The small, dense LDL phenotype and the risk of coronary heart disease: Epidemiology, patho-physiology and therapeutic aspects

More than decade ago, several cross-sectional studies have reported differe nces in LDL particle size, density and composition between coronary heart d isease (CHD) patients and healthy controls. Three recent prospective, neste d case-control studies have since confirmed that the presence of small, den se LDL particles was associated with more than a three-fold increase in the risk of CHD. The small, dense LDL phenotype rarely occurs as an isolated d isorder. It is most frequently accompanied by hypertriglyceridemia, reduced HDL cholesterol levels, abdominal obesity insulin resistance and by a seri es of other metabolic alterations predictive of an impaired endothelial fun ction and increased susceptibility to thrombosis. Whether or not the small, dense LDL phenotype should be considered an independent CHD risk factor re mains to be clearly established. The cluster of metabolic abnormalities associated with small, dense LDL par ticles has been referred to as the insulin resistance-dyslipidemic phenotyp e of abdominal obesity. Results from the Quebec Cardiovascular Study have i ndicated that individuals displaying three of the numerous features of insu lin resistance (elevated plasma insulin and apolipoprotein B concentrations and small, dense LDL particles) showed a remarkable increase in CHD risk. Our data suggest that the increased risk of CHD associated with having smal l, dense LDL particles may be modulated to a significant extent by the pres ence/absence of insulin resistance, abdominal obesity and increased LDL par ticle concentration. We suggest that the complex interactions among the met abolic alterations of the insulin resistance syndrome should be considered when evaluating the risk of CHD associated with the small, dense LDL phenot ype. From a therapeutic standpoint, the treatment of this condition should not only aim at reducing plasma triglyceride levels, but also at improving all features of the insulin resistance syndrome, for which body weight loss and mobilization of abdominal fat appear as key elements. Finally, interve ntions leading to reduction in fasting triglyceride levels will increase LD L particle size and contribute to reduce CHD risk, particularly if plasma a polipoprotein B concentration (as a surrogate of the number of atherogenic particles) is also reduced.