Visit-to-Visit Variability of BP and CKD Outcomes

Abstract

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.

Finding a Signal in the Noise

“…Their findings are consistent with those of a post hoc analysis evaluating the association of VVV with renal events in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Trial of individuals with type 2 diabetes (mostly without CKD), supporting the argument that the association is present among individuals without existing kidney disease (9). The findings from the work by Whittle et al (10) and the ADVANCE Trial beg several questions. Why does a variable BP signal a more rapid decline in renal function?…”

“…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. As a result, Whittle et al (10) analyzed the association of VVV with ESRD occurring through the first 3.7 years of follow-up separately from events after 3.7 years.…”

“…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). 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.…”

“…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. As a result, Whittle et al (10) analyzed the association of VVV with ESRD occurring through the first 3.7 years of follow-up separately from events after 3.7 years. Interestingly, VVV was associated with ESRD during the initial 3.7 years but not after 3.7 years; this result could be caused by temporal instability VVV.…”

e impact of visit-to-visit systolic blood pressure variability on residual renal function and le ventricular hypertrophy in peritoneal dialysis patients

“…The SD of at least 5 visits' BP readings was used for the analyses in each patient (22). Patients were then divided into HBPV (higher BP variability) group and LBPV (lower BP variability) group, according to the mean BP variation (23).…”