New Intermediate Phenotype of Resistant Hypertension
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See related article, pp 827–835
Hypertension is the world’s leading risk factor for morbidity and mortality and ranks first in disability-adjusted life years at 7%.1–3 However, understanding the pathophysiology of primary (essential) hypertension has been confounded by its complex polygenic foundations and the variable interplay among multiple genetic and environmental factors, each providing small contributions to the development and maintenance of disease. Genome-wide association studies have collectively identified genes that influence only ≈2% of blood pressure variability.4 Aside from the rare monogenic forms of hypertension and the less common, relatively well-defined secondary causes of hypertension, the fundamental mechanisms of hypertension continue to be elusive.
Because hypertension is a complex disease, identification and study of intermediate phenotypes characterizing genetic and environmental interactions in hypertensive subpopulations with specific disease characteristics might be expected to simplify the experimental approach. Hypertension phenotyping also might provide a more discrete basis for specific antihypertensive therapy than does the current trial-and-error approach. However, at present only a very limited number of hypertensive phenotypes …