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Background: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values., Methods: SPRINT data were linked with EHR data from 49 (of 102) study sites. The primary outcome was the total slope of decline in eGFR for the intervention phase and the post-trial slope of decline during the observation phase using trial and outpatient EHR values. Secondary outcomes included a ≥30% decline in eGFR to <60 ml/min per 1.73 m 2 and a ≥50% decline in eGFR or kidney failure among participants with baseline eGFR ≥60 and <60 ml/min per 1.73 m 2 , respectively., Results: EHR creatinine values were available for a median of 8.3 years for 3041 participants. The total slope of decline in eGFR during the intervention phase was -0.67 ml/min per 1.73 m 2 per year (95% confidence interval [CI], -0.79 to -0.56) in the standard treatment group and -0.96 ml/min per 1.73 m 2 per year (95% CI, -1.08 to -0.85) in the intensive treatment group ( P < 0.001). The slopes were not significantly different during the observation phase: -1.02 ml/min per 1.73 m 2 per year (95% CI, -1.24 to -0.81) in the standard group and -0.85 ml/min per 1.73 m 2 per year (95% CI, -1.07 to -0.64) in the intensive group. Among participants without CKD at baseline, intensive treatment was associated with higher risk of a ≥30% decline in eGFR during the intervention (hazard ratio, 3.27; 95% CI, 2.43 to 4.40), but not during the postintervention observation phase. In those with CKD at baseline, intensive treatment was associated with a higher hazard of eGFR decline only during the intervention phase (hazard ratio, 1.95; 95% CI, 1.03 to 3.70)., Conclusions: Intensive BP lowering was associated with a steeper total slope of decline in eGFR and higher risk for kidney events during the intervention phase of the trial, but not during the postintervention observation phase., (Copyright © 2023 by the American Society of Nephrology.)

Background: Randomized trials are the gold standard for generating clinical practice evidence, but follow-up and outcome ascertainment are resource-intensive. Electronic health record (EHR) data from routine care can be a cost-effective means of follow-up, but concordance with trial-ascertained outcomes is less well-studied., Methods: We linked EHR and trial data for participants of the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial comparing intensive and standard blood pressure targets. Among participants with available EHR data concurrent to trial-ascertained outcomes, we calculated sensitivity, specificity, positive predictive value, and negative predictive value for EHR-recorded cardiovascular disease (CVD) events, using the gold standard of SPRINT-adjudicated outcomes (myocardial infarction (MI)/acute coronary syndrome (ACS), heart failure, stroke, and composite CVD events). We additionally compared the incidence of non-CVD adverse events (hyponatremia, hypernatremia, hypokalemia, hyperkalemia, bradycardia, and hypotension) in trial versus EHR data., Results: 2468 SPRINT participants were included (mean age 68 (SD 9) years; 26% female). EHR data demonstrated ≥80% sensitivity and specificity, and ≥ 99% negative predictive value for MI/ACS, heart failure, stroke, and composite CVD events. Positive predictive value ranged from 26% (95% CI; 16%, 38%) for heart failure to 52% (95% CI; 37%, 67%) for MI/ACS. EHR data uniformly identified more non-CVD adverse events and higher incidence rates compared with trial ascertainment., Conclusions: These results support a role for EHR data collection in clinical trials, particularly for capturing laboratory-based adverse events. EHR data may be an efficient source for CVD outcome ascertainment, though there is clear benefit from adjudication to avoid false positives., Competing Interests: Declaration of Competing Interest CDC receives research support from Bayer Healthcare, Inc. outside the submitted work. AM reports ownership interest in iEnroll, LLC. The remaining authors have nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics., Methods: We conducted an individual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists' Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up., Results: There were 363 684 participants (42% women), with baseline mean age=65 years and mean systolic/diastolic BP=152/87 mm Hg, and among whom 19% were current smokers, 49% had cardiovascular disease, 28% had diabetes and 69% were taking antihypertensive treatment at baseline. Drugs were effective in lowering BP showing maximal effect after 12 months and gradually attenuating towards later years. Based on measures taken ≥12 months postrandomisation, mean systolic/diastolic BP difference (95% CI) between more and less intense BP-lowering treatment was -11.1 (-11.3 to -10.8)/-5.6 (-5.7 to -5.4) mm Hg; between active treatment and placebo was -5.1 (-5.3 to -5.0)/-2.3 (-2.4 to -2.2) mm Hg; and between active and control arms for drug comparison trials was -1.4 (-1.5 to -1.3)/-0.6 (-0.7 to -0.6) mm Hg. BP reductions were observed across different baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes and prior antihypertensive treatment use., Conclusion: These findings suggest that BP-lowering pharmacotherapy is effective in lowering BP, up to 4 years on average, in people with different characteristics. Appropriate treatment strategies are needed to sustain substantive long-term BP reductions., Competing Interests: Competing interests: DC reports grants from the British Heart Foundation, during the conduct of the study. MN and AP reports grants from the British Heart Foundation outside the submitted work. JS reports ownership in companies providing services to Itrim, Amgen, Janssen, Novo Nordisk, Eli Lilly, Boehringer, Bayer, Pfizer and AstraZeneca outside the submitted work. MW reports personal fees from Amgen, Kyowa Kirin and Freeline outside the submitted work. KR reports grants from the British Heart Foundation, UK Research and Innovation Global Challenges Research Fund, Oxford Martin School, and National Institute for Health Research Oxford Biomedical Research Centre, during the conduct of the study, and personal fees from BMJ Heart and PLOS Medicine, outside the submitted work. EC, RR, AS, JD, FF and BRD declare no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Adjudication of inpatient AKI in the Systolic Blood Pressure Intervention Trial (SPRINT) was based on billing codes and admission and discharge notes. The purpose of this study was to evaluate the effect of intensive versus standard BP control on creatinine-based inpatient and outpatient AKI, and whether AKI was associated with cardiovascular disease (CVD) and mortality., Methods: We linked electronic health record (EHR) data from 47 clinic sites with trial data to enable creatinine-based adjudication of AKI. Cox regression was used to evaluate the effect of intensive BP control on the incidence of AKI, and the relationship between incident AKI and CVD and all-cause mortality., Results: A total of 3644 participants had linked EHR data. A greater number of inpatient AKI events were identified using EHR data (187 on intensive versus 155 on standard treatment) as compared with serious adverse event (SAE) adjudication in the trial (95 on intensive versus 61 on standard treatment). Intensive treatment increased risk for SPRINT-adjudicated inpatient AKI (HR, 1.51; 95% CI, 1.09 to 2.08) and for creatinine-based outpatient AKI (HR, 1.40; 95% CI, 1.15 to 1.70), but not for creatinine-based inpatient AKI (HR, 1.20; 95% CI, 0.97 to 1.48). Irrespective of the definition (SAE or creatinine based), AKI was associated with increased risk for all-cause mortality, but only creatinine-based inpatient AKI was associated with increased risk for CVD., Conclusions: Creatinine-based ascertainment of AKI, enabled by EHR data, may be more sensitive and less biased than traditional SAE adjudication. Identifying ways to prevent AKI may reduce mortality further in the setting of intensive BP control., Competing Interests: A.K. Agarwal reports serving in an advisory or leadership role for American Society of Diagnostic and Interventional Nephrology (ASDIN), Clinical Nephrology, International Journal of Nephrology, International Society of Nephrology (ISN), Journal of Vascular Access, Kidney Self-Assessment Program, National Kidney Foundation (NKF), and The Open Urology and Nephrology Journal; having other interests in, or relationships with, the American Society of Nephrology, ASDIN, ISN, and NKF; serving on a speakers bureau for AstraZeneca; having consultancy agreements with, and receiving honoraria from, AstraZeneca and Otsuka Pharmaceuticals. S. Beddhu reports receiving research funding from Bayer, Boehringer Ingelheim, and Novartis; having consultancy agreements with Bayer and Reata; and serving in an advisory or leadership role for CJASN and Kidney Reports. M. Dobre reports receiving honoraria from Relypsa and Tricida; and serving in an advisory or leadership role for Relypsa (Resistant Hypertension Working Group) and Tricida (Metabolic Acidosis Working Group). J.P. Dwyer reports having consultancy agreements with Acuta Capital, Akcea, Aleon, Ardelyx, AstraZeneca, Aurinia, Axsome, Bayer, BioRasi, BioVie, Boeringher Ingelheim, Botanix, Caladrius, Cincor, Contrafect, Cumberland, Eli Lilly, ES, Fibrogen, Genentech, Hope Pharma, Icon, Ionis, Innovative Renal Care, Keros, LifeSci Venture, Medpace, MicuRx, PSI, Rarestone, Reata, RenalytixAI, Sanofi, Spero, Tricida, ValenzaBio, and Worldwide Clinical Trials; having ownership interest in BioRasi, Innovative Renal Care, PathEx, ValenzaBio, and Venostent; serving in an advisory or leadership role for Collaborative Study Group (board of directors and president) and The Bolles School (high school in Jacksonville, FL; board of directors); and having other interests in, or relationships with, The Bolles School Board of Visitors. E. Horwitz reports having other interests in, or relationships with, MetroHealth Medical Center, contracted with Fresenius Kidney Care (serving as medical director for inpatient dialysis services). J. Lash reports serving in an advisory or leadership role for Kidney360. A. McWilliams reports having ownership interest in iEnroll. S. Oparil reports receiving research funding from Bayer (site principal investigator [PI] in diabetic kidney disease), CinCor Pharma (site PI for primary aldosterone study), George Clinical (site PI for GMRx2 treatment of hypertension), and Higi (site PI for BP validation study); having ownership interest in CinCor Pharma; serving in an advisory or leadership role for CinCor Pharma (scientific advisory board for primary aldosteronism and hypertension) and Preventric Diagnostics (chair medical and technology committee; from March 2019 to present); and serving as editor-in-chief of Current Hypertension Reports (journal published by Springer Science Business Media LLC; annual stipend of $5000; editor-in-chief term until December 2022). N.M. Pajewski reports having ownership interest in Eyenovia and Ocuphire Pharma. M.A. Parkulo reports having ownership interest in Apple, Blackberry, Carnival, JPMorgan Chase, Marriott, StitchFix, and Zoom. J. Powell reports receiving research funding from Idorsia (for acting as site PI). F.F. Rahbari-Oskoui reports having consultancy agreements with Astute, Kadmon, Keryx, Phoenix (client Otsuka), Sanofi, and UpToDate; serving in an advisory or leadership role for BMC Nephrology (as associate editor), Journal of Cardiology and Vascular Medicine (as editorial board member), and PKD Foundation; receiving research funding from Duke University, Kadmon, NIH, Otsuka, Reata, and Sanofi/Genzyme; serving on a speakers bureau for Otsuka (unbranded speakers bureau; only raising disease awareness in autosomal dominant polycystic kidney disease without any reference to commercial products); receiving honoraria from Otsuka and Sanofi; and having other interests in, or relationships with, PKD Foundation (scientific advisory board member) and UpToDate (as author, receiving authorship royalties). M. Rahman reports serving as an editorial board member of American Journal of Nephrology and as an associate editor of CJASN; having consultancy agreements with Barologics; receiving research funding from Bayer Pharmaceuticals and Duke Clinical Research Institute; and receiving honoraria from Bayer, Reata, and Relypsa. D.S. Raj reports having other interests in, or relationships with, the American Association of Kidney Patients; serving in an advisory or leadership role for National Heart, Lung, and Blood Institute (NHLBI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Novo Nordisk; receiving research funding from the NIH; having consultancy agreements with, and receiving honoraria from, Novo Nordisk. M.V. Rocco reports having consultancy agreements with Bayer, Baxter, and George Clinical; receiving research funding from Bayer, Boehringer Ingelheim, and GlaxoSmithKline; serving as cochair of the ISN Kidney Care Network Project and as chair of NKF Kidney Disease Outcomes Quality Initiative; and serving in an advisory or leadership role for NKF. S. Soman reports serving in an advisory or leadership role for the American Medical Informatics Association, NKF, and NKF of Michigan; having other interests in, or relationships with, American Medical Informatics Association, Cardiorenal Society of America (CRSA), NKF (education committee), and NKF of Michigan (scientific advisory board); being employed by Henry Ford Hospital; and having ownership interest in Nephroceuticals and Pfizer. G. Thomas reports receiving honoraria from UpToDate. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Importance: There are concerns with translating results from the Systolic Blood Pressure Intervention Trial (SPRINT) into clinical practice because the standardized protocol used to measure blood pressure (BP) may not be consistently applied in routine clinical practice., Objectives: To evaluate the concordance between BPs obtained in routine clinical practice and those obtained using the SPRINT protocol and whether concordance varied by target trial BP., Design, Setting, and Participants: This observational prognostic study linking outpatient vital sign information from electronic health records (EHRs) with data from 49 of the 102 SPRINT sites was conducted from November 8, 2010, to August 20, 2015, among 3074 adults 50 years or older with hypertension without diabetes or a history of stroke. Statistical analysis was performed from May 21, 2019, to March 20, 2020., Main Outcomes and Measures: Blood pressures measured in routine clinical practice and SPRINT., Results: Participant-level EHR data was obtained for 3074 participants (2482 men [80.7%]; mean [SD] age, 68.5 [9.1] years) with 3 or more outpatient and trial BP measurements. In the period from the 6-month study visit to the end of the study intervention, the mean systolic BP (SBP) in the intensive treatment group from outpatient BP recorded in the EHR was 7.3 mm Hg higher (95% CI, 7.0-7.6 mm Hg) than BP measured at trial visits; the mean difference between BP recorded in the outpatient EHR and trial SBP was smaller for participants in the standard treatment group (4.6 mm Hg [95% CI, 4.4-4.9 mm Hg]). Bland-Altman analyses demonstrated low agreement between outpatient BP recorded in the EHR and trial BP, with wide agreement intervals ranging from approximately -30 mm Hg to 45 mm Hg in both treatment groups. In addition, the difference between BP recorded in the EHR and trial BP varied widely by site., Conclusions and Relevance: Outpatient BPs measured in routine clinical practice were generally higher than BP measurements taken in SPRINT, with greater mean SBP differences apparent in the intensive treatment group. There was a consistent high degree of heterogeneity between the BPs recorded in the EHR and trial BPs, with significant variability over time, between and within the participants, and across clinic sites. These results highlight the importance of proper BP measurement technique and an inability to apply 1 common correction factor (ie, approximately 10 mm Hg) to approximate research-quality BP estimates when BP is not measured appropriately in routine clinical practice., Trial Registration: SPRINT ClinicalTrials.gov Identifier: NCT01206062.

Background: The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear., Methods: In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR)., Results: About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm ( P <0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval [95% CI], 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar., Conclusions: Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality., (Copyright © 2019 by the American Society of Nephrology.)

Hypertension is a global health problem and without adequate diagnosis and treatment is a risk factor for morbidity and mortality. Proper assessment of blood pressure is key to diagnosis and management of hypertension. Different methods of measurement are available for use and varying techniques are applied to patient care. Understanding the proper methods of blood pressure measurement both in and out of the physician's office is crucial for providing appropriate care to an individual patient. In addition, understanding the techniques used in research, on which current guidelines are based, is critical for proper application to daily practice. In this article, we review the types of blood pressure measurement techniques, discuss the benefits and limitations to each, explore future technological advances in measurement devices, and provide insight into research techniques, which ultimately guide our practice., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Arterial stiffness, typically assessed as the aortic pulse wave velocity (PWV), and central blood pressure levels may be indicators of cardiovascular disease (CVD) risk. This ancillary study to the Systolic Blood Pressure Intervention Trial (SPRINT) obtained baseline assessments (at randomization) of PWV and central systolic blood pressure (C-SBP) to: 1) characterize these vascular measurements in the SPRINT cohort, and 2) test the hypotheses that PWV and C-SBP are associated with glucose homeostasis and markers of chronic kidney disease (CKD). The SphygmoCor® CPV device was used to assess carotid-femoral PWV and its pulse wave analysis study protocol was used to obtain C-SBP. Valid results were obtained from 652 participants. Mean (±SD) PWV and C-SBP for the SPRINT cohort were 10.7 ± 2.7 m/s and 132.0 ± 17.9 mm Hg respectively. Linear regression analyses for PWV and C-SBP results adjusted for age, sex, and race/ethnicity in relation to several markers of glucose homeostasis and CKD did not identify any significant associations with the exception of a marginally statistically significant and modest association between PWV and urine albumin-to-creatinine ratio (linear regression estimate ± SE, 0.001 ± 0.0006; P-value 0.046). In a subset of SPRINT participants, PWV was significantly higher than in prior studies of normotensive persons, as expected. For older age groups in the SPRINT cohort (age > 60 years), PWV was compared with a reference population of hypertensive individuals. There were no compelling associations noted between PWV or C-SBP and markers of glucose homeostasis or CKD., Clinical Trial Registration: NCT01206062., Competing Interests: Suzanne Oparil has received research grant support or support/reimbursement for travel to meetings or other, non-financial support from: Actelion Clinical Research/George Clinical; AstraZeneca AB; Bayer; Lundbeck; Novartis; Novo Nordisk; ROX Medical; and has consulted for: Actelion/George Clinical, Lundbeck and Novo Nordisk. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Intensive systolic blood pressure (SBP) control improved outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Our objective was to expand on reported findings by analysis of baseline characteristics, primary outcomes, adverse events, follow-up blood pressure, and medication use differences by baseline SBP (tertile 1 [T1], <132; tertile 2 [T2], 132-145; and tertile 3 [T3], >145 mm Hg). Participants with higher baseline SBP tertile were more often women and older, had higher cardiovascular risk, and lower utilization of antihypertensive medications, statins, and aspirin. Achieved SBP in both treatment arms was slightly higher in T2 and T3 compared with T1 and fewer in the T3 groups achieved SBP targets compared with T1 and T2 groups. The primary composite outcome with intensive versus standard SBP treatment was reduced by 30% in T1, 23% in T2, and 17% in T3 with no evidence of an interaction ( P =0.77). Event rates were lower in the intensive arm, and there was no evidence that this benefit differed by SBP tertile. There was no difference in the hazard for serious adverse events in any of the 3 tertiles. Medication utilization differed across the SBP tertiles at baseline with a lesser percentage of diuretics and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker drugs in the higher tertiles-a finding that reversed during the trial. The beneficial effects of intensive SBP lowering were not modified by the level of baseline SBP. Within the parameters of this population, these findings add support for clinicians to treat blood pressure to goal irrespective of baseline SBP., (© 2018 American Heart Association, Inc.)

Background: Treating to a lower blood pressure (BP) may increase acute kidney injury (AKI) events., Study Design: Data for AKI resulting in or during hospitalization or emergency department visits were collected as part of the serious adverse events reporting process of the Systolic Blood Pressure Intervention Trial (SPRINT)., Setting & Participants: 9,361 participants 50 years or older with 1 or more risk factors for cardiovascular disease., Interventions: Participants were randomly assigned to a systolic BP target of <120 (intensive arm) or <140mmHg (standard arm)., Outcomes & Measurements: Primary outcome was the number of adjudicated AKI events. Secondary outcomes included severity of AKI and degree of recovery of kidney function after an AKI event. Baseline creatinine concentration was defined as the most recent SPRINT outpatient creatinine value before the date of the AKI event., Results: There were 179 participants with AKI events in the intensive arm and 109 in the standard arm (3.8% vs 2.3%; HR, 1.64; 95% CI, 1.30-2.10; P<0.001). Of 288 participants with an AKI event, 248 (86.1%) had a single AKI event during the trial. Based on modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria for severity of AKI, the number of AKI events in the intensive versus standard arm by KDIGO stage was 128 (58.5%) versus 81 (62.8%) for AKI stage 1, 42 (19.2%) versus 18 (14.0%) for AKI stage 2, and 42 (19.2%) versus 25 (19.4%) for AKI stage 3 (P=0.5). For participants with sufficient data, complete or partial resolution of AKI was seen for 169 (90.4%) and 9 (4.8%) of 187 AKI events in the intensive arm and 86 (86.9%) and 4 (4.0%) of 99 AKI events in the standard arm, respectively., Limitations: Trial results are not generalizable to patients with diabetes mellitus or without risk factors for cardiovascular disease., Conclusions: More intensive BP lowering resulted in more frequent episodes of AKI. Most cases were mild and most participants had complete recovery of kidney function., Trial Registration: Registered at ClinicalTrials.gov with study number NCT01206062., (Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.)

The effect of clinic-based intensive hypertension treatment on ambulatory blood pressure (BP) is unknown. The goal of the SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory BP ancillary study was to evaluate the effect of intensive versus standard clinic-based BP targets on ambulatory BP. Ambulatory BP was obtained within 3 weeks of the 27-month study visit in 897 SPRINT participants. Intensive treatment resulted in lower clinic systolic BP (mean difference between groups=16.0 mm Hg; 95% confidence interval, 14.1-17.8 mm Hg), nighttime systolic BP (mean difference=9.6 mm Hg; 95% confidence interval, 7.7-11.5 mm Hg), daytime systolic BP (mean difference=12.3 mm Hg; 95% confidence interval, 10.6-13.9 mm Hg), and 24-hour systolic BP (mean difference=11.2 mm Hg; 95% confidence interval, 9.7-12.8 mm Hg). The night/day systolic BP ratio was similar between the intensive (0.92±0.09) and standard-treatment groups (0.91±0.09). There was considerable lack of agreement within participants between clinic systolic BP and daytime ambulatory systolic BP with wide limits of agreement on Bland-Altman plots. In conclusion, targeting a systolic BP of <120 mm Hg, when compared with <140 mm Hg, resulted in lower nighttime, daytime, and 24-hour systolic BP, but did not change the night/day systolic BP ratio. Ambulatory BP monitoring may be required to assess the effect of targeted hypertension therapy on out of office BP. Further studies are needed to assess whether targeting hypertension therapy based on ambulatory BP improves clinical outcomes., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01835249., Competing Interests: The remaining authors report no conflicts of interest., (© 2016 American Heart Association, Inc.)

Thiazides and thiazide-type diuretics are recommended as first-line agents for the treatment of hypertension, but contemporary information on their use in clinical practice is lacking. We examined patterns and correlates of thiazide prescription in a cross-sectional analysis of baseline data from participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). We examined baseline prescription of thiazides in 7582 participants receiving at least 1 antihypertensive medication by subgroup, and used log-binomial regression to calculate adjusted prevalence ratios for thiazide prescription (versus no thiazide). Forty-three percent of all participants were prescribed a thiazide at baseline, but among participants prescribed a single agent, the proportion was only 16%. The prevalence of thiazide prescription differed significantly by demographic factors, with younger participants, women, and blacks all having higher adjusted prevalence of thiazide prescription than other corresponding subgroups. Participants in the lowest category of kidney function (estimated glomerular filtration rate <30 mL/min per 1.73 m2) were half as likely to be prescribed a thiazide as participants with preserved kidney function. In conclusion, among persons with hypertension and heightened cardiovascular risk, we found that thiazide prescription varied significantly by demographics and kidney disease status, despite limited evidence about relative differences in effectiveness., (© 2016 American Heart Association, Inc.)

Hypertension is a common problem among patients with glomerular disease and CKD. Optimal blood pressure targets for these patients have been the source of much debate. Careful review of the available data supports a blood pressure target of less than 140/90 mmHg. Consideration for a lower goal of less than 130/80 mmHg should be given for patients with heavy proteinuria. Renin-angiotensin system inhibitors should be used as the cornerstone of therapy for all patients with glomerular disease and CKD., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

From 88 subjects with labile high blood pressure (LHBP), we collected blood pressure variability (BPV) and assessed relationships with age, medications, and nocturnal pattern via ambulatory blood pressure monitoring. The average age of the subjects was 64 ± 13 years and they were on 1.5 ± 1.3 antihypertensives. BPV did not differ diurnally and was not influenced by medication. Aging associates with increasing daytime systolic but not diastolic BPV, with increasing nighttime systolic BP, and decreasing diastolic BP diurnally. Subjects had widened pulse pressure and abnormal diurnal pattern with age. Further studies are needed to stratify an individual's risk associated with LHBP.

BACKGROUND: Randomized trials are the gold standard for generating clinical practice evidence, but follow-up and outcome ascertainment are resource-intensive. Electronic health record (EHR) data from routine care can be a cost-effective means of follow-up, but concordance with trial-ascertained outcomes is less well-studied. METHODS: We linked EHR and trial data for participants of the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial comparing intensive and standard blood pressure targets. Among participants with available EHR data concurrent to trial-ascertained outcomes, we calculated sensitivity, specificity, positive predictive value, and negative predictive value for EHR-recorded cardiovascular disease (CVD) events, using the gold standard of SPRINT-adjudicated outcomes (myocardial infarction (MI)/acute coronary syndrome (ACS), heart failure, stroke, and composite CVD events). We additionally compared the incidence of non-CVD adverse events (hyponatremia, hypernatremia, hypokalemia, hyperkalemia, bradycardia, and hypotension) in trial versus EHR data. RESULTS: 2468 SPRINT participants were included (mean age 68 (SD 9) years; 26% female). EHR data demonstrated ≥80% sensitivity and specificity, and ≥ 99% negative predictive value for MI/ACS, heart failure, stroke, and composite CVD events. Positive predictive value ranged from 26% (95% CI; 16%, 38%) for heart failure to 52% (95% CI; 37%, 67%) for MI/ACS. EHR data uniformly identified more non-CVD adverse events and higher incidence rates compared with trial ascertainment. CONCLUSIONS: These results support a role for EHR data collection in clinical trials, particularly for capturing laboratory-based adverse events. EHR data may be an efficient source for CVD outcome ascertainment, though there is clear benefit from adjudication to avoid false positives.

Intensive systolic blood pressure (SBP) control improved outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Our objective was to expand on reported findings by analysis of baseline characteristics, primary outcomes, adverse events, follow-up blood pressure, and medication use differences by baseline SBP (tertile 1 [T1], <132; tertile 2 [T2], 132-145; and tertile 3 [T3], >145 mm Hg). Participants with higher baseline SBP tertile were more often women and older, had higher cardiovascular risk, and lower utilization of antihypertensive medications, statins, and aspirin. Achieved SBP in both treatment arms was slightly higher in T2 and T3 compared with T1 and fewer in the T3 groups achieved SBP targets compared with T1 and T2 groups. The primary composite outcome with intensive versus standard SBP treatment was reduced by 30% in T1, 23% in T2, and 17% in T3 with no evidence of an interaction (P=0.77). Event rates were lower in the intensive arm, and there was no evidence that this benefit differed by SBP tertile. There was no difference in the hazard for serious adverse events in any of the 3 tertiles. Medication utilization differed across the SBP tertiles at baseline with a lesser percentage of diuretics and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker drugs in the higher tertiles-a finding that reversed during the trial. The beneficial effects of intensive SBP lowering were not modified by the level of baseline SBP. Within the parameters of this population, these findings add support for clinicians to treat blood pressure to goal irrespective of baseline SBP. [ABSTRACT FROM AUTHOR]

Thiazides and thiazide-type diuretics are recommended as first-line agents for the treatment of hypertension, but contemporary information on their use in clinical practice is lacking. We examined patterns and correlates of thiazide prescription in a cross-sectional analysis of baseline data from participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). We examined baseline prescription of thiazides in 7582 participants receiving at least 1 antihypertensive medication by subgroup, and used log-binomial regression to calculate adjusted prevalence ratios for thiazide prescription (versus no thiazide). Forty-three percent of all participants were prescribed a thiazide at baseline, but among participants prescribed a single agent, the proportion was only 16%. The prevalence of thiazide prescription differed significantly by demographic factors, with younger participants, women, and blacks all having higher adjusted prevalence of thiazide prescription than other corresponding subgroups. Participants in the lowest category of kidney function (estimated glomerular filtration rate <30 mL/min per 1.73 m2) were half as likely to be prescribed a thiazide as participants with preserved kidney function. In conclusion, among persons with hypertension and heightened cardiovascular risk, we found that thiazide prescription varied significantly by demographics and kidney disease status, despite limited evidence about relative differences in effectiveness. [ABSTRACT FROM AUTHOR]