Effects of losartan compared with atenolol on lipids in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension study.
OBJECTIVE
Beta-blockers and angiotensin II receptor blockers have different effects on lipids.


METHODS
We examined lipid levels in the Losartan Intervention For Endpoint reduction in hypertension study and their impact on the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke. We measured total and high-density lipoprotein cholesterol at baseline and annually during 4.8 years of losartan-based compared with atenolol-based treatment in 8611 patients with hypertension and left ventricular hypertrophy.


RESULTS
Patients randomized to losartan-based or atenolol-based treatment had similar baseline total (6.04 +/- 1.12 vs. 6.05 +/- 1.13 mmol/l, NS) and high-density lipoprotein (HDL) cholesterol (1.50 +/- 0.44 vs. 1.49 +/- 0.44 mmol/l, NS). Total cholesterol decreased significantly but equally (-0.37 +/- 1.05 vs. -0.34 +/- 1.09 mmol/l, NS), whereas HDL cholesterol decreased less during the first 2 years in patients randomized to losartan compared with atenolol (-0.13 +/- 0.24 vs. -0.19 +/- 0.25 mmol/l) and remained higher each year (1.38, 1.37, 1.42, 1.47, and 1.48 mmol/l vs. 1.32, 1.30, 1.36, 1.40, and 1.42 mmol/l, all P < 0.001) independent of hydrochlorothiazide or statin treatment. In Cox regression analysis, baseline total cholesterol [hazard ratio (HR) = 1.08 (1.02-1.14) per mmol/l, P < 0.01], HDL cholesterol [HR = 0.56 (0.48-0.66) per mmol/l, P < 0.001], and treatment allocation [HR = 0.86 (0.76-0.98), P < 0.05] predicted composite endpoint independently. Using time-varying analyses, the predictive strength of HDL cholesterol was increased [HR = 0.36 (0.30-0.44) per mmol/l, P < 0.001], whereas that of total cholesterol [HR = 1.03 (0.97-1.09) per mmol/l, NS] and treatment allocation [HR = 0.91 (0.80-1.03), NS] were reduced.


CONCLUSIONS
Losartan blunted the decrease in HDL cholesterol during antihypertensive treatment in the LIFE study. Higher intreatment HDL cholesterol was associated with fewer composite endpoints and may partly explain the better outcome of losartan-based treatment.
Olsen
Michael Hecht
MH
Glostrup University Hospital, Glostrup, Denmark. mho@dadlnet.dk
Wachtell
Kristian
K
Beevers
Gareth
G
Dahlöf
Björn
B
de Simone
Giovanni
G
Devereux
Richard B
RB
de Faire
Ulf
U
Fyhrquist
Frej
F
Ibsen
Hans
H
Kjeldsen
Sverre E
SE
Lederballe-Pedersen
Ole
O
Lindholm
Lars H
LH
Lyle
Paulette A
PA
Nieminen
Markku S
MS
Omvik
Per
P
Oparil
Suzanne
S
Wedel
Hans
H
D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000401:mortality; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003971:Diastole; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000188:drug therapy*; D050356:Lipid Metabolism / Q000187:drug effects*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D008076:Cholesterol, HDL; D002784:Cholesterol; D019808:Losartan