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

Abstract

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.

Keywords: Brain natriuretic peptide; Natriuretic peptide; Orthostatic hypotension.