The initial pooled sample included 85
261 adults. Table 1 shows details of individual studies. We excluded participants who declined linkage to mortality records (n=9325; web table 1 compares those who consented to record linkage with those who did not); with missing GHQ-12 data (n=2532); with baseline cardiovascular disease (n=3492), cancer (n=1511), or both (n=159); and with no cause of death recorded or for whom no survival time could be calculated (n=20). The final analytic sample comprised 68
222 people (37
649 (55.2%) women) with a mean age of 55.1 years (standard deviation 14.1, range 35-102). The composition of the sample is shown in figure 1. Table 2 shows details of the study members’ baseline characteristics. People with higher GHQ-12 scores generally had unfavourable levels of covariates and mortality risk, apart from being slightly younger and having a lower systolic blood pressure than those with lower GHQ-12 scores. Participants with the highest GHQ-12 scores were slightly less likely to drink heavily than those with lower scores.
Table 1 Characteristics of participants* according to individual cohort studies
Fig 1 Flow chart of participants from initial pooled sample to analytic sample showing subsequent mortality
Table 2 Baseline characteristics of study participants according to GHQ-12 score
Of 8365 deaths during a mean follow-up of 8.2 years (standard deviation 3.5), 3382 death certificates mentioned cardiovascular disease, 2552 mentioned cancer, and 386 mentioned an external cause of death. Figure 2 shows the numbers of participants, total deaths, and the number related to major causes of death. It also provides the age and sex adjusted hazard ratio for the relation of increased psychological distress (one standard deviation increase in GHQ-12 score) with overall mortality, cardiovascular disease death, cancer death, and death from external causes for each annual cohort in addition to the totals and overall effect from meta-analysis. Overall, we saw increases of 21% in age and sex adjusted risk of all cause mortality, 22% in risk of cardiovascular disease death, 9% in risk of cancer death, and 26% in risk of death from external causes per standard deviation increase in GHQ-12 score. Individually, all cohorts showed a similar effect, although the strength of the association between GHQ-12 score and mortality was somewhat weaker for 1997 and 2002—the reason for this is unclear. However, when we conducted sensitivity analyses by excluding the 1997 and 2002 cohorts from pooled analyses, the hazard ratio was unchanged. Therefore, we included participants from these surveys in the main analyses.
Fig 2 Number of participants, total mortality, and deaths plus age and sex adjusted hazard ratios (95% confidence intervals) per standard deviation disadvantage in GHQ-12 score, by survey year and cause of death
Deaths from all causes
We saw a significant association, across the full range of severity, between psychological distress and all cause mortality. Table 3 shows the results for the four categories of GHQ-12 score; even the subclinically symptomatic group (score 1-3) had a 20% increased risk of mortality after adjusting for age and sex. This association was essentially unchanged after adjusting for a range of covariates that included occupational social class, alcohol intake, and smoking. We saw strong evidence of a dose-response effect (age and sex adjusted hazard ratio per standard deviation disadvantage in GHQ-12 score 1.21, 95% confidence interval 1.15 to 1.27; P<0.001 for trend). Figure 3 shows the association between risk of death from all causes and the full range of psychological distress.
Table 3 Association between psychological distress and cause specific mortality
Fig 3 Association between psychological distress (GHQ-12 score) and risk of cause specific death (age and sex adjusted hazard ratio (95% confidence interval)). Reference=GHQ-12 score 0; higher GHQ-12 score indicates greater distress
Cardiovascular disease death
Focusing on cardiovascular disease death in particular showed a similarly increased risk in association with psychological distress, again across the full range of severity; subclinically symptomatic patients were at a 29% increased risk of cardiovascular disease death (table 3). This association remained after adjustment for each covariate individually and in a model incorporating all covariates. The magnitude of the increase in risk in the fully adjusted model was little attenuated. Again, there was strong evidence of a dose-response effect (age and sex adjusted hazard ratio per standard deviation disadvantage in GHQ-12 score 1.22, 95% confidence interval 1.14 to 1.31; P<0.001 for trend) across the full range of GHQ-12 scores (fig 3).
Cancer death was not associated with low levels of psychological distress in the same way as cardiovascular disease death (table 3). However, psychological distress in highly symptomatic patients (GHQ-12 scores 6-12) was associated with a 41% increased risk of cancer death. Figure 3 confirms that this association was only present in GHQ-12 scores greater than six. Nevertheless, we saw a significant dose-response effect (age and sex adjusted hazard ratio per standard deviation disadvantage in GHQ-12 score 1.09, 95% confidence interval 1.04 to 1.13; P<0.001 for trend). This association remained after adjustment for all covariates individually and in the fully adjusted model (hazard ratio per standard deviation disadvantage in GHQ-12 score 1.05, 0.99 to 1.11, P=0.141).
Deaths from external causes
Death from external causes was also associated with psychological distress across the full range of scores; subclinically symptomatic patients were at a 29% increased risk of death from external causes (table 3). This association remained on adjustment for covariates individually and remained unchanged in the fully adjusted model. Once again, we saw strong evidence of a dose-response effect (age and sex adjusted hazard ratio per standard deviation disadvantage in GHQ-12 score 1.26, 95% confidence interval 1.14 to 1.40; P<0.001 for trend) across the full range of GHQ-12 scores (fig 3).
The population proportional attributable risk summarises the population effect of an exposure taking into account its prevalence. For the subclinically symptomatic category of psychological distress, the proportional attributable risk was 3.8% for overall mortality (fully adjusted hazard ratio 1.16), 5.8% for cardiovascular disease mortality (1.25), −1.2% for cancer mortality (0.95), and 5.4% for deaths from external causes (1.23).
Data were missing for one or more variables in 39.4% (n=26
860) of the sample. People with missing data were older and were more likely to be female, be overweight, have lower blood pressure, be less active, not smoke, drink alcohol within recommended limits, and have diabetes at baseline. However, they were no more likely to belong to a non-manual occupational social class (web table 2). Therefore, participants with missing data did not always have unfavourable levels of risk factors. Accounting for missing data by multiple imputation did not alter the effect sizes found (table 4).
Table 4 Sensitivity analysis of association between psychological distress and cause specific mortality, with and without multiple imputation
We excluded deaths occurring within the first five years of follow-up to examine reverse causality. This subgroup analysis slightly attenuated the effect size for the association between psychological distress and all cause mortality (age and sex adjusted hazard ratio per standard deviation disadvantage in GHQ-12 score [all data] 1.21, 95% confidence interval 1.15 to 1.27, P<0.001 v 1.13, 1.10 to 1.17, P<0.001) and cardiovascular disease death (web table 3). The association with cancer deaths was further attenuated towards the null by excluding deaths within the first five years of follow-up (web table 3). Comparing a narrow case definition (that the condition was the underlying cause of death) and a broad case definition (that any mention of the condition on the death certificate was sufficient) had essentially no effect on the results (web table 4).