Gout is associated with increased cardiovascular risk: results from analysis of the CPRD dataset

Abstract Background Gout, a common crystal arthropathy, has been associated with higher cardiovascular risk. However, the degree to which this risk is potentially mediated by traditional risk factors, and whether this risk differs across individual cardiovascular disorders (CVD), inclusive of heart failure, is unclear. Purpose We aimed to determine the risk of incident cardiovascular disease in patients with newly diagnosed gout, whether this varied across a range of cardiovascular disorders, and the potential impact of traditional risk factors. Methods We used linked primary and secondary electronic health records from 22 million individuals in the Clinical Practice Research Datalink (CPRD) to assemble a cohort of individuals newly diagnosed with gout between 01/01/2000 and 31/12/2017 and free of cardiovascular disorders (CVD) up to 12 months after diagnosis, and up to five individuals matched on age, sex, socioeconomic status and region, with follow-up until 30/06/2019. We investigated the incidence of twelve cardiovascular outcomes and used Cox-proportional hazards models to examine differences in patients with and without gout. In sensitivity analyses, models were further adjusted for known cardiovascular risk factors (blood pressure, BMI, smoking, cholesterol, and type 2 diabetes). Results We identified 153 645 individuals with Gout and 714 192 matched controls. Of these, 31479 people with and 106 520 without gout developed incident CVD during a median of 6.5 years of follow-up. Patients with gout had a higher risk of cardiovascular outcomes than controls: hazard ratio (HR) [95% confidence interval (CI)] 1.57 [1.52, 1.63]. Excess cardiovascular risk disproportionally affected women (HR in women: 1.88 [1.75, 2.02], HR in men: 1.50 [1.40, 1.62]), and was highest in the very young (HR in people aged 45 years or less: 2.20 [1.91, 2.54]) (Figure 1). Excess risk was visible across all 12 cardiovascular diseases investigated, and was particularly pronounced for heart failure, arrhythmias, and valve disease (HR for heart failure: 1.84 [1.73, 1.96], HR for atrial fibrillation and flutter: 1.81 [1.72, 1.91], HR for valve diseases: 1.83 [1.71, 1.97]). Patients with gout presented with on average 3 units higher body mass index than matched controls, and had higher prevalence of chronic kidney disease, dyslipidaemia, and hypertension. In sensitivity analyses, adjusting for known cardiovascular risk factors attenuated the strength of the associations by around half, although gout remained an independent CVD risk factor. Conclusion Patients with gout present a higher risk of developing a range of cardiovascular outcomes, in particular heart failure, arrhythmias, and valve disease. These findings suggest patients with gout should have formal CV risk assessment, and stronger attention to lifestyle interventions to mitigate future atherosclerotic and cardiorenal risks.Fig1 CVD rates & HRs in gout vs controls