High progesterone levels are associated with family history of premature coronary artery disease in young healthy adult men.

Background & Aims: The offspring of patients with premature coronary artery disease (P-CAD) are at higher risk for cardiovascular disease, compared with subjects without a family history (FH) of P-CAD. The increased risk for cardiovascular disease in subjects with FH of early-onset CAD results from unfavorable genetic variants as well as social, behavioral and environmental factors, which are more prevalent in this group. Previous studies have shown that specific sex hormone levels may be associated with the risk of cardiovascular disease. The aim of this study was to compare wide range of biochemical marker levels including i.e. the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, estradiol, testosterone and sex-hormone binding globulin (SHBG) between young healthy male adults with and without FH of P-CAD.

Methods: The study group consisted of young healthy Polish male adults enrolled in a MAGNETIC case-control study, who were recruited between July 2015 and October 2017. The inclusion criteria were as follows: male sex, age ≥18 and ≤35 years old, FH of P-CAD (cases) or no P-CAD in first-degree relatives (controls). The comparison of continuous and categorical variables was performed using the Student's t-test or the U-Mann-Whitney test, and Fisher's exact test, respectively. The correlations between FSH, LH, testosterone, progesterone, SHBG and other laboratory parameters were assessed using the Spearman rank correlation test. Both univariable and multivariable logistic regression analyses were performed to assess the association between analyzed variables and FH of P-CAD.

Results: A total of 411 subjects (223 cases and 188 controls) were included in the study. There was a higher prevalence of major cardiovascular risk factors in subjects with FH of P-CAD (smoking, higher total and LDL cholesterol levels, higher body mass index and lower HDL cholesterol level). Moreover, the offspring of patients with P-CAD had lower SHBG level, and higher LH and progesterone levels in the crude comparison, compared with individuals without FH of P-CAD. After adjustment for confounding variables, progesterone and LH were determined to be independently associated with FH of P-CAD.

Conclusion: Progesterone and LH levels are significantly associated with FH of P-CAD, independent of traditional risk factors for CAD.