Periodontitis Is Associated with Endothelial Dysfunction in a General Population: A Cross-Sectional Study
Identifieur interne : 000777 ( Ncbi/Merge ); précédent : 000776; suivant : 000778Periodontitis Is Associated with Endothelial Dysfunction in a General Population: A Cross-Sectional Study
Auteurs : Birte Holtfreter [Allemagne] ; Klaus Empen [Allemagne] ; Sven Gl Ser [Allemagne] ; Roberto Lorbeer [Allemagne] ; Henry Völzke [Allemagne] ; Ralf Ewert [Allemagne] ; Thomas Kocher [Allemagne] ; Marcus Dörr [Allemagne]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Abstract
A large body of evidence underlines an association between periodontal disease and cardiovascular disease. In contrast, data on its relation with endothelial dysfunction as a marker of early subclinical atherosclerosis is inconclusive and limited to patient-cohort studies. We therefore investigated the association between periodontal disease and flow-mediated dilation of the brachial artery (FMD) as a measure of endothelial dysfunction in a general population, and also addressed a possible mediation via inflammation. The study population comprised 1,234 subjects (50.5% men) aged 25–85 years from the 5-year follow-up of the Study of Health in Pomerania, a population-based cohort study. Clinical attachment loss (CAL) and pocket probing depth (PPD) as measures of periodontal disease were assessed half-mouth at four sites per tooth. Subjects were classified according to the periodontitis case definition proposed by Tonetti and Claffey (2005). Measurements of FMD and nitroglycerin-mediated dilation (NMD) were performed using standardized ultrasound techniques. High-sensitive C-reactive protein, fibrinogen and leukocyte count were measured. Fully adjusted multivariate linear regression analyses revealed significant associations of the percentage of sites with PPD ≥6 mm with FMD (ptrend=0.048), with subjects within the highest category having a 0.74% higher FMD compared to subjects within the lowest category (p<0.05). Consistently, FMD values increased significantly across categories of the percentage of sites with CAL ≥6 mm (ptrend=0.01) and the periodontitis case definition (ptrend=0.006). Restrictions to subjects without antihypertensive or statin medication or current non-smokers confirmed previous results. Systemic inflammation did not seem to mediate the relation. Both PPD and CAL were not consistently associated with NMD. In contrast to previous studies, high levels of periodontal disease were significantly associated with high FMD values. This association was not mediated via systemic inflammation. This study revives the discussion on whether and how periodontitis contributes to endothelial dysfunction.
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DOI: 10.1371/journal.pone.0084603
PubMed: 24386401
PubMed Central: 3873439
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Greifswald</wicri:regionArea><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion></affiliation></author><author><name sortKey="Empen, Klaus" sort="Empen, Klaus" uniqKey="Empen K" first="Klaus" last="Empen">Klaus Empen</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Internal Medicine, University Medicine, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Internal Medicine, University Medicine, University of Greifswald, Greifswald</wicri:regionArea><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion></affiliation></author><author><name sortKey="Gl Ser, Sven" sort="Gl Ser, Sven" uniqKey="Gl Ser S" first="Sven" last="Gl Ser">Sven Gl Ser</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Internal Medicine, University Medicine, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Internal Medicine, University Medicine, University of Greifswald, Greifswald</wicri:regionArea><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion></affiliation></author><author><name sortKey="Lorbeer, Roberto" sort="Lorbeer, Roberto" uniqKey="Lorbeer R" first="Roberto" last="Lorbeer">Roberto Lorbeer</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Institute for Community Medicine, SHIP/Clinical-Epidemiological Research, University Medicine, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Community Medicine, SHIP/Clinical-Epidemiological Research, University Medicine, University of Greifswald, Greifswald</wicri:regionArea><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion></affiliation></author><author><name sortKey="Volzke, Henry" sort="Volzke, Henry" uniqKey="Volzke H" first="Henry" last="Völzke">Henry Völzke</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Institute for Community Medicine, SHIP/Clinical-Epidemiological Research, University Medicine, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Community Medicine, SHIP/Clinical-Epidemiological Research, University Medicine, University of Greifswald, Greifswald</wicri:regionArea><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion></affiliation></author><author><name sortKey="Ewert, Ralf" sort="Ewert, Ralf" uniqKey="Ewert R" first="Ralf" last="Ewert">Ralf Ewert</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Internal Medicine, University Medicine, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Internal Medicine, University Medicine, University of Greifswald, Greifswald</wicri:regionArea><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion></affiliation></author><author><name sortKey="Kocher, Thomas" sort="Kocher, Thomas" uniqKey="Kocher T" first="Thomas" last="Kocher">Thomas Kocher</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Unit of Periodontology, Department of Restorative Dentistry, Periodontology, and Endodontology, University Medicine, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Unit of Periodontology, Department of Restorative Dentistry, Periodontology, and Endodontology, University Medicine, University of Greifswald, Greifswald</wicri:regionArea><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion></affiliation></author><author><name sortKey="Dorr, Marcus" sort="Dorr, Marcus" uniqKey="Dorr M" first="Marcus" last="Dörr">Marcus Dörr</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Internal Medicine, University Medicine, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Internal Medicine, University Medicine, University of Greifswald, Greifswald</wicri:regionArea><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald</wicri:regionArea><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion><wicri:noRegion>Greifswald</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>A large body of evidence underlines an association between periodontal disease and cardiovascular disease. In contrast, data on its relation with endothelial dysfunction as a marker of early subclinical atherosclerosis is inconclusive and limited to patient-cohort studies. We therefore investigated the association between periodontal disease and flow-mediated dilation of the brachial artery (FMD) as a measure of endothelial dysfunction in a general population, and also addressed a possible mediation via inflammation. The study population comprised 1,234 subjects (50.5% men) aged 25–85 years from the 5-year follow-up of the Study of Health in Pomerania, a population-based cohort study. Clinical attachment loss (CAL) and pocket probing depth (PPD) as measures of periodontal disease were assessed half-mouth at four sites per tooth. Subjects were classified according to the periodontitis case definition proposed by Tonetti and Claffey (2005). Measurements of FMD and nitroglycerin-mediated dilation (NMD) were performed using standardized ultrasound techniques. High-sensitive C-reactive protein, fibrinogen and leukocyte count were measured. Fully adjusted multivariate linear regression analyses revealed significant associations of the percentage of sites with PPD ≥6 mm with FMD (p<sub>trend</sub>=0.048), with subjects within the highest category having a 0.74% higher FMD compared to subjects within the lowest category (p<0.05). Consistently, FMD values increased significantly across categories of the percentage of sites with CAL ≥6 mm (p<sub>trend</sub>=0.01) and the periodontitis case definition (p<sub>trend</sub>=0.006). Restrictions to subjects without antihypertensive or statin medication or current non-smokers confirmed previous results. Systemic inflammation did not seem to mediate the relation. Both PPD and CAL were not consistently associated with NMD. In contrast to previous studies, high levels of periodontal disease were significantly associated with high FMD values. This association was not mediated via systemic inflammation. This study revives the discussion on whether and how periodontitis contributes to endothelial dysfunction.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Sanz, M" uniqKey="Sanz M">M Sanz</name></author><author><name sortKey="D Aiuto, F" uniqKey="D Aiuto F">F D'Aiuto</name></author><author><name sortKey="Deanfield, J" uniqKey="Deanfield J">J Deanfield</name></author><author><name sortKey="Fernandes Aviles, F" uniqKey="Fernandes Aviles F">F Fernandes-Avilés</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lockhart, Pb" uniqKey="Lockhart P">PB Lockhart</name></author><author><name sortKey="Bolger, Af" uniqKey="Bolger A">AF Bolger</name></author><author><name sortKey="Papapanou, Pn" uniqKey="Papapanou P">PN Papapanou</name></author><author><name sortKey="Osinbowale, O" uniqKey="Osinbowale O">O Osinbowale</name></author><author><name sortKey="Trevisan, M" uniqKey="Trevisan M">M Trevisan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dietrich, T" uniqKey="Dietrich T">T Dietrich</name></author><author><name sortKey="Sharma, P" uniqKey="Sharma P">P Sharma</name></author><author><name sortKey="Walter, C" uniqKey="Walter C">C Walter</name></author><author><name sortKey="Weston, P" uniqKey="Weston P">P Weston</name></author><author><name sortKey="Beck, J" uniqKey="Beck J">J Beck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bouchard, P" uniqKey="Bouchard P">P Bouchard</name></author><author><name sortKey="Boutouyrie, P" uniqKey="Boutouyrie P">P Boutouyrie</name></author><author><name sortKey="D Aiuto, F" uniqKey="D Aiuto F">F D'Aiuto</name></author><author><name sortKey="Deanfield, J" uniqKey="Deanfield J">J Deanfield</name></author><author><name sortKey="Deliargyris, E" uniqKey="Deliargyris E">E Deliargyris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ebersole, Jl" uniqKey="Ebersole J">JL Ebersole</name></author><author><name sortKey="Machen, Rl" uniqKey="Machen R">RL Machen</name></author><author><name sortKey="Steffen, Mj" uniqKey="Steffen M">MJ Steffen</name></author><author><name sortKey="Willmann, De" uniqKey="Willmann D">DE Willmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Loos, Bg" uniqKey="Loos B">BG Loos</name></author><author><name sortKey="Craandijk, J" uniqKey="Craandijk J">J Craandijk</name></author><author><name sortKey="Hoek, Fj" uniqKey="Hoek F">FJ Hoek</name></author><author><name sortKey="Wertheim Van Dillen, Pm" uniqKey="Wertheim Van Dillen P">PM Wertheim-van Dillen</name></author><author><name sortKey="Van Der Velden, U" uniqKey="Van Der Velden U">U van der Velden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dietrich, T" uniqKey="Dietrich T">T Dietrich</name></author><author><name sortKey="Jimenez, M" uniqKey="Jimenez M">M Jimenez</name></author><author><name sortKey="Krall Kaye, Ea" uniqKey="Krall Kaye E">EA Krall Kaye</name></author><author><name sortKey="Vokonas, Ps" uniqKey="Vokonas P">PS Vokonas</name></author><author><name sortKey="Garcia, Ri" uniqKey="Garcia R">RI Garcia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Paraskevas, Ki" uniqKey="Paraskevas K">KI Paraskevas</name></author><author><name sortKey="Baker, Dm" uniqKey="Baker D">DM Baker</name></author><author><name sortKey="Vrentzos, Ge" uniqKey="Vrentzos G">GE Vrentzos</name></author><author><name sortKey="Mikhailidis, Dp" uniqKey="Mikhailidis D">DP Mikhailidis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Slade, Gd" uniqKey="Slade G">GD Slade</name></author><author><name sortKey="Ghezzi, Em" uniqKey="Ghezzi E">EM Ghezzi</name></author><author><name sortKey="Heiss, G" uniqKey="Heiss G">G Heiss</name></author><author><name sortKey="Beck, Jd" uniqKey="Beck J">JD Beck</name></author><author><name sortKey="Riche, E" uniqKey="Riche E">E Riche</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Libby, P" uniqKey="Libby P">P Libby</name></author><author><name sortKey="Ridker, Pm" uniqKey="Ridker P">PM Ridker</name></author><author><name sortKey="Maseri, A" uniqKey="Maseri A">A Maseri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kiechl, S" uniqKey="Kiechl S">S Kiechl</name></author><author><name sortKey="Egger, G" uniqKey="Egger G">G Egger</name></author><author><name sortKey="Mayr, M" uniqKey="Mayr M">M Mayr</name></author><author><name sortKey="Wiedermann, Cj" uniqKey="Wiedermann C">CJ Wiedermann</name></author><author><name sortKey="Bonora, E" uniqKey="Bonora E">E Bonora</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Danesh, J" uniqKey="Danesh J">J Danesh</name></author><author><name sortKey="Whincup, P" uniqKey="Whincup P">P Whincup</name></author><author><name sortKey="Walker, M" uniqKey="Walker M">M Walker</name></author><author><name sortKey="Lennon, L" uniqKey="Lennon L">L Lennon</name></author><author><name sortKey="Thomson, A" uniqKey="Thomson A">A Thomson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ridker, Pm" uniqKey="Ridker P">PM Ridker</name></author><author><name sortKey="Cushman, M" uniqKey="Cushman M">M Cushman</name></author><author><name sortKey="Stampfer, Mj" uniqKey="Stampfer M">MJ Stampfer</name></author><author><name sortKey="Tracy, Rp" uniqKey="Tracy R">RP Tracy</name></author><author><name sortKey="Hennekens, Ch" uniqKey="Hennekens C">CH Hennekens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deanfield, Je" uniqKey="Deanfield J">JE Deanfield</name></author><author><name sortKey="Halcox, Jp" uniqKey="Halcox J">JP Halcox</name></author><author><name sortKey="Rabelink, Tj" uniqKey="Rabelink T">TJ Rabelink</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ross, R" uniqKey="Ross R">R Ross</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Faulx, Md" uniqKey="Faulx M">MD Faulx</name></author><author><name sortKey="Wright, At" uniqKey="Wright A">AT Wright</name></author><author><name sortKey="Hoit, Bd" uniqKey="Hoit B">BD Hoit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suwaidi, Ja" uniqKey="Suwaidi J">JA Suwaidi</name></author><author><name sortKey="Hamasaki, S" uniqKey="Hamasaki S">S Hamasaki</name></author><author><name sortKey="Higano, St" uniqKey="Higano S">ST Higano</name></author><author><name sortKey="Nishimura, Ra" uniqKey="Nishimura R">RA Nishimura</name></author><author><name sortKey="Holmes, Dr" uniqKey="Holmes D">DR Holmes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shimbo, D" uniqKey="Shimbo D">D Shimbo</name></author><author><name sortKey="Grahame Clarke, C" uniqKey="Grahame Clarke C">C Grahame-Clarke</name></author><author><name sortKey="Miyake, Y" uniqKey="Miyake Y">Y Miyake</name></author><author><name sortKey="Rodriguez, C" uniqKey="Rodriguez C">C Rodriguez</name></author><author><name sortKey="Sciacca, R" uniqKey="Sciacca R">R Sciacca</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heitzer, T" uniqKey="Heitzer T">T Heitzer</name></author><author><name sortKey="Baldus, S" uniqKey="Baldus S">S Baldus</name></author><author><name sortKey="Von Kodolitsch, Y" uniqKey="Von Kodolitsch Y">Y von Kodolitsch</name></author><author><name sortKey="Rudolph, V" uniqKey="Rudolph V">V Rudolph</name></author><author><name sortKey="Meinertz, T" uniqKey="Meinertz T">T Meinertz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amar, S" uniqKey="Amar S">S Amar</name></author><author><name sortKey="Gokce, N" uniqKey="Gokce N">N Gokce</name></author><author><name sortKey="Morgan, S" uniqKey="Morgan S">S Morgan</name></author><author><name sortKey="Loukideli, M" uniqKey="Loukideli M">M Loukideli</name></author><author><name sortKey="Van Dyke, Te" uniqKey="Van Dyke T">TE Van Dyke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mercanoglu, F" uniqKey="Mercanoglu F">F Mercanoglu</name></author><author><name sortKey="Oflaz, H" uniqKey="Oflaz H">H Oflaz</name></author><author><name sortKey="Oz, O" uniqKey="Oz O">O Oz</name></author><author><name sortKey="Gokbuget, Ay" uniqKey="Gokbuget A">AY Gökbuget</name></author><author><name sortKey="Genchellac, H" uniqKey="Genchellac H">H Genchellac</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blum, A" uniqKey="Blum A">A Blum</name></author><author><name sortKey="Kryuger, K" uniqKey="Kryuger K">K Kryuger</name></author><author><name sortKey="Mashiach Eizenberg, M" uniqKey="Mashiach Eizenberg M">M Mashiach Eizenberg</name></author><author><name sortKey="Tatour, S" uniqKey="Tatour S">S Tatour</name></author><author><name sortKey="Vigder, F" uniqKey="Vigder F">F Vigder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seinost, G" uniqKey="Seinost G">G Seinost</name></author><author><name sortKey="Wimmer, G" uniqKey="Wimmer G">G Wimmer</name></author><author><name sortKey="Skerget, M" uniqKey="Skerget M">M Skerget</name></author><author><name sortKey="Thaller, E" uniqKey="Thaller E">E Thaller</name></author><author><name sortKey="Brodmann, M" uniqKey="Brodmann M">M Brodmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tonetti, Ms" uniqKey="Tonetti M">MS Tonetti</name></author><author><name sortKey="Claffey, N" uniqKey="Claffey N">N Claffey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="John, U" uniqKey="John U">U John</name></author><author><name sortKey="Greiner, B" uniqKey="Greiner B">B Greiner</name></author><author><name sortKey="Hensel, E" uniqKey="Hensel E">E Hensel</name></author><author><name sortKey="Ludemann, J" uniqKey="Ludemann J">J Lüdemann</name></author><author><name sortKey="Piek, M" uniqKey="Piek M">M Piek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Volzke, H" uniqKey="Volzke H">H Völzke</name></author><author><name sortKey="Alte, D" uniqKey="Alte D">D Alte</name></author><author><name sortKey="Schmidt, Co" uniqKey="Schmidt C">CO Schmidt</name></author><author><name sortKey="Radke, D" uniqKey="Radke D">D Radke</name></author><author><name sortKey="Lorbeer, R" uniqKey="Lorbeer R">R Lorbeer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Keil, U" uniqKey="Keil U">U Keil</name></author><author><name sortKey="Stieber, J" uniqKey="Stieber J">J Stieber</name></author><author><name sortKey="Doring, A" uniqKey="Doring A">A Döring</name></author><author><name sortKey="Chambless, L" uniqKey="Chambless L">L Chambless</name></author><author><name sortKey="H Rtel, U" uniqKey="H Rtel U">U Härtel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lowel, H" uniqKey="Lowel H">H Löwel</name></author><author><name sortKey="Doring, A" uniqKey="Doring A">A Döring</name></author><author><name sortKey="Schneider, A" uniqKey="Schneider A">A Schneider</name></author><author><name sortKey="Heier, M" uniqKey="Heier M">M Heier</name></author><author><name sortKey="Thorand, B" uniqKey="Thorand B">B Thorand</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schneider, Hj" uniqKey="Schneider H">HJ Schneider</name></author><author><name sortKey="Friedrich, N" uniqKey="Friedrich N">N Friedrich</name></author><author><name sortKey="Klotsche, J" uniqKey="Klotsche J">J Klotsche</name></author><author><name sortKey="Pieper, L" uniqKey="Pieper L">L Pieper</name></author><author><name sortKey="Nauck, M" uniqKey="Nauck M">M Nauck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Demmer, Rt" uniqKey="Demmer R">RT Demmer</name></author><author><name sortKey="Kocher, T" uniqKey="Kocher T">T Kocher</name></author><author><name sortKey="Schwahn, C" uniqKey="Schwahn C">C Schwahn</name></author><author><name sortKey="Volzke, H" uniqKey="Volzke H">H Völzke</name></author><author><name sortKey="Jacobs, Dr" uniqKey="Jacobs D">DR Jacobs</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hensel, E" uniqKey="Hensel E">E Hensel</name></author><author><name sortKey="Gesch, D" uniqKey="Gesch D">D Gesch</name></author><author><name sortKey="Biffar, R" uniqKey="Biffar R">R Biffar</name></author><author><name sortKey="Bernhardt, O" uniqKey="Bernhardt O">O Bernhardt</name></author><author><name sortKey="Kocher, T" uniqKey="Kocher T">T Kocher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corretti, Mc" uniqKey="Corretti M">MC Corretti</name></author><author><name sortKey="Anderson, Tj" uniqKey="Anderson T">TJ Anderson</name></author><author><name sortKey="Benjamin, Ej" uniqKey="Benjamin E">EJ Benjamin</name></author><author><name sortKey="Celermajer, D" uniqKey="Celermajer D">D Celermajer</name></author><author><name sortKey="Charbonneau, F" uniqKey="Charbonneau F">F Charbonneau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Volzke, H" uniqKey="Volzke H">H Völzke</name></author><author><name sortKey="Robinson, Dm" uniqKey="Robinson D">DM Robinson</name></author><author><name sortKey="Spielhagen, T" uniqKey="Spielhagen T">T Spielhagen</name></author><author><name sortKey="Nauck, M" uniqKey="Nauck M">M Nauck</name></author><author><name sortKey="Obst, A" uniqKey="Obst A">A Obst</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Empen, K" uniqKey="Empen K">K Empen</name></author><author><name sortKey="Lorbeer, R" uniqKey="Lorbeer R">R Lorbeer</name></author><author><name sortKey="Dorr, M" uniqKey="Dorr M">M Dörr</name></author><author><name sortKey="Haring, R" uniqKey="Haring R">R Haring</name></author><author><name sortKey="Nauck, M" uniqKey="Nauck M">M Nauck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hamburg, Nm" uniqKey="Hamburg N">NM Hamburg</name></author><author><name sortKey="Keyes, Mj" uniqKey="Keyes M">MJ Keyes</name></author><author><name sortKey="Larson, Mg" uniqKey="Larson M">MG Larson</name></author><author><name sortKey="Vasan, Rs" uniqKey="Vasan R">RS Vasan</name></author><author><name sortKey="Schnabel, R" uniqKey="Schnabel R">R Schnabel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vita, Ja" uniqKey="Vita J">JA Vita</name></author><author><name sortKey="Keaney, Jf" uniqKey="Keaney J">JF Keaney</name></author><author><name sortKey="Larson, Mg" uniqKey="Larson M">MG Larson</name></author><author><name sortKey="Keyes, Mj" uniqKey="Keyes M">MJ Keyes</name></author><author><name sortKey="Massaro, Jm" uniqKey="Massaro J">JM Massaro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Henry, Rm" uniqKey="Henry R">RM Henry</name></author><author><name sortKey="Ferreira, I" uniqKey="Ferreira I">I Ferreira</name></author><author><name sortKey="Kostense, Pj" uniqKey="Kostense P">PJ Kostense</name></author><author><name sortKey="Dekker, Jm" uniqKey="Dekker J">JM Dekker</name></author><author><name sortKey="Nijpels, G" uniqKey="Nijpels G">G Nijpels</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tonetti, Ms" uniqKey="Tonetti M">MS Tonetti</name></author><author><name sortKey="D Aiuto, F" uniqKey="D Aiuto F">F D'Aiuto</name></author><author><name sortKey="Nibali, L" uniqKey="Nibali L">L Nibali</name></author><author><name sortKey="Donald, A" uniqKey="Donald A">A Donald</name></author><author><name sortKey="Storry, C" uniqKey="Storry C">C Storry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Royston, P" uniqKey="Royston P">P Royston</name></author><author><name sortKey="Ambler, G" uniqKey="Ambler G">G Ambler</name></author><author><name sortKey="Sauerbrei, W" uniqKey="Sauerbrei W">W Sauerbrei</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Little, Rj" uniqKey="Little R">RJ Little</name></author><author><name sortKey="Vartivarian, S" uniqKey="Vartivarian S">S Vartivarian</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Elter, Jr" uniqKey="Elter J">JR Elter</name></author><author><name sortKey="Hinderliter, Al" uniqKey="Hinderliter A">AL Hinderliter</name></author><author><name sortKey="Offenbacher, S" uniqKey="Offenbacher S">S Offenbacher</name></author><author><name sortKey="Beck, Jd" uniqKey="Beck J">JD Beck</name></author><author><name sortKey="Caughey, M" uniqKey="Caughey M">M Caughey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Piconi, S" uniqKey="Piconi S">S Piconi</name></author><author><name sortKey="Trabattoni, D" uniqKey="Trabattoni D">D Trabattoni</name></author><author><name sortKey="Luraghi, C" uniqKey="Luraghi C">C Luraghi</name></author><author><name sortKey="Perilli, E" uniqKey="Perilli E">E Perilli</name></author><author><name sortKey="Borelli, M" uniqKey="Borelli M">M Borelli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Higashi, Y" uniqKey="Higashi Y">Y Higashi</name></author><author><name sortKey="Goto, C" uniqKey="Goto C">C Goto</name></author><author><name sortKey="Hidaka, T" uniqKey="Hidaka T">T Hidaka</name></author><author><name sortKey="Soga, J" uniqKey="Soga J">J Soga</name></author><author><name sortKey="Nakamura, S" uniqKey="Nakamura S">S Nakamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tomiyama, H" uniqKey="Tomiyama H">H Tomiyama</name></author><author><name sortKey="Matsumoto, C" uniqKey="Matsumoto C">C Matsumoto</name></author><author><name sortKey="Yamada, J" uniqKey="Yamada J">J Yamada</name></author><author><name sortKey="Teramoto, T" uniqKey="Teramoto T">T Teramoto</name></author><author><name sortKey="Abe, K" uniqKey="Abe K">K Abe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author><author><name sortKey="Tse, Hf" uniqKey="Tse H">HF Tse</name></author><author><name sortKey="Yiu, Kh" uniqKey="Yiu K">KH Yiu</name></author><author><name sortKey="Li, Ls" uniqKey="Li L">LS Li</name></author><author><name sortKey="Jin, L" uniqKey="Jin L">L Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Loos, Bg" uniqKey="Loos B">BG Loos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kweider, M" uniqKey="Kweider M">M Kweider</name></author><author><name sortKey="Lowe, Gd" uniqKey="Lowe G">GD Lowe</name></author><author><name sortKey="Murray, Gd" uniqKey="Murray G">GD Murray</name></author><author><name sortKey="Kinane, Df" uniqKey="Kinane D">DF Kinane</name></author><author><name sortKey="Mcgowan, Da" uniqKey="Mcgowan D">DA McGowan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schwahn, C" uniqKey="Schwahn C">C Schwahn</name></author><author><name sortKey="Volzke, H" uniqKey="Volzke H">H Völzke</name></author><author><name sortKey="Robinson, Dm" uniqKey="Robinson D">DM Robinson</name></author><author><name sortKey="Luedemann, J" uniqKey="Luedemann J">J Luedemann</name></author><author><name sortKey="Bernhardt, O" uniqKey="Bernhardt O">O Bernhardt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ablij, H" uniqKey="Ablij H">H Ablij</name></author><author><name sortKey="Meinders, A" uniqKey="Meinders A">A Meinders</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Janket, Sj" uniqKey="Janket S">SJ Janket</name></author><author><name sortKey="Jones, Ja" uniqKey="Jones J">JA Jones</name></author><author><name sortKey="Meurman, Jh" uniqKey="Meurman J">JH Meurman</name></author><author><name sortKey="Baird, Ae" uniqKey="Baird A">AE Baird</name></author><author><name sortKey="Van Dyke, Te" uniqKey="Van Dyke T">TE Van Dyke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fichtlscherer, S" uniqKey="Fichtlscherer S">S Fichtlscherer</name></author><author><name sortKey="Rosenberger, G" uniqKey="Rosenberger G">G Rosenberger</name></author><author><name sortKey="Walter, Dh" uniqKey="Walter D">DH Walter</name></author><author><name sortKey="Breuer, S" uniqKey="Breuer S">S Breuer</name></author><author><name sortKey="Dimmeler, S" uniqKey="Dimmeler S">S Dimmeler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sinisalo, J" uniqKey="Sinisalo J">J Sinisalo</name></author><author><name sortKey="Paronen, J" uniqKey="Paronen J">J Paronen</name></author><author><name sortKey="Mattila, Kj" uniqKey="Mattila K">KJ Mattila</name></author><author><name sortKey="Syrj L, M" uniqKey="Syrj L M">M Syrjälä</name></author><author><name sortKey="Alfthan, G" uniqKey="Alfthan G">G Alfthan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="D Aiuto, F" uniqKey="D Aiuto F">F D'Aiuto</name></author><author><name sortKey="Orlandi, M" uniqKey="Orlandi M">M Orlandi</name></author><author><name sortKey="Gunsolley, Jc" uniqKey="Gunsolley J">JC Gunsolley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bergstrom, J" uniqKey="Bergstrom J">J Bergstrom</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bergstrom, J" uniqKey="Bergstrom J">J Bergström</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ambrose, Ja" uniqKey="Ambrose J">JA Ambrose</name></author><author><name sortKey="Barua, Rs" uniqKey="Barua R">RS Barua</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Puranik, R" uniqKey="Puranik R">R Puranik</name></author><author><name sortKey="Celermajer, Ds" uniqKey="Celermajer D">DS Celermajer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Demmer, Rt" uniqKey="Demmer R">RT Demmer</name></author><author><name sortKey="Desvarieux, M" uniqKey="Desvarieux M">M Desvarieux</name></author><author><name sortKey="Holtfreter, B" uniqKey="Holtfreter B">B Holtfreter</name></author><author><name sortKey="Jacobs, Dr" uniqKey="Jacobs D">DR Jacobs</name></author><author><name sortKey="Wallaschofski, H" uniqKey="Wallaschofski H">H Wallaschofski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Demmer, Rt" uniqKey="Demmer R">RT Demmer</name></author><author><name sortKey="Holtfreter, B" uniqKey="Holtfreter B">B Holtfreter</name></author><author><name sortKey="Desvarieux, M" uniqKey="Desvarieux M">M Desvarieux</name></author><author><name sortKey="Jacobs, Dr" uniqKey="Jacobs D">DR Jacobs</name></author><author><name sortKey="Kerner, W" uniqKey="Kerner W">W Kerner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Desvarieux, M" uniqKey="Desvarieux M">M Desvarieux</name></author><author><name sortKey="Schwahn, C" uniqKey="Schwahn C">C Schwahn</name></author><author><name sortKey="Volzke, H" uniqKey="Volzke H">H Völzke</name></author><author><name sortKey="Demmer, Rt" uniqKey="Demmer R">RT Demmer</name></author><author><name sortKey="Ludemann, J" uniqKey="Ludemann J">J Lüdemann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hannemann, A" uniqKey="Hannemann A">A Hannemann</name></author><author><name sortKey="Wallaschofski, H" uniqKey="Wallaschofski H">H Wallaschofski</name></author><author><name sortKey="Ludemann, J" uniqKey="Ludemann J">J Lüdemann</name></author><author><name sortKey="Volzke, H" uniqKey="Volzke H">H Völzke</name></author><author><name sortKey="Markus, Mr" uniqKey="Markus M">MR Markus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lorbeer, R" uniqKey="Lorbeer R">R Lorbeer</name></author><author><name sortKey="Empen, K" uniqKey="Empen K">K Empen</name></author><author><name sortKey="Dorr, M" uniqKey="Dorr M">M Dörr</name></author><author><name sortKey="Arndt, M" uniqKey="Arndt M">M Arndt</name></author><author><name sortKey="Schipf, S" uniqKey="Schipf S">S Schipf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Empen, K" uniqKey="Empen K">K Empen</name></author><author><name sortKey="Lorbeer, R" uniqKey="Lorbeer R">R Lorbeer</name></author><author><name sortKey="Volzke, H" uniqKey="Volzke H">H Völzke</name></author><author><name sortKey="Robinson, Dm" uniqKey="Robinson D">DM Robinson</name></author><author><name sortKey="Friedrich, N" uniqKey="Friedrich N">N Friedrich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reffelmann, T" uniqKey="Reffelmann T">T Reffelmann</name></author><author><name sortKey="Krebs, A" uniqKey="Krebs A">A Krebs</name></author><author><name sortKey="Ittermann, T" uniqKey="Ittermann T">T Ittermann</name></author><author><name sortKey="Empen, K" uniqKey="Empen K">K Empen</name></author><author><name sortKey="Hummel, A" uniqKey="Hummel A">A Hummel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Savage, A" uniqKey="Savage A">A Savage</name></author><author><name sortKey="Eaton, Ka" uniqKey="Eaton K">KA Eaton</name></author><author><name sortKey="Moles, Dr" uniqKey="Moles D">DR Moles</name></author><author><name sortKey="Needleman, I" uniqKey="Needleman I">I Needleman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kingman, A" uniqKey="Kingman A">A Kingman</name></author><author><name sortKey="Susin, C" uniqKey="Susin C">C Susin</name></author><author><name sortKey="Albandar, Jm" uniqKey="Albandar J">JM Albandar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beck, Jd" uniqKey="Beck J">JD Beck</name></author><author><name sortKey="Pankow, J" uniqKey="Pankow J">J Pankow</name></author><author><name sortKey="Tyroler, Ha" uniqKey="Tyroler H">HA Tyroler</name></author><author><name sortKey="Offenbacher, S" uniqKey="Offenbacher S">S Offenbacher</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24386401</article-id><article-id pub-id-type="pmc">3873439</article-id><article-id pub-id-type="publisher-id">PONE-D-13-25105</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0084603</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Periodontitis Is Associated with Endothelial Dysfunction in a General Population: A Cross-Sectional Study</article-title><alt-title alt-title-type="running-head">Periodontitis and Endothelial Dysfunction</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Holtfreter</surname><given-names>Birte</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Empen</surname><given-names>Klaus</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gläser</surname><given-names>Sven</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lorbeer</surname><given-names>Roberto</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Völzke</surname><given-names>Henry</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ewert</surname><given-names>Ralf</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kocher</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dörr</surname><given-names>Marcus</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Unit of Periodontology, Department of Restorative Dentistry, Periodontology, and Endodontology, University Medicine, University of Greifswald, Greifswald, Germany</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Department of Internal Medicine, University Medicine, University of Greifswald, Greifswald, Germany</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Institute for Community Medicine, SHIP/Clinical-Epidemiological Research, University Medicine, University of Greifswald, Greifswald, Germany</addr-line></aff><aff id="aff4"><label>4</label><addr-line>German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Rogers</surname><given-names>Lynette K.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>The Ohio State Unversity, United States of America</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>birte.holtfreter@uni-greifswald.de</email></corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>We have the following interests. BH was financed by an unlimited grant from GABA, Switzerland. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: KE SG HV RE TK MD. Performed the experiments: HV TK MD. Analyzed the data: BH RL. Contributed reagents/materials/analysis tools: KE SG HV RE TK MD. Wrote the manuscript: BH KE RL HV RE TK MD. </p></fn></author-notes><pub-date pub-type="collection"><year>2013</year></pub-date><pub-date pub-type="epub"><day>26</day><month>12</month><year>2013</year></pub-date><volume>8</volume><issue>12</issue><elocation-id>e84603</elocation-id><history><date date-type="received"><day>17</day><month>6</month><year>2013</year></date><date date-type="accepted"><day>16</day><month>11</month><year>2013</year></date></history><permissions><copyright-year>2013</copyright-year><copyright-holder>Holtfreter et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><p>A large body of evidence underlines an association between periodontal disease and cardiovascular disease. In contrast, data on its relation with endothelial dysfunction as a marker of early subclinical atherosclerosis is inconclusive and limited to patient-cohort studies. We therefore investigated the association between periodontal disease and flow-mediated dilation of the brachial artery (FMD) as a measure of endothelial dysfunction in a general population, and also addressed a possible mediation via inflammation. The study population comprised 1,234 subjects (50.5% men) aged 25–85 years from the 5-year follow-up of the Study of Health in Pomerania, a population-based cohort study. Clinical attachment loss (CAL) and pocket probing depth (PPD) as measures of periodontal disease were assessed half-mouth at four sites per tooth. Subjects were classified according to the periodontitis case definition proposed by Tonetti and Claffey (2005). Measurements of FMD and nitroglycerin-mediated dilation (NMD) were performed using standardized ultrasound techniques. High-sensitive C-reactive protein, fibrinogen and leukocyte count were measured. Fully adjusted multivariate linear regression analyses revealed significant associations of the percentage of sites with PPD ≥6 mm with FMD (p<sub>trend</sub>=0.048), with subjects within the highest category having a 0.74% higher FMD compared to subjects within the lowest category (p<0.05). Consistently, FMD values increased significantly across categories of the percentage of sites with CAL ≥6 mm (p<sub>trend</sub>=0.01) and the periodontitis case definition (p<sub>trend</sub>=0.006). Restrictions to subjects without antihypertensive or statin medication or current non-smokers confirmed previous results. Systemic inflammation did not seem to mediate the relation. Both PPD and CAL were not consistently associated with NMD. In contrast to previous studies, high levels of periodontal disease were significantly associated with high FMD values. This association was not mediated via systemic inflammation. This study revives the discussion on whether and how periodontitis contributes to endothelial dysfunction.</p></abstract><funding-group><funding-statement>This work was supported by the Community Medicine Research network of the University of Greifswald, Germany that is funded by the German Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, 01ZZ0403, 01ZZ0701), the German Ministry of Cultural Affairs, as well as by the Social Ministry of the German Federal State of Mecklenburg-West Pomerania. Furthermore, this work is part of the research project Greifswald Approach to Individualized Medicine (GANI_MED). The GANI_MED consortium is funded by the German Federal Ministry of Education and Research and as well as by the Ministry of Cultural Affairs of the German Federal State of Mecklenburg – West Pomerania (03IS2061A). This study was further supported by the DZHK (German Centre for Cardiovascular Research) and by the Kompetenznetz Asthma/COPD (Competence Network Asthma/COPD) funded by the Federal Ministry of Education and Research (FKZ 01GI0881-0888). BH was financed by an unlimited grant from GABA, Switzerland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
</funding-statement></funding-group></article-meta></front></pmc><affiliations><list><country><li>Allemagne</li></country></list><tree><country name="Allemagne"><noRegion><name sortKey="Holtfreter, Birte" sort="Holtfreter, Birte" uniqKey="Holtfreter B" first="Birte" last="Holtfreter">Birte Holtfreter</name></noRegion><name sortKey="Dorr, Marcus" sort="Dorr, Marcus" uniqKey="Dorr M" first="Marcus" last="Dörr">Marcus Dörr</name><name sortKey="Dorr, Marcus" sort="Dorr, Marcus" uniqKey="Dorr M" first="Marcus" last="Dörr">Marcus Dörr</name><name sortKey="Empen, Klaus" sort="Empen, Klaus" uniqKey="Empen K" first="Klaus" last="Empen">Klaus Empen</name><name sortKey="Ewert, Ralf" sort="Ewert, Ralf" uniqKey="Ewert R" first="Ralf" last="Ewert">Ralf Ewert</name><name sortKey="Gl Ser, Sven" sort="Gl Ser, Sven" uniqKey="Gl Ser S" first="Sven" last="Gl Ser">Sven Gl Ser</name><name sortKey="Kocher, Thomas" sort="Kocher, Thomas" uniqKey="Kocher T" first="Thomas" last="Kocher">Thomas Kocher</name><name sortKey="Lorbeer, Roberto" sort="Lorbeer, Roberto" uniqKey="Lorbeer R" first="Roberto" last="Lorbeer">Roberto Lorbeer</name><name sortKey="Volzke, Henry" sort="Volzke, Henry" uniqKey="Volzke H" first="Henry" last="Völzke">Henry Völzke</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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