How can we better manage hypotensive syndromes in older adults?

KEYWORDS:

• Delayed orthostatic hypotension
• postprandial hypotension
• vasovagal syndrome
• Orthostatic hypotension
• carotid sinus syndrome

1. Introduction

Hypotensive syndromes are low blood pressure (BP) conditions seen with postural changes, such as standing and head turning, as well as in the supine position after meals. The most common hypotensive syndromes seen in older adults (65 years and older) are orthostatic hypotension (OH), postprandial hypotension (PPH), hypotension with carotid sinus syndrome (CSS), and vasovagal syncope type 1(VVS type 1). Prevalence of these conditions (OH 5–50%, PPH 38–69%, CSS 30–40%, VVS type 1–20%) varies with age, different comorbid conditions (diabetes, hypertension, heart failure, Parkinson’s), and different living situations. The elderly are prone to these hypotensive syndromes, mainly because of cardiovascular, hemodynamic, and autonomic changes seen with aging [1,2]. In older adults, there are many challenges with the diagnosis and management of hypotensive syndromes. Dizziness, syncope, and falls are common presentations of these conditions. The evolving evidence suggests that these hypotensive syndromes are risk factors for different cardiovascular conditions.

1.1. Orthostatic or postural hypotension

The classical OH is diagnosed based on the 2011 consensus committee definition [3]. It is defined as “a sustained reduction of systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of 10 mm Hg within 3 min of standing or head-up tilt to at least 60° on a tilt table” [3]. Heart rate changes with posture should be included in the definition as it gives information about volume loss and autonomic dysfunction. A heart rate increase of at least 0.5 beats/min for each 1 mm Hg fall in systolic blood pressure is sensitive and specific to diagnose non-neurogenic OH [4]. Delayed OH (drop after 3 minutes and up to 10 minutes) are also missed with that definition.

1.2. Management

A stepwise approach with non-pharmacological and then pharmacological management is done for all hypotensive syndromes. In asymptomatic patients, non – pharmacological management alone can improve the blood pressure to some extent with substantial clinical improvement. Some of the non-pharmacological measures, including intermittent fluid bolus drinking, standing slowly from supine position, and leg crossing, have been shown in the literature to reduce the postural drop in blood pressure. If conservative or nonpharmacological measures fail, pharmacotherapy with midodrine, droxidopa, fludrocortisone, pyridostigmine, atomoxetine, erythropoietin, and caffeine can help to ameliorate symptoms, even though the evidence is weaker for most of the medications except midodrine and droxidopa [1]. Pharmacological therapy should be considered immediately by health-care professionals along with conservative measures in cases of severe OH. The current evidence for their use in older adults, especially those with frailty and multimorbid individuals, is not of high quality, and more research is needed in the future.

Treatment of orthostatic hypotension should be geared to the patient’s symptoms and their impact on daily function rather than a target blood pressure. The main goal is symptom relief in treating OH, not bringing it to a target BP value, such as the drop of systolic blood pressure (SBP) <20 or diastolic blood pressure (DBP) <10 mm of Hg. Discontinuation of medications by changing, stopping, or decreasing the dose of the offending medications that cause hypotensive syndromes is the first step in medical management. Adequate control of hypertension is also important in reducing the OH episodes. The Epicardian study pointed out that among older adults with adequate control of hypertension, the prevalence of OH is low [5]. At the same time, overtreatment of hypertension, especially in the frail elderly, can also result in hypotensive syndromes.

Two main approaches are used in the management of OH: 1) increasing blood volume, and 2) increasing peripheral vascular resistance. Midodrine and droxidopa possess the most evidence with respect to increasing blood pressure and alleviating symptoms. Emerging evidence of low-dose atomoxetine is also promising, especially in those with central autonomic failure. While other medical treatment options have failed, atomoxetine may be a viable alternative. Recent evidence from a systematic review has shown that caffeine therapy may be helpful in neurogenic OH [6].

The importance of looking for supine hypertension in patients who are on OH medications is to prevent the end organ damage secondary to it. Supine hypertension (defined as supine systolic blood pressure ≥140 mmHg) is seen with neurogenic OH and with medications used for OH, such as midodrine, fludrocortisone, atomoxetine, and droxidopa [7]. Managing supine hypertension with OH is by sleeping with the head of the bed raised to 30–45 degrees, as well as by using medications like pyridostigmine which has less effect on supine hypertension. Clinical trials showing the effectiveness of sleeping with the head of the bed raised intervention are variable, even though some observational studies have shown some benefits.

When OH occurs with hypertension, it can cause treatment dilemma in clinicians. Four steps are important in the management of this combination situation. Step 1: if multiple antihypertensives medications are causing OH, consider stopping or tapering one medication at a time. Step 2: is adequate control of BP. In the Epicardian study of 2700 elderly subjects, the incidence of OH with adequate control of blood pressure was low [5]. Even the recent SPRINT trial showed that patients with symptomless or asymptomatic OH during hypertension treatment should not be viewed as a reason to down-titrate BP therapy even in the setting of a lower BP goal. This trial studied only early OH (at 1 min), not classical or late OH [8], Step 3: using the right type of antihypertensive medications. A prospective study of older adults with hypertension had demonstrated an improvement in postural blood pressure changes with certain antihypertensive medications. Vasodilators (alpha-adrenoceptor antagonists), diuretics, and certain short-acting calcium channel blockers can exacerbate postural blood pressure changes, whereas beta-blockers with intrinsic sympathomimetic activity, ACE inhibitors, and angiotensin-receptor antagonists are less likely to worsen postural changes [9]. Slavachevsky et al. in their cross-over study found that enalapril reduces the episodes of OH when compared to long-acting nifedipine, even though they had equal potency in reducing supine blood pressure levels [10]. Overtreatment of hypertension, especially in the frail elderly, can also result in OH. Step 4: check for medications used for other conditions that can also contribute to OH.

2. Postprandial Hypotension (PPH)

There is a significant drop in blood pressure after eating. It is commonly defined as a supine systolic blood pressure (SBP) drop of 20 mmHg or a SBP decrease to less than 90 mmHg when the pre-prandial SBP is greater than 100 mmHg, within 2 h of eating [11]. A recent study showed asymptomatic PPH with diabetes mellitus (DM) subjects [12]. PPH is common among older adults as well as patients with DM, Parkinson's disease, and other chronic diseases. Caffeine, Alpha-Glucosidase Inhibitors, Dipeptidyl peptidase-4 (DPP-4) inhibitors are found to be useful in the treatment of PPH [13–15]. Even though the evidence is evolving, more clinical trials are needed specifically to document their effects over prolonged period and also to prevent the complications of PPH.

3. Sinus Syndrome (CSS) and Vasovagal Syncope (VVS)

Head turning is an important trigger for hypotension in the elderly with carotid sinus hypersensitivity (CSH). The CSS syndrome is rare and it occurs approximately in 1% of patients with documented syncope, mainly in older men. Carotid sinus massage is used to confirm CSH. In addition to hydration and salt tablets, adding fludrocortisone or midodrine can be considered in the management [1]. The treatment of the vasodepressive type of CSS is difficult.

Vasovagal syncope is another common cause of hypotension in older adults. It affects 20% of the elderly, during their lifetime. VVS type 1 is a condition where there is loss of consciousness/syncope due to decreased perfusion to the brain, with blood pressure drop [2]. In type 1 VVS, blood pressure falls before the heart rate, and the heart rate does not fall below 40 beats per minute. Treatment of VVS is avoidance of triggers, and in very resistant cases, fludrocortisone or midodrine can be tried [1].

4. Conclusions

Hypotensive syndromes should be considered in any elderly patient with falls, syncope, dizziness, or cardiac or cerebral ischemic symptoms. The evolving evidence points out that it is a cardiovascular risk factor. Both non-pharmacological and medication management can be considered in subjects with these syndromes. Nonpharmacologic treatment is always the first step in the management of these conditions. Most of the current medications used for hypotensive syndromes were evaluated in fewer clinical trials, and there is a need for high-quality large, randomized clinical studies for these medications. The predominant outcome measure used in these studies is related to BP values. Only few studies have used symptom or function improvement as an outcome measure. Long-term follow-up studies are lacking with the medications used to treat hypotensive syndromes. Future clinical trials are needed to better manage these conditions.

Declaration of interest

K Alagiakrishnan receives royalties for book on Hypotensive Syndromes in Geriatric Patients, published by Springer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A peer reviewer on this manuscript has previously consulted for Lundbeck. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.