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

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. ### Competing Interest Statement Conflict of interest: SM is an employee of Agilent Technologies Inc. JS interests are managed by the University of Wisconsin-Madison in accordance with their conflict-of-interest policy. ### Funding Statement The NIA through the University of Wisconsin Madison Center for Demography of Health and Aging Pilot Grant (P30AG017266); the NIH/BIRCWH (K12HD101368); JDRF (JDRF201309442); the Glenn and AFAR Junior Faculty Grant; NIH/NIDDK (R01DK133479); startup funds from the University of Wisconsin-Madison School Department of Biochemistry to JS; Hatch Grant to RJ and JS. Publicly available data from the MIDUS study was used for this research. MIDUS is funded by NIA through the John D. and Catherine T. MacArthur Foundation Research Network (P01-AG020166; U19-AG051426). MIDUS biomarker data was supported by NCATS and CTSA programs (UL1TR001409, UL1TR001881, 1UL1RR025011) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All specimen collection and testing for MIDUS are approved by the Health Sciences Institutional Review Board at the University of Wisconsin-Madison as well as the Institutional Review Boards at the University of California-Los Angeles and Georgetown University. Independent validation of MIDUS findings were conducted using 119 plasma samples from women enrolled in the SHOW study (show.wisc.edu; IRB #2013-0251, #2020-0752). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All code used in this analysis will be made freely available on Github (RJain52). Due to IRB restrictions, all data collected for the MIDUS study must be requested through the appropriate process () while SHOW data is available through SHOW study (show.wisc.edu).