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(Circulation. 2006;113:1588-1596.)
© 2006 American Heart Association, Inc.

Hypertension

Impact of Diabetes Mellitus on Regression of Electrocardiographic Left Ventricular Hypertrophy and the Prediction of Outcome During Antihypertensive Therapy

The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study

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

From the Department of Medicine (P.M.O., R.B.D.), Division of Cardiology, Cornell University Medical Center, New York, NY; University of Bergen (E.G.), Bergen, Norway; Amgen, Inc (S.M.S.), Thousand Oaks, Calif; Merck Research Laboratories (K.E.H.), West Point, Pa; Sahlgrenska University Hospital/Östra (S. Jern, B.D.), Göteborg, Sweden; Ullevål University Hospital (S.E.K.), Oslo, Norway; University of Michigan Medical Center (S. Julius), Ann Arbor, Mich; Merck & Co, Inc (J.M.E.), Whitehouse Station, NJ; and Umeå University (L.H.L.), Umeå, Sweden.

Correspondence to Peter M. Okin, MD, Cornell University Medical Center, 525 E 68th St, New York, NY 10021. E-mail pokin{at}med.cornell.edu

Received July 11, 2005; revision received January 25, 2006; accepted January 27, 2006.

Background— Diabetes mellitus is associated with increased cardiovascular (CV) morbidity and mortality and with greater ECG left ventricular hypertrophy (LVH); however, it is unclear whether diabetes attenuates regression of hypertensive LVH and whether regression of ECG LVH has similar prognostic value in diabetic and nondiabetic hypertensive individuals.

Methods and Results— A total of 9193 hypertensive patients (1195 with diabetes) in the Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study were treated with losartan- or atenolol-based regimens and followed up with serial ECG and blood pressure determinations at baseline and 6 months and then yearly until death or study end. ECG LVH was defined with gender-adjusted Cornell voltage-duration product (CP) criteria >2440 mm · ms. After a mean follow-up of 4.8±0.9 years, patients with diabetes had less regression of CP LVH (–138±866 versus –204±854 mm · ms, P<0.001), remained more likely to have LVH by CP (56.0% versus 48.1%, P<0.001), and had higher rates of CV death, myocardial infarction, stroke, and all-cause mortality and of the LIFE composite end point of CV death, myocardial infarction, or stroke. In multivariable Cox proportional hazards models, in-treatment regression or absence of ECG LVH by CP was associated with between 17% and 35% reductions in event rates in patients without diabetes but did not significantly predict outcome in patients with diabetes.

Conclusions— Hypertensive patients with diabetes have less regression of CP LVH in response to antihypertensive therapy than patients without diabetes, and regression of ECG LVH is less useful as a surrogate marker of outcomes in hypertensive patients with diabetes. These findings may in part explain the higher CV morbidity and mortality in hypertensive patients with diabetes, and the absence of a demonstrable improvement in prognosis in diabetic patients in response to regression of ECG LVH suggests a more complex interrelation between underlying LV structural and functional abnormalities and outcome in these patients.

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