Gluconic Acid Could Serve as Race-Specific Biomarker for Hypertension and Stroke Risk

Naruchorn Kijpaisalratana, MD, PhD

Data from an analysis presented at the American Stroke Association’s International Stroke Conference (ISC) 2023 suggests gluconic acid could serve as a useful biomarker for identifying increased risk of stroke among in Black adults in the US.¹

Using data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, results suggest glycolic acid was associated with hypertension, increased risk of ischemic stroke, lower education level, lack of exercise and more among Black adults, which investigators purport could help improve identification and management of cardiovascular risk among Black patients.

“We have identified a biomarker called gluconic acid that we believe is a lifestyle-related biomarker, providing a direct link to diet and exercise,” said lead investigator Naruchorn Kijpaisalratana, MD, PhD, a research fellow in neurology at Massachusetts General Hospital in Boston.² “Gluconic acid may be considered as a dietary-related oxidative stress marker due to its availability in food, potentially produced by the gut microbiome, and related to diseases with oxidative stress. We think that this biomarker may provide a pathway to improve diet and exercise habits to help prevent a future stroke.“

With previous research establishing gaps in optimal care for people of color and minority populations³, an ability to leverage biomarkers and identify race-specific metabolites stands to play a significant role in the improvement in management of these patient populations. With this in mind, Kijpaisalratana and a team of investigators performed a case-cohort study tested within the REGARDS study with the intent of identifying race-specific metabolites for cardiovascular and cerebrovascular risk. Using the study, investigators identified 1075 ischemic stroke cases and a comparative cohort of 968, which were identified randomly, for inclusion in the current study.

As part of the protocol for the REGARDS study, participants underwent liquid chromatography-tandem mass spectrometry, which was used to identify metabolites. For the purpose of analyses, weighted logistic regression and Cox proportional hazard model were used to estimate associations between potential race-specific metabolites and risk of prevalent hypertension and incident stroke. Investigators noted candidate metabolites when assessed for mediation between hypertension and incident stroke. Additionally, investigators pointed out linear regression was used to explore the association of metabolites with lifestyle factors.

Overall, investigators quantified 162 plasma metabolites. After identifying gluconic acid as a potential race-specific metabolite, results of the investigators’ analyses indicated gluconic acid was associated with prevalent hypertension in Black adults (odds ratio [OR], 1.86 [95% CI, 1.39-2.47] P=2.58x10-5) but not in White adults (OR, 1.00 [95% CI, 0.80-1.24]; P=.97) (P for interaction=4.57x10-4). Further analysis indicated gluconic acid was associated with incident ischemic stroke among Black adults (HR, 1.53 [95% CI< 1.28-1.81]; P=1.76x10-6)but not White adults (HR, 1.16 [95% CI, 1.00-1.34]; P=.057) (P for interaction=.019). investigators pointed gluconic acid mediated 25.4% (95% CI, 4.1-46.8; P=.02) of the association between hypertension and ischemic stroke among Black adults. In additional analyses, investigators found a Southern diet (β, 0.18 [95% CI, 0.08-0.28]; P <.001), lower educational attainment (β, 0.45 [95% CI, 0.19-0.72] P=.001), and lack of exercise (β, 0.26 [95% CI, 0.01-0.51]; P=0.045).

“In the future, we envision that a metabolite like gluconic acid may be used as a biomarker to inform health care professionals whether the patient is eating healthy enough or exercising enough,” Kijpaisalratana said. “A biomarker like gluconic acid may point individuals toward more targeted guidance for stroke prevention.”

References

1. Kijpaisalratana N. International Stroke Conference 2023. In: Racial Disparities In Gluconic Acid, A Lifestyle-Related Biomarker Associated With Stroke In REGARDS. American Stroke Association; 2023. https://eppro02.ativ.me/appinfo.php?page=IntHtml&project=ISC23&id=306&server=eppro02.ativ.me #ISC23 . Accessed February 2, 2023.
2. Lifestyle biomarker linked to high blood pressure, increased stroke risk among Black adults. American Heart Association. https://newsroom.heart.org/news/lifestyle-biomarker-linked-to-high-blood-pressure-increased-stroke-risk-among-black-adults. Published February 2, 2023. Accessed February 2, 2023.
3. Black patients with heart failure half as likely to receive device therapy, transplant as white patients. Practical Cardiology. https://www.practicalcardiology.com/view/black-patients-with-heart-failure-half-as-likely-to-receive-device-therapy-transplant-as-white-patients. Published October 20, 2022. Accessed February 1, 2023.