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ABSTRACT: Background
Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), 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 IMT.Methods and results
Baseline plasma adiponectin concentration was tested for association with baseline IMT, IMT 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 IMT after adjustment for established risk factors (β=-0.018, P<0.001) in men but not in women (β=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (β=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82, 95% CI 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 IMT in men (β=-0.0008, P=0.004) but not in women (β=-0.0003, P=0.522; P for interaction=0.007).Conclusions
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.
SUBMITTER: Persson J
PROVIDER: S-EPMC4599454 | biostudies-literature | 2015 Aug
REPOSITORIES: biostudies-literature
Persson Jonas J Strawbridge Rona J RJ McLeod Olga O Gertow Karl K Silveira Angela A Baldassarre Damiano D Van Zuydam Natalie N Shah Sonia S Fava Cristiano C Gustafsson Stefan S Veglia Fabrizio F Sennblad Bengt B Larsson Malin M Sabater-Lleal Maria M Leander Karin K Gigante Bruna B Tabak Adam A Kivimaki Mika M Kauhanen Jussi J Rauramaa Rainer R Smit Andries J AJ Mannarino Elmo E Giral Philippe P Humphries Steve E SE Tremoli Elena E de Faire Ulf U Lind Lars L Ingelsson Erik E Hedblad Bo B Melander Olle O Kumari Meena M Hingorani Aroon A Morris Andrew D AD Palmer Colin N A CN Lundman Pia P Öhrvik John J Söderberg Stefan S Hamsten Anders A
Journal of the American Heart Association 20150814 8
<h4>Background</h4>Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), 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 IMT.<h4>Methods and results</h4>Baseline plasma adiponectin concentration was tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular ...[more]