Prevention of myocardial infarction and primary atherogenic cardiovascular disease from a sex-specific life course perspective

Leiden University Medical Centre

Lay summary

Despite several medications have been marketed for the prevention of atherogenic cardiovascular disease, still a considerable proportion of the users experience the disease. First-line prevention of atherogenic cardiovascular disease is difficult due to the increased number of individuals over 65 years of age. With increasing age, many biological processes in the body change or attenuate. In addition, it is unclear to what extend classical risk factors of atherogenic cardiovascular disease show similar increases in risk in individuals of middle and old age. These facts questions whether all pharmaceutical interventions prescribed to individuals still show clear clinical benefit. With medications having clear risks of adverse drug reactions, prescribing a drug at a certain age should have a clear clinical benefit to balance the risk of adverse drug reactions.

This project will identify the biological background of atherogenic cardiovascular diseases developed at different ages, using genetic association analyses using the genetic data collected in the UK Biobank. Using the genetics information, we will furthermore determine whether the combination of risk factors (e.g., a high blood pressure and a high LDL cholesterol level) still increase the risk of atherogenic cardiovascular disease in different stages over the life course.

The use of these kind of studies usually require immense sample sizes, which are available in the UK Biobank. Using the data collected in UK Biobank, we will determine the biological background and will identify the most suitable targets for interventions to prevent atherogenic cardiovascular disease in younger and older individuals.

Scope extension:

* Identify targets for (pharmaceutical) interventions that contribute most to the primary prevention of atherogenic cardiovascular disease in the general population from a sex-specific life course perspective.

* Identify targets for (pharmaceutical) interventions that contribute most to the prevention of myocardial infarction in patients with angina pectoris from a sex-specific life course perspective.

Extended scope:

* Identify targets for (pharmaceutical) interventions that contribute most to risk factors for atherogenic cardiovascular disease (including risk factors as obesity, dyslipidemia and diabetes) in the general population from a sex-specific life course perspective

Using regression-based and Mendelian Randomization approaches, we aim to assess the causal drivers for atherogenic cardiovascular disease in the general population in different age groups, and aim to develop new research methodology to be able to perform unbiased causal inference analyses in ageing populations.