Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study.

BACKGROUND: Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain. OBJECTIVES: Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF). METHODS: This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312), and HF (4,526/18,400). As a positive control, this study also investigated our genetic instrument in 3,151 gout cases and 68,350 controls. RESULTS: Serum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations. CONCLUSIONS: Evidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions.

Endoscopic ligation vs. sclerotherapy in adults with extrahepatic portal venous obstruction: a prospective randomized study.

BACKGROUND: Endoscopic sclerotherapy is a well-established treatment for bleeding esophageal varices, although it has a substantial complication rate. A prospective randomized trial was conducted to determine whether endoscopic variceal ligation is safer and more effective than sclerotherapy in adults with bleeding esophageal varices because of extrahepatic portal venous obstruction. METHODS: Thirty-six patients underwent sclerotherapy and 37 had band ligation. RESULTS: Ligation and sclerotherapy were equally effective for achieving variceal eradication (94.6% vs. 91.7%, respectively; p=0.67). However, ligation achieved eradication with fewer endoscopic sessions (3.7 [1.2] vs. 7.7 [3.3]; p <0.0001) and within a shorter time interval (50.1 [17.7] days vs. 99 [54.8] days; p <0.0001). In the ligation group, recurrent bleeding was less frequent (2.7% vs. 19.4%; p=0.028; however, Bonferroni correction for multiple testing removes this significance) and the rate of major complications was lower (2.7% vs. 22.2%; p=0.014). Total cost per patient was significantly higher in the sclerotherapy vs. the ligation group ($216.6 [71.8] vs. $182.6 [63.4]; p=0.035). During the follow-up period after variceal eradication, no significant differences were found between the sclerotherapy and the ligation groups with respect to recurrent bleeding (3% vs. 2.9%; p=1.0), esophageal variceal recurrence (9.1% vs. 11.4%; p=1.0), and formation of new gastric varices (9.1% vs. 14.3%; p=0.51). CONCLUSIONS: Variceal band ligation is superior to sclerotherapy, because it is less costly and achieves variceal eradication more quickly, with lower relative frequencies of recurrent variceal bleeding and complications.