Remnant Lipoprotein Levels in Fasting Serum Predict Coronary Events in Patients With Coronary Artery Disease

Abstract

Background-Remnant lipoproteins are atherogenic, but assays of remnants have not been available in routine clinical laboratories because of the lack of practical and validated methods. A simple and reliable method for such an assay, using an immunochemical approach, has recently been developed. This study prospectively examined whether remnant lipoprotein levels in fasting serum, measured by our method, may have prognostic value in patients with coronary artery disease (CAD). Methods and Results-Remnant lipoprotein levels in fasting serum were measured in 135 patients with CAD by an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. Patients were followed up for Յ36 months until occurrence of 1 of the following clinical coronary events: recurrent or refractory angina pectoris requiring coronary revascularization, nonfatal myocardial infarction, or cardiac death. Kaplan-Meier analysis demonstrated a significantly higher probability of developing coronary events in patients with the highest tertile of remnant levels (Ͼ5.1 mg cholesterol/dL; 75th percentile of distribution of remnant levels) than in those with the lowest tertile of remnant levels (Յ3.3 mg cholesterol/dL; 50th percentile of the distribution). Higher levels of remnants were a significant and independent predictor of developing coronary events in multivariate Cox hazard analysis including the following covariates: extent of coronary artery stenosis, age, sex, smoking, hypertension, diabetes mellitus, hypercholesterolemia, low HDL cholesterol, and hypertriglyceridemia. Conclusions-Higher levels of remnant lipoproteins in fasting serum predict future coronary events in patients with CAD independently of other risk factors. Thus, measurement of fasting remnant levels, assessed by the current immunoseparation method, may be helpful in assessment of CAD risk. (Circulation. 1999;99:2858-2860.)

Predictive Value of Remnant-like Particle Cholesterol as an Indicator of Coronary Artery Stenosis in Patients with Normal Serum Triglyceride Levels.

“…Associations of RLP-Clevels with coronary events have recently been reported (24,25). Wehave previously reported that RLP-C levels are markedly high in patients who have established coronary artery stenosis (26).…”

Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Offspring Cohort Studies

“…Notably, there are strikingly different RLP‐C levels across studies 10, 27, 28, 43. These differences strongly suggest that the methods used (ie, immunoseparation, ultracentrifugation) have significantly different profiles or sensitivities for separating and measuring remnant lipoproteins.…”

“…In a prospective study of 135 patients with coronary artery disease who presented to a hospital in Japan and were followed for up to 3 years, higher RLP‐C levels were an independent predictor of recurrent coronary events 27. A prospective analysis of >1100 older Japanese American men from the Honolulu Heart Study found that RLP levels were independently predictive of incident CHD during 17 years 11.…”

The Renin-Angiotensin System Is Involved in the Production of Plasminogen Activator Inhibitor Type 1 by Cultured Endothelial Cells in Response to Chylomicron Remnants

“…These remnants are formed after hydrolysis of triglycerides by lipoprotein lipase from intestine-derived chylomicrons, and they are rapidly removed from the circulation. Delayed clearance of these triglyceride-rich lipoprotein particles induced by genetic or metabolic abnormalities is often associated with accelerated atherosclerosis (18,20,21). However, no evidence has yet been found for a connection between chylomicron remnants and PAI-1 production.…”