Highlights
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Extracoronary arteriopathies were identified in 47.2% of SCAD patients.
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The most affected arteries included carotid, renal, vertebral, and iliac/femoral.
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Fibromuscular dysplasia was present in 40.9% of the study cohort.
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Intracranial aneurysms and extracoronary dissections were also prevalent.
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Findings support routine comprehensive vascular imaging in SCAD for risk stratification.
Spontaneous coronary artery dissection (SCAD) is increasingly recognized as a cause of acute coronary syndrome and has been associated with extracoronary arteriopathies, such as fibromuscular dysplasia (FMD), aneurysms, and dissections across other vascular beds. However, these associations remain understudied in the literature. This study aims to characterize the prevalence and distribution of extracoronary arteriopathies in a large cohort of SCAD patients. Patients diagnosed with SCAD were extracted from 2018 to 2024. Baseline characteristics and comorbidities were collected. Available vascular imaging, including echocardiograms, computed tomography, and magnetic resonance, were used to assess for extracoronary arteriopathies. The prevalence and location of FMD, aneurysms, and dissections in extracoronary vascular beds were documented. Among 1,380 SCAD patients, 564 (40.9%) were found to have FMD, 166 (12.0%) had extra-coronary arterial dissections, and 228 (16.5%) had aneurysms in at least 1 extracoronary vascular bed. The most common sites of FMD were renal, carotid, vertebral, and iliac/femoral arteries. Aneurysms were most frequently located in cerebral, carotid, renal, and splenic arteries. Dissections were most prevalent in the carotid, vertebral, extremity, and celiac arteries. Thoracic aortic aneurysms were rare, with only 4 patients showing thoracic aortic dissection. Extracoronary arteriopathies are prevalent in patients with SCAD, affecting more than 47% of the cohort described here. These findings underscore the importance of comprehensive vascular imaging in patients with SCAD to detect extracoronary vascular abnormalities, which may have implications for surveillance and management strategies.
Spontaneous coronary artery dissection (SCAD) has emerged as a significant nonatherosclerotic cause of acute coronary syndrome, particularly affecting younger women, and is now recognized as a main contributor to myocardial infarction in this population. Unlike traditional coronary events driven by thrombosis and plaque rupture, SCAD results from an intimal tear or spontaneous hemorrhage within the arterial wall, leading to the formation of a false lumen and vessel occlusion. Notably, a growing body of evidence indicates that SCAD may not be an isolated vascular event but a manifestation of a broader, systemic arteriopathy. Multiple studies have documented that many SCAD patients concurrently exhibit extracoronary vascular abnormalities, including fibromuscular dysplasia (FMD), aneurysms, and arterial dissections, in diverse vascular beds.
These findings support the notion that SCAD is linked to an underlying vascular fragility, predisposing patients to extracoronary arterial pathology. , The recognition of these extracoronary findings has important implications. First, it suggests that the underlying vascular pathology in SCAD is not confined to the coronary arteries but reflects a diffuse arteriopathic process that may predispose individuals to vascular events in other territories. Second, these observations underscore the importance of comprehensive vascular imaging to detect noncoronary abnormalities that could influence management and long‐term surveillance. ,, Given the high prevalence of extracoronary abnormalities in SCAD patients, advanced imaging techniques such as computed tomography angiography (CTA), magnetic resonance angiography (MRA), and catheter-based angiography have been frequently utilized to screen for associated vascular pathology. This approach is particularly vital in guiding patient counseling and education, since identifying these extracoronary abnormalities may impact decisions regarding follow-up, lifestyle modifications, and preventative strategies for secondary vascular events. ,
Furthermore, emerging genetic data suggest that SCAD shares common genetic variants and biological mechanisms with other vascular disorders, such as FMD. ,, Genetic variants at the PHACTR1/EDN1 locus have been implicated in both conditions FMD and SCAD, suggesting a genetic predisposition to arterial dissections and other vascular abnormalities. ,, However, these loci explain only a fraction of the pathophysiology of SCAD, with whole genome sequencing studies showing that these pathogenic variants are detected in only a small subset of patients. These associations provide valuable insight into the complex, polygenic pathophysiology of SCAD and its complications, offering advancements in risk stratification and personalized management. There is limited published data with detailed characterizations of the prevalence and distribution of extracoronary arteriopathies in SCAD patients. Identifying the prevalence of extracoronary diseases, including FMD, dissections, and aneurysms, will help clinicians tailor treatment and follow-up based on their distribution across different vascular territories. This study aims to address this gap by evaluating a large, multicenter cohort of SCAD patients. By delineating the spectrum of extracoronary vascular abnormalities in this population, the findings may inform both clinical screening practices and the understanding of the pathophysiological mechanisms that predispose to SCAD, ultimately enhancing personalized medicine.
Methods
Study design and population
A retrospective cohort analysis of patients (age ≥18 years) diagnosed with SCAD between 2018 and 2024 at all 3 Mayo Clinic sites (Rochester, Minnesota; Jacksonville, Florida; and Phoenix, Arizona) was conducted. Patients were identified through electronic medical record query using ICD-10 diagnosis codes indicative of SCAD, which was manually confirmed through chart review. Patients with iatrogenic coronary dissection were excluded.
Data collection
Demographic data (age, sex, etc.) and clinical comorbidity details (e.g., hypertension, obesity, dyslipidemia, diabetes mellitus) were collected. Data on established connective tissue disease (CTD) as well as specific CTD features (defined as any clinical features suggestive of connective tissue disorders [e.g., joint hypermobility, high arched palate, skin hyperextensibility]) were collected. All patients diagnosed with SCAD at our institution underwent at least 1 noninvasive imaging study as part of the institutional protocol to screen for associated FMD and extracoronary arteriopathies. Imaging was also guided by clinical indications, including symptoms suggestive of arterial dissections, aneurysms, and manifestations of FMD (e.g., hypertension due to renal artery involvement or neurological symptoms due to cervical or cerebral artery abnormalities). All available vascular imaging reports (CT, MR, duplex ultrasound, echocardiography, or conventional angiography) from head to extremities were reviewed manually for evidence of vascular abnormalities outside the coronaries. Echocardiography measurements were used to assess the size of the thoracic aorta only if other more advanced imaging modalities (i.e. CT and MRI) were unavailable. The diagnosis of SCAD was confirmed through coronary angiography in all patients who presented to our institutional emergency department (ED), per institutional guidelines, and all patients who underwent coronary angiography had an ACS diagnosis through electrocardiography in the ED. Vascular abnormalities were classified as FMD, aneurysms, and dissections as reported by radiologists along with details on the vascular bed affected. These findings were mainly taken from the official radiologist reports. In the event of ambiguities, senior authors independently reviewed the images for adjudication. Vascular abnormalities were classified using standard imaging criteria (e.g., ‘beading’ pattern on angiography suggestive of FMD; increase of ≥1.5x normal in arterial diameter to define an aneurysm; an intimal flap or intramural hematoma suggestive of dissection). Finally, specific vascular beds that were affected (e.g., renal, carotid, vertebral) were documented in a dedicated research database.
Statistical analysis
Descriptive statistics were used to summarize the cohort. Continuous variables were presented as mean ± standard deviation, and categorical variables were summarized as frequencies (%). Group comparisons were performed to explore differences between patients with versus without extracoronary vessel involvement. For categorical variables, Pearson’s chi-square test (or Fisher’s exact test when cell counts were small) to assess differences in proportions. For continuous variables, a Student’s t-test for was used. Statistical analysis was performed in SPSS. This study was exempt by the Mayo Clinic Institutional Review Board.
With the primary goal of this study being to investigate extracoronary manifestations and arteriopathies in SCAD patients, data on the total acute coronary syndrome (ACS) population during the study period were not systematically collected. Thus, the institutional prevalence of SCAD within the broader ACS population could not be determined.
Results
Overall cohort characteristics
Baseline demographics and comorbidities
A total of 1,380 patients with SCAD were identified between 2018 and 2024. Median follow-up duration was 2.02 years (interquartile range [IQR]: 1.1–5.2 years). The median age of the entire cohort was 51 years (IQR: 43–58), with a majority being females (91.8%). Of these patients, 651 (47.17%) had evidence of at least 1 extracoronary arteriopathy on imaging, while 729 (52.83%) did not. All patients underwent at least 1 form of noninvasive imaging; specifically, CT imaging was performed in 1,337 patients, echocardiography in 799 patients, and MRI in 247 patients. Baseline demographics and clinical comorbidities among patients with (n = 651) versus without (n = 729) extracoronary arteriopathies are summarized in Table 1 . The extracoronary group was predominantly females (94.50% vs 5.5% males, p < 0.001). When comparing the extracoronary vs nonextracoronary (coronary only) groups, there were no differences in median age between the 2 groups (51 vs 51 years, p = 0.585). There were no statistically significant differences in comorbidities between the extracoronary and nonextracoronary groups, including hypertension (36.1% vs. 32.2%, p = 0.131), diabetes mellitus (5.8% vs. 5.6%, p = 0.865), dyslipidemia (38.6% vs. 36.4%, p = 0.398), obesity (11.7% vs. 10.3%, p = 0.41), or heart failure (17.2% vs. 15.2%, p = 0.319). Additionally, migraine prevalence (18.7% vs. 16.2%, p = 0.211) was similar between groups, as well as the rates of atrial fibrillation (5.5% vs. 5.5%, p = 0.972) and thyroid disorders (13.7% vs. 12.3%, p = 0.464). ’Prior myocardial infarction’ refers to any myocardial infarction documented prior to the index SCAD event, which could potentially represent undiagnosed SCAD or independent atherosclerotic events. Twenty-three patients (1.7%) out of the total cohort had a confirmed diagnosis of a connective tissue disorder (CTD), including 13 with Ehlers-Danlos syndrome (vascular subtype) and 10 with Marfan syndrome. These diagnoses were based on genetic testing or formal clinical criteria documented in the medical record.
Table 1
Baseline characteristics, comorbidities, and connective tissue disease features in scad patients with and without extracoronary vascular involvement
| Variable | Coronary only (n = 729) (n, %) | Extracoronary (n = 651) (n, %) | p-value |
|---|---|---|---|
| Age | 51 (IQR: 43–58) | 51 (IQR: 43–58) | 1.000 |
| Females | 656 (90.0%) | 615 (94.5%) | 0.002 |
| Comorbidities | |||
| Obesity | 75 (10.3%) | 76 (11.7%) | 0.41 |
| DM | 41 (5.6%) | 38 (5.8%) | 0.865 |
| HTN | 235 (32.2%) | 235 (36.1%) | 0.131 |
| Migraine | 118 (16.2%) | 122 (18.7%) | 0.211 |
| Atrial fibrillation | 40 (5.5%) | 36 (5.5%) | 0.972 |
| Hyperlipidemia | 265 (36.4%) | 251 (38.6%) | 0.398 |
| Heart failure | 111 (15.2%) | 112 (17.2%) | 0.319 |
|
Thyroid disorder
Prior myocardial infarction |
90 (12.3%)
225 (30.9%) |
89 (13.7%)
221 (33.9%) |
0.464
0.221 |
| Depression | 107 (14.7%) | 91 (14.0%) | 0.711 |
| Anxiety | 156 (21.4%) | 141 (21.7%) | 0.907 |
| Connective tissue disorders | 8 (1.1%) | 15 (2.3%) | 0.08 |
| Physical exam features | |||
| Joint conditions | 135 (18.5%) | 141 (21.7%) | 0.145 |
| Hypermobility | 1 (0.1%) | 1 (0.2%) | 0.936 |
| Scoliosis | 9 (1.2%) | 6 (0.9%) | 0.576 |
| Pectus | 8 (1.1%) | 6 (0.9%) | 0.745 |
| Pneumothorax | 0 (0.0%) | 3 (0.5%) | 0.067 |
| Pes planus | 7 (1.0%) | 5 (0.8%) | 0.701 |
| Valgus/Varum | 2 (0.3%) | 4 (0.6%) | 0.338 |
| Hammertoes | 4 (0.5%) | 5 (0.8%) | 0.613 |
| Skin conditions | 7 (1.0%) | 12 (1.8%) | 0.16 |
| Hollow organ perforation | 39 (5.3%) | 34 (5.2%) | 0.916 |
| Varicose veins | 11 (1.5%) | 13 (2.0%) | 0.489 |
| Mitral valve prolapse | 25 (3.4%) | 20 (3.1%) | 0.709 |
| POTS | 1 (0.1%) | 1 (0.2%) | 0.936 |
Values shown as n (%) or median (IQR). Abbreviations: SCAD = spontaneous coronary artery dissection; IQR = interquartile range; DM = diabetes mellitus; HTN = hypertension; POTS = postural orthostatic tachycardia syndrome.
Coronary-artery involvement
Angiographic data were available for 725 patients who experienced coronary artery involvement. SCAD most frequently affected the left anterior descending (LAD) artery (45.8 %), followed by obtuse marginal (OM) branches (15.3 %), left circumflex (LCX) (8.4 %), right coronary artery (RCA) (8.1 %), posterior descending artery (PDA) (4.4 %) and left main coronary artery (LMCA) (2.3 %); 13.1 % involved more than 1 coronary territory.
Clinical outcomes
Patients with extracoronary disease were more likely to experience SCAD recurrence compared to those without extracoronary findings (16.7% vs 9.9%, p<0.001). In contrast, mortality rates did not differ statistically (0.6% vs 1.5%, p = 0.11).
Prevalence and distribution of fibromuscular dysplasia
FMD was prevalent in 40.9% (564 patients of 1,380) of the study cohort. The renal (25.0%) and carotid (25.0%) arteries were the most frequently affected vascular beds. In contrast, FMD involving cerebral (1.1%) and mesenteric (1.3%) arteries was notably less common ( Table 2 ). Most patients had involvement in 1 (13.6%) or 2 (14.2%) vascular territories.
Table 2
Distribution of fibromuscular dysplasia (FMD) vascular territories (n = 564)
| Vascular territory | Frequency (n, %) |
|---|---|
| Head and neck | |
| Cervical artery | 386 (28.0%) |
| Carotid artery | 345 (25.0%) |
| Vertebral artery | 217 (15.7%) |
| Cerebral arteries | 15 (1.1%) |
| Abdomen | |
| Renal artery | 345 (25.0%) |
| Celiac artery | 29 (2.1%) |
| Splenic and intrahepatic arteries | 19 (1.4%) |
| Superior/Inferior mesenteric arteries | 18 (1.3%) |
| Other | |
| Iliac and femoral arteries | 199 (14.4%) |
| Subclavian artery | 5 (0.4%) |
| Number of affected vessels | |
| 0 | 816 (59.1%) |
| 1 | 187 (13.6%) |
| 2 | 196 (14.2%) |
| 3 | 117 (8.5%) |
| 4 or more | 54 (3.9%) |
Renal and carotid arteries were the most frequently affected sites; the number of involved vascular beds per patient is also shown.
Prevalence and distribution of aneurysms
Extracoronary aneurysms were identified in 16.5% (228 patients) of the cohort, predominantly involving cerebral (4.8%), carotid (4.2%), renal (2.8%), and splenic (2.8%) arteries. Aneurysms of the thoracic (1.9%) and abdominal (0.6%) aorta were less common ( Table 3 ). Most patients had aneurysms in only a single extracoronary vascular territory (11.4%).
Table 3
Anatomic distribution and burden of extracoronary aneurysms in SCAD patients
| Vascular territory | Frequency (n, %) |
|---|---|
| Head and neck | |
| Cervical artery | 70 (5.1%) |
| Carotid artery | 58 (4.2%) |
| Vertebral artery | 17 (1.2%) |
| Cerebral artery | 66 (4.8%) |
| Chest | |
| Thoracic aorta | 26 (1.9%) |
| Coronary artery | 16 (1.2%) |
| Abdomen | |
| Splanchnic artery | 97 (7.0%) |
| Renal artery | 39 (2.8%) |
| Splenic artery | 39 (2.8%) |
| Celiac artery | 16 (1.2%) |
| Superior mesenteric artery | 10 (0.7%) |
| Abdominal aorta | 8 (0.6%) |
| Other | |
| Extremity artery (upper & lower) | 34 (2.5%) |
| Number of arteries involved | |
| 0 | 1152 (83.5%) |
| 1 | 157 (11.4%) |
| 2 | 49 (3.6%) |
| 3 | 15 (1.1%) |
| 4 or more | 7 (0.5%) |
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