Natural language processing to identify lupus nephritis phenotype in electronic health records.

BACKGROUND: Systemic lupus erythematosus (SLE) is a rare autoimmune disorder characterized by an unpredictable course of flares and remission with diverse manifestations. Lupus nephritis, one of the major disease manifestations of SLE for organ damage and mortality, is a key component of lupus classification criteria. Accurately identifying lupus nephritis in electronic health records (EHRs) would therefore benefit large cohort observational studies and clinical trials where characterization of the patient population is critical for recruitment, study design, and analysis. Lupus nephritis can be recognized through procedure codes and structured data, such as laboratory tests. However, other critical information documenting lupus nephritis, such as histologic reports from kidney biopsies and prior medical history narratives, require sophisticated text processing to mine information from pathology reports and clinical notes. In this study, we developed algorithms to identify lupus nephritis with and without natural language processing (NLP) using EHR data from the Northwestern Medicine Enterprise Data Warehouse (NMEDW). METHODS: We developed five algorithms: a rule-based algorithm using only structured data (baseline algorithm) and four algorithms using different NLP models. The first NLP model applied simple regular expression for keywords search combined with structured data. The other three NLP models were based on regularized logistic regression and used different sets of features including positive mention of concept unique identifiers (CUIs), number of appearances of CUIs, and a mixture of three components (i.e. a curated list of CUIs, regular expression concepts, structured data) respectively. The baseline algorithm and the best performing NLP algorithm were externally validated on a dataset from Vanderbilt University Medical Center (VUMC). RESULTS: Our best performing NLP model incorporated features from both structured data, regular expression concepts, and mapped concept unique identifiers (CUIs) and showed improved F measure in both the NMEDW (0.41 vs 0.79) and VUMC (0.52 vs 0.93) datasets compared to the baseline lupus nephritis algorithm. CONCLUSION: Our NLP MetaMap mixed model improved the F-measure greatly compared to the structured data only algorithm in both internal and external validation datasets. The NLP algorithms can serve as powerful tools to accurately identify lupus nephritis phenotype in EHR for clinical research and better targeted therapies.

Vaccine Effectiveness Against Long COVID in Children.

OBJECTIVES: Vaccination reduces the risk of acute coronavirus disease 2019 (COVID-19) in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years. METHODS: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record program for visits after vaccine availability. We examined both probable (symptom-based) and diagnosed long COVID after vaccination. RESULTS: The vaccination rate was 67% in the cohort of 1 037 936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, whereas diagnosed long COVID was 0.8%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5-44.7) against probable long COVID and 41.7% (15.0-60.0) against diagnosed long COVID. VE was higher for adolescents (50.3% [36.6-61.0]) than children aged 5 to 11 (23.8% [4.9-39.0]). VE was higher at 6 months (61.4% [51.0-69.6]) but decreased to 10.6% (-26.8% to 37.0%) at 18-months. CONCLUSIONS: This large retrospective study shows moderate protective effect of severe acute respiratory coronavirus 2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including electronic health record sources and prospective data.

Vaccine Effectiveness Against Long COVID in Children: A Report from the RECOVER EHR Cohort.

Objective: Vaccination reduces the risk of acute COVID-19 in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5-17 years. Methods: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record (EHR) Program for visits between vaccine availability, and October 29, 2022. Conditional logistic regression was used to estimate VE against long COVID with matching on age group (5-11, 12-17) and time period and adjustment for sex, ethnicity, health system, comorbidity burden, and pre-exposure health care utilization. We examined both probable (symptom-based) and diagnosed long COVID in the year following vaccination. Results: The vaccination rate was 56% in the cohort of 1,037,936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, while diagnosed long COVID was 0.7%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5 - 44.5) against probable long COVID and 41.7% (15.0 - 60.0) against diagnosed long COVID. VE was higher for adolescents 50.3% [36.3 - 61.0]) than children aged 5-11 (23.8% [4.9 - 39.0]). VE was higher at 6 months (61.4% [51.0 - 69.6]) but decreased to 10.6% (-26.8 - 37.0%) at 18-months. Discussion: This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data. Article Summary: Vaccination against COVID-19 has a protective effect against long COVID in children and adolescents. The effect wanes over time but remains significant at 12 months. What's Known on This Subject: Vaccines reduce the risk and severity of COVID-19 in children. There is evidence for reduced long COVID risk in adults who are vaccinated, but little information about similar effects for children and adolescents, who have distinct forms of long COVID. What This Study Adds: Using electronic health records from US health systems, we examined large cohorts of vaccinated and unvaccinated patients <18 years old and show that vaccination against COVID-19 is associated with reduced risk of long COVID for at least 12 months. Contributors' Statement: Drs. Hanieh Razzaghi and Charles Bailey conceptualized and designed the study, supervised analyses, drafted the initial manuscript, and critically reviewed and revised the manuscript.Drs. Christopher Forrest and Yong Chen designed the study and critically reviewed and revised the manuscript.Ms. Kathryn Hirabayashi, Ms. Andrea Allen, and Dr. Qiong Wu conducted analyses, and critically reviewed and revised the manuscript.Drs. Suchitra Rao, H Timothy Bunnell, Elizabeth A. Chrischilles, Lindsay G. Cowell, Mollie R. Cummins, David A. Hanauer, Benjamin D. Horne, Carol R. Horowitz, Ravi Jhaveri, Susan Kim, Aaron Mishkin, Jennifer A. Muszynski, Susanna Nagie, Nathan M. Pajor, Anuradha Paranjape, Hayden T. Schwenk, Marion R. Sills, Yacob G. Tedla, David A. Williams, and Ms. Miranda Higginbotham critically reviewed and revised the manuscript.All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Authorship statement: Authorship has been determined according to ICMJE recommendations.

Adherence to the 2017 Clinical Practice Guidelines for Pediatric Hypertension in Safety-Net Clinics.

Importance: The 2017 Clinical Practice Guideline (CPG) for the diagnosis and management of pediatric hypertension (PHTN) categorizes a greater proportion of children with elevated blood pressure and PHTN, yet several barriers to CPG adherence have been noted. Objective: To assess adherence to the 2017 CPG for the diagnosis and management of PHTN and use of a clinical decision support (CDS) tool to calculate blood pressure percentiles. Design, Setting, and Participants: This cross-sectional study used electronic health record-extracted data from January 1, 2018, to December 31, 2019, among patients visiting 1 of 74 federally qualified health centers in AllianceChicago, a national Health Center Controlled Network. Children and adolescents (aged 3-17 years; hereinafter referred to as children) who attended at least 1 visit and had at least 1 blood pressure reading at or above the 90th percentile or diagnosis of elevated blood pressure or PHTN were eligible for data to be included in the analysis. Data were analyzed from September 1, 2020, to February 21, 2023. Exposures: Blood pressure at or above the 90th or 95th percentile. Main Outcomes and Measures: Diagnosis of PHTN (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10], code I10) or elevated blood pressure (ICD-10 code R03.0) and CDS tool use; blood pressure management (antihypertensive medication, lifestyle counseling, referral); and follow-up visit attendance. Descriptive statistics described the sample and rates of guideline adherence. Logistic regression analyses identified patient- and clinic-level associations with guideline adherence. Results: The sample consisted of 23 334 children (54.9% boys; 58.6% White race; median age, 8 [IQR, 4-12] years). Guideline-adherent diagnosis was observed in 8810 children (37.8%) with blood pressure at or above the 90th percentile and 146 of 2542 (5.7%) with blood pressure at or above the 95th percentile at 3 or more visits. The CDS tool was used to calculate blood pressure percentiles in 10 524 cases (45.1%) and was associated with significantly greater odds of PHTN diagnosis (odds ratio, 2.14 [95% CI, 1.10-4.15]). Among 15 422 children with blood pressure at or above the 95th percentile, antihypertensive medication was prescribed to 831 (5.4%), lifestyle counseling was provided to 14 841 (96.2%), and blood pressure-related referrals were given to 848 (5.5%). Guideline-adherent follow-up was observed in 8651 of 19 049 children (45.4%) with blood pressure at or above the 90th percentile and 2598 of 15 164 (17.1%) with blood pressure at or above the 95th percentile. Differences in guideline adherence by patient- and clinic-level factors were observed. Conclusions and Relevance: In this study, fewer than 50% of children with elevated blood pressure had a guideline-adherent diagnosis code or attended guideline-adherent follow-up. Using a CDS tool was associated with guideline-adherent diagnosis, but the tool was underused. Further work is needed to understand how to best support implementation of tools promoting PHTN diagnosis, management, and follow-up.

Joint effect of highly-sensitive cardiac troponin T and ankle-brachial index on incident cardiovascular events: The MESA and CHS.

Background: Elevated highly-sensitive cardiac troponin-T (hs-cTnT≥14 ng/L) and low ankle-brachial index (ABI<0.9) are risk factors for atherosclerotic cardiovascular diseases (ASCVD) but their joint effect on the risk of ASCVD events is unknown. Methods: We used data from the two population-based cohort studies, the Multi-Ethnic study of Atherosclerosis (MESA) and Cardiovascular Heart Study (CHS) among 10,897 participants free of CVD events at baseline (mean age 66.3 years, 44.7% males). Incident ASCVD was defined as CHD (fatal/non-fatal MI or revascularization), transient ischemic attack, or stroke,. Hazard ratio (HR) and 95% CI was calculated from a Cox regression model. Interaction on the additive scale was assessed using relative excess risk due to interaction (RERI) and interaction on the multiplicative scale was assessed by Likelihood ratio (LR) test. Results: At baseline (2000-2002 for MESA and 1989-1990 for CHS), 10.2% of participants had elevated hs-cTnT and 7.5% had low ABI. During a median follow-up of 13.6 years (interquartile range, 7.5-14.7 years), there were 2590 incident ASCVD and 1542 incident CHD events. The hazard of CHD and ASCVD was higher in participants with both elevated hs-cTnT and low ABI [HR(95% CI): CHD: 2.04 (1.45, 2.88), ASCVD: 2.05 (1.58, 2.66)] than those with only elevated hs-cTnT [CHD: 1.65 (1.37, 1.99), ASCVD: 1.67 (1.44, 1.99)] or only low ABI [CHD: 1.87 (1.52, 2.31), ASCVD: 1.67 (1.42, 1.97)]. Antagonistic multiplicative interaction was observed for CHD (LR test p-value=0.042) but not for ASCVD (LR test p-value =0.08). No significant additive interaction was detected for CHD and ASCVD (RERI p-value ≥0.23). Conclusion: The observed joint effect of elevated cTnT and low ABI on ASCVD risk was smaller (i.e., antagonistic interaction) than that expected by the combined independent effects of each risk factor.

Carotid Artery Stiffness Mechanisms Are Associated With End Organ Damage and All-Cause Mortality: MESA (Multi-Ethnic Study of Atherosclerosis).

Background Arterial stiffness can be separated into 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to remodeling of the vessel wall. The relationship between stiffness mechanisms and end organ damage is unknown. Methods and Results MESA (Multi-Ethnic Study of Atherosclerosis) participants with carotid ultrasound were included in this study (n=6147). Carotid pulse wave velocity (cPWV) was calculated to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 mm Hg blood pressure with participant-specific models. Load-dependent stiffness was the difference of total and structural stiffness. Associations with incident chronic kidney disease (CKD), dementia, and mortality were assessed with adjusted Cox models. During 14.3±4.8 years of follow-up, 773 CKD events, 535 dementia events, and 1529 deaths occurred. Total cPWV was associated with mortality (hazard ratio [HR], per 1 m/s, 1.04 [95% CI, 1.01-1.08], P=0.02) and dementia (HR, 1.06 [95% CI, 1.01-1.12], P=0.03) but not CKD (HR, 1.03 [95% CI, 0.98-1.08], P=0.33). Structural cPWV was significantly associated with mortality (HR, 1.04 [95% CI, 1.00-1.08], P=0.04) but not CKD (HR, 1.00 [95% CI, 0.94-1.05], P=0.86) or dementia (HR, 1.06 [95% CI, 0.99-1.13], P=0.06). Load-dependent cPWV was significantly associated with CKD (HR, 1.38 [95% CI, 1.17-1.63], P<0.001) but not mortality (HR, 1.11 [95% CI, 0.99-1.25], P=0.07) or dementia (HR, 1.14 [95% CI, 0.94-1.38], P=0.19). Conclusions The mechanisms of arterial stiffness were associated with all-cause mortality and CKD. Structural stiffness was associated with all-cause mortality, and load-dependent stiffness was associated with CKD. Total stiffness was associated with dementia but load-dependent and structural stiffness were not.

Methods of arterial stiffness calculation and cardiovascular disease events: the multiethnic study of atherosclerosis.

BACKGROUND: A wide variety of different formulae have been used to calculate local arterial stiffness with little external validation in relationship to cardiovascular events. We compared the associations of several arterial stiffness calculations in a large, multiethnic cohort. METHODS: The multi-ethnic study of atherosclerosis (MESA) is a longitudinal study of 6814 adults without clinical cardiovascular disease (CVD) at enrollment. MESA participants with CVD surveillance through year 2018 and carotid ultrasound ( n  = 5873) or aorta MRI ( n  = 3175) at the baseline exam (2000-2002) were included. We analyzed 21 different calculations of local arterial stiffness. Cross-sectional and longitudinal statistical analyses were performed in addition to Cox hazard modeling for associations with CVD events (myocardial infarction, resuscitated cardiac arrest, stroke, adjudicated angina, and cardiovascular death). RESULTS: Carotid artery stiffness calculations had variable correlations with each other ( r  = 0.56-0.99); aortic stiffness measures were similar ( r  = 0.66-0.99). Nevertheless, for CVD events, the hazard ratio (HR) per standard deviation change were similar for all carotid stiffness calculations with HRs in the range of 1.00-1.10 (equivalence P  < 0.001). For the aorta, aortic distensibility coefficient had a stronger association with CVD events (HR 1.18 [1.02-1.37]) compared to aorta Peterson's elastic modulus (HR 0.98 [0.89-1.07]) and aorta pulse wave velocity (HR 1.00 [0.90-1.11]). HRs between all other aortic stiffness calculations were equivalent ( P  < 0.01). CONCLUSION: Different methods of calculating local arterial stiffness largely gave equivalent results, indicating that the variety of different arterial stiffness calculations in use do not cause inconsistent findings.

Supermarket Proximity and Risk of Hypertension, Diabetes, and CKD: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Living in environments with low access to food may increase the risk of chronic diseases. We investigated the association of household distance to the nearest supermarket (as a measure of food access) with the incidence of hypertension, diabetes, and chronic kidney disease (CKD) in a metropolitan area of the United States. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 777,994 individuals without hypertension, diabetes, or CKD at baseline within the HealthLNK Data Repository, which contains electronic health records from 7 health care institutions in Chicago, Illinois. EXPOSURE: Zip code-level average distance between households and nearest supermarket. OUTCOME: Incidence of hypertension, diabetes, and CKD based on presence of ICD-9 code and/or blood pressure≥140/90mm Hg, hemoglobin A1c≥6.5%, and eGFR<60mL/min/1.73m2, respectively. ANALYTICAL APPROACH: Average distance to nearest supermarket was aggregated from street-level metrics for 56 Chicagoland zip codes. The cumulative incidence of hypertension, diabetes, and CKD from 2007-2012 was calculated for each zip code in patients free of these diseases in 2006. Spatial analysis of food access and disease incidence was performed using bivariate local indicator of spatial association (BiLISA) maps and bivariate local Moran I statistics. The relationship between supermarket access and outcomes was analyzed using logistic regression. RESULTS: Of 777,994 participants, 408,608 developed hypertension, 51,380 developed diabetes, and 56,365 developed CKD. There was significant spatial overlap between average distance to supermarket and incidence of hypertension and diabetes but not CKD. Zip codes with large average supermarket distances and high incidence of hypertension and diabetes were clustered in southern and western neighborhoods. Models adjusted only for neighborhood factors (zip code-level racial composition, access to vehicles, median income) revealed significant associations between zip code-level average distance to supermarket and chronic disease incidence. Relative to tertile 1 (shortest distance), ORs in tertiles 2 and 3, respectively, were 1.27 (95% CI, 1.23-1.30) and 1.38 (95% CI, 1.33-1.43) for diabetes, 1.03 (95% CI, 1.02-1.05) and 1.04 (95% CI, 1.02-1.06) for hypertension, and 1.18 (95% CI, 1.15-1.21) and 1.33 (95% CI, 1.29-1.37) for CKD. Models adjusted for demographic factors and health insurance showed significant and positive association with greater odds of incident diabetes (tertile 2: 1.29 [95% CI, 1.26-1.33]; tertile 3: 1.35 [95% CI, 1.31-1.39]) but lesser odds of hypertension (tertile 2: 0.95 [95% CI, 0.94-0.97]; tertile 3: 0.91 [95% CI, 0.89-0.92]) and CKD (tertile 2: 0.80 [95% CI, 0.78-0.82]; tertile 3: 0.73 [95% CI, 0.72-0.76]). After adjusting for both neighborhood and individual covariates, supermarket distance remained significantly associated with greater odds of diabetes and lesser odds of hypertension, but there was no significant association with CKD. LIMITATIONS: Unmeasured neighborhood and social confounding variables, zip code-level analysis, and limited individual-level information. CONCLUSIONS: There are significant disparities in supermarket proximity and incidence of hypertension, diabetes, and CKD in Chicago, Illinois. The relationship between supermarket access and chronic disease is largely explained by individual- and neighborhood-level factors.

Association of statin therapy with progression of carotid arterial stiffness: the Multi-Ethnic Study of Atherosclerosis (MESA).

Arterial stiffness progresses with age and is a predictor of adverse cardiovascular disease events. Studies examining associations of statin therapy with arterial stiffness have yielded mixed results. Associations between the duration and intensity of statin therapy and arterial stiffness have not been studied in a prospective multiethnic cohort. MESA participants (n = 1242) with statin medication use data at each exam (1-5) and who had undergone B-mode carotid ultrasound at baseline and at Exam 5 after (mean ± [SD]) 9.4 ± 0.5 years were analyzed. Carotid arterial stiffness was measured using the distensibility coefficient (DC) and Young's elastic modulus (YEM). Linear regression models were used to evaluate associations between DC and YEM and statin treatment duration and intensity. At baseline, participants were 66.5 ± 8.1 years old, 41% female, 36% White, 30% African American, 14% Chinese American, and 20% Hispanic. The mean baseline low-density lipoprotein cholesterol (LDL-C) was 149.5 ± 14.5 mg/dL. After adjusting for age, sex, race/ethnicity, and CVD risk factors, the percent changes in DC and YEM were found to not be significantly different in individuals on statin therapy at any combination of visits (1-4) compared to participants never on statin therapy (all p > 0.32). There were also no differences in the percent change in DC and YEM based on statin therapy intensity by quartile (all p > 0.14) over the 10-year follow-up period. Based on the aforementioned results, statin therapy was not associated with changes in carotid artery stiffness over nearly a decade of follow-up regardless of therapy duration or intensity.

Planning the Implementation of a Multilevel Blood Pressure Control Intervention in Chicago: Community and Clinical Perspectives.

Objectives: Hypertension is associated with high morbidity and mortality. The complications of hypertension disproportionately impact African American residents in Chicago's South Side neighborhood. To inform the implementation of an evidence-based multilevel hypertension management intervention, we sought to identify community member- and clinician-level barriers to diagnosing and treating hypertension, and strategies for addressing those barriers. Methods: We conducted 5 focus groups with members of faith-based organizations (FBOs) (n=40) and 8 focus groups with clinicians and administrators (n=26) employed by community health centers (CHCs) located in Chicago's South Side. Results: Participants across groups identified the physical environment, including lack of access to clinics and healthy food, as a risk factor for hypertension. Participants also identified inconsistent results from home blood pressure monitoring and medication side effects as barriers to seeking diagnosis and treatment. Potential strategies raised by participants to address these barriers included (1) addressing patients' unmet social needs, such as food security and transportation; (2) offering education that meaningfully engages patients in discussions about managing hypertension (eg, medication adherence, diet, follow-up care); (3) coordinating referrals via community-based organizations (including FBOs) to CHCs for hypertension management; and (4) establishing a setting where community members managing hypertension diagnosis can support one another. Conclusions: Clinic-level barriers to the diagnosis and treatment of hypertension, such as competing priorities and resource constraints, are exacerbated by community-level stressors. Community members and clinicians agreed that it is important to select implementation strategies that leverage and enhance both community- and clinic-based resources.

Process of Engaging Community and Scientific Partners in the Development of the CIRCL-Chicago Study Protocol.

Objectives: Hypertension affects 1 in 3 adults in the United States and disproportionately affects African Americans. Kaiser Permanente demonstrated that a "bundle" of evidence-based interventions significantly increased blood pressure control rates. This paper describes a multiyear process of developing the protocol for a trial of the Kaiser bundle for implementation in under-resourced urban communities experiencing cardiovascular health disparities during the planning phase of this biphasic award (UG3/UH3). Methods: The protocol was developed by a collaboration of faith-based community members, representatives from community health center practice-based research networks, and academic scientists with expertise in health disparities, implementation science, community-engaged research, social care interventions, and health informatics. Scientists from the National Institutes of Health and the other grantees of the Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) Alliance also contributed to developing our protocol. Results: The protocol is a hybrid type 3 effectiveness-implementation study using a parallel cluster randomized trial to test the impact of practice facilitation on implementation of the Kaiser bundle in community health centers compared with implementation without facilitation. A central strategy to the Kaiser bundle is to coordinate implementation via faith-based and other community organizations for recruitment and navigation of resources for health-related social risks. Conclusions: The proposed research has the potential to improve identification, diagnosis, and control of blood pressure among under-resourced communities by connecting community entities and healthcare organizations in new ways. Faith-based organizations are a trusted voice in African American communities that could be instrumental for eliminating disparities.

Carotid Artery Stiffness Mechanisms in Hypertension and Their Association with Echolucency and Texture Features: The Multi-ethnic Study of Atherosclerosis (MESA).

Arterial stiffness, echolucency and texture features are altered with hypertension and associated with increased cardiovascular disease risk. The relationship between these markers and structural and load-dependent artery wall changes in hypertension are poorly understood. The Multi-ethnic Study of Atherosclerosis (MESA) is a longitudinal study of 6814 adults from six communities across the United States designed to study subclinical cardiovascular disease. From B-mode imaging of the right common carotid artery at the baseline MESA examination, we calculated carotid artery Young's elastic modulus (YEM, n = 5894) and carotid artery gray-scale texture features (n = 1403). The standard YEM calculation represented total arterial stiffness. Structural stiffness was calculated by adjusting YEM to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. We found that load-dependent YEM was elevated in hypertensive individuals compared with normotensive individuals (35.7 ± 105.5 vs. -62.0 ± 112.4 kPa, p < 0.001) but that structural YEM was similar (425.3 ± 274.8 vs. 428.4 ± 293.0 kPa, p = 0.60). Gray-scale measures of heterogeneity in carotid artery wall texture (gray-level difference statistic contrast) had small but statistically signification correlations with carotid artery stiffness mechanisms. This association was positive for structural YEM (0.107, p < 0.001), while for load-dependent YEM, the association was negative (-0.064, p = 0.02). In conclusion, increased arterial stiffness in hypertension was owing solely to the non-linear mechanics of having higher blood pressure, not structural changes in the artery wall, and high load-dependent stiffness was associated with a more homogenous carotid artery wall texture. This is potentially related to arterial remodeling associated with subclinical atherosclerosis and future cardiovascular disease development. These results also indicate that gray-scale texture features from ultrasound imaging had a small but statistically significant association with load-dependent arterial stiffness and that gray-scale texture features may be partially load dependent.

Optimal lifestyle behaviors and 10-year progression of arterial stiffness: The Multi-Ethnic Study of Atherosclerosis.

Majority of previous studies showed no association between a single health behavior and arterial stiffness, but the benefit of simultaneously having multiple healthy behaviors (optimal lifestyle) on the progression of arterial stiffness is unknown. Among 2810 individuals (age 60.0 ± 9.4, 46.5% male), optimal lifestyle marker (yes/no) on four health behaviors (ie, BMI < 25 kg/m2 , never or former smoker, never or moderate drinker, exercised > 500 METS min/week) across four visits (≈ 5 years) were summed to create an optimal lifestyle score. Carotid arterial stiffness was measured using distensibility coefficient (DC) and Young's elastic modulus (YEM) at visit 1 and after a mean of 9.5 years (visit 5). The association of optimal lifestyle with 10-year percent change in DC and YEM was assessed using multiple linear regression. DC decreased by 5.3% and YEM increased by 24.4% over 10 years. Mean optimal lifestyle score was 9.4 ± 3.1 (range: 0-16). Individuals in quintiles 2-5 of optimal lifestyle score compared to quintile 1 (with the least optimal lifestyle score) did not show slower deceleration of DC [Q2, -0.3% (95% CI: -6.0, 5.4); Q3, -0.01% (-4.5, 4.5); Q4, -0.6% (-5.2, 3.9); Q5, -0.4% (-5.3, 4.4)], trend p-value = .82] or slower progression of YEM [Q2, 0.1% (-7.1, 7.3); Q3, -0.8% (-8.0, 6.5); Q4, 4.5% (-2.3, 11.3); Q5, -0.2% (-8.3, 7.9)], trend p-value = .49] after adjusting for risk factors. The association remained non-significant when stratified by categories of age, sex, race, BP control, and diabetes. Our findings indicate that optimal score on multiple health behaviors may not independently slow arterial stiffness progression.

Carotid Artery Stiffness Mechanisms Associated With Cardiovascular Disease Events and Incident Hypertension: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to changes in the vessel wall. It is unknown how these different mechanisms contribute to incident cardiovascular disease (CVD) events. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6814 men and women without CVD at enrollment, from 6 communities in the United States. MESA participants with B-mode carotid ultrasound and brachial blood pressure at baseline Exam in (2000-2002) and CVD surveillance (mean follow-up 14.3 years through 2018) were included (n=5873). Peterson's elastic modulus was calculated to represent total arterial stiffness. Structural stiffness was calculated by adjusting Peterson's elastic modulus to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. RESULTS: In Cox models adjusted for traditional risk factors, load-dependent stiffness was significantly associated with higher incidence of CVD events (hazard ratio/100 mm Hg, 1.21 [95% CI, 1.09-1.34] P<0.001) events while higher structural stiffness was not (hazard ratio, 1.03 [95% CI, 0.99-1.07] P=0.10). Analysis of participants who were normotensive (blood pressure <130/80, no antihypertensives) at baseline exam (n=2122) found higher load-dependent stiffness was also associated with significantly higher incidence of hypertension (hazard ratio, 1.53 [95% CI, 1.35-1.75] P<0.001) while higher structural stiffness was not (hazard ratio, 1.03 [95% CI, 0.99-1.07] P=0.16). CONCLUSIONS: These results provide valuable new insights into mechanisms underlying the association between arterial stiffness and CVD. Load-dependent stiffness was significantly associated with CVD events but structural stiffness was not.

A Cohort Analysis of Statin Treatment Patterns Among Small-Sized Primary Care Practices.

BACKGROUND: Small-sized primary care practices, defined as practices with fewer than 10 clinicians, delivered the majority of outpatient visits in the USA. Statin therapy in high-risk individuals reduces atherosclerotic cardiovascular disease (ASCVD) events, but prescribing patterns in small primary care practices are not well known. This study describes statin treatment patterns in small-sized primary care practices and examines patient- and practice-level factors associated with lack of statin treatment. METHODS: We conducted a retrospective cohort analysis of statin-eligible patients from practices that participated in Healthy Hearts in the Heartland (H3), a quality improvement initiative aimed at improving cardiovascular care measures in small primary care practices. All statin-eligible adults who received care in one of 53 H3 practices from 2013 to 2016. Statin-eligible adults include those aged at least 21 with (1) clinical ASCVD, (2) low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, or (3) diabetes aged 40-75 and with LDL-C 70-189 mg/dL. Eligible patients with no record of moderate- to high-intensity statin prescription are defined by ACC/AHA guidelines. RESULTS: Among the 13,330 statin-eligible adults, the mean age was 58 years and 52% were women. Overall, there was no record of moderate- to high-intensity statin prescription among 5,780 (43%) patients. Younger age, female sex, and lower LDL-C were independently associated with a lack of appropriate intensity statin therapy. Higher proportions of patients insured by Medicaid and having only family medicine trained physicians (versus having at least one internal medicine trained physician) at the practice were also associated with lower appropriate intensity statin use. Lack of appropriate intensity statin therapy was higher in independent practices than in Federally Qualified Health Centers (FQHCs) (50% vs. 40%, p value < 0.01). CONCLUSIONS: There is an opportunity for improved ASCVD risk reduction in small primary care practices. Statin treatment patterns and factors influencing lack of treatment vary by practice setting, highlighting the importance of tailored approaches to each setting.

Developing and evaluating the Teen-Strong life skills programme in Southern Thailand.

Risk sexual behaviours are known as a threat to health and wellbeing of adolescents. Although there are standard sexual education curriculums in Thai schools, most schools use traditional teaching methods rather than participatory teaching activities. This study aimed to (i) develop 'Teen-Strong' programme by combining the concept of the World Health Organization's life skills programme with Thai sexual education curriculum and (ii) investigate the association of Teen-Strong programme with knowledge and decision-making regarding risky sexual behaviours and teenage pregnancy in Thai adolescents. The Teen-Strong programme was developed by means of experts review and cognitive interviewing process and evaluated in 66 adolescents in Grades 7-9 from six schools in southern Thailand. Twenty-six students were assigned to the experimental group (attended Teen-Strong programme and standard sexual education) and 40 to the control group (attended only the standard sexual education). A pre-post-test quasi-experimental design was used and the Teen-Strong questionnaire (TSQ) was administered to measure knowledge and decision-making at three time points: before (T1), immediately after (T2) and 1 month after (T3) attending the programme. A 2 × 3 mixed-design ANOVA was used to analyse the data. TSQ scores in the experimental and control groups were higher at T2 and T3 as compared with T1. Mean increase in TSQ scores at T2 and T3 compared with T1 were significantly higher in the experiment than the control group [T2 vs. T1: t (64) = 4.07, p-values < 0.0001; T3 vs. T1: t (64) = 3.32, p-values = 0.017]. This study showed that Teen-Strong programme could increase adolescent's knowledge and decision-making skills regarding risk sexual behaviours.

Sexual practices during adolescence are shown to cause teenage pregnancy and other threats to the health and wellbeing of adolescents in Thailand. Adolescent sexual education that considers the culture and environment where adolescents grow up is essential. Although there are sexual education programmes in Thai schools, most schools use traditional teaching methods (i.e. learning through memorization) rather than participatory teaching activities (i.e. learning through activities and sharing experiences from and with peers). We developed a programme called 'Teen-Strong' by combining participatory learning technique proposed by the World Health Organization with the Thai sexual education programme and evaluate whether this hybrid programme helped Thai adolescents in Grades 7­9 to better understand and avoid risky sexual behaviours. We found that adolescents who were involved in the Teen-Strong programme showed better knowledge and decision-making skills at avoiding risky sexual practices than adolescents who were not involved in the programme. Our findings show participatory sexual education programme could enhance adolescents' understanding of risky sexual practices and strategies to avoid these risky practices.

Carotid Artery Stiffening With Aging: Structural Versus Load-Dependent Mechanisms in MESA (the Multi-Ethnic Study of Atherosclerosis).

Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to changes in the vessel wall. Differentiating these closely coupled mechanisms is important to understanding vascular aging. MESA (Multi-Ethnic Study of Atherosclerosis) participants with B-mode carotid ultrasound and brachial blood pressure at exam 1 and exam 5 (year 10) were included in this study (n=2604). Peterson and Young elastic moduli were calculated to represent total stiffness. Structural stiffness was calculated by adjusting Peterson and Young elastic moduli to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. Changes in carotid artery stiffness mechanisms over 10 years were compared by age groups with ANCOVA models adjusted for baseline cardiovascular disease risk factors. The 75- to 84-year age group had the greatest change in total, structural, and load-dependent stiffening compared with younger groups (P<0.05). Only age and cessation of antihypertensive medication were predictive of structural stiffening, whereas age, race/ethnicity, education, blood pressure, cholesterol, and antihypertensive medication were predictive of increased load-dependent stiffening. On average, structural stiffening accounted for the vast majority of total stiffening, but 37% of participants had more load-dependent than structural stiffening. Rates of structural and load-dependent carotid artery stiffening increased with age. Structural stiffening was consistently observed, and load-dependent stiffening was highly variable. Heterogeneity in arterial stiffening mechanisms with aging may influence cardiovascular disease development.

Under-recognition of pediatric hypertension diagnosis: Examination of 1 year of visits to community health centers.

Pediatric hypertension is associated with significant target organ damage in children and cardiovascular morbidity in adulthood. Appropriate diagnosis and management per guideline recommendations are inconsistent. In this study, we determined the proportion of missed diagnosis of hypertension and prehypertension and appropriate follow-up in pediatric patients, stratified by sex, age, race/ethnicity, and weight status. Based on the electronic health record (EHR) data from eight federally qualified health centers, among 62,982 children aged 3 to 18 years, 6233 (10%) had at least one abnormal blood pressure (BP) measurement over twelve months. Among those children whose recorded BPs met the criteria for prehypertension (N = 6178), 14.6% had a diagnosis in the EHR. These children were more likely to be White and have obesity compared with children who met the criteria but were not diagnosed with prehypertension. Among those who met the criteria for hypertension (N = 55), 41.8% had a diagnosis of hypertension in the EHR. Being diagnosed with hypertension was not associated with any examined patient characteristics. Over eleven months, 2837 children had BP ≥ 95th percentile on ≥ 1 visit. Only 13% had guideline-adherent follow-up within 1 month and were more likely to be older, female, and of Hispanic ethnicity or "other" race. Over six months, 2902 children had BP ≥ 90th percentile on one visit. 41% had guideline-adherent follow-up within 6 months and were more likely to be older, of either White, Hispanic, Asian race, or Hispanic ethnicity. In a community-based setting, pediatric hypertension and prehypertension were persistently underdiagnosed with low adherence to recommended follow-up.

Optimizing the implementation of a population panel management intervention in safety-net clinics for pediatric hypertension (The OpTIMISe-Pediatric Hypertension Study).

BACKGROUND: Though clinical practice guidelines are available, the diagnosis of pediatric hypertension (HTN) is often missed. Management may not follow guidelines due to the measurement challenges in children, complexity of interpreting youth blood pressure standards that are dependent on height, age, and sex, familiarity with diagnostic criteria, and variable comfort with management of pediatric HTN among providers. Evidence suggests that wide adoption and adherence to pediatric HTN guidelines would result in lower cardiovascular disease and kidney damage in adulthood. The proposed project will develop an implementation strategy package to increase adherence to clinical practice guidelines for pediatric HTN within safety-net community health centers (CHCs). The centerpiece of which is a provider-facing population panel management (PPM) tool and point-of-care clinical decision support (CDS). Prior research indicates that multiple discrete implementation strategies (e.g., stakeholder involvement, readiness planning, training, ongoing audit and feedback) are needed to institute practice- and provider-level adoption of such tools. METHODS: Using participatory research methods involving stakeholders from a practice-based research network of CHCs, with input from scientific advisors, the project aims to (1) employ user-centered design methods to tailor an existing CDS tool for use at the point of care and optimize cohort management with a PPM tool to support adherence to the latest pediatric HTN guidelines, and (2) use a stakeholder-driven method for selecting implementation strategies that support tool adoption and increase guideline-adherent physician behaviors. Multilevel process evaluation using surveys and key informant interview data will assess the acceptability, adoption, appropriateness, cost, and feasibility of the PPM tool and its multicomponent implementation strategy package. Usability testing will be conducted with the PPM tool to iteratively refine features and ensure proper functionality. DISCUSSION: The proposed research has the potential to improve identification, diagnosis, and management of HTN in primary care settings for high-risk youth by assisting healthcare providers in implementing the American Academy of Pediatrics' 2017 guidelines using an EHR-integrated PPM tool with CDS. Should the strategy package for PPM tool adoption be successful for pediatric HTN, findings will be translatable to other settings and PPM of other chronic cardiovascular conditions affecting overall population health.

Racial Disparity in the Prescription of Anticoagulants and Risk of Stroke and Bleeding in Atrial Fibrillation Patients.

BACKGROUND: Oral anticoagulant (OAC) therapy is proven to be effective at reducing risk of stroke in patients with atrial fibrillation (AF). However, racial minorities with AF are less likely to be prescribed vitamin K anticoagulants (VKA). There is little information on the racial disparity in the prescription of the non-vitamin K oral anticoagulants (NOACs) and the associated risks of stroke and bleeding. METHODS: We used data from the Northwestern Medicine Enterprise Data Warehouse - a joint initiative across 11 Northwestern Medicine affiliated healthcare centers within metropolitan Chicago, Illinois. Newly diagnosed AF patients between Jan, 2011 and Dec, 2017 with CHA2DS2VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, female sex) score of 2 or more and no prior history of stroke or major bleeding were eligible. Logistic regression was used to examine differences in the prescription of any OAC and NOACs by race. Racial differences in the associations of NOACs prescription with incident stroke (a composite of ischemic and hemorrhagic stroke and cerebral embolism) and major bleeding were evaluated using Cox regression. RESULTS: Among 11,575 newly diagnosed AF patients with CHA2DS2VASc score of 2 or more, 48.7% (47.8-49.6) were on any OAC and among those 40.1% (38.8.3-41.4) received any NOACs. After adjusting for age, gender, income, insurance status, and stroke risk factors, the odds of receiving any OAC was .69 (95% CI: .58-.83) in blacks, .74 (.53-1.903) in Hispanics, and .75 (.58-.95) in Asians compared to whites. Among anticoagulated patients, blacks and Hispanics had significantly lower odds of receiving NOACs: .72 (.53-.97) and .53 (.29-.99), respectively. Use of NOACs, as compared to VKAs, was associated with significantly lower risk of stroke [.52(.31-.85)] and bleeding [.72(.54-.95)] in whites but not in non-whites [stroke: .71 (.22-2.31); bleeding .83(.43-1.57)] independent of other risk factors. CONCLUSIONS: Racial minorities with AF who are at risk of stroke were less likely to receive any OAC and NOACs specifically compared to whites even after accounting for insurance status, income, and stroke risk factors. Independent of other risk factors, use of NOACs as compared to VKA was associated with significantly lower risk of stroke and bleeding only in whites but not in non-whites.