Orthostatic Hypotension: A Few Questions

A consensus statement defines orthostatic hypotension (OH) as a drop in BP of at least 20 mmHg systolic or 10 mmHg diastolic within 3 minutes of standing. But this definition leads to a few questions. 

Questions

What if orthostatic hypotension occurs after 3 minutes of standing?

Delayed orthostatic hypotension (DOH), by definition, occurs after 3 minutes of standing, although there is limited data on its incidence. In a recent 2023 study among nearly 500 community-dwelling adults (age, ≥70) at high risk for falling, OH occurred in 32% of people during the first 3 minutes after standing; DOH occurred in 16% (measured during the subsequent 3 minutes). During median follow-up of 9 months, 425 falls occurred among the participants. People with either OH or DOH were significantly more likely to fall than those without orthostasis (overall hazard ratios, 1.7), but those with DOH were at somewhat higher risk than those with OH.

In 2006, researchers found that, among 230 patients who had been referred for autonomic testing for various reasons, 50 had OH, 58 had DOH, and 122 had neither. In 2016, ten-year follow-up data of the 2006 study revealed that ten-year mortality was 64% (!) in patients with OH, 29% in patients with DOH, and 9% among 75 age- and sex-matched patients without OH or DOH from the original cohort. Interestingly, among 48 DOH patients with follow-up data, 26 progressed to OH, and 14 of the latter developed a synucleinopathy such as Parkinson disease. In contrast, synucleinopathies developed in none of the 22 DOH patients without progression. As such, this study suggests that, in some patients, DOH progresses to OH and can be an early manifestation of Parkinson disease or related disorders.

Does heart rate matter?

It’s important to remember that heart rate (HR) is not a part of the definition of OH. Physiologically, we expect the HR to increase when changing positions from supine to standing. Upon standing, blood pools in the legs and in the splanchnic circulation, leading to a decrease in venous return to the heart, thereby decreasing cardiac output and BP, and provoking a compensatory sympathetic reflex. Overall, in normal patients, this leads to a small fall in SBP (5-10 mmHg), a small increase in DBP (5-10 mmHg), and an increase in HR (10-25 bpm). 

  • The absence of an increase in HR is a useful clinical marker of neurogenic OH in the setting of autonomic failure; however, the presence of a HR increase does not exclude autonomic failure. 
  • An increase in HR >30 bpm in the absence of OH may suggest postural tachycardia syndrome (POTS), which usually does not include OH.

In patients with hypertension, should the presence of orthostatic hypotension affect treatment of hypertension?

A recent 2023 meta-analysis provides reassurance that OH should not deter us from adopting more-intensive BP management in patients with HTN. The meta-analysis included 9 trials consisting of over 29,000 participants (mean age, 69 years) followed for a median of 4 years. At baseline, 9% had OH. The researchers found that more-intensive BP goals or active treatment reduced risk for nonfatal CVD events or all-cause mortality regardless of the presence of OH. Of note, OH was independently associated with higher risks for CVD or all-cause mortality and for all-cause mortality alone.

What medications can induce orthostatic hypotension?

A 2021 systematic review and meta-analysis of 69 placebo-controlled RCTs reviewed the extent to which specific medications are associated with OH in adults. Compared with placebo, beta-blockers and TCAs were associated with a 6- to 7-fold increased odds of OH. Alpha-blockers, second-generation antipsychotics, centrally acting antihypertensives, and SGLT-2 inhibitors were associated with up to a 2-fold increased risk of OH, compared to placebo.

  • Beta-blockers induce OH through sympathetic inhibition decreasing heart rate and contractility, alongside combined independent vasodilatory effects
  • TCAs similarly exert their effects on postural BP through combined sympathetic inhibition and reduced vascular resistance

All the drugs associated with higher odds of OH share a common key mechanism of sympathetic inhibition causing cardioinhibitory effects. Of note, there was no difference in odds of OH with calcium channel blockers, ACE inhibitors, ARBs, or SSRIs, compared to placebo.

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