The study protocol was approved by the Institutional Ethical Committee, and an informed consent was obtained from each participant. This was a prospective study performed in the period from July 2016 to March 2017 on 120 patients with stable coronary artery disease who had complete coronary revascularization by coronary angioplasty performed in the 12 months before enrollment in the study and were on optimal guideline-directed medical therapy.
Subjects were classified into obese and non-obese patient groups. A patient was considered obese if their body mass index (BMI) was more than or equal to 30 kg/m2 while they were considered non-obese if their BMI was less than 30 kg/m2. BMI was calculated using the following formula: BMI = weight (kg)/height (m2) [15].
All patients were enrolled in the phase 2 cardiac rehabilitation program offered at our institution. The presence of any of the following criteria led to patient exclusion from the study: exertional angina, significant coronary stenosis on angiography, recent (less than 3 months) myocardial infarction or acute coronary syndrome, left ventricular ejection fraction (LVEF) less than 40%, recent (less than 3 months) hospitalization for decompensated heart failure, prior participation in a cardiac rehabilitation program, a physical or mental disability that would impede exercise training, having a heart rhythm other than sinus rhythm, hypertrophic cardiomyopathy, more than mild pulmonary hypertension, more than moderate valvular stenosis or regurgitation, prior implantation of a permanent pacemaker or other cardiac implantable electric device, significant peripheral arterial disease, any acute illness, chronic renal impairment, a history of transient ischemic attacks or cerebrovascular stroke, and chronic obstructive airway disease. Additionally, patients were excluded from the study if they had missed more than three sessions of exercise training during the study period or if any of the previously mentioned exclusion criteria developed after inclusion in the study.
Doses of lipid-lowering, anti-hypertensives, and hypoglycemic medications are needed to remain unchanged for 2 weeks before enrollment in the program and during the whole length of the study period. If a patient required a change in the doses of such medications, they were excluded from the study.
Clinical and anthropometric assessment
Thorough history taking and clinical examination were performed for all subjects. Weight and height were measured to calculate BMI. Resting blood pressure was recorded using an appropriately sized cuff where an average of three measurements taken 2 min apart with the patient seated having their back supported and their feet resting on a flat surface according to current practice guidelines [16, 17]. Current smoking status was assessed. Patients were assessed for the presence of coronary artery disease risk factors, namely hypertension, diabetes mellitus, and dyslipidemia.
Laboratory blood tests
Two antecubital venous blood samples were obtained from each patient: one after 8 h of fasting and the other after 12 h of fasting. The first sample was used to measure fasting blood sugar levels and the latter to measure total cholesterol, triglyceride, and high-density lipoprotein cholesterol (HDL-C) levels using enzymatic methods. Low-density lipoprotein cholesterol (LDL-C) was calculated using the Friedewald formula: LDL-C (mg/dl) = total cholesterol (mg/dl) − HDL-C (mg/dl) − 1/5 of triglycerides (mg/dl) [18].
Trans-thoracic echocardiography
Standard trans-thoracic echocardiography was performed for all patients in the left lateral decubitus position using a Vivid S5 machine (GE Vingmed, Netherlands) equipped with an M4S matrix array probe with a frequency range of 1.7–3.5 MHz. Echocardiography was performed by an echocardiographer accredited by the European Association of Cardiovascular Imaging.
From the parasternal short-axis view at the level of the papillary muscles, left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were measured following the practice guidelines. Left ventricular ejection fraction (LVEF) was measured using the modified biplane Simpson’s method of discs from the apical 4- and 2-chamber views [19].
The cardiac rehabilitation program
All patients were enrolled in the program provided at the cardiac rehabilitation unit in our institution which is a 12-week twice-weekly (24 sessions) comprehensive program with progressive prescribed treadmill exercise training being its cornerstone.
Patients were assessed at baseline using a symptom-limited treadmill exercise test according to the modified Bruce protocol to identify their peak heart rate [20]. During that test, the metabolic equivalent of tasks (METs) achieved was automatically recorded by the treadmill. One MET was defined as the amount of oxygen consumed while sitting at rest which equals 3.5 ml of oxygen per kilogram of body weight per minute [21].
The program is run by a group of cardiologists, nutritionists, psychiatrists, trained nurses, and physiotherapists.
The program provides dedicated educational sessions and handouts covering the diagnosis of coronary artery disease, its risk factors, and the importance of risk factor modification; smoking cessation; the importance of adherence to medications; nutritional guidance and counseling; stress management; and psychological counseling sessions. Such sessions are provided generally as group meetings with individual sessions provided on demand.
Prescribed exercise training
At the beginning of each training session, the patients’ symptoms were evaluated, and their blood pressure and blood sugar level were checked before being cleared to join the session. Any abnormality before or during the session would lead to its postponement.
Exercise sessions were performed using a treadmill. Each patient was directly observed by a trained nurse with a physician overseeing up to three patients at a time.
Each session lasted up to 45 min including a 5- to 10-min warm-up period (with an average speed of 3 km/h), at least 20 min of aerobic training (with speed adjusted so that the patient was at or below their target heart rate), and a 5- to 10-min cool-down period (with an average speed of 3 km/h). Sessions started short (15 to 20 min) and were progressively prolonged reaching 45 min in all patients towards the end of the program.
The target heart rate was calculated using the Karvonen formula [22] with an exercise intensity of 50 to 75%: the target heart rate = resting heart rate + (training percentage required [50–75%] × heart rate reserve); heart rate reserve = peak heart rate (estimated from the symptom-limited exercise test) − resting heart rate.
Follow-up assessments
After completion of the 12-week cardiac rehabilitation program, each patient was re-assessed using the same methods described before for BMI, resting blood pressure, METs achieved on symptom-limited exercise testing, fasting blood sugar, lipid profile, and trans-thoracic echocardiography.
Statistical analysis
Data were collected, revised, coded, and entered into the IBM Statistical Package for Social Science (SPSS) version 24. Data were tested for normality. Categorical data were presented as numbers and percentages while continuous data were presented as means and standard deviations. A comparison of categorical data was performed using the chi-square test while that of continuous data was performed using a paired sample t test. p value was considered significant at less than 0.05.