Copenhagen study of overweight patients with coronary artery disease undergoing low energy diet or interval training: the randomized CUT-IT trial protocol

BACKGROUND: Coronary artery disease (CAD) is accountable for more than 7 million deaths each year according to the World Health Organization (WHO). In a European population 80% of patients diagnosed with CAD are overweight and 31% are obese. Physical inactivity and overweight are major risk factors in CAD, thus central strategies in secondary prevention are increased physical activity and weight loss. METHODS/DESIGN: In a randomized controlled trial 70 participants with stable CAD, age 45–75, body mass index 28–40 kg/m(2) and no diabetes are randomized (1:1) to 12 weeks of intensive exercise or weight loss both succeeded by a 40-week follow-up. The exercise protocol consist of supervised aerobic interval training (AIT) at 85-90% of VO(2)peak 3 times weekly for 12 weeks followed by supervised AIT twice weekly for 40 weeks. In the weight loss arm dieticians instruct the participants in a low energy diet (800–1000 kcal/day) for 12 weeks, followed by 40 weeks of weight maintenance combined with supervised AIT twice weekly. The primary endpoint of the study is change in coronary flow reserve after the first 12 weeks’ intervention. Secondary endpoints include cardiovascular, metabolic, inflammatory and anthropometric measures. DISCUSSION: The study will compare the short and long-term effects of a protocol consisting of AIT alone or a rapid weight loss followed by AIT. Additionally, it will provide new insight in mechanisms behind the benefits of exercise and weight loss. We wish to contribute to the creation of effective secondary prevention and sustainable rehabilitation strategies in the large population of overweight and obese patients diagnosed with CAD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0172456

Insulin resistance and exercise tolerance in heart failure patients:linkage to coronary flow reserve and peripheral vascular function

BACKGROUND: Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage. METHODS: 39 patients with LVEF < 35% (median LV ejection fraction (LVEF) 31 (interquartile range (IQ) 26–34), 23/39 of ischemic origin) underwent echocardiography with measurement of CFR. Peak coronary flow velocity (CFV) was measured in the LAD and coronary flow reserve was calculated as the ratio between CFV at rest and during a 2 minutes adenosine infusion. All patients performed a maximal symptom limited exercise test with measurement of peak oxygen uptake (VO(2)peak), digital measurement of endothelial function and arterial stiffness (augmentation index), dual X-ray absorptiometry scan (DEXA) for body composition and insulin sensitivity by a 2 hr hyperinsulinemic (40 mU/min/m(2)) isoglycemic clamp. RESULTS: Fat free mass adjusted insulin sensitivity was significantly correlated to VO(2)peak (r = 0.43, p = 0.007). Median CFR was 1.77 (IQ 1.26-2.42) and was correlated to insulin sensitivity (r 0.43, p = 0.008). CFR (r = 0.48, p = 0.002), and arterial stiffness (r = −0.35, p = 0.04) were correlated to VO(2)peak whereas endothelial function and LVEF were not (all p > 0.15). In multivariable linear regression adjusting for age, CFR remained independently associated with VO2peak (standardized coefficient (SC) 1.98, p = 0.05) whereas insulin sensitivity (SC 1.75, p = 0.09) and arterial stiffness (SC −1.17, p = 0.29) were no longer associated with VO2peak. CONCLUSIONS: The study confirms that insulin resistance is associated with exercise intolerance in heart failure patients and suggests that this is partly through reduced CFR. This is the first study to our knowledge that shows an association between CFR and exercise capacity in heart failure patients and links the relationship between insulin resistance and exercise capacity to CFR

Comprehensive treatment of microvascular angina in overweight women - a randomized controlled pilot trial.

AimsCoronary microvascular dysfunction (CMD) carries a poor cardiovascular prognosis and may explain angina in women without obstructive coronary artery disease (CAD). Currently, no evidence-based treatment for CMD exists. We investigated whether reducing cardiovascular risk factors improves symptoms and microvascular function in women with non-endothelial dependent CMD and no obstructive CAD.MethodsWe randomized 62 women aged 40-75, with body mass index (BMI) >25 kg/m2, angina ≥monthly, and coronary flow velocity reserve (CFVR) ≤2.5 to a 24-week intervention comprising low energy diet, exercise training, and optimized treatment of hypertension, dyslipidemia and diabetes or to control. Patients were assessed before randomization and after 24 weeks. Primary outcomes were CFVR assessed by transthoracic Doppler stress-echocardiography and angina burden by Seattle Angina Questionnaire (SAQ). Secondary outcomes were exercise capacity, body composition, glycemic control, myocardial function, and anxiety and depression symptoms.ResultsFifty-six participants (90%) completed the study. Median (IQR) age was 65.2 (57.1;70.7) years, BMI was 30.1 (28.4;32.7) kg/m2. The intervention resulted in relevant improvement in angina symptoms (9-21-point increase on SAQ-scales (all pConclusionA major weight loss and intensified risk factor control resulted in significantly improved angina burden but no improvement of coronary microvascular function among women with microvascular angina

Coronary microvascular function, insulin sensitivity and body composition in predicting exercise capacity in overweight patients with coronary artery disease

BACKGROUND: Coronary artery disease (CAD) has a negative impact on exercise capacity. The aim of this study was to determine how coronary microvascular function, glucose metabolism and body composition contribute to exercise capacity in overweight patients with CAD and without diabetes. METHODS: Sixty-five non-diabetic, overweight patients with stable CAD, BMI 28–40 kg/m(2) and left ventricular ejection fraction (LVEF) above 35 % were recruited. A 3-hour oral glucose tolerance test was used to evaluate glucose metabolism. Peak aerobic exercise capacity (VO(2)peak) was assessed by a cardiopulmonary exercise test. Body composition was determined by whole body dual-energy X-ray absorptiometry scan and magnetic resonance imaging. Coronary flow reserve (CFR) assessed by transthoracic Doppler echocardiography was used as a measure of microvascular function. RESULTS: Median BMI was 31.3 and 72 % had impaired glucose tolerance or impaired fasting glucose. VO(2)peak adjusted for fat free mass was correlated with CFR (r = 0.41, p = 0.0007), LVEF (r = 0.33, p = 0.008) and left ventricular end-diastolic volume (EDV) (r = 0.32, p = 0.01) while it was only weakly linked to measures of glucose metabolism and body composition. CFR, EDV and LVEF remained independent predictors of VO(2)peak in multivariable regression analysis. CONCLUSION: The study established CFR, EDV and LVEF as independent predictors of VO(2)peak in overweight CAD patients with no or only mild functional symptoms and a LVEF > 35 %. Glucose metabolism and body composition had minor impact on VO(2)peak. The findings suggest that central hemodynamic factors are important in limiting exercise capacity in overweight non-diabetic CAD patients