Significantly more middle-aged and older women are being diagnosed with “broken heart” syndrome (Takotsubo cardiomyopathy) – a condition often triggered by stress or loss, and which can lead to long-term heart injury and impaired heart function – up to 10 times more often than younger women or men of any age, found a study in the Journal of the American Heart Association.
The research also suggests that the rare condition has become more common, and the incidence has been rising steadily since well before the COVID-19 pandemic.
“Although the global COVID-19 pandemic has posed many challenges and stressors for women, our research suggests the increase in Takotsubo diagnoses was rising well before the public health outbreak,” said Dr Susan Cheng, director of the Institute for Research on Healthy Aging in the Department of Cardiology at the Smidt Heart Institute and senior author of the study. “This study further validates the vital role the heart-brain connection plays in overall health, especially for women.”
What the data show
Cheng and her research team used national hospital data collected from more than 135,000 women and men who were diagnosed with Takotsubo syndrome between 2006 and 2017. While confirming that women are diagnosed more frequently than men, the results also revealed that diagnoses have been increasing at least six to 10 times more rapidly for women ages 50 to 74 than for any other demographic.
Additional findings include:
Of the 135,463 documented cases of Takotsubo cardiomyopathy, the annual incidence increased steadily in both sexes, with women contributing most cases (83.3%), especially those over 50. In particular, researchers observed a significantly greater increase in incidence among middle-aged women and older women, compared with younger women. For every additional diagnosis of Takotsubo in younger women, or men of all age groups, there were 10 additional cases diagnosed for middle-aged women and six additional diagnoses for older women.
Before this study, researchers only knew that women are more prone than men to developing Takotsubo syndrome. This latest study is the first to ask whether there are age-based sex differences and if case rates may be changing over time.
The brain and heart connection
As Cheng, who also serves as professor of cardiology and the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science, explains, the way the brain and nervous system respond to different types of stressors is something that changes as women age.
“There is possibly a tipping point, just beyond midlife, where an excess response to stress can impact the heart,” said Cheng, director of Cardiovascular Population Sciences in the Barbra Streisand Women’s Heart Center. “Women in this situation are at especially affected, and the risk seems to be increasing.”
The researchers are next investigating the longer-term implications of a Takotsubo diagnosis, molecular markers of risk, and the factors that may be contributing to rising case rates.
The Smidt Heart Institute has played a leading role in identifying female-pattern heart disease and conditions, developing new diagnostic tools and advancing specialised care for women. Although medical professionals understand that the connection between stress and heart disease risk are critically important, there is still a lot to discern.
“This particular study helps to clarify that women of a certain age range are disproportionately at higher risk for stress cardiomyopathy, and that the risk is increasing,” said Dr Christine Albert, chair of the Department of Cardiology at the Smidt Heart Institute.
“The upswing could be due to changes in susceptibility, the environment, or both. More work is needed to unravel the underlying disease drivers in Takotsubo condition and other women-dominated conditions.”
Study details
Sex‐ and Age‐Based Temporal Trends in Takotsubo Syndrome Incidence in the United States
Varun K. Pattisapu, Hua Hao, Yunxian Liu, Trevor‐Trung Nguyen,
Amy Hoang, C. Noel Bairey Merz, Susan Cheng
Published in JAHA on 13 October 2021
Takotsubo syndrome (TTS) is an uncommon but important cause of myocardial infarction that has been increasingly recognised in the United States. The extent to which documented TTS incidence in the United States may have changed over time, across age groups as well as by sex, is not well understood.
We investigated age‐ and sex‐based temporal trends in TTS incidence, using NIS3 data from years 2006 to 2017. We included patients aged ≥18 years with a primary or secondary TTS diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD‐9‐CM] code 429.83 or International Classification of Diseases, Tenth Revision, Clinical Modification [ICD‐10‐CM] code I51.81). We excluded those without coronary angiography or with coronary angiography and subsequent percutaneous coronary intervention. Per Healthcare Cost and Utilization Project analysis guidelines, we applied “trend weights” and estimated incidence (and SEs) using PROC SURVEYMEANS. We used generalised linear regression to test for differences in temporal trends across sex‐stratified age groups.
All analyses were performed using SAS v9.4 and R v3.6.3. Over the total study period, we identified 135,463 documented cases of TTS. The annual incidence increased steadily in both sexes, with women contributing most cases (88.3%), especially those aged ≥50 years. In particular, we observed a significantly greater increase in TTS incidence among middle‐aged (128 cases per million per year) and older (96 cases per million per year) women compared with younger (15 cases per million per year) women (P<0.001). Increase in TTS incidence among middle‐aged (20 cases per million per year) men was also significant compared with younger (10 cases per million per year) men (P<0.001), but not significant for older (16 cases per million per year) men (P=0.082). In more granular analyses of TTS incidence by quarter year periods, we observed no appreciable difference in temporal trends across the quarters of year 2015 (ie, the transition from ICD‐9 to ICD‐10 coding). In addition, we observed that the average age of the NIS source sample remained stable for women, with a slight increase for men (0.7 year older per year) over the entire study period.
Accordingly, we also observed relatively stable proportions of sex‐based age groups comprising the larger US population at risk over the entire study period. Consistent with reports from national and international cohorts, women have continued to contribute the vast majority of TTS diagnoses over time. Although TTS case diagnoses have steadily increased in both sexes, and across all age groups, the increase over time has been especially pronounced among women aged ≥50 years. Notwithstanding the importance of increased recognition, advancing diagnostic techniques, and improved documentation of the TTS diagnosis, additional factors contributing to the observed temporal trends may include the following: (1) continued increase in size of the at‐risk population, which includes aging adults and aging women in particular; (2) secular changes in socioeconomic and environmental stressors that may be particularly relevant to susceptible middle‐aged and particularly older‐aged individuals; and (3) potential evolution in the nature of TTS as a disease entity, which is known to be heterogeneous in cause as well as presentation.
Notably, potential drivers appear more relevant to older women than older men at risk, for reasons that are currently unclear. Intriguingly, the most prominent at‐risk group was women aged 50 to 74 years. This finding could be caused by the greater propensity for excess sympathetic activation in younger age, combined with a greater susceptibility to cardiac stress and injury in older age, converging in middle‐aged people at risk and particularly women. Our analyses using NIS data were limited by dependence on appropriate ICD‐9 or ICD‐10 coding of diagnoses, procedures, and other in‐hospital measures. Notwithstanding uniform labeling of TTS codes over time and consistent results observed for temporal trends, data from before and after the ICD‐9 to ICD‐10 coding transition should be interpreted with caution. In addition, NIS data do not include biomarkers, echocardiographic measures, and angiographic measures typically used to evaluate TTS cases.
Thus, follow‐up studies that can more comprehensively differentiate between TTS and alternate or overlapping diagnoses (eg, myocarditis, pericarditis, or coronary vasospasm) are warranted. Nonetheless, the availability of diagnosis data on >135 000 cases documented over a span of almost 2 decades offered ample statistical power to detect not only increasing incidence of TTS in the United States, but a steep increase among especially middle‐aged to older women. This overall trend was disproportionate to that seen in other subgroups and appears not completely explained by improvements in clinical recognition.
Future studies are needed to validate and extend from our results as part of efforts to clarify the susceptibility, pathophysiological features, and outcomes related to TTS for those individuals at the highest risk.
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