Association of systemic inflammatory indicators with incident valvular heart disease: a prospective analysis of the UK Biobank

BACKGROUND: Systemic inflammation has been implicated in valvular degeneration, but prospective evidence across major non-rheumatic valvular phenotypes remains limited. We investigated the associations of circulating inflammatory indicators with incident valvular heart disease in the UK Biobank. METHODS: This prospective cohort study included 250,532 participants free of cardiovascular disease, valvular heart disease, and autoimmune disease at baseline. Baseline systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-platelet ratio (NPR), lymphocyte-to-monocyte ratio (LMR), and C-reactive protein were assessed. Multivariable Cox proportional hazards models were used to examine associations with clinically diagnosed incident aortic stenosis (AS), mitral regurgitation (MR), aortic regurgitation (AR), and valve-related events. Restricted cubic spline analyses, subgroup analyses, and sensitivity analyses were performed. RESULTS: Over a median follow-up of 13.22 years, incident AS occurred in 1,904 participants, incident MR in 2,140, and incident AR in 757; 1,369 valve-related events were also recorded. Higher SIRI was associated with increased risks of AS (hazard ratio [HR] per 1-standard deviation [SD], 1.07; 95% CI, 1.03-1.11), MR (1.10; 1.05-1.14), and valve-related events (1.08; 1.03-1.13). Higher LMR was associated with lower risks of AS (0.91; 0.86-0.96), MR (0.93; 0.89-0.98), and valve-related events (0.88; 0.82-0.94). NPR was positively associated with MR and valve-related events, whereas no indicators showed a clear association with AR after full adjustment. These patterns were broadly consistent across dose-response, subgroup, and sensitivity analyses. CONCLUSIONS: Systemic inflammatory indices, particularly SIRI and LMR, were independently associated with incident AS, MR, and valve-related events, whereas no clear association was detected for AR. These findings support a phenotype-specific relationship between systemic inflammation and non-rheumatic valvular heart disease.