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High-density lipoprotein cholesterol raising: does it matter?

Schofield, Jonathan D.a,b; France, Michaela,b,c; Ammori, Basilb,d; Liu, Yifenb; Soran, Handreana,b,e

Current Opinion in Cardiology: July 2013 - Volume 28 - Issue 4 - p 464–474
doi: 10.1097/HCO.0b013e328362210d
LIPIDS AND HEART DISEASE: Edited by Anthony S. Wierzbicki and Dimitri P. Mikhailidis

Purpose of review Cardiovascular disease (CVD) is the leading cause of morbidity and premature mortality in Europe and the United States, and is increasingly common in developing countries. High-density lipoprotein cholesterol (HDL-C) is an independent risk factor for CVD and is superior to low-density lipoprotein cholesterol (LDL-C) as a predictor of cardiovascular events. The residual risk conferred by low HDL-C in patients with a satisfactory LDL-C was recently highlighted by the European Atherosclerosis Society. Despite the lack of randomized controlled trials, it has been suggested that raising the level of HDL-C should be considered as a therapeutic strategy in high-risk patients because of the strong epidemiological evidence, compelling biological plausibility, and both experimental and clinical research supporting its cardioprotective effects.

Recent findings Three recent large randomized clinical trials investigating the effect of HDL-C raising with niacin and dalcetrapib in statin-treated patients failed to demonstrate an improvement in cardiovascular outcomes.

Summary There is evidence to support the view that HDL functionality and the mechanism by which a therapeutic agent raises HDL-C are more important than plasma HDL-C levels. Future therapeutic agents will be required to improve this functionality rather than simply raising the cholesterol cargo.

aCardiovascular Trials Unit, Central Manchester University Hospitals

bCardiovascular Research Group, University of Manchester

cDepartment of Clinical Biochemistry, Central Manchester University Hospitals, Manchester

dDepartment of Surgery, Salford Royal NHS Foundation Trust, Salford

eUniversity Department of Medicine, Central Manchester University Hospitals, Manchester, UK

Correspondence to Handrean Soran, MSc, MD, FRCP, Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK. Tel: +44 161 276 4443; e-mail:

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins