What causes coronary microvascular disease?

Causes of Coronary Microvascular Disease

Coronary microvascular dysfunction results from both traditional cardiovascular risk factors and systemic inflammatory conditions that cause structural and functional alterations in the coronary microvasculature, with hypertension, diabetes, dyslipidemia, smoking, and age being the most consistently associated factors. 1

Traditional Cardiovascular Risk Factors

Hypertension

• Hypertension is one of the most important causes of CMD, inducing both functional and structural alterations in the microvasculature. 2
• Causes endothelial dysfunction and capillary rarefaction, which are the primary mechanisms driving CMD development in hypertensive patients. 2
• Promotes microvascular remodeling and increased vascular resistance even before obstructive coronary disease develops. 3

Diabetes Mellitus and Metabolic Dysfunction

• Diabetes is strongly associated with CMD through multiple pathophysiological mechanisms. 1
• Metabolic syndrome components (obesity, insulin resistance, dyslipidemia) cause coronary microvascular remodeling in early pre-atherosclerotic phases. 4
• CMD appears as an early subclinical culprit in the pathogenesis of heart disease in type 2 diabetes, often preceding macrovascular disease. 4

Dyslipidemia

• Elevated lipid levels contribute to endothelial dysfunction and microvascular structural changes. 1
• Relatively more prevalent in patients with angina and non-obstructive CAD compared to diabetes. 1

Smoking

• Cigarette smoking causes direct microvascular injury and promotes endothelial dysfunction. 1
• Associated with abnormal vasomotion throughout the coronary microcirculation. 5

Age

• Advancing age is independently associated with progressive microvascular dysfunction. 1
• Age-related structural changes in the microvasculature reduce coronary flow reserve. 1

Inflammatory and Autoimmune Conditions

Systemic Inflammatory Diseases

• Systemic lupus erythematosus (SLE) and rheumatoid arthritis are associated with MVA and frequently encountered in patients with angina. 1
• Inflammatory diseases occur more often in women after menopause than in men, contributing to sex differences in MVA prevalence. 1
• Chronic inflammatory and autoimmune rheumatic disorders cause CMD through inflammatory-mediated microvascular injury. 3

Pathophysiological Mechanisms

Endothelial Dysfunction

• Risk factors that promote epicardial atherosclerosis simultaneously cause endothelial dysfunction and abnormal vasomotion throughout the entire coronary tree, including arterioles regulating coronary flow. 5
• Endothelial dysfunction is present in 80% of patients with ANOCA tested with acetylcholine. 1
• Results in lack of flow-mediated vasodilation and promotes macro- and microcirculatory vasoconstriction. 1, 5

Structural Microvascular Changes

• Capillary rarefaction reduces microvascular density and impairs myocardial perfusion. 1, 5
• Microvascular remodeling increases resistance and reduces coronary flow reserve. 6, 7
• Structural abnormalities include thickening of arteriolar walls and perivascular fibrosis. 6

Functional Abnormalities

• Impaired coronary flow reserve (CFR <2.0-2.5) is present in 50% of patients with ANOCA. 1
• Abnormal vasoconstriction of coronary arterioles causes dynamic arteriolar obstruction. 1
• Reduced microcirculatory conductance limits blood flow response to metabolic demand. 1

Cardiac-Specific Conditions

Myocardial Hypertrophy and Fibrosis

• Left ventricular hypertrophy secondary to hypertension or aortic stenosis contributes to CMD. 1, 5
• Interstitial myocardial fibrosis impairs microvascular perfusion and increases oxygen demand. 2
• Hypertrophic cardiomyopathy causes CMD through increased wall stress and microvascular compression. 3

Aortic Valve Stenosis

• Severe aortic stenosis causes CMD through increased myocardial oxygen demand and reduced diastolic perfusion pressure. 3

Systemic Conditions

Chronic Kidney Disease

• Chronic kidney disease is associated with CMD through multiple mechanisms including endothelial dysfunction, inflammation, and oxidative stress. 3

Hypertensive Pregnancy Disorders

• Preeclampsia and gestational hypertension cause microvascular dysfunction that may persist postpartum. 3

Psychosocial Factors

• Psychosocial stress is increasingly recognized as involved in coronary vasomotor disorders. 1
• Stress-mediated mechanisms include sympathetic activation and endothelial dysfunction. 1

Clinical Pitfall

A critical error is assuming that normal epicardial coronary arteries on angiography exclude significant coronary disease—CMD can cause myocardial ischemia and adverse cardiovascular outcomes even with completely normal-appearing epicardial vessels. 1 The prevalence of CMD ranges from 26% to 54% in patients with non-obstructive CAD depending on assessment technique, emphasizing that this is not a rare condition but rather a common cause of angina that requires specific diagnostic testing beyond standard angiography. 1