The inflammatory biomarker interleukin (IL)-6 identified residual inflammatory risk of incident heart failure (HF) in patients with type 2 diabetes (T2D) and overweight/obesity, particularly among those with no history of cardiovascular disease, according to results of a Look AHEAD ancillary study published Sept. 3 in JACC: Heart Failure. Furthermore, an intensive lifestyle intervention (ILI) targeting weight loss, compared with diabetes support and education alone, reduced IL-6 over one year of follow-up.

This ancillary study of a subset of Look AHEAD trial participants collected baseline measurements for the inflammatory biomarkers hs-CRP (n=1,902; median baseline, 4.04 mg/L) and IL-6 (n=1,507; median baseline, 2.07 pg/mL). In the hs-CRP cohort, participants had a mean age of 58 years and 58% were women; the IL-6 subgroup had a comparable demographic profile.

Results showed that over a median follow-up of 12 years, 5% of participants had an incident HF event and 19% had a composite ASCVD event, including nonfatal myocardial infarction, nonfatal stroke, cardiovascular death or hospitalization for angina. After adjustment for demographic, cardiovascular disease risk factors and statin use, a level of high IL-6 was not independently associated with ASCVD but was significantly associated with higher risk of incident HF among the overall cohort (HR, 1.43), with a stronger association among those with no history of cardiovascular disease (n=1,323; HR, 1.92; p_int<0.05).

After the same full adjustment, hs-CRP was not independently associated with risk of ASCVD or incident HF. Risk of HF was highest among participants with both high hs-CRP and high IL-6, although IL-6 appeared more strongly associated with HF risk when the biomarkers were discordant.

Investigators Kershaw V. Patel, MD, and colleagues write these findings indicate that IL-6 may be superior to hs-CRP as a biomarker for identifying residual inflammatory risk of HF. It could help identify patients who may benefit from therapies targeting this risk and enhance the efficiency of clinical trial design.

Additionally, the reduction of IL-6 at one year was greater with ILI than diabetes support and education (–28.7% vs. –11.8%; p=0.01). "These findings suggest that weight loss may be an important factor related to the reduction in inflammation and that reduction in weight and inflammation may potentially explain some of the cardiovascular benefits observed with incretin-based therapies," write Patel and colleagues. "This is particularly relevant considering the growing role of weight loss therapies among adults with T2D and overweight or obesity."