Educational inequalities in all-cause and cause-specific mortality among people with gout: a register-based matched cohort study in southern Sweden

Gout is the most common inflammatory arthritis with a rising prevalence around the globe [1]. Previous studies estimated a prevalence range of 0.6%—1.8% and incidence of 16—24 cases per 10,000 person-years for gout in Sweden [2‐4]. In addition, Sweden had the 15th highest rate of years lived with disability for gout among 195 countries in 2015 [5]. In addition to causing pain, joint damage, functional impairment, and reduced health-related quality of life, gout is associated with increased mortality [1, 6‐8]. A recent study in southern Sweden reported a 17% higher hazard of all-cause mortality among persons with gout than those without gout [8]. Socioeconomic status (SES) including education is a well-documented predictor of health outcomes including mortality. According to the framework proposed by the World Health Organization (WHO) Commission on Social Determinants of Health, SES is considered as a “structural determinant” of health inequalities that through a set of “intermediary determinants” (material circumstances, psychosocial circumstances, behavioural and/or biological factors, and the health system itself) influences exposure and vulnerability to health-compromising conditions [9]. While very few studies assessed associations between SES and incidence and prevalence of gout [4, 10‐12], to our knowledge, no previous study investigated association between SES and mortality among people with gout. Assessing educational inequalities in cause-specific mortality provides valuable information to identify major causes responsible for inequalities in mortality. To address this, we assessed the absolute and relative educational inequalities in all-cause and cause-specific mortality among people with gout in comparison with a randomly selected age- and sex matched cohort without gout in southern Sweden.

A total of 24,877 patients with a doctor-diagnosed gout during 1998–2013 were identified. We identified 99,504 age- and sex-matched individuals without gout as the reference population (1 patient had no comparator). After exclusion of 842 (3.4%) individuals with missing level of education, we observed 8133 deaths during 127,910 person-years follow up among gout patients (Table 1). In the reference population, we excluded 1670 (1.7%) who did not enter the study (died or emigrated prior to the index date), 3457 (3.5%) with missing data on level of education, and 6 with missing on country of birth. There were 24,051 deaths over 554,054 person-years follow up in the reference population included in the study. In both groups, those with low level of education constituted the largest portion of the sample (45.1% in gout patients vs. 40.2% in the reference population). Cardiovascular diseases (CVDs) accounted for 50.3% of the causes of deaths among people with gout versus 41.2% in the reference population (Supplementary Fig. S1). On the other hand, neoplasms constituted 18.4% of deaths among gout patients versus 24.5% in the reference cohort.

The RII showed that all-cause mortality rate in the low educated gout patients was 1.3 (95% CI: 1.2, 1.4) times higher than the highly educated ones (Table 2). These educational inequalities persisted across sex and age subgroups. For CVDs as the leading cause of death, the RII was 1.4 (95% CI: 1.2, 1.6). Across remaining causes of death, the RII ranged from 0.89 (95% CI: 0.58, 1.38) for mental and nervous diseases to 1.65 (1.07, 2.55) for blood and endocrine diseases. The magnitude of RII in all-cause mortality among gout patients was smaller than in the reference population (Table 3). The similar pattern was seen across subgroups except women who had almost identical RIIs regardless of their gout status.

The SII revealed that there were, on average, 1547 (95% CI: 1001, 2092) more deaths per 100,000 person-years in the least vs. most educated gout patients. CVDs made the largest contribution (64%) to this difference, followed by neoplasms (12.7%) and blood& endocrine diseases (8.5%, Fig. 1). The magnitude of absolute educational inequality in all-cause mortality was greater in people with gout compared with those without (SII 1255 per 100,000 person-years, 95% CI: 1038, 1472). The contributions of CVDs (64% vs. 54%), blood & endocrine diseases (8.5% vs. 2.2%), and genitourinary diseases (5.0% vs. 1.1%) to the absolute inequalities in all-cause mortality were more pronounced in gout patients than in the reference population. While among people with gout, the absolute educational inequality in all-cause mortality was greater in women than men (2052 vs. 1411 deaths per 100,000 person-years), the opposite was observed among those without gout (1139 vs. 1320 deaths per 100,000 person-years). In both groups, the SIIs were larger in people aged≥75 years than younger ones. There were variations by age, sex, cause, and gout status in the patterns of absolute educational inequalities and contributions of causes of death to these inequalities. For instance, in both groups, neoplasms had a substantially larger contribution to the absolute educational inequalities in all-cause mortality among younger people compared with those older.

The magnitude of relative inequalities were generally greater using the “weighted multiple-cause” approach compared with the UCD approach (further distance from 1). Furthermore, in contrast with the UCD approach, the “weighted multiple-cause” approach did not evidence an inverse association between education and cause-specific mortality for infectious diseases, digestive diseases, and other causes among gout patients. As expected, the “any mention” approach resulted in narrower 95% CIs for RIIs (Table 4).

In this study, for the first time, we quantified the absolute and relative educational inequalities in all-cause and cause-specific mortality in gout patients and contrasted these with the estimates from a randomly selected age- and sex matched cohort free of gout. Our results suggested that while the magnitude of relative educational inequalities were smaller in gout patients compared with the reference population, the former experienced greater degree of the absolute educational inequalities reflecting a larger mortality burden. Although CVDs were the main driver of absolute educational inequalities in both groups, their relative importance was more pronounced in gout patients than in the reference population. The strengths of associations between level of education and mortality varied by cause of death and its attribution approach, sex, as well as age.

Previous studies have relatively consistently shown that people with lower SES have higher incidence and prevalence of gout [4, 10, 11], suffer from more severe gout [16], and are more prone to discontinue therapy [17]. In our sample, gout patients were, on average, less educated than their non-gout comparators. In addition, higher prevalence of unhealthy behaviours (e.g. alcohol consumption, smoking, physical inactivity) and multi-morbidity among low educated people might partially explain the observed inequalities in our study [18, 19]. Furthermore, despite universal healthcare access in Sweden, educational differences in healthcare utilisation should not be overlooked.

Our results revealed that the magnitude of relative educational inequalities were less pronounced in people with gout than those without. While underlying pathways for this finding need further investigation, one potential explanation is that contacts with healthcare service might decline educational inequalities in health and mortality risk among patients with gout. In contrast, the magnitude of absolute educational inequality in all-cause mortality was larger in gout patients than in the reference population. This finding is mainly driven by larger absolute inequalities in deaths from CVDs and blood & endocrine diseases in gout patients compared with the reference population. Smaller relative inequalities and larger absolute inequalities in a disease group compared with those without the disease has previously been reported [20, 21]. This finding highlights the importance of assessing both relative and absolute inequalities in presenting an accurate picture of socioeconomic inequalities in health.

The substantial contribution of CVDs to the absolute inequalities in all-cause mortality highlights the need for improved prevention and treatment of these diseases among gout patients with lower education, particularly considering that gout patients have a higher CVDs mortality rate than those without gout [6]. The contribution of CVDs to the absolute inequalities in all-cause mortality rose with age while the opposite was observed for neoplasms. Similar patterns have been observed in the reference population in our study and also in the general population in other countries and have been attributed to reduction in socioeconomic differences in the prevalence of risk factors for cancer (e.g. smoking) with increasing age [22].

Quantifying, for the first time, both absolute and relative educational inequalities in all-cause and several cause-specific mortality in a large cohort of gout patients and comparing it with those without gout are the main strengths of the current study. Furthermore, we applied the recent methodology advances in studying SII [13] and multiple-cause of death data [15]. Despite these, several limitations of the current study should be acknowledged. We studied only gout patients diagnosed by a physician and possibility of misdiagnosis and occasional coding errors cannot be ruled out, but is expected to be non-differential. While Sweden has a high quality cause of death register [23], death certificates are subject to misclassification including over-reporting of some causes (e.g. CVDs). If there are educational differences in quality of cause of death data, then our estimates would be biased. However, a previous study found no educational differences in the use of ill-defined causes of death in Sweden [24]. Due to the lack of data, we did not control for several important confounders of the education-mortality or (age at diagnosis of) gout-mortality associations, which could lead to confounding or selection bias, respectively. These include, for instance, cognitive ability, family background, body mass index, and early life health status. This suggests that no causal inference should be made from the findings. It also should be noted that the reference cohort in our study included age-and sex-matched comparators free of gout which might not be representative of the general population and hence any extrapolation of the results to the general population should be avoided.

Our study showed that low level of education was associated with increased mortality among gout patients. Although the magnitude of relative inequality was smaller in people with gout than in the reference cohort, the absolute inequality was larger in those with gout reflecting a major mortality burden among those with lower education, especially low educated women. The strength of these associations varied by cause of death and its attribution approach, sex, and age. Our results call for improvements in management of gout and comorbidities in Sweden. In particular, decreasing exposure to CVDs risk factors through implementing effective interventions for all, with greater intensity for low educated individuals, should be a public health priority.