Background Obesity, defined by body mass index (BMI) alone, is a metabolically heterogeneous disorder with distinct cardiovascular manifestations across individuals. This study aimed to investigate the associations of a proteomic signature of BMI with risk of major subtypes of cardiovascular disease (CVD). Methods A total of 40 089 participants from UK Biobank, free of CVD at baseline, had complete data on proteomic data measured by the Olink assay. A BMI-proteomic score (pro-BMI score) was calculated from 67 pre-identified plasma proteins associated with BMI. Results A higher pro-BMI score was significantly associated with higher risks of ischemic heart disease (IHD) and heart failure (HF), but not with risk of stroke. Comparing the highest with the lowest quartiles, the adjusted hazard ratio (HR) for IHD was 1.49 (95% CI, 1.32–1.67) (P-trend < 0.001), and the adjusted HR for HF was 1.52 (95% CI, 1.25–1.85) (P-trend < 0.001). Further analyses showed that the association of pro-BMI score with HF risk was largely driven by the actual BMI, whereas the association of the pro-BMI score with IHD risk was independent of actual BMI and waist-to-hip ratio (WHR). The association between pro-BMI score and IHD risk appeared to be stronger in the normal BMI group than other BMI groups (P-interaction = 0.004) and stronger in the normal WHR group than the high WHR group (P-interaction = 0.049). Conclusions Higher pro-BMI score is significantly associated with higher IHD risk, independent of actual BMI levels. Our findings suggest that plasma proteins hold promise as complementary markers for diagnosing obesity and may facilitate personalized interventions.

中文翻译：

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BMI 的蛋白质组学特征和心血管疾病风险


背景 肥胖，仅由体重指数 （BMI） 定义，是一种代谢异质性疾病，个体之间具有不同的心血管表现。本研究旨在探讨 BMI 的蛋白质组学特征与心血管疾病 （CVD） 主要亚型风险的相关性。方法 来自英国生物样本库的共有 40 089 名参与者，基线时无 CVD，通过 Olink 测定测量的蛋白质组学数据的完整数据。根据 67 种预先确定的与 BMI 相关的血浆蛋白计算 BMI 蛋白质组学评分 （pro-BMI 评分）。结果 较高的 pro-BMI 评分与缺血性心脏病 （IHD） 和心力衰竭 （HF） 风险较高显著相关，但与卒中风险无关。比较最高和最低四分位数，IHD 的调整后风险比 （HR） 为 1.49 （95% CI，1.32-1.67） （P 趋势 < 0.001），HF 的调整后 HR 为 1.52 （95% CI，1.25-1.85） （P 趋势 < 0.001）。进一步分析表明，pro-BMI 评分与 HF 风险的关联主要由实际 BMI 驱动，而 pro-BMI 评分与 IHD 风险的关联与实际 BMI 和腰臀比 （WHR） 无关。正常 BMI 组的 pro-BMI 评分与 IHD 风险之间的相关性似乎比其他 BMI 组强 （P-交互作用 = 0.004），正常 WHR 组比高 WHR 组强 （P-交互作用 = 0.049）。结论 较高的 pro-BMI 评分与较高的 IHD 风险显著相关，与实际 BMI 水平无关。我们的研究结果表明，血浆蛋白有望作为诊断肥胖的补充标志物，并可能促进个性化干预。