Autonomic Dysfunction Common in Early Parkinson's

June 9, 2017

Baseline data from STEADY-PD show 9% have significant orthostatic hypotension

VANCOUVER -- Orthostatic hypotension (OH) and autonomic instability is a common finding in a cohort of patients with early Parkinson's disease, researchers reported here.

In an analysis of baseline data from a randomized drug trial called STEADY-PD III, about 80% of participants had at least one home blood pressure measurement consistent with OH, Christopher Tarolli, MD, of the University of Rochester in New York, and colleagues reported during a late-breaking poster session at the Movement Disorder Society meeting here.

When focusing on those who had at least half of their readings in the OH range, the figure fell to 9% -- but that number is still concerning, Tarolli said.

"It's an extremely common finding to have at least one reading that met criteria for OH," Tarolli said in an interview at his poster. "The median values we saw look pretty stable. But there is a subset in early Parkinson's who have significant autonomic dysfunction."

He also cautioned that since this is such an early disease cohort, that it's possible this subset of patients with more significant autonomic dysfunction actually has another diagnosis like multiple systems atrophy.

STEADY-PD III is a phase III, double-blind, placebo-controlled trial of isradipine, an anti-hypertensive calcium-channel blocker, as a disease-modifying agent in Parkinson's disease. The old, generic drug has been shown in basic science, animal models, and in early clinical trials to hold benefit for Parkinson's disease.

The NIH-sponsored trial enrolled quickly, in less than a year -- ahead of its year-and-a-half recruitment deadline, researchers told MedPage Today at last year's MDS meeting.

Patients with Parkinson's often have autonomic instability such as decreased heart rate variability and orthostatic hypotension. Early orthostatic hypotension may be associated with more rapid motor decline in Parkinson's, but there are limited data from patients with new disease, the researchers said.

To get a better idea of autonomic dysfunction early in the disease, Tarolli and colleagues looked at baseline data collected during the STEADY-PD III trial. All patients wore a remote blood pressure monitor that wirelessly transmitted BP and heart rate data to a remote monitoring center.

They were asked to obtain sitting and standing BP and HR readings two minutes apart, twice a day for at least 7 days prior to study enrollment -- although monitoring continued during study drug titration as well.

OH was defined as a decrease in systolic BP by 20 mm Hg or higher, in diastolic BP by 10 mm Hg or higher, or an increase in HR by 20 bpm or more, from sitting to standing.

Data from 332 of the patients were analyzed for this study, and Tarolli noted that about 4% of readings were discarded because they were unlikely to be physiologically plausible, as assessed by a cardiologist. Patients' median age was 62, 32% were female, 92% were Caucasian, and all had their diagnosis of Parkinson's within the past year. 

Tarolli said the overall median values were stable, with mean sitting systolic and diastolic BP readings of 128 mm Hg and 77 mm Hg; mean standing systolic and diastolic BP readings were 126 mm Hg and 80 mm Hg; and mean sitting HR was 70 bpm and standing HR was 77 bpm.

The proportion of patients with at least one OH reading was high (80.4%), and the total unique recordings meeting OH criteria occurred in 16.3%.

Tarolli cautioned that it's unclear if this group represents a subset of patients with both Parkinson's and prominent autonomic dysfunction, or if an alternative diagnosis such as multiple system atrophy should beconsidered. Further evaluation in the STEADY-PD III trial will help to better characterize the natural history of autonomic dysfunction in Parkinson's and further define the utility of OH as a vasomotor biomarker of Parkinson's progression, he said.

"What we really want to do next," Tarolli said, "is look at this group and say, what are the predictors as to what happens with these patients. Do they have faster motor progression? Or can we do something to treat these patients, like prescribe droxidopa? The other question is, do these patients have another diagnosis, like multiple system atrophy, that just isn't manifest at this point? These are baseline data, and we haven't yet looked at what happens once they start their calcium channel blocker."

STEADY-PD III is funded by the National Institute of Neurologic Disorders and Stroke.

http://www.medpagetoday.com/MeetingCoverage/MDS/65910