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STUDY OBJECTIVES: Myocardial infarction with angiographically normal coronary arteries (MINC) is a life-threatening event with many open questions for physicians and patients. There are little data concerning the prognosis for patients with MINC. DESIGN: Retrospective follow-up study. SETTING: Tertiary referral center. PATIENTS: Patients with MINC were investigated and compared to age- and sex-matched control subjects with myocardial infarction due to coronary artery disease (CAD). The patients were examined clinically using stress exercise and hyperventilation tests. Migraine and Raynaud's symptoms were determined by means of a standardized questionnaire. Serum lipoproteins; the seroprevalence of cytomegalovirus, Helicobacter pylori, and Chlamydia pneumoniae infections; and the most frequent causes of thrombophilia were assessed. Measurements and results: From > 4,300 angiographies that were performed between 1989 and 1996, 21 patients with MINC were identified. The mean +/- SD patient age at the time of myocardial infarction was 42 +/- 7.5 years. When compared to control subjects (n = 21), patients with MINC had fewer risk factors for CAD. In contrast, MINC patients had more frequent febrile reactions prior to myocardial infarction (six patients vs zero patients; p < 0.05), and the migraine score was significantly higher (7.1 +/- 6.3 vs 2.2 +/- 4.1; p < 0.01). The seroprevalence of antibodies against cytomegalovirus, C pneumoniae, and H pylori tended to be higher in patients with MINC and CAD as compared to matched healthy control subjects. Three patients with MINC vs none with CAD had coagulopathy. During follow-up (53 +/- 37 months), no major cardiac event occurred in the MINC group; no patients with MINC vs nine with CAD (p = 0.0001) underwent repeated angiography. CONCLUSION: High migraine score and prior febrile infection together with a lower cardiovascular risk profile are compatible with an inflammatory and a vasomotor component in the pathophysiology of the acute coronary event in MINC patients. The prognosis for these patients is excellent.