Identification of novel plasma lipid markers of cardiovascular disease risk in White and Black women

Abstract

Rationale: Cardiovascular disease (CVD) is the leading cause of mortality for women in the USA. Current clinical biomarkers are inadequate to determine CVD risk in women, especially Black women, who disproportionately suffer from CVD. Methods: Clinical data and LC-MS lipidomics from two independent study cohorts were used to identify novel circulating markers of CVD risk in White and Black women. Machine learning assessed predictive efficacy of identified lipids, and targeted oxylipid analysis provided insight into dysregulated inflammatory pathways. Results: Select phospholipids and triglycerides containing acyl chains in the arachidonic acid (ARA) pathway were predictive of systolic blood pressure (BP) after adjusting for biological factors including age, obesity, and glycemic status in White and Black women. Oxylipid levels indicated increased conversion of ARA through the COX and LOX enzymes to pro-inflammatory cytokines in Black women. Conclusion: ARA-containing phospholipid are independent predictors of CVD risk in White and Black women. Predisposition to CVD risk in Black women may further be explained by increased production of pro-inflammatory oxylipids relative to White women, regardless of blood pressure status. Future studies investigating the clinical utility of phospholipid ARA abundance as a marker of CVD risk in White and Black women are warranted.