Headache among patients undergoing cardiac stress testing: Prevalence, clinical characteristics, and identification of myocardial ischemia

Abstract Background Cardiac cephalalgia is an uncommon secondary headache disorder caused by myocardial ischemia and may occur with or without typical anginal symptoms. Most available literature consists of isolated case reports, and data regarding its prevalence among patients undergoing evaluation for coronary artery disease (CAD) are limited. Objective To determine the prevalence and clinical characteristics of headache among patients undergoing treadmill stress test(ing) (TMT) and to identify patients with cardiac cephalalgia. Methods This cross‐sectional study with a nested case series was conducted in the cardiology‐stress testing laboratory of a tertiary care teaching hospital in Western India between August 2024 and January 2026. Consecutive adult patients undergoing TMT were screened. Demographic characteristics, cardiovascular symptoms, headache history, cardiovascular risk factors, stress‐test findings, laboratory investigations, and cardiac evaluations were recorded. Patients developing headache during TMT underwent detailed assessment for cardiac cephalalgia according to the International Classification of Headache Disorders, 3rd Edition (ICHD‐3) based on clinical criteria. Clinical characteristics of patients with cardiac cephalalgia were compared with those of patients with other exertional headaches. Results A total of 243 patients underwent TMT during the study period. After exclusion of 22 patients, 221 patients were included in the final analysis. Sixty‐nine of 221 patients (69/221, 31.2%) had a positive TMT suggestive of myocardial ischemia. Overall, headache occurred in 21/221 (9.5%; 95% confidence interval [CI], 6.0%–14.1%) patients, including 8/69 (11.6%) TMT‐positive patients and 13/152 (8.6%) TMT‐negative patients. Cardiac cephalalgia fulfilling ICHD‐3 diagnostic criteria was identified in 8/221 (3.6%; 95% CI, 1.6%–7.0%) patients, representing 8/69 (11.6%; 95% CI, 5.1%–21.6%) of TMT‐positive patients and 8/21 (38.1%; 95% CI, 18.1%–61.6%) patients reporting headache. Patients with cardiac cephalalgia had a mean age of 63.9 ± 5.8 years, and 75% (6/8) of patients were male. Seven of eight patients (7/8; 87.5%) reported headache episodes during the preceding 3 months, including three with occasional exertional headaches; however, none sought medical attention because of headache. All patients developed their characteristic headache during TMT in association with ischemic electrocardiograph (ECG) changes. Four of eight patients (4/8; 50%) did not report typical anginal chest pain. Compared with patients with other exertional headaches, patients with cardiac cephalalgia were older and had a greater burden of cardiovascular risk factors and adverse cardiometabolic profiles in these exploratory analyses. Coronary angiography demonstrated significant CAD in all eight patients. At the 8‐week follow‐up, headache resolved completely in 7/8 (87.5%) patients and improved markedly in the remaining 1/8 (12.5%) patient. Conclusions Headache occurred in approximately one in 10 patients undergoing TMT, with a similar prevalence among TMT‐positive and TMT‐negative patients. Cardiac cephalalgia was identified in a small but clinically important subset of patients with myocardial ischemia based on reproduction of headache during stress testing, objective evidence of ischemia, and angiographic confirmation of CAD. Recognition of cardiac cephalalgia is important because treatment of the underlying CAD can substantially improve or resolve headache.