Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave. E, Boston, MA 02215, USA.
Circulation. 2011 Nov 22;124(21):2303-11. doi: 10.1161/CIRCULATIONAHA.111.045187. Epub 2011 Oct 24.
Adiponectin is linked to reduced diabetes risk and may be antiatherogenic, yet clinical data show no consistent relationship with incident cardiovascular events, especially among women. To our knowledge, no prior prospective studies have evaluated adiponectin, including high-molecular-weight (HMW) adiponectin, and incident peripheral artery disease (PAD).
We evaluated the relationship of total adiponectin, HMW adiponectin, and the HMW-to-total adiponectin ratio with incident symptomatic PAD in a prospective, nested case-control study conducted within the Women's Health Study (n=110 cases, n=230 controls, frequency matched in strata defined by 5-year age categories, smoking, fasting status, and follow-up time; median cohort follow-up=13.2 years). Baseline median levels of HMW and total adiponectin were significantly lower in women developing PAD than in those remaining event free (HMW: 3.3 versus 3.8 μg/mL, P=0.0005; total: 5.6 versus 7.4 μg/mL, P<0.0001). The ratio did not differ significantly between groups. Age-adjusted PAD odds ratios (95% confidence intervals) across tertiles were 1.0, 0.66 (0.39-1.13), and 0.40 (0.22-0.74) for HMW and 1.0, 0.74 (0.43-1.25), and 0.35 (0.18-0.65) for total adiponectin (P(trend)=0.004 and 0.001, respectively). Results were similar after adjustment for traditional cardiovascular risk factors, use of postmenopausal hormone therapy, high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, leptin, hemoglobin A(1c), and fasting insulin (adjusted odds ratio and 95% confidence interval for HMW: 1.0, 0.62 [0.29-1.34], 0.30 [0.12-0.74]; total: 1.0, 0.46 [0.22-1.00], 0.30 [0.12-0.76]; P(trend)=0.01 for both).
Total and HMW adiponectin are inversely associated with incident PAD among initially healthy women. These prospective data support a protective role for this adipokine in peripheral atherosclerosis development.
脂联素与降低糖尿病风险有关，可能具有抗动脉粥样硬化作用，但临床数据显示其与心血管事件的发生没有一致的关系，尤其是在女性中。据我们所知，之前没有前瞻性研究评估过脂联素，包括高分子量（HMW）脂联素与外周动脉疾病（PAD）的发生。
我们在妇女健康研究（n=110 例病例，n=230 例对照，按 5 年年龄类别、吸烟、禁食状态和随访时间分层进行了前瞻性嵌套病例对照研究，频率匹配；中位队列随访时间为 13.2 年）中，评估了总脂联素、HMW 脂联素和 HMW 与总脂联素的比值与有症状 PAD 发生的关系。与无事件发生的女性相比，发生 PAD 的女性的 HMW 和总脂联素基线中位数水平明显降低（HMW：3.3 与 3.8 μg/mL，P=0.0005；总：5.6 与 7.4 μg/mL，P<0.0001）。两组之间的比值无显著差异。HMW 脂联素三分位数的年龄调整 PAD 比值（95%置信区间）分别为 1.0、0.66（0.39-1.13）和 0.40（0.22-0.74），总脂联素分别为 1.0、0.74（0.43-1.25）和 0.35（0.18-0.65）（P 趋势=0.004 和 0.001）。调整传统心血管危险因素、使用绝经后激素治疗、高敏 C 反应蛋白、可溶性细胞间黏附分子-1、瘦素、糖化血红蛋白 A1c 和空腹胰岛素后，结果相似（调整后的 HMW 比值和 95%置信区间为 1.0、0.62（0.29-1.34）和 0.30（0.12-0.74）；总：1.0、0.46（0.22-1.00）和 0.30（0.12-0.76）；P 趋势=0.01）。
总脂联素和 HMW 脂联素与最初健康女性的 PAD 发生呈负相关。这些前瞻性数据支持这种脂肪因子在外周动脉粥样硬化发展中具有保护作用。
