Publications by authors named "Roger S Blumenthal"

575 Publications

Inflammation, atrial fibrillation, and the potential role for colchicine therapy.

Heart Rhythm O2 2021 Jun 2;2(3):298-303. Epub 2021 Apr 2.

Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland.

Increasing evidence suggests that the "NACHT-LRR and PYD domain-containing protein 3" (NLRP3) inflammasome plays an important role in atherosclerotic cardiovascular disease (ASCVD). Recent preclinical evidence has suggested that the NLRP3 inflammasome may play a prominent role in the pathogenesis of atrial fibrillation (AF). As such, the therapies that have shown efficacy in reducing ASCVD events may also prove beneficial in AF. In this article, we review the findings that implicate the NLRP3 inflammasome in the pathogenesis of AF, discuss existing evidence behind the use of anti-inflammatory agents for AF, and discuss the future role that colchicine and other anti-inflammatory agents may play in the prevention and treatment of AF.
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http://dx.doi.org/10.1016/j.hroo.2021.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322795PMC
June 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

Mental health disorders among patients with acute myocardial infarction in the United States.

Am J Prev Cardiol 2021 Mar 8;5:100133. Epub 2020 Dec 8.

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

Objective: To assess the prevalence, temporal trends and sex- and racial/ethnic differences in the burden of mental health disorders (MHD) and outcomes among patients with myocardial infarction (MI) in the United States.

Methods: Using the National Inpatient Sample Database, we evaluated a contemporary cohort of patients hospitalized for acute MI in the United States over 10 years period from 2008 to 2017. We used multivariable logistic regression analysis for in-hospital outcomes, yearly trends and estimated annual percent change (APC) in odds of MHD among MI patients.

Results: We included a total sample of 6,117,804 hospitalizations for MI (ST elevation MI in 30.4%), with a mean age of 67.2 ​± ​0.04 years and 39% females. Major depression (6.2%) and anxiety disorders (6.0%) were the most common MHD, followed by bipolar disorder (0.9%), schizophrenia/psychotic disorders (0.8%) and post-traumatic stress disorder (PTSD) (0.3%). Between 2008 and 2017, the prevalences significantly increased for major depression (4.7%-7.4%, APC +6.2%,  ​< ​.001), anxiety disorders (3.2%-8.9%, APC +13.5%,  ​< ​.001), PTSD (0.2%-0.6%, +12.5%,  ​< ​.001) and bipolar disorder (0.7%-1.0%, APC +4.0%,  ​< ​.001). Significant sex- and racial/ethnic-differences were also noted. Major depression, bipolar disorder or schizophrenia/psychotic disorders were associated with a lower likelihood of coronary revascularization.

Conclusion: MHD are common among patients with acute MI and there was a concerning increase in the prevalence of major depression, bipolar disorder, anxiety disorders and PTSD over this 10-year period. Focused mental health interventions are warranted to address the increasing burden of comorbid MHD among acute MI.
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http://dx.doi.org/10.1016/j.ajpc.2020.100133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315415PMC
March 2021

Same evidence, varying viewpoints: Three questions illustrating important differences between United States and European cholesterol guideline recommendations.

Am J Prev Cardiol 2020 Dec 13;4:100117. Epub 2020 Nov 13.

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

In 2018, the AHA/ACC Multisociety Guideline on the Management of Blood Cholesterol was released. Less than one year later, the 2019 ESC/EAS Dyslipidemia Guideline was published. While both provide important recommendations for managing atherosclerotic cardiovascular disease (ASCVD) risk through lipid management, differences exist. Prior to the publication of both guidelines, important randomized clinical trial data emerged on non-statin lipid lowering therapy and ASCVD risk reduction. To illustrate important differences in guideline recommendations, we use this data to help answer three key questions: 1) Are ASCVD event rates similar in high-risk primary and stable secondary prevention? 2) Does imaging evidence of subclinical atherosclerosis justify aggressive use of statin and non-statin therapy (if needed) to reduce LDL-C levels below 55 ​mg/dL as recommended in the European Guideline? 3) Do LDL-C levels below 70 ​mg/dL achieve a large absolute risk reduction in secondary ASCVD prevention? The US guideline prioritizes both the added efficacy and cost implications of non-statin therapy, which limits intensive therapy to individuals with the highest risk of ASCVD. The European approach broadens the eligibility criteria by incorporating goals of therapy in both primary and secondary prevention. The current cost and access constraints of healthcare worldwide, especially amidst a COVID-19 pandemic, makes the European recommendations more challenging to implement. By restricting non-statin therapy to a subgroup of high- and, in particular, very high-risk individuals, the US guideline provides primary and secondary ASCVD prevention recommendations that are more affordable and attainable. Ultimately, finding a common ground for both guidelines rests on our ability to design trials that assess cost-effectiveness in addition to efficacy and safety.
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http://dx.doi.org/10.1016/j.ajpc.2020.100117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315633PMC
December 2020

Age-specific differences in patient reported outcomes among adults with atherosclerotic cardiovascular disease: Medical expenditure panel survey 2006-2015.

Am J Prev Cardiol 2020 Sep 27;3:100083. Epub 2020 Aug 27.

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

Objective: The prevalence of atherosclerotic cardiovascular disease (ASCVD) in younger adults has increased over the past decade. However, it is less well established whether patient reported outcomes differ between younger and older adults with ASCVD. We sought to evaluate age-specific differences in patient reported outcomes among adults with ASCVD.

Methods: This was a retrospective cross-sectional survey study. We used data from the 2006-2015 Medical Expenditure Panel Survey (MEPS), a nationally representative sample of the United States population. Adults ≥18 years with a diagnosis of ASCVD, ascertained by ICD9 codes or self-reported data, were included. Logistic regression was used to compare self-reported patient-clinician communication, patient satisfaction, perception of health, emergency department (ED) visits, and use of preventive medications (aspirin and statins) by age category [Young: 18-44, Middle: 45-64, Older: ≥65 years]. We used two-part econometric modeling to evaluate age-specific annual healthcare expenditure.

Results: There were 21,353 participants included. Over 9000 (42.6%-weighted) of the participants were young or middle aged, representing ~9.9 million adults aged <65 years with ASCVD nationwide. Compared with older adults, middle-aged and young adults with ASCVD were more likely to report poor patient-clinician communication [OR 1.73 (95% CI 1.28-2.33) and 2.49 (1.76-3.51), respectively], poor healthcare satisfaction, and poor perception of health status, have increased ED utilization and were also less likely to be using aspirin and statins. The mean annual healthcare expenditure was highest among middle-aged adults [$10,798 (95% CI, $10,012 to $11,583)].

Conclusion: Compared with older adults, younger adults with ASCVD were more likely to report poor patient experience and poor health status and less likely to be using preventive medications. More effort needs to be geared towards understanding the age-specific differences in healthcare quality and delivery to improve outcomes among high-risk young adults with ASCVD.
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http://dx.doi.org/10.1016/j.ajpc.2020.100083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315315PMC
September 2020

Duration of Diabetes and Incident Heart Failure: The ARIC (Atherosclerosis Risk In Communities) Study.

JACC Heart Fail 2021 Aug;9(8):594-603

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Objectives: This study assessed the association of diabetes duration with incident heart failure (HF).

Background: Diabetes increases HF risk. However, the independent effect of diabetes duration on incident HF is unknown.

Methods: We included 9,734 participants (mean age 63 years, 58% women, 22% Black) at ARIC (Atherosclerosis Risk In Communities) Visit 4 (1996-1998) without HF or coronary heart disease. We calculated diabetes duration at Visit 4 (baseline), utilizing diabetes status at the first 4 ARIC visits spaced 3 years apart, and self-reported diagnosis date for those with diabetes diagnosed before Visit 1. We used Cox regression to estimate associations of diabetes duration with incident HF, accounting for intercurrent coronary heart disease and other risk factors. We performed analyses stratified by age (<65 years or ≥65 years), race, sex, and glycemic control (hemoglobin A [HbA] consistently <7%, vs HbA ≥7%), with tests for interaction.

Results: Over 22.5 years of follow-up, there were 1,968 HF events. Compared to those without diabetes, HF risk rose with longer diabetes duration, with the highest risk among those with ≥15 y diabetes duration (HR: 2.82; 95% CI: 2.25-3.63). Each 5-year increase in diabetes duration was associated with a 17% (95% CI: 11-22) relative increase in HF risk. Similar results were observed across HF subtypes. The HF and diabetes duration associations were stronger among those aged <65 years, those with HbA ≥7%, those with a body mass index ≥30 kg/m, women, and Blacks (all P interactions <0.05).

Conclusions: Delaying diabetes onset may augment HF prevention efforts, and therapies to improve HF outcomes might target those with long diabetes duration.
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http://dx.doi.org/10.1016/j.jchf.2021.06.005DOI Listing
August 2021

Update on the omega-3 fatty acid trial landscape: A narrative review with implications for primary prevention.

J Clin Lipidol 2021 Jun 15. Epub 2021 Jun 15.

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

Residual risk mediated by hypertriglyceridemia among statin-treated individuals is an important clinical and public health challenge. Niacin, fibrates and omega-3 FA are three classes of non-statin agents with demonstrated TG-lowering effects. Randomized controlled trials of niacin and fibrates have been consistently negative, but the trial landscape for two key sources of omega-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is more complex. Clinical trials evaluating omega-3 FA can be differentiated into those that studied mixed formulations (EPA + DHA) and those that studied EPA alone. Those assessing the impact of mixed formulations have not consistently demonstrated CVD risk reduction, whereas trials of EPA alone have been successful. Two recent trials of mixed formulations - STRENGTH (Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia) and OMEMI (Omega-3 fatty acids in Elderly patients with Myocardial Infarction) - studied contemporarily treated patients with mixed EPA + DHA formulations at higher doses than before and showed no benefit, thus adding valuable information to our overall understanding of this evolving therapeutic class. In this review, we contextualize the findings of STRENGTH and OMEMI within the existing omega-3 FA clinical trial landscape and look ahead to how future trials can inform existing knowledge gaps, particularly with regards to the applicability of these agents within the primary prevention realm.
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http://dx.doi.org/10.1016/j.jacl.2021.06.004DOI Listing
June 2021

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

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

Coronary Artery Disease Evaluation and Management Considerations for High Risk Occupations: Commercial Vehicle Drivers and Pilots.

Circ Cardiovasc Interv 2021 Jun 7;14(6):e009950. Epub 2021 Jun 7.

Division of Cardiology, Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD (A.A.-Z., R.S.B.).

Optimal treatment of stable ischemic heart disease for those in the transportation industry is considered in the context of the individual's health, as well as with the perspective that sudden impairment could have catastrophic consequences for others. This article focuses on two high risk occupations that one may encounter in practice: commercial motor vehicle drivers and commercial pilots. This article discusses coronary heart disease in patients in high risk occupations and covers current guideline recommendations for screening, treatment, and secondary prevention. The importance of the complimentary perspectives of the regulatory agency, medical examiners, physicians, and pilot or driver are considered in this narrative review, as are considerations for future guideline updates.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009950DOI Listing
June 2021

Coronary artery calcium is associated with increased risk for lung and colorectal cancer in men and women: the Multi-Ethnic Study of Atherosclerosis (MESA).

Eur Heart J Cardiovasc Imaging 2021 Jun 4. Epub 2021 Jun 4.

Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Blalock 524D1, 600 N Wolfe St, Baltimore, MD 21287, USA.

Aims: This study explored the association of coronary artery calcium (CAC) with incident cancer subtypes in the Multi-Ethnic Study of Atherosclerosis (MESA). CAC is an established predictor of cardiovascular disease (CVD), with emerging data also supporting independent predictive value for cancer. The association of CAC with risk for individual cancer subtypes is unknown.

Methods And Results: We included 6271 MESA participants, aged 45-84 and without known CVD or self-reported history of cancer. There were 777 incident cancer cases during mean follow-up of 12.9 ± 3.1 years. Lung and colorectal cancer (186 cases) were grouped based on their strong overlap with CVD risk profile; prostate (men) and ovarian, uterine, and breast cancer (women) were considered as sex-specific cancers (in total 250 cases). Incidence rates and Fine and Gray competing risks models were used to assess relative risk of cancer-specific outcomes stratified by CAC groups or Log(CAC+1). The mean age was 61.7 ± 10.2 years, 52.7% were women, and 36.5% were White. Overall, all-cause cancer incidence increased with CAC scores, with rates per 1000 person-years of 13.1 [95% confidence interval (CI): 11.7-14.7] for CAC = 0 and 35.8 (95% CI: 30.2-42.4) for CAC ≥400. Compared with CAC = 0, hazards for those with CAC ≥400 were increased for lung and colorectal cancer in men [subdistribution hazard ratio (SHR): 2.2 (95% CI: 1.1-4.7)] and women [SHR: 2.2 (95% CI: 1.0-4.6)], but not significantly for sex-specific cancers across sexes.

Conclusion: CAC scores were associated with cancer risk in both sexes; however, this was stronger for lung and colorectal when compared with sex-specific cancers. Our data support potential synergistic use of CAC scores in the identification of both CVD and lung and colorectal cancer risk.
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http://dx.doi.org/10.1093/ehjci/jeab099DOI Listing
June 2021

Association Between Omega-3 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA.

J Am Heart Assoc 2021 Jun 27;10(11):e021431. Epub 2021 May 27.

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

Background Randomized trials of pharmacologic strength omega-3 fatty acid (n3-FA)-based therapies suggest a dose-dependent cardiovascular benefit. Whether blood n3-FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3-FA levels would be associated with incident bleeding and AF events in MESA (Multi-Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline. Methods and Results We examined the association between baseline plasma n3-FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization (), and (), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3-FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1 years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA. Conclusions In MESA, higher plasma levels of n3-FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.
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http://dx.doi.org/10.1161/JAHA.121.021431DOI Listing
June 2021

Temporal Trends and Interest in Coronary Artery Calcium Scoring Over Time: An Infodemiology Study.

Mayo Clin Proc Innov Qual Outcomes 2021 Apr 8;5(2):456-465. Epub 2021 Apr 8.

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

Objective: To evaluate interest in coronary artery calcium (CAC) among the general public during the past 17 years and to compare trends with real-world data on number of CAC procedures performed.

Methods: We used Google Trends, a publicly available database, to access search query data in a systematic and quantitative fashion to search for CAC-related key terms. Search terms included , , , , and . We accessed Google Trends in January 2021 and analyzed data from 2004 to 2020.

Results: From 2004 to December 31, 2020, CAC-related search interest (in relative search volume) increased continually worldwide (+201.9%) and in the United States (+354.8%). Three main events strongly influenced search interest in CAC: reports of a CAC scan of the president of the United States led to a transient 10-fold increase in early January 2018. American College of Cardiology/American Heart Association guideline release led to a sustained increase, and lockdown after the global pandemic due to COVID-19 led to a transient decrease. Real-world data on performed CAC scans showed an increase between 2006 and 2017 (+200.0%); during the same time period, relative search volume for CAC-related search terms increased in a similar pattern (+70.6%-1511.1%). For the search term , a potential representative of active online search for CAC scanning, we found a +28.8% increase in 2020 compared with 2017.

Conclusion: Google Trends, a valuable tool for assessing public interest in health-related topics, suggests increased overall interest in CAC during the last 17 years that mirrors real-world usage data. Increased interest is seemingly linked to reports of CAC testing in world leaders and endorsement in major guidelines.
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http://dx.doi.org/10.1016/j.mayocpiqo.2021.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105517PMC
April 2021

Global Prevalence and Impact of Hostility, Discrimination, and Harassment in the Cardiology Workplace.

J Am Coll Cardiol 2021 May;77(19):2398-2409

Division of Cardiology, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Background: Discrimination and emotional and sexual harassment create a hostile work environment (HWE). The global prevalence of HWE in cardiology is unknown, as is its impact.

Objectives: This study sought to evaluate emotional harassment, discrimination, and sexual harassment experienced by cardiologists and its impact on professional satisfaction and patient interactions worldwide.

Methods: The American College of Cardiology surveyed cardiologists from Africa, Asia, the Caribbean, Eastern Europe, the European Union, the Middle East, Oceana, and North, Central, and South America. Demographics, practice information, and HWE were tabulated and compared, and their impact was assessed. The p values were calculated using the chi-square, Fisher exact, and Mann-Whitney U tests. Univariate and multivariate logistic regression analysis determined the association of characteristics with HWE and its subtypes.

Results: Of 5,931 cardiologists (77% men; 23% women), 44% reported HWE. Higher rates were found among women (68% vs. 37%; odds ratio [OR]: 3.58 vs. men), Blacks (53% vs. 43%; OR: 1.46 vs. Whites), and North Americans (54% vs. 38%; OR: 1.90 vs. South Americans). Components of HWE included emotional harassment (29%; n = 1,743), discrimination (30%; n = 1,750), and sexual harassment (4%; n = 221), and they were more prevalent among women: emotional harassment (43% vs. 26%), discrimination (56% vs. 22%), and sexual harassment (12% vs. 1%). Gender was the most frequent cause of discrimination (44%), followed by age (37%), race (24%), religion (15%), and sexual orientation (5%). HWE adversely affected professional activities with colleagues (75%) and patients (53%). Multivariate analysis showed that women (OR: 3.39; 95% confidence interval: 2.97 to 3.86; p < 0.001) and cardiologists early in their career (OR: 1.27; 95% confidence interval: 1.14 to 1.43; p < 0.001) had the highest odds of experiencing HWE.

Conclusions: There is a high global prevalence of HWE in cardiology, including discrimination, emotional harassment, and sexual harassment. HWE has an adverse effect on professional and patient interactions, thus confirming concerns about well-being and optimizing patient care. Institutions and practices should prioritize combating HWE.
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http://dx.doi.org/10.1016/j.jacc.2021.03.301DOI Listing
May 2021

Atherosclerotic cardiovascular disease events among statin eligible individuals with and without long-term healthy arterial aging.

Atherosclerosis 2021 06 26;326:56-62. Epub 2021 Mar 26.

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

Background And Aims: A large proportion of statin eligible candidates have a baseline absence of coronary artery calcium (CAC) and low 10-year atherosclerotic cardiovascular disease (ASCVD) risk. We sought to determine the proportion of statin eligible individuals who had long-term healthy arterial aging (persistent CAC = 0) and their examined 15-year ASCVD outcomes.

Methods: We included 561 statin eligible candidates from the Multi-Ethnic Study of Atherosclerosis who were not on statin therapy with CAC = 0 at Visit 1 (2000-02) and underwent a subsequent CAC scan at Visit 5 (2010-11). Adjusted Cox proportional hazards regression assessed the association between persistent CAC = 0 and ASCVD events over 15.9 years.

Results: Participants were on average 61.7 years old, 50% were women, and 43% maintained long-term CAC = 0. Individuals with an LDL-C ≥190 mg/dL (54%) and those with an ASCVD risk ≥20% (33%) had the highest and lowest proportion of persistent CAC = 0, respectively. There were 57 ASCVD events, and 15-year ASCVD event rates were low for individuals with and without healthy arterial aging (4.3 versus 8.6 per 1,000 persons-years), but the 10-year number needed to treat to prevent one ASCVD event differed by more than two fold (117 versus 54). In multivariable modeling, persistent CAC = 0 conferred a 51% lower risk of ASCVD compared to those with incident CAC (HR = 0.49, 95% CI: 0.27-0.90, p=0.02).

Conclusions: More than 40% of statin eligible individuals with baseline CAC = 0 had long-term healthy arterial aging. Statin eligible candidates with persistent CAC = 0 had a very low 15-year ASCVD risk, suggesting that statin therapy may be of limited benefit among this group of individuals.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215721PMC
June 2021

Is Maternal Obesity the Achilles' Heel of Sustainable Efforts to Reduce Adverse Pregnancy Outcomes?

J Am Coll Cardiol 2021 Mar;77(10):1327-1330

Division of Cardiology, Department of Medicine, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, USA.

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http://dx.doi.org/10.1016/j.jacc.2021.01.023DOI Listing
March 2021

Can We Reduce Premature Mortality Associated With Hypertensive Disorders of Pregnancy?: A Window of Opportunity.

J Am Coll Cardiol 2021 Mar;77(10):1313-1316

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

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http://dx.doi.org/10.1016/j.jacc.2021.01.021DOI Listing
March 2021

A cohort study and meta-analysis of isolated diastolic hypertension: searching for a threshold to guide treatment.

Eur Heart J 2021 06;42(21):2119-2129

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

Aims: Whether isolated diastolic hypertension (IDH), as defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline, is associated with cardiovascular disease (CVD) has been disputed. We aimed to further study the associations of IDH with (i) subclinical CVD in the form of coronary artery calcium (CAC), (ii) incident systolic hypertension, and (iii) CVD events.

Methods And Results: We used multivariable-adjusted logistic and Cox regression to test whether IDH by 2017 ACC/AHA criteria (i.e. systolic blood pressure <130 mmHg and diastolic blood pressure ≥80 mmHg) was associated with the above outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA). In a random-effects meta-analysis of the association between IDH and CVD events, we combined the MESA results with those from seven other previously published cohort studies. Among the 5104 MESA participants studied, 7.5% had IDH by the 2017 ACC/AHA criteria. There was no association between IDH and CAC [e.g. adjusted prevalence odds ratio for CAC >0 of 0.88 (95% CI 0.66, 1.17)]. Similarly, while IDH was associated with incident systolic hypertension, there was no statistically significant associations with incident CVD [hazard ratio 1.19 (95% CI 0.77, 1.84)] or death [hazard ratio 0.94 (95% CI 0.65, 1.36)] over 13 years in MESA. In a stratified meta-analysis of eight cohort studies (10 037 843 participants), the 2017 IDH definition was also not consistently associated with CVD and the relative magnitude of any potential association was noted to be numerically small [e.g. depending on inclusion criteria applied in the stratification, the adjusted hazard ratios ranged from 1.04 (95% CI 0.98, 1.10) to 1.09 (95% 1.03, 1.15)].

Conclusion: The lack of consistent excess in CAC or CVD suggests that emphasis on healthy lifestyle rather than drug therapy is sufficient among the millions of middle-aged or older adults who now meet the 2017 ACC/AHA criteria for IDH, though they require follow-up for incident systolic hypertension. These findings may not extrapolate to adults younger than 40 years, motivating further study in this age group.
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http://dx.doi.org/10.1093/eurheartj/ehab111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169158PMC
June 2021

Comparison of the Relation of Carotid Intima-Media Thickness With Incident Heart Failure With Reduced Versus Preserved Ejection Fraction (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Am J Cardiol 2021 06 3;148:102-109. Epub 2021 Mar 3.

Section of Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina; Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Pediatrics, Saint Joseph University Medical Center, Paterson, New Jersey; Department of Medicine, Lundquist Institute, Torrance, California; Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA; Kaiser Permanente Health Research Institute, Seattle, Washington; Johns Hopkins University School of Medicine, Baltimore, Maryland; Ultrasound Reading Center, Tufts Medical Center, Boston, Massachusetts; National University of Ireland and National Institute for Prevention and Cardiovascular Health, Galway, Ireland.

Increased carotid intima-media thickness (cIMT) is associated with heart failure (HF) in previous studies, but it is not known whether the association of cIMT differs between HF with reduced (HFrEF) versus preserved ejection fraction (HFpEF). We studied 6699 participants (mean age 62 ± 10 years, 47% male, and 38% white) from the Multi-Ethnic Study of Atherosclerosis (MESA) with baseline cIMT measurements. We classified HF events as HFrEF (EF <50%) or HFpEF (EF ≥ 50%) at the time of diagnosis. Cox proportional hazard regression was used to compute hazard ratios (HR), and 95% confidence intervals (CI) for the association between the IMT Z-score (measured maximum IMT of Internal Carotid (IC) and Common Carotid (CC) sites as the mean of the maximum IMT of the near and far walls of right and left sides), and incident HFrEF or HFpEF. Models were adjusted for covariates and interim coronary artery disease (CAD) events. A total of 191 HFrEF and 167 HFpEF events occurred during follow-up. In multivariable analysis, each 1 standard deviation increase in the measured maximum IMT (Z-score) was associated with both HFrEF and HFpEF in the unadjusted and demographically adjusted models [HR, 95% CI 1.57 (1.43 to 1.73)] and [HR, 95% CI 1.61 (1.47 to 1.77)] but not in the fully adjusted models [HR, 95% CI 1.11 (0.96 to 1.28)] and [HR, 95% CI 1.13 (0.98 to 1.30)]. In conclusion, cIMT was significantly associated with incident HF, but the association is partially attenuated with adjustment for demographic factors and becomes non-significant after adjustment for other traditional heart failure risk factors and interim CAD events. There was no difference in the association of IMT measures with HFrEF versus HFpEF.
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http://dx.doi.org/10.1016/j.amjcard.2021.02.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113133PMC
June 2021

Very High Coronary Artery Calcium (≥1000) and Association With Cardiovascular Disease Events, Non-Cardiovascular Disease Outcomes, and Mortality: Results From MESA.

Circulation 2021 Apr 2;143(16):1571-1583. Epub 2021 Mar 2.

Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD (A.W.P., Z.A.D., R.S.B., O.D., O.H.O., S.M.I.U., M.B.M., M.J.Blaha).

Background: There are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations.

Methods: Our study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk).

Results: Compared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63-6.11), 7.57- (5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25-2.16), 1.66- (1.22-2.25), 1.51- (1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups.

Conclusions: Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058297PMC
April 2021

Efficacy and safety for the achievement of guideline-recommended lower low-density lipoprotein cholesterol levels: a systematic review and meta-analysis.

Eur J Prev Cardiol 2020 Nov 28. Epub 2020 Nov 28.

Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, 600 North Wolfe Street, Blalock 524-D1, Baltimore, MD 21287.

Aim: The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors).

Methods And Results: Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD -1.56; RR 0.94 (0.89-1.00)], cardiovascular mortality [ARD -1.49; RR 0.90 (0.81-1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy.

Conclusion: This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.
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http://dx.doi.org/10.1093/eurjpc/zwaa093DOI Listing
November 2020

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

Relationship of Preeclampsia With Maternal Place of Birth and Duration of Residence Among Non-Hispanic Black Women in the United States.

Circ Cardiovasc Qual Outcomes 2021 02 10;14(2):e007546. Epub 2021 Feb 10.

Department of Population, Family and Reproductive Health (Y.A.K., X.H., Y.J., A.A.C., X.W.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Background: Preeclampsia is one of the leading causes of maternal mortality in the United States. It disproportionately affects non-Hispanic Black (NHB) women, but little is known about how preeclampsia and other cardiovascular disease risk factors vary among different subpopulations of NHB women in the United States. We investigated the prevalence of preeclampsia by nativity (US born versus foreign born) and duration of US residence among NHB women.

Methods: We analyzed cross-sectional data from the Boston Birth Cohort (1998-2016), with a focus on NHB women. We performed multivariable logistic regression to investigate associations between preeclampsia, nativity, and duration of US residence after controlling for potential confounders.

Results: Of 2697 NHB women, 40.5% were foreign born. Relative to them, US-born NHB women were younger, in higher percentage current smokers, had higher prevalence of obesity (body mass index ≥30 kg/m) and maternal stress, but lower educational level. The age-adjusted prevalence of preeclampsia was 12.4% and 9.1% among US-born and foreign-born women, respectively. When further categorized by duration of US residence, the prevalence of all studied cardiovascular disease risk factors except for diabetes was lower among foreign-born NHB women with <10 versus ≥10 years of US residence. Additionally, the odds of preeclampsia in foreign-born NHB women with duration of US residence <10 years was 37% lower than in US-born NHB women. In contrast, the odds of preeclampsia in foreign-born NHB women with duration of US residence ≥10 years was not significantly different from that of US-born NHB women after adjusting for potential confounders.

Conclusions: The prevalence of preeclampsia and other cardiovascular disease risk factors is lower in foreign-born than in US-born NHB women. The healthy immigrant effect, which typically results in health advantages for foreign-born women, appears to wane with longer duration of US residence (≥10 years). Further research is needed to better understand these associations.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.007546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887058PMC
February 2021

How low is safe? The frontier of very low (<30 mg/dL) LDL cholesterol.

Eur Heart J 2021 06;42(22):2154-2169

Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1462 Clifton Way NE, Atlanta, GA 30322, USA.

Low-density lipoprotein cholesterol (LDL-C) is a proven causative factor for developing atherosclerotic cardiovascular disease. Individuals with genetic conditions associated with lifelong very low LDL-C levels can be healthy. We now possess the pharmacological armamentarium (statins, ezetimibe, PCSK9 inhibitors) to reduce LDL-C to an unprecedented extent. Increasing numbers of patients are expected to achieve very low (<30 mg/dL) LDL-C. Cardiovascular event reduction increases log linearly in association with lowering LDL-C, without reaching any clear plateau even when very low LDL-C levels are achieved. It is still controversial whether lower LDL-C levels are associated with significant clinical adverse effects (e.g. new-onset diabetes mellitus or possibly haemorrhagic stroke) and long-term data are needed to address safety concerns. This review presents the familial conditions characterized by very low LDL-C, analyses trials with lipid-lowering agents where patients attained very low LDL-C, and summarizes the benefits and potential adverse effects associated with achieving very low LDL-C. Given the potential for cardiovascular benefit and short-term safe profile of very low LDL-C, it may be advantageous to attain such low levels in specific high-risk populations. Further studies are needed to compare the net clinical benefit of non-LDL-C-lowering interventions with very low LDL-C approaches, in addition to comparing the efficacy and safety of very low LDL-C levels vs. current recommended targets.
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http://dx.doi.org/10.1093/eurheartj/ehaa1080DOI Listing
June 2021

Prognostic significance of aortic valve calcium in relation to coronary artery calcification for long-term, cause-specific mortality: results from the CAC Consortium.

Eur Heart J Cardiovasc Imaging 2020 Dec 17. Epub 2020 Dec 17.

Department of Imaging, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA.

Aims: Aortic valve calcification (AVC) has been shown to be associated with increased cardiovascular disease (CVD) risk; however, whether this is independent of traditional risk factors and coronary artery calcification (CAC) remains unclear.

Methods And Results: From the multicentre CAC Consortium database, 10 007 patients (mean 55.8±11.7 years, 64% male) with concomitant CAC and AVC scoring were included in the current analysis. AVC score was quantified using the Agatston score method and categorized as 0, 1-99, and ≥100. The endpoints were all-cause, CVD, and coronary heart disease (CHD) deaths. AVC (AVC>0) was observed in 1397 (14%) patients. During a median 7.8 (interquartile range: 4.7-10.6) years of study follow-up, 511 (5.1%) deaths occurred; 179 (35%) were CVD deaths, and 101 (19.8%) were CHD deaths. A significant interaction between CAC and AVC for mortality was observed (P<0.001). The incidence of mortality events increased with higher AVC; however, AVC ≥100 was not independently associated with all-cause, CVD, and CHD deaths after adjusting for CVD risk factors and CAC (P=0.192, 0.063, and 0.206, respectively). When further stratified by CAC<100 or ≥100, AVC ≥100 was an independent predictor of all-cause and CVD deaths only in patients with CAC <100, after adjusting for CVD risk factors and CAC [hazard ratio (HR): 1.93, 95% confidence interval (CI): 1.14-3.27; P=0.013 and HR: 2.71, 95% CI: 1.15-6.34; P=0.022, respectively].

Conclusion: Although the overall prognostic significance of AVC was attenuated after accounting for CAC, high AVC was independently associated with all-cause and CVD deaths in patients with low coronary atherosclerosis burden.
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http://dx.doi.org/10.1093/ehjci/jeaa336DOI Listing
December 2020

Clinical characteristics and outcomes of young adults with first myocardial infarction: Results from Gulf COAST.

Int J Cardiol Heart Vasc 2020 Dec 30;31:100680. Epub 2020 Nov 30.

Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait.

Introduction: Limited data exists on the risk factor profile and outcomes of young patients suffering their first acute myocardial infarction (AMI).

Methods: We examined 1562 Gulf-Arabs without prior cardiovascular disease presenting with first AMI enrolled in the Gulf COAST prospective cohort. Clinical characteristics were compared in patients ≤50 years of age (young) vs. >50 years (older). Associations between age group and in-hospital adverse events (re-infarction, heart failure, cardiogenic shock, cardiac arrest, stroke, and in-hospital death) or post-discharge mortality were estimated using logistic regression.

Results: Young patients represented 26.1% (n = 407) of first AMI cases and were more likely to be men (82.8% vs. 66.5%), current smokers (49.9% vs 19.0%), obese (38.3% vs 28.0%), and have family history of premature coronary artery disease (21.4% vs 10.4%) compared with older patients (all P < 0.001). Young patients were more likely to receive β-blockers (83.0% vs 74.4%; P < 0.001), clopidogrel (82.3% vs 76.0%; P = 0.009) and primary reperfusion therapy (85.6% vs. 75.6%; P = 0.003). Young adults had lower in-hospital death (adjusted odds ratio [aOR] = 0.37; 95%CI = 0.16-0.86) or any in-hospital adverse cardiovascular events (aOR = 0.53; 95%CI = 0.34-0.83). Young adults had lower likelihood of cumulative death at 12-month post-discharge (aOR = 0.34; 95%CI = 0.19-0.59) after adjusting for potential confounders.

Conclusion: Young patients with first AMI were more likely to be obese, smokers and have family history of premature coronary artery disease compared to older adults. Young patients were more likely to receive guideline-proven therapies and have better in-hospital and post-discharge mortality. These data highlight important age-related care gaps in patients suffering AMI for the first time.
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http://dx.doi.org/10.1016/j.ijcha.2020.100680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710649PMC
December 2020
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