Treatment of Supine Hypertension in Autonomic Failure
Status:
Completed
Trial end date:
2017-01-01
Target enrollment:
Participant gender:
Summary
Supine hypertension is a common problem that affects at least 50% of patients with primary
autonomic failure. Supine hypertension can be severe, and complicates the treatment of
orthostatic hypotension. Drugs used for the treatment of orthostatic hypotension (eg,
fludrocortisone and pressor agents), worsen supine hypertension. High blood pressure may also
cause target organ damage in this group of patients. The pathophysiologic mechanisms causing
supine hypertension in patients with autonomic failure have not been defined.
In a study, we, the investigators at Vanderbilt University, examined 64 patients with AF, 29
with pure autonomic failure (PAF) and 35 with multiple system atrophy (MSA). 66% of patients
had supine systolic (systolic blood pressure [SBP] > 150 mmHg) or diastolic (diastolic blood
pressure [DBP] > 90 mmHg) hypertension (average blood pressure [BP]: 179 ± 5/89 ± 3 mmHg in
21 PAF and 175 ± 5/92 ± 3 mmHg in 21 MSA patients). Plasma norepinephrine (92 ± 15 pg/mL) and
plasma renin activity (0.3 ± 0.05 ng/mL per hour) were very low in a subset of patients with
AF and supine hypertension. (Shannon et al., 1997).
Our group has showed that a residual sympathetic function contributes to supine hypertension
in patients with severe autonomic failure and that this effect is more prominent in patients
with MSA than in those with PAF (Shannon et al., 2000). MSA patients had a marked depressor
response to low infusion rates of trimethaphan, a ganglionic blocker; the response in PAF
patients was more variable. At 1 mg/min, trimethaphan decreased supine SBP by 67 +/- 8 and 12
+/- 6 mmHg in MSA and PAF patients, respectively (P < 0.0001). MSA patients with supine
hypertension also had greater SBP response to oral yohimbine, a central alpha2 receptor
blocker, than PAF patients. Plasma norepinephrine decreased in both groups, but heart rate
did not change in either group. This result suggests that residual sympathetic activity
drives supine hypertension in MSA; in contrast, supine hypertension in PAF.
It is hoped that from this study will emerge a complete picture of the supine hypertension of
autonomic failure. Understanding the mechanism of this paradoxical hypertension in the
setting of profound loss of sympathetic function will improve our approach to the treatment
of hypertension in autonomic failure, and it could also contribute to our understanding of
hypertension in general.
Phase:
Phase 1
Details
Lead Sponsor:
Vanderbilt University Vanderbilt University Medical Center