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Sex-Based Differences in Cardiometabolic Biomarkers
Jeanney Lew1, Monika Sanghavi1, Colby R Ayers1
1From Departments of Medicine (J.L., M.S., D.K.M., M.O.G., I.N., J.D.B., A.K., A.R., J.A.d.L.) and Clinical Sciences (C.R.A., D.K.M., J.D.B.), UT Southwestern Medical Center, Dallas, TX; Division of Medicine, Akershus University Hospital, Lørenskog, and University of Oslo, Norway (T.O.); Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany (D.A.); and Department of Cardiovascular Medicine, University of Oxford, United Kingdom (D.A.).
Insights
Cardiovascular disease (CVD) biomarker profiles significantly differ between men and women. These sex-based differences are most notable in biomarkers related to obesity, endothelial dysfunction, inflammation, and cardiac stress, warranting further investigation into CVD development.
Area of Science:
- Cardiovascular Medicine
- Biomarker Research
- Sex Differences in Health
Background:
- Limited data exist comparing cardiovascular disease (CVD) biomarker profiles between sexes in the general population.
- Understanding sex-based differences in biomarkers is crucial for personalized CVD risk assessment and management.
- Previous studies have not comprehensively analyzed multiple biomarker categories across distinct pathophysiological pathways.
Purpose of the Study:
- To analyze sex-based differences in a wide array of biomarkers reflecting distinct pathophysiological pathways.
- To account for confounding factors such as CVD risk factors, body composition, and cardiac morphology in the comparison.
- To identify specific biomarkers that exhibit significant sex-based variations in the general population.
Main Methods:
- A cross-sectional analysis of the Dallas Heart Study, a multiethnic population-based cohort.
- Evaluation of associations between sex and 30 distinct biomarkers across 6 pathophysiological categories.
- Multivariable linear regression models were adjusted for age, race, CVD risk factors, kidney function, insulin resistance, body composition, and cardiac morphology.
Main Results:
- Significant sex-based differences were observed in multiple biomarker categories, including lipids, adipokines, inflammation, endothelial dysfunction, myocyte injury/stress, and kidney function.
- Women exhibited higher levels of HDL cholesterol, leptin, d-dimer, and NT-proBNP, while men had higher levels of LDL cholesterol, adiponectin, and hs-Troponin T.
- Adjusted models revealed distinct sex-specific patterns in biomarkers related to adiposity, endothelial function, inflammation, and cardiac stress.
Conclusions:
- Biomarker profiles demonstrate significant sex-based differences in the general population.
- These differences are particularly pronounced for biomarkers associated with adiposity, endothelial dysfunction, inflammatory cell recruitment, and cardiac stress/injury.
- Further research is necessary to determine if these biomarker-defined pathophysiological processes contribute to sex-based disparities in CVD development and outcomes.
Background:
Few data are available comparing cardiovascular disease (CVD) biomarker profiles between women and men in the general population. We analyzed sex-based differences in multiple biomarkers reflecting distinct pathophysiological pathways, accounting for differences between women and men in CVD risk factors, body composition, and cardiac morphology.
Methods:
A cross-sectional analysis was performed using data from the Dallas Heart Study, a multiethnic population-based study. Associations between sex and 30 distinct biomarkers representative of 6 pathophysiological categories were evaluated using multivariable linear regression adjusting for age, race, traditional CVD risk factors, kidney function, insulin resistance, MRI and dual-energy x-ray absorptiometry measures of body composition and fat distribution, and left ventricular mass.
Results:
After excluding participants with CVD, the study population included 3439 individuals, mean age 43 years, 56% women, and 52% black. Significant sex-based differences were seen in multiple categories of biomarkers, including lipids, adipokines, and biomarkers of inflammation, endothelial dysfunction, myocyte injury and stress, and kidney function. In fully adjusted models, women had higher levels of high-density lipoprotein cholesterol and high-density lipoprotein particle concentration, leptin, d-dimer, homoarginine, and N-terminal pro B-type natriuretic peptide, and lower levels of low-density lipoprotein cholesterol, adiponectin, lipoprotein-associated phospholipase A2 mass and activity, monocyte chemoattractant protein-1, soluble endothelial cell adhesion molecule, symmetrical dimethylarginine, asymmetrical dimethylarginine, high-sensitivity troponin T, and cystatin C.
Conclusions:
Biomarker profiles differ significantly between women and men in the general population. Sex differences were most apparent for biomarkers of adiposity, endothelial dysfunction, inflammatory cell recruitment, and cardiac stress and injury. Future studies are needed to characterize whether pathophysiological processes delineated by these biomarkers contribute to sex-based differences in the development and complications of CVD.
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