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Biomedical subjects

S Yusuf

Publications and source records attributed to S Yusuf.

At least 127 records · Page 7Linked to original sources

Beta-blocker therapy for congestive heart failure: a systemic overview and critical appraisal of the published trials.

OBJECTIVE: To evaluate the effect of beta-blockers on mortality and morbidity, and to provide an appraisal of the reliability of the available data. DATA SOURCES: MEDLINE search for trials of beta-blockers for congestive heart failure (CHF). STUDY SELECTION: All randomized trials of beta-blockers versus placebo, or greater than one month's duration, in patients with CHF. Eighteen published trials involving 2986 patients were selected. DATA EXTRACTION: Independently by two authors. DATA SYNTHESIS: The Yusuf-Peto method for combining data was used. Data were available on mortality in 2841 patients (95%), on hospitalization for heart failure in 1514 (51%) and on heart transplantation in 2330 (79%). There was a lower rate of death in the active treatment group (131 of 1606) [8.2] versus 155 of 1235 [12.6%]; OR = 72; 99% CI 0.51 to 1.00), a lower rate of hospitalization for heart failure (137 of 756 [18.1%] versus 218 of 758 [28.7%]; OR = 0.54; 99% CI 0.39 to 0.74) and a trend towards a lower proportion of patients receiving heart transplantation (15 of 1354 [l.1%] versus 26 of 976 [2.7%]; OR = 0.45; 99% CI 0.20 to 1.03). Ventricular function improved; however, there was no effect on exercise duration. Although the effects on mortality were nominally statistically significant, the use of formal methods of interim monitoring adapted for meta-analyses suggests that substantially more patients still need to be studied in large scales trials to provide reliable and conclusive evidence. CONCLUSIONS: While the available data on the use of beta-blockers in CHF appear to be promising, they are neither complete nor robust. The routine use of beta-blockers in patients with heart failure should wait the results of ongoing studies.

Adrenergic beta-Antagonists↗

Anti-ischaemic effects of ACE inhibitors: review of current clinical evidence and ongoing clinical trials.

Important ongoing experimental and clinical research is evaluating the potential use of ACE inhibitors in a wider range of patients, in addition to their well accepted use in heart failure, left ventricular dysfunction and hypertension. We review briefly the clinical data supporting a potential role for ACE inhibitors in the prevention of myocardial infarction and stroke and the wider use of these agents in hypertension, renal disease and diabetes. We also briefly review the major ongoing trials evaluating these hypotheses.

Adult↗

The Study of Health Assessment and Risk in Ethnic groups (SHARE): rationale and design. The SHARE Investigators.

The Study of Health Assessment and Risk in Ethnic groups (SHARE) is a study to determine the risk factors for atherosclerosis among three ethnic populations in Canada. Three hundred and thirty South Asian Canadian, 320 Chinese Canadian and 320 European Canadian men and women between 35 and 75 years of age are being randomly sampled from communities in Hamilton and Toronto, Ontario and Edmonton, Alberta for assessment of conventional (i.e., smoking, dyslipidemia, diabetes and hypertension) and emerging (i.e., candidate genes for atherosclerosis, homocysteine, fibrinolytic parameters, neurohormones, glucose intolerance, markers of infection, socioeconomic status, psychosocial status and diet) cardiovascular disease risk factors. Subclinical atherosclerosis is measured by quantitative B-mode ultrasonography of the carotid arteries, and other objective measures of vascular disease are a 12-lead electrocardiogram, a two-dimensional echocardiogram, ankle to arm blood pressure ratio and urine microalbumin concentration. The relationship between the conventional and emerging risk factors, and atherosclerosis, vascular disease and markers of end-organ damage will be evaluated between and within ethnic groups.

Adult↗

The global problem of cardiovascular disease.

The greatest cause of death throughout the world today is noncommunicable disease. In Western societies, coronary artery disease is a principal cause of death. In developing countries, the incidence of coronary disease is rising as well. Heart disease often occurs in younger persons in developing societies, resulting in a disproportionately greater number of years of life lost. The reason for this change in global patterns of mortality is that deaths from infectious diseases are declining, resulting in greater life expectancy and changing lifestyles.

Adult↗

Emerging approaches in the prevention of atherosclerotic cardiovascular diseases.

This presentation reviews data from epidemiologic and clinical trials on antioxidant vitamins, angiotensin-converting enzyme inhibitors, and homocysteine and their effect on atherosclerotic cardiovascular disease. Each of these areas seems promising, but the results of large, on-going studies must be determined before definitive conclusions can be made as to the effectiveness of these therapies.

Adult↗

Acute and long-term effects of the angiotensin-converting enzyme inhibitor, enalapril, on adrenergic activity and sensitivity during exercise in patients with left ventricular systolic dysfunction.

Patients with heart failure and left ventricular systolic dysfunction exhibit increased adrenergic activity but blunted adrenergic responsiveness. We studied patients enrolled in the Studies of Left Ventricular Dysfunction, examining exercise responses of heart rate (HR) and plasma norepinephrine (PNE). Eighty-seven patients were studied before randomization; 65 of these were examined 1 year after randomization to placebo or enalapril. Compared with prevention trial (asymptomatic) patients, patients in the treatment trial (symptomatic) had higher resting HR and PNE levels and less increase in HR with a greater increase in PNE with exercise. Acute administration of enalapril increased the resting HR in patients in the prevention trial only but had no significant effect on PNE. After 1 year of therapy, patients in the prevention trial exhibited no change. Within the treatment trial, the placebo group displayed both a higher peak PNE and increase in PNE with exercise than did the enalapril group, whose HR response was maintained in spite of a reduction of exercise PNE. We conclude that (1) compared with asymptomatic patients, symptomatic patients with reduced left ventricular ejection fraction manifest greater resting and exercise adrenergic activity, with blunted HR response; and (2) in symptomatic patients, 1 year of enalapril treatment effected an augmented HR response to adrenergic stimulation, supporting an interaction between the renin/angiotensin and adrenergic nervous systems. Normalization of adrenergic tone and response likely contributes to the benefits of long-term angiotensin-converting enzyme inhibitor therapy.

Aged↗

Strengths and limitations of meta-analysis: larger studies may be more reliable.

Meta-analysis of randomized controlled trials combines information from independent studies that address a similar question to provide more reliable estimates of treatment effects. At the present time, the methodology and usefulness of meta-analysis is under scrutiny. In the first part of this paper, we summarize the limitations of meta-analysis and make suggestions for improvements. In the second part, we illustrate strengths and limitations using examples of meta-analyses and subsequent large trials that address the same question. We develop the hypothesis that the size of the meta-analysis may be a useful measure of reliability. Small meta-analyses (i.e., those with less than 200 outcome events) may only be useful for summarizing the available information and generating hypotheses for future research. The results of small meta-analyses should be regarded with caution, even if the p value shows extreme statistical significance. Larger meta-analyses (i.e., those with several hundred events) are likely to be more reliable and may be clinically useful. Well-conducted meta-analyses of large trials using individual patient data may provide the best estimates of treatment effects in the cohort overall and in clinically important subgroups.

Bias↗

Cumulating evidence from randomized trials: utilizing sequential monitoring boundaries for cumulative meta-analysis.

We propose the adaptation of classical monitoring boundaries for use in cumulative meta-analysis as guidelines for deciding when accumulating evidence is statistically significant and medically convincing. The interpretation of information from a randomized controlled trial is compared with that from a meta-analysis. The concept of optimal information size for a meta-analysis is developed and used to adapt monitoring boundaries to cumulative meta-analysis.

Fibrinolytic Agents↗

Meta-analysis of randomized trials: looking back and looking ahead.

Meta-analyses as currently practiced are usually retrospective. They can be made more rigorous by developing a protocol that incorporates prospectively the elements that are usually necessary in a well-designed trial. Meta-analysis and large trials are complementary. Meta-analysis of small trials is useful in generating the hypotheses and assisting in the design of the large trials that are needed. Once the large trials have been completed, they could be brought together within the framework of a meta-analysis to estimate the overall treatment effect with greater confidence and to explore the effects in various subgroups. This article explores the value and limitations of meta-analyses and suggests ways of improving their conduct and interpretation.

Humans↗

Classifying ethnicity utilizing the Canadian Mortality Data Base.

UNLABELLED: The study of ethnic differences in disease is a methodological challenge as ethnicity is often not identified in existing datasets and surrogate measures need to be used. We have developed a novel methodology combining last name and country of birth to study mortality patterns of Canadians of South Asian (SA) and Chinese (CH) ethnic origin and have compared death rates among SA, CH, and White (WH) Canadians. METHODS: SA and CH were identified in the Canadian Mortality Data Base (CMDB) using the last name and country of birth of the deceased. Records of people who had been born in countries with large South Asian and Chinese populations (e.g. India, Pakistan, China, Hong Kong) were selected and manually screened by last name. A name directory was then created of distinct South Asian and Chinese names and this directory was used to search all other records in the CMDB for SA and CH deaths. Where necessary, other identifying characteristics such as first name and parents' last name were also used. Population counts were obtained from the Census self-reported question on ethnicity for SA and CH. WH were identified as non-immigrant Canadians who were neither SA nor CH. The method of assigning ethnicity in the CMDB and Census were assessed for comparability and issues of validity and reliability were addressed. RESULTS: Using this method, 10,989 SA and 21,548 CH deaths were identified. There was marked heterogeneity in birthplace, with only 56% of SA born in South Asia and only 74% of CH born in Greater China. Last names had high validity for self-reported ethnicity in a population sample of SA and were highly reproducible. Mortality rates varied dramatically between groups studied. SA and WH had high rates of ischemic heart disease while stroke mortality was similar among all three groups. Cancer death rates were high in CH and WH and much lower in SA. CONCLUSION: Last names and country of birth can be used to determined ethnicity of SA and CH with validity and reliability, and leads to a more accurate classification than country of birth alone. The contrasting patterns observed in mortality from major causes of death suggest many interesting hypotheses for further study.

Adult↗

Risk factors for cardiovascular disease in Canadians of South Asian and European origin: a pilot study of the Study of Heart Assessment and Risk in Ethnic Groups (SHARE).

OBJECTIVE: To test the feasibility of recruitment strategies and a 2-hour cardiovascular (CV) health assessment (including laboratory tests and questionnaires) in preparation for a national, population-based study to determine CV risk factors among Canadians of different ethnic origins. DESIGN: Cross-sectional study of people of South Asian and European origin from Hamilton, Ont., identified by community-based stratified random sampling. SETTING: University-affiliated research clinic in Hamilton, Ont. PARTICIPANTS: Thirty-one Canadians of South Asian origin and 20 Canadians of European origin 35 to 75 years of age. INTERVENTIONS: Subjects attended a clinic at which they completed a health questionnaire, provided fasting and postprandial blood samples, and underwent B-mode carotid ultrasonographic examination as well as anthropometric, nutritional and psychosocial assessments. RESULTS: The participants of South Asian origin had lived in Canada for 18 years, on average, compared with 48 years for those of European origin. More participants of South Asian origin were married than those of European origin, and fewer smoked or consumed alcohol. Participants of South Asian origin were more likely to have some university education. The prevalence of impaired glucose tolerance was 34.5% in the participants of South Asian origin and 9.5% in those of European origin (p < 0.04). The total cholesterol to high-density lipoprotein ratio was elevated in the participants of South Asian origin (5.1), compared with those of European origin (4.2) (p < 0.05), as was the lipoprotein (a) concentration (log transformed) (5.5 v. 4.6 mg/dL, p < 0.02). CONCLUSIONS: This pilot study revealed intriguing lifestyle and metabolic differences between participants of South Asian and European origin. Those of South Asian origin had a higher prevalence of impaired glucose tolerance, dyslipidemia and elevated lipoprotein (a) concentrations-factors thought to be associated with premature CVD in this group.

Asia↗