Gerd Assmann

Dose-Response Relationships of Serum Lipid Measurements With the Extent of Coronary Stenosis Strong, Independent, and Comprehensive

Abstract Serum lipids, lipoproteins, and more recently apolipoproteins and lipoprotein(a) [Lp(a)] have been shown to be independent risk factors for coronary vessel disease and its prognosis. However, the relationships between serum lipid levels and the extent of coronary artery disease (CAD) have not been consistently shown. Twenty-five hundred male and female patients with suspected angina pectoris were recruited from 18 European medical centers. The independent relations of total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apo A-I and B, and Lp(a) with the presence and extent of CAD, as assessed by coronary angiography, were investigated. All of the lipid measures showed strong relations ( P <.0001) with the presence of CAD, defined by the existence of at least one ≥50% coronary vessel stenosis. Total cholesterol, LDL cholesterol, apo B, triglycerides, and Lp(a) were substantially higher and HDL cholesterol and apo A-I lower in patients with CAD. The odds ratio of CAD, in the high-risk tertile of each lipid’s distribution compared with the low-risk tertile, was in the range 1.5 to 2.3. Each of total cholesterol (or LDL cholesterol or apo B), HDL cholesterol (or apo A), and Lp(a) had an independent effect in predicting the presence of CAD. In addition, all lipids showed a strong association ( P =.0006 for triglycerides, P <.0001 otherwise) with the extent of CAD as defined by the number of stenosed coronary vessels. These relations, which conform to a “dose-response” effect, remained after adjusting for other coronary risk factors. This study provides direct evidence of the role of serum lipid levels in determining not only the presence but also the extent of atherosclerotic disease in coronary arteries.

HDL and Reverse Transport of Cholesterol: Insights from Mutants

Several epidemiological and clinical studies revealed an inverse correlation between low plasma concentrations of high density lipoprotein (HDL) cholesterol as well as its major protein component apolipoprotein A–I (apo A–I) and the risk of myocardial infarction (reviewed in 1). Family and twin studies suggested partial heredity of low HDL-cholesterol levels and have put the influence of genes at 35 to 50% (2,3). Frequently, familial HDL cholesterol- deficiency was paralleled with a family history of premature coronary heart disease (CHD) (4,5).

Relationship of HDL Cholesterol to Incidence of Atherosclerotic Coronary Heart Disease: The Procam Experience

The incidence of atherosclerotic coronary heart disease (CHD) was assessed in 4559 male partecipants of the Prospective Cardiovascular Munster (PROCAM) study, aged 40 to 64 years, over — 6 year follow-up period. In this time, 186 study partecipants developed atherosclerotic CHD (134 definite nonfatal myocardial infarctions and 52 definite atherosclerotic CHD deaths including 21 sudden cardiac deaths and 31 fatal myocardial infarctions). Univariate analysis revealed — significant association between the incidence of atherosclerotic CHD, and high density lipoprotein (HDL) cholesterol (p<0.001), which remained after adjustment for other risk factors.

Molecular Genetics Approach to Polygenic Disease—Initial Results from Atherosclerosis Research

Progress in the development of molecular genetics techniques has led in recent years to the identification of a variety of basic defects in genetic disease. This success in understanding inborn errors of metabolism, however, has been largely restricted to monogenic disease or to defects that involve large aberrations in the DNA primary structure. A much more complicated situation is present in common disease where important roles for disease expression have been attributed to endogenous as well as exogenous factors (1).