Novel markers of resistant hypertension observed in Black patients
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Xanthine oxidase and mitochondrial DNA damage-associated molecular patterns may represent novel biomarkers of resistant hypertension among Black patients, researchers reported.
According to research published in Hypertension, measures of uric acid, plasma xanthine oxidase activity and mitochondrial DNA damage-associated molecular patterns were associated with resistant hypertension among Black individuals, but not white individuals.
“We first published 2 years ago that xanthine oxidase was increased in patients with resistant hypertension. Then, we got the idea to look at whether there were any racial differences. It was astounding, the differences that we saw,” Louis Dell’Italia, MD, professor of medicine at the University of Alabama at Birmingham Comprehensive Diabetes Center at the Heersink School of Medicine and recipient of the 2021 John B. Barnwell Award, told Healio. “We knew what xanthine oxidase did to mitochondria and, lo and behold, it was higher in Black patients. It fits hand-in-hand that the xanthine oxidase being higher was also reflected by the increase in the mitochondrial [DNA damage-associated molecular patterns].
“[Xanthine oxidase] produces free radicals that damage mitochondria and caused mitochondria to not produce enough ATP and produce more reactive oxygen species, causing damage within the cell, to myofibrils and other proteins,” Dell’Italia told Healio. “Scott Ballinger, PhD, our co-investigator, has been working on these mitochondrial damage-associated molecular patterns, or DAMPs. Mitochondria have their own DNA, but it’s not protected as much by histones as nuclear DNA. It is very prone to damage by free radicals and reactive oxygen species. When it’s bad, fragments of mitochondrial DNA can be released as DAMPs into the system. There are very few publications on this with CVD; mostly with sepsis and other trauma do these DAMPs predict outcome.”
Therefore, Dell’Italia and colleagues evaluated the racial differences in xanthine oxidase activity and mitochondrial DNA DAMPs and their relationship to resistant hypertension.
In this cohort of 91 patients with resistant hypertension (47% women; 44% Black), Black patients were younger (52 years vs. 59 years; P = .001), had higher diastolic BP and were more likely to have diabetes compared with white patients. Black patients also had a greater wall thickness with trends toward lower mid-wall radius/wall thickness ratio and LV end diastole mass/volume ratio compared with white patients, according to the study.
All participants had BP of more than 140/90 mm Hg, were already taking maximally tolerated antihypertensive medications at baseline and had cardiac MRI data for left ventricular morphology and function.
Novel markers of resistant hypertension
Researchers reported that 24-hour urinary sodium was associated with left ventricular end-diastolic volume (r = 0.527; P = .001), LV mass (r = 0.394; P = .02) and LV wall thickness (r = 0.356; P = .04) among Black patients but not white patients.
Urinary aldosterone was associated with LV end diastole wall thickness, LV end diastolic volume index and LV end diastole mass index among both Black and white patients, but the association for LV end diastolic mass/volume ratio was only significant for Black patients (r = 0.404; P = .01).
Plasma xanthine oxidase activity was higher among Black patients with resistant hypertension compared with white patients, and researchers identified, controlling for blood creatinine, a relationship between xanthine oxidase activity and uric acid (r = 0.442; P = .001).
Researchers reported that diastolic BP was associated with xanthine oxidase activity among both Black and white participants (r for Black = 0.8; r for white = 0.648; P for both < .001).
The relationship between xanthine oxidase activity and LV end diastole wall thickness (r = 0.401; P = .03) and LV mid-wall radius/wall thickness ratio (r = 0.427; P = .02) was significant among Black patients but not white patients.
Patients with resistant hypertension had elevated serum mitochondrial DNA DAMPs compared with normotensive controls, according to the researchers.
For nicotinamide adenine dinucleotide + hydrogen dehydrogenase (NADH) subunit 1, Black patients with resistant hypertension had greater mitochondrial DNA DAMPs compared with Black patients who were normotensive (P < .001) and white patients with resistant hypertension (P < .001).
For NADH subunit 6, Black patients with resistant hypertension had more mitochondrial DNA DAMPs compared with race-matched normotensive controls (P < .001); however, no differences were observed among white patients with resistant hypertension and race-matched normotensive controls (P = .664).
Researchers reported that Black patients with resistant hypertension had more mitochondrial DNA DAMPs compared with white patients with resistant hypertension (P < .001).
‘New important biomarkers’
“In a way, it doesn’t tell us anything new. We know that Black individuals have a higher incidence of HF, higher death rates and levels of oxidative stress and hypertrophy,” Dell’Italia told Healio. “However, oxidase, uric acid and mitochondrial DNA DAMPs may be new important biomarkers that may lead us to investigate targeted medical therapy to decrease oxidative stress in Black patients and, hopefully, improve outcomes. Does this mean that we should have a trial with allopurinol or some xanthine oxidase inhibitor in Black patients? I don’t know at this point. But it clearly states that these biomarkers are an indication of increased oxidative stress, even in the presence of full-dose renin angiotensin system blockade.”
For more information:
Louis Dell’Italia, MD, can be reached at ldellitalia@uabmc.edu.
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