Background: Early left ventricular systolic dysfunction is common after moderate-severe traumatic brain injury (TBI). Echocardiography (Echo) can evaluate cardiac function across various clinical scenarios; however, its utilization in isolated TBI remains poorly understood. To address this gap, we aim to examine Echo utilization in hospitalized adults with isolated TBI. Methods: Using a propensity-matched cohort based on All Patient Refined Diagnosis Related Group severity of illness, we performed a multivariable logistic regression analysis (adjusting for demographics, admitting hospital characteristics, TBI characteristics, cardiac comorbidities, and cardiac complications) to examine factors associated with Echo utilization in patients with isolated TBI in the US National Inpatient Sample (2016-2020). We reported adjusted odds ratio (aOR) and 95% confidence intervals. Results: In 4874 patients matched by APR-DRG severity of illness, the factors associated with Echo utilization were as follows: Older age compared to 18-44 years, Urban teaching hospital: aOR 1.44 [1.05;1.98], TBI associated with syncope: 3.29 [2.68;4.07], ICP monitoring: 2.26 [1.18, 4.45), hypertension: 1.35 [1.18, 1.54], myocardial infarction: 2.89 [2.14, 3.94], atrial fibrillation:1.38 [1.10, 1.74], heart failure: 1.57 [1.31, 1.87], ventricular tachycardia: 1.85 [1.28, 2.71), and pulmonary embolism: 2.61 [1.51, 4.66]. Conclusions: Echo utilization was associated with TBI etiology, pre-existing cardiac comorbidities, and in-hospital cardiac complications. These findings need validation in prospective studies.

Importance:Aspirin use for primary prevention of cardiovascular diseases (CVD) is widespread with over a third of the adult population using despite guidelines recommending against. Objective:This population-based research documents rates of use and reasons for cessation from 2015 to 2020, a period when guidelines changed. Design:Three cross-sectional telephone surveys were conducted during 2015, 2017, and 2019-20. Setting:A population-based survey in the states of Iowa, Minnesota, North Dakota, South Dakota, and Wisconsin. Participants:The surveys included non-institutionalized resident adults ages 55-79 for women and 45-79 for men with landline telephones. Main Outcomes and Measures:The analysis included 8,197 participants, 4,161 women and 4,036 men after excluding those with a history of cardiovascular disease (secondary prevention). Aspirin use for primary prevention was stable for the first two survey years (39 % in 2015 and 41 % in 2017) but fell significantly to 34 % in the final survey (2019-2020). The most common reason for cessation was "doctor's advice" (38 % of quitters) followed by "heard negative news" with a significant increase from 2015 to 2020 (4 % to 29 % of quitters). Conclusions and Relevance:Despite recent research findings and new guidelines, aspirin is still widely used for primary prevention of CVD in the general population. A combination of slow diffusion and implementation of guidelines, self-medication, and wide availability of low-cost aspirin underlies these trends. Physician advice is effective but more is needed. The influence of the popular media is also substantial. Appropriate implementation of aspirin guidelines requires additional clinician effort. Trial Registration:Clinicaltrials.gov registered on December 1, 2014, NCT02607917.

Background: Protein is essential for optimal growth, function, and maintenance of health. Its impact on bone, kidney health, and sarcopenia progression remains debated. Objectives: This review examines the association between dietary protein intake and the risk of bone disease, kidney disease, and sarcopenia to inform protein dietary reference intake updates. Methods: We searched Medline, EMBASE, AGRICOLA, and Scopus from January 2000 to May 2024, supplemented by citation searching for relevant reviews and original research. We included randomized and nonrandomized controlled trials, prospective cohort studies, and nested case-control studies examining dietary protein intake without exercise. We assessed the risk of bias (RoB), performed a qualitative synthesis of low to moderate RoB studies, and evaluated the strength of evidence. Results: Of 82 articles detailing 81 unique studies, only 13 were assessed with low to moderate RoB and synthesized, comprising bone disease [4 randomized controlled trials (RCTs) and 1 prospective cohort study], kidney disease (1 RCT), and sarcopenia (9 RCTs). The overarching evidence was insufficient, largely due to the limited number of low to moderate RoB studies, the diversity of dietary protein interventions, and the broad range of outcomes, which complicated synthesis and comparison. Notably, sparse literature addressed children and adolescents, and only a single study each examined the impact of dietary protein intake on bone disease risk (yielding mixed findings) in these populations and on kidney disease risk (showing no significant effects) in adults. The findings on the impact of protein intake on bone disease in adults and sarcopenia risk were mixed; some studies showed no effect, whereas others indicated benefits. Conclusions: The evidence since 2000 on associations between dietary protein intake and the risks of bone disease, kidney disease, and sarcopenia is unclear, indicating a need for more rigorous research.This trial was registered at PROSPERO as CRD42023446621.

IntroductionFew tests are validated for ischemia grading in chronic limb-threatening ischemia (CLTI). An additional, easily accessible and validated technique would be beneficial. This study aimed to determine whether transmetatarsal pressure (TMP) is valid in the evaluation of CLTI ischemia grade. We also aimed to assess if values for TMP were meaningful in patients with noncompressible ankle-brachial indices (ABI).MethodsA cohort of patients with peripheral artery disease (PAD) presenting to our vascular center from March 1 to May 1, 2022, underwent TMP measurement concurrent with ABI and toe pressure (TP) measurement. Linear and quadratic regression models were used to assess the relation between TMP and TP or ABI.ResultsA total of 108 patients who were being followed for PAD underwent testing. Half had a history of CLTI (55% of patients with diabetes and 43% of patients without diabetes). The relation between TP and TMP was best described by a quadratic formula with an R2 value of 0.41. By combining the existing WIfI ischemia ranges defined by TP and the quadratic formula, new ischemia grades were calculated for TMP. Ischemia grades 0, 1, 2, and 3 corresponded to ranges of TMP pressure (mmHg) of ≥ 75, 45-74, 30-44, and < 30. There were 25 instances where a patient had an abnormally elevated ABI. None of these patients had a noncompressible TP or TMP.ConclusionWe demonstrated that TMP can be integrated into the WIfI classification. We believe that TMP evaluation may increase the reliability, accuracy, and accessibility of CLTI assessment and management.

Background Significant race and sex disparities exist in the prevalence, diagnosis, and outcomes of peripheral artery disease (PAD). However, clinical trials evaluating treatments for PAD often lack representative patient populations. This systematic review aims to summarize the demographic representation and enrollment strategies in clinical trials of lower-extremity endovascular interventions for PAD. Methods Following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched multiple sources (Medline, EMBASE, Cochrane, Clinicaltrials.gov, WHO clinical trial registry) for randomized controlled trials (RCTs), RCT protocols, and peer-reviewed journal publications of RCTs conducted between January 2012 and December 2022. Descriptive analysis was used to summarize trial characteristics, publication or study protocol characteristics, and the reporting of demographic characteristics. Meta-regression was used to explore associations between demographic characteristics and certain trial characteristics. Results A total of 2,374 records were identified. Of these, 59 met the inclusion criteria, consisting of 35 trials, 14 publications, and 10 protocols. Information regarding demographic representation was frequently missing. While all 14 trial publications reported age and sex, only 4 reported race/ethnicity, and none reported socioeconomic or marital status. Additionally, only 4 publications reported clinical outcomes by demographic characteristics. Meta-regression analysis revealed that 6% more women were enrolled in non-European trials (36%) than in European trials (30%). Conclusions The findings of this review highlight potential issues that may compromise the reliability and external validity of study findings in lower-extremity PAD RCTs when applied to the real-world population. Addressing these issues is crucial to enhance the generalizability and impact of clinical trial results in the field of PAD, ultimately leading to improved clinical outcomes for patients in underrepresented populations. Registration The systematic review methodology was published in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022378304).

Despite high prevalence of cardiovascular disease (CVD) and CVD risk factors among American Indian or Alaska Native adults (AI/AN), there is little information on aspirin use in this population. This survey-based study seeks to understand prevalence of aspirin use in a sample of AI/AN adults in the Upper Midwestern United States. In-person and telephone based surveys were conducted querying self-reported CVD and CVD risk factors, aspirin use, and aspirin related discussion with clinicians. A total of 237 AI/AN participants were included: mean age (SD) was 60.8 (8.4) years; 143 (60 %) were women; 59 (25 %) reported CVD history. CVD risk factors were common particularly smoking (37 %) and diabetes (37 %). Aspirin use was much higher among those with CVD (secondary prevention, 76 %) than those without (primary prevention, 33 %). Primary prevention aspirin use was significantly associated with age and all CVD risk factors in unadjusted analyses. After adjustment for demographics and CVD risk factors, only age (aRR 1.13 per 5 years, 95 % CI 1.02, 1.25) and diabetes (aRR 2.44, 95 % CI 1.52, 3.92) remained significantly associated with aspirin. Regardless of CVD status, a higher proportion of those taking aspirin reported a conversation about aspirin with their doctor compared to those not taking aspirin. Among participants with no CVD, those who had such a conversation were 2.6 times more likely to use aspirin than those who did not have a conversation (aRR 2.64, 95 % CI 1.58, 4.44). The findings of this study emphasize the importance of the patient-provider relationship for preventive therapy.

Background: Active compression-decompression cardiopulmonary resuscitation (ACD-CPR) combined with an impedance threshold device (ITD) and controlled head-up positioning, collectively termed AHUP-CPR, is associated with improved outcomes compared with conventional CPR (C-CPR). Active decompression (AD) forcibly lifts the anterior chest wall with suction after each compression, while the ITD simultaneously impedes airflow into the lungs. AD and ITD synergistically lower intrathoracic pressure during decompression, improving venous return, ventricular refilling and cardiac output. Concurrently, head-up positioning lowers intracranial pressures and improves cardiac preload. This pig study focused on the physiological role of AD during AHUP-CPR, simulating real clinical scenarios. Methods: Ten male and female farm pigs (~40 kg) were anesthetized, intubated and ventilated. Hemodynamic parameters, end-tidal CO2 (ETCO2), and biventricular pressure-volume loops were recorded continuously. Ventricular fibrillation was induced and left untreated for 10 mins. Then, after 2 min of automated C-CPR in the flat position, AHUP-CPR with a 3 cm lift above the neutral position of the chest was performed for 13 min. AD was then abruptly discontinued, restarted 1 min later, and increased incrementally every min to up to 4 cm of active lift. Data were analyzed with a linear mixed-effects model, using random intercepts for individual pigs. Results: Upon cessation of AD, coronary and cerebral perfusion pressures, compression and decompression aortic pressures, compression right atrial pressure, ETCO2, right and left ventricular preload, compliance, stroke volume and cardiac output all decreased immediately and significantly (p<0.01), whereas decompression right atrial and biventricular pressures increased. With restoration of AD, physiological parameters returned to ≥ 90% of pre-AD discontinuation values (Figures 1 and 2). Conclusion: Full chest wall lift, achieved with > 3 cm of AD, was needed to maintain and optimize hemodynamics during AHUP-CPR in pigs. After pausing AD, incremental restoration of AD resulted in nearly complete restoration of peripheral and central hemodynamic measures. These observations support the benefit of and need for ≥3 cm of AD to optimize AHUP-CPR. Effective means to generate ≥3 cm of AD should be considered when implementing and developing AHUP-CPR devices to optimize outcomes.

Background: The combination of active compression-decompression cardiopulmonary resuscitation (ACD-CPR) with an impedance threshold device (ITD) and controlled head-up positioning (AHUP-CPR) is associated with improved outcomes compared with conventional CPR (C-CPR). This study focused on the role of active decompression (AD) during AHUP-CPR. Methods: Farm pigs (n = 10, 40 kg) were anesthetized, intubated and ventilated. Physiological parameters and right ventricular pressure-volume loops were recorded continuously. Ventricular fibrillation was induced and left untreated for 10 mins, followed by automated C-CPR (2 min), ACD + ITD CPR in the flat position (2 min), and then AHUP-CPR with 3 cm of lift above the neutral chest position. After 15 min of CPR, AD was discontinued and then restarted incrementally to 4 cm. Data were analyzed with a linear mixed-effects model, using random intercepts for individual pigs. Results: Upon cessation of AD during AHUP-CPR, decompression right atrial pressure (+59%) increased (p < 0.01), whereas multiple hemodynamic parameters positively associated with perfusion, including coronary (-25%)- 25%) and cerebral perfusion pressures (-11%),- 11%), end-tidal CO2 (-13%),- 13%), stroke volume and cardiac output (-26%),- 26%), decreased immediately and significantly with p < 0.05. Restoration of AD reduced right atrial pressure and increased positive perfusion parameters in an incremental manner. Only with >= 3 cm of AD were all hemodynamic parameters restored to >= 90% of pre-AD discontinuation levels. Conclusion: Full chest wall lift, achieved with >= 3 cm of AD, was needed to maintain and optimize hemodynamics during AHUP-CPR in pigs. These findings should be considered when optimizing care with this new approach.

Background: Patients taking beta-blockers (BBs) commonly experience weight gain. There is limited research exploring how BBs impact weight loss after bariatric surgery. Objectives: We examined how BBs impact 12 -month weight loss in patients undergoing sleeve gastrectomy (SG) or Roux -en -Y gastric bypass (RYGB). Setting: Large midwest health system. Methods: We reviewed health records of SG and RYGB patients (2011-2022) and categorized them by BB usage (none, pre-, post-, or pre- and postoperative). Multivariable linear regression models examined the relation between BB use, percent total body weight loss (%TBWL), and percent excess body mass index lost (%EBMIL). Results: A total of 889 individuals (SG, n = 485; RYGB, n = 404) had complete data. RYGB led to greater %TBWL compared to SG (31% versus 26%, P < .01) and greater %EBMIL (79% versus 64%, P < .01). BB status did not significantly affect 12 -month %TBWL or %EBMIL. Conclusions: BB use may not significantly affect weight loss 12 months after bariatric surgery. This finding could enable physicians to prescribe BBs for improved blood pressure control in bariatric surgery patients with less concern of blunting weight loss. Longer term follow-up with a larger sample size would be an important next step to better characterize the relationship between BB usage and bariatric surgery. (Surg Obes Relat Dis 2023;19:1415-1420.) (c) 2023 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.

Background A total of 40% of patients with severe aortic stenosis (AS) have low‐gradient AS, raising uncertainty about AS severity. Aortic valve calcification, measured by computed tomography (CT), is guideline‐endorsed to aid in such cases. The performance of different CT‐derived aortic valve areas (AVAs) is less well studied. Methods and Results Consecutive adult patients with presumed moderate and severe AS based on echocardiography (AVA measured by continuity equation on echocardiography <1.5 cm 2 ) who underwent cardiac CT were identified retrospectively. AVAs, measured by direct planimetry on CT (AVA CT ) and by a hybrid approach (AVA measured in a hybrid manner with echocardiography and CT [AVA Hybrid ]), were measured. Sex‐specific aortic valve calcification thresholds (≥1200 Agatston units in women and ≥2000 Agatston units in men) were applied to adjudicate severe or nonsevere AS. A total of 215 patients (38.0% women; mean±SD age, 78±8 years) were included: normal flow, 59.5%; and low flow, 40.5%. Among the different thresholds for AVA CT and AVA Hybrid , diagnostic performance was the best for AVA CT <1.2 cm 2 (sensitivity, 85%; specificity, 26%; and accuracy, 72%), with no significant difference by flow status. The percentage of patients with correctly classified AS severity (correctly classified severe AS+correctly classified moderate AS) was as follows; AVA measured by continuity equation on echocardiography <1.0 cm 2 , 77%; AVA CT <1.2 cm 2 , 73%; AVA CT <1.0 cm 2 , 58%; AVA Hybrid <1.2 cm 2 , 59%; and AVA Hybrid <1.0 cm 2 , 45%. AVA CT cut points of 1.52 cm 2 for normal flow and 1.56 cm 2 for low flow, provided 95% specificity for excluding severe AS. Conclusions CT‐derived AVAs have poor discrimination for AS severity. Using an AVA CT <1.2‐cm 2 threshold to define severe AS can produce significant error. Larger AVA CT thresholds improve specificity.

Background Recent guidelines have emphasized the use of medical management, early diagnosis, and a multidisciplinary team to effectively treat patients with critical limb ischemia (CLI). Previous literature briefly highlighted the current racial disparities in its intervention. Herein, we analyze the trend over a 14-year time period to investigate whether the disparities gap in CLI management is closing.Methods and Results The National Inpatient Sample was queried between 2005 and 2018 for hospitalizations involving CLI. Nontraumatic amputations and revascularization were identified. Utilization trends of these procedures were compared between races (White, Black, Hispanic, Asian and Pacific Islander, Native American, and Other). Multivariable regression assessed differences in race regarding procedure usage. There were 6 904 562 admissions involving CLI in the 14-year study period. The rate of admissions in White patients who received any revascularization decreased by 0.23% (P<0.001) and decreased by 0.25% (P=0.025) for Asian and Pacific Islander patients. Among all patients, the annual rate of admission in White patients who received any amputation increased by 0.21% (P<0.001), increased by 0.19% (P=0.001) for Hispanic patients, and increased by 0.19% (P=0.012) for the Other race patients. Admissions involving Black, Hispanic, Asian and Pacific Islander, or Other race patients had higher odds of receiving any revascularization compared with White patients. All races had higher odds of receiving major amputation compared with White patients.Conclusions Our analysis highlights disparities in CLI treatment in our nationally representative sample. Non-White patients are more likely to receive invasive treatments, including major amputations and revascularization for CLI, compared with White patients.

Aspirin use for cardiovascular disease (CVD) prevention is common among adults 60 years and older.1 Although some use aspirin for secondary prevention, many older adults use daily aspirin for primary prevention despite guidelines recommending limiting such use.2, 3 Widely-cited research published in 2018 suggest the risk–benefit balance of aspirin use in CVD prevention in older adults is outweighed by bleeding and other side effects.4 In the context of new data and guidelines, this study describes the prevalence and trends in aspirin use from 2015 to 2020 among adults ages 60–79 living in five Upper Midwestern states. Three cross-sectional telephone surveys of non-institutionalized resident adults ages 60–79 from June–December 2015, June–December 2017, and October–March 2019–20 were conducted among adults living in Iowa, Minnesota, North Dakota, South Dakota, and Wisconsin. Addresses with zip codes and associated landline telephone numbers were used to generate random samples within states proportional to population size. Sampled households were sent a letter describing the study. One respondent per household was selected. The overall participation was 48% after accounting for refusals, address errors, and disconnected telephones. Trained interviewers administered a 10-min telephone survey that included questions about aspirin use, history of cardiovascular disease (CVD), cardiovascular risk factors, media exposure, doctor discussions about aspirin, health behaviors and demographic characteristics. In a previously published study, using the same telephone survey, self-reported aspirin use was evaluated with blood levels of thromboxane B2.5 Sensitivity and specificity were over 90%. Data are presented as n (%) for categorical variables and mean (SD) for continuous variables. Categorical data were compared using chi-square tests. Analyses were performed in Stata version 16.1 (StataCorp. 2019. Stata Statistical Software: Release 16. College Station, TX: StataCorp LLC). The University of Minnesota Institutional Review Board approved this study and participants provided verbal consent. The surveys included 7921 individuals ages 60–79, of which 4194 were women and 3727 were men. Participants without a history of CVD or bleeding met the definition for primary prevention and included 3533 women and 2709 men. Demographic characteristics were similar to census data for these states. Aspirin use for primary prevention was stable for the first two survey years (46% in both 2015 and 2017) but fell to 37% in the last survey (2019–2020), (Figure 1). The use for secondary prevention was flat at over 70% for all three surveys (Figure 1). Self-report of discontinuing aspirin rose from 17% to 26% from 2015 to 2019–20. Reasons for stopping aspirin use in 2019–20 are shown in Table 1. The leading reasons were doctor advice and/or “heard negative news”. The number of negative messages heard in the media was greatest in the 2019–20 survey (Table 1). Reports on the use of aspirin for “coronary thrombosis” are over seven decades old but it was not until early clinical trials that aspirin became widely used for prevention of myocardial infarction and stroke. In the United States, the U.S. Preventive Services Task Force (USPSTF) released guidelines for the use of aspirin for primary prevention in 2002, 2009 and 2016.5 In 2002, there was no upper age limit. In 2009, the USPSTF added an upper age limit of 79. The 2016 USPSTF provided Class C advice for those 60–69 years and cited insufficient evidence for those 70 and older.2 In 2018, three large clinical trials of aspirin initiation (ASCEND, ASPREE, ARRIVE) produced mixed results with the ASPREE trial of healthy older adults finding increased bleeding and other complications.4, 6, 7 Following the release of these studies, substantial media and professional discussion of inappropriate aspirin use ensued. The USPSTF 2022 report recommended against aspirin initiation for those 60 years and older.3 Similar recommendations against use of aspirin for primary prevention were published in American Heart Association guidelines and the updated Beers criteria.8, 9 The current survey finds aspirin use for primary prevention continues to be common among those over age 60 with the highest use in those 70–79 years. It also finds that aspirin use significantly declined between 2017 and 2019–20 among this older age group (46%–37%, p < 0.001). Continued use of aspirin in those 60 years and above, despite national guidelines, probably stems from a number of factors. These include self-prescription without a clinician's advice and the availability of aspirin, without prescription, at a low price. Aspirin is also heavily advertised for secondary CVD prevention and the distinction between primary and secondary prevention is not always apparent. Finally, some suggest that continuation of aspirin use is not the same as the initiation of aspirin.10 Observational data from the national Swedish Registry finds that those who were taking aspirin and discontinue use have a 30% increase in CVD events beginning almost immediately and continuing for several years.11 The issue of discontinuation has not been well studied. In the context of new guidelines, what can the practicing clinician do? This study provides some insights. Many older adults still take a daily aspirin. Those who do use aspirin are frequently self-prescribing and/or not at high risk.12 Those who quit, do so based on consultation with a clinician or media reports. There is an opportunity during routine clinical visits to explore the appropriateness of aspirin use and make recommendations. Russell V. Luepker: Concept and design, acquisition of subjects and/or data, analysis and interpretation of data, and preparation of manuscript. Jeremy R. Van't Hof: Acquisition of subjects and/or data, analysis and interpretation of data, and preparation of manuscript. Milton Eder: Concept and design, analysis and interpretation of data, and preparation of manuscript. John R. Finnegan: Concept and design, and preparation of manuscript. Niki Oldenburg: Acquisition of data. Sue Duval: Concept and design, acquisition of subjects and/or data, analysis and interpretation of data, and preparation of manuscript. This work was supported by the National Institutes of Health (R01HL126041), and the Lillehei Heart Institute of the University of Minnesota. The authors declare that there is no conflict of interest. Not involved.

There is currently a lack of uniformity in methods of aortic diameter measurements across different imaging modalities. In this study, we sought to evaluate the accuracy of transtho-racic echocardiography (TTE) in comparison with magnetic resonance angiography (MRA) for the measurement of proximal thoracic aorta diameters. This is a retrospective analysis of 121 adult patients at our institution who had TTE and electrocardiogram (ECG)-gated MRA performed within 90 days of each other between 2013 and 2020. Meas-urements were made at the level of sinuses of Valsalva (SoV), sinotubular junction (STJ), and ascending aorta (AA) using leading edge-to-leading edge (LE) convention for TTE and inner-edge-to-inner-edge (IE) convention for MRA. Agreement was assessed using Bland-Altman methods. Intra-and interobserver variability were assessed by intraclass correlation. The average age of patients in the cohort was 62 years, and 69% of patients were male. The prevalence of hypertension, obstructive coronary artery disease, and dia-betes was 66%, 20%, and 11%, respectively. The mean aortic diameter by TTE was SoV 3.8 +/- 0.5 cm, STJ 3.5 +/- 0.4 cm, and AA 4.1 +/- 0.6 cm. The TTE-derived measurements were larger than the MRA ones by 0.2 +/- 2 mm, 0.8 +/- 2 mm, and 0.4 +/- 3 mm at the level of SoV, STJ, and AA, respectively, but the differences were not statistically significant. There were no significant differences in the aorta measurements by TTE compared with MRA, when stratified by gender. In conclusion, transthoracic echocardiogram-derived proximal aorta measurements are comparable to MRA measurements. Our study vali-dates current recommendations that TTE is an acceptable modality for screening and serial imaging of the proximal aorta.(c) 2023 Elsevier Inc. All rights reserved.

Aim: This review provides a study protocol for a systematic review of peripheral artery disease (PAD) clinical trials to examine the eligibility criteria, demographic representation, and enrollment strategies among PAD patients undergoing lower extremity (LE) endovascular interventions. Methods: This systematic review will be conducted according to the Cochrane Collaboration methodology for systematic reviews and following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Eligible studies will include randomized controlled trials (RCTs) between January 2012 and December 2022. The primary outcome will be a description and summary of the frequency of the reporting of demographic characteristics. The feasibility of a meta-analysis or meta-regression will be explored, but if determined to be infeasible, the Synthesis Without Meta-analysis (SWiM) reporting guideline will be followed for the reporting of findings. Discussion: The findings may help to quantify existing inequities in clinical trial participation that may be addressed through optimizing enrollment strategies for future PAD trials. Systematic review registration: PROSPERO (CRD42022378304)

IMPORTANCE Low-dose aspirin is used for primary prevention of cardiovascular disease in approximately one-third of the US adult population. Overuse and underuse are common and not concordant with guidelines. OBJECTIVE To test a community and clinic education intervention to improve guideline-based aspirin use for the primary prevention of cardiovascular disease. DESIGN, SETTING, AND PARTICIPANTS The Ask About Aspirin project was a nonrandomized controlled trial conducted from, July 1, 2015, to March 31, 2020, using professional education, traditional media, and digital media to improve guideline-based aspirin use. The adult population (aged 45-79 years for men and 55-79 years for women) and primary care clinics in Minnesota were the education targets. The 4 adjacent states were controls. INTERVENTIONS The statewide campaign distributed billboards, newspaper articles and other print material, and radio announcements. An Ask About Aspirin website was heavily promoted. Primary care clinics identified appropriate aspirin candidates, and clinicians received continuing education about aspirin. MAIN OUTCOMES AND MEASURES Guideline-based aspirin use by the target population. RESULTS Cross-sectional random telephone surveys of 8342 men aged 45 to 79 years and women aged 55 to 79 years were conducted at baseline, 2 years, and 4 years after the intervention. Participation was similar between men and women (baseline: 973 [49%] vs 1001 [51%]; year 4: 912 [50%] vs 930 [50%]). Age during the study also was similar (baseline: 64.7 [IQR. 64.4-65.1] years; year 4: 66.2 [IQR, 65.8-66.5] years). A validated questionnaire evaluated aspirin use. The Ask About Aspirin website had more than 1 million visits; 124 primary care clinics with more than 1000 participating clinicians were part of the education program. Small, nonsignificant increases in discussions with clinicians regarding aspirin resulted (baseline: 341 of 1001 [34%]; year 4: 339 of 930 [36%]; P = .27). Overall aspirin use decreased after the release of new US Preventive Services Task Force guidelines in 2016 and 3 aspirin randomized clinical trials in 2018 suggested reduced aspirin use (baseline: 816 of 1974 [41%]; year 4: 629 of 1842 [34%); P < .001). Decreases were also noted from year 2 to year 4 in appropriate use (year 2:597 of 1208 [49%]; year 4: 478 of 1191 [40%]; P < .001) and overuse (year 2:170 of 602 [28%]; year 4: 151 of 651 [23%]; P = .04). There were no significant differences between Minnesota and the control states. CONCLUSIONS AND RELEVANCE In this nonrandomized controlled trial, a multiyear statewide campaign was not associated with increased appropriate aspirin use for cardiovascular disease prevention. Contextual factors during the project, including guideline changes and media controversy following the new trials, undermined study goals. These findings suggest that although education programs using social media for cardiovascular disease prevention can result in millions of hits, the use of this strategy to encourage behavior change is problematic, even with supportive clinical sites.