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Background APOL1 high-risk genotypes are associated with increased risk for hypertension-attributed kidney disease among Black adults in the United States. Biopsy studies show differences in kidney vasculature by APOL1 status; less is known about the variants' associations with systemic vascular and endothelial function. Whether APOL1 risk variants are associated with blood pressure (BP) is also uncertain. Methods and Results Using linear regression, we examined cross-sectional associations of APOL1 risk genotypes (high=2 risk alleles, low=0 or 1 risk allele) with subclinical measures of vascular function (small arterial elasticity, n=1586; large arterial elasticity, n=1586; ascending aortic distensibility, n=985) and endothelial function (flow-mediated dilation, n=777). Using linear mixed-effects models, we studied longitudinal associations of APOL1 risk genotypes with BP (n=1619), adjusting for age, sex, and African ancestry. Among 1619 (12% APOL1 high-risk) Black participants in MESA (Multi-Ethnic Study of Atherosclerosis), mean age was 62 years old, 58% had hypertension, and mean systolic BP was 131 mm Hg at baseline. At examination 1 (2000-2002), there was no significant difference in small arterial elasticity, large arterial elasticity, ascending aortic distensibility, or flow-mediated dilation in participants with APOL1 high- versus low-risk genotypes ( P >0.05 for all). Over a mean follow-up of 7.8 years, relative annual changes in systolic and diastolic BP and pulse pressure did not differ significantly by APOL1 risk status (between-group differences of -0.20, -0.14, and -0.25, respectively; P >0.05 for all). Conclusions Among Black participants in MESA, APOL1 high-risk genotypes were not associated with subclinical vascular and endothelial function or BP trajectories. The relationship of APOL1 with kidney disease may be intrinsic to the kidney rather than through peripheral effects on systemic vasculature or BP.

Objective: To determine whether cerebral small vessel disease or disability modify the effect of SBP treatment on cognitive and vascular outcomes in older patients with recent lacunar stroke., Methods: Participants aged at least 65 years of the Secondary Prevention of Small Subcortical Strokes Trial were randomized to a higher (130-149 mmHg) or lower (<130 mmHg) SBP target. The primary outcome was change in cognitive function (Cognitive Abilities Screening Instrument); secondary outcomes were incident mild cognitive impairment, stroke, major vascular events (all-stroke, myocardial infarction), and all-cause death. Results were stratified by severity of white matter hyperintensities (WMH; none/mild, moderate, severe) on baseline MRI, and by disability (no vs. at least one limitation in activities of daily living)., Results: One thousand, two hundred and sixty-three participants (mean age 73.8 ± 5.9 years, 40% women) were included. Participants with severe WMH or disability had worse cognitive function at baseline and after a mean follow-up of 3.9 years. No significant interactions existed between treatment group and effect modifiers (WMH, disability) for change in cognitive function (P for interaction 0.42 and 0.66, respectively). A lower SBP target appeared more beneficial among those with worse WMH burden for vascular outcomes (P for interaction = 0.01 for stroke and 0.03 for major vascular events)., Conclusion: There was no difference in the effect of lowering SBP to less than 130 mmHg on cognitive function by cerebral small vessel disease or disability among older adults with a history of lacunar stroke. Those with evidence of small vessel disease may derive greater benefit from lower SBP on prevention of subsequent vascular events., Trial Registration: Clinicaltrials.gov Identifier: NCT00059306.

Background and Objectives: We conducted a pilot, pragmatic, cluster-randomized trial to evaluate feasibility and preliminary effectiveness of screening for CKD using a triple-marker approach (creatinine, cystatin C, and albumin/creatinine ratio), followed by education and guidance, to improve care of hypertensive veterans in primary care. We used the electronic health record for identification, enrollment, intervention delivery, and outcome ascertainment., Design, Setting, Participants, & Measurements: We randomized 1819 veterans without diabetes but with hypertension (41 clusters) into three arms: ( 1 ) CKD screening followed by patient and provider education; ( 2 ) screening, education, plus pharmacist comanagement; or ( 3 ) usual care. The primary clinical outcome was BP change over 1 year. Implementation and process measures included proportion screened; CKD detection rate; and total and new use of renin-angiotensin system inhibitors, nonsteroidal anti-inflammatory drugs, and diuretics., Results: Median age was 68 years, 55% were white, 1658 (91%) had a prior creatinine measure, but only 172 (9%) had prior urine albumin/creatinine ratio, and 83 (5%) had a prior cystatin C measure. Among those in the intervention, 527 of 1215 (43%) were identified with upcoming appointments to have CKD screening. Of these, 367 (69%) completed testing. Among those tested, 77 (21%) persons had newly diagnosed CKD. After 1 year, change in systolic BP was -1 mm Hg (interquartile range, -11 to 11) in usual care, -2 mm Hg (-11 to 11) in the screen-educate arm, and -2 mm Hg (-13 to 10) in the screen-educate plus pharmacist arm; P =0.49. There were no significant differences in secondary outcomes in intention-to-treat analyses. In as-treated analyses, higher proportions of participants in the intervention arms initiated a renin-angiotensin system inhibitor (15% and 12% versus 7% in usual care, P =0.01) or diuretic (9% and 12% versus 4%, P =0.03)., Conclusions: The pragmatic design made identification, enrollment, and intervention delivery highly efficient. The limited ability to identify appointments resulted in inadequate between-arm differences in CKD testing rates to determine whether screening improves clinical outcomes., (Copyright © 2020 by the American Society of Nephrology.)

Heterogeneous exposure associations (HEAs) can be defined as differences in the association of an exposure with an outcome among subgroups that differ by a set of characteristics. In this article, we intend to foster discussion of HEAs in the epidemiologic literature and present a variant of the random forest algorithm that can be used to identify HEAs. We demonstrate the use of this algorithm in the setting of the association between systolic blood pressure and death in older adults. The training set included pooled data from the baseline examination of the Cardiovascular Health Study (1989-1993), the Health, Aging, and Body Composition Study (1997-1998), and the Sacramento Area Latino Study on Aging (1998-1999). The test set included data from the National Health and Nutrition Examination Survey (1999-2002). The hazard ratios ranged from 1.25 (95% confidence interval: 1.13, 1.37) per 10-mm Hg increase in systolic blood pressure among men aged ≤67 years with diastolic blood pressure greater than 80 mm Hg to 1.00 (95% confidence interval: 0.96, 1.03) among women with creatinine concentration ≤0.7 mg/dL and a history of hypertension. HEAs have the potential to improve our understanding of disease mechanisms in diverse populations and guide the design of randomized controlled trials to control exposures in heterogeneous populations., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To examine whether self-reported functional status modified the association between blood pressure (BP) and cognitive decline among older adults., Methods: The study included 2097 US adults aged 75 years and older from the Cardiovascular Health Study, followed for up to 6 years. Functional status was ascertained by self-reported limitation in activities of daily living (ADL; none vs. any). Cognitive function was assessed by the Modified Mini Mental State Exam (3MSE). We used linear mixed models to examine whether the presence of at least one ADL limitation modified the association between BP and cognitive decline. Potential confounders included demographics, physiologic measures, antihypertensive medication use and apolipoprotein E ε4 allele. We conducted stratified analyses for significant interactions between BP and ADL., Results: The association between BP and change in 3MSE differed by baseline ADL limitation. Among participants without ADL limitation, elevated systolic BP (≥140 mmHg) was associated with a 0.15 decrease (95% CI -0.24 to -0.07); P value for interaction less than 0.001, whereas in those with an ADL limitation, elevated systolic BP was independently associated with a 0.30 increase in 3MSE scores per year (95% CI 0.06-0.55). Elevated diastolic BP (≥80 mmHg) was associated with an increase in cognitive function in both groups, although the increase was greater in those with ADL limitation (0.47 points per year vs. 0.18 points per year, P value for interaction = 0.01)., Conclusion: Elevated BP appears to be associated with a decrease in cognitive scores among functioning older adults, and modest improvements in cognitive function among poorly functioning elders.

Background We aimed to determine whether cerebral white matter hyperintensities ( WMHs ) can distinguish stroke survivors susceptible to rapid kidney function decline from intensive blood pressure ( BP ) lowering. Methods and Results The SPS3 (Secondary Prevention of Small Subcortical Strokes) trial randomized participants with recent lacunar stroke to systolic BP targets of 130 to 149 and <130 mm Hg. We included 2454 participants with WMH measured by clinical magnetic resonance imaging at baseline and serum creatinine measured during follow-up. We tested interactions between BP target and WMH burden on the incidence of rapid kidney function decline (≥30% decrease from baseline estimated glomerular filtration rate at 1-year follow-up) and recurrent stroke. Rapid kidney function decline incidence was 11.0% in the lower- BP -target arm and 8.1% in the higher-target arm (odds ratio=1.40; 95% CI=1.07-1.84). Odds ratio for rapid kidney function decline between lower- and higher-target groups ranged from 1.26 in the lowest WMH tertile (95% CI , 0.80-1.98) to 1.71 in the highest tertile (95% CI , 1.05-2.80; P for interaction=0.65). Overall incidence of recurrent stroke was 7.9% in the lower-target arm and 9.6% in the higher-target arm (hazard ratio=0.80; 95% CI , 0.63-1.03). Hazard ratio for recurrent stroke in the lower-target group was 1.13 (95% CI , 0.73-1.75) within the lowest WMH tertile compared with 0.73 (95% CI , 0.49-1.09) within the highest WMH tertile ( P for interaction=0.04). Conclusions Participants with higher WMH burden appeared to experience greater benefit from intensive BP lowering in prevention of recurrent stroke. By contrast, intensive BP lowering increased the odds of kidney function decline, but WMH burden did not significantly distinguish this risk. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00059306.

Background: Many studies have focused on the association between a single blood pressure (BP) measurement and risk for adverse outcomes. However, the association of BP trajectories during young adulthood with subsequent decline in kidney function has not been well defined., Study Design: Observational cohort study., Setting & Participants: 3,429 participants in the Coronary Artery Risk Development in Young Adulthood (CARDIA) Study enrolled between the ages of 18 and 30 years., Predictors: BP slope during the first 10 years of participation in CARDIA, derived from linear mixed models incorporating all repeated BP measures., Outcome: Decline in estimated glomerular filtration rate (eGFR) during the interval between years 10 and 20 of CARDIA participation using cystatin C measured at years 10, 15, and 20., Results: Mean age of CARDIA participants at year 0 was 25.1 years, 56% were women, and 53% were white. Every 10-mmHg higher level of systolic (SBP) and diastolic BP (DBP) in year 10 was associated with change in eGFR of -0.09 (95% CI, -0.13 to -0.06) and -0.07 (95% CI, -0.12 to -0.03) mL/min/1.73m 2 per year, respectively. Every 10-mmHg increase in SBP slope between years 0 and 10 was associated with a subsequent -0.52 (95% CI, -1.02 to -0.03) mL/min/1.73m 2 per year change in kidney function after adjustment for comorbid conditions and SBP at year 10. Similarly, every 10-mmHg increase in DBP slope between years 0 and 10 was associated with a subsequent change in kidney function of -0.65 (95% CI, -1.23 to -0.07) mL/min/1.73m 2 per year, after adjustment for comorbid conditions and DBP in year 10., Limitations: Observational design., Conclusions: During young adulthood, increasing SBP and DBP are associated with a higher rate of subsequent kidney function decline, independent of BP measured at the beginning of eGFR assessment., (Copyright © 2018 National Kidney Foundation, Inc. All rights reserved.)

Background: While changes in blood pressure (BP) are independently associated with cardiovascular events, less is known about the association between changes in BP and subsequent changes in renal function in adults with an estimated glomerular filtration rate (eGFR) of >60 ml/min/1.73 m2., Methods: The present study included 3,920 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study who had ≥2 BP measurements during the first 5 years of MESA and had eGFR measurements at both year 5 and 10. Change in BP was estimated as the annualized slope of BP between year 0 and 5 based on linear mixed models (mean number of measurements = 4.0). Participants were then grouped into 1 of 3 categories based on the distribution of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) change (top 20%, middle 21-79%, bottom 20%). We calculated eGFR from cystatin C (ml/min/1.73 m2), estimated annual change in eGFR (ml/min/1.73 m2/year), and defined rapid kidney function decline as a >30% decrease in eGFR from year 5 to 10. We used multivariable logistic regression adjusting for year 0 demographic and clinical characteristics, including eGFR and BP, to determine associations of BP change with rapid kidney function decline., Results: Median age was 59 [interquartile range (IQR): 52, 67] and median eGFR at year 0 was 95.5 (IQR: 81.7, 105.9) ml/min/1.73 m2. Median SBP at year 0 was 111, 121, and 147 mm Hg for increasing, stable, and decreasing SBP change, respectively. Increasing SBP and widening PP change were each associated with higher odds of rapid kidney function decline compared with stable SBP and PP groups, respectively [odds ratio, OR 1.7 (95% confidence interval, CI 1.3, 2.4) for SBP; OR 1.4 (95% CI 1.1, 1.9) for PP]. Decreasing SBP was associated with rapid kidney function decline after adjusting for all covariates except for year 0 BP [OR 1.4 (95% CI 1.0, 1.8)], but this association was no longer statistically significant after adjustment for year 0 BP. There were no significant associations between DBP change and rapid decline in the fully adjusted models. Similar findings were seen with annual change in eGFR., Conclusions: Increasing SBP and widening PP over time were associated with greater risk for accelerated kidney function decline even at BP levels below established hypertension thresholds.

Purpose: We applied cluster analysis to identify discrete patterns of concomitant responses of systolic (SBP), diastolic (DBP) and pulse pressure (PP) during intensive BP lowering; and to evaluate their clinical relevance and association with risk of mortality, major vascular events (MVEs), and stroke., Material and Methods: We used an unsupervised cluster procedure to identify distinct patterns of BP change during the first 9 months of anti-hypertensive therapy intensification among 1,331 participants in the Secondary Prevention of Small Subcortical Strokes Trial who were previously randomized to lower BP target (SBP < 130 mm Hg) after lacunar stroke., Results: The cluster procedure partitioned participants into three groups in the lower SBP target arm, persons with: 1) mildly elevated baseline SBP and minimal visit-to-visit BP variability (mild reducers); 2) moderately elevated baseline SBP and moderate visit-to-visit BP variability (moderate reducers); and 3) very elevated baseline SBP with very large visit-to-visit BP variability during intensification (large reducers). In the lower SBP target group, moderate reducers had a higher risk of death (adjusted HR 1.6 [95% CI 1.0-2.7]), MVE (adjusted HR 2.1 [95% CI 1.4-3.2]), and stroke (adjusted HR 2.6[95% CI 1.7-4.1]) compared to mild reducers. Large reducers had the highest risk of death (adjusted HR 2.3 [95% CI 1.2-4.4]), but risk of MVE (HR = 1.7 [95%CI 0.9-3.1]) and stroke (HR = 1.6 [95%CI: 0.8-3.5]) were not statistically significantly different compared to mild reducers., Conclusions: Among persons with prior lacunar stroke, baseline BP levels, and BP variability in the setting of intensive BP lowering can identify discrete groups of persons at higher risk of adverse outcomes.

Objectives: Research has demonstrated that the association between high blood pressure and outcomes is attenuated among older adults with functional limitations, compared with healthier elders. However, it is not known whether these patterns vary by racial/ethnic group. We evaluated race/ethnicity-specific patterns of effect modification in the association between blood pressure and incident cardiovascular disease (CVD) by functional status., Setting: We used data from the Multi-Ethnic Study of Atherosclerosis (2002-2004, with an average of 8.8 years of follow-up for incident CVD). We assessed effect modification of systolic blood pressure and cardiovascular outcomes by self-reported physical limitations and by age., Participants: The study included 6117 participants (aged 46 to 87; 40% white, 27% black, 22% Hispanic and 12% Chinese) who did not have CVD at the second study examination (when self-reported physical limitations were assessed)., Outcome Measures: Incident CVD was defined as an incident myocardial infarction, coronary revascularisation, resuscitated cardiac arrest, angina, stroke (fatal or non-fatal) or death from CVD., Results: We observed weaker associations between systolic blood pressure (SBP) and CVD among white adults with physical limitations (incident rate ratio (IRR) per 10 mm Hg higher SBP: 1.09 (95% CI 0.99 to 1.20)) than those without physical limitations (IRR 1.29 (1.19, 1.40); P value for interaction <0.01). We found a similar pattern among black adults. Poor precision among the estimates for Hispanic or Chinese participants limited the findings in these groups. The attenuated associations were consistent across both multiplicative and additive scales, though physical limitations showed clearer patterns than age on an additive scale., Conclusion: Attenuated associations between high blood pressure and incident CVD were observed for blacks and whites with poor function, though small sample sizes remain a limitation for identifying differences among Hispanic or Chinese participants. Identifying the characteristics that distinguish those in whom higher SBP is associated with less risk of morbidity or mortality may inform our understanding of the consequences of hypertension among older adults., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Importance: Trials in patients with hypertension have demonstrated that intensive blood pressure (BP) lowering reduces the risk of cardiovascular disease and all-cause mortality but may increase the risk of chronic kidney disease (CKD) incidence and progression. Whether intensive BP lowering is associated with a mortality benefit in patients with prevalent CKD remains unknown., Objectives: To conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to investigate if more intensive compared with less intensive BP control is associated with reduced mortality risk in persons with CKD stages 3 to 5., Data Sources: Ovid MEDLINE, Cochrane Library, EMBASE, PubMed, Science Citation Index, Google Scholar, and clinicaltrials.gov electronic databases., Study Selection: All RCTs were included that compared 2 defined BP targets (either active BP treatment vs placebo or no treatment, or intensive vs less intensive BP control) and enrolled adults (≥18 years) with CKD stages 3 to 5 (estimated glomerular filtration rate <60 mL/min/1.73 m2) exclusively or that included a CKD subgroup between January 1, 1950, and June 1, 2016., Data Extraction and Synthesis: Two of us independently evaluated study quality and extracted characteristics and mortality events among persons with CKD within the intervention phase for each trial. When outcomes within the CKD group had not previously been published, trial investigators were contacted to request data within the CKD subset of their original trials., Main Outcome and Measure: All-cause mortality during the active treatment phase of each trial., Results: This study identified 30 RCTs that potentially met the inclusion criteria. The CKD subset mortality data were extracted in 18 trials, among which there were 1293 deaths in 15 924 participants with CKD. The mean (SD) baseline systolic BP (SBP) was 148 (16) mm Hg in both the more intensive and less intensive arms. The mean SBP dropped by 16 mm Hg to 132 mm Hg in the more intensive arm and by 8 mm Hg to 140 mm Hg in the less intensive arm. More intensive vs less intensive BP control resulted in 14.0% lower risk of all-cause mortality (odds ratio, 0.86; 95% CI, 0.76-0.97; P = .01), a finding that was without significant heterogeneity and appeared consistent across multiple subgroups., Conclusions and Relevance: Randomization to more intensive BP control is associated with lower mortality risk among trial participants with hypertension and CKD. Further studies are required to define absolute BP targets for maximal benefit and minimal harm.

Whether APOL1 polymorphisms contribute to the excess risk of hypertension among blacks is unknown. To assess this we evaluated whether self-reported race and, in blacks, APOL1 risk variants (high-risk [2 risk alleles] versus low-risk [0-1 risk allele]) were associated with longitudinal blood pressure. Blood pressure trajectories were determined using linear mixed-effects (slope) and latent class models (5 distinct groups) during 25 years of follow-up in the Coronary Artery Risk Development in Young Adults Study. Associations of race and APOL1 genotypes with blood pressure change, separately, using linear mixed-effects and multinomial logistic regression models, adjusting for demographic, socioeconomic, and traditional hypertension risk factors, anti-hypertensive medication use, and kidney function were evaluated. Among 1700 whites and 1330 blacks (13% APOL1 high-risk, mean age 25 years; 46% male) mean mid-, ([systolic + diastolic blood pressure]/2), systolic, and diastolic blood pressures were 89, 110, and 69 mm Hg, respectively. One percent of participants used anti-hypertensive medications at baseline. Compared to whites, blacks, regardless of APOL1 genotype, had significantly greater increases in mid-blood pressure and were more likely to experience significantly increasing mid-blood pressure trajectories with adjusted relative risk ratios of 5.21 and 7.27 for moderate-increasing and elevated-increasing versus low-stable blood pressure, respectively. Among blacks, longitudinal mid-blood pressure changes and mid-blood pressure trajectory classification were similar by APOL1 risk status. Modeling systolic and diastolic blood pressure as outcomes yielded similar findings. From young adulthood to mid-life, blacks have greater blood pressure increases versus whites that are not fully explained by traditional risk factors. Thus APOL1 variants are not associated with longitudinal blood pressure in blacks., (Copyright © 2017 International Society of Nephrology. All rights reserved.)

Objective: To examine whether grip strength, gait speed, and the combination of the two physical functioning measures modified the association of systolic BP (SBP) and diastolic BP (DBP) with mortality., Design: Nationally representative cohort study., Setting: Health and Retirement Study., Participants: 7,492 U.S. adults aged ≥65 years., Measurements: Grip strength was measured by a hand dynamometer and classified as normal (≥16 kg for female; ≥26 kg for male) and weak. Gait speed was assessed over a 98.5-inch walk and classified as non-slow (≥0.60 m/s for female; ≥0.52 m/s for male) and slow., Results: Over an average follow-up time of 6.0 years, 1,870 (25.0%) participants died. After adjustment for socio-demographic, behavioral, and clinical measures, elevated SBP (≥150 mmHg) and DBP (≥90 mmHg) was associated with a 24% (95% CI, 7-43%) and 25% (95% CI, 5-49%) higher mortality among participants with normal grip strength. In contrast, elevated SBP and DBP was associated with a 6% (95% CI, 31 to -27%) and a 16% (95% CI, 46 to -26%) lower mortality among those with weak grip strength (P-values of interactions: both=.07). The inverse relations between BP with death were most pronounced among slow walkers with weak grip strength. The HRs of elevated SBP and DBP for death was 0.85 (95% CI, 0.56-1.29) and 0.53 (95% CI, 0.30-0.96), respectively, and was substantially different from non-slow walkers with normal grip strength (HR = 1.24 and 1.15, respectively; P-values of interactions: both <.001). Therefore, associations of BP with death varied modestly by gait speed., Conclusion: Grip strength modified the association of BP with death. Combination of grip strength and gait speed has incremental value for modifying the association of BP with death., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Background: Common blood pressure (BP) trajectories are not well established in elderly persons, and their association with clinical outcomes is uncertain., Methods: We used hierarchical cluster analysis to identify discrete BP trajectories among 4,067 participants in the Cardiovascular Health Study using repeated BP measures from years 0 to 7. We then evaluated associations of each BP trajectory cluster with all-cause mortality, incident cardiovascular disease (CVD, defined as stroke or myocardial infarction) (N = 2,837), and incident congestive heart failure (HF) (N = 3,633) using Cox proportional hazard models., Results: Median age was 77 years at year 7. Over a median 9.3 years of follow-up, there were 2,475 deaths, 659 CVD events, and 1,049 HF events. The cluster analysis identified 3 distinct trajectory groups. Participants in cluster 1 (N = 1,838) had increases in both systolic (SBP) and diastolic (DBP) BPs, whereas persons in cluster 2 (N = 1,109) had little change in SBP but declines in DBP. Persons in cluster 3 (N = 1,120) experienced declines in both SBP and DBP. After multivariable adjustment, clusters 2 and 3 were associated with increased mortality risk relative to cluster 1 (hazard ratio = 1.21, 95% confidence interval: 1.06-1.37 and hazard ratio = 1.20, 95% confidence interval: 1.05-1.36, respectively). Compared to cluster 1, cluster 3 had higher rates of incident CVD but associations were not statistically significant in demographic-adjusted models (hazard ratio = 1.16, 95% confidence interval: 0.96-1.39). Findings were similar when stratified by use of antihypertensive therapy., Conclusions: Among community-dwelling elders, distinct BP trajectories were identified by integrating both SBP and DBP. These clusters were found to have differential associations with outcomes., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: Higher blood pressure during young adulthood may increase cardiovascular and kidney disease risk later in life. This study examined the association of cumulative systolic blood pressure (SBP) exposure during young adulthood through midlife with urine albumin-to-creatinine ratios (ACR) measured during midlife., Methods: We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a biracial cohort recruited in 4 urban areas during years 1985-1986. Cumulative SBP was calculated as the average SBP between 2 exams multiplied by years between exams over 20 year years. ACR was measured 20 years after baseline when participants were age 43-50 years (midlife). A generalized additive model was used to examine the association of log ACR as a function of cumulative SBP with adjustment for covariates including SBP measured concurrently with ACR., Results: Cumulative SBP ranged from a low of 1,671 to a high of 3,260 mm Hg. Participants in the highest cumulative SBP quartile were more likely to be male (61.4% vs. 20.7%; P < 0.001), Black (61.5% vs. 25.6%; P < 0.001) and have elevated ACR (18.7% vs. 4.8%; P < 0.001) vs. lowest quartile. Spline regression curves of ACR vs. cumulative SBP demonstrated an inflection point in ACR with cumulative SBP levels >2,350 mm Hg with linear increases in ACR above this threshold. Adjusted geometric mean ACR values were significantly higher with cumulative SBP ≥2,500 vs. <2500 (9.18 [1.06] vs. 6.92 [1.02]; P < 0.0001)., Conclusion: Higher SBP during young adulthood through midlife is associated with higher ACR during midlife., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: Level of blood pressure (BP) is strongly associated with cardiovascular (CV) events and mortality. However, it is questionable whether mean BP can fully capture BP-related vascular risk. Increasing attention has been given to the value of visit-to-visit BP variability., Methods: We examined the association of visit-to-visit BP variability with mortality, incident myocardial infarction (MI), and incident stroke among 1,877 well-functioning elders in the Health, Aging, and Body Composition Study. We defined visit-to-visit diastolic BP (DBP) and systolic BP (SBP) variability as the root-mean-square error of person-specific linear regression of BP as a function of time. Alternatively, we counted the number of considerable BP increases and decreases (separately; 10mm Hg for DBP and 20mm Hg for SBP) between consecutive visits for each individual., Results: Over an average follow-up of 8.5 years, 623 deaths (207 from CV disease), 153 MIs, and 156 strokes occurred. The median visit-to-visit DBP and SBP variability was 4.96 mmHg and 8.53 mmHg, respectively. After multivariable adjustment, visit-to-visit DBP variability was related to higher all-cause (hazard ratio (HR) = 1.18 per 1 SD, 95% confidence interval (CI) = 1.01-1.37) and CV mortality (HR = 1.35, 95% CI = 1.05-1.73). Additionally, individuals having more considerable decreases of DBP (≥10mm Hg between 2 consecutive visits) had higher risk of all-cause (HR = 1.13, 95% CI = 0.99-1.28) and CV mortality (HR = 1.30, 95% CI = 1.05-1.61); considerable increases of SBP (≥20mm Hg) were associated with higher risk of all-cause (HR = 1.18, 95% CI = 1.03-1.36) and CV mortality (HR = 1.37, 95% CI = 1.08-1.74)., Conclusions: Visit-to-visit DBP variability and considerable changes in DBP and SBP were risk factors for mortality in the elderly., (© American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The present study aimed to (i) evaluate previous observations that the association of blood pressure (BP) with outcomes varies by gait speed and (ii) evaluate the association of subsequent changes in BP and cardiovascular risk., Methods: Participants included 2,669 adults aged 70-79 years in the Health, Aging, and Body Composition (Health ABC) study. Gait speed was dichotomized at ≥1.0 m/s over a 20-m test at baseline. BP was measured at baseline, and changes in BP over 5 years were evaluated using (i) population-based trajectory models and (ii) intraindividual mean and slope., Results: Over a mean of 10 years, there were 1,366 deaths, 336 first myocardial infarctions, and 295 first strokes. There was a differential pattern of association between baseline systolic BP and diastolic BP and outcomes among brisk and moderate speed walkers. For example, the association between higher diastolic BP and mortality was in the protective direction for moderate speed walkers (hazard ratio = 0.75; 95% confidence interval: 0.63, 0.91) per 10 mmHg higher, whereas it was null in brisk walkers (hazard ratio = 1.05; 95% confidence interval: 0.98, 1.11), p value for interaction .01. The 5-year population-based trajectories did not add important information beyond baseline BP. Individual slopes in both systolic BP and diastolic BP did not appear to have important associations with the outcomes., Conclusions: In this study, we found that the overall level of BP was associated with myocardial infarction, stroke, and death, and this association differed by baseline gait speed, whereas changes in BP were not associated with these outcomes., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The effect of intensive blood pressure (BP) lowering on kidney function among individuals with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established., Methods and Results: Among 2610 participants randomized to a lower (<130 mm Hg) versus higher (130-149 mm Hg) systolic BP target with repeated measures of serum creatinine, we evaluated differences by study arm in annualized eGFR decline and rapid decline (eGFR decline >30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with stroke, major vascular events, and the composite of stroke, death, major vascular events, or myocardial infarction using multivariable Cox regression, separately and jointly including a test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11 years; 949 participants (36%) were diabetic; and mean eGFR was 80±19 mL·min(-1)·1.73 m(-2). At 9 months, achieved systolic BP was 137±15 versus 127±14 mm Hg in the higher versus lower BP group, and differences were maintained throughout follow-up (mean, 3.2 years). Compared with the higher target, the lower BP target had a -0.50-mL·min(-1)·1.73 m(-2) per year (95% confidence interval [CI], -0.79 to -0.21) faster eGFR decline. Differences were most pronounced during the first year (-2.1 mL·min(-1)·1.73 m(-2); 95% CI, -0.97 to -3.2), whereas rates of eGFR decline did not differ after year 1 (-0.095; 95% CI, -0.47 to 0.23). A total of 313 patients (24%) in the lower BP group had rapid kidney function decline compared with 247 (19%) in the higher BP group (odds ratio, 1.4; 95% CI, 1.1-1.6). Differences in rapid decline by treatment arm were apparent in the first year (odds ratio, 1.4; 95% CI, 1.1-1.8) but were not significant after year 1 (odds ratio, 1.0; 95% CI, 0.73-1.4). Rapid decline was associated with higher risk for stroke, major vascular events, and composite after full adjustment among individuals randomized to the higher BP target (stroke hazard ratio, 1.93; 95% CI, 1.15-3.21) but not the lower BP arm (stroke hazard ratio, 0.93; 95% CI, 0.50-1.75; all P for interaction <0.06)., Conclusions: In patients with prior lacunar stroke and relatively preserved kidney function, intensive BP lowering was associated with a greater likelihood of rapid kidney function decline. Differences were observed primarily during the first year of antihypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering., Clinical Trial Registration: URL: http://www.clinicalTrials.gov. Unique identifier: NCT00059306., (© 2016 American Heart Association, Inc.)

Unlabelled: Studies suggest a J-shaped association between blood pressure and cardiovascular events in the setting of intensive systolic blood pressure control; whether there is a similar association with stroke remains less well established. The Secondary Prevention of Small Subcortical Strokes was a randomized trial to evaluate higher (130-149 mm Hg) versus lower (<130 mm Hg) systolic blood pressure targets in participants with recent lacunar infarcts. We evaluated the association of mean achieved blood pressure, 6 months after randomization, and recurrent stroke, major vascular events, and all-cause mortality. After a mean follow up of 3.7 years, there was a J-shaped association between achieved blood pressure and outcomes; the lowest risk was at ≈124 and 67 mm Hg systolic and diastolic blood pressure, respectively. For example, above a systolic blood pressure of 124 mm Hg, 1 standard deviation higher (11.1 mm Hg) was associated with increased mortality (adjusted hazard ratio: 1.9; 95% confidence interval: 1.4, 2.7), whereas below this level, this relationship was inverted (0.29; 0.10, 0.79), P<0.001 for interaction. Above a diastolic blood pressure of 67 mm Hg, a 1 standard deviation higher (8.2 mm Hg) was associated with an increased risk of stroke (2.2; 1.4, 3.6), whereas below this level, the association was in the opposite direction (0.34; 0.13, 0.89), P=0.02 for interaction. The lowest risk of all events occurred at a nadir of ≈120 to 128 mm Hg systolic blood pressure and 65 to 70 mm Hg diastolic blood pressure. Future studies should evaluate the impact of excessive blood pressure reduction, especially in older populations with preexisting vascular disease., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306., (© 2015 American Heart Association, Inc.)

The importance of high blood pressure (BP) and the effect of BP lowering in older adults remain controversial due to the mixed evidence in this population. Frailty status may resolve the apparently conflicting findings and identify subpopulations who share common risk. Emerging evidence demonstrates that low BP is associated with poor outcomes in older frail adults or those with poor functional status. In contrast, in non-frail older adults, low BP appears beneficial. Frail older adults may be at increased risk of hypotension, serious fall injuries, and polypharmacy. Additionally, peripheral BP may not be the best prognostic measure in this population. The majority of clinical practice guidelines give little recommendation for frail older adults, which is likely due to their systematic underrepresentation in randomized controlled trials. Future studies need to consider modifications to safely include frail older adults, and guidelines should consider inclusion of evidence beyond randomized controlled trials.

Whether limitation in the ability to perform activities of daily living (ADL) or gait speed can identify elders in whom the association of systolic and diastolic blood pressure (DBP) with cardiovascular events (CVDs) and death differs is unclear. We evaluated whether limitation in ADL or gait speed modifies the association of systolic blood pressure or DBP with incident CVD (n=2358) and death (n=3547) in the Cardiovascular Health Study. Mean age was 78±5 and 21% reported limitation in ≥1 ADL. There were 778 CVD and 1289 deaths over 9 years. Among persons without and those with ADL limitation, systolic blood pressure was associated with incident CVD: hazard ratio [HR] (per 10-mm Hg increase) 1.08 (95% confidence interval, 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL modified the association of DBP with incident CVD. Among those without ADL limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for DBP >80, compared with <65 mm Hg. Among those with ADL limitation, DBP was inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66 to 80 mm Hg and HR 0.49 (0.25, 0.94) for DBP >80, compared with DBP ≤65. Among people with ADL limitation, a DBP of 66 to 80 had the lowest risk of death, HR 0.72 (0.57, 0.91), compared with a DBP of ≤65. Associations did not vary by 15-feet walking speed. ADL can identify elders in whom diastolic hypotension is associated with higher cardiovascular risk and death. Functional status, rather than chronologic age alone, should inform design of hypertension trials in elders., (© 2014 American Heart Association, Inc.)

Background: Although hypertension contributes to kidney dysfunction in the general population, the contributions of elevated systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) to kidney function decline in community-dwelling older adults are unknown., Methods: We used linear and logistic regression to examine the separate and combined associations of SBP, DBP, and PP at baseline with kidney function decline among 4,365 older adults in the Cardiovascular Health Study. We used cystatin C to estimate glomerular filtration rate on 3 occasions over 7 years of follow-up. We defined rapid decline ≥ 3ml/min/year., Results: Average age was 72.2 and mean (standard deviation) SBP, DBP, and PP were 135 (21), 71 (11), and 65 (18) mm Hg, respectively. SBP and PP, rather than DBP, were most significantly associated with kidney function decline. In adjusted linear models, each 10-mm Hg increment in SBP and PP was associated with 0.13ml/min/year (-0.19, -0.08, P < 0.001) and 0.15-ml/min/year faster decline (-0.21, -0.09, P < 0.001), respectively. Each 10-mm Hg increment in DBP was associated with a nonsignificant 0.10-ml/min/year faster decline (95% confidence interval, -0.20, 0.01). In adjusted logistic models, SBP had the strongest associations with rapid decline, with 14% increased hazard of rapid decline (95% confidence interval, 10% to 17%, P < 0.01) per 10mm Hg. In models combining BP components, only SBP consistently had independent associations with rapid decline., Conclusions: Our findings suggest that elevated BP, particularly SBP, contributes to declining kidney function in older adults.

Background: In some older adults, higher blood pressure (BP) is associated with a lower risk of mortality. We hypothesized that higher BP would be associated with greater mortality in high-functioning elders and lower mortality in elders with lower functional status., Methods: Participants were 1,562 Latino adults aged 60-101 years in the Sacramento Area Latino Study on Aging. Functional status was measured by self-reported walking speed, and BP was measured by automatic sphygmomanometer. Death information was determined from vital statistics records., Results: There were 442 deaths from 1998 to 2010; 53% were cardiovascular. Mean BP levels (mmHg) varied across fast, medium, and slow walkers: 136, 139, and 140 mmHg (systolic), p = .02 and 75, 76, and 77 mmHg (diastolic), p = .08, respectively. The relationship between systolic BP and mortality varied by self-reported walking speed: The adjusted hazard ratio for mortality in slow walkers was 0.96 per 10 mmHg higher systolic BP (95% confidence interval: 0.89, 1.02) and 1.29 (95% confidence interval: 1.08, 1.55) in fast walkers (p value for interaction <.001). We found a similar pattern for diastolic BP, although the interaction did not reach statistical significance; the adjusted hazard ratio per 10 mmHg higher diastolic BP was 0.89 (95% confidence interval: 0.78, 1.02) in slow walkers and 1.20 (95% confidence interval: 0.82, 1.76) in fast walkers (p value for interaction = .06)., Conclusions: In high-functioning older adults, elevated systolic BP is a risk factor for all-cause mortality. If confirmed in other studies, the assessment of functional status may help to identify persons who are most at-risk for adverse outcomes related to high BP.

Background: The association of subclinical vascular disease and early declines in kidney function has not been well studied., Study Design: Prospective cohort study., Setting & Participants: Multi-Ethnic Study of Atherosclerosis (MESA) participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) with follow-up of 5 years., Predictors: Pulse pressure, small (SAE) and large arterial elasticity (LAE), and flow-mediated dilation., Outcomes: Kidney function decline., Measurements: SAE and LAE were measured by pulse contour analysis of the radial artery. Kidney function was assessed by eGFR based on serum creatinine (eGFR(SCr)) and cystatin C (eGFR(SCysC))., Results: For 4,853 adults, higher pulse pressure and lower SAE and LAE had independent and linear associations with faster rates of kidney function decline. Compared with persons with pulse pressure of 40-50 mm Hg, eGFR(SCysC) declines were 0.29 (P = 0.006), 0.56 (P < 0.001), and 0.91 (P < 0.001) mL/min/1.73 m(2)/y faster in persons with pulse pressure of 50-60, 60-70, and >70 mm Hg, respectively. Compared with the highest quartile of SAE (most elastic), eGFR(SCysC) declines were 0.26 (P = 0.009), 0.35 (P = 0.001), and 0.70 (P < 0.001) mL/min/1.73 m(2)/y faster for the second, third, and fourth quartiles, respectively. For LAE, compared with the highest quartile, eGFR(SCysC) declines were 0.28 (P = 0.004), 0.58 (P < 0.001), and 0.83 (P < 0.001) mL/min/1.73 m(2)/y faster for each decreasing quartile of LAE. Findings were similar for eGFR(SCr). In contrast, for 2,997 adults with flow-mediated dilation and kidney function measures, flow-mediated dilation was not associated significantly with kidney function decline. For every 1-standard deviation greater flow-mediated dilation, eGFR(SCysC) and eGFR(SCr) changed by 0.05 (P = 0.3) and 0.06 mL/min/1.73 m(2)/y (P = 0.04), respectively., Limitations: We had no direct measure of GFR, in common with nearly all large population-based studies., Conclusions: Higher pulse pressure and lower arterial elasticity, but not flow-mediated dilation, were associated linearly and independently with faster kidney function decline in persons with eGFR ≥60 mL/min/1.73 m(2). Future studies should investigate whether treatments to decrease the stiffness of large and small arteries may slow the rate of kidney function loss., (Copyright © 2011 National Kidney Foundation, Inc. All rights reserved.)

The extent to which chronic kidney disease (CKD) affects achievement of blood pressure targets is not comprehensively understood. We evaluated the effects of CKD (estimated glomerular filtration rate: <60 mL/min per 1.73 m(2)) on achievement of blood pressure control (nondiabetic: <140/90 mm Hg; diabetic: <130/85 mm Hg) using data from the Guidelines for Drug Therapy of Hypertension Trial. This 15-month study obtained outpatient blood pressures from 3 Veteran's Affairs institutions. Among 9985 subjects with hypertension, we evaluated the association of CKD with achieved control and antihypertensive medication use. We also explored the association between the number of antihypertensives and systolic, diastolic, and pulse pressure. After 15 months, 41% of participants met blood pressure targets. CKD was not associated with control (adjusted odds ratio: 1.04; 95% CI: 0.93 to 1.15). However, CKD was associated with higher odds of use of >or=3 medications among nondiabetic subjects (odds ratio: 1.46; 95% CI: 1.25 to 1.71) and diabetic subjects (odds ratio: 1.40; 95% CI: 1.17 to 1.66). A significant interaction was observed between CKD and the number of antihypertensives as determinants of diastolic and pulse pressures. Among non-CKD participants, a greater number of antihypertensives (0 compared with 4) was associated with wider pulse pressure (Delta5.2 mm Hg; P<0.001), mainly because of higher systolic pressures (Delta3.6 mm Hg; P=0.001). Among participants with CKD, although greater numbers of antihypertensives were associated with even wider pulse pressures (Delta8.3 mm Hg; P<0.001), this was primarily because of lower diastolic pressures (Delta4.8 mm Hg; P<0.01). Among participants with CKD, greater use of antihypertensives was associated with lower diastolic pressures. Given recent evidence suggesting adverse effects of diastolic hypotension, these results suggest potential risks in patients with CKD from aggressive attempts to control systolic blood pressure.

Background: Control of hypertension is paramount in treating chronic kidney disease. The relationship between kidney function and blood pressure (BP) components has been studied in persons with diagnosed CKD, diabetes, or hypertension. Whether kidney function in the normal range is associated with systolic BP (SBP), diastolic BP (DBP), and pulse pressure is unclear., Methods: We evaluated the association between kidney function and each BP component using cystatin C and 24-h creatinine clearance (CrCl) among 906 participants in the Heart and Soul Study., Results: We observed that SBP was linearly associated with cystatin C concentrations (1.19+/-0.55 mm Hg increase per 0.4 mg/L cystatin C, P=.03) across the range of kidney functions. In contrast, using CrCl, SBP was significantly associated with kidney function only in subjects with CrCl<60 mL/min (6.4+/-2.13 mm Hg increase per 28 mL/min, P=.003) but not >60 mL/min (0.36+/-0.77 mm Hg per 28 mL/min, P=.64). Slopes differed significantly (for spline term P=.001). We found that DBP was not associated with cystatin C (0.34+/-0.40 mm Hg per 0.4 mg/L cystatin, P=.39) or CrCl (0.62+/-0.44 mm Hg per 28 mL/min clearance, P=.16). Pulse pressure was linearly associated with cystatin C (1.28+/-0.55 mm Hg per 0.4 mg/L cystatin, P=.02) and with CrCl<60 mL/min (7.27+/-2.16 mm Hg per 28 mL/min, P=.001)., Conclusions: Both SBP and pulse pressure were significantly associated with kidney function across a wide range of cystatin C concentrations, even in subjects with presumably normal kidney function, by creatinine-based measures. Cystatin C may provide new insights into the association of CKD and hypertension, a relationship that may be an underappreciated barrier to hypertension control.

Although improved control of hypertension is known to attenuate progression of chronic kidney disease (CKD), little is known about the adequacy of hypertension treatment in adults with CKD in the United States. Using data from the Fourth National Health and Nutrition Survey, we assessed adherence to national hypertension guideline targets for patients with CKD (blood pressure <130/80 mm Hg), we assessed control of systolic (<130 mm Hg) and diastolic (<80 mm Hg) blood pressure, and we evaluated determinants of adequate blood pressure control. Presence of CKD was defined as glomerular filtration rate <60 mL/min per 1.73 m2 or presence of albuminuria (albumin:creatinine ratio >30 microg/mg). Multivariable logistic regression with appropriate weights was used to determine predictors of inadequate hypertension control and related outcomes. Among 3213 participants with CKD, 37% had blood pressure <130/80 mm Hg (95% confidence interval [CI], 34.5% to 41.8%). Of those with inadequate blood pressure control, 59% (95% CI, 54% to 64%) had systolic >130 mm Hg, with diastolic < or =80 mm Hg, whereas only 7% (95% CI, 3.9 to 9.8%) had a diastolic pressure >80 mm Hg, with systolic blood pressure < or =130 mm Hg. Non-Hispanic black race (odds ratio [OR], 2.4; 95% CI, 1.5 to 3.9), age >75 years (OR, 4.7; 95% CI, 2.7 to 8.2), and albuminuria (OR, 2.4; 95% CI, 1.4 to 4.1) were independently associated with inadequate blood pressure control. We conclude that control of hypertension is poor in participants with CKD and that lack of control is primarily attributable to systolic hypertension. Future guidelines and antihypertensive therapies for patients with CKD should target isolated systolic hypertension.

BACKGROUND: Urine biomarkers of kidney tubule health may distinguish aspects of kidney damage that cannot be captured by current glomerular measures. Associations of clinical risk factors with specific kidney tubule biomarkers have not been evaluated in detail. METHODS: We performed a cross-sectional study in the Systolic Blood Pressure Intervention Trial among 2,436 participants with a baseline estimated glomerular filtration rate (eGFR)

BACKGROUND: Inadequate treatment of high blood pressure (BP) can lead to preventable adverse events in nursing home residents, while excessive treatment can lead to associated harms. METHODS: Data were extracted from the VA electronic health record and Bar Code Medication Administration system on 40,079 long-term care residents aged ≥65 years from October 2006 through September 2018 (FY2007-2018). Hypertension prevalence at admission was identified by ICD code(s) in the year prior, and antihypertensive medication use was defined as administration ≥50% of days. BP measures were averaged over 2-year epochs. RESULTS: The age-standardized prevalence of hypertension diagnosis at admission increased from 75.2% in FY2007-2008 to 85.1% in FY2017-2018 (p-value for trend 140/90 mmHg. Future research is needed to better understand the benefits and harms of BP control in nursing home residents.

BackgroundAging is accompanied by an overall dysregulation of many dynamic physiologic processes including those related to blood pressure (BP). While year-to-year BP variability is associated with cardiovascular events and mortality, no studies have examined this trend with more frequent BP assessments. Our study objective is to take the next step to examine week-to-week BP dynamics-pattern, variability, and complexity-before death.MethodsUsing a retrospective study design, we assessed BP dynamics in the 6 months before death in long-term nursing home residents between 1 October 2006 and 30 September 2017. Variability was characterized using SD and mean squared error after adjusting for diurnal variations. Complexity (i.e., amount of novel information in a trend) was examined using Shannon's entropy (bits). Generalized linear models were used to examine factors associated with overall BP variability.ResultsWe identified 17,953 nursing home residents (98.0% male, 82.5% White, mean age 80.2 years, and mean BP 125.7/68.6 mm Hg). Despite a slight trend of decreasing systolic week-to-week BP over time (delta = 7.2 mm Hg), week-to-week complexity did not change in the 6 months before death (delta = 0.02 bits). Average weekly BP variability was stable until the last 3-4 weeks of life, at which point variability increased by 30% for both systolic and diastolic BP. Factors associated with BP variability include average weekly systolic/diastolic BP, days in the nursing home, days in the hospital, and changes to antihypertensive medications.ConclusionsWeek-to-week BP variability increases substantially in the last month of life, but complexity does not change. Changes in care patterns may drive the increase in BP variability as one approaches death.

ObjectivesTo evaluate the incidence of deprescribing of antihypertensive medication among older adults residing in Veterans Affairs (VA) nursing homes for long-term care and rates of deprescribing after potentially triggering events.DesignRetrospective cohort study.Setting and participantsLong-term care residents aged 65 years and older admitted to a VA nursing home from 2006 to 2019 and using blood pressure medication at admission.MethodsData were extracted from the VA electronic health record, and Centers for Medicare & Medicaid Services Minimum Data Set and Bar Code Medication Administration. Deprescribing was defined on a rolling basis as a reduction in the number or dose of antihypertensive medications, sustained for ≥2 weeks. We examined potentially triggering events for deprescribing, including low blood pressure (

Background We aimed to determine whether cerebral white matter hyperintensities ( WMHs ) can distinguish stroke survivors susceptible to rapid kidney function decline from intensive blood pressure ( BP ) lowering. Methods and Results The SPS3 (Secondary Prevention of Small Subcortical Strokes) trial randomized participants with recent lacunar stroke to systolic BP targets of 130 to 149 and

BackgroundWhether screening for chronic kidney disease (CKD) can improve the care of persons at high risk for complications remains uncertain. We describe the design and early implementation experience of a pilot, cluster-randomized pragmatic trial to evaluate the feasibility, implementation, and effectiveness of a "triple marker" CKD screening program (creatinine, cystatin C and albumin to creatinine ratio) for improving care among hypertensive veterans seen in primary care at one Veterans Administration Hospital.Methods/designNon-diabetic hypertensive veterans age 18-80 without known CKD were randomized in clusters determined by primary care provider (unit of randomization) into three arms. Usual care will be compared with two incrementally intensified treatment strategies: (1) screen for CKD followed by patient and provider education or (2) screen-educate plus a clinical pharmacist-led CKD and BP management program. The primary clinical outcome is systolic blood pressure (BP) change from baseline. Secondary clinical outcome is BP control. The primary process outcomes is triple marker screening (across three arms), and secondary process outcomes include use of inhibitors of the renin-angiotensin system (ACE/ARB) overall and in persons with albuminuria, CKD recognition by PCP, use of non-steroidal anti-inflammatory drugs (NSAIDs) and NSAID education by PCP. The design uses the Veterans Health Administration electronic health record (EHR) to identify participants, deliver the interventions and ascertain study outcomes. Assessment of the program implementation will use the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Study duration is 12 months.ResultsA total of 1,819 patients have been randomized within 41 provider clusters. The median age (interquartile range) is 68 years (61-72), and 99% of participants are male. Approximately 16% are Black, and 5% Hispanic. In the first 6 months of the trial, 434 triple marker screening tests have been ordered, and 217(50%) have been tested. A total of 48 new CKD cases have been identified among those tested, for a preliminary yield of 22%.ConclusionWe have successfully implemented a pragmatic protocol that uses the EHR to identify and characterize eligible participants, deliver the intervention, and ascertain study outcomes with high rates of participation by providers and patients. Results from this study can guide design of pragmatic trials in the field of CKD.Trial registrationNCT01978951 ; Date or Registration: 1/17/2014.

ObjectivesTo evaluate the potential for gait speed to inform decisions regarding optimal systolic blood pressure targets in older adults.DesignForecasting study from 2014 to 2023 using the Cardiovascular Disease Policy Model, a Markov model.SettingNational Health and Nutrition Examination Survey.ParticipantsU.S. adults aged 60-94 stratified into fast walking, slow walking, and poor functioning (noncompleters) based on measured gait speed.MeasurementsLowering SBP to a target of 140 or 150 mmHg was modeled in persons with (secondary prevention) and without (primary prevention) a history of coronary heart disease or stroke. Based on clinical trials and observational studies, it was projected that slow-walking and poor-functioning participants would have greater noncardiovascular mortality. Myocardial infarctions (MIs), strokes, deaths, cost, and disability-adjusted life years (DALYs) were measured.ResultsRegardless of gait speed, it was projected that secondary prevention to a systolic blood pressure (SBP) of 140 mmHg would prevent more events and save more money than secondary prevention to 150 mmHg. Similarly, primary prevention to 140 mmHg in fast-walking adults was projected to prevent events and save money. In slow-walking adults, primary prevention to 150 mmHg was projected to prevent MIs and strokes and save DALYs but was cost saving only in men; intensification to 140 mmHg is of uncertain benefit in slow-walking individuals. Primary prevention in poor-functioning adults to a target of 140 or 150 mmHg SBP is projected to decrease DALYs.ConclusionThe most cost-effective SBP target varies according to history of cardiovascular disease and gait speed in persons aged 60-94. These projections highlight the need for better estimates of the benefits and harms of antihypertensive medications in a diverse group of older adults, because the net benefit is sensitive to the characteristics of the population treated.

ObjectiveHigh circulating concentrations of parathyroid hormone (PTH) have been associated with increased risks of hypertension, left ventricular hypertrophy, congestive heart failure and cardiovascular mortality. Impaired arterial function is a potential mechanism for these associations. We tested whether serum PTH concentration is associated with measures of arterial function.DesignCross-sectional study.ParticipantsA total of 6545 persons without clinical cardiovascular disease participating in the community-based Multi-Ethnic Study of Atherosclerosis.MeasurementsBrachial artery flow-mediated dilation (FMD) as well as aortic pulse pressure and arterial pulse parameters derived from Windkessel modelling of the radial pressure waveform.ResultsHigher serum PTH concentration was associated with lower brachial artery FMD (mean difference -0·09% per 10 pg/ml PTH), higher aortic pulse pressure (0·53 mmHg per 10 pg/ml) and reduced Windkessel capacitive index C1 (large artery elasticity, -0·12 ml/mmHg × 10 per 10 pg/ml), adjusting for potential confounding variables (all P-values ≤ 0·001). These relationships were independent of serum calcium concentration, serum 25-hydroxyvitamin D concentration and estimated glomerular filtration rate and were consistent across relevant participant subgroups. Associations of PTH with aortic pulse pressure and capacitive index C1 were attenuated after adjustment for blood pressure. Serum PTH concentration was not associated with the oscillatory index C2 (small artery elasticity).ConclusionsHigher serum PTH concentration was associated with impaired endothelial function, increased aortic pulse pressure and decreased capacitive index C1 in a large, diverse, community-based population. These relationships may help explain previously observed associations of elevated PTH with cardiovascular disease.

BackgroundGiven the increasing costs and poor outcomes of end-stage renal disease (ESRD), we sought to identify risk factors for ESRD in people with preserved estimated glomerular filtration rate (eGFR), with or without albuminuria, who were at high risk of ESRD.MethodsThis cohort study included participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP) with eGFR ≥ 60 mL/min/1.73 m(2) at baseline stratified by the presence or absence of albuminuria. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate eGFR. Urine was tested for albuminuria by semiquantitative dipstick. The outcome was the development of treated chronic kidney failure, defined as initiation of maintenance dialysis therapy or kidney transplantation, determined by linkage to the US Renal Data System. We used a Cox model with the Fine-Gray method to assess risk factors for treated chronic kidney failure while accounting for the competing risk of death.ResultsDuring a median follow-up of 4.8 years, 126 of 13,923 participants with albuminuria (16/10,000 patient-years) and 56 of 109,135 participants without albuminuria (1.1/10,000 patient-years) developed treated chronic kidney failure. Diabetes was a strong risk factor for developing treated chronic kidney failure in participants with and without albuminuria (adjusted HRs of 9.3 [95% CI, 5.7-15.3] and 7.8 [95% CI, 4.1-14.8], respectively). Black race, lower eGFR, and higher systolic blood pressure also were associated with higher adjusted risks of developing treated chronic kidney failure.ConclusionsIn a diverse high-risk cohort of KEEP participants with preserved eGFR, we showed that diabetes, higher systolic blood pressure, lower eGFR, and black race were risk factors for developing treated chronic kidney failure irrespective of albuminuria status, although the absolute risk of kidney failure in participants without albuminuria was very low. Our findings support testing for kidney disease in high-risk populations, which often have otherwise unrecognized kidney disease.

BackgroundThe association of hypertension and mortality is attenuated in elderly adults. Walking speed, as a measure of frailty, may identify which elderly adults are most at risk for the adverse effects of hypertension. We hypothesized that elevated blood pressure (BP) would be associated with a greater risk of mortality in faster-, but not slower-, walking older adults.MethodsParticipants included 2340 persons 65 years and older in the National Health and Nutrition Examination Survey, 1999-2000 and 2001-2002. Mortality data were linked to death certificates in the National Death Index. Walking speed was measured over a 20-ft (6 m) walk and classified as faster (≥ 0.8 m/s [n = 1307]), slower (n = 790), or incomplete (n = 243). Potential confounders included age, sex, race, survey year, lifestyle and physiologic variables, health conditions, and antihypertensive medication use.ResultsAmong the participants, there were 589 deaths through December 31, 2006. The association between BP and mortality varied by walking speed. Among faster walkers, those with elevated systolic BP (≥ 140 mm Hg) had a greater adjusted risk of mortality compared with those without (hazard ratio [HR], 1.35; 95% CI, 1.03-1.77). Among slower walkers, neither elevated systolic nor diastolic BP (≥ 90 mm Hg) was associated with mortality. In participants who did not complete the walk test, elevated BP was strongly and independently associated with a lower risk of death: HR, 0.38; 95% CI, 0.23-0.62 (systolic); and HR, 0.10; 95% CI, 0.01-0.81 (diastolic).ConclusionsWalking speed could be a simple measure to identify elderly adults who are most at risk for adverse outcomes related to high BP.

Background: Inadequate treatment of high blood pressure (BP) can lead to preventable adverse events in nursing home residents, while excessive treatment can lead to associated harms. Methods: Data were extracted from the VA electronic health record and Bar Code Medication Administration system on 40,079 long‐term care residents aged ≥65 years from October 2006 through September 2018 (FY2007‐2018). Hypertension prevalence at admission was identified by ICD code(s) in the year prior, and antihypertensive medication use was defined as administration ≥50% of days. BP measures were averaged over 2‐year epochs. Results: The age‐standardized prevalence of hypertension diagnosis at admission increased from 75.2% in FY2007‐2008 to 85.1% in FY2017‐2018 (p‐value for trend <0.001). Rates of BP treatment and control among residents with hypertension at admission declined slightly over time (p‐values for trend <0.001) but remained high (80.3% treated in FY2017‐2018, 80.1% with average BP <140/90 mmHg). The age‐adjusted prevalence of chronic low BP (average <90/60 mmHg) also declined from 11.1% in FY2007‐2008 to 4.7% in FY2017‐2018 (p‐value for trend <0.001). Persons identified as Black race or Hispanic ethnicity and those with a history of diabetes, stroke, and renal disease were less likely to have an average BP <140/90 mmHg. Conclusions: Hypertension is well controlled in VA nursing homes, and recent trends of less intensive BP control were accompanied by a lower prevalence of chronic low BP. Nonetheless, some high‐risk populations have average BP levels >140/90 mmHg. Future research is needed to better understand the benefits and harms of BP control in nursing home residents. [ABSTRACT FROM AUTHOR]

Background Hypertension has been implicated as a smoking-related risk factor for cardiovascular disease but the dose–response relationship is incompletely described. Hispanics, who often have relatively light smoking exposures, have been understudied in this regard. Methods We used data from a 6-year follow-up study of US Hispanic adults aged 18–76 to address the dose–response linking cigarette use with incident hypertension, which was defined by measured blood pressure above 140/90 mm Hg or initiation of antihypertensive medications. Adjustment was performed for potential confounders and mediators, including urinary albumin-to-creatinine ratio which worsened over time among smokers. Results Current smoking was associated with incident hypertension, with a threshold effect above 5 cumulative pack-years of smoking (vs. never smokers, hazard ratio for hypertension [95% confidence interval] of 0.95 [0.67, 1.35] for 0–5 pack-years, 1.47 [1.05, 2.06] for 5–10 pack-years, 1.40 [1.00, 1.96] for 10–20 pack-years, and 1.34 [1.09, 1.66] for ≥20 pack-years, P = 0.037). In contrast to current smokers, former smokers did not appear to have increased risk of hypertension, even at the highest cumulative pack-years of past exposure. Conclusions The results confirm that smoking constitutes a hypertension risk factor in Hispanic adults. A relatively modest cumulative dose of smoking, above 5 pack-years of exposure, raises risk of hypertension by over 30%. The increased hypertension risk was confined to current smokers, and did not increase further with higher pack-year levels. The lack of a smoking–hypertension association in former smokers underscores the value of smoking cessation. [ABSTRACT FROM AUTHOR]

Arterial dysfunction has been linked to decline in cardiac function and increased risk of cardiovascular disease events. We calculated the value of arterial function, measured at baseline (2000-2002), in predicting time to first coronary heart disease (CHD) event (median follow-up, 10.2 years) among participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Measures included the following: C1 and C2, derived from diastolic pulse contour analysis from the radial artery blood pressure waveform obtained by tonometry (n = 6,336); carotid distensibility and Young's elastic modulus at the carotid artery, derived from carotid artery ultrasonography (n = 6,531 and 6,528); and aortic distensibility, measured using cardiac magnetic resonance imaging (n = 3,677). After adjustment, the hazard ratio for a CHD event per standard-deviation increment in arterial function was 0.97 (95% confidence interval (CI): 0.86, 1.10) for C1, 0.73 (95% CI: 0.63, 0.86) for C2, 0.98 (95% CI: 0.86, 1.11) for carotid distensibility, 0.99 (95% CI: 0.90, 1.09) for Young's modulus, and 0.90 (95% CI: 0.74, 1.10) for aortic distensibility. We examined the area under the receiver operating characteristic curve for the model with full adjustment plus the addition of each measure individually. C2 provided additional discrimination for the prediction of CHD (area under the curve = 0.736 vs. 0.743; P = 0.04). Lower C2 was associated with a higher risk of future CHD events. [ABSTRACT FROM AUTHOR]

Functional status may be useful for identifying older adults who benefit from lower blood pressure. We examined whether functional status modifies the effect of antihypertensive treatment among older adults. METHODS Post hoc analyses of the Systolic Hypertension in the Elderly Program (SHEP), a randomized trial of antihypertensive therapy vs. placebo (1985-1991) in 4,736 adults aged 60 years or older with isolated systolic hypertension. Outcomes were all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, falls, and symptoms of hypotension. The effect modifier of interest was functional status, assessed by self-reported physical ability limitation (PAL). RESULTS Among persons with no PAL, those receiving treatment had a lower rate of death, CV death, and MI compared with placebo (4.0, 2.9, and 4.2 per 1,000 person-years lower, respectively). In contrast, among persons with a PAL, those receiving treatment had a higher rate of death, CV death, and MI compared with placebo (8.6, 5.3, and 2.7 per 1,000 person-years higher, respectively). These patterns persisted in Cox models, although interaction terms did not reach statistical significance. Treatment remained protective for stroke regardless of functional status. The rate of falls associated with treatment differed by functional status; incidence-rate ratio = 0.81, 95% confidence interval (CI) = (0.66, 0.99), and 1.32, 95% CI = (0.87, 2.00) in participants without and with a PAL, respectively, in models adjusted for demographics and baseline blood pressure (P-value for interaction, 0.04). CONCLUSIONS Functional status may modify the effect of antihypertensive treatment on MI, mortality, and falls, but not stroke, in older adults. Functional status should be examined in other trial settings. [ABSTRACT FROM AUTHOR]

The article discusses a study to determine whether the relationship between elevated blood pressure (BP) and mortality varies by objectively measured walking speed among elderly adults. The study included data from participants who were 65 years and older who were given standardized questionnaires that were administered in the home and followed by a detailed physical examination at a mobile examination center. It suggests that the association of BP with mortality varied with the walking speed.

The article discusses a research study on the treatment of hypertension and end-stage renal disease (ESRD) in patients with chronic kidney disease (CKD). Studied were the associations of pulse pressure (PP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) with the risk of ESRD in 16,129 participants in the Kidney Early Evaluation Program (KEEP). Conclusions indicated that high SBP is contributing to the risk of ESRD progression starting at 140 millimeters of mercury (mm Hg).

BackgroundDisorders in mineral metabolism are associated with risk for cardiovascular disease (CVD) events in patients with kidney disease as well as in the general population. This risk is thought to be mediated, in part, through the mechanism of stiffening of the arteries.MethodsThe objective of this study was to evaluate the relationships between serum calcium, phosphorus, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D levels and arterial pulse wave velocity (aPWV) among 2,229 community-dwelling elderly persons participating in the Health Aging and Body Composition (Health ABC) study.ResultsThe mean age of the participants was 72 years; 52% were woman, 39% were black, and 17% had chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2). In parallel unadjusted analyses, the following associations were observed: 2.86% greater aPWV per 12 ng/ml (s.d.) lower 25-hydroxyvitamin D (95% confidence interval −4.38%, −1.31%), 3.04% greater aPWV per 28 pg/ml (s.d.) higher iPTH (95% confidence interval 1.42−4.68%), and 2.37% lower aPWV per 0.5 mg/dl (s.d.) higher phosphorus (95% confidence interval −3.90% to - 0.81%). Except for phosphorus, these associations were attenuated and rendered no longer statistically significant after adjustment for demographic risk factors, clinical site, season, medications and other CVD risk factors. The results were similar in men and women and were not dependent on the presence of CKD.ConclusionsAmong well-functioning community-dwelling elderly persons, only serum phosphorus was associated with aPWV; and this association was in the opposite direction of the one hypothesized. Factors other than vascular stiffening may mediate the relationship between disordered mineral metabolism and CVD events in community-living elders.American Journal of Hypertension (2011). doi:10.1038/ajh.2011.43 [ABSTRACT FROM AUTHOR]

Introduction: We have previously demonstrated that high blood pressure is not associated with mortality in elders with impairments in functional status. Whether functional status modifies the effectiveness of treatment to lower blood pressure is not known. Methods: The Systolic Hypertension in the Elderly Program (SHEP) was a multicenter, randomized, double-blind, placebo-controlled trial of 4,736 adults aged 60 and older with isolated systolic hypertension. Participants were randomized to chlorthalidone +/- atenolol or reserpine or matching placebo and followed for an average of 4.5 years. Functional limitation was assessed by the selfreported inability to do any one of the following activities: i) heavy work around the house, ii) walk up and down stairs, or iii) walk a half a mile. Analyses were conducted by intention-to-treat within the post-hoc subgroups. Results: There was a pattern of effect modification by functional limitation, where the association of active treatment was attenuated or inverted in persons with functional limitation compared with those without (Table). The interaction of treatment and functional limitation was strongest for the outcomes of myocardial infarction: hazard ratio = 0.57 (95% confidence interval (CI): 0.40, 0.81) and 1.33 (95% CI: 0.57, 3.07) in persons without and with functional limitation, respectively; and for mortality: 0.78 (95% CI: 0.66, 1.01) and 1.27 (95% CI: 0.83, 1.95) in persons without and with functional limitation, respectively. Conclusions: Antihypertensive therapy appears less effective in persons with selfreported functional limitation. More evidence is needed to guide optimal blood pressure control in elderly adults with functional limitation. [ABSTRACT FROM AUTHOR]

Introduction: Microvascular abnormalities delay the access of glucose and insulin to target tissues, which may lead to insulin resistance, a major mechanism underlying type 2 diabetes (DM). C2, derived from the radial artery pulse wave is a measure designed to estimate the global arterial function of the more distal part of the arterial circulation. C2 is inversely associated with visceral fat, incident hypertension and cardiovascular disease (CVD) events (i.e., lower C2 suggests pathology). We studied the association of C2 with new onset of diabetes in subjects free of overt CVD. Methods: 5214 multi-ethnic participants, initially aged 45- 84 years, with no DM at baseline underwent radial artery pulse wave applanation tonometry. C2 was derived from radial artery pulse contour analysis. Incident DM was diagnosed by fasting glucose ≥126 mg/dl or antidiabetic medicine in any of 4 clinic visits over 10 years. The associations of C2 were estimated using proportional hazards regression in model 1 adjusted for demographics (age, sex, and race/ethnicity), while model 2 additionally adjusted for baseline values of height, heart rate, BMI, resting blood pressure and antihypertensive medication, lipids and lipid-lowering medication, renal function, and 5 inflammatory biomarkers Results: Mean C2 at baseline was 4.58 ± 2.85 mL/mm Hgх100. Incident DM occurred in 651 participants during 10 years of follow-up. After adjustment for demographics, the Hazard ratio (HR) for incident DM, per standard deviation of C2, was 0.90 (95% CI: 0.82, 0.99, P = 0.03). After additional adjustment for CV risk factors and inflammatory markers, the corresponding HR was 0.88 (95% CI: 0.80 - 0.98, p = 0.02). For the lowest vs highest C2 quartile, the HR was 1.35 (1.03 - 1.79). No race/ethnic interaction with C2 was observed. Conclusions: In a multi-ethnic population free of overt CVD, C2, a derivative of the radial artery pulse contour, predicted incident DM beyond demographics, CVD risk factors and inflammatory markers. Changes in arterial pulse wave morphology may already manifest a long-term risk trajectory for type 2 diabetes independently of the classical risk factors. [ABSTRACT FROM AUTHOR]