Cardiovascular comorbidity in Leber’s hereditary optic neuropathy mtDNA 11778

Abstract

Purpose : Systemic neurological and cardiovascular manifestations of the mitochondrial disease, Leber’s hereditary optic neuropathy (LHON), have been described, including various studies detailing symptomatic palpitations, syncope, and abnormal electrocardiographic findings in affected subjects [Ortiz RG Am J Ophthalmol 1992; Bower SC Lancet 1992; Nikoskelainen E Lancet 1994]. Given our previously presented findings of cardiac conduction abnormalities in the largest known pedigree of LHON 11778, the aim of this study was to investigate cardiovascular comorbidity in subjects with LHON 11778 mitochondrial DNA (mtDNA) mutation.

Methods : A retrospective chart review of data compiled from the Soave-Brazil pedigree, LHON 11778 mtDNA mutation, was performed. Two patient cohorts comprised of affected patients (n₁=17) and asymptomatic carriers (n₂=56) were compared to an age- and sex-matched off-pedigree controls (n₃=29). All subjects had completed a multiple choice questionnaire, in their native language, pertaining to their cardiovascular history, including history of stroke, history of myocardial infarction, history of angina and history of palpitations. Descriptive statistics, such as age, gender and body mass index were also obtained.

Results : The overall prevalence of cardiovascular comorbidity in the study population was 51.3% (1.4% stroke, 0% myocardial infarction, 12.2% angina, 47.3% palpitations). History of cardiovascular comorbidity was present in 37.5% of affected patients, 48.7% of carriers, and 63.0% of controls. Age, gender, and LHON status were found to be associated with cardiovascular comorbidity at α=0.75 level, however, the final multivariate model found that LHON status was not associated with cardiovascular comorbidity after controlling for age and gender, based on an α=0.95 level. Female gender and increasing age were associated with an increased prevalence of cardiovascular comorbidity.

Conclusions : We did not find an increased prevalence of cardiovascular comorbidity in either affected or carrier LHON patients in this pedigree when compared to age matched controls by multivariant analysis. This suggests that the cardiac conduction changes in this same patient population are subclinical in nature.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.