Genetic, lipid and other risk factors in early-onset acute myocardial infarction in Malaysia.
Lead Research Organisation:
University of Cambridge
Department Name: Public Health and Primary Care
Abstract
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.
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.
Technical Summary
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.
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.
Planned Impact
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
(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
Publications
Hendricks AE
(2017)
Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity.
in Scientific reports
Ismail S
(2023)
Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia
in Journal of Cardiovascular Development and Disease
Liu DJ
(2017)
Exome-wide association study of plasma lipids in >300,000 individuals.
in Nature genetics
Malik R
(2018)
Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
in Nature genetics
Description | Ministry of Health Research Grant |
Amount | RM244,900 (MYR) |
Funding ID | NMRR-16-2399-33768 |
Organisation | Ministry of Health Malaysia |
Sector | Public |
Country | Malaysia |
Start | 11/2019 |
End | 12/2020 |
Title | MAVERIK Samples |
Description | 5000 blood and 1000 nail samples have been collected from participants of the MAVERIK study. These participants were recruited in the MAVERIK case-control study of acute MI in Malaysia. 5000 participants were recruited (2500 MI patients or "cases" aged <50 years and 2500 healthy participants or "controls"). These samples will be used to 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 the study were 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. |
Type Of Material | Biological samples |
Year Produced | 2019 |
Provided To Others? | No |
Impact | None yet, samples are currently being analysed. |
Title | MAVERIK Database |
Description | MAVERIK is a case-control study of acute vascular events in Malaysia. Data has been collected on 5,000 participants (2,500 MI cases and 2,500 control participants) from hospitals across Malaysia. Participants answer questionnaires and provide blood samples which will help the understanding a cardiovascular events, including risk factors specific to Malaysia. Using this data, 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 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. |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | Several publications using the MAVERIK data are in preparation, including a design paper and a paper on lipidomics. |
Description | IMR Malaysia |
Organisation | Ministry of Health Malaysia |
Department | Institute for Medical Research |
Country | Malaysia |
Sector | Public |
PI Contribution | This collaboration led to securing of additional £200000 funding from the Malaysian Academy of Science. We are working closely with the IMR researchers to implement the MAVERIK study. |
Collaborator Contribution | IMR researchers are contributing to design and implementation of the study. |
Impact | None so far as the research study is still in progress. |
Start Year | 2017 |
Description | Nightingale Collaboration |
Organisation | Nightingale Health Ltd. |
Country | Finland |
Sector | Private |
PI Contribution | Collaboration with Nightingale Health Ltd enabled us to increase data for our analysts, providing strategic and analytical input. |
Collaborator Contribution | Nightingale health provided lab support and Bristol shared strategic and analytical input. |
Impact | No outputs to date |
Start Year | 2020 |
Description | Nightingale Collaboration |
Organisation | University of Bristol |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Collaboration with Nightingale Health Ltd enabled us to increase data for our analysts, providing strategic and analytical input. |
Collaborator Contribution | Nightingale health provided lab support and Bristol shared strategic and analytical input. |
Impact | No outputs to date |
Start Year | 2020 |
Description | CAPABLE General Assembly |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The annual general assembly of the MRC UKRI funded CAPABLE programme was a gathering of all collaborators, staff members, donors, other stakeholders and an extended network of global health researchers. This was attended by members of the MAVERIK research team from Malaysia and Cambridge. The Malaysian PI gave a talk on MAVERIK and there were discussions and plans made for future activities within the MAVERIK study. |
Year(s) Of Engagement Activity | 2018 |
Description | MAVERIK Newsletter - IMR |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Malaysian Institute of Medical Research circulated a newsletter on the MAVERIK study to research team members at the IMR, Cambridge and collaborating hospitals throughout Malaysia. This newsletter was to provide updates on the study progress to research collaborators. This led to increased awareness of the study and further strengthened support from collaborators and other stakeholders. |
Year(s) Of Engagement Activity | 2019 |
Description | MAVERIK Study Poster at IMR Open Day |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | A poster on the MAVERIK Study was presented at the Institute of Medical Research Malaysia (IMR) Open Day, which was attended 2500 people, including lecturers, students, professional practitioners, media and the general public. The Deputy Minister of Health of Malaysia also attended this event. This was to introduce IMR's research activities to the general public. |
Year(s) Of Engagement Activity | 2018 |
Description | MAVERIK Study Poster at MOH-AMM Scientific Meeting and NIH Scientific Seminar |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | A poster on the MAVERIK Study was presented at the MOH-AMM (Ministry of Health- Academy of Medicine Malaysia) Scientific Meeting and NIH Scientific Seminar in August 2019 at the National Institutes of Health, Malaysia. These events were attended by 1000 people including media, policy-makers and professional practitioners. These events were for the dissemination of research findings. |
Year(s) Of Engagement Activity | 2019 |
Description | MAVERIK Study Presentation to Deputy Minister of Health, IMR, Malaysia |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Dr Mohd Fairulnizal Md Noh gave a presentation on the MAVERIK Study to the Deputy Minister of Health, Head of Centre from the Institute of Medical Research Malaysia (IMR) and other officials from the Ministry of Health. This presentation was to introduce research activities conducted at IMR to the new Deputy Minister of Health. |
Year(s) Of Engagement Activity | 2018 |
Description | NIH Bulletin Malaysia |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | The NIH Bulletin was circulated throughout the National Institutes of Health and Ministry of Health in Malaysia. This was to inform researchers, healthcare workers and policymakers of research activities. This led to increased awareness of research activities and challenges, and to additional support from the Ministry of Health. |
Year(s) Of Engagement Activity | 2019 |
Description | SEAMEO-TROPMED Regional Meeting, Bangkok |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | The SEAMEO-TROPMED Regional Meeting in Bangkok was attended by representatives from South Asian countries, including policy-makers and researchers. The Director of the Institute for Medical Research (IMR) presented on the MAVERIK study at the meeting, as well as other projects conducted by IMR. |
Year(s) Of Engagement Activity | 2019 |