Association between gout and cardiovascular outcomes in adults with no history of cardiovascular disease: large data linkage study in New Zealand

OBJECTIVE: To examine the association of gout with cardiovascular outcomes using linked administrative health data in Aotearoa New Zealand. DESIGN: Data linkage study. SETTING: National registries of pharmaceutical dispensing, hospital admission, and deaths linked to the Auckland/Northland regional repository of laboratory results to create a regional health contact population as of 31 December 2011. PARTICIPANTS: 942 416 residents of the Auckland/Northland region, aged 20-79 years with no history of cardiovascular disease. MAIN OUTCOME MEASURES: Time to first fatal or non-fatal cardiovascular event, identified from national datasets on hospital admissions and mortality, between 1 January 2012 and 31 December 2016. Cardiovascular disease was broadly defined as comprising ischaemic heart disease, ischaemic or haemorrhagic stroke, transient ischaemic attack, peripheral vascular disease, and heart failure. INTERVENTIONS: A history of gout identified from a discharge diagnosis of gout from a public hospital admission or previous dispensing of gout specific drug treatments. The cohort was then linked to national hospital admissions and deaths through to 31 December 2016 (ie, 5 years' follow-up). Multivariable Cox proportional hazard models were constructed to assess the associations between gout, other risk factors, and cardiovascular outcomes. RESULTS: Of 942 416 people included in the study, 31 907 (3.4%) had gout (6261 women and 25 646 men). After adjustment for multiple risk factors for cardiovascular disease, gout was associated with increased cardiovascular events (adjusted hazard ratio 1.34 (95% confidence interval 1.23 to 1.45) in women; 1.18 (1.12 to 1.24) in men). For men with gout, there was an increased risk of cardiovascular disease in those who were not dispensed regular allopurinol (1.15 (1.05 to 1.25)) and those with a serum urate above the treatment target of 0.36 mmol/L (1.16 (1.04 to 1.30)). Risk of cardiovascular events was lower for men with gout who were not dispensed colchicine compared with those who were (0.84 (0.77 to 0.92)). These findings were not observed in women. CONCLUSION: These results indicate that gout is associated with an increased risk of cardiovascular events. In men with gout without history of cardiovascular disease, the cardiovascular risk was lower in those regularly dispensed allopurinol and those with serum urate levels at the recommended treatment target. By contrast, colchicine dispensing was associated with an increased risk of cardiovascular events in men with gout without a cardiovascular history. The potential causal mechanisms of these associations require further exploration, including casual inference modelling in future studies.