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Peter M. Okin, MD; Richard B. Devereux, MD; Sverker Jern, MD; Sverre E. Kjeldsen, MD, PhD; Stevo Julius, MD, ScD; Markku S. Nieminen, MD, PhD; Steven Snapinn, PhD; Katherine E. Harris, DrPH; Peter Aurup, MD; Jonathan M. Edelman, MD; Hans Wedel, PhD; Lars H. Lindholm, MD, PhD; Björn Dahlöf, MD, PhD; for the LIFE Study Investigators

JAMA. 2004;292:2343-2349.

Context  Electrocardiographic left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular (CV) morbidity and mortality. However, the predictive value of changes in the magnitude of electrocardiographic LVH criteria during antihypertensive therapy remains unclear.

Objective  To test the hypothesis that lesser severity of electrocardiographic LVH during antihypertensive treatment is associated with decreased CV morbidity and mortality, independent of blood pressure levels and reduction and treatment modality.

Design, Setting, and Participants  Double-blind, randomized, parallel-group study conducted in 1995-2001 among 9193 men and women with hypertension aged 55 through 80 years (mean, 67 years), with electrocardiographic LVH by Cornell voltage-duration product or Sokolow-Lyon voltage criteria and enrolled in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study.

Interventions  Losartan- or atenolol-based treatment regimens, with follow-up assessments for at least 4 (mean, 4.8 [SD, 0.9]) years.

Main Outcome Measure  Composite end point of CV death, myocardial infarction (MI), or stroke in relation to severity of electrocardiographic LVH determined at baseline and on subsequent electrocardiograms obtained at 1 or more annual revisits.

Results  Cardiovascular death, nonfatal MI, or stroke occurred in 1096 patients (11.9%). In Cox regression models controlling for treatment type, baseline Framingham risk score, baseline and in-treatment blood pressure, and severity of baseline electrocardiographic LVH by Cornell product and Sokolow-Lyon voltage, less-severe in-treatment LVH by Cornell product and Sokolow-Lyon voltage were associated with 14% and 17% lower rates, respectively, of the composite CV end point (adjusted hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.82-0.90; P<.001 for every 1050-mm x ms [1-SD] decrease in Cornell product; and HR, 0.83; 95% CI, 0.78-0.88; P<.001 for every 10.5-mm [1-SD] decrease in Sokolow-Lyon voltage). In parallel analyses, lower Cornell product and Sokolow-Lyon voltage were each independently associated with lower risks of CV mortality (HR, 0.78; 95% CI, 0.73-0.83; P<.001; and HR, 0.80; 95% CI, 0.73-0.87; P<.001, respectively), MI (HR, 0.90; 95% CI, 0.82-0.98; P=.01; and HR, 0.90; 95% CI, 0.81-1.00; P = .04), and stroke (HR, 0.90; 95% CI, 0.84-0.96; P=.002; and HR, 0.81; 95% CI, 0.75-0.89; P<.001).

Conclusions  Less-severe electrocardiographic LVH by Cornell product and Sokolow-Lyon voltage criteria during antihypertensive therapy is associated with lower likelihoods of CV morbidity and mortality, independent of blood pressure lowering and treatment modality in persons with essential hypertension. Antihypertensive therapy targeted at regression or prevention of electrocardiographic LVH may improve prognosis.

Author Affiliations: Department of Medicine, Division of Cardiology, Cornell University Medical Center, New York, NY (Drs Okin and Devereux); Sahlgrenska University Hospital/Östra, Göteborg, Sweden (Drs Jern and Dahlöf); Ullevål University Hospital, Oslo, Norway (Dr Kjeldsen); University of Michigan Medical Center, Ann Arbor (Dr Julius); Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (Dr Nieminen); Amgen Inc, Thousand Oaks, Calif (Dr Snapinn); Merck Research Laboratories, West Point, Pa (Drs Harris and Aurup); Merck & Co Inc, Whitehouse Station, NJ (Dr Edelman); Nordic School of Public Health, Göteborg, Sweden (Dr Wedel); and Umeå University, Umeå, Sweden (Dr Lindholm).

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