In recent years, cardiologists and the broader medical community have become increasingly aware that psychological disorders, particularly depression, are common in patients with ACS and are associated with adverse clinical outcomes 
. Even so, abundant evidence suggests that psychological disorders are underrecognized and undertreated in cardiac populations 
. While awareness of depression has increased in cardiology practice, awareness of the possibility of PTSD due to ACS has lagged, possibly because many still see PTSD as primarily a disorder of combat veterans or sexual assault survivors. Indeed, even in academic and community mental health clinics, only a very small proportion of PTSD cases from all causes are identified 
. This under-diagnosis is likely more pronounced in cardiology practice.
To our knowledge, this is the first meta-analytic review of ACS-induced PTSD. We found a 12% prevalence of clinically significant ACS-induced PTSD among ACS patients and, based on a small number of studies, a doubling of risk of mortality and recurrent cardiac events among ACS patients with PTSD symptoms. In previous qualitative literature reviews, 
investigators have examined the possible risk for PTSD following ACS. However, those reviews do not include more recent, larger, and methodologically rigorous studies that investigated both prevalence of ACS-induced PTSD and its association with risk of ACS recurrence and mortality. Given that 1.4 million patients are discharged from US hospitals each year with a diagnosis of ACS 
, these results suggest that 168 000 ACS patients in the United States alone will develop clinically significant PTSD symptoms due to ACS. Among ACS patients in the United States, 20% are hospitalized again within 1 year of the ACS event 
, and 60% of the $1.5 billion spent annually to treat ACS in the United States is due to subsequent hospitalizations 
. It appears that ACS-induced PTSD may contribute to repeated hospitalization and mortality at a rate very similar to that reported for depression (approximate doubling of risk 
Prevalence of ACS-Induced PTSD
Although the overall prevalence of ACS-induced PTSD was 12%, individual study prevalence estimates ranged from 0% to 32%, suggesting a considerable degree of heterogeneity. As expected, prevalence estimates based on screening questionnaires were greater than estimates based on clinical interviews. Also, similar to within-study findings that younger age is associated with greater likelihood of ACS-induced PTSD, younger mean sample age was related to greater prevalence estimates across studies. Finally, later publication date was associated with lower prevalence rates, though the association was modest, which may reflect reduced psychological trauma due to advances in treatment or the fact that the definition of ACS has broadened in recent years to include less severe disease. However, since we found that the inclusion of patients with less severe ACS (ie, NSTEMI and UA) was unrelated to prevalence estimates, advances in treatment may well be responsible for slightly better post-ACS psychological outcomes in recent years. Timing of PTSD assessment, study location, and sex of the sample were unrelated to prevalence estimates.
Symptoms and Clinical Outcomes of ACS-Induced PTSD
Our analyses indicated that ACS-induced PTSD symptoms are associated with an approximate doubling of risk for recurrent cardiac events or mortality. Two of the 3 studies included in the analysis 
adjusted for multiple demographic and clinical covariates, suggesting that the association is not likely to be confounded by demographic characteristics and disease severity.
Important caveats to this review include the fact that only studies with relatively small sample sizes have addressed ACS-induced PTSD, many of which were marginally powered to detect associations with outcomes over relatively short intervals. Furthermore, no study to date has been sufficiently powered to test for potential mechanisms or effect modifiers of the relationship between ACS-induced PTSD and adverse clinical outcomes. Thus, although this meta-analysis was able to quantify more precisely the magnitude of the increased risk of clinical events due to ACS-induced PTSD symptoms, a clear need for additional research remains.
Caveats aside, there is now considerable evidence for a link between PTSD due to various life stressors and subsequent heart disease 
, but the mechanisms for this association are not yet known 
. If the apparent association between ACS-induced PTSD and ACS recurrence and mortality holds up to further scrutiny, many of the candidate mechanisms that require years to develop and be associated with an increase in risk, and so more proximate or trigger mechanisms should be explored, as the follow-up between PTSD and a recurrence/mortality is fairly short in this review (ie, follow-up periods for the 3 included studies ranged from 1–3 years). We know that both ACS and PTSD are associated with sympathetic activation and elevated proinflammatory cytokines, including C-reactive protein 
, tumor necrosis factor, and interleukin 1 
. It is likely that the additive effects of the inflammation found in patients with PTSD may adversely affect the heart 
. Pharmacologic and psychotherapy treatments for PTSD due to noncardiac events reduce PTSD symptoms 
and might reduce accompanying inflammation, potentially producing more favorable clinical outcomes in ACS patients. It seems likely, but has not yet been tested, that reducing symptoms of PTSD could improve adherence to post-ACS treatment regimens 
The present review has several limitations. First, since we did not include unpublished articles or articles from non–peer-reviewed journals, we are more likely to have excluded negative findings 
. Second, although some articles included in this review 
were from samples large enough to report useful data on within-sex, race, or ethnicity estimates, or rates by ACS type, our findings were based on cruder estimates, such as the proportion of each sample that was male, which may limit our conclusions about the relationship of demographic factors to prevalence. Finally, none of the studies included in this review reported on the severity of the ACS event in terms of the types of critical care that may have become necessary after the ACS, such as intensive care unit (ICU) admission or major surgery. While there seemed to be no difference in PTSD rates by ACS type (STEMI vs NSTEMI/UA), a growing literature suggests that exposure to critical care for other types of medical events can induce PTSD in up to 64% of ICU patients 
We were able to locate only one PTSD treatment study in ACS patients: a phase I safety trial of cognitive behavioral therapy for ACS-induced PTSD 
. The study was not powered to detect differences between the treatment and control groups (the intent-to-treat analysis included 51 participants), but small-to-moderate reductions in PTSD symptoms were reported, and no adverse clinical outcomes or safety concerns were associated with treatment. Thus, more research is needed to determine whether treatment can reduce ACS-induced PTSD symptoms and reduce the associated risk for ACS recurrence and mortality.
While little research exists on treatment of ACS-induced PTSD, a growing body of literature suggests risk factors for PTSD diagnosis and symptom severity after ACS. These risk factors include intense fear 
, perceived life threat, lack of control 
, helplessness and chest pain 
during the ACS, dissociation during the event, acute stress disorder 
, depression symptoms during hospitalization 
, and history of psychiatric disorder before ACS 
, alexithymia 
, or neuroticism 
. Demographic factors associated with ACS-induced PTSD in some studies include younger age 
, female sex 
, ethnic minority status, and low socioeconomic status 
. While these scattered risk factor studies have been useful, a unified risk stratification strategy is warranted for predicting which patients are most likely to develop ACS-induced PTSD.
In conclusion, across published studies concerning the prevalence of ACS-induced PTSD and its associations with clinical outcomes, a few general conclusions can be drawn: (1) ACS is a traumatic event for many, and ACS-induced PTSD is relatively common, with approximately 12% experiencing clinically significant PTSD symptoms and 4% meeting full diagnostic criteria for the disorder, and (2) based on a small number of studies, clinically significant symptoms of ACS-induced PTSD appear to double patients’ risk of recurrent cardiac events and mortality. These results identify areas requiring further research; in particular, studies testing treatments for ACS-induced PTSD are needed.