Gout is the monosodium urate (MSU) crystal deposition disease. The experts from the Gout, Hyperuricemia, and Crystal-Associated Disease Network (G-CAN) defined the disease as being present when MSU crystal deposition is accompanied by clinical manifestations such as flares, persistent arthritis, and/or tophi. Gout is intimately associated with cardiovascular disease—especially in cases of an atherosclerosis origin, but also with others such as heart failure, atrial fibrillation, or aortic valve stenosis. Besides the common presence of vascular comorbidities in gout sufferers, the disease is—in itself—an independent cardiovascular risk factor, with disease events and mortality attributable to having this condition. Crystal-derived persistent inflammation is likely behind the association.
1. Introduction
Gout is the monosodium urate (MSU) crystal deposition disease. The experts from the Gout, Hyperuricemia, and Crystal-Associated Disease Network (G-CAN) have defined the disease as being present when MSU crystal deposition is accompanied by clinical manifestations such as flares, persistent arthritis, and/or tophi
[1]. However, the transition from asymptomatic hyperuricemia to gout may be sometimes blurred—especially when MSU crystals are already formed
[2]. The disease is clinically characterized by recurrent, self-limited episodes of joint inflammation, and in long-duration cases with insufficient or absent treatment, subcutaneous tophi and/or chronic arthritis. Moreover, patients with gout suffer from disabilities and an impaired quality of life, with higher scores (worse status) on several scales such as the Gout Assessment Questionnaire, Health Assessment Questionnaire–Disease Index, or the Short-Form 36 compared to controls—even during flare-free periods
[3]. Hospitalizations due to gout have almost doubled in the last decades
[4][5][6] and, more importantly, mortality rates in patients with gout greatly surpass those of the general population (all-cause standardized mortality ratio of 2.21)
[7].
There is a close relationship between gout and cardiovascular diseases (CVD). Patients with gout present myriad comorbidities, in which cardiovascular risk factors such as hypertension, dyslipidemia, a smoking habit, obesity, diabetes mellitus, and chronic kidney disease
[8][9][10][11][12][13] stand out. Vascular diseases account for more than half of deaths among gout sufferers; indeed, for up to six points higher than the cardiovascular mortality of the general population, according to European data
[7][14][15]. Interestingly, there is a bidirectional effect between gout and CVD; after a gout flare, the risk of cardiovascular events increases—especially in the short-term
[16]. In addition, having gout worsens a patient’s prognosis following a cardiovascular event
[17][18] or success rates following coronary revascularization
[19]. Furthermore, gout flares are common during hospitalizations due to CVD
[20]. Data also exists for other types of CVD not purely related to atherosclerosis, such as atrial fibrillation
[21][22][23][24], heart failure
[25][26], and aortic valve stenosis
[27]. Pooled data from DATA-HF and DELIVER trials on dapagliflozin recently reported worse heart failure outcomes in the gout population
[28].
Cardiovascular risk factors do not fully explain the increased incidence of CVD, as there remains a residual risk even after adjusting for those covariates. Accordingly, gout must be considered an independent cardiovascular risk factor—indicating that patients with gout have a heightened cardiovascular risk merely from suffering the condition. The risk associated with gout has been demonstrated for all forms of atherosclerotic CVD and their derived mortality rates
[15][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44], as shown in
Table 1. In this sense, aggregate data show that the risk of gout patients dying due to CVD is 1.29-fold higher, and up to 1.42-fold higher for coronary disease-related deaths
[36]. Compared to diabetes, gout shows an equivalent risk of leading to stroke—though less so for cases of myocardial infarction
[45] or limb amputation
[46]. Cardiovascular risk is heightened in cases of larger MSU crystal burden, such as patients with subcutaneous tophi
[7][14][47][48] or with a large crystal load as assessed by ultrasound
[49] or dual-energy computed tomography (DECT)
[50]. Interestingly, the presence of a sonographic power-Doppler signal in tandem with crystal deposits—a surrogate marker of inflammation—was also associated with carotid atherosclerosis
[49].
Table 1. Published studies linking gout and the different forms of atherosclerotic cardiovascular disease.
Paper |
Population |
Type of Cardiovascular Disease |
Gout Population, Compared to Controls a |
Choi, 2007 [29] |
Health Professionals Follow-up Cohort |
Cardiovascular mortality |
RR 1.35 (1.19–1.55) |
Kuo, 2010 [30] |
Chang Gung Memorial Hospital, Taiwan |
Cardiovascular mortality |
HR 1.97 (1.08–3.59) |
Kuo, 2011 [31] |
National Death Registry of Taiwan |
Cardiovascular mortality |
SMR 1.58 (1.39–1.78) in men |
SMR 1.81 (1.46–2.23) in women |
Stack, 2013 [32] |
NHANES-III |
Cardiovascular mortality |
HR 1.46 (1.07–2.00) |
Dehlin, 2022 [15] |
Western Sweden |
Cardiovascular mortality |
HR 1.17 (1.12–1.23) |
Abbott, 1988 [33] |
Framingham Study |
Coronary heart disease |
RR 1.6 (1.1–2.5) |
Krishnan, 2006 [34] |
Multiple Risk Factor Intervention Trial |
Coronary heart disease |
OR 1.26 (1.14–1.40) |
Seminog, 2013 [35] |
UK National Linked Dataset of Admissions and Deaths |
Coronary heart disease |
RR 1.82 (1.78–1.85) in England data |
Clarson, 2015 [36] |
UK Clinical Practice Research Datalink |
Coronary heart disease |
HR 1.08 (1.01–1.15) in men |
HR 1.25 (1.12–1.39) in women |
Huang, 2021 [38] |
Taiwan National Health Insurance database |
Coronary heart disease |
HR 1.36 (1.04–2.76) |
Singh, 2018 [37] |
US Medicare dataset |
Coronary heart disease (older adults) |
HR 1.79 (1.68–1.90) |
De Vera, 2010 [39] |
Former Medical Students Cohort |
Coronary heart disease (women) |
RR 1.39 (1.20–1.61) in females |
RR 1.11 (0.99–1.23) in males |
Kuo, 2013 [40] |
Taiwan National Health Insurance Database |
Coronary heart disease (Young patients with no CVDRF) |
HR 1.59 (1.12–2.24) in age 20–44 |
HR 1.24 (1.08–1.41) in age 45–69 |
HR 1.11 (0.94–1.32) in age ≥ 70 |
Seminog, 2013 [35] |
UK National Linked Dataset Admissions and Deaths |
Stroke |
RR 1.71 (1.68–1.75) in England data |
Haddadin, 2021 [41] |
US National Inpatient Sample |
Stroke |
OR 1.10 (1.01–1.11) in an AF population |
Clarson, 2015 [36] |
UK Clinical Practice Research Datalink |
Peripheral artery disease |
HR 1.18 (1.01–1.38) in men, HR 1.89 (1.50–2.38) in women |
Schlesinger, 2015 [42] |
Rutgers-Robert Wood Johnson Rheumatology Department |
Erectile dysfunction |
OR 2.94 (1.41–6.06) |
Chen, 2015 [43] |
Taiwan National Health Insurance Database |
Erectile dysfunction |
HR 1.40 (1.11–1.77) in those without comorbidities |
HR 2.04 (1.63–2.57) in those with comorbidities |
Abdul Sultan, 2017 [44] |
UK Clinical Practice Research Datalink |
Erectile dysfunction |
HR 1.31 (1.24–1.40) |
This entry is adapted from the peer-reviewed paper 10.3390/gucdd1030014