Women With High Genetic and Female-Specific Risks Face Greater Cardiometabolic Disease Risk: Study Finds

"Each one-unit increase in the female-specific risk score (FSRC) was linked to a 24% rise in CMD risk, with the highest risk (243%) observed in individuals with both high genetic susceptibility and female-specific risk factors. These findings highlight the importance of incorporating FSRC into risk assessments for more accurate disease prediction and prevention strategies," the researchers reported in the BMJ Journal Heart.

The influence of female-specific health factors on the development and progression of cardiometabolic disease remains an area of ongoing research, particularly in the context of genetic susceptibility. While traditional risk models primarily consider lifestyle and metabolic factors, the impact of conditions such as premature menopause, adverse pregnancy outcomes, and polycystic ovary syndrome (PCOS) is not fully understood. Recognizing this gap, Jiayu Yin, Department of Cardiology, Second Affiliated Hospital of Soochow University, Suzhou, China, and colleagues aimed to comprehensively evaluate how these female-specific factors contribute to CMD risk and interact with genetic predisposition, providing valuable insights for enhancing risk assessment and developing more effective preventive strategies for women.

For this purpose, the researchers conducted a prospective cohort study involving 150,413 women from the UK Biobank. They examined various female-specific factors, including premature menopause, adverse pregnancy outcomes, early or late menarche, multiparity, infertility, use of oral contraceptives or hormone therapy, and autoimmune diseases. A weighted female-specific risk score (FSRS) ranging from 0 to 6 was developed to quantify these risks.

The researchers analyzed the association between these female-specific factors and the occurrence and progression of cardiometabolic disease across different levels of genetic susceptibility.

The study led to the following findings:

• Over a median follow-up of 13.7 years, 16,636 cardiometabolic disease events were recorded
• Each one-point increase in the female-specific risk score (FSRS) was linked to a 24% higher risk of developing CMD.
• FSRS remained consistently associated with progression to the first CMD event, cardiometabolic multimorbidity, and mortality.
• Female-specific factors and genetic susceptibility had a synergistic effect on CMD risk.
• Women with both high female-specific and genetic risk had a 243% greater likelihood of developing CMD compared to those with low risk in both categories.
• FSRS demonstrated a strong predictive value for CMD, particularly in individuals with higher genetic susceptibility, and modestly enhanced the performance of two established cardiovascular risk algorithms.
• Phenotypic aging, inflammation, metabolic factors, renal function, and estradiol collectively accounted for 21.6% of the association between FSRS and CMD.

The findings highlight the significant role of female-specific health factors in influencing cardiometabolic disease risk, particularly in combination with genetic susceptibility.

"Integrating these factors into risk assessment models could improve predictive accuracy, allowing for more personalized and effective prevention strategies, especially for women with a high genetic predisposition to CMD," the authors concluded.

Reference:

Yin J, Li T, Yu Z, et al. Synergistic effects of female-specific conditions and genetic risk on cardiometabolic disease: a cohort studyHeart Published Online First: 26 March 2025. doi: 10.1136/heartjnl-2024-325355