Sex differences in the risk of incident systemic sclerosis: a nationwide population-based study with subgroup analyses

Although higher prevalence of systemic sclerosis (SSc) in women than in men is well-known, it is unclear to what degree women are at higher risk of developing incident SSc. This study aims to assess the risk of incident SSc comparing women vs. men, and to identify subsets of individuals in whom the risk difference according to sex is more prominent. An analysis of a Korean nationwide cohort of 9,894,996 individuals was conducted. All individuals were followed up from 2009 to 2019. Cox proportional hazard models were used to assess the risk of incident SSc comparing women vs. men. Subgroup analysis was conducted by stratifying individuals according to multiple covariates. The absolute risk of SSc in men (i.e., background risk) was 0.004% (95% CI 0.003-0.004), and the absolute risk of SSc in women was 0.025% (95% CI 0.023-0.027). The absolute risk difference between women and men was 0.021% (95% CI 0.019-0.024). Women had a significantly higher risk of incident SSc than men (adjusted hazard ratio [aHR], 5.275; 95% confidence interval, 4.346-6.403). The effect size was more pronounced in middle-aged individuals (aHR 5.020 [< 40 years] vs. 5.868 [40-64 years] vs. 2.734 [≥ 65 years]; p-interaction < 0.001); those without abdominal obesity (aHR 5.863 vs. 3.658; p-interaction = 0.005); those who did not exercise regularly (aHR 5.701 vs. 3.932; p-interaction = 0.030); and those without hypertension (aHR 5.996 vs. 4.053; p-interaction = 0.010) or dyslipidemia (aHR 5.857 vs. 3.330; p-interaction = 0.001). Women had a 5-fold higher risk of incident SSc than men. The higher risk was more prominent in middle-aged individuals, those without abdominal obesity, those who do not exercise regularly, and do not have hypertension or dyslipidemia.