Antihypertensive medication nonadherence and target organ damage in children with chronic kidney disease.

BACKGROUND: Nonadherence is common in children with chronic kidney disease (CKD). This may contribute to inadequate blood pressure control and adverse outcomes. This study examined associations between antihypertensive medication nonadherence, ambulatory blood pressure monitoring (ABPM) parameters, kidney function, and cardiac structure among children with CKD. METHODS: We performed secondary analyses of data from the CKD in Children (CKiD) study, including participants with treated hypertension who underwent ABPM, laboratory testing, and echocardiography biannually. Nonadherence was defined by self-report of any missed antihypertensive medication 7 days prior to the study visit. Linear regression and mixed-effects models were used to assess the association of nonadherence with baseline and time-updated ABPM profiles, estimated glomerular filtration rate (eGFR), urine protein to creatinine ratio (UPCR), and left ventricular mass index (LVMI). RESULTS: Five-hundred and eight participants met inclusion criteria, followed for a median of 2.9 years; 212 (42%) were female, with median age 13 years (IQR 10-16), median baseline eGFR 49 (33-64) ml/min/1.73 m2 and median UPCR 0.4 (0.1-1.0) g/g. Nonadherence occurred in 71 (14%) participants. Baseline nonadherence was not significantly associated with baseline 24-h ABPM parameters (for example, mean 24-h SBP [ß - 0.1, 95% CI - 2.7, 2.5]), eGFR (ß 1.0, 95% CI - 0.9, 1.2), UCPR (ß 1.1, 95% CI - 0.8, 1.5), or LVMI (ß 0.6, 95% CI - 1.6, 2.9). Similarly, there were no associations between baseline nonadherence and time-updated outcome measures. CONCLUSIONS: Self-reported antihypertensive medication nonadherence occurred in 1 in 7 children with CKD. We found no associations between nonadherence and kidney function or cardiac structure over time. A higher resolution version of the Graphical abstract is available as Supplementary information.

Knowledge Gaps, Challenges, and Opportunities in Health and Prevention Research for Asian Americans, Native Hawaiians, and Pacific Islanders: A Report From the 2021 National Institutes of Health Workshop.

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.

Association of Serum Aldosterone and Plasma Renin Activity With Ambulatory Blood Pressure in African Americans: The Jackson Heart Study.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) is an important driver of blood pressure (BP), but the association of the RAAS with ambulatory BP (ABP) and ABP monitoring phenotypes among African Americans has not been assessed. METHODS: ABP and ABP monitoring phenotypes were assessed in 912 Jackson Heart Study participants with aldosterone and plasma renin activity (PRA). Multivariable linear and logistic regression analyses were used to analyze the association of aldosterone and PRA with clinic, awake, and asleep systolic BP and diastolic BP (DBP) and ABP monitoring phenotypes, adjusting for important confounders. RESULTS: The mean age of participants was 59±11 years and 69% were female. In fully adjusted models, lower log-PRA was associated with higher clinic, awake, and asleep systolic BP and DBP (all P<0.05). A higher log-aldosterone was associated with higher clinic, awake, and asleep DBP (all P<0.05). A 1-unit higher log-PRA was associated with lower odds of daytime hypertension (odds ratio [OR] 0.59 [95% CI, 0.49-0.71]), nocturnal hypertension (OR, 0.68 [95% CI, 0.58-0.79]), daytime and nocturnal hypertension (OR, 0.59 [95% CI, 0.48-0.71]), sustained hypertension (OR, 0.52 [95% CI, 0.39-0.70]), and masked hypertension (OR 0.75 [95% CI, 0.62-0.90]). A 1-unit higher log-aldosterone was associated with higher odds of nocturnal hypertension (OR, 1.38 [95% CI, 1.05-1.81]). Neither PRA nor aldosterone was associated with percent dipping, nondipping BP pattern, or white-coat hypertension. Patterns for aldosterone:renin ratio were similar to patterns for PRA. CONCLUSIONS: Suppressed renin activity and higher aldosterone:renin ratios were associated with higher systolic BP and DBP in the office and during the awake and asleep periods as evidenced by ABP monitoring. Higher aldosterone levels were associated with higher DBP, but not systolic BP, in the clinic and during the awake and asleep periods. Further clinical investigation of novel and approved medications that target low renin physiology such as epithelial sodium channel inhibitors and mineralocorticoid receptor antagonists may be paramount in improving hypertension control in African Americans.

Rare coding variants in RCN3 are associated with blood pressure.

BACKGROUND: While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries. RESULTS: Associations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10- 7). CONCLUSIONS: Low frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits.

Factors associated with antihypertensive monotherapy among US adults with treated hypertension and uncontrolled blood pressure overall and by race/ethnicity, National Health and Nutrition Examination Survey 2013-2018.

BACKGROUND: Treating hypertension with antihypertensive medications combinations, rather than one medication (ie, monotherapy), is underused in the United States, particularly in certain race/ethnic groups. Identifying factors associated with monotherapy use despite uncontrolled blood pressure (BP) overall and within race/ethnic groups may elucidate intervention targets in under-treated populations. METHODS: Cross-sectional analysis of National Health and Nutrition Examination Surveys (NHANES; 2013-2014 through 2017-2018). We included participants age ≥20 years with hypertension, taking at least one antihypertensive medication, and uncontrolled BP (systolic BP [SBP] ≥ 140 mmHg or diastolic BP [DBP] ≥ 90 mmHg). Demographic, clinical, and healthcare-access factors associated with antihypertensive monotherapy were determined using multivariable-adjusted Poisson regression. RESULTS: Among 1,597 participants with hypertension and uncontrolled BP, age- and sex- adjusted prevalence of monotherapy was 42.6% overall, 45.4% among non-Hispanic White, 31.9% among non-Hispanic Black, 39.6% among Hispanic, and 50.9% among non-Hispanic Asian adults. Overall, higher SBP was associated with higher monotherapy use, while older age, having a healthcare visit in the previous year, higher body mass index, and having heart failure were associated with lower monotherapy use. CONCLUSION: Clinical and healthcare-access factors, including a healthcare visit within the previous year and co-morbid conditions were associated with a higher likelihood of combination antihypertensive therapy.

Prospective associations between neighborhood violence and monocyte pro-inflammatory transcriptional activity in children.

Individuals exposed to persistent neighborhood violence are at increased risk for developing mental and physical health problems across the lifespan. The biological mechanisms underlying this phenomenon are not well understood. Thus, we examined the relationship between children's exposure to neighborhood violence and inflammatory activity, a process involved in the pathogenesis of multiple health problems. 236 children from the Chicago area participated in a two-year longitudinal study (mean age at baseline, 13.9 years; 67% female; 39% White, 34% Black, 33% Hispanic). Neighborhood violence was measured as the homicide frequency in a child's Census block group in the five years before study entry. Fasting blood was drawn at study entry and two years later (in eighth and tenth grade). The blood was used to quantify protein biomarkers of systemic inflammatory activity and perform genome-wide expression profiling of isolated monocytes. Neighborhood violence was associated with higher systemic inflammatory activity at both assessments. It also was associated with a monocyte transcriptional profile indicative of increased signaling along the nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1) control pathways, which are key orchestrators of pro-inflammatory effector functions. Neighborhood violence also was associated with transcriptional indications of higher beta-adrenergic and lower glucocorticoid signaling, which could function as neuroendocrine conduits linking threatening experiences with inflammatory activity. Neighborhood violence was not associated with two-year changes in protein biomarkers, although it did presage a transcriptional profile indicative of increasing AP-1 and declining glucocorticoid signaling over follow-up. Collectively, these observations highlight cellular and molecular pathways that could underlie health risks associated with neighborhood violence.

Self-Measured Blood Pressure Monitoring at Home: A Joint Policy Statement From the American Heart Association and American Medical Association.

The diagnosis and management of hypertension, a common cardiovascular risk factor among the general population, have been based primarily on the measurement of blood pressure (BP) in the office. BP may differ considerably when measured in the office and when measured outside of the office setting, and higher out-of-office BP is associated with increased cardiovascular risk independent of office BP. Self-measured BP monitoring, the measurement of BP by an individual outside of the office at home, is a validated approach for out-of-office BP measurement. Several national and international hypertension guidelines endorse self-measured BP monitoring. Indications include the diagnosis of white-coat hypertension and masked hypertension and the identification of white-coat effect and masked uncontrolled hypertension. Other indications include confirming the diagnosis of resistant hypertension and detecting morning hypertension. Validated self-measured BP monitoring devices that use the oscillometric method are preferred, and a standardized BP measurement and monitoring protocol should be followed. Evidence from meta-analyses of randomized trials indicates that self-measured BP monitoring is associated with a reduction in BP and improved BP control, and the benefits of self-measured BP monitoring are greatest when done along with cointerventions. The addition of self-measured BP monitoring to office BP monitoring is cost-effective compared with office BP monitoring alone or usual care among individuals with high office BP. The use of self-measured BP monitoring is commonly reported by both individuals and providers. Therefore, self-measured BP monitoring has high potential for improving the diagnosis and management of hypertension in the United States. Randomized controlled trials examining the impact of self-measured BP monitoring on cardiovascular outcomes are needed. To adequately address barriers to the implementation of self-measured BP monitoring, financial investment is needed in the following areas: improving education and training of individuals and providers, building health information technology capacity, incorporating self-measured BP readings into clinical performance measures, supporting cointerventions, and enhancing reimbursement.

Platelet bound complement split product (PC4d) is a marker of platelet activation and arterial vascular events in Systemic Lupus Erythematosus.

Platelet-bound complement activation products (PC4d) are associated with thrombosis in Systemic Lupus Erythematosus (SLE). This study investigated the effect of PC4d on platelet function, as a mechanistic link to arterial thrombosis. In a cohort of 150 SLE patients, 13 events had occurred within five years of enrollment. Patients with arterial events had higher PC4d levels (13.6 [4.4-24.0] vs. 4.0 [2.5-8.3] net MFI), with PC4d 10 being the optimal cutoff for event detection. The association of arterial events with PC4d remained significant after adjusting for antiphospholipid status, smoking, and prednisone use (p = 0.045). PC4d levels correlated with lower platelet counts (r = -0.26, p = 0.002), larger platelet volumes (r = 0.22, p = 0.009) and increased platelet aggregation: the adenosine diphosphate (ADP) concentration to achieve 50% maximal aggregation (EC50) was lower in patients with PC4d 10 compared with PC4d < 10 (1.6 vs. 3.7, p = 0.038, respectively). These results suggest that PC4d may be a mechanistic marker for vascular disease in SLE.

Does This Adult Patient Have Hypertension?: The Rational Clinical Examination Systematic Review.

Importance: Office blood pressure (BP) measurements are not the most accurate method to diagnose hypertension. Home BP monitoring (HBPM) and 24-hour ambulatory BP monitoring (ABPM) are out-of-office alternatives, and ABPM is considered the reference standard for BP assessment. Objective: To systematically review the accuracy of oscillometric office and home BP measurement methods for correctly classifying adults as having hypertension, defined using ABPM. Data Sources: PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and DARE databases and the American Heart Association website (from inception to April 2021) were searched, along with reference lists from retrieved articles. Data Extraction and Synthesis: Two authors independently abstracted raw data and assessed methodological quality. A third author resolved disputes as needed. Main Outcomes and Measures: Random effects summary sensitivity, specificity, and likelihood ratios (LRs) were calculated for BP measurement methods for the diagnosis of hypertension. ABPM (24-hour mean BP ≥130/80 mm Hg or mean BP while awake ≥135/85 mm Hg) was considered the reference standard. Results: A total of 12 cross-sectional studies (n = 6877) that compared conventional oscillometric office BP measurements to mean BP during 24-hour ABPM and 6 studies (n = 2049) that compared mean BP on HBPM to mean BP during 24-hour ABPM were included (range, 117-2209 participants per analysis); 2 of these studies (n = 3040) used consecutive samples. The overall prevalence of hypertension identified by 24-hour ABPM was 49% (95% CI, 39%-60%) in the pooled studies that evaluated office measures and 54% (95% CI, 39%-69%) in studies that evaluated HBPM. All included studies assessed sensitivity and specificity at the office BP threshold of 140/90 mm Hg and the home BP threshold of 135/85 mm Hg. Conventional office oscillometric measurement (1-5 measurements in a single visit with BP ≥140/90 mm Hg) had a sensitivity of 51% (95% CI, 36%-67%), specificity of 88% (95% CI, 80%-96%), positive LR of 4.2 (95% CI, 2.5-6.0), and negative LR of 0.56 (95% CI, 0.42-0.69). Mean BP with HBPM (with BP ≥135/85 mm Hg) had a sensitivity of 75% (95% CI, 65%-86%), specificity of 76% (95% CI, 65%-86%), positive LR of 3.1 (95% CI, 2.2-4.0), and negative LR of 0.33 (95% CI, 0.20-0.47). Two studies (1 with a consecutive sample) that compared unattended automated mean office BP (with BP ≥135/85 mm Hg) with 24-hour ABPM had sensitivity ranging from 48% to 51% and specificity ranging from 80% to 91%. One study that compared attended automated mean office BP (with BP ≥140/90 mm Hg) with 24-hour ABPM had a sensitivity of 87.6% (95% CI, 83%-92%) and specificity of 24.1% (95% CI, 16%-32%). Conclusions and Relevance: Office measurements of BP may not be accurate enough to rule in or rule out hypertension; HBPM may be helpful to confirm a diagnosis. When there is uncertainty around threshold values or when office and HBPM are not in agreement, 24-hour ABPM should be considered to establish the diagnosis.

Cryptococcus neoformans infective endocarditis after lung transplantation: a case report and review of the literature.

Cryptococcus neoformans infective endocarditis is rarely reported. In this report, we present a case of infective endocarditis secondary to Cryptococcus neoformans in a lung-transplant recipient and review the relevant literature. A 65-year-old man was hospitalized with hypoxemic respiratory failure and underwent left-sided single lung transplantation. In the setting of worsening hypoxemia, blood cultures were drawn, which grew C. neoformans. Lumbar puncture was performed, and CSF PCR was also positive for Cryptococcus. Further exposure history revealed that he had raised chickens while living in Peru. Transesophageal echocardiography showed an aortic valve vegetation, and he was diagnosed with cryptococcal infective endocarditis. He received liposomal amphotericin B and flucytosine for two weeks and was later transitioned to fluconazole. This case highlights the need for thorough social history prior to lung transplantation, as pulmonary colonization with C. neoformans may result in infective endocarditis after immunosuppression.

Incorporation of Biomarkers Into Risk Assessment for Allocation of Antihypertensive Medication According to the 2017 ACC/AHA High Blood Pressure Guideline: A Pooled Cohort Analysis.

BACKGROUND: Risk for atherosclerotic cardiovascular disease was a novel consideration for antihypertensive medication initiation in the 2017 American College of Cardiology/American Heart Association Blood Pressure (BP) guideline. Whether biomarkers of chronic myocardial injury (high-sensitivity cardiac troponin T ≥6 ng/L] and stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥100 pg/mL) can inform cardiovascular (CV) risk stratification and treatment decisions among adults with elevated BP and hypertension is unclear. METHODS: Participant-level data from 3 cohort studies (Atherosclerosis Risk in Communities Study, Dallas Heart Study, and Multiethnic Study of Atherosclerosis) were pooled, excluding individuals with prevalent CV disease and those taking antihypertensive medication at baseline. Participants were analyzed according to BP treatment group from the 2017 American College of Cardiology/American Heart Association BP guideline and those with high BP (120 to 159/<100 mm Hg) were further stratified by biomarker status. Cumulative incidence rates for CV event (atherosclerotic cardiovascular disease or heart failure), and the corresponding 10-year number needed to treat to prevent 1 event with intensive BP lowering (to target systolic BP <120 mm Hg), were estimated for BP and biomarker-based subgroups. RESULTS: The study included 12 987 participants (mean age, 55 years; 55% women; 21.5% with elevated high-sensitivity cardiac troponin T; 17.7% with elevated NT-proBNP) with 825 incident CV events over 10-year follow-up. Participants with elevated BP or hypertension not recommended for antihypertensive medication with versus without either elevated high-sensitivity cardiac troponin T or NT-proBNP had a 10-year CV incidence rate of 11.0% and 4.6%, with a 10-year number needed to treat to prevent 1 event for intensive BP lowering of 36 and 85, respectively. Among participants with stage 1 or stage 2 hypertension recommended for antihypertensive medication with BP <160/100 mm Hg, those with versus without an elevated biomarker had a 10-year CV incidence rate of 15.1% and 7.9%, with a 10-year number needed to treat to prevent 1 event of 26 and 49, respectively. CONCLUSIONS: Elevations in high-sensitivity cardiac troponin T or NT-proBNP identify individuals with elevated BP or hypertension not currently recommended for antihypertensive medication who are at high risk for CV events. The presence of nonelevated biomarkers, even in the setting of stage 1 or stage 2 hypertension, was associated with lower risk. Incorporation of biomarkers into risk assessment algorithms may lead to more appropriate matching of intensive BP control with patient risk.

Potential Cardiovascular Disease Events Prevented with Adoption of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline.

BACKGROUND: Over 10 years, achieving and maintaining 2017 ACC/AHA guideline goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), and 1.4 million (UR, 0.6-2.0 million) cardiovascular disease (CVD) events compared with maintaining current blood pressure (BP) levels, achieving 2003 Seventh Joint National Committee Report goals, and achieving 2014 Eighth Joint National Committee goals, respectively. We estimated the number of cardiovascular disease events prevented and treatment-related serious adverse events incurred over 10 years among US adults with hypertension by achieving 2017 ACC/AHA guideline-recommended BP goals compared with (1) current BP levels, (2) achieving 2003 Seventh Joint National Committee Report BP goals, and (3) achieving 2014 Eighth Joint National Committee panel member report BP goals. METHODS: US adults aged ≥45 years with an indication for BP treatment were grouped according to recommendations for antihypertensive drug therapy in the 2017 ACC/AHA guideline, 2003 Seventh Joint National Committee Report, and 2014 Eighth Joint National Committee. Population sizes were estimated from the 2011 to 2014 National Health and Nutrition Examination Surveys. Rates for fatal and nonfatal CVD events (stroke, coronary heart disease, or heart failure) were estimated from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study, weighted to the US population. CVD risk reductions with treatment to BP goals and risk for serious adverse events were obtained from meta-analyses of BP-lowering trials. CVD events prevented and treatment-related nonfatal serious adverse events over 10 years were calculated. Uncertainty surrounding main data inputs was expressed in uncertainty ranges (UR). RESULTS: Over ten years, achieving and maintaining 2017 ACC/AHA guideline goals compared with current BP levels, achieving 2003 Seventh Joint National Committee Report goals, or achieving 2014 Eighth Joint National Committee goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), or 1.4 million (UR, 0.6-2.0 million) CVD events, respectively. Compared with current BP levels, achieving and maintaining 2017 goals could prevent 71.9 (UR, 26.6-122.3) CVD events per 1000 treated. Achieving 2017 guideline BP goals compared with current BP levels could also lead to nearly 3.3 million more serious adverse events over 10 years (UR, 2.2-4.4 million). CONCLUSIONS: Achieving and maintaining 2017 ACC/AHA BP goals could prevent a greater number of CVD events than achieving 2003 Seventh Joint National Committee Report or 2014 Eighth Joint National Committee BP goals but could also lead to more serious adverse events.

Electronic Cigarette Use and Blood Pressure Endpoints: a Systematic Review.

PURPOSE OF REVIEW: E-cigarettes (e-cigs) release toxic chemicals known to increase blood pressure (BP) levels. The effects of e-cigs on BP, however, remain unknown. Studying BP may help characterize potential cardiovascular risks of short- and long-term e-cig use. We summarized published studies on the association of e-cig use with BP endpoints. RECENT FINDINGS: Thirteen e-cig trials (12 cross-over designs) and 1 observational study evaluated systolic and diastolic blood pressure (SBP and DBP). All trials included at least one e-cig arm with nicotine, 6 a no-nicotine e-cig arm, and 3 a placebo arm. SBP/DBP increased in most nicotine e-cig arms, in some non-nicotine e-cig arms, and in none of the placebo arms. The observational study followed e-cig users and nonsmokers for 3.5 years with inconsistent findings. The use of e-cigs with and without nicotine may result in short-term elevations of both SBP and DBP. Prospective studies that investigate the long-term cardiovascular impact of e-cig use are needed.

Occupational standing and change in the Ankle-Brachial Index: the Jackson Heart Study.

BACKGROUND: A growing interest in reducing occupational sitting has resulted in public health efforts to encourage intermittent standing in workplaces. However, concerns have been raised that standing for prolonged periods may expose individuals to new health hazards, including lower limb atherosclerosis. These concerns have yet to be corroborated or refuted. The purpose of this study was to investigate the association between occupational standing and adverse changes in the Ankle-Brachial Index (ABI). METHODS: We studied 2121 participants from the Jackson Heart Study, a single-site community-based study of African-Americans residing in Jackson, MS. Occupational standing ('never/seldom', 'sometimes', 'often/always') was self-reported at baseline (2000-2004). ABI was measured at baseline and again at follow-up (2009-2013). RESULTS: Over a median follow-up of 8 years, 247 participants (11.6%) exhibited a significant decline in ABI (eg, ABI decline >0.15). In multivariable-adjusted models, higher occupational standing was not significantly associated with ABI decline (occupational standing sometimes vs never/seldom: OR 1.05; 95% CI 0.67, 1.66; occupational standing often/always vs never/seldom: OR 1.22; 95% CI 0.77, 1.94). Similarly, higher occupational standing was not associated with low ABI at follow-up reflective of peripheral artery disease (ABI <0.90) or high ABI at follow-up reflective of incompressible vessels (ABI >1.40). CONCLUSIONS: In this community-based study of African-Americans, we found no evidence that occupational standing is deleteriously associated with adverse changes in ABI over a median follow-up of 8.0 years. These findings do not provide evidence implicating occupational standing as a risk factor for lower limb atherosclerosis.

Testing the cross-stressor hypothesis under real-world conditions: exercise as a moderator of the association between momentary anxiety and cardiovascular responses.

The cross-stressor adaptation hypothesis of exercise training has not been investigated under real-life conditions. Using ecological momentary assessment, we tested whether usual exercise level moderates the relationship of self-reported anxiety to concurrent ambulatory heart rate (HR) and systolic/diastolic blood pressure (SBP/DBP). Participants (N = 832) completed 24-h ambulatory monitoring of HR/BP, using a brachial BP cuff that took readings at 28-min intervals. Anxiety levels were concurrently reported on a visual analog scale (VAS) using a Palm Pilot. Usual exercise behavior was assessed by a self-report questionnaire. Random coefficients linear regression models predicting momentary HR/BP readings from time-matched anxiety scores were estimated, yielding the average within-person effect (slope) of anxiety. The interaction of exercise level (i.e., no weekly exercise, 1-149, and ≥ 150 min/week; a between-person factor) with anxiety was added to the model in order to estimate the average anxiety slope for participants in each exercise category. The relationship of HR/BP to anxiety did not differ significantly among exercise categories, hence not providing evidence for the cross-stressor hypothesis. In an exploratory analysis of the difference in HR/BP between occasions when anxiety was in the top versus bottom person-specific quintiles of responses, the difference in HR (but not SBP or DBP) varied significantly by exercise level (F(2,625) = 4.92, p = 0.008). Though our pre-specified analysis did not support the hypothesis, we provide some post hoc evidence supporting the cross-stressor hypothesis of exercise training for the HR response to anxiety.

Leveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data.

In this study, we investigated low-frequency and rare variants associated with blood pressure (BP) by focusing on a linkage region on chromosome 16p13. We used whole genome sequencing (WGS) data obtained through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program on 395 Cleveland Family Study (CFS) European Americans (CFS-EA). By analyzing functional coding variants and non-coding rare variants with CADD score > 10 residing within the chromosomal region in families with linkage evidence, we observed 25 genes with nominal statistical evidence (burden or SKAT p < 0.05). One of the genes is RBFOX1, an evolutionarily conserved RNA-binding protein that regulates tissue-specific alternative splicing that we previously reported to be associated with BP using exome array data in CFS. After follow-up analysis of the 25 genes in ten independent TOPMed studies with individuals of European, African, and East Asian ancestry, and Hispanics (N = 29,988), we identified variants in SLX4 (p = 2.19 × 10-4) to be significantly associated with BP traits when accounting for multiple testing. We also replicated the associations previously reported for RBFOX1 (p = 0.007). Follow-up analysis with GTEx eQTL data shows SLX4 variants are associated with gene expression in coronary artery, multiple brain tissues, and right atrial appendage of the heart. Our study demonstrates that linkage analysis of family data can provide an efficient approach for detecting rare variants associated with complex traits in WGS data.

Longer Sleep Duration and Endothelial Cell Health Among a Multiethnic Sample of Adolescents.

OBJECTIVE: Adverse endothelial cell health, an early pathogenic process underlying atherosclerosis and cardiovascular disease, is evident in childhood and adolescence. Sleep duration, a modifiable cardiovascular health behavior, may be an important cardiovascular disease prevention target that may affect endothelial cell health. We examined the associations of longer sleep duration with endothelial cell injury among youth. METHODS: In a multiethnic sample of 235 children (63.0% female, mean age = 13.9 years), we conducted multivariable linear regressions to test the cross-sectional association of sleep duration and circulating levels of endothelial cell-derived microparticles (EMPs), phenotypic for endothelial cell activation and apoptosis (CD62E+ EMPs, CD31+/CD42b- EMPs, and CD31+/Annexin V+ EMPs). Sleep duration and EMPs were both treated as continuous variables. Models were adjusted for age, sex, race, pubertal status, household economic resources, and waist circumference. RESULTS: Overall, 69.2% had short sleep duration (<8 hours of sleep per night). Longer sleep duration was significantly associated with lower levels of CD62E+ EMPs and CD31+/CD42b- EMPs. A 60-minute increase in sleep duration was associated with an 8.40 (95% confidence interval = -205.20 to -1.80, p = .046) decrease in CD62E+ EMPs and a 9.00 (95% confidence interval = -153.60 to -9.60, p = .027) decrease in CD31+/CD42b- EMPs. Sleep duration was not associated with CD31+/Annexin V+ EMPs. CONCLUSIONS: Our results support the hypothesis that sleeping longer has beneficial effects on endothelial cell health during childhood. Primordial prevention efforts might incorporate sleep extension to offset cardiovascular risk in youth.

Increasing the Precision of Hypertension Treatment Through Personalized Trials: a Pilot Study.

BACKGROUND: There are substantial differences in the effects of blood pressure (BP) medications in individual patients. Yet, the current standard approach to prescribing BP medications is not personalized. OBJECTIVE: To determine the feasibility of individualizing the selection of BP medications through pragmatic personalized (i.e., N-of-1) trials. DESIGN: Series of N-of-1 trials. SETTING: Outpatient. PATIENTS: Hypertensive adults prescribed none or one BP medication. INTERVENTION: Participation in a flexible, open-label personalized trial of two to three BP medications (NCT02744456). MEASUREMENTS: BP was measured twice per day with a validated home BP device. Frequency and severity of side effects were assessed at the end of the day via an electronic questionnaire. Patients' BP medication preference was assessed after reviewing BP lowering and side effect results with a study clinician. Feasibility was assessed by determining the proportion of patients who adhered to self-assessments. Benefit was assessed by asking patients to rate the helpfulness of participation and whether they would recommend personalized trials to other hypertensive patients. KEY RESULTS: Of ten patients enrolled, two dropped out prior to initiation, one discovered white coat hypertension through ambulatory BP monitoring, and seven (mean age 58 years, 71% of women) completed personalized trials. All seven were compliant with home BP monitoring and side effect tracking. All seven recommended personalized trials of BP medications to others. Thiazides were preferred by three patients, renin-angiotensin system-blocking agents by two patients, a combination of thiazide and beta-blocker by one patient, and any of three classes by one patient. CONCLUSIONS: Personalized trials of BP medications were feasible and led to improved treatment precision. Heterogeneity of patient preferences and of therapeutic BP response for first-line BP medications can be determined through a personalized trial approach.

Calibrating Local Population-Based Blood Pressure Data from NYC HANES 2013-2014.

New York City Health and Nutrition Examination Survey (NYC HANES) was a population-based cross-sectional survey of NYC adults conducted twice, in 2004 and again in 2013-2014, to monitor the health of NYC adults 20 years or older. While blood pressure was measured in both surveys, an auscultatory mercury sphygmomanometer was used to measure blood pressure in clinics in 2004, and an oscillometric LifeSource UA-789AC monitor was used in homes in 2013-2014. To assess comparability of blood pressure results across both surveys, we undertook a randomized study comparing blood pressure (BP) readings by the two devices. Blood pressure measuring protocols followed the 2013 Association for the Advancement in Medical instrumentation guidelines for non-invasive blood pressure device. Data from 167 volunteers were analyzed for this purpose.Paired t tests were used to test for significant difference in mean systolic and diastolic blood pressure between devices for overall and by mid-arm circumference categories. To test for systematic differences between the two devices, we generated Bland-Altman graphs. Sensitivity, specificity, and Kappa statistics were calculated to assess between-device agreement for high (≥ 130/80 mmHg) and not high (< 130/80 mmHg) blood pressure, with mercury set as the reference.Systolic and diastolic blood pressure measured by LifeSource UA-789AC were on average 2.0 and 1.1 mmHg higher, respectively, than those of the mercury sphygmomanometer systolic and diastolic blood pressure readings (P < 0.05). Sensitivity was 81%, specificity was 96%, and the Kappa coefficient was 75%. The Bland-Altman graphs showed that the between-device difference did not vary as a function of the average of the two devices for systolic blood pressure and was larger in the lower and upper ends for diastolic blood pressure. Given the observed differences in systolic and diastolic blood pressure readings between the two blood pressure measurement approaches, we calibrated NYC HANES 2013-2014 blood pressure data by predicting mercury blood pressure values from LifeSource blood pressure values. The mean systolic and diastolic blood pressure in NYC HANES 2013-2014 were lower when data were calibrated.

Thresholds for Ambulatory Blood Pressure Among African Americans in the Jackson Heart Study.

BACKGROUND: Ambulatory blood pressure (BP) monitoring is the reference standard for out-of-clinic BP measurement. Thresholds for identifying ambulatory hypertension (daytime systolic BP [SBP]/diastolic BP [DBP] ≥135/85 mm Hg, 24-hour SBP/DBP ≥130/80 mm Hg, and nighttime SBP/DBP ≥120/70 mm Hg) have been derived from European, Asian, and South American populations. We determined BP thresholds for ambulatory hypertension in a US population-based sample of African American adults. METHODS: We analyzed data from the Jackson Heart Study, a population-based cohort study comprised exclusively of African American adults (n=5306). Analyses were restricted to 1016 participants who completed ambulatory BP monitoring at baseline in 2000 to 2004. Mean SBP and DBP levels were calculated for daytime (10:00 am-8:00 pm), 24-hour (all available readings), and nighttime (midnight-6:00 am) periods, separately. Daytime, 24-hour, and nighttime BP thresholds for ambulatory hypertension were identified using regression- and outcome-derived approaches. The composite of a cardiovascular disease or an all-cause mortality event was used in the outcome-derived approach. For this latter approach, BP thresholds were identified only for SBP because clinic DBP was not associated with the outcome. Analyses were stratified by antihypertensive medication use. RESULTS: Among participants not taking antihypertensive medication, the regression-derived thresholds for daytime, 24-hour, and nighttime SBP/DBP corresponding to clinic SBP/DBP of 140/90 mm Hg were 134/85 mm Hg, 130/81 mm Hg, and 123/73 mm Hg, respectively. The outcome-derived thresholds for daytime, 24-hour, and nighttime SBP corresponding to a clinic SBP ≥140 mm Hg were 138 mm Hg, 134 mm Hg, and 129 mm Hg, respectively. Among participants taking antihypertensive medication, the regression-derived thresholds for daytime, 24-hour, and nighttime SBP/DBP corresponding to clinic SBP/DBP of 140/90 mm Hg were 135/85 mm Hg, 133/82 mm Hg, and 128/76 mm Hg, respectively. The corresponding outcome-derived thresholds for daytime, 24-hour, and nighttime SBP were 140 mm Hg, 137 mm Hg, and 133 mm Hg, respectively, among those taking antihypertensive medication. CONCLUSIONS: On the basis of the outcome-derived approach for SBP and regression-derived approach for DBP, the following definitions for daytime, 24-hour, and nighttime hypertension corresponding to clinic SBP/DBP ≥140/90 mm Hg are proposed for African American adults: daytime SBP/DBP ≥140/85 mm Hg, 24-hour SBP/DBP ≥135/80 mm Hg, and nighttime SBP/DBP ≥130/75 mm Hg, respectively.