Orthostatic hypotension is Associated with Higher Levels of Circulating Endostatin

The pathophysiology of orthostatic hypotension (OH), a common clinical condition, associated with adverse outcomes, is incompletely understood. We examined the relationship between OH and circulating endostatin, an endogenous angiogenesis inhibitor with antitumor effects proposed to be involved in blood pressure (BP) regulation. We compared endostatin levels in 146 patients with OH and 150 controls. A commercial chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin. Linear and multivariate logistic regressions were conducted to test the association between endostatin and OH. Endostatin levels were significantly higher in OH patients (59,024 ± 2513 pg/mL) versus controls (44,090 ± 1978 pg/mL, p<0.001). A positive linear correlation existed between endostatin and the magnitude of systolic BP decline upon standing (p<0.001). Using multivariate analysis, endostatin was associated with OH (adjusted odds ratio per 10% increase of endostatin in the whole study population = 1.264, 95%CI 1.141-1.402), regardless of age, sex, prevalent cancer, and cardiovascular disease, as well as traditional cardiovascular risk factors. Circulating endostatin is elevated in patients with orthostatic hypotension and may serve as a potential clinical marker of increased cardiovascular risk in patients with orthostatic hypotension. Our findings call for external validation. Further research is warranted to clarify the underlying pathophysiological mechanisms.