Psychotic experiences as an independent risk factor for angina pectoris in 48 low‐ and middle‐income countries
Authors: Ai Koyanagi, Hans Oh, Brendon Stubbs, Nicola Veronese, Davy Vancampfort, Josep Maria Haro, Jordan E. DeVylder
Journal: World Psychiatry (2018)

People with schizophrenia are known to have a life expectancy reduced by 10-20 years compared to the general population1, which is largely attributable to their increased risk for cardiovascular diseases (CVDs)2. There is some evidence that people with psychotic experiences (PEs) who do not reach the clinical threshold for a psychosis diagnosis are also at higher risk of premature mortality (by 5 years)3, which likewise may be explained by a higher likelihood of CVDs4, 5. Furthermore, similar to schizophrenia, there is increasing evidence that PEs are associated with adverse health behaviors, diabetes and mental health problems, which may all increase CVD risk5. PEs are common in the general population (their lifetime prevalence is estimated to be 7.2%6), with an onset earlier than many other known risk factors for CVDs. Thus, if epidemiological data show that PEs are associated with clinically meaningful elevated odds of CVDs, and this association is present also in younger adults, being independent from other known vulnerability factors, then PEs may constitute an important risk factor for CVDs, a leading cause of death worldwide. The aims of the current study were to examine the association between PEs and angina pectoris, and to explore the factors influencing this association. We analyzed cross-sectional, community-based data from 48 low- and middle-income countries that participated in the World Health Surveys7. Multistage clustered sampling was used to select individuals aged ≥18 years. Angina pectoris was operationalized as a previous medical diagnosis of that condition and/or a positive result on the World Health Organization (WHO) Rose Angina Questionnaire. Participants were asked questions on psychotic symptoms (delusional mood, delusions of reference and persecution, delusions of control, hallucinations) which came from the WHO Composite International Diagnostic Interview (CIDI) 3.0. They were considered to have PEs if they endorsed at least one psychotic symptom. The potential mediators in our study included past 7-day heavy episodic drinking, current smoking, low physical activity (<150 minutes of moderate-to-vigorous physical activity per week), inadequate fruit and vegetable consumption (<2 fruit or <3 vegetable servings/day), diabetes (self-reported), obesity (defined as a body mass index ≥30 kg/m2 based on self-reported weight and height), depression (lifetime or past 12-month DSM-IV diagnosis based on CIDI), antipsychotic use (past 2 weeks), and past 30-day perceived stress, anxiety and sleep problems. Socio-demographic variables included gender, age, education, wealth quintiles, and living environment (urban/rural). Statistical analyses were performed with Stata 14.1. Multivariable logistic regression analysis was conducted to assess the association between PEs (exposure) and angina pectoris (outcome). Analyses using the overall and country-, age- and gender-stratified samples were conducted. We carried out mediation analysis with the khb (Karlson Holm Breen) command in Stata. This method decomposes the total effect of a variable into direct and indirect effects, and allows calculation of the mediated percentage. Each potential mediator was included in the model individually. All regression models were adjusted for age, gender, education, wealth, living environment and country. The sample weighting and complex study design were taken into account. The level of statistical significance was set at p<0.05. The mean age of the final sample (N=224,842) was 38.3±16.0 years, and 49.3% were males. Overall, after adjustment for age, gender, education, wealth, living environment and country, the presence of PEs was associated with a 2.29 (95% CI: 2.13-2.47) times higher odds for angina pectoris. Similar associations were observed among males (OR=2.45, 95% CI: 2.16-2.78) and females (OR=2.20, 95% CI: 2.00-2.42). The association was strongest in the youngest age group: OR=2.59, 95% CI: 2.36-2.85 for 18-44 years; OR=2.06, 95% CI: 1.80-2.37 for 45-64 years; OR=1.62, 95% CI: 1.31-2.01 for ≥65 years. The OR was >1 in all countries, with a significant association being observed in all but five countries (OR range: 1.24 for Ukraine to 10.85 for Myanmar). Mediation analysis showed that depression, anxiety, perceived stress and sleep problems explained 20.6%, 11.4%, 10.1% and 9.5% of the PE-angina pectoris association, respectively (collectively 33.0%). Diabetes (1.7%) and alcohol consumption (0.8%) explained a small proportion of the association. Smoking, physical activity, fruit/vegetable consumption, obesity and antipsychotic use were not significant mediators. The association between PEs and angina pectoris continued to be significant even after adjustment for all eleven potential mediators (OR=1.72, 95% CI: 1.52-1.93). The value of PEs as a clinically useful predictor depends on their independent associations with CVD when adjusting for known CVD risk factors. We found that PEs are indeed associated with greater odds of angina pectoris even when accounting for a broad range of psychiatric, demographic, behavioral and lifestyle risk factors. Even more intriguing, we found that this effect was greatest among younger and middle-aged adults, when the effect of risk factors for CVD is expected to be attenuated due to shorter lifetime exposure. This, therefore, provides compelling epidemiological evidence that screening for PEs in young adulthood may provide independent predictive information regarding lifetime CVD risk, which can potentially facilitate clinical prevention of CVDs, pending future translational research studies. In particular, prospective studies of clinical samples of adults at risk for CVDs can be used to determine whether screening for PEs adds unique predictive value to existing CVD risk screens. If so, PE screening can be a valuable contribution to CVD risk detection, particularly given the early onset of PEs relative to CVDs. Ai Koyanagi1,2, Hans Oh3, Brendon Stubbs4-6, Nicola Veronese7,8, Davy Vancampfort9,10, Josep Maria Haro1,2, Jordan E. DeVylder11 1Research and Development Unit, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain; 2Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain; 3School of Social Work, University of Southern California, Los Angeles, CA, USA; 4Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK; 5Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; 6Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK; 7Neuroscience Institute, National Research Council, Padua, Italy; 8Department of Geriatric Care, OrthoGeriatrics and Rehabilitation, E.O. Galliera Hospital, Genoa, Italy; 9KU Leuven Department of Rehabilitation Sciences, Leuven, Belgium; 10University Psychiatric Center KU Leuven, Leuven-Kortenberg, Belgium; 11School of Social Service, Fordham University, New York, NY, USA