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Sex‐Specific Effects of Adiponectin on Carotid Intima‐Media Thickness and Incident Cardiovascular Disease

Persson, Jonas and Strawbridge, Rona J and McLeod, Olga and Gertow, Karl and Silveira, Angela and Baldassarre, Damiano and Van Zuydam, Natalie and Shah, Sonia and Fava, Cristiano and Gustafsson, Stefan and Veglia, Fabrizio and Sennblad, Bengt and Larsson, Malin and Sabater‐Lleal, Maria and Leander, Karin and Gigante, Bruna and Tabak, Adam and Kivimaki, Mika and Kauhanen, Jussi and Rauramaa, Rainer and Smit, Andries J and Mannarino, Elmo and Giral, Philippe and Humphries, Steve E and Tremoli, Elena and de Faire, Ulf and Lind, Lars and Ingelsson, Erik and Hedblad, Bo and Melander, Olle and Kumari, Meena and Hingorani, Aroon and Morris, Andrew D and Palmer, Colin NA and Lundman, Pia and Öhrvik, John and Söderberg, Stefan and Hamsten, Anders (2015) 'Sex‐Specific Effects of Adiponectin on Carotid Intima‐Media Thickness and Incident Cardiovascular Disease.' Journal of the American Heart Association, 4 (8). e001853-. ISSN 2047-9980

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<jats:sec xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en"> Plasma adiponectin levels have previously been inversely associated with carotid intima‐media thickness ( <jats:styled-content style="fixed-case">IMT</jats:styled-content> ), a marker of subclinical atherosclerosis. In this study, we used a sex‐stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on <jats:styled-content style="fixed-case">IMT</jats:styled-content> . </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> Baseline plasma adiponectin concentration was tested for association with baseline <jats:styled-content style="fixed-case">IMT</jats:styled-content> , <jats:styled-content style="fixed-case">IMT</jats:styled-content> progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation <jats:styled-content style="fixed-case">IMT</jats:styled-content> after adjustment for established risk factors (β=−0.018, <jats:italic>P</jats:italic> &lt;0.001) in men but not in women (β=−0.006, <jats:italic>P</jats:italic> =0.185; <jats:italic>P</jats:italic> for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid <jats:styled-content style="fixed-case">IMT</jats:styled-content> in men (β=−0.0022, <jats:italic>P</jats:italic> =0.047), whereas no association was seen in women (0.0007, <jats:italic>P</jats:italic> =0.475; <jats:italic>P</jats:italic> for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 0.37 to 0.87) but not in men (hazard ratio 0.82, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 0.54 to 1.25). A gene score of adiponectin‐raising alleles in 6 loci, reported recently in a large multi‐ethnic meta‐analysis, was inversely associated with baseline mean bifurcation <jats:styled-content style="fixed-case">IMT</jats:styled-content> in men (β=−0.0008, <jats:italic>P</jats:italic> =0.004) but not in women (β=−0.0003, <jats:italic>P</jats:italic> =0.522; <jats:italic>P</jats:italic> for interaction=0.007). </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en">This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted.</jats:p> </jats:sec>

Item Type: Article
Uncontrolled Keywords: adiponectin; atherosclerosis; carotid intima-media thickness; genetics; Mendelian randomization
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences
Faculty of Social Sciences > Institute for Social and Economic Research
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 25 Sep 2015 09:15
Last Modified: 18 Aug 2022 12:09

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