Rio de Janeiro, Brazil - In the largest study of its kind to date, Brazilian researchers have shown that continually monitoring blood pressure (BP)—called ambulatory BP monitoring (ABPM)—is a predictor of future cardiovascular events in patients with resistant hypertension, but office BP is not [1]. Dr Gil F Salles (University Hospital Clementino Fraga Filho, Rio de Janeiro, Brazil) and colleagues report their findings in the November 24, 2008 issue of the Archives of Internal Medicine.

Salles told heartwire: "This suggests that all patients with resistant (hard-to-treat) hypertension must perform ABPM to control daytime and, particularly, nighttime BP levels and that these should be the therapeutic targets, instead of office BPs. This is the second study [on this subject] in resistant hypertension and the largest one," he notes. He adds that the fact that ABPM is better at predicting cardiovascular risk than office BP has been demonstrated both in mild to moderate hypertension and in the general population, but the superiority of ABPM over office BP is not generally accepted, and the availability of ABPM is not wide enough to recommend its use in all hypertensives.

Salles et al explain that about 10% to 30% of individuals with high BP have resistant hypertension. In these patients, BP remains high despite treatment with at least three antihypertensive drugs, including a diuretic. ABPM—which measures blood pressure at regular intervals throughout the day—is increasingly important in managing patients with this condition because of the possibility of a white-coat effect, when an individual has high BP only at the physician's office.

In their prospective study, they followed 556 patients with resistant hypertension who attended an outpatient clinic between 1999 and 2004. Participants underwent a clinical examination and had their blood pressure monitored continuously during a 24-hour period (every 15 minutes throughout the day and every 30 minutes at night). They were followed up at least three or four times a year until December 2007.

The primary end point was a composite of fatal and nonfatal cardiovascular events and all-cause and cardiovascular mortalities. Multiple Cox regression was used to assess associations between BP and subsequent end points.

After a median follow-up period of 4.8 years, 109 participants (19.6%) had had a cardiovascular event or had died of cardiovascular disease. This included 44 strokes, 21 MIs, 10 new cases of heart failure, and five sudden deaths. Seventy patients (12.6%) died, 46 (8.3%) of cardiovascular causes.

After multivariate adjustment, office BP did not predict any of these events, whereas higher mean ambulatory BPs (both systolic and diastolic) were independent predictors of the composite end point.

Ambulatory systolic and diastolic BPs were equivalent predictors, and both were better than pulse pressure; nighttime BP was superior to daytime BP.

But ABPM did not predict cardiovascular deaths alone or coronary heart disease (CHD) events, although it did predict some outcomes, such as stroke.

"The relatively few cardiovascular deaths and CHD events probably contributed to the failure to demonstrate the prognostic value of ambulatory BPs for these end points, owing to insufficient statistical power," the researchers observe.

"This study has important clinical implications," the authors write. "First, it reinforces the importance of ABPM performance in resistant hypertensive patients . . . [which] should be performed during the whole 24 hours, with separate analyses of the daytime and nighttime periods, because it seems that nighttime blood pressures are better cardiovascular risk factors than are daytime blood pressures."

Salles notes: "In this particular subgroup of hypertensives, those with resistant hypertension, the antihypertensive treatment should be based on ambulatory BP levels, with particular attention to nighttime BP, instead of on office BPs."

The work raises the question of whether therapeutic interventions directed specifically at controlling nighttime hypertension will be able to improve cardiovascular prognosis compared with the traditional approach of controlling daytime blood-pressure levels, he adds. "This important clinical question should be addressed in future prospective interventional studies."

The researchers also point out that a simple ABPM diagnosis of true or "white-coat" resistant hypertension at baseline "provides useful independent prognostic information for cardiovascular morbidity and for all-cause mortality."

Salles explained to heartwire: "After ABPM, resistant hypertension patients are further divided into two categories: those with uncontrolled ambulatory BP levels (mean daytime BP >135/85 mm Hg), called true resistant hypertension; and those with controlled BP (daytime BP <135/85 mm Hg), called white-coat resistant hypertension.

"Hence, the simple diagnosis of true resistant hypertension by ABPM identifies a very high-risk subgroup of resistant hypertension patients in whom management should be more aggressive, both from a diagnostic and a therapeutic perspective," he observes.