Placebo Adherence and Its Association with Morbidity and Mortality in the Studies of Left Ventricular Dysfunction

A provocative finding from several double-blind clinical trials has been the association between greater adherence to placebo study medication and better health outcomes. We used data from the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial (SOLVD-TT) and the SOLVD Prevention Trial (SOLVD-PT) to examine whether such associations could be validated and to examine several sources of bias and potential confounding. Survival analytic methods were used to estimate the association between placebo adherence and several health outcomes, employing a number of modeling techniques to test for the existence of alternative explanations for the association. Higher adherence was defined as having taken ≥75% of prescribed study medication. Higher placebo adherence was associated with improved overall survival in both SOLVD-TT and SOLVD-PT [hazard ratio (HR) = 0.52, 95% confidence interval (CI): 0.35 to 0.79 and HR = 0.52, 95%CI: 0.38 to 0.71, respectively]. Associations were similar for fatal or non-fatal cardiovascular or coronary heart disease events. Adjustment for both modifiable and non-modifiable cardiac risk factors (including age, gender, diabetes, blood pressure, smoking, weight, alcohol use, and levels of education) had minimal effect on the strength of the association. Little evidence of bias was found as an explanation for this relationship. In these two trials, better adherence to placebo was associated with markedly superior health outcomes, including total in-study mortality and incident cardiovascular events. No important confounders were identified. These data suggest there may exist strong but unrecognized determinants of health outcomes for which placebo adherence is a marker

Colesevelam lowers glucose and lipid levels in type 2 diabetes: the clinical evidence

Simultaneous control of blood glucose and other risk factors such as hypertension and dyslipidaemia is essential for reducing the risk of complications associated with type 2 diabetes mellitus (T2DM). As relatively few patients with T2DM have their risk factors managed to within the limits recommended by the American Diabetes Association, American College of Endocrinology or National Cholesterol Education Program Adult Treatment Panel III guidelines, treatment that can simultaneously control more than one risk factor is of therapeutic benefit. Clinical studies have shown that bile acid sequestrants have glucose-lowering effects in addition to their low-density lipoprotein cholesterol-lowering effects in patients with T2DM. The bile acid sequestrant colesevelam hydrochloride is approved as an adjunct to antidiabetes therapy for improving glycaemic control in adults with T2DM. This review examines data from three phase III clinical trials that evaluated the glucose- and lipid-lowering effects of colesevelam when added to the existing antidiabetes treatment regimen of patients with T2DM

Univariate and bivariate analyses of cholesterol and triglyceride levels in pedigrees

A multivariate normal model for pedigree analysis is applied to fasting total serum cholesterol and total serum triglyceride measurements on 771 individuals in 95 pedigrees from Rochester, MN. Univariate and bivariate analyses are carried out to determine to what extent the aggregation and coaggregation in families of these two traits may be attributed to shared genetic and environmental factors. Pedigrees were ascertained through a sample of schoolchildren enriched for those with serum cholesterol levels in the highest and lowest deciles of their age- and sex-specific distributions. Ascertainment is corrected for by conditioning the likelihood on the trait values of the probands. Univariate results confirm the findings of previous studies indicating that familial aggregation of serum cholesterol and triglyceride levels is due both to shared genes and to shared environmental factors. Results of the bivariate analyses suggest that the coaggregation of cholesterol and triglyceride levels in these families is strongly influenced by both shared genes (pleiotropy) and shared environmental factors. These findings are consistent with our understanding of lipid metabolism and of specific environmental factors known to influence both traits.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38240/1/1320230306_ftp.pd

Food Use and Health Effects of Soybean and Sunflower Oils

This review provides a scientific assessment of current knowledge of health effects of soybean oil (SBO) and sunflower oil (SFO). SBO and SFO both contain high levels of polyunsaturated fatty acids (PUFA) (60.8 and 69%, respectively), with a PUFA:saturated fat ratio of 4.0 for SBO and 6.4 for SFO. SFO contains 69% C18:2n-6 and less than 0.1% C18:3n-3, while SBO contains 54% C18:2n-6 and 7.2% C18:3n-3. Thus, SFO and SBO each provide adequate amounts of C18:2n-6, but of the two, SBO provides C18:3n-3 with a C18:2n-6:C18:3n-3 ratio of 7.1. Epidemiological evidence has suggested an inverse relationship between the consumption of diets high in vegetable fat and blood pressure, although clinical findings have been inconclusive. Recent dietary guidelines suggest the desirability of decreasing consumption of total and saturated fat and cholesterol, an objective that can be achieved by substituting such oils as SFO and SBO for animal fats. Such changes have consistently resulted in decreased total and low-density-lipoprotein cholesterol, which is thought to be favorable with respect to decreasing risk of cardiovascular disease. Also, decreases in high-density-lipoprotein cholesterol have raised some concern. Use of vegetable oils such as SFO and SBO increases C18:2n-6, decreases C20:4n-6, and slightly elevated C20:5n-3 and C22:6n-3 in platelets, changes that slightly inhibit platelet generation of thromboxane and ex vivo aggregation. Whether chronic use of these oils will effectively block thrombosis at sites of vascular injury, inhibit pathologic platelet vascular interactions associated with atherosclerosis, or reduce the incidence of acute vascular occlusion in the coronary or cerebral circulation is uncertain. Linoleic acid is needed for normal immune response, and essential fatty acid (EFA) deficiency impairs B and T cell-mediated responses. SBO and SFO can provide adequate linoleic acid for maintenance of the immune response. Excess linoleic acid has supported tumor growth in animals, an effect not verified by data from diverse human studies of risk, incidence, or progression of cancers of the breast and colon. Areas yet to be investigated include the differential effects of n-6- and n-3-containing oil on tumor development in humans and whether shorter-chain n-3 PUFA of plant origin such as found in SBO will modulate these actions of linoleic acid, as has been shown for the longer-chain n-3 PUFA of marine oil