Of the 10308 participants of the Whitehall II Study, the current analysis where the follow-up starts at Phase 7 of the study is based on a total of 5936 participants. Those not included in the analyses due to missing data were more likely to be: women (39.9% vs. 28.1%, p<0.001), non-white (15.5% vs. 7.7%, p <0.001), in the 70–74 age group (14.5% vs. 9.2%, p<0.001), and from lower SEP (34 % vs. 15 %, p<0.001). Of those included in the analysis, 170 died during the mean follow-up of 5.6 years (SD 0.7, range 0.03–6.6), of which, 47 from CVD. The mean age of participants at phase 7 was 61 years (SD 6.0). The prevalence of elevated depressive symptoms (CES-D score ≥16) was 14.9%. Participants with a history of CHD were more likely to have depressive symptoms (20% vs. 14%, p=0.001) than those without CHD.
shows the baseline characteristics of the study participants. Participants with both depressive symptoms and CHD, as compared to those free of both conditions, were older and more likely to be from low socioeconomic position, non-White, antidepressant users, current smokers (along with those depressed participants without CHD), less physically active, obese, diabetic, treated by CVD medication and less likely to have high total blood cholesterol (all p≤0.009). As expected, results from additional analyses conducted separately for depression and CHD (data not shown in table), revealed that they both were associated with all cause mortality, the age-sex-adjusted hazards ratios (HRs) being 2.41 (p<0.001) and 2.02 (p<0.001) respectively. The corresponding HRs for CVD mortality were 2.83 (p=0.001) and 2.61 (p=0.004).
Baseline characteristics by presence or absence of CHD and depressive symptoms at phase 7
presents the HRs for the associations with mortality, from all-causes and from CVD, in the groups resulting from the cross classification of CHD and depressive symptoms. Model 1 shows that compared with participants without CHD and depressive symptoms (the reference group) the age- and sex-adjusted hazard ratio for death from all-causes was higher in all three exposed groups: those with depressive participants but not CHD (1.67, 95% confidence interval (CI) 1.05–2.66), those with CHD but not depression (2.10, 95% CI 1.47– 3.13), and those with depression and CHD (4.99, 95% CI 2.89–8.62). After successive adjustments for sociodemographic characteristics (model 2), biobehavioural risk factors (model 3), antidepressant and CVD medications (model 4) and for all of these covariates (model 5), the magnitude of the associations was substantially reduced except in the “depressed but no CHD” group. Almost all attenuation of the association was related to controlling for biobehavioural risk factors. The fully-adjusted HR was highest in the group with both depression and CHD (HR=2.94, 95% CI 1.63–5.34) but the group with CHD but no depression was not robust to successive adjustment for covariates (HR=1.10, 95% CI 0.66– 1.82).
Hazard ratios of mortality from all causes and cardiovascular disease according to CHD and depressive symptoms.
The results for CVD mortality are essentially similar to those obtained for all-cause mortality. The age- and sex-adjusted HRs were 2.52 (95% CI, 1.17–5.43) for depressive participants without CHD, 2.29 (95% CI 1.02–5.14) for those with CHD but not depression and 6.69 (2.54–17.54) for those with both depression and CHD. The fully adjusted HRs attenuated by 49% in the group with both CHD and depression (HR= 3.91, 95% CI 1.34–11.43), and by 74% for participants with CHD but not depression (HR=1.33, 95% CI 0.54–3.28). For participants who were depressed but without CHD no substantial risk reduction was observed (HR= 2.37, 95% CI 1.07–5.34).
presents the risk of mortality, first all cause and then CVD mortality, among participants who were depressed and had CHD compared to those who were depressed but free from CHD. These results show 2.4-fold (p<0.006) and 2.7-fold higher (p=0.08) risk for all cause and CVD mortality respectively when adjustments were made for sex and age. Serial multivariable adjustment substantially attenuated these associations leading to non-significant associations for all-cause mortality (HR=1.66, p=0.13), and for CVD mortality (HR=1.65, p=0.40).
Hazard ratios of mortality for participants with both CHD and depressive symptoms comparatively to those with depressive symptoms but without CHD
For results presented in , the reference category is set to the group of individuals with CHD but no depressive symptoms. In model 1 (age and sex adjusted) the HRs associated with co-existing depression and CHD were 2.99 (p=0.001) and 2.92 (p=0.06) for all cause and CVD mortality, respectively. Serial multivariable adjustment showed no substantial attenuation for these associations.
Hazard ratios of mortality for participants with both CHD and depressive symptoms comparatively to those with CHD but without depressive symptoms
The RERI between depressive symptoms and CHD for all-cause mortality was 3.58 (95% CI, −0.09–7.26), providing some evidence for the presence of an additive interaction. The corresponding RERI for CVD mortality was 4.61 (95% CI, −4.04–13.26).