Visit-to-visit blood pressure variability and renal outcomes: results from ONTARGET and TRANSCEND trials.

AIMS There is conflicting evidence on whether in treated hypertensive patients the risk of renal outcomes is associated with visit-to-visit SBP variability. Furthermore, limited evidence is available on how important is SBP variability for prediction of renal outcomes compared with on-treatment mean SBP. We addressed these issues in 28 790 participants of the Ongoing Treatment Alone and in combination with Ramipril Global End point Trial and Telmisartan Randomized Assessment Study in ace iNtolerant Subjects with Cardiovascular Disease trials. METHODS AND RESULTS SBP variability was expressed as the coefficient of variation of the mean with which it showed no relationship. SBP variability and mean values were obtained from five visits during the first 2 years of treatment after the end of the titration phase. Incidence of several renal outcomes (end-stage renal disease, doubling of serum creatinine, new microalbuminuria, new macroalbuminuria and their composite) was calculated from the third year of treatment onward. Patients were divided in quintiles of SBP-coefficient of variation (SBP-CV) or mean SBP, which exhibited superimposable mean blood pressure and SBP-CV values, respectively. A progressive increase of SBP-CV was not accompanied by a parallel increase in a widely adjusted (baseline and on-treatment confounders) risk of most renal outcomes (end-stage renal disease, new macroalbuminuria, new microalbuminuria and their composite) in the subsequent on-treatment years. In contrast, the adjusted risk of most renal outcomes increased progressively from the lowest to the highest quintile of on-treatment mean SBP. Progression from lowest to highest mean on-treatment SBP, but not SBP-CV, was also associated with a less frequent return to normoalbuminuria in patients with initial micro or macroalbuminuria. Renal outcome prediction was slightly improved by the combined use of SBP-CV and mean SBP quintiles. CONCLUSION Visit-to-visit SBP variability had no major predictive value for the risk of renal outcomes, which, in contrast, was sensitively predicted by mean on-treatment SBP. A further slight increase in prediction of renal outcomes was seen by combining on-treatment mean SBP and variability.

[1]  H. Choi,et al.  Association Between Systolic and Diastolic Blood Pressure Variability and the Risk of End-Stage Renal Disease , 2019, Hypertension.

[2]  Thomas Kahan,et al.  [2018 ESC/ESH Guidelines for the management of arterial hypertension]. , 2019, Kardiologia polska.

[3]  S. Yusuf,et al.  Relative and Combined Prognostic Importance of On-Treatment Mean and Visit-to-Visit Blood Pressure Variability in ONTARGET and TRANSCEND Patients , 2017, Hypertension.

[4]  B. Jeffers,et al.  Relationship Between Visit-to-Visit Blood Pressure Variability (BPV) and Kidney Function in Patients with Hypertension , 2017, Kidney and Blood Pressure Research.

[5]  R. Holman,et al.  Association Between More Intensive vs Less Intensive Blood Pressure Lowering and Risk of Mortality in Chronic Kidney Disease Stages 3 to 5: A Systematic Review and Meta-analysis , 2017, JAMA internal medicine.

[6]  K. Kalantar-Zadeh,et al.  Association of Systolic Blood Pressure Variability With Mortality, Coronary Heart Disease, Stroke, and Renal Disease. , 2016, Journal of the American College of Cardiology.

[7]  J. Wetzels,et al.  What is the relationship between renal function and visit-to-visit blood pressure variability in primary care? Retrospective cohort study from routinely collected healthcare data , 2016, BMJ Open.

[8]  S. Anderson,et al.  Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis , 2016, The Lancet.

[9]  Barry R. Davis,et al.  Visit-to-Visit Variability of Blood Pressure and Coronary Heart Disease, Stroke, Heart Failure, and Mortality , 2015, Annals of Internal Medicine.

[10]  G. Parati,et al.  Effects of blood pressure lowering on outcome incidence in hypertension: 2. Effects at different baseline and achieved blood pressure levels – overview and meta-analyses of randomized trials , 2014, Journal of hypertension.

[11]  H. Parving,et al.  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. , 2014, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[12]  K. Reynolds,et al.  Visit-to-Visit Variability of Blood Pressure and Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis , 2014, Hypertension.

[13]  K. Kalantar-Zadeh,et al.  Impact of achieved blood pressures on mortality risk and end-stage renal disease among a large, diverse hypertension population. , 2014, Journal of the American College of Cardiology.

[14]  S. Yusuf,et al.  Mortality and morbidity in relation to changes in albuminuria, glucose status and systolic blood pressure: an analysis of the ONTARGET and TRANSCEND studies , 2014, Diabetologia.

[15]  G. Parati,et al.  Clinical relevance of visit-to-visit blood pressure variability: impact on renal outcomes , 2014, Journal of Human Hypertension.

[16]  K. Kario,et al.  Visit‐to‐Visit Variability of Blood Pressure and Renal Function Decline in Patients With Diabetic Chronic Kidney Disease , 2014, Journal of clinical hypertension.

[17]  C. Reid,et al.  Systolic blood pressure variability is an important predictor of cardiovascular outcomes in elderly hypertensive patients , 2014, Journal of hypertension.

[18]  B. Davis,et al.  Visit‐to‐Visit Blood Pressure Variability and Cardiovascular Death in the Systolic Hypertension in the Elderly Program , 2014, Journal of clinical hypertension.

[19]  Hassan Khan,et al.  Adherence to cardiovascular therapy: a meta-analysis of prevalence and clinical consequences. , 2013, European heart journal.

[20]  Peter Meredith,et al.  Long-Term and Ultra Long–Term Blood Pressure Variability During Follow-Up and Mortality in 14 522 Patients With Hypertension , 2013, Hypertension.

[21]  M. Woodward,et al.  Effects of Visit-to-Visit Variability in Systolic Blood Pressure on Macrovascular and Microvascular Complications in Patients With Type 2 Diabetes Mellitus: The ADVANCE Trial , 2013, Circulation.

[22]  H. Tighiouart,et al.  Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis , 2013, Canadian Medical Association Journal.

[23]  K. Kario,et al.  Impact of visit-to-visit variability of blood pressure on deterioration of renal function in patients with non-diabetic chronic kidney disease , 2013, Hypertension Research.

[24]  Nish Chaturvedi,et al.  Cardiorenal end points in a trial of aliskiren for type 2 diabetes. , 2012, The New England journal of medicine.

[25]  A. Bellasi,et al.  Blood pressure variability and outcomes in chronic kidney disease. , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[26]  S. Oparil,et al.  Blood Pressure Measurement Device, Number and Timing of Visits, and Intra‐Individual Visit‐to‐Visit Variability of Blood Pressure , 2012, Journal of clinical hypertension.

[27]  G. Mancia.  Short- and long-term blood pressure variability: present and future. , 2012, Hypertension.

[28]  G. Parati,et al.  Visit-to-Visit Blood Pressure Variability, Carotid Atherosclerosis, and Cardiovascular Events in the European Lacidipine Study on Atherosclerosis , 2012, Circulation.

[29]  G. Parati,et al.  Visit-to-visit blood pressure variability in the European Lacidipine Study on Atherosclerosis: methodological aspects and effects of antihypertensive treatment , 2012, Journal of hypertension.

[30]  M. Hsieh,et al.  Visit‐to‐visit variability in blood pressure strongly predicts all‐cause mortality in patients with type 2 diabetes: a 5·5‐year prospective analysis , 2012, European journal of clinical investigation.

[31]  G. Mancia,et al.  Usefulness of heart rate to predict cardiac events in treated patients with high-risk systemic hypertension. , 2012, The American journal of cardiology.

[32]  S. Yusuf,et al.  Blood Pressure Targets Recommended by Guidelines and Incidence of Cardiovascular and Renal Events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) , 2011, Circulation.

[33]  L. Ruilope,et al.  Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. , 2011, The New England journal of medicine.

[34]  G. Mancia,et al.  Better compliance to antihypertensive medications reduces cardiovascular risk , 2011, Journal of hypertension.

[35]  J. Cutler,et al.  Effects of intensive blood-pressure control in type 2 diabetes mellitus. , 2010, The New England journal of medicine.

[36]  E. O’Brien,et al.  Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension , 2010, The Lancet.

[37]  S. Yusuf,et al.  Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial , 2008, The Lancet.

[38]  S. Yusuf,et al.  Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial , 2008, The Lancet.

[39]  S. Yusuf,et al.  Telmisartan, ramipril, or both in patients at high risk for vascular events. , 2008, The New England journal of medicine.

[40]  G. Mancia,et al.  Blood Pressure Control and Improved Cardiovascular Outcomes in the International Verapamil SR-Trandolapril Study , 2007, Hypertension.

[41]  G. Beck,et al.  The Effect of a Lower Target Blood Pressure on the Progression of Kidney Disease: Long-Term Follow-up of the Modification of Diet in Renal Disease Study , 2005, Annals of Internal Medicine.

[42]  A Pedotti,et al.  Blood Pressure and Heart Rate Variabilities in Normotensive and Hypertensive Human Beings , 1983, Circulation research.

[43]  P. Whelton,et al.  Visit-to-Visit Office Blood Pressure Variability and Cardiovascular Outcomes in SPRINT (Systolic Blood Pressure Intervention Trial) , 2017, Hypertension.