Blood pressure variability and outcomes in chronic kidney disease (original) (raw)

Blood Pressure and Risk of All-Cause Mortality in Advanced Chronic Kidney Disease and Hemodialysis: The Chronic Renal Insufficiency Cohort Study

Hypertension, 2014

H ypertension is common in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) on hemodialysis. 1,2 Although there is considerable information on the association of higher systolic blood pressure (SBP) and progression of CKD, 3-6 less is known about the association of blood pressure with mortality. Previous studies have suggested a U-shaped association between SBP and risk of mortality in moderate stages of CKD 7,8 ; however, less is known about these relationships among patients with advanced stages of CKD, when estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m 2 , which is a particularly high-risk subgroup of the overall CKD population. Furthermore, numerous studies have also reported a U-shaped association between SBP and risk of mortality in hemodialysis patients, with higher mortality associated with both lower (even within the normal range) and high blood pressures. 9-13 A limitation of these investigations has been reliance on SBP measured in the dialysis-unit. Prior single-center studies have suggested that the setting of SBP measurement (dialysis-unit versus outof-dialysis-unit) may affect the measurement and associated outcomes of SBP. Consequently, national and international guidelines have concluded that there is uncertainty about how to measure blood pressure in hemodialysis patients and a poor understanding of the association between blood pressure and risk of adverse outcomes. 2 It is unclear which blood pressure reading should be used as the guide for therapy for dialysis patients. 14 Thus, there remains uncertainty on SBP targets in patient with advanced CKD and those on hemodialysis, particularly Abstract-Studies of hemodialysis patients have shown a U-shaped association between systolic blood pressure (SBP) and mortality. These studies have largely relied on dialysis-unit SBP measures and have not evaluated whether this U-shape also exists in advanced chronic kidney disease, before starting hemodialysis. We determined the association between SBP and mortality at advanced chronic kidney disease and again after initiation of hemodialysis. This was a prospective study of Chronic Renal Insufficiency Cohort participants with advanced chronic kidney disease followed through initiation of hemodialysis. We studied the association between SBP and mortality when participants (1) had an estimated glomerular filtration rate <30 mL/min/1.73 m 2 (n=1705), (2) initiated hemodialysis and had dialysis-unit SBP measures (n=403), and (3) initiated hemodialysis and had out-of-dialysis-unit SBP measured at a Chronic Renal Insufficiency Cohort study visit (n=326). Cox models were adjusted for demographics, cardiovascular risk factors, and dialysis parameters. A quadratic term for SBP was included to test for a U-shaped association. At advanced chronic kidney disease, there was no association between SBP and mortality (hazard ratio, 1.02 [95% confidence interval, 0.98-1.07] per every 10 mm Hg increase). Among participants who started hemodialysis, a U-shaped association between dialysis-unit SBP and mortality was observed. In contrast, there was a linear association between out-of-dialysis-unit SBP and mortality (hazard ratio, 1.26 [95% confidence interval, 1.14-1.40] per every 10 mm Hg increase). In conclusion, more efforts should be made to obtain out-of-dialysis-unit SBP, which may merit more consideration as a target for clinical management and in interventional trials.

Pre-Dialysis Systolic Blood Pressure-Variability Is Independently Associated with All-Cause Mortality in Incident Haemodialysis Patients

PLoS ONE, 2014

Systolic blood pressure variability is an independent risk factor for mortality and cardiovascular events. Standard measures of blood pressure predict outcome poorly in haemodialysis patients. We investigated whether systolic blood pressure variability was associated with mortality in incident haemodialysis patients. We performed a longitudinal observational study of patients commencing haemodialysis between 2005 and 2011 in East Anglia, UK, excluding patients with cardiovascular events within 6 months of starting haemodialysis. The main exposure was variability independent of the mean (VIM) of systolic blood pressure from short-gap, pre-dialysis blood pressure readings between 3 and 6 months after commencing haemodialysis, and the outcome was all-cause mortality. Of 203 patients, 37 (18.2%) patients died during a mean follow-up of 2.0 (SD 1.3) years. The age and sex-adjusted hazard ratio (HR) for mortality was 1.09 (95% confidence interval (CI) 1.02-1.17) for a one-unit increase of VIM. This was not altered by adjustment for diabetes, prior cardiovascular disease and mean systolic blood pressure (HR 1.09, 95% CI 1.02-1.16). Patients with VIM of systolic blood pressure above the median were 2.4 (95% CI 1.17-4.74) times more likely to die during follow-up than those below the median. Results were similar for all measures of blood pressure variability and further adjustment for type of dialysis access, use of antihypertensives and absolute or variability of fluid intake did not alter these findings. Diastolic blood pressure variability showed no association with all cause mortality. Our study shows that variability of systolic blood pressure is a strong and independent predictor of all-cause mortality in incident haemodialysis patients. Further research is needed to understand the mechanism as this may form a therapeutic target or focus for management.

Changing Relationship of Blood Pressure with Mortality over Time among Hemodialysis Patients

Journal of the American Society of Nephrology, 2006

High BP is a major risk factor for atherosclerotic cardiovascular disease mortality in the general population. Surprising, studies that have been conducted among hemodialysis (HD) patients have yielded conflicting data on the relationship between BP and mortality. This study explores two hypotheses among HD patients: (1) The relationship between BP and mortality changes over time, and (2) mild to moderate hypertension is well tolerated. Incident HD patients who were treated at Dialysis Clinic Inc. facilities between 1993 and 2003 were studied. Primary end points were atherosclerotic cardiovascular disease and all-cause mortality. The relationship between BP and mortality was analyzed in two sets of Cox proportional hazards models. Model-B explored the relationship between baseline BP and mortality in sequential time periods. Model-TV assessed the relationship between BP, treated as time-varying, and mortality. The study sample (n ‫؍‬ 16,959) was similar in characteristics to the United States Renal Data Systems population, although black patients were slightly overrepresented. Model-B demonstrated that the relationship between baseline BP and mortality changes over time. Low systolic BP (<120 mmHg) was associated with increased mortality in years 1 and 2. High systolic BP (>150 mmHg) was associated with increased mortality among patients who survived >3 yr. Low pulse pressure was associated with increased mortality. Model-TV demonstrated that mild to moderate systolic hypertension may be relatively well tolerated. In conclusion, the relationship between baseline BP and mortality changes over time. Mild to moderate systolic hypertension was associated with only modest increases in mortality.

Association of blood pressure with decline in renal function and time until the start of renal replacement therapy in pre-dialysis patients: a cohort study

BMC Nephrology, 2011

Background: To investigate whether high blood pressure accelerates renal function decline in patients with advanced chronic kidney disease (CKD), we studied the association of systolic (SBP) and diastolic blood pressure (DBP) with decline in renal function and time until the start of renal replacement therapy (RRT) in patients with CKD stages IV-V on pre-dialysis care. Methods: In the PREPARE-1 cohort 547 incident pre-dialysis patients, referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included between 1999 and 2001 and followed until the start of RRT, mortality, or end of follow-up (January 1 st 2008). Main outcomes were rate of decline in renal function, estimated as the slope of available eGFR measurements, and time until the start of RRT.

Blood Pressure and Mortality Risk on Peritoneal Dialysis

American Journal of Kidney Diseases, 2009

Background: The association of baseline blood pressure (BP) and mortality in incident peritoneal dialysis patients has not been adequately studied. Study Design: Cohort study. Setting & Participants: 2,770 patients on PD therapy at 180 days from start of renal replacement therapy in England and Wales between 1997 and 2004.

The Epidemiology of Systolic Blood Pressure and Death Risk in Hemodialysis Patients

American Journal of Kidney Diseases, 2006

Background: This study compares the associations of predialysis systolic blood pressure (SBP) with mortality risk in both incident and prevalent hemodialysis (HD) cohorts by using both conventional and time-varying Cox analyses, thus addressing limitations of prior studies. Methods: A total of 56,338 incident patients starting HD therapy during 1997 to 2001 and 69,590 prevalent HD patients on January 1, 2002, were grouped into the following categories: (1) SBP less than 120 mm Hg, (2) 120 < SBP < 140 mm Hg, (3) 140 < SBP < 160 mm Hg, (4) 160 < SBP < 180 mm Hg, (5) 180 < SBP < 200 mm Hg, and (6) SBP of 200 mm Hg or greater. Conventional and time-varying models evaluated 1-year and 3-year (incident patients only) survival. Results: Nine percent and 26.0% of incident patients and 5.7% and 20.1% of prevalent patients were in categories 1 and 2, respectively. Their associated 1-year hazard ratios (HRs) were 2.63 to 3.68 and 1.57 to 1.68 compared with category 4, the reference group. HRs for categories 3, 5, and 6 were not different from category 4. Time-varying models magnified category 1 and 2 HRs to 5.54 to 7.42 and 1.92 to 2.21, such that 25% to 35% of patients in the target SBP range (<140 mm Hg) had the greatest risk. A "reversed J-shaped" risk profile emerged in the time-varying models, with very high SBP (category 6) associated with HRs of 1.52 to 1.55, but only 1% of patients were in category 6. Three-year outcomes were similar. Conclusion: Epidemiological characteristics of predialysis SBP consistently differ from those in the general population despite different analytic perspectives. The data suggest a need for greater investigative, diagnostic, and therapeutic focus on HD patients with normal and prehypertensive blood pressure ranges. Am J Kidney Dis 48:606-615.

Long-term visit-to-visit office blood pressure variability increases the risk of adverse cardiovascular outcomes in patients with chronic kidney disease

Kidney International, 2013

Long-term visit-to-visit blood pressure (BP) variability predicts a high risk for cardiovascular events in patients with essential hypertension. Whether long-term visit-to-visit BP variability holds the same predictive power in predialysis patients with chronic kidney disease (CKD) is unknown. Here we tested the relationship between long-term visit-to-visit office BP variability and a composite end point (death and incident cardiovascular events) in a cohort of 1618 patients with stage 2-5 CKD. Visit-to-visit systolic BP variability was significantly and independently related to baseline office, maximal, and average systolic BPs, age, glucose, estimated glomerular filtration rate, and albumin, and to the number of visits during the follow-up. Both the standard deviation of systolic BP (hazard ratio: 1.11, 95% confidence interval: 1.01-1.20) and the coefficient of variation of systolic BP (hazard ratio: 1.15, 95% confidence interval: 1.02-1.29) were significant predictors of the combined end point independent of peak and average systolic BP, cardiovascular comorbidities, Framingham risk factors, and CKD-related risk factors. Antihypertensive treatment (b-blockers and sympatholytic drugs) significantly abrogated the excess risk associated with high systolic BP variability. Thus, large visit-to-visit systolic BP variability in patients with CKD predicts a higher risk of death and nonfatal cardiovascular events independent of underlying BP levels.