Publications by authors named "Matthew J Budoff"

891 Publications

LDL receptor and pathogen processes: Functions beyond normal lipids.

J Clin Lipidol 2021 Oct 1. Epub 2021 Oct 1.

Division of Cardiology, The Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA 90502, USA. Electronic address:

Although the role of the LDL receptor concerning lipids is well known, its role in various viral and parasitic infections, and in regulating the inflammatory response is poorly understood. Several infectious agents use the LDL receptor as a port of entry, and others depend on it for their cycle of infection. In this review, we focus on the discovery, structure, and normal function of the LDL receptor, as well as its role in a selection of infections. The LDL receptor plays an important role in certain infections and is a potential target for treatment deserving further research.
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http://dx.doi.org/10.1016/j.jacl.2021.09.048DOI Listing
October 2021

Comparative Reductions in Investigator-Reported and Adjudicated Ischemic Events in REDUCE-IT.

J Am Coll Cardiol 2021 Oct;78(15):1525-1537

Department of Cardiovascular Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Background: REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) randomized statin-treated patients with elevated triglycerides to icosapent ethyl (IPE) or placebo. There was a significant reduction in adjudicated events, including the primary endpoint (cardiovascular [CV] death, myocardial infarction [MI], stroke, coronary revascularization, unstable angina requiring hospitalization) and key secondary endpoint (CV death, MI, stroke) with IPE.

Objectives: The purpose of this study was to determine the effects of IPE on investigator-reported events.

Methods: Potential endpoints were collected by blinded site investigators and subsequently adjudicated by a blinded Clinical Endpoint Committee (CEC) according to a prespecified charter. Investigator-reported events were compared with adjudicated events for concordance.

Results: There was a high degree of concordance between investigator-reported and adjudicated endpoints. The simple Kappa statistic between CEC-adjudicated vs site-reported events for the primary endpoint was 0.89 and for the key secondary endpoint was 0.90. Based on investigator-reported events in 8,179 randomized patients, IPE significantly reduced the rate of the primary endpoint (19.1% vs 24.6%; HR: 0.74 [95% CI: 0.67-0.81]; P < 0.0001) and the key secondary endpoint (10.5% vs 13.6%; HR: 0.75 [95% CI: 0.66-0.85]; P < 0.0001). Among adjudicated events, IPE similarly reduced the rate of the primary and key secondary endpoints.

Conclusions: IPE led to consistent, significant reductions in CV events, including MI and coronary revascularization, as determined by independent, blinded CEC adjudication as well as by blinded investigator-reported assessment. These results highlight the robust evidence for the substantial CV benefits of IPE seen in REDUCE-IT and further raise the question of whether adjudication of CV outcome trial endpoints is routinely required in blinded, placebo-controlled trials. (Evaluation of the Effect of AMR101 on Cardiovascular Health and Mortality in Hypertriglyceridemic Patients With Cardiovascular Disease or at High Risk for Cardiovascular Disease: REDUCE-IT [Reduction of Cardiovascular Events With EPA - Intervention Trial]; NCT01492361).
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http://dx.doi.org/10.1016/j.jacc.2021.08.009DOI Listing
October 2021

The Miami Heart Study (MiHeart) at Baptist Health South Florida, A prospective study of subclinical cardiovascular disease and emerging cardiovascular risk factors in asymptomatic young and middle-aged adults: The Miami Heart Study: Rationale and Design.

Am J Prev Cardiol 2021 Sep 28;7:100202. Epub 2021 May 28.

Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, FL, USA.

Objective: The Miami Heart Study (MiHeart) at Baptist Health South Florida is an ongoing, community-based, prospective cohort study aimed at characterizing the prevalence, characteristics, and prognostic value of diverse markers of early subclinical coronary atherosclerosis and of various potential demographic, psychosocial, and metabolic risk factors. We present the study objectives, detailed research methods, and preliminary baseline results of MiHeart.

Methods: MiHeart enrolled 2,459 middle-aged male and female participants from the general population of the Greater Miami Area. Enrollment occurred between May 2015 and September 2018 and was restricted to participants aged 40-65 years free of clinical cardiovascular disease (CVD). The baseline examination included assessment of demographics, lifestyles, medical history, and a detailed evaluation of psychosocial characteristics; a comprehensive physical exam; measurement of multiple blood biomarkers including measures of inflammation, advanced lipid testing, and genomics; assessment of subclinical coronary atherosclerotic plaque and vascular function using coronary computed tomography angiography, the coronary artery calcium score, carotid intima-media thickness, pulse wave velocity, and peripheral arterial tonometry; and other tests including 12-lead electrocardiography and assessment of pulmonary function. Blood samples were biobanked to facilitate future ancillary research.

Results: MiHeart enrolled 1,261 men (51.3%) and 1,198 women (48.7%). Mean age was 53 years, 85.6% participants were White and 47.4% were of Hispanic/Latino ethnicity. The study included 7% individuals with diabetes, 33% with hypertension, and 15% used statin therapy at baseline. Overweight or obese participants comprised 72% of the population and 3% were smokers. Median 10-year estimated atherosclerotic CVD risk using the Pooled Cohort Equations was 4%.

Conclusion: MiHeart will provide important, novel insights into the pathophysiology of early subclinical atherosclerosis and further our understanding of its role in the genesis of clinical CVD. The study findings will have important implications, further refining current cardiovascular prevention paradigms and risk assessment and management approaches moving forward.
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http://dx.doi.org/10.1016/j.ajpc.2021.100202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387278PMC
September 2021

Coronary artery plaque progression and cardiovascular risk scores in men with and without HIV-infection.

AIDS 2021 Oct 7. Epub 2021 Oct 7.

Lundquist Institute of Biomedical Research at Harbor-UCLA Medical Center, Torrance, California Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland Division of Cardiology, Creighton University Medical Center, Omaha, Nebraska Feinberg School of Medicine, Division of Infectious Diseases, Northwestern University, Chicago, Illinois Department of Medicine, Johns Hopkins University School of Medicine Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania. Contributed equally.

Objective: To assess the association of cardiovascular disease (CVD) risk scores and coronary artery plaque (CAP) progression in HIV-infected participants.

Methods: We studied men with and without HIV-infection enrolled in the Multicenter AIDS Cohort Study (MACS) CVD study. Coronary artery plaque (CAP) at baseline and follow-up was assessed with cardiac computed tomography angiography (CCTA). We examined the association between baseline risk scores including pooled cohort equation (PCE), Framingham risk score (FRS) and Data collect of Adverse effects of anti-HIV drugs equation (D:A:D) and CAP progression.

Results: We studied 495 men (211 HIV-uninfected, 284 HIV-infected). The adjusted odds ratio (aOR) of total plaque volume (TPV) and non-calcified plaque volume (NCPV) progression in the highest relative to lowest tertile was 9.4 (95% CI 2.4, 12.1, p < 0.001) and 7.7 (3.1,19.1, p < 0.001) times greater, respectively, among HIV-uninfected men in the PCE atherosclerotic cardiovascular disease (ASCVD) high vs. low risk category. Among HIV-infected men, the association for TPV and NCPV progression for the same PCE risk categories, OR 2.8 (1.4, 5.8, p < 0.01) and OR 2.4 (1.2, 4.8, p < 0.05) respectively (p-values for interaction by HIV = 0.02 and 0.08, respectively). Similar results were seen for the FRS risk scores. Among HIV-uninfected men, PCE high risk category identified the highest proportion of men with plaque progression in the highest tertile. While, in HIV-infected men, high risk category by D:A:D identified the greatest percentage of men with plaque progression albeit with lower specificity than FRS and PCE.

Conclusions: PCE and FRS categories predict CAP progression better in HIV-uninfected compared to HIV-infected men. Improved CVD risk scores are needed to identify high risk HIV-infected men for more aggressive CVD risk prevention strategies.
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http://dx.doi.org/10.1097/QAD.0000000000003093DOI Listing
October 2021

Short Communication: Plasma Lymphocyte Activation Gene 3 and Subclinical Coronary Artery Disease in the Multicenter AIDS Cohort Study.

AIDS Res Hum Retroviruses 2021 Sep 20. Epub 2021 Sep 20.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Chronic inflammation, including among people with HIV (PWH), elevates immune cell expression of lymphocyte activation gene 3 (LAG3); however, low plasma LAG3 predicts cardiovascular disease (CVD) events in the general population. The associations among LAG3 plasma levels, subclinical atherosclerosis, inflammation, and HIV infection have not been well described. We measured plasma LAG3 in 704 men with and without HIV from the multicenter AIDS cohort study, who underwent coronary computed tomography angiography. HIV serostatus was not independently associated with LAG3 after adjustment for sociodemographic and CVD risk factors. Current smoking status and African American race were associated with lower LAG3, and age and sTNFαRI concentration were associated with greater LAG3. LAG3 was not associated with coronary artery stenosis. Thus, no difference was found in plasma LAG3 concentration by HIV serostatus, and no association between LAG3 and subclinical coronary atherosclerosis in men with and without HIV was observed.
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http://dx.doi.org/10.1089/aid.2021.0035DOI Listing
September 2021

Bone mineral density and long-term progression of aortic valve and mitral annular calcification: The Multi-Ethnic Study of Atherosclerosis.

Atherosclerosis 2021 Oct 26;335:126-134. Epub 2021 Aug 26.

Cardiology Section, San Francisco Veterans Affairs Health Care System, and Department of Medicine, University of California San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA. Electronic address:

Background And Aims: Bone and mineral metabolism has been implicated in the pathophysiology of cardiac valve calcification. Whether bone demineralization, a common aging-related disorder, promotes calcific valve disease remains uncertain. We tested the hypothesis that low bone mineral density (BMD) is associated with greater incidence/progression of cardiac valve calcification in the Multi-Ethnic Study of Atherosclerosis.

Methods: Using linear mixed-effects models, we related baseline measurement of BMD of the thoracic vertebrae by computed tomography (CT) in 6768 participants to serial CT assessments of aortic valve calcification (AVC) and mitral annular calcification (MAC) obtained over a >10-year period.

Results: After multivariable adjustment, lower BMD (per SD decrement) was associated with accelerated increase in AVC over time in women (0.76 [95% CI 0.42,1.09] Agatston -units [AU]/year) and men (1.41 [95% CI 0.48,2.33] AU/year), as well as for MAC in women (3.22 [95% CI 1.16,5.28] AU/year) and men (3.59 [95% CI 2.09,5.09] AU/year). Significant effect modification was observed, with more pronounced BMD-related acceleration of AVC and MAC progression in older or white participants of one or both sexes, as well as by estimated glomerular filtration rate, though the latter differed by sex for AVC and MAC.

Conclusions: In this multi-ethnic cohort, low thoracic BMD was significantly, but modestly, associated with increased AVC and MAC progression. This suggests that altered bone mineral metabolism does not have a major impact on calcific valve disease in the general population, but the possibility of a more meaningful influence in higher-risk individuals with osteoporosis will require further investigation.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.08.031DOI Listing
October 2021

Measurement of compensatory arterial remodelling over time with serial coronary computed tomography angiography and 3D metrics.

Eur Heart J Cardiovasc Imaging 2021 Sep 1. Epub 2021 Sep 1.

Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea.

Aims: The magnitude of alterations in which coronary arteries remodel and narrow over time is not well understood. We aimed to examine changes in coronary arterial remodelling and luminal narrowing by three-dimensional (3D) metrics from serial coronary computed tomography angiography (CCTA).

Methods And Results: From a multicentre registry of patients with suspected coronary artery disease who underwent clinically indicated serial CCTA (median interscan interval = 3.3 years), we quantitatively measured coronary plaque, vessel, and lumen volumes on both scans. Primary outcome was the per-segment change in coronary vessel and lumen volume from a change in plaque volume, focusing on arterial remodelling. Multivariate generalized estimating equations including statins were calculated comparing associations between groups of baseline percent atheroma volume (PAV) and location within the coronary artery tree. From 1245 patients (mean age 61 ± 9 years, 39% women), a total of 5721 segments were analysed. For each 1.00 mm3 increase in plaque volume, the vessel volume increased by 0.71 mm3 [95% confidence interval (CI) 0.63 to 0.79 mm3, P < 0.001] with a corresponding reduction in lumen volume by 0.29 mm3 (95% CI -0.37 to -0.21 mm3, P < 0.001). Serial 3D arterial remodelling and luminal narrowing was similar in segments with low and high baseline PAV (P ≥ 0.496). No differences were observed between left main and non-left main segments, proximal and distal segments and side branch and non-side branch segments (P ≥ 0.281).

Conclusions: Over time, atherosclerotic coronary plaque reveals prominent outward arterial remodelling that co-occurs with modest luminal narrowing. These findings provide additional insight into the compensatory mechanisms involved in the progression of coronary atherosclerosis.
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http://dx.doi.org/10.1093/ehjci/jeab138DOI Listing
September 2021

Implication of thoracic aortic calcification over coronary calcium score regarding the 2018 ACC/AHA Multisociety cholesterol guideline: results from the CAC Consortium.

Am J Prev Cardiol 2021 Dec 8;8:100232. Epub 2021 Aug 8.

Department of Imaging and Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, United States.

Objective: TAC is associated with an increased atherosclerotic cardiovascular disease (ASCVD) risk, but it is unclear how to interpret thoracic aortic calcification (TAC) findings in conjunction with ASCVD risk and coronary artery calcium (CAC) score according to 2018 ACC/AHA Multisociety cholesterol guidelines. We evaluate the incremental value of thoracic aortic calcification TAC over CAC for predicting and reclassifying ASCVD mortality risk.

Method: The study included 30,630 asymptomatic individuals (mean age: 55 ± 8 years, male: 64%) from the CAC Consortium. TAC was categorized as TAC 0, 1-300, and >300. Patients were categorized as low (<5%), borderline (5-7.5%), intermediate (7.5-20%), or high (≥20%) 10-year ASCVD risk according to the Pooled Cohorts Equation. In the intermediate risk group, the utility of TAC beyond CAC for statin eligibility was assessed according to the guideline. CAC was categorized as CAC=0 (no statin), CAC 1-100 (favors statin), or CAC>100 (initiate stain).

Results: During the median 11.2 years (IQR 9.2-12.4) follow-up, 345 (1.1%) CVD deaths occurred. TAC>300 was associated with increased CVD mortality after adjusting for ASCVD risk and CAC (HR:4.72, 95% CI: 3.39-6.57, p<0.001). In borderline and intermediate risk groups, TAC improved discrimination when added to a model included ASCVD risk and CAC (C-statistic: 0.77 vs. 0.68 in borderline group; 0.67 vs. 0.63 in intermediate group, both  < 0.05). The addition of TAC over CAC improved risk reclassification in borderline, intermediate and high-risk groups (categorical net reclassification index: 0.40, 0.29, and 0.49, respectively, all  < 0.001). Of intermediate risk participants for whom consideration of CAC was recommended based on the guideline, TAC >300 was associated with an increased CVD mortality risk across each statin eligibility group (all  < 0.001, compared to TAC 0).

Conclusion: TAC was independently associated with CVD death. Among individuals with borderline or intermediate ASCVD risk, a TAC threshold of 300 may provide added prognostic and reclassification value beyond the current guideline-based approach.
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http://dx.doi.org/10.1016/j.ajpc.2021.100232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385171PMC
December 2021

Plaque Character and Progression According to the Location of Coronary Atherosclerotic Plaque.

Am J Cardiol 2021 11 29;158:15-22. Epub 2021 Aug 29.

Cardiovascular Imaging Unit, SDN IRCCS, Naples, Italy.

Although acute coronary syndrome culprit lesions occur more frequently in the proximal coronary artery, whether the proximal clustering of high-risk plaque is reflected in earlier-stage atherosclerosis remains unclarified. We evaluated the longitudinal distribution of stable atherosclerotic lesions on coronary computed tomography angiography (CCTA) in 1,478 patients (mean age, 61 years; men, 58%) enrolled from a prospective multinational registry of consecutive patients undergoing serial CCTA. Of 3,202 coronary artery lesions identified, 2,140 left lesions were classified (based on the minimal lumen diameter location) into left main (LM, n = 128), proximal (n = 739), and other (n = 1,273), and 1,062 right lesions were classified into proximal (n = 355) and other (n = 707). Plaque volume (PV) was the highest in proximal lesions (median, 26.1 mm), followed by LM (20.6 mm) and other lesions (15.0 mm, p <0.001), for left lesions, and was lager in proximal (25.8 mm) than in other lesions (15.2 mm, p <0.001) for right lesions. On both sides, proximally located lesions tended to have greater necrotic core and fibrofatty components than other lesions (left: LM, 10.6%; proximal, 5.8%; other, 3.4% of the total PV, p <0.001; right: proximal, 8.4%; other 3.1%, p <0.001), with less calcified plaque component (left: LM, 18.3%; proximal, 30.3%; other, 37.7%, p <0.001; right: proximal, 23.3%, other, 36.6%, p <0.001), and tended to progress rapidly (adjusted odds ratios: left: LM, reference; proximal, 0.95, p = 0.803; other, 0.64, p = 0.017; right: proximal, reference; other, 0.52, p <0.001). Proximally located plaques were larger, with more risky composition, and progressed more rapidly.
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http://dx.doi.org/10.1016/j.amjcard.2021.07.040DOI Listing
November 2021

Differential progression of coronary atherosclerosis according to plaque composition: a cluster analysis of PARADIGM registry data.

Sci Rep 2021 08 24;11(1):17121. Epub 2021 Aug 24.

Yonsei-Cedars-Sinai Integrative Cardiovascular Imaging Research Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea.

Patient-specific phenotyping of coronary atherosclerosis would facilitate personalized risk assessment and preventive treatment. We explored whether unsupervised cluster analysis can categorize patients with coronary atherosclerosis according to their plaque composition, and determined how these differing plaque composition profiles impact plaque progression. Patients with coronary atherosclerotic plaque (n = 947; median age, 62 years; 59% male) were enrolled from a prospective multi-national registry of consecutive patients who underwent serial coronary computed tomography angiography (median inter-scan duration, 3.3 years). K-means clustering applied to the percent volume of each plaque component and identified 4 clusters of patients with distinct plaque composition. Cluster 1 (n = 52), which comprised mainly fibro-fatty plaque with a significant necrotic core (median, 55.7% and 16.0% of the total plaque volume, respectively), showed the least total plaque volume (PV) progression (+ 23.3 mm), with necrotic core and fibro-fatty PV regression (- 5.7 mm and - 5.6 mm, respectively). Cluster 2 (n = 219), which contained largely fibro-fatty (39.2%) and fibrous plaque (46.8%), showed fibro-fatty PV regression (- 2.4 mm). Cluster 3 (n = 376), which comprised mostly fibrous (62.7%) and calcified plaque (23.6%), showed increasingly prominent calcified PV progression (+ 21.4 mm). Cluster 4 (n = 300), which comprised mostly calcified plaque (58.7%), demonstrated the greatest total PV increase (+ 50.7mm), predominantly increasing in calcified PV (+ 35.9 mm). Multivariable analysis showed higher risk for plaque progression in Clusters 3 and 4, and higher risk for adverse cardiac events in Clusters 2, 3, and 4 compared to that in Cluster 1. Unsupervised clustering algorithms may uniquely characterize patient phenotypes with varied atherosclerotic plaque profiles, yielding distinct patterns of progressive disease and outcome.
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http://dx.doi.org/10.1038/s41598-021-96616-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385056PMC
August 2021

Association of Tube Voltage With Plaque Composition on Coronary CT Angiography: Results From Paradigm Registry.

JACC Cardiovasc Imaging 2021 Aug 11. Epub 2021 Aug 11.

Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Objectives: This study sought to investigate the impact of low tube voltage scanning heterogeneity of coronary luminal attenuation on plaque quantification and characterization with coronary computed tomography angiography (CCTA).

Background: The impact of low tube voltage and coronary luminal attenuation on quantitative coronary plaque remains uncertain.

Methods: A total of 1,236 consecutive patients (age: 60 ± 9 years; 41% female) who underwent serial CCTA at an interval of ≥2 years were included from an international registry. Patients with prior revascularization or nonanalyzable coronary CTAs were excluded. Total coronary plaque volume was assessed and subclassified based on specific Hounsfield unit (HU) threshold: necrotic core, fibrofatty plaque, and fibrous plaque and dense calcium. Luminal attenuation was measured in the aorta.

Results: With increasing luminal HU (<350, 350-500, and >500 HU), percent calcified plaque was increased (16%, 27%, and 40% in the median; P < 0.001), and fibrofatty plaque (26%, 13%, and 4%; P < 0.001) and necrotic core (1.6%, 0.3%, and 0.0%; P < 0.001) were decreased. Higher tube voltage scanning (80, 100, and 120 kV) resulted in decreasing luminal attenuation (689 ± 135, 497 ± 89, and 391 ± 73 HU; P < 0.001) and calcified plaque volume (59%, 34%, and 23%; P < 0.001) and increased fibrofatty plaque (3%, 9%, and 18%; P < 0.001) and necrotic core (0.2%, 0.1%, and 0.6%; P < 0.001). Mediation analysis showed that the impact of 100 kV on plaque composition, compared with 120 kV, was primarily caused by an indirect effect through blood pool attenuation. Tube voltage scanning of 80 kV maintained a direct effect on fibrofatty plaque and necrotic core in addition to an indirect effect through the luminal attenuation.

Conclusions: Low tube voltage usage affected plaque morphology, mainly through an increase in luminal HU with a resultant increase in calcified plaque and a reduction in fibrofatty and necrotic core. These findings should be considered as CCTA-based plaque measures are being used to guide medical management and, in particular, when being used as a measure of treatment response. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411).
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http://dx.doi.org/10.1016/j.jcmg.2021.07.011DOI Listing
August 2021

Association of Statin Treatment With Progression of Coronary Atherosclerotic Plaque Composition.

JAMA Cardiol 2021 Aug 18. Epub 2021 Aug 18.

Department of Pathology, CVPath Institute, Gaithersburg, Maryland.

Importance: The density of atherosclerotic plaque forms the basis for categorizing calcified and noncalcified morphology of plaques.

Objective: To assess whether alterations in plaque across a range of density measurements provide a more detailed understanding of atherosclerotic disease progression.

Design, Setting, And Participants: This cohort study enrolled 857 patients who underwent serial coronary computed tomography angiography 2 or more years apart and had quantitative measurements of coronary plaques throughout the entire coronary artery tree. The study was conducted from 2013 to 2016 at 13 sites in 7 countries.

Main Outcomes And Measures: The main outcome was progression of plaque composition of individual coronary plaques. Six plaque composition types were defined on a voxel-level basis according to the plaque attenuation (expressed in Hounsfield units [HU]): low attenuation (-30 to 75 HU), fibro-fatty (76-130 HU), fibrous (131-350 HU), low-density calcium (351-700 HU), high-density calcium (701-1000 HU), and 1K (>1000 HU). The progression rates of these 6 compositional plaque types were evaluated according to the interaction between statin use and baseline plaque volume, adjusted for risk factors and time interval between scans. Plaque progression was also examined based on baseline calcium density. Analysis was performed among lesions matched at baseline and follow-up. Data analyses were conducted from August 2019 through March 2020.

Results: In total, 2458 coronary lesions in 857 patients (mean [SD] age, 62.1 [8.7] years; 540 [63.0%] men; 548 [63.9%] received statin therapy) were included. Untreated coronary lesions increased in volume over time for all 6 compositional types. Statin therapy was associated with volume decreases in low-attenuation plaque (β, -0.02; 95% CI, -0.03 to -0.01; P = .001) and fibro-fatty plaque (β, -0.03; 95% CI, -0.04 to -0.02; P < .001) and greater progression of high-density calcium plaque (β, 0.02; 95% CI, 0.01-0.03; P < .001) and 1K plaque (β, 0.02; 95% CI, 0.01-0.03; P < .001). When analyses were restricted to lesions without low-attenuation plaque or fibro-fatty plaque at baseline, statin therapy was not associated with a change in overall calcified plaque volume (β, -0.03; 95% CI, -0.08 to 0.02; P = .24) but was associated with a transformation toward more dense calcium. Interaction analysis between baseline plaque volume and calcium density showed that more dense coronary calcium was associated with less plaque progression.

Conclusions And Relevance: The results suggest an association of statin use with greater rates of transformation of coronary atherosclerosis toward high-density calcium. A pattern of slower overall plaque progression was observed with increasing density. All findings support the concept of reduced atherosclerotic risk with increased densification of calcium.
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http://dx.doi.org/10.1001/jamacardio.2021.3055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374741PMC
August 2021

Identification and Predictors for Cardiovascular Disease Risk Equivalents among Adults With Diabetes Mellitus.

Diabetes Care 2021 Aug 11. Epub 2021 Aug 11.

Department of Epidemiology, University of California Los Angeles, Los Angeles, CA.

Objective: We examined diabetes mellitus (DM) as a cardiovascular disease (CVD) risk equivalent based on diabetes severity and other CVD risk factors.

Research Design And Methods: We pooled 4 US cohorts (ARIC, JHS, MESA, FHS-Offspring) and classified subjects by baseline DM/CVD. CVD risks between DM+/CVD- vs. DM-/CVD+ were examined by diabetes severity and in subgroups of other CVD risk factors. We developed an algorithm to identify subjects with CVD risk equivalent diabetes by comparing the relative CVD risk of being DM+/CVD- vs. DM-/CVD+.

Results: The pooled cohort included 27,730 subjects (mean age of 58.5 years, 44.6% male). CVD rates per 1000 person-years were 16.5, 33.4, 43.2 and 71.4 among those with DM-/CVD-, DM+/CVD-, DM-/CVD+ and DM+/CVD+, respectively. Compared with those with DM-/CVD+, CVD risks were similar or higher for those with HbA1c ≥ 7%, diabetes duration ≥10 years, or diabetes medication use while those with less severe diabetes had lower risks. Hazard ratios (95%CI) for DM+/CVD- vs. DM-/CVD+ were 0.96(0.86-1.07), 0.97(0.88-1.07), 0.96(0.82-1.13), 1.18(0.98-1.41), 0.93(0.85-1.02) and 1.00(0.89-1.13) among women, white race, age <55 years, triglycerides ≥2.26 mmol/L, hs-CRP ≥ 2 mg/L and eGFR<60 mL/min/1.73m, respectively. In DM+/CVD- group, 19.1% had CVD risk equivalent diabetes with a lower risk score but a higher observed CVD risk.

Conclusion: Diabetes is a CVD risk equivalent in one-fifth of CVD-free adults living with diabetes. High HbA1c, long diabetes duration, and diabetes medication use were predictors of CVD risk equivalence. Diabetes is a CVD risk equivalent for women, white people, those of younger age, with higher triglycerides or CRP, or reduced kidney function.
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http://dx.doi.org/10.2337/dc21-0431DOI Listing
August 2021

The impact of statins on coronary atherosclerosis progression and long-term cardiovascular disease risk in rheumatoid arthritis.

Rheumatology (Oxford) 2021 Aug 9. Epub 2021 Aug 9.

Division of Cardiology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA.

Objectives: To evaluate whether statins lower cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) and if tentative benefits are related to changes in coronary plaque burden or composition.

Methods: In an observational cohort study, 150 patients without CVD underwent coronary atherosclerosis evaluation (total, noncalcified, partially and fully calcified plaque) with computed tomography angiography. Prespecified cardiovascular events including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and heart failure were prospectively recorded. Change in plaque burden and composition was re-assessed in 102 patients within 6.9±0.3 years.

Results: Time varying statin therapy, modeled using inverse probability treatment and censoring weights, did not significantly attenuate CVD risk in RA overall (adjusted- OR = 0.39 [95%CI=0.15-1.07], p = 0.067). However, statins associated with lower CVD risk in patients with baseline CRP>0.5mg/dL (adjusted-OR=0.09 [95%CI=0.03-0.30], p < 0.001) but not in those with CRP<0.5mg/dL (p-interaction=0.023), after controlling for Framingham-CVD score and time-varying bDMARD use. In patients treated with statin >50% of follow-up time, CRP did not associate with new plaque formation (adjusted-OR=0.42 [95%CI=0.09-1.94]), in contrast to statin-naïve (adjusted-OR=1.89 [95%CI=1.41-2.54]) and statin-treated <50% time (adjusted-OR=1.41 [95%CI=1.03-1.95], p-interaction=0.029). Statin therapy >50% follow-up time predicted dissipation (adjusted-OR=5.84 [95%CI=1.29-26.55]) and calcification of prevalent noncalcified lesions (adjusted-OR=4.16 [95%CI=1.11-15.54]), as well as new calcified plaque formation in segments without baseline plaque (adjusted-OR=2.84 [95%CI=1.09-7.41]).

Conclusion: Statin therapy associated with lower long-term cardiovascular risk in RA patients with higher inflammation. Moreover, statin therapy modified the impact of inflammation on new coronary plaque formation and predicted both regression and calcification of prevalent noncalcified lesions.
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http://dx.doi.org/10.1093/rheumatology/keab642DOI Listing
August 2021

Current methods to assess mitral annular calcification and its risk factors.

Expert Rev Cardiovasc Ther 2021 Sep 12;19(9):787-800. Epub 2021 Aug 12.

Division Of Cardiology, Lundquist Institute For Biomedical Innovation At Harbor-UCLA, Torrance, California, USA.

Introduction: Mitral annulus calcification (MAC) is a chronic, non-inflammatory, degenerative mechanism of the fibrous base of the mitral valve. While MAC was originally thought to be an age-related degenerative process, there is evidence that other mechanisms, such as atherosclerosis and abnormal calcium phosphorus metabolism, also contribute to the development of MAC.

Areas Covered: This paper summarizes, existing perception of clinically valid definition of MAC and the pathophysiological processes that lead to the development of MAC and the diagnostic implications of this disease entity.

Expert Opinion: Minimal evidence exists on the natural history and progression of MAC. Characterization of MAC progression and identification of predisposing risk factors can help to validate hypotheses. MAC is most commonly asymptomatic and incidental finding. Echocardiography is the primary imaging modality for identification and characterization of MAC and associated mitral valve (MV) disease. For patients with an indication for MV surgery, computed tomography (CT) is a complementary imaging modality for MAC. MAC is generally recognized by its characteristic density, location, and shape on echocardiography and CT, unusual variants are sometimes confused with other lesions.
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http://dx.doi.org/10.1080/14779072.2021.1964361DOI Listing
September 2021

Ten things to know about ten imaging studies: A preventive cardiology perspective ("ASPC top ten imaging").

Am J Prev Cardiol 2021 Jun 27;6:100176. Epub 2021 Mar 27.

CGH Medical Cener, Sterling, IL 61081 USA.

Knowing the patient's current cardiovascular disease (CVD) status, as well as the patient's current and future CVD risk, helps the clinician make more informed patient-centered management recommendations towards the goal of preventing future CVD events. Imaging tests that can assist the clinician with the diagnosis and prognosis of CVD include imaging studies of the heart and vascular system, as well as imaging studies of other body organs applicable to CVD risk. The American Society for Preventive Cardiology (ASPC) has published "Ten Things to Know About Ten Cardiovascular Disease Risk Factors." Similarly, this "ASPC Top Ten Imaging" summarizes ten things to know about ten imaging studies related to assessing CVD and CVD risk, listed in tabular form. The ten imaging studies herein include: (1) coronary artery calcium imaging (CAC), (2) coronary computed tomography angiography (CCTA), (3) cardiac ultrasound (echocardiography), (4) nuclear myocardial perfusion imaging (MPI), (5) cardiac magnetic resonance (CMR), (6) cardiac catheterization [with or without intravascular ultrasound (IVUS) or coronary optical coherence tomography (OCT)], (7) dual x-ray absorptiometry (DXA) body composition, (8) hepatic imaging [ultrasound of liver, vibration-controlled transient elastography (VCTE), CT, MRI proton density fat fraction (PDFF), magnetic resonance spectroscopy (MRS)], (9) peripheral artery / endothelial function imaging (e.g., carotid ultrasound, peripheral doppler imaging, ultrasound flow-mediated dilation, other tests of endothelial function and peripheral vascular imaging) and (10) images of other body organs applicable to preventive cardiology (brain, kidney, ovary). Many cardiologists perform cardiovascular-related imaging. Many non-cardiologists perform applicable non-cardiovascular imaging. Cardiologists and non-cardiologists alike may benefit from a working knowledge of imaging studies applicable to the diagnosis and prognosis of CVD and CVD risk - both important in preventive cardiology.
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http://dx.doi.org/10.1016/j.ajpc.2021.100176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315431PMC
June 2021

Association between coronary artery calcium and cardiovascular disease as a supporting cause in cancer: The CAC consortium.

Am J Prev Cardiol 2020 Dec 12;4:100119. Epub 2020 Nov 12.

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

Background: Identifying cancer patients at high risk of CVD is important for targeting CVD prevention strategies and evaluating chemotherapy options in the context of cardiotoxicity. Coronary artery calcium (CAC), a strong marker of coronary atherosclerosis, is used clinically to enhance risk assessment, yet the value of CAC for assessing risk of CVD complications in cancer is poorly understood.

Objective: In cases of cancer mortality, to determine the value of CAC for predicting risk of CVD as a supporting cause of death.

Methods: The CAC Consortium is a multi-center cohort of 66,636 asymptomatic adults without CVD who underwent CAC scanning. During a follow-up of 12.5 years, 1129 patients died of cancer and were included in this analysis. The primary outcome was presence of CVD listed as a supporting cause of cancer mortality on official death certificates obtained from the National Death Index. Logistic regression models were used to assess the odds of CVD being listed as a supporting cause of death by CAC.

Results: CVD was listed as a supporting cause of death in 306 (27%) cancer mortality cases. Baseline CAC was significantly higher in individuals with CVD-supported mortality. Odds ratios of having CVD-supported death increased by ASCVD risk score category [1.15 (0.81, 1.65) for 5-20% 10-year risk and 1.97 (1.36, 2.89) for ≥20% risk, in reference to <5% 10-year ASCVD risk] and CAC category [1.07 (0.73, 1.57) for CAC 1-99, 1.29 (0.87, 1.93) for CAC 100-399, and 2.14 (1.48, 3.09) for CAC ≥400 relative to CAC 0]. In the CAC ≥400 group, these associations remained significantly elevated after adjustment for traditional CVD risk factors [1.66 (1.08, 2.55)]. A sensitivity analysis using a more specific ASCVD-supported mortality outcome, defined as coronary heart disease, stroke, and peripheral artery disease, demonstrated that adjusted odds of ASCVD-supported cancer mortality were significantly elevated in the CAC ≥400 group relative to CAC 0 [3.09 (1.39, 7.38)].

Conclusions: In cancer mortality cases, high antecedent CAC predicted risk of having CVD as a supporting cause of death on official death certificates, independently of ASCVD risk score and CVD risk factors. CAC may be useful for identifying cancer patients at high CVD risk who might benefit from more intense preventive cardiovascular therapies.
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http://dx.doi.org/10.1016/j.ajpc.2020.100119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315471PMC
December 2020

20-Year trend of high prevalence of zero coronary artery calcium in beach cities of Southern California: A blue zone?

Am J Prev Cardiol 2020 Dec 21;4:100098. Epub 2020 Oct 21.

Lundquist Institute of Biomedical Innovation and Research at Harbor UCLA Medical Center, Torrance, CA, USA.

Background: Blue zones are longevity hotspots around the world characterized by highest concentrations of healthy centenarians. Certified blue zone communities are designed by implementation of environmental and policy changes that promote healthy behaviors.

Objective: To examine the trends of prevalence of zero CAC, a marker of ideal cardiovascular and overall health status and burden of cardiovascular risk factors in Beach Cities/certified blue zones of Southern California and rest of California.

Methods: This is a population-based cohort study of persons aged 50 years or older in California, who underwent CAC screening between 2000 and 2019. A total of 3864 participants from Beach Cities of Southern California were identified by Zip Codes and compared with 35,537 participants from rest of California. We compared trends of prevalence of zero CAC and cardiovascular risk factors between the two groups, in 5-year intervals.

Results: Among 39,401 participants (mean age, 58.1 years; 36% women), 13,374 (34%) had zero CAC. The prevalence of CAC ​= ​0 was significantly higher in Beach Cities compared to the rest of California (p ​< ​0.001). Across the study period, the prevalence of cardiac risk factors including obesity, smoking, diabetes and hypertension remain significantly lower in Beach Cities. (p ​< ​0.001).

Conclusions: This study, shows for the first time, that higher prevalence of zero CAC in Beach Cities of California, adds validity to excellent prognosis and longevity in these areas. The impact of policy implementation and environmental changes on lifestyle patterns, cardiovascular health and healthy ageing needs to be evaluated.
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http://dx.doi.org/10.1016/j.ajpc.2020.100098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315595PMC
December 2020

Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes.

Circ Genom Precis Med 2021 Aug 9;14(4):e003258. Epub 2021 Jul 9.

Department of Epidemiology (N.F., G.H.), University of North Carolina, Chapel Hill.

Background: Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.

Methods: We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.

Results: We replicated 2 loci (rs9369640 and rs9349379 near and rs10757278 near ) for CAC and one locus for cIMT (rs7412 and rs445925 near ) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near at 13q13.3) at =2.0×10 in EA. No additional loci were identified with the meta-analyses of EA and African ancestry. The expression quantitative trait loci analysis with nearby expressed genes derived from arterial wall and metabolic tissues from the Genotype-Tissue Expression project pinpoints , encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations (<3.1×10) for 3 previously reported coronary artery disease loci for these subclinical atherosclerotic phenotypes (rs2891168 near and rs11170820 near for CAC, and rs7412 near for cIMT).

Conclusions: Our results provide potential biological mechanisms that could link CAC and cIMT to increased cardiovascular disease risk in individuals with T2D.
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http://dx.doi.org/10.1161/CIRCGEN.120.003258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435075PMC
August 2021

Temporal change in inflammatory biomarkers and risk of cardiovascular events: the Multi-ethnic Study of Atherosclerosis.

ESC Heart Fail 2021 Oct 9;8(5):3769-3782. Epub 2021 Jul 9.

Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD, 21287-0409, USA.

Aims: Little is known about the association of temporal changes in inflammatory biomarkers and the risk of death and cardiovascular diseases. We aimed to evaluate the association between temporal changes in C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6) and risk of heart failure (HF), cardiovascular disease (CVD), and all-cause mortality in individuals without a history of prior CVD.

Methods And Results: Participants from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort with repeated measures of inflammatory biomarkers and no CVD event prior to the second measure were included. Quantitative measures, annual change, and biomarker change categories were used as main predictors in Cox proportional hazard models stratified based on sex and statin use. A total of 2258 subjects (50.6% female, mean age of 62 years) were studied over an average of 8.1 years of follow-up. The median annual decrease in CRP levels was 0.08 mg/L. Fibrinogen and IL-6 levels increased by a median of 30 mg/dL and 0.24 pg/mL annually. Temporal changes in CRP were positively associated with HF risk among females (HR: 1.18 per each standard deviation increase, P < 0.001) and other CVD in both female (HR: 1.12, P = 0.004) and male participants (HR: 1.24, P = 0.003). The association of CRP change with HF and other CVD was consistently observed in statin users (HR: 1.23 per SD increase, P = 0.001 for HF and HR: 1.19 per SD increase, P < 0.001 for other CVD). There were no significant associations between temporal changes of fibrinogen or IL-6 with HF or other CVD. Men with sustained high values of IL-6 had a 2.3-fold higher risk of all-cause mortality (P < 0.001) compared with those with sustained low values.

Conclusions: Temporal change in CRP is associated with HF only in women and statin users, and other CVD in both women and men, and statin users. Annual changes in fibrinogen and IL-6 were not predictive of cardiovascular outcomes in either sex.
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http://dx.doi.org/10.1002/ehf2.13445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497383PMC
October 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

Pericardial Fat and the Risk of Heart Failure.

J Am Coll Cardiol 2021 Jun;77(21):2638-2652

Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.

Background: Obesity is a well-established risk factor for heart failure (HF). However, implications of pericardial fat on incident HF is unclear.

Objectives: This study sought to examine the association between pericardial fat volume (PFV) and newly diagnosed HF.

Methods: This study ascertained PFV using cardiac computed tomography in 6,785 participants (3,584 women and 3,201 men) without pre-existing cardiovascular disease from the MESA (Multi-Ethnic Study of Atherosclerosis). Cox proportional hazards regression was used to evaluate PFV as continuous and dichotomous variable, maximizing the J-statistic: (Sensitivity + Specificity - 1).

Results: In 90,686 person-years (median: 15.7 years; interquartile range: 11.7 to 16.5 years), 385 participants (5.7%; 164 women and 221 men) developed newly diagnosed HF. PFV was lower in women than in men (69 ± 33 cm vs. 92 ± 47 cm; p < 0.001). In multivariable analyses, every 1-SD (42 cm) increase in PFV was associated with a higher risk of HF in women (hazard ratio [HR]: 1.44; 95% confidence interval [CI]: 1.21 to 1.71; p < 0.001) than in men (HR: 1.13; 95% CI: 1.01 to 1.27; p = 0.03) (interaction p = 0.01). High PFV (≥70 cm in women; ≥120 cm in men) conferred a 2-fold greater risk of HF in women (HR: 2.06; 95% CI: 1.48 to 2.87; p < 0.001) and a 53% higher risk in men (HR: 1.53; 95% CI: 1.13 to 2.07; p = 0.006). In sex-stratified analyses, greater risk of HF remained robust with additional adjustment for anthropometric indicators of obesity (p ≤ 0.008), abdominal subcutaneous or visceral fat (p ≤ 0.03) or biomarkers of inflammation and hemodynamic stress (p < 0.001) and was similar among Whites, Blacks, Hispanics, and Chinese (interaction p = 0.24). Elevated PFV predominantly augmented the risk of HF with preserved ejection fraction (p < 0.001) rather than reduced ejection fraction (p = 0.31).

Conclusions: In this large, community-based, ethnically diverse, prospective cohort study, pericardial fat was associated with an increased risk of HF, particularly HF with preserved ejection fraction, in women and men.
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http://dx.doi.org/10.1016/j.jacc.2021.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218602PMC
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 06 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483537PMC
June 2021

Utilizing coronary artery calcium to guide statin use.

Atherosclerosis 2021 06 7;326:17-24. Epub 2021 May 7.

Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. Electronic address:

Cardiovascular disease (CVD) is the leading cause of death worldwide, and accounts for over 30% of annual global fatality. Coronary artery calcium (CAC) screening, a highly distinct marker of coronary atherosclerosis, serves as an important arbitrator of atherosclerotic cardiovascular disease (ASCVD). Particularly in asymptomatic individuals, CAC testing offers a model for initiating or prolonging preventative statin therapies and subsequently up- or down-risking of patients. Though recent 2018 ACC/AHA Guidelines on Blood Cholesterol recommend CAC as an arbitrator of statin use, it remains uncertain whether these recommendations have been universally followed. Thus, we present a thorough discussion about CAC as an important determinator of ASCVD risk. In this regard we highlight the key points behind coronary artery calcium scoring, as a critical platform for stratifying risk and guiding future preventative treatments. This review paper supplies a background for the 2018 Cholesterol Guidelines: the rationalization behind CAC as a crucial arbitrator of cardiovascular risk. This paper will first (1) outline the role of CAC in reclassifying ASCVD risk. Next, it will (2) discuss studies that illustrate CAC's markedly novel reduction in the number needed to treat (NNT) to ameliorate one major cardiac event. Being years removed from 2018 Guidelines provides this paper the lens to (3) elucidate upcoming value-based advantages, cost effectiveness, and patient adherence brought by CAC. Last, this paper will also (4) extend the utility of CAC beyond that of the general population, and (5) discuss pertinent limitations brought by CAC score. By summarizing the framework behind recent cholesterol guidelines for ASCVD risk assessment, this review will address the debate of use of CAC for both the clinical setting and preventative therapy applications.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.04.011DOI Listing
June 2021

Association between Aortic Valve Calcification Progression and Coronary Atherosclerotic Plaque Volume Progression in the PARADIGM Registry.

Radiology 2021 07 11;300(1):79-86. Epub 2021 May 11.

From the Division of Cardiology, Department of Internal Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, South Korea (S.E.L.); Yonsei-Cedars-Sinai Integrative Cardiovascular Imaging Research Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea (S.E.L., J.M.S., H.J.C.); Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Yonsei University Health System, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea (J.M.S., S.S., H.J.C.); Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.A., E.C., G.P.); Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, Tex (M.H.A.); Department of Medicine, Los Angeles Biomedical Research Institute, Torrance, Calif (M.J.B.); Cardiovascular Imaging Unit, SDN IRCCS, Naples, Italy (F.C.); Department of Cardiology, William Beaumont Hospital, Royal Oak, Mich (K.C.); Pusan University Hospital, Busan, South Korea (J.H.C.); Seoul National University Bundang Hospital, Seongnam, South Korea (E.J.C.); Department of Radiology, Casa de Saude São Jose, Rio de Janeiro, Brazil (I.G.); Department of Radiology and Nuclear Medicine, German Heart Center Munich, Munich, Germany (M.H.); Department of Internal Medicine, Seoul National University College of Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea (Y.J.K.); Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea (B.K.L.); Department of Medicine and Radiology, University of British Columbia, Vancouver, Canada (J.A.L.); Department of Radiology, Area Vasta 1/ASUR Marche, Urbino, Italy (E.M.); UNICA, Unit of Cardiovascular Imaging, Hospital da Luz, Lisbon, Portugal (H.M., P.d.A.G.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Mass (P.H.S.); Division of Cardiology, Emory University School of Medicine, Atlanta, Ga (H.S.); Department of Pathology, CVPath Institute, Gaithersburg, Md (R.V.); Icahn School of Medicine at Mount Sinai, New York, NY (J.N.); Department of Imaging and Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif (D.S.B.); Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, NY (L.J.S., F.Y.L., J.K.M.); Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands (J.J.B.).

Background Aortic valve calcification (AVC) is a key feature of aortic stenosis, and patients with aortic stenosis often have coronary -artery disease. Therefore, proving the association between the progression of AVC and coronary atherosclerosis could improve follow-up and treatment strategies. Purpose To explore the association between the progression of AVC and the progression of total and plaque volume composition from a large multicenter registry of serial coronary CT angiographic examinations. Materials and Methods A prospective multinational registry (PARADIGM) of consecutive participants who underwent serial coronary CT angiography at intervals of every 2 years or more was performed (January 2003-December 2015). AVC and the total and plaque volume composition at baseline and follow-up angiography were quantitatively analyzed. Plaque volumes were normalized by using the mean total analyzed vessel length of the study population. Multivariable linear mixed-effects models were constructed. Results Overall, 594 participants (mean age ± standard deviation, 62 years ± 10; 330 men) were included (mean interval between baseline and follow-up angiography, 3.9 years ± 1.5). At baseline, the AVC score was 31 Agatston units ± 117, and the normalized total plaque volume at baseline was 122 mm ± 219. After adjustment for age, sex, clinical risk factors, and medication use, AVC was independently associated with total plaque volume (standardized β = 0.24; 95% CI: 0.16, 0.32; < .001) and both calcified (β = 0.26; 95% CI: 0.18, 0.34; < .001) and noncalcified (β = 0.17; 95% CI: 0.08, 0.25; < .001) plaque volumes at baseline. The progression of AVC was associated with the progression of total plaque volume (β = 0.13; 95% CI: 0.03, 0.22; = .01), driven solely by calcified plaque volume (β = 0.24; 95% CI: 0.14, 0.34; < .001) but not noncalcified plaque volumes (β = -0.06; 95% CI: -0.14, 0.03; = .17). Conclusion The overall burden of coronary atherosclerosis was associated with aortic valve calcification at baseline. However, the progression of aortic valve calcification was associated with only the progression of calcified plaque volume but not with the -progression of noncalcified plaque volume. Clinical trial registration no. NCT02803411 © RSNA, 2021 See also the editorial by Sinitsyn in this issue.
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http://dx.doi.org/10.1148/radiol.2021202630DOI Listing
July 2021

Effect of body mass index on bone mineral density is age-specific.

Nutr Metab Cardiovasc Dis 2021 06 4;31(6):1767-1773. Epub 2021 Mar 4.

Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. Electronic address:

Background And Aims: Obesity and osteoporosis are two important and growing public health problems worldwide. Body mass index (BMI) has been found to be inversely related to the risk of osteoporotic fracture. We aimed to assess the association of BMI with thoracic vertebral bone mineral density (BMD) measured from a quantitative computed tomography (QCT).

Methods And Results: We retrospectively evaluated the data from 15,758 consecutive patients (5675 females and 10,083 males) between age 20-90 years, who underwent Coronary Artery Calcium (CAC) scoring. Quantitative data analyses of thoracic trabecular BMD (mg/cm) was performed with a phantom system or phantomless using validated software. The gender-specific subgroup was divided based on age (<45, 45-55, 55-65, >65 yrs in females; <40,40-60,>60 yrs in Males) and weight by BMI (kg/m) as < 25 (normal or low weight), >25 - <30 (overweight) and >30 (obesity). Analysis of variance (ANOVA) and Scheffe's post hoc procedure tested the association of body weight/BMI on BMD. A significant positive association between the body weight and BMD existed in obese population in elder groups in both genders (p < 0.05). There was no significant difference in BMD in 40-60 years in men and <55 years in women with normal or low weight compared to overweight or obese cohorts.

Conclusions: We concluded that the effect of weight on BMD is age-specific and the BMD should be monitored routinely with a cardiac CT scan in the senile population.
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http://dx.doi.org/10.1016/j.numecd.2021.02.027DOI Listing
June 2021

EPA's pleiotropic mechanisms of action: a narrative review.

Postgrad Med 2021 Aug 13;133(6):651-664. Epub 2021 May 13.

Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Treatment with icosapent ethyl 4 g/day, a highly purified and stable ethyl ester of eicosapentaenoic acid (EPA), demonstrated a significant reduction in atherosclerotic cardiovascular disease (ASCVD) events and death in REDUCE-IT. However, analyses of REDUCE-IT and meta-analyses have suggested that this clinical benefit is greater than can be achieved by triglyceride reduction alone. EPA therefore may have additional pleiotropic effects, including anti-inflammatory and anti-aggregatory mechanisms. EPA competes with arachidonic acid for cyclooxygenase and lipoxygenase, producing anti-inflammatory and anti-aggregatory metabolites rather than the more deleterious metabolites associated with arachidonic acid. Changing the EPA:arachidonic acid ratio may shift metabolic status from pro-inflammatory/pro-aggregatory to anti-inflammatory/anti-aggregatory. EPA also has antioxidant effects and increases synthesis of nitric oxide. Incorporation of EPA into phospholipid bilayers influences membrane structure and may help to prevent cardiac arrhythmias. Clinically, this may translate into improved vascular health, including regression of atherosclerotic plaque. Overall, EPA has a range of pleiotropic effects that contribute to a reduction in ASCVD.
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http://dx.doi.org/10.1080/00325481.2021.1921491DOI Listing
August 2021
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