Abstract
As dyslipidaemia is a prominent CVD risk factor, improvements in its management are crucial, as dyslipidaemia (quantified by hypercholesterolemia and treated with statins), incompletely addresses the residual CVD risk attributed to non-traditional markers and lipoprotein subfractions. Such markers include triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and small- dense low-density lipoproteins. This project investigated the utility of the atherogenic index of plasma (AIP; log(TG/HDL-C)), as an alternative CVD risk marker in elderly New Zealanders. Comprehensive biostatistical and bioinformatic post-hoc analyses were performed on elderly cohorts of CVD patients (including coronary artery disease (CAD), peripheral arterial disease (PAD), stroke, and abdominal aortic aneurysm) and self-reported healthy controls previously recruited by the Otago Vascular Research Group. AIP values above a binary risk threshold (AIP > -0.039) were independently associated with an increased risk of CVD prevalence; however, no significant correlation between AIP and CVD severity was observed. Similarly, AIP values above a different binary risk threshold (AIP > 0.12) did not independently predict 5-year outcomes (major adverse cardiovascular events or death) in a cohort of CAD patients with elevated CVD risk (> 10%). Likewise, the capacity for AIP to be modified by two acute 12-week lifestyle interventions (exercise or heat) in PAD patients was insignificant. Finally, AIP-associated DNA methylation biology reflected the existing biology for traditional lipids and cardiometabolic risk factors. DNA methylation also identified loci independent of traditional lipids, which suggested that this biology may be attributed to an independent AIP residual CVD risk beyond individual lipid markers. Overall, the results of this project indicate that AIP may have utility as an alternative risk marker for CVD risk modelling in elderly New Zealanders; however, this may be limited to assessments of CVD prevalence.