Leveraging circulating DNase I activity to detect silent coronary artery disease among hypertensive diabetes individuals.

Abstract

In individuals with diabetic hypertension, silent coronary artery disease (CAD) is common due to underlying chronic inflammation, but there is no biomarker to monitor this high-risk group of individuals before noticeable symptoms emerge clinically. cfDNA from dying endothelial cells triggers chronic inflammation, leading us to hypothesize that enzymes that degrade cfDNA, DNase I and/or II, could serve as more sensitive biomarkers for silent CAD. To test this, we conducted a study with 30 hypertensive diabetic patients with clinical symptoms of CAD (CAD-HTN-DM) and 30 controls without CAD (HTN-DM). Negligible serum DNase II activity was detected in both groups. Student's t test was used to compare cfDNA, DNase I activity, and groups. We observed elevated serum DNase I activity in the CAD-HTN-DM group (1.71 ± 0.1 U/mL) compared with the HTN-DM group (1.12 ± 0.1 U/mL) (P < 0.0001). Among the CAD-HTN-DM group, DNase I activity was significantly higher in patients with all three coronary arteries blocked, even though the cfDNA levels were similar in both groups. Elevated DNase I activity was associated with a 1.5-fold increased risk of major adverse cardiac events despite ongoing treatment with statins, antihypertensive medications, and antidiabetic therapies. Surprisingly, serum DNase I activity was lower in patients who suffered a myocardial infarction. By leveraging our observations, we hope that regular monitoring of serum DNase I activity will identify individuals at high risk for the clinical onset of CAD, enabling early intervention to mitigate its adverse effects and slow its progression.NEW & NOTEWORTHY Our observation suggests that the progression of cardiac disease among hypertensive patients with diabetes is associated with elevated DNase I activity that maintains optimal cfDNA levels, thereby reducing its inflammatory potential and worsening of cardiac dysfunction. Thus, DNase I activity may be both a protective factor early on and a potential biomarker for cardiac health among hypertensive patients with diabetes.