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

Jonas Persson, Rona J Strawbridge, Olga McLeod, Karl Gertow, Angela Silveira, Damiano Baldassarre, Natalie Van Zuydam, Sonia Shah, Cristiano Fava, Stefan Gustafsson, Fabrizio Veglia, Bengt Sennblad, Malin Larsson, Maria Sabater-Lleal, Karin Leander, Bruna Gigante, Adam Tabak, Mika Kivimaki, Jussi Kauhanen, Rainer Rauramaa, Andries J Smit, Elmo Mannarino, Philippe Giral, Steve E Humphries, Elena Tremoli, Ulf de Faire, Lars Lind, Erik Ingelsson, Bo Hedblad, Olle Melander, Meena Kumari, Aroon Hingorani, Andrew D Morris, Colin N A Palmer, Pia Lundman, John Öhrvik, Stefan Söderberg, Anders Hamsten
Journal of the American Heart Association 2015 August 14, 4 (8): e001853

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.

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