Visit-to-Visit Variability in Blood Pressure and Kidney and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Nephropathy: A Post Hoc Analysis From the RENAAL Study and the Irbesartan Diabetic Nephropathy Trial

McMullan, Ciaran J.; Heerspink, Hiddo J L; Parving, Hans‐Henrik; Dwyer, Jamie P.; Forman, John P.; Zeeuw, Dick de

doi:10.1053/j.ajkd.2014.06.008

Cited by 68 publications

(59 citation statements)

References 31 publications

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“…and the Irbesartan Diabetic Nephropathy Trial showed that SBP variability was associated with risk for ESRD and other renal end points, even after adjusting for baseline renal disease. However, this study was restricted to patients with diabetes with .500 mg/d albumin excretion (14). We now extend these results to show that SBP variability is associated with renal outcomes, including ESRD, among nonpatients with diabetes.…”

Section: 001mentioning

confidence: 59%

“…For example, we did not have a measure of albuminuria, which has been related to both renal outcomes and BP variability. It is possible that BP variability simply identifies persons with albuminuria, which is the actual marker of higher risk for renal outcomes; this was not the case in a prior study among patients with diabetes (14).…”

Section: 001mentioning

confidence: 88%

“…In some but not all studies, persons with higher BP variability had more rapid CKD progression as measured by declines in eGFR or increases in urinary albumin (9)(10)(11)(12)(13). Some studies of persons with diabetes have shown an association of BP variability with more clinically impactful renal outcomes, including ESRD (10,14), but such an association has not been shown among persons without diabetes.…”

Section: Introductionmentioning

confidence: 99%

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Visit-to-Visit Variability of BP and CKD Outcomes

Whittle

Lynch²,

Tanner³

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background and objectives Increased visit-to-visit variability of BP is associated with cardiovascular disease risk. We examined the association of visit-to-visit variability of BP with renal outcomes among 21,245 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.Design, setting, participants, & measurements We measured mean BP and visit-to-visit variability of BP, defined as SD, across five to seven visits occurring 6-28 months after participants were randomized to chlorthalidone, amlodipine, or lisinopril. The composite outcome included incident ESRD after assessment of SD of systolic BP or $50% decline in eGFR between 24 months and 48 or 72 months after randomization. We repeated the analyses using average real variability and peak value of systolic BP and for visit-to-visit variability of diastolic BP.Results Over a mean follow-up of 3.5 years, 297 outcomes occurred. After multivariable adjustment, including baseline eGFR and mean systolic BP, the hazard ratios for the composite end point were 1.29 (95% confidence interval [95% CI], 0.75 to 2.22), 1.76 (95% CI, 1.06 to 2.91), 1.46 (95% CI, 0.88 to 2.45), and 2.05 (95% CI, 1.25 to 3.36) for the second through fifth (SD of systolic BP =6. 63-8.82, 8.83-11.14, 11.15-14.56, and .14.56 mmHg, respectively) versus the first (SD of systolic BP ,6.63 mmHg) quintile of SD of systolic BP, respectively (P trend =0.004). The association was similar when ESRD and a 50% decline in eGFR were analyzed separately, for other measures of visit-to-visit variability of systolic BP, and for visit-to-visit variability of diastolic BP. ConclusionsHigher visit-to-visit variability of BP is associated with higher risk of renal outcomes independent of mean BP.

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Section: 001mentioning

confidence: 59%

Section: 001mentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Visit-to-Visit Variability of BP and CKD Outcomes

Whittle

Lynch²,

Tanner³

et al. 2016

Clinical Journal of the American Society of Nephrology

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“…As an example, in the original paper by Rothwell et al (5), the correlation coefficient of VVV ascertained during one time period with VVV ascertained during a later time period was only 0.34 (95% confidence interval, 0.26 to 0.41); in a more recent study of patients with diabetes, this "intraclass" correlation coefficient was 0.42 (95% confidence interval, 0.35 to 0.49) (8). This variability of VVV over time may explain, at least in part, the finding from the work by Whittle et al (10) that, in the analysis of ESRD during 10 years of follow-up, the proportional hazards assumption was violated.…”

mentioning

confidence: 96%

“…Using the SD of systolic BP measured over successive clinic visits, a common VVV metric, several groups have shown that greater VVV is associated with increased risk for cardiovascular events in patients with diabetic and nondiabetic CKD; the corresponding relation of VVV with renal events has largely been limited to diabetic individuals (6)(7)(8)(9). In this issue of the Clinical Journal of the American Society of Nephrology, Whittle et al (10) report the association of VVV with renal events in 21,245 participants from the Antihypertensive and LipidLowering Treatment to Prevent Heart Attack Trial (ALLHAT).…”

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confidence: 99%

Finding a Signal in the Noise

McMullan

Forman

2016

Clinical Journal of the American Society of Nephrology

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The importance of BP as a risk factor for cardiovascular and renal disease is well established. In all BP trials, precise protocols are enforced when measuring BP to minimize extraneous factors that could obscure an individual's true BP free from noise (1). However, despite these protocols, an individual's BP varies from visit to visit, even within the context of a trial. Far from being unwelcome noise, there may well be a useful signal embedded in this visit to visit variability. The association of visit to visit variability in clinic BP (VVV) with cardiovascular disease was first appreciated in the Honolulu Heart Study (2); however, it was a seminal series of papers by Rothwell and coworkers (3-5) in 2010 and 2011 describing the relation of greater VVV with higher risk of stroke that spurred the recent interest in BP variability as a predictor of cardiovascular events.Nephrologists, who value BP control as a key means of preventing and slowing progression of CKD in addition to reducing cardiovascular events in patients with CKD, have asked whether VVV holds similar predictive value for renal events. Using the SD of systolic BP measured over successive clinic visits, a common VVV metric, several groups have shown that greater VVV is associated with increased risk for cardiovascular events in patients with diabetic and nondiabetic CKD; the corresponding relation of VVV with renal events has largely been limited to diabetic individuals (6-9). In this issue of the Clinical Journal of the American Society of Nephrology, Whittle et al. (10) report the association of VVV with renal events in 21,245 participants from the Antihypertensive and LipidLowering Treatment to Prevent Heart Attack Trial (ALLHAT). Those individuals in the highest compared with lowest quintile of VVV (defined over five to seven visits) were more than twice as likely to develop a composite renal event, defined as either a 50% decline in eGFR or incident ESRD, after controlling for age, sex, baseline eGFR, mean systolic BP, adherence to BP medications, history of diabetes, and cardiovascular disease. The association was similar among both participants who were nondiabetic and participants who were diabetic (65% and 35% of the population, respectively), suggesting that the relation of greater VVV with renal end points does not depend on diabetic status. As with all observational studies, reverse causality may be responsible for the association described. In this study underlying kidney disease, present at baseline but undetected by baseline eGFR, may lead to increased VVV and also predict future eGFR decline. For example, albuminuria is associated with increased VVV and also predicts eGFR decline but was not available at baseline for inclusion in multivariate adjustment.A unique characteristic of the study by Whittle et al. (10) is the extended duration of follow-up gained by incorporation of ESRD information from the US Renal Data Systems. The availability of this information allowed the investigators to determine if the association of VVV with re...

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Finerenone for Albuminuria in Patients With Diabetic Nephropathy

Feng

Zeng

2016

JAMA

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Visit-to-Visit Variability in Blood Pressure and Kidney and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Nephropathy: A Post Hoc Analysis From the RENAAL Study and the Irbesartan Diabetic Nephropathy Trial

Cited by 68 publications

References 31 publications

Visit-to-Visit Variability of BP and CKD Outcomes

Visit-to-Visit Variability of BP and CKD Outcomes

Finding a Signal in the Noise

Finerenone for Albuminuria in Patients With Diabetic Nephropathy

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