Circulating TNFrII levels predict incidence of ischemic heart disease and total mortality, independently of intima media thickness and pulse wave velocity in male with type 2 diabetes.

New and clinically useful markers of cardiovascular risk are of great importance in patients with type 2 diabetes since cardiovascular disease is a major cause of death in these patients. We analyzed inflammatory markers and other risk factors for heart disease in 761 patients who participated in the CARDIPP-study, Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care. All participants had type 2 diabetes and were 55-66 years old at recruitment during the years 2005-2008. Patients were followed for incidence of stroke, myocardial infarction, or death from cardiovascular disease until the end of the year 2018 using the national Swedish Cause of Death and Hospitalization Registries. Besides traditional risk-markers for vascular disease, we also measured carotid-femoral pulse-wave velocity and intima-media thickness of carotid arteries. During a median period of 13 years, 165 men and 65 women died or were hospitalized for ischemic heart disease and stroke. TNFrII showed statistically significance as a risk factor for stroke, ischemic heart disease, and total mortality in male patients with diabetes type 2, independently of age, diabetes duration, BMI, Hba1c, systolic blood pressure, triglycerides, IMT and PWV (p = 0.002, HR 2.70, CI 1.42:5.13, p = 0.002). Circulating TNFrII levels failed to present a similar correlation in women (p = 0.48, CI 0.48:4.84). TNFrII stayed significant in males when HDL/LDL-ratio, CRP and smoking were added to the statistical analysis. Our data support the use of serum TNFrII in male type 2 diabetes patients to add independent prognostic information in terms of mortality and heart disease independently of other strong and well-established risk markers including cholesterol, inflammatory cytokines, PWV and IMT.Trial registration: ClinicalTrials.gov NCT01049737.