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Background: The association with cardiovascular disease (CVD) is stronger for mean systolic blood pressure (SBP) estimated using ambulatory blood pressure monitoring (ABPM) versus office measurements. Determining whether this is due to ABPM providing more measurement reliability or greater ecological validity can inform its use., Methods: We estimated the association of mean SBP based on 2 office measurements and 2, 5, 10, and 20 measurements on ABPM with incident CVD in the Jackson Heart Study (n=773). Hazard ratios (HRs) for CVD were estimated per standard deviation higher mean SBP. CVD events were defined by incident fatal or non-fatal stroke, non-fatal myocardial infarction, or fatal coronary heart disease., Results: There were 80 CVD events over a median 15 years. The adjusted HRs for incident CVD were 1.03 (95%CI: 0.90-1.19) for mean office SBP and 1.30 (95%CI: 1.12-1.50), 1.34 (95%CI: 1.15-1.56), 1.36 (95%CI: 1.17-1.59), and 1.38 (95%CI: 1.17-1.63) for mean SBP using the first 2, 5, 10 and 20 ABPM readings. The difference in the HRs for incident CVD ranged from 0.26 (95%CI: 0.07-0.46) to 0.35 (95%CI: 0.15-0.54) when comparing mean office SBP versus 2, 5, 10, or 20 sequential ABPM readings. The association with incident CVD was also stronger for mean SBP based on 2, 5, 10, and 20 randomly-selected ABPM readings versus 2 office readings., Conclusion: Mean SBP based on two ABPM readings versus two office measurements had a stronger association with CVD events. The increase in the strength of the association with more ABPM readings was small., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Apparent treatment-resistant hypertension (aTRH) is characterized by the use of four or more antihypertensive (AHT) classes to achieve blood pressure (BP) control. In the current study, we conducted single-variant and gene-based analyses of aTRH among individuals from 12 Trans-Omics for Precision Medicine cohorts with whole-genome sequencing data. Methods: Cases were defined as individuals treated for hypertension (HTN) taking three different AHT classes, with average systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg, or four or more medications regardless of BP ( n = 1,705). A normotensive control group was defined as individuals with BP < 140/90 mmHg ( n = 22,079), not on AHT medication. A second control group comprised individuals who were treatment responsive on one AHT medication with BP < 140/ 90 mmHg ( n = 5,424). Logistic regression with kinship adjustment using the Scalable and Accurate Implementation of Generalized mixed models (SAIGE) was performed, adjusting for age, sex, and genetic ancestry. We assessed variants using SKAT-O in rare-variant analyses. Single-variant and gene-based tests were conducted in a pooled multi-ethnicity stratum, as well as self-reported ethnic/racial strata (European and African American). Results: One variant in the known HTN locus, KCNK3 , was a top finding in the multi-ethnic analysis ( p = 8.23E-07) for the normotensive control group [rs12476527, odds ratio (95% confidence interval) = 0.80 (0.74-0.88)]. This variant was replicated in the Vanderbilt University Medical Center's DNA repository data. Aggregate gene-based signals included the genes AGTPBP, MYL4, PDCD4, BBS9, ERG, and IER3 . Discussion: Additional work validating these loci in larger, more diverse populations, is warranted to determine whether these regions influence the pathobiology of aTRH., Competing Interests: BP serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson and Johnson. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Armstrong, Srinivasasainagendra, Ammous, Assimes, Beitelshees, Brody, Cade, Ida Chen, Chen, de Vries, Floyd, Franceschini, Guo, Hellwege, House, Hwu, Kardia, Lange, Lange, McDonough, Montasser, O’Connell, Shuey, Sun, Tanner, Wang, Zhao, Carson, Edwards, Kelly, Kenny, Kooperberg, Loos, Morrison, Motsinger-Reif, Psaty, Rao, Redline, Rich, Rotter, Smith, Smith, Irvin and Arnett.)

Protease-activated receptor 4 (PAR4) (gene F2RL3) harbors a functional dimorphism, rs773902 A/G (encoding Thr120/Ala120, respectively) and is associated with greater platelet aggregation. The A allele frequency is more common in Black individuals, and Black individuals have a higher incidence of ischemic stroke than White individuals. However, it is not known whether the A allele is responsible for worse stroke outcomes. To directly test the in vivo effect of this variant on stroke, we generated mice in which F2rl3 was replaced by F2RL3, thereby expressing human PAR4 (hPAR4) with either Thr120 or Ala120. Compared with hPAR4 Ala120 mice, hPAR4 Thr120 mice had worse stroke outcomes, mediated in part by enhanced platelet activation and platelet-neutrophil interactions. Analyses of 7,620 Black subjects with 487 incident ischemic strokes demonstrated the AA genotype was a risk for incident ischemic stroke and worse functional outcomes. In humanized mice, ticagrelor with or without aspirin improved stroke outcomes in hPAR4 Ala120 mice, but not in hPAR4 Thr120 mice. P selectin blockade improved stroke outcomes and reduced platelet-neutrophil interactions in hPAR4 Thr120 mice. Our results may explain some of the racial disparity in stroke and support the need for studies of nonstandard antiplatelet therapies for patients expressing PAR4 Thr120.

Background: Prior studies have identified an association between hypertension and hyperuricemia; however, there has been limited research on the association between hypertension severity and hyperuricemia., Method: We studied 997 Black and white adults with serum urate data from the reasons for geographic and racial differences in stroke (REGARDS) study. Hypertension was defined as SBP ≥ 140 mmHg or DBP ≥ 90 mmHg or self-reported use of antihypertensive medication. Apparent treatment-resistant hypertension (aTRH) was defined as a SBP ≥ 140 mmHg or DBP ≥ 90 mmHg with concurrent use of three classes of antihypertensive medications, or taking four or more classes of antihypertensive medication regardless of BP level. Controlled BP was defined as SBP <140 mmHg and DBP <90 mmHg., Results: Overall 5.9% of participants had aTRH and 36.6% had hyperuricemia, defined as serum urate >7.0 mg/dl for men and >6.0 mg/dl for women. After full multivariable adjustment, the odds ratio (OR) for hyperuricemia associated with hypertension was 1.60 [95% confidence interval (95% CI): 1.06-2.40]. Compared to participants not taking antihypertensive medication, the ORs for hyperuricemia for participants taking one, two and three classes of antihypertensive medication without aTRH were 1.98 (95% CI: 1.23-3.20), 2.08 (95% CI: 1.25-3.43), 4.31 (95% CI: 2.07-8.97), respectively, and 3.96 (95% CI: 1.75-8.96) for aTRH. Compared to participants without hypertension, the odds ratios for hyperuricemia were 1.67 (95% CI: 1.08-2.58) and 1.46 (95% CI: 0.88-2.44) among those with hypertension with and without controlled BP, respectively. Diuretic use was associated with a higher odds of hyperuricemia., Conclusion: This study suggests that individuals taking more classes of antihypertensive medication may benefit from monitoring for hyperuricemia., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Hypertension is a leading risk factor for cardiovascular disease mortality. African Americans (AAs) have the highest prevalence of hypertension in the United States, and to alleviate the burden of hypertension in this population, better control of blood pressure (BP) is needed. Previous studies have shown considerable interpersonal differences in BP response to antihypertensive treatment, suggesting a genetic component. Utilizing data from 4297 AA participants randomized to chlorthalidone from the Genetics of Hypertension Associated Treatments (GenHAT) study, we aimed to identify variants associated with the efficacy of chlorthalidone. An additional aim was to find variants that contributed to changes in fasting glucose (FG) in these individuals. We performed genome-wide association analyses on the change of systolic and diastolic BP (SBP and DBP) over six months and FG levels over 24 months of treatment. We sought replication in the International Consortia of Pharmacogenomics Studies. We identified eight variants statistically associated with BP response and nine variants associated with FG response. One suggestive LINC02211-CDH9 intergenic variant was marginally replicated with the same direction of effect. Given the impact of hypertension in AAs, this study implies that understanding the genetic background for BP control and glucose changes during chlorthalidone treatment may help prevent adverse cardiovascular events in this population.

Background: African Americans (AAs) suffer a higher stroke burden due to hypertension. Identifying genetic contributors to stroke among AAs with hypertension is critical to understanding the genetic basis of the disease, as well as detecting at-risk individuals. Methods: In a population comprising over 10,700 AAs treated for hypertension from the Genetics of Hypertension Associated Treatments (GenHAT) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) studies, we performed an inverse variance-weighted meta-analysis of incident stroke. Additionally, we tested the predictive accuracy of a polygenic risk score (PRS) derived from a European ancestral population in both GenHAT and REGARDS AAs aiming to evaluate cross-ethnic performance. Results: We identified 10 statistically significant ( p < 5.00E-08) and 90 additional suggestive ( p < 1.00E-06) variants associated with incident stroke in the meta-analysis. Six of the top 10 variants were located in an intergenic region on chromosome 18 ( LINC01443-LOC644669 ). Additional variants of interest were located in or near the COL12A1, SNTG1 , PCDH7 , TMTC1 , and NTM genes . Replication was conducted in the Warfarin Pharmacogenomics Cohort (WPC), and while none of the variants were directly validated, seven intronic variants of NTM proximal to our target variants, had a p -value <5.00E-04 in the WPC. The inclusion of the PRS did not improve the prediction accuracy compared to a reference model adjusting for age, sex, and genetic ancestry in either study and had lower predictive accuracy compared to models accounting for established stroke risk factors. These results demonstrate the necessity for PRS derivation in AAs, particularly for diseases that affect AAs disproportionately. Conclusion: This study highlights biologically plausible genetic determinants for incident stroke in hypertensive AAs. Ultimately, a better understanding of genetic risk factors for stroke in AAs may give new insight into stroke burden and potential clinical tools for those among the highest at risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Armstrong, Srinivasasainagendra, Patki, Tanner, Hidalgo, Tiwari, Limdi, Lange, Lange, Arnett and Irvin.)

Background: The American Heart Association created the Life's Simple 7 (LS7) metrics to promote cardiovascular health (CVH) by achieving optimal levels of blood pressure, cholesterol, blood sugar, physical activity, diet, weight, and smoking status. The degree to which psychosocial factors such as stress and depression impact one's ability to achieve optimal CVH is unclear, particularly among hypertensive African Americans., Methods: Cross-sectional analyses included 1,819 African Americans with hypertension participating in the Jackson Heart Study (2000-2004). Outcomes were LS7 composite and individual component scores (defined as poor, intermediate, ideal). High perceived chronic stress was defined as the top quartile of Weekly Stress Inventory scores. High depressive symptoms were defined as Center for Epidemiologic Studies Depression scale scores of ≥16. We compared 4 groups: high stress alone; high depressive symptoms alone; high stress and high depressive symptoms; low stress and low depressive symptoms (reference) using linear regression for total LS7 scores and logistic regression for LS7 components., Results: Participants with both high stress and depressive symptoms had lower composite LS7 scores (B [95% confidence interval] = -0.34 [-0.65 to -0.02]) than those with low stress and depressive symptoms in unadjusted and age/sex-adjusted models. They also had poorer health status for smoking (odds ratio [95% confidence interval] = 0.52 [0.35-0.78]) and physical activity (odds ratio [95% confidence interval] = 0.71 [0.52-0.95]) after full covariate adjustment., Conclusions: The combination of high stress and high depressive symptoms was associated with poorer LS7 metrics in hypertensive African Americans. Psychosocial interventions may increase the likelihood of engaging in behaviors that promote optimal CVH., (© American Journal of Hypertension, Ltd 2021. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry. A total of 413 unique lipids were identified. Heritable and responsive lipid species were examined for association with single-nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array. The most statistically significant SNP findings were replicated in the Amish Heredity and Phenotype Intervention (HAPI) Heart Study. We further followed up findings from GOLDN with a regional analysis of cytosine-phosphate-guanine (CpGs) sites measured on the Illumina HumanMethylation450 array. A total of 132 lipids were both responsive to the meal challenge and heritable in the GOLDN study. After correction for multiple testing of 132 lipids (α = 5 × 10 -8 /132 = 4 × 10 -10 ), no SNP was statistically significantly associated with any lipid response. Four SNPs in the region of a known lipid locus (fatty acid desaturase 1 and 2/ FADS1 and FADS2 ) on chromosome 11 had p < 8.0 × 10 -7 for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with p < 3.3 × 10 -3 . CpGs around the FADS1/2 region were associated with arachidonic acid and the relationship of one SNP was partially mediated by a CpG ( p = 0.005). Both SNPs and CpGs from the fatty acid desaturase region on chromosome 11 contribute jointly and independently to the diet response to a high-fat meal.

Background: Guidelines recommend adults who discontinue statin therapy because of statin-associated symptoms be reinitiated. Low-density lipoprotein cholesterol (LDL-C) levels achieved after statin reinitiation are unknown., Objective: The objective of this study was to determine LDL-C levels after statin reinitiation., Methods: We analyzed data from 5498 participants in the REasons for Geographic And Racial Differences in Stroke study who reported ever taking a statin. We categorized participants according to their pattern of statin use including those taking a statin who did not experience statin-associated symptoms and continued treatment, and those who discontinued statins because of statin-associated symptoms and were not reinitiated, reinitiated and remained on treatment, and discontinued treatment after being reinitiated. Mortality and vascular event reduction with statin reinitiation was estimated using data from the Cholesterol-Lowering Treatment Trialists Collaboration., Results: After multivariable adjustment, LDL-C was 14.1 (95% CI: 9.9-18.3) mg/dL higher among participants reinitiated and taking a statin compared with those without statin-associated symptoms who continued statin therapy. Mean LDL-C was 18.1 mg/dL (95% CI: 13.0-23.1) and 27.5 mg/dL (95% CI: 20.7-34.4) lower among participants reinitiated and taking a statin compared with those who discontinued statin therapy and were not reinitiated and those who discontinued statins after being reinitiated, respectively. An LDL-C reduction of 18.1 mg/dL with statin reinitiation was projected to reduce all-cause and coronary heart disease mortality by 5.6% and 8.9%, respectively, and myocardial infarction or coronary heart disease death and major vascular events by 10.7% and 9.8%, respectively, over 5 years., Conclusion: Reinitiating individuals who discontinue statin therapy may reduce LDL-C and cardiovascular risk., (Copyright © 2020 National Lipid Association. All rights reserved.)

Objectives. To determine factors that explain the higher Black:White cardiovascular disease (CVD) mortality rates among US adults. Methods. We analyzed data from the Reasons for Geographic and Racial Differences in Stroke study from 2003 to 2017 to estimate Black:White hazard ratios (HRs) for CVD mortality within subgroups younger than 65 years and aged 65 years or older. Results. Among 29 054 participants, 41.0% who were Black and 54.9% who were women, 1549 CVD deaths occurred. Among participants younger than 65 years, the demographic-adjusted Black:White CVD mortality HR was 2.23 (95% confidence interval [CI] = 1.87, 2.65) and 1.21 (95% CI = 1.00, 1.47) after full adjustment. Among participants aged 65 years or older, the demographic-adjusted Black:White CVD mortality HR was 1.58 (95% CI = 1.39, 1.79) and 1.12 (95% CI = 0.97, 1.29) after full adjustment. When we used mediation analysis, socioeconomic status explained 21.2% (95% CI = 13.6%, 31.4%) and 38.0% (95% CI = 20.9%, 61.7%) of the Black:White CVD mortality risk difference among participants younger than 65 years and aged 65 years or older, respectively. CVD risk factors explained 56.6% (95% CI = 42.0%, 77.2%) and 41.3% (95% CI = 22.9%, 65.3%) of the Black:White CVD mortality difference for participants younger than 65 years and aged 65 years or older, respectively. Conclusions. The higher Black:White CVD mortality risk is primarily explained by racial differences in socioeconomic status and CVD risk factors.

Background and Objectives: Recent guidelines recommend out-of-clinic BP measurements., Design, Setting, Participants, & Measurements: We compared the prevalence of BP phenotypes between 561 black patients, with and without CKD, taking antihypertensive medication who underwent ambulatory BP monitoring at baseline (between 2000 and 2004) in the Jackson Heart Study. CKD was defined as an albumin-to-creatinine ratio ≥30 mg/g or eGFR <60 ml/min per 1.73 m 2 . Sustained controlled BP was defined by BP at goal both inside and outside of the clinic and sustained uncontrolled BP as BP above goal both inside and outside of the clinic. Masked uncontrolled hypertension was defined by controlled clinic-measured BP with uncontrolled out-of-clinic BP., Results: CKD was associated with a higher multivariable-adjusted prevalence ratio for uncontrolled versus controlled clinic BP (prevalence ratio, 1.44; 95% CI, 1.02 to 2.02) and sustained uncontrolled BP versus sustained controlled BP (prevalence ratio, 1.66; 95% CI, 1.16 to 2.36). There were no statistically significant differences in the prevalence of uncontrolled daytime or nighttime BP, nondipping BP, white-coat effect, and masked uncontrolled hypertension between participants with and without CKD after multivariable adjustment. After multivariable adjustment, reduced eGFR was associated with masked uncontrolled hypertension versus sustained controlled BP (prevalence ratio, 1.42; 95% CI, 1.00 to 2.00), whereas albuminuria was associated with uncontrolled clinic BP (prevalence ratio, 1.76; 95% CI, 1.20 to 2.60) and sustained uncontrolled BP versus sustained controlled BP (prevalence ratio, 2.02; 95% CI, 1.36 to 2.99)., Conclusions: The prevalence of BP phenotypes defined using ambulatory BP monitoring is high among adults with CKD taking antihypertensive medication., (Copyright © 2020 by the American Society of Nephrology.)

Human pluripotent stem cells (hPSCs) are an essential cell source in tissue engineering, studies of development, and disease modeling. Efficient, broadly amenable protocols for rapid lineage induction of hPSCs are of great interest in the stem cell biology field. We describe a simple, robust method for differentiation of hPSCs into mesendoderm in defined conditions utilizing single-cell seeding (SCS) and BMP4 and Activin A (BA) treatment. BA treatment was readily incorporated into existing protocols for chondrogenic and endothelial progenitor cell differentiation, while fine-tuning of BA conditions facilitated definitive endoderm commitment. After prolonged differentiation in vitro or in vivo, BA pretreatment resulted in higher mesoderm and endoderm levels at the expense of ectoderm formation. These data demonstrate that SCS with BA treatment is a powerful method for induction of mesendoderm that can be adapted for use in mesoderm and endoderm differentiation., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Recent studies have suggested that prediabetes is associated with an increased risk for cardiovascular disease (CVD) only among individuals with concomitant hypertension., Research Design and Methods: We analyzed the association between prediabetes and CVD by hypertension status among 3,313 black adults in the Jackson Heart Study (JHS) without diabetes or a history of CVD at baseline (2000-2004). Prediabetes was defined as fasting plasma glucose between 100 and 125 mg/dL or hemoglobin A 1c between 5.7 and 6.4% (39 and 46 mmol/mol). Hypertension was defined as systolic/diastolic blood pressure ≥140/90 mmHg and/or self-reported antihypertensive medication use. Participants were followed for incident CVD events and all-cause mortality through 31 December 2014., Results: Overall, 35% of JHS participants did not have prediabetes or hypertension, 18% had prediabetes alone, 22% had hypertension alone, and 25% had both prediabetes and hypertension. Compared with participants without either condition, the multivariable-adjusted hazard ratios for CVD events among participants with prediabetes alone, hypertension alone, and both prediabetes and hypertension were 0.86 (95% CI 0.51, 1.45), 2.09 (1.39, 3.14), and 1.93 (1.28, 2.90), respectively. Among participants with and without hypertension, there was no association between prediabetes and an increased risk for CVD (0.78 [0.46, 1.34] and 0.94 [0.70, 1.26], respectively). No association was present between prediabetes and all-cause mortality among participants with or without hypertension., Conclusions: Regardless of hypertension status, prediabetes was not associated with an increased risk for CVD or all-cause mortality in this cohort of black adults., (© 2019 by the American Diabetes Association.)

Background: Only a handful of genetic discovery efforts in apparent treatment-resistant hypertension (aTRH) have been described., Methods: We conducted a case-control genome-wide association study of aTRH among persons treated for hypertension, using data from 10 cohorts of European ancestry (EA) and 5 cohorts of African ancestry (AA). Cases were treated with 3 different antihypertensive medication classes and had blood pressure (BP) above goal (systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg) or 4 or more medication classes regardless of BP control (nEA = 931, nAA = 228). Both a normotensive control group and a treatment-responsive control group were considered in separate analyses. Normotensive controls were untreated (nEA = 14,210, nAA = 2,480) and had systolic BP/diastolic BP < 140/90 mm Hg. Treatment-responsive controls (nEA = 5,266, nAA = 1,817) had BP at goal (<140/90 mm Hg), while treated with one antihypertensive medication class. Individual cohorts used logistic regression with adjustment for age, sex, study site, and principal components for ancestry to examine the association of single-nucleotide polymorphisms with case-control status. Inverse variance-weighted fixed-effects meta-analyses were carried out using METAL., Results: The known hypertension locus, CASZ1, was a top finding among EAs (P = 1.1 × 10-8) and in the race-combined analysis (P = 1.5 × 10-9) using the normotensive control group (rs12046278, odds ratio = 0.71 (95% confidence interval: 0.6-0.8)). Single-nucleotide polymorphisms in this locus were robustly replicated in the Million Veterans Program (MVP) study in consideration of a treatment-responsive control group. There were no statistically significant findings for the discovery analyses including treatment-responsive controls., Conclusion: This genomic discovery effort for aTRH identified CASZ1 as an aTRH risk locus., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Importance: Little is known regarding health outcomes associated with higher blood pressure (BP) levels measured outside the clinic among African American individuals., Objective: To examine whether daytime and nighttime BP levels measured outside the clinic among African American individuals are associated with cardiovascular disease (CVD) and all-cause mortality independent of BP levels measured inside the clinic., Design, Setting, and Participants: This prospective cohort study analyzed data from 1034 African American participants in the Jackson Heart Study who completed ambulatory BP monitoring at baseline (September 26, 2000, to March 31, 2004). Mean daytime and nighttime BPs were calculated based on measurements taken while participants were awake and asleep, respectively. Data were analyzed from July 1, 2017, to April 30, 2019., Main Outcomes and Measures: Cardiovascular disease events, including coronary heart disease and stroke, experienced through December 31, 2014, and all-cause mortality experienced through December 31, 2016, were adjudicated. The associations of daytime BP and nighttime BP, separately, with CVD events and all-cause mortality were determined using Cox proportional hazards regression models., Results: A total of 1034 participants (mean [SD] age, 58.9 [10.9] years; 337 [32.6%] male; and 583 [56.4%] taking antihypertensive medication) were included in the study. The mean daytime systolic BP (SBP)/diastolic BP (DBP) was 129.4/77.6 mm Hg, and the mean nighttime SBP/DBP was 121.3/68.4 mm Hg. During follow-up (median [interquartile range], 12.5 [11.1-13.6] years for CVD and 14.8 [13.7-15.6] years for all-cause mortality), 113 CVD events and 194 deaths occurred. After multivariable adjustment, including in-clinic SBP and DBP, the hazard ratios (HRs) for CVD events for each SD higher level were 1.53 (95% CI, 1.24-1.88) for daytime SBP (per 13.5 mm Hg), 1.48 (95% CI, 1.22-1.80) for nighttime SBP (per 15.5 mm Hg), 1.25 (95% CI, 1.02-1.51) for daytime DBP (per 9.3 mm Hg), and 1.30 (95% CI, 1.06-1.59) for nighttime DBP (per 9.5 mm Hg). Nighttime SBP was associated with all-cause mortality (HR per 1-SD higher level, 1.24; 95% CI, 1.06-1.45), but no association was present for daytime SBP (HR, 1.13; 95% CI, 0.97-1.33) and daytime (HR, 0.95; 95% CI, 0.81-1.10) and nighttime (HR, 1.06; 95% CI, 0.90-1.24) DBP., Conclusions and Relevance: Among African American individuals, higher daytime and nighttime SBPs were associated with an increased risk for CVD events and all-cause mortality independent of BP levels measured in the clinic. Measurement of daytime and nighttime BP using ambulatory monitoring during a 24-hour period may help identify African American individuals who have an increased cardiovascular disease risk.

Background Left ventricular hypertrophy (LVH) is associated with an increased risk for cardiovascular disease (CVD) events and all-cause mortality. Many individuals without LVH have a left ventricular mass that exceeds the level predicted by their sex, body size, and cardiac workload, a condition called inappropriate left ventricular mass (iLVM). We investigated the association of iLVM with CVD events and all-cause mortality among blacks. Methods and Results We analyzed data from the Jackson Heart Study, a community-based cohort of blacks. The current analysis included 4424 participants without CVD and with an echocardiogram at baseline. Among this cohort, the prevalence of iLVM was 13.8%. There were 262 CVD events and 419 deaths over a median follow-up of 9.7 years (maximum, 12 years). Compared with participants without iLVM, participants with iLVM had a higher rate of CVD events and all-cause mortality. After multivariable adjustment, including for the presence of LVH, iLVM was associated with an increased risk of CVD events (hazard ratio, 1.87; 95% CI, 1.33-2.62). The multivariable-adjusted hazard ratio for all-cause mortality was 1.29 (95% CI, 0.98-1.70). Among participants without and with LVH, the multivariable-adjusted hazard ratios of iLVM for CVD events were 2.53 (95% CI, 1.68-3.81) and 1.21 (95% CI, 0.74-2.00), respectively (P interaction =0.029); and for all-cause mortality, the hazard ratios were 1.24 (95% CI, 0.81-1.89) and 1.26 (95% CI, 0.86-1.85), respectively (P interaction =0.664). Conclusions iLVM is associated with an increased risk for CVD events among blacks without LVH.

Background: Blacks have a high prevalence of hypertension and uncontrolled blood pressure (BP), each of which may be partially explained by untreated sleep apnea. We investigated the association of sleep apnea with uncontrolled BP and resistant hypertension in blacks., Methods: Between 2012 and 2016, Jackson Heart Sleep Study participants (N=913) underwent an in-home Type 3 sleep apnea study, clinic BP measurements, and anthropometry. Moderate or severe obstructive sleep apnea (OSA) was defined as a respiratory event index ≥15, and nocturnal hypoxemia was quantified as percent sleep time with <90% oxyhemoglobin saturation. Prevalent hypertension was defined as either a systolic BP ≥130 mm Hg or diastolic BP >80mm Hg, use of antihypertensive medication, or self-report of a diagnosis of hypertension. Controlled BP was defined as systolic BP <130 mm Hg and diastolic BP <80 mm Hg; uncontrolled BP as systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg with use of 1 to 2 classes of antihypertensive medication; and resistant BP as systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg with the use of ≥3 classes of antihypertensive medication (including a diuretic) or use of ≥4 classes of antihypertensive medication regardless of BP level. Multinomial logistic regression models were fit to determine the association between OSA severity and uncontrolled BP or resistant hypertension (versus controlled BP) after multivariable adjustment., Results: The analytic sample with hypertension (N=664) had a mean age of 64.0 (SD,10.6) years, and were predominately female (69.1%), obese (58.6%), and college educated (51.3%). Among the sample, 25.7% had OSA, which was untreated in 94% of participants. Overall, 48% of participants had uncontrolled hypertension and 14% had resistant hypertension. After adjustment for confounders, participants with moderate or severe OSA had a 2.0 times higher odds of resistant hypertension (95% confidence interval [CI], 1.14-3.67). Each standard deviation higher than <90% oxyhemoglobin saturation was associated with an adjusted odds ratio for resistant hypertension of 1.25 (95% CI 1.01-1.55). OSA and <90% oxyhemoglobin saturation were not associated with uncontrolled BP., Conclusion: Untreated moderate or severe OSA is associated with increased odds of resistant hypertension. These results suggest that untreated OSA may contribute to inadequate BP control in blacks.

Background The 2013 American College of Cardiology/American Heart Association cholesterol guidelines recognize cardiovascular disease and diabetes mellitus but not chronic kidney disease ( CKD ) as high-risk conditions warranting statin therapy. Statin use may be lower for adults with CKD compared with adults with conditions that have guideline indications for statin use. Methods and Results We analyzed data from the National Health and Nutrition Examination Surveys from 1999-2002 through 2011-2014 to determine trends in the percentage of US adults ≥20 years of age with and without CKD taking statins. CKD was defined by an estimated glomerular filtration rate <60 mL/min per 1.73m 2 or albumin-to-creatinine ratio ≥30 mg/g. Statin use was identified through a medication inventory. Between 1999-2002 and 2011-2014, the percentage of adults taking statins increased from 17.6% to 35.7% among those with CKD and from 6.8% to 14.7% among those without CKD . After multivariable adjustment, adults with CKD were not more likely to be taking statins compared with those without CKD (prevalence ratio, 1.01; 95% CI] 0.96-1.08). Among adults without a history of cardiovascular disease, those with CKD but not diabetes mellitus were less likely to be taking statins compared with those with diabetes mellitus but not CKD (prevalence ratio, 0.54; 95% CI , 0.44-0.66). Among adults with a history of cardiovascular disease, there was no difference in statin use between those with CKD but not diabetes mellitus versus those with diabetes mellitus but not CKD (prevalence ratio, 0.95; 95% CI , 0.79-1.15). Conclusions CKD does not appear to be a major stimulus for statin use among US adults.

Background: Higher dietary phosphorus is associated with left ventricular hypertrophy and mortality, which are blood pressure (BP)-related outcomes. For this reason, we hypothesized that dietary phosphorus may be associated with adverse clinic and ambulatory BP patterns., Methods: Our study included 973 African American adults enrolled in the Jackson Heart Study (2000-2004) with 24-hour ambulatory BP monitoring (ABPM) data at baseline. We quantified dietary phosphorus from a validated Food Frequency Questionnaire as follows: (i) absolute daily intake, (ii) ratio of phosphorus-to-protein intake, (iii) phosphorus density, and (iv) energy-adjusted phosphorus intake. Using multivariable linear regression, we determined associations between dietary phosphorus intake and systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure in clinic and over daytime, nighttime, and 24-hour periods from ABPM. Extent of nocturnal BP dipping was also assessed. Using logistic regression, we modeled relationships between dietary phosphorus intake and clinically relevant qualitative BP phenotypes, such as masked, sustained, or white-coat hypertension and normotension., Results: There were no statistically significant associations between phosphorus intake and SBP or pulse pressure in adjusted models. Most metrics of higher phosphorus intake were associated with lower daytime, nighttime, and clinic DBP. Higher phosphorus intake was not associated with clinic or ABPM-defined hypertension overall, but most metrics of higher phosphorus intake were associated with lower odds of sustained hypertension compared to sustained normotension, white-coat hypertension, and masked hypertension. There were no associations between dietary phosphorus and nocturnal BP dipping., Conclusions: These data do not support a role for higher phosphorus intake and higher BP in African Americans.

Guidelines recommend attempting to reinitiate statins in patients who discontinue treatment. Previous experiences while taking a statin, including side effects, may reduce a patient's willingness to reinitiate treatment. We determined the percentage of adults who are willing to reinitiate statin therapy after treatment discontinuation. Factors associated with willingness to reinitiate a statin were also examined. A statin questionnaire was administered and study examination conducted in black and white US adults enrolled in the nationwide REasons for Geographic And Racial Differences in Stroke study from 2013 to 2017. In participants who self-reported ever having taken a statin (n = 7,216, mean age 72 years, 53% women, 34% black), 1,081 (15%) reported having discontinued treatment. Among those who discontinued treatment, statin side effects, perceived lack of need for a statin, and cost were reported by 66%, 31%, and 3% of participants, respectively. Overall, 37% of participants who had discontinued treatment were willing to reinitiate statin therapy. Participants who discontinued treatment due to cost (prevalence ratio [PR] 1.61; 95% confidence interval (CI) 1.01, 2.57) were more likely to report a willingness to reinitiate therapy. Participants with a low-density lipoprotein-cholesterol ≥130 mg/dl versus <100 mg/dl (PR 0.69; 95% CI 0.53, 0. 88) and who discontinued treatment due to side effects (PR 0.51; 95% CI 0.41, 0.64) were less likely to report willingness to reinitiate statin therapy. In conclusion, a substantial proportion of participants who discontinued statin therapy were willing to reinitiate treatment. Healthcare providers should discuss reinitiation of statin therapy with their patients who have discontinued treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

99mTechnetium sestamibi scans (MIBI) can provide negative or inaccurate results in patients with biochemical primary hyperparathyroidism. Reliance on MIBI as a diagnostic modality rather than as a localization tool leads to misdiagnosis and inappropriate care. The aim of this study was to determine the impact of negative MIBI scans on referral patterns and surgical intervention. Adults with MIBI scans at our institution from January 1, 2011, to May 31, 2017, were retrospectively reviewed. Data collected include demographics, study date and results, ordering physician specialty, pre/postoperative laboratories, and operative and final pathology. Statistical analysis was performed with SPSS v24 (IBM Corp., Armonk, NY). Three hundred fifty-seven patients had a MIBI scan; 10 were excluded for incomplete data or incorrect diagnosis. One hundred eighty-six were interpreted as positive (53.6%) and 161 were interpreted as negative (46.4%). Of the 186 positive MIBI scans, 135 (72.6%) were seen by an endocrine surgeon (ES). Of these 135 patients, 111 (82.2%) underwent parathyroidectomy. Of the 161 negative MIBI scans, 69 (42.9%) were seen by an ES. Of these, 53 (76.8%) underwent parathyroidectomy. In all, 90/92 (97.8%) with a negative MIBI scan who were not seen by an ES did not have surgery. Nonendocrine surgeon physicians are more likely to use MIBI scans as diagnostic tools to assist with clinical decision-making. Patients with a negative MIBI scan not seen by an ES were significantly less likely to undergo parathyroidectomy. Patients with primary hyperparathyroidism should be referred to an experienced parathyroid surgeon for evaluation, regardless of the MIBI result.

It is unclear whether black patients with chronic kidney disease (CKD) vs those without CKD who take antihypertensive medication have an increased risk for apparent treatment-resistant hypertension (aTRH). The authors analyzed 1741 Jackson Heart Study participants without aTRH taking antihypertensive medication at baseline. aTRH was defined as uncontrolled blood pressure while taking three antihypertensive medication classes or taking four or more antihypertensive medication classes, regardless of blood pressure level. CKD was defined as an albumin to creatinine ratio ≥30 mg/g or estimated glomerular filtration rate <60 mL/min/1.73 m 2 . Over 8 years, 20.1% of participants without CKD and 30.5% with CKD developed aTRH. The multivariable-adjusted hazard ratio for aTRH comparing participants with CKD vs those without CKD was 1.45 (95% CI, 1.12-1.86). Participants with an albumin to creatinine ratio ≥30 vs <30 mg/g (hazard ratio, 1.44; 95% CI, 1.04-2.00) and estimated glomerular filtration rate of 45 to 59 mL/min/1.73 m 2 and <45 vs ≥60mL/min/1.73 m 2 (hazard ratio, 1.60 [95% CI, 1.16-2.20] and 2.05 [95% CI, 1.28-3.26], respectively) were more likely to develop aTRH., (©2017 Wiley Periodicals, Inc.)

The purpose of this study was to test the association between a self-report measure of 24-hour adherence to antihypertensive medication and blood pressure (BP) among African Americans. The primary analysis included 3558 Jackson Heart Study participants taking antihypertensive medication who had adherence data for at least one study examination. Nonadherence was defined by self-report of not taking one or more prescribed antihypertensive medications, identified during pill bottle review, in the past 24 hours. Nonadherence and clinic BP were assessed at Exam 1 (2000-2004), Exam 2 (2005-2008), and Exam 3 (2009-2013). Associations of nonadherence with clinic BP and uncontrolled BP (systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg) were evaluated using unadjusted and adjusted linear and Poisson repeated measures regression models. The prevalence of nonadherence to antihypertensive medications was 25.4% at Exam 1, 28.7% at Exam 2, and 28.5% at Exam 3. Nonadherence was associated with higher systolic BP (3.38 mm Hg) and diastolic BP (1.47 mm Hg) in fully adjusted repeated measures analysis. Nonadherence was also associated with uncontrolled BP (prevalence ratio = 1.26; 95% confidence interval = 1.16-1.37). This new self-report measure may be useful for identifying nonadherence to antihypertensive medication in future epidemiologic studies., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: Data from before the 2000s indicate that the majority of incident cardiovascular disease (CVD) events occur among US adults with systolic and diastolic blood pressure (SBP/DBP) ≥140/90 mm Hg. Over the past several decades, BP has declined and hypertension control has improved., Methods: We estimated the percentage of incident CVD events that occur at SBP/DBP <140/90 mm Hg in a pooled analysis of 3 contemporary US cohorts: the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), the MESA (Multi-Ethnic Study of Atherosclerosis), and the JHS (Jackson Heart Study) (n=31 856; REGARDS=21 208; MESA=6779; JHS=3869). Baseline study visits were conducted in 2003 to 2007 for REGARDS, 2000 to 2002 for MESA, and 2000 to 2004 for JHS. BP was measured by trained staff using standardized methods. Antihypertensive medication use was self-reported. The primary outcome was incident CVD, defined by the first occurrence of fatal or nonfatal stroke, nonfatal myocardial infarction, fatal coronary heart disease, or heart failure. Events were adjudicated in each study., Results: Over a mean follow-up of 7.7 years, 2584 participants had incident CVD events. Overall, 63.0% (95% confidence interval [CI], 54.9-71.1) of events occurred in participants with SBP/DBP <140/90 mm Hg; 58.4% (95% CI, 47.7-69.2) and 68.1% (95% CI, 60.1-76.0) among those taking and not taking antihypertensive medication, respectively. The majority of events occurred in participants with SBP/DBP <140/90 mm Hg among those <65 years of age (66.7%; 95% CI, 60.5-73.0) and ≥65 years of age (60.3%; 95% CI, 51.0-69.5), women (61.4%; 95% CI, 49.9-72.9) and men (63.8%; 95% CI, 58.4-69.1), and for whites (68.7%; 95% CI, 66.1-71.3), blacks (59.0%; 95% CI, 49.5-68.6), Hispanics (52.7%; 95% CI, 45.1-60.4), and Chinese-Americans (58.5%; 95% CI, 45.2-71.8). Among participants taking antihypertensive medication with SBP/DBP <140/90 mm Hg, 76.6% (95% CI, 75.8-77.5) were eligible for statin treatment, but only 33.2% (95% CI, 32.1-34.3) were taking one, and 19.5% (95% CI, 18.5-20.5) met the SPRINT (Systolic Blood Pressure Intervention Trial) eligibility criteria and may benefit from a SBP target goal of 120 mm Hg., Conclusions: Although higher BP levels are associated with increased CVD risk, in the modern era, the majority of incident CVD events occur in US adults with SBP/DBP <140/90 mm Hg. While absolute risk and cost-effectiveness should be considered, additional CVD risk-reduction measures for adults with SBP/DBP <140/90 mm Hg at high risk for CVD may be warranted., (© 2017 American Heart Association, Inc.)

Several modifiable health behaviors and health factors that comprise the Life's Simple 7-a cardiovascular health metric-have been associated with hypertension risk. We determined the association between cardiovascular health and incident hypertension in JHS (the Jackson Heart Study)-a cohort of blacks. We analyzed participants without hypertension or cardiovascular disease at baseline (2000-2004) who attended ≥1 follow-up visit in 2005 to 2008 or 2009 to 2012 (n=1878). Body mass index, physical activity, diet, cigarette smoking, blood pressure (BP), total cholesterol, and fasting glucose were assessed at baseline and categorized as ideal, intermediate, or poor using the American Heart Association's Life's Simple 7 definitions. Incident hypertension was defined at the first visit wherein a participant had systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or self-reported taking antihypertensive medication. The percentage of participants with ≤1, 2, 3, 4, 5, and 6 ideal Life's Simple 7 components was 6.5%, 22.4%, 34.4%, 25.2%, 10.0%, and 1.4%, respectively. No participants had 7 ideal components. During follow-up (median, 8.0 years), 944 (50.3%) participants developed hypertension, including 81.3% with ≤1 and 11.1% with 6 ideal components. The multivariable-adjusted hazard ratios (95% confidence interval) for incident hypertension comparing participants with 2, 3, 4, 5, and 6 versus ≤1 ideal component were 0.80 (0.61-1.03), 0.58 (0.45-0.74), 0.30 (0.23-0.40), 0.26 (0.18-0.37), and 0.10 (0.03-0.31), respectively ( P trend <0.001). This association was present among participants with baseline systolic BP <120 mm Hg and diastolic BP <80 mm Hg and separately systolic BP 120 to 139 mm Hg or diastolic BP 80 to 89 mm Hg. Blacks with better cardiovascular health have lower hypertension risk., (© 2017 American Heart Association, Inc.)

Apparent treatment-resistant hypertension (aTRH) is associated with adverse cardiovascular outcomes. aTRH is common and disproportionately affects African Americans. The objective of this study is to explore psychosocial correlates of aTRH in a population-based cohort of African Americans with hypertension. The sample included 1392 participants in the Jackson Heart Study with treated hypertension who reported being adherent to their antihypertensive medications. aTRH was defined as uncontrolled clinic BP (⩾140/90 mm Hg) with ⩾3 classes of antihypertensive medication or treatment with ⩾4 classes of antihypertensive medication, including a diuretic. Self-reported medication adherence was defined as taking all prescribed antihypertensive medication in the 24 h before the study visit. The association of psychosocial factors (chronic stress, depressive symptoms, perceived social support and social network) with aTRH was evaluated using Poisson regression with progressive adjustment for demographic, clinical and behavioural factors. The prevalence of aTRH was 15.1% (n=210). Participants with aTRH had lower social network scores (that is, fewer sources of regular social contact) compared with participants without aTRH (P<0.01). No other psychosocial factors differed between groups. Social network was also the only psychosocial factor that was associated with aTRH prevalence in regression analyses. In age-, sex-adjusted and fully adjusted models, one additional unique source of social contact was associated with a 19% (PR=0.81; 95% confidence interval (CI): 0.68-0.94, P=0.001) and a 13% (PR=0.87; 95% CI 0.74-1.0, P=0.041) lower prevalence of aTRH, respectively. Social network was independently associated with aTRH and warrants further investigation as a potentially modifiable determinant of aTRH in African Americans.

This corrects the article DOI: 10.1038/jhh.2016.100.

Purpose: Discontinuation of statin therapy represents a major challenge for effective cardiovascular disease prevention. It is unclear how often primary care physicians (PCPs) re-initiate statins and what barriers they encounter. We aimed to identify PCP perspectives on factors influencing statin re-initiation., Methods: We conducted six nominal group discussions with 23 PCPs from the Deep South Continuing Medical Education network. PCPs answered questions about statin side effects, reasons their patients reported for discontinuing statins, how they respond when discontinuation is reported, and barriers they encounter in getting their patients to re-initiate statin therapy. Each group generated a list of responses in round-robin fashion. Then, each PCP independently ranked their top three responses to each question. For each PCP, the most important reason was given a weight of 3 votes, and the second and third most important reasons were given weights of 2 and 1, respectively. We categorized the individual responses into themes and determined the relative importance of each theme using a "percent of available votes" metric., Results: PCPs reported that side effects, especially muscle/joint-related symptoms, were the most common reason patients reported for statin discontinuation (47% of available votes). PCPs reported statin re-challenge as their most common response when a patient discontinues statin use (31% of available votes). Patients' fear of side effects was ranked as the biggest challenge PCPs encounter in getting their patients to re-initiate statin therapy (70% of available votes)., Conclusion: PCPs face challenges getting their patients to re-initiate statins, particularly after a patient reports side effects.

Background: Abnormal diurnal blood pressure (BP), including nondipping patterns, assessed using ambulatory BP monitoring, have been associated with increased cardiovascular risk among white and Asian adults. We examined the associations of BP dipping patterns (dipping, nondipping, and reverse dipping) with cardiovascular target organ damage (left ventricular mass index and left ventricular hypertrophy), among participants from the Jackson Heart Study, an exclusively black population-based cohort., Methods and Results: Analyses included 1015 participants who completed ambulatory BP monitoring and had echocardiography data from the baseline visit. Participants were categorized based on the nighttime to daytime systolic BP ratio into 3 patterns: dipping pattern (≤0.90), nondipping pattern (>0.90 to ≤1.00), and reverse dipping pattern (>1.00). The prevalence of dipping, nondipping, and reverse dipping patterns was 33.6%, 48.2%, and 18.2%, respectively. In a fully adjusted model, which included antihypertensive medication use and clinic and daytime systolic BP, the mean differences in left ventricular mass index between reverse dipping pattern versus dipping pattern was 8.3±2.1 g/m 2 ( P <0.001) and between nondipping pattern versus dipping pattern was -1.0±1.6 g/m 2 ( P =0.536). Compared with participants with a dipping pattern, the prevalence ratio for having left ventricular hypertrophy was 1.65 (95% CI, 1.05-2.58) and 0.96 (95% CI, 0.63-1.97) for those with a reverse dipping pattern and nondipping pattern, respectively., Conclusions: In this population-based study of blacks, a reverse dipping pattern was associated with increased left ventricular mass index and a higher prevalence of left ventricular hypertrophy. Identification of a reverse dipping pattern on ambulatory BP monitoring may help identify black at increased risk for cardiovascular target organ damage., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Adults <50 years old, with diabetes mellitus, or a history of stroke were not enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). Estimating the size and characteristics of these excluded groups who meet the other SPRINT eligibility criteria may provide information on the potential impact of providers extending the SPRINT findings to these populations., Methods and Results: We analyzed the National Health and Nutrition Examination Survey 2003-2012 (n=25 076) to estimate the percentage and characteristics of US adults ≥20 years in 3 populations (age <50 years, diabetes mellitus, or history of stroke) excluded from SPRINT who otherwise meet the trial eligibility criteria: age ≥50 years, systolic blood pressure (SBP) 130-180 mm Hg, high cardiovascular disease risk, and not having trial exclusion criteria. Overall, 1.0% (95% CI 0.8-1.3) of US adults age <50 years, 25.4% (95% CI 23.4-27.6) with diabetes mellitus, and 19.0% (95% CI 16.0-22.4) with history of stroke met the other SPRINT eligibility criteria. Among US adults with SBP ≥130 mm Hg, other SPRINT eligibility criteria were met by 7.5% (95% CI 6.1-9.2) of those age <50 years, 32.9% (95% CI 30.5-35.4) with diabetes mellitus, and 23.0% (95% CI 19.4-27.0) with history of stroke. Among US adults meeting the other SPRINT eligibility criteria, antihypertensive medication was being taken by 31.0% (95% CI 23.9-41.3) of those <50 years, 63.0% (95% CI 58.2-67.6) with diabetes mellitus, and 68.9% (95% CI 59.4-77.1) with a history of stroke., Conclusions: A substantial percentage of US adults with diabetes mellitus or history of stroke and a small percentage <50 years old meet the other SPRINT eligibility criteria., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Studies consisting mostly of whites have shown that the prevalence of masked hypertension differs by prehypertension status. Using data from the Jackson Heart Study, an exclusively African American population-based cohort, we evaluated the association of masked hypertension and prehypertension with left ventricular mass index and common carotid intima media thickness., Methods and Results: At the baseline visit, clinic blood pressure (CBP) measurement and 24-hour ambulatory blood pressure monitoring were performed. Masked hypertension was defined as mean systolic/diastolic CBP <140/90 mm Hg and mean daytime systolic/diastolic ambulatory blood pressure ≥135/85 mm Hg. Clinic hypertension was defined as mean systolic/diastolic CBP ≥140/90 mm Hg. Normal CBP was defined as mean systolic/diastolic CBP <120/80 mm Hg and prehypertension as mean systolic/diastolic CBP 120 to 139/80 to 89 mm Hg. The analytic sample included 909 participants. Among participants with systolic/diastolic CBP <140/90 mm Hg, the prevalence of masked hypertension and prehypertension was 27.5% and 62.4%, respectively. The prevalence of masked hypertension among those with normal CBP and prehypertension was 12.9% and 36.3%, respectively. In a fully adjusted model, which included prehypertension status and antihypertensive medication use as covariates, left ventricular mass index was 7.94 g/m(2) lower among those without masked hypertension compared to participants with masked hypertension (P<0.001). Left ventricular mass index was also 4.77 g/m(2) lower among those with clinic hypertension, but this difference was not statistically significant (P=0.068). There were no significant differences in left ventricular mass index between participants with and without masked hypertension, or clinic hypertension., Conclusions: Masked hypertension was common among African Americans with prehypertension and also normal CBP, and was associated with subclinical cardiovascular disease., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background and Objectives: Increased visit-to-visit variability of BP is associated with cardiovascular disease risk. We examined the association of visit-to-visit variability of BP with renal outcomes among 21,245 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial., Design, Setting, Participants, & Measurements: We measured mean BP and visit-to-visit variability of BP, defined as SD, across five to seven visits occurring 6-28 months after participants were randomized to chlorthalidone, amlodipine, or lisinopril. The composite outcome included incident ESRD after assessment of SD of systolic BP or ≥50% decline in eGFR between 24 months and 48 or 72 months after randomization. We repeated the analyses using average real variability and peak value of systolic BP and for visit-to-visit variability of diastolic BP., Results: Over a mean follow-up of 3.5 years, 297 outcomes occurred. After multivariable adjustment, including baseline eGFR and mean systolic BP, the hazard ratios for the composite end point were 1.29 (95% confidence interval [95% CI], 0.75 to 2.22), 1.76 (95% CI, 1.06 to 2.91), 1.46 (95% CI, 0.88 to 2.45), and 2.05 (95% CI, 1.25 to 3.36) for the second through fifth (SD of systolic BP =6.63-8.82, 8.83-11.14, 11.15-14.56, and >14.56 mmHg, respectively) versus the first (SD of systolic BP <6.63 mmHg) quintile of SD of systolic BP, respectively (P trend =0.004). The association was similar when ESRD and a 50% decline in eGFR were analyzed separately, for other measures of visit-to-visit variability of systolic BP, and for visit-to-visit variability of diastolic BP., Conclusions: Higher visit-to-visit variability of BP is associated with higher risk of renal outcomes independent of mean BP., (Copyright © 2016 by the American Society of Nephrology.)

Background: In SPRINT (Systolic Blood Pressure Intervention Trial), a systolic blood pressure (SBP) goal of <120 mm Hg resulted in lower cardiovascular disease (CVD) risk compared with an SBP goal of <140 mm Hg., Objectives: The purpose of this study was to estimate the prevalence, number, and characteristics of U.S. adults meeting SPRINT eligibility criteria and determine the broader population to whom SPRINT could be generalized., Methods: We conducted a cross-sectional, population-based study using data from the National Health and Nutrition Examination Survey, 2007 to 2012. The SPRINT inclusion criteria were age ≥50 years, SBP 130 to 180 mm Hg depending on the number of antihypertensive medication classes being taken, and high CVD risk (history of coronary heart disease, estimated glomerular filtration rate of 20 to 59 ml/min/1.73 m(2), 10-year CVD risk ≥15%, or age ≥75 years). Exclusion criteria were diabetes, history of stroke, >1 g in 24 h of proteinuria daily, heart failure, estimated glomerular filtration rate <20 ml/min/1.73 m(2), or receiving dialysis. Treated hypertension was defined by self-reported use of medication to lower blood pressure with ≥1 class of antihypertensive medication identified through a pill bottle review., Results: Overall, 7.6% (95% confidence interval [CI]: 7.0% to 8.3%) or 16.8 million (95% CI: 15.7 to 17.8 million) U.S. adults, and 16.7% (95% CI: 15.2% to 18.3%) or 8.2 million (95% CI: 7.6 to 8.8 million) adults with treated hypertension met the SPRINT eligibility criteria. Among both the overall U.S. population and adults with treated hypertension, the percentage meeting SPRINT eligibility criteria increased with older age, was higher among males than females, and was higher among non-Hispanic whites compared with non-Hispanic blacks or Hispanics. Of U.S. adults eligible for SPRINT, 51.0% (95% CI: 47.8% to 54.1%) or 8.6 million (95% CI: 8.0 to 9.1 million) were not treated for hypertension., Conclusions: A substantial percentage of U.S. adults meet the eligibility criteria for SPRINT., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Current guidelines suggest using cystatin-C to confirm a reduced creatinine-based estimated glomerular filtration rate (eGFRcr) when the latter is thought to be inaccurate. Older adults have reduced muscle mass, which may affect the accuracy of eGFRcr. We evaluated the use of cystatin-C-based eGFR (eGFRcys) to confirm reduced eGFRcr among adults ≥ 80 years of age and, for comparison, younger adults., Material and Methods: We analyzed data from 3,059 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants with reduced eGFRcr (< 60 ml/min/1.73 m(2)) enrolled in 2003-2007 who were not on dialysis. eGFRcr and eGFRcys were calculated using age, sex and race-adjusted equations. Confirmed reduced eGFRcr was defined as eGFRcys < 60 ml/min/1.73 m(2). Prevalence of chronic kidney disease complications at baseline and all-cause mortality up to March 2012 were calculated. Analyses were stratified by age: < 65, 65-79 and ≥ 80 years., Results: Among participants < 65, 65-79 and ≥ 80 years of age, 76.5%, 85.7% and 92.5%, respectively, had reduced eGFRcr confirmed with eGFRcys (p < 0.001). Among participants ≥ 80 years of age, those with reduced eGFRcr confirmed with eGFRcys had higher prevalence of hypertension (79.1% vs. 65.1%, p = 0.03) and albuminuria (38.3% vs. 22.7%, p = 0.04) and higher risk for all-cause mortality (hazard ratio: 2.43; 95% confidence interval: 1.19-5.01) as compared with those in whom reduced eGFRcr was not confirmed by eGFRcys., Conclusions: Reduced eGFRcr was confirmed using eGFRcys for the vast majority of adults ≥ 80 years. These results suggest that using cystatin-C to confirm a reduced eGFRcr may not be necessary among the oldest old.

Many adults with elevated clinic blood pressure (BP) have lower BP when measured outside the clinic. This phenomenon, the "white-coat effect," may be larger among older adults, a population more susceptible to the adverse effects of low BP. The authors analyzed data from 257 participants in the Jackson Heart Study with elevated clinic BP (systolic/diastolic BP [SBP/DBP] ≥140/90 mm Hg) who underwent ambulatory BP monitoring (ABPM). The white-coat effect for SBP was larger for participants 60 years and older vs those younger than 60 years in the overall population (12.2 mm Hg, 95% confidence interval [CI], 9.2-15.1 mm Hg and 8.4 mm Hg, 95% CI, 5.7-11.1, respectively; P=.06) and among those without diabetes or chronic kidney disease (15.2 mm Hg, 95% CI, 10.1-20.2 and 8.6 mm Hg, 95% CI, 5.0-12.3, respectively; P=.04). After multivariable adjustment, clinic SBP ≥150 mm Hg vs <150 mm Hg was associated with a larger white-coat effect. Studies are needed to investigate the role of ABPM in guiding the initiation and titration of antihypertensive treatment, especially among older adults., (©2015 Wiley Periodicals, Inc.)

Objective: Recurrent stroke affects 5%-15% of stroke survivors, is higher among Blacks, and preventable with secondary stroke prevention medications. Our study aimed to examine racial differences in risk factors being addressed (defined as either on active treatment or within guideline levels) among stroke survivors and those at risk for stroke., Methods: A cross-sectional study using NHANES 2009-2010 standardized interviews of Whites and Blacks aged ≥18 years. Risk factors were defined as being addressed if: 1) for hypertension, SBP <140, DBP <90 (SBP<130, DBP<80 for diabetics) or using BP-lowering medications; 2) for current smoking, using cessation medications; and 3) for hyperlipidemia, LDL<100 (LDL<70 for stroke survivors) or using lipid-lowering medications. Participants were stratified by stroke history. Prevalence of addressed risk factors was compared by race., Results: Among 4005 participants (mean age 48, 52% women, 15% Black), 4% reported a history of stroke. Among stroke survivors, there were no statistically significant differences in Blacks and Whites having their hypertension or hyperlipidemia addressed. Among stroke naïve participants, the prevalence of addressed hypertension (P<.01) and hyperlipidemia (P<.01) was lower in Blacks compared with Whites., Conclusions: We found that addressed hypertension and hyperlipidemia in stroke naïve participants were significantly lower in Blacks than Whites. Our observations call attention to areas that require further investigation, such as why Black Americans may not be receiving evidence-based pharmacologic therapy for hypertension and hyperlipidemia or why Black Americans are not at goal blood pressure or goal LDL. A better understanding of this information is critical to preventing stroke and other vascular diseases.

Background: The association between waist circumference and end-stage renal disease (ESRD) remains poorly explored., Study Design: Longitudinal population-based cohort., Setting & Participants: Participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study (n=30,239) with information for body mass index (BMI), waist circumference, spot urine albumin-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR; n=26,960)., Predictor: Elevated waist circumference or BMI., Outcomes & Measurements: Incident cases of ESRD were identified through linkage of REGARDS participants with the US Renal Data System., Results: Mean baseline age was 64.8 years, 45.8% were men, and 40.3% were black. Overall, 297 (1.1%) individuals developed ESRD during a median of 6.3 years. After adjustment for all covariates including waist circumference, no significant association was noted between BMI categories and ESRD incidence compared to BMI of 18.5 to 24.9 kg/m2 (referent). Higher waist circumference categories showed significantly increased hazard rates of ESRD, with waist circumference ≥ 108 cm in women and ≥122 cm in men (highest category) showing a 3.97-fold higher hazard rate (95% CI, 2.10-6.86) for ESRD compared to waist circumference < 80 cm in women and <94 cm in men (referent) after adjusting for demographic factors and BMI. However, no significant association was noted between any waist circumference category and ESRD incidence after adjustment for obesity-associated comorbid conditions and baseline ACR and eGFR., Limitations: Short follow-up period (6.3 years) to assess ESRD risk among adults with eGFRs>60 mL/min/1.73 m2., Conclusions: In this cohort of older adults, obesity as measured by waist circumference is associated with higher ESRD risk even with adjustment for BMI, whereas obesity as measured by BMI is not associated with higher ESRD risk after adjustment for waist circumference. However, no significant association is noted between increased waist circumference and ESRD risk after adjustment for obesity-related comorbid conditions, eGFR, and ACR., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: We previously developed an 8-item self-assessment tool to identify individuals with a high probability of having albuminuria. This tool was developed and externally validated among non-Hispanic Whites and non-Hispanic Blacks. We sought to validate it in a multi-ethnic cohort that also included Hispanics and Chinese Americans., Design: This is a cross-sectional study., Setting: Data were collected using standardized questionnaires and spot urine samples at a baseline examination in 2000-2002. The 8 items in the self-assessment tool include age, race, gender, current cigarette smoking, history of diabetes, hypertension, or stroke, and self-rated health., Participants: Of 6,814 community-dwelling adults aged 45-84 years participating in the Multi-Ethnic Study of Atherosclerosis (MESA), 6,542 were included in the primary analysis., Main Outcome Measures: Albuminuria was defined as urine albumin-to-creatinine ratio ≥ 30 mg/g at baseline., Results: Among non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and Chinese Americans, the prevalence of albuminuria was 6.0%, 11.3%, 11.6%, and 10.8%, respectively. The c-statistic for discriminating participants with and without albuminuria was .731 (95% CI: .692, .771), .728 (95% CI: .687, .761), .747 (95% CI: .709, .784), and .761 (95% CI: .699, .814) for non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and Chinese Americans, respectively. The self-assessment tool over-estimated the probability of albuminuria for non-Hispanic Whites and Blacks, but was well-calibrated for Hispanics and Chinese Americans., Conclusions: The albuminuria self-assessment tool maintained good test characteristics in this large multi-ethnic cohort, suggesting it may be helpful for increasing awareness of albuminuria in an ethnically diverse population.

In embryonic stem cells (ESCs), gene regulatory networks (GRNs) coordinate gene expression to maintain ESC identity; however, the complete repertoire of factors regulating the ESC state is not fully understood. Our previous temporal microarray analysis of ESC commitment identified the E3 ubiquitin ligase protein Makorin-1 (MKRN1) as a potential novel component of the ESC GRN. Here, using multilayered systems-level analyses, we compiled a MKRN1-centered interactome in undifferentiated ESCs at the proteomic and ribonomic level. Proteomic analyses in undifferentiated ESCs revealed that MKRN1 associates with RNA-binding proteins, and ensuing RIP-chip analysis determined that MKRN1 associates with mRNAs encoding functionally related proteins including proteins that function during cellular stress. Subsequent biological validation identified MKRN1 as a novel stress granule-resident protein, although MKRN1 is not required for stress granule formation, or survival of unstressed ESCs. Thus, our unbiased systems-level analyses support a role for the E3 ligase MKRN1 as a ribonucleoprotein within the ESC GRN., (© 2015 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Background: Blood pressure control is a paramount goal in secondary stroke prevention; however, high prevalence of uncontrolled blood pressure and use of multiple antihypertensive medication classes in stroke patients suggest this goal is not being met. We determined the prevalence and factors associated with apparent treatment-resistant hypertension in persons with/without stroke or transient ischemic attack., Methods: Data came from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a national, population-based cohort of 30,239 black and white adults aged ≥45 years, enrolled 2003-2007, restricted to 11,719 participants with treated hypertension. Apparent treatment-resistant hypertension was defined as (1) uncontrolled blood pressure (systolic ≥140 mm Hg or diastolic ≥90 mm Hg) with ≥3 antihypertensive medication classes, or (2) use of ≥4 antihypertensive medication classes, regardless of blood pressure level. Poisson regression was used to calculate characteristics associated with apparent treatment-resistant hypertension., Results: Among hypertensive participants, prevalence of apparent treatment-resistant hypertension was 24.9% (422 of 1694) and 17.0% (1708 of 10,025) in individuals with and without history of stroke or transient ischemic attack, respectively. After adjustment for cardiovascular risk factors, the prevalence ratio for apparent treatment-resistant hypertension for those with versus without stroke or transient ischemic attack was 1.14 (95% confidence interval, 1.03-1.27). Among hypertensive participants with stroke or transient attack, male sex, black race, larger waist circumference, longer duration of hypertension, and reduced kidney function were associated with apparent treatment-resistant hypertension., Conclusions: The high prevalence of apparent treatment-resistant hypertension among hypertensive persons with history of stroke or transient ischemic attack suggests the need for more individualized blood pressure monitoring and management., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Studies suggest 24-h blood pressure (BP) variability has prognostic value for cardiovascular disease. Several factors associated with high 24-h BP variability are also common among individuals with chronic kidney disease (CKD). We hypothesized 24-h BP variability would be higher for individuals with versus without CKD., Methods: We analyzed 1,022 Jackson Heart Study participants who underwent ambulatory blood pressure monitoring (ABPM). Twenty-four hour BP variability was defined by two metrics: day-night standard deviation (SDdn) and average real variability (ARV). CKD was defined as ACR ≥ 30 mg/g or eGFR <60 mL/min/1.73 m(2)., Results: The mean SDdn of systolic BP (SBP) was 10.2 ± 0.2 and 9.1 ± 0.1 mmHg and the mean ARV of SBP was 9.2 ± 0.2 and 8.6 ± 0.1 mmHg for those with and without CKD, respectively (each p ≤ 0.001). After adjustment for age and sex, SDdn and ARV were 0.98 mmHg (95 % CI 0.59, 1.38) and 0.52 mmHg (95 % CI 0.18, 0.86), respectively, higher among participants with versus without CKD. These differences were not statistically significant after further multivariable adjustment including 24-h mean SBP. Older age, and higher total cholesterol and 24-h mean SBP were associated with higher SDdn and ARV of SBP among participants with CKD. Mean SDdn and ARV of diastolic BP (DBP) were higher for participants with versus without CKD but these associations were not present after multivariable adjustment., Conclusion: Data from the current study suggest that CKD is associated with higher 24-h BP variability, but the association is primarily explained by higher mean BP among those with CKD.

Obesity is associated with chronic kidney disease progression. Whether metabolic risk factors modify this association is unclear. Here we examined associations of body mass index (BMI) and metabolic health with risk of end-stage renal disease (ESRD) in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Among 21,840 participants eligible for analysis, 247 developed ESRD (mean follow-up of 6.3 years). Metabolic health significantly modified the association of BMI with ESRD. In models stratified by the presence or absence of the metabolic syndrome and adjusted for demographic, lifestyle, and clinical factors, higher BMI was associated with lower risk of ESRD in those without (hazard ratio per 5 kg/m2 increase in BMI 0.70, 95% CI 0.52, 0.95) but not those with (hazard ratio, 1.06) the metabolic syndrome. In models stratified by weight and metabolic health, compared with normal weight (BMI 18.5-24.9 kg/m2) participants without the metabolic syndrome the overweight individuals (BMI 25-29.9) and obese individuals (BMI of 30 or more) with the metabolic syndrome had greater risk of ESRD (hazard ratios of 2.03 and 2.29, respectively), whereas obesity without the metabolic syndrome was associated with lower risk of ESRD (hazard ratio 0.47). Thus, higher BMI is associated with lower ESRD risk in those without but not those with the metabolic syndrome.

The Kidney Disease Improving Global Outcomes Lipid Work Group recommends statins for adults ≥50 years old with CKD. The American College of Cardiology/American Heart Association endorses statins for adults with atherosclerotic cardiovascular disease, adults with LDL cholesterol≥190 mg/dl, and adults 40-79 years old with LDL cholesterol=70-189 mg/dl and diabetes or a 10-year predicted risk for atherosclerotic cardiovascular disease ≥7.5% estimated using the Pooled Cohort risk equations. Using data from the Reasons for Geographic and Racial Differences in Stroke Study, we calculated the agreement for statin treatment between these two guidelines for adults 50-79 years old with CKD (eGFR<60 ml/min per 1.73 m(2) or albuminuria≥30 mg/g) not on dialysis. We assessed the validity of the Pooled Cohort risk equations in individuals with CKD. Study participants were enrolled between 2003 and 2007, and we report incident cardiovascular disease events (stroke and coronary heart disease) through December of 2010. Among 4726 participants with CKD, 2366 (50%) were taking statins, and 1984 (42%) were recommended statins by the American College of Cardiology/American Heart Association guideline but not taking them. Overall, 376 (8%) participants did not meet the American College of Cardiology/American Heart Association criteria for initiating statin treatment. Cardiovascular disease incidence was low (3.0/1000 person-years; 95% confidence interval, 0.1 to 5.9) among these participants. The Pooled Cohort risk equations were well calibrated (Hosmer-Lemeshow chi-squared=2.7, P=0.45) with moderately good discrimination (C index, 0.71; 95% confidence interval, 0.65 to 0.77). In conclusion, these guidelines show high concordance for statin treatment for adults with CKD., (Copyright © 2015 by the American Society of Nephrology.)

Introduction: Atrial fibrillation (AF) is an independent risk factor for end-stage renal disease (ESRD) among persons with chronic kidney disease (CKD), however, the association between AF and incident ESRD has not been examined in the general United States population., Methods: A total of 24,953 participants (mean age 65 ± 9.0 years; 54% women; 40% blacks) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were included in this analysis. AF was identified at baseline (2003-2007) from electrocardiogram data and self-reported history. Incident cases of ESRD were identified through linkage with the United States Renal Data System. Cox proportional-hazards regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between AF and incident ESRD., Results: A total of 2,155 (8.6%) participants had AF at baseline. Over a median follow-up of 7.4 years, 295 (1.2%) persons developed ESRD. In a model adjusted for demographics and potential confounders, AF was associated with an increased risk of incident ESRD (HR=1.51, 95% CI=1.08, 2.11). The association between AF and ESRD became non-significant after further adjustment for CKD markers (eGFR <60 mL/min/1.73 m(2) and urine albumin-to-creatinine ratio ≥ 30 mg/dL) (HR=1.24, 95% CI=0.89, 1.73)., Conclusion: AF is associated with an increased risk of ESRD in the general United States population and this association potentially is explained by underlying CKD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)