Contribution of High Plasma Triglycerides and Low High-Density Lipoprotein Cholesterol to Residual Risk of Coronary Heart Disease After Establishment of Low-Density Lipoprotein Cholesterol Control

To determine the relative contributions of triglycerides (TGs) and high-density lipoprotein (HDL) cholesterol in the residual risk of coronary heart disease (CHD) after the reduction of low-density lipoprotein (LDL) cholesterol to guideline-recommended levels, we conducted a hospital-based, case-control study with optimal matching in the strata of LDL cholesterol, gender, ethnicity, and age. The 170 cases and 175 controls were patients at Brigham and Women's Hospital (Boston, Massachusetts) from 2005 to 2008 who had an LDL cholesterol level <130 mg/dl. The cases had incident CHD, and the controls had diagnoses unrelated to CHD. The 170 cases and 175 controls had a mean LDL cholesterol level of 73 and 87 mg/dl, respectively. The association between TG and HDL cholesterol levels and CHD risk was assessed using conditional and unconditional logistic regression analysis. The models investigated accommodated the possibility of an interaction between lipid factors. The odds of CHD increased by approximately 20% per 23-mg/dl increase in TGs and decreased by approximately 40% per 7.5-mg/dl decrease in HDL cholesterol. High TGs and low HDL cholesterol interacted synergistically to increase the odds ratio to 10 for the combined greatest TG (≥190 mg/dl) and lowest HDL cholesterol quintiles (<30 mg/dl). High TG levels were more strongly associated with CHD when the HDL cholesterol was low than average or high; and low HDL cholesterol levels were more strongly associated with CHD when the TGs were high. TGs and HDL cholesterol were associated with CHD in patients with a LDL cholesterol level of ≤70 mg/dl, with a risk similar to, or greater than, those in the total group. In conclusion, high TG and low HDL cholesterol levels contribute strongly and synergistically to CHD when LDL cholesterol is well controlled. Thus, high TGs might have greater importance in patients with optimal rather than greater LDL cholesterol concentrations.