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Biomedical subjects

J E Rossouw

Publications and source records attributed to J E Rossouw.

At least 19 recordsLinked to original sources
PubMed1999

Hormone replacement therapy and cardiovascular disease.

A large amount of research continues to be conducted on the mechanisms of hormone replacement therapy (HRT) effects, and the first of the large clinical trials published its results during the past year. In addition to the well known effects on LDL-cholesterol, HDL-cholesterol, and triglycerides, recent studies confirmed that estrogen with or without a progestin lowers lipoprotein (a) concentrations in women (but not in men). In men, estrogen appears to have a similar effect on other lipids and lipoproteins and on plasminogen activator inhibitor-1 as in women. A comparison of estrogen with simvastatin indicated that simvastatin is better at lowering LDL-cholesterol while estrogen is better at raising HDL-cholesterol; when given in combination the additional effects were modest. Estrogen and simvastatin had similar beneficial effects on endothelial function. The estrogen effect on endothelial function may be blocked by medroxyprogesterone, but the data are inconsistent. These studies of intermediate outcomes were put in perspective by the results of a landmark secondary prevention trial of coronary heart disease (CHD). This randomized placebo-controlled trial (Heart and Estrogen/Progestin Replacement Study) of conjugated equine estrogens plus medroxyprogesterone failed to show the anticipated reduction in CHD, and at the same time the threefold increase in venous thromboembolism confirmed that HRT is procoagulant. Therefore, it is still not known whether HRT is a viable option for the prevention of CHD. The preliminary data on selective estrogen receptor modulators are not overly promising, but a definitive trial to test whether raloxifene will reduce CHD is ongoing.

Cardiovascular Diseases↗
PubMed1998

Cholesterol reduction yields clinical benefit: impact of statin trials.

BACKGROUND: We determined the effect of incorporating the results of eight recently published trials of Hmg CoA reductase inhibitors ("statins") on the conclusions from our previously published meta-analysis regarding the clinical benefit of cholesterol lowering. METHODS AND RESULTS: We used the same analytic approach as in our previous investigation, separating the specific effects of cholesterol lowering from the effects attributable to the different types of intervention studied. The reductions in coronary heart disease (CHD) and total mortality risk observed for the statins fell near the predictions from our earlier meta-analysis. Including the statin trial findings into the calculations led to a prediction that for every 10 percentage points of cholesterol lowering, CHD mortality risk would be reduced by 15% (P<.001), and total mortality risk would be reduced by 11% (P<.001), as opposed to the values of 13% and 10%, respectively, reported previously. Cholesterol lowering in general and by the statins in particular does not increase non-CHD mortality risk. CONCLUSIONS: Adding the results from the statin trials confirmed our original conclusion that lowering cholesterol is clinically beneficial. The relationships (slope) between cholesterol lowering and reduction in CHD and total mortality risk became stronger, and the standard error of the estimated slopes decreased by about half. Use of statins does not increase non-CHD mortality risk. The effect of the statins on CHD and total mortality risk can be explained by their lipid-lowering ability and appears to be directly proportional to the degree to which they lower lipids.

Cholesterol↗
PubMed1997

Twelve-year results of the Coronary Risk Factor Study (CORIS).

BACKGROUND: After 4 years a coronary heart disease risk factor intervention programme produced equally large and significantly reduced risk profiles in two intervention towns compared with a control town. Intervention effects through community participation were assessed after cessation of the active intervention programme. The impact of secular trends was assessed in the control town and in two previously unstudied towns. METHODS: Cross-sectional surveys were done in a random sample of 1620 participants aged 15-64 years in the three original towns 12 years after the initial quasi-experimental study. Two years later 327 subjects, aged 35-44 years, were studied in the original control town and in two non-intervention towns. Risk factor knowledge, smoking and medical histories were determined by questionnaire. Blood pressure, anthropometry and blood lipids were recorded. Data were compared across towns, and with previous surveys. RESULTS: At 12 years the low intensity intervention town maintained a significantly better risk factor profile than the control town, while the high intensity intervention town now matched the control town. No differences in risk factor profiles were found between the control town and the two new towns. Deaths from coronary heart disease and strokes showed a downward trend in the study area. CONCLUSIONS: Outcome suggests large ongoing secular trends during the study could have overtaken the intervention effects in the high intensity town, but not in the low intensity intervention town, which showed an advantage over the control town. These results support the effectiveness of media-based, long term health promotion strategies to reduce cardiovascular disease risk profiles.

Adolescent↗
PubMed1996

Apolipoprotein B levels and related factors in a rural white South African community--the CORIS study. Coronary Risk Factor Study.

OBJECTIVE: In a survey of the Coronary Risk Factor Study (CORIS), apolipoprotein B (apoB) levels were determined to ascertain their impact on coronary heart disease (CHD) risk. Other CHD risk factors associated with apoB were also identified. DESIGN: Cross-sectional analytical study, which included CHD risk factor and dietary questionnaires, electrocardiography, anthropometric and blood pressure measurements, and a blood sample for a lipid profile. SETTING AND PARTICIPANTS: The three districts of Riversdale, Robertson and Swellendam in the south-western Cape; a 25% random sample of 1,528 white respondents aged 15-68 years. RESULTS: Men tended to have higher mean apoB levels than women. Classification of CHD risk by apoB levels and total cholesterol (TC) levels did not correspond, as only 61% of men and 58.5% of women were classified in the same risk categories. Respondents in the highest apoB risk category reported a medical history of hypercholesterolaemia and hypertension more frequently than those in lower categories. There was a significant increase from the low to the high apoB risk category of TC, low-density lipoprotein (LDL) cholesterol, triglyceride levels, body mass index and percentage body fat. Using stepwise multiple regression, 84.9% of the variation in apoB of men and 85.8% in apoB of women were accounted for by significantly associated variables. CONCLUSION: Although apoB may be a better predictor of CHD than TC or LDL cholesterol concentrations, its easy approximation with the formula (TC-HDLC)/2 + 20, high cost, measurement variability and an approach in management similar to that for raised TC discourage its routine use in the screening of patients for CHD.

Adolescent↗
PubMed1995

Lipid-lowering interventions in angiographic trials.

This analysis examines the pooled data from all 14 published randomized angiographic trials (with 16 treatment arms) by type of cholesterol-lowering intervention evaluated, and for all the trials combined. All interventions reduced low density lipoprotein (LDL) cholesterol levels (average reduction, 26%), whereas the effects on high density lipoprotein (HDL) cholesterol and triglycerides varied by type of intervention. Meta-analyses of the angiographic outcomes indicated that treatment reduced the odds for disease progression by 49%, increased the odds for no change by 33%, and increased the odds for regression by 219%. Cardiovascular events were reduced by 47%. Thus, lipid reduction is effective for modifying the angiographic outcome and for reducing the incidence of coronary artery disease events. All types of intervention (lifestyle, drugs, or surgery) had overall favorable effects on angiographic and clinical outcomes. There was no class effect for the statin group of drugs. Surgery (partial ileal bypass) had the most favorable angiographic outcome, possibly because of a longer duration of therapy. Trials with higher baseline LDL levels tended to have more favorable angiographic outcomes. Analyses of in-trial levels of LDL were confounded by baseline levels, and analyses of change in LDL levels in the treatment groups were confounded by not including zero change (i.e., no treatment). It is hypothesized that lowering LDL levels by 30 mg/dl (0.8 mmol/liter) is sufficient on average to modify the angiographic outcome, with modest gains from further reductions in LDL levels.

Anticholesteremic Agents↗
PubMed1995

Cholesterol reduction yields clinical benefit. A new look at old data.

BACKGROUND: There has been a continuing debate about the overall benefit of cholesterol lowering. We performed a novel meta-analysis of all randomized trials of more than 2 years' duration (n = 35 trials) to describe how coronary-heart-disease (CHD), non-CHD, and total mortality are related to cholesterol lowering and to type of intervention. METHODS AND RESULTS: The analytic approach was designed to separate the effects of cholesterol lowering itself from the other effects of the different types of intervention used. For every 10 percentage points of cholesterol lowering, CHD mortality was reduced by 13% (P < .002) and total mortality by 10% (P < .03). Cholesterol lowering had no effect on non-CHD mortality. Certain types of intervention had specific effects independent of cholesterol lowering. Fibrates (clofibrates, 7 trials; gemfibrozil, 2 trials) increased non-CHD mortality by about 30% (P < .01) and total mortality by about 17% (P < .02). Hormones (estrogen, 2 trials; dextrothyroxin, 2 trials) increased CHD mortality in men by about 27% (P < .04), non-CHD mortality by about 55% (P < .03), and total mortality by about 33% (P < .01). No specific effects independent of cholesterol lowering were found due to diet (n = 11) or other interventions (resins, 5; niacin, 3; statins, 2; partial ileal bypass, 1). CONCLUSIONS: The results suggest that cholesterol lowering itself is beneficial but that specific adverse effects of fibrates and hormones increase the risk of CHD (hormones only), non-CHD, and total mortality.

Cholesterol↗
PubMed1994

The effects of lowering serum cholesterol on coronary heart disease risk.

The clinical trials and angiographic studies of cholesterol lowering have been of decisive importance in persuading scientific and public opinion that elevated serum cholesterol is a causal element in the chain of events leading to CHD and that treatment by diet and drugs is effective in lowering the risk of CHD. The appropriateness of these opinions is well illustrated by the analyses of the combined trials, which show that the clinical event rate can be lowered by about 20% if cholesterol levels are lowered by 10%. The reduced risk for CHD applies to both primary and secondary prevention. Further, the angiographic studies have now demonstrated that vigorous lipid-lowering therapy leads to improvements in the angiographic appearance of coronary vessels, which are accompanied by large reductions in CHD risk. Diet and a variety of drugs appear to modify the risk of CHD. The results of studies using combinations of drugs, for example, bile acid-binding resins with either niacin or hydroxymethylglutaryl coenzyme A reductase inhibitors, are particularly impressive. The primary purpose of treatment remains the reduction of total and LDL cholesterol; however, the possibility of an additional benefit from improving other aspects of the lipid profile (such as raising HDL cholesterol levels) at the same time should not be ignored. In many instances, combinations of drugs are needed to achieve optimal lowering of serum cholesterol or to treat all elements of the disorder. Although the treatment of high-risk but apparently healthy individuals should not be neglected, it would be particularly appropriate to institute intensive diet and combination drug therapy in patients with existing CHD, in view of their high risk of reinfarction if left untreated. The secondary prevention trials provide evidence that clinical events can be reduced in such patients. The angiographic studies strongly suggest that large reductions in cholesterol to much lower levels (in-treatment LDL cholesterol levels below 100 mg/dL were frequently observed) than those achieved in the secondary prevention trials markedly reduce the rate of coronary events in patients with existing disease.

Anticholesteremic Agents↗
PubMed1993

Does low cholesterol cause death?

Data linking low cholesterol with excess mortality have been gathered from both observational and clinical trials. The data are probably unrelated, as the levels of total cholesterol associated with excess mortality in observational studies are well below 160 mg/dl (4.1 mmol/l), whereas the levels achieved in clinical trials average around 230 mg/dl (5.9 mmol/l). Likely explanations of the association are that low cholesterol is a consequence of disease or is a confounder associated with other variables. The authors assess the relevance of the data to public health policy and medical practice. They conclude that evidence suggesting low cholesterol is a cause of excess mortality currently lacks breadth and rigor, and find no basis for changing cholesterol-management guidelines.

Cholesterol↗