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

Circulation. 2006 Mar 28;113(12):1588-96. doi: 10.1161/CIRCULATIONAHA.105.574822. Epub 2006 Mar 13.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Atenolol / pharmacology
  • Atenolol / therapeutic use
  • Diabetes Complications / drug therapy
  • Diabetes Complications / mortality
  • Diabetes Complications / physiopathology
  • Diabetes Mellitus / mortality
  • Diabetes Mellitus / physiopathology*
  • Double-Blind Method
  • Electrocardiography
  • Female
  • Humans
  • Hypertension / drug therapy
  • Hypertension / mortality
  • Hypertrophy, Left Ventricular / drug therapy*
  • Hypertrophy, Left Ventricular / mortality
  • Losartan / pharmacology
  • Losartan / therapeutic use
  • Male
  • Middle Aged
  • Prognosis
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Atenolol
  • Losartan