Coronary and Basilar Artery Ectasia Are Associated
Results From an Autopsy Case–Control Study
Background and Purpose—Intracranial artery dolichoectasia (IADE) and coronary artery ectasia have been associated with stroke and myocardial infarction, respectively. Only rarely have cases of coexisting IADE and coronary artery ectasia been reported. We investigated this association in a large consecutive autopsy series.
Methods—Sixteen stroke patients with IADE were identified among 381 stroke patients and were matched with 16 stroke patients without IADE. The heart and coronary arteries from all patients were examined after a prespecified protocol.
Results—Coronary artery ectasia was observed in 8 of the stroke patients with IADE, and in none of the stroke patients without IADE (P=0.008). The diameters of basilar and right coronary arteries were positively correlated (IADE patients, r=0.51; P=0.003 and coronary artery ectasia patients, P=0.006).
Conclusions—This autopsy study examining the association of coronary artery ectasia and IADE in stroke patients suggests a common pathogenesis.
Despite a fundamental difference between intracranial and coronary arteries, with the former perfused in systole and the latter in diastole, the coexistence of intracranial artery dolichoectasia (IADE) and coronary artery ectasia (CAE) has been reported in a few case reports.1,2 IADE consists of dilated and elongated intracranial arteries and is present in <15% of strokes.3,4 The basilar artery is affected in 80% of these cases.3 This arteriopathy may also affect arterial beds other than the intracranial arteries, such as the thoracic aorta.5 CAE is a fusiform dilatation of coronary arteries and is observed in ≤5% of coronary angiographies.6 CAE has been associated with angina pectoris and myocardial infarction independently of coronary atherosclerosis.7
A relationship between IADE and a higher incidence of coronary events has been reported.3,8 This finding raises the possibility that muscular arteries (such as coronary and basilar arteries) may simultaneously dilate and remodel in several arterial beds.9 We performed a case–control study to investigate the coexistence of CAE and IADE in a large consecutive autopsy database.
Materials and Methods
The Multiple Atherosclerosis Site in Stroke (MASS) study is an autopsy database of patients who died with neurological diseases at La Salpêtrière Hospital in Paris from November 1982 to February 1989. The autopsy rate during this period was 73%. Autopsies were performed according to French legislation and the published guidelines of the La Salpêtrière Neuropathology Department.10,11 The study methods as well as the diagnosis and characterization of patients with IADE have been described elsewhere.10,11
In brief, among 886 autopsies, 381 were performed in patients with stroke, 23 (6%) of whom had IADE.10 Two more patients with IADE were further identified in the sample and are included in the present study. IADE was defined as an increased length and diameter of the intracranial arteries and was diagnosed on gross examination (visual enlargement and tortuosity of the intracranial large arteries). To further characterize IADE severity, 2 of the authors (F.P. and J-J.H.) measured the basilar artery diameter at the midpons in 25 stroke patients with IADE(+) and in an equivalent number of stroke patients without IADE(–) who were randomly selected and matched on age, sex, stroke subtype, and year of death (±5 years).10 For this study, we examined the formalin-fixed specimens of intracranial and extracranial arteries, including the aortic arch and the heart stored with the brain. To diagnose CAE, right and left coronary arteries were cut perpendicularly each centimeter from their ostia and the diameters were measured. The presence of CAE was defined as a diameter ≥1.5× larger than the upstream healthy arterial segment.12 Sixteen IADE(+) patients had exploitable heart and coronary arteries and were matched to 16 IADE(–) patients on age (±5 years), sex, stroke subtype, and year of death (±5 years) and constituted the study sample size.
Data are presented as median (range) for continuous variables, and count (percentage) for qualitative variables. We compared clinical and autopsy characteristics between the IADE(+) and IADE(–) stroke patients using McNemar exact test for dichotomous variables and the Wilcoxon signed-rank test for quantitative variables. No statistical comparisons were done for dichotomous variables with a frequency of <5. Correlations between basilar and coronary artery diameters were calculated in both groups (pooled) using the Spearman rank correlation coefficient. Comparison of basilar artery diameter between CAE(+) and CAE(–) stroke patients was done using the Mann–Whitney U test. Statistical testing was done at the 2-tailed α level of 0.05. Data were analyzed using SAS, release 9.1 (SAS Institute, Cary, NC).
The clinical characteristics and main atherosclerosis risk factors in IADE(+) and IADE(–) stroke patients are given in Table 1 and Table I in the online-only Data Supplement. Age at death (80 years), proportion of men (44%), and prevalence of hypertension (69%) were the same in both groups. IADE(+) patients had higher prevalences of coronary artery stenosis (75% versus 25%; P=0.008), basilar artery plaques (63% versus 31%; P=0.12), and ulcerated plaques in the abdominal or thoracic aorta (62% versus 18%; P=0.09; Table II in the online-only Data Supplement).
CAE was observed in 8 of 16 IADE(+) patients versus none of the IADE(–) patients (P=0.008); 2 IADE(+) patients had 2 ectatic coronary arteries. The characteristics of the 8 patients with coexisting CAE and IADE are provided in Table 2. One IADE(+) patient with 2 CAEs had a thoracic aortic aneurysm. One IADE(+) stroke patient had an abdominal aortic aneurysm but no CAE. Atherosclerotic plaque was present in 10 of 13 (77%) dolichoectatic basilar arteries and in 5 of 10 (50%) CAE.
In comparison with IADE(–) stroke patients, IADE(+) patients had a larger median right coronary artery diameter (median, 3.8 mm; range, 2.0–4.5 versus 3.0 mm, 2.0–4.0 mm; P=0.0029); the diameter of the left coronary artery did not differ between the 2 groups (median, 3.0 mm; range, 1.5–4.1 versus 3.5, 2.0–4.7 mm; P=0.22). When the diameter of the basilar artery was considered as a continuous variable, the same relationships were found. A significant positive correlation between basilar artery diameter and right coronary artery diameter was observed (r=0.51; P=0.003), but no association was found for the left coronary artery (r=–0.07; P=0.71).
The same observations were made after grouping patients by CAE(+) and CAE(–). Basilar artery diameter was significantly larger in CAE(+) stroke patients (median, 6.0 mm; range 5–9 versus 3.8 mm, 2–9 mm in CAE(–) patients; P=0.006). An illustrative case of coexisting IADE and CAE is presented in the Figure.
In this case–control autopsy study, we found a significant association between IADE and CAE. This finding suggests that dilative arteriopathy may be a systemic process, involving several arterial beds simultaneously, such as the intracranial arteries, coronary arteries, and, based on the literature, the aorta.
In our series, dolichoectasia occurred in patients with similar risk profiles (advanced age, male sex, and arterial hypertension).3,12 A common pathological pattern of affected muscular arteries has been reported, including rarefaction of elastic tissue of the media with degeneration of the internal elastic lamina,12,13 as well as matrix metalloproteinases dysfunction, in particular, matrix metalloproteinase-3 with the same genotype involved (5A/5A genotype in the promoter region).6,14 Of interest, abdominal aortic aneurysm has also been found to be associated with both CAE15 and IADE patients.13 Both arterial dilatations have been associated with ischemic events, even in the absence of concomitant atherosclerotic lesions.7 It is thought that slow blood flow in ectatic vessels may promote thromboembolic phenomena.
This study is limited by its postmortem nature and by the origin of the recruitment, which was from the neurology departments of La Salpêtrière Hospital. Thus, our results apply only to patients with fatal strokes. In addition, our results should be interpreted with caution because of the small sample size and number of statistical comparisons. Furthermore, we did not measure the diameter of the arteries under pressure, which is likely to underevaluate the true diameter. The inclusion of fatal strokes only may explain the relatively low percentage of aortic aneurysm in IADE(+) patients because patients who had a ruptured aortic aneurysm were unlikely to die in neurological departments. In our study, 8 IADE(+) stroke patients had CAE, and only 1 had abdominal aortic aneurysm. Further prospective studies are needed to determine the relative frequency of these 3 arterial ectasias.
We thank Dr Véronique Sazdovitch for interpretation of microscopic materials (Department of Neuropathology Escourolle, La Salpêtrière Hospital, Paris).
Sources of Funding
This study was funded by SOS-Attaque Cérébrale Association. We thank the Centre Hospitalier Versailles for funding the revision of the English of the final version of the article, performed by Sophie Rushton-Smith, PhD.
Guest Editor for this article was Bo Norrving, MD, PhD.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.115.010797/-/DC1.
- Received July 11, 2015.
- Revision received September 28, 2015.
- Accepted September 30, 2015.
- © 2015 American Heart Association, Inc.
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