Study Population

The present study was an observational, case–control, and comparative study. The relationship between the FAR and the presence of CSF was investigated. Approximately 2500 participants who underwent elective diagnostic coronary angiography at our institution were scanned to identify patients with apparent CSF. The indications for coronary angiography were either the presence of typical angina pectoris or positive or equivocal results from noninvasive screening tests for myocardial ischemia. We selected 65 consecutive patients (24 males and 39 females; mean age, 57.6 + 10.2 years) diagnosed with CSF without any obstructive atherosclerotic lesions (CSF group), 65 consecutive patients (27 males and 34 females; mean age, 55.1 + 10.7 years) with completely normal coronary arteries (control group), and 65 consecutive patients (44 males and 21 females; mean age, 59.6 + 10.5 years) who were catheterized during the same study period and who had ≥50% stenotic lesions on coronary angiogram (CAD group).

The following patients were excluded: those who developed secondary CSF following percutaneous coronary angioplasty, those who experienced myocardial infarction or had coronary artery bypass grafting surgery, those with significant organic valvular heart disease, congestive heart failure, congenital heart disease, atrial fibrillation, hypo/hyperthyroidism, any known collagen vascular disease, any known hematologic disease including anemia (hemoglobin level <12 g/dL in women or <13 g/dL in men according to World Health Organization criteria), any autoimmune or neoplastic disease, chronic kidney (creatinine >1.5 mg/dL) or hepatic failure (aspartate transaminase or alanine transaminase levels more than 3 times the normal value) or actively infectious diseases (history of any acute infection in the last 10 days), and those receiving active treatment with any antithrombocyte drugs except for acetylsalicylic acid, anticoagulants, or steroids. Patients with plasma d-dimer levels above the normal range were also excluded.

All cases with CSF included in the study were patients with primary CSF. Patients with secondary CSF were excluded from the study. In this context, cases with slow flow due to Percutaneous Coronary Intervention (PCI) (including no-reflow cases), cases with CSF due to coronary thromboembolism (including cases with microbubble during coronary angiography), cases with CSF due to coronary ectasia, patients with visible coronary atherosclerotic plaques, and patients with a history of substance use that may cause coronary spasm (eg, cocaine) were excluded from the study.¹⁶ In addition, cases with secondary CSF associated with bradycardia and / or hypotension were excluded from the study. All patients who were hypotensive or bradycardic during coronary angiography were excluded from the study.

The study protocol was approved by the local ethics committee, and written informed consent was obtained from all patients. The study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice and International Conference on Harmonization guidelines.