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Review
. 2014 May;40(2):251-78.
doi: 10.1016/j.rdc.2014.01.005. Epub 2014 Feb 19.

Comorbidities in patients with crystal diseases and hyperuricemia

Sebastian E Sattui  1 , Jasvinder A Singh  2 , Angelo L Gaffo  3
Affiliations
Review

Comorbidities in patients with crystal diseases and hyperuricemia

Sebastian E Sattui et al. Rheum Dis Clin North Am. 2014 May.

Abstract

Crystal arthropathies are among the most common causes of painful inflammatory arthritis. Gout, the most common example, has been associated with cardiovascular and renal disease. In recent years, evidence for these associations and those involving other comorbidities, such as the metabolic syndrome, have emerged, and the importance of asymptomatic hyperuricemia has been established. In this review, an update on evidence, both experimental and clinical, is presented, and associations between hyperuricemia, gout, and several comorbidities are described. Causality regarding calcium pyrophosphate arthropathy and associated comorbidities is also reviewed.

Keywords: Calcium pyrophosphate arthropathy; Cardiovascular disease; Comorbidities; Crystal arthropathies; Gout; Hyperuricemia; Metabolic syndrome; Renal disease.

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Conflict of interest statement

Competing interests

There are no financial conflicts related directly to this study. JAS has received research grants from Takeda and Savient; and consultant fees from Savient, Takeda, Allergan and Regeneron. DGL has received royalties/speaker fees from Zimmer, has been a paid consultant to Zimmer and has received institutional research funds from DePuy, Stryker and Zimmer. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.

Figures

Figure 1
Figure 1
Proposed two-stage Urate-mediated hypertension An initial stage of urate-dependent vasoreactive hypertension is induced. Later, when anatomical changes that include wall thickening and smooth muscle proliferation have occurred, a second and definitive sodium-dependent hypertension is established. Adapted with permission from Feig, DI, The role of urate in the pathogenesis of hypertension in the young. J Clin Hypertens (Greenwich), 2012. 14(6): p. 346–52. RAS = renin-angiotensin system; NO = nitric oxide; UA = urate; VSMC = vascular smooth muscle cell; PDGF = platelet-derived growth factor; MCP-1 = monocyte chemotactic protein-1; Na = sodium
Figure 2
Figure 2
Association and causality between hyperuricemia and coronary heart disease Hyperuricemia has an indirect effect in the development of coronary heart disease through the development of hypertension and atherosclerosis. However, evidence on a direct and independent effect (dashed arrow) on the development of coronary heart disease is still not conclusive. Adapted from Gaffo, A.L., N.L. Edwards, and K.G. Saag, Gout. Hyperuricemia and cardiovascular disease: how strong is the evidence for a causal link? Arthritis Res Ther, 2009. 11(4): p. 240.
Figure 3
Figure 3
Hyperuricemia, insulin resistance and the metabolic syndrome Experimental models have shown that hyperuricemia-induced vascular dysfunction, inflammation and increased oxidative stress lead to insulin resistance, which later leads to impaired glucose tolerance and predisposes to the other components of the metabolic syndrome. NO = nitric oxide; TG = triglycerides; HDLc = high-density lipoprotein-cholesterol; RAS = renin-angiotensin system.
See this image and copyright information in PMC

References

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