Hepatocyte growth factor and risk of incident stroke in Black and White Americans in the Reasons for Geographic and Racial Differences in Stroke study.

Background: Hepatocyte growth factor (HGF) is a cytokine produced in response to endothelial damage. Higher levels correlate with cardiovascular risk factors, including hypertension and diabetes. Objectives: We hypothesized that HGF is associated with stroke. Methods: The Reasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black and White Americans aged ≥45 years from 2003 to 2007. In this case-cohort study, after 5.5 years of follow-up, circulating baseline HGF was measured in 557 participants with incident ischemic stroke and in a cohort random sample of 964 participants. Hazard ratios (HRs) per SD log-transformed HGF and by HGF quintile were calculated using Cox proportional hazards models adjusting for stroke risk factors and other correlates of HGF. Differences by race and sex were tested using interaction terms. Results: Median HGF was 295 (IQR, 209-402) pg/mL. HGF was higher with older age, male sex, prevalent cardiovascular disease, smoking, and warfarin use, but did not differ by race. The adjusted HR of incident ischemic stroke per SD higher baseline HGF (145 pg/mL) was 1.30 (CI, 1.00-1.70), with no difference by sex or race. HGF in the highest (>434 pg/mL) vs lowest quintile (<135 pg/mL) was associated with an adjusted HR of incident stroke of 2.12 (CI, 1.31-3.41). Conclusion: In the REGARDS study, higher HGF was associated with increased risk of incident ischemic stroke in Black and White adults, with a doubling in risk of HGF in the top quintile compared with the lowest quintile after adjusting for other stroke risk factors.

Sherman Lecture: Are We Aiming at the Correct Targets to Reduce Disparities in Stroke Mortality? Celebration, Reflection, and Redirection.

Although deaths from stroke have been reduced by 75% in the past 54 years, there has been virtually no reduction in the relative magnitude of Black-to-White disparity in stroke deaths, or the heavier burden of stroke deaths in the Stroke Belt region of the United States. Furthermore, although the rural-urban disparity has decreased in the past decade, this reduction is largely attributable to an increased stroke mortality in the urban areas, rather than reduced stroke mortality in rural areas. We need to focus our search for interventions to reduce disparities on those that benefit the disadvantaged populations, and support this review using relatively recently developed statistical approaches to estimate the magnitude of the potential reduction in the disparities.

Cytokines, C-Reactive Protein, and Risk of Incident Hypertension in the REGARDS Study.

BACKGROUND: Hypertension is a highly prevalent cardiovascular disease risk factor that may be related to inflammation. Whether adverse levels of specific inflammatory cytokines relate to hypertension is unknown. The present study sought to determine whether higher levels of IL (interleukin)-1ß, IL-6, TNF (tumor necrosis factor)-α, IFN (interferon)-γ, IL-17A, and CRP (C-reactive protein) are associated with a greater risk of incident hypertension. METHODS: The REGARDS study (Reasons for Geographic and Racial Difference in Stroke) is a prospective cohort study that recruited 30 239 community-dwelling Black and White adults from the contiguous United States in 2003 to 2007 (visit 1), with follow-up 9 years later in 2013 to 2016 (visit 2). We included participants without prevalent hypertension who attended follow-up 9 years later and had available laboratory measures and covariates of interest. Poisson regression estimated the risk ratio of incident hypertension by level of inflammatory biomarkers. RESULTS: Among 1866 included participants (mean [SD] aged of 62 [8] years, 25% Black participants, 55% women), 36% developed hypertension. In fully adjusted models comparing the third to first tertile of each biomarker, there was a greater risk of incident hypertension for higher IL-1ß among White (1.24 [95% CI, 1.01-1.53]) but not Black participants (1.01 [95% CI, 0.83-1.23]) and higher TNF-α (1.20 [95% CI, 1.02-1.41]) and IFN-γ (1.22 [95% CI, 1.04-1.42]) among all participants. There was no increased risk with IL-6, IL-17A, or CRP. CONCLUSIONS: Higher levels of IL-1ß, TNF-α, and IFN-γ, representing distinct inflammatory pathways, are elevated in advance of hypertension development. Whether modifying these cytokines will reduce incident hypertension is unknown.

Differences in Receipt of Neurologist Evaluation During Hospitalization for Ischemic Stroke by Race, Sex, Age, and Region: The REGARDS Study.

BACKGROUND AND OBJECTIVES: Improving access to health care providers with clinical expertise in stroke care may influence the use of recommended strategies for reducing disparities in quality of care. Few studies have examined differences in the receipt of evaluation by neurologists during the hospital stay. We examined the proportion of individuals hospitalized for acute ischemic stroke who received evaluation by a neurologist during the hospital stay and characterized differences in receipt of neurologist evaluation by race (Black vs White), sex, age, and study region (Stroke Belt residence vs other) among those experiencing a stroke who were participating in a national cohort study. METHODS: This cross-sectional study was conducted using medical record data abstracted from 1,042 participants enrolled in the national Reasons for Geographic and Racial Differences in Stroke cohort study (2003-2007) who experienced an adjudicated ischemic stroke between 2003 and 2016. Participants with a history of stroke before baseline, in-hospital death, hospice discharge following their stroke, or incomplete records were excluded resulting in 839 cases. Differences were assessed using modified Poisson regression adjusting for participant-level and hospital-level factors. RESULTS: Of the 839 incident strokes, 722 (86%) received evaluation by a neurologist during the hospital stay. There were no significant differences by age, race, or sex, yet Stroke Belt residents and those receiving care in rural hospitals were significantly less likely to receive neurologist evaluation compared with non-Stroke Belt residents (relative risk [RR] 0.95; 95% CI 0.90-1.01) and participants receiving care in urban hospitals (RR 0.74; 95% CI 0.63-0.86). Participants with a greater level of poststroke functional impairment (modified Rankin scale) and those with a greater number of risk factors were more likely to receive neurologist evaluation compared with those with lower levels of poststroke functional impairment (RR 1.04; 95% CI 1.01-1.06) and fewer risk factors (RR 1.02; 95% CI 1.00-1.04). DISCUSSION: While differences in access to neurologists during the hospital stay were partially explained by patient need in our study, there were also significant differences in access by region and urban-rural hospital status. Ensuring access to neurologists during the hospital stay in such settings may require policy-level and/or system-level changes.

Comparative Discrimination of Life's Simple 7 and Life's Essential 8 to Stratify Cardiovascular Risk: Is the Added Complexity Worth It?

BACKGROUND: Life's Simple 7 (LS7) is an easily calculated and interpreted metric of cardiovascular health based on 7 domains: smoking, diet, physical activity, body mass index, blood pressure, cholesterol, and fasting glucose. The Life's Essential 8 (LE8) metric was subsequently introduced, adding sleep metrics and revisions of the previous 7 domains. Although calculating LE8 requires additional information, we hypothesized that it would be a more reliable index of cardiovascular health. METHODS: Both the LS7 and LE8 metrics yield scores with higher values indicating lower risk. These were calculated among 11 609 Black and White participants free of baseline cardiovascular disease (CVD) in the Reasons for Geographic and Racial Differences in Stroke study, enrolled in 2003 to 2007, and followed for a median of 13 years. Differences in 10-year risk of incident CVD (coronary heart disease or stroke) were calculated as a function LS7, and LE8 scores were calculated using Kaplan-Meier and proportional hazards analyses. Differences in incident CVD discrimination were quantified by difference in the c-statistic. RESULTS: For both LS7 and LE8, the 10-year risk was approximately 5% for participants around the 99th percentile of scores, and a 4× higher 20% risk for participants around the first percentile. Comparing LS7 to LE8, 10-year risk was nearly identical for individuals at the same relative position in score distribution. For example, the "cluster" of 2013 participants with an LS7 score of 7 was at the 35.8th percentile in distribution of LS7 scores, and had an estimated 10-year CVD risk of 8.4% (95% CI, 7.2%-9.8%). In a similar location in the LE8 distribution, the 1457 participants with an LE8 score of 60±2.5 at the 39.4th percentile of LE8 scores had a 10-year risk of CVD of 8.5% (95% CI, 7.1%-10.1%), similar to the cluster defined by LS7. The age-race-sex adjusted c-statistic of the LS7 model was 0.691 (95% CI, 0.667-0.705), and 0.695 for LE8 (95% CI, 0.681-0.709) (P for difference, 0.12). CONCLUSIONS: Both LS7 and LE8 were associated with incident CVD, with discrimination of the 2 indices practically indistinguishable. As a simpler metric, LS7 may be favored for use by the general population and clinicians.

Global stroke statistics 2023: Availability of reperfusion services around the world.

BACKGROUND: Disparities in the availability of reperfusion services for acute ischemic stroke are considerable globally and require urgent attention. Contemporary data on the availability of reperfusion services in different countries are used to provide the necessary evidence to prioritize where access to acute stroke treatment is needed. AIMS: To provide a snapshot of published literature on the provision of reperfusion services globally, including when facilitated by telemedicine or mobile stroke unit services. METHODS: We searched PubMed to identify original articles, published up to January 2023 for the most recent, representative, and relevant patient-level data for each country. Keywords included thrombolysis, endovascular thrombectomy and telemedicine. We also screened reference lists of review articles, citation history of articles, and the gray literature. The information is provided as a narrative summary. RESULTS: Of 11,222 potentially eligible articles retrieved, 148 were included for review following de-duplications and full-text review. Data were also obtained from national stroke clinical registry reports, Registry of Stroke Care Quality (RES-Q) and PRE-hospital Stroke Treatment Organization (PRESTO) repositories, and other national sources. Overall, we found evidence of the provision of intravenous thrombolysis services in 70 countries (63% high-income countries (HICs)) and endovascular thrombectomy services in 33 countries (68% HICs), corresponding to far less than half of the countries in the world. Recent data (from 2019 or later) were lacking for 35 of 67 countries with known year of data (52%). We found published data on 74 different stroke telemedicine programs (93% in HICs) and 14 active mobile stroke unit pre-hospital ambulance services (80% in HICs) around the world. CONCLUSION: Despite remarkable advancements in reperfusion therapies for stroke, it is evident from available patient-level data that their availability remains unevenly distributed globally. Contemporary published data on availability of reperfusion services remain scarce, even in HICs, thereby making it difficult to reliably ascertain current gaps in the provision of this vital acute stroke treatment around the world.

Application of marginalized zero-inflated models when mediators have excess zeroes.

Mediation analysis has become increasingly popular over the last decade as researchers are interested in assessing mechanistic pathways for intervention. Although available methods have increased, there are still limited options for mediation analysis with zero-inflated count variables where the distribution of response has a "cluster" of data at the zero value (i.e. distribution of number of cigarettes smoked per day, where nonsmokers cluster at zero cigarettes). The currently available methods do not obtain unbiased population average effects of mediation effects. In this paper, we propose an extension of the counterfactual approach to mediation with direct and indirect effects to scenarios where the mediator is a count variable with excess zeroes by utilizing the Marginalized Zero-Inflated Poisson Model (MZIP) for the mediator model. We derive direct and indirect effects for continuous, binary, and count outcomes, as well as adapt to allow mediator-exposure interactions. Our proposed work allows straightforward calculation of direct and indirect effects for the overall population mean values of the mediator, for scenarios in which researchers are interested in generalizing direct and indirect effects to the population. We apply this novel methodology to an application observing how alcohol consumption may explain sex differences in cholesterol and assess model performance via a simulation study comparing the proposed MZIP mediator framework to existing methods for marginal mediator effects.

The predictive validity of a Brain Care Score for dementia and stroke: data from the UK Biobank cohort.

Introduction: The 21-point Brain Care Score (BCS) was developed through a modified Delphi process in partnership with practitioners and patients to promote behavior changes and lifestyle choices in order to sustainably reduce the risk of dementia and stroke. We aimed to assess the associations of the BCS with risk of incident dementia and stroke. Methods: The BCS was derived from the United Kingdom Biobank (UKB) baseline evaluation for participants aged 40-69 years, recruited between 2006-2010. Associations of BCS and risk of subsequent incident dementia and stroke were estimated using Cox proportional hazard regressions, adjusted for sex assigned at birth and stratified by age groups at baseline. Results: The BCS (median: 12; IQR:11-14) was derived for 398,990 UKB participants (mean age: 57; females: 54%). There were 5,354 incident cases of dementia and 7,259 incident cases of stroke recorded during a median follow-up of 12.5 years. A five-point higher BCS at baseline was associated with a 59% (95%CI: 40-72%) lower risk of dementia among participants aged <50. Among those aged 50-59, the figure was 32% (95%CI: 20-42%) and 8% (95%CI: 2-14%) for those aged >59 years. A five-point higher BCS was associated with a 48% (95%CI: 39-56%) lower risk of stroke among participants aged <50, 52% (95%CI, 47-56%) among those aged 50-59, and 33% (95%CI, 29-37%) among those aged >59. Discussion: The BCS has clinically relevant and statistically significant associations with risk of dementia and stroke in approximately 0.4 million UK people. Future research includes investigating the feasibility, adaptability and implementation of the BCS for patients and providers worldwide.

A rationale and framework for addressing physician cognitive impairment.

Medical error is costly, in terms of the health and wellbeing of the patient, their family, and the financial burden placed on the medical system. Reducing medical error is paramount to minimizing harm and improving outcomes. One potential source of medical error is physician cognitive impairment. Determining how to effectively assess and mange physician cognitive impairment is an important, albeit difficult problem to address. There have been calls and attempts to implement age-based cognitive screening, but this approach is not optimal. Instead, we propose that neuropsychological assessment is the gold standard for fitness-for-duty evaluations and that there is a need for the development of physician-based, normative data to improve these evaluations. Here, we outline the framework of our research protocol in a large, academic medical center, in partnership with hospital leadership and legal counsel, which can be modeled by other medical centers. With high rates of physician burnout and an aging physician population, the United States is facing a looming public health crisis that requires proactive management.

Serum antinuclear autoantibodies are associated with measures of oxidative stress and lifestyle factors: analysis of LIPIDOGRAM2015 and LIPIDOGEN2015 studies.

Introduction: Oxidative stress is one of many factors suspected to promote antinuclear autoantibody (ANA) formation. Reactive oxygen species can induce changes in the antigenic structure of macromolecules, causing the immune system to treat them as "neo-antigens" and start production of autoantibodies. This study was designed to evaluate the relationship between oxidative stress markers, lifestyle factors and the detection of ANA. Material and methods: We examined measures of oxidative stress indices of free-radical damage to lipids and proteins, such as total oxidant status (TOS), concentration of protein thiol groups (PSH), and malondialdehyde (MDA), activity of superoxide dismutase (SOD) in 1731 serum samples. The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid (UA) concentration, were also measured and the oxidative stress index (OSI-index) was calculated. All samples were tested for the presence of ANA using an indirect immunofluorescence assay (IIFA). Results: The presence of ANA in women was associated with lower physical activity (p = 0.036), less frequent smoking (p = 0.007) and drinking of alcohol (p = 0.024) accompanied by significant changes in SOD isoenzymes activity (p < 0.001) and a higher uric acid (UA) concentration (p < 0.001). In ANA positive males we observed lower concentrations of PSH (p = 0.046) and increased concentrations of MDA (p = 0.047). Conclusions: The results indicate that local oxidative stress may be associated with increased probability of ANA formation in a sex-specific manner.

Association of hypertension severity and control with risk of incident atrial fibrillation: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

BACKGROUND: The association of hypertension (HTN) severity and control with the risk of incident atrial fibrillation (AF) is unclear. HYPOTHESIS: Increased HTN severity and poorer blood pressure control would be associated with an increased risk of incident AF. METHODS: This analysis included 9485 participants (mean age 63 ± 8 years; 56% women; 35% Black). Participants were stratified into six mutually exclusive groups at baseline-normotension (n = 1629), prehypertension (n = 704), controlled HTN (n = 2224), uncontrolled HTN (n = 4123), controlled apparent treatment-resistant hypertension (aTRH) (n = 88), and uncontrolled aTRH (n = 717). Incident AF was ascertained at the follow-up visit, defined by either electrocardiogram or self-reported medical history of a physician diagnosis. Multivariable logistic regression analyses adjusted for demographic and clinical variables. RESULTS: Over an average of 9.3 years later, 868 incident AF cases were detected. Compared to those with normotension, incident AF risk was highest for those with aTRH (controlled aTRH: odds ratio (OR) 2.95; 95% confidence interval (CI) 1.60, 5.43, & uncontrolled aTRH: OR 2.47; 95% CI 1.76, 3.48). The increase in AF risk was smaller for those on no more than three antihypertensive agents regardless of their blood pressure control (controlled OR 1.72; 95% CI 1.30, 2.29 and uncontrolled OR 1.56; 95% CI 1.14, 2.13). CONCLUSIONS: The risk of developing AF is increased in all individuals with HTN. Risk is highest in those aTRH regardless of blood pressure control. A more aggressive approach that focuses on lifestyle and pharmacologic measures to either prevent HTN or better control HTN during earlier stages may be particularly beneficial in reducing related AF risk.

Methods of a Study to Assess the Contribution of Cerebral Small Vessel Disease and Dementia Risk Alleles to Racial Disparities in Vascular Cognitive Impairment and Dementia.

Background Non-Hispanic Black adults have a higher proportion of vascular cognitive impairment and Alzheimer's disease and related dementias compared with non-Hispanic White adults that may be due to differences in the burden of cerebral small vessel disease and risk alleles for Alzheimer's disease and related dementias. We describe here the methods of an ancillary study to the REGARDS (Reason for Geographic and and Racial Difference in Stroke) study, which will examine the role of magnetic resonance imaging markers of cerebral small vessel disease and vascular as well as genetic risk factors for Alzheimer's disease and related dementias in racial disparity in the prevalence and trajectory of vascular cognitive impairment and dementia in non-Hispanic White and non-Hispanic Black participants. Methods In participants with no prior history of stroke who had an incident stroke or transient ischemic attack after enrollment in the study, magnetic resonance imaging scans will be evaluated using the Standards for Reporting Vascular Changes on Neuroimaging international consensus criteria and automated analysis pipelines for quantification of cerebral small vessel disease. Participants will be genotyped for APOE ε4 and TREM2 risk alleles for Alzheimer's disease and related dementias. The 6-item screener will define global cognitive function and be the primary cognitive outcome. Conclusions With at least 426 non-Hispanic Black and 463 non-Hispanic White participants who have at least 2 prior and 2 poststroke or transient ischemic attack cognitive assessments, we will have at least 80% power to detect a minimum effect size of 0.09 SD change in Z score, with correction for as many as 20 tests (ie, at P<0.0025, after adjusting for up to 20 covariates) for cognitive decline.

Alpha globin gene copy number and incident ischemic stroke risk among Black Americans.

Introduction: People with African ancestry have greater stroke risk and greater heritability of stroke risk than people of other ancestries. Given the importance of nitric oxide (NO) in stroke, and recent evidence that alpha globin restricts nitric oxide release from vascular endothelial cells, we hypothesized that alpha globin gene (HBA) deletion would be associated with reduced risk of incident ischemic stroke. Methods: We evaluated 8,947 participants self-reporting African ancestry in the national, prospective Reasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Incident ischemic stroke was defined as non-hemorrhagic stroke with focal neurological deficit lasting ≥ 24 hours confirmed by the medical record or focal or non-focal neurological deficit with positive imaging confirmed with medical records. Genomic DNA was analyzed using droplet digital PCR to determine HBA copy number. Multivariable Cox proportional hazards regression was used to estimate the hazard ratio (HR) of HBA copy number on time to first ischemic stroke. Results: Four-hundred seventy-nine (5.3%) participants had an incident ischemic stroke over a median (IQR) of 11.0 (5.7, 14.0) years' follow-up. HBA copy number ranged from 2 to 6: 368 (4%) -α/-α, 2,480 (28%) -α/αα, 6,014 (67%) αα/αα, 83 (1%) ααα/αα and 2 (<1%) ααα/ααα. The adjusted HR of ischemic stroke with HBA copy number was 1.04; 95%CI 0.89, 1.21; p = 0.66. Conclusions: Although a reduction in HBA copy number is expected to increase endothelial nitric oxide signaling in the human vascular endothelium, HBA copy number was not associated with incident ischemic stroke in this large cohort of Black Americans.

Urban-rural differences in hypertension prevalence, blood pressure control, and systolic blood pressure levels.

Higher rates of cardiovascular events have been observed among rural residents compared with urban. Hypertension and lack of blood pressure (BP) control are risk factors for cardiovascular events. We compared the prevalence of hypertension and controlled BP, and the distribution of systolic blood pressure (SBP), by urban-rural residence. Participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a prospective cohort of Black and White adults aged ≥45 years, were categorized as either urban, large rural, or small-isolated rural, by using the Rural-Urban Commuting Area (RUCA) categorization B system. Oucomes were hypertension prevalence (BP ≥ 140/90 mmHg or antihypertensive use), BP control (BP < 140/90 among participants on antihypertensive medication), and the distribution of SBP. Counfounders were age, race, sex, antihypertensive medication use, and US Census Bureau division. The analysis included 26,133 participants (80.3% urban, 11.6% large-rural, 8.2% small-isolated rural). The unadjusted prevalence of hypertension was not different between groups. However, after adjustment, the odds of hypertension was higher among participants in the large rural group (odds ratio [OR] 1.17; 95% confidence interval [CI], 1.08-1.27) and small-isolated rural group (OR 1.19; 95% CI, 1.08-1.30), compared with the urban group. There was no evidence of an adjusted difference in BP control for those taking antihypertensive medications. Adjusted differences in SBP were greater for both rural groups, compared with urban, at the higher percentiles of SBP. Rural residence was associated with a higher adjusted odds of hypertension and higher SBP.

Dietary patterns in rural and metropolitan Australia: a cross-sectional study exploring dietary patterns, inflammation and association with cardiovascular disease risk factors.

OBJECTIVES: This study sought first to empirically define dietary patterns and to apply the novel Dietary Inflammation Score (DIS) in data from rural and metropolitan populations in Australia, and second to investigate associations with cardiovascular disease (CVD) risk factors. DESIGN: Cross-sectional study. SETTING: Rural and metropolitan Australia. PARTICIPANTS: Adults over the age of 18 years living in rural or metropolitan Australia who participated in the Australian Health survey. PRIMARY OUTCOMES: A posteriori dietary patterns for participants separated into rural and metropolitan populations using principal component analysis. SECONDARY OUTCOMES: association of each dietary pattern and DIS with CVD risk factors was explored using logistic regression. RESULTS: The sample included 713 rural and 1185 metropolitan participants. The rural sample was significantly older (mean age 52.7 compared with 48.6 years) and had a higher prevalence of CVD risk factors. Two primary dietary patterns were derived from each population (four in total), and dietary patterns were different between the rural and metropolitan areas. None of the identified patterns were associated with CVD risk factors in metropolitan or rural areas, aside diet pattern 2 being strongly associated with from self-reported ischaemic heart disease (OR 13.90 95% CI 2.29 to 84.3) in rural areas. There were no significant differences between the DIS and CVD risk factors across the two populations, except for a higher DIS being associated with overweight/obesity in rural areas. CONCLUSION: Exploration of dietary patterns between rural and metropolitan Australia shows differences between the two populations, possibly reflective of distinct cultures, socioeconomic factors, geography, food access and/or food environments in the different areas. Our study provides evidence that action targeting healthier dietary intakes needs to be tailored to rurality in the Australian context.

Estimated Population Health Benefits of Intensive Systolic Blood Pressure Treatment Among SPRINT-Eligible US Adults.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated an intensive (<120 mm Hg) vs. standard (<140 mm Hg) systolic blood pressure (SBP) goal lowered cardiovascular disease (CVD) risk. Estimating the effect of intensive SBP lowering among SPRINT-eligible adults most likely to benefit can guide implementation efforts. METHODS: We studied SPRINT participants and SPRINT-eligible participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study and National Health and Nutrition Examination Surveys (NHANES). A published algorithm of predicted CVD benefit with intensive SBP treatment was used to categorize participants into low, medium, or high predicted benefit. CVD event rates were estimated with intensive and standard treatment. RESULTS: Median age was 67.0, 72.0, and 64.0 years in SPRINT, SPRINT-eligible REGARDS, and SPRINT-eligible NHANES participants, respectively. The proportion with high predicted benefit was 33.0% in SPRINT, 39.0% in SPRINT-eligible REGARDS, and 23.5% in SPRINT-eligible NHANES. The estimated difference in CVD event rate (standard minus intensive) was 7.0 (95% confidence interval [CI] 3.4-10.7), 8.4 (95% CI 8.2-8.5), and 6.1 (95% CI 5.9-6.3) per 1,000 person-years in SPRINT, SPRINT-eligible REGARDS participants, and SPRINT-eligible NHANES participants, respectively (median 3.2-year follow-up). Intensive SBP treatment could prevent 84,300 (95% CI 80,800-87,920) CVD events per year in 14.1 million SPRINT-eligible US adults; 29,400 and 28,600 would be in 7.0 million individuals with medium or high predicted benefit, respectively. CONCLUSIONS: Most of the population health benefit from intensive SBP goals could be achieved by treating those characterized by a previously published algorithm as having medium or high predicted benefit.

The association of baseline depressive symptoms and stress on withdrawal in a national longitudinal cohort: the REGARDS study.

PURPOSE: To measure the association of baseline psychological symptoms (depressive symptoms and perceived stress) with withdrawal from a cohort study. METHODS: Depressive symptoms and perceived stress were obtained using validated measures during the baseline computer-assisted telephonic interview for the REasons for Geographic and Racial Differences in Stroke study a national longitudinal cohort (≥45 years, 42% Black, 55% women) recruited between 2003 and 2007. Participants who completed follow-up after September 1, 2019, were considered active. Primary outcome was time to study withdrawal. The association of psychological symptoms and time-to-withdrawal was measured using Cox proportional hazard regression models with incremental adjustments by demographic and clinical factors. RESULTS: Out of 29,964 participants included in the analysis, 11,111 (37.1%) participants withdrew over the follow-up period (median: 11 years). Compared to participants with low depressive symptoms, those with moderate symptoms had 5% higher risk (aHR= 1.05; 95% CI= 1.00-1.10) and those with high level of depressive had 19% higher risk (aHR= 1.19; 95% CI= 1.11-1.27) of withdrawal in fully adjusted models. No significant association between perceived stress and withdrawal risk was observed. CONCLUSIONS: Depressive symptoms were significantly associated with withdrawal. Prevalence of depressive symptoms at baseline is an important indicator of participant retention in large prospective cohorts.

Hypertension severity, apparent treatment resistant hypertension and hyperuricemia in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

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.

Social Determinants of Health and Uncontrolled Blood Pressure in a National Cohort of Black and White US Adults: the REGARDS Study.

BACKGROUND: Determining the contribution of social determinants of health (SDOH) to the higher proportion of Black adults with uncontrolled blood pressure (BP) could inform interventions to improve BP control and reduce cardiovascular disease. METHODS: We analyzed data from 7306 White and 7497 Black US adults taking antihypertensive medication from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study (2003-2007). SDOH were defined using the Healthy People 2030 domains of education, economic stability, social context, neighborhood environment, and health care access. Uncontrolled BP was defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg. RESULTS: Among participants taking antihypertensive medication, 25.4% of White and 33.7% of Black participants had uncontrolled BP. The SDOH included in the current analysis mediated the Black-White difference in uncontrolled BP by 33.0% (95% CI, 22.1%-46.8%). SDOH that contributed to excess uncontrolled BP among Black compared with White adults included low annual household income (percent-mediated 15.8% [95% CI, 10.8%-22.8%]), low education (10.5% [5.6%-15.4%]), living in a health professional shortage area (10.4% [6.5%-14.7%]), disadvantaged neighborhood (11.0% [4.4%-18.0%]), and high-poverty zip code (9.7% [3.8%-15.5%]). Together, the neighborhood-domain accounted for 14.1% (95% CI, 5.9%-22.9%), the health care domain accounted for 12.7% (95% CI, 8.4%-17.3%), and the social-context-domain accounted for 3.8% (95% CI, 1.2%-6.6%) of the excess likelihood of uncontrolled BP among Black compared with White adults, respectively. CONCLUSIONS: SDOH including low education, low income, living in a health professional shortage area, disadvantaged neighborhood, and high-poverty zip code contributed to the excess likelihood of uncontrolled BP among Black compared with White adults.