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

Abstract

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.

Levels of soluble tumor necrosis factor receptor 1 and 2 are associated with survival after ST segment elevation myocardial infarction

“…When comparing our data to theirs, our control group was younger and with more female donors, and we observed lower levels of sTNFR1 but higher levels of sTNFR2, but in both studies, the sTNFR levels in the patients were significantly higher than in the control group. However, it has to be noted that the levels of sTNFR1 reported by us and others 16 – 18 in STEMI patients are relatively similar to the ones reported in prospective studies in patients with stable CAD 7 , 8 , 20 , and also to levels reported in population-based studies in older adults 9 , 11 – 13 . Thus, the level of sTNFR1 may not be of diagnostic interest on the population level in this age group.…”

“…In prospective studies, high levels of sTNFRs have been associated with cardiovascular events and increased mortality both in patients with stable coronary artery disease 7 , 8 , non-calcified atherosclerotic plaque 9 , and diabetes 10 . It has also been associated with increased risk for heart failure 11 , incident myocardial infarction 12 and cardiovascular death 13 in population-based studies.…”

Neighbourhood‐level social deprivation and the risk of recurrent heart failure hospitalizations in type 2 diabetes

“…There are several known explanations linking neighbourhood deprivation and increased cardiovascular risk. However, in addition to issues related to limited access to health care, 13 financial toxicity, 14 food insecurity 15 and lack of resources, it is also possible that there are differences in knowledge, attitudes and beliefs among socioeconomic groups that may lead to variations in lifestyles, particularly among the more vulnerable such as people with T2D. Thus, there is need to investigate the importance of neighbourhood factors (as mediators, risk enhancers, or modifiers) in the prediction of cardiovascular risk in patients with T2D.…”