Gout and incidence of 12 cardiovascular diseases: a case-control study including 152 663 individuals with gout and 709 981 matched controls

Abstract

Background Gout, a common crystal arthropathy, is associated with increased risk of cardiovascular disease. We aimed to identify how this risk varies by individual cardiovascular disease across a broad spectrum of conditions. Methods In this matched case-control study, we used linked primary and secondary electronic health records from the UK Clinical Practice Research Datalink to assemble a cohort of individuals with a first-time diagnosis of gout between Jan 1, 2000 and Dec 31, 2017, who were aged 80 years or younger at diagnosis, and free of cardiovascular diseases up to 12 months after diagnosis. The control cohort comprised up to five control individuals per patient with gout, matched on age, sex, socioeconomic status, geographical region, and calendar time, randomly selected among individuals free of gout at any time before and during the study period. The cohorts were followed up until June 30, 2019. We investigated the incidence of 12 cardiovascular diseases and used Cox proportional hazards models to examine differences in people with and without gout, overall and by subgroups of sex, age, socioeconomic status, and year of study inclusion. We further adjusted models for known cardiovascular risk factors (blood pressure, BMI, smoking status, cholesterol, type 2 diabetes, chronic kidney disease, and history of hypertension). Findings We identified 152 663 individuals with gout (mean age 56 center dot 2 years [SD 13 center dot 3]; 120 324 [78 center dot 8%] men and 32 339 [21 center dot 2%] women) and 709 981 matched controls (mean age 56 center dot 5 years [13 center dot 2]; 561 002 [79 center dot 0%] men and 148 979 [21 center dot 0%] women). Of these individuals, 31 479 (20 center dot 6%) with gout and 106 520 (15 center dot 0%) without gout developed cardiovascular disease during a median follow-up of 6 center dot 5 years (IQR 3 center dot 1-10 center dot 5). Patients with gout had higher risk of cardiovascular diseases than matched controls (hazard ratio [HR] 1 center dot 58 [95% CI 1 center dot 52-1 center dot 63]). Excess risk of cardiovascular disease in gout was greater in women than men (women: HR 1 center dot 88 [1 center dot 75-2 center dot 02]; men: HR 1 center dot 49 [1 center dot 43-1 center dot 56]), and, among all age groups, was highest in younger individuals (HR in people aged <45 years: 2 center dot 22 [1 center dot 92-2 center dot 57]). Excess risk was observed across all 12 cardiovascular diseases investigated. Patients with gout had higher BMI than matched controls (mean difference 2 center dot 90 kg/m(2) [95% CI 2 center dot 87-2 center dot 93]) and higher prevalence of chronic kidney disease, dyslipidaemia, history of hypertension, obesity, and type 2 diabetes. Adjusting for known cardiovascular risk factors attenuated but did not eliminate the excess risk of cardiovascular disease related to gout (adjusted HR 1 center dot 31 [1 center dot 27-1 center dot 36]). Interpretation Patients with gout had an excess risk of developing a broad range of cardiovascular diseases that extend beyond atherosclerotic diseases and include heart failure, arrhythmias, valve disease, and thromboembolic diseases. Excess risk was highest in women and younger individuals. These findings suggest that strategies to reduce cardiovascular risk in patients with gout need to evolve and be implemented in clinical practice. Copyright Copyright (c) 2024 Elsevier Ltd. All rights reserved.