High density lipoproteins and coronary atherosclerosis. A strong inverse relation with the largest particles is confined to normotriglyceridemic patients.

Abstract

The relations of high density lipoprotein (HDL) subclasses to severity and rate of progression of coronary atherosclerosis were investigated in 60 men who had survived a myocardial infarction before the age of 45 years and who had subsequently undergone two coronary angjographies, with an intervening time interval of 4-7 years between angiographies. Five HDL subclasses with different particle sizes were determined by gradient gel electrophoresis, and the major serum lipoprotein classes were separated by preparative ultracentrifugation in connection with the second angiography. Highly significant inverse correlations were found between the plasma levels of the largest HDL particles, the HDLa, subclass, and both disease severity as observed on the second coronary angiogram (r=-0.53, p<0.001) and progression of coronary lesions between angiographies (r=-038, /?<0.01). Grouping the patients according to the presence or absence of very low density lipoprotein (VLDL) triglyceride elevation revealed striking differences in the relations of HDL subspecies to coronary atherosclerosis between normotriglyceridemic and hvpertriglyceridemic subjects. There were strong inverse correlations between the plasma HDL^ concentration and both severity of lesions (r=-0.72,p<0.001) and rate of lesion progression (r=-0.58, p<0.01) in the normotriglyceridemic patients, whereas this relation was absent in subjects with hypertriglyceridemia. Although it was retrospective in design, affected by an inherent selection bias due to unavoidable dropouts and exclusions, and limited to young, male, postinfarction patients, the study suggests that the inverse relation between HDL level and coronary heart disease or coronary atherosclerosis seen in previous epidemiological and angiographlc studies is accounted for by the largest HDL particles, the HDLy, subclass. Furthermore, the hvpertriglyceridemic state appears to markedly influence the relations between plasma concentrations of HDL subclasses and coronary atherosclerosis. Prospective studies of unselected patients are needed to corroborate these findings. (Arteriosclerosis and Thrombosis 1991;11:174-182) M ost prospective epidemiological studies have shown an independent inverse relation between high density lipoprotein (HDL) cholesterol concentration and risk of development of coronary heart disease (CHD).

Antioxidant Supplements Block the Response of HDL to Simvastatin-Niacin Therapy in Patients With Coronary Artery Disease and Low HDL

“…A low level of Lp(A-I) with or without a concomitant reduction of Lp(A-I, A-II), 29,31,32 an increased presence of small HDL, and a reduced level of large HDL have been associated with CAD and the severity and progression of arteriosclerotic lesions. 26,33 Treatment with S-N resulted in reductions of 25% to 57% of apo B and of plasma, VLDL, and LDL lipid and 13% to 42% increases in HDL-C, HDL 2 -C, HDL 3 -C, and apo A-I ( Table 2). The LDL-C to HDL-C ratio improved from Ͼ4 at baseline to Ͻ2 after 12 months of therapy.…”

Dyslipoproteinemic changes in borderline hypertension.

“…911 Furthermore, it has been shown that this inverse relationship between HDL cholesterol and CHD is mainly due to the HDL subclass HDL 2 , 1213 while the HDL gradient gel electrophoresis (GGE) subclass HDL3 b correlates positively with the progression of coronary atherosclerosis. 14 The factors that regulate the concentrations of the different HDL subclasses are not fully elucidated, but LPL and hepatic lipase (HL) appear to be involved in a reciprocal manner.…”

Influence of plasma cholesteryl ester transfer activity on the LDL and HDL distribution profiles in normolipidemic subjects.

“…Some recent studies have demonstrated that both the severity and progression of coronary artery disease are related to the plasma concentration of individual HDL subclasses. 34 - 35 Thus, the heterogeneity of HDL could have important implications, and it appears to be of great interest to study the factors that can affect the HDL distribution in human plasma. CETP could be a key factor in determining the size distribution of plasma HDL in vivo.…”

“…The significant negative correlation between the relative abundance of HDLa, and LCAT activity is of great interest because, in normotriglyceridemic subjects, strong inverse correlations were found between the plasma levels of H D L a and both the severity and the rate of progression of coronary lesions. 34 However, the mechanism of formation of H D L a is unclear, and by now it seems hazardous to try to connect these observations with previous in vitro studies. In fact, it is possible that the level of HDLa, particles is dependent on other factors that can potentially affect the distribution of HDL.…”