Abstract
ObjectiveObjective: Although serum C-peptide has increasingly received attention as a new and important risk factor for cardiovascular disease (CVD), the potential mechanisms remain unclear. This study aimed to investigate the association between serum C-peptide as a risk factor for CVD and high-density lipoprotein cholesterol (HDL-C) levels.MethodsThe present study included 13,185 participants aged ≥20 years. Serum C-peptide and HDL-C levels were measured according to a standard protocol. Stratified analysis of covariance was used to compare serum HDL-C levels between different quartiles of serum C-peptide levels. Logistic regression analysis was used to determine the association between serum C-peptide and HDL-C levels. Cox proportional hazard regression analysis was conducted to determine the hazard ratio of serum HDL-C for CVD-related mortality.ResultsThe results of the ANCOVA analysis showed a significant linear trend between the mean serum HDL-C level and the different quartiles of serum C-peptide. Compared to the first quartile (25th percentile), the second, third, and fourth quartiles had gradual reduction in serum HDL-C levels. Logistic regression analyses showed a strong negative association between serum C-peptide levels and HDL-C levels; the p value for the linear trend was <0.001. In men, compared with the lowest quartile of the serum C-peptide level, the relative risk was 1.75, 2.79, and 3.07 for the upper three quartiles of the serum C-peptide level. The relative risk was 1.60, 2.61, and 3.67 for women. The results of the survival analysis showed that serum HDL-C levels were negatively associated with CVD-related death in both men and women.ConclusionSerum C-peptide as a risk factor for CVD was significantly and negatively associated with serum HDL-C levels in individuals without diabetes. These findings suggest that serum C-peptide levels association with CVD death can be caused, at least in part, by the low serum HDL-C level.
Highlights
Cardiovascular disease (CVD) is the most prevalent disease and leading cause of mortality in the worldwide
Serum C-peptide as a risk factor for CVD was significantly and negatively associated with serum high-density lipoprotein cholesterol (HDL-C) levels in individuals without diabetes. These findings suggest that serum C-peptide levels association with CVD death can be caused, at least in part, by the low serum HDL-C level
It has been established that serum C-peptide is a marker of insulin resistance and obesity, in type 2 diabetes, and basal C-peptide levels are significantly elevated in patients with metabolic syndrome and diabetes [15], more recent studies have reported that serum C-peptide levels are strongly and positively associated with stroke events independent of serum insulin level in people with diabetes [16]
Summary
Cardiovascular disease (CVD) is the most prevalent disease and leading cause of mortality in the worldwide. Recent studies have reported serum C-peptide as a new and important risk factor for CVD-related or overall death in nondiabetic adults [6]. A nationwide study suggested that serum C-peptide levels are a better predictor of cardiovascular-related and total mortality than serum insulin and other derived measures of insulin resistance in nondiabetic individuals; the effects are independent of several major risk factors for the development of diabetes or CVD [17]. Increasing attention is being paid to the potential mechanisms for serum C-peptide as an independent risk factor for CVD-related mortality in nondiabetic individuals
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