Adverse effects of left ventricular hypertrophy in the reduction of endpoints in NIDDM with the angiotensin II antagonist losartan (RENAAL) study.
OBJECTIVE
We explored the impact of baseline left ventricular hypertrophy (LVH) and losartan treatment on renal and cardiovascular (CV) events in 1,513 patients from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial, which studied the effects of losartan on the progression of renal disease and/or death in patients with type 2 diabetes and nephropathy.


METHODS
LVH was assessed using ECG criteria (Cornell product and/or Sokolow-Lyon voltage). The risk of renal or CV events was determined by a proportional hazards model fit with treatment allocation and presence of LVH. Covariates at baseline included age, sex, systolic BP, mean arterial pressure, pulse, proteinuria, serum creatinine, albumin and haemoglobin.


RESULTS
A total of 187 subjects (12%) had LVH at baseline. Treatment with losartan resulted in a significant decrease in the Cornell product (-6.2%) and Sokolow-Lyon voltage (-6.3%). LVH was shown to be significantly associated with the primary endpoint, which was a composite of doubling of serum creatinine (DSCR), endstage renal disease (ESRD) or death (hazard ratio [HR]=1.44, p=0.011), as well as with the composite renal endpoint of DSCR/ESRD (HR=1.42, p=0.031) and CV events (HR=1.68, p=0.001). Losartan treatment of patients with LVH decreased the CV as well as renal risk to a level similar to that of patients without LVH.


CONCLUSIONS
In patients with type 2 diabetes and nephropathy, LVH is associated with significantly increased risk of CV events and the progression of kidney disease. Importantly, in patients with LVH, losartan reduced the CV as well as the renal risk to a level similar to that seen in subjects without LVH.
Boner
G
G
Department of Internal Medicine, Sackler Faculty of Medicine, University of Tel Aviv, Ramat Aviv, Tel Aviv, Israel. gboner1@barak-online.net
Cooper
M E
ME
McCarroll
K
K
Brenner
B M
BM
de Zeeuw
D
D
Kowey
P R
PR
Shahinfar
S
S
Dickson
T
T
Crow
R S
RS
Parving
H-H
HH
D000368:Aged; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D048909:Diabetes Complications / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D004311:Double-Blind Method; D004562:Electrocardiography; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D000804:Angiotensin II; D019808:Losartan