Mortality Risk Following Acute Coronary Syndrome Among Patients With Schizophrenia Spectrum Disorders—Addressing the Gaps

It is well established that patients with severe mental illness die prematurely from cardiovascular disease (CVD). Recently, a large meta-analysis within and across major psychiatric diagnostic groups further demonstrated that CVD-related deaths were highest in schizophrenia.¹ By the same token, CVD can be viewed as a preventable contributor to early mortality. Advancements in preventative medicine and acute cardiac care have led to a decline in cardiovascular and acute coronary syndrome (ACS)-related mortality in the general population. Unfortunately, similar trends of decline in mortality related to CVD have not been observed in severe mental illness, with findings that the mortality gap may be increasing, particularly in those with schizophrenia.² The widening mortality gap from CVD suggests that people with schizophrenia are not benefitting from advancements in cardiovascular care.

An important topic connected to the CVD-induced mortality gap relates to the events that occur following an ACS, including timely diagnosis, receipt of appropriate interventions, and survival rates. Notably, an earlier meta-analysis has demonstrated that having a mental illness reduced the likelihood of receiving an indicated acute coronary intervention by 14%, while a diagnosis of schizophrenia increased this disparity to 47%.³ While at the time there was insufficient data to examine mortality rates post-ACS, subsequent studies have since largely supported reduced survival rates following cardiac events in schizophrenia. Less is known, however, as to the impact of revascularization procedures, and/or receipt of cardiac medications on mortality outcomes in this population.

In this issue,⁴ Chang and colleagues re-examine the question of mortality following an index ACS hospital admission in schizophrenia spectrum disorders, compared to patients without psychosis. Using a territory-wide medical database of public services in Hong Kong, the authors demonstrate a 2-fold increase in odds ratio of mortality risk following ACS in schizophrenia spectrum patients as compared to controls, a number that remains consistent across 30-day or 1-year follow-up. Schizophrenia spectrum patients also demonstrate higher CV complication rates, and moreover, in keeping with previously published work, are less likely to receive an indicated coronary intervention³ or post-discharge cardioprotective medications.⁵ Concerningly, even if receipt of revascularization treatment is adjusted for, the authors report only a modest impact on elevated mortality.⁴ The latter observation may suggest an issue of “too little too late,” or reduced physiological capacity to tolerate the ischemic insult, even if appropriate acute care is provided.

While the reasons underlying the association between schizophrenia and mortality following an ACS are not fully elucidated, several factors are hypothesized to play a role. A delay in diagnosis may lead to increases in both infarct severity and related complications at the point of acute management. Poorer access to care, diagnostic overshadowing (assumption that physical symptoms occur as a consequence of psychotic symptoms), and physician bias have all been suggested to play a role in less timely diagnosis and management of medical comorbidity.⁶ Similarly, somatic comorbidities (ie, anemia, cardiomyopathy, chronic obstructive pulmonary disease) that adversely influence outcomes following an ACS occur at higher rates in schizophrenia.⁷ Antipsychotic drugs also contribute to observed increases in traditional cardiovascular risk factors (ie, obesity, dyslipidemia, hypertension and type 2 diabetes), which bode a poorer prognosis following an ACS. These drugs may also prolong QT, decrease heart rate variability, and increase autonomic nervous system drive. These factors may help to explain increases in short-term mortality and worse outcomes, in spite of appropriate revascularization, and will be important to examine in future work.

Additional key factors that might influence mortality, particularly over the longer term following an ACS, may relate to the access to, and compliance with tertiary prevention strategies. In the current issue, Chang et al,⁴ demonstrate only small reductions at 1-year in mortality once post-discharge CV medications are entered into the regression analysis. A recent Danish cohort study similarly demonstrated lower receipt of cardioprotective medications in schizophrenia patients.⁵ Notably, in those who did not receive these indicated drugs, mortality rate was 9 times higher compared to treated individuals in the general population. From a more hopeful perspective, in schizophrenia patients receiving more intensive, “triple” cardiovascular medication therapy, the gap in mortality became insignificant.⁵ These findings will need to be replicated in long-term follow-up studies but highlight that our patients should receive cardioprotective medications post-ASC according to general population guidelines, and may, in fact, require more intensive tertiary prevention approaches.

Taken together, disparities in medical care in schizophrenia spectrum disorders also apply to survival post-ACS. In future work, it will be critical to identify specific moderators that account for the striking increase in mortality. Moreover, it is plausible that addressing key treatment inequities after an ACS has occurred could be insufficient to reverse mortality. This implies that preventative strategies are needed to address other fundamental disparities in care, such as early identification (ie, screening), and treatment of modifiable CV risk factors, which occur at the earliest stages of psychosis.⁸ To this point, in the current issue, patients with an index ACS admission were significantly younger than controls (yet had higher comorbidities),⁴ supporting previous findings that CV risk is accrued early on, cumulating in premature CV mortality. As a silver lining, many of the factors hypothesized to account for increases in CVD, and to drive mortality following an ACS are actionable. However, reductions in mortality from CVD in schizophrenia will require better engagement of implementation science, collaboration between different health sectors and specialists, as well as coordinated population-level approaches.