Apical ballooning syndrome (ABS), migraine, and Raynaud phenomenon are characterized by female predominance, identifiable triggers, and, likely, vascular dysfunction. Estrogen deficiency, such as in menopause, is considered to be a predisposing factor for ABS. We investigated the association of ABS with migraine, Raynaud phenomenon, and hormonal factors. We compared 25 consecutive residents (all women) of Olmsted County, Minnesota, presenting with ABS, to 2 age-matched control groups from the same community: 25 women presenting with ST-segment elevation myocardial infarction (STEMI), matched for the index ABS event date, and 50 women with neither diagnosis. The patients with ABS were more likely to have a migraine history (11 [44%] vs 4 [16%] STEMI controls, p = 0.031, and vs 6 [12%] population controls, p = 0.003), and “possible migraine” (including other headache syndromes suggestive of migraine; 15 [60%] vs 6 [24%] STEMI controls, p = 0.012; and vs 12 [24%] population controls, p = 0.003). Of the patients with ABS, 4 (16%) had Raynaud phenomenon compared to no STEMI controls and 1 (2%) population control (p = 0.038). No differences were present in parity, menopausal status, years since the onset of menopause, and frequency of oophorectomy. Current hormonal replacement therapy use was greater in those with ABS than in the population controls: 4 (16%) versus none (p = 0.002). In conclusion, the association of ABS with migraine and Raynaud phenomenon supports a role of vasomotor dysfunction in the pathogenesis of ABS. The absence of an association with reproductive characteristics and the finding that ABS occurred despite exogenous hormonal use in some patients suggests that estrogen deficiency per se is not the primary factor in the pathophysiology.
Apical ballooning syndrome (ABS) shows a marked female predominance. We have previously reported that anxiety and depression, which also predominate in women, are associated with ABS. This led us to speculate that ABS might also be associated with other conditions that are more prevalent in women, especially those that have a vascular component to their pathophysiology, such as Raynaud phenomenon and migraine. Similar to ABS, both Raynaud phenomenon and migraine are precipitated by a variety of emotional and physical triggers. Given these similarities, we hypothesized that ABS might be associated with migraine and Raynaud phenomenon, supporting a role for vascular dysfunction in the pathophysiology of ABS. In addition, because ABS typically develops in postmenopausal women, it is possible that alterations in the female sex hormone profile could contribute to the pathophysiology of ABS. Thus, determining the reproductive characteristics, including the timing of menopause and the use of hormonal replacement therapy, could add to our understanding of this disorder. Therefore, the aims of the present study were to investigate the frequency of a premorbid diagnosis of migraine or Raynaud phenomenon and to evaluate the reproductive characteristics among patients previously diagnosed with ABS.
Methods
We conducted a retrospective case-control study of patients who were residents of Olmsted County, Minnesota. As of the 2000 United States census, the Olmsted county population was 124,000 (90% white), with 81% of the population residing within the city limits of Rochester. Epidemiologic research in Olmsted County is facilitated by the presence of the Mayo Clinic within the county and its relative isolation from other major tertiary care centers. The Mayo Clinic serves as the sole tertiary care center for the region and has the only cardiac catheterization laboratory in the county at which ABS can be diagnosed. We had access to the complete medical records from all medical facilities within Olmsted County, often encompassing the entire period from birth to the present.
We identified 25 consecutive patients, all women, who had been prospectively diagnosed with ABS according to the Mayo Clinic diagnostic criteria from 2002 to 2007. Two control groups were identified and were matched by date of birth, gender, and follow-up duration. The first control group consisted of 25 women who had been diagnosed with an anterior ST-segment elevation myocardial infarction (STEMI), with the STEMI diagnosis dates matched for the index ABS diagnosis dates. The second group consisted of 50 subjects, drawn from the general Olmsted County population, who had been seen at Mayo Clinic within 5 years of the ABS event date. The Mayo Clinic institutional review board approved the present study, and all subjects provided written informed consent to the use of their medical records for research.
The complete medical record of each subject was reviewed. Details of the medical history of each subject before the index event were recorded. These included risk factors such as smoking and chronic medical conditions such as diabetes mellitus, hypertension, and dyslipidemia. These were defined through patient-reported history, physician diagnosis, or a specific treatment documented in the medical record.
Study data were collected using the Research Electronic Data Capture tools hosted at Mayo Clinic. Research Electronic Data Capture is a secure, web-based application designed to support data capture for research studies.
Migraine was defined as a documented diagnosis by a healthcare provider or a patient report of a previous diagnosis of migraine. Because migraine is often underdiagnosed, a second category of “possible migraine” using a broader definition of migraine was recorded. This category included subjects with headache syndromes that suggested migraine but were not specifically diagnosed as such (e.g., “vascular headache” or “premenstrual headache” and other unspecified headache syndromes). Tension headaches were also included in this category to account for the possibility of misdiagnosis and overlap. In the population control group, 1 subject was described as having “vascular tension headache with menses, associated with photophobia.” Because this description is classic for a diagnosis of migraine, this was included in the definite migraine category.
Raynaud phenomenon was defined as a documented diagnosis of Raynaud phenomenon by a healthcare provider, except for 1 subject in the ABS group, who was described as having “cold-induced vasospasm of the fingers,” which was consequently classified as Raynaud phenomenon. The reproductive history included details of parity, menopause (whether surgical or natural), and the use of hormonal contraception before menopause, and hormonal therapy after menopause.
Continuous variables are presented as the mean ± SD. Categorical variables are presented as the frequency and group percentages. Differences between the matched controls and cases were tested using logistic regression analysis for categorical variables and linear regression analysis for continuous variables, adjusting for age. For logistic regression analysis, Wald-based confidence intervals and p values are reported, unless noted otherwise. A value of p <0.05 was considered statistically significant. The data were analyzed using the JMP statistical software package, version 9 (SAS Institute, Cary, North Carolina).
Results
The mean age of the patients with ABS was 71 ± 12 years. All the patients with ABS were women. A specific stressor was identified in 88% of the patients with ABS: physical illness in 15 (60%) and a psychological stressor in 10. Most patients were presumed to have an acute coronary syndrome on presentation, with 23 (92%) presenting with chest pain and/or dyspnea and an electrocardiogram showing ST-segment elevation in 15 (60%) or ischemic-appearing ST-T changes in 6 (24%). The cardiovascular disease risk factors and the rates of established vascular disease before the index event compared to the control groups are listed in Table 1 . Women with a diagnosis of ABS were more likely to have a smoking history than the population controls, but no difference was seen between the ABS cases and STEMI controls. Otherwise, no significant difference was seen in the frequency of the conventional risk factors of diabetes mellitus, dyslipidemia, and hypertension between the ABS group and either control group. Also, no differences were seen in the rates of a previous diagnosis of coronary artery disease, peripheral vascular disease, or stroke.
| Variable | ABS Group (n = 25) | STEMI Control Group (n = 25) | p Value (ABS vs STEMI) | Population Control Group (n = 50) | p Value (ABS vs Population) |
|---|---|---|---|---|---|
| Age (yrs) | 71 ± 12 | 70 ± 13 | 0.87 | 71 ± 12 | 0.99 |
| Hypertension | 20 (80%) | 20 (80%) | 0.97 | 31 (62%) | 0.11 |
| Diabetes mellitus | 5 (20%) | 5 (20%) | 0.99 | 7 (14%) | 0.51 |
| Dyslipidemia | 10 (40%) | 14 (56%) | 0.26 | 25 (50%) | 0.41 |
| Smoking (current or previous) | 17 (68%) | 12 (48%) | 0.15 | 19 (38%) | 0.016 |
| Coronary artery disease history | 7 (28%) | 9 (36%) | 0.49 | 9 (18%) | 0.29 |
| Stroke history | 2 (8%) | 4 (16%) | 0.37 | 4 (8%) | 1.0 |
| All vascular disease ∗ | 8 (32%) | 11 (44%) | 0.32 | 13 (26%) | 0.55 |
| Alcohol abuse | 5 (20%) | 3 (12%) | 0.69 | 4 (8%) | 0.14 |
| Body mass index (kg/m 2 ) | 27 ± 6 | 28 ± 6 | 0.65 | 27 ± 6 | 0.92 |
∗ Coronary artery disease, stroke, peripheral arterial disease.
Compared to both control groups, the women with ABS were more likely to have a history of migraine ( Figure 1 and Table 2 ). When the migraine category was expanded to include reports of headache syndromes suggestive of migraine but not actually diagnosed as such, (“possible migraine”), a significant difference remained between the ABS cases and the 2 control groups. Raynaud phenomenon was less frequently reported ( Table 2 ). Of the 4 patients with ABS who had a diagnosis of Raynaud phenomenon, 3 also had migraine. The single patient in the population control group with Raynaud phenomenon developed symptoms after being diagnosed with carpal tunnel syndrome, and the symptoms resolved after carpal tunnel release surgery.
| ABS Group (n = 25) | STEMI Control Group (n = 25) | OR (95% CI) | p Value (ABS vs STEMI) | Population Control Group (n = 50) | OR (95% CI) | p Value (ABS vs Population) | |
|---|---|---|---|---|---|---|---|
| Migraine | 11 (44%) | 4 (16%) | 4.6 (1.2–21) | 0.031 | 6 (12%) | 6.5 (2.0–24) | 0.003 |
| Possible migraine ∗ | 15 (60%) | 6 (24%) | 4.7 (1.5–17) | 0.012 | 12 (24%) | 4.8 (1.7–14) | 0.003 |
| Raynaud phenomenon | 4 (16%) | 0 (0%) | NA | 0.009 † | 1 (2%) | 12.2 (1.5–264) | 0.038 |
∗ Broader headache category, including descriptions such as “tension headache” and “premenstrual headache.”
The reproductive characteristics in the ABS cases and controls are listed in Table 3 . When the ABS group was compared to the control groups, no difference was found in parity, menopausal status, including the specific subgroup of surgical menopause (oophorectomy), or years of menopause. A significant difference was noted in the current use of hormonal replacement therapy at ABS diagnosis compared to the population controls alone. Almost ½ of the ABS group had a history of hysterectomy; however, this proportion was not significantly greater than that in the control groups. The medical records were also examined for details of pregnancies, including pregnancy complications such as gestational hypertensive disorders or gestational diabetes mellitus; however, insufficient data on the details of pregnancy were present.
| Variable | ABS Group (n = 25) | STEMI Control Group (n = 25) | p Value (ABS vs STEMI) | Population Control Group (n = 50) | p Value (ABS vs Population) |
|---|---|---|---|---|---|
| Menopausal | 23 (92%) | 24 (96%) | 0.48 | 44 (88%) ∗ | 0.75 |
| Menopause age (yrs) | 49 ± 5 † | 47 ± 6 ‡ | 0.26 | 47 ± 8 | 0.40 |
| Duration of menopause at index event (yrs) | 23 ± 13 | 25 ± 13 | 0.36 | 24 ± 13 | 0.35 |
| Hormonal therapy (past or present) | 14 (56%) | 15 (60%) | 0.35 | 26 (52%) | 0.74 |
| Current use of hormonal therapy | 4 (16%) | 3 (12%) | 0.67 | 0 (0%) | 0.002 § |
| Any history of pregnancy | 23 (92%) ∗ | 22 (88%) | 0.99 | 42 (84%) | 0.68 |
| Total pregnancies (n) | 3.9 ± 2.2 | 4.3 ± 3.3 | 0.60 | 3.3 ± 2.5 | 0.27 |
| Total births (n) | 3.1 ± 1.9 | 3.2 ± 2.3 | 0.76 | 2.8 ± 2.3 | 0.48 |
| History of bilateral oophorectomy | 7 (28%) | 6 (24%) | 0.75 | 16 (32%) | 0.72 |
| History of hysterectomy (with or without oophorectomy) | 12 (48%) | 8 (32%) | 0.25 | 18 (36%) | 0.31 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
