Abstract
The prevalence and progression of cardiovascular disease (CVD) are significantly influenced by low-grade chronic inflammation. Our aim was to investigate the association of blood-count-based inflammatory markers with atrial fibrillation (AF), heart failure (HF), and cardiovascular mortality. We utilized prospective follow-up data from the UK Biobank, including 334,674 individuals (aged between 39 and 70 years) free of HF and AF at baseline. The exposures were blood-count-based inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), aggregate index of systemic inflammation (AISI), and systemic inflammatory response index (SIRI), which were computed using leukocyte counts (lymphocytes, monocytes, and neutrophils). The primary outcomes were the occurrence of AF, HF and cardiovascular-related deaths. Cox proportional hazards models were employed to determine hazard ratios (HRs) and their 95% confidence intervals (CIs) for assessing the longitudinal association between inflammatory markers and the development of cardiovascular events. Survival analysis was illustrated using Kaplan-Meier curves with the occurrence of AF, HF and CVD mortality as the endpoint. There were 16,994 incidences of AF and 7342 incidences of HF over a median follow-up of 10.4 years (range, 2.4-12.1). Additionally, there were 3434 deaths from CVD causes. A higher risk of cardiovascular mortality was significantly associated with NLR, MLR, SIRI, AISI, and SII in multivariable adjusted models (HR 1.44, 95% CI 1.30-1.58; HR 1.46, 95% CI 1.31-1.61; HR 1.57, 95% CI 1.41-1.75; HR 1.57, 95% CI 1.41-1.73; and HR 1.36, 95% CI 1.24-1.49, respectively). Furthermore, our analysis revealed positive associations between NLR, MLR, SIRI, and AISI and the risk for AF (HR 1.18, 95% CI 1.13-1.24; HR 1.19, 95% CI 1.14-1.25; HR 1.22, 95% CI 1.16-1.27; and HR 1.08, 95% CI 1.03-1.13, respectively), and HF (HR 1.42, 95% CI 1.33-1.52; HR 1.28, 95% CI 1.19-1.37; HR 1.45, 95% CI 1.35-1.56; and HR 1.32, 95% CI 1.23-1.41, respectively). Furthermore, the SII demonstrated a positive association with HF (HR 1.24, 95% CI 1.16-1.32). However, the association with AF was not statistically significant (HR 1.01, 95% CI 0.97-1.06). In summary, our research provides preliminary evidence that blood cell indices associated with the systemic inflammatory response, may serve as potential biomarkers for the risk of developing AF, HF and CVD mortality. Additionally, it is likely that a systemic inflammatory-immune response existed before the clinical diagnosis. Identifying high-risk populations based on the levels of inflammatory markers could help reduce the risk of death and prevent the onset of AF and HF. Further investigation is warranted to determine whether reducing inflammatory markers causally improves cardiovascular outcomes.