Triglycerides and Coronary Heart Disease Revisited (Again)

Despite the extensive literature on the relationship of lipid and lipoprotein particles to coronary heart disease (CHD) incidence, the specific association of triglycerides with incident CHD has arguably generated more disagreement than any other measure. The most parsimonious explanations for this controversy are that contradictory results abound and that positive studies typically show a modest effect size. Two published meta-analyses concurred that triglycerides were independent risk factors for CHD, even after adjustment for high-density lipoprotein (HDL) cholesterol, which is strongly and inversely correlated with triglycerides (1, 2). In the first meta-analysis, published in 1996 (1), the overall relative risk for CHD was 1.12 for men and 1.37 for women per 1 mmol/L (88.6 mg/dL) of triglycerides. The second meta-analysis, published in 2007 and updated with recent studies (2), showed a relative risk of about 1.4 comparing the top triglyceride tertile with the bottom triglyceride tertile. The relative risk increased to about 1.7 with correction for regression dilution bias (due to within-individual triglyceride variation) (2). Against this background, many studies have reported effect modification—differing relative risks for CHD in specific subgroups. The most consistent findings have been higher relative risks in women (1), those with lower total cholesterol or low-density lipoprotein (LDL) cholesterol levels (3–5), those with lower HDL cholesterol levels (3, 5), those with diabetes (6, 7), and younger persons (3, 8). The effect in younger persons is of particular interest because aging has complex effects on cardiovascular risk factor associations.

In this issue, Tirosh and colleagues (9) examine a specific subset: young men. They report the association between the first of 2 triglyceride measurements obtained 5 years apart with incident CHD in 13 953 younger (age 26 to 45 years) men (9). The results are striking: Triglycerides were strongly associated …