Identification of Protective Biologic Factors in High-Risk Patients with Multiple Risk Factors, But Normal Coronary Arteries

Background: There is a distinctive group of patients, who despite suffering from multiple cardiovascular risk factors do not develop significant coronary artery disease (CAD). This discrepancy raises the question regarding potential protective mechanisms against the development of CAD. Our aim was to assess various cellular and molecular factors, in patients with multiple cardiovascular risk factors and normal coronary arteries.

Methods: We included patients aged 50-75 years, with recent coronary computed tomography angiography demonstrating normal coronaries, and a high-risk of cardiovascular disease (>10% by the ACC/AHA ASCVD). Two control groups were included: 1. patients with similar high-risk profile, but with established CAD, and 2. a group of healthy volunteers, matched by age and gender. We isolated peripheral blood mononuclear cells (PBMC), and measured endothelial progenitor cells (EPCs) levels using flow cytometry for cellular markers CD34, CD133 and function using cell culture colonies quantification (CFU). We also determined PBMC telomere length by Southern blotting technique.

Results: We recruited 48 patients, 16 in each group. There were no differences in EPCs levels between the 3 groups, as measured by CD34 and CD133. EPCs function (measured by CFU), however, was numerously higher in the study and the “healthy” group, compared with the CAD group (study and healthy groups were similar) (Figure 1). A similar pattern was observed when measuring telomere length, as the study group had longer telomeres compared with the CAD control group and similar to the healthy control group. (10.99, 11.1 and 2.7 kBase respectively, p=0.1)

Conclusions: Patients with a high risk for CAD, but anatomically normal coronary arteries, have EPCs function and telomere length which is similar to healthy volunteers, but augmented compared with patients with established CAD. These unique patterns in EPCs and telomere biological profile may contribute to the protection against CAD development in these high-risk patients.