The association between severe mental illness and cardiovascular disease: systematic review and retrospective cohort studies using routinely collected electronic primary care data

Lambert, Amanda Margaret (2024). The association between severe mental illness and cardiovascular disease: systematic review and retrospective cohort studies using routinely collected electronic primary care data. University of Birmingham. Ph.D.

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Abstract

Compared with the general population, people with severe mental illness (SMI), such as schizophrenia and bipolar disorder (BD) have shorter life expectancy, dying up to 20 years earlier. Death rates are two to three times higher than those without SMI and the mortality gap has not reduced in recent decades. Much of the premature mortality is due to preventable causes, with cardiovascular disease (CVD) being the most common cause of death in those with SMI.
This thesis aims to summarise the evidence on the relationship between SMI and CVD, describe changes over time, explore the factors associated with highest CVD risk and quantify their relative importance.

Methods
Three different methodologies were used to assess the association between BD, schizophrenia, and CVD. A large-scale systematic review of SMI and CVD-related mortality and incidence; matched and unmatched cohort studies, which explored the effects of SMI on all-cause mortality, post-CVD case-fatality and CVD incidence; and a mediation analysis, which explored the effect of four mediators (smoking, diabetes mellitus (DM), obesity and blood pressure) on the causal pathway between SMI and CVD.

Results
The systematic review found that CVD-related mortality was elevated for those with SMI compared with the general population. Meta-analyses showed that pooled standardised mortality ratios were 1.96, 95% confidence interval (CI): 1.61-2.39 and 1.65, 95% CI: 1.53-1.77 for schizophrenia and BD, respectively. Deaths from individual CVD diagnoses of coronary heart disease (CHD), cerebrovascular accident (CVA) and heart failure (HF) were also high for people with SMI compared with the general population. There was a consistent association between SMI and increased incidence of CVA, CVD events and HF, and between BD and CHD. However, most pooled estimates showed no evidence of difference in CHD incidence between those with schizophrenia and the general population. Excess risk of CVD-related mortality appeared higher in the 1990s and 2000s compared with earlier decades and relative risk of CVD incidence appeared highest during 2000-2004. Risk of bias was high for most included studies, with only 12 incidence studies judged to be at low risk of bias.

The cohort studies found the risk of all-cause mortality was two to three times higher for people with SMI compared with the general population. Relative risk of death after CVD diagnosis for those with SMI was also around two-fold higher than the general population. Hazard ratios (HRs) adjusted for confounders were 1.67, 95% CI 1.42-1.96 and 1.97, 95% CI: 1.75-2.21 for BD and schizophrenia, respectively. Excess risks of CVD incidence, however, were more modest: HR=1.21, 95% CI: 1.15-1.29 and HR=1.12, 95% CI: 1.07-1.17 for BD and schizophrenia, respectively. There was no consistent evidence of changes in mortality over time, although some increases in relative risk of CVD incidence found during the period 2005-2014 in the matched study disappeared after 2015. In the unmatched study, there was no evidence of temporal changes when adjusted for all measured confounders.

Mediation analysis found that smoking was an important mediator of the association between SMI and CVD incidence, mediating 34.5% and 53.5% of the excess risk for BD and schizophrenia, respectively. DM also had a substantial effect. However, obesity and hypertension had no significant mediating effect, after accounting for smoking and DM.

Conclusions
This research highlights health disparities for people with SMI compared with the general population and the evidence that they are not improving over time suggests that current interventions are not effective. Development of smoking cessation and physical health monitoring interventions and investigation of differential access to treatments are important recommendations to improve the cardiovascular health of people with SMI.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):