Diet, nutrition, and heart disease

Everyone should know his or her cholesterol level. The means are now available for lowering cholesterol in the general population. Such efforts should be coupled with identification of moderate- and high-risk individuals for whom special efforts should be made in cholesterol lowering. The dietary approach outlined by the American Heart Association, which is clearly described in The Living Heart Diet (6), provides the best overall strategy for reducing cholesterol and for battling the epidemic of cardiovascular deaths that represents the No. 1 health problem in our society.     

Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -     

Effect of triglyceride levels on methyl and methylene envelope line widths in proton nuclear magnetic resonance spectroscopy of human plasma

Recent studies have described a relation between the line widths of the methyl and methylene resonance envelopes in the proton nuclear magnetic resonance spectrum of human plasma and the occurrence of cancer. An average line width of less than 33 Hz has been reported to correlate with the presence of cancer, whereas greater line widths have not. In 26 normal volunteers, we found a significant inverse correlation between fasting triglyceride level and plasma spectral line width. We also observed that dietary lipids have measurable effects on spectral line widths. In another sample of seven normal persons (three of whom had elevated plasma triglyceride levels), the line widths of whole plasma varied widely (mean, 35.6 +/- 8.8 Hz); however, the mean line widths of the lipoprotein fractions isolated from those samples differed greatly, but the variance within each fraction was small (very-low-density lipoprotein, 22.0 +/- 1.9 Hz; low-density lipoprotein, 35.0 +/- 2.8; high-density lipoprotein, 28.8 +/- 1.9). The results of this study indicate that the plasma triglyceride level has a profound effect on the average spectral line width of plasma. This effect can be explained by the relative amounts of lipoprotein fractions in whole plasma. Plasma triglyceride concentrations of more than 1.24 mmol per liter (greater than 110 mg per deciliter), whatever the source, produce average plasma methyl and methylene line widths of less than 33 Hz.     

Plasma lipid and lipoprotein response of humans to beef fat, coconut oil and safflower oil

This study's purpose was to evaluate the fasting human plasma lipid and lipoprotein responses to dietary beef fat (BF) by comparison with coconut oil (CO) and safflower oil (SO), fats customarily classified as saturated and polyunsaturated. Nineteen free-living normolipidemic men aged 25.6 +/- 3.5 yr consumed centrally-prepared lunches and dinners of common foods having 35% fat calories, 60% of which was the test fat. The test fats were isocalorically substituted, and each fed for five weeks in random sequences with intervening five weeks of habitual diets. Plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) concentrations among individuals follows the same relative rank regardless of diet. Triglycerides (TG) concentrations among individuals also maintain their relative rank regardless of diet but in a different order from that of the cholesterols. Plasma TC, HDL-C, and LDL-C responses to BF were significantly lower and TG higher than to CO. As compared to SO, BF produced equivalent levels of TG, HDL-C, and LDL-C and marginally higher TC. Thus, the customary consideration of BF as "saturated" and grouping it with CO appears unwarranted.     

Results of Lipid-Lowering Trials in the Elderly and a Look to the Future

A lack of clinical research in the elderly hampers the creation of specific therapeutic regimens to treat dyslipidemia in this group. However, extrapolation of data from studies in middle-aged men may be appropriate since the mechanisms of atherogenesis do not appear to change significantly with advancing age. The results of the secondary prevention Scandinavian Simvastatin Survival Study (in which 52% of the patient population was 60 years of age or older) and the primary prevention West of Scotland Coronary Prevention Study (in which the mean age of the patient population was older than those of other primary prevention trials) suggest the benefit of lipid-lowering in older populations. More clinical trials that include elderly subjects are needed to evaluate fully the efficacy of lipid-regulating therapy in older patients.     

Interactions between angiotensin-I converting enzyme insertion/deletion polymorphism and response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin: the lipoprotein and coronary atherosclerosis study

OBJECTIVES: Our objectives were to determine whether angiotensin-1 converting enzyme (ACE) insertion/deletion (I/D) polymorphism was associated with the severity of coronary artery disease (CAD) and its progression/regression in response to fluvastatin therapy in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) population. BACKGROUND: Genetic factors are involved in susceptibility to CAD. Angiotensin-1 converting enzyme I/D polymorphism, which accounts for half of the variance of plasma and tissue levels of ACE, has been implicated in susceptibility to CAD and myocardial infarction (MI). METHODS: Angiotensin-1 converting enzyme genotypes were determined by polymerase chain reaction (PCR). Fasting plasma lipids were measured and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo. RESULTS: Ninety-one subjects had DD, 198 ID and 75 II genotypes. The mean blood pressure, minimum lumen diameter (MLD), number of coronary lesions and total occlusions were not significantly different at baseline or follow-up among the genotypes. There was a significant genotype-by-treatment interaction for total cholesterol (p = 0.018), low-density lipoprotein cholesterol (LDL-C) (p = 0.005) and apolipoprotein (apo) B (p = 0.045). In response to fluvastatin therapy, subjects with DD, compared with those with ID and II genotypes, had a greater reduction in total cholesterol (19% vs. 15% vs. 13%), LDL-C (31% vs. 25% vs. 21%) and apo B (23% vs. 15% vs. 12%). Definite progression was less (14%) and regression was more common (24%) in DD as compared with those with ID (32% and 17%) and II (33% and 3%) genotypes (p = 0.023). Changes in the mean MLD and lesion-specific MLD also followed the same trend. CONCLUSIONS: Angiotensin-1 converting enzyme I/D polymorphism is associated with the response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin. Subjects with DD genotype had a greater reduction in LDL-C, a higher rate of regression and a lower rate of progression of CAD.