Recent publications on Residual Risk

A study using Mendelian randomization highlighted an association between elevated triglycerides and increased coronary artery disease risk; in contrast, higher triglycerides were associated with lower risk of type 2 diabetes. The study used data from genome-wide association studies, comprising 130 single-nucleotide polymorphisms (SNPs) for low-density lipoprotein cholesterol (LDL-C), 140 SNPs for triglycerides and 140 SNPs for high-density lipoprotein cholesterol (HDL-C), to construct genetic risk scores. A 1 standard deviation (SD) genetic increase in LDL-C levels (~38 mg/dL) and triglyceride levels (~89 mg/dL) increased coronary artery disease risk by 68% (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.51-1.87) and 28% (OR 1.28, 95% CI, 1.13-1.45), respectively. In contrast, 1 SD increase in HDL-C (~ 16-mg/dL) decreased risk by 5% (OR 0.95, 95% CI, 0.85-1.06). However, the study showed that all three lipid traits were associated with a lower risk of type 2 diabetes, decreasing risk by 21% (for LDL-C), 17% for HDL-C and 17% for triglycerides per 1 SD increase. These genetic data raise a number of questions for the design of studies evaluating the effects of therapeutic modulation on risk for diabetes and cardiovascular disease.