18472<hr></hr></td><td align="center" valign="bottom">12108<hr></hr></td><td align="center" valign="bottom">10873<hr></hr></td><td align="center" valign="bottom">15952<hr></hr></td><td align="center" valign="bottom">21928<hr></hr></td><td align="center" valign="bottom">17029<hr></hr></td><td align="center" valign="bottom">10776<hr></hr></td><td align="center" valign="bottom">8958<hr></hr></td><td align="center" valign="bottom">14057<hr></hr></td><td align="center" valign="bottom">22697<hr></hr></td><td align="center" valign="bottom">0.288<hr></hr></td></tr><tr><td align="left" valign="bottom">ULF<hr></hr></td><td align="center" valign="bottom">15018<hr></hr></td><td align="center" valign="bottom">10082<hr></hr></td><td align="center" valign="bottom">8177<hr></hr></td><td align="center" valign="bottom">12029<hr></hr></td><td align="center" valign="bottom">18491<hr></hr></td><td align="center" valign="bottom">13872<hr></hr></td><td align="center" valign="bottom">9043<hr></hr></td><td align="center" valign="bottom">7093<hr></hr></td><td align="center" valign="bottom">11412<hr></hr></td><td align="center" valign="bottom">18656<hr></hr></td><td align="center" valign="bottom">0.347<hr></hr></td></tr><tr><td align="left" valign="bottom">VLF<hr></hr></td><td align="center" valign="bottom">1892<hr></hr></td><td align="center" valign="bottom">1255<hr></hr></td><td align="center" valign="bottom">1074<hr></hr></td><td align="center" valign="bottom">1668<hr></hr></td><td align="center" valign="bottom">2393<hr></hr></td><td align="center" valign="bottom">1697<hr></hr></td><td align="center" valign="bottom">1206<hr></hr></td><td align="center" valign="bottom">923<hr></hr></td><td align="center" valign="bottom">1336<hr></hr></td><td align="center" valign="bottom">2086<hr></hr></td><td align="center" valign="bottom">0.105<hr></hr></td></tr><tr><td align="left" valign="bottom">LF<hr></hr></td><td align="center" valign="bottom">896<hr></hr></td><td align="center" valign="bottom">782<hr></hr></td><td align="center" valign="bottom">429<hr></hr></td><td align="center" valign="bottom">704<hr></hr></td><td align="center" valign="bottom">1092<hr></hr></td><td align="center" valign="bottom">744<hr></hr></td><td align="center" valign="bottom">619<hr></hr></td><td align="center" valign="bottom">369<hr></hr></td><td align="center" valign="bottom">556<hr></hr></td><td align="center" valign="bottom">912<hr></hr></td><td align="center" valign="bottom">0.072<hr></hr></td></tr><tr><td align="left" valign="bottom">HF<hr></hr></td><td align="center" valign="bottom">666<hr></hr></td><td align="center" valign="bottom">694<hr></hr></td><td align="center" valign="bottom">210<hr></hr></td><td align="center" valign="bottom">483<hr></hr></td><td align="center" valign="bottom">757<hr></hr></td><td align="center" valign="bottom">716<hr></hr></td><td align="center" valign="bottom">622<hr></hr></td><td align="center" valign="bottom">261<hr></hr></td><td align="center" valign="bottom">502<hr></hr></td><td align="center" valign="bottom">965<hr></hr></td><td align="center" valign="bottom">0.316<hr></hr></td></tr><tr><td align="left">LF/HF</td><td align="center">1.74</td><td align="center">0.99</td><td align="center">1.03</td><td align="center">1.60</td><td align="center">2.08</td><td align="center">1.28</td><td align="center">0.74</td><td align="center">0.81</td><td align="center">1.03</td><td align="center">1.51</td><td align="center"><bold><0.001</bold></td></tr></tbody></table><table-wrap-foot><p>St. Dev. standard deviation.</p><p>The p-values refer to Wilcoxon test.</p></table-wrap-foot></table-wrap><table-wrap position="float" id="T8"><label>Table 8</label><caption><p>Multinomial or binary logistic regression models</p></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="top"><tr><th align="left"><bold>Compared groups</bold></th><th align="center"><bold>HRV measure, factor or covariate</bold></th><th align="center"><bold>β</bold></th><th align="center"><bold>p</bold></th><th align="center"><bold>OR</bold></th><th colspan="3" align="center"><bold>95% CI of OR</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="bottom">Normal eGFR versus Moderate decreased eGFR<hr></hr></td><td align="center" valign="bottom">Intercept<hr></hr></td><td align="char" valign="bottom" char=".">5.971<hr></hr></td><td align="char" valign="bottom" char=".">0.021<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">LF/HF<hr></hr></td><td align="char" valign="bottom" char=".">1.000<hr></hr></td><td align="char" valign="bottom" char="."><bold>0.038</bold><hr></hr></td><td align="char" valign="bottom" char=".">2.718<hr></hr></td><td align="char" valign="bottom" char=".">1.057<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">6.984<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Systolic BP<hr></hr></td><td align="char" valign="bottom" char=".">−0.003<hr></hr></td><td align="char" valign="bottom" char=".">0.779<hr></hr></td><td align="char" valign="bottom" char=".">0.997<hr></hr></td><td align="char" valign="bottom" char=".">0.974<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">1.020<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Age<hr></hr></td><td align="char" valign="bottom" char=".">−0.109<hr></hr></td><td align="char" valign="bottom" char="."><bold><0.001</bold><hr></hr></td><td align="char" valign="bottom" char=".">0.897<hr></hr></td><td align="char" valign="bottom" char=".">0.847<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">0.948<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Absence of family history of hypertension<hr></hr></td><td align="char" valign="bottom" char=".">1.082<hr></hr></td><td align="char" valign="bottom" char="."><bold>0.047</bold><hr></hr></td><td align="char" valign="bottom" char=".">2.951<hr></hr></td><td align="char" valign="bottom" char=".">1.014<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">8.588<hr></hr></td></tr><tr><td align="left" valign="bottom">Mild decreased eGFR versus Moderate decreased eGFR<hr></hr></td><td align="center" valign="bottom">Intercept<hr></hr></td><td align="char" valign="bottom" char=".">0.527<hr></hr></td><td align="char" valign="bottom" char=".">0.819<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">LF/HF<hr></hr></td><td align="char" valign="bottom" char=".">0.969<hr></hr></td><td align="char" valign="bottom" char="."><bold>0.034</bold><hr></hr></td><td align="char" valign="bottom" char=".">2.637<hr></hr></td><td align="char" valign="bottom" char=".">1.075<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">6.465<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Systolic BP<hr></hr></td><td align="char" valign="bottom" char=".">0.024<hr></hr></td><td align="char" valign="bottom" char="."><bold>0.027</bold><hr></hr></td><td align="char" valign="bottom" char=".">1.024<hr></hr></td><td align="char" valign="bottom" char=".">1.003<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">1.046<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Age<hr></hr></td><td align="char" valign="bottom" char=".">−0.058<hr></hr></td><td align="char" valign="bottom" char="."><bold>0.020</bold><hr></hr></td><td align="char" valign="bottom" char=".">0.943<hr></hr></td><td align="char" valign="bottom" char=".">0.898<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">0.991<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Absence of family history of hypertension<hr></hr></td><td align="char" valign="bottom" char=".">0.710<hr></hr></td><td align="char" valign="bottom" char=".">0.122<hr></hr></td><td align="char" valign="bottom" char=".">2.034<hr></hr></td><td align="char" valign="bottom" char=".">0.827<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">5.001<hr></hr></td></tr><tr><td align="left" valign="bottom">Normal IMT group versus Plaque group<sup>1</sup><hr></hr></td><td align="center" valign="bottom">Intercept<hr></hr></td><td align="char" valign="bottom" char=".">5.552<hr></hr></td><td align="char" valign="bottom" char="."><bold>0.002</bold><hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">SDNN<hr></hr></td><td align="char" valign="bottom" char=".">0.018<hr></hr></td><td align="char" valign="bottom" char="."><bold>0.024</bold><hr></hr></td><td align="char" valign="bottom" char=".">1.018<hr></hr></td><td align="char" valign="bottom" char=".">1.002<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">1.033<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Age<hr></hr></td><td align="char" valign="bottom" char=".">−0.169<hr></hr></td><td align="char" valign="bottom" char="."><bold><0.001</bold><hr></hr></td><td align="char" valign="bottom" char=".">0.844<hr></hr></td><td align="char" valign="bottom" char=".">0.796<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">0.896<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Absence of family history of hypertension<hr></hr></td><td align="char" valign="bottom" char=".">0.347<hr></hr></td><td align="char" valign="bottom" char=".">0.532<hr></hr></td><td align="char" valign="bottom" char=".">1.415<hr></hr></td><td align="char" valign="bottom" char=".">0.476<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">4.211<hr></hr></td></tr><tr><td align="left" valign="bottom">Thickening group versus Plaque group<sup>1</sup><hr></hr></td><td align="center" valign="bottom">Intercept<hr></hr></td><td align="char" valign="bottom" char=".">2.688<hr></hr></td><td align="char" valign="bottom" char=".">0.101<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">SDNN<hr></hr></td><td align="char" valign="bottom" char=".">0.005<hr></hr></td><td align="char" valign="bottom" char=".">0.446<hr></hr></td><td align="char" valign="bottom" char=".">1.005<hr></hr></td><td align="char" valign="bottom" char=".">0.992<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">1.019<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Age<hr></hr></td><td align="char" valign="bottom" char=".">−0.080<hr></hr></td><td align="char" valign="bottom" char="."><bold>0.001</bold><hr></hr></td><td align="char" valign="bottom" char=".">0.923<hr></hr></td><td align="char" valign="bottom" char=".">0.879<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">0.970<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Absence of family history of hypertension<hr></hr></td><td align="char" valign="bottom" char=".">−1.072<hr></hr></td><td align="char" valign="bottom" char=".">0.071<hr></hr></td><td align="char" valign="bottom" char=".">0.342<hr></hr></td><td align="char" valign="bottom" char=".">0.107<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">1.096<hr></hr></td></tr><tr><td align="left" valign="bottom">Normal IMT group versus Plaque group<sup>1</sup><hr></hr></td><td align="center" valign="bottom">Intercept<hr></hr></td><td align="char" valign="bottom" char=".">5.777<hr></hr></td><td align="char" valign="bottom" char=".">0.001<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">SDANN<hr></hr></td><td align="char" valign="bottom" char=".">0.017<hr></hr></td><td align="char" valign="bottom" char="."><bold>0.021</bold><hr></hr></td><td align="char" valign="bottom" char=".">1.017<hr></hr></td><td align="char" valign="bottom" char=".">1.003<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">1.032<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Age<hr></hr></td><td align="char" valign="bottom" char=".">−0.169<hr></hr></td><td align="char" valign="bottom" char="."><bold><0.001</bold><hr></hr></td><td align="char" valign="bottom" char=".">0.845<hr></hr></td><td align="char" valign="bottom" char=".">0.797<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">0.696<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Absence of family history of hypertension<hr></hr></td><td align="char" valign="bottom" char=".">0.357<hr></hr></td><td align="char" valign="bottom" char=".">0.523<hr></hr></td><td align="char" valign="bottom" char=".">1.429<hr></hr></td><td align="char" valign="bottom" char=".">0.478<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">4.270<hr></hr></td></tr><tr><td align="left" valign="bottom">Thickening group versus Plaque group<sup>1</sup><hr></hr></td><td align="center" valign="bottom">Intercept<hr></hr></td><td align="char" valign="bottom" char=".">2.626<hr></hr></td><td align="char" valign="bottom" char=".">0.101<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">SDANN<hr></hr></td><td align="char" valign="bottom" char=".">0.006<hr></hr></td><td align="char" valign="bottom" char=".">0.351<hr></hr></td><td align="char" valign="bottom" char=".">1.006<hr></hr></td><td align="char" valign="bottom" char=".">0.993<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">1.020<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Age<hr></hr></td><td align="char" valign="bottom" char=".">−0.080<hr></hr></td><td align="char" valign="bottom" char="."><bold>0.001</bold><hr></hr></td><td align="char" valign="bottom" char=".">0.923<hr></hr></td><td align="char" valign="bottom" char=".">0.879<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">0.970<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Absence of family history of hypertension<hr></hr></td><td align="char" valign="bottom" char=".">−1.059<hr></hr></td><td align="char" valign="bottom" char=".">0.075<hr></hr></td><td align="char" valign="bottom" char=".">0.347<hr></hr></td><td align="char" valign="bottom" char=".">0.108<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">1.112<hr></hr></td></tr><tr><td align="left" valign="bottom">group with Hypertrophy versus group without Hypertrophy<sup>2</sup><hr></hr></td><td align="center" valign="bottom">Intercept<hr></hr></td><td align="char" valign="bottom" char=".">−5.240<hr></hr></td><td align="char" valign="bottom" char="."><bold>0.004</bold><hr></hr></td><td align="char" valign="bottom" char=".">0.005<hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td><td align="center" valign="bottom"> <hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">LF/HF<hr></hr></td><td align="char" valign="bottom" char=".">−0.155<hr></hr></td><td align="char" valign="bottom" char=".">0.528<hr></hr></td><td align="char" valign="bottom" char=".">0.856<hr></hr></td><td align="char" valign="bottom" char=".">0.563<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">1.302<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Age<hr></hr></td><td align="char" valign="bottom" char=".">0.068<hr></hr></td><td align="char" valign="bottom" char="."><bold><0.001</bold><hr></hr></td><td align="char" valign="bottom" char=".">1.071<hr></hr></td><td align="char" valign="bottom" char=".">1.036<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">1.107<hr></hr></td></tr><tr><td align="left" valign="bottom"> <hr></hr></td><td align="center" valign="bottom">Cholesterol<hr></hr></td><td align="char" valign="bottom" char=".">−0.006<hr></hr></td><td align="char" valign="bottom" char="."><bold>0.141</bold><hr></hr></td><td align="char" valign="bottom" char=".">0.994<hr></hr></td><td align="char" valign="bottom" char=".">0.986<hr></hr></td><td align="center" valign="bottom">to<hr></hr></td><td align="center" valign="bottom">1.002<hr></hr></td></tr><tr><td align="left"> </td><td align="center">Diuretics</td><td align="char" char=".">−0.854</td><td align="char" char="."><bold>0.011</bold></td><td align="char" char=".">0.426</td><td align="char" char=".">0.220</td><td align="center">To</td><td align="center">0.823</td></tr></tbody></table><table-wrap-foot><p>β: regression coefficient.</p><p>p: p-value referred to each variable in the regressions (multinomial or binary logistic).</p><p>OR: odds ratio, which is exp(β).</p><p>95% CI: 95% confidence interval.</p><p><sup>1</sup> multinomial logistic regression.</p><p><sup>2</sup> binary logistic regression.</p></table-wrap-foot></table-wrap></sec><sec sec-type="discussion"><title>Discussion</title><p>To our knowledge, the current study is the first one to investigate standard linear HRV measures, both in time and in frequency domains, in hypertensive patients, categorised by severity of TOD at different levels (cardiac, vascular and renal) and considering adjusted models for age and other clinical parameters (such as gender, metabolic variables). Time and power spectral analysis of 24-hour electrocardiographic monitoring was performed in 200 hypertensive patients in basal conditions. At these same times, patients underwent echocardiographic and carotid ultrasonography study evaluations and routine laboratory evaluations in order to assess TOD at different level. The data of the current study showed that significantly lower values of some HRV measures were found in patients with CV involvement at different levels. Particularly, decreased LF/HF, which is a marker of sympatho-vagal balance, was found in the patients with moderate decreased eGFR, the highest grade of kidney involvement considered in this study. Similarly, depressed values of indexes of the overall ANS modulation on the heart, such SDNN and SDANN, were found in patients with plaque compared to patients with a normal IMT. These associations remained significant after adjustment for other factors known to contribute to the development of TOD, including diabetes, hypertension, and metabolic variables. Moreover, depressed LF/HF was found also in patients with LVH but this association was not significant after adjustment for other factors. As stated in a recent paper by Garcia-Garcia [<xref ref-type="bibr" rid="B23">23</xref>] the association between HRV and the development of TOD or vascular alterations has not been clearly established. Garcia-Garcia [<xref ref-type="bibr" rid="B23">23</xref>] investigated the association between 24-hours heart rate and IMT, LVMi, and eGFR, by performing a cross-sectional study including 360 hypertensive patients without heart rate lowering drugs, aged 30–80 years. We underline that they computed only two HR parameters: the mean HR and the standard deviation of HR (which are similar to AVNN and SDNN computed in the current study, respectively), while in this study almost all the linear HRV measures were computed as recommended and standardised in International Guidelines [<xref ref-type="bibr" rid="B8">8</xref>] and confirmed by recent literature [<xref ref-type="bibr" rid="B9">9</xref>]. Moreover, we proposed a larger number of covariates than Garcia-Garcia [<xref ref-type="bibr" rid="B23">23</xref>] in the adjusted model, for instance, the familiarity for hypertension or stroke. They found no association between AVNN and SDNN with LVH, consistently with our results. Moreover, they found associations between AVNN and SDNN with respect to IMT and eGFR, but these were lost after adjusting for age. Our results were coherent with these findings, even if in our studies the association of SDNN with IMT was significant also after adjustment. However, the patients in the study by Garcia-Garcia [<xref ref-type="bibr" rid="B23">23</xref>] were younger (56 ± 11 years versus 62 ± 12 years) and with a lower percentage of heart (18% vs 60%), and vascular (23% vs 75%) TOD. Moreover, the HRV analysis in this study was performed after a one-month antihypertensive therapy wash-out while many patients in the sample studied by Garcia-Garcia received drug therapy (not HR lowering drugs). We underline that the therapy before ECG holter measurement among selected groups was comparable as no significant differences occurred. The only exception was represented by diuretics, as a larger proportion of patients in the moderate eGFR group assumed diuretics compared with the other two groups (mild and normal eGFR) and a larger proportion of patients in the hypertrophy group assumed them compared to the group without hypertrophy. This difference was due to the fact that the antihypertensive treatment of patients with moderate decreased eGFR or with hypertrophy was based on the combination of diuretics with other drugs (i.e. Beta-blockers, ACE inhibitor, AT1 Antagonist and Dihydropyridine) which were usually prescribed also in the other groups of patients. We underline that the association of diuretics with a lower HRV has been already shown by the ARIC study [<xref ref-type="bibr" rid="B41">41</xref>] in 3577 hypertensive patients and by a recent study [<xref ref-type="bibr" rid="B42">42</xref>] in general male population, for that reason we performed the HRV analysis after a drug washout. The comparison of our results with those by Garcia-Garcia re-enforces the importance of computing several HRV parameters, especially the frequency-domain measures, such as LF/HF, which is considered as a non-invasive marker of the sympatho-vagal balance. However, the plausible mechanisms by which abnormal autonomic balance may lead to TOD and, particularly, renal organ damage one are not clearly known. Our results were consistent with two recent studies [<xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B21">21</xref>], investigating HRV and kidney disease, which concluded that lower HRV (particularly, frequency domain measures) was associated with higher risk of progression to end-stage renal disease and suggested that autonomic imbalance may lead to kidney damage. For that reason, prospective longitudinal studies are needed to evaluate a causal effect between HRV and TOD. In future studies, additional HRV measures, derived from nonlinear [<xref ref-type="bibr" rid="B43">43</xref>] and/or point process time-frequency [<xref ref-type="bibr" rid="B44">44</xref>] analysis, could be selected either in short-term recordings under standardised conditions [<xref ref-type="bibr" rid="B45">45</xref>] or in long-term continuous monitoring [<xref ref-type="bibr" rid="B46">46</xref>]. Moreover, other non-invasive parameters related to ANS activity, such as pupillometric features [<xref ref-type="bibr" rid="B47">47</xref>,<xref ref-type="bibr" rid="B48">48</xref>], could be adopted to provide additional information on autonomic cardiac control. As regards the other factors which entered the adjusted models, the age is the most significant variable, confirming that cardiac, vascular, and renal abnormalities increase progressively with age [<xref ref-type="bibr" rid="B49">49</xref>,<xref ref-type="bibr" rid="B50">50</xref>]. The absence of hypertensive familiarity seems to be associated with no renal involvement. Significantly higher systolic BP values were found in the mild decreased eGFR group, maybe because the blood pressure values are controlled in patients with moderate renal eGFR by the (significantly higher) use of diuretics. Higher systolic BP values were associated with LVH, coherently with the fact that it is an established cardiac manifestation of chronic hypertension [<xref ref-type="bibr" rid="B51">51</xref>]. Moreover, other factors associated with LVH are higher assumption rate of diuretics and higher values of cholesterol. Although previous studies have shown that gender influences HRV parameters both in healthy subjects [<xref ref-type="bibr" rid="B52">52</xref>] and hypertensive patients [<xref ref-type="bibr" rid="B53">53</xref>], this factor entered no final adjusted models. This means that within the selected sample of patients the gender-related differences in HRV were smaller than differences related to other factors and covariates, in particular age or progression of TOD. We consider in any case that the main limitations of this study were the inherent ones of observational and cross-sectional design, which precludes longitudinal analysis between HRV and TOD.</p></sec><sec sec-type="conclusions"><title>Conclusions</title><p>In conclusion, depressed HRV appeared to be associated with vascular and renal TOD. In particular, depressed values of indexes of the overall ANS modulation on heart were found in patients with plaque compared to those with a normal IMT. These associations remained significant after adjustment for other factors known to contribute to the development of TOD. Moreover LF/HF, a marker of sympatho-vagal balance, was significantly decreased in the groups with mild and moderate decreased eGFR, confirming the involvement of autonomic imbalance in TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD are not clearly known, we suggested that further prospective studies with longitudinal design would be performed to investigate HRV in the early stages of hypertension and of TOD development.</p></sec><sec><title>Abbreviations</title><p>AVNN: Average of all NN intervals; BP: Blood Pressure; CI: Confidence Interval; CV: Cardiovascular; ECG: Electrocardiogram; eGFR: estimated Glomerular Filtration Rate; HF: Spectral power of all NN intervals between 0.15 and 0.4 Hz; HR: Heart Rate; HRV: Heart Rate Variability; IMT: Maximum arterial Intima Media Thickness; LF: Spectral power of all NN intervals between 0.04 and 0.15 Hz; LF/HF: Ratio of low to high frequency power; LV: Left Ventricle; LVH: Left Ventricular Hypertrophy; LVMi: LV Mass index; MDRD: Modification of Diet in Renal Disease; OR: Odds Ratio; pNN50: Percentage of differences between adjacent NN intervals that are longer than 50 ms; PSD: Power Spectral Density; RMSSD: Square root of the mean of the sum of the squares of differences between adjacent NN intervals; SDANN: Standard deviation of the averages of NN intervals in all 5-min segments of a 24-h recording; SDNN: Standard deviation of all NN intervals; SDNN IDX: Mean of the standard deviations of NN intervals in all 5-min segments of a 24-h recording; TOD: Target Organ Damage; TOTPWR: Total spectral power of all NN intervals up to 0.4 Hz; ULF: Spectral power of all NN intervals between 0 and 0.003 Hz; VLF: Spectral power of all NN intervals between 0.003 and 0.04 Hz.</p></sec><sec><title>Competing interests</title><p>The authors declare that they have no competing interests.</p></sec><sec><title>Authors’ contributions</title><p>PM participated in study conception and design, analysed data, contributed to interpretation of data and drafted the manuscript. RI collected the
data, contributed to interpretation of data and revised critically the manuscript. NDL conceived the study, participated in its design and interpretation of data and helped to draft the manuscript. LP participated in study conception and design, data analysis and interpretation, helped
to draft the manuscript. All authors read and approved the final manuscript.</p></sec><sec><title>Authors’ information</title><p>PM and LP are biomedical engineers with research interest in biomedical signal processing for cardiologic risk assessment, particularly, by Heart Rate Variability analysis and using artificial intelligence methods. PM acquired ECTS-credits in the field of medicine, particularly cardiology. Moreover, PM and LP got their Ph.D. at the Faculty of Medicine of the University of Naples Federico II (in partnership with the Department of Biomedical, Electronic and Telecommunication Engineering of the same University). RI is a researcher in cardiologic science. NDL is an associate professor in cardiologic science.</p></sec><sec><title>Pre-publication history</title><p>The pre-publication history for this paper can be accessed here:</p><p><ext-link ext-link-type="uri" xlink:href="http://www.biomedcentral.com/1471-2261/12/105/prepub">http://www.biomedcentral.com/1471-2261/12/105/prepub</ext-link></p></sec></body><back><sec><title>Acknowledgements</title><p>The study was conceived and designed in the framework of the research project Remote Health Monitoring (R.H.M.), involving all the authors, and funded by the Regione Campania and of the Ph.D. Scholarship by PM. Moreover, the current work was supported by Italian Ministry of Education, University and Research with the project Smart Health and Artificial intelligence for Risk Estimation (SHARE). LP acknowledges support of this work through the MATCH Programme (EPSRC Grant EP/F063822/1) although the views expressed are entirely his own. 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