Cardiovascular disease prognosis among women with anxiety: just the tip of the iceberg?

Symptoms of anxiety are pervasive in the aftermath of an acute coronary event or diagnosis. Approximately 40% of patients with coronary artery disease (CAD) report symptoms of anxiety during hospitalization or immediately post-event (range = 14–55%).1 For some, symptoms can persist, meeting diagnostic criteria for an anxiety disorder (15–20% of patients). These reported rates are approximately twice as common as in primary care patients and three times more prevalent than in the general population. The effects of anxiety permeate into multiple facets of patients’ lives and increase the risk for additional cardiovascular events and cardiac and all-cause mortality. To illustrate, a meta-analysis aggregating data from nearly 6000 patients with myocardial infarction (MI) documented that post-event anxiety was associated with a 71% increased risk of new cardiac events and a 23% increased risk of cardiac mortality.2 A similar meta-analysis of 16 studies including 9373 patients with MI determined patients with anxiety had a 23% and 27% increased risk of short-term complications and long-term major adverse cardiovascular events (MACE), respectively, in comparison with those without anxiety.3 Rates of anxiety after a cardiovascular diagnosis are approximately twice as high for women as compared with men.4 As reported in several Western and Eastern healthcare contexts, anxiety in women is markedly higher than men throughout hospitalization, immediately post-discharge, and up to 12 months post-event. The cardiovascular effects of anxiety for women are not benign: in a prospective cohort study (n = 662; 28% women), each standard deviation increase in psychological distress was associated with a 44% increased risk of cardiovascular events in patients with CAD, but only among women.5 In addition, data generated from a study of 227 647 women and 321 894 men with ischaemic heart disease determined that after adjustments (i.e. demographic and lifestyle factors, cardiac history and severity, psychological comorbidities, medication use, and cardiac treatment), psychological distress [defined broadly as anger, hostility, anxiety, depression, social support, Type A behaviour pattern, Type D personality, and post-traumatic stress disorder (PTSD)] was associated with a 21% increased risk of MACE among women.6 Taken together, burgeoning research demonstrates that anxiety is prevalent following a cardiovascular event or diagnosis, particularly among women, and that elevated anxiety symptoms may be correlated with an increase in cardiovascular risk. We fear, however, that this is just the tip of the iceberg: the problem of anxiety among women with established disease may be grossly under-estimated. This is due to several factors (Figure 1). First, screening for anxiety during hospitalization is not currently standardized practice in many cardiovascular care centres. Secondary prevention programmes (e.g. cardiac rehabilitation) are settings that provide the most opportunities to screen for anxiety, but women are less likely to participate in these programmes. As such, it is possible that these symptoms are not being formally identified among women. Second, research on the effects of anxiety on clinical endpoints among women with established cardiovascular disease is limited, partially attributed to the ongoing reality that participation in cardiovascular clinical research is lower amongst women and those with elevated levels of distress. To illustrate, across the existing six meta-analyses and systematic reviews of studies measuring the prognostic significance of anxiety on cardiovascular outcomes, women comprise only 24.5% of participant samples. In addition, a systematic review and meta-analysis of sex and gender differences in depression and anxiety prevalence and cardiovascular prognosis determined that sex- and gender-based analyses were conducted in only 24% of the 49 studies.6 Studies using all women samples may help to clarify the potency of anxiety. Unfortunately, after a thorough review of the published literature (English-only; 2000–2022) and studies profiled in existing meta-analyses and reviews, no studies among women with established CAD were identified. In women with suspected CAD, however, more severe anxiety symptoms predicted time to mortality over a median of 9.3 years, which may provide some insight into the effects of anxiety on women’s outcomes after an established cardiac event or diagnosis.7 Anxiety among women with established CAD: What is below the surface? Third, young women (18–55 years of age) report the highest psychological distress pre- and post-acute coronary syndrome (ACS) in comparison with older women and men. Several studies have indicated that higher anxiety scores at hospitalization and up to 12 months post-MI are significantly predicted by female sex and young age.8 However, there have been missed opportunities for measuring anxiety and related clinical outcomes among younger women with CAD. One large prospective study measured the role of psychological factors on young women’s outcomes (mortality and functional and psychosocial outcomes) at 1 and 12 months post-MI but did not measure anxiety. The YOUNG-MI registry, a retrospective study examining a cohort of young adults <50 years of age with a first-time MI (19% female), determined that women had a higher all-cause mortality over a median follow-up of more than 10 years, but, again, post-event anxiety was not measured. There is simply not enough evidence to estimate the clinical risks of anxiety in women with CAD because young women’s outcomes have been sparsely investigated. Indeed, the mean age of women included across prior systematic reviews on anxiety and cardiovascular disease outcomes is >60 years. Targeted research on younger women is especially warranted as the annual incidence of MI hospitalizations has increased to a greater extent for young women vs. young men over the last two decades (10% increase for young women vs. 3% for young men). Younger women are also more likely to report a worse quality of life and higher rates of 1-year all-cause re-hospitalizations in comparison with younger men (34% vs. 23%).9 Fourth, emerging evidence indicates that cardiac diagnostic sub-groups, such as those with non-obstructive CAD, may be more prone to developing elevated anxiety,10 potentially because patients may have unremarkable medical histories so the shock of experiencing a cardiac event may be more anxiety-provoking. Recent investigations report that anxiety (14–17%) and traumatic stress symptoms (23–43%) are pervasive among patients with spontaneous coronary artery dissection (∼90% women) and takotsubo cardiomyopathy (∼80% women). Higher anxiety levels among patients with non-obstructive CAD in comparison with age- and sex-matched patients with CAD have been observed. The outcomes of these elevated levels of anxiety are unclear, however. A review and meta-analysis determined that the risk of MACE associated with psychological factors is more pronounced in women with non-obstructive CAD than obstructive CAD,6 but results were generated from sub-group analyses on a small number of women and should be interpreted with caution. In conclusion, we do not know the true prevalence and clinical importance of anxiety among women with cardiovascular disease, but our clinical intuition tells us the impact permeates far below the surface of our current knowledge. There remains limited screening of anxiety in cardiovascular disease contexts, an under-representation of women and a paucity of sex- and gender-based analyses in cardiovascular disease research, and an under-assessment of anxiety in important cardiovascular sub-groups. In order to fully understand the scope of the problem, it will be important to recalibrate research population targets to include women, especially younger women, with non-obstructive CAD. Prospective longitudinal research is also warranted. It is likely that the currently known prevalence and impact of anxiety among women with CAD is just the tip of the iceberg. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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