TY - JOUR
T1 - An initial reduction in serum uric acid during angiotensin receptor blocker treatment is associated with cardiovascular protection
T2 - A post-hoc analysis of the RENAAL and IDNT trials
AU - Smink, Paul A.
AU - Bakker, Stephan J.L.
AU - Laverman, Gozewijn D.
AU - Berl, Tomas
AU - Cooper, Mark E.
AU - De Zeeuw, Dick
AU - Heerspink, Hiddo J. Lambers
PY - 2012/5
Y1 - 2012/5
N2 - Objective: Increased levels of serum uric acid (SUA) are thought to be an independent risk marker for cardiovascular complications. Treatment with the angiotensin receptor blocker (ARB) losartan lowers SUA in contrast to other ARBs. Whether reductions in SUA during ARB therapy are associated with cardiovascular protection is unclear. We aimed to investigate this. Method: In a post-hoc analysis of the Reduction of Endpoints in Non insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) and Irbesartan Diabetic Nephropathy (IDNT) trials we determined whether the short-term effect of losartan and of irbesartan on SUA is related with long-term cardiovascular outcome by means of Cox regression. Results: Compared to placebo, losartan significantly changed SUA [-0.16 mg/dl; 95% confidence interval (CI)-0.01 to-0.30; P = 0.031], whereas irbesartan did not (-0.09 mg/dl; (95% CI 0.09 to-0.28; P = 0.30). Each 0.5 mg/dl decrement in SUA during losartan treatment in the first 6 months resulted in a reduction in the risk of cardiovascular outcomes by 5.3% (95% CI 0.9 to 9.9; P = 0.017). Losartan reduced the risk of cardiovascular outcomes by 9.2% (95% CI-7.9 to 23.6). Adjustment for the 6-month change in SUA attenuated the treatment effect to 4.6% (95% CI-16.2 to 22.0), suggesting that part of the cardiovascular protective effect of losartan is attributable to its short-term effect on SUA. Conclusion: Losartan but not irbesartan significantly lowers SUA compared to placebo in patients with type 2 diabetes and nephropathy. The degree of reduction in SUA explains part of the cardiovascular effect of losartan. This supports the hypothesis that SUA is a modifiable risk factor for cardiovascular disease, at least in type 2 diabetics with nephropathy.
AB - Objective: Increased levels of serum uric acid (SUA) are thought to be an independent risk marker for cardiovascular complications. Treatment with the angiotensin receptor blocker (ARB) losartan lowers SUA in contrast to other ARBs. Whether reductions in SUA during ARB therapy are associated with cardiovascular protection is unclear. We aimed to investigate this. Method: In a post-hoc analysis of the Reduction of Endpoints in Non insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) and Irbesartan Diabetic Nephropathy (IDNT) trials we determined whether the short-term effect of losartan and of irbesartan on SUA is related with long-term cardiovascular outcome by means of Cox regression. Results: Compared to placebo, losartan significantly changed SUA [-0.16 mg/dl; 95% confidence interval (CI)-0.01 to-0.30; P = 0.031], whereas irbesartan did not (-0.09 mg/dl; (95% CI 0.09 to-0.28; P = 0.30). Each 0.5 mg/dl decrement in SUA during losartan treatment in the first 6 months resulted in a reduction in the risk of cardiovascular outcomes by 5.3% (95% CI 0.9 to 9.9; P = 0.017). Losartan reduced the risk of cardiovascular outcomes by 9.2% (95% CI-7.9 to 23.6). Adjustment for the 6-month change in SUA attenuated the treatment effect to 4.6% (95% CI-16.2 to 22.0), suggesting that part of the cardiovascular protective effect of losartan is attributable to its short-term effect on SUA. Conclusion: Losartan but not irbesartan significantly lowers SUA compared to placebo in patients with type 2 diabetes and nephropathy. The degree of reduction in SUA explains part of the cardiovascular effect of losartan. This supports the hypothesis that SUA is a modifiable risk factor for cardiovascular disease, at least in type 2 diabetics with nephropathy.
KW - angiotensin receptor blocker
KW - cardiovascular disease
KW - losartan
KW - type 2 diabetes
KW - uric acid
UR - http://www.scopus.com/inward/record.url?scp=84859913590&partnerID=8YFLogxK
U2 - 10.1097/HJH.0b013e32835200f9
DO - 10.1097/HJH.0b013e32835200f9
M3 - Article
C2 - 22388234
AN - SCOPUS:84859913590
SN - 0263-6352
VL - 30
SP - 1022
EP - 1028
JO - Journal of Hypertension
JF - Journal of Hypertension
IS - 5
ER -