. Author manuscript; available in PMC: 2014 Sep 10.

Published in final edited form as: Rheum Dis Clin North Am. 2014 Feb 19;40(2):251–278. doi: 10.1016/j.rdc.2014.01.005

Table 1.

Comorbidities and their association with hyperuricemia and gout

Comorbidity	Evidence on association and causality	Evidence on impact of urate therapies
Hypertension	Several population studies have proven an independent association between SU and development of hypertension.^32,33 SU plays a key role in the initial stages of the development of hypertension.²¹⁷	Small-sampled controlled studies have shown BP reduction with ULT in young individuals^37,38 and adults.³⁹ However, evidence to recommend use of ULT is still not conclusive. ⁴⁰
Coronary heart disease	Although still not conclusive, evidence shows a small but significant increased risk of CHD in individuals with hyperuricemia,^52,53 and patients with gout. ⁵¹	Trials on the use of allopurinol and angina exist, although evidence on CHD incidence and prognosis is still lacking.
Congestive heart failure	Although a constant association with increased incidence^58,59,65 and mortality,^60,61 causality is still in debate since hyperuricemia may just reflect increased xanthine oxidase activity.^66,63	Small trials showing improvement in myocardial function and ejection fraction with allopurinol suggest benefits secondary to xanthine-oxidase inhibition rather than SU lowering.^69,70,71
Stroke	Associations with cerebral ischemia, ⁷² increased incidence of stroke⁷⁵ and poorer prognosis in stroke patients have been reported.^73,74 However causality is still not clear.	Trials using ULT have shown conflicting results in subclinical parameters.^76–78
Chronic kidney disease	Experimental evidence on crystal-independent renal injury models^82–84 have supported epidemiological evidence for a causative role of hyperuricemia on CKD.^95–97 However, data on effects of disease progression are still not conclusive.^106,110	Interventional studies with allopurinol have shown improvement in eGFR in normal individuals^39,112 and a decrease in renal function deterioration in CKD patients.^113–115 Data is still scarce to generalize recommendations for use of ULT.
Insulin resistance and metabolic syndrome	Experimental data has shown a causative role for UA in the development on IR and an association with the development of IR^151,152 and the MS has been established.^165,166,169 Associations with dyslipidemia¹⁷⁰ and obesity have been reported. ¹⁷³	A role for ULT in animal models with MS has been shown,^140,147 and improvement in IR was seen in one trial with CHF patients.⁷¹ Further trials are needed.
Type 2 diabetes mellitus	Increasing incidence in individuals with hyperuricemia has been shown.^152,154,155 Studies studying an association between gout and diabetes are still not conclusive, with some studies even showing an inverse relation between both.^159,160,162	Data on this subject is still lacking to consider further recommendations.
Neuro-degenerative disorders	An association between hyperuricemia and a decreased incidence with Parkinson’s Disease^186–188 as a slower development of multiples sclerosis¹⁹⁰ and Huntington’s disease has been reported. Data on the subject is still scarce.¹⁹¹	A small trial in multiple sclerosis patients showed clinical improvements in 3 of the patients while increasing SU with inosine.¹⁹² Further trials are needed.

SU = urate; UA = urate; ULT = urate-lowering therapy; CHD = coronary heart disease; eGFR = estimated glomerular filtration rate; CKD = chronic kidney disease; IR = insulin resistance; MS = metabolic syndrome; CHF = congestive heart failure.