Orthostatic hypotension of unknown cause: Unanticipated association with elevated circulating N-terminal brain natriuretic peptide (NT-proBNP)

Background The pathophysiology of orthostatic hypotension (OH) is multifactorial, with the most frequent causes being adverse effects of cardioactive drugs. In 20%-40% of cases, the etiology is unknown. In recent reports, altered levels of endogenous neuropeptides have been observed in noncardiac syncope, but B-type natriuretic peptide (BNP) and its amino-terminal cleavage fragment (NT-proBNP) have not been studied. Objective The purpose of this study was to assess the possibility that BNP with its diuretic and vasorelaxant properties could contribute to OH. Methods This prospective observational study comprised 85 consecutive OH subjects (58 women, age 49 ± 23 years) referred to a tertiary-care syncope clinic. All patients had normal left ventricular systolic and diastolic function, and clinical and laboratory findings consistent with euvolemia or modest hypovolemia. In 45 of 85 individuals (53%), an OH cause was determined. Results Among the remaining 40 patients (21 women, age 57 ± 16 years) with OH of unknown cause, 6 of 40 (15%) exhibited unexpectedly elevated plasma NT-proBNP levels (14000, 5210, 2570, 7990, 3480, and 6680 pg/mL). In contrast, NT-proBNP values were normal (ie, <300 pg/mL) in the remaining 34 patients with OH of unknown cause and 45 patients with OH of known etiology. At 8 to 12 months of follow-up, volume repletion therapy requirements in patients with initial increased NT-proBNP diminished in conjunction with gradual fall of NT-proBNP concentrations. Conclusion In select patients, markedly elevated levels of BNP or NT-proBNP may be associated with and possibly contribute to symptomatic OH.