Genetics in Ischemic Stroke: Current Perspectives and Future Directions.

Ischemic stroke is a heterogeneous condition influenced by a combination of genetic and environmental factors. Recent advancements have explored genetics in relation to various aspects of ischemic stroke, including the alteration of individual stroke occurrence risk, modulation of treatment response, and effectiveness of post-stroke functional recovery. This article aims to review the recent findings from genetic studies related to various clinical and molecular aspects of ischemic stroke. The potential clinical applications of these genetic insights in stratifying stroke risk, guiding personalized therapy, and identifying new therapeutic targets are discussed herein.

Platform for the interdisciplinary study of cardiovascular, metabolic and neurovascular diseases (PICMAN) protocol.

Through extensive multisystem phenotyping, the central aim of Project PICMAN is to correlate metabolic flexibility to measures of cardiometabolic health, including myocardial diastolic dysfunction, coronary and cerebral atherosclerosis, body fat distribution and severity of non-alcoholic fatty liver disease. This cohort will form the basis of larger interventional trials targeting metabolic inflexibility in the prevention of cardiovascular disease. Participants aged 21-72 years with no prior manifest atherosclerotic cardiovascular disease (ASCVD) are being recruited from a preventive cardiology clinic and an existing cohort of non-alcoholic fatty liver disease (NAFLD) in an academic medical centre. A total of 120 patients will be recruited in the pilot phase of this study and followed up for 5 years. Those with 10-year ASCVD risk ≥ 5% as per the QRISK3 calculator are eligible. Those with established diabetes mellitus are excluded. Participants recruited undergo a detailed assessment of health behaviours and physical measurements. Participants also undergo a series of multimodality clinical phenotyping comprising cardiac tests, vascular assessments, metabolic tests, liver and neurovascular testing. Blood samples are also being collected and banked for plasma biomarkers, 'multi-omics analyses' and for generation of induced pluripotent stem cells (iPSC). Extensive evidence points to metabolic dysregulation as an early precursor of cardiovascular disease, particularly in Asia. We hypothesise that quantifiable metabolic inflexibility may be representative of an individual in his/her silent, but high-risk progression towards insulin resistance, diabetes and cardiovascular disease. The platform for interdisciplinary cardiovascular-metabolic-neurovascular diseases (PICMAN) is a pilot, prospective, multi-ethnic cohort study.

Epigenetics in cardiovascular health and disease.

Conrad Waddington's epigenetics landscape has provided a metaphorical framework for how cells progress from undifferentiated states to one of several discrete, distinct, differentiated cell fates. The understanding of epigenetics has evolved over time, with DNA methylation being the most studied epigenetic modification, followed by histone modifications and non-coding RNA. Cardiovascular diseases (CVD) are leading contributors to death worldwide, with the prevalence of CVDs increasing across the last couple of decades. Significant amount of resources being poured into researching key mechanisms and underpinnings of the various CVDs. These molecular studies looked at the genetics, epigenetics as well as the transcriptomics of various cardiovascular conditions, aiming to provide mechanistic insights. It has paved the way for therapeutics to be developed and in recent years, epi-drugs for the treatment of CVDs. This chapter aims to cover the various roles of epigenetics in the context of cardiovascular health and disease. The following will be examined in detail: the developments in basic experimental techniques used to study epigenetics, the role of epigenetics in various CVDs (hypertension, atrial fibrillation, atherosclerosis, and heart failure), and current advances in epi-therapeutics, providing a holistic view of the current concerted efforts in advancing the field of epigenetics in CVDs.