Impact of cardiovascular–kidney–metabolic syndrome on clinical outcomes in bullous pemphigoid

The autoimmune blistering disease bullous pemphigoid (BP) predominantly burdens older patients, with higher all-cause and cardiovascular mortality compared with age- and sex-matched populations. Recently, the American Heart Association (AHA) proposed cardiovascular–kidney–metabolic (CKM) syndrome as a novel framework for cardiometabolic risk stratification. We aimed to establish whether baseline CKM staging predicts BP outcomes. We conducted a retrospective cohort study of patients with BP from February 2003 to August 2025, using data from electronic records in a tertiary centre. Baseline CKM stages were assigned per the AHA criteria. All-cause mortality, cardiovascular mortality and off-therapy remission were compared across subgroups using log-rank and Cox proportional hazards models. In total, 394 patients were identified, with a mean age of 80.8 years (SD 13.5) and a median follow-up of 18 months (range 6–44). Baseline disease activity by body surface area was mild in 43.4%, moderate in 42.4% and severe in 14.2%, with mucosal involvement in 9.1%. Baseline CKM staging was stage 0 in 4.8%, stage 1 in 1.5%, stage 2 in 22.8%, stage 3 in 18.8% and stage 4 in 52.0%. CKM stage progressed in 21.3% during follow-up, whereas improvement occurred in 0.5%. Overall, 22.8% achieved remission. All-cause mortality was 68.3%, with 1-, 2- and 3-year mortality rates of 33.3%, 48.9% and 58.8%, respectively. Among deaths, 62.1% were infection related and 15.6% were cardiovascular related. Risks of all-cause mortality (adjusted hazard ratio 1.49, 95% confidence interval 1.12–1.99; P = 0.006) and cardiovascular mortality (adjusted hazard ratio 2.13, 95% confidence interval 0.94–4.83; P = 0.07) were higher with baseline CKM stage 3–4. More patients with baseline CKM stage 0–2 achieved complete remission (31.3%) than with stage 3–4 (19.4%) (P = 0.01). In patients with BP, higher baseline CKM staging was associated with increased all-cause mortality, reduced remission rates and a trend towards increased cardiovascular mortality. Incorporating cardiometabolic risk stratification may help inform holistic management.

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