Premature Mortality Gap Persists Among Patients with Gout

Natalie McCormick, PhD

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Patients with gout experience a mortality gap in all-cause and cardiovascular death, independent of serum urate and atherosclerotic cardiovascular disease (ASCVD) risk factors, according to new research.

Analysis of a nationwide cohort in the United States revealed that premature mortality in gout did not improve during the three decades of study, despite survival improvements in the general population. This risk was later replicated among contemporary cases of gout in the United Kingdom and suggested a larger magnitude of risk among women and Black individuals.

“These findings corroborate the potential mechanistic role of non-urate, gout-related pathways (e.g., flare inflammation) and suggest shortcomings in current gout care, especially for women and possibly for Black patients,” wrote the investigative team, led by Natalie McCormick, PhD, Rheumatology & Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital and Harvard Medical School.

The global burden of gout has risen considerably in recent decades – given its pathogenesis of metabolic dysregulation, it has been closely linked to hypertension, type 2 diabetes, and chronic kidney disease. Recent evidence has linked recurrent gout flare episodes with a transient increased risk of major cardiovascular events, with implications for the role of inflammation. However, no prior trials have fully adjusted for the potential impact of gout independent of serum urate and/or ASCVD risk factors identified by the American College of Cardiology (ACC).

For this analysis, McCormick and colleagues prospectively assessed the association between gout and premature mortality risk using early (1988 - 1994 baseline) and late cohorts (2007 - 2017) obtained from the National Health and Nutrition Examination Surveys (NHANES). The current analysis included 37,839 participants in NHANES who were aged ≥18 years at baseline. Death information was obtained from data linkage to the National Death Index until December 2019.

Then, McCormick and colleagues sought to replicate the late US cohort results among incident gout cases in the nationwide UK Biobank cohort (2006 - 2010 baseline). The UK population consisted of all participants in the cohort who developed incident gout during the follow-up (n = 7541) and up to 5 matched individuals with no history of gout (n = 36,316). Mortality data were obtained from nationwide death registry data in the National Health Service (NHS) in the UK through November 2021.

Among 303,492 person-years of follow-up in 37,839 individuals, the analysis reported 4,566 deaths. Upon analysis, investigators found the age, sex-, and race and ethnicity-adjusted hazard ratio (HR) for all-cause mortality comparing gout and non-gout individuals was 1.20 (95% CI, 1.08 - 1.33). This risk changed minimally after the introduction of serum urate levels (HR, 1.19; 95% CI, 1.08 - 1.32), with the same risk estimate identified in the early and late cohorts (HR, 1.19; 95% CI, 1.02 - 1.38 and HR, 1.19; 95% CI, 1.03 - 1.37, respectively).

Meanwhile, the adjusted hazard ratios for all-cause mortality were higher among women (HR, 1.33; 95% CI, 1.11 - 1.60) than among men (HR, 1.13; 95% CI, 1.00 - 1.28) (P for interaction = .04), as well as among Black individuals (HR, 1.40; 95% CI, 1.12 - 1.74) versus White individuals (HR, 1.13; 95% CI, 1.00 - 1.28) (P for interaction = .18).

Over 277,695 person-years of follow-up in the UK database, investigators documented 3566 deaths, including 1033 among gout and 2533 among non-gout individuals. Upon analysis, the full multivariable HR for all-cause mortality, including serum urate adjustment, was 1.61 (95% CI, 1.47 - 1.75).

In the UK cohort, McCormick and colleagues identified a significant interaction among women (HR, 1.90; 95% CI, 1.55 - 2.32) versus men (HR, 1.55; 95% CI, 1.41 - 1.71) (P for interaction = .04). Like the US cohort, the team found a prominent premature mortality risk among Black individuals (HR, 2.18; 95% CI, 1.00 - 4.78).

“It is conceivable that suboptimal gout and comorbidity care and worse outcomes contribute to a potentially higher premature risk of all-cause and CVD mortality among women and among Black patients, though confirmation of these disparities in larger samples is needed,” they wrote.

References

1. _{McCormick N, Lin K, Yokose C, Lu N, Zhang Y, Choi HK. Unclosing Premature Mortality Gap Among Gout Patients in the US General Population, Independent of Serum Urate and Atherosclerotic Cardiovascular Risk Factors. Arthritis Care Res (Hoboken). Published online January 8, 2024. doi:10.1002/acr.25292}