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Orthostatic hypertension in younger hypertensives a predictor of adverse outcomes

Reuters Health - 28/03/2022 -Young to middle-age adults with Stage 1 hypertension whose systolic blood pressure rises with standing are at increased risk for adverse cardiovascular and renal events over the long term, researchers say.

Early pharmacologic intervention may be appropriate for young hypertensive patients with a hyperreactive BP response to standing, according to their report in Hypertension.

The findings are drawn from the longitudinal HARVEST study, in which 1,207 subjects ages 18 to 45 (mean age, 33; 72% male) were identified with untreated Stage 1 hypertension (systolic BP 140-159 mmHg and diastolic BP 90-99 mmHg).

At the start, study participants underwent three sets of supine and standing orthostatic BP measurements on two occasions separated by two weeks, in addition to 24 hour ambulatory BP monitoring. Participants were then followed with office BP measurements at regular intervals; if BP remained above guideline limits despite nonpharmacological interventions, antihypertensive drugs were initiated.

At baseline, the mean office supine BP was 145.5/93.5; the mean standing BP was 143.0/98.2 mmHg. The lower limit of the upper decile of systolic hyperreactivity orthostatic hypertension was 6.5 mmHg, with no significant changes in diastolic BP, according to Dr. Paolo Palatini of Studium Patavinum and Department of Medicine, Padova, Italy and colleagues.

Mean supine systolic BP was higher in the normoreactive group (146.0 mmHg, versus 140.5 mmHg in hyperreactors), with no significant difference in resting diastolic BP. As these patients had higher baseline BP levels, they were more likely to be treated for hypertension (81.7% vs 69.7%).

Upon standing, normoreactive patients had a mean 3.8 mmHg rise in systolic BP, compared to a mean rise of 11.4 mmHg in the hyperreactors. The difference in orthostatic diastolic BP changes was <3 mmHg, with increases in both groups. Orthostatic heart rate increases were also similar (5.7 versus 6.7 BPM in normoreactors and hyperreactors, respectively).

Ambulatory 24 hour BP monitoring showed higher mean daytime and nighttime systolic BP in hyperreactors (90.8%, versus 76.4% in nonreactors).

During follow-up (median, 17.3 years), there were 105 fatal and nonfatal events major adverse cardiac events (MACE), including 48 acute coronary syndromes (12 revascularizations), 13 fatal and non-fatal strokes, 3 cases of heart failure requiring hospitalization, 3 aortic aneurysms, 6 cases of peripheral vascular disease, 20 cases of atrial fibrillation, and 12 renal events (glomerular filtration rate <60 ml/min/1.73m2).

When MACE incidence in the two reactivity groups was stratified according to baseline BP status, the rates in patients without hypertension were 3.5% and 3.0% in the normoreactive and hyperreactive groups, respectively, Dr. Palatini told Reuters Health by email. Among study participants found to have Stage 1 hypertension, however, MACE rates were 9.4% in the normoreactive group and 17.1% in the hyperreactive group.

The two groups were similar in age, sex distribution, BMI and baseline creatine levels. Hyperreactors to standing were more likely to be coffee drinkers and frequent smokers, and they had a higher mean 24-hour epinephrine level (as opposed to norepinephrine) and better lipid parameters, with lower total cholesterol and higher HDL.

After adjustment for age, gender, parental history of cardiovascular disease, smoking, alcohol drinking, coffee use, physical activity habits, body mass index, office systolic and diastolic BP, postural diastolic BP changes, office heart rate, serum glucose and total cholesterol, participants with hyperreactivity to standing had an almost doubled risk of MACE, the research team found.

Adjusting for ambulatory 24-hour monitoring did not change the analysis, nor did incident hypertension during follow up.

Even though the hyperreactive group had less incident hypertension and less anti-hypertensive medication, given the nearly double rate of MACE in those who did have hypertension, the findings "call for early pharmacologic intervention in young hypertensive patients with elevated BP to response to standing," the authors said.

They point out that because the study enrolled only white patients, findings might vary in other ethnic groups.

There were too few events to allow various outcomes to be analyzed separately, Dr. Palatini said. He also said his team did not have information on the type of antihypertensive drugs prescribed.

Multivariate Cox analysis did not appear to implicate unhealthy lifestyle behaviors. Still, the researchers concluded, "As orthostatic hyperreactivity is often associated with smoking, alcohol use, and heavy coffee drinking, our efforts should be focused primarily on management of unhealthy lifestyle behaviors. These measures can reduce the risk of developing MACE not only directly but also through a reduction of the BP response to standing."

SOURCE: https://bit.ly/3tHJw4O Hypertension, online March 17, 2022.

By Austin Kutscher MD FACC

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