Key result
Current smoking linked to ~141% higher major cardiovascular events risk versus never-smokers despite negative noninvasive testing.
Why the study?
It remained uncertain whether noninvasive testing results influence the relationship between smoking and cardiovascular events, and how systemic biomarkers aid risk stratification in chest pain.
Does smoking increase the risk of major adverse cardiovascular events in patients with stable chest pain despite negative noninvasive testing?
Cohort (n=9,100)
Does smoking increase the risk of major adverse cardiovascular events in patients with stable chest pain despite negative noninvasive testing?
Answers are grounded in this paper and cite their sources.
Negative noninvasive testing does not eliminate the substantial cardiovascular risk associated with smoking in patients with stable chest pain, highlighting the need for aggressive smoking cessation.
Background Although the relationship between smoking and cardiovascular events is well established, it remains uncertain whether the outcomes of noninvasive testing (NIT) influence this relationship and how systemic biomarkers may aid risk stratification in patients presenting with chest pain. Methods This study included PROMISE participants with stable chest pain and available smoking status (current, ever, or never) and NIT results (Positive NIT: ≥70% coronary stenosis on CT angiography or inducible ischemia on stress testing). Smoking was associated with systemic biomarkers (e.g., hsCRP, IL-6, MMP-9), NIT results, and major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, unstable angina), using regression and mediation models adjusted for traditional cardiovascular risk factors (median follow-up 24.4 months). Results Among 9,100 individuals (mean age 61±8 years; 53% female), 51% were ever-smokers, including 18% current smokers. Smoking was independently associated with MACE, with positive NIT mediating this relationship (current: 16%; ever: 12%, p≤0.006). Compared with never-smokers, smoking was associated with MACE despite negative NIT (current: aHR 2.41, 95%CI 1.49-3.89; ever: aHR 1.80, 95%CI 1.25-2.59), with the most pronounced differences seen in men vs. women and CV death/MI (sex interaction p=0.047). Smoking was associated with high levels of inflammatory biomarkers, particularly MMP-9 (+51%; current vs. never-smokers), which partially mediated the smoking-MACE association (current: 25%; ever: 8%, ≤0.05). Conclusions Negative NIT does not reduce smoking-associated MACE risk in patients with stable chest pain. Particularly, current smoking confers substantial residual cardiovascular risk, potentially mediated by MMP-9-related matrix remodeling not captured by standard testing, supporting aggressive smoking cessation irrespective of NIT results.
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Kerkovits et al. (2026) conducted a cohort in Stable chest pain (n=9,100). Smoking (current or ever) vs. Never-smokers was evaluated on Major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, unstable angina) (aHR 2.41, 95% CI 1.49-3.89). Current smoking was associated with a higher risk of major cardiovascular events compared with never-smokers, even in patients with negative noninvasive testing.
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