E-Mail karger@karger.com Turning Basic Research into Clinical Success Cardiology 2013;124:116–125 DOI: 10.1159/000346463 High-Density Lipoprotein Subfractions – What the Clinicians Need to Know Angela Pirillo   a, b Giuseppe Danilo Norata   c, d Alberico Luigi Catapano   b, c   a  Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, b  IRCCS Multimedica, and c  Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; d  The Blizard Institute, Centre for Diabetes, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, UK Background The inverse relationship between plasma levels of high-density lipoprotein (HDL) and cardiovascular dis- ease has been extensively described [1, 2]. However, sev- eral lines of evidence have indicated that HDL functional- ity can be impaired under pathological conditions [3, 4], suggesting that the assessment of HDL function might be more relevant than that of HDL-cholesterol (HDL-C) plasma levels. HDLs are a class of structurally and functionally het- erogeneous particles [5]. In atherosclerosis-related dis- eases, variations in HDL subfraction levels and functions are frequently observed, suggesting that large HDL par- ticles are inversely associated while small HDL particles are positively associated with cardiovascular disease [5]. These considerations, supported by several studies, in- dicate that beside the measurement of standard lipids, in- cluding HDL-C levels, the measurement of specific HDL subfractions might help to better evaluate the risk of car- diovascular events. HDL Classification, Metabolism and Functions HDLs are a class of heterogeneous lipoproteins [5]; their heterogeneity is attributable to a different content of apolipoproteins, lipids and enzymes and to the remod- elling of HDL particles by lipolytic enzymes, lipid trans- Key Words High-density lipoprotein · High-density lipoprotein function · High-density lipoprotein subpopulations · Coronary heart disease Abstract Although the inverse relationship between plasma levels of high-density lipoprotein (HDL) and cardiovascular disease has been largely demonstrated, many observations have suggested that the assessment of HDL functionality might be more informative than a simple measurement of HDL- cholesterol plasma levels. HDLs are a class of structurally and functionally heterogeneous particles; in atherosclerosis-re- lated diseases, changes in HDL subfraction levels and func- tions are frequently observed. Circulating levels of large HDL particles are decreased in dyslipidaemic conditions, while levels of small dense HDL particles are increased in patients with coronary heart disease. Furthermore, specific genetic defects in proteins involved in HDL metabolism significantly impact the distribution of HDL subpopulations. Finally, many drugs used for dyslipidaemia induce changes in HDL sub- fractions strictly related to cardiovascular disease. Although several methods exist to evaluate HDL subclass levels, most of them are not easily applicable in clinical practice, due to the costs and high variability. However, the possibility to measure the levels of specific HDL subfractions in patients with atherosclerosis-related diseases might help to better define their cardiovascular risk. Copyright © 2013 S. Karger AG, Basel Received: September 25, 2012 Accepted after revision: December 6, 2012 Published online: February 20, 2013 Prof. Alberico L. Catapano Department of Pharmacological Sciences, University of Milan Via Balzaretti, 9 IT–20133 Milan (Italy) E-Mail alberico.catapano  @  unimi.it © 2013 S. Karger AG, Basel 0008–6312/13/1242–0116$38.00/0 www.karger.com/crd Downloaded by: 198.143.37.97 - 3/27/2016 5:30:27 PM