Elevated Remnant-Like Particle Cholesterol Concentration

Abstract

Patients at increased risk of coronary artery disease (CAD) frequently exhibit an atherogenic lipoprotein phenotype characterized by elevated plasma levels of both triglyceride-rich lipoproteins (TRL) and small, dense LDL and low concentrations of HDL cholesterol. Recently, in a large observational study, the calculated non-HDL plasma cholesterol concentration (the sum of the cholesterol contents of LDL, intermediate-density lipoprotein [IDL], and very-low-density lipoprotein [VLDL]) was a stronger predictor of cardiovascular events than plasma cholesterol alone.1–3 Improvement in the predictability of CAD on inclusion of VLDL and IDL cholesterol emphasizes the proatherogenic nature of TRL and their remnant particles. The atherogenic lipoprotein phenotype has been defined by Austin et al4 as the presence of a predominance of small, dense LDL particles, elevated plasma triglyceride (TG) levels, and low plasma HDL cholesterol levels in the lipoprotein profile, which is associated with an approximately 3-fold increased risk of atherosclerotic disease.5–8 It is now commonly accepted that small, dense LDL particles are the products of the intravascular remodeling of TG-rich VLDL particles after interaction primarily with lipoprotein lipase, hepatic lipase, and cholesterol ester transfer protein9,10 (Figure). The atherogenic lipoprotein phenotype is strongly linked to obesity, insulin resistance, familial combined hyperlipidemia (FCHL), hypertension, and abnormalities in postprandial lipid metabolism.7,11,12 Epidemiological data from the Framingham study have already revealed that plasma TG concentration is an important independent risk indicator of CAD in women13; additional evidence supporting this observation was obtained by Yarnell et al14 in a 10-year follow-up study and confirmed by others.15,16 In the PROCAM (Prospective Cardiovascular Munster) study,17 this relationship was dependent on plasma HDL cholesterol concentration. Criqui et al,18 however, could not demonstrate an independent relationship between plasma TG and cardiovascular mortality in a North American population participating in the Lipid Research Clinics Follow-up. …