Background
Increased LDL cholesterol is a major risk factor for morbidity and mortality from cardiovascular disease, though this association is attenuated by the widespread use of statins. Moreover, despite attainment of LDL cholesterol goals, a residual cardiovascular risk remains, partly attributed to atherogenic dyslipidaemia, the relationship of which with all-cause death has not been sufficiently explored. This analysis evaluated the independent association of atherogenic dyslipidaemia with total mortality in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian Multicentre Study.
Methods
This observational, prospective study enrolled 15,773 patients in 19 Diabetes Clinics throughout Italy in the years 2006–2008. Triglycerides and total and HDL cholesterol were measured by colorimetric enzymatic methods, whereas LDL cholesterol was estimated using the Friedewald formula. Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%). Participants were stratified by quartiles of triglycerides, HDL cholesterol, and triglyceride:HDL cholesterol ratio (TG:HDL).
Results
A total of 3,602 deaths occurred over a follow-up 7.42 ± 2.05 years (31.0 × 1,000 person-years). In the unadjusted analyses, the highest TG:HDL (but not triglyceride) and the lowest HDL cholesterol quartile were associated with increased death rate and mortality risk. When sequentially adjusting for confounders, including total or LDL cholesterol and lipid-lowering treatment, mortality risk was significantly higher in the highest triglyceride (hazard ratio 1.167 [95% confidence interval 1.055–1.291], p = 0.003) and TG:HDL (1.192 [1.082–1.314], p < 0.0001) and the lowest HDL cholesterol (1.232 [1.117–1.360], p < 0.0001) quartile, though the association of triglycerides and HDL cholesterol disappeared after further adjustment for each other. Interaction with gender was significant only for HDL cholesterol (p = 0.0009). The relationship with death was stronger for triglycerides in males and HDL cholesterol in females, with the latter remaining even after adjustment for triglycerides (1.366 [1.176–1.587], p < 0.0001, for the lowest vs the highest quartile).
Conclusions
In patients with type 2 diabetes, higher triglycerides and TG:HDL and lower HDL cholesterol were independently associated with increased all-cause mortality, with a modifying effect of gender for triglycerides and HDL cholesterol. These data suggest that atherogenic dyslipidaemia, especially TG:HDL, may serve as predictor of death in these individuals.
Trial registration
ClinicalTrials.gov, NCT00715481, 15 July, 2008.