comorbidities
Gout and cardiovascular disease
The large body of evidence supporting the cardiovascular implications of gout, clearly
suggest the importance of urate-lowering treatment on the progression and clinical
outcome of cardiovascular comorbidities
Claudio Borghi MD
Department of Medicine,
Hypertension Unit,
Policlinico S. Orsola-
Malpighi, Bologna, Italy
Over the last century, there has been a huge
increase in the number of subjects affected by
metabolic disorders, including obesity, hypertension,
and diabetes and metabolic syndrome, which has
resulted in significantly increased incidence of
major cardiovascular diseases (CVD). 1–3 However,
the burden of cardiovascular risk in the general
population cannot be entirely explained by
interaction of the most common risk factors, with
a residual risk largely due to emerging risk factors
such as hyperuricaemia. 4,5 to be related pathophysiologically to gout (for
example, renal disease). Nowadays, the risk of CVD
in gout is well established 8,9 and several potential
mechanisms directly or indirectly related to the
degree of persistent inflammation are recognised. 10
The European League Against Rheumatism (EULAR)
recommendations suggest the importance of
treating gout from the time of diagnosis with the
goal of avoiding further gout attacks, reducing the
crystal load and possibly preventing cardiovascular
complications. 11
Epidemiology and cardiovascular risk
Gout was a neglected disease for a very long time.
It is the most common inflammatory arthritis
worldwide, with a recent estimated prevalence
of 2.49% in the UK but significantly less in
northern European (0.8–1.5%) and Mediterranean
countries (for example, Italy and France 0.9%). 6 The
classic initial presentation is usually with acute
arthritis eventually complicated by chronic joint
damage, subcutaneous tophi and periarticular
inflammation. However, gout is also associated
with several important comorbidities affecting the
wellbeing and the life expectancy of the patient,
including CVD. 7 Over the last ten years, there
has been a progressive increase in the interest in
the association of gout and heart disease, guided
by emerging epidemiologic data linking the two
diseases and by the understanding that gout arthritis
and hyperuricaemia are distinct pathophysiologic
entities, leading, through different pathways, to an
increased inflammatory activity involved in CVD
risk. Major guidelines agree on the importance of
comorbidities for gout management, even when
they are largely focused on those diseases considered Gout and vascular damage
From the clinical point of view, the problem of CVD
in patients with gout is initially focused on the
possibility that uric acid deposition can promote
heart and vascular damage in patients with gout
but without heart disease. In particular, the
presence of gout significantly affects the coronary
circulation and the presence of asymptomatic
hyperuricaemia complicated by urate deposition
and its association with a more severe form of
coronary atherosclerosis has been demonstrated. 12
A second study carried out in patients with
recent diagnosis of untreated gout showed a high
prevalence of carotid atherosclerotic plaques (46.5%)
associated with a very high risk profile for CVD. 13
In addition, elevated levels of uric acid can
significantly modify the characteristics of the
atherosclerotic plaque by increasing the lipid
content and reducing the thickness of the fibrous
cap. 14 The changes are proportional to the serum
urate levels and increase the instability of the
atherosclerotic lesion and the risk of athero-
thrombotic complications such as myocardial
infarction (MI), angina and stroke.
Figure 1
Relative risk of cardiovascular diseases in major observational studies in patients with elevated
serum uric acid levels (red bars: significant RR, yellow bars: not significant RR)
2.5
2.0
1.5
1.0
0.5
0
Abbott 16
Chen 15
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