title: Left Ventricular Wall Stress-Mass-Heart Rate Product and Cardiovascular Events in Treated Hypertensive Patients: LIFE Study.
abstract: 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.
authors.affiliation: From the Department of Medicine, Weill Medical College of Cornell University, New York, NY (R.B.D., C.N.B., M.J.R., V.P.); Research Unit, Department of Medicine Skellefteå, Umeå University, Skellefteå, Sweden (K.B.); Department of Clinical Science, University of Bergen, Bergen, Norway (E.G.); Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland (M.S.N.); Division of Cardiology, A.O.S.G. Moscati, Avellino, Italy (V.P.); Department of Medicine, Glostrup University Hospital, Glostrup, Denmark (K.W.); Section on Biostatistics, Merck Research Laboratories, North Wales, PA (D.A.H.); and Department of Medicine, Sahlgrenska University Hospital, Östra, Sweden (B.D.). rbdevere@med.cornell.edu.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Devereux
authors.affiliation: From the Department of Medicine, Weill Medical College of Cornell University, New York, NY (R.B.D., C.N.B., M.J.R., V.P.); Research Unit, Department of Medicine Skellefteå, Umeå University, Skellefteå, Sweden (K.B.); Department of Clinical Science, University of Bergen, Bergen, Norway (E.G.); Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland (M.S.N.); Division of Cardiology, A.O.S.G. Moscati, Avellino, Italy (V.P.); Department of Medicine, Glostrup University Hospital, Glostrup, Denmark (K.W.); Section on Biostatistics, Merck Research Laboratories, North Wales, PA (D.A.H.); and Department of Medicine, Sahlgrenska University Hospital, Östra, Sweden (B.D.).
authors.forename: Casper N
authors.initials: CN
authors.lastname: Bang
authors.affiliation: From the Department of Medicine, Weill Medical College of Cornell University, New York, NY (R.B.D., C.N.B., M.J.R., V.P.); Research Unit, Department of Medicine Skellefteå, Umeå University, Skellefteå, Sweden (K.B.); Department of Clinical Science, University of Bergen, Bergen, Norway (E.G.); Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland (M.S.N.); Division of Cardiology, A.O.S.G. Moscati, Avellino, Italy (V.P.); Department of Medicine, Glostrup University Hospital, Glostrup, Denmark (K.W.); Section on Biostatistics, Merck Research Laboratories, North Wales, PA (D.A.H.); and Department of Medicine, Sahlgrenska University Hospital, Östra, Sweden (B.D.).
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Roman
authors.affiliation: From the Department of Medicine, Weill Medical College of Cornell University, New York, NY (R.B.D., C.N.B., M.J.R., V.P.); Research Unit, Department of Medicine Skellefteå, Umeå University, Skellefteå, Sweden (K.B.); Department of Clinical Science, University of Bergen, Bergen, Norway (E.G.); Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland (M.S.N.); Division of Cardiology, A.O.S.G. Moscati, Avellino, Italy (V.P.); Department of Medicine, Glostrup University Hospital, Glostrup, Denmark (K.W.); Section on Biostatistics, Merck Research Laboratories, North Wales, PA (D.A.H.); and Department of Medicine, Sahlgrenska University Hospital, Östra, Sweden (B.D.).
authors.forename: Vittorio
authors.initials: V
authors.lastname: Palmieri
authors.affiliation: From the Department of Medicine, Weill Medical College of Cornell University, New York, NY (R.B.D., C.N.B., M.J.R., V.P.); Research Unit, Department of Medicine Skellefteå, Umeå University, Skellefteå, Sweden (K.B.); Department of Clinical Science, University of Bergen, Bergen, Norway (E.G.); Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland (M.S.N.); Division of Cardiology, A.O.S.G. Moscati, Avellino, Italy (V.P.); Department of Medicine, Glostrup University Hospital, Glostrup, Denmark (K.W.); Section on Biostatistics, Merck Research Laboratories, North Wales, PA (D.A.H.); and Department of Medicine, Sahlgrenska University Hospital, Östra, Sweden (B.D.).
authors.forename: Kurt
authors.initials: K
authors.lastname: Boman
authors.affiliation: From the Department of Medicine, Weill Medical College of Cornell University, New York, NY (R.B.D., C.N.B., M.J.R., V.P.); Research Unit, Department of Medicine Skellefteå, Umeå University, Skellefteå, Sweden (K.B.); Department of Clinical Science, University of Bergen, Bergen, Norway (E.G.); Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland (M.S.N.); Division of Cardiology, A.O.S.G. Moscati, Avellino, Italy (V.P.); Department of Medicine, Glostrup University Hospital, Glostrup, Denmark (K.W.); Section on Biostatistics, Merck Research Laboratories, North Wales, PA (D.A.H.); and Department of Medicine, Sahlgrenska University Hospital, Östra, Sweden (B.D.).
authors.forename: Eva
authors.initials: E
authors.lastname: Gerdts
authors.affiliation: From the Department of Medicine, Weill Medical College of Cornell University, New York, NY (R.B.D., C.N.B., M.J.R., V.P.); Research Unit, Department of Medicine Skellefteå, Umeå University, Skellefteå, Sweden (K.B.); Department of Clinical Science, University of Bergen, Bergen, Norway (E.G.); Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland (M.S.N.); Division of Cardiology, A.O.S.G. Moscati, Avellino, Italy (V.P.); Department of Medicine, Glostrup University Hospital, Glostrup, Denmark (K.W.); Section on Biostatistics, Merck Research Laboratories, North Wales, PA (D.A.H.); and Department of Medicine, Sahlgrenska University Hospital, Östra, Sweden (B.D.).
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.affiliation: From the Department of Medicine, Weill Medical College of Cornell University, New York, NY (R.B.D., C.N.B., M.J.R., V.P.); Research Unit, Department of Medicine Skellefteå, Umeå University, Skellefteå, Sweden (K.B.); Department of Clinical Science, University of Bergen, Bergen, Norway (E.G.); Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland (M.S.N.); Division of Cardiology, A.O.S.G. Moscati, Avellino, Italy (V.P.); Department of Medicine, Glostrup University Hospital, Glostrup, Denmark (K.W.); Section on Biostatistics, Merck Research Laboratories, North Wales, PA (D.A.H.); and Department of Medicine, Sahlgrenska University Hospital, Östra, Sweden (B.D.).
authors.forename: Vasilios
authors.initials: V
authors.lastname: Papademetriou
authors.affiliation: From the Department of Medicine, Weill Medical College of Cornell University, New York, NY (R.B.D., C.N.B., M.J.R., V.P.); Research Unit, Department of Medicine Skellefteå, Umeå University, Skellefteå, Sweden (K.B.); Department of Clinical Science, University of Bergen, Bergen, Norway (E.G.); Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland (M.S.N.); Division of Cardiology, A.O.S.G. Moscati, Avellino, Italy (V.P.); Department of Medicine, Glostrup University Hospital, Glostrup, Denmark (K.W.); Section on Biostatistics, Merck Research Laboratories, North Wales, PA (D.A.H.); and Department of Medicine, Sahlgrenska University Hospital, Östra, Sweden (B.D.).
authors.forename: Kristian
authors.initials: K
authors.lastname: Wachtell
authors.affiliation: From the Department of Medicine, Weill Medical College of Cornell University, New York, NY (R.B.D., C.N.B., M.J.R., V.P.); Research Unit, Department of Medicine Skellefteå, Umeå University, Skellefteå, Sweden (K.B.); Department of Clinical Science, University of Bergen, Bergen, Norway (E.G.); Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland (M.S.N.); Division of Cardiology, A.O.S.G. Moscati, Avellino, Italy (V.P.); Department of Medicine, Glostrup University Hospital, Glostrup, Denmark (K.W.); Section on Biostatistics, Merck Research Laboratories, North Wales, PA (D.A.H.); and Department of Medicine, Sahlgrenska University Hospital, Östra, Sweden (B.D.).
authors.forename: Darcy A
authors.initials: DA
authors.lastname: Hille
authors.affiliation: From the Department of Medicine, Weill Medical College of Cornell University, New York, NY (R.B.D., C.N.B., M.J.R., V.P.); Research Unit, Department of Medicine Skellefteå, Umeå University, Skellefteå, Sweden (K.B.); Department of Clinical Science, University of Bergen, Bergen, Norway (E.G.); Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland (M.S.N.); Division of Cardiology, A.O.S.G. Moscati, Avellino, Italy (V.P.); Department of Medicine, Glostrup University Hospital, Glostrup, Denmark (K.W.); Section on Biostatistics, Merck Research Laboratories, North Wales, PA (D.A.H.); and Department of Medicine, Sahlgrenska University Hospital, Östra, Sweden (B.D.).
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlöf
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000503:physiopathology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000453:epidemiology / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism; D015995:Prevalence; D020521:Stroke / Q000453:epidemiology* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001262:Atenolol; D019808:Losartan; D010100:Oxygen
keywords: hypertension; hypertrophy; myocardial infarction; oxygen; prognosis