Coronary atherosclerosis in outlier subjects at the opposite extremes of traditional risk factors: Rationale and preliminary results of the Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation (CAPIRE) study

Although it is generally accepted that cardiac ischemic events develop when coronary atherosclerosis (coronary artery disease [CAD]) has reached a critical threshold, this is true only to a first approximation. Indeed, there are patients with severe CAD who do not develop ischemic events; conversely, at the other extreme, individuals with minimal CAD may do. Similar exceptions to this paradigm include patients with diffuse CAD with a low risk factor (RF) profile and others with multiple RFs who develop only mild or no CAD. Therefore, the CAPIRE project was designed to investigate whether the specific study of these extreme outlier populations could provide clues for identification of yet unknown risk or protective factors for CAD and ischemic events. In the CAPIRE study, 481 subjects without previous symptoms or history of ischemic heart disease and normal left ventricular systolic function undergoing coronary computed tomography angiography have been selected based on coronary computed tomography angiography findings and cardiovascular RF profile. Therefore, in the whole population, 2 extreme outlier populations have been identified: (1) subjects with no CAD despite multiple RFs, and (2) at the opposite extreme, subjects with diffuse CAD despite a low-risk profile. Each subject has been characterized by clinical, anatomical imaging variables of CAD and baseline circulating biomarkers. Blood samples were collected and stored in a biological bank for further advanced investigations. The project is designed as a prospective, observational, international multicenter study with an initial cross-sectional analysis of clinical, imaging, and biomolecular variables in the selected groups and a longitudinal 5-year follow-up

Usefulness of High-Sensitivity Cardiac Troponin T for the Identification of Outlier Patients with Diffuse Coronary Atherosclerosis and Low-Risk Factors

Novel high-sensitivity assay can detect very low levels of circulating cardiac troponin (hs-cTnT) in apparently healthy subjects. Within normal range, higher levels are associated with coronary artery disease (CAD) and cardiac abnormalities commonly associated to traditional risk factors (RFs) for CAD. Therefore, we investigated the relation between circulating hs-cTnT and CAD in patients with a spectrum of RF burden aiming to assess the added value of hs-cTnT to identify "outlier" patients with CAD despite a low RF burden. Hs-cTnT was measured in 525 stable patients without previous diagnosis of ischemic heart disease with 0 to 1 RF, excluded diabetes, (low-RF group, n = 263) or \ue2\u89\ua52 RFs (multiple-RF group, n = 262) and without CAD (segment involvement score = 0) or diffuse CAD (segment involvement score >5) at coronary computed tomography angiography. Outlier patients with diffuse CAD despite low-RF burden had similar extent, severity, and plaque composition than patients with multiple RFs. Overall, hs-cTnT was measurable in 81% of patients with median value of 6.0 ng/L. In both groups, hs-cTnT concentration was higher in patients with CAD than in patients with normal coronary arteries (p <0.0001). Hs-cTnT was more accurate to detect patients with CAD in the low-RF group than in the multiple-RF group (p = 0.04). In multivariate analysis, higher level of hs-cTnT (>6 ng/L) was independently associated with CAD in low-RF group only. Despite very low circulating concentrations, hs-cTnT may identify with a good accuracy the outlier patients with diffuse CAD despite low-RF burden