Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease.
Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease.
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DOI：
10.1161/jaha.115.001853
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发表时间：
2015-08-14
影响因子：
5.4
通讯作者：
IMPROVE Study Group
中科院分区：
文献类型：
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作者：
Persson J;Strawbridge RJ;McLeod O;Gertow K;Silveira A;Baldassarre D;Van Zuydam N;Shah S;Fava C;Gustafsson S;Veglia F;Sennblad B;Larsson M;Sabater-Lleal M;Leander K;Gigante B;Tabak A;Kivimaki M;Kauhanen J;Rauramaa R;Smit AJ;Mannarino E;Giral P;Humphries SE;Tremoli E;de Faire U;Lind L;Ingelsson E;Hedblad B;Melander O;Kumari M;Hingorani A;Morris AD;Palmer CN;Lundman P;Öhrvik J;Söderberg S;Hamsten A;IMPROVE Study Group
血浆脂联素水平与颈动脉内膜-中膜厚度（IMT）呈负相关，IMT是亚临床动脉粥样硬化的标志。在这项研究中，我们采用性别分层的孟德尔随机化方法来研究脂联素是否对IMT具有因果保护作用。基线血浆脂联素浓度与基线IMT、IMT在30个月内的进展以及3年内心血管事件发生的关系在3430名参与者（女性，n =1777；男性，n =1653）中进行了检测，这些参与者心血管风险高，但没有流行疾病。经确定的危险因素调整后，男性血浆脂联素水平与基线平均分岔IMT呈负相关（β = - 0.018， P<0.001），而女性血浆脂联素水平与基线平均分岔IMT呈负相关（β = - 0.006, P =0.185；相互作用P =0.061）。脂联素水平与男性平均颈总动脉IMT进展呈负相关（β = - 0.0022, P =0.047），而在女性中未见相关（0.0007,P =0.475；相互作用P =0.018）。此外，我们观察到脂联素水平与女性冠状动脉事件呈负相关（风险比0.57,95% CI 0.37至0.87），但与男性无关（风险比0.82,95% CI 0.54至1.25）。最近在一项大型多民族荟萃分析中报道，6个基因座中脂联素升高等位基因的基因评分与男性基线平均分岔IMT呈负相关（β = - 0.0008, P =0.004），但与女性无相关（β = - 0.0003, P =0.522；相互作用P =0.007）。本报告提供了一些证据，证明脂联素可以预防动脉粥样硬化，但其作用仅限于男性；然而，与已确定的心血管危险因素相比，血浆脂联素的影响是温和的。有必要进行包括机理研究在内的进一步调查。
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. 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). 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.