Associations of total and high-molecular-weight adiponectin with all-cause and cardiovascular mortality in older persons: the Cardiovascular Health Study.
Associations of total and high-molecular-weight adiponectin with all-cause and cardiovascular mortality in older persons: the Cardiovascular Health Study.
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DOI：
10.1161/circulationaha.112.135202
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发表时间：
2012-12-18
期刊：
影响因子：
37.8
通讯作者：
Djousse L
中科院分区：
文献类型：
--
作者：
Kizer JR;Benkeser D;Arnold AM;Mukamal KJ;Ix JH;Zieman SJ;Siscovick DS;Tracy RP;Mantzoros CS;Defilippi CR;Newman AB;Djousse L
脂联素在健康中年人群（风险较低）和患有心血管疾病（CVD）、心力衰竭（HF）或高龄人群（风险较高）中显示出与不良结局相反的相关性。在一项老年人群研究中，我们检查了总脂联素和高分子量（HMW）脂联素与基线心血管状态定义的亚组死亡率的关系：无CVD、HF或房颤（AF）（第1组）; CVD但无HF/AF（第2组）; HF/AF（第3组）。我们发现各组之间全因死亡率的相关性存在显著差异。第1组的相关性呈U形;调整混杂因素后，总脂联素水平升高至12.4 mg/L与死亡率降低相关（HR=0.81/1-SD [0.65-0.95]），但高于此临界点，较高水平的风险更大（HR=1.19 [1.12-1.27]）。进一步调整糖尿病或胰岛素抵抗，预防已被提出介导脂联素与结果的有益关系，减弱了较低范围内的关联。在第2组中没有显著的相关性，但在第3组中，总脂联素显示出直接调整的相关性。对假定的代谢/炎症中间体进行的额外调整表明第2组存在直接相关性，并放大了第3组的相关性（HR=1.31 [1.15-1.50]）。HMW脂联素和心血管死亡率的结果相似。脂联素与老年人的死亡率具有明显的相关性，其从U形转变为平坦，直接与更大的基线心血管功能障碍相关，但在考虑到代谢/炎症因子后变得更加一致，这些代谢/炎症因子被认为是由脂肪因子有利地调节的。这些发现推进了对脂联素悖论与老年人相关的理解。
Adiponectin shows opposite associations with adverse outcomes in healthy middle-aged populations (lower risk), and cohorts with prevalent cardiovascular disease (CVD), heart failure (HF) or advanced age (higher risk). In a population-based study of older adults, we examined the relationships of total and high-molecular-weight (HMW) adiponectin with mortality among subgroups defined by baseline cardiovascular status: no CVD, HF or atrial fibrillation (AF) (Group 1); CVD but no HF/AF (Group 2); and HF/AF (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 (HR=0.81 per 1-SD [0.65–0.95]), but above this cutpoint, higher levels conferred greater risk (HR=1.19 [1.12–1.27]). Further adjustment for diabetes or insulin resistance, protection against which has been proposed to mediate adiponectin’s beneficial relationships 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 (HR=1.31 [1.15–1.50]). Results were similar for HMW 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 relates to older adults.