Adiposity, lipids and risk for myocardial infarction in the Maltese population

Abstract

Background Myocardial infarction (MI) is a complex disease influenced by both genetic and environmental factors. Aim The Maltese Acute Myocardial Infarction (MAMI) Study is a case-control study that was set up to identify genetic and environmental factors relevant to MI in the Maltese population. Hyperlipidaemia and adiposity as risk factors for myocardial infarction in the Maltese population will be focused on. Furthermore, this study will investigate and apply alternative approaches using high throughput sequencing, extreme phenotypes and biological pathway approaches to determine their use in acquiring more knowledge on the genetic factors of MI. Methods The study includes 423 cases with a first MI between 2011 and 2013, 465 controls that were sex and age-matched in ten year age groups to the cases and 210 relatives of cases. Data on all participants was collected after written informed consent through an extensive interviewer-led questionnaire, measurements and testing and through medical history and records. Results This case-control study identified several important genetic and environmental factors particularly pertinent to the Maltese population. The association of adiposity with risk of MI varied significantly depending on how adiposity was classified, with BMI, the most widely used clinical measure of adiposity, underestimating risk. Waist-hip ratio was more strongly associated with risk of myocardial infarction. Similarly, total cholesterol to high density

vii cholesterol ratio and the Non high density cholesterol levels were more strongly associated with risk of MI than the most commonly used clinical measures of dyslipidaemia. The study also gives important insights into how dietary habits in a central Mediterranean climate are influencing the risk of MI with consumption of soft drinks (even diet soft drinks) and bread being strong risk factors whilst nuts, legumes, fruit and red vegetables being protective. The modulation of risk by combinations of different environmental risk factors is exemplified in an analysis performed on smoking and alcohol. The risk associated with APOE and PTPN1 were minimal in the Maltese population. Using an extreme phenotype approach and high throughput sequencing a novel frameshift variant in LDLR likely to cause familial hypercholesterolaemia was identified and polymorphisms in APOB that increase the risk of MI in the Maltese population are described. Conclusions Using the extreme phenotype approach and high throughput sequencing, pathways related to the control of adipogenesis were examined and the findings presented highlight the importance of studying combinations of polymorphisms and using a systems biology approach to analyse the risk of MI in complex pathways.