Negative Association of Smoking History With Clinically Manifest Cardiac Sarcoidosis: A Case-Control Study

BACKGROUND: The etiology of sarcoidosis is still unknown and is likely related to a genetic susceptibility to unidentified environmental trigger(s). Our group and others have extensively described a specific phenotype of primarily Caucasian patients who have clinically manifest cardiac sarcoidosis (CS). In this study, we sought to explore whether smoking is associated with this specific phenotype of sarcoidosis. METHODS: We performed a case-control study. Cases with clinically manifest CS were prospectively enrolled in the Cardiac Sarcoidosis Multi-Center Prospective Cohort Study (CHASM-CS registry; NCT01477359) and answered a standardized smoking history questionnaire. Cases were matched 10:1 with controls from the Ontario Health Study. Pretreatment positron emission tomography scans with (18)F-fluorodeoxyglucose were compared for smokers vs nonsmokers. RESULTS: Eighty-seven cases met the inclusion criteria. A total of 82 of 87 (94.3%) answered the questionnaire and were matched with 820 controls. A clear negative association of sarcoidosis and smoking was found, with 23 of 82 CS cases (28.0%) being current or ex-smokers, vs 392 of 820 controls (47.8%; P = 0.0006). CS patients with a smoking history had significantly less lifetime consumption (8.31 ± 9.20 pack-years) than the controls (15.34 ± 10.84 pack-years; P < 0.003). On (18)F-fluorodeoxyglucose-positron emission tomography scan, the mean standardized uptake value of the left ventricle was 4.2 ± 8.98 in lifetime nonsmokers vs 2.89 ± 2.07 in patients with a smoking history (P < 0.0001). CONCLUSIONS: We describe a strong negative association between smoking history and clinically manifest CS. Nonsmokers had more severe myocardial inflammation (greater mean standardized uptake value of the left ventricle) than did patients with a smoking history. Further research is needed to understand these associations and whether they have therapeutic potential.