JACC Heart Fail. 2026 Sep 2:103296. doi: 10.1016/j.jchf.2026.103296. Online ahead of print.
ABSTRACT
BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 are inflammatory biomarkers associated with cardiovascular disease (CVD) risk.
OBJECTIVES: This study aims to examine the associations of hs-CRP and IL-6 with risk of atherosclerotic cardiovascular disease (ASCVD) and incident heart failure (HF) and to evaluate the effect of an intensive lifestyle intervention (ILI) targeting weight loss on IL-6 in type 2 diabetes (T2D).
METHODS: Look AHEAD trial participants with T2D and overweight/obesity underwent measurement of hs-CRP (n = 1,902) and IL-6 (n = 1,507) at baseline. Associations of inflammatory biomarkers with risk of ASCVD and incident HF were evaluated using adjusted Cox models. Associations were evaluated among participants with and without CVD history. A generalized linear model compared 1-year change in IL-6 across the ILI and diabetes support and education treatment groups.
RESULTS: Median baseline hs-CRP and IL-6 were 4.04 mg/L and 2.07 pg/mL, respectively. After adjusting for demographics, CVD risk factors, and statin use, hs-CRP was not significantly associated with the risk of ASCVD or incident HF. Higher IL-6 was significantly associated with higher risk of incident HF in the overall cohort (HR: 1.43; 95% CI: 1.16-1.75 per 1-SD higher log[IL-6]) with a stronger association among those with no history of CVD (HR: 1.92; 95% CI: 1.38-2.66 per 1-SD higher log[IL-6]; IL-6 × CVD history P interaction < 0.05). The reduction in IL-6 at 1-year was greater with the ILI than with the diabetes support and education (-28.7% vs -11.8%; P = 0.01).
CONCLUSIONS: Among adults with T2D and overweight/obesity, IL-6 identified residual inflammatory risk of incident HF, particularly among adults with no CVD history. An ILI targeting weight loss reduced IL-6 over 1-year of follow-up. (Look AHEAD: Action for Health in Diabetes [Look AHEAD]; NCT00017953).
PMID:42687462 | DOI:10.1016/j.jchf.2026.103296