A rise in blood pressure (BP) on standing in young and middle-aged hypertensive adults or orthostatic hyperreactivity to standing is predictive of high risk of serious cardiovascular events, suggests a new Italian study reported in the journal Hypertension.

The study investigators enrolled 1207 young to middle-aged patients from the HARVEST study with untreated stage 1 hypertension defined as systolic BP 140-159 mm Hg or diastolic BP 90-100 mm Hg. They sought to examine the association between orthostatic hyperreactivity with major adverse cardiovascular events in this group of patients. Their ages ranged from 18 to 45 years with an average age of 33 years; 72% of the study subjects were males. Three BP readings were measured in a lying down position followed by three readings in the standing position with a gap of one minute during two separate visits. Hyperreactivity to standing was defined as the difference between standing and supine systolic BP. They were then categorized “as having a normal or exaggerated (top decile, lower limit > 6.5 mm Hg) systolic BP response to standing”.

Orthostatic hyperreactivity was noted in 120 participants. An average increase of 11.4 mmHg in systolic BP was observed in these patients; all increases in systolic BP in this group were greater than 6.5 mm Hg. On the other hand, the remaining participants showed an average fall of 3.8 mm Hg in the systolic BP upon standing.

The probability of hyperreactors being smokers at baseline was higher (32.1% vs 19.9%); they also had higher chances of having ambulatory hypertension (90.8% vs 76.4%). However, they tended to have lower supine systolic BP (140.5 mm Hg vs 146.0 mm Hg) as well as a better cholesterol profile with  lower total cholesterol levels (4.93 mmol/L vs 5.13 mmol/L) and higher HDL cholesterol levels (1.42 mmol/L vs 1.35 mmol/L). But they had similar levels of physical activity and also did not have a higher likelihood of a positive family history of cardiovascular events.

Urinary catecholamines were measured from 24-hour urinary samples in a subgroup of 630 subjects. The epinephrine/creatinine ratio was higher in the hyperreactors compared to those who did not show a rise in standing blood pressure; 118.4 nmol/mol vs 77.0 nmol/mol, respectively.

A total of 105 major adverse cardiovascular and renal events, which included acute coronary syndrome, stroke, heart failure,  peripheral vascular disease, CKD, atrial fibrillation, aortic aneurysms, were recorded during the follow-up of 17.2 years. The hyperreactors had twice the risk of developing a major cardiovascular event with a hazard of 1.97.

Orthostatic hypotension i.e., drop in BP on standing is a well-established cause of morbidity and mortality particularly in the elderly and has been shown to increase the incidence of myocardial infarction, stroke, heart failure. In hypertensive patients, it may make it difficult to control the high BP.

The present study has now shown that rise in systolic BP of more than 6.5 mm Hg on standing in young-to-middle-age hypertensive patients was associated with 2-folds increase in the risk of major adverse cardiovascular events (MACE). According to the authors, this orthostatic hyperreactivity was correlated with sympatho-adrenergic overrreactivity. This association was seen to persist even after adjusting for traditional risk factors and can be considered as predictor of adverse cardiovascular outcomes. Hence, measuring orthostatic BP has prognostic significance in addition to ambulatory BP.

Reference

1. Palatini P, et al. Blood pressure hyperreactivity to standing: a predictor of adverse outcome in young hypertensive patients. Hypertension. 2022 Mar 17;HYPERTENSIONAHA12118579. doi: 10.1161/HYPERTENSIONAHA.121.18579.