Blood pressure variability across physician's office visits among hypertensive patients is strongly linked to an increased risk for stroke, heart attack and death, according to a secondary analysis of the ALLHAT hypertension treatment study.
Increased visit-to-visit variability (VVV) of systolic blood pressure among patients on various blood pressure medications was also strongly associated with a higher incidence of heart disease, nonfatal myocardial infarction and heart failure, when compared to patients who had little visit-to-visit fluctuation in systolic blood pressure, researchers Paul Muntner, PhD, of the University of Alabama at Birmingham, and colleagues wrote in Annals of Internal Medicine, published online July 27.
Mixed Findings in Earlier BP Variability Studies
Blood pressure variability across physician office visits has been shown in some previous studies, but not others, to be a significant risk factor for stroke, heart disease, and death. Significant heterogeneity in study designs, including large differences in the number of physician visits and the length of time between them, may have contributed to the conflicting findings, the researchers wrote.
"In our (2014) review of the literature we found that many of the studies just weren't that well done," Muntner told MedPage Today, adding that only a few trials provided sufficient data for pooling risk estimates and these studies strongly linked blood pressure visit-to-visit variability to increased cardiovascular risk.
Begun in 1994, the NHLBI's Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) followed more than 40,000 hypertensive patients to compare the efficacy of various antihypertensives and found that although all the tested drugs were effective, chlorthalidone—the the cheapest of the drugs tested—was superior and should be the preferred first step in BP management.
The secondary analysis by Muntner and colleagues included 25,814 ALLHAT participants, and physician visit-to-visit variability was determined from data on 7 follow-up visits occurring 6, 9, 12, 16, 20, 24, and 28 months after study randomization.
Stroke, fatal coronary heart disease (CHD) or nonfatal MI, all-cause mortality, and heart failure were the four primary study endpoints, and study participants who did not have one of these events during the first 28 months of follow-up were followed from the 28-month visit through the end of the active ALLHAT follow-up.
During this period, 606 stroke events occurred, as well as 1,194 fatal CHD or nonfatal MI, 1,948 deaths, and 921 heart failure events.
After multivariable adjustments were made, including adjustment for mean SBP, the hazard ratio comparing participants in the highest versus lowest quintile of standard deviation (SD) of systolic blood pressure (≥14.4 mm Hg versus <6.5 mm Hg) was 1.30 (95% CI, 1.06 to 1.59) for fatal CHD or nonfatal MI, 1.58 (CI, 1.32 to 1.90) for all-cause mortality, 1.46 (CI, 1.06 to 2.01) for stroke, and 1.25 (CI, 0.97 to 1.61) for heart failure.
The association was mostly consistent across subgroups defined by age, sex, race, diabetes status, antihypertensive medication adherence, BP control, left ventricular hypertrophy, and history of CVD and randomization.
A statistically significant association was also seen between VVV of diastolic BP and the measured outcomes.
Less Variability with Diuretics, Calcium Channel Blockers
In a separate analysis of ALLHAT data, also published last year, Muntner and colleagues compared systolic blood pressure VVV across drug classes. Their analysis suggested that patients taking the diuretic chlorthalidone and the calcium channel blocker amlodipine had lower visit-to-visit variability in systolic blood pressure than patients taking the ace inhibitor lisinopril.
"We don't know if switching patients with visit-to-visit variability to either a diuretic or calcium channel blocker will reduce this variability and cardiovascular risk," Muntner and colleagues wrote. "Studies to address this issue are needed."
But he added that it is premature to recommend switching patients who seem to be tolerating their antihypertension regimen and whose hypertension appears to be otherwise well controlled based on the findings.
Muntner added that visit-to-visit blood pressure variation should, instead, be considered an additional marker of cardiovascular risk.
This article was first published on MedPage Today and reprinted with permission from UBM Medica. Free registration is required.
From the American Heart Association:
The research was funded by the National Heart, Lung, and Blood Institute.
Lead researcher Paul Muntner reported receiving personal fees not related to the research from Amgen. Principal researcher Susan Oparil reports receiving consulting fees from AstraZeneca, Bayer, and Daiichi Sankyo and receiving research funding from Novartis, Medtronic, Bayer HealthCare Pharmaceuticals, AstraZeneca, and Merck.
Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Primary Source: Annals of Internal Medicine
Source Reference: Muntner P, et al "Visit-to-visit variability of blood pressure and coronary heart disease, stroke, heart failure, and mortality" Ann Intern Med 2015; DOI: 10.7326/M14-2803.