Cardiovascular Clinical Research Unit, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
Circulation. 2012 Dec 18;126(25):2951-61. doi: 10.1161/CIRCULATIONAHA.112.135202. Epub 2012 Nov 16.
Adiponectin shows opposite associations with adverse outcomes in healthy middle-aged populations (lower risk) and cohorts with prevalent cardiovascular disease, heart failure, or advanced age (higher risk).
In a population-based study of older adults, we examined the relationships of total and high-molecular-weight adiponectin with mortality among subgroups defined by baseline cardiovascular status: No cardiovascular disease, heart failure, or atrial fibrillation (group 1); cardiovascular disease but no heart failure/atrial fibrillation (group 2); and heart failure/atrial fibrillation (group 3). We found significant differences in the associations with all-cause mortality across the groups. The association in group 1 was U-shaped; increasing levels of total adiponectin up to 12.4 mg/L were associated with lower mortality after adjustment for confounders (hazard ratio=0.81 per 1 SD [95% confidence interval, 0.65-0.95]), but above this cut point, higher levels conferred greater risk (hazard ratio=1.19 [95% confidence interval, 1.12-1.27]). Further adjustment for diabetes mellitus or insulin resistance, protection against which has been proposed to mediate the beneficial relationships of adiponectin with outcome, attenuated the association in the lower range. There was no significant association in group 2, but in group 3, total adiponectin showed a direct adjusted association. Additional adjustment for putative metabolic/inflammatory intermediates suggested a direct association for group 2, and magnified the one for group 3 (hazard ratio=1.31 [1.15-1.50]). Results were similar for high-molecular-weight adiponectin and for cardiovascular mortality.
Adiponectin exhibits distinct associations with mortality in elders, which shift from U-shaped to flat to direct with greater baseline cardiovascular dysfunction but become more consistently adverse after accounting for metabolic/inflammatory factors presumed to be favorably regulated by the adipokine. These findings advance understanding of the adiponectin paradox as it relates to older adults.
脂联素在健康中年人群（风险较低）和患有心血管疾病、心力衰竭或高龄的队列中（风险较高）与不良结局呈相反关联。
在一项基于人群的老年人研究中，我们根据基线心血管状况将人群分为亚组，检查总脂联素和高分子量脂联素与死亡率的关系：无心血管疾病、心力衰竭或心房颤动（第 1 组）；有心血管疾病但无心力衰竭/心房颤动（第 2 组）；以及心力衰竭/心房颤动（第 3 组）。我们发现，各亚组之间的全因死亡率存在显著差异。第 1 组的关联呈 U 型；调整混杂因素后，总脂联素水平在 12.4mg/L 以内与死亡率降低相关（风险比=每 1SD 降低 0.81[95%置信区间，0.65-0.95]），但超过该切点后，较高水平则增加风险（风险比=1.19[95%置信区间，1.12-1.27]）。进一步调整糖尿病或胰岛素抵抗，脂联素与结局的有益关系被认为是通过对其的保护来介导的，这降低了低值范围内的关联。第 2 组无显著关联，但第 3 组总脂联素呈直接调整关联。对假定的代谢/炎症中间产物进行进一步调整表明，第 2 组存在直接关联，并放大了第 3 组的关联（风险比=1.31[1.15-1.50]）。高分子量脂联素和心血管死亡率的结果相似。
脂联素在老年人中的死亡率存在明显的关联，随着基线心血管功能障碍的增加，从 U 型变为平坦，再变为直接，而在考虑到被认为受该脂肪因子有利调节的代谢/炎症因素后，这种关联变得更加一致地不利。这些发现加深了对与老年人相关的脂联素悖论的理解。
