Understanding the cardiac vulnerabilities driving early mortality in schizophrenia

Individuals living with schizophrenia have a substantially reduced life expectancy compared with the general population, with SCD occurring at a rate approximately four times higher than in the general population.^1,2 According to different studies, the most common causes of sudden deaths in people living with schizophrenia are cardiac causes, followed by drug intoxication and suicide.²⁻⁴ 

People living with schizophrenia are at higher risk of SCD compared with the general population

People diagnosed with schizophrenia exhibit a higher prevalence of traditional cardiovascular risk factors, including smoking and excess alcohol intake.^2,5 Another factor that can impact the risk of SCD in people living with schizophrenia is the lower socioeconomic status, which leads to poorer access to health care, and delayed treatment and interventions.² Studies suggest that patients that do have access to health care, may receive inequitable care for their symptoms and less follow-up care.^2,6 

High levels of social isolation and limited social support mean that cardiac arrests in people living with schizophrenia are often unwitnessed and are frequently identified only after a prolonged period, such as during welfare checks.² 

Antipsychotic medications may contribute to the increased incidence of SCD in people living with schizophrenia 

Most people diagnosed with schizophrenia are treated with antipsychotic medications, which have remained the cornerstone of schizophrenia management since their introduction.⁷ However, the use of antipsychotic medication has been associated with the increased incidence of SCD in people living with schizophrenia.¹ Risks factors include the use of high doses or rapid administration, and the presence of pre-existing hypertension or ischemic heart disease.⁸ 

One of the mechanisms proposed that explains this downside effect is the prolongation of the QT interval, which refers to an extension of the interval between the onset of electrical depolarisation of the ventricles and the end of repolarisation, and can lead to ventricular arrhythmias.^2,8,9 A meta-analysis including data from 15,540 patients living with schizophrenia who were treated with antipsychotics found that approximately 4% experienced QT interval prolongation.¹⁰ However, no consistent association has been found between QT prolongation and cardiovascular mortality, limiting its use as a clinical marker of risk.¹¹

A QT interval exceeding 500 ms in absolute value, or an increase of more than 60 ms from baseline, is considered clinically concerning and is generally regarded as the threshold for reducing the dose or modifying the antipsychotic treatment regimen.^1,9 In cases where QT prolongation is modest, additional risk factors may further increase the associated risk, including cocaine use, chronic alcohol use, female sex, bradycardia, hypokalemia, hypomagnesemia, congestive heart failure, atrial fibrillation and ion channel polymorphisms.⁸

Noninvasive test to identify people at risk for SCD

Several noninvasive tools are available to help identify people living with schizophrenia who may be at increased risk for SCD, particularly those receiving antipsychotic therapy. An electrocardiogram (ECG) is the primary method for monitoring QT interval changes, both at baseline and during treatment.¹¹ 

Another ECG marker of risk is the Tpeak-end interval, which represents the time between the peak and the end of the T wave.¹¹ This interval has been found to predict the risk of malignant cardiac arrhythmias in a number of clinical settings, showing an increased risk of arrhythmias in patients presenting with prolonged Tpeak-end intervals.¹¹

In conclusion, SCD represents a major contributor to the reduced life expectancy observed in individuals living with schizophrenia. Multiple factors including cardiovascular risk profiles, social determinants of health and antipsychotic treatment likely interact to increase vulnerability. Improved cardiovascular risk assessment, careful monitoring of antipsychotic therapy and the use of noninvasive markers may help identify high-risk patients and reduce the burden of SCD in this population.