TY - JOUR
T1 - Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease
AU - Persson, Jonas
AU - Strawbridge, Rona J.
AU - McLeod, Olga
AU - Gertow, Karl
AU - Silveira, Angela
AU - Baldassarre, Damiano
AU - Van Zuydam, Natalie
AU - Shah, Sonia
AU - Fava, Cristiano
AU - Gustafsson, Stefan
AU - Veglia, Fabrizio
AU - Sennblad, Bengt
AU - Larsson, Malin
AU - Sabater-Lleal, Maria
AU - Leander, Karin
AU - Gigante, Bruna
AU - Tabak, Adam
AU - Kivimaki, Mika
AU - Kauhanen, Jussi
AU - Rauramaa, Rainer
AU - Smit, Andries J.
AU - Mannarino, Elmo
AU - Giral, Philippe
AU - Humphries, Steve E.
AU - Tremoli, Elena
AU - de Faire, Ulf
AU - Lind, Lars
AU - Ingelsson, Erik
AU - Hedblad, Bo
AU - Melander, Olle
AU - Kumari, Meena
AU - Hingorani, Aroon
AU - Morris, Andrew D.
AU - Palmer, Colin N. A.
AU - Lundman, Pia
AU - Öhrvik, John
AU - Söderberg, Stefan
AU - Hamsten, Anders
AU - IMPROVE Study Group
N1 - © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
PY - 2015/8/14
Y1 - 2015/8/14
N2 - 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.
AB - 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.
U2 - 10.1161/JAHA.115.001853
DO - 10.1161/JAHA.115.001853
M3 - Article
C2 - 26276317
SN - 2047-9980
VL - 4
JO - Journal of the American Heart Association Cardiovascular and Cerebrovascular Disease (JAHA)
JF - Journal of the American Heart Association Cardiovascular and Cerebrovascular Disease (JAHA)
IS - 8
M1 - e001853
ER -