Genetic, lipid and other risk factors in early-onset acute myocardial infarction in Malaysia.

Coronary heart disease (CHD), with myocardial infarction (MI) or "heart attack" as the main manifestation, is the leading cause of death worldwide, and is also the leading cause of death in Malaysia. It is estimated that in Malaysia and other South-East Asian countries, nearly a quarter of CHD events occur in people younger than 50 years, resulting in a significant loss of productive working years due to death and disability. This is why we have deigned a case-control study of acute MI in Malaysia to recruit 5000 participants (2500 MI patients or "cases" aged <50 years and 2500 healthy participants or "controls"). In this study, we will initially investigate the hereditary and lipid-related risk factors of heart attack in Malaysia's population - which has distinctive features of multi-ethnicity and consanguinity (or intermarriage).

The specific objectives of our proposed study are to:

(1) investigate genetic risk factors of premature heart attack in Malaysia;

(2) evaluate cardiovascular risk factors of specific relevance to the Malaysian population, such as indigenous forms of tobacco consumption and local dietary patterns, with potential implications of results for public health policy; and

(3) create collaborations between Malaysian and UK scientists, who will jointly manage and further harvest the dataset and bioresource of this nationally-important research platform.

Coronary heart disease (CHD), with myocardial infarction (MI) as the main manifestation, is the single leading cause of death worldwide1 and is the leading cause of death in Malaysia.9,10 It is estimated that in Malaysia and other South-East Asian countries, nearly a quarter of CHD events occur in people younger than 50, resulting in a significant loss of productive working years due to death and disability. This background provides the rationale for the current Malaysia-UK funding call for research into "cardiovascular disease, especially young myocardial infarctions". We propose to establish the first large-scale CHD bioresource in Malaysia, ie, a case-control study that, in the first instance, will comprise 5000 participants (2500 MI patients aged <50 years). The overarching goal is to advance understanding of risk factors for CHD in Malaysia both to enrich mechanistic understanding and to inform public health action. We will initially focus on genomic and lipid-related risk factors, harnessing Malaysia's population's distinctive features of multi-ethnicity and consanguinity.

The key objective of this study is to establish the first large-scale CHD bioresource in Malaysia to enable:
(1) assumption-free discovery science that leverages Malaysia's unique history of multi-ethnicity and consanguinity through genomic studies of MI and cardiometabolic traits, with potential implications of results for downstream studies to elucidate the mechanistic basis of CHD and inform therapeutic target identification and prioritisation;
(2) detailed evaluation of candidate cardiovascular risk factors of specific relevance to the Malaysian population, such as indigenous forms of tobacco consumption and local dietary patterns, with potential implications of results for public health policy; and
(3)enduring collaboration between Malaysian and UK scientists, who will jointly manage and harvest the dataset and bioresource of this distinctive and important research platform.

A. Progressing science: The MAVERIK study will establish the first large-scale CHD epidemiology resource in Malaysia to enable:

(1) assumption-free discovery science that leverages Malaysia's unique history of multi-ethnicity and consanguinity through genomic studies of MI and cardiometabolic traits, with potential implications of results for downstream studies to elucidate the mechanistic basis of CHD and inform therapeutic target identification and prioritisation.

(2) detailed evaluation of candidate cardiovascular risk factors of specific relevance to the Malaysian population, such as indigenous forms of tobacco consumption and local dietary patterns, with potential implications of results for public health policy.

(3) enduring collaboration between Malaysian and UK scientists, who will jointly manage and harvest the dataset and bioresource of this distinctive and important research platform

B. Translational activities Translation of scientific discovery to improve the health of the population in Malaysia (and elsewhere) will be the key objective of the MAVERIK study. In this regard, the senior stakeholders and study collaborators based in Malaysia will be well-placed to facilitate rapid translation of findings important to clinical practice and public health policy in Malaysia:

- Dr Mohd Fairulnizal Bin Md Noh is the Head of the National Cardiovascular, Diabetes & Nutrition Research Centre in the National Institute for Medical Research (IMR) within the National Institute of Health in Malaysia.

- Datuk Dr Aizai Azan Bin Abdul Rahim is the Head of Cardiology at the National Heart Institute (IJN), Malaysia.

- Datuk Dr A. Rahman Bin A. Jamal is the Project Leader for the Malaysian Cohort Project and Malaysian Cancer Genome Consortium, funded by Malaysian Government.

Furthermore, support is sought for an annual Dissemination Symposium in Malaysia involving the national health Ministry, clinical and scientific leaders, in order to share and review the key scientific findings in MAVERIK as they emerge and to explore implications for clinical practice and local public health.

C. Mechanisms of dissemination: It is anticipated that this epidemiological resource will yield a wealth of highly informative data that will be reported in high-impact, peer-reviewed publications and will be disseminated to relevant scientific and professional groups, such as the US National Institute of Health, governments and health ministries in South-East Asian countries, the World Health Organization, the World Bank, the Departments of Health in the USA and UK, British Heart Foundation, American Heart Association, the national cardiovascular agencies throughout Europe, the US National Educational Program-Adult Treatment Panel and HuGENet. We will also forward data on allele frequencies in the Malaysia population to the National Center for Biotechnology and Information (NCBI) SNP database, enabling other investigators to select appropriate variants for genetic studies in Malaysians (such information is currently lacking). Given the nature of the project, MAVERIK proposes to make all results rapidly available to the wider community. Results of all biochemical investigations will be communicated to the participants in person when possible by our designated research medical officers or alternatively will be mailed in a standard test report format.

D. Capacity building initiatives: An important objective of MAVERIK will be to develop human scientific capacity in Malaysia in cardiovascular epidemiology and public health research methods through establishment of scientific linkages with the University of Cambridge, IMR, IJN and other Western academic institutions. Such activities will include:
(1) conducting intensive training seminars in Malaysia on epidemiology for the several field workers;
(2) training scientists from Malaysia
(3) cardiovascular epidemiology course