Optimal blood pressure targets in patients with hypertension may need to be reconsidered in light of the findings of recently published studies.
In one study, researchers led by Csaba P. Kovesdy, MD, chief of nephrology at the Memphis VA Medical Center in Memphis, found that stricter control of systolic blood pressure (SBP) is associated with higher all-cause mortality in patients with chronic kidney disease (CKD).
The other study, led by John J. Sim, MD, area research chair, Kaiser Permanente Los Angeles Medical Center, demonstrated that systolic and diastolic pressures higher and lower than 130–139 mm Hg systolic and 60–79 diastolic are associated with an increased risk of death and development of end-stage renal disease (ESRD) in patients with and without CKD.
In a study using a nationwide cohort of U.S. veterans, Dr. Kovesdy’s group analyzed data from 77,765 CKD patients with uncontrolled hypertension who then received 1 or more additional antihypertensive medications with evidence of a decrease in SBP. Of the 77,765 patients, 5,760 had a treated SBP of less than 120 mm Hg and 72,005 patients had SBP of 120–139 mm Hg at follow-up.
During a median follow-up of 6 years, 19,517 died. The death rate was 80.9 per 1,000 patient-years in the SBP below 120 mm Hg group compared with 41.8 per 1,000 patient-years in the SBP 120–139 mm Hg group, Dr. Kovesdy’s team reported online ahead of print in JAMA Internal Medicine. After adjusting for propensity scores, the SBP less than 120 mm Hg group had a 70% increased risk of death compared with the SBP 120–139 mm Hg group.
“Our goal was to model a clinical trial, capitalizing on the availability of a very large clinical database that allowed us to select patients whose blood pressure trajectory suggested a change from uncontrolled level to different BP goals using pharmacologic intervention,” Dr. Kovesdy told Renal & Urology News.
“The observational nature of the study does not allow us to claim that the higher mortality was a direct result of the lower observed BP. Nevertheless, our results are similar to those reported by other studies done in the CKD population, and suggest that blood pressure has a J-shaped association with mortality, and that it may be advisable to avoid over-treating hypertension in patients with kidney disease.”
In clinical practice, Dr. Kovesdy pointed out, this would mean that targeting an SBP range of about 120–140 mmHg rather than an SBP of below140 mm Hg may be more beneficial. The approach may require the tapering of antihypertensive regimens in patients whose SBP is less than 120 mm Hg, especially if they display symptoms or signs of organ hypo-perfusion, such as lightheadedness or an increase in serum creatinine.
Direct extrapolation of these results to ESRD patients is not possible, he said, although observational data in dialysis patients also suggests the presence of a J-shaped curve. In dialysis patient the situation is, however, more complex due to differences in pre-, post-, and interdialytic blood pressures.
The study by Dr. Sim’s team, which was published in the Journal of the American College of Cardiology (2014;64:588-597), included 398,419 treated hypertensive patients (30% of whom had diabetes mellitus) in the Kaiser Permanenete Southern California health system. Of these, 25,182 (6.3%) died and ESRD developed in 4,957 (1.2%).
Compared with an SBP of 130–139 mm Hg, an SBP below 110 mm Hg was associated with a 4-fold increased risk of a composite outcome of death or ESRD. An SBP of 110–119 mm Hg was associated with a 1.8 times increased risk. Patients with an SBP of 150–159, 160-169, and 170 mm Hg or higher had a 2.3, 3.3, and 4.9 times increased risk. Diastolic BP of 60–79 mm Hg was associated with the lowest risk. The nadir systolic and diastolic pressures associated with the lowest risk were 137 and 71 mm Hg, respectively.
“Controlling hypertension is the priority,” Dr. Sim said. “As a nation, we have been able to steadily improve our hypertension treatment and subsequent control rates to the degree that now we have to better establish the ideal treatment ranges. Our Kaiser Permanente study suggests that ‘the lower the better’ approach is not ideal and that there may be a subpopulation where clinicians may be adding risk with aggressive treatment. For those individuals, clinicians should consider down titration and withdrawal of medications in order to achieve more appropriate blood pressures.”
In an editorial accompanying the report by Dr. Sim’s team (pp.598–600), Charlotte Andersson, MD, of Gentofte Hospital in Hellerup, Denmark, and Ramachandran S. Vasan, MD, of Boston University School of Medicine, noted that available randomized trials have not convincingly demonstrated improved mortality rates with aggressive antihypertensive treatment.
“Ultimately, we need further studies to establish the optimal BP treatment target for patients with various comorbidities,” the authors wrote. “It may make sense to treat younger people with less comorbidity more aggressively than older patients or people with a large burden of comorbidity, but the exact numerical BP targets are yet to be determined.”
Drs. Andersson and Vasan added that truly uncontrolled hypertension remains a challenge, “and we still must be concerned about undertreatment of hypertension, even as we sort out the optimal treatment target.”