Exercise-Induced Myocardial Ischemia is Accompanied by Increased Serum Creatine Concentrations (Technical Briefs‪)‬

Coronary artery disease remains the leading cause of mortality in adults in the westernized world (1, 2). Coronary artery disease can present itself as a wide range of diseases, from uncomplicated stable angina, to unstable angina, to myocardial infarction. The diagnosis of myocardial ischemia in patients with stable angina depends on the patient's history and various technical investigations, such as electrocardiography (ECG) and stress testing. Exercise ECG is a simple and inexpensive investigation with diagnostic, prognostic, and functional information in selected populations (3). Exercise testing has an overall sensitivity of 66% and a specificity of 84% (4), but its diagnostic performance is much lower in asymptomatic individuals and females. The diagnosis and grading of unstable angina or myocardial infarction depend on biochemical markers together with clinical and electrocardiographic data (5). The currently used routine biochemical markers for the assessment of myocardial infarction or unstable angina require tissue necrosis to be detected in plasma. Serum and urine creatine concentrations have been described as markers for myocardial infarction. In contrast to other markers, creatine is a nonprotein nitrogenous compound, present in heart and skeletal muscle. It has a considerably lower molecular mass (131 Da) compared with conventional markers; release into the circulation therefore occurs at an early stage of myocardial ischemia, allowing rapid diagnosis (6, 7). We hypothesized that creatine could be released from ischemic myocardial tissue without the necessity of tissue necrosis. This study investigates the relationship between serum creatine and electrocardiographic indices during exercise testing. We recruited 47 male Caucasians with a mean (SD) age of 61 (10) years from patients referred for exercise testing. Patients referred for detection of exercise-induced arrhythmias or with major arrhythmias (pacemaker rhythm, ventricular tachycardia, or conduction disorders) during exercise, excessive increase (250 mmHg systolic, 120 mmHg diastolic) or decrease (10 mmHg systolic blood pressure) in blood pressure during exercise, myocardial infarction 6 months, and symptomatic heart failure were excluded from the study. This study was approved by the local ethics committee. All participants underwent exercise testing on an electromagnetically braked bicycle ergometer with stepwise incremental workloads [50 W + 25 W/2 min (41 individuals); 50 W + 50 W/2 min (6 individuals)]. ECG recordings were acquired during exercise and during recovery. ST-segment depression was quantified 60 ms (ST60) after the J-point in lead V5. ST-segment depression [greater than or equal to]1.5 mm (0.15 mV) was considered to be diagnostic for myocardial ischemia. ST-segment depression was adjusted to heart rate (ST/HR index) (8). Exercise was stopped on achieving the age-matched maximal exercise level, severe ST-depression 2.0 mm (0.2 mV), or severe symptoms (incapacitating fatigue, grade III/IV angina, severe dyspnea).