Abstract
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 (> or =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 < or =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.
Highlights
Similar reasoning can be applied to high-density lipoprotein (HDL) cholesterol as a risk factor in statin-treated patients
The strengths of the presented analyses include the use of population data obtained during the previous 3 years; the use of optimal matching to create strata that were homogenous with respect to gender and race and reasonably homogenous with respect to age and low-density lipoprotein (LDL) cholesterol levels; and the use of straightforward statistical analyses to identify trends and interactions among key biomarkers of cardiovascular disease risk
The limitations of the present study included the nature of the population analyzed, which was derived from the catchment area of a specific tertiary care center; the retrospective nature of the study, in which lipid measures could not be obtained at specified calendar intervals before the index event; the lack of availability of uniform information on potential confounders of lipid-coronary heart disease (CHD) risk associations, given the basis of the study using an electronic records database; and the possibility that the hospital-based control series included those with some morbidity related to CHD
Summary
Similar reasoning can be applied to high-density lipoprotein (HDL) cholesterol as a risk factor in statin-treated patients. Low HDL cholesterol is associated with increased event rates in statin-treated patients,[2] and the risk of low HDL cholesterol levels increases at lower LDL cholesterol levels.[4,5] We hypothesized first that high TG and low HDL cholesterol levels are each associated with CHD events in those with LDL cholesterol at the goals recommended by the National Cholesterol Education Program Adult Treatment Panel III, and, second, that these 2 associations remain strong as the LDL cholesterol level decreases. We interrogated an automated patient data registry at a major United States hospital to perform a matched case-control analysis of the relation between the TG levels and cardiovascular disease risk among subjects with LDL cholesterol levels
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