Aortic valve sclerosis and albuminuria predict cardiovascular events independently in hypertension: a losartan intervention for endpoint-reduction in hypertension (LIFE) substudy.
BACKGROUND
Aortic valve (AV) sclerosis and urine albumin/creatinine ratio (UACR) are both markers of atherosclerosis. We aimed to investigate whether they predicted cardiovascular (CV) events independently in patients with hypertension and electrocardiographic left ventricular (LV) hypertrophy.


METHODS
After 2 weeks of placebo treatment, clinical, laboratory, and echocardiographic variables were assessed in 960 hypertensive patients from the LIFE Echo substudy who had electrocardiographic LV hypertrophy. Morning urine albumin and creatinine were measured calculating UACR. The presence of AV sclerosis was defined as valve thickening or calcification. Fifteen patients with mild AV stenosis were excluded. The patients were followed for 60 +/- 4 months and the composite endpoint (CEP) of CV death, nonfatal stroke, or nonfatal myocardial infarction was recorded.


RESULTS
A value of UACR above the median value of 1.406 was associated with higher incidence of CEP and CV death in patients with AV sclerosis (CEP: 18.8% v 9.0% P < 0.05, CV death: 7.1% v 0.7% P < 0.01) and in patients without AV sclerosis (CEP: 14.0% v 4.9% P < 0.001, CV death: 5.1% v 1.1% P < 0.01). In Cox regression analysis, AV sclerosis predicted CEP (hazard ratio [HR] = 1.52, P < .05), but not CV death (HR = 1.30 [0.62 to 2.70], NS) independently of logUACR (HR = 1.70 and HR = 3.25, both P < .001). After adjusting for the Framingham Risk Score, CV disease, diabetes, smoking, and treatment allocation, AV sclerosis predicted CEP (HR = 1.5, P < .05) but not CV death (HR = 1.4, NS) independently of logUACR (HR = 1.2, P = .09 and HR = 1.94, P < .05).


CONCLUSIONS
In hypertensive patients with electrocardiographic LV hypertrophy, AV sclerosis predicted CEP but not CV death independently of UACR after adjusting for CV risk factors and treatment allocation, indicating that AV sclerosis and UACR might be markers of different aspects of the atherosclerotic process.
Olsen
Michael H
MH
Department of Internal Medicine, Glostrup University Hospital, Glostrup, Denmark. mho@dadlnet.dk
Wachtell
Kristian
K
Bella
Jonathan N
JN
Palmieri
Vittorio
V
Gerdts
Eva
E
Smith
Gunnar
G
Nieminen
Markku S
MS
Dahlöf
Björn
B
Ibsen
Hans
H
Devereux
Richard B
RB
D000368:Aged; D000419:Albuminuria / Q000652:urine*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001021:Aortic Valve / Q000473:pathology*; D001262:Atenolol / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000473:pathology; D004311:Double-Blind Method; D004562:Electrocardiography; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000652:urine; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000175:diagnosis; D019808:Losartan / Q000627:therapeutic use; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D012598:Sclerosis; D016019:Survival Analysis; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D001262:Atenolol; D019808:Losartan