Clinical Geriatrics

Lewy body disorders (LBDs) represent a spectrum of neurodegenerative disease, of which Parkinson’s disease (PD) with dementia (PDD) and dementia with Lewy bodies (DLB) are prevalent phenotypes.¹ Patients with PD and DLB often develop autonomic dysfunction. Although not a movement disorder like PD nor associated with dementia, pure autonomic failure (PAF) is increasingly recognized as another phenotype of LBD. PAF shares many features with PD and DLB,² particularly urinary, gastrointestinal, and cardiovascular dysfunction.^3,4 Postmortem studies of patients with PAF have observed Lewy bodies in the sympathetic ganglia, but not in the cerebellum, and an accumulation of alfa-synuclein,³ which also occurs in patients with DLB and PD.⁵ In 2011, Goldstein and associates⁶ proposed a figure to explain the spectrum and interaction of these disorders.

In part I of this two-part series (http://bit.ly/LBDpart1), we reviewed the proposed origin of cardiovascular autonomic dysfunction in patients with LBD. We also reviewed the symptoms and management of orthostatic hypotension (OH), one of the most significant manifestations of cardiovascular autonomic dysfunction in this patient population. In part II, we examine other important indicators of autonomic failure of the cardiovascular system in patients with LBD, including supine hypertension, postprandial hypotension, carotid sinus syndrome, and rhythm abnormalities. We discuss how to evaluate patients for these cardiovascular phenomena and review management strategies. 

Hypertension

Although LBDs are more often associated with hypotension, patients with an LBD may experience any of several types of hypertension (Table 1[click thumbnail for full view]). The most common are general hypertension, defined as blood pressure ≥140/90 mm Hg; nocturnal hypertension, which is blood pressure ≥120/70 mm Hg during sleep or a failure of mean arterial pressure to decrease by ≥10% during sleep; and supine hypertension, defined as blood pressure ≥140/90 mm Hg when reclining.⁷ Anecdotal reports suggest that some patients with PAF can even experience exercise-induced hypertension, although this phenomenon appears to be rare.³ Decisions regarding the management of these hypertensive disorders depends on the severity of the condition and the individual patient.

Supine Hypertension

Supine hypertension can be as severe as essential hypertension⁸ and is increasingly being recognized as a separate clinical disease process in patients with PD and DLB that requires management.^7-9 The reported prevalence of supine hypertension among patients with autonomic failure is 50%,^7,10 and it is especially prevalent in those with OH.⁸

When supine hypertension occurs during sleep, it is sometimes referred to as nocturnal hypertension. Whereas supine hypertension can occur any time a patient is laying flat, nocturnal hypertension refers specifically to the failure of mean arterial blood pressure to decrease by ≥10% as part of the normal nocturnal circadian rhythm.¹¹ Nocturnal hypertension is thought to increase the risk of nocturnal natriuresis (sodium loss induced by elevated arterial pressure), contributing to volume loss and a greater likelihood of morning OH.⁷ Supine hypertension and nocturnal hypertension are typically diagnosed using a 24-hour, ambulatory blood pressure monitor.⁷

Although the mechanism of supine hypertension in patients with an LBD is not fully understood, it has been linked to dysfunction in the cardiovagal baroreflex (ie, decreased baroreflex gain), which regulates beat-to-beat arterial blood pressure.¹² Supine hypertension may also involve pressor mechanisms independent of the sympathetic nervous system.⁸ Certain medications used to treat OH have been reported to induce supine hypertension in patients and subsequently increase their risk of cardiovascular disease.

The literature is conflicted regarding the impact of supine hypertension on a patient’s health and how to manage it, especially in the setting of concomitant OH.⁹ The theoretical goal of treating supine hypertension is to decrease blood pressure levels, thus preventing the likelihood of end-organ damage and worsening of OH through pressure natriuresis. Due to the serious risks of prolonged hypertension, however, some have recommended that management of supine hypertension should be aggressive and take precedence over managing OH.⁷ The counterargument is that failing to treat OH aggressively places patients with an LBD at immediate risk of severe injury (eg, hip and other fractures) due to falls.¹³

Nonpharmacological therapies should be considered as first-line management for patients with supine hypertension, along with educating patients and any caregivers on the condition, when possible. Options include elevating the head of the bed during sleep or while reclining, decreasing fluid intake before bedtime, and removing compression stockings prior to sleep.

A handful of pharmacological therapies for supine hypertension have been discussed in the literature, such as transdermal nitroglycerine, short-acting calcium channel blockers, and clonidine.⁷ None of these medications has been studied specifically in the treatment of supine hypertension in patients with PD or DLB and autonomic failure, and their appropriateness as therapy is theoretical. The choice of medication will likely depend on whether the patient is also experiencing OH. When considering pharmacological management of supine hypertension, clinicians may first wish to read some of the in-depth reviews available on this subject.^7,8

Postprandial Hypotension

PPH occurs in up to 60% of patients with PD and DLB. This phenomena is defined as a >20 mm Hg drop in systolic blood pressure or a symptomatic decrease in blood pressure that occurs within 2 hours of eating. Like supine hypertension, PPH is frequently associated with OH and can be a severe problem, greatly increasing mortality risk in LBD patients who are >65 years of age.^7,14-16 PPH is also thought to worsen parkinsonian symptoms after meals.^7,16

PPH may cause syncope or orthostatic intolerance (near syncope) and is thought to result from increased vasodilation in the splanchnic circulation upon consumption of large or carbohydrate-dense meals.^13,16,17 Various strategies aimed at preventing vascular dilation have been proposed for managing PPH in this patient population.^7,16-18 Nonpharmacological management strategies include eating smaller meals and decreasing overall carbohydrate consumption.

Pharmacological management strategies discussed in the literature include caffeine and octreotide. Caffeine is an adenosine receptor blocker, and it has been suggested that taking 250 mg (the equivalent of approximately 2 cups of coffee) two to three times daily 30 minutes after eating, may reduce the risk of vascular dilation.^17,19 Octreotide—a somatostatin analog and a direct vasoconstrictor—has been recommended at a total daily dose of 25 to 200 µg per day, administered subcutaneously every 8 hours.^19,20 This drug is extremely expensive, however, and poorly tolerated, with an adverse effects profile that includes nausea, abdominal cramping, and diarrhea.

Carotid Sinus Syndrome

Carotid sinus syndrome (CSS) falls under the umbrella term of neurocardiovascular instability (NCVI), which encompasses OH and vasovagal syndrome. Three variants of carotid sinus syndrome exist (Table 2 [click thumbnail for full view]): cardioinhibitory, diagnosed when cardioinhibition (asystole) lasts ≥3 seconds; vasodepressive, categorized as a ≥50 mm Hg drop in systolic blood pressure during carotid sinus stimulation; and a mixed type that is cardioinhibitory and vasodepressive.^21-26 CSS affects nearly 20% of older adults²⁷ and is more prevalent in men.²⁹ In up to 20% of older adults, CSS causes cardiovascular-related syncope^21-23,29 and is thought to be an underdiagnosed cause of syncope and falls. Up to 30% of people who test positive for CSS are asymptomatic, however.²⁸

Approximately 40% of patients with DLB and PD are thought to have CSS.^21,30 In cases where a CSS-related drop in blood pressure would normally not be sufficient to cause syncope, patients with an LBD are more susceptible to syncope and falling due to the combined effects of their various comorbidities (eg, OH, postural sway/instability, vision problems, and core muscle weakness).

In persons with CSS, carotid sinus stimuli often trigger a bradyarrhythmic response, mediated by the vagus nerve. Even mild neck stimulation can precipitate bradycardia, a sudden drop in blood pressure, and dizziness.²⁸ Response to carotid sinus stimuli is even further exaggerated in patients with DLB.²⁷

Diagnosis of CSS is generally made by massaging the anterior margin of the sternocleidomastoid muscle—which essentially runs from the base of the skull, down and across the side of the neck, to the clavicle—for at least one complete cardiac cycle (approximately 10-15 seconds), waiting 1 to 2 minutes, and repeating the process on the other side. For each side, patients should be evaluated while supine and again in an upright position.^31,32 Response is generally measured using a continuous electrocardiogram (ECG) and a blood pressure monitor, but a beat-to-beat blood pressure monitor or intra-arterial monitor can also be used. Before the procedure, patients suspected of having carotid artery disease should undergo ultrasonography to  evaluate for critical carotid stenosis.²⁴

Acetylcholinesterase (AChE) inhibitor use may worsen bradyarrhythmic response in patients with CSS and may unmask undiagnosed CSS in patients with PD and DLB.²⁷ Patients with an LBD should therefore be screened for CSS before beginning AChE-inhibitor therapy.²⁴

No therapy has been proven to be effective in managing CSS. Dual-chamber cardiac pacing has been used to treat cardioinhibitory CSS, but has not been found to reduce a patient’s risk of falling.³² The literature includes peripheral discussions of pharmacological therapy for CSS, and a few case reports describe the use of selective serotonin reuptake inhibitor in patients with CSS,^33,34 but no one has made any specific recommendations for management.²⁵