Interaction of Impaired Coronary Flow Reserve and Cardiomyocyte Injury on Adverse Cardiovascular Outcomes in Patients Without Overt Coronary Artery Disease
Background—Minimally elevated serum cardiac troponin (Tn) reflects myocardial injury and is associated with increased mortality, even absent coronary artery disease (CAD). We sought to investigate the relationship between low-level Tn elevation and impaired coronary flow reserve (CFR), an integrated measure of coronary vasomotor function, and assess their contributions to adverse outcomes in patients without overt CAD.
Methods and Results—Consecutive patients (N=761) undergoing evaluation for suspected CAD with Tn before stress myocardial perfusion positron emission tomography (PET), were followed (median 2.8 years) for major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction or late revascularization. Patients with flow-limiting CAD, left ventricular ejection fraction (LVEF) <40%, and/or revascularization within 60 days of imaging were excluded. CFR was quantified from stress/rest myocardial blood flow using PET. Compared to patients with negative Tn, those with at least one positive Tn (n=97) had higher pretest clinical scores, more renal dysfunction, and lower LVEF and CFR. In adjusted analysis, impaired CFR remained independently associated with positive Tn (odds ratio 2.18, 95%CI 1.37-3.47, P=0.001), and both impaired CFR and positive Tn independently associated with MACE (hazard ratio 2.25; 95%CI 1.31-3.86; P=0.003 and 2.42; 95%CI 1.34-4.40; P=0.004, respectively). Impaired CFR and positive Tn identified patients at highest risk of MACE (log-rank P<0.0001), with a significant interaction (P<0.007) seen between CFR and Tn.
Conclusions—In patients without overt CAD, impaired CFR independently associated with minimally elevated Tn and MACE. Impaired CFR, here reflecting microvascular dysfunction, modified the effect of a positive Tn on adverse outcomes.
- Received February 25, 2014.
- Revision received November 3, 2014.
- Accepted December 1, 2014.