# Non-coding RNA biomarkers in resistant hypertension: a scoping review

## TL;DR

This review explores non-coding RNA biomarkers in resistant hypertension, highlighting gaps in evidence and potential for future research.

## Contribution

The study maps current human evidence on ncRNA biomarkers in resistant hypertension, identifying key areas for further investigation.

## Key findings

- Eight studies were identified, focusing on miRNAs and circRNAs in peripheral blood.
- Some ncRNAs showed potential as biomarkers for RH phenotypes and treatment response.
- Methodological inconsistencies and lack of validation limit clinical applicability.

## Abstract

To map and synthesize human evidence on circulating non-coding RNAs (ncRNAs) evaluated as biomarkers in resistant hypertension (RH), including associations with RH phenotypes, target-organ damage, and short-term treatment response.

A scoping review was conducted and reported in line with PRISMA-ScR guidance. PubMed, Web of Science, and Google Scholar were searched using RH-related terms combined with ncRNA keywords. After deduplication, titles/abstracts and full texts were screened in Covidence. Eligible records included full-length articles and conference abstracts reporting original human research explicitly addressing RH; case reports, narrative reviews, and animal/in vitro-only studies were excluded. Data were charted using a standardized extraction form and synthesized qualitatively due to heterogeneity.

Eight studies met inclusion criteria (five full-length articles and three congress abstracts) published between 2013 and 2024. Across studies, RH sample sizes ranged from 10 to 115 (total RH participants: 338; mean ≈ 42 per study). All studies assessed peripheral-blood matrices (serum, plasma, or PBMCs) and focused on microRNAs (miRNAs) or circular RNAs (circRNAs); no eligible study evaluated other circulating ncRNA classes (e.g., lncRNAs, snoRNAs, siRNAs, piRNAs) specifically in RH. Evidence clustered into four clinical contexts: baseline RH comparisons (and separately, internal comparison of RH with versus without type 2 diabetes mellitus), RH with obstructive sleep apnoea (OSA) and blood-pressure response to CPAP, RH with and without OSA, and RH treated with renal sympathetic denervation (RDN). Reported signals included elevated serum miR-21 in RH versus comparators (AUC ≈0.82 in one study), higher PBMC miR-1-1 and miR-195 in RH with diabetes, a three-miRNA panel (miR-378a-3p/miR-486-5p/miR-100-5p) discriminating CPAP responders versus non-responders (AUCs ≈0.88 training and ≈0.92 validation), increased miR-133a after RDN (≈7.2-fold), and early post-RDN circRNA changes (hsa_circRNA_000367↑; hsa_circRNA_405119↓). Methodology (platforms and normalization) and analytic rigor varied substantially; most analyses were univariable and external validation was absent.

Human evidence on circulating ncRNA biomarkers in RH is sparse and fragmented. Although individual studies have reported biologically plausible associations between selected miRNAs/circRNAs and RH-related phenotypes or short-term treatment response, current data are insufficient for clinical implementation. Larger, well-phenotyped, multicentre studies using standardized assays and independent, robust multivariable validation are needed.