Sit-to-Stand BP Spike Tied to MACE in Younger Hypertensives

A sudden drop in blood pressure when standing is a common and concerning problem in elderly hypertensive people. Now, research suggests a large BP swing in the opposite direction on standing may be equally concerning in younger hypertensive people.

Young and middle-aged adults with a systolic BP response to standing greater than 6.5 mm Hg had almost double the risk of major adverse cardiovascular events (MACE) during follow-up compared with other participants.

An exaggerated BP response remained an independent predictor of MACE, even after adjusting for traditional risk factors, including 24-hour BP (hazard ratio [HR], 1.94; 95% CI, 1.10 to 3.44), the study showed.

“The clinical implication is important because now doctors measure blood pressure in young people in the upright posture, but what we say is it must be measured also while standing,” said Paolo Palatini, MD, a professor of internal medicine at the University of Padova, Italy, who led the study.

Previous studies have found that an exaggerated BP response to standing is a predictor of future hypertension, CV events, and mortality particularly in older patients, but few prognostic data exist in those who are young to middle age, he noted.

The study, published today in Hypertension, included 1207 participants ages 18 to 45 years with untreated stage 1 hypertension (systolic BP 140 to 159 mm Hg or diastolic BP 90 to 100 mm Hg) in the prospective multicenter HARVEST study that began in Italy in 1990. The average age at enrollment was 33 years.

BP was measured at two visits 2 weeks apart, with each visit including three supine measurements taken after the patient had lain down for a minimum of 5 minutes, followed by three standing measurements taken 1 minute apart.

Based on the average of standing-lying BP differences during the two visits, participants were then classified as having a normal or exaggerated (top decile, lower limit > 6.5 mm Hg) systolic BP response to standing.

The 120 participants classified as “hyperreactors” averaged an 11.4 mm Hg systolic BP increase upon standing, whereas the rest of the participants averaged a 3.8 mm Hg fall in systolic BP upon standing.

At their initial visit, hyperreactors were more likely to be smokers (32.1% vs 19.9%) and coffee drinkers (81.7% vs 73%) and to have ambulatory hypertension (90.8% vs 76.4%).

They were, however, no more likely to have a family history of cardiovascular events and had a lower supine systolic BP (140.5 mm Hg vs 146.0 mm Hg), lower total cholesterol (4.93 mmol/L vs 5.13 mmol/L), and higher HDL cholesterol (1.42 mmol/L vs 1.35 mmol/L).

Age, sex, and body mass index were similar between the two groups, as was BP variability, nocturnal BP dip, and the frequency of extreme dippers. Participants with a normal systolic BP response were more likely to be treated for hypertension during follow-up (81.7% vs 69.7%; P = .003).

In 630 participants who had catecholamines measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in hyperreactors than normal responders (118.4 nmol/mol vs 77.0 nmol/mol; P = .005).

During a median follow-up of 17.3 years, there were 105 major cardiovascular events, broadly defined to include acute coronary syndromes (48), any stroke (13), heart failure requiring hospitalization (3), aortic aneurysms (3), peripheral vascular disease (6), chronic kidney disease (12), and permanent atrial fibrillation (20).

The near doubling of MACE risk among hyperreactors remained when atrial fibrillation was excluded and when 24-hour ambulatory systolic BP was included in the model, the author reported.

The results are in line with previous studies indicating that hyperreactors to standing have normal sympathetic activity at rest but an increased sympathetic response to stressors, observed Palatini and colleagues. This neurohumoral overshoot seems to be peculiar to young adults, whereas vascular stiffness seems to be the driving mechanism of orthostatic hypertension in older adults.

If a young person’s BP spikes upon standing, “then you have to treat them according to the average of the lying and the standing pressure,” Palatini said. “In these people, blood pressure should be treated earlier than in the past.”

“The study is important because it identified a new marker for hypertension that is easily evaluated in clinical practice,” Nieca Goldberg, MD, medical director of the Atria Institute and an associate professor of medicine at New York University Grossman School of Medicine, both in New York City, commented to Medscape via email.

She noted that standing blood pressures are usually not taken as part of a medical visit and, in fact, seated blood pressures are often taken incorrectly while the patient is seated on the exam table rather than with their feet on the floor and using the proper cuff size.

“By incorporating standing BP, we will improve our diagnosis for hypertension and with interventions, such as diet and exercise, salt reduction, and medication when indicated, lower risk for heart attack, stroke, heart failure, [and] kidney and eye disease,” said Goldberg, who is also a spokesperson for the American Heart Association.

“The biggest barrier is that office visits are limited to 15 minutes and not enough time is spent on the vital signs,” she noted. “We need changes to the healthcare system that value our ability to diagnose BP and take the time to counsel patients and explain treatment options.”

Limitations of the present study are that 72.7% of participants were men and all were white, Palatini said. Future work is also needed to create a uniform definition of BP hyperreactivity to standing, possibly based on risk estimates, for inclusion in future hypertension guidelines.

The study was funded by the Association 18 Maggio 1370 in Italy. The authors have disclosed no relevant financial relationships. Goldberg reported being a spokesperson for the American Heart Association.

Hypertension. Published online March 17, 2022. Abstract

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