This study of South African primary care patients with hypertension provides insights into the complex and dynamic effects of sociodemographic factors, multimorbidity, depression symptoms, perceived stress and disability on each other and on cardiovascular risk factors. The results suggest that disability was a key variable in this web of causal paths, as a cause, effect and mediator of a variety of physical and mental health problems. Depression and disability appeared to have bidirectional effects on each other, with worse depression at baseline, associated with more disability at baseline and at follow-up, and vice versa (Fig. 3). This confirms similar evidence of bidirectional effects reported by Ormel and colleagues [10]. However the coefficient for disability as a predictor of depression (0.225) was larger than the coefficient for depression as a predictor of disability (0.092) – supporting our placement of disability before depression in the path model for baseline data (Fig. 1). Kelley-Moore and Ferraro also demonstrated a similar pattern regarding NCDs, disability and depression, with the presence of each factor at baseline predicting the others three years later [9]. In the present study, perceived stress was more strongly associated with disability at baseline than depression was, but we did not find equivalent evidence of bidirectional effects between stress and disability over time.
Most directly relevant to hypertension management were the findings that higher depression scores at baseline were directly associated with higher blood pressure at baseline and at follow-up, which could be due to poor treatment adherence among patients with more severe depression symptoms, or due to psycho-biological mechanisms. Longitudinal analysis suggested that disability and blood pressure also had bidirectional effects on each other. It is plausible that the effects of hypertension on disability could be mediated through cardiovascular disease and stroke, and that the effects of disability on blood pressure could be mediated through obesity or medication adherence, did not find evidence of such mediation.
These results, together with the finding that myocardial infarction was strongly associated with greater depression symptoms, are in keeping with previous studies showing associations between depression and cardiovascular disease. Several studies have shown depression to be associated with concurrent hypertension or cardiovascular disease and also to predict incident cardiovascular disease in the future [6, 8, 27, 28]. A cohort study of United States Medicare beneficiaries aged 65 years or older, found bidirectional relationships between depression and cardiovascular disease over time [11].
In the present study, age and sex variables were not independently associated with depression symptoms, but older age was predictably associated with higher BMI, systolic blood pressure and disability. However, because older age was associated with less perceived stress, it was indirectly associated with less disability at baseline, so that the direct and indirect of effects of age on disability cancelled each other out (Table 3). Females were much more likely than males to be obese (53% versus 18% having BMI > 30 kg/m2) but female sex was not independently associated with any endogenous variable other than BMI.
Socioeconomic factors were generally not associated with differences in physical or mental health. Higher income was associated with higher BMI, possibly because it enabled purchase of more food. This finding contrasts with high income settings in which higher income is usually associated with less overweight and obesity [29]. Considering that 75% of participants earned less than US$100 per month, this discrepancy could be because higher earners in our study were only relatively so, and could possibly only afford poor quality high calorie food. Education, employment and income had no other independent effects, which differs from our previous study which found all three variables to be independently associated with depression symptoms among South African primary care patients with long term conditions [18, 19]. This difference between our studies may be partly because of the higher prevalence of poverty, and less socioeconomic variability, in the present study.
Comorbid physical conditions appeared to have a variety of adverse effects. Previous myocardial infarction was associated with higher depression, perceived stress and disability scores. The association between myocardial infarction and higher BMI is probably due to obesity and overweight causing myocardial infarction, but the reverse could also be true if myocardial infarction resulted in reduced physical activity. Tuberculosis was associated with disability but HIV was not, possibly because most people with HIV were well controlled on antiretroviral treatment (84% had undetectable viral loads at baseline). However, both tuberculosis and HIV were associated with lower BMI.
The study has several limitations. Firstly, although the SEMs represent supposed causal pathways, the associations could have been biased by unmeasured confounding factors. Secondly, the self-reported measures of depression, perceived stress and disability are inevitably prone to error. Self-reported comorbidities are also prone to error. Random measurement error in outcome measurement could bias associations between independent variables measured at baseline and changes in dependent variables, when modelled using baseline adjustment [30]. Alternative models using change score as outcome could avoid this bias, but could instead be biased by regression to the mean. That is, if baseline covariates are associated with baseline values of a variable, they would tend to be inversely associated with changes in that variable due to chance alone. Thirdly, the study population was restricted to participants with both depressive symptoms and a previous diagnosis of hypertension. This inclusion criterion of hypertension treatment and depressive symptoms could bias associations between depression symptoms and blood pressure, and means that these results should not be generalised to populations without both hypertension and depressive symptoms [30]. Fourthly, analyses of cross-sectional baseline data were unable to identify directions of effects, but longitudinal data provided insights about directions of effects between depression, disability and blood pressure. Fifthly, one year of follow-up may be insufficient for gradual processes such as disability to develop, but there were several statistically significant predictors of changes in disability, depression score and blood pressure. Sixthly, outcome variables were not all normally distributed, as assumed for linear regression. Notably, baseline depression score was truncated at a lower limit of 9, and most participants smoked zero cigarettes. However sensitivity analysis using bootstrapping supported the robustness of the primary analyses despite departures from normality. Finally, the cluster sample design reduced statistical power, so that robust adjustment for differences between clinics made many apparent associations non-significant, and precluded conventional goodness of fit estimates.
The study is original in its attempt to disentangle complex causal processes in a LMIC setting. The path models are arguably more informative than conventional regression models that simply pool diverse covariates without considering the mechanisms or directions of effect linking them. Inappropriate adjustment for mediating variables, or for covariates that are themselves affected by outcomes, can obscure effects. What is needed in future, to confirm or refute these exploratory findings, are larger longitudinal studies with longer follow-up in similar populations with high disease burdens in LMIC settings.