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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.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.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.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.

BACKGROUND: Despite evidence supporting the cardiovascular and cognitive benefits of intensive blood pressure management, older adults have the lowest rates of blood pressure control. We determined the association between age and therapeutic inertia (TI) in SPRINT (Systolic Blood Pressure Intervention Trial), and whether frailty, cognitive function, or gait speed moderate or mediate these associations. METHODS: We performed a secondary analysis of SPRINT of participant visits with blood pressure above randomized treatment goal. We categorized baseline age as RESULTS: Participants 60 to P interaction , >0.10). CONCLUSIONS: Older age is associated with greater TI independent of physical or cognitive function, implying age bias in hypertension management.

IMPORTANCE: Antihypertensive treatments benefit cerebrovascular health and cognitive function in patients with hypertension, but it is uncertain whether an intensive blood pressure target leads to potentially harmful cerebral hypoperfusion. OBJECTIVE: To investigate the association of intensive systolic blood pressure (SBP) control vs standard control with whole-brain cerebral blood flow (CBF). DESIGN, SETTING, AND PARTICIPANTS: This substudy of the Systolic Blood Pressure Intervention Trial (SPRINT) randomized clinical trial compared the efficacy of 2 different blood pressure–lowering strategies with longitudinal brain magnetic resonance imaging (MRI) including arterial spin labeled perfusion imaging to quantify CBF. A total of 1267 adults 50 years or older with hypertension and increased cardiovascular risk but free of diabetes or dementia were screened for the SPRINT substudy from 6 sites in the US. Randomization began in November 2010 with final follow-up MRI in July 2016. Analyses were performed from September 2020 through December 2021. INTERVENTIONS: Study participants with baseline CBF measures were randomized to an intensive SBP target less than 120 mm Hg or standard SBP target less than 140 mm Hg. MAIN OUTCOMES AND MEASURES: The primary outcome was change in whole-brain CBF from baseline. Secondary outcomes were change in gray matter, white matter, and periventricular white matter CBF. RESULTS: Among 547 participants with CBF measured at baseline, the mean (SD) age was 67.5 (8.1) years and 219 (40.0%) were women; 315 completed follow-up MRI at a median (IQR) of 4.0 (3.7-4.1) years after randomization. Mean whole-brain CBF increased from 38.90 to 40.36 (difference, 1.46 [95% CI, 0.08-2.83]) mL/100 g/min in the intensive treatment group, with no mean increase in the standard treatment group (37.96 to 37.12; difference, –0.84 [95% CI, –2.30 to 0.61] mL/100 g/min; between-group difference, 2.30 [95% CI, 0.30-4.30; P = .02]). Gray, white, and periventricular white matter CBF showed similar changes. The association of intensive vs standard treatment with CBF was generally similar across subgroups defined by age, sex, race, chronic kidney disease, SBP, orthostatic hypotension, and frailty, with the exception of an indication of larger mean increases in CBF associated with intensive treatment among participants with a history of cardiovascular disease (interaction P = .05). CONCLUSIONS AND RELEVANCE: Intensive vs standard antihypertensive treatment was associated with increased, rather than decreased, cerebral perfusion, most notably in participants with a history of cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062

The Systolic Blood Pressure Intervention Trial (SPRINT) results have influenced clinical practice but have also generated discussion regarding the validity, generalizability and importance of the findings. Following the SPRINT primary results manuscript in 2015, additional results and analyses of the data have addressed these concerns. The primary objective of this manuscript is to respond to key questions that have been raised. The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated the effectiveness of treating SBP to levels well below those previously recommended in US and European BP guidelines.(1) The SPRINT results have informed guideline committees in recommending treatment to SBP targets lower than previously advised.(2–4) However, some of the SPRINT findings have generated discussion, and questions have been raised regarding their application in clinical practice. These include generalizability, validity of the outcome measures (especially heart failure), the methods used for event ascertainment, the effect size of the intervention benefit, and safety and tolerability of the

The cardiovascular and renal outcomes of angiotensin-II receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) treatment are well-known; however, few studies have evaluated initiation of these agents and cognitive impairment.To emulate a target trial to evaluate the cognitive outcomes of initiating an ARB- vs ACEI-based antihypertensive regimen in individuals at risk for mild cognitive impairment (MCI) and probable dementia (PD).Active comparator, new-user observational cohort study design using data from the Systolic Blood Pressure Intervention Trial (SPRINT), conducted November 2010 through July 2018. Marginal cause-specific hazard ratios (HRs) and treatment-specific cumulative incidence functions were estimated with inverse probability (IP) weighting to account for confounding. Participants were using neither an ARB nor ACEI at baseline. Data analysis was conducted from April 7, 2021, to April 26, 2022.New users of ARB vs ACEI during the first 12 months of trial follow-up.Composite of adjudicated amnestic MCI or PD.Of 9361 participants, 727 and 1313 new users of an ARB or ACEI, respectively, with well-balanced baseline characteristics between medication exposure groups after inverse probability weighting (mean [SD] age, 67 [9.5] years; 1291 ]63%] male; 240 [33%] Black; 89 [12%] Hispanic; 383 [53%] White; and 15 [2%] other race or ethnicity. In the primary analysis, during a median follow-up of 4.9 years, the inverse probability-weighted rate of amnestic MCI or PD was 4.3 vs 4.6 per 100 person-years among participants initiating ARB vs ACEI (HR, 0.93; 95% CI, 0.76-1.13). In subgroup analyses, new users of an ARB vs ACEI had a lower rate of amnestic MCI or PD among those in the standard systolic blood pressure treatment arm (HR, 0.61; 95% CI, 0.41-0.91) but not in the intensive arm (HR, 1.17; 95% CI, 0.90-1.52) (P = .007 for interaction).In this observational cohort study of US adults at high cardiovascular disease risk, there was no difference in the rate of amnestic MCI or PD among new users of an ARB compared with ACEI, although 95% CIs were wide.

Background Clinic blood pressure (BP) when measured in the seated position, can miss meaningful BP phenotypes, including low ambulatory BP (white coat effects [WCE]) or high supine BP (nocturnal non-dipping). Orthostatic hypotension (OH) measured using both seated (or supine) and standing BP, could identify phenotypes poorly captured by seated clinic BP alone. Methods We examined the association of OH with WCE and night-to-daytime systolic BP (SBP) in a subpopulation of SPRINT, a randomized trial testing the effects of intensive or standard (1. Results Of 897 adults (mean age 71.5±9.5 years, 29% female, 28% black), 128 had OH at least once. Among those with OH, 15% had WCE (vs. 7% without OH). Moreover, 25% of those with OH demonstrated a non-dipping pattern (vs. 14% without OH). OH was positively associated with both WCE (OR=2.24; 95%CI: 1.28, 4.27) and reverse dipping (OR=2.29; 95% CI: 1.31, 3.99). Conclusions The identification of OH in clinic was associated with two BP phenotypes often missed with traditional seated BP assessments. Further studies on mechanisms of these relationships are needed. Clinical trials registration Trial Number NCT03569020.

Background Intensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients. Objectives The aim of this study was to predict the magnitude of benefit (reduced CVD and all-cause mortality risk) along with adverse event (AE) risk from intensive versus standard SBP treatment. Methods This was a secondary analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Separate benefit outcomes were the first occurrence of: 1) a CVD composite of acute myocardial infarction or other acute coronary syndrome, stroke, heart failure, or CVD death; and 2) all-cause mortality. Treatment-related AEs of interest included hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, and acute kidney injury. Modified elastic net Cox regression was used to predict absolute risk for each outcome and absolute risk differences on the basis of 36 baseline variables available at the point of care with intensive versus standard treatment. Results Among 8,828 SPRINT participants (mean age 67.9 years, 35% women), 600 CVD composite events, 363 all-cause deaths, and 481 treatment-related AEs occurred over a median follow-up period of 3.26 years. Individual participant risks were predicted for the CVD composite (C index = 0.71), all-cause mortality (C index = 0.75), and treatment-related AEs (C index = 0.69). Higher baseline CVD risk was associated with greater benefit (i.e., larger absolute CVD risk reduction). Predicted CVD benefit and predicted increased treatment-related AE risk were correlated (Spearman correlation coefficient = −0.72), and 95% of participants who fell into the highest tertile of predicted benefit also had high or moderate predicted increases in treatment-related AE risk. Few were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%). Similar results were obtained for all-cause mortality. Conclusions SPRINT participants with higher baseline predicted CVD risk gained greater absolute benefit from intensive treatment. Participants with high predicted benefit were also most likely to experience treatment-related AEs, but AEs were generally mild and transient. Patients should be prioritized for intensive SBP treatment on the basis of higher predicted benefit. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062 )

ImportanceIntensive vs standard treatment to lower systolic blood pressure (SBP) reduces risk of mild cognitive impairment (MCI) or dementia; however, the magnitude of cognitive benefit likely varies among patients.ObjectiveTo estimate the magnitude of cognitive benefit of intensive vs standard systolic BP (SBP) treatment.Design, Setting, and ParticipantsIn this ad hoc secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 9361 randomized clinical trial participants 50 years or older with high cardiovascular risk but without a history of diabetes, stroke, or dementia were followed up. The SPRINT trial was conducted between November 1, 2010, and August 31, 2016, and the present analysis was completed on October 31, 2022.InterventionSystolic blood pressure treatment to an intensive (Main Outcomes and MeasuresThe primary outcome was a composite of adjudicated probable dementia or amnestic MCI.ResultsA total of 7918 SPRINT participants were included in the analysis; 3989 were in the intensive treatment group (mean [SD] age, 67.9 [9.2] years; 2570 [64.4%] men; 1212 [30.4%] non-Hispanic Black) and 3929 were in the standard treatment group (mean [SD] age, 67.9 [9.4] years; 2570 [65.4%] men; 1249 [31.8%] non-Hispanic Black). Over a median follow-up of 4.13 (IQR, 3.50-5.88) years, there were 765 and 828 primary outcome events in the intensive treatment group and standard treatment group, respectively. Older age (hazard ratio [HR] per 1 SD, 1.87 [95% CI, 1.78-1.96]), Medicare enrollment (HR per 1 SD, 1.42 [95% CI, 1.35-1.49]), and higher baseline serum creatinine level (HR per 1 SD, 1.24 [95% CI, 1.19-1.29]) were associated with higher risk of the primary outcome, while better baseline cognitive functioning (HR per 1 SD, 0.43 [95% CI, 0.41-0.44]) and active employment status (HR per 1 SD, 0.44 [95% CI, 0.42-0.46]) were associated with lower risk of the primary outcome. Risk of the primary outcome by treatment goal was estimated accurately based on similar projected and observed absolute risk differences (C statistic = 0.79). Higher baseline risk for the primary outcome was associated with greater benefit (ie, larger absolute reduction of probable dementia or amnestic MCI) of intensive vs standard treatment across the full range of estimated baseline risk.Conclusions and RelevanceIn this secondary analysis of the SPRINT trial, participants with higher baseline projected risk of probable dementia or amnestic MCI gained greater absolute cognitive benefit from intensive vs standard SBP treatment in a monotonic fashion.Trial RegistrationClinicalTrials.gov Identifier: NCT01206062

ImportanceLittle is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers.ObjectiveTo investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF).Design, Setting, and ParticipantsThe Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter randomized clinical trial that compared intensive systolic BP (SBP) control (SBP target InterventionsAt baseline, 355 participants received intensive SBP treatment and 315 participants received standard SBP treatment.Main Outcomes and MeasuresThe main outcomes were regional changes in WMLs, FA, MD (in white matter regions of interest), and CBF (in gray matter regions of interest).ResultsAt baseline, 355 participants (mean [SD] age, 67.7 [8.0] years; 200 men [56.3%]) received intensive BP treatment and 315 participants (mean [SD] age, 67.0 [8.4] years; 199 men [63.2%]) received standard BP treatment. Intensive treatment was associated with smaller mean increases in WML volume compared with standard treatment (644.5 mm3 vs 1258.1 mm3). The smaller mean increases were observed specifically in the deep white matter regions of the left anterior corona radiata (intensive treatment, 30.3 mm3 [95% CI, 16.0-44.5 mm3]; standard treatment, 80.5 mm3 [95% CI, 53.8-107.2 mm3]), left tapetum (intensive treatment, 11.8 mm3 [95% CI, 4.4-19.2 mm3]; standard treatment, 27.2 mm3 [95% CI, 19.4-35.0 mm3]), left superior fronto-occipital fasciculus (intensive treatment, 3.2 mm3 [95% CI, 0.7-5.8 mm3]; standard treatment, 9.4 mm3 [95% CI, 5.5-13.4 mm3]), left posterior corona radiata (intensive treatment, 26.0 mm3 [95% CI, 12.9-39.1 mm3]; standard treatment, 52.3 mm3 [95% CI, 34.8-69.8 mm3]), left splenium of the corpus callosum (intensive treatment, 45.4 mm3 [95% CI, 25.1-65.7 mm3]; standard treatment, 83.0 mm3 [95% CI, 58.7-107.2 mm3]), left posterior thalamic radiation (intensive treatment, 53.0 mm3 [95% CI, 29.8-76.2 mm3]; standard treatment, 106.9 mm3 [95% CI, 73.4-140.3 mm3]), and right posterior thalamic radiation (intensive treatment, 49.5 mm3 [95% CI, 24.3-74.7 mm3]; standard treatment, 102.6 mm3 [95% CI, 71.0-134.2 mm3]).Conclusions and RelevanceThis study suggests that intensive BP treatment, compared with standard treatment, was associated with a slower increase of WMLs, improved diffusion tensor imaging, and FA and CBF changes in several brain regions that represent vulnerable areas that may benefit from more strict BP control.Trial RegistrationClinicalTrials.gov Identifier: NCT01206062

Summary Background Results from the Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive control of systolic blood pressure significantly reduced the occurrence of mild cognitive impairment, but not probable dementia. We investigated the effects of intensive lowering of systolic blood pressure on specific cognitive functions in a preplanned substudy of participants from SPRINT. Methods SPRINT was an open-label, multicentre, randomised controlled trial undertaken at 102 sites, including academic medical centres, Veterans Affairs medical centres, hospitals, and independent clinics, in the USA and Puerto Rico. Participants were adults aged 50 years or older with systolic blood pressure higher than 130 mm Hg, but without diabetes, history of stroke, or dementia. Participants were randomly assigned (1:1) to a systolic blood pressure goal of less than 120 mm Hg (intensive treatment) versus less than 140 mm Hg (standard treatment). All major classes of antihypertensive agents were included. A subgroup of randomly assigned participants including, but not limited to, participants enrolled in an MRI substudy was then selected for a concurrent substudy of cognitive function (target 2800 participants). Each individual was assessed with a screening cognitive test battery and an extended cognitive test battery at baseline and biennially during the planned 4-year follow-up. The primary outcomes for this substudy were standardised composite scores for memory (Logical Memory I and II, Modified Rey-Osterrieth Complex Figure [immediate recall], and Hopkins Verbal Learning Test-Revised [delayed recall]) and processing speed (Trail Making Test and Digit Symbol Coding). SPRINT was registered with ClinicalTrials.gov , NCT01206062 . Findings From Nov 23, 2010, to Dec 28, 2012, 2921 participants (mean age 68·4 years [SD 8·6], 1080 [37%] women) who had been randomly assigned in SPRINT were enrolled in the substudy (1448 received intensive treatment and 1473 received standard treatment). SPRINT was terminated early due to benefit observed in the primary outcome (composite of cardiovascular events). After a median follow-up of 4·1 years (IQR 3·7–5·8), there was no between-group difference in memory, with an annual decline in mean standardised domain score of −0·005 (95% CI −0·010 to 0·001) in the intensive treatment group and −0·001 (–0·006 to 0·005) in the standard treatment group (between-group difference −0·004, 95% CI −0·012 to 0·004; p=0·33). Mean standardised processing speed domain scores declined more in the intensive treatment group (between-group difference −0·010, 95% CI −0·017 to −0·002; p=0·02), with an annual decline of −0·025 (–0·030 to −0·019) for the intensive treatment group and −0·015 (–0·021 to 0·009) for the standard treatment group. Interpretation Intensive treatment to lower systolic blood pressure did not result in a clinically relevant difference compared with standard treatment in memory or processing speed in a subgroup of participants from SPRINT. The effect of blood pressure lowering might not be evident in specific domains of cognitive function, but instead distributed across multiple domains. Funding National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Alzheimer's Association.

Objective This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. Methods Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. Results After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). Conclusions An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.

Background Individuals are often counseled to use behavioral weight loss strategies to reduce risk for cardiovascular disease (CVD). We examined whether any benefits for CVD risk from weight loss intervention extend uniformly to individuals across a range of underlying health states. Methods The time until first occurrence of a composite of fatal and nonfatal myocardial infarction and stroke, hospitalized angina, or CVD death was analyzed from 8 to 11 years of follow-up of 4,859 adults who were overweight or obese, aged 45–76 years with Type 2 diabetes. Individuals had been randomly assigned to either an intensive lifestyle intervention (ILI) or diabetes support and education (DSE). Participants were grouped by intervention assignment and a frailty index (FI) based on deficit accumulation, ordered from fewer (first tertile) to more (third tertile) deficits. Results Baseline FI scores were unrelated to intervention-induced weight losses and increased physical activity. The relative effectiveness of ILI on CVD incidence was inversely related to baseline FI in a graded fashion (p = .01), with relative benefit (hazard ratio = 0.73 [95% CI 0.55,0.98]) for individuals in the first FI tertile to no benefit (hazard ratio = 1.15 [0.94,1.42]) among those in the third FI tertile. This graded relationship was not seen for individuals ordered by age tertile (p = .52), and was stronger among participants aged 45–59 years (three-way interaction p = .04). Conclusions In overweight/obese adults with diabetes, multidomain lifestyle interventions may be most effective in reducing CVD if administered before individuals have accrued many age-related health deficits. However, these exploratory analyses require confirmation by other studies. Clinical Trial Registration NCT00017953

Key Points Question Are antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, compared with those that do not stimulate these receptors, associated with a lower risk of incident cognitive impairment? Findings In a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), this cohort study of 8685 patients found that prevalent use of medication regimens that contain exclusively angiotensin II receptor type 2 and 4–stimulating antihypertensives was associated with an approximately 25% lower risk of incident amnestic mild cognitive impairment or probable dementia during 4.8 years of follow-up. Meaning These results, if replicated in randomized clinical trials, suggest that certain antihypertensive medications could be used to prevent the development of cognitive decline., Importance Use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, compared with those that do not stimulate these receptors, has been associated with a lower risk of dementia. However, this association with cognitive outcomes in hypertension trials, with blood pressure levels in the range of current guidelines, has not been evaluated. Objective To examine the association between use of exclusively antihypertensive medication regimens that stimulate vs inhibit type 2 and 4 angiotensin II receptors on mild cognitive impairment (MCI) or dementia. Design, Setting, and Participants This cohort study is a secondary analysis (April 2011 to July 2018) of participants in the randomized Systolic Blood Pressure Intervention Trial (SPRINT), which recruited individuals 50 years or older with hypertension and increased cardiovascular risk but without a history of diabetes, stroke, or dementia. Data analysis was conducted from March 16 to July 6, 2021. Exposures Prevalent use of angiotensin II receptor type 2 and 4–stimulating or –inhibiting antihypertensive medication regimens at the 6-month study visit. Main Outcomes and Measures The primary outcome was a composite of adjudicated amnestic MCI or probable dementia. Results Of the 8685 SPRINT participants who were prevalent users of antihypertensive medication regimens at the 6-month study visit (mean [SD] age, 67.7 [11.2] years; 5586 [64.3%] male; and 935 [10.8%] Hispanic, 2605 [30.0%] non-Hispanic Black, 4983 [57.4%] non-Hispanic White, and 162 [1.9%] who responded as other race or ethnicity), 2644 (30.4%) were users of exclusively stimulating, 1536 (17.7%) inhibiting, and 4505 (51.9%) mixed antihypertensive medication regimens. During a median of 4.8 years of follow-up (95% CI, 4.7-4.8 years), there were 45 vs 59 cases per 1000 person-years of amnestic MCI or probable dementia among prevalent users of regimens that contained exclusively stimulating vs inhibiting antihypertensive medications (hazard ratio [HR], 0.76; 95% CI, 0.66-0.87). When comparing stimulating-only vs inhibiting-only users, amnestic MCI occurred at rates of 40 vs 54 cases per 1000 person-years (HR, 0.74; 95% CI, 0.64-0.87) and probable dementia at rates of 8 vs 10 cases per 1000 person-years (HR, 0.80; 95% CI, 0.57-1.14). Negative control outcome analyses suggested the presence of residual confounding. Conclusions and Relevance In this secondary analysis of SPRINT, prevalent users of regimens that contain exclusively antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors had lower rates of incident cognitive impairment. Residual confounding cannot be ruled out. If these results are replicated in randomized clinical trials, certain antihypertensive medications could be prioritized to prevent cognitive decline., This secondary analysis cohort study of Systolic Blood Pressure Intervention Trial (SPRINT) participants assesses the association between antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors with the risk of incident cognitive impairment.

Urine biomarker concentrations reflecting kidney tubule injury and dysfunction were not associated with brain MRI measures. Higher eGFR was associated with lower total brain cerebral blood flow. This is the first evaluation of the relationship of kidney tubule biomarkers with brain imaging by MRI in patients with CKD.

BACKGROUND: To examine the effect of intensive blood pressure control on the occurrence of subtypes of mild cognitive impairment (MCI) and determine the risk of progression to dementia or death. METHODS: Secondary analysis of a randomized trial of community-dwelling adults (≥50 years) with hypertension. Participants were randomized to a systolic blood pressure (SBP) goal of

BackgroundBeing homebound is independently associated with increased mortality but the homebound population is heterogeneous. In order to improve precision medicine, we analyzed potentially modifiable factors that contribute to homebound progression (from independent to needing assistance, to homebound), stratified by dementia status.MethodsUsing National Aging and Trends Survey (NHATS), a nationally-representative, longitudinal annual survey from 2011 to 2017 (n = 11,528), we categorized homebound progression if one transitioned from independent or needing assistance to homebound, including competing risks of institutionalization or death between 2011 and last year of data available for each unique respondent. Using proportional hazards regression, we calculated hazard ratios of potentially modifiable risk factors on homebound progression.ResultsDepressive symptoms, mobility impairment, and pain increased risk of homebound progression regardless of dementia status. Social isolation increased risk of homebound progression only among those without dementia at baseline.ConclusionFuture clinical care and research should focus on the treatment of depressive symptoms, mobility, and pain to potentially delay progression to homebound status.

Intermediate endpoints are needed to evaluate the effect of interventions targeting the biology of aging in clinical trials. A working group identified five blood-based biomarkers that may serve such a purpose as an integrated index. We evaluated the responsiveness of the panel to caloric restriction or aerobic exercise in the context of a randomized clinical trial conducted in patients with heart failure with preserved ejection fraction (HFpEF) with obese phenotype who were predominantly female. Obese HFpEF is highly prevalent in women, and is a geriatric syndrome whose disease pathology is driven by non-cardiac factors and shared drivers of aging. We measured serum Interleukin-6, TNF-α-receptor-I, growth differentiating factor-15, cystatin C, and N-terminal pro-b-type natriuretic peptide at baseline and after 20 weeks in older participants with stable obese HFpEF participating in a randomized, controlled, 2 × 2 factorial trial of caloric restriction and/or aerobic exercise. We calculated a composite biomarker index, summing baseline quintile scores for each biomarker, and analyzed the effect of the interventions on the index and individual biomarkers and their associations with changes in physical performance. This post hoc analysis included 88 randomized participants (71 women [81%]). The mean ± SD age was 66.6 ± 5.3 years, and body mass index (BMI) was 39.3 ± 6.3 kg/m(2). Using mixed models, mean values of the biomarker index improved over 20 weeks with caloric restriction (− 0.82 [Formula: see text] 0.58 points, p = 0.05), but not with exercise (− 0.28 [Formula: see text] 0.59 points, p = [Formula: see text] ), with no evidence of an interaction effect of CR [Formula: see text] EX [Formula: see text] time (p = 0.80) with adjustment for age, gender, and BMI. At baseline, the biomarker index was inversely correlated with 6-min walk distance, scores on the short physical performance battery, treadmill test peak workload and exercise time to exhaustion (all [Formula: see text] (s) = between − 0.21 and − 0.24). A reduction in the biomarker index was also associated with increased 4-m usual walk speed ([Formula: see text] (s) = − 0.31). Among older patients with chronic obese HFpEF, caloric restriction improved a biomarker index designed to reflect biological aging. Moreover, the index was associated with physical performance and exercise tolerance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-021-00509-9.

RATIONALE AND OBJECTIVE: The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in those with and without CKD. STUDY DESIGN: Neuroimaging substudy of a randomized trial. SETTING & PARTICIPANTS: A subset of participants in the Systolic Blood Pressure Intervention Trial who underwent brain MRI studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). INTERVENTION: Participants were randomly assigned to intensive (systolic BP 30 mg/g (N=151), the effects of intensive versus standard BP treatment on change in global cerebral blood flow, WMLs and total brain volume were 1.91 ml/100g/min (95% CI −3.01, 6.82), 0.003 cm(3) (asinh transformed, 95% CI −0.13, 0.13), and −7.0 cm(3) (95% CI −13.3, −0.3), respectively. The overall treatment effects on cerebral blood flow and total brain volume were not modified by baseline eGFR or UACR; however the effect on WMLs was attenuated in participants with albuminuria (interaction p-value 0.04). LIMITATIONS: Measurement variability due to multi-site design. CONCLUSIONS: Among hypertensive adults with primarily early kidney disease, intensive versus standard blood pressure treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive blood pressure treatment targets on brain health in persons with early kidney disease. FUNDING: The Systolic Blood Pressure Intervention Trial was funded by the National Institutes of Health (including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke), and this substudy was funded by the National Institutes of Diabetes and Digestive and Kidney Diseases. TRIAL REGISTRATION: SPRINT was registered at ClinicalTrials.gov with the study number NCT01206062.

Background: Guidelines recommend less stringent glycemic goals for older adults with type 2 diabetes mellitus (T2DM) and frailty or comorbidity. However, pragmatic, scalable approaches to identify candidates for de-intensification of T2DM regimens are lacking. Methods: Analysis of electronic health record (EHR) data for patients ≥65 years with T2DM from an accountable care organization as of 11/1/2020. Frailty was determined based on a 54-item electronic Frailty Index (eFI) derived from the EHR. Other data included the level of glycemic control, use of higher-risk medications regimens (active prescription of insulin, sulfonylurea, or combinations of the two), the incidence of emergency department (ED) visits and hospitalizations, and all-cause mortality. Results: Amongst 16973 patients, 53.9% were female, 77.8% white, with a mean age of 75.5 (SD=6.9) years. Based on the eFI, 6218 (36.6%) patients were classified as frail (eFI>0.21). During short-term follow-up (median=116 days), compared to fit patients (eFI≤0.10), patients classified as frail exhibited a higher incidence of ED visits and hospitalizations (hazard ratio = 3.05, 95% CI: 2.35 to 3.95) and all-cause mortality (hazard ratio = 7.33, 95% CI: 3.61 to 14.88). A large number of patients classified as frail based on the eFI had HbA1c levels Conclusions: The eFI is a pragmatic and scalable tool to identify vulnerable older adults with T2DM that may benefit from de-prescribing consistent with guideline recommendations. Disclosure C. Usoh: None. K. M. Lenoir: None. N. M. Pajewski: None. K. E. Callahan: None.

Background Low serum bicarbonate level is associated with increased mortality, but its role as a predictor of cardiovascular disease (CVD) is unclear. This study evaluates the association between serum bicarbonate concentration and CVD and whether the effect of intensive blood pressure (BP) lowering on CVD outcomes is modified by serum bicarbonate level. Methods The Systolic Blood Pressure Intervention Trial (SPRINT) randomized participants to a systolic BP target Results Over a median follow-up of 3.33 years (interquartile range 2.87–3.87 years), 618 (6.6%) participants experienced a primary CVD outcome. Participants with serum bicarbonate Conclusions In hypertensive individuals, serum bicarbonate level

Total medication burden (antihypertensive and nonantihypertensive medications) may be associated with poor systolic blood pressure (SBP) control. We investigated the association of baseline medication burden and clinical outcomes and whether the effect of the SBP intervention varied according to baseline medication burden in SPRINT (Systolic Blood Pressure Intervention Trial). Participants were randomized to intensive or standard SBP goal (below 120 or 140 mm Hg, respectively); n=3769 participants with high baseline medication burden (≥5 medications) and n=5592 with low burden (P interaction P interaction >0.5). Medication burden had minimal association with adherence or satisfaction. High baseline medication burden was associated with worse intensive SBP control and higher rates of cardiovascular disease events and serious adverse events. The relative benefits and risks of intensive SBP goals were similar regardless of medication burden. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01206062

Objective To examine the association of global cognitive function assessed via the Montreal Cognitive Assessment (MoCA) and deficiencies in instrumental activities of daily living (IADL) on the Functional Activity Questionnaire (FAQ) in hypertensive older adults in the Systolic Blood Pressure Intervention Trial (SPRINT). Methods In cross-sectional analysis, 9,296 SPRINT participants completed the MoCA at baseline. The FAQ was obtained from 2,705 informants for SPRINT participants scoring Results Participants who triggered FAQ administration were older, less educated, and more likely to be Black or Hispanic (p < 0.001). Sixty-one percent (n = 1,661) of participants’ informants reported no functional difficulties in IADLs. An informant report, however, of any difficulty on the FAQ was associated with lower MoCA scores after controlling for age, sex, race/ethnicity, and education (p < 0.05). Partial proportional odds regression indicates that participants scoring lower on the MoCA (in the 10th to Conclusions While lower global cognitive function was strongly associated with IADL deficits on FAQ, informants indicated no functional difficulties for the majority of SPRINT participants, despite low MoCA scores. These findings can help with designing future studies which aim to detect mild cognitive impairment and/or dementia in large, community-dwelling populations.

Background After the passage of the 21st Century Cures Act in the U.S., the Inclusion Across the Lifespan policy eliminates upper-age limits for research participation unless risk justified. Broader inclusion will necessitate the use of reliable instruments in research that characterize the health status and function of older adults with multiple chronic conditions. As there is a plethora of such instruments, the Geriatrics Research Instrument Library (GRIL) was developed as freely available online resource of data collection instruments commonly used in gerontological research. GRIL has been revised and updated by the Advancing Geriatrics Infrastructure and Network Growth (AGING) Initiative, a joint endeavor of the Health Care Systems Research Network (HCSRN) and the Older Americans Independence Centers (OAICs). Methods Extensive PubMed literature searches and domain expert feedback were utilized to inventory and update GRIL through the addition of instruments and compiling of instrument metadata. GRIL is hosted on the National Institute on Aging OAIC Coordinating Center website with a platform utilizing Microsoft Structured Query Language (SQL) and an Adobe ColdFusion application server. Tracking statistics are collected using Google Analytics. Results Presently, GRIL includes 175 instruments across 18 domains, including instrument metadata such as instrument description, copyright information, completion time estimates, keywords, available translations, and a link and reference to the original manuscript describing the instrument. The GRIL website includes user-friendly features such as mobile platforming and resource links. Conclusions GRIL provides a user-friendly public resource that facilitates clinical researchers in efficiently selecting appropriate instruments to measure clinical outcomes relevant to older adults across a full range of domains.

In a subgroup of 337 participants (mean age 64±9 years; 45% women) from the SPRINT (Systolic Blood Pressure Intervention Trial), where participants were randomly assigned to intensive treatment (target systolic blood pressure P 2 [95% CI, 1.34–1.41] versus 1.48 mm Hg/mL per m 2 [95% CI, 1.44–1.51], P =0.002) compared with standard treatment. No significant between-group differences were observed for aortic distensibility and compliance. We conclude that intensive treatment significantly attenuated increases in carotid-femoral pulse wave velocity and aortic elastance index. Attenuation of increases in aortic stiffness may be one of the mechanisms contributing to the benefit of intensive blood pressure treatment observed in SPRINT. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01206062.

Rationale: Cognitive impairment after critical illness is common in observational studies of older intensive care unit (ICU) survivors. The rate of screening for and diagnosis of cognitive impairment in ICU survivors in nonresearch settings is unknown. Objectives: To determine how often cognitive impairment was detected in older adults in the year after critical illness at an academic medical center as part of 1) the Medicare Annual Wellness Visit (AWV) and 2) routine clinical care. Methods: This study was a retrospective cohort study conducted at an urban academic medical center. The study included 696 patients aged 65 years and older admitted to the medical ICU between October 1, 2016, and October 1, 2018, and discharged alive. Patients were also required to have a health system–affiliated primary care provider. Patients were followed for 1 year. We defined cognitive impairment detected in the AWV as either an indicated diagnosis of cognitive impairment or dementia or patient, family, or provider indication of memory concerns during the AWV. We modeled the incidence of AWV completion and the detection of cognitive impairment using semiparametric additive models accounting for the competing risk of death. Results: Over 1 year of follow-up, the cumulative incidence of mortality was 23.0% (95% confidence interval [CI], 19.9–26.1%), with 24.7% (95% CI, 21.5–27.9%) completing the AWV. The cumulative incidence of cognitive impairment first detected through the AWV was 3.4% (95% CI, 1.8–5.0%) at 1 year, with a higher cumulative incidence for diagnoses of cognitive impairment or dementia first indicated via encounter diagnosis codes or the electronic health record problem list (5.9%; 95% CI, 3.9–7.9%). Conclusions: The results of our study suggest that the currently implemented AWV is unlikely to be an adequate mechanism for detecting cognitive impairment in a high-risk population such as those recovering from critical illness.

Background Cardiovascular health is of increasing concern to breast cancer survivors and their health care providers, as many survivors are more likely to die from cardiovascular disease than cancer. Implementing clinical decision support tools to address cardiovascular risk factor awareness in the oncology setting may enhance survivors’ attainment or maintenance of cardiovascular health. Objective We sought to evaluate survivors’ awareness of cardiovascular risk factors and examine the usability of a novel electronic health record enabled cardiovascular health tool from the perspective of both breast cancer survivors and oncology providers. Methods Breast cancer survivors (n=49) recruited from a survivorship clinic interacted with the cardiovascular health tool and completed pre and posttool assessments about cardiovascular health knowledge and perceptions of the tool. Oncologists, physician assistants, and nurse practitioners (n=20) who provide care to survivors also viewed the cardiovascular health tool and completed assessments of perceived usability and acceptability. Results Enrolled breast cancer survivors (84% White race, 4% Hispanic ethnicity) had been diagnosed 10.8 years ago (SD 6.0) with American Joint Committee on Cancer stage 0, I, or II (45/49, 92%). Prior to viewing the tool, 65% of survivors (32/49) reported not knowing their level for one or more cardiovascular health factors (range 0-4). On average, only 45% (range 0%-86%) of survivors’ known cardiovascular health factors were at an ideal level. More than 50% of survivors had ideal smoking status (45/48, 94%) or blood glucose level (29/45, 64%); meanwhile, less than 50% had ideal blood pressure (12/49, 24%), body mass index (12/49, 24%), cholesterol level (17/35, 49%), diet (7/49, 14%), and physical activity (10/49. 20%). More than 90% of survivors thought the tool was easy to understand (46/47, 98%), improved their understanding (43/47, 91%), and was helpful (45/47, 96%); overall, 94% (44/47 survivors) liked the tool. A majority of survivors (44/47, 94%) thought oncologists should discuss cardiovascular health during survivorship care. Most (12/20, 60%) oncology providers (female: 12/20, 60%; physicians: 14/20, 70%) had been practicing for more than 5 years. Most providers agreed the tool provided useful information (18/20, 90%), would help their effectiveness (18/20, 90%), was easy to use (20/20, 100%), and presented information in a useful format (19/20, 95%); and 85% of providers (17/20) reported they would use the tool most or all of the time when providing survivorship care. Conclusions These usability data demonstrate acceptability of a cardiovascular health clinical decision support tool in oncology practices. Oncology providers and breast cancer survivors would likely value the integration of such apps in survivorship care. By increasing awareness and communication regarding cardiovascular health, electronic health record–enabled tools may improve survivorship care delivery for breast cancer and ultimately patient outcomes.

Aims To assess whether there is an opportune window when intensive lifestyle intervention (ILI) benefits cognitive function. Methods Standardized cognitive assessments were collected following ≥8 years of either ILI or a control condition of diabetes support and education (DSE) in 3708 individuals, ages 45-76 years at enrollment, with type 2 diabetes and overweight or obesity. Frailty index (FI) scores were used to group individuals at baseline into tertiles according to their age-related health status. Linear models were used to describe intervention adherence and cognitive function, with interaction terms to examine the consistency of relationships among tertiles. Results Worse baseline FI scores were associated with poorer subsequent performance in tests of attention, processing speed, and executive function. No differences in any measure of cognitive function were observed between intervention groups within any FI tertile (all p > 0.10). Among individuals with worse baseline FI scores, weight gain was associated with poorer global cognitive function among participants assigned to DSE. There was no association between weight changes and cognitive function among participants assigned to ILI. Conclusions Among adults with type 2 diabetes and overweight/obesity, we found no evidence that there is a window of opportunity based on FI when ILI benefits cognitive function.

BACKGROUND: Frailty is associated with numerous post-operative adverse outcomes in older adults. Current pre-operative frailty screening tools require additional data collection or objective assessments, adding expense and limiting large-scale implementation. OBJECTIVE: To evaluate the association of an automated measure of frailty integrated within the Electronic Health Record (EHR) with post-operative outcomes for nonemergency surgeries. DESIGN: Retrospective cohort study. SETTING: Academic Medical Center. PARTICIPANTS: Patients 65 years or older that underwent nonemergency surgery with an inpatient stay 24 hours or more between October 8th, 2017 and June 1st, 2019. EXPOSURES: Frailty as measured by a 54-item electronic frailty index (eFI). OUTCOMES AND MEASUREMENTS: Inpatient length of stay, requirements for post-acute care, 30-day readmission, and 6-month all-cause mortality. RESULTS: Of 4,831 unique patients (2,281 females (47.3%); mean (SD) age, 73.2 (5.9) years), 4,143 (85.7%) had sufficient EHR data to calculate the eFI, with 15.1% categorized as frail (eFI > 0.21) and 50.9% pre-frail (0.10 < eFI ≤ 0.21). For all outcomes, there was a generally a gradation of risk with higher eFI scores. For example, adjusting for age, sex, race/ethnicity, and American Society of Anesthesiologists class, and accounting for variability by service line, patients identified as frail based on the eFI, compared to fit patients, had greater needs for post-acute care (odds ratio (OR) = 1.68; 95% confidence interval (CI) = 1.36–2.08), higher rates of 30-day readmission (hazard ratio (HR) = 2.46; 95%CI = 1.72–3.52) and higher all-cause mortality (HR = 2.86; 95%CI = 1.84–4.44) over 6 months’ follow-up. CONCLUSIONS: The eFI, an automated digital marker for frailty integrated within the EHR, can facilitate pre-operative frailty screening at scale.

Background:Patients with end-stage renal disease (ESRD) have a high burden of physical and psychological symptoms. Many remain unrecognized for long periods of time, particularly in older adults. The best strategy to monitor patient-reported outcome measures (PROMs) has not been identified.Objective:To assess the feasibility of implementing an iPad-based symptom assessment tool in older adults with ESRD on hemodialysis (HD).Methods:We designed an iPad application-delivery system for collecting electronic PROMs (ePROMs). Patient’s ≥60 years of age with ESRD on HD were recruited from a single outpatient dialysis unit. Feasibility was evaluated based on recruitment, retention, and the system usability score (SUS). Assessments were completed at baseline, 3 months, and 6 months after enrollment. ANOVA was used to assess longitudinal symptom variability.Results:Twenty-two patients (49% recruitment rate) were enrolled, with an 82% retention at 6 months. Mean age was 69.4 years (SD 6.6), 63.6% were female, and 81.8% were African American. Participants reported minimal difficulty in using the app, with an overall SUS score of 77.6. There were no significant relationships between demographic characteristics (age, race, or education) and SUS. Baseline SF-12 physical score and SF-12 mental score were 40.4 (SD 9.1) and 33.9 (SD 6.7), respectively. No significant changes were seen in longitudinal ePROMs of pain, depression, or anxiety; but was seen in the dialysis symptom index.Conclusion:In older patients with ESRD, collection of iPad-based ePROMs is feasible. This process can overcome inefficiencies associated with paper questionnaires and enable systematic monitoring of symptom burden.

Background: Clinic blood pressure (BP) is measured in the seated position, which can miss important home BP phenotypes such as low ambulatory BP (white coat effects) or high supine BP (nocturnal non-dippers). Orthostatic hypotension (OH) is determined based on BP measurements in both seated (or supine) and standing positions, and thus could theoretically identify these important phenotypes in clinic. Objective: To determine the association of OH with white coat effects or night-to-daytime systolic BP (SBP) Methods: SPRINT was a randomized trial testing the effects of intensive (0.9. Results: Of 897 adults (mean age 71.5 [SD, 9.5] yrs, 28.7% female, 28.0% black), 128 had OH at least once. Among those with OH, 14.8% had white coat effects versus 7.2% among those without OH. Moreover, 68.8% of those with OH demonstrated non-dipping patterns versus only 52.0% of those without OH. OH was positively associated with both white coat effects (OR=2.24; 95% CI: 1.28, 4.27) and higher night-to-daytime SBP (β=0.04; 95% CI: 0.02, 0.06) ( Table ). Conclusions: Clinic-based assessments of OH may be a useful tool for identifying BP phenotypes often missed with traditional seated BP assessments.

RATIONALE & OBJECTIVE: In prior research and in practice, the difference between estimated glomerular filtration rate (eGFR) calculated from cystatin C level and eGFR calculated from creatinine level has not been assessed for clinical significance and relevance. We evaluated whether these differences contain important information about frailty. STUDY DESIGN: A cohort analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS: 9,092 hypertensive SPRINT participants who had baseline measurements of serum creatinine, cystatin C, and frailty. EXPOSURE: eGFRs calculated using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (eGFR(cys) and eGFR(cr)), and eGFR(Diff), calculated as eGFR(cys) – eGFR(cr). OUTCOMES: A validated 35-item frailty index that included questionnaire data for general and physical health, limitations of activities, pain, depression, sleep, energy level, self-care, and smoking status, as well as medical history, cognitive assessment, and laboratory data. We defined frailty as frailty index score > 0.21 (range, 0-1). The incidence of injurious falls, hospitalizations, cardiovascular events, and mortality was also recorded. ANALYTICAL APPROACH: We used logistic regression to model the cross-sectional association of baseline eGFR(Diff) with frailty among all SPRINT participants. Adjusted proportional hazards regression was used to evaluate the association of eGFR(Diff) with adverse outcomes and mortality. RESULTS: Mean age was 68 ± 9 (SD) years, mean eGFR(cys) and eGFR(cr) were 73 ± 23 and 72 ± 20 mL/min/1.73 m(2), and mean eGFR(Diff) was 0.5 ± 15 mL/min/1.73 m(2). In adjusted models, each 1-SD higher eGFR(Diff) was associated with 24% lower odds of prevalent frailty (OR, 0.76; 95% CI, 0.71-0.81), as well as with lower incidence rate of injurious falls (HR, 0.84; 95% CI, 0.77-0.92), hospitalization (HR, 0.91; 95% CI, 0.88-0.95), cardiovascular events (HR, 0.89; 95% CI, 0.81-0.97), and all-cause mortality (HR, 0.71; 95% CI, 0.63-0.82); P < 0.01. LIMITATIONS: Gold-standard measure of kidney function and assessment of muscle mass were not available. CONCLUSIONS: The difference between eGFR(cys) and eGFR(cr) is associated with frailty and health status. Positive eGFR(Diff) is strongly associated with lower risks for longitudinal adverse outcomes and mortality, even after adjusting for chronic kidney disease stage and baseline frailty.

BACKGROUND Cardiovascular health is of increasing concern to breast cancer survivors and their health care providers, as many survivors are more likely to die from cardiovascular disease than cancer. Implementing clinical decision support tools to address cardiovascular risk factor awareness in the oncology setting may enhance survivors’ attainment or maintenance of cardiovascular health. OBJECTIVE We sought to evaluate survivors’ awareness of cardiovascular risk factors and examine the usability of a novel electronic health record enabled cardiovascular health tool from the perspective of both breast cancer survivors and oncology providers. METHODS Breast cancer survivors (n=49) recruited from a survivorship clinic interacted with the cardiovascular health tool and completed pre and posttool assessments about cardiovascular health knowledge and perceptions of the tool. Oncologists, physician assistants, and nurse practitioners (n=20) who provide care to survivors also viewed the cardiovascular health tool and completed assessments of perceived usability and acceptability. RESULTS Enrolled breast cancer survivors (84% White race, 4% Hispanic ethnicity) had been diagnosed 10.8 years ago (SD 6.0) with American Joint Committee on Cancer stage 0, I, or II (45/49, 92%). Prior to viewing the tool, 65% of survivors (32/49) reported not knowing their level for one or more cardiovascular health factors (range 0-4). On average, only 45% (range 0%-86%) of survivors’ known cardiovascular health factors were at an ideal level. More than 50% of survivors had ideal smoking status (45/48, 94%) or blood glucose level (29/45, 64%); meanwhile, less than 50% had ideal blood pressure (12/49, 24%), body mass index (12/49, 24%), cholesterol level (17/35, 49%), diet (7/49, 14%), and physical activity (10/49. 20%). More than 90% of survivors thought the tool was easy to understand (46/47, 98%), improved their understanding (43/47, 91%), and was helpful (45/47, 96%); overall, 94% (44/47 survivors) liked the tool. A majority of survivors (44/47, 94%) thought oncologists should discuss cardiovascular health during survivorship care. Most (12/20, 60%) oncology providers (female: 12/20, 60%; physicians: 14/20, 70%) had been practicing for more than 5 years. Most providers agreed the tool provided useful information (18/20, 90%), would help their effectiveness (18/20, 90%), was easy to use (20/20, 100%), and presented information in a useful format (19/20, 95%); and 85% of providers (17/20) reported they would use the tool most or all of the time when providing survivorship care. CONCLUSIONS These usability data demonstrate acceptability of a cardiovascular health clinical decision support tool in oncology practices. Oncology providers and breast cancer survivors would likely value the integration of such apps in survivorship care. By increasing awareness and communication regarding cardiovascular health, electronic health record–enabled tools may improve survivorship care delivery for breast cancer and ultimately patient outcomes.

BACKGROUND: Intensively treating hypertension may benefit cardiovascular disease and cognitive function, but at the short-term expense of reduced kidney function. METHODS: We investigated markers of kidney function and the effect of intensive hypertension treatment on incidence of dementia and mild cognitive impairment (MCI) in 9361 participants in the randomized Systolic Blood Pressure Intervention Trial, which compared intensive versus standard systolic BP lowering (targeting

IntroductionPatients with multimorbidity plus additional impairments (eg, mobility limitations, disability, cognitive impairments or frailty) are at the highest risk for poor healthcare outcomes. Advanced care planning (ACP) provides patients and their surrogates the opportunity to discuss their goals, values and priorities for healthcare—particularly in the context of end-of-life care. ACP discussions promote more person-centred care; however, it is currently underused. There is a tremendous need for systematic, scalable approaches to individualised ACP that promotes patient and family engagement. Here we describe the study protocol for a randomised effectiveness trial of a nurse navigator and informatics intervention designed to improve the documentation and quality of ACP discussions.Methods and analysisThis is a randomised, pragmatic, effectiveness trial; patients aged 65 years and older who have multimorbidity plus impairments in either physical function (eg, mobility limitations or disability) or cognition, and/or frailty within an affiliated Accountable Care Organization were eligible. The electronic health record was used to develop an automatic prescreening system for eligible patients (n=765) and participants were randomised in a 1:1 ratio to either the nurse navigator-led ACP pathway or usual care. Our primary outcomes are documentation of ACP discussions within the EHR along with the quality of ACP discussions. Secondary outcomes include a broad range of ACP actions (eg, usage of ACP billing codes, choosing a surrogate decision-maker and advance directive documentation). Outcomes will be measured over 12 months of follow-up.Ethics and disseminationThis study has been approved by the appropriate Institutional Review Boards and is guided by input from patient and clinical advisory boards. The results of this study will inform a scalable solution to ACP discussions throughout our healthcare system and statewide.Trials registration numberNCT03609658.

OBJECTIVES To evaluate the effect of intensive systolic blood pressure (SBP) control in older adults with hypertension, considering cognitive and physical function. DESIGN Secondary analysis. SETTING Systolic Blood Pressure Intervention Trial (SPRINT) PARTICIPANTS: Adults 80 years or older. INTERVENTION Participants with hypertension but without diabetes (N = 1167) were randomized to an SBP target below 120 mm Hg (intensive treatment) vs a target below 140 mm Hg (standard treatment). MEASUREMENTS We measured the incidence of cardiovascular disease (CVD), mortality, changes in renal function, mild cognitive impairment (MCI), probable dementia, and serious adverse events. Gait speed was assessed via a 4-m walk test, and the Montreal Cognitive Assessment (MoCA) was used to quantify baseline cognitive function. RESULTS Intensive treatment led to significant reductions in cardiovascular events (hazard ratio [HR] = .66; 95% confidence interval [CI] = .49-.90), mortality (HR = .67; 95% CI = .48-.93), and MCI (HR = .70; 95% CI = .51-.96). There was a significant interaction (P

Introduction Assessment of frailty is central to medical decision-making for older adults with newly diagnosed acute myeloid leukemia (AML), but validated frailty tools used at the point of care are lacking in this setting. An electronic frailty index (eFI), based on the theory of deficit accumulation, has been developed from routinely collected outpatient primary care data and embedded in the electronic health record (EHR) at Wake Forest Baptist Health (WFBH). The embedded eFI predicts hospitalization and mortality for older adults in a primary care cohort but has yet to be assessed for older adults with AML. The objectives of this analysis were to evaluate this tool among a cohort of newly diagnosed older adults with AML by determining the percent with available data to calculate a score, assessing the distribution of eFI categories (fit, pre-frail, and frail) at the time of treatment by therapy type, and exploring an association of eFI categories with survival. Methods Participants in this retrospective cohort study were adults aged ≥ 60 years with newly diagnosed AML from January 2018 - October 2020 who received treatment at WFBH. Patients with acute promyelocytic leukemia (APL) were excluded. Calculation of the EHR embedded eFI requires at least two ambulatory visits over a 2-year period. The eFI comprises demographic information, vital signs, smoking status, ICD-10 diagnosis codes, select outpatient laboratory measurements, and functional information (if available from past Medicare Annual Wellness Visits) during the 2 years prior to diagnosis. For this analysis, eFI was derived using date of treatment initiation as the reference date. Frailty status is categorized as fit (eFI ≤0.10), pre-frail (0.100.21) based on the proportion of deficits present over the total number evaluated. Intensive therapy is defined as receipt of anthracycline-based chemotherapy. Less-intensive therapy includes hypomethylating agents, low dose cytarabine, and/or venetoclax. The association of eFI category to therapy type was evaluated using a chi square test. Median survival was estimated using the Kaplan-Meier method and compared using log-rank tests. Results Among N=163 older adults treated for non-APL AML, 78 (43.3%) had a calculable eFI score. Among those with a calculable score, average age was 74.7 years (range 60 to 90), 68% were male, 90% were white, and average hematopoietic cell transplantation-comorbidity index (HCT-CI) score was 3.5 ± 2.7. Approximately 17% had favorable, 23% had intermediate, and 59% had unfavorable cytogenetics; 54% had secondary AML. Among those with a calculable eFI, 38.5% were classified as fit, 48.7% as pre-frail, and 12.8% as frail. For those who received intensive therapy (N=35), the majority were classified as fit (60%) and the remaining were pre-frail (40%); none were frail. The distribution of eFI categories differed for patients who received less-intensive therapies (N=43), with the majority classified as pre-frail (56%), a smaller proportion classified as fit (21%), and almost one-quarter as frail (23 %) (p Conclusions The embedded eFI derived from a longitudinal primary care population was not calculable using available data for most older adults with AML. This may reflect a skewed population referred to a Comprehensive Cancer Center that has higher-risk cytogenetics and/or does not receive primary care through the academic medical center. Among those with a calculable eFI, frailty categories significantly differed by treatment type. There was no association between survival and eFI category within treatment type in exploratory analyses. Our observations highlight the opportunity to adapt the EHR embedded eFI data capture process, including incorporation of inpatient labs, to the AML setting to effectively test the utility of a cancer-adapted passive digital marker for frailty. Disclosures Pardee: Rafael Pharmaceuticals: Consultancy, Research Funding; Karyopharm Pharmaceuticals: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees; BMS: Speakers Bureau; Pharmacyclics: Speakers Bureau.

RATIONALE AND OBJECTIVE: The associations of glomerular markers of kidney disease (eGFR and albuminuria) with frailty and cognition are well established. However, the relationship of kidney tubular injury and dysfunction with frailty and cognition are unknown. STUDY DESIGN: Observational cross-sectional study. SETTING & PARTICIPANTS: 2,253 participants with eGFR < 60 ml/min/1.73m(2) in the Systolic Blood Pressure Intervention Trial EXPOSURES: Eight urine biomarkers: Interleukin-18 [IL-18, pg/mL], kidney injury molecule-1 [KIM-1, pg/mL], neutrophil gelatinase-associated lipocalin [NGAL, ng/mL], chitinase-3-like protein-1 [YKL-40, pg/mL], monocyte chemoattractant protein-1 [MCP-1, pg/mL], α−1 microglobulin [α1M mg/g], beta-2 microglobulin [β2M ng/mL], and uromodulin [Umod ng/mL]. OUTCOMES: Frailty was measured using a previously validated frailty index (FI), categorized as fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21) and frail (FI > 0.21). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). ANALYTICAL APPROACH: Associations between kidney tubule biomarkers with categorical FI were evaluated using multinomial logistic regression with the fit group as the reference. Cognitive function was evaluated using linear regression. Models were adjusted for demographic, behavioral and clinical variables including eGFR and urine albumin. RESULTS: Three of the 8 urine biomarkers of tubule injury and dysfunction were independently associated with FI. Each two-fold higher level of urine KIM-1, a marker of tubule injury, was associated with a 1.22 [95% CI: 1.01, 1.49) fold greater odds of being in frail group. MCP-1, a marker of tubulo-interstitial fibrosis, was associated with a 1.30 [95% CI 1.04, 1.64] greater odds of being in frail group, and α1M, a marker of tubule re-absorptive capacity, was associated with a 1.48 [95% CI 1.11, 1.96] greater odds. These associations were independent of confounders including eGFR and urine albumin, and were stronger than those of urine albumin with frailty index (1.15 [95% CI 0.99, 1.34]). Higher urine β2M, another marker of tubule reabsorptive capacity, was associated with worse cognitive scores at baseline (β: ‒0.09; 95% CI ‒0.17, ‒0.01). Urine albumin was not associated with cognitive function. LIMITATIONS: Cross-sectional design, FI may not be generalizable in other populations. CONCLUSIONS: Urine biomarkers of tubule injury, fibrosis and proximal tubule reabsorptive capacity are variably associated with FI and worse cognition, independent of glomerular markers of kidney health. Future studies are needed to validate these results among other patient populations.