title: Albuminuria and blood pressure, independent targets for cardioprotective therapy in patients with diabetes and nephropathy: a post hoc analysis of the combined RENAAL and IDNT trials.
abstract: OBJECTIVE
  The long-term cardioprotective effect of angiotensin receptor blockers (ARBs) is associated with the short-term lowering of its primary target blood pressure, but also with the lowering of albuminuria. Since the individual blood pressure and albuminuria response to an ARB varies between and within an individual, we tested whether the variability and discordance in systolic blood pressure (SBP) and albuminuria response to ARB therapy are associated with its long-term effect on cardiovascular outcomes.
  
  
  RESULTS
  The combined data of the RENAAL and IDNT trials were used. We first investigated the extent of variability and discordance in SBP and albuminuria response (baseline to 6 months). Subsequently, we assessed the combined impact of residual Month 6 SBP and albuminuria level with cardiovascular outcome. In ARB-treated patients, 421 patients (34.5%) either had a reduction in SBP but no reduction in albuminuria, or vice versa, indicating substantial discordance in response in these parameters. The initial reduction in SBP and albuminuria independently correlated with cardiovascular protection: HR per 5 mmHg SBP reduction 0.97 (95% CI 0.94-0.99) and HR per decrement log albuminuria 0.87 (95% CI 0.76-0.99). Across all SBP categories at Month 6, a progressively lower cardiovascular risk was observed with a lower albuminuria level. This was particularly evident in patients who reached the guideline recommended SBP target of ≤130 mmHg.
  
  
  CONCLUSIONS
  The SBP and albuminuria response to ARB therapy is variable and discordant. Therapies intervening in the renin-angiotensin-aldosterone system with the aim of improving cardiovascular outcomes may therefore require a dual approach targeting both blood pressure and albuminuria.
authors.affiliation: Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, Groningen, The Netherlands.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Holtkamp
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.forename: Pieter A
authors.initials: PA
authors.lastname: de Graeff
authors.forename: Gozewijn D
authors.initials: GD
authors.lastname: Laverman
authors.forename: Tom
authors.initials: T
authors.lastname: Berl
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: David
authors.initials: D
authors.lastname: Packham
authors.forename: Julia B
authors.initials: JB
authors.lastname: Lewis
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Hiddo J
authors.initials: HJ
authors.lastname: Lambers Heerspink
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000517:prevention & control*; D017311:Amlodipine / Q000627:therapeutic use; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D005260:Female; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D006973:Hypertension / Q000517:prevention & control*; D000077405:Irbesartan; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000209:etiology; D013777:Tetrazoles / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D013777:Tetrazoles; D017311:Amlodipine; D000077405:Irbesartan; D019808:Losartan