HPE Grunenthal handbook - Page 16

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 16 | 2018 | hospitalpharmacyeurope.com Choi 9 De Vere Janssen Kok 22 Krishnan 8 Kuo 21 Stack 18