58 results on '"Orringer CE"'
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2. High-intensity statins vs. moderate-intensity statin-ezetimibe combination therapy: A patient centered approach.
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Grant JK and Orringer CE
- Abstract
Competing Interests: Declaration of competing interest All authors confirm no relationship with industry, disclosures, or source of funding for the work presented in this manuscript.
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- 2024
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3. Overcoming barriers to implementation: Improving incidental coronary calcium reporting on non-EKG gated chest CT scans.
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Grant JK, Bokhari A, Manoharan A, Koester M, Dangl M, Martillo M, Whelton SP, Martin SS, Blumenthal RS, Blaha MJ, Eng D, Fishman J, and Orringer CE
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- Humans, Female, Male, Middle Aged, Aged, Incidental Findings, Coronary Vessels diagnostic imaging, Thorax diagnostic imaging, Calcium analysis, Calcinosis diagnostic imaging, Radiography, Thoracic, Electrocardiography, Tomography, X-Ray Computed methods, Coronary Artery Disease diagnostic imaging
- Abstract
Background: Current guidelines recommend the reporting of incidental coronary artery calcification (CAC) on non-electrocardigram-gated computed tomography (CT) scans of the chest. The finding of incidental moderate or severe CAC on non-cardiac non-contrast chest CT correlates with a CAC score ≥ 100 Agatston units, a guideline-based indication for a clinician-patient discussion regarding the initiation of statin therapy. In contemporary practice, whether the presence and severity of incidental CAC are routinely reported on such CT scans of the chest is unknown., Methods: At a major university hospital, we collected a one-month convenience sample of 297 patients who had chest CT imaging for indications other than lung cancer screening (OICT) and 42 patients who underwent lung cancer chest CT screening (LSCT). We evaluated reporting patterns of incidental CAC in the body and impression of the reports as compared to the overreading of such studies by a board-certified CT chest radiologist. We hypothesized and demonstrated that there was underreporting of incidental CAC on these scans. We then undertook an initiative to educate reporting radiologists on the importance of reporting CAC and implemented a reporting template change to encourage routine reporting. Then we repeated another one-month sample (n= 363 for the OICT and n= 63 for the LSCT groups) to evaluate reporting patterns following our intervention., Results: The presence of incidental moderate and severe CAC was systematically underreported in the OICT group (0 and 4.8 %) and the severity was never mentioned in the impression of reports. In the LSCT group, the presence of incidental moderate and severe CAC was also underreported (66.7 % and 75 %) and the severity of CAC was mentioned 50 % of the time in the impression of the reports. Following the initiation of an educational program and radiology reporting template change, there was a significant increase in reporting of moderate or severe CAC in the OICT group (0 vs. 80.0 %, p < 0.001) and (4.8 vs. 93.5 %, p < 0.001) respectively and a significant increase in the reporting of the severity of incidental CAC for those with severe CAC in the LSCT group (50 vs. 94.1 %, p=0.006)., Conclusion: Despite guideline recommendations, incidental CAC was underreported at a large academic center. We implemented a system that significantly improved reporting patterns of incidental CAC. Failure to report incidental CAC represents a missed opportunity to initiate preventive therapies. Hospital systems interested in improving the quality of their radiology reporting procedures should examine their practices to assure that CAC quantification is routinely performed., Competing Interests: Declaration of competing interest All authors confirm no relationship with industry, disclosures, or source of funding for the work presented in this manuscript., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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4. Over-the-Counter Statins: Revisited After a Generation.
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Orringer CE
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- Humans, Cardiovascular Diseases prevention & control, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Nonprescription Drugs
- Abstract
Competing Interests: Funding Support and Author Disclosures The author has reported that he has no relationships relevant to the contents of this paper to disclose.
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- 2024
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5. Inclisiran: Where Are We on Safety, Efficacy, and Clinical Effectiveness of siRNA Therapies for Prevention?
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Ballantyne CM, Minhas AMK, and Orringer CE
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- Humans, RNA, Small Interfering therapeutic use, Treatment Outcome, Proprotein Convertase 9 genetics, Hypercholesterolemia drug therapy, Anticholesteremic Agents therapeutic use
- Abstract
Competing Interests: Funding Support and Author Disclosures Dr Ballantyne has received institutional grant/research support and consulting fees from Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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- 2023
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6. Coronary and Extra-coronary Subclinical Atherosclerosis to Guide Lipid-Lowering Therapy.
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Grant JK and Orringer CE
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- Adult, Humans, Proprotein Convertase 9, Cholesterol, LDL, Calcium, Risk Assessment methods, Risk Factors, Coronary Vessels, Vascular Calcification diagnostic imaging, Vascular Calcification drug therapy, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease drug therapy, Atherosclerosis diagnostic imaging, Atherosclerosis drug therapy
- Abstract
Purpose of Review: To discuss and review the technical considerations, fundamentals, and guideline-based indications for coronary artery calcium scoring, and the use of other non-invasive imaging modalities, such as extra-coronary calcification in cardiovascular risk prediction., Recent Findings: The most robust evidence for the use of CAC scoring is in select individuals, 40-75 years of age, at borderline to intermediate 10-year ASCVD risk. Recent US recommendations support the use of CAC scoring in varying clinical scenarios. First, in adults with very high CAC scores (CAC ≥ 1000), the use of high-intensity statin therapy and, if necessary, guideline-based add-on LDL-C lowering therapies (ezetimibe, PCSK9-inhibitors) to achieve a ≥ 50% reduction in LDL-C and optimally an LDL-C < 70 mg/dL is recommended. In patients with a CAC score ≥ 100 at low risk of bleeding, the benefits of aspirin use may outweigh the risk of bleeding. Other applications of CAC scoring include risk estimation on non-contrast CT scans of the chest, risk prediction in younger patients (< 40 years of age), its value as a gatekeeper for the decision to perform nuclear stress testing, and to aid in risk stratification in patients presenting with low-risk chest pain. There is a correlation between extra-coronary calcification (e.g., breast arterial calcification, aortic calcification, and aortic valve calcification) and incident ASCVD events. However, its role in informing lipid management remains unclear. Identification of coronary calcium in selected patients is the single best non-invasive imaging modality to identify future ASCVD risk and inform lipid-lowering therapy decision-making., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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7. C-reactive protein in people with high lipoprotein a: a partner in crime or an innocent bystander?
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Orringer CE
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- Humans, Lipoprotein(a), Crime, C-Reactive Protein, Aortic Valve Stenosis
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Competing Interests: Conflict of interest None declared.
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- 2023
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8. A Review of Statin Intolerance: a Focus on Statin-Attributed Muscle Symptoms.
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Orringer CE, Grant JK, and Tokgozoglu L
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- Calcium, Humans, Muscles, Nocebo Effect, Prevalence, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects
- Abstract
Purpose of Review: To provide a systematic approach to management of the patient with statin-attributed muscle symptoms., Recent Findings: We examined the prevalence of statin intolerance, the role of the nocebo effect, key findings in the patient's history and laboratory studies, the potential value of coronary calcium scoring, and the importance of shared decision-making in considering statin re-initiation. Most patients with statin-attributed muscle symptoms can be successfully treated with statins or a combination of statins and non-statins to achieve successful ASCVD risk reduction., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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9. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Solution Set Oversight Committee.
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Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Covington AM, DePalma SM, Minissian MB, Orringer CE, Smith SC Jr, Waring AA, and Wilkins JT
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- Cholesterol, LDL, Consensus, Ezetimibe, Humans, United States epidemiology, Anticholesteremic Agents therapeutic use, Cardiology, Cardiovascular Diseases drug therapy, Cardiovascular Diseases epidemiology, Cardiovascular Diseases prevention & control, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
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- 2022
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10. Under-reporting and under-representation of non-Hispanic Black subjects in lipid-lowering atherosclerotic cardiovascular disease outcomes trials: A systematic review.
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Grant JK, Dangl M, Koester M, Tegegn M, Knijnik L, Singh H, and Orringer CE
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- Humans, United States epidemiology, Cholesterol, LDL, Ezetimibe, Proprotein Convertase 9, Anticholesteremic Agents pharmacology, Cardiovascular Diseases prevention & control, Hypercholesterolemia, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Atherosclerosis drug therapy
- Abstract
Background: Non-Hispanic (NH) Black participants have been under-represented in studies of cardiovascular disease., Objective: We sought to determine the trends of reporting and representation of NH Black subjects in randomized controlled trials (RCTs) of lipid-lowering therapies demonstrating atherosclerotic cardiovascular disease (ASCVD) risk reduction benefit., Methods: The electronic databases of MEDLINE, EMBASE and ClinicalTrials.gov were searched from 1990-2020. Studies of lipid-lowering therapies (i.e., statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors [PCSK9], and icosapent ethyl) with proven ASCVD benefit, sample sizes of at least 1000 subjects and follow-up of at least 1 year were included (40 RCTs, N=306 747 total participants). We examined articles and supplementary material for participant-level race data. Using United States disease prevalence data, the participation-to-prevalence ratio (PPR) metric was used to estimate the representation of NH Black subjects compared with their reported disease burden (i.e., < 0.8 indicated under-representation; > 1.2, over-representation; and 0.8 to <1.2, adequate representation)., Results: The median (interquartile range) number of participants per trial was 4871 (2434-10077). NH Black enrollees comprised 7.3% (95% CI, 0.9%-15.4%) of the total number of subjects reported. During the time intervals 1990-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015 and 2016-2020, NH Black participation was 0%, 1.1%, 4.4%, 4.8%, 0.2% and 0.7% respectively (P for trend <0.001). For statin trials, the participation of NH Black subjects was reported in 0 studies between 1990-1995 and in 9 of 28 trials from 1996-2020. For ezetimibe and icosapent ethyl, NH Black participants were reported in 0 of 3 and 0 of 1 studies, respectively. For trials of PCSK9 inhibitors, NH Black subjects were reported in 2 of 5 (40%). NH Black participants were under-represented compared with their disease burden in studies evaluating subjects with diabetes, hypercholesterolemia, stable coronary artery disease, and acute coronary syndrome (PPR < 0.8 for all)., Conclusion: NH Black participants are markedly under-represented, and results are under-reported. The inclusion of population and disease specific representation of NH Black persons and their related social determinants of health will help to address the disparity in preventive care for this historically undertreated population., (Copyright © 2022. Published by Elsevier Inc.)
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- 2022
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11. Use of Lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association.
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Wilson DP, Jacobson TA, Jones PH, Koschinsky ML, McNeal CJ, Nordestgaard BG, and Orringer CE
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Lipoprotein(a) [Lp(a)] is a well-recognized, independent risk factor for atherosclerotic cardiovascular disease, with elevated levels estimated to be prevalent in 20% of the population. Observational and genetic evidence strongly support a causal relationship between high plasma concentrations of Lp(a) and increased risk of atherosclerotic cardiovascular disease-related events, such as myocardial infarction and stroke, and valvular aortic stenosis. In this scientific statement, we review an array of evidence-based considerations for testing of Lp(a) in clinical practice and the utilization of Lp(a) levels to inform treatment strategies in primary and secondary prevention., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2022 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
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- 2022
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12. Global think tank on the clinical considerations and management of lipoprotein(a): The top questions and answers regarding what clinicians need to know.
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Virani SS, Koschinsky ML, Maher L, Mehta A, Orringer CE, Santos RD, Shapiro MD, and Saseen JJ
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- Humans, Lipoprotein(a), Risk Assessment, Risk Factors, Atherosclerosis, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Cardiovascular Diseases prevention & control
- Abstract
Evidence from Mendelian randomization studies suggest that lipoprotein(a) (Lp(a)) has a causal role in the development of atherosclerotic cardiovascular disease risk. However, guidelines and consensus statement recommendations vary regarding how clinicians should incorporate Lp(a) into patient care. To provide practical answers to key questions pertaining to Lp(a) that clinicians will find useful when assessing and treating patients, a global think tank was convened. Representatives from seven national and international stakeholder organizations answered questions that were focused on: Lp(a) measurement; ethnic, gender, and age considerations; factoring Lp(a) into risk assessment; and current and emerging treatment options for elevated Lp(a). This manuscript summarizes the finding from this global think tank. Areas requiring further investigation were identified, and the need to standardize reporting of Lp(a) levels to ensure harmonization and comparability across laboratories and research studies is emphasized., Competing Interests: Declaration of Competing Interest JJS, CEO, LM, and AM have none. RDS has received honoraria outside this work related to consulting, speaker, or research activities from: Abbott, Ache, Amgen, Amryt, Astra Zeneca, EMS, Esperion, Getz Pharma, Kowa, Hypera, MSD, Merck, Novartis, Novo-Nordisk, Pfizer, PTC Therapeutics, Roche and Sanofi. SV has received research support from the National Institutes of Health, Department of Veterans Affairs, World Heart Federation, Tahir and Jooma Family and honorarium from the American College of Cardiology in his role as the Associate Editor for Innovations (acc.org). MLK has received honoraria related to consulting, research and/or speaker activities from Ayma, Novartis, Abcentra, and Amgen. MDS has served on Scientific Advisory Boards with the following entities: Amgen, Novartis, Novo Nordisk., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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13. Managing Atherosclerotic Cardiovascular Risk in Young Adults: JACC State-of-the-Art Review.
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Stone NJ, Smith SC Jr, Orringer CE, Rigotti NA, Navar AM, Khan SS, Jones DW, Goldberg R, Mora S, Blaha M, Pencina MJ, and Grundy SM
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- Atherosclerosis epidemiology, Humans, Risk Factors, Young Adult, Atherosclerosis diagnosis, Atherosclerosis therapy, Heart Disease Risk Factors
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There is a need to identify high-risk features that predict early-onset atherosclerotic cardiovascular disease (ASCVD). The authors provide insights to help clinicians identify and address high-risk conditions in the 20- to 39-year age range (young adults). These include tobacco use, elevated blood pressure/hypertension, family history of premature ASCVD, primary severe hypercholesterolemia such as familial hypercholesterolemia, diabetes with diabetes-specific risk-enhancing factors, or the presence of multiple other risk-enhancing factors, including in females, a history of pre-eclampsia or menopause under age 40. The authors update current thinking on lipid risk factors such as triglycerides, non-high-density lipoprotein cholesterol, apolipoprotein B, or lipoprotein (a) that are useful in understanding an individual's long-term ASCVD risk. The authors review emerging strategies, such as coronary artery calcium and polygenic risk scores in this age group, that have potential clinical utility, but whose best use remains uncertain. Finally, the authors discuss both the obstacles and opportunities for addressing prevention in early adulthood., Competing Interests: Funding Support and Author Disclosures Dr Rigotti received support from National Institutes of Health (NIH) grant # R01HL111821; has received grants from NCI, NIDA, and Achieve Life Sciences; has been a consultant for Achieve Life Sciences; and has received royalties from UpToDate. Dr Mora received support from NIH grant # K24HL136852; has received grants from the NIH, outside this work; and has been a consultant for Pfizer and Quest Diagnostics. Dr Khan has received support from American Heart Association grant #19TPA34890060 and the NIH grants P30AG059988 and P30DK092939, outside this work. Dr Navar has received funding for research to her institution from Bristol Myers Squibb, Esperion, Amgen, and Janssen; and has received honoraria and consulting fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Esperion, Janssen, Lilly, Sanofi, Regeneron, NovoNordisk, Novartis, The Medicines Company, New Amsterdam, Cerner, 89Bio, and Pfizer. Dr Blaha has received grants from the NIH, the Food and Drug Administration, American Heart Association, Amgen Foundation, Bayer, and Novo Nordisk; and has served on advisory boards for Amgen, Sanofi, Regeneron, Novartis, Novo Nordisk, Bayer, Akcea, Kowa, 89Bio, Kaleido, Inozyme, and Roche. Dr Pencina has received funding outside the work from the nonprofit Doggone Foundation/McGill University Health Centre; has received grants from Regeneron/Sanofi and Amgen to his institution; and has served on an advisory board for Boehringer Ingelheim. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2022
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14. LDL-C Estimation: The Perils of Living With Imperfection.
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Maki KC, Grant JK, and Orringer CE
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- Humans, Triglycerides, Cholesterol, LDL
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Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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- 2022
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15. PCSK9 inhibition for acute arterial events: more than LDL lowering.
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Orringer CE
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- Cholesterol, LDL, Humans, Anticholesteremic Agents therapeutic use, Proprotein Convertase 9
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- 2021
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16. Coronary artery calcium scoring in patients with statin associated muscle symptoms: Prescribing statins for those most likely to benefit.
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Orringer CE, Blaha MJ, and Stone NJ
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- Atherosclerosis prevention & control, Cardiovascular Diseases prevention & control, Coronary Artery Disease diagnosis, Coronary Vessels pathology, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Muscular Diseases diagnosis, Primary Prevention methods, Risk Assessment methods, Risk Factors, Vascular Calcification diagnosis, Coronary Artery Disease metabolism, Coronary Vessels metabolism, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Muscular Diseases chemically induced, Vascular Calcification metabolism
- Abstract
For primary prevention, statin therapy reduces the incidence of atherosclerotic cardiovascular disease (ASCVD) events in adults with intermediate or high estimated 10-year risk using traditional population-based risk calculators. While a variety of reported symptoms may limit statin adherence, muscle complaints, whether typical or atypical of that associated with statin therapy, are the most common reported by patients. Because additional testing, alteration in the patient's medical regimen and subsequent medical visits are often required, an informed clinician-patient discussion and shared decision making are necessary to achieve the best outcomes. The authors provide support for the perspective that coronary calcium scoring, by individualizing estimated risk and helping to identify those most likely to benefit, plays a vital role in preventive therapy decision-making for the primary prevention patient with troublesome muscle complaints attributed to statin therapy., (Copyright © 2021. Published by Elsevier Inc.)
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- 2021
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17. Modeling the Recommended Age for Initiating Coronary Artery Calcium Testing Among At-Risk Young Adults.
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Dzaye O, Razavi AC, Dardari ZA, Shaw LJ, Berman DS, Budoff MJ, Miedema MD, Nasir K, Rozanski A, Rumberger JA, Orringer CE, Smith SC Jr, Blankstein R, Whelton SP, Mortensen MB, and Blaha MJ
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- Adult, Cohort Studies, Computed Tomography Angiography, Disease Susceptibility, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Coronary Artery Disease diagnostic imaging, Models, Cardiovascular, Risk Assessment, Vascular Calcification diagnostic imaging
- Abstract
Background: There are currently no recommendations guiding when best to perform coronary artery calcium (CAC) scanning among young adults to identify those susceptible for developing premature atherosclerosis., Objectives: The purpose of this study was to determine the ideal age at which a first CAC scan has the highest utility according to atherosclerotic cardiovascular disease (ASCVD) risk factor profile., Methods: We included 22,346 CAC Consortium participants aged 30-50 years who underwent noncontrast computed tomography. Sex-specific equations were derived from multivariable logistic modeling to estimate the expected probability of CAC >0 according to age and the presence of ASCVD risk factors., Results: Participants were on average 43.5 years of age, 25% were women, and 34% had CAC >0, in whom the median CAC score was 20. Compared with individuals without risk factors, those with diabetes developed CAC 6.4 years earlier on average, whereas smoking, hypertension, dyslipidemia, and a family history of coronary heart disease were individually associated with developing CAC 3.3-4.3 years earlier. Using a testing yield of 25% for detecting CAC >0, the optimal age for a potential first scan would be at 36.8 years (95% CI: 35.5-38.4 years) in men and 50.3 years (95% CI: 48.7-52.1 years) in women with diabetes, and 42.3 years (95% CI: 41.0-43.9 years) in men and 57.6 years (95% CI: 56.0-59.5 years) in women without risk factors., Conclusions: Our derived risk equations among health-seeking young adults enriched in ASCVD risk factors inform the expected prevalence of CAC >0 and can be used to determine an appropriate age to initiate clinical CAC testing to identify individuals most susceptible for early/premature atherosclerosis., Competing Interests: Funding Support and Author Disclosures This project was supported in part by a research grant from the National Institutes of Health-National Heart, Lung, and Blood Institute (L30 HL110027). Dr Blaha has received grants from the National Institutes of Health, U.S. Food and Drug Administration, American Heart Association, Amgen, and Aetna Foundation; and has received honoraria from Amgen, Sanofi, Regeneron, Novartis, Novo Nordisk, Bayer, Akcea, 89Bio, Zogenix, Tricida, and Gilead. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2021
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18. High-Intensity Statins Benefit High-Risk Patients: Why and How to Do Better.
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Grundy SM, Stone NJ, Blumenthal RS, Braun LT, Heidenreich PA, Lloyd-Jones D, Orringer CE, Saseen JJ, Smith SC Jr, Sperling LS, and Virani SS
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- Anticholesteremic Agents therapeutic use, Cholesterol, LDL blood, Ezetimibe therapeutic use, Humans, Hypercholesterolemia drug therapy, Primary Prevention, Secondary Prevention, Coronary Artery Disease prevention & control, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
- Abstract
Review of the US and European literature indicates that most patients at high risk for atherosclerotic cardiovascular disease (ASCVD are not treated with high-intensity statins, despite strong clinical-trial evidence of maximal statin benefit. High-intensity statins are recommended for 2 categories of patients: those with ASCVD (secondary prevention) and high-risk patients without clinical ASCVD. Most patients with ASCVD are candidates for high-intensity statins, with a goal for low-density lipoprotein cholesterol reduction of 50% or greater. A subgroup of patients with ASCVD are at very high risk and can benefit by the addition of nonstatin drugs (ezetimibe with or without bile acid sequestrant or bempedoic acid and/or a proprotein convertase subtilisin/kexin type 9 inhibitor). High-risk primary prevention patients are those with severe hypercholesterolemia, diabetes with associated risk factors, and patients aged 40 to 75 years with a 10-year risk for ASCVD of 20% or greater. In patients with a 10-year risk of 7.5% to less than 20%, coronary artery calcium scoring is an option; if the coronary artery calcium score is 300 or more Agatston units, the patient can be up-classified to high risk. If high-intensity statin treatment is not tolerated in high-risk patients, a reasonable approach is to combine a moderate-intensity statin with ezetimibe. In very high-risk patients, proprotein convertase subtilisin/kexin type 9 inhibitors lower low-density lipoprotein cholesterol levels substantially and hence reduce risk as well., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)
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- 2021
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19. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) guidelines for management of dyslipidemia and cardiovascular disease risk reduction: Putting evidence in context.
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Al Rifai M, Blumenthal RS, Stone NJ, Schofield RS, Orringer CE, Michos ED, Heidenreich PA, Braun L, Birtcher KK, Smith SC, Nambi V, Grundy S, and Virani SS
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- Biomarkers blood, Cardiovascular Diseases diagnosis, Cardiovascular Diseases mortality, Clinical Decision-Making, Consensus, Drug Monitoring standards, Dyslipidemias blood, Dyslipidemias diagnosis, Dyslipidemias mortality, Heart Disease Risk Factors, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Protective Factors, Risk Assessment, Time Factors, Treatment Outcome, United States epidemiology, United States Department of Defense, United States Department of Veterans Affairs, Cardiovascular Diseases prevention & control, Cholesterol blood, Dyslipidemias drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Military Medicine standards, Primary Prevention standards, Secondary Prevention standards
- Abstract
Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the United States (U.S.) and incurs significant cost to the healthcare system. Management of cholesterol remains central for ASCVD prevention and has been the focus of multiple national guidelines. In this review, we compare the American Heart Association (AHA)/American College of Cardiology (ACC) and the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) Cholesterol guidelines. We review the evidence base that was used to generate recommendations focusing on 4 distinct themes: 1) the threshold of absolute 10-year ASCVD risk to start a clinician-patient discussion for the initiation of statin therapy in primary prevention patients; 2) the utility of coronary artery calcium score to guide clinician-patient risk discussion pertaining to the initiation of statin therapy for primary ASCVD prevention; 3) the use of moderate versus high-intensity statin therapy in patients with established ASCVD; and 4) the utility of ordering lipid panels after initiation or intensification of lipid lowering therapy to document efficacy and monitor adherence to lipid lowering therapy. We discuss why the VA/DoD and AHA/ACC may have reached different conclusions on these key issues., Competing Interests: Declaration of Competing Interest Salim S. Virani, Research support: Department of Veterans Affairs, World Heart Federation, Tahir and Jooma Family. Honorarium: American College of Cardiology (Associate Editor for Innovations, acc.org). Vijay Nambi, Site PI for study sponsored by AMGEN. Supported by VA MERIT award. Provisional patent along with BCM, Roche on use of biomarkers in prediction of Heart failure, (Published by Elsevier Inc.)
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- 2021
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20. 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia: A Report of the American College of Cardiology Solution Set Oversight Committee.
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Virani SS, Morris PB, Agarwala A, Ballantyne CM, Birtcher KK, Kris-Etherton PM, Ladden-Stirling AB, Miller M, Orringer CE, and Stone NJ
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- Cardiometabolic Risk Factors, Clinical Decision Rules, Consensus, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Patient Care Management standards, Risk Assessment methods, United States, Cardiology methods, Cardiology trends, Coronary Artery Disease prevention & control, Coronary Artery Disease therapy, Diet Therapy methods, Hypertriglyceridemia etiology, Hypertriglyceridemia metabolism, Hypertriglyceridemia psychology, Hypertriglyceridemia therapy, Nutrition Policy, Risk Reduction Behavior
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- 2021
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21. How low is safe? The frontier of very low (<30 mg/dL) LDL cholesterol.
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Karagiannis AD, Mehta A, Dhindsa DS, Virani SS, Orringer CE, Blumenthal RS, Stone NJ, and Sperling LS
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- Cholesterol, LDL, Ezetimibe therapeutic use, Humans, Proprotein Convertase 9, Anticholesteremic Agents therapeutic use, Cardiovascular Diseases prevention & control, Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Abstract
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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)
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- 2021
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22. In Reply-Coronary Artery Calcium Scores I and II.
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Orringer CE and Maki KC
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- Calcium, Coronary Angiography, Coronary Vessels diagnostic imaging, Humans, Coronary Artery Disease diagnostic imaging, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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- 2021
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23. The National Lipid Association scientific statement on coronary artery calcium scoring to guide preventive strategies for ASCVD risk reduction.
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Orringer CE, Blaha MJ, Blankstein R, Budoff MJ, Goldberg RB, Gill EA, Maki KC, Mehta L, and Jacobson TA
- Abstract
An Expert Panel of the National Lipid Association reviewed the evidence related to the use of coronary artery calcium (CAC) scoring in clinical practice for adults seen for primary prevention of atherosclerotic cardiovascular disease. Recommendations for optimal use of this test in adults of various races/ethnicities, ages and multiple domains of primary prevention, including those with a 10-year ASCVD risk <20%, those with diabetes or the metabolic syndrome, and those with severe hypercholesterolemia were provided. Recommendations were also made on optimal timing for repeat calcium scoring after an initial test, use of CAC scoring in those taking statins, and its role in informing the clinician patient discussion on the benefit of aspirin and anti-hypertensive drug therapy. Finally, a vision is provided for the future of coronary calcium scoring., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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24. Transatlantic Lipid Guideline Divergence: Same Data But Different Interpretations.
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Orringer CE, Tokgozoglu L, Maki KC, Ray KK, Saseen JJ, and Catapano AL
- Subjects
- Cardiovascular Diseases epidemiology, Europe, Humans, Hypolipidemic Agents therapeutic use, Practice Guidelines as Topic, Risk Factors, United States, Cardiovascular Diseases blood, Cardiovascular Diseases prevention & control, Lipids blood
- Abstract
Despite consensus that excessive circulating concentrations of apoB-lipoproteins is a key driver for the atherosclerotic process and that treatments that low-density lipoprotein cholesterol lowering by up-regulation of low-density lipoprotein cholesterol receptor expression reduces that risk, divergent viewpoints on interpretation of study data have resulted in substantial differences in European and American lipid guideline recommendations. This article explores those differences and highlights the importance of understanding guideline-based lipid management to improve patient care and reduce the risk of clinical atherosclerotic cardiovascular disease.
- Published
- 2020
- Full Text
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25. HOPE for Rational Statin Allocation for Primary Prevention: A Coronary Artery Calcium Picture Is Worth 1000 Words.
- Author
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Orringer CE and Maki KC
- Subjects
- Adult, Aged, Clinical Decision-Making, Coronary Artery Disease diagnosis, Coronary Artery Disease etiology, Decision Making, Shared, Female, Health Care Costs, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Male, Middle Aged, Practice Guidelines as Topic, Primary Prevention economics, Risk Assessment, Risk Factors, Severity of Illness Index, Vascular Calcification diagnosis, Coronary Artery Disease prevention & control, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Primary Prevention methods
- Abstract
Allocation of statin therapy for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in borderline- and intermediate-risk patients has traditionally been based on population-based global risk assessment and other clinical and laboratory characteristics. Patient-specific treatment decisions are needed to provide maximal benefit and avoid unnecessary treatment. Guideline-based lipid management proposes that coronary artery calcium scoring is reasonable to implement in patients with a 10-year risk of 5.0% to 19.9% (borderline to intermediate risk) by using the pooled cohort equations when the decision about whether to initiate statin therapy is uncertain. We report data from both observational studies and a large primary prevention randomized controlled trial that support the position that this decision is, in fact, uncertain in about half of such patients because of risk misclassification. Such misclassification can be largely avoided by more widespread implementation of coronary calcium scoring, which helps to identify those with coronary artery calcium scores of 0, a finding associated with a less than 5.0% 10-year probability of an ASCVD event. Deferral of statin therapy in such patients, in the absence of smoking, diabetes, or a family history of premature ASCVD, provides more individualized and appropriate care and avoids the expense and potential adverse effects of statin therapy in those with low potential for absolute risk reduction. A rationale is also provided for the importance of coronary artery calcium scoring in women 50 years and older, possibly in place of 1 screening mammogram in women at least 55 years of age to avoid incremental radiation exposure, on the basis of the substantially higher lifetime risk of morbidity and mortality from ASCVD than from breast cancer. In patients with borderline or intermediate ASCVD risk, coronary artery calcium scoring should be used, whenever possible, as an aid to rational statin allocation for the primary prevention of ASCVD., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
26. When a "normal" cholesterol level is not normal: Exposing an unusual presentation of familial hypercholesterolemia.
- Author
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Orringer CE and Grant JK
- Subjects
- Adult, Female, Genetic Testing, Humans, Hyperlipoproteinemia Type II diagnosis, Hyperlipoproteinemia Type II genetics, Male, Pedigree, Cholesterol blood, Hyperlipoproteinemia Type II blood
- Abstract
A classic finding in patients with familial hypercholesterolemia is the presence of markedly elevated levels of total and low-density lipoprotein cholesterol (LDL-C) with an LDL-C concentration of 190 mg/dL or greater. However, severe hypercholesterolemia is not inevitably present, and many patients who carry this diagnosis may have lower LDL-C levels. This case history describes a young woman whose mother and brother met clinical and genetic criteria for heterozygous familial hypercholesterolemia, but who had only a mild elevation in LDL-C, falling to <130 mg/dL after dietary intervention. Despite this finding, genetic testing revealed the presence of the same genetic variants as were noted in her mother and brother. In addition, a second genetic variant predisposing them to cholesterol gallstone formation was identified in all three family members. If genetic testing had not been performed, the diagnosis may have been missed or delayed, resulting in an increased risk for the vascular complications associated with familial hypercholesterolemia. This case supports the value of genetic testing of family members of those with familial hypercholesterolemia, even when LDL-C levels are not severely elevated., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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27. Icosapent ethyl: Where will it fit into guideline-based medical therapy for high risk atherosclerotic cardiovascular disease?
- Author
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Orringer CE
- Subjects
- Adult, Aged, Atherosclerosis blood, Atherosclerosis diagnosis, Atherosclerosis epidemiology, Biomarkers blood, Clinical Decision-Making, Consensus, Dyslipidemias blood, Dyslipidemias diagnosis, Dyslipidemias epidemiology, Eicosapentaenoic Acid adverse effects, Eicosapentaenoic Acid therapeutic use, Female, Humans, Hypolipidemic Agents adverse effects, Male, Middle Aged, Risk Assessment, Risk Factors, Treatment Outcome, Young Adult, Atherosclerosis prevention & control, Dyslipidemias drug therapy, Eicosapentaenoic Acid analogs & derivatives, Evidence-Based Medicine standards, Hypolipidemic Agents therapeutic use, Lipids blood, Practice Guidelines as Topic standards
- Abstract
Patients who are at high or very high risk for atherosclerotic cardiovascular disease (ASCVD) events derive the greatest benefit when clinicians prescribe evidence-based preventive therapies. The writing process used in the creation of the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol employed a thorough evaluation of the highest quality evidence, and synthesis of this evidence into actionable recommendations for ASCVD risk reduction. Clinical trials supporting the addition of ezetimibe, PCSK9 inhibitors, or both to evidence-based statins provide the basis for the updated recommendations for the preventive care of these patients. The publication in late 2018 of a randomized controlled trial supporting the net ASCVD risk reduction benefit of adding icosapent ethyl to statins in selected hypertriglyceridemic patients with clinical ASCVD and/or type 2 diabetes with multiple additional risk markers provides the rationale for incorporation of icosapent ethyl therapy into future ASCVD preventive care regimens., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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- View/download PDF
28. National Lipid Association Scientific Statement on the use of icosapent ethyl in statin-treated patients with elevated triglycerides and high or very-high ASCVD risk.
- Author
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Orringer CE, Jacobson TA, and Maki KC
- Subjects
- American Heart Association, Atherosclerosis blood, Cardiovascular Diseases blood, Cardiovascular Diseases drug therapy, Congresses as Topic, Docosahexaenoic Acids therapeutic use, Eicosapentaenoic Acid therapeutic use, Fatty Acids, Omega-3 therapeutic use, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors blood, Hypertriglyceridemia blood, Hypertriglyceridemia drug therapy, Randomized Controlled Trials as Topic, Risk Factors, Societies, Medical, Triglycerides blood, United States, Anticholesteremic Agents therapeutic use, Atherosclerosis drug therapy, Eicosapentaenoic Acid analogs & derivatives, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
- Abstract
Representatives from the National Lipid Association (NLA) participated in the development of the 2018 American Heart Association/American College of Cardiology/Multisociety Guideline on the Management of Blood Cholesterol, which reaffirmed that lifestyle changes and statin treatment are therapeutic cornerstones for atherosclerotic cardiovascular disease (ASCVD) risk reduction. It also updated prior recommendations to incorporate newer data demonstrating ASCVD risk reduction with ezetimibe and proprotein convertase subtilisin kexin type 9 inhibitors as adjuncts to statin therapy for patients at high and very-high ASCVD risk. The 2018 Guideline was finalized shortly before full results were available from a randomized, placebo-controlled cardiovascular outcomes trial [Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT)] that examined the effects of icosapent ethyl (IPE) 4 g/d on major adverse cardiovascular events in selected high- or very high-risk, statin-treated patients with elevated triglycerides. The primary outcome variable of first major adverse cardiovascular event (cardiovascular death, myocardial infarction, stroke, coronary revascularization and hospitalization for unstable angina) was reduced by 25% (95% confidence interval 17%-32%, P < .001). REDUCE-IT served as the primary basis for the NLA's review of evidence for the use of IPE for ASCVD risk reduction. Based on this review, the NLA position is that for patients aged ≥45 years with clinical ASCVD, or aged ≥50 years with diabetes mellitus requiring medication plus ≥1 additional risk factor, with fasting triglycerides 135 to 499 mg/dL on high-intensity or maximally tolerated statin therapy (±ezetimibe), treatment with IPE is recommended for ASCVD risk reduction (evidence rating: class I; evidence level: B-R)., (Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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29. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
- Author
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Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, and Yeboah J
- Subjects
- American Heart Association, Anticholesteremic Agents pharmacology, Biomarkers blood, Cardiovascular Diseases psychology, Humans, Medication Therapy Management standards, Risk Assessment methods, Risk Reduction Behavior, United States, Cardiology methods, Cardiology standards, Cardiovascular Diseases prevention & control, Ezetimibe pharmacology, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Hypercholesterolemia blood, Hypercholesterolemia diagnosis, Hypercholesterolemia epidemiology, Hypercholesterolemia therapy, PCSK9 Inhibitors
- Published
- 2019
- Full Text
- View/download PDF
30. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
- Author
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Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, and Yeboah J
- Subjects
- American Heart Association, Anticholesteremic Agents pharmacology, Biomarkers blood, Cardiovascular Diseases psychology, Humans, Medication Therapy Management standards, Risk Assessment methods, Risk Reduction Behavior, United States, Cardiology methods, Cardiology standards, Cardiovascular Diseases prevention & control, Ezetimibe pharmacology, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Hypercholesterolemia blood, Hypercholesterolemia diagnosis, Hypercholesterolemia epidemiology, Hypercholesterolemia therapy, PCSK9 Inhibitors
- Published
- 2019
- Full Text
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31. JCL roundtable. The 2018 AHA/ACC/Multisociety Cholesterol Guidelines: Process and product.
- Author
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Braun LT, Saseen JJ, Orringer CE, Stone NJ, and Guyton JR
- Subjects
- Humans, Hyperlipoproteinemia Type II epidemiology, Hyperlipoproteinemia Type II metabolism, Risk Factors, Cholesterol metabolism, Guidelines as Topic, Societies, Medical
- Abstract
In this NLA Roundtable four members of the writing committee join the Editor to discuss the process of developing the AHA/ACC/Multisociety Cholesterol Guidelines, which were unveiled in November 2018. They also provide personal insights on the finished product. Highlights include 1) the committee's decision to summarize 10 take-home messages providing rapid communication of key points, 2) emphasis on clinician -patient discussion, which may bring up issues specific to women or other population groups at risk, 3) personalizing risk with risk-enhancing factors such as LDL-C ≥ 160 mg/dl, metabolic syndrome, chronic kidney disease, pre-eclampsia, premature menopause, high risk ethnicity, inflammatory diseases, hypertriglyceridemia and in selected cases, Lp(a), hs-CRP and apoB; 4) using coronary artery calcium scoring when a risk decision is uncertain in intermediate risk patients 5) monitoring for goals of moderate or intensive LDL cholesterol reduction, 6) thresholds for adding nonstatin LDL-lowering therapy in those at very high risk or for heterozygous familial hypercholesterolemia and 7) cost value assessment for expensive treatment., (Copyright © 2019. Published by Elsevier Inc.)
- Published
- 2019
- Full Text
- View/download PDF
32. Use of Lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association.
- Author
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Wilson DP, Jacobson TA, Jones PH, Koschinsky ML, McNeal CJ, Nordestgaard BG, and Orringer CE
- Subjects
- Biomarkers blood, Humans, Hypolipidemic Agents pharmacology, Practice Guidelines as Topic, Blood Chemical Analysis, Lipoprotein(a) blood, Societies, Scientific
- Abstract
Lipoprotein(a) [Lp(a)] is a well-recognized, independent risk factor for atherosclerotic cardiovascular disease, with elevated levels estimated to be prevalent in 20% of the population. Observational and genetic evidence strongly support a causal relationship between high plasma concentrations of Lp(a) and increased risk of atherosclerotic cardiovascular disease-related events, such as myocardial infarction and stroke, and valvular aortic stenosis. In this scientific statement, we review an array of evidence-based considerations for testing of Lp(a) in clinical practice and the utilization of Lp(a) levels to inform treatment strategies in primary and secondary prevention., (Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
33. How Much Do Lipid Guidelines Help the Clinician? Reading Between the (Guide)lines.
- Author
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Orringer CE
- Subjects
- Adult, Aged, Biomarkers blood, Cardiovascular Diseases blood, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Clinical Decision-Making, Dyslipidemias blood, Dyslipidemias diagnosis, Dyslipidemias epidemiology, Evidence-Based Medicine standards, Female, Guideline Adherence standards, Humans, Male, Middle Aged, Risk Factors, Treatment Outcome, Cardiovascular Diseases prevention & control, Dyslipidemias drug therapy, Hypolipidemic Agents therapeutic use, Lipids blood, Practice Guidelines as Topic standards, Practice Patterns, Physicians' standards
- Abstract
Although lipid guidelines provide updated, practical, and clinically relevant information that may be used in patient care, the continuing publication of new evidence and the inevitable treatment gaps present in all guidelines reinforce the importance of clinical judgment in shared decision making. This article explores the development of the 2013 American College of Cardiology/American Heart Association Blood Cholesterol Guidelines and the evidence base for managing patients with severe hypercholesterolemia, provides more recent high-quality evidence, and identifies existing treatment gaps that should be considered when caring for such patients. Although it was submitted prior to publication of the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol, this review also includes key takeaway messages from the updated guideline., Competing Interests: Conflict of Interest Disclosure: The author has completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported.
- Published
- 2019
- Full Text
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34. 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways.
- Author
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Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly DD Jr, DePalma SM, Minissian MB, Orringer CE, and Smith SC Jr
- Subjects
- Chemoprevention methods, Cholesterol, LDL analysis, Consensus, Enzyme Inhibitors pharmacology, Humans, Hypercholesterolemia diagnosis, Sequestering Agents pharmacology, United States, Anticholesteremic Agents pharmacology, Cardiology methods, Coronary Artery Disease prevention & control, Ezetimibe pharmacology, Hypercholesterolemia drug therapy, Medication Therapy Management organization & administration
- Abstract
In 2016, the American College of Cardiology published the first expert consensus decision pathway (ECDP) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in the management of atherosclerotic cardiovascular disease (ASCVD) risk. Since the publication of that document, additional evidence and perspectives have emerged from randomized clinical trials and other sources, particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in secondary prevention of ASCVD. Most notably, the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial and SPIRE-1 and -2 (Studies of PCSK9 Inhibition and the Reduction of Vascular Events), assessing evolocumab and bococizumab, respectively, have published final results of cardiovascular outcomes trials in patients with clinical ASCVD and in a smaller number of high-risk primary prevention patients. In addition, further evidence on the types of patients most likely to benefit from the use of ezetimibe in addition to statin therapy after acute coronary syndrome has been published. Based on results from these important analyses, the ECDP writing committee judged that it would be desirable to provide a focused update to help guide clinicians more clearly on decision making regarding the use of ezetimibe and PCSK9 inhibitors in patients with clinical ASCVD with or without comorbidities. In the following summary table, changes from the 2016 ECDP to the 2017 ECDP Focused Update are highlighted, and a brief rationale is provided. The content of the full document has been changed accordingly, with more extensive and detailed guidance regarding decision making provided both in the text and in the updated algorithms. Revised recommendations are provided for patients with clinical ASCVD with or without comorbidities on statin therapy for secondary prevention. The ECDP writing committee judged that these new data did not warrant changes to the decision pathways and algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C <190 mg/dL with or without diabetes mellitus or patients without ASCVD and LDL-C ≥190 mg/dL not due to secondary causes. Based on feedback and further deliberation, the ECDP writing committee down-graded recommendations regarding bile acid sequestrant use, recommending bile acid sequestrants only as optional secondary agents for consideration in patients intolerant to ezetimibe. For clarification, the writing committee has also included new information on diagnostic categories of heterozygous and homozygous familial hypercholesterolemia, based on clinical criteria with and without genetic testing. Other changes to the original document were kept to a minimum to provide consistent guidance to clinicians, unless there was a compelling reason or new evidence, in which case justification is provided., (Copyright © 2017. Published by Elsevier Inc.)
- Published
- 2017
- Full Text
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35. Update on the use of PCSK9 inhibitors in adults: Recommendations from an Expert Panel of the National Lipid Association.
- Author
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Orringer CE, Jacobson TA, Saseen JJ, Brown AS, Gotto AM, Ross JL, and Underberg JA
- Subjects
- Adult, Atherosclerosis blood, Atherosclerosis drug therapy, Clinical Trials as Topic, Evidence-Based Medicine, Homozygote, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Hypercholesterolemia blood, Hypercholesterolemia drug therapy, Hypercholesterolemia genetics, Phenotype, Protease Inhibitors therapeutic use, Risk, Expert Testimony, PCSK9 Inhibitors, Protease Inhibitors pharmacology, Societies, Medical
- Abstract
An Expert Panel convened by the National Lipid Association was charged with updating the recommendations on the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody therapy that were provided by the 2015 National Lipid Association Recommendations for the Patient-Centered Management of Dyslipidemia: Part 2. Recent studies have demonstrated the efficacy of these agents in reducing low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol and have confirmed their excellent safety profile. A cardiovascular outcomes study has shown that these agents reduce incident atherosclerotic cardiovascular disease (ASCVD) events in patents with stable ASCVD and concomitant risk factors. The current update provides the Expert Panel's evidence-based recommendations on the clinical utility of PCSK9 inhibitors in patients with stable ASCVD, progressive ASCVD, LDL-C ≥ 190 mg/dL (including polygenic hypercholesterolemia, heterozygous familial hypercholesterolemia and the homozygous familial hypercholesterolemia phenotype) and very-high-risk patients with statin intolerance., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
36. Visualization of atherosclerosis as detected by coronary artery calcium and carotid intima-media thickness reveals significant atherosclerosis in a cross-sectional study of psoriasis patients in a tertiary care center.
- Author
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Santilli S, Kast DR, Grozdev I, Cao L, Feig RL, Golden JB, Debanne SM, Gilkeson RC, Orringer CE, McCormick TS, Ward NL, Cooper KD, and Korman NJ
- Subjects
- Atherosclerosis epidemiology, C-Reactive Protein metabolism, Cohort Studies, Cross-Sectional Studies, Demography, Female, Humans, Male, Middle Aged, Prevalence, Atherosclerosis complications, Calcium metabolism, Carotid Intima-Media Thickness, Coronary Vessels metabolism, Coronary Vessels pathology, Psoriasis complications, Tertiary Care Centers
- Abstract
Background: Psoriasis is a chronic inflammatory disease of the skin and joints that may also have systemic inflammatory effects, including the development of cardiovascular disease (CVD). Multiple epidemiologic studies have demonstrated increased rates of CVD in psoriasis patients, although a causal link has not been established. A growing body of evidence suggests that sub-clinical systemic inflammation may develop in psoriasis patients, even from a young age. We aimed to evaluate the prevalence of atherosclerosis and identify specific clinical risk factors associated with early vascular inflammation., Methods: We conducted a cross-sectional study of a tertiary care cohort of psoriasis patients using coronary artery calcium (CAC) score and carotid intima-media thickness (CIMT) to detect atherosclerosis, along with high sensitivity C-reactive protein (hsCRP) to measure inflammation. Psoriasis patients and controls were recruited from our tertiary care dermatology clinic. Presence of atherosclerosis was defined using validated numeric values within CAC and CIMT imaging. Descriptive data comparing groups was analyzed using Welch's t test and Pearson Chi square tests. Logistic regression was used to analyze clinical factors associated with atherosclerosis, and linear regression to evaluate the relationship between psoriasis and hsCRP., Results: 296 patients were enrolled, with 283 (207 psoriatic and 76 controls) having all data for the hsCRP and atherosclerosis analysis. Atherosclerosis was found in 67.6 % of psoriasis subjects versus 52.6 % of controls; Psoriasis patients were found to have a 2.67-fold higher odds of having atherosclerosis compared to controls [95 % CI (1.2, 5.92); p = 0.016], after adjusting for age, gender, race, BMI, smoking, HDL and hsCRP. In addition, a non-significant trend was found between HsCRP and psoriasis severity, as measured by PASI, PGA, or BSA, again after adjusting for confounders., Conclusions: A tertiary care cohort of psoriasis patients have a high prevalence of early atherosclerosis, increased hsCRP, and psoriasis remains a risk factor for the presence of atherosclerosis even after adjustment of key confounding clinical factors. Psoriasis may contribute to an accelerated systemic inflammatory cascade resulting in increased risk of CVD and CV events.
- Published
- 2016
- Full Text
- View/download PDF
37. 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents.
- Author
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Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly DD Jr, DePalma SM, Minissian MB, Orringer CE, and Smith SC Jr
- Subjects
- Atherosclerosis blood, Cholesterol, LDL drug effects, Decision Support Techniques, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, United States, American Heart Association, Anticholesteremic Agents therapeutic use, Atherosclerosis drug therapy, Cardiology, Cholesterol, LDL blood, Consensus, Consensus Development Conferences as Topic
- Published
- 2016
- Full Text
- View/download PDF
38. Triglyceride-lowering therapies reduce cardiovascular disease event risk in subjects with hypertriglyceridemia.
- Author
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Maki KC, Guyton JR, Orringer CE, Hamilton-Craig I, Alexander DD, and Davidson MH
- Subjects
- Humans, Hypertriglyceridemia drug therapy, Hypertriglyceridemia metabolism, Hypolipidemic Agents therapeutic use, Risk, Cardiovascular Diseases complications, Hypertriglyceridemia complications, Hypolipidemic Agents pharmacology, Triglycerides metabolism
- Abstract
Background: Cardiovascular outcomes trials of fibrates, niacin, or omega-3 fatty acids alone, or added to a statin, have not consistently demonstrated reduced risk, but larger, statistically significant clinical benefits have been reported in subgroups with elevated triglycerides (TG) and/or elevated TG plus low high-density lipoprotein cholesterol (HDL-C)., Objective: To perform a meta-analysis of the effects of therapies targeting TG and TG-rich lipoprotein cholesterol on cardiovascular disease event risk in subjects with elevated TG or elevated TG paired with low HDL-C., Methods: Publications were identified using PubMed, the Cochrane Central Register of Controlled Trials, clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, and Internet Stroke Center. Random-effects meta-analysis models were used to generate summary relative risk estimates and 95% confidence intervals. Heterogeneity was assessed by χ(2) and I(2) statistics, and the impact of each trial was assessed in one study-removed sensitivity analyses., Results: Six trials of fibrates, 2 of niacin, 1 of fibrate + niacin, and 1 of omega-3 eicosapentaenoic acid ethyl esters were identified. For the prespecified primary cardiovascular disease or coronary heart disease end point used in each trial, the summary relative risk estimate (95% confidence interval) for subjects with elevated TG was 0.82 (0.73-0.91), p-heterogeneity = 0.13, I(2) = 36.2, and for subjects with elevated TG and low-HDL-C, it was 0.71 (0.63-0.81), p-heterogeneity = 0.52, I(2) = 0.0. There was no evidence of publication bias, and the results remained statistically significant when each individual trial was removed., Conclusion: Drugs that substantially, but not exclusively, lower TG and TG-rich lipoprotein cholesterol may have cardiovascular benefits in individuals with elevated TG, particularly if accompanied by low HDL-C., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
39. Consensus between the American College of Cardiology and the National Lipid Association on the use of non-statin therapy for atherosclerotic cardiovascular disease prevention.
- Author
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Orringer CE and Morris PB
- Subjects
- Atherosclerosis, Cardiovascular Diseases prevention & control, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, United States, American Heart Association, Cardiology standards, Consensus, Practice Guidelines as Topic
- Published
- 2016
- Full Text
- View/download PDF
40. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: EXECUTIVE SUMMARY.
- Author
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Bays HE, Jones PH, Jacobson TA, Cohen DE, Orringer CE, Kothari S, Azagury DE, Morton J, Nguyen NT, Westman EC, Horn DB, Scinta W, and Primack C
- Subjects
- Adipose Tissue metabolism, Animals, Bile Acids and Salts metabolism, Cholesterol metabolism, Gastrointestinal Hormones metabolism, Gastrointestinal Microbiome, Humans, Obesity microbiology, Obesity pathology, United States, Bariatric Surgery, Lipid Metabolism, Obesity metabolism, Obesity surgery, Societies, Medical
- Abstract
Bariatric procedures often improve lipid levels in patients with obesity. This 2-part scientific statement examines the potential lipid benefits of bariatric procedures and represents contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on data published through June 2015. Part 1 of this 2-part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of: (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on cardiovascular disease; and finally (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the executive summary of part 1., (Copyright © 2016 National Lipid Association. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
41. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: FULL REPORT.
- Author
-
Bays HE, Jones PH, Jacobson TA, Cohen DE, Orringer CE, Kothari S, Azagury DE, Morton J, Nguyen NT, Westman EC, Horn DB, Scinta W, and Primack C
- Subjects
- Adipose Tissue metabolism, Animals, Bile Acids and Salts metabolism, Biological Transport, Cholesterol metabolism, Endocrine System physiopathology, Gastrointestinal Microbiome, Humans, Lipids biosynthesis, Obesity microbiology, Obesity pathology, United States, Bariatric Surgery, Lipid Metabolism, Obesity metabolism, Obesity surgery, Societies, Medical
- Abstract
Bariatric procedures often improve lipid levels in patients with obesity. This 2 part scientific statement examines the potential lipid benefits of bariatric procedures and represents the contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on published data through June 2015. Part 1 of this 2 part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease (CVD) risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on CVD; and finally, (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the full report of part 1., (Copyright © 2016 National Lipid Association. All rights reserved.)
- Published
- 2016
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42. National Lipid Association Annual Summary of Clinical Lipidology 2016.
- Author
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Bays HE, Jones PH, Orringer CE, Brown WV, and Jacobson TA
- Subjects
- Animals, Dyslipidemias complications, Dyslipidemias drug therapy, Dyslipidemias genetics, Dyslipidemias metabolism, Humans, Hypolipidemic Agents pharmacology, Hypolipidemic Agents therapeutic use, Lipid Metabolism drug effects, Lipids
- Abstract
The National Lipid Association (NLA) Annual Summary of Clinical Lipidology is a yearly updated summary of principles important to the patient-centered evaluation, management, and care of patients with dyslipidemia. This summary is intended to be a "living document," with future annual updates based on emerging science, clinical considerations, and new NLA Position, Consensus, and Scientific Statements, thus providing an ongoing resource that applies the latest in medical science towards the clinical management of patients with dyslipidemia. Topics include the NLA Recommendations for Patient-Centered Management of Dyslipidemia, genetics, Familial Hypercholesterolemia, secondary causes of dyslipidemia, biomarkers and advanced lipid testing, nutrition, physical activity, obesity, adiposopathy, metabolic syndrome, diabetes mellitus, lipid pharmacotherapy, lipid-altering drug interactions, lipoprotein apheresis, dyslipidemia management and treatment based upon age (children, adolescents, and older individuals), dyslipidemia considerations based upon race, ethnicity and gender, dyslipidemia and human immune virus infection, dyslipidemia and immune disorders, adherence strategies and collaborative care, and lipid-altering drugs in development. Hyperlinks direct the reader to sentinel online tables, charts, and figures relevant to lipidology, access to online atherosclerotic cardiovascular disease risk calculators, worldwide lipid guidelines, recommendations, and position/scientific statements, as well as links to online audio files, websites, slide shows, applications, continuing medical education opportunities, and patient information., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
43. National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2.
- Author
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Jacobson TA, Maki KC, Orringer CE, Jones PH, Kris-Etherton P, Sikand G, La Forge R, Daniels SR, Wilson DP, Morris PB, Wild RA, Grundy SM, Daviglus M, Ferdinand KC, Vijayaraghavan K, Deedwania PC, Aberg JA, Liao KP, McKenney JM, Ross JL, Braun LT, Ito MK, Bays HE, Brown WV, and Underberg JA
- Subjects
- Adolescent, Adult, Aged, Child, Dyslipidemias diet therapy, Dyslipidemias drug therapy, Female, Humans, Male, Middle Aged, Pregnancy, Young Adult, Dyslipidemias therapy, Patient-Centered Care
- Abstract
An Expert Panel convened by the National Lipid Association previously developed a consensus set of recommendations for the patient-centered management of dyslipidemia in clinical medicine (part 1). These were guided by the principle that reducing elevated levels of atherogenic cholesterol (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) reduces the risk for atherosclerotic cardiovascular disease. This document represents a continuation of the National Lipid Association recommendations developed by a diverse panel of experts who examined the evidence base and provided recommendations regarding the following topics: (1) lifestyle therapies; (2) groups with special considerations, including children and adolescents, women, older patients, certain ethnic and racial groups, patients infected with human immunodeficiency virus, patients with rheumatoid arthritis, and patients with residual risk despite statin and lifestyle therapies; and (3) strategies to improve patient outcomes by increasing adherence and using team-based collaborative care., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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44. JCL Roundtable: Gender differences in reduction of CVD in response to lipid-lowering drugs.
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Brown WV, Mackey RH, Orringer CE, and Pearson TA
- Subjects
- Cardiovascular Diseases epidemiology, Cardiovascular Diseases metabolism, Female, Humans, Lipoproteins metabolism, Male, Observational Studies as Topic, Sex Distribution, Cardiovascular Diseases prevention & control, Hypolipidemic Agents pharmacology
- Abstract
The Roundtable in this issue of the journal has to do with a very important topic that has generated much debate and confusion over the years. Do women and men need and receive the same type and intensity of drug therapy to appropriately reduce the incidence of major vascular events? Second, do women respond to lipid-lowering medications with similar changes in lipoprotein levels and with equivalent reduction in major cardiovascular clinical events? I am very pleased to have 3 experts in different aspects of this issue. Dr Rachel Mackey is a cardiovascular epidemiologist in the University of Pittsburgh who is now actively involved in analyzing large data sets from community-based observational studies. Dr Thomas Pearson has many years of cardiovascular experience in clinical trials and observational studies that go to the issues faced by physicians in practice. He is the current Executive Vice President for Research and Education at the University of Florida Health Science Center. Dr Carl Orringer is a professor at the University of Miami School of Medicine who has years of experience in teaching preventive cardiology., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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45. Clinical lipidology: A subspecialty whose time has come.
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Orringer CE, Bays HE, and Brown WV
- Subjects
- Documentation, Education, Medical, Evidence-Based Medicine, Humans, Lipoproteins metabolism, Medicine
- Published
- 2015
- Full Text
- View/download PDF
46. National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report.
- Author
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Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH, McKenney JM, Grundy SM, Gill EA, Wild RA, Wilson DP, and Brown WV
- Subjects
- Apolipoproteins B blood, Atherosclerosis blood, Atherosclerosis pathology, Cardiovascular Diseases blood, Cardiovascular Diseases pathology, Cholesterol, LDL blood, Disease Management, Dyslipidemias blood, Dyslipidemias pathology, Government Agencies, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Risk Factors, Atherosclerosis drug therapy, Cardiovascular Diseases drug therapy, Dyslipidemias drug therapy
- Abstract
The leadership of the National Lipid Association convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. An Executive Summary of those recommendations was previously published. This document provides support for the recommendations outlined in the Executive Summary. The major conclusions include (1) an elevated level of cholesterol carried by circulating apolipoprotein B-containing lipoproteins (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol [LDL-C], termed atherogenic cholesterol) is a root cause of atherosclerosis, the key underlying process contributing to most clinical atherosclerotic cardiovascular disease (ASCVD) events; (2) reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle and drug therapies; (3) the intensity of risk-reduction therapy should generally be adjusted to the patient's absolute risk for an ASCVD event; (4) atherosclerosis is a process that often begins early in life and progresses for decades before resulting a clinical ASCVD event. Therefore, both intermediate-term and long-term or lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies; (5) for patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk; (6) nonlipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus; and (7) the measurement and monitoring of atherogenic cholesterol levels remain an important part of a comprehensive ASCVD prevention strategy., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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47. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 - executive summary.
- Author
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Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH, McKenney JM, Grundy SM, Gill EA, Wild RA, Wilson DP, and Brown WV
- Subjects
- Adult, Disease Progression, Dyslipidemias drug therapy, Dyslipidemias epidemiology, Dyslipidemias metabolism, Expert Testimony, Goals, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Life Style, Lipoproteins metabolism, Risk Assessment, Dyslipidemias therapy, Societies, Medical
- Abstract
Various organizations and agencies have issued recommendations for the management of dyslipidemia. Although many commonalities exist among them, material differences are present as well. The leadership of the National Lipid Association (NLA) convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel and includes: (1) background and conceptual framework for formulation of the NLA Expert Panel recommendations; (2) screening and classification of lipoprotein lipid levels in adults; (3) targets for intervention in dyslipidemia management; (4) atherosclerotic cardiovascular disease risk assessment and treatment goals based on risk category; (5) atherogenic cholesterol-non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol-as the primary targets of therapy; and (6) lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia., (Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
48. Soluble CD14 is independently associated with coronary calcification and extent of subclinical vascular disease in treated HIV infection.
- Author
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Longenecker CT, Jiang Y, Orringer CE, Gilkeson RC, Debanne S, Funderburg NT, Lederman MM, Storer N, Labbato DE, and McComsey GA
- Subjects
- Adolescent, Adult, Asymptomatic Diseases epidemiology, Cross-Sectional Studies, Female, HIV Infections immunology, Humans, Male, Middle Aged, Young Adult, Calcinosis, Coronary Disease epidemiology, Coronary Vessels pathology, HIV Infections complications, HIV Infections drug therapy, Lipopolysaccharide Receptors blood
- Abstract
Objective: To use multimodality imaging to explore the relationship of biomarkers of inflammation, T-cell activation and monocyte activation with coronary calcification and subclinical vascular disease in a population of HIV-infected patients on antiretroviral therapy (ART)., Design: Cross-sectional., Methods: A panel of soluble and cellular biomarkers of inflammation and immune activation was measured in 147 HIV-infected adults on ART with HIV RNA less than 1000 copies/ml and low-density lipoprotein cholesterol (LDL-C) 130 mg/dl or less. We examined the relationship of biomarkers to coronary calcium (CAC) score and multiple ultrasound measures of subclinical vascular disease., Results: Overall, median (interquartile range, IQR) age was 46 (40-53) years; three-quarters of participants were male and two-thirds African-American. Median 10-year Framingham risk score was 6%. Participants with CAC more than 0 were older, less likely to be African-American and had higher current and lower nadir CD4 T-cell counts. Most biomarkers were similar between those with and without CAC; however, soluble CD14 was independently associated with CAC after adjustment for traditional risk factors. Among those with a CAC score of zero, T-cell activation and systemic inflammation correlated with carotid intima-media thickness and brachial hyperemic velocity, respectively. Compared with normal participants and those with CAC only, participants with increasing degrees of subclinical vascular disease had higher levels of sCD14, hs-CRP and fibrinogen (all P<0.05)., Conclusion: Soluble CD14 is independently associated with coronary artery calcification, and, among those with detectable calcium, predicts the extent of subclinical disease in other vascular beds. Future studies should investigate the utility of multimodality imaging to characterize vascular disease phenotypes in this population.
- Published
- 2014
- Full Text
- View/download PDF
49. Psoriasis and cardiovascular risk factors: increased serum myeloperoxidase and corresponding immunocellular overexpression by Cd11b(+) CD68(+) macrophages in skin lesions.
- Author
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Cao LY, Soler DC, Debanne SM, Grozdev I, Rodriguez ME, Feig RL, Carman TL, Gilkeson RC, Orringer CE, Kern EF, McCormick TS, Cooper KD, and Korman NJ
- Abstract
Background: Recent studies report independent associations between psoriasis, cardiovascular (CV) events and risk factors. Blood Myeloperoxidase (MPO) from activated myeloid cells is associated with CV risk mainly through lipid oxidation, induction of endothelial dysfunction and release of IL-12 from macrophages., Objectives: To elucidate associations between psoriasis and conventional CV risk factors., Methods: We performed a cross-sectional study of 100 psoriasis patients and 53 controls, group matched on age, gender and body mass index, to assess levels of MPO in serum, as well as immunohistochemical staining from psoriasis skin lesions, psoriasis uninvolved skin, and normal skin., Results: Although the groups did not differ on waist circumference, glucose, cholesterol, triglycerides, creatinine or personal history of CV events, psoriasis patients had significantly higher waist-to-hip ratios, blood pressures, proportion of current smokers, and lower high density lipoprotein level than controls. Serum MPO level was elevated 2.5 fold (P<0.001) in psoriasis patients, even after adjusting for the CV risk factors on which the groups differed. MPO did correlate with coronary artery calcification, carotid plaque, carotid intima media thickness and flow mediated dilation, but did not correlate with psoriasis severity. However, MPO was highly expressed in lesional psoriatic skin and colocalized predominantly with CD45(+) CD11b(+) leukocytes. CD11b(+) cell density correlated with circulation MPO levels., Conclusion: Lesional skin CD11b(+) leukocytes activated to generate MPO may contribute to serum levels of MPO. Lesional CD11b(+) cell activity may be an alternative measure of disease burden to PASI that underlies the MPO biomarker for systemic inflammation related to Cardiovascular Disease.
- Published
- 2013
50. Assessment of coronary artery calcium using dual-energy subtraction digital radiography.
- Author
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Mafi JN, Fei B, Roble S, Dota A, Katrapati P, Bezerra HG, Wang H, Wang W, Ciancibello L, Costa M, Simon DI, Orringer CE, and Gilkeson RC
- Subjects
- Case-Control Studies, Coronary Angiography methods, Coronary Artery Disease physiopathology, Feasibility Studies, Female, Humans, Male, Middle Aged, Pilot Projects, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Severity of Illness Index, Statistics, Nonparametric, Angiography, Digital Subtraction methods, Calcinosis diagnostic imaging, Coronary Artery Disease diagnostic imaging
- Abstract
Cardiovascular disease is the leading cause of global mortality, yet its early detection remains a vexing problem of modern medicine. Although the computed tomography (CT) calcium score predicts cardiovascular risk, relatively high cost ($250-400) and radiation dose (1-3 mSv) limit its universal utility as a screening tool. Dual-energy digital subtraction radiography (DE; <$60, 0.07 mSv) enables detection of calcified structures with high sensitivity. In this pilot study, we examined DE radiography's ability to quantify coronary artery calcification (CAC). We identified 25 patients who underwent non-contrast CT and DE chest imaging performed within 12 months using documented CAC as the major inclusion criteria. A DE calcium score was developed based on pixel intensity multiplied by the area of the calcified plaque. DE scores were plotted against CT scores. Subsequently, a validation cohort of 14 additional patients was independently evaluated to confirm the accuracy and precision of CAC quantification, yielding a total of 39 subjects. Among all subjects (n = 39), the DE score demonstrated a correlation coefficient of 0.87 (p < 0.0001) when compared with the CT score. For the 13 patients with CT scores of <400, the correlation coefficient was -0.26. For the 26 patients with CT scores of ≥400, the correlation coefficient yielded 0.86. This pilot study demonstrates the feasibility of DE radiography to identify patients at the highest cardiovascular risk. DE radiography's accuracy at lower scores remains unclear. Further evaluation of DE radiography as an inexpensive and low-radiation imaging tool to diagnose cardiovascular disease appears warranted.
- Published
- 2012
- Full Text
- View/download PDF
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