Last updated on February 2018

Comprehensive Treatment of Angina in Women With Microvascular Dysfunction

Brief description of study

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 Study 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.

Clinical Study Identifier: NCT02910154

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Eva Prescott, MD, DMSc

Bispebjerg Hospital, Dept. of Cardiology Y builing 67, 1.floor, Bispebjerg Bakke 23
Copenhagen, Denmark
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Eva Prescott, MD, DMSc

Frederiksberg Hospital, Dept. of Cardiology, Building 16, Y3, Nordre Fasanvej 57
Frederiksberg, Denmark
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