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.
Sex-specific effects of adiponectin on carotid intima-media thickness and incident cardiovascular disease / J. Persson, R.J. Strawbridge, O. Mcleod, K. Gertow, A. Silveira, D. Baldassarre, N. Van Zuydam, S. Shah, C. Fava, S. Gustafsson, F. Veglia, B. Sennblad, M. Larsson, M. Sabater-Lleal, K. Leander, B. Gigante, A. Tabak, M. Kivimaki, J. Kauhanen, R. Rauramaa, A.J. Smit, E. Mannarino, P. Giral, S.E. Humphries, E. Tremoli, U. de Faire, L. Lind, E. Ingelsson, B. Hedblad, O. Melander, M. Kumari, A. Hingorani, A.D. Morris, C.N.A. Palmer, P. Lundman, J. Öhrvik, S. Söderberg, A. Hamsten. - In: JOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE. - ISSN 2047-9980. - 4:8(2015 Aug 14), pp. 1-13. [10.1161/JAHA.115.001853]
Sex-specific effects of adiponectin on carotid intima-media thickness and incident cardiovascular disease
D. Baldassarre;E. Tremoli;
2015
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.Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.