Approved Research

Investigating the role of lipids, lipoproteins, and other risk factors in determining cardiovascular outcomes to support target identification, validation, and prioritization

Lay summary

Cardiovascular disease is the leading cause of death worldwide. Despite the wide availability of agents to control dyslipidemia/hyperlipidemia, significant cardiovascular residual risk exists even among patients achieving LDL-C treatment goals. Reducing lipids and ApoB-containing lipoprotein particles that are contributing risk factors for ASCVD is a viable therapeutic approach to address residual cardiovascular risk.

Human genetics, epidemiologic studies, preclinical evidence, and clinical trial results support a causal association between lipoprotein(a) [Lp(a)], triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischemic stroke, calcified aortic valve stenosis, and other events. To note, Lp(a) is a major and independent cardiovascular risk factor for which there is no currently approved medical therapy, and evidence suggests that TRL and their remnants may contribute significantly to residual cardiovascular risk in patients on optimized low-density lipoprotein-lowering therapy. Thus, the goal of this proposal is (1) to identify and characterize the individuals both with and without atherosclerotic cardiovascular disease at baseline who are most likely to benefit from Lp(a) or other novel lipid lowering therapies (2) to evaluate causal relationships for clinical outcomes using human genetics and related risk factors utilizing mendelian randomization approach. 

Through this proposed research, we expect to gain better understanding of Lp(a) and risk of cardiovascular events in sub-populations of the UK Biobank, and how TRLs causally relates with the risk of cardiovascular events. Furthermore, outcome will also help to characterize the population at the nexus of cardiovascular risk from Lp(a) and the myriad risk factors, with the aim to maximally improve public health. Subsequently, this approach would be applied to other lipid risk factors.

Full cohort and estimated duration of the project is 3yrs.