Impaired Nocturnal BP Dipping Holds Prognostic Value, Regardless of 24-Hour BPs

Patrice Wendling

March 07, 2016

RIO DE JANEIRO, BRAZIL — A massive meta-analysis confirms the prognostic effect of the nocturnal blood-pressure fall in hypertensive patients and parses out the deleterious effects of extreme and reverse dipping patterns[1].

The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) meta-analysis also provides ambulatory BP monitoring indices for predicting cardiovascular mortality and morbidity.

"Ambulatory BP monitoring is important not only to assess BP control during treatment, but also to refine cardiovascular risk stratification in hypertensive patients and should be used whenever possible," lead author Dr Gil Salles (Universidade Federal do Rio de Janeiro, Brazil) told heartwire from Medscape in an email.

Dr Cynthia Cheng (Thomas Jefferson University, Philadelphia, PA), who was not associated with the study, commented: "Some of this information has been known, but it's not really out there in terms of being used clinically. So the large numbers of patients in this study, hopefully, will put this as a concept on the map."

Prior reports have provided inconsistent results but didn't comprehensively evaluate all aspects of the circadian BP variability profile, the authors note.

To tackle this, data from 17,312 hypertensive patients across three continents were used to evaluate nocturnal BP fall by the continuous systolic-BP night-to-day ratio (SBP-NDR), traditional dipping/nondipping groups, and the four dipping subgroups: extreme dippers (SBP-NDR <0.8), reduced dippers (SBP-NDR >0.9 and <1.0), and reverse dippers (SBP-NDR >0.10) vs normal dippers (SBP-NDR >0.8 and <0.9).

The primary outcome of interest was total fatal or nonfatal cardiovascular events (CVEs), but also measured were coronary events, strokes, all-cause mortality, and cardiovascular mortality. There were 1769 total CVEs.

Average 24-hour systolic BP varied from 131 to 140 mm Hg and systolic night-to-day ratio from 0.88 to 0.93.

Systolic night-to-day ratio, with or without adjustment for 24-hour systolic BP, predicted all adverse outcomes, the authors reported in their paper, published online February 22, 2016 in Hypertension.

Adjusted hazard ratios varied from 1.12 for coronary events and strokes and 1.15 for total CVEs to 1.23 for cardiovascular mortality for a 1-SD increment in SBP-NDR.

The nondipping pattern also predicted all adverse outcomes, except coronary events, after adjustment for 24-hour systolic BP.

Reverse dippers, also called risers or patients whose BP increases during sleep, had the worst prognosis for all outcomes. That said, reduced dippers were at 27% higher adjusted risk for total cardiovascular events (P<.05).

A prior Belgian meta-analysis[2] suggested that the entire increased cardiovascular risk of the nondipping pattern was due to the reverse dippers and that reduced dipping carried no additional risk, Salles observed.

"We've shown that isn't entirely true," he wrote. "Although most of the risk was explained by the reverse dippers, the reduced-dipping group still had a significant 27% excess cardiovascular risk in relation to normal dippers. This means that this specific BP dipping pattern should not be considered 'benign' in terms of future cardiovascular morbidity and mortality."

Extreme Dippers

Controversy has also swirled around extreme dippers, but here the data were less decisive.

The Belgian meta-analysis suggested extreme dipping might be protective for mortality, while a cohort study[3] in untreated elderly Japanese hypertensives reported it was associated with future stroke occurrence.

Extreme dippers in ABC-H had a nonsignificant increased risk of total CVEs, coronary events, and stroke but a nonsignificant lower risk of all-cause and cardiovascular mortality than normal dippers, Salles reported.

Their heterogeneity was high, however, particularly for total CVEs, prompting the investigators to test trial characteristics using meta-regression. It revealed that hypertensive treatment status at baseline significantly modified the effect of extreme dipping (P<.001).

Extreme dipping in treated patients carried no increased risk or might even be protective for CVEs (HR 0.72), but in untreated patients carried an elevated risk for total CVEs (HR 1.92) that was higher than that for reduced dippers (HR 1.3) and similar to that for reverse dippers (HR 1.8).

Possible mechanisms underlying this differential prognostic effect could involve orthostatic hypertension, exaggerated morning BP surge, increased BP variability, or increased arterial stiffness in extreme dippers, the authors speculate.

The data will not end debate because they came from a meta-regression, but should be viewed as "hypothesis-generating and confirmed (or not) ideally in individual-data meta-analyses," Salles told heartwire . "Other unknown factors, beyond the antihypertensive treatment, might be causing the observed heterogeneity."

Overall, however, "our meta-analysis had four- to fivefold greater number of hypertensive patients than the previous two meta-analysis; hence our point estimates of risk are much more precise," he noted.

Better Reimbursement

The results highlight the urgent need for studies to determine whether restoring normal dipping patterns will reduce cardiovascular events and mortality, the authors conclude.

In the interim, the ABC-H results may provide cardiologists, primary-care physicians, or even politicians with ammunition to put pressure on insurance companies to provide greater reimbursement for ambulatory monitoring, on which the assessment of nocturnal blood pressure is based, Cheng said.

"There's a little bit of reimbursement in very specific situations; the assessment of resistant hypertension and also for white-coat hypertension, but this study with the large numbers certainly shows adverse prognosis, which we can't tell from office blood pressures, across all kinds of hypertensives, not just those two subcategories," she added. "So really indicates that ambulatory monitoring should be done on a more widespread basis, as those of who are fans of ambulatory monitoring, particularly in England and Spain, who are the leaders, have been pushing for decades."

The authors and Cheng report no relevant financial relationships.


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