Left ventricular hypertrophy and the insulin resistance ...

Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 992

_____________________________

_____________________________

Left Ventricular Hypertrophy and the Insulin Resistance Syndrome

BY

JOHAN SUNDSTR?M

ACTA UNIVERSITATIS UPSALIENSIS UPPSALA 2001

Dissertation for the Degree of Doctor of Philosophy (Faculty of Medicine) in Geriatrics presented at Uppsala University in 2001

Abstract

Sundstr?m, J. 2001. Left ventricular hypertrophy and the insulin resistance syndrome. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 992. 68 pp. Uppsala. ISBN 91-554-4919-0.

Left ventricular hypertrophy (LVH) and the insulin resistance syndrome are common conditions associated with a markedly increased cardiovascular risk. In a fairly large prospective longitudinal study of men from the general population, we found that an unfavorable serum fatty acid profile and components of the insulin resistance syndrome such as dyslipidemia, obesity and hypertension at age 50 predicted the prevalence of LVH at age 70. In cross-sectional analyses at age 70, several components of the insulin resistance syndrome were significantly related to left ventricular relative wall thickness and concentric remodeling, but less to LVH. Left ventricular relative wall thickness was inversely related to insulin sensitivity in skeletal muscle and borderline significantly directly related to insulin sensitivity in the myocardium in a healthy, normotensive sample of the cohort investigated with positron emission tomography, whereas left ventricular mass index was not related to myocardial or skeletal muscle insulin sensitivity. At age 70, echocardiographic LVH was related to a variety of common electrocardiographic diagnoses. In a prospective mortality analysis with baseline at age 70 and a median follow-up time of five years, echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of other cardiovascular risk factors, implying that echocardiographic and electrocardiographic LVH in part carry different prognostic information.

In summary, components of the insulin resistance syndrome predicted LVH twenty years later, but were cross-sectionally more related to increased left ventricular relative wall thickness and concentric remodeling. Echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of components of the insulin resistance syndrome.

Key words: Left ventricular hypertrophy, insulin, glucose, lipids, mortality.

Johan Sundstr?m, Department of Public Health & Caring Sciences, Section for Geriatrics, Box 609, SE-751 25 Uppsala, Sweden

? Johan Sundstr?m 2001 ISSN 0282-7476 ISBN 91-554-4919-0 Printed in Sweden by Uppsala University, Tryck & Medier, Uppsala 2001

to Anna

Left ventricular hypertrophy and the insulin resistance syndrome

This thesis is based on the following investigations, which will be referred to by their Roman numerals:

I. Sundstr?m J, Lind L, Vessby B, Andr?n B, Aro A, Lithell H. Dyslipidemia and an unfavorable fatty acid profile predict left ventricular hypertrophy 20 years later. Circulation 2001; in press.

II. Sundstr?m J, Lind L, Nystr?m N, Zethelius B, Andr?n B, Hales CN, Lithell H. Left ventricular concentric remodeling rather than left ventricular hypertrophy is related to the insulin resistance syndrome in elderly men. Circulation 2000;101:2595-600.

III. Sundstr?m J, Lind L, Valind S, Holm?ng A, Bj?rntorp P, Andr?n B, Waldenstr?m A, Lithell H. Myocardial insulin-mediated glucose uptake and left ventricular geometry. Blood Pressure 2001; in press.

IV. Sundstr?m J, Lind L, Andr?n B, Lithell H. Left ventricular geometry and function are related to electrocardiographic characteristics and diagnoses. Clin Physiol 1998;18:463-470.

V. Sundstr?m J, Lind L, ?rnl?v J, Zethelius B, Andr?n B, Lithell H. Echocardiographic and electrocardiographic left ventricular hypertrophy predict mortality independently of each other in a population of elderly men. Submitted for publication.

The original articles were reprinted with permission from the publishers.

Contents

ABBREVIATIONS _________________________________________________________________________ 6 INTRODUCTION _________________________________________________________________________ 7

THE ETIOLOGY OF LEFT VENTRICULAR HYPERTROPHY ______________________________________________ 8 LEFT VENTRICULAR HYPERTROPHY AND THE INSULIN RESISTANCE SYNDROME ____________________________ 9 ELECTROPHYSIOLOGIC CO-MORBIDITY OF LEFT VENTRICULAR HYPERTROPHY __________________________ 12 PROGNOSTIC SIGNIFICANCE OF LEFT VENTRICULAR HYPERTROPHY __________________________________ 12 AIMS OF THE STUDY_____________________________________________________________________ 13 METHODS______________________________________________________________________________ 14 THE COHORT __________________________________________________________________________ 14

Study populations _________________________________________________________________ 15 INVESTIGATIONS AT AGE 50 _______________________________________________________________ 15 INVESTIGATIONS AT AGE 70 _______________________________________________________________ 16

Echocardiography ________________________________________________________________ 16 Electrocardiography ______________________________________________________________ 17 Blood pressure measurements _____________________________________________________ 19 Hyperinsulinemic euglycemic clamp _______________________________________________ 19 Oral glucose tolerance test ________________________________________________________ 20 Lipid measurements_______________________________________________________________ 20 Positron emission tomography _____________________________________________________ 20 FOLLOW-UP AFTER AGE 70________________________________________________________________ 21 STATISTICAL ANALYSIS ____________________________________________________________________ 21 RESULTS _______________________________________________________________________________ 23 STUDY I ______________________________________________________________________________ 23 STUDY II ______________________________________________________________________________ 25 STUDY III______________________________________________________________________________ 26 STUDY IV _____________________________________________________________________________ 28 STUDY V______________________________________________________________________________ 30 DISCUSSION ___________________________________________________________________________ 34 LEFT VENTRICULAR HYPERTROPHY AND THE INSULIN RESISTANCE SYNDROME ___________________________ 34 Components of the insulin resistance syndrome are risk factors for later left ventricular hypertrophy ______________________________________________________________________ 34 Fatty acids and left ventricular hypertrophy ________________________________________ 34 Relative wall thickness is related to components of the insulin resistance syndrome ___ 36 Relative wall thickness is related to skeletal muscle insulin resistance _________________ 38 INSULIN RESISTANCE AND LEFT VENTRICULAR HYPERTROPHY: CAUSE OR CONSEQUENCE? ________________ 39 Potential mechanisms whereby insulin resistance or hyperinsulinemia may cause left ventricular hypertrophy____________________________________________________________ 39 Insulin resistance and left ventricular hypertrophy as parallel phenomena ____________ 42 Left ventricular hypertrophy as a causal factor for hypertension and insulin resistance_ 42 THE CLINICAL IMPORTANCE OF LEFT VENTRICULAR HYPERTROPHY ___________________________________ 43 Electrophysiologic co-morbidity of left ventricular hypertrophy_______________________ 43 Prognostic significance of echocardiographic and electrocardiographic left ventricular hypertrophy ______________________________________________________________________ 44 STRENGTHS AND LIMITATIONS OF THE STUDY ___________________________________________________ 45 CONCLUSIONS_________________________________________________________________________ 47 FUTURE PERSPECTIVES ___________________________________________________________________ 48 ACKNOWLEDGEMENTS _________________________________________________________________ 51 SUMMARY IN SWEDISH / SAMMANFATTNING P? SVENSKA _________________________________ 52 REFERENCES ___________________________________________________________________________ 53

 ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download