# Allopurinol Improves Diastolic Function in African Americans with Resistant Hypertension

> **NIH VA I21** · BIRMINGHAM VA MEDICAL CENTER · 2024 · —

## Abstract

Heart failure (HF) is a leading cause of morbidity, mortality and escalating health care costs within the VA. The
type of HF that is increasing disproportionately is HF with a preserved ejection fraction (HFpEF), commonly
caused by hypertension and left ventricular (LV) pressure overload. An estimated 10% to 20% of hypertensive
patients have resistant hypertension (RHTN), defined as having controlled or uncontrolled blood pressure with
the use of ≥ 3 medications that includes a diuretic. We previously reported significant LV hypertrophy and
diastolic dysfunction with normal systolic function in persons with RHTN. Hypertension among Black adults in
the US has one of the highest prevalence rates in the world and is related to adverse changes in LV structure
and function. Hypertension is an underlying factor in >50% of Black adults with HF and is the strongest risk
factor for HF in that population.8 Black adults have a 50% increased incidence of HF, due in large part to the
greater prevalence and severity of hypertension, and HF occurs 8 years earlier in Black adults as compared
with Whites. Although Black adults have the highest death rate for HF, they are consistently underrepresented
in clinical trials. The greater HF burden among Black adults calls for further work to discover effective
preventive and therapeutic strategies for this higher-risk population. The greater HF burden among Black
adults calls for further work to discover effective preventive and therapeutic strategies for this higher-risk
population. The long-term goal of this project is to develop an effective strategy to improve the health of African
American Veterans with HFpEF. We have recently reported increased plasma xanthine oxidase (XO) activity
and mtDNA damage associated molecular products (DAMPs) levels in Black adults with RHTN, compared with
White adults with RHTN. This supports the general consensus that oxidative stress is higher in black adults.
XO oxidizes hypoxanthine and xanthine to generate hydrogen peroxide and superoxide as a byproduct. These
products damage mitochondria leading to bioenergetic dysfunction and further amplification of oxidant
generation and production of mtDNA DAMPs. mtDNA DAMPs are potent activators of the innate immune
response through several pathways including activation of TLR (toll-like receptor) with promotion of pro-
inflammatory cytokine release. We have shown diastolic blood pressure (r=0.876, p<.001), LV end-diastolic
mass index (r=0.503, p=0.012), fractional shortening (r=-0.546, p=0.006), wall thickness (r=0.428, p=0.001),
mid-wall radius to wall thickness ratio (r=0.354, p=0.008), and early diastolic filling rate (r=-0.422, p=0.04) were
related to XO activity at six months among the Blacks but not White RHTN patients. Given the higher level of
XO activity and mtDNA DAMPs in blacks, we hypothesize that inhibition of XO improves LV diastolic
function in Black African Americans with RHTN. We will address this hypothesis in the followin...

## Key facts

- **NIH application ID:** 10869948
- **Project number:** 5I21RX004655-02
- **Recipient organization:** BIRMINGHAM VA MEDICAL CENTER
- **Principal Investigator:** Louis J. Dell'Italia
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869948

## Citation

> US National Institutes of Health, RePORTER application 10869948, Allopurinol Improves Diastolic Function in African Americans with Resistant Hypertension (5I21RX004655-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10869948. Licensed CC0.

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