A PROSPECTIVE-STUDY OF TRIGLYCERIDE LEVEL, LOW-DENSITY-LIPOPROTEIN PARTICLE DIAMETER, AND RISK OF MYOCARDIAL-INFARCTION

Objective.-To test whether a predominance of small, dense low-density lipoprotein (LDL) particles and elevated triglyceride levels are indep endent risk factors for myocardial infarction (MI). Design.-Nested cas e-control study with prospectively collected samples. Setting.-Prospec tive cohort study. Participants.-Blood samples were collected at basel ine (85% nonfasting samples) from 14 916 men aged 40 to 84 years in th e Physicians' Health Study. Main Outcome Measurements.-Myocardial infa rction diagnosed during 7 years of follow-up. Results.-Cases (n=266) h ad a significantly smaller LDL diameter (mean [SD], 25.6 [0.9] nm) tha n did controls (n=308) matched on age and smoking (mean [SD], 25.9 [8] nm; P<.001). Cases also had higher median triglyceride levels (1.90 v s 1.49 mmol/L [168 vs 132 mg/dL]; P<.001), The LDL diameter had a high inverse correlation with triglyceride level (r=-0.71), and a high dir ect correlation with high-density lipoprotein cholesterol (HDL-C) leve l (r=0.60). We observed a significant multiplicative interaction betwe en triglyceride and total cholesterol (TC) levels (P=.01). After simul taneous adjustment for lipids and a variety of coronary risk factors, LDL particle diameter was no longer a statistically significant risk i ndicator, with a relative risk (RR) of 1.09 (95% confidence interval [ CI], 0.85-1.40) per 0.8-nm decrease. However, triglyceride level remai ned significant with an RR of 1.40 (95% CI, 1.10-1.77) per 1.13 mmol/L (100-mg/dL) increase. The association between triglyceride level and MI risk appeared linear across the distribution; men in the highest qu intile had a risk about 2.5 times that of those in the lowest quintile , The TC level, but not HDL-C level, also remained significant, with a n RR of 1.80 (95% CI, 1.44-2.26) per 1.03-mmol/L (40-mg/dL) increase, Conclusions.-These findings indicate that nonfasting triglyceride leve ls appear to be a strong and independent predictor of future risk of M I, particularly when the total cholesterol level is also elevated, In contrast, LDL particle diameter is associated with risk of MI, but not after adjustment for triglyceride level. Increased triglyceride level , small LDL particle diameter, and decreased HDL-C levels appear to re flect underlying metabolic perturbations with adverse consequences for risk of MI; elevated triglyceride levels may help identify high-risk individuals.