as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III. Small, dense LDL, with elevated triglyceride levels and low HDL-cholesterol concentrations, constitute the 'atherogenic lipoprotein phenotype (ALP)', a form of atherogenic dyslipidemia that is a feature of type 2 diabetes and the metabolic syndrome.
14 Evidence type: meta-analysis of prospective studies
Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Prospective Studies Collaboration, Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R, Collins R. Lancet. 2007 Dec 1;370(9602):1829-39.
Of various simple indices involving HDL cholesterol, the ratio total/HDL cholesterol was the strongest predictor of IHD mortality (40% more informative than non-HDL cholesterol and more than twice as informative as total cholesterol). Total cholesterol was weakly positively related to ischaemic and total stroke mortality in early middle age (40-59 years), but this finding could be largely or wholly accounted for by the association of cholesterol with blood pressure. Moreover, a positive relation was seen only in middle age and only in those with below-average blood pressure; at older ages (70-89 years) and, particularly, for those with systolic blood pressure over about 145 mm Hg, total cholesterol was negatively related to haemorrhagic and total stroke mortality.
15 Evidence type: post-hoc analysis
Low Levels of High Density Lipoprotein Cholesterol and Increased Risk of Cardiovascular Events in Stable Ischemic Heart Disease Patients: A Post Hoc Analysis from the COURAGE Trial. Acharjee S, Boden WE, Hartigan PM, Teo KK, Maron DJ, Sedlis SP, Kostuk W, Spertus JA, Dada M, Chaitman BR, Mancini GB, Weintraub WS. J Am Coll Cardiol. 2013 Aug 8. pii: S0735-1097(13)03082-9. doi: 10.1016/j.jacc.2013.07.051. [Epub ahead of print]
OBJECTIVES: The aim of this study was to assess 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 pro