Gender Variations in Cardiovascular–Kidney–Metabolic Risk Factors and Degenerative Valvular Heart Disease

Overview

This large UK Biobank study of over 436,000 adults identified hypertension as the leading cardiovascular–kidney–metabolic (CKM) risk factor for degenerative valvular heart disease (VHD) in both sexes. Women exhibited higher risks of specific VHD subtypes associated with obesity, chronic kidney disease, hypertension, and hypertriglyceridaemia compared to men. Tailoring prevention strategies by sex may improve outcomes.

Background

Degenerative valvular heart disease (VHD) is a growing global health issue with increasing prevalence due to aging populations. Current treatments are limited to advanced-stage interventions, with no medications to halt progression. The cardiovascular–kidney–metabolic (CKM) health framework highlights the importance of early multidisciplinary management of interconnected risk factors such as hypertension, diabetes, obesity, dyslipidaemia, and chronic kidney disease (CKD). Prior studies have not comprehensively assessed these risk factors together or explored sex differences in their impact on VHD.

Data Highlights

Incidence rates per 10,000 person-years (men vs women): Aortic Stenosis (11.18 vs 5.42), Aortic Regurgitation (3.64 vs 2.19), Mitral Regurgitation (10.39 vs 6.94).

Population-attributable risk (PAR) of hypertension for incident VHD subtypes in women vs men: AS (29.07% vs 25.17%), AR (24.21% vs 16.51%), MR (19.55% vs 13.01%).

Key Findings

• Hypertension was the largest attributable risk factor for incident degenerative VHD in both sexes.
• Women had higher risks of aortic valve stenosis when obese compared to men (HR 1.17).
• Women with chronic kidney disease had increased risk of aortic valve regurgitation compared to men (HR 1.59).
• Women with hypertension or hypertriglyceridaemia had higher risk of mitral valve regurgitation than men (HR 1.25 and 1.22, respectively).
• Over 81% of participants had at least one CKM risk factor at baseline, highlighting the high prevalence of these conditions in the general population.
• Sex-specific differences in CKM risk factor impact suggest the need for gender-tailored prevention strategies for degenerative VHD.

Clinical Implications

Clinicians should prioritize hypertension management as a key strategy to reduce degenerative VHD risk in both men and women. Additionally, recognizing that women may have heightened vulnerability to certain VHD subtypes in the presence of obesity, CKD, hypertension, or hypertriglyceridaemia can guide personalized risk assessment and targeted interventions. Early multidisciplinary approaches addressing the full spectrum of CKM risk factors may improve prevention and delay progression of VHD.

Conclusion

This study underscores the significant role of CKM risk factors, particularly hypertension, in the development of degenerative VHD and reveals important sex differences in risk profiles. Tailoring prevention efforts by gender holds promise for enhancing the effectiveness of strategies to mitigate the growing burden of VHD.

References

1. Bernard & Aboyans 2023 -- Valves from Venus, valves from Mars?