 the independent effect of high-density lipoprotein cholesterol (HDL-C) level on cardiovascular risk in patients with stable ischemic heart disease (SIHD) while on optimal medical therapy (OMT).
BACKGROUND: While low HDL-C level is a powerful and independent predictor of cardiovascular risk, recent data suggest that this may not apply when low-density lipoprotein cholesterol (LDL-C) is reduced to optimal levels using intensive statin therapy.
METHODS: We performed a post hoc analysis in 2,193 men and women with stable ischemic heart disease (SIHD) from the COURAGE trial. The primary outcome measure was the composite of death from any cause or nonfatal myocardial infarction (MI). The independent association between HDL-C levels measured after 6 months on optimal medical therapy (OMT) and the rate of cardiovascular events after 4 years was assessed. Similar analyses were performed separately in subjects with LDL-C levels below 70 mg/dL (1.8 mmol/L).
RESULTS: In the overall population, the rate of death/MI was 33% lower in the highest HDL-C quartile as compared with the lowest quartile, with quartile of HDL-C being a significant, independent predictor of death/MI (P = 0.05), but with no interaction for LDL-C category (P=0.40). Among subjects with LDL-C levels < 70 mg/dL, those in the highest quintile of HDL-C had a 65% relative risk reduction in death or MI as compared to the lowest quintile, with HDL-C quintile demonstrating a significant, inverse predictive effect (P=0.02).
CONCLUSIONS: In this post hoc analysis, patients with SIHD continued to experience incremental cardiovascular risk associated with low HDL-C levels despite OMT during long-term follow-up. This relationship persisted and appeared more prominent even when LDL-C was reduced to optimal levels with intensive dyslipidemic therapy.
16 Evidence type: meta-analysis of prospective studies
Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. Hokanson JE, Austin MA. J Cardiovasc Risk. 1996 Apr;3(2):213-9.
Seventeen studies were selected for the analysis based on published reports of population-based, prospective studies, including 46413 men and 10864 women. To insure comparability, only studies reporting the association between fasting triglyceride levels and incident cardiovascular endpoints were included. Using standard meta-analysis calculations, relative risks (RR) and 95% confidence intervals (CI) were calculated and standardized with respect to a 1 mmol/l increase in triglyceride. Multivariable-adjusted RRs were determined for the six studies in men and two studies in women that reported adjustments for HDL cholesterol.http://www.ncbi.nlm.nih.gov/pubmed/8782637
RESULTS: For men and women, the univariate RRs for triglyceride were 1.32 (95% Cl 1.26-1.39) and 1.76 (95% Cl 1.50-2.07), respectively, indicating an approximately 30% increased risk in men and a 75% increase in women. Adjustment of HDL cholesterol and other risk factors attenuated these RRs to 1.14 (95% Cl 1.05-1.28) and 1.37 (95% Cl 1.13-1.66), respectively, which were still statistically significant values.
CONCLUSION: Based on combined data from prospective studies, triglyceride is a risk factor for cardiovascular disease for both men and women in the general population, independent of HDL cholesterol. These finding demonstrate the necessity for clinical trials to evaluate whether lowering plasma triglyceride decreases the risk of cardiovascular disease.
17 Evidence type: prospective cohort study
A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. Stampfer MJ, Krauss RM, Ma J, Blanche PJ, Holl LG, Sacks FM, Hennekens CH. JAMA. 1996 Sep 18;276(11):882-8.
RESULTS: Cases (n=266) had a significantly smaller LDL diameter (mean [SD], 25.6 [0.9] nm) than did controls (n=308) matched on age and smoking (mean [SD], 25.9  nm; P<.001). Cases also had higher median triglyceride levels (1.90 vs 1.49 mmol/L [168 