Sex Differences in the Relationship Between Schizophrenia and the Development of Cardiovascular Disease

Abstract

Background: There are few data on sex differences in the association between schizophrenia and the development of cardiovascular disease (CVD). We sought to clarify the relationship of schizophrenia with the risk of developing CVDs and to explore the potential modification effect of sex differences.

Methods and results: We conducted a retrospective analysis using the JMDC Claims Database between 2005 and 2022. The study population included 4 124 508 individuals aged 18 to 75 years without a history of CVD or renal replacement therapy. The primary end point is defined as a composite end point that includes myocardial infarction, angina pectoris, stroke, heart failure, atrial fibrillation, and pulmonary thromboembolism. During a mean follow-up of 1288±1001 days, we observed 182 158 composite end points. We found a significant relationship of schizophrenia with a greater risk of developing composite CVD events in both men and women, with a stronger association observed in women. The hazard ratio for the composite end point was 1.63 (95% CI, 1.52-1.74) in women and 1.42 (95% CI, 1.33-1.52) in men after multivariable adjustment (P for interaction=0.0049). This sex-specific difference in the association between schizophrenia and incident CVD was consistent for angina pectoris, heart failure, and atrial fibrillation.

Conclusions: Our analysis using a large-scale epidemiologic cohort demonstrated that the association between schizophrenia and subsequent CVD events was more pronounced in women than in men, suggesting the clinical importance of addressing schizophrenia and tailoring the CVD prevention strategy based on sex-specific factors.

Keywords: cardiovascular disease; epidemiology; schizophrenia; sex difference.

Figure 1. Flowchart.

We identified 5 127 304 individuals with available health checkup data on physical examination and laboratory data at health checkup in the JMDC Claims Database. We excluded individuals with a history of myocardial infarction, angina pectoris, stroke, heart failure, atrial fibrillation, pulmonary embolism, and renal replacement therapy, and those with missing data on cigarette smoking, alcohol consumption, and physical activity. Finally, we obtained 4 124 508 participants in our study.

Figure 2. Subgroup analyses.

We examined the association of schizophrenia with the risk of developing cardiovascular disease between men and women stratified by age and obesity. Models were adjusted for age, body mass index, hypertension, diabetes, dyslipidemia, cigarette smoking, alcohol consumption, and physical inactivity. HR indicates hazard ratio.