Beyond low-density lipoprotein cholesterol: respective contributions of non-high-density lipoprotein cholesterol levels, triglycerides, and the total cholesterol/high-density lipoprotein cholesterol ratio to coronary heart disease risk in apparently healthy men and women

Abstract

Objectives: This study was designed to test the hypothesis that at any low-density lipoprotein cholesterol (LDL-C) level, other lipid parameters such as non-high-density lipoprotein cholesterol (HDL-C) levels, triglyceride (TG) levels, and the total cholesterol (TC)/HDL-C are still associated with an increased coronary heart disease (CHD) risk.

Background: Although LDL-C is considered to be the primary target of lipid-lowering therapy, other parameters of the lipoprotein-lipid profile may more closely associated with CHD risk.

Methods: In the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Norfolk prospective population study, 21,448 participants without diabetes or CHD between age 45 and 79 years were followed for 11.0 years. A total of 2,086 participants developed CHD during follow-up.

Results: Among individuals with low LDL-C levels (<100 mg/dl), after adjustment for age, sex, smoking, systolic blood pressure, waist circumference, physical activity, and hormone replacement therapy (in women), those with non-HDL-C >130 mg/dl had a hazard ratio (HR) for future CHD of 1.84 (95% confidence interval [CI]: 1.12 to 3.04) when compared with those with non-HDL-C levels <130 mg/dl. In a similar model, individuals with TG levels >150 mg/dl had an HR of 1.63 (95% CI: 1.02 to 2.59) when compared with those with TG levels <150 mg/dl, and individuals with a TC/HDL-C ratio >5 had an HR of 2.19 (95% CI: 1.22 to 3.93) when compared with those with a TC/HDL-C ratio <5.

Conclusions: In this prospective study, independently of their plasma LDL-C levels, participants with high non-HDL-C levels, high TG levels, or with an elevated TC/HDL-C ratio were at increased CHD risk. CHD risk assessment algorithms as well as lipid targets of lipid-lowering trials may also need to consider other easily available parameters such as non-HDL-C.