Association of inflammatory markers with incident heart failure or cancer in the HUNT3 and Health ABC population studies

Abstract

Abstract Aims To investigate the relationship between chronic low-grade inflammation, as measured by high-sensitivity C-reactive protein (hsCRP) levels, and incident heart failure (HF) or cancer. Methods and results We assessed the relationship between baseline hsCRP concentrations and subsequent HF or cancer in two community-based cohorts, the Trøndelag Health Study (HUNT3) and the Health, Aging and Body Composition (ABC) study. In the latter, the analysis was replicated with interleukin (IL)-1, IL-6, or tumour necrosis factor (TNF)-α instead of hsCRP. In HUNT3, hsCRP was measured in 47 163 subjects (mean age 52.3 ± 15.8 years). During a median follow-up of 12.1 years, 2034 (4.3%) individuals developed HF and 5024 (10.7%) cancer, with 442 (0.9%) being diagnosed with both. After adjusting for age, male sex, diabetes, obesity, previous or current smoking, and comorbidities, elevated baseline hsCRP was associated with a higher risk of HF or cancer [hazard ratio (HR) 1.09; 95% confidence interval (CI), 1.07–1.10]. In the Health ABC study, hsCRP levels were assessed in 2803 participants, who had a mean age of 72.6 ± 2.9 years and a higher burden of comorbidities than in HUNT3. During a median follow-up of 8.2 years, HF and cancer were diagnosed in 346 (12.3%) and 776 (27.7%) subjects, respectively, with 77 (2.7%) having both conditions. After adjusting for the same variables used for the HUNT3 cohort, hsCRP remained significantly associated with incident HF or cancer (HR 1.11; 95% CI, 1.05–1.18), as were IL-1 (HR 1.15; 1.07–1.24), IL-6 (HR 1.09; 1.02–1.17), and TNF-α (HR 1.15; 1.07–1.24). Conclusion A state of chronic, low-grade inflammation captured by an increase in hsCRP levels is associated with an increased risk of developing HF or cancer, with potential implications for clinical trials with anti-inflammatory therapies.