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Reducing residual cardiovascular risk: the relevance of raising high-density lipoprotein cholesterol in patients on cholesterol-lowering treatment

University of Oslo and Centre for Preventive Medicine, Ullevål University Hospital, Oslo, Norway.

Gerd Assmann

University of Munster, Germany.

Jean-Pierre Bassand

University Hospital Jean Minjoz, Besançon, France.

M John Chapman

Dyslipidaemia & Atherosclerosis Research Unit, National Institute for Health & Medical Research (INSERM), Unité 551, Hôpital de la Pitié, Paris, France.

Raimund Erbel

Department of Cardiology, West-German Heart Center, University Duisburg-Essen, Germany

Cesare Sirtori

Department of Pharmacological Sciences, University of Milan, Italy

Reducing low-density lipoprotein cholesterol (LDL-C) with statin therapy represents the cornerstone of dyslipidaemia management in patients with cardiovascular disease, as reflected in current treatment guidelines. Yet even among statin-treated patients who achieve LDL-C targets (< 2.59 mmol/L [100 mg/dL]), the residual risk of further cardiovascular events remains unacceptably high. Although clinical studies indicate that intensive LDL-C lowering may provide some additional benefit, this does not suppress the excess cardiovascular risk sufficiently. This European Expert Panel therefore recognises that there is an unmet clinical need in the management of these patients. Additional intervention to modify other clinically important risk factors should be viewed as a priority.

A reduced level of high-density lipoprotein cholesterol (HDL-C) < 1.03 mmol/L (40 mg/dL) in men and < 1.29 mmol/L (50 mg/dL) in women is an important independent predictive factor for coronary heart disease. HDL-C levels are also predictive of cardiovascular risk in statin-treated patients, irrespective of their LDL-C levels. Therefore, HDL-C represents a logical therapeutic target for reducing cardiovascular risk further in statin-treated patients, including those who achieve LDL-C targets. Given that low HDL-C is common among dyslipidaemic patients with cardiovascular disease, a therapeutic strategy aimed at effectively raising HDL-C, while at the same time lowering LDL-C to target levels, would be expected to offer clinical benefit beyond that achieved through LDL-C reduction alone. Although both nicotinic acid and fibrates raise HDL-C, nicotinic acid has greater potency. Studies show that combination therapy with prolonged-release (PR) nicotinic acid and a statin has an acceptable tolerability profile, normalises an atherogenic lipoprotein profile, and is able to induce regression of atherosclerosis and reduce coronary risk in patients with established cardiovascular disease and suboptimal HDL-C levels.

In conclusion, this European Expert Panel recommends that combination therapy with a statin and an HDL-C raising agent, such as PR nicotinic acid, should be considered in these patients, who remain at high residual risk despite achieving target LDL-C levels with statin monotherapy. Ongoing studies are essential to confirm the clinical outcome benefits of this approach.

Diabetes and Vascular Disease Research, Vol. 3, No. 2 Suppl, S1-S12 (2006)
DOI: 10.3132/dvdr.2006.011


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