Reducing Hypertrophy in Hypertension Patients May Shrink Diabetes Risk

NEW YORK, Nov. 1 -- Regression or prevention of left-ventricular hypertrophy in hypertension patients may reduce their risk of developing new-onset diabetes, according to a study.
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The LIFE study from which these findings came reflects a potentially important association but do not establish causality between decreasing an enlarged heart and preventing new diabetes.
The risk of developing new-onset diabetes was reduced by 38% among those whose left-ventricular hypertrophy regressed during hypertension treatment with losartan (Cozaar, Hyzaar), Peter Okin, M.D., of Cornell University Medical Center here, and colleagues, reported in the November issue of Hypertension.
After adjusting for drug treatment, blood pressure lowering, and diabetes risk factors, the risk, though attenuated, was still 26% lower, the researchers reported.
The Cornell study, supported in part by Merck, maker of losartan, used data from the blinded Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study.
The LIFE study, conducted from 1995 through 2001, of losartan versus atenolol-based therapy for hypertensive patients with left- ventricular hypertrophy, found losartan therapy associated with a lower incidence of diabetes and greater regression of hypertrophy.
But whether treatment resolution or continued absence of hypertrophy is independently associated with a decreased incidence of diabetes remained unclear, Dr. Okin said.
Accordingly, the present study evaluated hypertrophy in 7,998 hypertensive patients without diabetes at baseline in the LIFE study who were treated with losartan-based or atenolol-based regimens and followed with serial electrocardiograms and blood pressure determinations.
Electrocardiographic hypertrophy was defined using gender-adjusted Cornell voltage-duration criteria > 2,440 mm.ms.
During mean follow-up of 4.6 ± 1.2 years, 562 patients (7%) developed diabetes.
In a Cox model adjusting for drug treatment assignment, in-treatment resolution or continued absence of hypertrophy was associated with a 38% lower risk of new diabetes (HR 0.62, 95% CI 0.50 to 0.78).
After adjusting for the association of new diabetes with a series of risk confounders, continued absence or resolution of hypertrophy remained associated with a 26% lower risk of new diabetes (HR 0.74, 95% CI 0.58 to 0.93), the researchers reported.
Confounders included prior antihypertensive treatment, baseline glucose, Framingham risk score, baseline and in-treatment systolic and diastolic pressure, HDL, uric acid, body mass index, and, also, the decreased incidence associated with losartan-based therapy.
Thus, compared with the presence of hypertrophy during antihypertensive treatment, resolution or continued absence of hypertrophy was associated with a lower rate of diabetes, even after adjusting for the impact of treatment with losartan and other diabetes risk factors, the researcher said.
In contrast, higher values of left-ventricular hypertrophy were associated with higher rates of new diabetes, they said.
Study limitations included the fact that the study population was mainly white and was derived from a high-risk population.
Also, the researchers emphasized that the favorable association reported was attenuated after adjustment for other risk factors, and the LIFE study was not designed to test whether treatment specifically aimed at producing regression of hypertrophy will decrease the incidence of diabetes.
As a result, they said, these findings reflect a potentially important association but do not establish causality between resolution of hypertrophy and diabetes.
These results and previous findings with ACE-inhibitor and angiotensin-receptor-blocker therapy, they added, suggest that antihypertensive therapies that independently reduce the occurrence of diabetes and also produce left-ventricular hypertrophy regression may provide long-term benefits by reducing cardiovascular morbidity and mortality, at least in part by preventing new-onset diabetes.
Further study will be necessary to determine whether regression of hypertrophy will become a valid independent target for therapeutic intervention in hypertensive patients to prevent development of diabetes and other adverse cardiovascular outcomes, the researchers concluded.
This study was supported in part by a grant from Merck, maker of losartan. The drug maker took no part in the interpretation or writing of the study. Dr. Okin reported that he has received grant support from Merck while other study authors reported various financial relationships with Merck.Primary source: HypertensionSource reference: Okin PM, et al "In-Treatment Resolution or Absence of Electrocardiographic Left Ventricular Hypertrophy Is Associated With Decreased Incidence of New-Onset Diabetes Mellitus in Hypertensive Patients: The Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study"Hypertension 2007; 50: 984-990.