title: 'Trig-onometry': non-high-density lipoprotein cholesterol as a therapeutic target in dyslipidaemia.
abstract: Targeting elevations in low-density lipoprotein cholesterol (LDL-C) remains the cornerstone of cardiovascular prevention. However, this fraction does not adequately capture elevated triglyceride-rich lipoproteins (TRLs; e.g. intermediate-density lipoprotein, very low density lipoprotein) in certain patients with metabolic syndrome or diabetic dyslipidaemia. Many such individuals have residual cardiovascular risk that might be lipid/lipoprotein related despite therapy with first-line agents (statins). Epidemiological evidence encompassing > 100,000 persons supports the contention that non-high-density lipoprotein cholesterol (non-HDL-C) is a superior risk factor vs. LDL-C for incident coronary heart disease (CHD) in certain patient populations. In studies with clinical end-points evaluated in the current article, a 1:1 to 1:3 relationship was observed between reductions in non-HDL-C and in the relative risk of CHD after long-term treatment with statins, niacin (nicotinic acid) and fibric-acid derivatives (fibrates); this relationship increased to 1:5 to 1:10 in smaller subgroups of patients with elevated triglycerides and low HDL-C levels. Treatment with statin-, niacin-, fibrate-, ezetimibe-, and omega 3 fatty acid-containing regimens reduced non-HDL-C by approximately 9-65%. In a range of clinical trials, long-term treatment with these agents also significantly decreased the incidence of clinical/angiographic/imaging efficacy outcome variables. For patients with dyslipidaemia, consensus guidelines have established non-HDL-C treatment targets 30 mg/dl higher than LDL-C goals. Ongoing prospective randomised controlled trials should help to resolve controversies concerning (i) the clinical utility of targeting non-HDL-C in patients with dyslipidaemia; (ii) the most efficacious and well-tolerated therapies to reduce non-HDL-C (e.g. combination regimens); and (iii) associations between such reductions and clinical, angiographic, and/or imaging end-points.
authors.affiliation: Office of Health Promotion and Disease Prevention, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30303, USA. tjaco02@emory.edu
authors.forename: T A
authors.initials: TA
authors.lastname: Jacobson
mesh_terms: D000328:Adult; D001384:Azetidines / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000037:antagonists & inhibitors*; D050171:Dyslipidemias / Q000188:drug therapy*; D000069438:Ezetimibe; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D005260:Female; D058607:Fibric Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D012307:Risk Factors; D055815:Young Adult
chemical_list: D001384:Azetidines; D008076:Cholesterol, HDL; D015525:Fatty Acids, Omega-3; D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D009525:Niacin; D000069438:Ezetimibe