People with severe mental illness (SMI), especially those with psychotic disorders such as schizophrenia, reportedly have a shorter life expectancy compared to the general population. This shorter life expectancy is associated with increased rates of risk factors like hypertension, diabetes, obesity, strokes, myocardial infarction, coronary heart disease, peripheral vascular disease, congestive heart failure, as well as other cardiovascular diseases (CVDs).^1,2,3 Evidence suggests that the incidence of CVD increases with antipsychotic use, higher body mass index (BMI) and higher baseline CVD prevalence.¹ Second-generation antipsychotic (SGA) use is particularly associated with metabolic syndrome, which is associated with increased CVD risk factors including hypertension, insulin resistance, hypercholesterolemia and obesity.^4,5

The first antipsychotic, chlorpromazine, was introduced in 1952.⁶ The introduction of first-generation antipsychotics (FGAs) led to significant improvements in the symptoms of schizophrenia, including hallucinations and delusions, but were unfortunately associated with an increased risk for extra-pyramidal side effects.⁷ Aside from schizophrenia, FGAs are also used to treat symptoms of bipolar disorder, such as mania.⁸ Some commonly used FGAs include haloperidol, flupentixol and zuclopenthixol.⁹

Second-generation or ‘atypical’ antipsychotic drugs (SGAs) are compounds that are efficacious against the symptoms of schizophrenia, but with nil or minimal extra-pyramidal side effects.¹⁰ Clozapine was the first SGA to be described. Its clinical effects were first reported in 1966, and it was first approved in the United States in 1990.¹⁰ Second-generation antipsychotics are used to treat schizophrenia, bipolar disorder, schizoaffective disorder, major depressive disorder as well as acute agitation or irritability that may be associated with illnesses such as schizophrenia, bipolar disorder and autistic disorder. They are also used off-label to treat anxiety disorders, delirium, dementia and insomnia.¹¹ Although SGAs gained popularity because of their reduced risk of extra-pyramidal side effects, evidence from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study indicates that SGAs may lead to an increased risk of metabolic side effects, including type 2 diabetes, central obesity and hyperlipidaemia in patients with SMI.¹²

Different antipsychotics seem to affect weight gain differently. The SGAs clozapine and olanzapine are associated with the greatest weight gain.^3,13 Chlorpromazine, an FGA, is also associated with weight gain, while quetiapine and risperidone, both SGAs, have an intermediate risk. Asenapine, amisulpride, fluphenazine, haloperidol and ziprasidone have little effect on weight, while aripiprazole promotes weight loss.² Recommendations suggest that patients should be screened for CVD risk factors when initiating antipsychotics.¹⁴

In psychiatric settings, a simple measure for screening for CVD risk may be useful, because people with SMI are twice as likely to have metabolic syndrome compared to the general population.^4,5 Currently, the recommended body measures for the assessment of cardiovascular risk in patients with SMI on antipsychotics are BMI and waist circumference (WC), which are measures of overall adiposity and central adiposity, respectively.¹⁴ There is still no clarity about which body measures would be the best predictors of CVD risk despite years of research.^15,16,17,18

Other body measures include anthropometric indices such as waist-to-hip ratio (WHR) and WC, which are measures of central obesity. These measures are both convenient and cost-effective ways of assessing CVD risk and are suitable for use in busy, poorly resourced settings.¹⁵ Several studies have investigated the value of different anthropometric indices in predicting CVD risk as summarised in Table 1. Increased BMI, WC and WHR were all significantly correlated to 5- or 10-year CVD risk in the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study.¹⁶ The strongest correlations were observed between WHR and absolute risk estimates.¹⁶ In Caucasian men and women, WC is a stronger predictor of CVD risk than BMI.¹⁷ In Chinese people, waist-to-height ratio (WHtR) was a better indicator of dyslipidaemia, hyperglycaemia and CVD risk than BMI, WC, hip circumference (HC), WHR and body shape index (ABSI).¹⁸ In sub-Saharan men and women, WHtRs of greater than 0.5 predicted risk of CVD.¹⁵ In adults from Southeast Asia, BMI and WHtR had the best clinical utility in predicting CVD risk in patients overall, even better than a combination of BMI and WC.¹⁹ In Egypt, CVD risk was best predicted by increased WC regardless of the presence of other comorbidities and general obesity, with men at higher risk if their WC was greater than 100.5 cm and women at higher risk if their WC was greater than 96.25 cm.²⁰ As indicated by the studies referenced above, CVD risk is associated with BMI, WC, WHtR and WHR, accordingly, these body measures were used in our study.

Most of the studies that have investigated the metabolic effects of FGAs and SGAs measured biological markers of metabolic risk, but very few studies have investigated the influence of antipsychotic medication on body measures associated with CVD risk.^13,21,22,23 Even fewer studies have investigated CVD risk based on body measures in people with SMI, who are on FGAs or SGAs. In our study, we compared body measures of long-term male inpatients on FGAs and those on SGAs to obtain an impression of their risk for CVD and to record possible differences between the two groups. Firstly, we gathered the body measures including WHR, WHtR, BMI, WC and HR of long-term inpatients at Weskoppies Psychiatric hospital, who were on either SGAs or FGAs. Secondly, we assessed if body measures of patients on FGAs and SGAs differed significantly.

The age of the participants ranged from 24 to 74 years, with a mean age of 48.4 years. Participants on FGAs were slightly older (mean = 50.7 years) than those on SGAs (mean = 46.2 years). Age was not correlated to any of the continuous variables. Thus, there was no need to control for age.

All participants in the FGA group (n = 15) had been diagnosed with a psychotic disorder, including schizophrenia (n = 13), a psychotic disorder as a result of another medical condition (n = 1) and a cannabis induced psychotic disorder (n = 1). In the SGA group (n = 15), participants were diagnosed with schizophrenia (n = 13), mild intellectual disability (n = 1) and major neurocognitive disorder (n = 1).

Participants had the following comorbid conditions, hypertension (FGA [n = 3]; SGA [n = 3]), diabetes (FGA [n = 2]; SGA [n = 3]), hypercholesterolemia (FGA [n = 3]; SGA [n = 3]), HIV (FGA [n = 1); SGA (n = 1]), benign prostate hyperplasia (FGA [n = 1]; SGA [n = 0]), cannabis use disorder (FGA [n = 2]; SGA [n = 1]), chronic obstructive pulmonary disease (FGA [n = 1]; SGA [n = 0]) and somatisation disorder (FGA [n = 0]; SGA [n = 1]). In the FGA group, five patients had no comorbidities and in the SGA group six patients had no comorbidities.

Body measures associated with CVD risk in a population of long-term male inpatients who had been admitted for several years and were relatively stable on treatment, on either FGAs or SGAs were done. Participants in our study had similar body measures and similar high risk for CVD. These long-term patients had relatively similar lifestyles, including a similar level of activity, diet and smoking habits. We would thus expect that these patients would have similar body measures, and that any differences could be attributed to factors other than lifestyle, such as prescription medication.

In our study, participants had very similar body measures, irrespective of taking FGAs or SGAs. The two groups were also similar in terms of the presence of comorbidities such as hypertension, diabetes, and hypercholesterolaemia. In the literature, SGAs are generally expected to have more metabolic side effects that increase the risk of CVDs than FGAs.^25,26,27 In our study, the lack of difference in body measures and CVD risk may be explained by the variety of SGAs prescribed to participants. Second-generation antipsychotics are a heterogenous group of drugs with different metabolic effects. That being so, some SGAs may not be worse culprits than FGAs regarding cardiovascular risk. This has been suggested in a systemic review and meta-analysis done in 2019.²² Other studies have suggested that overall cardiovascular risk in patients with SMI may be because of a genetic predisposition.²⁸ Clinicians usually assess CVD risk before initiating antipsychotic medication per the recommendations,⁹ resulting in the tendency for patients with high CVD risk being initiated on FGAs, while patients with low CVD risk tend to be initiated on SGAs. This practice may even out CVD risk between the two groups, possibly explaining the similarities in body measures and CVD risk. In our study, participants’ body measures indicated significant CVD risk. The WHO states that men who have a WC greater than 94 are at risk for CVD.²⁴ In our study, men had an average WC of 100.6 cm, indicating high cardiovascular risk. Men in our study had greater WCs than men in another South African study that found a WC of greater than 86 cm to be predictive of at least two components of metabolic syndrome.²⁹ Men in our study had HCs of almost 100 cm. While larger HC is protective against CVD in women, it seems to have no effect on CVD risk in men.³⁰ However, when considered together with WC (but not as a ratio measure), WC and HC have been found to improve risk prediction models for CVD.³¹ A possible explanation for this is that WC values indicate subcutaneous and visceral adipose tissue while HC is a more specific measure of subcutaneous adipose tissue, albeit in a different location in the body.³¹ When considered together, these body measures give a more accurate predictive value than either WC or HC on its own. That being so, the exact interplay between HC and WC needs further clarification.³¹

Other body measure values in our study also suggested higher CVD risk. The participants in our study had a mean BMI of > 25 kg/m² and < 30 kg/m² indicating overweight and increased risk of CVD mortality.³² The mean WHtR was 0.59, which is greater than the cut-off value of 0.5, the threshold for increased CVD risk.¹⁵

In our study, all the participants had similar body measures irrespective of using FGAs or SGAs. Overall the body measures reflected that this sample of chronic, male inpatients with SMI is at high risk for CVD.