University of Oulu

Cardiovascular abnormalities in adult patients with the 3243A>G mutation in mitochondrial DNA

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Author: Majamaa-Voltti, Kirsi1,2
Organizations: 1University of Oulu, Faculty of Medicine, Department of Internal Medicine
2University of Oulu, Faculty of Medicine, Department of Neurology
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.9 MB)
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Language: English
Published: 2007
Publish Date: 2007-05-04
Thesis type: Doctoral Dissertation
Defence Note: Academic dissertation to be presented, with the assent of the Faculty of Medicine of the University of Oulu, for public defence in Auditorium 10 of Oulu University Hospital, on May 16th, 2007, at 12 noon
Reviewer: Docent Tiina Heliö
Professor John Vissing


The 3243A>G mutation in mitochondrial DNA (mtDNA), the most common cause of the syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes, is also associated with many other phenotypes such as hearing loss, diabetes mellitus, epilepsy, cognitive decline, myopathy and cardiomyopathy. The prevalence of the mutation has been shown to be 16.3/100 000 adults in Northern Finland. The present study was performed to estimate the frequency and progression of cardiac abnormalities and to examine causes of death in patients with 3243A>G.

Left ventricular hypertrophy (LVH) was found in echocardiography in 56% of patients with 3243A>G and in 15% of age and sex-matched controls. The median thickness of the diastolic interventricular septum or posterior wall was 14 mm in the patients with LVH. The prevalence of LVH determined by echocardiography increased from 40% to 56% in 25 patients with 3243A>G during three years of follow-up, this trend being especially marked among the diabetic patients. The ultra-low-frequency (ULF) and very-low-frequency (VLF) components of the spectral analysis of heart rate variability (HRV) were lower among the patients with 3243A>G than in matched controls (p = 0.02 in ULF and p = 0.04 in VLF), and the short-term fractal scaling exponent in detrended fluctuation analysis of HRV was lower in the patients with 3243A>G (1.16 ± 0.18 vs. 1.28 ± 0.13) (p < 0.01). Survival analysis of a birth cohort from pedigrees with 3243A>G revealed excess mortality before the age of 50 years. Neurological and cardiovascular diseases accounted for 32% of all the underlying causes of death in families with 3243A>G. Death was sudden and unexpected in 31% of cases in which 3243A>G was considered to be involved in the cause of death.

The results show that cardiac abnormalities are frequent and progressive in patients with the 3243A>G mtDNA mutation and that cardiac autonomic regulation is disturbed. Patients with the 3243A>G mutation and their first degree maternal relatives died younger than was presupposed by their life expectancy at birth or at 15 years. The most common causes of death were neuropsychiatric and cardiovascular diseases.

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Series: Acta Universitatis Ouluensis. D, Medica
ISSN-E: 1796-2234
ISBN: 978-951-42-8430-4
ISBN Print: 978-951-42-8429-8
Issue: 921
Copyright information: © University of Oulu, 2007. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.