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Objectives: The Dietary Approaches to Stop Hypertension (DASH) diet reduces blood pressure, but the mechanisms underlying DASH diet-blood pressure relations are not well understood. Proteomic measures may provide insights into the pathophysiological mechanisms through which the DASH diet reduces blood pressure., Methods: The DASH (1994-1996) and DASH-Sodium (1997-1999) trials were multicenter, randomized-controlled feeding trials. Proteomic profiling was conducted in serum collected at the end of the feeding period (DASH, N = 215; DASH-Sodium, N = 390). Multivariable linear regression models were used to identify interactions between 71 DASH diet-related proteins and changes in systolic and diastolic blood pressure. Estimates were meta-analyzed across both trials. Elastic net models were used to identify proteins that predict changes in blood pressure., Results: Ten significant interactions were identified [systolic blood pressure: seven proteins; diastolic blood pressure: three proteins], which represented nine unique proteins. A high level of renin at the end of the feeding period was associated with greater reductions in diastolic blood pressure in individuals consuming the control than DASH diets. A high level of procollagen c-endopeptidase enhancer 1 (PCOLCE) and collagen triple helix repeat-containing protein 1 (CTHRC1) were associated with greater reductions in systolic blood pressure in individuals consuming the DASH than control diets, and with elevations in systolic blood pressure in individuals consuming the control diets (P for interaction for all tests < 0.05). Elastic net models identified six additional proteins that predicted change in blood pressure., Conclusions: Several novel proteins were identified that may provide some insight into the relationship between the DASH diet and blood pressure., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Despite increasing obesity rates in adolescents, data regarding early kidney sequelae are lacking., Objective: To assess the association between adolescent body mass index (BMI) and early chronic kidney disease (CKD) in young adulthood (<45 years of age)., Design, Setting, and Participants: This cohort study linked screening data of mandatory medical assessments of Israeli adolescents to data from a CKD registry of a national health care system. Adolescents who were aged 16 to 20 years; born since January 1, 1975; medically evaluated for mandatory military service through December 31, 2019; and insured by Maccabi Healthcare Services were assessed. Individuals with kidney pathology, albuminuria, hypertension, dysglycemia, or missing blood pressure or BMI data were excluded. Body mass index was calculated as weight in kilograms divided by height in meters squared and categorized by age- and sex-matched percentiles according to the US Centers for Disease Control and Prevention. Follow-up started at the time of medical evaluation or January 1, 2000 (whichever came last), and ended at early CKD onset, death, the last day insured, or August 23, 2020 (whichever came first). Data analysis was performed from December 19, 2021, to September 11, 2023., Main Outcomes and Measures: Early CKD, defined as stage 1 to 2 CKD by moderately or severely increased albuminuria, with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or higher., Results: Of 629 168 adolescents evaluated, 593 660 (mean [SD] age at study entry, 17.2 [0.5] years; 323 293 [54.5%] male, 270 367 [45.5%] female) were included in the analysis. During a mean (SD) follow-up of 13.4 (5.5) years for males and 13.4 (5.6) years for females, 1963 adolescents (0.3%) developed early CKD. Among males, the adjusted hazard ratios were 1.8 (95% CI, 1.5-2.2) for adolescents with high-normal BMI, 4.0 (95% CI, 3.3-5.0) for those with overweight, 6.7 (95% CI, 5.4-8.4) for those with mild obesity, and 9.4 (95% CI, 6.6-13.5) for those with severe obesity. Among females, the hazard ratios were 1.4 (95% CI, 1.2-1.6) for those with high-normal BMI, 2.3 (95% CI, 1.9-2.8) for those with overweight, 2.7 (95% CI, 2.1-3.6) for those with mild obesity, and 4.3 (95% CI, 2.8-6.5) for those with severe obesity. The results were similar when the cohort was limited to individuals who were seemingly healthy as adolescents, individuals surveyed up to 30 years of age, or those free of diabetes and hypertension at the end of the follow-up., Conclusions and Relevance: In this cohort study, high BMI in late adolescence was associated with early CKD in young adulthood. The risk was also present in seemingly healthy individuals with high-normal BMI and before 30 years of age, and a greater risk was seen among those with severe obesity. These findings underscore the importance of mitigating adolescent obesity rates and managing risk factors for kidney disease in adolescents with high BMI.

Background: Physical function and its decline in older age may be connected to treatable vascular risk factors in mid-life. This study aimed to evaluate whether these factors affect the underlying rate of decline., Methods: This prospective cohort included 5 481 older adults aged 67-91 in the Atherosclerosis Risk in Communities Study (mean [standard deviation {SD}] age = 75.8 [5.0], 58% women, 21% Black race) without a history of stroke. The main outcome was the rate of Short Physical Performance Battery (SPPB) decline over a median late-life follow-up of 4.8 years. Primary mid-life (aged 45-64) exposures were Visit 1 hypertension (>140/90 mm Hg or treatment), diabetes (>126 mg/dL or treatment), high cholesterol (>240 mg/dL or treatment), and smoking, and number of decades of vascular risk exposure across Visits 1-4., Results: The average adjusted rate of SPPB decline (points per 5 years) for older adults was -0.79 (confidence interval [CI]: -0.87, 0.71) and was accelerated by mid-life hypertension (+57% decline vs normotension: additional decline of -0.47, 95% CI: -0.64, -0.30), diabetes (+73% decline vs no diabetes: additional decline of -0.67, 95% CI: -1.09, -0.24), elevated systolic blood pressure (+17% decline per SD: -0.16, 95% CI: -0.23, -0.10), and elevated fasting blood glucose (+16% decline per SD: -0.015, 95% CI: -0.24, -0.06). Each decade greater mid-life exposure to hypertension (+32% decline: -0.93, 95% CI: -1.25, -0.61) and diabetes (+35% decline: -1.03, 95% CI: -1.68, -0.38) was associated with faster SPPB decline., Conclusions: Mid-life control of blood pressure and diabetes may offset aging-related functional decline., (© The Author(s) 2023. 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: Management of orthostatic hypotension (OH) prioritizes prevention of standing hypotension, sometimes at the expense of supine hypertension. It is unclear whether supine hypertension is associated with adverse outcomes relative to standing hypotension., Objectives: To compare the long-term clinical consequences of supine hypertension and standing hypotension among middle-aged adults with and without OH., Methods: The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure (BP) in adults aged 45 to 64 years, without neurogenic OH, between 1987 and 1989. We defined OH as a positional drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg, supine hypertension as supine BP≥140/≥90 mm Hg, and standing hypotension as standing BP≤105/≤65 mm Hg. Participants were followed for >30 years. We used Cox regression models to examine associations with cardiovascular disease events, all-cause mortality, falls, and syncope., Results: Of 12 489 participants (55% female, 26% Black, mean age 54 years, SD 6), 4.4% had OH. Among those without OH (N=11 943), 19% had supine hypertension and 21% had standing hypotension, while among those with OH (N=546), 58% had supine hypertension and 38% had standing hypotension. Associations with outcomes did not differ by OH status ( P -interactions >0.25). Supine hypertension was associated with heart failure (hazard ratio, 1.83 [95% CI, 1.68-1.99]), falls (hazard ratio, 1.12 [95% CI, 1.02-1.22]), and all-cause mortality (hazard ratio, 1.45 [95% CI, 1.37-1.54]), while standing hypotension was only significantly associated with mortality (hazard ratio, 1.06 [95% CI, 1.00-1.14])., Conclusions: Supine hypertension was associated with higher risk of adverse events than standing hypotension, regardless of OH status. This challenges conventional OH management, which prioritizes standing hypotension over supine hypertension., Competing Interests: Disclosures None.

Background: ACC/AHA guidelines caution against the use of antihypertensive therapy in the setting of low standing systolic BP (SBP) < 110 mm Hg due to unclear benefits., Methods: The Atherosclerosis Risk in Communities (ARIC) Study measured supine and standing SBP in adults aged 45-64 years between 1987 and 1989. We used Cox regression to evaluate the associations of low standing SBP (<110 mm Hg) with risk of falls, syncope, coronary heart disease (CHD), and mortality through December 31, 2019. Falls and syncope were ascertained by hospitalization and outpatient claims; CHD events were adjudicated. Associations were examined overall and in strata of hypertension stage, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and sex., Results: Among 12,467 adults followed a median of 24 years (mean age at enrollment 54.1 ± 5.8 years, 55% women, 26% Black adults), 3,000 (24%) had a standing SBP < 110 mm Hg. A standing SBP < 110 mm Hg compared to standing SBP ≥ 110 mm Hg was not significantly associated with falls or syncope, and was associated with a lower risk of CHD events and mortality with HRs of 1.02 (95% CI 0.94, 1.11), 1.02 (0.93, 1.11), 0.88 (0.80, 0.97), and 0.91 (0.86, 0.97), respectively. There were no clinically meaningful differences when stratified by hypertension stage, 10-year ASCVD risk, age, and sex., Conclusions: In this community-based population, low standing SBP was common and not significantly associated with falls or syncope, but was associated with a lower risk of CHD and mortality. These findings do not support screening for low standing BP as a risk factor for adverse events., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The fraction of dementia attributable to hypertension might vary depending on the age of the population considered and the age through which dementia occurs., Methods: In the Atherosclerosis Risk in Communities study, we quantified population attributable fractions (PAF) of dementia by age 80 and 90 from hypertension assessed at ages of 45-54 (n = 7572), 55-64 (n = 12,033), 65-74 (n = 6561), and 75-84 (n = 2086)., Results: The PAF for dementia by age 80 from all non-normal blood pressure at ages 45-54 was 15.3% (95% confidence interval [CI] = 6.9%-22.3%), 19.1% (95% CI = 9.9%-26.9%) at ages 55-64, and 19.9% (95% CI = -4.4%-38.5%) at ages 65-74. The strongest PAFs were from stage 2 hypertension (11.9%-21.3%). For dementia by age 90, PAFs from non-normal blood pressure up through age 75 were smaller (10.9%-13.8%), and non-significant by age 75-84., Discussion: Interventions targeting hypertension even in early late life might reduce a sizeable proportion of dementia., Highlights: We estimated prospective population attributable risks of dementia for hypertension. 15%-20% of dementia cases by age 80 are from non-normal blood pressure (BP). Associations between hypertension and dementia persisted through age 75. Midlife to early late-life BP control might reduce a large proportion of dementia., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Significance Statement: We describe circulating proteins associated with albuminuria in a population of African American Study of Kidney Disease and Hypertension with CKD (AASK) using the largest proteomic platform to date: nearly 7000 circulating proteins, representing approximately 2000 new targets. Findings were replicated in a subset of a general population cohort with kidney disease (ARIC) and a population with CKD Chronic Renal Insufficiency Cohort (CRIC). In cross-sectional analysis, 104 proteins were significantly associated with albuminuria in the Black group, of which 67 of 77 available proteins were replicated in ARIC and 68 of 71 available proteins in CRIC. LMAN2, TNFSFR1B, and members of the ephrin superfamily had the strongest associations. Pathway analysis also demonstrated enrichment of ephrin family proteins., Background: Proteomic techniques have facilitated understanding of pathways that mediate decline in GFR. Albuminuria is a key component of CKD diagnosis, staging, and prognosis but has been less studied than GFR. We sought to investigate circulating proteins associated with higher albuminuria., Methods: We evaluated the cross-sectional associations of the blood proteome with albuminuria and longitudinally with doubling of albuminuria in the African American Study of Kidney Disease and Hypertension (AASK; 38% female; mean GFR 46; median urine protein-to-creatinine ratio 81 mg/g; n =703) and replicated in two external cohorts: a subset of the Atherosclerosis Risk in Communities (ARIC) study with CKD and the Chronic Renal Insufficiency Cohort (CRIC)., Results: In cross-sectional analysis, 104 proteins were significantly associated with albuminuria in AASK, of which 67 of 77 available proteins were replicated in ARIC and 68 of 71 available proteins in CRIC. Proteins with the strongest associations included LMAN2, TNFSFR1B, and members of the ephrin superfamily. Pathway analysis also demonstrated enrichment of ephrin family proteins. Five proteins were significantly associated with worsening albuminuria in AASK, including LMAN2 and EFNA4, which were replicated in ARIC and CRIC., Conclusions: Among individuals with CKD, large-scale proteomic analysis identified known and novel proteins associated with albuminuria and suggested a role for ephrin signaling in albuminuria progression., (Copyright © 2023 by the American Society of Nephrology.)

Background The Dietary Approaches to Stop Hypertension (DASH) diet is recommended for cardiovascular disease prevention. We aimed to identify protein biomarkers of the DASH diet using data from 2 randomized feeding studies and validate them in an observational study, the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results Large-scale proteomic profiling was conducted in serum specimens (SomaLogic) collected at the end of 8-week and 4-week DASH diet interventions in multicenter, randomized controlled feeding studies of the DASH trial (N=215) and the DASH-Sodium trial (N=396), respectively. Multivariable linear regression models were used to compare the relative abundance of 7241 proteins between the DASH and control diet interventions. Estimates from the 2 trials were meta-analyzed using fixed-effects models. We validated significant proteins in the ARIC study (N=10 490) using the DASH diet score. At a false discovery rate <0.05, there were 71 proteins that were different between the DASH diet and control diet in the DASH and DASH-Sodium trials. Nineteen proteins were validated in the ARIC study. The 19 proteins collectively improved the prediction of the DASH diet intervention in the feeding studies (range of difference in C statistics, 0.267-0.313; P <0.001 for both tests) and the DASH diet score in the ARIC study (difference in C statistics, 0.017; P <0.001) beyond participant characteristics. Conclusions We identified 19 proteins robustly associated with the DASH diet in 3 studies, which may serve as biomarkers of the DASH diet. These results suggest potential pathways that are impacted by consumption of the DASH diet. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03403166, NCT00000608.

Background: Proteins and metabolites are essential for many biological functions and often linked through enzymatic or transport reactions. Individual molecules have been associated with all-cause mortality. Many of these are correlated and might jointly represent pathways or endophenotypes involved in diseases., Results: We present an integrated analysis of proteomics and metabolomics via a local dimensionality reduction clustering method. We identified 224 modules of correlated proteins and metabolites in the Atherosclerosis Risk in Communities (ARIC) study, a general population cohort of older adults (N = 4046, mean age 75.7, mean eGFR 65). Many of the modules displayed strong cross-sectional associations with demographic and clinical characteristics. In comprehensively adjusted analyses, including fasting plasma glucose, history of cardiovascular disease, systolic blood pressure and kidney function among others, 60 modules were associated with mortality. We transferred the network structure to the African American Study of Kidney Disease and Hypertension (AASK) (N = 694, mean age 54.5, mean mGFR 46) and identified mortality associated modules relevant in this disease specific cohort. The four mortality modules relevant in both the general population and CKD were all a combination of proteins and metabolites and were related to diabetes / insulin secretion, cardiovascular disease and kidney function. Key components of these modules included N-terminal (NT)-pro hormone BNP (NT-proBNP), Sushi, Von Willebrand Factor Type A, EGF And Pentraxin (SVEP1), and several kallikrein proteases., Conclusion: Through integrated biomarkers of the proteome and metabolome we identified functions of (patho-) physiologic importance related to diabetes, cardiovascular disease and kidney function., (© 2022. The Author(s).)

Investigations into the causal underpinnings of disease processes can be aided by the incorporation of genetic information. Genetic studies require populations varied in both ancestry and prevalent disease in order to optimize discovery and ensure generalizability of findings to the global population. Here, we report the genetic determinants of the serum proteome in 466 African Americans with chronic kidney disease attributed to hypertension from the richly phenotyped African American Study of Kidney Disease and Hypertension (AASK) study. Using the largest aptamer-based protein profiling platform to date (6,790 proteins or protein complexes), we identified 969 genetic associations with 900 unique proteins; including 52 novel cis (local) associations and 379 novel trans (distant) associations. The genetic effects of previously published cis-protein quantitative trait loci (pQTLs) were found to be highly reproducible, and we found evidence that our novel genetic signals colocalize with gene expression and disease processes. Many trans- pQTLs were found to reflect associations mediated by the circulating cis protein, and the common trans-pQTLs are enriched for processes involving extracellular vesicles, highlighting a plausible mechanism for distal regulation of the levels of secreted proteins. Thus, our study generates a valuable resource of genetic associations linking variants to protein levels and disease in an understudied patient population to inform future studies of drug targets and physiology., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objective: Midlife vascular risk factors (MVRFs) are associated with incident dementia, as are amyloid β (Aβ) deposition and neurodegeneration. Whether vascular and Alzheimer disease-associated factors contribute to dementia independently or interact synergistically to reduce cognition is poorly understood., Methods: Participants in the Atherosclerosis Risk in Communities-Positron Emission Tomography study were followed from 1987-1989 (45-64 years old) through 2016-2017 (74-94 years old), with repeat cognitive assessment and dementia adjudication. In 2011-2013, dementia-free participants underwent brain magnetic resonance imaging (with white matter hyperintensity [WMH] and brain volume measurement) and florbetapir (Aβ) positron emission tomography. The relative contributions of vascular risk and injury (MVRFs, WMH volume), elevated Aβ standardized uptake value ratio (SUVR), and neurodegeneration (smaller temporoparietal brain regions) to incident dementia were evaluated with adjusted Cox models., Results: In 298 individuals, 36 developed dementia (median follow-up = 4.9 years). Midlife hypertension and Aβ each independently predicted dementia risk (hypertension: hazard ratio [HR] = 2.57, 95% confidence interval [CI] = 1.16-5.67; Aβ SUVR [per standard deviation (SD)]: HR = 2.57, 95% CI = 1.72-3.84), but did not interact significantly, whereas late life diabetes (HR = 2.50, 95% CI = 1.18-5.28) and Aβ independently predicted dementia risk. WMHs (per SD: HR = 1.51, 95% CI = 1.03-2.20) and Aβ SUVR (HR = 2.52, 95% CI = 1.83-3.47) independently contributed to incident dementia, but WMHs lost significance when MVRFs were included. Smaller temporoparietal brain regions were associated with incident dementia, independent of Aβ and MVRFs (HR = 2.18, 95% CI = 1.18-4.01)., Interpretation: Midlife hypertension and late life Aβ are independently associated with dementia risk, without evidence for synergy on a multiplicative scale. Given the independent contributions of vascular and amyloid mechanisms, multiple pathways should be considered when evaluating interventions to reduce the burden of dementia. ANN NEUROL 2022;92:607-619., (© 2022 American Neurological Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Uromodulin (UMOD) is a major risk gene for monogenic and complex forms of kidney disease. The encoded kidney-specific protein uromodulin is highly abundant in urine and related to chronic kidney disease, hypertension, and pathogen defense. To gain insights into potential systemic roles, we performed genome-wide screens of circulating uromodulin using complementary antibody-based and aptamer-based assays. We detected 3 and 10 distinct significant loci, respectively. Integration of antibody-based results at the UMOD locus with functional genomics data (RNA-Seq, ATAC-Seq, Hi-C) of primary human kidney tissue highlighted an upstream variant with differential accessibility and transcription in uromodulin-synthesizing kidney cells as underlying the observed cis effect. Shared association patterns with complex traits, including chronic kidney disease and blood pressure, placed the PRKAG2 locus in the same pathway as UMOD. Experimental validation of the third antibody-based locus, B4GALNT2, showed that the p.Cys466Arg variant of the encoded N-acetylgalactosaminyltransferase had a loss-of-function effect leading to higher serum uromodulin levels. Aptamer-based results pointed to enzymes writing glycan marks present on uromodulin and to their receptors in the circulation, suggesting that this assay permits investigating uromodulin's complex glycosylation rather than its quantitative levels. Overall, our study provides insights into circulating uromodulin and its emerging functions.

Background: Recent guidelines classified blood pressure above 130/80 mm Hg as hypertension. However, outcome data were lacking., Objective: To determine the association between blood pressure in adolescence and the risk for early kidney damage in young adulthood., Methods: In this nationwide cohort study, we included 629 168 adolescents aged 16 to 20 who underwent medical examinations before mandatory military service in Israel. We excluded 30 466 adolescents with kidney pathology, hypertension, or missing blood pressure or anthropometric data at study entry. Blood pressure measurements at study entry were categorized according to the Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents: group A (<120/<80 mm Hg; Reference group), group B (120/<80-129/<80 mm Hg), group C (130/80-139/89 mm Hg), and group D (≥140/90 mm Hg). Early kidney damage in young adulthood was defined as albuminuria of ≥30 mg/g with an estimated glomerular filtration rate of 60 mL/(min·1.73 m 2 ) or over., Results: Of 598 702 adolescents (54% men), 2004 (0.3%) developed early kidney damage during a mean follow-up of 15.1 (7.2) years. The adjusted hazard ratios for early kidney damage in blood pressure group C were 1.17 (1.03-1.32) and 1.51 (1.22-1.86) among adolescents with lean (body mass index <85th percentile) and high body mass index (body mass index ≥85th percentile), respectively. Corresponding hazard ratios for kidney disease in group D were 1.49 (1.15-1.93) and 1.79 (1.35-2.38) among adolescents with lean and high body mass index, respectively., Conclusions: Blood pressure of ≥130/80 mm Hg was associated with early kidney damage in young adulthood, especially in adolescents with overweight and obesity.

Objectives: Less than half of United States adults with hypertension have controlled blood pressure (BP). Higher BMI is associated with an increased risk for hypertension but the association between BMI and BP control is not well characterized. We examined hypertension awareness, antihypertensive medication use, and BP control, by BMI category., Methods: Data for 3568 United States adults aged at least 18 years with hypertension (BP at least 140/90 mmHg or taking antihypertensive medication) from the 2015 to 2018 National Health and Nutrition Examination Survey were analyzed. BMI was categorized as normal (<25 kg/m2), overweight (25 to <30 kg/m2), class 1 obesity (30 to <35 kg/m2), or class 2 or 3 obesity (≥35 kg/m2). Hypertension awareness and antihypertensive medication use were self-reported. BP control was defined as BP less than 140/90 mmHg using the average of up to three measurements., Results: Among United States adults with hypertension, 15.6% had normal BMI, 31.3% had overweight, 26.2% had class 1 obesity, and 26.8% had class 2 or 3 obesity. Among those with normal BMI, overweight, class 1 obesity, and class 2 or 3 obesity: 67.9, 76.8, 84.0, and 87.8% were aware they had hypertension, respectively; 88.1, 88.1, 90.9, and 90.2% of those aware were taking antihypertensive medication, respectively; 63.5, 65.9, 71.1, and 64.1% of those taking antihypertensive medication had controlled BP, respectively; and 37.1, 44.3, 53.8, and 50.8% of those with hypertension had controlled BP, respectively., Conclusion: United States adults with hypertension and normal BMI were less likely to be aware they had hypertension and have controlled BP compared with those with overweight or obesity., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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More stringent blood pressure (BP) goals have led to greater prevalence of apparent resistant hypertension (ARH), yet the long-term prognostic impact of ARH diagnosed according to these goals in the general population remains unknown. We assessed the prognostic impact of ARH according to contemporary BP goals in 9612 participants of the Atherosclerosis Risk in Communities (ARIC) study without previous cardiovascular disease. ARH, defined as BP above goal (traditional goal <140/90 mmHg, more stringent goal <130/80 mmHg) despite the use of ≥3 antihypertensive drug classes or any BP with ≥4 antihypertensive drug classes (one of which was required to be a diuretic) was compared with controlled hypertension (BP at goal with 1-3 antihypertensive drug classes). Cox regression models were adjusted for age, sex, race, study center, BMI, heart rate, smoking, eGFR, LDL, HDL, triglycerides, and diabetes. Using the traditional BP goal, 133 participants (3.8% of the treated) had ARH. If the more stringent BP goal was instead applied, 785 participants (22.6% of the treated) were reclassified from controlled hypertension to uncontrolled hypertension (n = 725) or to ARH (n = 60). Over a median follow-up time of 19 years, ARH was associated with increased risk for a composite end point (all-cause mortality, hospitalization for myocardial infarction, stroke, or heart failure) regardless of whether traditional (adjusted HR 1.50, 95% CI: 1.23-1.82) or more stringent (adjusted HR 1.43, 95% CI: 1.20-1.70) blood pressure goals were applied. We conclude that in patients free from cardiovascular disease, ARH predicted long-term risk regardless of whether traditional or more stringent BP criteria were applied., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

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The genome-wide association study (GWAS) is a powerful means to study genetic determinants of disease traits and generate insights into disease pathophysiology. To date, few GWAS of circulating metabolite levels have been performed in African Americans with chronic kidney disease. Hypothesizing that novel genetic-metabolite associations may be identified in a unique population of African Americans with a lower glomerular filtration rate (GFR), we conducted a GWAS of 652 serum metabolites in 619 participants (mean measured glomerular filtration rate 45 mL/min/1.73m 2 ) in the African American Study of Kidney Disease and Hypertension, a clinical trial of blood pressure lowering and antihypertensive medication in African Americans with chronic kidney disease. We identified 42 significant variant metabolite associations. Twenty associations had been previously identified in published GWAS, and eleven novel associations were replicated in a separate cohort of 818 African Americans with genetic and metabolomic data from the Atherosclerosis Risk in Communities Study. The replicated novel variant-metabolite associations comprised eight metabolites and eleven distinct genomic loci. Nine of the replicated associations represented clear enzyme-metabolite interactions, with high expression in the kidneys as well as the liver. Three loci (ACY1, ACY3, and NAT8) were associated with a common pool of metabolites, acetylated amino acids, but with different individual affinities. Thus, extensive metabolite profiling in an African American population with chronic kidney disease aided identification of novel genome-wide metabolite associations, providing clues about substrate specificity and the key roles of enzymes in modulating systemic levels of metabolites., (Copyright © 2021. Published by Elsevier Inc.)

Background: 2014 hypertension guidelines raised treatment goals in older adults. The objective was to examine changes in blood pressure (BP) control (<140/90 mm Hg) from 2011-2013 to 2016-2017 among Black and white older adults with treated hypertension., Methods: Participants were 1,600 white and 650 Black adults aged 71-90 years in the Atherosclerosis Risk in Communities (ARIC) Study with treated hypertension in 2011-2013 (baseline) who had BP measured in 2016-2017 (follow-up). Predictors of changes in BP control were examined by race., Results: BP was controlled among 75.3% of white and 65.7% of Black participants at baseline and 59.0% of white and 56.5% of Black participants at follow-up. Among those with baseline BP control, risk factors for incident uncontrolled BP included age (relative risk [RR] 1.15 per 5 years, 95% confidence interval [CI] 1.07-1.25), female sex (RR 1.36, 95% CI 1.16-1.60), and chronic kidney disease (RR 1.19, 95% CI 1.01-1.40) among white participants, and hypertension duration (RR 1.14 per 5 years, 95% CI 1.03-1.27) and diabetes (RR 1.48, 95% CI 1.15-1.91) among Black participants. Among those with uncontrolled BP at baseline, white females vs. males (RR 0.60, 95% CI 0.46-0.78) and Black participants with chronic kidney disease vs. without (RR 0.58, 95% CI 0.36-0.93) were less likely to have incident controlled BP., Conclusions: BP control decreased among white and Black older adults. Black individuals with diabetes or chronic kidney disease were less likely to have controlled BP at follow-up. Higher treatment goals may have contributed to these findings and unintended differences by race., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Blood pressure (BP) measurement error may lead to under- or overtreatment of hypertension. One common source of error is terminal digit preference, most often a terminal digit of "0." The objective was to evaluate national trends in terminal digit preference in office BP measurements among adults with treated hypertension., Methods: Data were from IQVIA's National Disease and Therapeutic Index, a nationally representative, serial cross-sectional survey of office-based physicians. The analysis included office visits from 2015 to 2019 among adults aged ≥18 years receiving antihypertensive treatment. Annual trends were examined in the percent of systolic and diastolic BP measurements ending in zero by patient sex, age, and race/ethnicity, physician specialty, and first or subsequent hypertension treatment visit., Results: From 2015 to 2019, there were ~60 million hypertension treatment visits annually (unweighted N: 5,585-9,085). There was a decrease in the percent of visits with systolic (41.7%-37.7%) or diastolic (42.7%-37.8%) BP recordings ending in zero. Trends were similar by patient characteristics. However, a greater proportion of measurements ended in zero among patients aged ≥80 (vs. 15-59 or 60-79) years, first (vs. subsequent) treatment visits, visits to cardiologists (vs. primary care physicians), and visits with systolic BP ≥140 or diastolic BP ≥90 (vs. <140/90) mm Hg., Conclusions: Despite modest improvement, terminal digit preference remains a common problem in office BP measurement in the United States. Without bias, 10%-20% of measurements are expected to end in zero. Reducing digit preference is a priority for improving BP measurement accuracy and hypertension management., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease (CKD) recommends a target systolic blood pressure under 120 mmHg based on standardized office blood pressure measurement. Here, we examined the potential implications of this new guideline for blood pressure lowering with antihypertensive medication among adults in the United States with CKD compared to the 2012 KDIGO guideline (target blood pressure 130/80 mmHg or under with albuminuria or 140/90 mmHg or under without albuminuria) and the 2017 American College of Cardiology/American Heart Association (target blood pressure under 130/80 mmHg) guideline. Additionally, we determined implications of the 2021 KDIGO guideline for angiotensin converting enzyme inhibitor (ACEi) or angiotensin II-receptor blocker (ARB) use for those with albuminuria (recommended at systolic blood pressure of 120 mmHg or over) compared to the 2012 KDIGO guideline (recommended at blood pressures over 130/80 mmHg). Data were analyzed from 1,699 adults with CKD (estimated glomerular filtration rate 15-59 ml/min/1.73m 2 or a urinary albumin-to-creatinine ratio of 30 mg/g or more) in the 2015-2018 National Health and Nutrition Examination Survey and averaged up to three standardized blood pressure measurements. Among adults with CKD, 69.5% were eligible for blood pressure lowering according to the 2021 KDIGO guideline, compared with 49.8% as per 2012 KDIGO or 55.6% as per 2017 American College of Cardiology/American Heart Association guidelines. Among those with albuminuria, 78.2% were eligible for ACEi/ARB use by the 2021 KDIGO guideline compared with 71.0% by the 2012 KDIGO guideline. However, only 39.1% were taking an ACEi/ARB. Thus, our findings highlight opportunities to improve blood pressure management and reduce cardiovascular risk among adults in the United States with CKD., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Blood pressure and kidney function have a bidirectional relation. Hypertension has long been considered as a risk factor for kidney function decline. However, whether intensive blood pressure control could promote kidney health has been uncertain. The kidney is known to have a major role in affecting blood pressure through sodium extraction and regulating electrolyte balance. This bidirectional relation makes causal inference between these two traits difficult. Therefore, to examine the causal relations between these two traits, we performed two-sample Mendelian randomization analyses using summary statistics of large-scale genome-wide association studies. We selected genetic instruments more likely to be specific for kidney function using meta-analyses of complementary kidney function biomarkers (glomerular filtration rate estimated from serum creatinine [eGFRcr], and blood urea nitrogen from the CKDGen Consortium). Systolic and diastolic blood pressure summary statistics were from the International Consortium for Blood Pressure and UK Biobank. Significant evidence supported the causal effects of higher kidney function on lower blood pressure. Based on the mode-based Mendelian randomization method, the effect estimates for one standard deviation (SD) higher in log-transformed eGFRcr was -0.17 SD unit (95 % confidence interval: -0.09 to -0.24) in systolic blood pressure and -0.15 SD unit (95% confidence interval: -0.07 to -0.22) in diastolic blood pressure. In contrast, the causal effects of blood pressure on kidney function were not statistically significant. Thus, our results support causal effects of higher kidney function on lower blood pressure and suggest preventing kidney function decline can reduce the public health burden of hypertension., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The 2017 American College of Cardiology/American Heart Association guideline defines hypertension as a blood pressure ≥130/80 mm Hg, whereas the 2018 European Society of Cardiology (ESC) and 2019 National Institute for Health and Care Excellence (NICE) guidelines use a ≥140/90 mm Hg threshold. Our objective was to study the associations between isolated diastolic hypertension (IDH), diagnosed using these 2 blood pressure thresholds, and cardiovascular disease (CVD) in a large cohort of UK adults. We analyzed data from UK Biobank, which enrolled participants between 2006 and 2010 with follow-up through March 2019. We excluded persons with systolic hypertension or baseline CVD. We defined incident CVD as a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. We used Cox regression to quantify associations between IDH and CVD, as well as the individual outcomes included in the composite outcome. We studied 151 831 participants with normal systolic blood pressure (mean age 54 years, 40% male). Overall, 24.5% had IDH by the American College of Cardiology/American Heart Association definition compared with 6% by the ESC/NICE definition. Compared with normal diastolic blood pressure, IDH by the American College of Cardiology/American Heart Association definition was not significantly associated with CVD risk (hazard ratio, 1.08 [95% CI, 0.98-1.18]) whereas IDH by the ESC/NICE definition was significantly associated with a modest increase in CVD (hazard ratio, 1.15 [95% CI, 1.04-1.29]). Similar results were found by sex and among participants not taking baseline antihypertensives. Furthermore, neither IDH definition was associated with the individual outcomes of nonfatal myocardial infarction or stroke. In conclusion, the proportion of UK Biobank participants with IDH was significantly higher by the American College of Cardiology/American Heart Association definition compared with the ESC/NICE definitions; however, only the ESC/NICE definition was statistically associated with increased CVD risk.

Background: Several distinct plant-based diet indices (PDIs) have been developed to characterize adherence to plant-based diets., Objective: We contrasted 5 PDIs in a community-based cohort by assessing characteristics of the diet and evaluating whether these PDIs are associated with risk of incident hypertension., Methods: Using FFQ data from adults (45-64 y, n = 8041) without hypertension at baseline in the Atherosclerosis Risk in Communities (ARIC) Study, we scored participants' diets using the overall PDI (oPDI), healthy PDI (hPDI), less healthy (unhealthy) PDI (uPDI), provegetarian diet index, and PDI from the Rotterdam Study (PDI-Rotterdam). For the oPDI, provegetarian diet, and PDI-Rotterdam, higher intakes of all or selected plant foods received higher scores. For the hPDI, higher intakes of plant foods identified as healthful received higher scores. For the uPDI, higher intakes of less healthy plant foods received higher scores. All indices scored higher intakes of animal foods lower. We examined agreement between indices, and whether scores on these indices were associated with risk of hypertension using Cox proportional hazard models., Results: The PDIs were moderately-to-strongly correlated and largely ranked subjects consistently, except for the uPDI. Over a median follow-up of 13 y, 6044 incident hypertension cases occurred. When adjusted for sociodemographic characteristics, other dietary factors, and health behaviors, the highest compared with the lowest quintile for adherence to the oPDI, hPDI, and provegetarian diet was associated with a 12-16% lower risk of hypertension (all P-trend <0.05). Highest adherence to the uPDI was associated with a 13% higher risk of hypertension, when clinical factors were further adjusted for (P-trend = 0.03). No significant association was observed with the PDI-Rotterdam. The oPDI, hPDI, and provegetarian diet moderately improved the prediction of hypertension., Conclusions: In middle-aged US adults, despite moderate agreement in ranking subjects across PDIs, operational differences can affect the ability to detect diet-disease associations, such as hypertension., (Copyright © The Author(s) 2019.)

Importance: In the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline, the definition of hypertension was lowered from a blood pressure (BP) of greater than or equal to 140/90 to greater than or equal to 130/80 mm Hg. The new diastolic BP threshold of 80 mm Hg was recommended based on expert opinion and changes the definition of isolated diastolic hypertension (IDH)., Objective: To compare the prevalence of IDH in the United States, by 2017 ACC/AHA and 2003 Joint National Committee (JNC7) definitions, and to characterize cross-sectional and longitudinal associations of IDH with outcomes., Design, Setting, and Participants: Cross-sectional analyses of the National Health and Nutrition Examination Survey (NHANES 2013-2016) and longitudinal analyses of the Atherosclerosis Risk in Communities (ARIC) Study (baseline 1990-1992, with follow-up through December 31, 2017). Longitudinal results were validated in 2 external cohorts: (1) the NHANES III (1988-1994) and NHANES 1999-2014 and (2) the Give Us a Clue to Cancer and Heart Disease (CLUE) II cohort (baseline 1989)., Exposures: IDH, by 2017 ACC/AHA (systolic BP <130 mm Hg, diastolic BP ≥80 mm Hg) and by JNC7 (systolic BP <140 mm Hg, diastolic BP ≥90 mm Hg) definitions., Main Outcomes and Measures: Weighted estimates for prevalence of IDH in US adults and prevalence of US adults recommended BP pharmacotherapy by the 2017 ACC/AHA guideline based solely on the presence of IDH. Risk of incident atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD) in the ARIC Study., Results: The study population included 9590 adults from the NHANES (mean [SD] baseline age, 49.6 [17.6] years; 5016 women [52.3%]) and 8703 adults from the ARIC Study (mean [SD] baseline age, 56.0 [5.6] years; 4977 women [57.2%]). The estimated prevalence of IDH in the NHANES was 6.5% by the 2017 ACC/AHA definition and 1.3% by the JNC7 definition (absolute difference, 5.2% [95% CI, 4.7%-5.7%]). Among those newly classified as having IDH, an estimated 0.6% (95% CI, 0.5%-0.6%) also met the guideline threshold for antihypertensive therapy. Compared with normotensive ARIC participants, IDH by the 2017 ACC/AHA definition was not significantly associated with incident ASCVD (n = 1386 events; median follow-up, 25.2 years; hazard ratio [HR], 1.06 [95% CI, 0.89-1.26]), HF (n = 1396 events; HR, 0.91 [95% CI, 0.76-1.09]), or CKD (n = 2433 events; HR, 0.98 [95% CI, 0.65-1.11]). Results were also null for cardiovascular mortality in the 2 external cohorts (eg, HRs of IDH by the 2017 ACC/AHA definition were 1.17 [95% CI, 0.87-1.56] in the NHANES [n = 1012 events] and 1.02 [95% CI, 0.92-1.14] in CLUE II [n = 1497 events])., Conclusions and Relevance: In this analysis of US adults, the estimated prevalence of IDH was more common when defined by the 2017 ACC/AHA BP guideline compared with the JNC7 guideline. However, IDH was not significantly associated with increased risk for cardiovascular outcomes.

Aims: The aim of this study was to evaluate the associations of blood pressure categorization based on the 2017 American College of Cardiology and American Heart Association guideline with the risk of peripheral artery disease (PAD)., Methods: Among 13,113 middle-aged participants, we investigated the associations of 2017 blood pressure categories (systolic <120 and diastolic <80 mmHg (normal if no anti-hypertensive medications; reference), 120-129 and <80 (elevated), 130-139 and/or 80-89 (stage 1 hypertension), and ≥140 and/or ≥90 (stage 2 hypertension)) with incident PAD (hospitalizations with a diagnosis or leg revascularization) using Cox regression models. Analyses were separately conducted in individuals with and without anti-hypertensive medications., Results: During a median follow-up of 25.4 years, 466 incident PAD occurred (271 cases in 9858 participants without anti-hypertensive medications). In participants without anti-hypertensive medications, we observed significant hazard ratios of PAD in elevated blood pressure (1.80 (1.28-2.51)) and stage 2 hypertension (2.40 (1.72-3.34)), but not in stage 1 hypertension. Analyzing systolic and diastolic blood pressure separately, higher systolic blood pressure categories showed significant associations with incident PAD in a graded fashion whereas, for diastolic blood pressure, only ≥90 mmHg did. Generally similar patterns were seen among participants on anti-hypertensive medication, while they had higher risk of PAD than those without at each blood pressure category., Conclusions: Systolic blood pressure, including the category of 130-139 mmHg, showed stronger associations with incident PAD than did diastolic blood pressure. Consequently, elevated blood pressure conferred similar or even greater risk of PAD than stage 1 hypertension, with implications on how to interpret new blood pressure categories in terms of leg vascular health.

Rationale & Objective: The relationship between hypertension, antihypertension medication use, and change in glomerular filtration rate (GFR) over time among individuals with preserved GFR requires investigation., Study Design: Observational study., Setting & Participants: 14,854 participants from the Atherosclerosis Risk in Communities (ARIC) Study., Predictors: Baseline hypertension status (1987-1989) was categorized according to the 2017 American College of Cardiology/American Heart Association Clinical Practice Guideline as normal blood pressure, elevated blood pressure, stage 1 hypertension, stage 2 hypertension without medication, or stage 2 hypertension with medication., Outcomes: Slope of estimated GFR (eGFR) at 5 study visits over 30 years., Analytical Approach: Mixed models with random intercepts and random slopes were fit to evaluate the association between baseline hypertension status and slope of eGFR., Results: At baseline, 13.2%, 7.3%, and 19.4% of whites and 15.8%, 14.9%, and 39.9% of African Americans had stage 1 hypertension, stage 2 hypertension without medication, and stage 2 hypertension with medication. Compared with those with normal blood pressure, the annual eGFR decline was greater in people with higher blood pressure (whites: elevated blood pressure, -0.11mL/min/1.73m 2 ; stage 1 hypertension, -0.15mL/min/1.73m 2 ; stage 2 hypertension without medication, -0.36mL/min/1.73m 2 ; stage 2 hypertension with medication, -0.17mL/min/1.73m 2 ; African Americans: elevated blood pressure, -0.21mL/min/1.73m 2 ; stage 1 hypertension, -0.16mL/min/1.73m 2 ; stage 2 hypertension without medication, -0.50mL/min/1.73m 2 ; stage 2 hypertension with medication, -0.16mL/min/1.73m 2 ). The 30-year predicted probabilities of developing chronic kidney disease stage G3a+with normal blood pressure, elevated blood pressure, stage 1 hypertension, stage 2 hypertension without medication, or stage 2 hypertension with medication among whites were 54.4%, 61.6%, 64.7%, 78.1%, and 70.9%, respectively, and 55.4%, 62.8%, 60.9%, 76.1%, and 66.6% among African Americans., Limitations: Slope estimated using a maximum of 5 eGFR assessments; differential loss to follow-up., Conclusions: Compared to normotension, baseline hypertension status was associated with faster kidney function decline over 30-year follow-up in a general population cohort. This difference was attenuated among people using antihypertensive medications., (Copyright © 2019. Published by Elsevier Inc.)

Importance: The association between late-life blood pressure (BP) and cognition may depend on the presence and chronicity of past hypertension. Late-life declines in blood pressure following prolonged hypertension may be associated with poor cognitive outcomes., Objective: To examine the association of midlife to late-life BP patterns with subsequent dementia, mild cognitive impairment, and cognitive decline., Design, Setting, and Participants: The Atherosclerosis Risk in Communities prospective population-based cohort study enrolled 4761 participants during midlife (visit 1, 1987-1989) and followed-up over 6 visits through 2016-2017 (visit 6). BP was examined over 24 years at 5 in-person visits between visits 1 and 5 (2011-2013). During visits 5 and 6, participants underwent detailed neurocognitive evaluation. The setting was 4 US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis, Minnesota. Follow-up ended on December 31, 2017., Exposures: Five groups based on longitudinal patterns of normotension, hypertension (>140/90 mm Hg), and hypotension (<90/60 mm Hg) at visits 1 to 5., Main Outcomes and Measures: Primary outcome was dementia onset after visit 5, based on Ascertain Dementia-8 informant questionnaires, Six-Item Screener telephone assessments, hospital discharge and death certificate codes, and the visit 6 neurocognitive evaluation. Secondary outcome was mild cognitive impairment at visit 6, based on the neurocognitive evaluation., Results: Among 4761 participants (2821 [59%] women; 979 [21%] black race; visit 5 mean [SD] age, 75 [5] years; visit 1 mean age range, 44-66 years; visit 5 mean age range, 66-90 years), there were 516 (11%) incident dementia cases between visits 5 and 6. The dementia incidence rate for participants with normotension in midlife (n = 833) and late life was 1.31 (95% CI, 1.00-1.72 per 100 person-years); for midlife normotension and late-life hypertension (n = 1559), 1.99 (95% CI, 1.69-2.32 per 100 person-years); for midlife and late-life hypertension (n = 1030), 2.83 (95% CI, 2.40-3.35 per 100 person-years); for midlife normotension and late-life hypotension (n = 927), 2.07 (95% CI, 1.68-2.54 per 100 person-years); and for midlife hypertension and late-life hypotension (n = 389), 4.26 (95% CI, 3.40-5.32 per 100 person-years). Participants in the midlife and late-life hypertension group (hazard ratio [HR], 1.49 [95% CI, 1.06-2.08]) and in the midlife hypertension and late-life hypotension group (HR, 1.62 [95% CI, 1.11-2.37]) had significantly increased risk of subsequent dementia compared with those who remained normotensive. Irrespective of late-life BP, sustained hypertension in midlife was associated with dementia risk (HR, 1.41 [95% CI, 1.17-1.71]). Compared with those who were normotensive in midlife and late life, only participants with midlife hypertension and late-life hypotension had higher risk of mild cognitive impairment (37 affected individuals (odds ratio, 1.65 [95% CI, 1.01-2.69]). There was no significant association of BP patterns with late-life cognitive change., Conclusions and Relevance: In this community-based cohort with long-term follow-up, sustained hypertension in midlife to late life and a pattern of midlife hypertension and late-life hypotension, compared with midlife and late-life normal BP, were associated with increased risk for subsequent dementia.

Background and Objectives: Hypertension in older kidney donor candidates is viewed as safe. However, hypertension guidelines have evolved and long-term outcomes have not been explored. We sought to quantify the 15-year risk of ESKD and mortality in older donors (≥50 years old) with versus those without hypertension., Design, Setting, Participants, & Measurements: A United States cohort of 24,533 older donors from 1999 to 2016, including 2265 with predonation hypertension, were linked to Centers for Medicare and Medicaid Services data and the Social Security Death Master File to ascertain ESKD development and mortality. The exposure of interest was predonation hypertension. From 2004 to 2016, hypertension was defined as documented predonation use of antihypertensive therapy, regardless of systolic BP or diastolic BP; from 1999 to 2003, when there was no documentation of antihypertensive therapy, hypertension was defined as predonation systolic BP ≥140 or diastolic BP ≥90 mm Hg., Results: Older donors were 82% white, 6% black, 7% Hispanic, and 3% Asian. The median follow-up was 7.1 years (interquartile range, 3.4-11.1; maximum, 18). There were 24 ESKD and 252 death events during the study period. The 15-year risk of ESKD was 0.8% (95% confidence interval [95% CI], 0.4 to 1.6) for donors with hypertension (mean systolic BP, 138 mm Hg) versus 0.2% (95% CI, 0.1 to 0.4) for donors without hypertension (mean systolic BP, 123 mm Hg; adjusted hazard ratio, 3.04; 95% CI, 1.28 to 7.22; P =0.01). When predonation antihypertensive therapy was available, the risk of ESKD was 6.21-fold higher (95% CI, 1.20 to 32.17; P =0.03) for donors using antihypertensive therapy (mean systolic BP, 132 mm Hg) versus those not using antihypertensive therapy (mean systolic BP, 124 mm Hg). There was no significant association between donor hypertension and 15-year mortality (hazard ratio, 1.18; 95% CI, 0.84 to 1.66; P =0.34)., Conclusions: Compared with older donors without hypertension, older donors with hypertension had higher risk of ESKD, but not mortality, for 15 years postdonation. However, the absolute risk of ESKD was small., (Copyright © 2019 by the American Society of Nephrology.)

Background: Proteinuria screening is recommended for patients with hypertension to screen for kidney disease and identify those at elevated risk for cardiovascular disease. However, screening rates among hypertensive patients are low. Home testing strategies may be useful in improving proteinuria screening adherence., Methods: We conducted an individual-level, randomized trial at 55 primary care clinic sites in the Geisinger Health System to evaluate the effectiveness of a strategy using home smartphone urinalysis test (Dip.io) to complete proteinuria screening in previously unscreened non-diabetic patient portal users with hypertension. All patients received an educational letter and a standing urinalysis lab order, and then were randomized to control (usual care) or intervention. Intervention arm participants were invited to complete proteinuria screening with a mailed home smartphone urinalysis test. Co-primary outcomes were completion of proteinuria screening and number of albuminuria cases (albumin/creatinine ratio [ACR] ≥ 30 mg/g or protein/creatinine ratio ≥ 150 mg/g) at the end of 3 months. We also evaluated patient satisfaction with the home test, and compliance with recommendations for patients with newly detected albuminuria., Results: A total of 999 patients were randomized to intervention or control. Out of 499 patients assigned to the intervention arm, 253 were reached by phone, and 69/97 (71.1%) consented patients completed the home test. Overall, the intervention increased proteinuria screening completion (28.9% vs. 18.0%; p < 0.001) with no effect on the number of albuminuria cases (4 vs. 4) although only 6/57 (10.5%) patients with trace or 1+ urine dipstick protein had a follow-up quantitative test. Among the 55 patients who completed a survey after the home test, 89% preferred testing at home rather than the physician's office., Conclusions: A strategy using a home urinalysis smartphone test increased proteinuria screening rates in previously unscreened patients with hypertension and may be useful in increasing rates of proteinuria screening compliance. Future studies should evaluate use of home testing kits to screen for and confirm albuminuria, and determine whether improving early detection of kidney disease can improve future kidney health., Trial Registration: Clinical Trial Registry: NCT03470701 (First posted 3/20/2018) https://clinicaltrials.gov/ct2/show/NCT03470701 . This study was retrospectively registered.

Background: The Dietary Approaches to Stop Hypertension (DASH) dietary pattern is recommended for cardiovascular disease risk reduction. Assessment of dietary intake has been limited to subjective measures and a few biomarkers from 24-h urine collections., Objective: The aim of the study was to use metabolomics to identify serum compounds that are associated with adherence to the DASH dietary pattern., Design: We conducted untargeted metabolomic profiling in serum specimens collected at the end of 8 wk following the DASH diet (n = 110), the fruit and vegetables diet (n = 111), or a control diet (n = 108) in a multicenter, randomized clinical feeding study (n = 329). Multivariable linear regression was used to determine the associations between the randomized diets and individual log-transformed metabolites after adjustment for age, sex, race, education, body mass index, and hypertension. Partial least-squares discriminant analysis (PLS-DA) was used to identify a panel of compounds that discriminated between the dietary patterns. The area under the curve (C statistic) was calculated as the cumulative ability to distinguish between dietary patterns. We accounted for multiple comparisons with the use of the Bonferroni method (0.05 of 818 metabolites = 6.11 × 10-5)., Results: Serum concentrations of 44 known metabolites differed significantly between participants randomly assigned to the DASH diet compared with both the control diet and the fruit and vegetables diet, which included an amino acid, 2 cofactors and vitamins (n = 2), and lipids (n = 41). With the use of PLS-DA, component 1 explained 29.4% of the variance and component 2 explained 12.6% of the variance. The 10 most influential metabolites for discriminating between the DASH and control dietary patterns were N-methylproline, stachydrine, tryptophan betaine, theobromine, 7-methylurate, chiro-inositol, 3-methylxanthine, methyl glucopyranoside, β-cryptoxanthin, and 7-methylxanthine (C statistic = 0.986)., Conclusions: An untargeted metabolomic platform identified a broad array of serum metabolites that differed between the DASH diet and 2 other dietary patterns. This newly identified metabolite panel may be used to assess adherence to the DASH dietary pattern. This trial was registered at http://www.clinicaltrials.gov as NCT03403166.

Objective: To investigate the association between individual and area-level socioeconomic status and hypertension risk among individuals later in life., Methods: We used Cox proportional hazards models to examine the association of socioeconomic status with incident hypertension using race-specific neighborhood socioeconomic status, median household income, and education among 3372 participants (mean age, 61 years) from the Atherosclerosis Risk in Communities Study at Visit 4 (1996-1998). Incident hypertension was defined as self-reported diagnosis or reported use of antihypertensive medications., Results: Over a median follow-up time of 9.4 years, there were 1874 new cases of hypertension (62.1 per 1000 person-years). Overall, being in high as compared with low socioeconomic status categories was associated with a lower risk of developing hypertension in late life, with hazard ratios (95% confidence intervals) of 0.87 (0.77-0.98) for high neighborhood socioeconomic status tertile, 0.79 (0.69-0.90) for high individual income, and 0.75 (0.63-0.89) for college education after adjustment for traditional risk factors. These findings were consistent and robust whenever accounting for competing risks of all-cause mortality. No significant interactions by race and age (dichotomized at age 65) were observed., Conclusion: Among participants free of hypertension in midlife, high neighborhood and individual socioeconomic status are associated with a decreased risk of incident hypertension. Our findings support population-level interventions, such as blood pressure screening at senior centers and faith-based organizations, that are tailored to shift the distribution of blood pressure and reduce hypertension health inequalities among older adults.

Background: In older adults (aged 70-74 years), African-Americans have 4-fold higher risk of developing hypertension-attributed end-stage renal disease (ESRD) than European-Americans. A hypothesized mechanism linking hypertension and progressive chronic kidney disease (CKD) is the innate immune response and inflammation. Persons with CKD are also more susceptible to infection. Gene expression in peripheral blood can provide a view of the innate immune activation profile. We aimed to identify differentially expressed genes, microRNAs, and pathways in peripheral blood between cases with CKD and high blood pressure under hypertension treatment versus controls without CKD and with controlled blood pressure in African Americans., Methods: Case and control pairs (N = 15x2) were selected from those without diabetes and were matched for age, sex, body mass index, APOL1 risk allele count, and hypertension medication use. High blood pressure under hypertension treatment was defined as hypertension medication use and systolic blood pressure (SBP) ≥ 145 mmHg. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. Cases were selected from those with CKD and high blood pressure under hypertension treatment, and controls were selected from those without CKD (eGFR: 75-120 mL/min/1.73m2 and urine albumin-to-creatinine ratio < 30mg/g) and with blood pressure controlled by hypertension medication use (SBP < 135 mmHg and D(diastolic)BP < 90 mm Hg). We perform RNA sequencing of mRNA and microRNA and conducted differential expression and co-expression network analysis., Results: Of 347 miRNAs included in the analysis, 14 were significantly associated with case status (Benjamini-Hochberg adjusted p-value [BH p] < 0.05). Of these, ten were downregulated in cases: three of each belong to the miR-17 and miR-15 families. In co-expression network analysis of miRNA, one module, which included 13 of the 14 significant miRNAs, had significant association with case status. Of the 14,488 genes and 41,739 transcripts included in the analysis, none had significant association with case status. Gene co-expression network analyses did not yield any significant associations for mRNA., Conclusion: We have identified 14 differentially expressed miRNAs in the peripheral blood of CKD cases with high blood pressure under hypertension treatment as compared to appropriate controls. Most of the significant miRNAs were downregulated and have critical roles in immune cell functions. Future studies are needed to replicate our findings and determine whether the downregulation of these miRNAs in immune cells may influence CKD progression or complications.

Background: Diffusion tensor imaging measures of white matter (WM) microstructural integrity appear to provide earlier indication of WM injury than WM hyperintensities; however, risk factors for poor WM microstructural integrity have not been established. Our study quantifies the association between vascular risk factors in midlife and late life with measures of late-life WM microstructural integrity., Methods and Results: We used data from 1851 participants in ARIC (Atherosclerosis Risk in Communities Study) who completed 3-T magnetic resonance imaging, including diffusion tensor imaging, as part of the ARIC Neurocognitive Study (ARIC-NCS). We quantified the association among lipids, glucose, and blood pressure from the baseline ARIC visit (1987-1989, ages 44-65, midlife) and visit 5 of ARIC (2011-2013, ages 67-90, late life, concurrent with ARIC-NCS) with regional and overall WM mean diffusivity and fractional anisotropy obtained at ARIC visit 5 for ARIC participants. We also considered whether these associations were independent of or modified by WM hyperintensity volumes. We found that elevated blood pressure in midlife and late life and elevated glucose in midlife, but not late life, were associated with worse late-life WM microstructural integrity. These associations were independent of the degree of WM hyperintensity, and the association between glucose and WM microstructural integrity appeared stronger for those with the least WM hyperintensity. There was little support for an adverse association between lipids and WM microstructural integrity., Conclusions: Hypertension in both midlife and late life and elevated glucose in midlife are related to worse WM microstructural integrity in late life., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Impaired functional status attenuates the relationship of systolic blood pressure (SBP) with mortality in older adults but has not been studied in middle-aged populations., Method: Among 10,264 stroke-free Atherosclerosis Risk in Communities participants (mean age 62.8 [5.7] years; 6,349 [62%] younger [<65 years]; 5,148 [50%] men; 2,664 [26%] Black), function was defined as good function (GF) for those self-reporting no difficulty performing functional tasks and basic or instrumental tasks of daily living; all others were defined as impaired function (IF). SBP categories were normal (<120 mmHg), prehypertension (120-139 mmHg), and hypertension (≥140 mmHg). Mortality risk associated with SBP was estimated using adjusted Cox proportional hazard models with a triple interaction between age, functional status, and SBP., Results: Mean follow-up was 12.9 years with 2,863 (28%) deaths. Among younger participants, 3,017 (48%) had IF; 2,279 of 3,915 (58%) older participants had IF. Prehypertension (hazard ratio [HR] = 1.48 [1.03, 2.15] p = .04) and hypertension (HR = 1.97 [1.29, 3.03] p = .002) were associated with mortality in younger GF and older (≥65 years) GF participants (prehypertension HR = 1.21 [1.06, 1.37] p = .005; hypertension HR = 1.47 [1.36, 1.59] p < .001). Among IF participants, prehypertension was not associated with mortality in younger participants (HR = 0.99 [0.85, 1.15] p = .93) and was protective in older participants (HR = 0.87 [0.85, 0.90] p < .001). Hypertension was associated with mortality in younger IF participants (HR = 1.54 [1.30, 1.82] p < .001) but not in older IF participants (HR = 0.99 [0.87, 1.14] p = .93)., Conclusions: Compared with younger and well-functioning persons, the additional contribution of blood pressure to mortality is much lower with older age and impaired function, particularly if both are present. Functional status and age could potentially inform optimal blood pressure targets., (© The Author 2015. 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: There are established guidelines for recommended dietary intake for hypertension treatment and cardiovascular disease prevention. Evidence is lacking for effective dietary patterns for kidney disease prevention., Study Design: Prospective cohort study., Setting & Participants: Atherosclerosis Risk in Communities (ARIC) Study participants with baseline estimated glomerular filtration rate (eGFR) ≥ 60mL/min/1.73m 2 (N=14,882)., Predictor: The Dietary Approaches to Stop Hypertension (DASH) diet score was calculated based on self-reported dietary intake of red and processed meat, sweetened beverages, sodium, fruits, vegetables, whole grains, nuts and legumes, and low-fat dairy products, averaged over 2 visits., Outcomes: Cases were ascertained based on the development of eGFRs<60mL/min/1.73m 2 accompanied by ≥25% eGFR decline from baseline, an International Classification of Diseases, Ninth/Tenth Revision code for a kidney disease-related hospitalization or death, or end-stage renal disease from baseline through 2012., Results: 3,720 participants developed kidney disease during a median follow-up of 23 years. Participants with a DASH diet score in the lowest tertile were 16% more likely to develop kidney disease than those with the highest score tertile (HR, 1.16; 95% CI, 1.07-1.26; P for trend < 0.001), after adjusting for sociodemographics, smoking status, physical activity, total caloric intake, baseline eGFR, overweight/obese status, diabetes status, hypertension status, systolic blood pressure, and antihypertensive medication use. Of the individual components of the DASH diet score, high red and processed meat intake was adversely associated with kidney disease and high nuts, legumes, and low-fat dairy products intake was associated with reduced risk for kidney disease., Limitations: Potential measurement error due to self-reported dietary intake and lack of data for albuminuria., Conclusions: Consuming a DASH-style diet was associated with lower risk for kidney disease independent of demographic characteristics, established kidney risk factors, and baseline kidney function. Healthful dietary patterns such as the DASH diet may be beneficial for kidney disease prevention., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Little is known about the frequency and patterns of hyperkalemia in clinical settings. We evaluated the association between baseline antihypertensive medications that may affect potassium levels (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, loop/thiazide diuretics, and potassium-sparing diuretics) and hyperkalemia, defined by potassium >5 mEq/L and >5.5 mEq/L, over a 3-year time period in 194 456 outpatients in the Geisinger Health System, as well as actions taken after an episode of hyperkalemia. The proportions of patients with 0, <2, 2 to 4, and ≥4 potassium measurements per year were 20%, 58%, 16%, and 6%. Potassium levels >5 mEq/L and >5.5 mEq/L occurred in 10.8% and 2.3% of all patients over the 3-year period; among patients with ≥4 measurements per year, corresponding values were 39.4% and 14.6%. Most cases of hyperkalemia occurred only once during follow-up. The antihypertensive medication class most strongly associated with hyperkalemia was angiotensin-converting enzyme inhibitors. Among patients with a measurement of potassium >5.5 mEq/L, only 24% were seen by a nephrologist and 5.2% were seen by a dietician during the 3-year period. Short-term actions after a potassium measurement >5.5 mEq/L included emergency room visit (3.1% within 7 days), remeasurement of potassium (44.3% with 14 days), and change in a potassium-altering medication (26.4% within 60 days). The most common medication changes were discontinuation/dose reduction of an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or potassium-sparing diuretic, which occurred in 29.1% and 49.6% of people taking these medications, respectively. In conclusion, hyperkalemia is common. Future research may enable optimal renin-angiotensin-aldosterone system inhibitor use with improved management of hyperkalemia., (© 2016 American Heart Association, Inc.)

The recent 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults from the Eight Joint National Committee Panel may significantly affect the aging US population. We performed a cross-sectional analysis of black and white participants in Atherosclerosis Risk in Communities who participated in the fifth study visit (2011-2013). Sitting blood pressure was calculated from the average of 3 successive readings taken after a 5-minute rest. Currently, prescribed antihypertensive medications were recorded by reviewing medication containers brought to the visit. Blood pressure control was defined using both the Seventh and Eighth Joint National Committee thresholds. Of 6088 participants (mean age, 75.6 [range, 66-90] years, 58.4% women; 23.2% black), 54.9% had either diabetes mellitus or chronic kidney disease. The prevalence of hypertension according to Seventh Joint National Committee thresholds was 81.9%, and 62.8% of the entire sample were at blood pressure goal. Using the Eighth Joint National Committee thresholds, 79.4% were at blood pressure goal (16.6% were reclassified as at-goal). Reclassification was higher for individuals with diabetes mellitus or chronic kidney disease (20.6%) when compared with individuals without either condition (11.6%). The use of antihypertensive medications in our cohort was high, with 75.0% prescribed at least 1 antihypertensive medication and 46.7% on ≥2 antihypertensive agents. In conclusion, in a US cohort of aging white and black individuals, ≈1 in 6 individuals were reclassified as having blood pressure at goal by Eighth Joint National Committee guidelines. Despite these less aggressive goals, >20% remain uncontrolled by the new criteria., (© 2015 American Heart Association, Inc.)

Background: Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking., Methods and Results: We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996-1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], -43, -36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP., Conclusions: African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in this population., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Decreased kidney function and kidney damage may predate hypertension, but only a few studies have investigated both types of markers simultaneously, and these studies have obtained conflicting results., Study Design: Cross-sectional for prevalent and prospective observational study for incident hypertension., Setting & Participants: 9,593 participants from the ARIC (Atherosclerosis Risk in Communities) Study, aged 53-75 years in 1996-1998., Predictors: Several markers of kidney function (estimated glomerular filtration rate using serum creatinine and/or cystatin C and 2 novel markers [β-trace protein and β2-microglobulin]) and 1 marker of kidney damage (urinary albumin-creatinine ratio [ACR]). Every kidney marker was categorized by its quintiles (top quintile as a reference for estimated glomerular filtration rates and bottom quintile for the rest)., Outcomes: Prevalent and incident hypertension., Measurements: Prevalence ratios and HRs of hypertension based on modified Poisson regression and Cox proportional hazards models, respectively., Results: There were 4,378 participants (45.6%) with prevalent hypertension at baseline and 2,175 incident hypertension cases during a median follow-up of 9.8 years. Although all 5 kidney function markers were associated significantly with prevalent hypertension, prevalent hypertension was associated most notably with higher ACR (adjusted prevalence ratio, 1.60 [95% CI, 1.50-1.71] for the highest vs lowest ACR quintile). Similarly, ACR was associated consistently with incident hypertension in all models tested (adjusted HR, 1.28 [95% CI, 1.10-1.49] for top quintile), while kidney function markers demonstrated significant associations in some, but not all, models. Even mildly increased ACR (9.14-14.0mg/g) was associated significantly with incident hypertension., Limitations: Self-reported use of antihypertensive medication for defining incident hypertension, single assessment of kidney markers, and relatively narrow age range., Conclusions: Although all kidney markers were associated with prevalent hypertension, only elevated albuminuria was associated consistently with incident hypertension, suggesting that kidney damage is related more closely to hypertension than moderate reduction in overall kidney function., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Whether the association of chronic kidney disease (CKD) with cardiovascular risk differs based on diabetes mellitus (DM) and hypertension (HTN) status remains unanswered., Methods: We investigated 11,050 participants from the Atherosclerosis Risk in Communities Study (fourth examination (1996-1998)) with follow-up for cardiovascular outcomes (coronary disease, heart failure and stroke) through 2009. Using the Cox regression models, we quantified cardiovascular risk associated with estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) in individuals with and without DM and/or HTN and assessed their interactions., Results: Individuals with DM and HTN generally had higher cardiovascular risk relative to those without at all the levels of eGFR and ACR. Cardiovascular risk increased with lower eGFR and higher ACR regardless of DM and HTN status (e.g. adjusted hazards ratio (HR) for eGFR 30-44 vs. 90-104 ml/min/1.73 m(2), 2.32 (95% CI, 1.66-3.26) in non-diabetics vs. 1.83 (1.25-2.67) in diabetics and 2.45 (2.20-5.01) in non-hypertensives vs. 1.51 (1.27-1.81) in hypertensives and corresponding adjusted HR for ACR 30-299 vs. <10 mg/g, 1.70 (1.45-2.00) vs. 1.34 (1.10-1.64) and 1.42 (1.10-1.85) vs. 1.57 (1.36-1.81), respectively). Only the ACR-DM interaction reached significance, with a shallower relative risk gradient among diabetics than among non-diabetics (p = 0.02). Analysis of individual cardiovascular outcomes showed similar results., Conclusion: Although individuals with DM and HTN generally had higher cardiovascular risk relative to those without these complications, both low eGFR and high ACR were associated with cardiovascular diseases regardless of the presence or absence of DM and HTN. These findings reinforce the importance of CKD in cardiovascular outcomes., (© 2015 S. Karger AG, Basel.)

Importance: Hypertension is a treatable potential cause of cognitive decline and dementia, but its greatest influence on cognition may occur in middle age., Objective: To evaluate the association between midlife (48-67 years of age) hypertension and the 20-year change in cognitive performance., Design, Setting, and Participants: The Atherosclerosis Risk in Communities cohort (1990-1992 through 2011-2013) underwent evaluation at field centers in Washington County, Maryland, Forsyth County, North Carolina, Jackson, Mississippi, and the Minneapolis, Minnesota, suburbs. Of 13 476 African American and white participants with baseline cognitive data, 58.0% of living participants completed the 20-year cognitive follow-up., Exposures: Hypertension, prehypertension, or normal blood pressure (BP) at visit 2 (1990-1992) constituted the primary exposure. Systolic BP at visit 2 or 5 (2011-2013) and indication for treatment at visit 2 based on the Eighth Joint National Committee (JNC-8) hypertension guidelines constituted the secondary exposures., Main Outcomes and Measures: Prespecified outcomes included the 20-year change in scores on the Delayed Word Recall Test, Digit Symbol Substitution Test, and Word Fluency Test and in global cognition., Results: During 20 years, baseline hypertension was associated with an additional decline of 0.056 global z score points (95% CI, -0.100 to -0.012) and prehypertension was associated nonsignificantly with 0.040 more global z score points of decline (95% CI, -0.085 to 0.005) compared with normal BP. Individuals with hypertension who used antihypertensives had less decline during the 20 years than untreated individuals with hypertension (-0.050 [95% CI, -0.003 to -0.097] vs -0.079 [95% CI, -0.156 to -0.002] global z score points). Having a JNC-8-specified indication for initiating antihypertensive treatment at baseline was associated with a greater 20-year decline (-0.044 [95% CI, -0.085 to -0.003] global z score points) than not having an indication. We observed effect modification by race for the continuous systolic BP analyses (P = .01), with each 20-mm Hg increment at baseline associated with an additional decline of 0.048 (95% CI, -0.074 to -0.022) points in global cognitive z score in whites but not in African Americans (decline, -0.020 [95% CI, -0.026 to 0.066] points). Systolic BP at the end of follow-up was not associated with the preceding 20 years of cognitive change in either group. Methods to account for bias owing to attrition strengthened the magnitude of some associations., Conclusions and Relevance: Midlife hypertension and elevated midlife but not late-life systolic BP was associated with more cognitive decline during the 20 years of the study. Greater decline is found with higher midlife BP in whites than in African Americans.

Background: The extent to which the relative contributions of traditional cardiovascular risk factors to incident cardiovascular disease (CVD) may have changed over time remains unclear., Methods and Results: We studied 13 541 participants (56% women, 26% black) in the Atherosclerosis Risk in Communities Study, aged 52 to 66 years and free of CVD at exams in 1987 through 1989, 1990 through 1992, 1993 through 1995, or 1996 through 1998. At each examination, we estimated the population attributable risks (PAR) of traditional risk factors (hypertension, diabetes mellitus, obesity, hypercholesterolemia, and smoking) for the 10-year incidence of CVD. Overall, the PAR of all risk factors combined appeared to decrease from the late 1980s to the late 1990s (0.58 to 0.53). The combined PAR was higher in women than men in 1987 through 1989 (0.68 versus 0.51, P<0.001) but not by the late 1990s (0.58 versus 0.48, P=0.08). The combined PAR was higher in blacks than whites in the late 1980s (0.67 versus 0.57, P=0.049), and this difference was more pronounced by the late 1990s (0.67 versus 0.48, P=0.002). By the late 1990s, the PAR of hypertension had become higher in women than men (P=0.02) and also appeared higher in blacks than whites (P=0.08). By the late 1990s, the PAR of diabetes mellitus remained higher in women than men (P<0.0001) and in blacks than whites (P<0.0001)., Conclusions: The contribution to CVD of all traditional risk factors combined is greater in blacks than whites, and this difference may be increasing. The contributions of hypertension and diabetes mellitus remain especially high, in women as well as blacks. These findings underscore the continued need for individual as well as population approaches to CVD risk factor modification., (© 2014 American Heart Association, Inc.)

Objective: To test for a urate gene-by-diuretic interaction on incident gout., Methods: The Atherosclerosis Risk in Communities Study is a prospective population-based cohort of 15 792 participants recruited from four US communities (1987-1989). Participants with hypertension and available single nucleotide polymorphism (SNP) genotype data were included. A genetic urate score (GUS) was created from common urate-associated SNPs for eight genes. Gout incidence was self-reported. Using logistic regression, the authors estimated the adjusted OR of incident gout by diuretic use, stratified by GUS median., Results: Of 3524 participants with hypertension, 33% used a diuretic and 3.1% developed gout. The highest 9-year cumulative incidence of gout was in those with GUS above the median and taking a thiazide or loop diuretic (6.3%). Compared with no thiazide or loop diuretic use, their use was associated with an OR of 0.40 (95% CI 0.14 to 1.15) among those with a GUS below the median and 2.13 (95% CI 1.23 to 3.67) for those with GUS above the median; interaction p=0.006. When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney., Conclusions: Participants who were genetically predisposed to hyperuricaemia were susceptible to developing gout when taking thiazide or loop diuretics, an effect not evident among those without a genetic predisposition. These findings argue for a potential benefit of genotyping individuals with hypertension to assess gout risk, relative in part to diuretic use.

Background: Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease. However, whether the association of the kidney disease measures, estimated glomerular filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status is unknown., Methods: We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and ESRD associated with eGFR and albuminuria in individuals with and without hypertension., Findings: We analysed data for 45 cohorts (25 general population, seven high-risk, and 13 chronic kidney disease) with 1,127,656 participants, 364,344 of whom had hypertension. Low eGFR and high albuminuria were associated with mortality irrespective of hypertensive status in the general population and high-risk cohorts. All-cause mortality risk was 1·1-1·2 times higher in individuals with hypertension than in those without hypertension at preserved eGFR. A steeper relative risk gradient in individuals without hypertension than in those with hypertension at eGFR range 45-75 mL/min per 1·73 m(2) led to much the same mortality risk at lower eGFR. With a reference eGFR of 95 mL/min per 1·73 m(2) in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min per 1·73 m(2) was 1·77 (95% CI 1·57-1·99) in individuals without hypertension versus 1·24 (1·11-1·39) in those with hypertension (p for overall interaction=0·0003). Similarly, for albumin-creatinine ratio of 300 mg/g (vs 5 mg/g), HR was 2·30 (1·98-2·68) in individuals without hypertension versus 2·08 (1·84-2·35) in those with hypertension (p for overall interaction=0·019). We recorded much the same results for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, did not differ by hypertensive status. Results for chronic kidney disease cohorts were similar to those for general and high-risk population cohorts., Interpretation: Chronic kidney disease should be regarded as at least an equally relevant risk factor for mortality and ESRD in individuals without hypertension as it is in those with hypertension., Funding: US National Kidney Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The authors quantified the impact of hypertension on gout incidence in middle-aged white and African American men and women. The Atherosclerosis Risk in Communities Study (ARIC) was a prospective population-based cohort that recruited patients between 1987 and 1989 from 4 US communities. Using a time-dependent Cox proportional hazards model, the authors estimated the adjusted hazard ratio (HR) of incident gout by time-varying hypertension and tested for mediation by serum urate level. There were 10,872 participants among whom 45% had hypertension during follow-up; 43% were men and 21% were African American. Over 9 years, 274 (2.5%) participants developed gout (1.8% of women and 3.5% of men). The unadjusted HR of incident gout was approximately 3 times (HR, 2.87; 95% confidence interval [CI], 2.24-3.78) greater for those with hypertension. Adjusting for confounders resulted in an attenuated but still significant association between hypertension and gout (HR, 2.00; 95% CI, 1.54-2.61). Adjustment for serum urate level further attenuated but did not abrogate the association (HR, 1.36, 95% CI, 1.04-1.79). There was no evidence of effect modification by sex (P=.35), race (P=.99), or obesity at baseline (P=.82). Hypertension was independently associated with increased gout risk in middle-aged African American and white adults. Serum urate level may be a partial intermediate on the pathway between hypertension and gout., (© 2012 Wiley Periodicals, Inc.)

Objective: To quantify the role of diuretic use in gout development in an adult population with hypertension., Methods: The Atherosclerosis Risk in Communities study, a prospective population-based cohort from 4 US communities, consisted of 4 visits over a 9-year period. Participants were included in this analysis if they answered a query about gout, were free of gout at baseline, and had hypertension (defined as taking medication to treat hypertension or having blood pressure of ≥140/90 mm Hg). Trained interviewers recorded use of antihypertensive drugs. Incident gout was defined as self-reported onset of gout after baseline. Using a time-dependent Cox proportional hazards model, we estimated hazard ratios (HRs; with 95% confidence intervals [95% CIs]) for incident gout by time-varying diuretic use, both adjusted for confounders and tested for mediation by serum urate level., Results: There were 5,789 participants with hypertension; 37% were treated with a diuretic. Use of any diuretic (HR 1.48 [95% CI 1.11, 1.98]), a thiazide diuretic (HR 1.44 [95% CI 1.00, 2.10]), or a loop diuretic (HR 2.31 [95% CI 1.36, 3.91]) was associated with incident gout as compared with not using any diuretic, not using a thiazide diuretic, or not using a loop diuretic, respectively. After adjusting for serum urate level, the association between diuretic use and gout was null. Use of antihypertensive medication other than diuretic agents was associated with decreased gout risk (adjusted HR 0.64 [95% CI 0.49, 0.86]) compared to untreated hypertension. The longitudinal change in serum urate levels was 0.72 mg/dl (95% CI 0.57, 0.87) higher in those who began treatment with a diuretic than in those who did not (P<0.001)., Conclusion: Thiazide and loop diuretics were associated with increased gout risk, an association mediated by a change in serum urate levels., (Copyright © 2012 by the American College of Rheumatology.)

Hypertension status among spouses is known to be concordant, but previous studies relied on history rather than direct measurement, and few data exist on treatment and control between spouses. The goal of this study was to estimate the spousal association of hypertension status, treatment, and control in adults. The authors identified and analyzed data on 4,500 pairs from the Atherosclerosis Risk in Communities (ARIC) cohort, which sampled middle-aged adults and their spouses in 1986-1989, with 3 follow-up visits 3 years apart. Generalized estimating equations were used in logistic regression analyses to calculate the odds ratio of a spouse's being hypertensive on the basis of the other spouse's hypertension status across 4 visits, adjusting for age, race, body mass index, smoking status, and sodium intake in both individuals. There are marginally increased odds of hypertension for spouses married to someone with hypertension (odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.06, 1.25). Treatment was positively associated between spouses (OR = 1.35, 95% CI: 1.10, 1.67). Control was suggestive of an association, although it was not statistically significant (OR = 1.21, 95% CI: 0.93, 1.56). In middle-aged adults, hypertension status and treatment were moderately associated between spouses after controlling for shared environment. Physicians may target hypertension education and prevention to spouses as a pair rather than as 2 separate patients.