SUN-256 - International Hypertensive Pathotypes Cohort: A Mechanistically Phenotyped Human Cohort for Precision Hypertension and Metabolic Research

Background:
The International Hypertensive Pathotypes (HyperPATH) Consortium is a multicenter cohort designed to elucidate mechanisms of blood pressure regulation under rigorously standardized physiological conditions, providing a platform for precision medicine in hypertension and metabolic disease. By combining diet-controlled inpatient testing with long-term biobanking and genome-wide profiling, HyperPATH offers a unique resource for linking genotype, mechanistic pathways, and cardiovascular phenotypes across diverse populations.

Methods:
Since 1992, six centers (Boston, Salt Lake City, Nashville, Charlottesville, Paris, and Rome) have enrolled participants who complete two strictly supervised diets: restricted-sodium and liberal-sodium diets, following washout of all antihypertensive medications. Inpatient testing includes seated, supine, and upright blood pressure measurements; graded angiotensin II and norepinephrine infusions; oral glucose tolerance testing; and an extensive biochemical panel (renin-angiotensin-aldosterone system (RAAS) hormones, inflammatory markers, lipids, and electrolytes). DNA, plasma, serum, and urine are stored for future use. Genotyping progressed from candidate variants to a 1.7-million-marker genome-wide array in 2022.

Results:
To date, over 2,550 participants (median age 46 years; 57% men) have completed the protocol: 48% are hypertensive, 34% normotensive, and 18% have diabetes. The racial distribution is 77% White, 18% Black, 4% Asian, and 1% other/mixed race. HyperPATH data have identified multiple reproducible cardiometabolic phenotypes, including salt-sensitive blood pressure, differential angiotensin II responsiveness, and aldosterone and renin subtypes, which have been reported in more than 165 publications.

Conclusions:
HyperPATH integrates the breadth of an international cohort with the experimental control of a clinical research unit, delivering diet-verified hemodynamic and multi-omic data to enable mechanistic discovery in hypertension and cardiometabolic diseases. Several independent investigators have used HyperPATH, and it remains available for future collaboration to support ongoing investigations.

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