Hypertension is the leading cause of preventable deaths globally, driven by complications such as myocardial infarction, stroke, heart failure, and kidney disease. Recent updates in hypertension classification by the American Heart Association (AHA) place nearly half of the U.S. population in the hypertensive category. Excess dietary salt is a major risk factor for hypertension, with 50% of hypertensive individuals exhibiting salt-sensitivity of blood pressure (SSBP). SSBP is an independent predictor of cardiovascular events and death. While kidney mechanisms in salt-sensing have been extensively studied, emerging evidence suggests that immune cells can also sense sodium (Na+).
This trial hypothesizes that myeloid cell-derived isolevuglandins (IsoLGs) drive endothelial dysfunction, perpetuating the salt-sensitive phenotype. Preliminary data indicate that targeting IsoLGs with the IsoLG scavenger 2-hydroxybenzylamine (2-HOBA) may interrupt this immune-vascular axis, reducing salt sensitivity and associated cardiovascular risks.
This phase 2 clinical trial aims to investigate the role of 2-HOBA in modulating immune cell function within blood vessels in hypertensive patients. The study will explore the impact of immunity on salt sensitivity and assess 2-HOBA's potential to reduce endothelial dysfunction, improve immune cell activation, and alleviate SSBP.
We will perform analyses in participants previously phenotyped for SSBP, defined as a change in systolic blood pressure ≥10 mmHg from salt-loading to salt-depletion,
Over 18 years of age. Able to give informed consent,
Salt-resistant people,
Acute cardiovascular event(s) within the previous 6 months,
inability to understand the nature, scope, and possible consequences of the study or to participate in/comply with the protocol,
Current excessive alcohol or illicit drug use,
Vanderbilt University Medical Center
Lead sponsor