What causes coronary microvascular disease?

Causes of Coronary Microvascular Disease

Coronary microvascular disease results from traditional cardiovascular risk factors—hypertension, diabetes, dyslipidemia, smoking, and advancing age—which cause both structural and functional alterations in the coronary microvasculature, along with inflammatory/autoimmune conditions that are particularly prevalent in postmenopausal women. 1

Traditional Cardiovascular Risk Factors

The primary drivers of CMD mirror those of epicardial atherosclerosis but specifically target the microvasculature through distinct pathophysiological mechanisms:

Diabetes Mellitus

• Diabetes is strongly associated with CMD through multiple pathophysiological mechanisms, causing both endothelial dysfunction and structural microvascular changes 1
• The metabolic abnormalities in diabetes directly influence coronary microvasculature function and structure 2

Hypertension

• Hypertension causes both functional and structural alterations in the microvasculature, with endothelial dysfunction and capillary rarefaction playing the most significant roles 3
• Hypertension-induced left ventricular hypertrophy, interstitial myocardial fibrosis, and diastolic dysfunction are directly linked to CMD development 3
• CMD associated with hypertension serves as a subclinical marker of end-organ damage and heart failure with preserved ejection fraction 3

Dyslipidemia

• Elevated lipid levels contribute to endothelial dysfunction and microvascular structural changes 1
• Low HDL cholesterol independently predicts cardiovascular disease incidence 4

Cigarette Smoking

• Smoking causes direct microvascular injury and promotes endothelial dysfunction 1
• Smoking is a common trigger for coronary vasospasm, which frequently coexists with microvascular dysfunction 5

Advancing Age

• Age is independently associated with progressive microvascular dysfunction 1
• The prevalence of CMD increases with age across both sexes 6

Inflammatory and Autoimmune Conditions

A critical distinction: inflammatory diseases occur more often in women after menopause than in men, contributing to sex differences in microvascular angina prevalence. 1

Systemic Autoimmune Diseases

• Systemic lupus erythematosus and rheumatoid arthritis are associated with microvascular angina and frequently encountered in patients with angina 1
• Persistent systemic inflammation directly influences the coronary microvasculature 2

Chronic Inflammatory States

• HIV, viral hepatitis, and systemic autoimmune diseases are associated with poor cardiovascular outcomes and contribute to CMD pathogenesis 1
• These conditions create a pro-inflammatory milieu that damages microvascular endothelium 2

Pathophysiological Mechanisms

Understanding the mechanisms helps explain why patients with normal epicardial arteries still experience ischemia:

Endothelial Dysfunction

• Endothelial dysfunction is present in 80% of patients with angina and non-obstructive coronary artery disease when tested with acetylcholine 1
• This represents impaired endothelium-dependent vasodilation in response to physiological stimuli 6

Impaired Coronary Flow Reserve

• Impaired coronary flow reserve is present in 50% of patients with angina and non-obstructive coronary artery disease 1
• This reflects the inability of the microvasculature to increase blood flow adequately in response to increased myocardial oxygen demand 6

Abnormal Vasoconstriction

• Abnormal vasoconstriction of coronary arterioles causes dynamic arteriolar obstruction 1
• This can occur independently or in conjunction with epicardial vasospasm 5

Structural Microvascular Changes

• Capillary rarefaction results from adverse effects on myocardial capillaries 4
• Microvascular remodeling includes both functional and structural abnormalities 6

Sex-Specific Considerations

• CMD is more prevalent in women than men, with 2/3 of women versus 1/3 of men with angina showing no epicardial stenosis 2
• Postmenopausal women show higher rates of inflammatory conditions contributing to CMD 1
• Women more commonly present with microvascular angina during menopause 2

Critical Clinical Pitfall

A critical error is assuming that normal epicardial coronary arteries on angiography exclude significant coronary disease—coronary microvascular disease can cause myocardial ischemia and adverse cardiovascular outcomes even with completely normal-appearing epicardial vessels. 1

• Risk factors that promote epicardial atherosclerosis simultaneously cause endothelial dysfunction and abnormal vasomotion throughout the entire coronary tree, including the arterioles regulating coronary flow and resistance 4
• Different ischemic mechanisms frequently act concomitantly in the same patient, requiring comprehensive evaluation beyond simple angiographic assessment 5
• CMD prevalence ranges from 26% to 54% in patients with non-obstructive CAD, depending on assessment technique 5