Immune-mediated inflammatory disease and coronary calcium: Elevated baseline risk and attenuated prognostic gradient

Immune-mediated inflammatory diseases (IMID) are associated with accelerated atherosclerosis, yet it is unclear whether CT coronary artery calcium scoring (CTCS) captures this excess cardiovascular risk accurately. We hypothesized that in adults undergoing CTCS, IMID modifies the relationship between coronary artery calcium (CAC) score and incident major adverse cardiac events (MACE).

Among 43,420 individuals in the CLARIFY Registry (University Hospitals Cleveland, 2014-2020) who underwent no-cost CTCS scans, we identified 545 individuals with IMID. After propensity-score matching on age, sex, race, hypertension, diabetes, and smoking status with a 2:1 ratio, 1635 matched individuals were analyzed (545 with IMID and 1090 matched non-IMID controls). CAC was categorized as 0, 1-99, 100-399, ≥400. The primary outcome of 4-point MACE was analyzed over a median 4.2-year follow-up. Cox models tested CAC categories compared to CAC 0, stratified by IMID. Additionally, a log(CAC+1) × IMID interaction term was modeled, to assess whether the risk gradient of CAC differed by IMID status.

Individuals with IMID exhibited over twice the MACE incidence of matched controls (40.8 vs 17.6 per 1000 person-years). Among those with zero CAC, those with IMID had a three-fold higher event rate (21.98 vs 7.18 per 1000 person-years). In controls, MACE risk rose stepwise with CAC, quadrupling from CAC 0 to ≥400 (adjusted HR = 4.74; p < 0.001), whereas in IMID increasing CAC conferred no significant gradient (p = 0.21). The interaction between CAC and IMID was significant (β = -0.27; HR 0.76, 95% CI 0.55-1.00), indicating an attenuated CAC-MACE relationship in IMID.

In IMID, baseline risk is elevated even with zero CAC, with attenuation of the traditional CAC-risk gradient observed in non-IMID controls. These findings suggest that, in IMID (1) a CAC score of zero may not guarantee low cardiovascular risk and (2) CAC has less incremental prognostic value than in the general population.