Greater visit-to-visit variability in systolic blood pressure (SBP) is associated with an increased risk of adverse renal outcomes, according to a new study.

In a study of 21,245 hypertensive adults, researchers found that patients in the second, third, fourth, and fifth quintile of standard deviation (SD) of SBP (6.63–8.82, 8.83–11.14, 11.15–14.56, and greater than 14.56 mm Hg, respectively) had a 29%, 76%, 46%, and 2-fold increased risk of a composite endpoint of either end-stage renal disease or a 50% of greater decline in estimated glomerular filtration rate (eGFR), respectively, compared with patients in the first quintile (less than 6.63 mm Hg), after adjusting for numerous potential confounders.

The investigators reported finding a similar association when they analyzed ESRD and a 50% or greater decline in eGFR separately.

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The study, led by Jeff Whittle, MD, of the Clement J. Zablocki Veterans Affairs Medical Center in Milwaukee, Wis., included participants in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial). Investigators measured mean BP and visit-to-visit variability of BP, defined as SD, across 5–7 visits occurring 6–28 months after subjects were randomized to receive chlorthalidone, amlodipine, or lisinopril. Over a mean follow-up of 3.5 years, 297 participants experienced the composite endpoint, the researchers reported online ahead of print in the Clinical Journal of the American Society of Nephrology.

Previous research has demonstrated that SBP variability is a risk factor for cardiovascular disease, dementia, and all-cause mortality.

Dr. Whittle and his colleagues mentioned some potential etiologies for the association between SBP variability and adverse renal outcomes, noting some authors have suggested that variable medication adherence explains the association between BP variability and cardiovascular endpoints. They pointed out, however, that a previous study suggests that adherence explains only a small percentage of BP variability. Dr. Whittle’s group noted that in their study, the association of SBP variability with renal endpoints persisted after adjusting for medication adherence. It also is possible is that increased BP variability may reflect vascular dysfunction, such as increased arterial stiffness or vascular inflammation or endothelial dysfunction, they stated.

Although ALLHAT has numerous strengths, it had limitations as well. It was an observational study, so the association between SBP variability and renal outcomes may not be causal, the researchers stated. “Indeed, reverse causality is plausible, because persons with more significant renal disease might have greater BP variability.”

The investigators noted they lacked the data needed to identify a 50% decrease in eGFR during follow-up for 35% of their analyzed cohort. Although many subjects changed their antihypertensive regimen during the period when the investigators ascertained BP variability, the association between BP variability and renal endpoints persisted even after adjusting for such changes, according to their report.