Background
Orthostatic hypotension (OH) is defined as a sustained reduction in systolic blood pressure (BP) of ≥20 mmHg or in diastolic BP of ≥10 mmHg upon standing [
1]. OH generally results from 3 common etiologies: (1) medications such as antidepressants or antihypertensive agents, (2) non-neurologic conditions such as hypovolemia or cardiovascular disorders causing cardiac failure, or (3) impaired vasoconstriction due to dysfunction of the autonomic nervous system (also referred to as neurogenic OH [nOH]). The neurogenic form of OH is commonly associated with neurodegenerative disorders that affect the central or peripheral autonomic nervous system, such as Parkinson disease (PD), multiple system atrophy (MSA), and pure autonomic failure, or it may be secondary to conditions such as diabetic peripheral neuropathy [
1‐
6]. Although differential diagnosis is often challenging, nOH can be distinguished from non-neurogenic forms of OH, such as medication effects and volume depletion, through autonomic testing [
5,
7]. Common symptoms of nOH include postural lightheadedness or dizziness, presyncope, falls, and syncope [
1,
5]. Additional symptoms can include visual disturbances, fatigue, generalized weakness, cognitive dysfunction, neck pain or discomfort in the suboccipital and paracervical region (i.e., in a “coat hanger” configuration), and orthostatic dyspnea [
1,
5].
Neurogenic OH can increase the risk of falls, particularly among older patients [
8,
9]. However, only limited information regarding the impact of nOH on quality of life among patients and caregivers has been published [
10‐
12]. We designed a survey to gain a better understanding of the following areas: (1) scope of symptoms and burden of disease among patients with nOH, (2) effect of nOH symptoms on lives of patients from the perspective of caregivers, and (3) insights on the patient and caregiver journey from diagnosis to symptom management.
Methods
A survey designed by the authors was conducted online by Harris Poll on behalf of Lundbeck between August 26, 2016, and October 3, 2016. Respondents for the survey included individuals who agreed to participate in Harris Poll online surveys or who are members of certain advocacy organizations (American Parkinson Disease Association, Davis Phinney Foundation, Michael J. Fox Foundation, MSA Coalition, National Parkinson Foundation, and Parkinson’s Disease Foundation) who also met eligibility criteria and agreed to participate in the current survey. For research in which participants are intended to remain anonymous, Harris Poll uses tools and methods to ensure that there is no reasonable possibility of identifying an individual participant in the reports created (e.g., individual responses collected are combined to produce “aggregated” reports). Eligible patient participants were US residents aged ≥18 years who self-selected a diagnosis of PD, MSA, or pure autonomic failure based on a diagnosis received from their treating physicians. Individuals also met ≥1 of the following criteria: (1) received a formal diagnosis of OH or nOH, (2) were informed by a health care provider that their symptoms are caused by low blood pressure or a sudden drop in blood pressure upon standing, or (3) experience the following upon sitting up, standing up, standing for long periods of time, or with a change in position: 2 or more listed OH/nOH symptoms at least every time, daily, weekly, monthly, or a few times a year and at least 1 of the following symptoms: dizziness or lightheadedness, feeling faint, or fainting. Because of the underlying neurologic diagnosis criteria, eligible patient responders were presumed to have "nOH" for the purposes of this study, even if they did not receive a formal diagnosis. Eligible caregiver participants cared for patients who met these criteria but were not necessarily linked to any patient responders (i.e., patient and caregiver responses to surveys were not paired in the analysis of survey results). The survey included questions regarding the frequency and impact of nOH symptoms, management, and communication with health care providers regarding symptoms (see Additional File
1 for the full list of survey questions). Descriptive statistics are reported. The study was performed in accordance with ethical standards (e.g., 1964 Helsinki Declaration and later amendments or the comparable). As an anonymous survey, the study was exempt from ethics approval based on Code of Federal Regulations Title 45, Part 46, Subpart A, Section 46.101b, Category 2 criteria.
Discussion
The results of this patient and caregiver survey strongly support the premise that nOH symptoms have a substantial negative impact on patient function and quality of life. Data from both patients and caregivers suggest that nOH symptoms are associated with impaired mobility, such as difficulty with positional changes, increased frequency of falls, and decreased ability to maintain activities of daily life. Despite the high level of symptom burden and longstanding symptoms of nOH (e.g., 48% of patients with symptoms for ≥5 years), the majority of respondents did not report having a formal diagnosis of OH or nOH. Stratification of patients based on their duration of symptoms (< 10 years or ≥ 10 years) did not increase the likelihood of a formal diagnosis of OH or nOH. Further, there were minimal differences on the impact of nOH symptoms between these 2 subgroups of patients.
In this survey, the majorities of patients and caregivers did not report that nOH symptoms occurred more frequently or with greater severity first thing in the morning, after meals, or when getting out of bed during the night. Rather, more respondents indicated that nOH symptoms were more likely to occur or be more severe throughout the day. These results are contrary to the general clinical understanding that nOH symptoms are often worse in the morning and can be exacerbated after eating [
13]. The lack of a distinct daily pattern for the frequency and severity of nOH symptoms emphasizes that symptoms do not always occur at a specific time or event (e.g., morning, after a meal) and is an important point of awareness for clinicians in the evaluation of patients for nOH.
This survey also revealed factors that may contribute to the relatively low rate of formal nOH diagnosis. The majority of patients reported hiding or minimizing their nOH symptoms. Further, patients indicated that they were uncomfortable discussing the impact of symptoms with health care providers and did not discuss the impact of their symptoms unless they were severe. Finally, some patients and caregivers reported that symptoms had to be discussed several times in order to draw them to the attention of the treating provider.
Reticence of patients to share symptoms with caregivers and health care providers has been observed with depression, pain, and other chronic conditions [
14‐
16]. Patients may hide or minimize their nOH symptoms because they view symptoms as a sign of weakness or because they are embarrassed, in denial, do not want to be a “bother” to others, or other reasons [
14‐
16]. Of note, among patients in the current survey with a diagnosis of nOH, many (70%) perceived that their symptoms had improved after receiving the diagnosis. However, a substantial proportion of patients were not counseled on how to manage nOH, were not prescribed medication for nOH symptoms, and felt they did not have adequate control of their nOH symptoms.
Inadequate management of nOH symptoms appears to be a cause of distress for many patients. Nonpharmaceutical treatment recommendations for nOH include ensuring adequate salt and fluid intake, avoiding rapid postural changes, adjusting medications, and sleeping with the head of the bed elevated [
5,
17]. Patients and caregivers indicated that such nonpharmaceutical interventions were commonly recommended and frequently helpful. However, a substantial proportion of respondents indicated that they did not achieve symptomatic relief, and only a third of patients indicated that they received a prescription for a medication to treat symptoms of nOH. These results provide greater understanding of the disease burden of nOH. Previously, a negative impact of nOH symptoms was found in a single-center study of 141 inpatients with PD, in which 53% of patients reported that orthostatic dizziness had “a lot” or “very much” impact on daily life [
11]. A 2-center study of patients with PD has suggested that both symptomatic (
n = 14) and asymptomatic (
n = 23) nOH were associated with worse measures of functionality and quality of life compared with patients with PD but without nOH (
n = 84) [
18]. Our study adds to the evidence by inclusion of data from a larger cohort of patients (
N = 363) who experience nOH symptoms due to a variety of underlying conditions, including MSA and pure autonomic failure (however, most of the cohort reported a PD diagnosis). Further, to the best of our knowledge, our study is the first to investigate the impact of nOH from both the patient and caregiver perspective. nOH is one of the many manifestations of autonomic dysfunction, and patients may also have their quality of life affected by other symptoms, including gastrointestinal dysfunction (e.g., dysphagia, constipation), bladder dysfunction (e.g., urinary urgency, incontinence), sexual dysfunction (e.g., erectile dysfunction), cardiovascular dysfunction (e.g., hypertension, supine hypertension), and thermoregulation and sweating abnormalities (e.g., dyshidrosis) [
19,
20].
Survey methodology has inherent limitations, such as selection bias and recall bias. Patient and caregiver responses were not paired; therefore, it is not possible to draw conclusions regarding consistency of responses between patients and their caregivers. Pairing each patient’s response with their caregiver’s response for each question should be considered in future studies. Many participants (64% of patients, 84% of caregivers) did not have a formal diagnosis of OH or nOH; therefore, the survey may underestimate the burden of symptoms of those formally diagnosed with OH or nOH.