Comprehensive Treatment of Angina in Women With Microvascular Dysfunction
Condition: Angina Pectoris; Coronary Microvascular Disease
MeSH terms: Angina Pectoris; Microvascular Angina
Study type: Interventional

Summary: 
      Angina is the most common symptom of coronary heart disease among women but unlike men most
      women do not have stenosis of the coronary arteries. In a large proportion of these women,
      coronary microvascular dysfunction (CMD) is thought to be the cause of angina. However, CMD
      is also demonstrable in the asymptomatic population, and may merely be an innocent bystander
      related to the presence of cardiovascular risk factors rather than a cause of angina
      symptoms.

      The aim of this study is to determine whether comprehensive intervention is feasible and
      results in improvement in both angina and microvascular function in these patients.
    

Detailed description: 
      Coronary microvascular dysfunction is found to be associated with a significant adverse
      prognosis. The condition is strongly associated with increased future risk of major
      cardiovascular events, frequent hospital readmission, continued angina and loss of quality of
      life compared to the general population.

      Pathophysiology of microvessel disease:

      In the heart 95% of the blood flow is controlled by the microcirculation. When oxygen demand
      is increased the normal response of the microvessels is to reduce resistance in order to
      increase flow. When microvessels are dysfunctional the blood flow in the larger coronary
      vessels does not increase sufficiently to meet oxygen demand, thus leading to ischemia and
      pain. The main causes are thought to be dysfunction of endothelium and structural changes
      such as perivascular fibrosis and changes in vascular smooth muscle cells. In addition to
      vasodilation the endothelium plays a central role in the atherosclerotic process by
      generating vasoactive and anticoagulant factors that are important mediators of thrombosis.
      Coronary microvessel dysfunction (CMD) has been shown to be a strong predictor of poor
      cardiovascular prognosis in a wide group of cardiac patients.

      Rationale for intervention:

      In women with angina and no obstructive stenosis of the coronary vessels cardiovascular risk
      factors are common. Among 3000 Danish women with angina and open arteries, 12% had diabetes,
      48% hypertension, 20% were smokers and the mean body mass index was 27 kg/m2. In a randomized
      trial among overweight patients with coronary artery disease both a large weight loss and
      intensive exercise training have shown to significantly improve coronary flow velocity
      reserve (CFVR). Small studies addressing risk factors individually suggest an effect on
      peripheral vascular function of exercise training, statin therapy, and weight loss.
      Pre-diabetes is found in eighty percent of these patients and is strongly associated to
      microvessel disease. Lifestyle intervention significantly reduces risk of developing
      diabetes. Medical treatment targeting microvessel dysfunction in patients with angina has not
      been systematically tested but small studies indicate an effect of beta-blockers and
      Angiotensin Converting Enzyme (ACE)-inhibition on coronary microvessel function. Small
      studies indicate effect of individual interventions but mainly on the function of peripheral
      vessels. A comprehensive intervention simultaneously targeting CMD and angina has not
      previously been attempted.

      The rationale for this present intervention is to test this concept in women with angina and
      CMD.The study is a pilot study which, if successful, will be expanded to a multicentre,
      intervention trial with prognostic outcome. A large study showing improved prognosis is of
      crucial importance for treatment of this patient group to become part of guidelines.
    

Intervention name(s): Diet; Training; Medication (with statin and ACE-inhibition)
Intervention type(s): Dietary Supplement; Behavioral; Drug
Intervention description(s): Weight loss achieved by following an evidence-based low energy diet of 800-1200 kcal/day for 12 weeks (Cambridge Weight Plan). Hereafter follow 12 weeks of 'weight maintenance' with consumption of normal heart healthy diet. Goal: total weight loss of at least 10% without significant loss of muscle mass. Monitored and supervised by a dietician; Aerobic interval training and resistance exercise in group sessions twice weekly throughout the 24-week intervention. Training intensity individually adapted to the restricted calorie intake. Goal: Improved VO2 peak (at least 10%). Monitored by a physiotherapist.; Medical treatment for hypertension and/or hypercholesterolemia if systolic blood pressure > 130 and/or low density lipoprotein (LDL) > 2.0.
Other intervention name(s): Low Energy Diet; Aerobic Exercise Training; Medical treatment for hypertension and hypercholesterolemia
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention