Protocol for investigating the association between Helicobacter pylori exposure, antigen-specific serological responses, and resistant versus non-resistant hypertension in a South African cohort

Background Hypertension is a leading contributor to cardiovascular morbidity and mortality, with poor control in low- and middle-income countries. Helicobacter pylori (H. pylori ) has been associated with hypertension through inflammatory, endothelial, metabolic and immune pathways, but data from sub-Saharan Africa, particularly in resistant hypertension, are limited. Methods This cross-sectional observational study will enrol 200 adults aged ≥18 at a tertiary academic hospital in Cape Town, South Africa: 80 with resistant hypertension, 80 with non-resistant hypertension and 40 with normotension. Participants will undergo standardised clinical assessment, blood pressure measurement, and collection of blood, urine and saliva. H. pylori exposure will be assessed using the Pylori DuoTect® point-of-care assay, which detects antibodies to CagA and FliD. Laboratory analyses will include lipid profile, inflammatory and nitric oxide-related markers, homocysteine, insulin indices, complete blood count, ghrelin, multiplex cytokine profiling and flow cytometric immunophenotyping. PAXgene® blood RNA samples will be retained for future exploratory analyses. Saliva will undergo exploratory H. pylori antigen testing using CerTest® kits, which are validated for stool rather than saliva. Saliva analysis will be exploratory, and results will not define the primary H. pylori exposure variable. Remaining saliva will be kept for potential future oral microbiome analyses not defined in this protocol. Multivariable logistic regression will evaluate associations between H. pylori exposure and hypertension phenotype, adjusting for demographic, lifestyle, and clinical covariates. Discussion To our knowledge, this will be the first African study to integrate point-of-care H. pylori serology with detailed clinical, inflammatory, metabolic, and immunological profiling across resistant hypertension, non-resistant hypertension and normotension. Findings may clarify biological pathways linking H. pylori exposure to blood pressure dysregulation and inform future mechanistic and interventional studies.