A collaborative project between University of the Witwatersrand, Republic of South Africa and McMaster University, Toronto, Canada (Prof Salim Yusuf)

Team (South Africa):

• Prof Karen Sliwa
• Dr Anthony Becker
• Elisabeth Tsele – research assistant
• Nomsa Molefe – research assistant

Summary

This study has been designed by Prof Salim Yusuf, Population Health Research Institute, McMaster University, and international collaborators of the INTERHEART I research team (including Prof Sliwa). The findings of the INTERHEART I study were published in several publications, including The Lancet, and provided findings very relevant for South Africa (The INTERHEART Africa Study. Steyn K, Sliwa K, Hawken S, Ounpuu S, Yusuf S. Africa Interheart Study. Circulation 2005;112:3554-3561).

The proposed investigation, INTERHEART II, is an international, standardised family case-control study. The objectives are:

1. to compare the Coronary Heart Disease (CHD) risk factor levels of family members of an individual with CHD with similar family members of matched controls;
2. to explore the risk factor aggregation patterns within and between case and control families;
3. to understand the relative contributions of shared lifestyles and common genetic endowment to risk factor presence;
4. to explore the gene-environment interactions related to CHD risk factor expression. These major goals are motivated by the primary hypothesis that “high risk” individuals with CHD are markers of “high risk” families by virtue of increased risk factor levels in family members, as compared with family members of individuals without CHD.

The study is presently conducted in four centres worldwide.

Funding

• McMaster University

Hope-3 Trial

Principal Investigator
Salim Yusuf, DPhil, FRCPC
Professor, Department of Medicine
Director, Population Health Research Institute
McMaster University

Co-Principal Investigator
Eva Lonn, MD, MSc, FRCPC
Professor of Medicine
McMaster University

National Leader and Steering Committee
Prof Karen Sliwa
Soweto Cardiovascular Research Unit

Cardiovascular disease (CVD) is a major cause of death and disability worldwide. CVD is largely preventable, as cardiovascular (CV) risk factors are related to lifestyle and can be modified, using pharmacological interventions and possibly behavioural changes. Most previous studies have evaluated therapies in high-risk patient subsets, such as those with pre-existent CVD and/or those with substantial elevations in the level of one or multiple CV risk factors.

The approach to CV prevention in people at average risk remains uncertain. This question is important, as most CV events occur in people at average risk, who represent a substantial proportion of the adult population worldwide.

Epidemiological studies have clearly established that elevated cholesterol and blood pressure levels are major CV risk factors and account for a substantial proportion (>50%) of the population at risk for CVD. Moreover, such studies have shown that the relationships between cholesterol and blood pressure respectively and CV risk are continuous, extending well below average (“normal”) levels.

Clinical trials have demonstrated that cholesterol and blood pressure levels can be effectively and safely lowered with statins and combination blood pressure lowering drugs and that these therapies can reduce CV risk in high-risk people, although there are only limited data in people at average risk. Intensive lifestyle interventions have been shown to reduce levels of CV risk factors and in some studies have reduced clinical events in high-risk individuals. However, these interventions are expensive and not readily practicable. There is only limited evidence for less intensive lifestyle interventions that could be feasible, sustainable and thus applicable in populations.

This is why the Soweto Cardiovascular Research Unit is now undertaking a trial known as HOPE-3. The trial will evaluate the effects of lipid modification with rosuvastatin, of combination blood pressure lowering with candesartan/hydrochlorothiazide (HCTZ) and of a simple, structured lifestyle intervention in preventing CV events and reducing levels of CV risk factors, in a wide range of middle-aged people who are at moderate risk for vascular events. Under the leadership of Prof K Sliwa, Dr Elena Libhaber, Dr Nunkoo and Elisabeth Thele, the SOCRU trial will recruit a total of 400 patients at four centres in South Africa.

Infective Endocarditis in HIV-positive patients: A Literature Review and Case Reports

MMED project by Dr Robert Mvungi

Funding: University of the Witwatersrand