Lipoprotein (a) and Vascular Regenerative Cell Content

Lipoprotein (a) \[Lp(a)\] is an independent, genetically determined, causal risk factor for the development of atherosclerotic cardiovascular disease. It is estimated that 20-30% of the global population have elevated Lp(a) and recent multinational guideline endorsements strongly advise the routine measuring of Lp(a), at least once in a person's life. Current Lp(a) risk level thresholds are described as \<75 nmol/L for low risk and \>125 nmol/L for high risk individuals. Despite ongoing clinical trials, there exists no approved therapeutic medication to specifically lower Lp(a). Vascular regenerative cell exhaustion (VRCE) is described as the depletion of circulating pro-vascular reparative cells responsible for angiogenesis, vasculogenesis and arteriogenesis. Evidence in recent years has implicated VRCE as a novel mechanistic factor contributing to the aberrant cardiometabolic state present in type 2 diabetes, obesity, and in people of South Asian descent. It has been demonstrated that the VRCE phenotype can be reversed by treatment with sodium glucose co-transporter 2 inhibitors or bariatric surgery. Lp(a)-VRCE is a cross-sectional, observational, two arm study enrolling 20 patients with elevated Lp(a) (≥100 nmol/L) and 20 patients with non-elevated Lp(a) (\<100 nmol/L). From peripheral blood, mononuclear cells are isolated and enumerated via a multi-parametric flow cytometry assay utilizing aldehyde dehydrogenase activity and side scatter properties. The hypothesis is that people with elevated Lp(a) have comparatively different progenitor cell phenotypes to people with normal Lp(a) levels.