Large population-based study underscores link between gout, CVD event risk

ATLANTA – Gout is associated with an increased risk of both fatal and nonfatal cardiovascular disease events, according to a large population-based health data linkage study in New Zealand.

^{Sharon Worcester/MDedge News}

Dr. Ken Cai

“Overall, the survival was quite good within both cohorts, but … there is a clear and statistically significant difference in the survival between the people with gout and those without gout,” Ken Cai, MBBS, reported at the annual meeting of the American College of Rheumatology, noting that a similarly “significant and clear” difference was seen in nonfatal CVD events between the groups.

Of 968,387 individuals included in the analysis, 34,056 had gout, said Dr. Cai, a rheumatology clinical fellow at the University of Auckland (New Zealand). After adjusting for population-level estimated 5-year CVD risk for cardiovascular death, nonfatal myocardial infarction, stroke, or other vascular event, the adjusted hazard ratios were 1.20 for fatal and 1.32 for nonfatal first CVD events in patients with gout. The CVD risk score used in the analysis accounted for age, gender, ethnicity, level of social deprivation, diabetes status, previous hospitalization for atrial fibrillation, and baseline dispensing of blood pressure–lowering, lipid-lowering, and antiplatelet/anticoagulant medications.

“To allow for any other differences between the gout and nongout cohorts with respect to gender, age, ethnicity, and social deprivation, we further adjusted for these factors again, even though they had been accounted for within our CVD risk score,” he said, noting that “gout continued to demonstrate an increased adjusted hazard ratio” for fatal and nonfatal events after that adjustment (HRs, 1.40 and 1.35, respectively)

Additional analysis in the gout patients showed that CVD risk was similarly increased both in those who had been dispensed allopurinol at least once in the prior 5 years and those who had not (adjusted HRs for fatal events, 1.41 and 1.33; and for nonfatal, first CVD events, 1.34 and 1.38, respectively), and “there was no significant difference between these two groups, compared to people without gout,” he said.

Adjustment for serum urate levels in gout patients also showed similarly increased risk for fatal and nonfatal events for those with levels less than 6 mg/dL and those with levels of 6 mg/dL or greater (adjusted HRs of 1.32 and 1.42 for fatal events, and 1.27 and 1.43 for nonfatal first CVD events, respectively).

Again, no significant difference was seen in the risk of events between these two groups and those without gout, Dr. Cai said, noting that patients with no serum urate monitoring also had an increased risk of events (adjusted HR of 1.41 for fatal events and 1.29 for nonfatal, first CVD events).

Gout and hyperuricemia have previously been reported to be independent risk factors for CVD and CVD events, and urate-lowering therapy such as allopurinol have been thought to potentially be associated with reduced risk of CVD, he said, noting that the relationships are of particular concern in New Zealand, where gout affects more than 4% of the adult population.

“Maori, who are the indigenous people of New Zealand, and Pasifika people are disproportionately affected by gout; 8.5% of Maori, and 13.9% of Pasifika adults have gout,” he said, adding that an estimated one-third of Maori and Pasifika adults over age 65 years have gout.

To further assess the relationships between gout and CVD risk, he and his colleagues used validated population-level risk-prediction equations and linked National Health Identifier (NHI) data, he said.

National registries of medicines dispensing data, hospitalization, and death were linked to the Auckland/Northland regional repository of laboratory results from Jan. 1, 2012 to Dec. 31, 2016.

“We included all New Zealand residents aged 20 years or older who were in contact with publicly funded services in 2011 and were alive at the end of December, 2011,” he said, adding that those with a previous hospitalization for CVD or heart failure prior to the end of December 2011 were excluded, as were those with primary residence outside of the region for the prior 3 years and those missing predictor variable data.

Although the findings are limited by an inability to adjust for smoking status, body mass index, and blood pressure – as such data are not collected at the national level, and by the population-based nature of the study, which does not allow determination about causation, they nevertheless reinforce the association between gout and an increased estimated risk of CVD events, Dr. Cai said.

“Even after adjustment for estimated 5-year CVD risk and the additional weighting of risk factors within it, gout independently increased the hazard ratio for fatal and nonfatal events,” he said. “In our study, this effect was not ameliorated by allopurinol use or serum urate lowering to treatment target.”

Similar studies are needed in other populations, he said.

Dr. Cai reported grant support from Arthritis Australia.

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SOURCE: Cai K et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2732.