Background and Methods. The effect of intensive lipid-lowering therapy on coronary atherosclerosis among men at high risk for cardiovascular events was assessed by quantitative arteriography. Of 146 men no more than 62 years of age who had apolipoprotein B levels ≥125 mg per deciliter, documented coronary artery disease, and a family history of vascular disease, 120 completed the 2 1/2-year double-blind study, which included arteriography at base line and after treatment. Patients were given dietary counseling and were randomly assigned to one of three treatments: lovastatin (20 mg twice a day) and colestipol (10 g three times a day); niacin (1 g four times a day) and colestipol (10 g three times a day); or conventional therapy with placebo (or colestipol if the low-density lipoprotein [LDL] cholesterol level was elevated). Results. The levels of LDL and high-density lipoprotein (HDL) cholesterol changed only slightly in the conventional-therapy group (mean changes, −7 and +5 percent, respectivel...

https://www.nejm.org/doi/pdf/10.1056/NEJM199011083231901

Regression of Coronary Artery Disease as a Result of Intensive Lipid-Lowering Therapy in Men with High Levels of Apolipoprotein B

The association of low-density lipoprotein (LDL) subclass patterns with coronary heart disease was investigated in a case-control study of nonfatal myocardial infarction. Subclasses of LDL were analyzed by gradient gel electrophoresis of plasma samples from 109 cases and 121 controls. The LDL subclass pattern characterized by a preponderance of small, dense LDL particles was significantly associated with a threefold increased risk of myocardial infarction, independent of age, sex, and relative weight. Plasma levels of high-density lipoprotein cholesterol were decreased, and levels of triglyceride, very low—density lipoproteins, and intermediate-density lipoproteins were increased in subjects with this LDL subclass pattern. Multivariate logistic regression analyses showed that both high-density lipoprotein cholesterol and triglyceride levels contributed to the risk associated with the small, dense LDL subclass pattern. Thus, the metabolic trait responsible for this LDL subclass pattern results in a set of interrelated lipoprotein changes that lead to increased risk of coronary heart disease. (JAMA1988;260:1917-1921)

Low-Density Lipoprotein Subclass Patterns and Risk of Myocardial Infarction

Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention.

In a community-based study of 301 subjects from 61 nuclear families, two distinct phenotypes (denoted A and B) were identified by nondenaturing gradient gel electrophoretic analysis of low density lipoprotein (LDL) subclasses. Phenotype A was characterized by predominance of large, buoyant LDL particles, and phenotype B consisted of a major peak of small, dense LDL particles. Previous analysis of the family data by complex segregation analysis demonstrated that these phenotypes appear to be inherited as a single-gene trait. In the present study, the phenotypes were found to be closely associated with variations in plasma levels of other lipid, lipoprotein, and apolipoprotein measurements. Specifically, phenotype B was associated with increases in plasma levels of triglyceride and apolipoprotein B, with mass of very low and intermediate density lipoproteins, and with decreases in high density lipoprotein (HDL) cholesterol, HDL2 mass, and plasma levels of apolipoprotein A-I. Thus, the proposed genetic locus responsible for LDL subclass phenotypes also results in an atherogenic lipoprotein phenotype.

Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk.

Several epidemiological studies have reported that the regional distribution of body fat is a significant and independent risk factor for cardiovascular disease (CVD) and related mortality. Although these associations are well established, the causal mechanisms are not fully understood. Numerous studies have, however, shown that specific topographic features of adipose tissue are associated with metabolic complications that are considered as risk factors for CVD such as insulin resistance, hyperinsulinemia, glucose intolerance and type II diabetes mellitus, hypertension, and changes in the concentration of plasma lipids and lipoproteins. The present article summarizes the evidence on the metabolic correlates of body fat distribution. Potential mechanisms for the association between body fat distribution, metabolic complications, and CVD are reviewed, with an emphasis on plasma lipoprotein levels and plasma lipid transport. From the evidence available, it seems likely that subjects with visceral obesity represent the subgroup of obese individuals with the highest risk for CVD. Although body fat distribution is now considered as a more significant risk factor for CVD and related death rate than obesity per se, further research is clearly needed to identify the determinants of body fat distribution and the causal mechanisms involved in the metabolic alterations. It appears certain, however, that an altered plasma lipid transport is a significant component of the relation between body fat distribution and CVD.

Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease.

Most patients with coronary artery disease do not have elevated plasma or low density lipoprotein (LDL) cholesterol. To test whether the protein moiety of LDL, LDL B, might be a parameter to identify ischemic heart disease, the plasma cholesterol, triglyceride, LDL cholesterol, and LDL B were measured in 100 consecutive patients undergoing cardiac catheterization. On the basis of coronary angiography, these patients were divided into two groups: group I, 31 patients without, and group II, 59 patients with significant coronary artery disease. Although cholesterol, triglyceride, and LDL cholesterol levels were all significantly higher in group II, discriminant analysis indicated that LDL B concentrations most clearly separated the two groups. In group I (noncoronary), LDL B was 82 +/- 22 mg/100 ml, whereas in group II, LDL B was 118 +/- 22 mg/100 ml. The B protein level in group I was similar to other normal groups studied (35 asymptomatic male physicians, 83 +/- 11 mg/100 ml; 90 normolipidemic medical students, 72 +/- 17 mg/100 ml). The results therefore indicate that not only does LDL B better separate coronary and noncoronary groups than other lipid parameters studied, but also, among those with coronary artery disease, there exists a group with normal LDL cholesterol but with levels of LDL B protein similar to those observed in type II hyperlipoproteinemia. The explanation for the altered LDL composition observed in this group remains to be elucidated.

https://www.pnas.org/content/pnas/77/1/604.full.pdf

Association of coronary atherosclerosis with hyperapobetalipoproteinemia [increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins].

Bernard Skinner

Papers

Association of coronary atherosclerosis with hyperapobetalipoproteinemia [increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins].