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

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 Trondelag 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)-alpha 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-alpha (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. There is an increasing recognition that cardiovascular (CV) risk factors portend an increased risk of both heart failure (HF) and cancer. Chronic, low-grade inflammation might represent a shared pathogenic pathway underlying the association between these risk factors, HF, and malignancy. The biomarker high-sensitivity C-reactive protein (hsCRP) might add prognostic information on CV and cancer risk by capturing this inflammatory state. In this study, we analysed the association of inflammation, as assessed by baseline measurement of hsCRP, and the risk of developing HF and cancer in two community-based prospective studies, the Trondelag Health Study (HUNT3) and the Health, Aging and Body Composition (Health ABC) study. In these cohorts, comprising more than 50 000 individuals, inflammation at baseline was associated with an increased risk of incident HF or cancer during a median follow-up of 8-12 years, after adjusting for traditional risk factors and comorbidities.In the Health ABC study sample, three inflammatory markers other than hsCRP, namely interleukin (IL)-1, IL-6, or tumour necrosis factor alpha, performed similarly to hsCRP in predicting the risk of incident HF or cancer.These results provide insights into the interconnection between HF and cancer and reinforce the concept that low-grade, chronic inflammation promotes the development of both HF and cancer and, thereby, might be targeted for prevention of either condition. Furthermore, our findings confirm the reliability of hsCRP as a biomarker to select individuals who may benefit from anti-inflammatory treatments to reduce CV and cancer events.