Different associations between HDL cholesterol and cardiovascular diseases in people with diabetes mellitus and people without diabetes mellitus: a prospective community-based study

Background: Experimental studies have found that the functionality of HDL cholesterol may be lost in the presence of diabetes mellitus (DM). Objectives: We aimed to elucidate whether DM modified the association between HDL-cholesterol concentrations and cardiovascular disease (CVD) outcomes. Methods: Included were 91,354 Chinese adults (8244 participants with DM and 83,110 participants without DM) free of CVD or cancer at baseline (2006) and without use of lipid-lowering drugs at baseline and during follow-up. The primary endpoint of interest was a composite of CVDs (myocardial infarction, ischemic stroke, and hemorrhagic stroke). Cumulative average HDL-cholesterol concentrations were calculated from all available HDL-cholesterol measures at baseline (2006) and during the follow-up period (2008, 2010, 2012, and 2014). Results: During a mean of 10.4 y of follow-up, there were 5076 CVD events identified. There was a significant interaction between DM and HDL-cholesterol concentrations on CVD risk (Pinteraction = 0.003). The association between HDL-cholesterol concentrations and CVD followed a U-shaped curve in individuals without DM (Pnonlinearity < 0.001). The adjusted HR of CVD was 1.26 (95% CI: 1.07, 1.48) for HDL-cholesterol concentrations < 1.04 mmol/L and 1.76 (95% CI: 1.53, 2.03) for HDL-cholesterol concentrations > 2.07 mmol/L, relative to the lowest-risk group (HDL-cholesterol concentrations of 1.30-1.42 mmol/L). In participants with DM, higher HDL-cholesterol concentrations were associated with a higher risk of CVD, in a dose-response manner (Pnonlinearity = 0.44; Ptrend < 0.001). The adjusted HR of CVD was 1.62 (95% CI: 1.19, 2.20) for HDL-cholesterol concentrations >2.07 mmol/L, relative to HDL-cholesterol concentrations of 1.30-1.42 mmol/L. Conclusions: High HDL-cholesterol concentrations were paradoxically associated with high risk of composite CVD outcomes in individuals with or without DM. However, low HDL-cholesterol concentrations failed to predict future CVD risk in individuals with DM.