Underrepresentation of sex in reporting traditional and emerging biomarkers for primary prevention of cardiovascular disease: a systematic review

Background: Primary prevention of cardiovascular disease (CVD) relies on the identification of individuals at increased risk of developing cardiovascular events. Circulating biomarkers mirroring the (subclinical) disease process are valuable tools for CVD risk prediction. Evidence is accumulating that the clinical presentation and mechanisms for CVD differ between men and women. A systematic review of sex-specific data was performed on biomarker levels and their association with CVD in primary prevention in order to investigate the availability of sex-specific data and to explore for any differences in the associations between men and women.

Methods and results: PubMed MEDLINE and Embase were searched on 2 February 2014 and updated on 15 January 2015. Biomarkers included represented pathophysiological pathways of lipids, inflammation, kidney function, and of the heart. Data on patient characteristics, sex-specific biomarker levels, biomarker association with future CVD events and clinical value were extracted. Only 54 studies of 360 publications provided sex-specific information. Most of the remaining 306 publications not providing sex-specific results only corrected for sex in multivariable models. The additional clinical utility of biomarkers was reported in seven publications, one of which was stratified by sex.

Conclusion: Sex-specific data on biomarkers for CVD in the general population exist, but it is underreported. There is inconsistency in sex-specific differences in levels of traditional biomarkers and in their relation to CVD. To improve personalized cardiovascular diagnoses and care for men and women, reporting sex-specific data on clinical utility of biomarkers is crucial and should be encouraged in publications of sufficiently powered studies.