Increased Prevalence of Hypertension in Young Adults with High Heteroplasmy Levels of the MELAS M.3243A>G Mutation

Background: The pathophysiology of hypertension in patients with mitochondrial diseases is different from that of the general population. Growing evidence exists linking mtDNA, its mutations, and mitochondrial dysfunction to the pathogenesis of hypertension. No reports on the prevalence of hypertension in late-onset mtDNA diseases have been described.

Methods: We performed a retrospective chart review of adult patients with late-onset mtDNA diseases between January 1999 and January 2012 at our center. We grouped them into age categories to allow comparison with previously reported Canadian Health Measures Survey (CHMS) prevalence data.

Results: Twenty-three subjects with hypertension were identified for a crude prevalence of 39.7 % (95 % CI 27-53 %) as compared to the CHMS age-predicted prevalence of 30.5 %. When analyzed by individual age group, there were no significant differences between the observed and the CHMS predicted prevalence rates in the 40 years and older cohorts (age category 40-59, p = 0.63; age category 60-79, p = 0.85). However, hypertension rates were significantly higher than predicted in the under 40 years cohort (55.6 vs. 2.8 %, p < 0.001, CI 21-86 %), in which hypertensive patients with the MELAS m.3243A>G mutation were significantly clustered (p < 0.01). This younger MELAS cohort (n = 4, mean age = 24 years) with hypertension had heteroplasmy levels (mean = 68 %) that were significantly higher than the levels found in the older non-hypertensive MELAS cohort (n = 8, mean age = 52 years, mean = 33 %) (p = 0.04).

Conclusion: Relative to age, gender, and mtDNA disease subtype, young adults with high heteroplasmy levels of the MELAS m.3243A>G mutation demonstrate an increased prevalence of hypertension. Further prospective data are needed to confirm this initial finding, which has potentially important treatment implications.