Publications by authors named "Seth S Martin"

237 Publications

The Use of Blood Biomarkers in Precision Medicine for the Primary Prevention of Atherosclerotic Cardiovascular Disease: a Review.

Expert Rev Precis Med Drug Dev 2021 26;6(4):247-258. Epub 2021 May 26.

Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Introduction: A biomarker is a substance, structure, or process that indicates the presence of a disease, infection, or environmental exposure. Clinically useful biomarkers are measurable, improve diagnostic or prognostic performance, and ultimately aid clinicians in determining the initiation, duration, or magnitude of therapy.

Areas Covered: The purpose of this review is to explore the roles of various blood biomarkers of atherosclerotic cardiovascular disease (ASCVD) and how their use may improve the precision with which clinicians can identify, treat, and ultimately prevent ASCVD. Our review will include lipid biomarkers, markers of cardiac injury and wall stress, markers of inflammation, and a few others.

Expert Opinion: Several biomarkers have recently been highlighted as "risk-enhancing factors" in the 2019 American College of Cardiology/American Heart Association Guideline for the Primary Prevention of ASCVD, which can help guide shared decision-making. These included elevated low-density lipoprotein cholesterol, triglycerides, lipoprotein(a), apolipoprotein B, or high-sensitivity C-reactive protein. However, some other biomarkers mentioned in this review are not commonly used despite showing initial promise as prognostic of ASCVD risk, as it is not clear how treatment decisions should be changed after their measurement among asymptomatic individuals. Future studies should focus on whether biomarker-directed management strategies can improve clinical outcomes.
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http://dx.doi.org/10.1080/23808993.2021.1930531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372373PMC
May 2021

Health Information Technology Use Among Persons With Self-reported Atherosclerotic Cardiovascular Disease: Analysis of the 2011-2018 National Health Interview Survey.

J Med Internet Res 2021 Aug 13;23(8):e23765. Epub 2021 Aug 13.

Johns Hopkins University School of Nursing, Baltimore, MD, United States.

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in the United States. Health information technologies (HITs) have recently emerged as a viable intervention to mitigate the burden of ASCVD. Approximately 60% of US adults report searching the internet for health information; however, previous research has not examined the prevalence of general technology or HIT use among adults with and without ASCVD. In addition, social determinants in HIT use among adults with ASCVD are not well understood.

Objective: The aim of this study was to evaluate the prevalence and social determinants of HIT use among US adults with versus without self-reported ASCVD.

Methods: We pooled cross-sectional data from the 2011-2018 National Health Interview Survey (NHIS) to examine the general technology and HIT use among adults aged ≥18 years with and without self-reported ASCVD (coronary heart disease, stroke, or both). General technology use was defined as mobile phone ownership, internet use, and computer use. HIT use was defined as looking up health information on the internet, filling a web-based prescription, scheduling a medical appointment on the internet, communicating with a health care provider by email, or using web-based group chats to learn about health topics. We evaluated sociodemographic differences in HIT use among respondents by using Poisson regression. Analyses were weighted according to NHIS standards.

Results: A total sample of 256,117 individuals were included, of which 2194 (0.9%) reported prior ASCVD. Among adults with prior ASCVD, the mean age was 70.6 (SD 11.5) years, and 47.4% (1048/2194) of the adults were females. General technology use differed between participants with and without prior ASCVD, with 36.0% (614/1826) and 76.2% (157,642/213,816) indicating internet usage and 24.6% (374/1575) and 60.7% (107,742/184,557) indicating using a computer every day, respectively. Similarly, adults with ASCVD were less likely to use HIT than those without ASCVD (515/2194, 25.1% vs 123,966/253,923, 51.0%; P<.001). Among adults with prior ASCVD, social determinants that were associated with HIT use included younger age, higher education, higher income, being employed, and being married.

Conclusions: HIT use was low among adults with a history of ASCVD, which may represent a barrier to delivering care via emerging HIT. Given the associations with social determinants such as income, education, and employment, targeted strategies and policies are needed to eliminate barriers to impact HIT usage.
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http://dx.doi.org/10.2196/23765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398708PMC
August 2021

Daily Step Counts are Associated with Hospitalization Risk in Pulmonary Arterial Hypertension.

Am J Respir Crit Care Med 2021 Aug 10. Epub 2021 Aug 10.

Vanderbilt University Medical Center, 12328, Medicine, Nashville, Tennessee, United States;

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http://dx.doi.org/10.1164/rccm.202104-1035LEDOI Listing
August 2021

The Johns Hopkins Ciccarone Center's expanded 'ABC's approach to highlight 2020 updates in cardiovascular disease prevention.

Am J Prev Cardiol 2021 Jun 5;6:100181. Epub 2021 Apr 5.

The Ciccarone Center for the Prevention of Cardiovascular Disease, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.

In recent years, improvement in outcomes related to cardiovascular disease is in part due to the prioritization and progress of primary and secondary prevention efforts. The Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease expanded 'ABC's approach is used to highlight key findings in Preventive Cardiology from 2020 and further emphasize the importance of cardiovascular prevention. This simplified approach helps clinicians focus on the most relevant and up to date recommendations for optimizing cardiovascular disease risk through accurate risk assessment and appropriate implementation of lifestyle, behavioral and pharmacologic interventions. While 2020 not only provided practice changing updates by way of clinical guidelines and randomized controlled trials on topics related to antithrombotic and lipid lowering therapy, diabetes management and risk assessment, it also provided promising data on how to improve dietary and exercise adherence and manage genetic risk. By providing clinicians with a systematic approach to cardiovascular prevention and key highlights from the prior year, the goal of significantly reducing the burden of cardiovascular disease worldwide can be achieved.
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http://dx.doi.org/10.1016/j.ajpc.2021.100181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315585PMC
June 2021

Opportunities to improve cardiovascular health in the new American workplace.

Am J Prev Cardiol 2021 Mar 8;5:100136. Epub 2020 Dec 8.

Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Adult working-class Americans spend on average 50% of their workday awake time at their jobs. The vast majority of these jobs involve mostly physically inactive tasks and frequent exposure to unhealthy food options. Traditionally, the workplace has been a challenging environment for cardiovascular prevention, where cardiovascular guidelines have had limited implementation. Despite the impact that unhealthy lifestyles at the workplace may have on the cardiovascular health of U.S. workers, there is currently no policy in place aimed at improving this. In this review, we discuss recent evidence on the prevalence of physical inactivity among Americans, with a special focus on the time spent at the workplace; and the invaluable opportunity that workplace-based lifestyle interventions may represent for improving the prevention of cardiovascular disease. We describe the current regulatory context, the key stakeholders involved, and present specific, guideline-inspired initiatives to be considered by both Congress and employers to improve the "cardiovascular safety" of US jobs. Additionally, we discuss how the COVID-19 pandemic has forever altered the workplace, and what lessons can be taken from this experience and applied to cardiovascular disease prevention in the new American workplace. For many Americans, long sitting hours at their job represent a risk to their cardiovascular health. We discuss how a paradigm shift in how we approach cardiovascular health, from focusing on leisure time to also focusing on work time, may help curtail the epidemic of cardiovascular disease in this country.
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http://dx.doi.org/10.1016/j.ajpc.2020.100136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315405PMC
March 2021

Inflammation and cardiovascular disease: From mechanisms to therapeutics.

Am J Prev Cardiol 2020 Dec 21;4:100130. Epub 2020 Nov 21.

Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Inflammation constitutes a complex, highly conserved cascade of molecular and cellular events. Inflammation has been labeled as "the fire within," is highly regulated, and is critical to host defense and tissue repair. In general, inflammation is beneficial and has evolved to promote survival. However, inflammation can also be maladaptive when chronically activated and sustained, leading to progressive tissue injury and reduced survival. Examples of a maladaptive response include rheumatologic disease and atherosclerosis. Despite evidence gathered by Virchow over 100 years ago showing that inflammatory white cells play a role in atherogenesis, atherosclerosis was until recently viewed as a disease of passive cholesterol accumulation in the subendothelial space. This view has been supplanted by considerable basic scientific and clinical evidence demonstrating that every step of atherogenesis, from the development of endothelial cell dysfunction to foam cell formation, plaque formation and progression, and ultimately plaque rupture stemming from architectural instability, is driven by the cytokines, interleukins, and cellular constituents of the inflammatory response. Herein we provide an overview of the role of inflammation in atherosclerotic cardiovascular disease, discuss the predictive value of various biomarkers involved in inflammation, and summarize recent clinical trials that evaluated the capacity of various pharmacologic interventions to attenuate the intensity of inflammation and impact risk for acute cardiovascular events.
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http://dx.doi.org/10.1016/j.ajpc.2020.100130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315628PMC
December 2020

Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study.

Eur Heart J 2021 Jul 19. Epub 2021 Jul 19.

Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD, USA.

Aims: Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD.

Methods And Results: We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45-1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08-1.35). Similar results were shown when examining discordance across clinical cutpoints.

Conclusions: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.
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http://dx.doi.org/10.1093/eurheartj/ehab432DOI Listing
July 2021

Digital Health Intervention in Acute Myocardial Infarction.

Circ Cardiovasc Qual Outcomes 2021 Jul 15;14(7):e007741. Epub 2021 Jul 15.

Digital Health Innovation Laboratory, Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (F.A.M., E.M.S., J.D., J.W., H.X., L.M.S., D.W., V.V., D.N.L., R.S., P.P.H., S.W., S.S.M.).

Background: Thirty-day readmissions among patients with acute myocardial infarction (AMI) contribute to the US health care burden of preventable complications and costs. Digital health interventions (DHIs) may improve patient health care self-management and outcomes. We aimed to determine if patients with AMI using a DHI have lower 30-day unplanned all-cause readmissions than a historical control.

Methods: This nonrandomized controlled trial with a historical control, conducted at 4 US hospitals from 2015 to 2019, included 1064 patients with AMI (DHI n=200, control n=864). The DHI integrated a smartphone application, smartwatch, and blood pressure monitor to support guideline-directed care during hospitalization and through 30-days post-discharge via (1) medication reminders, (2) vital sign and activity tracking, (3) education, and (4) outpatient care coordination. The Patient Activation Measure assessed patient knowledge, skills, and confidence for health care self-management. All-cause 30-day readmissions were measured through administrative databases. Propensity score-adjusted Cox proportional hazard models estimated hazard ratios of readmission for the DHI group relative to the control group.

Results: Following propensity score adjustment, baseline characteristics were well-balanced between the DHI versus control patients (standardized differences <0.07), including a mean age of 59.3 versus 60.1 years, 30% versus 29% Women, 70% versus 70% White, 54% versus 54% with private insurance, 61% versus 60% patients with a non ST-elevation myocardial infarction, and 15% versus 15% with high comorbidity burden. DHI patients were predominantly in the highest levels of patient activation for health care self-management (mean score 71.7±16.6 at 30 days). The DHI group had fewer all-cause 30-day readmissions than the control group (6.5% versus 16.8%, respectively). Adjusting for hospital site and a propensity score inclusive of age, sex, race, AMI type, comorbidities, and 6 additional confounding factors, the DHI group had a 52% lower risk for all-cause 30-day readmissions (hazard ratio, 0.48 [95% CI, 0.26-0.88]). Similar results were obtained in a sensitivity analysis employing propensity matching.

Conclusions: Our results suggest that in patients with AMI, the DHI may be associated with high patient activation for health care self-management and lower risk of all-cause unplanned 30-day readmissions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03760796.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.121.007741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288197PMC
July 2021

Assessment of Coronary Artery Calcium Scoring to Guide Statin Therapy Allocation According to Risk-Enhancing Factors: The Multi-Ethnic Study of Atherosclerosis.

JAMA Cardiol 2021 Jul 14. Epub 2021 Jul 14.

Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, Maryland.

Importance: The 2018 American Heart Association/American College of Cardiology Guideline on the Management of Blood Cholesterol recommends the use of risk-enhancing factor assessment and the selective use of coronary artery calcium (CAC) scoring to guide the allocation of statin therapy among individuals with an intermediate risk of atherosclerotic cardiovascular disease (ASCVD).

Objective: To examine the association between risk-enhancing factors and incident ASCVD by CAC burden among those at intermediate risk of ASCVD.

Design, Setting, And Participants: The Multi-Ethnic Study of Atherosclerosis is a multicenter population-based prospective cross-sectional study conducted in the US. Baseline data for the present study were collected between July 15, 2000, and July 14, 2002, and follow-up for incident ASCVD events was ascertained through August 20, 2015. Participants were aged 45 to 75 years with no clinical ASCVD or diabetes at baseline, were at intermediate risk of ASCVD (≥7.5% to <20.0%), and had a low-density lipoprotein cholesterol level of 70 to 189 mg/dL.

Exposures: Family history of premature ASCVD, premature menopause, metabolic syndrome, chronic kidney disease, lipid and inflammatory biomarkers, and low ankle-brachial index.

Main Outcomes And Measures: Incident ASCVD over a median follow-up of 12.0 years.

Results: A total of 1688 participants (mean [SD] age, 65 [6] years; 976 men [57.8%]). Of those, 648 individuals (38.4%) were White, 562 (33.3%) were Black, 305 (18.1%) were Hispanic, and 173 (10.2%) were Chinese American. A total of 722 participants (42.8%) had a CAC score of 0. Among those with 1 to 2 risk-enhancing factors vs those with 3 or more risk-enhancing factors, the prevalence of a CAC score of 0 was 45.7% vs 40.3%, respectively. Over a median follow-up of 12.0 years (interquartile range [IQR], 11.5-12.6 years), the unadjusted incidence rate of ASCVD among those with a CAC score of 0 was less than 7.5 events per 1000 person-years for all individual risk-enhancing factors (with the exception of ankle-brachial index, for which the incidence rate was 10.4 events per 1000 person-years [95% CI, 1.5-73.5]) and combinations of risk-enhancing factors, including participants with 3 or more risk-enhancing factors. Although the individual and composite addition of risk-enhancing factors to the traditional risk factors was associated with improvement in the area under the receiver operating curve, the use of CAC scoring was associated with the greatest improvement in the C statistic (0.633 vs 0.678) for ASCVD events. For incident ASCVD, the net reclassification improvement for CAC was 0.067.

Conclusions And Relevance: In this cross-sectional study, among participants with CAC scores of 0, the presence of risk-enhancing factors was generally not associated with an overall ASCVD risk that was higher than the recommended treatment threshold for the initiation of statin therapy. The use of CAC scoring was associated with significant improvements in the reclassification and discrimination of incident ASCVD. The results of this study support the utility of CAC scoring as an adjunct to risk-enhancing factor assessment to more accurately classify individuals with an intermediate risk of ASCVD who might benefit from statin therapy.
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http://dx.doi.org/10.1001/jamacardio.2021.2321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281019PMC
July 2021

Mobile health in preventive cardiology: current status and future perspective.

Curr Opin Cardiol 2021 Sep;36(5):580-588

Department of Medicine, Division of Cardiology.

Purpose Of Review: Despite cutting edge acute interventions and growing preventive strategies supported by robust clinical trials, cardiovascular disease (CVD) has stubbornly persisted as a leading cause of death in the United States and globally. The American Heart Association recognizes mobile health technologies (mHealth) as an emerging strategy in the mitigation of CVD risk factors, with significant potential for improving population health. The purpose of this review is to highlight and summarize the latest available literature on mHealth applications and provide perspective on future directions and barriers to implementation.

Recent Findings: While available randomized controlled trials and systematic reviews tend to support efficacy of mHealth, published literature includes heterogenous approaches to similar problems with inconsistent results. Some of the strongest recent evidence has been focused on the use of wearables in arrhythmia detection. Systematic reviews of mHealth approaches demonstrate benefit when applied to risk factor modification in diabetes, cigarette smoking cessation, and physical activity/weight loss, while also showing promise in multi risk factor modification via cardiac rehabilitation.

Summary: Evidence supports efficacy of mHealth in a variety of applications for CVD prevention and management, but continued work is needed for further validation and scaling. Future directions will focus on platform optimization, data and sensor consolidation, and clinical workflow integration. Barriers include application heterogeneity, lack of reimbursement structures, and inequitable access to technology. Policies to promote access to technology will be critical to evidence-based mHealth technologies reaching diverse populations and advancing health equity.
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http://dx.doi.org/10.1097/HCO.0000000000000891DOI Listing
September 2021

Understanding myocardial infarction trends during the early COVID-19 pandemic: an infodemiology study.

Intern Med J 2021 08 2;51(8):1328-1331. Epub 2021 Jul 2.

Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

During the first months of the coronavirus disease 2019 (COVID-19) pandemic in early 2020, Google Trends data in the United States showed a strong increase in search query frequency for chest pain symptoms despite a concurrent decrease in search interest for myocardial infarction. This suggests a reduced attention to acute coronary syndrome (ACS) and chest pain as its main symptom during this time period. These observations could help explain why cardiovascular mortality rose dramatically despite a strong decrease in hospitalisation rates for ACS.
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http://dx.doi.org/10.1111/imj.15399DOI Listing
August 2021

Sociodemographic Characteristics Predicting Digital Health Intervention Use After Acute Myocardial Infarction.

J Cardiovasc Transl Res 2021 May 17. Epub 2021 May 17.

Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Increasing evidence suggests that digital health interventions (DHIs) are an effective tool to reduce hospital readmissions by improving adherence to guideline-directed therapy. We investigated whether sociodemographic characteristics influence use of a DHI targeting 30-day readmission reduction after acute myocardial infarction (AMI). Covariates included age, sex, race, native versus loaner iPhone, access to a Bluetooth-enabled blood pressure monitor, and disease severity as marked by treatment with CABG. Age, sex, and race were not significantly associated with DHI use before or after covariate adjustment (fully adjusted OR 0.98 (95%CI: 0.95-1.01), 0.6 (95%CI: 0.29-1.25), and 1.22 (95% CI: 0.60-2.48), respectively). Being married was associated with high DHI use (OR 2.12; 95% CI 1.02-4.39). Our findings suggest that DHIs may have a role in achieving equity in cardiovascular health given similar use by age, sex, and race. The presence of a spouse, perhaps a proxy for enhanced caregiver support, may encourage DHI use.
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http://dx.doi.org/10.1007/s12265-021-10098-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127845PMC
May 2021

A Mobile Health Intervention to Increase Physical Activity in Pulmonary Arterial Hypertension.

Chest 2021 Sep 17;160(3):1042-1052. Epub 2021 Apr 17.

Division of Cardiovascular Medicine and Vanderbilt Translational and Clinical Cardiovascular Research Center, Nashville, TN. Electronic address:

Background: Supervised exercise training improves outcomes in patients with pulmonary arterial hypertension (PAH). The effect of an unsupervised activity intervention has not been tested.

Research Question: Can a text-based mobile health intervention increase step counts in patients with PAH?

Study Design And Methods: We performed a randomized, parallel arm, single-blind clinical trial. We randomized patients to usual care or a text message-based intervention for 12 weeks. The intervention arm received three automated text messages per day with real-time step count updates and encouraging messages rooted in behavioral change theory. Individual step targets increased by 20% every 4 weeks. The primary end point was mean week 12 step counts. Secondary end points included the 6-min walk test, quality of life, right ventricular function, and body composition.

Results: Among 42 randomized participants, the change in raw steps between baseline and week 12 was higher in the intervention group (1,409 steps [interquartile range, -32 to 2,220] vs -149 steps [interquartile range, -1,010 to 735]; P = .02), which persisted after adjustment for age, sex, baseline step counts, and functional class (model estimated difference, 1,250 steps; P = .03). The intervention arm took a higher average number of steps on all days between days 9 and 84 (P < .05, all days). There was no difference in week 12 six-minute walk distance. Analysis of secondary end points suggested improvements in the emPHasis-10 score (adjusted change, -4.2; P = .046), a reduction in visceral fat volume (adjusted change, -170 mL; P = .023), and nearly significant improvement in tricuspid annular plane systolic excursion (model estimated difference, 1.2 mm; P = .051).

Interpretation: This study demonstrated the feasibility of an automated text message-based intervention to increase physical activity in patients with PAH. Additional studies are warranted to examine the effect of the intervention on clinical outcomes.

Clinical Trial Registration: ClinicalTrials.gov; No. NCT03069716; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.04.012DOI Listing
September 2021

Coronary heart disease risk: Low-density lipoprotein and beyond.

Trends Cardiovasc Med 2021 Apr 17. Epub 2021 Apr 17.

Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD, USA; Community Hospital General Medical Center, Sterling, IL, USA. Electronic address:

Coronary heart disease (CHD) is the leading cause of morbidity and mortality world-wide and has been characterized as a chronic immunoinflammatory, fibroproliferative disease fueled by lipids. Great advances have been made in elucidating the complex mechanistic interactions among risk factors associated with CHD, yielding abundant success towards preventive measures and the development of pharmaceuticals to prevent and treat CHD via attenuation of lipoprotein-mediated risk. However, significant residual risk remains. Several potentially modifiable CHD risk factors ostensibly contributing to this residual risk have since come to the fore, including systemic inflammation, diabetes mellitus, high-density lipoprotein, plasma triglycerides (TG) and remnant lipoproteins (RLP), lipoprotein(a) (Lp[a]), and vascular endothelial dysfunction (ED). Herein, we summarize the body of evidence implicating each of these risk factors in residual CHD risk.
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http://dx.doi.org/10.1016/j.tcm.2021.04.002DOI Listing
April 2021

Smart wearable devices in cardiovascular care: where we are and how to move forward.

Nat Rev Cardiol 2021 08 4;18(8):581-599. Epub 2021 Mar 4.

Department of Medical Education, Weill Cornell Medicine, Doha, Qatar.

Technological innovations reach deeply into our daily lives and an emerging trend supports the use of commercial smart wearable devices to manage health. In the era of remote, decentralized and increasingly personalized patient care, catalysed by the COVID-19 pandemic, the cardiovascular community must familiarize itself with the wearable technologies on the market and their wide range of clinical applications. In this Review, we highlight the basic engineering principles of common wearable sensors and where they can be error-prone. We also examine the role of these devices in the remote screening and diagnosis of common cardiovascular diseases, such as arrhythmias, and in the management of patients with established cardiovascular conditions, for example, heart failure. To date, challenges such as device accuracy, clinical validity, a lack of standardized regulatory policies and concerns for patient privacy are still hindering the widespread adoption of smart wearable technologies in clinical practice. We present several recommendations to navigate these challenges and propose a simple and practical 'ABCD' guide for clinicians, personalized to their specific practice needs, to accelerate the integration of these devices into the clinical workflow for optimal patient care.
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http://dx.doi.org/10.1038/s41569-021-00522-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931503PMC
August 2021

Multidisciplinary prevention and management strategies for colorectal cancer and cardiovascular disease.

Eur J Intern Med 2021 May 18;87:3-12. Epub 2021 Feb 18.

Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address:

Colorectal cancer (CRC) and cardiovascular disease (CVD) are leading causes of morbidity and mortality worldwide. Their numerous shared and modifiable risk factors underscore the importance of effective prevention strategies for these largely preventable diseases. Conventionally regarded as separate disease entities, clear pathophysiological links and overlapping risk factors represent an opportunity for synergistic collaborative efforts of oncologists and cardiologists. In addition, current CRC treatment approaches can exert cardiotoxicity and thus increase CVD risk. Given the complex interplay of both diseases and increasing numbers of CRC survivors who are at increased risk for CVD, multidisciplinary cardio-oncological approaches are warranted for optimal patient care from primary prevention to acute disease treatment and long-term surveillance.
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http://dx.doi.org/10.1016/j.ejim.2021.02.003DOI Listing
May 2021

Summarizing 2019 in Cardiovascular Prevention Using the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease's 'ABC's Approach.

Am J Prev Cardiol 2020 Jun 6;2. Epub 2020 Jun 6.

The Ciccarone Center for the Prevention of Cardiovascular Disease, The Johns Hopkins Medical Institutions, Baltimore, MD.

In 2019, Preventive Cardiology welcomed many exciting discoveries that improve our ability to reduce the burden of cardiovascular disease (CVD) nationwide. Not only did 2019 further clarify how various environmental exposures and innate and acquired risk factors contribute to the development of CVD, but it also provided new guidelines and therapeutics to more effectively manage existing CVD. Cardiovascular disease prevention requires the prioritization of early and effective detection of CVD in order to implement aggressive lifestyle and pharmacologic therapies, which can slow, halt, or even reverse the progression of the disease. To help streamline and simplify the process of CVD prevention, The Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease has historically adopted an 'ABC' approach, which focuses on optimizing individual CVD risk through lifestyle, behavioral, and pharmacologic interventions. Given the practice changing research and innovation from the past year, this article intends to summarize the Ciccarone Center's key takeaways from CVD prevention in 2019 utilizing our expanded 'ABC' approach.
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http://dx.doi.org/10.1016/j.ajpc.2020.100027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874982PMC
June 2020

Heart Rate Measurements in Patients with Obstructive Sleep Apnea and Atrial Fibrillation: Prospective Pilot Study Assessing Apple Watch's Agreement With Telemetry Data.

JMIR Cardio 2021 Feb 8;5(1):e18050. Epub 2021 Feb 8.

School of Medicine, Johns Hopkins University, Baltimore, MD, United States.

Background: Patients with obstructive sleep apnea (OSA) are at a higher risk for atrial fibrillation (AF). Consumer wearable heart rate (HR) sensors may be a means for passive HR monitoring in patients with AF.

Objective: The aim of this study was to assess the Apple Watch's agreement with telemetry in measuring HR in patients with OSA in AF.

Methods: Patients with OSA in AF were prospectively recruited prior to cardioversion/ablation procedures. HR was sampled every 10 seconds for 60 seconds using telemetry and an Apple Watch concomitantly. Agreement of Apple Watch with telemetry, which is the current gold-standard device for measuring HR, was assessed using mixed effects limits agreement and Lin's concordance correlation coefficient.

Results: A total of 20 patients (mean 66 [SD 6.5] years, 85% [n=17] male) participated in this study, yielding 134 HR observations per device. Modified Bland-Altman plot revealed that the variability of the paired difference of the Apple Watch compared with telemetry increased as the magnitude of HR measurements increased. The Apple Watch produced regression-based 95% limits of agreement of 27.8 - 0.3 × average HR - 15.0 to 27.8 - 0.3 × average HR + 15.0 beats per minute (bpm) with a mean bias of 27.8 - 0.33 × average HR bpm. Lin's concordance correlation coefficient was 0.88 (95% CI 0.85-0.91), suggesting acceptable agreement between the Apple Watch and telemetry.

Conclusions: In patients with OSA in AF, the Apple Watch provided acceptable agreement with HR measurements by telemetry. Further studies with larger sample populations and wider range of HR are needed to confirm these findings.
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http://dx.doi.org/10.2196/18050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411424PMC
February 2021

Digital Health Interventions for Cardiac Rehabilitation: Systematic Literature Review.

J Med Internet Res 2021 02 8;23(2):e18773. Epub 2021 Feb 8.

Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. Despite strong evidence supporting the benefits of cardiac rehabilitation (CR), over 80% of eligible patients do not participate in CR. Digital health technologies (ie, the delivery of care using the internet, wearable devices, and mobile apps) have the potential to address the challenges associated with traditional facility-based CR programs, but little is known about the comprehensiveness of these interventions to serve as digital approaches to CR. Overall, there is a lack of a systematic evaluation of the current literature on digital interventions for CR.

Objective: The objective of this systematic literature review is to provide an in-depth analysis of the potential of digital health technologies to address the challenges associated with traditional CR. Through this review, we aim to summarize the current literature on digital interventions for CR, identify the key components of CR that have been successfully addressed through digital interventions, and describe the gaps in research that need to be addressed for sustainable and scalable digital CR interventions.

Methods: Our strategy for identifying the primary literature pertaining to CR with digital solutions (defined as technology employed to deliver remote care beyond the use of the telephone) included a consultation with an expert in the field of digital CR and searches of the PubMed (MEDLINE), Embase, CINAHL, and Cochrane databases for original studies published from January 1990 to October 2018.

Results: Our search returned 31 eligible studies, of which 22 were randomized controlled trials. The reviewed CR interventions primarily targeted physical activity counseling (31/31, 100%), baseline assessment (30/31, 97%), and exercise training (27/31, 87%). The most commonly used modalities were smartphones or mobile devices (20/31, 65%), web-based portals (18/31, 58%), and email-SMS (11/31, 35%). Approximately one-third of the studies addressed the CR core components of nutrition counseling, psychological management, and weight management. In contrast, less than a third of the studies addressed other CR core components, including the management of lipids, diabetes, smoking cessation, and blood pressure.

Conclusions: Digital technologies have the potential to increase access and participation in CR by mitigating the challenges associated with traditional, facility-based CR. However, previously evaluated interventions primarily focused on physical activity counseling and exercise training. Thus, further research is required with more comprehensive CR interventions and long-term follow-up to understand the clinical impact of digital interventions.
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http://dx.doi.org/10.2196/18773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899799PMC
February 2021

User Engagement With Smartphone Apps and Cardiovascular Disease Risk Factor Outcomes: Systematic Review.

JMIR Cardio 2021 Feb 3;5(1):e18834. Epub 2021 Feb 3.

Johns Hopkins University School of Nursing, Baltimore, MD, United States.

Background: The use of mobile health (mHealth) interventions, including smartphone apps, for the prevention of cardiovascular disease (CVD) has demonstrated mixed results for obesity, hypercholesterolemia, diabetes, and hypertension management. A major factor attributing to the variation in mHealth study results may be mHealth user engagement.

Objective: This systematic review aims to determine if user engagement with smartphone apps for the prevention and management of CVD is associated with improved CVD health behavior change and risk factor outcomes.

Methods: We conducted a comprehensive search of PubMed, CINAHL, and Embase databases from 2007 to 2020. Studies were eligible if they assessed whether user engagement with a smartphone app used by an individual to manage his or her CVD risk factors was associated with the CVD health behavior change or risk factor outcomes. For eligible studies, data were extracted on study and sample characteristics, intervention description, app user engagement measures, and the relationship between app user engagement and the CVD risk factor outcomes. App user engagement was operationalized as general usage (eg, number of log-ins or usage days per week) or self-monitoring within the app (eg, total number of entries made in the app). The quality of the studies was assessed.

Results: Of the 24 included studies, 17 used a randomized controlled trial design, 4 used a retrospective analysis, and 3 used a single-arm pre- and posttest design. Sample sizes ranged from 55 to 324,649 adults, with 19 studies recruiting participants from a community setting. Most of the studies assessed weight loss interventions, with 6 addressing additional CVD risk factors, including diabetes, sleep, stress, and alcohol consumption. Most of the studies that assessed the relationship between user engagement and reduction in weight (9/13, 69%), BMI (3/4, 75%), body fat percentage (1/2, 50%), waist circumference (2/3, 67%), and hemoglobin A (3/5, 60%) found statistically significant results, indicating that greater app user engagement was associated with better outcomes. Of 5 studies, 3 (60%) found a statistically significant relationship between higher user engagement and an increase in objectively measured physical activity. The studies assessing the relationship between user engagement and dietary and diabetes self-care behaviors, blood pressure, and lipid panel components did not find statistically significant results.

Conclusions: Increased app user engagement for prevention and management of CVD may be associated with improved weight and BMI; however, only a few studies assessed other outcomes, limiting the evidence beyond this. Additional studies are needed to assess user engagement with smartphone apps targeting other important CVD risk factors, including dietary behaviors, hypercholesterolemia, diabetes, and hypertension. Further research is needed to assess mHealth user engagement in both inpatient and outpatient settings to determine the effect of integrating mHealth interventions into the existing clinical workflow and on CVD outcomes.
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http://dx.doi.org/10.2196/18834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411427PMC
February 2021

Conventional and Novel Lipid Measures and Risk of Peripheral Artery Disease.

Arterioscler Thromb Vasc Biol 2021 03 28;41(3):1229-1238. Epub 2021 Jan 28.

Department of Medicine, Baylor College of Medicine, Houston, TX (C.M.B., R.C.H.).

Objective: The aim of this study was to comprehensively assess the association of multiple lipid measures with incident peripheral artery disease (PAD). Approach and Results: We used Cox proportional hazards models to characterize the associations of each of the fasting lipid measures (total cholesterol, LDL-C [low-density lipoprotein cholesterol], HDL-C [high-density lipoprotein cholesterol], triglycerides, RLP-C [remnant lipoprotein cholesterol], LDL-TG [LDL-triglycerides], sdLDL-C [small dense LDL-C], and Apo-E-HDL [Apo-E-containing HDL-C]) with incident PAD identified by pertinent () hospital discharge codes (eg, 440.2) among 8330 Black and White ARIC (Atherosclerosis Risk in Communities) participants (mean age 62.8 [SD 5.6] years) free of PAD at baseline (1996-1998) through 2015. Since lipid traits are biologically correlated to each other, we also conducted principal component analysis to identify underlying components for PAD risk. There were 246 incident PAD cases with a median follow-up of 17 years. After accounting for potential confounders, the following lipid measures were significantly associated with PAD (hazard ratio per 1-SD increment [decrement for HDL-C and Apo-E-HDL]): triglycerides, 1.21 (95% CI, 1.08-1.36); RLP-C, 1.18 (1.08-1.29); LDL-TG, 1.18 (1.05-1.33); HDL-C, 1.39 (1.16-1.67); and Apo-E-HDL, 1.27 (1.07-1.51). The principal component analysis identified 3 components (1: mainly loaded by triglycerides, RLP-C, LDL-TG, and sdLDL-C; 2: by HDL-C and Apo-E-HDL; and 3: by LDL-C and RLP-C). Components 1 and 2 showed independent associations with incident PAD.

Conclusions: Triglyceride-related and HDL-related lipids were independently associated with incident PAD, which has implications on preventive strategies for PAD. However, none of the novel lipid measures outperformed conventional ones. Graphic Abstract: A graphic abstract is available for this article.
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http://dx.doi.org/10.1161/ATVBAHA.120.315828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188625PMC
March 2021

Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association.

Circulation 2021 Feb 27;143(8):e254-e743. Epub 2021 Jan 27.

Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).

Methods: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease.

Results: Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics.

Conclusions: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
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http://dx.doi.org/10.1161/CIR.0000000000000950DOI Listing
February 2021

Factoring in ANGPTL3 When LDL Is Refractory.

Authors:
Seth S Martin

N Engl J Med 2020 12;383(24):2385-2386

From the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore.

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http://dx.doi.org/10.1056/NEJMe2032798DOI Listing
December 2020

Life's Simple 7 and Nonalcoholic Fatty Liver Disease: The Multiethnic Study of Atherosclerosis.

Am J Med 2021 04 5;134(4):519-525. Epub 2020 Dec 5.

Preventive Cardiology, Houston Methodist DeBakey Cardiology Associates, Houston Tex.

Background: The American Heart Association (AHA) has defined Life's Simple 7 (LS7) as a measure of overall cardiovascular health . Nonalcoholic fatty liver disease (NAFLD) has been involved as a risk factor for cardiovascular disease. We evaluated the association between LS7 and NAFLD.

Methods: We evaluated participants form the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Cardiovascular health score was calculated from the Life's Simple 7 metrics. A score of 0-8 was considered inadequate, 9-10 average, and 11-14 optimal. NAFLD was defined using noncontrast cardiac computed tomography (CT) and a liver/spleen attenuation ratio (L/S) < 1. Multivariable regression were performed to evaluate the association.

Results: Our cross-sectional analysis of 3901 participants showed 19% (n = 747) had optimal cardiovascular health, 33% (n = 1270) had average, and 48% (n = 1884) had inadequate. White participants were most likely to have an optimal score (51%, n = 378), whereas African American participants had the lowest proportion with optimal scores (16%, n = 120; P < 0.001). The overall prevalence of NAFLD was 18% with a distribution of 7%, 14%, and 25% in the optimal, average, and inadequate score categories, respectively (P < 0.001). Adjusted for risk factors, average and optimal health categories had lower odds of NAFLD compared to those with inadequate scores: odds ratio for average, 0.44 (95% confidence interval 0.36-0.54); optimal, odds ratio 0.19 (95% confidence interval 0.14-0.26). This association was similar across gender, race and age groups.

Conclusion: A more favorable cardiovascular health score was associated with a lower prevalence of NAFLD. This study may suggest a potential of Life's Simple 7 in the prevention of liver disease.
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http://dx.doi.org/10.1016/j.amjmed.2020.09.023DOI Listing
April 2021

Effects of Omega-3 Fatty Acids on Major Adverse Cardiovascular Events: What Matters Most: the Drug, the Dose, or the Placebo?

JAMA 2020 12;324(22):2262-2264

Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1001/jama.2020.22387DOI Listing
December 2020

Importance of the triglyceride level in identifying patients with a Type III Hyperlipoproteinemia phenotype using the ApoB algorithm.

J Clin Lipidol 2021 Jan-Feb;15(1):104-115.e9. Epub 2020 Oct 20.

Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology, and Clinical Research, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address:

Background: Hyperlipoproteinemia Type III (HLP3), also known as dysbetalipoproteinemia, is defined by cholesterol and triglyceride (TG) enriched remnant lipoprotein particles (RLP). The gold standard for diagnosis requires demonstration of high remnant lipoprotein particle cholesterol (RLP-C) by serum ultracentrifugation (UC), which is not readily available in daily practice. The apoB algorithm can identify HLP3 using total cholesterol (TC), plasma triglyceride (TG), and apoB. However, the optimal TG cutoff is unknown.

Objective: We analyzed apoB algorithm defined HLP3 at different TG levels to optimize the TG cutoff for the algorithm.

Methods: 128,485 UC lipid profiles in the Very Large Database of Lipids (VLDbL) were analyzed. RLP-C was assessed at TG ≥ 133 mg/dL, ≥175 mg/dL, ≥200 mg/dL, and ≥ 250 mg/dL. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and prevalence adjusted and bias-adjusted kappa (PABAK) were calculated against UC Criterion (VLDL-C/TG ≥ 0.25) for HLP3.

Results: The median age (IQR) was 57 years (46-68). 45% were men, 20.1% had diabetes, and 25.5% had hypertension. The median RLP-C level for the TG cutoffs (mg/dL) of ≥ 133, ≥ 175, ≥ 200, and ≥ 250 were 34, 43, 50, and 62 mg/dL, respectively, compared to 67 mg/dL in UC defined HLP3. TG ≥ 133 mg/dL yielded optimal results (Sn 29.5%, Sp 98.5%, PABAK 0.96, PPV 13.6%, NPV 99.4%).

Conclusion: TG ≥ 133 mg/dL allows for high sensitivity in screening for HLP3. Higher TG cutoffs may identify more severe HLP3 phenotypes, but with a large loss in sensitivity for HLP3.
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http://dx.doi.org/10.1016/j.jacl.2020.09.011DOI Listing
October 2020

Accuracy of New Equation to Calculate Low-Density Lipoprotein Cholesterol.

JAMA Cardiol 2021 Jan;6(1):121-122

Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1001/jamacardio.2020.4411DOI Listing
January 2021

Early blood pressure assessment after acute myocardial infarction: Insights using digital health technology.

Am J Prev Cardiol 2020 Sep 17;3:100089. Epub 2020 Sep 17.

Digital Health Innovation Laboratory, Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD, USA.

Objective: There is rising interest in digital health in preventive cardiology, particularly for blood pressure (BP) management. In a digital health study of early BP assessment following acute myocardial infarction (AMI), we sought to examine feasibility and the (1) proportion of post-AMI patients with controlled BP and hypotension, and (2) association between prior cardiovascular disease (CVD) and BP post-AMI.

Methods: In this substudy of the parent Myocardial infarction, COmbined-device, Recovery Enhancement (MiCORE) study, type 1 AMI patients were enrolled between October 2017 and April 2019. Participants self-monitored their BP through 30 days after hospital discharge using an FDA-approved wireless BP monitor connected with a smartphone application. Linear mixed-effects models assessed the association between prior CVD and BP trajectory post-discharge, adjusting for antihypertensive medications and a propensity score inclusive of CVD risk factors.

Results: Sixty-eight AMI patients (mean age 58 ​± ​10 years, 75% male, 68% white race, 68% history of hypertension, 24% prior CVD) provided 2638 measurements over 30 days. The percentage of BP control <130/80 ​mmHg was 59.6% (95% CI: 54.3-64.9%) and <140/90 ​mmHg was 83.7% (95% CI: 80.3-87.2%). The percentage of systolic BP ​<90 ​mmHg was 1.1% (95% CI: 0.17-2.0%) and the percentage of diastolic BP ​<60 ​mmHg was 3.9% (95% CI: 2.6-5.2%). Prior CVD was associated with 12.2 ​mmHg higher mean daily systolic BP during admission (95% CI: 3.5-20.9 ​mmHg), which persisted over follow-up. There was no association between prior CVD and diastolic BP.

Conclusion: The digital health program was feasible and ~40% of post-AMI patients who engaged in it had uncontrolled BP according to recent guideline cutpoints, while hypotension occurred rarely. The gap in BP control was especially large in patients in whom AMI represented recurrent CVD. These data suggest an opportunity for more aggressive secondary prevention early after MI as care models integrate digital health.
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http://dx.doi.org/10.1016/j.ajpc.2020.100089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497394PMC
September 2020

Modern prevalence of dysbetalipoproteinemia (Fredrickson-Levy-Lees type III hyperlipoproteinemia).

Arch Med Sci 2020 2;16(5):993-1003. Epub 2019 Aug 2.

Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Introduction: Dysbetalipoproteinaemia (HLP3) is a disorder characterized by excess cholesterol-enriched, triglyceride-rich lipoprotein remnants in genetically predisposed individuals that powerfully promote premature cardiovascular disease if untreated. The current prevalence of HLP3 is largely unknown.

Material And Methods: We performed cross-sectional analysis of 128,485 U.S. adults from the Very Large Database of Lipids (VLDbL), using four algorithms to diagnose HLP3 employing three Vertical Auto Profile ultracentrifugation (UC) criteria and a previously described apolipoprotein B (apoB) method. We evaluated 4,926 participants from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) with the apoB method. We examined demographic and lipid characteristics stratified by presence of HLP3 and evaluated lipid characteristics in those with HLP3 phenotype discordance and concordance as determined by apoB and originally defined UC criteria 1.

Results: In U.S. adults in VLDbL and NHANES, a 1.7-2.0% prevalence is observed for HLP3 with the novel apoB method as compared to 0.2-0.8% prevalence in VLDbL via UC criteria 1-3. Participants who were both apoB and UC criteria HLP3 positive had higher remnant particles as well as more elevated triglyceride/apoB and total cholesterol/apoB ratios (all < 0.001) than those who were apoB method positive and UC criteria 1 negative.

Conclusions: HLP3 may be more prevalent than historically and clinically appreciated. The apoB method increases HLP3 identification via inclusion of milder phenotypes. Further work should evaluate the clinical implications of HLP3 diagnosis at various lipid algorithm cut-points to evaluate the ideal standard in the modern era.
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http://dx.doi.org/10.5114/aoms.2019.86972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444722PMC
August 2019
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