Soluble Tumor Necrosis Factor Receptor 1 is Associated With Cardiovascular Risk in Persons With Coronary Artery Calcium Score of Zero

Background: A coronary artery calcium (CAC) score of zero confers a low but nonzero risk of atherosclerotic cardiovascular events (CVD) in asymptomatic patient populations, and additional risk stratification is needed to guide preventive interventions. Soluble tumor necrosis factor receptors (sTNFR-1 and sTNFR-2) are shed in the context of TNF-alpha signaling and systemic inflammation, which play a role in atherosclerosis and plaque instability. We hypothesized that serum sTNFR-1 concentrations may aid in cardiovascular risk stratification among asymptomatic patients with a CAC score of zero. Methods: We included all participants with CAC=0 and baseline sTNFR-1 measurements from the prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA). The primary outcome was a composite CVD event (myocardial infarction, stroke, coronary revascularization, cardiovascular death). Results: The study included 1471 participants (mean age 57.6 years, 64% female), with measured baseline sTNFR-1 ranging from 603 pg/mL to 5544 pg/mL (mean 1294 pg/mL ±378.8 pg/mL). Over a median follow-up of 8.5 years, 37 participants (2.5%) experienced a CVD event. In multivariable analyses adjusted for Framingham Score, doubling of sTNFR-1 was associated with a 3-fold increase in the hazards of CVD (HR 3.0, 95% CI: 1.48- 6.09, P = 0.002), which remained significant after adjusting for traditional CVD risk factors individually (HR 2.29; 95% CI: 1.04-5.06, P=0.04). Doubling of sTNFR-1 was also associated with progression of CAC >100, adjusted for age (OR 2.84, 95% CI: 1.33-6.03, P=0.007). Conclusions: sTNFR-1 concentrations are associated with more CVD events in participants with a CAC score of zero. Utilizing sTNFR-1 measurements may improve cardiovascular risk stratification and guide primary prevention in otherwise low-risk individuals.

Cardiovascular risk stratification by coronary computed tomography angiography imaging: current state-of-the-art

Current cardiovascular risk stratification by use of clinical risk score systems or plasma biomarkers is good but less than satisfactory in identifying patients at residual risk for coronary events. Recent clinical evidence puts now further emphasis on the role of coronary anatomy assessment by coronary computed tomography angiography (CCTA) for the management of patients with stable ischaemic heart disease. Available computed tomography (CT) technology allows the quantification of plaque burden, identification of high-risk plaques, or the functional assessment of coronary lesions for ischaemia detection and revascularization for refractory angina symptoms. The current CT armamentum is also further enhanced by perivascular Fat Attenuation Index (FAI), a non-invasive metric of coronary inflammation, which allows for the first time the direct quantification of the residual vascular inflammatory burden. Machine learning and radiomic features’ extraction and spectral CT for tissue characterization are also expected to maximize the diagnostic and prognostic yield of CCTA. The combination of anatomical, functional, and biological information on coronary circulation by CCTA offers a unique toolkit for the risk stratification of patients, and patient selection for targeted aggressive prevention strategies. We hereby provide a review of the current state-of-the art in the field and discuss how integrating the full capacities of CCTA into clinical care pathways opens new opportunities for the tailored management of coronary artery disease.