Hyperuricemia, gout and the associated comorbidities in China: findings from a prospective study of 0.5 million adults

Abstract

Background: Despite the growing prevalence of hyperuricemia and gout, their epidemiology and associated comorbidity burden remains poorly studied in many populations, including China. We aimed to examine the patterns of plasma urate level, prevalence of hyperuricemia, and incidence of gout, and investigate the associations of gout with a range of comorbidities and all-cause mortality in Chinese adults.

Methods: The prospective China Kadoorie Biobank recruited 512,724 adults aged 30-79 years from ten diverse areas in 2004-2008 and measured plasma urate level among 16,817 participants. The incidence of gout and other diseases and deaths were monitored by electronic linkages with registries and hospital records. Cox and logistic regression yielded adjusted HRs and ORs for risks of mortality and comorbidities associated with gout, hyperuricemia, and urate level.

Findings: The gout incidence rate was 23.4 per 100,000 person-years, and was higher in men and older participants, and varied substantially by region. Gout was associated with higher risks of all-cause mortality (HR = 1.58, 95% CI 1.37-1.82), CVD (1.87, 1.64-2.14), CKD (5.61, 4.45-7.07), urolithiasis (2.50, 1.85-3.38), diabetes (1.99, 1.51-2.62), diseases of the oesophagus, stomach, and duodenum (2.14, 1.72-2.66), infectious and parasitic diseases (1.91, 1.47-2.48), arthropathies (6.06, 4.98-7.38), and other musculoskeletal disorders (2.10, 1.77-2.51). Most of these associations were bi-directional, sustained over time and little affected by adjustment for cardiometabolic risk factors. Moreover, participants who developed gout were more likely to have multiple major diseases and more hospitalisations. Among the subset with plasma urate measured, 15% had hyperuricemia, which was more common in men, older women, and urban residents, and was associated with increased risks of gout, all-cause mortality, and several cardiometabolic, renal, digestive, and musculoskeletal diseases.

Interpretation: In Chinese adults, gout was associated with several comorbidities and a poor health trajectory. Our findings reinforce the need for prevention and management of gout and associated comorbidities.

Funding: Kadoorie Charitable Foundation, National Natural Science Foundation of China, Noncommunicable Chronic Diseases-National Science and Technology Major Project, British Heart Foundation, Cancer Research UK, Wellcome Trust, UK Medical Research Council, Nuffield Department of Population Health at the University of Oxford.

Keywords: China; Comorbidity; Gout; Hyperuricemia; Prospective study.

Fig. 1

Age-specific mean urate level, hyperuricemia prevalence, and incidence rate of gout, by sex. Adjusted mean urate level (a) and prevalence of hyperuricemia (b) were estimated using linear regression adjusted for study area and fasting time, with inverse probability weighting applied to account for the nested case–control study design. Incidence rates (c) were standardised by study area to the CKB study population. Each solid square represents the adjusted mean, prevalence, or incidence rate with the area inversely proportional to the variance of the estimate. The error bars indicate 95% CIs. CI, confidence interval; py, person-years.

Fig. 2

Bi-directional associations between gout and major diseases. Cox models were stratified by sex and study areas and were adjusted for baseline age, education, smoking, alcohol, physical activity, fish intake, red meat intake, poultry intake, soybean intake, dairy intake, and fresh fruit intake. (a) Displays adjusted HRs for risks of major diseases associated with gout, after excluding relevant prior diseases of interest. (b) Displays adjusted HRs for risk of gout associated with preceding prevalent (where recorded at baseline) and incident major diseases. FDR-adjusted P values were applied to correct for multiple testing within (a) and (b), respectively. Each solid square represents HR with the area inversely proportional to the variance of the log HR. The horizontal lines indicate 95% CIs. HR, hazard ratio; CI, confidence interval; FDR, false discovery rate.

Fig. 3

Associations of gout with risks of selected incident major diseases and all-cause mortality, among subgroups. Cox models were stratified by sex and study areas and adjusted for baseline age, education, smoking, alcohol, physical activity, fish intake, red meat intake, poultry intake, soybean intake, dairy intake, and fresh fruit intake. Each solid square represents HR with the area inversely proportional to the variance of the log HR. The horizontal lines indicate 95% CIs. HR, hazard ratio; CI, confidence interval.