Why does fibromuscular dysplasia (FMD) increase the risk for coronary dissection?

Fibromuscular Dysplasia and Coronary Artery Dissection: Pathophysiological Connection

Fibromuscular dysplasia (FMD) increases the risk for coronary artery dissection primarily due to inherent arterial wall abnormalities that create structural weakness and predisposition to intramural hematoma formation. 1

Pathophysiological Mechanisms

Arterial Wall Abnormalities

• FMD is a nonatherosclerotic, noninflammatory vascular disease characterized by stenosis due to thickening and structural abnormalities of the arterial wall 1
• These structural abnormalities include:
  • Deficient or absent muscular media in arterial walls 2
  • Segmental weakening of the arterial wall 3
  • Disruption of the normal arterial architecture 1

Spontaneous Coronary Artery Dissection (SCAD) Connection

• SCAD occurs when layers of the coronary arterial wall separate, leading to formation of an intramural hematoma that compresses the true lumen 1
• The development of hematoma in the tunica media precedes intimal dissection, typically due to disruption of transversing microvessels 1
• In FMD patients, the weakened arterial wall structure predisposes to this separation of layers and subsequent hematoma formation 3

Epidemiological Evidence

• 86% of patients with SCAD have FMD in at least one non-coronary territory 4
• 15-25% of patients with FMD present with arterial dissection in at least one arterial bed 5
• SCAD contributes to 24-35% of all acute coronary syndrome cases in women ≤50 years of age 1
• 87-95% of SCAD cases occur in women with a mean presentation age between 44-53 years 1

Genetic Factors

• Patients carrying the rs9349379-A variant in the PHACTR1/EDN1 locus have a higher risk of both SCAD and FMD 1
• Genome-wide association studies have identified additional loci associated with increased SCAD risk, including chromosome 1q21.2, chromosome 12q13.3 in LRP1, and chromosome 21q22.11 near LINC00310 (in females only) 1
• These genetic factors likely contribute to the arterial wall abnormalities that predispose to dissection

Clinical Implications

• Patients with FMD should be monitored for potential coronary complications, including SCAD
• When SCAD is identified, screening for FMD in other vascular territories is recommended 1
• Conservative management is generally preferred for SCAD lesions as many heal spontaneously 3

Diagnostic Considerations

• The classic "string of beads" appearance seen in renal FMD is not typically observed in coronary arteries 3
• Coronary FMD may manifest as:
  • Spontaneous coronary artery dissection
  • Distal tapering or long, smooth narrowing
  • Intramural hematoma
  • Arterial tortuosity 3

In summary, the structural abnormalities in arterial walls caused by FMD create inherent weaknesses that predispose to spontaneous dissection. This mechanism explains the strong association between FMD and coronary artery dissection, particularly in middle-aged women who represent the demographic most affected by both conditions.