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Stroke was the fifth leading cause of death in the United States in 2021, and cost U.S. residents approximately $56.2 billion during 2019-2020. During 2006-2010, self-reported stroke prevalence among noninstitutionalized adults had a relative decrease of 3.7%. Data from the Behavioral Risk Factor Surveillance System were used to analyze age-standardized stroke prevalence during 2011-2022 among adults aged ≥18 years. From 2011-2013 to 2020-2022, overall self-reported stroke prevalence increased by 7.8% nationwide. Increases occurred among adults aged 18-64 years; females and males; non-Hispanic Black or African American (Black), non-Hispanic White (White), and Hispanic or Latino (Hispanic) persons; and adults with less than a college degree. Stroke prevalence was higher among adults aged ≥65 years than among younger adults; among non-Hispanic American Indian or Alaska Native, non-Hispanic Native Hawaiian or Pacific Islander, and Black adults than among White adults; and among adults with less than a high school education than among those with higher levels of education. Stroke prevalence decreased in the District of Columbia and increased in 10 states. Initiatives to promote knowledge of the signs and symptoms of stroke, and the identification of disparities in stroke prevalence, might help to focus clinical and programmatic interventions, such as the Million Hearts 2027 initiative or the Paul Coverdell National Acute Stroke Program, to improve prevention and treatment of stroke., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Hypertension, or high blood pressure, is a major risk factor for heart disease and stroke. It increases with age and is highest among non-Hispanic Black or African American persons, men, persons aged ≥65 years, those of lower socioeconomic status, and those who live in the southern United States. Hypertension affects approximately one half of U.S. adults, and approximately one quarter of those persons have their blood pressure under control. Reducing population-level hypertension prevalence and improving control is a national priority. In 2017, updated guidelines for high blood pressure in adults recommended lowering the blood pressure threshold for diagnosis of hypertension. Analysis of data from the Behavioral Risk Factor Surveillance System found that age-standardized, self-reported diagnosed hypertension was approximately 30% during 2017-2021, with persistent differences by age, sex, race and ethnicity, level of education, and state of residence. During this period, the age-standardized prevalence of antihypertensive medication use among persons with hypertension increased by 3.1 percentage points, from 59.8% to 62.9% (p<0.001). Increases in antihypertensive medication use were observed in most sociodemographic groups and in many states. Assessing current trends in hypertension diagnosis and treatment can help guide the development of policies and implementation of interventions to reduce this important risk factor for cardiovascular disease and can aid in addressing health disparities., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: COVID-19 is associated with cardiac complications., Objectives: The purpose of this study was to estimate the prevalence, risk factors, and outcomes associated with acute cardiac events during COVID-19-associated hospitalizations among adults., Methods: During January 2021 to November 2021, medical chart abstraction was conducted on a probability sample of adults hospitalized with laboratory-confirmed SARS-CoV-2 infection identified from 99 U.S. counties in 14 U.S. states in the COVID-19-Associated Hospitalization Surveillance Network. We calculated the prevalence of acute cardiac events (identified by International Classification of Diseases-10th Revision-Clinical Modification codes) by history of underlying cardiac disease and examined associated risk factors and disease outcomes., Results: Among 8,460 adults, 11.4% (95% CI: 10.1%-12.9%) experienced an acute cardiac event during a COVID-19-associated hospitalization. Prevalence was higher among adults who had underlying cardiac disease (23.4%; 95% CI: 20.7%-26.3%) compared with those who did not (6.2%; 95% CI: 5.1%-7.6%). Acute ischemic heart disease (5.5%; 95% CI: 4.5%-6.5%) and acute heart failure (5.4%; 95% CI: 4.4%-6.6%) were the most prevalent events; 0.3% (95% CI: 0.1%-0.5%) experienced acute myocarditis or pericarditis. Risk factors varied by underlying cardiac disease status. Patients with ≥1 acute cardiac event had greater risk of intensive care unit admission (adjusted risk ratio: 1.9; 95% CI: 1.8-2.1) and in-hospital death (adjusted risk ratio: 1.7; 95% CI: 1.3-2.1) compared with those who did not., Conclusions: Acute cardiac events were common during COVID-19-associated hospitalizations, particularly among patients with underlying cardiac disease, and are associated with severe disease outcomes. Persons at greater risk for experiencing acute cardiac events during COVID-19-associated hospitalizations might benefit from more intensive clinical evaluation and monitoring during hospitalization., Competing Interests: Funding Support and Author Disclosures This work was supported by the Centers for Disease Control and Prevention through an Emerging Infections Program cooperative agreement (grant CK17-1701) and through a Council of State and Territorial Epidemiologists cooperative agreement (grant NU38OT000297-02-00). The findings and conclusions in this report are those of the authors do not necessarily represent the official position of the United States Department of Health and Human Services, the United States Public Health Service Commissioned Corps, the Centers for Disease Control and Prevention, or the authors’ institutions. Dr Anderson has served as a consultant for Pfizer, Sanofi Pasteur, Janssen, and Medscape; his institution receives funds to conduct clinical research unrelated to this work from MedImmune, Regeneron, PaxVax, Pfizer, GlaxoSmithKline, Merck, Sanofi-Pasteur, Janssen, and Micron; he serves on a safety monitoring board for Kentucky BioProcessing, Inc and Sanofi Pasteur; and his institution has also received funding from the National Institutes of Health to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. Drs Weigel, Shiltz, and Talbot have received funding through the Centers for Disease Control and Prevention’s Emerging Infections Program Cooperative Agreement and/or Epidemiology and Laboratory Capacity Program, or other programs. Drs Weigel, Henderson, and Shiltz have received funding through the Council on State and Territorial Epidemiology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Chronic conditions are common, costly, and major causes of death and disability.* Addressing chronic conditions and their determinants in young adulthood can help slow disease progression and improve well-being across the life course (1); however, recent prevalence estimates examining chronic conditions in young adults overall and by subgroup have not been reported. CDC analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS) to measure prevalence of 11 chronic conditions among adults aged 18-34 years overall and by selected characteristics, and to measure prevalence of health-related risk behaviors by chronic condition status. In 2019, more than one half (53.8%) of adults aged 18-34 years reported having at least one chronic condition, and nearly one quarter (22.3%) reported having more than one chronic condition. The most prevalent conditions were obesity (25.5%), depression (21.3%), and high blood pressure (10.7%). Differences in the prevalence of having a chronic condition were most noticeable between young adults with a disability (75.8%) and without a disability (48.3%) and those who were unemployed (62.3%) and students (45.8%). Adults aged 18-34 years with a chronic condition were more likely than those without one to report binge drinking, smoking, or physical inactivity. Coordinated efforts by public and private sectors might help raise awareness of chronic conditions among young adults and help improve the availability of evidence-based interventions, policies, and programs that are effective in preventing, treating, and managing chronic conditions among young adults (1)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Introduction: Adults with vision impairment (VI) have a higher prevalence of cardiovascular disease (CVD) compared with those without VI. We estimated the prevalence of CVD and CVD risk factors by VI status in US adults., Methods: We used nationally representative data from the 2018 National Health Interview Survey (N = 22,890 adults aged ≥18 years). We estimated the prevalence of self-reported diagnosis of CVD (coronary heart disease [including angina and myocardial infarction], stroke, or other heart disease) by VI status. We used separate logistic regression models to generate adjusted prevalence ratios (aPRs), controlling for sociodemographic covariates, for those with VI (reference group, no VI) for CVD and CVD risk factors: current smoking, physical inactivity, excessive alcohol intake, obesity, hypertension, high cholesterol, and diabetes., Results: Overall, 12.9% (95% CI, 12.3-13.5) of the sample had VI. The prevalence of CVD was 26.6% (95% CI, 24.7-28.6) in people with VI versus 12.2% (95% CI, 11.7-12.8) in those without VI (aPR = 1.65 [95% CI, 1.51-1.80]). Compared with adults without VI, those with VI had a higher prevalence of all risk factors examined: current smoking (aPR = 1.40 [95% CI, 1.27-1.53]), physical inactivity (aPR = 1.14 [95% CI, 1.06-1.22]), excessive alcohol intake (aPR = 1.29 [95% CI, 1.08-1.53]), obesity (aPR = 1.28 [95% CI, 1.21-1.36]), hypertension (aPR = 1.29 [95% CI, 1.22-1.36]), high cholesterol (aPR = 1.21 [95% CI, 1.14-1.29]), and diabetes (aPR = 1.54 [95% CI, 1.38-1.72])., Conclusion: Adults with VI had a higher prevalence of CVD and CVD risk factors compared with those without VI. Effective clinical and lifestyle interventions, adapted to accommodate VI-related challenges, may help reduce CVD risk in adults with VI.

Background: Diabetes mellitus (DM) is a leading contributor to morbidity and mortality in the United States (US). Prior DM prevalence estimates in Asian Americans are predominantly from Asians aggregated into a single group, but the Asian American population is heterogenous., Objective: To evaluate self-reported DM prevalence in disaggregated Asian American subgroups to inform targeted management and prevention., Design: Serial cross-sectional analysis., Participants: Respondents to the US Behavioral Risk Factor Surveillance System surveys who self-identify as non-Hispanic Asian American (NHA, N=57,001), comprising Asian Indian (N=11,089), Chinese (N=9458), Filipino (N=9339), Japanese (N=10,387), and Korean Americans (N=2843), compared to non-Hispanic White (NHW, N=2,143,729) and non-Hispanic Black (NHB, N=215,957) Americans., Main Measures: Prevalence of self-reported DM. Univariate Satterthwaite-adjusted chi-square tests compared the differences in weighted DM prevalence by sociodemographic and health status., Key Results: Self-reported fully adjusted DM prevalence was 8.7% (95% confidence interval 8.2-9.3) in NHA, compared to 14.3% (14.0-14.6) in NHB and 10.0% (10.0-10.1) in NHW (p<0.01 for difference). In NHA subgroups overall, DM prevalence was 14.4% (12.6-16.3) in Filipino, 13.4% (10.9-16.2) in Japanese, 10.7% (9.6-11.8) in Asian Indian, 5.1% (4.2-6.2) in Chinese, and 4.7% (3.4-6.3) in Korean Americans (p<0.01). Among those aged ≥65 years, DM prevalence was highest in Filipino (35.0% (29.4-41.2)) and Asian Indian (31.5% (25.9-37.8)) Americans. Adjusted for sex, education, and race/ethnicity-specific obesity category, NHA overall had a 21% higher DM prevalence compared to NHW (prevalence ratio 1.21 [1.14-1.27]), while prevalence ratios were 1.42 (1.24-1.63) in Filipinos and 1.29 (1.14-1.46) in Asian Indians., Conclusions: Adjusted self-reported DM prevalence is higher in NHA compared with NHW. Disaggregating NHA reveals heterogeneity in self-reported DM prevalence, highest in Filipino and Asian Indian Americans., (© 2021. Society of General Internal Medicine.)

Background Amid stagnating declines in national cardiovascular disease (CVD) mortality, documenting trends in county-level hypertension-related CVD death rates can help activate local efforts prioritizing hypertension prevention, detection, and control. Methods and Results Using death certificate data from the National Vital Statistics System, Bayesian spatiotemporal models were used to estimate county-level hypertension-related CVD death rates and corresponding trends during 2000 to 2010 and 2010 to 2019 for adults aged ≥35 years overall and by age group, race or ethnicity, and sex. Among adults aged 35 to 64 years, county-level hypertension-related CVD death rates increased from a median of 23.2 per 100 000 in 2000 to 43.4 per 100 000 in 2019. Among adults aged ≥65 years, county-level hypertension-related CVD death rates increased from a median of 362.1 per 100 000 in 2000 to 430.1 per 100 000 in 2019. Increases were larger and more prevalent among adults aged 35 to 64 years than those aged ≥65 years. More than 75% of counties experienced increasing hypertension-related CVD death rates among patients aged 35 to 64 years during 2000 to 2010 and 2010 to 2019 (76.2% [95% credible interval, 74.7-78.4] and 86.2% [95% credible interval, 84.6-87.6], respectively), compared with 48.2% (95% credible interval, 47.0-49.7) during 2000 to 2010 and 66.1% (95% credible interval, 64.9-67.1) for patients aged ≥65 years. The highest rates for both age groups were among men and Black populations. All racial and ethnic categories in both age groups experienced widespread county-level increases. Conclusions Large, widespread county-level increases in hypertension-related CVD mortality sound an alarm for intensified clinical and public health actions to improve hypertension prevention, detection, and control and prevent subsequent CVD deaths in counties across the nation.

Introduction: Although marijuana use has increased since 2012, the perceived risk of adverse outcomes has decreased. This systematic review summarizes articles that examined the association between nonmedical marijuana use (ie, observed smoking, self-report, or urinalysis) and cardiovascular events in observational or experimental studies of adults aged ≥18., Methods: We searched Medline, EMBASE, PsycInfo, CINAHL, Cochrane Library Database, and Global Health from January 1, 1970, through August 31, 2018. Of 3916 citations, 16 articles fit the following criteria: (1) included adults aged ≥18; (2) included marijuana/cannabis use that is self-reported smoked, present in diagnostic coding, or indicated through a positive diagnostic test; (3) compared nonuse of cannabis; (4) examined events related to myocardial infarction, angina, acute coronary syndrome, and/or stroke; (5) published in English; and (6) had observational or experimental designs., Results: Of the 16 studies, 4 were cohort studies, 8 were case-control studies, 1 was a case-crossover study, 2 were randomized controlled trials, and 1 was a descriptive study. Studies ranged from 10 participants to 118 659 619 hospitalizations. Marijuana use was associated with an increased likelihood of myocardial infarction within 24 hours in 2 studies and stroke in 6 studies. Results of studies suggested an increased risk for angina and acute coronary syndrome, especially among people with a history of a cardiovascular event., Conclusion: This review suggests that people who use marijuana may be at increased risk for cardiovascular events. As states expand new laws permitting marijuana use, it will be important to monitor the effect of marijuana use on cardiovascular disease outcomes, perhaps through the inclusion of data on nonmedical marijuana use in diverse national and local surveillance systems.

Background and Purpose: Healthy People establishes objectives to monitor the nation's health. Healthy People 2020 included objectives to reduce national stroke and coronary heart disease (CHD) mortality by 20% (to 34.8 and 103.4 deaths per 100 000, respectively). Documenting the proportion and geographic distribution of counties meeting neither the Healthy People 2020 target nor an equivalent proportional reduction can help identify high-priority geographic areas for future intervention., Methods: County-level mortality data for stroke ( International Classification of Diseases, Tenth Revision codes I60-I69) and CHD (I20-I25) and bridged-race population estimates were used. Bayesian spatiotemporal models estimated age-standardized county-level death rates in 2007 and 2017 which were used to calculate and map the proportion and 95% credible interval of counties achieving neither the national Healthy People 2020 target nor a 20% reduction in mortality., Results: In 2017, 45.8% of counties (credible interval, 42.9-48.3) met neither metric for stroke mortality. These counties had a median stroke death rate of 42.2 deaths per 100 000 in 2017, representing a median 12.8% decline. For CHD mortality, 26.1% (credible interval, 25.0-27.8) of counties met neither metric. These counties had a median CHD death rate of 127.1 deaths per 100 000 in 2017, representing a 10.2% decline. For both outcomes, counties achieving neither metric were not limited to counties with traditionally high stroke and CHD death rates., Conclusions: Recent declines in stroke and CHD mortality have not been equal across US counties. Focusing solely on high mortality counties may miss opportunities in the prevention and treatment of cardiovascular disease and in learning more about factors leading to successful reductions in mortality.

Primary care providers (PCPs) are uniquely positioned to promote physical activity for cardiovascular health. We sought to determine the types of physical activity that PCPs most often recommend to patients at risk for cardiovascular disease (CVD) and how these recommendations vary by PCPs' physical activity counseling practices. We examined the types of physical activity (walking, supervised exercise sessions, or other) PCPs most often suggested for CVD prevention among respondents to the 2018 DocStyles survey (N = 1,088). Most PCPs (80.0%) suggested walking to their patients at risk for CVD; however, PCPs who infrequently discussed physical activity with their patients at risk for CVD suggested walking less often than those who more frequently discussed physical activity. Walking is an easy and low-cost form of physical activity, and opportunities exist for certain PCPs to promote walking as part of their physical activity counseling practices for CVD prevention.

Background The American Heart Association and Healthy People 2020 established objectives to reduce coronary heart disease (CHD) and stroke death rates by 20% by the year 2020, with 2007 as the baseline year. We examined county-level achievement of the targeted reduction in CHD and stroke death rates from 2007 to 2017. Methods and Results Applying a hierarchical Bayesian model to National Vital Statistics data, we estimated annual age-standardized county-level death rates and the corresponding percentage change during 2007 to 2017 for those aged 35 to 64 and ≥65 years and by urban-rural classification. For those aged ≥35 years, 56.1% (95% credible interval [CI], 54.1%-57.7%) and 39.8% (95% CI, 36.9%-42.7%) of counties achieved a 20% reduction in CHD and stroke death rates, respectively. For both CHD and stroke, the proportions of counties achieving a 20% reduction were lower for those aged 35 to 64 years than for those aged ≥65 years (CHD: 32.2% [95% CI, 29.4%-35.6%] and 64.1% [95% CI, 62.3%-65.7%]), respectively; stroke: 17.9% [95% CI, 13.9%-22.2%] and 45.6% [95% CI, 42.8%-48.3%]). Counties achieving a 20% reduction in death rates were more commonly urban counties (except stroke death rates for those aged ≥65 years). Conclusions Our analysis found substantial, but uneven, achievement of the targeted 20% reduction in CHD and stroke death rates, defined by the American Heart Association and Healthy People. The large proportion of counties not achieving the targeted reduction suggests a renewed focus on CHD and stroke prevention and treatment, especially among younger adults living outside of urban centers. These county-level patterns provide a foundation for robust responses by clinicians, public health professionals, and communities.

Population cardiovascular health, or improving cardiovascular health among patients and the population at large, requires a redoubling of primordial and primary prevention efforts as declines in cardiovascular disease mortality have decelerated over the past decade. Great potential exists for healthcare systems-based approaches to aid in reversing these trends. A learning healthcare system, in which population cardiovascular health metrics are measured, evaluated, intervened on, and re-evaluated, can serve as a model for developing the evidence base for developing, deploying, and disseminating interventions. This scientific statement on optimizing population cardiovascular health summarizes the current evidence for such an approach; reviews contemporary sources for relevant performance and clinical metrics; highlights the role of implementation science strategies; and advocates for an interdisciplinary team approach to enhance the impact of this work.

Stroke is the fifth leading cause of death in the United States (1). In 2017, on average, a stroke-related death occurred every 3 minutes and 35 seconds in the United States, and stroke is a leading cause of long-term disability (1). To prevent mortality or long-term disability, strokes require rapid recognition and early medical intervention (2,3). Common stroke signs and symptoms include sudden numbness or weakness of the face, arm, or leg, especially on one side; sudden confusion or trouble speaking; sudden trouble seeing in one or both eyes; sudden trouble walking, dizziness, or loss of balance; and a sudden severe headache with no known cause. Recommended action at the first sign of a suspected stroke is to quickly request emergency services (i.e., calling 9-1-1) (2). Public education campaigns have emphasized recognizing stroke signs and symptoms and the importance of calling 9-1-1, and stroke knowledge increased 14.7 percentage points from 2009 to 2014 (4). However, disparities in stroke awareness have been reported (4,5). Knowledge of the five signs and symptoms of stroke and the immediate need to call emergency medical services (9-1-1), collectively referred to as "recommended stroke knowledge," was assessed among 26,076 adults aged ≥20 years as part of the 2017 National Health Interview Survey (NHIS). The prevalence of recommended stroke knowledge among U.S. adults was 67.5%. Stroke knowledge differed significantly by race and Hispanic origin (p<0.001). The prevalence of recommended stroke knowledge was highest among non-Hispanic White adults (71.3%), followed by non-Hispanic Black adults (64.0%) and Hispanic adults (57.8%). Stroke knowledge also differed significantly by sex, age, education, and urbanicity. After multivariable adjustment, these differences remained significant. Increasing awareness of the signs and symptoms of stroke continues to be a national priority. Estimates from this report can inform public health strategies for increasing awareness of stroke signs and symptoms., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Introduction: Medication adherence can improve hypertension management. How blood pressure medications are prescribed and purchased can promote or impede adherence., Methods: We used comprehensive dispensing data on prescription blood pressure medication from Symphony Health's 2017 Integrated Dataverse to assess how prescription- and payment-related factors that promote medication adherence (ie, fixed-dose combinations, generic formulations, mail order, low-cost or no-copay medications) vary across US states and census regions and across the market segments (grouped by patient age, prescriber type, and payer type) responsible for the greatest number of blood pressure medication fills., Results: In 2017, 706.5 million prescriptions for blood pressure medication were filled, accounting for $29.0 billion in total spending (17.0% incurred by patients). As a proportion of all fills, factors that promoted adherence varied by state: fixed-dose combinations (from 5.8% in Maine to 17.9% in Mississippi); generic formulations (from 95.2% in New Jersey to 98.4% in Minnesota); mail order (from 4.7% in Rhode Island to 14.5% in Delaware); and lower or no copayment (from 56.6% in Utah to 72.8% in California). Furthermore, mean days' supply per fill (from 43.1 in Arkansas to 63.8 in Maine) and patient spending per therapy year (from $38 in Hawaii to $76 in Georgia) varied. Concentration of adherence factors differed by market segment. Patients aged 18 to 64 with a primary care physician prescriber and Medicaid coverage had the lowest concentration of fixed-dose combination fills, mean days' supply per fill, and patient spending per therapy year. Patients aged 65 years or older with a primary care physician prescriber and commercial insurance had the highest concentration of fixed-dose combinations fills and mail order fills., Conclusion: Addressing regional and market segment variation in factors promoting blood pressure medication adherence may increase adherence and improve hypertension management.

Despite the importance of antihypertensive medication therapy for blood pressure control, no single data system provides estimates of medication nonadherence rates across age groups and health insurance plans types. Using multiple administrative datasets and national survey data, we determined health insurance plan-specific and overall weighted national rates of nonadherence to antihypertensive medications among insured hypertensive US adults in 2015. We used 2015 prescription claims data from Medicare Part D and 3 IBM MarketScan databases (Commercial, Medicaid, Medicare Supplemental) to calculate medication nonadherence rates among hypertensive adults aged ≥18 years with public or private health insurance using the proportion of days covered algorithm. These findings, in combination with National Health Interview Survey findings, were used to project national weighted estimates of nonadherence. We included 23.8 million hypertensive adults who filled 265.8 million prescriptions for antihypertensive medications. Nonadherence differed by health insurance plan type (highest for Medicaid members, 55.4%; lowest for Medicare Part D members, 25.2%). The overall weighted national nonadherence rate was 31.0%, with greater nonadherence among women versus men, younger versus older adults (aged 18-34 years, 58.1%; aged 65-74 years, 24.4%), fixed-dose combination medication nonusers (31.2%) versus users (29.4%), and by pharmacy outlet type (retail only, 30.7%; any mail order, 19.8%). In 2015, almost one-third (≈16.3 million) of insured US adults with diagnosed hypertension were considered nonadherent to their antihypertensive medication regimen, and considerable disparities were evident. Public health and healthcare professionals can use available evidence-based interventions to address nonadherence and improve blood pressure control.

Objective: Cardiovascular disease (CVD) is a common cause of morbidity and mortality among persons living with HIV (PLWH). We used individual cardiovascular risk factor profiles to estimate heart age for PLWH in medical care in the United States., Design: Cross-sectional analyses of HIV Outpatient Study (HOPS) data METHODS:: Included in this analysis were participants aged 30-74 years, without prior CVD, with at least two HOPS clinic visits during 2010-2017, at least 1-year of follow-up, and available covariate data. We calculated age and race/ethnicity-adjusted heart age and excess heart age (chronological age - heart age), using a Framingham risk score-based model., Results: We analyzed data from 2467 men and 619 women (mean chronologic age 49.3 and 49.1 years, and 23.6% and 54.6% Non-Hispanic/Latino black, respectively). Adjusted excess heart age was 11.5 years (95% confidence interval, 11.1-12.0) among men and 13.1 years (12.0-14.1) among women. Excess heart age was seen among all age groups beginning with persons aged 30-39 years [men, 7.8 (6.9-8.8); women, 7.7 (4.9-10.4)], with the highest excess heart age among participants aged 50-59 years [men, 13.7 years (13.0-14.4); women, 16.4 years (14.8-18.0)]. More than 50% of participants had an excess heart age of at least 10 years., Conclusions: Excess heart age is common among PLWH, begins in early adulthood, and impacts both women and men. Among PLWH, CVD risk factors should be addressed early and proactively. Routine use of the heart age calculator may help optimize CVD risk stratification and facilitate interventions for aging PLWH.

Background: Five guideline-recommended medication categories are available to treat patients who have heart failure (HF) with reduced ejection fraction. However, adherence to these medications is often suboptimal, which places patients at increased risk for poor health outcomes, including hospitalization. We aimed to examine the association between adherence to these medications and potentially preventable HF hospitalizations among younger insured adults with newly diagnosed HF., Methods and Results: Using the 2008-2012 IBM MarketScan Commercial database, we followed 26,439 individuals aged 18-64 years with newly diagnosed HF and calculated their adherence (using the proportion of days covered (PDC) algorithm) to the five guideline-recommended medication categories: angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers; beta blockers; aldosterone receptor antagonists; hydralazine; and isosorbide dinitrate. We determined the association between PDC and long-term preventable HF hospitalizations (observation years 3-5) as defined by the United States (U.S.) Agency for Healthcare Research and Quality. Overall, 49.0% of enrollees had good adherence (PDC≥80%), which was more common among enrollees who were older, male, residing in higher income counties, initially diagnosed with HF in an outpatient setting, and who filled prescriptions for fewer medication categories assessed. Adherence differed by medication category and was lowest for isosorbide dinitrate (PDC = 60.7%). In total, 7.6% of enrollees had preventable HF hospitalizations. Good adherers, compared to poor adherers (PDC<40%), were 15% less likely to have a preventable hospitalization (HR 0.85, 95% confidence interval, 0.75-0.96)., Conclusion: We found that approximately half of insured U.S. adults aged 18-64 years with newly diagnosed HF had good adherence to their HF medications. Patients with good adherence, compared to those with poor adherence, were less likely to have a potentially preventable HF hospitalization 3-5 years after their initial diagnosis. Because HF is a chronic condition that requires long-term management, future studies may want to assess the effectiveness of interventions in sustaining adherence., Competing Interests: TEC is employed by IHRC, Inc,. JB has received research support from the National Institutes of Health, PCORI and the European Union; and serves as a consultant for Amgen, Array, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squib, CVRx, G3 Pharmacautical, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Relypsa, StealthPeptide, SC Pharma, Vifor, and ZS Pharma. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Background Asian Americans are the fastest growing population in the United States, but little is known about their cardiovascular health (CVH). The objective of this study was to assess CVH among non-Hispanic Asian Americans (NHAAs) and to compare these estimates to those of non-Hispanic white (NHW) participants. Methods and Results Merging NHANES (National Health and Nutrition Examination Survey) data from 2011 to 2016, we examined 7 metrics (smoking, weight, physical activity, diet, blood cholesterol, blood glucose, and blood pressure) to assess CVH among 5278 NHW and 1486 NHAA participants aged ≥20 years. We assessed (1) the percentage meeting 6 to 7 metrics (ideal CVH), (2) the percentage meeting only 0 to 2 metrics (poor CVH), and (3) the overall mean CVH score. We compared these estimates between NHAAs and NHWs and among foreign-born NHAAs by birthplace and number of years living in the United States. The adjusted prevalence of ideal CVH was 8.7% among NHAAs and 5.9% among NHWs ( P<0.001). NHAAs were significantly more likely to have ideal CVH (adjusted prevalence ratio: 1.42; 95% CI, 1.29-1.55) compared with NHWs. Among NHAAs, there was no significant difference in ideal CVH between US- and foreign-born participants, nor by number of years living in the United States. With lower body mass index thresholds (<23, normal weight) for NHAAs, there were no statistically significant differences in the adjusted prevalence of ideal CVH (6.5% versus 5.9%, P=0.216) between NHAAs and NHWs. Conclusions NHAAs had a higher prevalence of overall ideal CVH compared with NHWs. However, when using a lower body mass index threshold for NHAAs, there was no difference in ideal CVH between the groups.

Introduction: Cardiovascular disease (CVD) is the leading cause of death in the United States, and increasing physical activity can help prevent and manage disease. Walking is an easy way for most adults to be more active and may help people at risk for CVD avoid inactivity, increase their physical activity levels, and improve their cardiovascular health. To guide efforts that promote walking for CVD prevention and management, we estimated the prevalence of walking among US adults by CVD risk status., Methods: Nationally representative data on walking from participants (N = 29,742) in the 2015 National Health Interview Survey Cancer Control Supplement were analyzed. We estimated prevalence of walking (ie, any, transportation, and leisure) overall and by CVD status. We defined CVD status as either not having CVD and not at risk for CVD; being at risk for CVD (overweight or having obesity plus 1 or more additional risk factors); or having CVD. We defined additional risk factors as diabetes, high cholesterol, or hypertension. Odds ratios were estimated by using logistic regression models adjusted for respondent characteristics., Results: Prevalence of any walking decreased with increasing CVD risk (no CVD/not at risk, 66.6%; at risk: overweight or has obesity with 1 risk factor, 63.0%; with 2 risk factors, 59.5%; with 3 risk factors, 53.6%; has CVD, 50.2%). After adjusting for respondent characteristics, the odds of any walking and leisure walking decreased with increasing CVD risk. However, CVD risk was not associated with walking for transportation., Conclusions: Promoting walking may be a way to help adults avoid inactivity and encourage an active lifestyle for CVD prevention and management.

The Healthy People Initiative has served as the leading disease prevention and health promotion roadmap for the nation since its inception in 1979. Healthy People 2020 (HP2020), the initiative's current iteration, sets a national prevention agenda with health goals and objectives by identifying nationwide health improvement priorities and providing measurable objectives and targets from 2010 to 2020. Central to the overall mission and vision of Healthy People is an emphasis on achieving health equity, eliminating health disparities, and improving health for all population groups. The Heart Disease and Stroke (HDS) Work Group of the HP2020 Initiative aims to leverage advances in biomedical science and prevention research to improve cardiovascular health across the nation. The initiative provides a platform to foster partnerships and empower professional societies and nongovernmental organizations, governments at the local, state, and national levels, and healthcare professionals to strengthen policies and improve practices related to cardiovascular health. Disparities in cardiovascular disease burden are well recognized across, for example, race/ethnicity, sex, age, and geographic region, and improvements in cardiovascular health for the entire population are only possible if such disparities are addressed through efforts that target individuals, communities, and clinical and public health systems. This article summarizes criteria for creating and tracking the 50 HDS HP2020 objectives in 3 areas (prevention, morbidity/mortality, and systems of care), reports on progress toward the 2020 targets for these objectives based on the most recent data available, and showcases examples of relevant programs led by participating agencies. Although most of the measurable objectives have reached the 2020 targets ahead of time (n=14) or are on track to meet the targets (n=7), others may not achieve the decade's targets if the current trends continue, with 3 objectives moving away from the targets. This summary illustrates the utility of HP2020 in tracking measures of cardiovascular health that are of interest to federal agencies and policymakers, professional societies, and other nongovernmental organizations. With planning for Healthy People 2030 well underway, stakeholders such as healthcare professionals can embrace collaborative opportunities to leverage existing progress and emphasize areas for improvement to maximize the Healthy People initiative's positive impact on population-level health.

Heart disease is the leading cause of death in the United States (1). Heart attacks (also known as myocardial infarctions) occur when a portion of the heart muscle does not receive adequate blood flow, and they are major contributors to heart disease, with an estimated 750,000 occurring annually (2). Early intervention is critical for preventing mortality in the event of a heart attack (3). Identification of heart attack signs and symptoms by victims or bystanders, and taking immediate action by calling emergency services (9-1-1), are crucial to ensure timely receipt of emergency care and thereby improve the chance for survival (4). A recent report using National Health Interview Survey (NHIS) data from 2014 found that 47.2% of U.S. adults could state all five common heart attack symptoms (jaw, neck, or back discomfort; weakness or lightheadedness; chest discomfort; arm or shoulder discomfort; and shortness of breath) and knew to call 9-1-1 if someone had a heart attack (5). To assess changes in awareness and response to an apparent heart attack, CDC analyzed data from NHIS to report awareness of heart attack symptoms and calling 9-1-1 among U.S. adults in 2008, 2014, and 2017. The adjusted percentage of persons who knew all five common heart attack symptoms increased from 39.6% in 2008 to 50.0% in 2014 and to 50.2% in 2017. The adjusted percentage of adults who knew to call 9-1-1 if someone was having a heart attack increased from 91.8% in 2008 to 93.4% in 2014 and to 94.9% in 2017. Persistent disparities in awareness of heart attack symptoms were observed by demographic characteristics and cardiovascular risk group. Public health awareness initiatives and systematic integration of appropriate awareness and action in response to a perceived heart attack should be expanded across the health system continuum of care., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Objective: We examined whether life course socioeconomic position (SEP) was associated with incidence of type 2 diabetes (t2DM) among African Americans., Design: Secondary analysis of data from the Jackson Heart Study, 2000-04 to 2012, using Cox proportional hazard regression to estimate hazard ratios (HR) with 95% CI for t2DM incidence by measures of life course SEP., Participants: Sample of 4,012 nondiabetic adults aged 25-84 years at baseline., Outcome Measure: Incident t2DM identified by self-report, hemoglobin A1c ≥6.5%, fasting plasma glucose ≥126 mg/dL, or use of diabetes medication., Results: During 7.9 years of follow-up, 486 participants developed t2DM (incidence rate 15.2/1000 person-years, 95% CI: 13.9-16.6). Among women, but not men, childhood SEP was inversely associated with t2DM incidence (HR=.97, 95% CI: .94-.99) but was no longer associated with adjustment for adult SEP or t2DM risk factors. Upward SEP mobility increased the hazard for t2DM incidence (adjusted HR=1.52, 95% CI: 1.05-2.21) among women only. Life course allostatic load (AL) did not explain the SEP-t2DM association in either sex., Conclusions: Childhood SEP and upward social mobility may influence t2DM incidence in African American women but not in men., Competing Interests: Competing Interests: None declared.

Background: Heart failure (HF)-a serious and costly condition-is increasingly prevalent. We estimated the US burden including emergency department (ED) visits, inpatient hospitalizations and associated costs, and mortality., Methods and Results: We analyzed 2006 to 2014 data from the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample, the Healthcare Cost and Utilization Project National (nationwide) Inpatient Sample, and the National Vital Statistics System. International Classification of Disease codes identified HF and comorbidities. Burden was estimated separately for ED visits, hospitalizations, and mortality. In addition, criteria were applied to identify total unique acute events. Rates of primary HF (primary diagnosis or underlying cause of death) and comorbid HF (comorbid diagnosis or contributing cause of death) were calculated, age standardized to the 2010 US population. In 2014, there were an estimated 1 068 412 ED visits, 978 135 hospitalizations, and 83 705 deaths with primary HF. There were 4 071 546 ED visits, 3 370 856 hospitalizations, and 230 963 deaths with comorbid HF. Between 2006 and 2014, the total unique acute event rate for primary HF declined from 536 to 449 per 100 000 (relative percent change of -16%; P for trend, <0.001) but increased for comorbid HF from 1467 to 1689 per 100 000 (relative percentage change, 15%; P for trend, <0.001). HF-related mortality decreased significantly from 2006 to 2009 but did not change meaningfully after 2009. For hospitalizations with primary HF, the estimated mean cost was $11 552 in 2014, totaling an estimated $11 billion., Conclusions: Given substantial healthcare and mortality burden of HF, rising healthcare costs, and the aging US population, continued improvements in HF prevention, management, and surveillance are important.

Application of the 2017 ACC/AHA Hypertension Guideline expands the number of US adults requiring blood pressure (BP) management. The authors use 2011-2014 NHANES data to describe the population groups most affected by the new guideline, compared with the previous JNC-7 guideline, and describe the previous interaction with the health care sector among those adults recommended new or intensified pharmacologic treatment and/or lifestyle modification. The 2017 Hypertension Guideline reclassifies 32.3 million US adults as newly hypertensive and recommends BP-related treatment of 133.7 million adults, including 57.8 million with uncontrolled BP recommended to initiate or intensify pharmacologic treatment and 50.5 million newly recommended lifestyle modification alone. An estimated 13.1 million (22.7%) adults recommended to initiate or intensify pharmacologic treatment, and 20.6 million (40.8%) adults newly recommended lifestyle modification alone report not having established health care linkages. Among the adults newly recommended lifestyle modification alone, the odds of reclassification from no recommended intervention, under JNC-7, to recommended lifestyle modification alone were lower for adults with established linkages to care (aOR: 0.78 [95% CI: 0.67-0.91]) compared to those without, decreased with increasing age, were greater for men (1.72 [1.52-1.94]) compared to women and were greater for obese adults (1.23 [1.00-1.53]) compared with normal or underweight adults. Application of the 2017 Hypertension Guideline increases the number and alters the distribution of US adults in need of initiating or intensifying BP treatment. This includes identifying millions of US adults who previously had limited interaction with health care and are now recommended new or intensified pharmacologic treatment and/or lifestyle modification., (©2018 Wiley Periodicals, Inc.)

Hypertension affects about one in three US adults, from recent surveillance, or four in nine based on the 2017 ACC/AHA Hypertension Guideline; about half of them have their blood pressure controlled, and nearly one in six are unaware of their hypertension status. National estimates of hypertension awareness, treatment, and control in the United States are traditionally based on measured BP from National Health and Nutrition Examination Survey (NHANES); however, at the state level, only self-reported hypertension awareness and treatment are available from BRFSS. We used national- and state-level representative samples of adults (≥20 years) from NHANES 2011-2014 and BRFSS 2013 and 2015, respectively. The authors generated multivariable logistic regression models using NHANES to predict the probability of hypertension and undiagnosed hypertension and then applied the fitted model parameters to BRFSS to generate state-level estimates. The predicted prevalence of hypertension was highest in Mississippi among adults (42.4%; 95% CI: 41.8-43.0) and among women (42.6%; 41.8-43.4) and highest in West Virginia among men (43.4%; 42.2-44.6). The predicted prevalence was lowest in Utah 23.7% (22.8-24.6), 26.4% (25.0-27.7), and 21.0% (20.0-22.1) for adults, men, and women, respectively. Hypertension predicted prevalence was higher in most Southern states and higher among men than women in all states except Mississippi and DC. The predicted prevalence of undiagnosed hypertension ranged from 4.1% (3.4-4.8; Kentucky) to 6.5% (5.5-7.5; Hawaii) among adults, from 5.0% (4.0-5.9; Kentucky) to 8.3% (6.9-9.7; Hawaii) among men, and from 3.3% (2.5-4.1; Kentucky) to 4.8% (3.4-6.1; Vermont) among women. Undiagnosed hypertension was more prevalent among men than women in all states and DC., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Vascular endothelial growth factor receptor-2 (VEGFR2) is a key mediator of angiogenesis and therefore a promising therapeutic target in malignancies including glioblastoma multiforme (GBM). Molecular imaging of VEGFR2 expression may enable patient stratification for antiangiogenic therapy. The goal of the current study was to evaluate the capacity of the novel anti-VEGFR2 biparatopic affibody conjugate (Z VEGFR2 -Bp 2 ) for in vivo visualization of VEGFR2 expression in GBM. Methods: Z VEGFR2 -Bp 2 coupled to a NODAGA chelator was generated and radiolabeled with indium-111. The VEGFR2-expressing murine endothelial cell line MS1 was used to evaluate in vitro binding specificity and affinity, cellular processing and targeting specificity in mice. Further tumor targeting was studied in vivo in GL261 glioblastoma orthotopic tumors. Experimental imaging was performed. Results: [ 111 In]In-NODAGA-Z VEGFR2 -Bp 2 bound specifically to VEGFR2 (K D =33±18 pM). VEGFR2-mediated accumulation was observed in liver, spleen and lungs. The tumor-to-organ ratios 2 h post injection for mice bearing MS1 tumors were approximately 11 for blood, 15 for muscles and 78 for brain. Intracranial GL261 glioblastoma was visualized using SPECT/CT. The activity uptake in tumors was significantly higher than in normal brain tissue. The tumor-to-cerebellum ratios after injection of 4 µg [ 111 In]In-NODAGA-Z VEGFR2 -Bp 2 were significantly higher than the ratios observed for the 40 µg injected dose and for the non-VEGFR2 binding size-matched conjugate, demonstrating target specificity. Microautoradiography of cryosectioned CNS tissue was in good agreement with the SPECT/CT images. Conclusion: The anti-VEGFR2 affibody conjugate [ 111 In]In-NODAGA-Z VEGFR2 -Bp 2 specifically targeted VEGFR2 in vivo and visualized its expression in a murine GBM orthotopic model. Tumor-to-blood ratios for [ 111 In]In-NODAGA-Z VEGFR2 -Bp 2 were higher compared to other VEGFR2 imaging probes. [ 111 In]In-NODAGA-Z VEGFR2 -Bp 2 appears to be a promising probe for in vivo noninvasive visualization of tumor angiogenesis in glioblastoma., Competing Interests: Competing Interests: VT, JL, AO, and SS are the members of the scientific advisory board of Affibody AB. SS, VT and AO are minority share owners of Affibody AB. Affibody AB holds intellectual property rights and trademarks for Affibody molecules. BM, RG, FPR, EL, RKS, FF, SSR, LCW declare no potential conflict of interest.

Approximately 11 million U.S. adults with a usual source of health care have undiagnosed hypertension, placing them at increased risk for cardiovascular events (1-3). Using data from the National Health and Nutrition Examination Survey (NHANES), CDC developed the Million Hearts Hypertension Prevalence Estimator Tool, which allows health care delivery organizations (organizations) to predict their patient population's hypertension prevalence based on demographic and comorbidity characteristics (2). Organizations can use this tool to compare predicted prevalence with their observed prevalence to identify potential underdiagnosed hypertension. This study applied the tool using medical billing data alone and in combination with clinical data collected among 8.92 million patients from 25 organizations participating in American Medical Group Association (AMGA) national learning collaborative* to calculate and compare predicted and observed adult hypertension prevalence. Using billing data alone revealed that up to one in eight cases of hypertension might be undiagnosed. However, estimates varied when clinical data were included to identify comorbidities used to predict hypertension prevalence or describe observed hypertension prevalence. These findings demonstrate the tool's potential use in improving identification of hypertension and the likely importance of using both billing and clinical data to establish hypertension and comorbidity prevalence estimates and to support clinical quality improvement efforts., Competing Interests: No conflicts of interest were reported.

Hypertension is an important modifiable risk factor for cardiovascular morbidity and mortality, and hypertension in adolescents and young adults is associated with long-term negative health effects (1,2).* In 2017, the American Academy of Pediatrics (AAP) released a new Clinical Practice Guideline (3), which updated 2004 pediatric hypertension guidance † with new thresholds and percentile references calculated from a healthy-weight population. To examine trends in youth hypertension and the impact of the new guideline on classification of hypertension status, CDC analyzed data from 12,004 participants aged 12-19 years in the 2001-2016 National Health and Nutrition Examination Survey (NHANES). During this time, prevalence of hypertension declined, using both the new (from 7.7% to 4.2%, p<0.001) and former (from 3.2% to 1.5%, p<0.001) guidelines, and declines were observed across all weight status categories. However, because of the new percentile tables and lower threshold for hypertension (4), application of the new guideline compared with the former guideline resulted in a weighted net estimated increase of 795,000 U.S. youths being reclassified as having hypertension using 2013-2016 data. Youths who were older, male, and those with obesity accounted for a disproportionate share of persons reclassified as having hypertension. Clinicians and public health professionals might expect to see a higher prevalence of hypertension with application of the new guideline and can use these data to inform actions to address hypertension among youths. Strategies to improve cardiovascular health include adoption of healthy eating patterns and increased physical activity (3)., Competing Interests: No conflicts of interest were reported.

Stroke is a leading cause of mortality and disability in the United States (1,2). Approximately 800,000 American adults experience a stroke each year (2,3). Currently, approximately 6 million stroke survivors live in the United States (2). Participation in stroke rehabilitation (rehab), which occurs in diverse settings (i.e., in-hospital, postacute care, and outpatient settings), has been determined to reduce stroke recurrence and improve functional outcomes and quality of life (3,4). Despite longstanding national guidelines recommending stroke rehab, it remains underutilized, especially in the outpatient setting. Professional associations and evidence-based guidelines support the increasing stroke rehab use in health systems and are promoted by the public health community (3-6). An analysis of 2005 Behavioral Risk Factor Surveillance System (BRFSS) data revealed that 30.7% of stroke survivors reported participation in outpatient rehab for stroke after hospital discharge in 21 states and the District of Columbia (DC) (7). To update these estimates, 2013 and 2015 BRFSS data were analyzed to assess outpatient rehab use among adult stroke survivors. Overall, outpatient rehab use was 31.2% (20 states and DC) in 2013 and 35.5% (four states) in 2015. Disparities were evident by sex, race, Hispanic origin, and level of education. Focused attention on system-level interventions that ensure participation is needed, especially among disparate populations with lower levels of participation., Competing Interests: No conflicts of interest were reported.

Background: The proportion of foreign-born US adults has almost tripled since 1970. However, less is known about the cardiovascular morbidity by birthplace among adults residing in the United States. This study's objective was to compare the prevalence of coronary heart disease (CHD) and stroke among US adults by birthplace., Methods and Results: We used data from the 2006 to 2014 National Health Interview Survey. Birthplace was categorized as United States or foreign born. Foreign born was then grouped into 6 birthplace regions. We defined CHD and stroke as ever being told by a physician that she or he had CHD or stroke. We adjusted for select demographic and health characteristics in the analysis. Of US adults, 16% were classified as foreign born. Age-standardized prevalence of both CHD and stroke were higher among US- than foreign-born adults (CHD: 8.2% versus 5.5% for men and 4.8% versus 4.1% for women; stroke: 2.7% versus 2.1% for men and 2.7% versus 1.9% for women; all P <0.05). Comparing individual regions with those of US- born adults, CHD prevalence was lower among foreign-born adults from Asia and Mexico, Central America, or the Caribbean. For stroke, although men from South America or Africa had the lowest prevalence, women from Europe had the lowest prevalence. Years of living in the United States was not related to risk of CHD or stroke after adjustment with demographic and health characteristics., Conclusions: Overall, foreign-born adults residing in the United States had a lower prevalence of CHD and stroke than US-born adults. However, considerable heterogeneity of CHD and stroke risk was found by region of birth., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Pragna Patel and colleagues describe the implementation of a hypertension management model for HIV-infected people in Malawi.

Background: With a cholesterol-lowering focus for diabetic adults and in the age of polypharmacy, it is important to understand how lipid profile levels differ among those with and without diabetes., Objective: Investigate the means, differences, and trends in lipid profile measures [TC, total cholesterol; LDL-c, low-density lipoprotein; HDL-c, high-density lipoprotein; and TG, triglycerides] among US adults by diabetes status and cholesterol-lowering medication., Methods: Population number and proportion of adults aged ≥21 years with diabetes and taking cholesterol-lowering medication were estimated using data on 10,384 participants from NHANES 2003-2012. Age-standardized means, trends, and differences in lipid profile measures were estimated by diabetes status and cholesterol medication use. For trends and differences, linear regression analysis were used adjusted for age, gender, and race/ethnicity., Results: Among diabetic adults, 52% were taking cholesterol-lowering medication compared to the 14% taking cholesterol-lowering medication without diabetes. Although diabetic adults had significantly lower TC and LDL-c levels than non-diabetic adults [% difference (95% confidence interval): TC = -5.2% (-6.8 --3.5), LDL-c = -8.0% (-10.4 --5.5)], the percent difference was greater among adults taking cholesterol medication [TC = -8.0% (-10.3 --5.7); LDL-c = -13.7% (-17.1 --10.2)] than adults not taking cholesterol medication [TC = -3.5% (-5.2 --1.6); LDL-c = -4.3% (-7.1 --1.5)] (interaction p-value: TC = <0.001; LDL-c = <0.001). From 2003-2012, mean TC and HDL-c significantly decreased among diabetic adults taking cholesterol medication [% difference per survey cycle (p-value for linear trend): TC = -2.3% (0.003) and HDL-c = -2.3% (0.033)]. Mean TC, HDL-c, and LDL-c levels did not significantly change from 2003 to 2012 in non-diabetic adults taking cholesterol medication or for adults not taking cholesterol medications., Conclusions: Diabetic adults were more likely to have lower lipid levels, except for triglyceride levels, than non-diabetic adults with profound differences when considering cholesterol medication use, possibly due to the positive effects from clinical diabetes management.

Hypertension, which affects nearly one third of adults in the United States, is a major risk factor for heart disease and stroke (1), and only approximately half of those with hypertension have their hypertension under control (2). The prevalence of hypertension is highest among non-Hispanic blacks, whereas the prevalence of antihypertensive medication use is lowest among Hispanics (1). Geographic variations have also been identified: a recent report indicated that the Southern region of the United States had the highest prevalence of hypertension as well as the highest prevalence of medication use (3). Using data from the Behavioral Risk Factor Surveillance System (BRFSS), this study found minimal change in state-level prevalence of hypertension awareness and treatment among U.S. adults during the first half of the current decade. From 2011 to 2015, the age-standardized prevalence of self-reported hypertension decreased slightly, from 30.1% to 29.8% (p = 0.031); among those with hypertension, the age-standardized prevalence of medication use also decreased slightly, from 63.0% to 61.8% (p<0.001). Persistent differences were observed by age, sex, race/ethnicity, level of education, and state of residence. Increasing hypertension awareness, as well as increasing hypertension control through lifestyle changes and consistent antihypertensive medication use, requires diverse clinical and public health intervention., Competing Interests: No conflicts of interest were reported.

Patients' adherence to antihypertensive medications is key to controlling high blood pressure. Evidence-based strategies to improve adherence exist, but their use, individually and in combination, has not been described. 2015-2016 DocStyles data were analyzed to describe health care professionals' and their practices' use of 10 strategies to improve antihypertensive medication adherence across 3 categories: prescribing, education, and tracking/encouragement. Among 1590 respondents, a mean of using 5 strategies was reported, with individual strategy use ranging from 17.2% (providing patients adherence-related rewards) to 69.4% (prescribing once-daily regimens). Those with higher odds of using ≥7 strategies and strategies across all 3 categories included: (1) nurse practitioners compared to family practitioners/internists and (2) health care professionals in practices with standardized hypertension treatment protocols who routinely recommend home blood pressure monitor use compared to respondents without those characteristics. Despite using an array of evidence-based adherence-promoting strategies, additional opportunities exist for health care professionals to provide adherence support among hypertensive patients., (©2018 Wiley Periodicals, Inc.)

Heart disease is the leading cause of death in the United States (1). Each year, approximately 790,000 adults have a myocardial infarction (heart attack), including 210,000 that are recurrent heart attacks (2). Cardiac rehabilitation (rehab) includes exercise counseling and training, education for heart-healthy living, and counseling to reduce stress. Cardiac rehab provides patients with education regarding the causes of heart attacks and tools to initiate positive behavior change, and extends patients' medical management after a heart attack to prevent future negative sequelae (3). A systematic review has shown that after a heart attack, patients using cardiac rehab were 53% (95% confidence interval [CI] = 41%-62%) less likely to die from any cause and 57% (95% CI = 21%-77%) less likely to experience cardiac-related mortality than were those who did not use cardiac rehab (3). However, even with long-standing national recommendations encouraging use of cardiac rehab (4), the intervention has been underutilized. An analysis of 2005 Behavioral Risk Factor Surveillance System (BRFSS) data found that only 34.7% of adults who reported a history of a heart attack also reported subsequent use of cardiac rehab (5). To update these estimates, CDC used the most recent BRFSS data from 2013 and 2015 to assess the use of cardiac rehab among adults following a heart attack. Overall use of cardiac rehab was 33.7% in 20 states and the District of Columbia (DC) in 2013 and 35.5% in four states in 2015. Cardiac rehab use was underutilized overall and differences were evident by sex, age, race/ethnicity, level of education, cardiovascular risk status, and by state. Increasing use of cardiac rehab after a heart attack should be encouraged by health systems and supported by the public health community.

Background: Antihypertension medication (antihypertensive) adherence lowers risk of cardiovascular disease (CVD); few studies have examined this association among older adults., Methods and Results: We assessed this association among Medicare fee-for-service beneficiaries aged 66 to 79 years who were newly diagnosed with hypertension and initiated on antihypertensives in 2008-2009 (n=155 597). We calculated proportion of days covered (PDC) during follow-up, using proportional subdistribution hazard models, to examine association between antihypertensive adherence and a composite CVD outcomes, including first incident of fatal/nonfatal acute myocardial infarction, ischemic heart disease, stroke/transient ischemic attack, and heart failure. During follow-up (median 5.8 years and 798 621 person-years), we documented 47 198 CVD events. Among beneficiaries, 60.8%, 30.3%, and 8.9% had PDC ≥80%, 40% to 79%, and <40%. Crude incidence of CVD events were 40.1 (95% CI, 40.0-40.1), 93.9 (93.8-93.9), and 98.1 (98.1-98.2) per 1000 person-years for PDC ≥80%, 40% to 79%, and <40%, respectively. Adjusted hazard ratios for CVD events were 1.0 (<40% as reference), 1.0 (0.97-1.03) for 40% to 79%, and 0.44 (0.42-0.45) for ≥80% ( P <0.001). Dose-response analysis suggested a nonlinear relationship between PDC and risk for CVD events with a protective effect of ≥80%. The pattern of associations between PDC and ischemic heart disease, stroke/transient ischemic attack, and heart failure were largely consistent as for CVD events and across different groups., Conclusions: Antihypertensive adherence was associated with a significantly lower risk of CVD events among older adults. There appeared to be a threshold effect in reducing CVD events at around PDC 80%, above which the risk for CVD reduced substantially., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Home blood pressure monitoring (HBPM) among hypertensive adults was assessed using the 2012 American Heart Association Cardiovascular Health Consumer Survey. The prevalence of hypertension was 25.5% and 53.8% of those reported HBPM. Approximately 63% of hypertensive adults 65 years and older reported HBPM followed by 51% and 34.6% (35-64 and 18-34 years, respectively; P=.001). Those who had seen a healthcare professional within a year reported HBPM compared with those who had not (54.8% vs 32.8%, P=.047). Those who believed that lowering blood pressure can reduce risk of heart attack and stroke had a higher percentage of HBPM compared with those who did not (55.5% vs 33.1%, P=.01). Age and the belief that lowering blood pressure could reduce cardiovascular disease risk were significant factors associated with HBPM. Half of the adult hypertensive patients reported HBPM and its use was greater among those who reported a positive attitude toward lowering blood pressure to reduce cardiovascular disease risk., (©Published 2017. This article is a U.S. Government work and is in the public domain in the USA.)

Background: This study describes the national surveillance and modeling methodology developed to monitor achievement of the Million Hearts initiative's aim of preventing 1 million acute myocardial infarctions, strokes, and other related cardiovascular events during 2012-2016., Methods and Results: We calculate sex- and age-specific cardiovascular event rates (combination of emergency department, hospitalization, and death events) among US adults aged ≥18 from 2006 to 2011 and, based on log-linear models fitted to the rates, calculate their annual percent change. We describe 2 baseline strategies to be used to compare observed versus expected event totals during 2012-2016: (1) stable baselines assume no rate changes, with modeled 2011 rates held constant through 2016; and (2) trend baselines assume 2006-2011 rate trends will continue, with the annual percent changes applied to the modeled 2011 rates to calculate expected 2012-2016 rates. Events prevented estimates during 2012-2013 were calculated using available data: 115 210 (95% CI, 60 858, 169 562) events were prevented using stable baselines and an excess of 43 934 (95% CI, -14 264, 102 132) events occurred using trend baselines. Women aged ≥75 had the most events prevented (stable, 76 242 [42 067, 110 417]; trend, 39 049 [1901, 76 197]). Men aged 45 to 64 had the greatest number of excess events (stable, 22 912 [95% CI, 855, 44 969]; trend, 38 810 [95% CI, 15 567, 62 053])., Conclusions: Around 115 000 events were prevented during the initiative's first 2 years compared with what would have occurred had 2011 rates remained stable. Recent flattening or reversals in some event rate trends were observed supporting intensifying national action to prevent cardiovascular events., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: High intakes of trans -fatty acids (TFAs), especially industrially produced TFAs, can lead to unfavorable lipid and lipoprotein concentrations and an increased risk of cardiovascular disease. It is unknown how this relation might change in a population after significant reductions in TFA intake. Objective: This study, which used a new analytical method for measuring plasma TFA concentrations, clarified the association between plasma TFA and serum lipid and lipoprotein concentrations before and after the US FDA enacted TFA food-labeling regulations in 2006. Methods: Data were selected from the NHANES of 1999-2000 and 2009-2010. Findings on 1383 and 2155 adults, respectively, aged ≥20 y, were evaluated. Multivariable linear regressions were used to examine the associations between plasma TFA concentration and lipid and lipoprotein concentrations. The outcome measures were serum concentrations of total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglycerides and the ratio of TC to HDL cholesterol. Results: The median plasma TFA concentration decreased from 80.6 μmol/L in 1999-2000 to 37.0 μmol/L in 2009-2010. Plasma TFA concentration continued to be associated with serum lipid and lipoprotein concentrations after significant reductions in TFA intake in the population. For example, by comparing the lowest with the highest quintiles of TFA concentration in 1999-2000, adjusted mean (95% CI) LDL-cholesterol concentrations increased from 118 mg/dL (112, 123 mg/dL) to 135 mg/dL (130, 141 mg/dL) ( P -trend < 0.001). The corresponding values for 2009-2010 were 102 mg/dL (97.4, 107 mg/dL) and 129 mg/dL (125, 133 mg/dL) for LDL cholesterol ( P -trend < 0.001). Differences between the highest and lowest quintiles were consistent across age groups, sexes, races/ethnicities, and other covariates. Conclusions: Despite a 54% reduction in plasma TFA concentrations in US adults from 1999-2000 to 2009-2010, concentrations remained significantly associated with serum lipid and lipoprotein concentrations. There does not appear to be a threshold under which the association between plasma TFA concentration and lipid profiles might become undetectable., Competing Interests: 2: Author disclosures: Q Yang, Z Zhang, F Loustalot, H Vesper, SP Caudill, M Ritchey, C Gillespie, R Merritt, Y Hong, and BA Bowman, no conflicts of interest., (© 2017 American Society for Nutrition.)

Background: Hypertension is a major risk factor for heart disease and stroke. Health insurance coverage affects hypertension treatment and control, but limited information is available for US adults with hypertension who are classified as underinsured., Methods and Results: Using Behavioral Risk Factor Surveillance System 2013 data, we identified adults with self-reported hypertension. On the basis of self-reported health insurance status and health care-related financial burdens, participants were categorized as uninsured, underinsured, or adequately insured. Proxies for health care received included whether they reported taking antihypertensive medications and whether they visited a doctor for a routine checkup in the past year. We assessed the association between health insurance status and health care received, adjusting for selected sociodemographic characteristics. Among 123 257 participants from 38 states and District of Columbia with self-reported hypertension, 12% were uninsured, 26% were underinsured, and 62% were adequately insured. In adjusted models using adequately insured participants as referent, both uninsured (adjusted odds ratio, 0.39; 95% CI, 0.35-0.43) and underinsured (0.83, 0.76-0.89) participants were less likely to report using antihypertensive medication than those of adequately insured participants. Similarly, adjusted odds ratio of visiting a doctor for routine checkup in the past year were 0.25 (0.23-0.28) for those who were uninsured and 0.78 (0.72-0.84) for those who were underinsured compared to those with adequate insurance., Conclusions: Uninsured and underinsured participants with hypertension were less likely to report receiving care compared to those with adequate insurance coverage. Disparities in health care coverage may necessitate targeted interventions, even among people with health insurance., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Introduction: Nonadherence to taking prescribed antihypertensive medication (antihypertensive) regimens has been identified as a leading cause of poor blood pressure control among persons with hypertension and an important risk factor for adverse cardiovascular disease outcomes. CDC and the Centers for Medicare and Medicaid Services analyzed geographic, racial-ethnic, and other disparities in nonadherence to antihypertensives among Medicare Part D beneficiaries in 2014., Methods: Antihypertensive nonadherence, defined as a proportion of days a beneficiary was covered with antihypertensives of <80%, was assessed using prescription drug claims data among Medicare Advantage or Medicare fee-for-service beneficiaries aged ≥65 years with Medicare Part D coverage during 2014 (N = 18.5 million). Analyses were stratified by antihypertensive class, beneficiaries' state and county of residence, type of prescription drug plan, and treatment and demographic characteristics., Results: Overall, 26.3% (4.9 million) of Medicare Part D beneficiaries using antihypertensives were nonadherent to their regimen. Nonadherence differed by multiple factors, including medication class (range: 16.9% for angiotensin II receptor blockers to 28.9% for diuretics); race-ethnicity (24.3% for non-Hispanic whites, 26.3% for Asian/Pacific Islanders, 33.8% for Hispanics, 35.7% for blacks, and 38.8% for American Indians/Alaska Natives); and state of residence (range 18.7% for North Dakota to 33.7% for the District of Columbia). Considerable county-level variation in nonadherence was found; the highest nonadherence tended to occur in the southern United States (U.S. Census region nonadherence = 28.9% [South], 26.7% [West], 24.1% [Northeast], and 22.8% [Midwest]), Conclusions and Implications for Public Health Practice: More than one in four Medicare Part D beneficiaries using antihypertensives were nonadherent to their regimen, and certain racial/ethnic groups, states, and geographic areas were at increased risk for nonadherence. These findings can help inform focused interventions among these groups, which might improve blood pressure control and cardiovascular disease outcomes.

Introduction: The American Heart Association established 7 cardiovascular health metrics as targets for promoting healthier lives. Cardiovascular health has been hypothesized to play a role in individuals' perception of quality of life; however, previous studies have mostly assessed the effect of cardiovascular risk factors on quality of life., Methods: Data were from the 2013 Behavioral Risk Factor Surveillance System, a state-based telephone survey of adults 18 years or older (N = 347,073). All measures of cardiovascular health and health-related quality of life were self-reported. The 7 ideal cardiovascular health metrics were normal blood pressure, cholesterol, body mass index, not having diabetes, not smoking, being physically active, and having adequate fruit or vegetable intake. Cardiovascular health was categorized into meeting 0-2, 3-5, or 6-7 ideal cardiovascular health metrics. Logistic regression models examined the association between cardiovascular health, general health status, and 3 measures of unhealthy days per month, adjusting for age, sex, race/ethnicity, education, and annual income., Results: Meeting 3 to 5 or 6 to 7 ideal cardiovascular health metrics was associated with a 51% and 79% lower adjusted prevalence ratio (aPR) of fair/poor health, respectively (aPR = 0.49, 95% confidence interval [CI] [0.47-0.50], aPR = 0.21, 95% CI [0.19-0.23]); a 47% and 72% lower prevalence of ≥14 physically unhealthy days (aPR = 0.53, 95% CI [0.51-0.55], aPR = 0.28, 95% CI [0.26-0.20]); a 43% and 66% lower prevalence of ≥14 mentally unhealthy days (aPR = 0.57, 95% CI [0.55-0.60], aPR = 0.34, 95% CI [0.31-0.37]); and a 50% and 74% lower prevalence of ≥14 activity limitation days (aPR = 0.50, 95% CI [0.48-0.53], aPR = 0.26, 95% CI [0.23-0.29]) in the past 30 days., Conclusion: Achieving a greater number of ideal cardiovascular health metrics may be associated with less impairment in health-related quality of life.

Background: Effective hypertension management often necessitates patients' adherence to the blood pressure (BP)-lowering medication regimen they are prescribed. Patients' adherence to that regimen can be affected by prescription- and payment-related factors that are typically controlled by prescribers, filling pharmacies, pharmacy benefit managers, and/or patients' health insurance plans. This study describes patterns and changes from 2009 to 2014 in factors that the literature reports are associated with increased adherence to BP-lowering medication., Methods and Findings: We use a robust source of United States prescription sales data-IMS Health's National Prescription Audit-to describe BP-lowering medication fill counts and spending in 2009 compared with 2014. Moreover, we describe patterns and changes in adherence-promoting factors across age groups, payment sources, and medication classes. From 2009 to 2014, the BP-lowering medication prescription fill count increased from 613.7 million to 653.0 million. Encouraging changes in adherence-promoting factors included: the share of generic fills increased from 82.5% to 95.0%; average days' supply per fill increased from 45.9 to 51.8 days; and average total (patient contribution) spending per years' supply decreased from $359 ($54) to $311 ($37). Possibly undesirable changes included: the percentage of fills for fixed-dose combinations decreased from 17.1% to 14.2% and acquired via mail order decreased from 10.7% to 8.2%. In 2014: 653.0 million fills occurred accounting for $28.81B in spending; adults aged 45-64 years had the highest percentage of fixed-dose combinations fills (16.9%); and fills with Medicaid as the payment source had the lowest average patient spending per fill ($1.19)., Conclusions: We identified both encouraging and possibly undesirable patterns and changes from 2009 to 2014 in factors that promote adherence to BP-lowering medications during this period. Continued tracking of these metrics using pharmacy sales data can help identify areas that can be addressed by clinical and policy interventions to improve adherence for medications commonly used to treat hypertension.

Angiogenesis denotes the formation of new blood vessels from pre-existing vasculature. Progression of diseases such as cancer and several ophthalmological disorders may be promoted by excess angiogenesis. Novel therapeutics to inhibit angiogenesis and diagnostic tools for monitoring angiogenesis during therapy, hold great potential for improving treatment of such diseases. We have previously generated so-called biparatopic Affibody constructs with high affinity for the vascular endothelial growth factor receptor-2 (VEGFR2), which recognize two non-overlapping epitopes in the ligand-binding site on the receptor. Affibody molecules have previously been demonstrated suitable for imaging purposes. Their small size also makes them attractive for applications where an alternative route of administration is beneficial, such as topical delivery using eye drops. In this study, we show that decreasing linker length between the two Affibody domains resulted in even slower dissociation from the receptor. The new variants of the biparatopic Affibody bound to VEGFR2-expressing cells, blocked VEGFA binding, and inhibited VEGFA-induced signaling of VEGFR2 over expressing cells. Moreover, the biparatopic Affibody inhibited sprout formation of endothelial cells in an in vitro angiogenesis assay with similar potency as the bivalent monoclonal antibody ramucirumab. This study demonstrates that the biparatopic Affibody constructs show promise for future therapeutic as well as in vivo imaging applications.

A high blood level of low-density lipoprotein cholesterol (LDL-C) remains a major risk factor for atherosclerotic cardiovascular disease (ASCVD), although data from 2005 through 2012 has shown a decline in high cholesterol (total and LDL cholesterol) along with an increase in the use of cholesterol-lowering medications. The most recent national guidelines (published in 2013) from the American College of Cardiology and the American Heart Association (ACC/AHA) expand previous recommendations for reducing cholesterol to include lifestyle modifications and medication use as part of complete cholesterol management and to lower risk for ASCVD. Because changes in cholesterol treatment guidelines might magnify existing disparities in care and medication use, it is important to describe persons currently eligible for treatment and medication use, particularly as more providers implement the 2013 ACC/AHA guidelines. To understand baseline estimates of U.S. adults on or eligible for cholesterol treatment, as well as to identify sex and racial/ethnic disparities, CDC analyzed data from the 2005-2012 National Health and Nutrition Examination Surveys (NHANES). Because the 2013 ACC/AHA guidelines focus on initiation or continuation of cholesterol treatment, adults meeting the guidelines' eligibility criteria as well as adults who were currently taking cholesterol-lowering medication were assessed as a group. Overall, 36.7% of U.S. adults or 78.1 million persons aged ≥21 years were on or eligible for cholesterol treatment. Within this group, 55.5% were currently taking cholesterol-lowering medication, and 46.6% reported making lifestyle modifications, such as exercising, dietary changes, or controlling their weight, to lower cholesterol; 37.1% reported making lifestyle modifications and taking medication, and 35.5% reported doing neither. Among adults on or eligible for cholesterol-lowering medication, the proportion taking cholesterol-lowering medication was higher for women than men and for non-Hispanic whites (whites) than Mexican-Americans and non-Hispanic blacks (blacks). Further efforts by clinicians and public health practitioners are needed to implement complementary and targeted patient education and disease management programs to reduce sex and racial/ethnic disparities among adults eligible for treatment of cholesterol.

Cardiovascular disease (CVD) is the leading cause of death in the United States, and physical inactivity is a major risk factor (1). Health care professionals have a role in counseling patients about physical activity for CVD prevention. In August 2014, the U.S. Preventive Services Task Force (USPSTF) recommended that adults who are overweight or obese and have additional CVD risk factors be offered or referred to intensive behavioral counseling interventions to promote a healthful diet and physical activity for CVD prevention. Although the USPSTF recommendation does not specify an amount of physical activity, the 2008 Physical Activity Guidelines for Americans state that for substantial health benefits adults should achieve ≥150 minutes per week of moderate-intensity aerobic physical activity or ≥75 minutes per week of vigorous-intensity aerobic activity, or an equivalent combination of moderate- and vigorous-intensity aerobic physical activity. To assess the proportion of adults eligible for intensive behavioral counseling and not meeting the aerobic physical activity guideline, CDC analyzed data from the 2013 Behavioral Risk Factor Surveillance System (BRFSS). This analysis indicated that 36.8% of adults were eligible for intensive behavioral counseling for CVD prevention. Among U.S. states and the District of Columbia (DC), the prevalence of eligible adults ranged from 29.0% to 44.6%. Nationwide, 19.9% of all adults were eligible and did not meet the aerobic physical activity guideline. These data can inform the planning and implementation of health care interventions for CVD prevention that are based on physical activity.

The effectiveness of regular aspirin therapy in reducing risk (secondary prevention) for myocardial infarction, ischemic stroke, and fatal coronary events among persons with preexisting atherosclerotic cardiovascular disease (ASCVD) is well established and recommended in current guidelines. Reported use of aspirin or other antiplatelet agents for secondary ASCVD prevention has varied widely across settings and data collection methods, from 54% of outpatient visits for those with ischemic vascular disease to 98% at the time of discharge for acute coronary syndrome. To estimate the prevalence of aspirin use for secondary ASCVD prevention among community-dwelling adults, CDC analyzed 2013 Behavioral Risk Factor Surveillance System (BRFSS) data from 20 states and the District of Columbia. Overall, 70.8% of adult respondents with existing ASCVD reported using aspirin regularly (every day or every other day). Within this group, 93.6% reported using aspirin for heart attack prevention, 79.6% for stroke prevention and 76.2% for both heart attack and stroke prevention. Differences in use were found by age, sex, race/ethnicity, and ASCVD risk status, and state. Most of the state differences were not statistically significant; however, these estimates can be used to promote the use of aspirin as a low-cost and highly effective intervention.

Background: Cell display technologies (e.g. bacterial display) are attractive in directed evolution as they provide the option to use flow-cytometric cell sorting for selection from combinatorial libraries. The aim of this study was to engineer and investigate an expression vector system with dual functionalities: i) recombinant display of Affibody libraries on Escherichia coli for directed evolution and ii) small scale secreted production of candidate affinity proteins, allowing initial downstream characterizations prior to subcloning. Autotransporters form a class of surface proteins in Gram-negative bacteria that have potential for efficient translocation and tethering of recombinant passenger proteins to the outer membrane. We engineered a bacterial display vector based on the E. coli AIDA-I autotransporter for anchoring to the bacterial surface. Potential advantages of employing autotransporters combined with E. coli as host include: high surface expression level, high transformation frequency, alternative promoter systems available, efficient translocation to the outer membrane and tolerance for large multi-domain passenger proteins., Results: The new vector was designed to comprise an expression cassette encoding for an Affibody molecule, three albumin binding domains for monitoring of surface expression levels, an Outer membrane Protease T (OmpT) recognition site for potential protease-mediated secretion of displayed affinity proteins and a histidine-tag for purification. A panel of vectors with different promoters were generated and evaluated, and suitable cultivation conditions were investigated. The results demonstrated a high surface expression level of the different evaluated Affibody molecules, high correlation between target binding and surface expression level, high signal-to-background ratio, efficient secretion and purification of binders in OmpT-positive hosts as well as tight regulation of surface expression for the titratable promoters. Importantly, a mock selection using FACS from a 1:100,000 background yielded around 20,000-fold enrichment in a single round and high viability of the isolated bacteria after sorting., Conclusions: The new expression vectors are promising for combinatorial engineering of Affibody molecules and the strategy for small-scale production of soluble recombinant proteins has the potential to increase throughput of the entire discovery process.

Angiogenesis plays an important role in cancer and ophthalmic disorders such as age-related macular degeneration and diabetic retinopathy. The vascular endothelial growth factor (VEGF) family and corresponding receptors are regulators of angiogenesis and have been much investigated as therapeutic targets. The aim of this work was to generate antagonistic VEGFR2-specific affinity proteins having adjustable pharmacokinetic properties allowing for either therapy or molecular imaging. Two antagonistic Affibody molecules that were cross-reactive for human and murine VEGFR2 were selected by phage and bacterial display. Surprisingly, although both binders independently blocked VEGF-A binding, competition assays revealed interaction with non-overlapping epitopes on the receptor. Biparatopic molecules, comprising the two Affibody domains, were hence engineered to potentially increase affinity even further through avidity. Moreover, an albumin-binding domain was included for half-life extension in future in vivo experiments. The best-performing of the biparatopic constructs demonstrated up to 180-fold slower dissociation than the monomers. The new Affibody constructs were also able to specifically target VEGFR2 on human cells, while simultaneously binding to albumin, as well as inhibit VEGF-induced signaling. In summary, we have generated small antagonistic biparatopic Affibody molecules with high affinity for VEGFR2, which have potential for both future therapeutic and diagnostic purposes in angiogenesis-related diseases.