Effects of Visit-to-Visit Variability in Systolic Blood Pressure on Macrovascular and Microvascular Complications in Patients With Type 2 Diabetes Mellitus

Hata, Jun; Arima, Hisatomi; Rothwell, Peter M.; Woodward, Mark; Zoungas, Sophia; Anderson, Craig S.; Patel, Anushka; Neal, Bruce; Glasziou, Paul; Hamet, Pavel; Mancia, Giuseppe; Poulter, Neil; Williams, Bryan; MacMahon, Stephen; Chalmers, John

doi:10.1161/circulationaha.113.002717

Cited by 185 publications

(152 citation statements)

References 26 publications

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“…We showed an association between higher SD_SBP and higher risk of renal outcomes similar in magnitude to the association that has been seen for the association of SBP variability with CVD outcomes (6,7,10); the association persisted after multivariable adjustment for important potential confounders, including baseline eGFR and mean BP. An association also tended to be present for average real variability and peak value, two alternative measures of SBP variability.…”

Section: Discussionsupporting

confidence: 81%

“…However, studies showing a higher risk for advanced renal disease, such as ESRD, have been restricted to persons with diabetes. An analysis of individuals participating in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE) Trial, all of whom had diabetes, found increasing risk for the combined end point of new macroalbuminuria (.300 mg albumin per 1 g creatinine), doubling of serum creatinine, need for RRT, or renal death with increasing decile of SBP variability (10). However, this analysis did not adjust for baseline renal function or albuminuria.…”

Section: Discussionmentioning

confidence: 94%

“…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: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 94%

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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“…In addition, diabetes was a modified factor based on our study. Consistent with the results from the Action in Diabetes and Vascular Disease (AD-VANCE) Trial, 23) which included 8811 patients, visit-to-visit variability of SBP clearly predicted the future development of major microvascular complications among patients with diabetes.…”

Section: Discussionsupporting

confidence: 77%

Time Rate of Blood Pressure Variation Is Associated With Endothelial Function in Patients With Metabolic Syndrome

et al. 2016

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SummaryThe time rate of blood pressure (BP) variation indicates the speed of BP fluctuations. Previous studies have demonstrated that the time rate of BP variation was associated with target organ damage. However, the association between time rate of BP variation and endothelial function has not been evaluated.24-hour ambulatory blood pressure monitoring (ABPM) was performed in 61 patients with metabolic syndrome. Time rate of BP variation was calculated from BP recordings of ABPM. Endothelial function was assessed using reactive hyperemia-peripheral arterial tonometry index (RHI) by EndoPat2000. Multiple linear regression models were used to detect the association between time rate of BP variation and RHI.Among all the subjects (n = 61), the multiple linear regression models revealed that the daytime rate of systolic blood pressure (SBP) variation was independently associated with RHI (β = -0.334, P = 0.008). A 0.1 mmHg/minute increase in the daytime rate of SBP variation correlated with a decline of 0.20 in RHI. The same effect was also found in the subjects with eGFR ≥ 60 mL/ (minute*1.73 m 2 ). A greater association was found in those who were not taking a statin, β-blocker, ACEI/ARB, or diuretic and those without diabetes compared with those with any antihypertensive medication or with diabetes. Other ambulatory blood pressure parameters and central hemodynamics were not found to be associated with RHI.Our findings have shown that the daytime rate of SBP variation was associated with endothelial function in patients with metabolic syndrome, independent of other BP parameters and central hemodynamics. (Int Heart J 2016; 57: 226-233) Key words: RHI, Ambulatory blood pressure monitoring, Target organ damage, Blood pressure variability A mbulatory blood pressure monitoring (ABPM) is widely used in patients with prehypertension and hypertension, and its use is gradually increasing. Many studies have suggested that systolic blood pressure (BP), diastolic BP, and the degree of BP variability (BPV) calculated from ABPM are associated with target organ damage, cardiovascular disease risk, and long-term prognosis.1,2) Mancia, et al described a new BP phenomenon called time rate of BP variation, which is a measure of the speed of BP fluctuations derived from a computerized analysis of ABPM data.3) Current evidence has suggested that the time rate of BP variation was associated with target organ damage, such as increased common carotid artery intima-media thickness, 4,5) increased left ventricular mass, 6) impaired renal function, 7) and coronary atherosclerosis. 8)Endothelial dysfunction is one of the important pathophysiological processes of the early stage in patients with metabolic syndrome (MetS), and is an early manifestation before atherosclerotic plaque detected by angiography or ultrasound, 9) and is a sign of poor cardiovascular prognosis.10) Early detection of endothelial dysfunction has attracted more and more attention in clinical practice. Reactive hyperemia-peripheral arterial tonometry index (RHI) is...

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“…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).…”

mentioning

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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Effects of Visit-to-Visit Variability in Systolic Blood Pressure on Macrovascular and Microvascular Complications in Patients With Type 2 Diabetes Mellitus

Cited by 185 publications

References 26 publications

Visit-to-Visit Variability of BP and CKD Outcomes

Visit-to-Visit Variability of BP and CKD Outcomes

Time Rate of Blood Pressure Variation Is Associated With Endothelial Function in Patients With Metabolic Syndrome

Finding a Signal in the Noise

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