Cardiometabolic Comorbidity Burden and Circulating Biomarkers in Patients with Chronic Coronary Disease in the ISCHEMIA Trials

Cardiometabolic comorbidities, diabetes (DM), hypertension (HTN), and obesity, contribute to cardiovascular disease (CVD). Circulating biomarkers facilitate prognostication for patients with CVD. We explored the relationship between cardiometabolic comorbidity burden in patients with chronic coronary disease (CCD) and biomarkers of myocardial stretch, injury, inflammation, and platelet activity. We analyzed participants from the ISCHEMIA Trials biorepository with plasma biomarkers (NT-proBNP, hs-cTnT, hs-CRP, IL-6, sCD40L, and GDF-15) and clinical risk factors [hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and body mass index (BMI)] at baseline. We defined cardiometabolic comorbidities as DM, HTN, and obesity at baseline. Comorbidity burden characterized by number and severity of comorbidities. Controlled comorbidities were defined as HbA1c <7% for those with DM, SBP <130 mmHg for those with HTN and BMI <30 kg/m2. Severely uncontrolled was defined as HbA1c ≥8%, SBP ≥160 mmHg, and BMI ≥35 kg/m2. We performed linear regression analyses to examine the association between comorbidity burden and log-transformed biomarker levels adjusting for age, sex, eGFR controlled for hemodialysis, and left ventricular ejection fraction. A total of 752 individuals (mean age 66, 19% female, 84% white) were included in this analysis. Self-reported Black race, current smokers, history of MI and HF had greater cardiometabolic comorbidity burden. The presence of ≥ 1 severely uncontrolled comorbidity was associated with significantly higher baseline levels of hs-cTnT, hs-CRP, IL-6, and GDF-15 compared to participants with no comorbidities. In conclusion, increasing cardiometabolic comorbidity burden in patients with CCD is associated with higher levels of circulating biomarkers of myocardial injury and inflammation.