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

Tony Dong, Graham Bevan, David A. Zidar, Miguel Cainzos Achirica, Khurram Nasir, Imran Rashid, Sanjay Rajagopalan, Sadeer Al-Kindi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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 addition-al 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 com-posite 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 mul-tivariable 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.

Original languageEnglish (US)
Pages (from-to)135-148
Number of pages14
JournalPathogens and Immunity
Issue number2
StatePublished - 2021


  • Cardiovascular risk stratification
  • Coronary calcium score
  • MESA
  • Soluble tumor necrosis factor receptor
  • TNF alpha

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Biology
  • Microbiology (medical)
  • Infectious Diseases


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