Sex Differences, Genetic and Environmental Influences on Dilated Cardiomyopathy

Area of Science:

• Cardiology
• Genetics
• Immunology

Background:

• Dilated cardiomyopathy (DCM) is a major cause of heart failure, characterized by left ventricular dilation and impaired systolic function.
• Etiologies of DCM are diverse, including genetic factors, infections, inflammation, autoimmune diseases, and toxic exposures.
• Genetic variants, particularly in TTN (Titin), are implicated in 20-50% of DCM cases.

Purpose of the Study:

• To investigate sex differences in the prevalence and pathogenesis of dilated cardiomyopathy (DCM).
• To review existing literature reporting sex-specific data for idiopathic and familial/genetic DCM.
• To explore potential biological mechanisms underlying the observed male predominance in DCM.

Main Methods:

• Systematic literature search for studies reporting sex-specific data on idiopathic or familial/genetic DCM.
• Analysis of sex ratios from 31 studies on non-genetic DCM and 7 studies on familial/genetic DCM.
• Review of basic and clinical research on sex differences in physiology, immune response, and fibrosis relevant to DCM.

Main Results:

• Non-genetic DCM showed an average male to female ratio of 2.5:1.
• Familial/genetic DCM exhibited an average male to female ratio of 1.7:1.
• No studies reviewed reported a higher prevalence of DCM in females compared to males.

Conclusions:

• Males are disproportionately affected by dilated cardiomyopathy compared to females across both genetic and non-genetic forms.
• Sex-based differences in physiology, immune responses, and fibrotic processes may contribute to the increased susceptibility of males to DCM.
• Further research is warranted to elucidate the specific mechanisms driving sex disparities in DCM pathogenesis.