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Presence of the Metabolic Syndrome Is Not a Better Predictor of Cardiovascular Disease Than the Sum of Its Components in HIV-Infected Individuals

Identifieur interne : 000492 ( Ncbi/Merge ); précédent : 000491; suivant : 000493

Presence of the Metabolic Syndrome Is Not a Better Predictor of Cardiovascular Disease Than the Sum of Its Components in HIV-Infected Individuals

Auteurs : Signe W. Worm [Danemark] ; Caroline A. Sabin [Royaume-Uni] ; Peter Reiss [Pays-Bas] ; Wafaa El-Sadr [États-Unis] ; Antonella D'Arminio Monforte [Italie] ; Christian Pradier [France] ; Rodolphe Thiebaut [France] ; Matthew Law [Australie] ; Martin Rickenbach [Suisse] ; Stephane De Wit [Belgique] ; Jens D. Lundgren [Danemark] ; Nina Friis-M Ller [Danemark]

Source :

RBID : PMC:2646032

Abstract

OBJECTIVE—It is much debated whether the metabolic syndrome contributes additional information over and above that provided by the individual components of the syndrome alone. Among HIV-infected individuals, we investigated whether any particular combinations of the components included in the definition of the metabolic syndrome are associated with a higher risk of cardiovascular disease (CVD).

RESEARCH DESIGN AND METHODS—We followed 33,347 HIV-infected individuals in a prospective observational study. The effect of combinations of components of the metabolic syndrome (low HDL cholesterol, high triglycerides, high BMI, hypertension, and diabetes) on the risk of CVD was assessed by Poisson regression incorporating interactions between each component pair and adjusting for age, sex, family history of CVD, smoking status, calendar year, and exposure to antiretroviral therapy. We reduced the risk of type 1 errors by randomly splitting the data set for training (70% of sample) and validation (remaining 30%).

RESULTS—In the training data set, 671 patients experienced a CVD event over 110,652 person-years. Unadjusted, the presence of metabolic syndrome at study enrollment (≥3 of the factors) was associated with a 2.89 higher risk of CVD (95% CI 2.34–3.59; P = 0.0001) compared with individuals without the metabolic syndrome. After adjustment for the individual components, the metabolic syndrome as an entity no longer predicted the risk of CVD (adjusted relative risk 0.85; 95% CI 0.61–1.17; P = 0.32). No significant positive interactions were found among the components of the metabolic syndrome.

CONCLUSIONS—The presence of the metabolic syndrome in HIV-infected individuals did not appear to increase the CVD risk over and above that conferred by the components of the syndrome separately.


Url:
DOI: 10.2337/dc08-1394
PubMed: 19056612
PubMed Central: 2646032

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PMC:2646032

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<name sortKey="D Arminio Monforte, Antonella" sort="D Arminio Monforte, Antonella" uniqKey="D Arminio Monforte A" first="Antonella" last="D'Arminio Monforte">Antonella D'Arminio Monforte</name>
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<name sortKey="Law, Matthew" sort="Law, Matthew" uniqKey="Law M" first="Matthew" last="Law">Matthew Law</name>
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</placeName>
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<name sortKey="Rickenbach, Martin" sort="Rickenbach, Martin" uniqKey="Rickenbach M" first="Martin" last="Rickenbach">Martin Rickenbach</name>
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<nlm:aff id="aff9">University Hospital, Lausanne, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>University Hospital, Lausanne</wicri:regionArea>
<placeName>
<settlement type="city">Lausanne</settlement>
<region nuts="3" type="region">Canton de Vaud</region>
</placeName>
</affiliation>
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<wicri:regionArea>University Hospital St. Pierre, Brussels</wicri:regionArea>
<placeName>
<settlement type="city">Bruxelles</settlement>
<region nuts="2">Région de Bruxelles-Capitale</region>
</placeName>
</affiliation>
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<name sortKey="Lundgren, Jens D" sort="Lundgren, Jens D" uniqKey="Lundgren J" first="Jens D." last="Lundgren">Jens D. Lundgren</name>
<affiliation wicri:level="3">
<nlm:aff id="aff1">Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Copenhagen HIV Programme, University of Copenhagen, Copenhagen</wicri:regionArea>
<placeName>
<settlement type="city">Copenhague</settlement>
<region type="région" nuts="2">Hovedstaden</region>
</placeName>
</affiliation>
</author>
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<name sortKey="Friis M Ller, Nina" sort="Friis M Ller, Nina" uniqKey="Friis M Ller N" first="Nina" last="Friis-M Ller">Nina Friis-M Ller</name>
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<nlm:aff id="aff1">Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Copenhagen HIV Programme, University of Copenhagen, Copenhagen</wicri:regionArea>
<placeName>
<settlement type="city">Copenhague</settlement>
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</placeName>
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<idno type="ISSN">0149-5992</idno>
<idno type="eISSN">1935-5548</idno>
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<date when="2009">2009</date>
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<p>
<bold>OBJECTIVE</bold>
—It is much debated whether the metabolic syndrome contributes additional information over and above that provided by the individual components of the syndrome alone. Among HIV-infected individuals, we investigated whether any particular combinations of the components included in the definition of the metabolic syndrome are associated with a higher risk of cardiovascular disease (CVD).</p>
<p>
<bold>RESEARCH DESIGN AND METHODS</bold>
—We followed 33,347 HIV-infected individuals in a prospective observational study. The effect of combinations of components of the metabolic syndrome (low HDL cholesterol, high triglycerides, high BMI, hypertension, and diabetes) on the risk of CVD was assessed by Poisson regression incorporating interactions between each component pair and adjusting for age, sex, family history of CVD, smoking status, calendar year, and exposure to antiretroviral therapy. We reduced the risk of type 1 errors by randomly splitting the data set for training (70% of sample) and validation (remaining 30%).</p>
<p>
<bold>RESULTS</bold>
—In the training data set, 671 patients experienced a CVD event over 110,652 person-years. Unadjusted, the presence of metabolic syndrome at study enrollment (≥3 of the factors) was associated with a 2.89 higher risk of CVD (95% CI 2.34–3.59;
<italic>P</italic>
= 0.0001) compared with individuals without the metabolic syndrome. After adjustment for the individual components, the metabolic syndrome as an entity no longer predicted the risk of CVD (adjusted relative risk 0.85; 95% CI 0.61–1.17;
<italic>P</italic>
= 0.32). No significant positive interactions were found among the components of the metabolic syndrome.</p>
<p>
<bold>CONCLUSIONS</bold>
—The presence of the metabolic syndrome in HIV-infected individuals did not appear to increase the CVD risk over and above that conferred by the components of the syndrome separately.</p>
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<journal-id journal-id-type="publisher-id">diacare</journal-id>
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<issn pub-type="epub">1935-5548</issn>
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<publisher-name>American Diabetes Association</publisher-name>
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<article-id pub-id-type="pmid">19056612</article-id>
<article-id pub-id-type="pmc">2646032</article-id>
<article-id pub-id-type="publisher-id">323474</article-id>
<article-id pub-id-type="doi">10.2337/dc08-1394</article-id>
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<subj-group subj-group-type="heading">
<subject>Cardiovascular and Metabolic Risk</subject>
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<title-group>
<article-title>Presence of the Metabolic Syndrome Is Not a Better Predictor of Cardiovascular Disease Than the Sum of Its Components in HIV-Infected Individuals</article-title>
<subtitle>Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study
<xref ref-type="fn" rid="fn1">*</xref>
</subtitle>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Worm</surname>
<given-names>Signe W.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sabin</surname>
<given-names>Caroline A.</given-names>
</name>
<degrees>PHD</degrees>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Reiss</surname>
<given-names>Peter</given-names>
</name>
<degrees>PHD</degrees>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>El-Sadr</surname>
<given-names>Wafaa</given-names>
</name>
<degrees>MD, MPH</degrees>
<xref ref-type="aff" rid="aff4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>d'Arminio Monforte</surname>
<given-names>Antonella</given-names>
</name>
<degrees>DMSC</degrees>
<xref ref-type="aff" rid="aff5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pradier</surname>
<given-names>Christian</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="aff6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Thiebaut</surname>
<given-names>Rodolphe</given-names>
</name>
<degrees>PHD</degrees>
<xref ref-type="aff" rid="aff7">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Law</surname>
<given-names>Matthew</given-names>
</name>
<degrees>PHD</degrees>
<xref ref-type="aff" rid="aff8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rickenbach</surname>
<given-names>Martin</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="aff9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>De Wit</surname>
<given-names>Stephane</given-names>
</name>
<degrees>PHD</degrees>
<xref ref-type="aff" rid="aff10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lundgren</surname>
<given-names>Jens D.</given-names>
</name>
<degrees>DMSC</degrees>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Friis-Møller</surname>
<given-names>Nina</given-names>
</name>
<degrees>PHD</degrees>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label>1</label>
Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark</aff>
<aff id="aff2">
<label>2</label>
Royal Free and University College, London, U.K.</aff>
<aff id="aff3">
<label>3</label>
Academic Medical Center, Amsterdam, the Netherlands</aff>
<aff id="aff4">
<label>4</label>
Harlem Hospital Center, Division of Infectious Diseases, New York, New York</aff>
<aff id="aff5">
<label>5</label>
University of Milan, Milan, Italy</aff>
<aff id="aff6">
<label>6</label>
Hôpital Archet 1, Nice, France</aff>
<aff id="aff7">
<label>7</label>
Université Victor Segalen, Bordeaux, France</aff>
<aff id="aff8">
<label>8</label>
National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia</aff>
<aff id="aff9">
<label>9</label>
University Hospital, Lausanne, Switzerland</aff>
<aff id="aff10">
<label>10</label>
University Hospital St. Pierre, Brussels, Belgium</aff>
<author-notes>
<fn>
<p>Corresponding author: Signe W. Worm,
<email>sww@cphiv.dk</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<month>3</month>
<year>2009</year>
</pub-date>
<volume>32</volume>
<issue>3</issue>
<fpage>474</fpage>
<lpage>480</lpage>
<history>
<date date-type="received">
<day>28</day>
<month>7</month>
<year>2008</year>
</date>
<date date-type="accepted">
<day>20</day>
<month>11</month>
<year>2008</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2009, American Diabetes Association</copyright-statement>
<license license-type="open-access">
<p>Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-nd/3.0/">http://creativecommons.org/licenses/by-nc-nd/3.0/</ext-link>
for details.</p>
</license>
</permissions>
<self-uri xlink:title="pdf" xlink:href="zdc00309000474.pdf"></self-uri>
<abstract>
<p>
<bold>OBJECTIVE</bold>
—It is much debated whether the metabolic syndrome contributes additional information over and above that provided by the individual components of the syndrome alone. Among HIV-infected individuals, we investigated whether any particular combinations of the components included in the definition of the metabolic syndrome are associated with a higher risk of cardiovascular disease (CVD).</p>
<p>
<bold>RESEARCH DESIGN AND METHODS</bold>
—We followed 33,347 HIV-infected individuals in a prospective observational study. The effect of combinations of components of the metabolic syndrome (low HDL cholesterol, high triglycerides, high BMI, hypertension, and diabetes) on the risk of CVD was assessed by Poisson regression incorporating interactions between each component pair and adjusting for age, sex, family history of CVD, smoking status, calendar year, and exposure to antiretroviral therapy. We reduced the risk of type 1 errors by randomly splitting the data set for training (70% of sample) and validation (remaining 30%).</p>
<p>
<bold>RESULTS</bold>
—In the training data set, 671 patients experienced a CVD event over 110,652 person-years. Unadjusted, the presence of metabolic syndrome at study enrollment (≥3 of the factors) was associated with a 2.89 higher risk of CVD (95% CI 2.34–3.59;
<italic>P</italic>
= 0.0001) compared with individuals without the metabolic syndrome. After adjustment for the individual components, the metabolic syndrome as an entity no longer predicted the risk of CVD (adjusted relative risk 0.85; 95% CI 0.61–1.17;
<italic>P</italic>
= 0.32). No significant positive interactions were found among the components of the metabolic syndrome.</p>
<p>
<bold>CONCLUSIONS</bold>
—The presence of the metabolic syndrome in HIV-infected individuals did not appear to increase the CVD risk over and above that conferred by the components of the syndrome separately.</p>
</abstract>
</article-meta>
<notes>
<fn-group>
<fn>
<p>Published ahead of print at
<ext-link ext-link-type="uri" xlink:href="http://care.diabetesjournals.org">http://care.diabetesjournals.org</ext-link>
on 3 December 2008.</p>
</fn>
<fn>
<p>The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.</p>
</fn>
</fn-group>
</notes>
</front>
<floats-wrap>
<table-wrap position="float" id="t1">
<label>Table 1</label>
<caption>
<p>Characteristics at enrollment in D:A:D of the 23,202 patients included in the training sample</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th colspan="1" rowspan="2" align="center" valign="bottom"></th>
<th colspan="1" rowspan="2" align="center" valign="bottom">All patients in training sample</th>
<th colspan="2" rowspan="1" align="center" valign="bottom">Metabolic syndrome at enrollment
<hr></hr>
</th>
</tr>
<tr>
<th colspan="1" rowspan="1" align="center" valign="bottom">Yes</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">No</th>
</tr>
</thead>
<tbody>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">
<italic>n</italic>
</td>
<td colspan="1" rowspan="1" align="center" valign="top">23,202</td>
<td colspan="1" rowspan="1" align="center" valign="top">1,025</td>
<td colspan="1" rowspan="1" align="center" valign="top">22,177</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Male sex</td>
<td colspan="1" rowspan="1" align="center" valign="top">17,168 (74.0)</td>
<td colspan="1" rowspan="1" align="center" valign="top">853 (83.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top">16,315 (73.6)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Age (years)</td>
<td colspan="1" rowspan="1" align="center" valign="top">38 (33–45)</td>
<td colspan="1" rowspan="1" align="center" valign="top">43 (37–52)</td>
<td colspan="1" rowspan="1" align="center" valign="top">38 (33–44)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">CD4 count (cells/mm
<sup>3</sup>
)</td>
<td colspan="1" rowspan="1" align="center" valign="top">410 (249–600)</td>
<td colspan="1" rowspan="1" align="center" valign="top">449 (274–660)</td>
<td colspan="1" rowspan="1" align="center" valign="top">408 (248–598)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">HIV RNA (log
<sub>10</sub>
cp/ml)</td>
<td colspan="1" rowspan="1" align="center" valign="top">2.7 (1.7–4.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top">1.9 (1.7–3.5)</td>
<td colspan="1" rowspan="1" align="center" valign="top">2.7 (1.7–4.3)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Current smoker</td>
<td colspan="1" rowspan="1" align="center" valign="top">7,823 (33.7)</td>
<td colspan="1" rowspan="1" align="center" valign="top">410 (40.0)</td>
<td colspan="1" rowspan="1" align="center" valign="top">7,413 (33.4)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Lipodystrophy</td>
<td colspan="1" rowspan="1" align="center" valign="top">4,309 (18.6)</td>
<td colspan="1" rowspan="1" align="center" valign="top">401 (39.1)</td>
<td colspan="1" rowspan="1" align="center" valign="top">3,908 (17.6)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Prior myocardial infarction</td>
<td colspan="1" rowspan="1" align="center" valign="top">172 (0.7)</td>
<td colspan="1" rowspan="1" align="center" valign="top">18 (1.8)</td>
<td colspan="1" rowspan="1" align="center" valign="top">154 (0.7)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Exposure to antiretroviral therapy</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    Any NRTI</td>
<td colspan="1" rowspan="1" align="center" valign="top">16,928 (73.0)</td>
<td colspan="1" rowspan="1" align="center" valign="top">884 (86.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top">16,044 (72.4)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">        Total exposure (years)</td>
<td colspan="1" rowspan="1" align="center" valign="top">3.1 (1.6–4.8)</td>
<td colspan="1" rowspan="1" align="center" valign="top">3.6 (2.2–5.3)</td>
<td colspan="1" rowspan="1" align="center" valign="top">3.0 (1.5–4.7)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    Any protease inhibitor</td>
<td colspan="1" rowspan="1" align="center" valign="top">13,505 (58.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top">794 (77.5)</td>
<td colspan="1" rowspan="1" align="center" valign="top">12,711 (57.3)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">        Total exposure (years)</td>
<td colspan="1" rowspan="1" align="center" valign="top">2.3 (1.2–3.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top">2.7 (1.7–3.6)</td>
<td colspan="1" rowspan="1" align="center" valign="top">2.3 (1.2–3.2)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    Any NNRTI</td>
<td colspan="1" rowspan="1" align="center" valign="top">7,652 (33.0)</td>
<td colspan="1" rowspan="1" align="center" valign="top">366 (35.7)</td>
<td colspan="1" rowspan="1" align="center" valign="top">7,286 (32.9)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">        Total exposure (years)</td>
<td colspan="1" rowspan="1" align="center" valign="top">0.9 (0.4–1.6)</td>
<td colspan="1" rowspan="1" align="center" valign="top">1.0 (0.5–1.7)</td>
<td colspan="1" rowspan="1" align="center" valign="top">0.9 (0.4–1.6)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">MS components present at enrollment in D:A:D
<xref ref-type="table-fn" rid="t1fn1">*</xref>
</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    High TRIG</td>
<td colspan="1" rowspan="1" align="center" valign="top">8,923 (38.5)</td>
<td colspan="1" rowspan="1" align="center" valign="top">979 (95.5)</td>
<td colspan="1" rowspan="1" align="center" valign="top">7,944 (35.8)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    Low HDL</td>
<td colspan="1" rowspan="1" align="center" valign="top">4,934 (21.3)</td>
<td colspan="1" rowspan="1" align="center" valign="top">872 (85.1)</td>
<td colspan="1" rowspan="1" align="center" valign="top">4,062 (18.3)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    High BP</td>
<td colspan="1" rowspan="1" align="center" valign="top">3,278 (14.1)</td>
<td colspan="1" rowspan="1" align="center" valign="top">838 (81.8)</td>
<td colspan="1" rowspan="1" align="center" valign="top">2,440 (11.0)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    High BMI</td>
<td colspan="1" rowspan="1" align="center" valign="top">1,019 (4.4)</td>
<td colspan="1" rowspan="1" align="center" valign="top">301 (29.4)</td>
<td colspan="1" rowspan="1" align="center" valign="top">718 (3.2)</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    Diabetes</td>
<td colspan="1" rowspan="1" align="center" valign="top">651 (2.8)</td>
<td colspan="1" rowspan="1" align="center" valign="top">238 (23.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top">413 (1.9)</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Data are
<italic>n</italic>
(%) or median (interquartile range).</p>
</fn>
<fn id="t1fn1">
<label>*</label>
<p>High triglycerides (TRIG): ≥1.7 mmol/l; low HDL cholesterol: ≤1.0 mmol/l (men) or ≤1.3 mmol/l (women); high blood pressure (BP): systolic BP >130 mmHg or diastolic BP >85 mmHg; high BMI: >30 kg/m
<sup>2</sup>
; diabetes: an established diagnosis of diabetes.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="t2">
<label>Table 2</label>
<caption>
<p>CVD incidence rates stratified by each metabolic syndrome component “pair”</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th colspan="1" rowspan="2" align="center" valign="bottom">Criterion 1
<xref ref-type="table-fn" rid="t2fn1">*</xref>
</th>
<th colspan="1" rowspan="2" align="center" valign="bottom">Criterion 2
<xref ref-type="table-fn" rid="t2fn1">*</xref>
</th>
<th colspan="2" rowspan="1" align="center" valign="bottom">At baseline (fixed)
<hr></hr>
</th>
<th colspan="2" rowspan="1" align="center" valign="bottom">Over follow-up (time-updated)
<hr></hr>
</th>
</tr>
<tr>
<th colspan="1" rowspan="1" align="center" valign="bottom">Rate/1,000 person-years (95% CI)</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">Interaction
<italic>P</italic>
value
<xref ref-type="table-fn" rid="t2fn2"></xref>
</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">Rate/1,000 person-years (95% CI)</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">Interaction
<italic>P</italic>
value
<xref ref-type="table-fn" rid="t2fn2"></xref>
</th>
</tr>
</thead>
<tbody>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">High HDL</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">4.0 (3.4–4.5)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">2.8 (2.2–3.5)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">Low HDL</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">5.9 (4.5–7.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.2 (0.8–1.6)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">High HDL</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">7.5 (6.5–8.6)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">5.1 (4.3–6.0)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">Low HDL</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">10.1 (8.7–11.6)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.78</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">8.6 (7.8–9.4)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.30</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">No high BP</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">3.7 (3.2–4.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">2.4 (1.8–2.9)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">High BP</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">9.1 (6.9–11.3)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">5.5 (3.8–7.1)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">No high BP</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">8.1 (7.2–9.0)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">5.9 (5.2–6.6)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">High BP</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">11.1 (8.8–13.4)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.06
<xref ref-type="table-fn" rid="t2fn3"></xref>
</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">9.3 (8.3–10.4)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.07</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">No diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">4.0 (3.5–4.5)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">2.9 (2.3–3.4)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">Diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">19.2 (11.7–2.7)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">11.0 (4.8–2.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">No diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">7.5 (6.7–8.3)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">6.4 (5.9–7.0)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">Diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">39.2 (29.5–48.8)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.19</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">25.9 (20.8–31.1)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.23</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">Low BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">4.3 (3.8–4.8)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">2.9 (2.3–3.5)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">High BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">4.8 (2.6–8.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">5.2 (2.7–9.0)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">Low BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">8.3 (7.5–9.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">7.2 (6.5–7.8)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High TRIG</td>
<td colspan="1" rowspan="1" align="left" valign="top">High BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">15.1 (9.7–20.5)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.38</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">10.1 (7.5. 12.8)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.14</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High HDL</td>
<td colspan="1" rowspan="1" align="left" valign="top">No high BP</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">4.5 (4.0–5.0)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">3.2 (2.7–3.8)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High HDL</td>
<td colspan="1" rowspan="1" align="left" valign="top">High BP</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">10.1 (8.0–12.1)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">6.7 (5.2–8.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low HDL</td>
<td colspan="1" rowspan="1" align="left" valign="top">No high BP</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">8.0 (6.9–9.1)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">6.3 (5.4–7.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low HDL</td>
<td colspan="1" rowspan="1" align="left" valign="top">High BP</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">10.3 (7.9–12.8)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.04
<xref ref-type="table-fn" rid="t2fn3"></xref>
</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">9.4 (8.3–10.6)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.05
<xref ref-type="table-fn" rid="t2fn3"></xref>
</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High HDL</td>
<td colspan="1" rowspan="1" align="left" valign="top">No diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">4.7 (4.2–5.1)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">3.7 (3.1–4.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High HDL</td>
<td colspan="1" rowspan="1" align="left" valign="top">Diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">24.7 (17.5–31.9)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">17.8 (10.9–24.6)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low HDL</td>
<td colspan="1" rowspan="1" align="left" valign="top">No diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">7.3 (6.4–8.3)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">6.8 (6.2–7.5)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low HDL</td>
<td colspan="1" rowspan="1" align="left" valign="top">Diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">39.4 (27.6–51.2)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.80</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">26.3 (20.5–32.1)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.53</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High HDL</td>
<td colspan="1" rowspan="1" align="left" valign="top">Low BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">5.0 (4.5–5.5)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">4.0 (3.4–4.5)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High HDL</td>
<td colspan="1" rowspan="1" align="left" valign="top">High BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">7.3 (4.5–10.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">5.0 (2.8–7.1)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low HDL</td>
<td colspan="1" rowspan="1" align="left" valign="top">Low BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">8.2 (7.2–9.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">7.5 (6.8–8.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Low HDL</td>
<td colspan="1" rowspan="1" align="left" valign="top">High BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">14.8 (8.6–23.6)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.52</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">12.6 (9.0–16.2)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.32</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">No high BP</td>
<td colspan="1" rowspan="1" align="left" valign="top">No diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">4.9 (4.4–5.3)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">4.1 (3.6–4.6)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">No high BP</td>
<td colspan="1" rowspan="1" align="left" valign="top">Diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">27.9 (20.8–35.0)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">20.7 (14.2–27.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High BP</td>
<td colspan="1" rowspan="1" align="left" valign="top">No diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">8.8 (7.3–10.3)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">7.5 (6.6–8.4)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High BP</td>
<td colspan="1" rowspan="1" align="left" valign="top">Diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">36.3 (23.1–49.6)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.55</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">25.5 (19.4–31.7)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.21</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">No high BP</td>
<td colspan="1" rowspan="1" align="left" valign="top">Low BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">5.3 (4.8–5.8)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">4.6 (4.0–5.1)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">No high BP</td>
<td colspan="1" rowspan="1" align="left" valign="top">High BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">8.3 (5.2–11.4)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">4.8 (2.9–7.6)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High BP</td>
<td colspan="1" rowspan="1" align="left" valign="top">Low BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">10.1 (8.4–11.7)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">8.2 (7.3–9.2)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">High BP</td>
<td colspan="1" rowspan="1" align="left" valign="top">High BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">11.4 (5.6–17.1)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.23</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">12.1 (8.8–15.5)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.43</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">No diabetes</td>
<td colspan="1" rowspan="1" align="left" valign="top">Low BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">5.4 (4.9–5.8)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">5.3 (4.8–5.7)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">No diabetes</td>
<td colspan="1" rowspan="1" align="left" valign="top">High BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">6.0 (3.7–8.4)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">6.1 (4.2–7.9)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Diabetes</td>
<td colspan="1" rowspan="1" align="left" valign="top">Low BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">28.2 (21.6–34.7)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">22.2 (17.3–27.1)</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Diabetes</td>
<td colspan="1" rowspan="1" align="left" valign="top">High BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">43.3 (25.2–69.3)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.12</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">28.7 (17.7–39.8)</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.44</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Data are CVD incidence rates per 1,000 person years (95 % CI).</p>
</fn>
<fn id="t2fn1">
<label>*</label>
<p>High triglycerides (TRIG): ≥ 1.7 mmol/l; low HDL cholesterol: ≤1.0 mmol/l (men) or ≤1.3 mmol/l (women); high blood pressure (BP): systolic BP >130 mmHg or diastolic BP >85 mmHg; diabetes: an established diagnosis of diabetes.</p>
</fn>
<fn id="t2fn2">
<label></label>
<p>
<italic>P</italic>
values for the interaction between each component pair were obtained from a multivariable Poisson regression model that included all main effects and all pairwise interactions, as well as adjustment for other potential confounders (see
<sc>research design and methods</sc>
).</p>
</fn>
<fn id="t2fn3">
<label></label>
<p>ARRs were all <1, suggesting an antagonistic rather than synergistic effect of each combination of components.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="t3">
<label>Table 3</label>
<caption>
<p>Association between the metabolic syndrome (time-updated analyses), its components, and CVD from main and sensitivity analyses</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th colspan="1" rowspan="1" align="center" valign="bottom">Factor
<xref ref-type="table-fn" rid="t3fn1">*</xref>
</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">Main analysis: training set (671 events, 110,652 person-years)</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">Main analysis: validation set (303 events, 48,741 person-years)</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">Metabolic syndrome components reversible (671 events, 110,652 person-years)</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">No missing data on metabolic syndrome components (377 events, 57,536 person-years)</th>
</tr>
</thead>
<tbody>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Unadjusted</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    MS</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">2.40 (2.06–2.79); 0.0001</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">2.71 (2.16–3.40); 0.0001</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">3.02 (2.54–3.59); 0.0001</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">3.34 (2.36–4.74); 0.0001</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">Adjusted
<xref ref-type="table-fn" rid="t3fn2"></xref>
</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    MS</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.94 (0.69–1.27); 0.67</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.00 (0.64–1.57); 0.99</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.03 (0.77–1.39); 0.83</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">0.88 (0.52–1.49); 0.63</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    High TRIG</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.50 (1.18–1.91); 0.001</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.26 (0.88–1.79); 0.20</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.47 (1.23–1.76); 0.0001</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.39 (1.10–1.76); 0.006</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    Low HDL</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.41 (1.12–1.76); 0.003</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.61 (1.12–2.30); 0.009</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.25 (1.03–1.51); 0.02</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.44 (1.12–1.86); 0.005</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    High BP</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.26 (0.98–1.62); 0.07</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.40 (0.95–2.05); 0.09</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.14 (0.92–1.41); 0.23</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.23 (0.98–1.53); 0.07</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    Diabetes</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">2.31 (1.83–2.92); 0.0001</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.96 (1.39–2.77); 0.0001</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">2.27 (1.77–2.92); 0.0001</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">2.07 (1.43–2.99); 0.0001</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top">    High BMI</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.33 (1.01–1.74); 0.04</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.38 (0.94–2.03); 0.10</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.13 (0.79–1.60); 0.51</td>
<td colspan="1" rowspan="1" align="char" char="." valign="top">1.09 (0.67–1.79); 0.72</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Data are ARRs (95% CI);
<italic>P</italic>
values.</p>
</fn>
<fn id="t3fn1">
<label>*</label>
<p>High triglycerides (TRIG): ≥1.7 mmol/l; low HDL cholesterol: ≤1.0 mmol/l (men) or ≤1.3 mmol/l (women); high blood pressure (BP): systolic BP >130 mmHg or diastolic BP >85 mmHg; diabetes: an established diagnosis of diabetes; high BMI: >30 kg/m
<sup>2</sup>
.</p>
</fn>
<fn id="t3fn2">
<label></label>
<p>Adjusted estimates obtained from a multivariable Poisson regression model that also includes adjustment for other potential confounders as sex, age, family history of CVD, smoking status, calendar year, cohort, HIV risk group, ethnic group, and exposure to the protease inhibitor, NRTI, and NNRTI classes of drugs.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-wrap>
</pmc>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>Belgique</li>
<li>Danemark</li>
<li>France</li>
<li>Italie</li>
<li>Pays-Bas</li>
<li>Royaume-Uni</li>
<li>Suisse</li>
<li>États-Unis</li>
</country>
<region>
<li>Angleterre</li>
<li>Aquitaine</li>
<li>Canton de Vaud</li>
<li>Grand Londres</li>
<li>Hollande-Septentrionale</li>
<li>Hovedstaden</li>
<li>Lombardie</li>
<li>Nouvelle-Aquitaine</li>
<li>Nouvelle-Galles du Sud</li>
<li>Provence-Alpes-Côte d'Azur</li>
<li>Région de Bruxelles-Capitale</li>
<li>État de New York</li>
</region>
<settlement>
<li>Amsterdam</li>
<li>Bordeaux</li>
<li>Bruxelles</li>
<li>Copenhague</li>
<li>Lausanne</li>
<li>Londres</li>
<li>Milan</li>
<li>Nice</li>
<li>Sydney</li>
</settlement>
</list>
<tree>
<country name="Danemark">
<region name="Hovedstaden">
<name sortKey="Worm, Signe W" sort="Worm, Signe W" uniqKey="Worm S" first="Signe W." last="Worm">Signe W. Worm</name>
</region>
<name sortKey="Friis M Ller, Nina" sort="Friis M Ller, Nina" uniqKey="Friis M Ller N" first="Nina" last="Friis-M Ller">Nina Friis-M Ller</name>
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</record>

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