New Study Shows Levels of Circulating Cardiovascular Biomarkers Are Different in Men and Women

A study led by Dr. Emily Lau published in the Journal of the American College of Cardiology showed that there were significant differences in circulating biomarkers in men and women. These differences in biomarker levels may reflect the distinct pathways implicated in the pathogenesis of cardiovascular disease in men and women.

The difference in cardiovascular disease risk between the two sexes has been well established but incompletely understood. Women are less likely to have ischemic heart disease, less likely to present with acute coronary syndrome, less likely to have flow limiting epicardial coronary disease but have an increased risk of microvascular dysfunction. Circulating biomarkers of cardiovascular disease may give an idea as to the different pathways contributing to cardiovascular disease. The investigators aimed to assess the differences in biochemical profiles of inflammation, metabolic dysfunction, coagulation, fibrosis and lipid metabolism in patients without cardiovascular disease. Additionally, they assessed if any of the given biomarkers were later associated with an increased risk of cardiovascular disease, and whether or not this was modified by sex.

The cohort consisted of all offspring of the first generation of the Framingham Heart Study population who attended an examination between 1998 and 2001 and all third-generation participants who attended an examination between 2002 and 2005. Participants with missing data or who did not have their biomarkers measured were excluded. A total of 7,184 individuals were included in the final study sample (3,895 women and 3,289 men). While the mean age was the same between the two sexes, men had a higher systolic and diastolic blood pressure, more likely to be on an antihypertensive, more likely to be diabetic, had a higher high-density lipoprotein (HDL) level, a higher estimated glomerular filtration rate, and a higher body mass index.

Of the 71 biomarkers measured, 61 (86%) were significantly different in men and women. Of the biomarkers that were different, 37 were higher in women. The largest differences in biomarkers, where women had higher levels, was noted with leptin, ceruloplasmin, and hemopexin. The investigators also noted that there were higher concentrations of CD56, myoglobin, and GMP140 in men. Overall, biomarkers that represented pathways associated with inflammation, immune response, and adiposity were overrepresented in women while pathways associated with fibrosis and platelet hemostasis were overrepresented in men. The authors also investigated the effect of menopause and found that the differences in biomarkers were greatest in premenopausal women and men as compared to post-menopausal women and men, especially those on hormone replacement therapy. Over an average follow up of 12 years, sex modified the association between certain biomarkers and certain cardiovascular events. These biomarkers included ApoB, CD14, and tetranectin and the occurrence of heart failure; REG1A, TSC22D3 and PPBP and cardiovascular death; and REG1A, CD56 and leptin, and all-cause mortality.

The study demonstrated that there is a difference in the biomarker profile between men and women, that the difference is greatest between pre-menopausal women and men, and that sex modified the association between some of these biomarkers and the occurrence of cardiovascular outcomes. When discussing the results of the study, Dr. Lau wrote, “several biomarkers were differentially associated with incident CVD events in women compared with men, including ApoB, CD14, and PPBP. Overall, our findings highlight widespread differences in CVD proteomic biomarkers representing inflammation, metabolism, coagulation, and fibrosis pathways and suggest that sex differences in clinical disease are complex and multifactorial in etiology.” It is important to note that the study still has its limitations. Because of the observational nature of this study, no statements about causation could be made. Additionally, when looking at the modulatory effect of sex on biomarkers and outcomes, the findings are exploratory. Regardless, clarifying how the biological pathways between men and women differ could ultimately improve on how cardiovascular disease is treated and prevented.