Measures of Resistant Hypertension Linked to Worse Outcomes Among Black Adults

A new study has investigated the influence of xanthine oxidase activity and mitochondrial DNA damage–associated molecular patterns on heart failure and cardiac remodeling among Black adults with resistant hypertension.

A new study has found marked differences between Black and White adults in 2 potential indicators of heart disease, both cardiac remodeling and heart failure: xanthine oxidase (XO) activity and mitochondrial DNA damage–associated molecular patterns (mtDNA DAMPs). The findings indicate a need for more study on these 2 markers among Black adults with resistant hypertension, concluded the study authors.

Findings were published in Hypertension, with patients included in their analysis all receiving care at the University of Alabama at Birmingham Hypertension Clinic. These patients were also participants of the authors’ Specialized Centers of Clinically Oriented Research project, and they were matched 2.5:1 (91 study subjects and 37 controls matched for XO and mtDNA DAMP levels). Racial identity was self-reported, and everyone underwent cardiac MRI.

XO is an enzyme that facilitates the hydroxylation of hypoxanthine to uric acid, which is then excreted by the kidneys, and mtDNA DAMPs are products of cell death. Both are markers of inflammation.

“Increased XO can cause mitochondrial DNA damage and promote release of fragments called mtDNA DAMPs,” the authors wrote. “In addition, Black adults have higher levels of oxidative stress, even after adjustment for differences in cardiovascular disease risk factors and inflammation. Given this higher level of oxidative stress, the purpose of this study is to examine racial differences XO activity and mtDNA DAMPs in patients with resistant hypertension.”

Among the Black study participants with resistant hypertension, who were younger than their White counterparts, were seen higher diastolic blood pressures, more instances of diabetes, and significantly higher blood creatinine. Data also show they had higher arterial wall thickness and indications of lower ratios of midwall radius/wall thickness and left ventricular end-diastolic (LVED) mass/volume.

After controlling for gender, body mass index (BMI), and age, the study investigators determined that the Black study participants also had positive correlations between 24-hour urinary sodium (mg/24 h/kg) and LVED volume (r = 0.527; P = .001), LV mass (r = 0.394; P =.02), and LV wall thickness (r = 0.356; P =.04). Among Black participants, a potential link was found between 24-hour urinary aldosterone and LVED mass/volume ratio (r = 0.404; P = .01).

For White and Black participants, however, positive associations were seen for LVED wall thickness, LVED volume, and LVED mass index after controlling for gender, BMI, and age.

Findings on plasma XO activity indicate this measure was overall higher among the Black vs the White study participants, for mean (SD) measures of 0.06 (0.08) vs 0.03 (0.03) mcU/mg. The authors noted a normal measure of plasma XO activity is 0.017 (0.004) mcU/mg. In addition, positive relationship were seen only between XO activity and both LVED wall thickness (r = 0.401; P = .03) and LV mid-wall radius/wall thickness ratio (r = 0.427; P = .02) for Blacks.

After polymerase chain reaction assessed mtDNA DAMPs within the NADH dehydrogenase subunit 1 (ND1) and NADH dehydrogenase subunit 6 (ND6) regions of the mtDNA, respectively, patients with resistent hypertension had higher serum DAMP copies vs normotensive controls (P < .001 and P = .018). However, when looking specifically at race, Black adults had higher mtDNA DAMPS than both race-matched normotensive controls (P < .001) and Whites with RHTN (P < .001) for ND1. Results for ND6 show the Black vs White participants with resistant hypertension also had increased mtDNA DAMPs (P < .001).

“This is the first study to show increased plasma XO activity and mtDNA DAMP levels in Black adults with resistant hypertension compared to White adults with resistant hypertension,” the authors concluded. “These results warrant a larger study that includes metabolic syndrome and XO as a potential therapeutic target to reduce mitochondrial damage and attenuate left ventricular diastolic dysfunction in Black adults with resistant hypertension.”

Reference

Butts B, Brown JA, Denney TS, et al. Racial differences in xanthine oxidase and mtDNA DAMPs in resistant hypertension. Hypertension. Published online February 15, 2022. doi:10.1161/HYPERTENSIONAHA.121.18298