Left Ventricular Wall Stress-Mass-Heart Rate Product and Cardiovascular Events in Treated Hypertensive Patients: LIFE Study

TY - JOUR

T1 - Left Ventricular Wall Stress-Mass-Heart Rate Product and Cardiovascular Events in Treated Hypertensive Patients

T2 - LIFE Study

AU - Devereux, Richard B

AU - Bang, Casper N

AU - Roman, Mary J

AU - Palmieri, Vittorio

AU - Boman, Kurt

AU - Gerdts, Eva

AU - Nieminen, Markku S

AU - Papademetriou, Vasilios

AU - Wachtell, Kristian

AU - Hille, Darcy A

AU - Dahlöf, Björn

N1 - © 2015 American Heart Association, Inc.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - In the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study, 4.8 years' losartan- versus atenolol-based antihypertensive treatment reduced left ventricular hypertrophy and cardiovascular end points, including cardiovascular death and stroke. However, there was no difference in myocardial infarction (MI), possibly related to greater reduction in myocardial oxygen demand by atenolol-based treatment. Myocardial oxygen demand was assessed indirectly by the left ventricular mass×wall stress×heart rate (triple product) in 905 LIFE participants. The triple product was included as time-varying covariate in Cox models assessing predictors of the LIFE primary composite end point (cardiovascular death, MI, or stroke), its individual components, and all-cause mortality. At baseline, the triple product in both treatment groups was, compared with normal adults, elevated in 70% of patients. During randomized treatment, the triple product was reduced more by atenolol, with prevalences of elevated triple product of 39% versus 51% on losartan (both P≤0.001). In Cox regression analyses adjusting for age, smoking, diabetes mellitus, and prior stroke, MI, and heart failure, 1 SD lower triple product was associated with 23% (95% confidence interval 13%-32%) fewer composite end points, 31% (18%-41%) less cardiovascular mortality, 30% (15%-41%) lower MI, and 22% (11%-33%) lower all-cause mortality (all P≤0.001), without association with stroke (P=0.34). Although losartan-based therapy reduced ventricular mass more, greater heart rate reduction with atenolol resulted in larger reduction of the triple product. Lower triple product during antihypertensive treatment was strongly, independently associated with lower rates of the LIFE primary composite end point, cardiovascular death, and MI, but not stroke.

AB - In the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study, 4.8 years' losartan- versus atenolol-based antihypertensive treatment reduced left ventricular hypertrophy and cardiovascular end points, including cardiovascular death and stroke. However, there was no difference in myocardial infarction (MI), possibly related to greater reduction in myocardial oxygen demand by atenolol-based treatment. Myocardial oxygen demand was assessed indirectly by the left ventricular mass×wall stress×heart rate (triple product) in 905 LIFE participants. The triple product was included as time-varying covariate in Cox models assessing predictors of the LIFE primary composite end point (cardiovascular death, MI, or stroke), its individual components, and all-cause mortality. At baseline, the triple product in both treatment groups was, compared with normal adults, elevated in 70% of patients. During randomized treatment, the triple product was reduced more by atenolol, with prevalences of elevated triple product of 39% versus 51% on losartan (both P≤0.001). In Cox regression analyses adjusting for age, smoking, diabetes mellitus, and prior stroke, MI, and heart failure, 1 SD lower triple product was associated with 23% (95% confidence interval 13%-32%) fewer composite end points, 31% (18%-41%) less cardiovascular mortality, 30% (15%-41%) lower MI, and 22% (11%-33%) lower all-cause mortality (all P≤0.001), without association with stroke (P=0.34). Although losartan-based therapy reduced ventricular mass more, greater heart rate reduction with atenolol resulted in larger reduction of the triple product. Lower triple product during antihypertensive treatment was strongly, independently associated with lower rates of the LIFE primary composite end point, cardiovascular death, and MI, but not stroke.

KW - Aged

KW - Aged, 80 and over

KW - Angiotensin II Type 1 Receptor Blockers

KW - Antihypertensive Agents

KW - Atenolol

KW - Blood Pressure

KW - Cardiovascular Diseases

KW - Female

KW - Heart Rate

KW - Heart Ventricles

KW - Humans

KW - Hypertension

KW - Hypertrophy, Left Ventricular

KW - Losartan

KW - Male

KW - Middle Aged

KW - Myocardial Infarction

KW - Oxygen

KW - Prevalence

KW - Stroke

KW - Treatment Outcome

U2 - 10.1161/hypertensionaha.114.05582

DO - 10.1161/hypertensionaha.114.05582

M3 - Journal article

C2 - 26418019

SN - 0194-911X

VL - 66

SP - 945

EP - 953

JO - Hypertension

JF - Hypertension

IS - 5

ER -