HIGHLIGHTS
- •
Spontaneous coronary artery dissection (SCAD) is a relatively rare but well-known cause of acute coronary syndrome in women.
- •
Premenopausal women with SCAD show a higher clinical and angiographic risk profile.
- •
Premenopausal women with SCAD often present as STEMI on admission.
- •
They often show proximal coronary artery and multisegment involvement.
- •
In-hospital outcomes are not different between pre and post-menopausal SCAD women.
Spontaneous coronary artery dissection (SCAD) is a relatively rare but well-known cause of acute coronary syndrome in women. The role of sexual hormones has been related to the pathophysiology of SCAD. However, clinical features, angiographic findings, management and outcomes of SCAD women in relation to menopause status remain unknown. The Spanish multicenter prospective SCAD registry ( NCT03607981 ), included 318 consecutive patients with SCAD. All coronary angiograms were analyzed in a centralized Corelab . In this substudy, 245 women were classified according to their menopause state (pre-menopausal and post-menopausal). In-hospital outcomes were analyzed: 148 patients (60.4%) were post-menopausal. These patients were older (57 [52 to 66] vs 49 [44 to 54] years, p <0.01) and had more often hypertension (49% vs 27%, p <0.01) and dyslipidemia (46% vs 25%, p <0.01). Post-menopausal women showed more often previous history of acute coronary syndrome, including previous SCAD (9% vs 3%, p = 0.046), and presented less frequently as ST-segment elevation myocardial infarction on admission, compared with premenopausal women (34% vs 49%, p = 0.014). On the other hand, premenopausal women showed more often proximal and multisegment involvement (24% vs 7%, and 32% vs 18%, respectively, both p <0.01). Post-menopausal women were more often managed conservatively (85% vs 71%, p <0.01) and presented less frequently left ventricular dysfunction (both, p <0.01). There were no differences between groups in terms of in-hospital stay or mortality, new acute myocardial infarction, unplanned coronary angiography or heart failure. In conclusion, post-menopausal women with SCAD show different clinical and angiographic characteristics compared with pre-menopausal SCAD patients. Initial treatment strategy was different between groups, though in-hospital outcomes did not significantly differ ( NCT03607981 ).
GRAPHICAL ABSTRACT
Spontaneous coronary artery dissection (SCAD) is a relatively uncommon, though increasingly recognized cause of acute coronary syndrome (ACS), especially in women. This entity, defined as a spontaneous separation of the coronary artery wall layers non-iatrogenic and not related to trauma, has been classically associated to young women, especially during pregnancy and peripartum. , Recent data from larger and prospective registries on SCAD have allowed to improve our knowledge on this entity, thus providing relevant information about the pathophysiology, diagnosis, management and prognosis of SCAD. Furthermore, recently two position papers have been published by the European Society of Cardiology and the American Heart Association , summarizing current knowledge on SCAD. Accordingly, SCAD predominantly affects young-to-middle aged women with usually classical cardiovascular risk factors as hypertension or hyperlipidemia, whilst peripartum-SCAD constitutes a small proportion of SCAD cases (less than 5%). At the same time, SCAD is still found to be the more frequent cause of ACS during pregnancy and peripartum period.
The pathophysiology of SCAD is still not fully understood. A hormonal influence has been often suggested to be involved in pathogenesis. This hypothesis is based on the clear predominance of female gender and the occurrence of pregnancy-related SCAD. Both estrogens and progesterone have been suggested as promoters of coronary vessel wall fragility potentially leading to dissection phenomena. However, no previous prospective study have specifically analyzed the role of changes in sexual hormonal profile in the characteristics of SCAD. Therefore, the aim of our study was to assess and better characterize differences between pre- and post-menopausal women affected by SCAD.
Methods
Since 2015, the prospective, nation-wide, Spanish Registry on SCAD (ClinicalTrials.gov registry number NCT03607981 ) includes consecutive patients with a diagnosis of SCAD from 31 academic centers in Spain. Clinical data is prospectively recorded in specific case-report forms with predefined SCAD-related variables, including gynecologic history. Specifically, information regarding the presence and age at menopause, the prescription of oral contraceptive pill, intrauterine contraceptive device, hormone replacement therapy and obstetric history was prospectively recorded. From June 2015 to April 2019, 344 consecutive patients (387 lesions) were included. All coronary angiograms were carefully analyzed jointly by 2 operators with experience in SCAD (MGG and FA) at a centralized Corelab in the coordinator center. After careful revision, a total of 26 patients were excluded (3 patients withdrew informed consent; 4 had no coronary angiography of the index event, and 19 additional patients were excluded after angiographic review due to a high probability of an alternative diagnosis other than SCAD). To avoid the potential influence of exogenous hormonal therapies in this cohort, both post-menopausal women receiving hormone replacement therapy (n=8) and pre-menopausal women receiving oral contraceptives (n = 22) or with an intrauterine device (n = 4) at the time of SCAD were excluded from the present analysis. Thereby, the present analysis includes data from 245 women with SCAD, who were classified according to their menopausal status. Baseline demographic characteristics, personal history, data on admission, as well as events during hospitalization and at hospital discharge, were prospectively recorded. Data regarding angiographic findings as coronary artery location, morphological characteristics, number of affected vessels, as well as the type of treatment and results in those lesions treated by percutaneous coronary intervention (PCI), were also included. A central Institutional Review Board approved the study for the entire country. All patients included signed the informed consent.
SCAD was defined as the spontaneous separation of the coronary artery wall not related to atherosclerosis, iatrogenic injury or trauma. Angiographic SCAD patterns were categorized according to a previously described specific classification. Type 1 lesions were defined as those lesions with classic double lumen image. Type 2 lesions were defined as lesions that showed diffuse narrowing (>20 mm) without double-lumen, sub classifying them as type 2a when the coronary artery recovered its normal caliber distally to the lesion and, 2b when the lesion extends to the most distal segment of the vessel without recovery of the caliber. Type 3 lesions were defined as more focal stenosis (<20 mm) resembling atherosclerotic lesions. A fourth pattern (type 4) was defined for lesions in which the first finding in angiography was an abrupt occlusion that does not allow its inclusion in any of the other patterns. Coronary tortuosity was analyzed according to the method previously described by Eleid et al and classified as mild, moderate, or severe. Coronary artery ectasia was considered when a coronary segment was more than 1.5 times the diameter of an adjacent normal coronary segment. PCI final success in SCAD was defined as flow improvement ≥1 in Thrombolysis in Myocardial Infarction (TIMI) grade with a final TIMI 2-3 flow.
Menopause was defined as the time when a woman no longer has menstrual periods for at least 12 months. For the present analysis, two groups were predefined for comparison. One group included women with regular menstrual periods or last menstrual period within the last 12 months before SCAD (premenopausal group), and a second group that includes women fulfilling criteria for menopause (post-menopausal group). Clinical and angiographic findings, management and in-hospital outcomes were compared between groups. A prespecified in-hospital major adverse cardiac event was defined as the presence of death, myocardial reinfarction, unplanned coronary angiography or congestive heart failure during the index admission. Reinfarction was defined according to the Third Universal Definition of Myocardial Infarction.
Quantitative variables are presented as mean ± standard deviation or median [interquartile range]. Categorical variables are presented as number (percentage). The Student’s t -test or the Mann–Whitney U were used to compare continuous variables. Pearson’s chi-square test was used for categorical variables. A value of p <0.05 was considered as statistically significant. All tests were performed with STATA 12 (StataCorp LLC, Texas, United States).
Results
Baseline characteristics and clinical presentation are summarized in Table 1 . 148 patients (60.4%) were post-menopausal (menopause occurred at the age of 50 [47 to 52] years). These patients were significantly older (57 [52 to 66] vs 49 [44 to 54] years, p <0.01) and had more often hypertension (49% vs 27%, p <0.01) and dyslipidemia (46% vs 25%, p <0.01), without differences between groups regarding history of diabetes mellitus or smoking habit. Regarding co-morbidities, post-menopausal women showed more often previous history of ACS (9% vs 3%, p = 0.046), that included a previous diagnosis of SCAD or myocardial infarction with nonobstructive coronary arteries (including unnoticed or misdiagnosed SCAD episodes). The presence of an identifiable potential trigger was similar in the two groups ( Table 1 ). Only two patients in our series had pregnancy associated SCAD. Long-term inflammatory disease was less frequent (1% vs 9%, p <0.01) in post-menopausal women and there were no differences regarding hypothyroidism or previous stroke. In addition, post-menopausal women were more often multiparous when compared with premenopausal women (39% vs 25%, p <0.01). Finally, with regard to the initial clinical presentation on admission, premenopausal women presented more frequently as ST-segment elevation myocardial infarction (STEMI) (49% vs 34%, p = 0.014) ( Table 1 ).
| Variable | Pre-menopausal (97 patients) | Post-menopausal (148 patients) | p Value |
|---|---|---|---|
| Age (years) | 49 [44-54] | 57 [52-66] | <0.01 |
| Hypertension | 26 (27%) | 72 (49%) | <0.01 |
| Hyperlipidemia | 24 (25%) | 68 (46%) | <0.01 |
| Diabetes mellitus | 4 (4%) | 9 (6%) | 0.49 |
| Smoker | 42 (43%) | 56 (38%) | 0.39 |
| Connective tissue disease | 1 (1%) | 1 (0.7%) | 0.76 |
| Long-term inflammatory disease | 9 (9%) | 2 (1%) | <0.01 |
| Previous stroke | 5 (5%) | 5 (3%) | 0.49 |
| Hypothyroidism | 11 (11%) | 24 (16%) | 0.28 |
| Previous acute coronary syndrome | 3 (3%) | 13 (9%) | 0.04 |
| Depression | 19 (20%) | 31 (21%) | 0.79 |
| Anxiety | 11 (11%) | 29 (20%) | 0.08 |
| Multiparous | 24 (25%) | 58 (39%) | <0.01 |
| Miscarriage | 13 (13%) | 21 (14%) | 0.95 |
| STEMI on admission | 48 (49%) | 50 (34%) | 0.01 |
| NSTEMI on admission | 41 (42%) | 91 (61%) | <0.01 |
| Identifiable trigger | 41 (42%) | 54 (36%) | 0.33 |
| Physical | 12 (12%) | 18 (12%) | |
| Emotional | 27 (28%) | 34 (23%) |
Angiographic findings of the patients are shown in Table 2 ( Figures 1 and 2 ). Premenopausal women had more often involvement of proximal coronary segments (24% vs 7%, p <0.01), showing more diffuse lesions frequently affecting more than one coronary segment (32% vs 18%, p <0.01) with longer lesions (43±21 mm vs. 35±21 mm; p = 0.034). They also presented more often left ventricular dysfunction (20% vs 5%, p <0.01). There were no significant differences regarding initial coronary TIMI flow, coronary artery tortuosity or coronary ectasia ( Table 2 ). Remarkably, the rate of screening of extra-coronary vascular abnormalities (including fibromuscular dysplasia) was relatively low (20%) compared with other contemporary cohorts on SCAD. We found no differences in the percentages of screening performed between pre and menopausal women, neither in the prevalence of extra-coronary vascular abnormalities between groups ( Table 2 ).
| Variable | Pre-menopausal (97 patients) | Post-menopausal (148 patients) | P Value |
|---|---|---|---|
| SCAD coronary artery Left main Left anterior descending coronary artery Left circumflex coronary artery Right coronary artery | 4 (4%) 48 (49%) 22 (23%) 23 (24%) | 1 (0.7%) 66 (45%) 54 (36%) 27 (18%) | 0.04 |
| Left main involvement | 4 (4%) | 1 (0.7%) | 0.06 |
| Proximal segment involvement | 23 (24%) | 10 (7%) | <0.01 |
| Multivessel involvement | 9 (9%) | 17 (11%) | 0.58 |
| Multi-segment involvement | 31 (32%) | 26 (18%) | <0.01 |
| Initial coronary flow (TIMI) | 2.2 ± 1.2 | 2.2 ± 1.1 | 0.59 |
| Initial TIMI flow 0-1 | 27 (28%) | 38 (26%) | 0.71 |
| Coronary artery tortuosity ( Eleid ) | 0.24 | ||
| None | 34 (35%) | 36 (24%) | |
| Mild | 33 (34%) | 67 (45%) | |
| Moderate | 16 (16%) | 23 (17%) | |
| Severe | 14 (14%) | 22 (15%) | |
| Coronary ectasia | 8 (8%) | 19 (11%) | 0.41 |
| Angiographic type (Saw) | 0.11 | ||
| 1 | 25 (26%) | 24 (16%) | |
| 2a | 38 (39%) | 61 (41%) | |
| 2b | 24 (25%) | 33 (22%) | |
| 3 | 2 (2%) | 12 (8%) | |
| 4 | 8 (8%) | 18 (12%) | |
| Diameter Stenosis (visual estimation) % | 79 ± 21 | 78 ± 21 | 0.77 |
| Lesion length (mm) | 43 ± 21 | 35 ± 21 | 0.03 |
| Extra-coronary vascular abnormalities screening (including fibromuscular dysplasia) | 17 (18%) | 32 (22%) | 0.32 |
| Extra-coronary vascular abnormalities | 7/17 (41%) | 9/32 (28%) | 0.35 |
| Fibromuscular dysplasia | 6/17 (35%) | 7/32 (22%) | 0.26 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
