MD/PhD (PECEM) Program, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico.
MD/PhD (PECEM) Program, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico; Research Division, Instituto Nacional de Geriatría, Mexico.
Atherosclerosis. 2024 Aug;395:117508. doi: 10.1016/j.atherosclerosis.2024.117508. Epub 2024 Mar 13.
Remnant cholesterol (RC) and insulin resistance (IR) have been independently associated with cardiovascular risk. Here, we evaluated the role of IR and RC on cardiovascular disease (CVD) mortality.
We conducted an analysis of 16,113 individuals ≥20 years without diabetes from the National Health and Nutrition Examination Survey (NHANES-III/IV). RC levels were calculated using total cholesterol, non-HDL-c, and LDL-c; IR was defined as HOMA2-IR≥2.5 and CVD mortality as a composite of cardiovascular and cerebrovascular mortality. Multiple linear regression was used to assess the relationship between HOMA2-IR and RC and Cox regression models to assess their joint role in CVD mortality. Causally ordered mediation models were used to explore the mediating role of IR in RC-associated CVD mortality.
We identified an association between higher HOMA2-IR and higher RC levels. The effect of IR on CVD mortality was predominant (HR 1.32, 95%CI 1.18-1.48) and decreased at older ages (HR 0.934, 95%CI 0.918-0.959) compared to RC (HR 0.983, 95%CI 0.952-1.014). Higher risk of CVD mortality was observed in individuals with IR but normal RC (HR 1.37, 95%CI 1.25-1.50) and subjects with IR and high RC (HR 1.24, 95%CI 1.13-1.37), but not in subjects without IR but high RC. In mediation models, HOMA2-IR accounted for 78.2% (95%CI 28.11-98.89) of the effect of RC levels on CVD mortality.
Our findings suggest that RC potentiates the risk of CVD mortality through its effect on whole-body insulin sensitivity, particularly among younger individuals.
残胆固醇（RC）和胰岛素抵抗（IR）与心血管风险独立相关。在此，我们评估了 IR 和 RC 对心血管疾病（CVD）死亡率的作用。
我们对来自国家健康和营养检查调查（NHANES-III/IV）的 16113 名年龄≥20 岁且无糖尿病的个体进行了分析。RC 水平通过总胆固醇、非高密度脂蛋白胆固醇和 LDL-c 计算；IR 定义为 HOMA2-IR≥2.5，CVD 死亡率为心血管和脑血管死亡率的综合。使用多元线性回归评估 HOMA2-IR 和 RC 之间的关系，使用 Cox 回归模型评估它们在 CVD 死亡率中的联合作用。因果有序中介模型用于探讨 IR 在 RC 相关 CVD 死亡率中的中介作用。
我们发现 HOMA2-IR 与更高的 RC 水平之间存在关联。IR 对 CVD 死亡率的影响更为显著（HR 1.32，95%CI 1.18-1.48），且在年龄较大时降低（HR 0.934，95%CI 0.918-0.959），而与 RC 相比（HR 0.983，95%CI 0.952-1.014）。在具有 IR 但正常 RC（HR 1.37，95%CI 1.25-1.50）和具有 IR 和高 RC（HR 1.24，95%CI 1.13-1.37）的个体中观察到 CVD 死亡率升高，但在没有 IR 但高 RC 的个体中则没有。在中介模型中，HOMA2-IR 解释了 RC 水平对 CVD 死亡率影响的 78.2%（95%CI 28.11-98.89）。
我们的研究结果表明，RC 通过对全身胰岛素敏感性的影响增强了 CVD 死亡率的风险，尤其是在年轻个体中。
