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  1. Article ; Online: Remnants, LDL, and the Quantification of Lipoprotein-Associated Risk in Atherosclerotic Cardiovascular Disease.

    Packard, Chris J

    Current atherosclerosis reports

    2022  Volume 24, Issue 3, Page(s) 133–142

    Abstract: Purpose of review: Implementation of intensive LDL cholesterol (LDL-C) lowering strategies and recognition of the role of triglyceride-rich lipoproteins (TRL) in atherosclerosis has prompted re-evaluation of the suitability of current lipid profile ... ...

    Abstract Purpose of review: Implementation of intensive LDL cholesterol (LDL-C) lowering strategies and recognition of the role of triglyceride-rich lipoproteins (TRL) in atherosclerosis has prompted re-evaluation of the suitability of current lipid profile measurements for future clinical practice.
    Recent findings: At low concentrations of LDL-C (< 1.8 mmol/l/70 mg/dl), the Friedewald equation yields estimates with substantial negative bias. New equations provide a more accurate means of calculating LDL-C. Recent reports indicate that the increase in risk per unit increment in TRL/remnant cholesterol may be greater than that of LDL-C. Hence, specific measurement of TRL/remnant cholesterol may be of importance in determining risk. Non-HDL cholesterol and plasma apolipoprotein B have been shown in discordancy analyses to identify individuals at high risk even when LDL-C is low. There is a need to adopt updated methods for determining LDL-C and to develop better biomarkers that more accurately reflect the abundance of TRL remnant particles.
    MeSH term(s) Atherosclerosis ; Biomarkers ; Cardiovascular Diseases/epidemiology ; Cholesterol, LDL ; Humans ; Lipoproteins ; Triglycerides
    Chemical Substances Biomarkers ; Cholesterol, LDL ; Lipoproteins ; Triglycerides
    Language English
    Publishing date 2022-02-17
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057369-8
    ISSN 1534-6242 ; 1523-3804
    ISSN (online) 1534-6242
    ISSN 1523-3804
    DOI 10.1007/s11883-022-00994-z
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    Zs.A 5534: Show issues Location:
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  2. Article ; Online: Realizing the Potential of PCSK9 Inhibition: A Novel Oral Macrocyclic Peptide on the Horizon.

    Chapman, M John / Packard, Chris J

    Journal of the American College of Cardiology

    2023  Volume 81, Issue 16, Page(s) 1565–1568

    MeSH term(s) Humans ; Proprotein Convertase 9 ; Lipoproteins ; Triglycerides
    Chemical Substances PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-) ; Lipoproteins ; Triglycerides
    Language English
    Publishing date 2023-02-03
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 605507-2
    ISSN 1558-3597 ; 0735-1097
    ISSN (online) 1558-3597
    ISSN 0735-1097
    DOI 10.1016/j.jacc.2023.03.384
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  3. Article ; Online: Biosynthesis and Metabolism of ApoB-Containing Lipoproteins.

    Borén, Jan / Taskinen, Marja-Riitta / Packard, Chris J

    Annual review of nutrition

    2024  

    Abstract: Recent advances in human genetics, together with a substantial body of epidemiological, preclinical and clinical trial evidence, strongly support a causal relationship between triglyceride-rich lipoproteins (TRLs) and atherosclerotic cardiovascular ... ...

    Abstract Recent advances in human genetics, together with a substantial body of epidemiological, preclinical and clinical trial evidence, strongly support a causal relationship between triglyceride-rich lipoproteins (TRLs) and atherosclerotic cardiovascular disease. Consequently, the secretion and metabolism of TRLs have a significant impact on cardiovascular health. This knowledge underscores the importance of understanding the molecular mechanisms and regulation of very-low-density lipoprotein (VLDL) and chylomicron biogenesis. Fortunately, there has been a resurgence of interest in the intracellular assembly, trafficking, degradation, and secretion of VLDL, leading to many ground-breaking molecular insights. Furthermore, the identification of molecular control mechanisms related to triglyceride metabolism has greatly advanced our understanding of the complex metabolism of TRLs. In this review, we explore recent advances in the assembly, secretion, and metabolism of TRLs. We also discuss available treatment strategies for hypertriglyceridemia.
    Language English
    Publishing date 2024-04-18
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 406980-8
    ISSN 1545-4312 ; 0199-9885
    ISSN (online) 1545-4312
    ISSN 0199-9885
    DOI 10.1146/annurev-nutr-062222-020716
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  4. Article ; Online: Triglyceride lowering 2.0: back to the future?

    Packard, Chris J

    European heart journal

    2020  Volume 41, Issue 1, Page(s) 95–98

    MeSH term(s) Humans ; Hypertriglyceridemia/drug therapy ; Hypolipidemic Agents/therapeutic use ; Triglycerides
    Chemical Substances Hypolipidemic Agents ; Triglycerides
    Language English
    Publishing date 2020-02-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 603098-1
    ISSN 1522-9645 ; 0195-668X
    ISSN (online) 1522-9645
    ISSN 0195-668X
    DOI 10.1093/eurheartj/ehz810
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    Zs.MO 640: Show issues

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  5. Article ; Online: Letter by Packard Regarding Article, "Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome: Role of Lipoprotein(a) and Modification by Alirocumab: Prespecified Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial".

    Packard, Chris J

    Circulation

    2020  Volume 142, Issue 20, Page(s) e333–e334

    MeSH term(s) Acute Coronary Syndrome/diagnosis ; Acute Coronary Syndrome/drug therapy ; Antibodies, Monoclonal, Humanized/adverse effects ; Humans ; Lipoprotein(a) ; Peripheral Arterial Disease/diagnosis ; Peripheral Arterial Disease/drug therapy ; Peripheral Arterial Disease/epidemiology
    Chemical Substances Antibodies, Monoclonal, Humanized ; Lipoprotein(a) ; alirocumab (PP0SHH6V16)
    Language English
    Publishing date 2020-11-16
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.120.050070
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  6. Article ; Online: Strategies to alter the trajectory of atherosclerotic cardiovascular disease.

    Packard, Chris J

    Current opinion in lipidology

    2019  Volume 30, Issue 6, Page(s) 438–445

    Abstract: Purpose of review: Cardiovascular disease prevention trials of lipid lowering with statins have shown unexpected long-term benefits after the formal randomized treatment stopped. This finding needs further exploration because it raises the possibility ... ...

    Abstract Purpose of review: Cardiovascular disease prevention trials of lipid lowering with statins have shown unexpected long-term benefits after the formal randomized treatment stopped. This finding needs further exploration because it raises the possibility that the trajectory of the disease can be modified.
    Recent findings: Extended follow up data are now available from further major primary prevention studies and from meta-analyses of the legacy effect of statin trials. New outcome studies have been proposed and launched to test the ability of early intervention to slow or regress atherosclerosis.
    Summary: Legacy effects are apparent in trials of LDL lowering in hypercholesterolemic and hypertensive patient cohorts. Over follow up periods of decades, both cardiovascular mortality and all-cause mortality are reduced in individuals who received 3 to 5 years of statin therapy. The phenomenon is observed also in studies of intensive glycemic control suggesting that it is possible to impact plaque development with long-term beneficial consequences. Novel strategies for primary prevention are being devised that include the early use of both prolonged-moderate and short-term aggressive LDL lowering.
    MeSH term(s) Atherosclerosis/blood ; Atherosclerosis/drug therapy ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Lipoproteins, LDL ; Randomized Controlled Trials as Topic
    Chemical Substances Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipoproteins, LDL
    Language English
    Publishing date 2019-10-14
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1045394-5
    ISSN 1473-6535 ; 0957-9672
    ISSN (online) 1473-6535
    ISSN 0957-9672
    DOI 10.1097/MOL.0000000000000643
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    Zs.A 3010: Show issues Location:
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  7. Article ; Online: Determinants of Achieved LDL Cholesterol and "Non-HDL" Cholesterol in the Management of Dyslipidemias.

    Packard, Chris J

    Current cardiology reports

    2018  Volume 20, Issue 8, Page(s) 60

    Abstract: Purpose of review: The advent of combination therapy to provide LDL lowering beyond that achieved with statins necessitates the development of greater understanding of how drugs work together, what changes occur in key lipoprotein fractions, and what ... ...

    Abstract Purpose of review: The advent of combination therapy to provide LDL lowering beyond that achieved with statins necessitates the development of greater understanding of how drugs work together, what changes occur in key lipoprotein fractions, and what residual risk remains.
    Recent findings: Clinical trials of agents that, when added to statins, generate profound LDL lowering have been successful in reducing further the risk of cardiovascular disease. LDL cholesterol can be now decreased to unprecedented levels, so the focus of attention then shifts to other apolipoprotein B-containing, atherogenic lipoprotein classes such as lipoprotein(a) and remnants of the metabolism of triglyceride-rich particles. "Non-HDL cholesterol" is used increasingly (especially if measured in the non-fasting state) as a more comprehensive index of risk. Metabolic studies reveal how current drugs act in combination to achieve profound lipid lowering. However, care is needed in interpreting achieved LDLc and non-HDLc levels in the emerging treatment paradigm.
    MeSH term(s) Anticholesteremic Agents/therapeutic use ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/prevention & control ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Clinical Trials as Topic ; Dyslipidemias/drug therapy ; Ezetimibe/therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Proprotein Convertase 9/antagonists & inhibitors ; Risk Management ; Triglycerides/blood
    Chemical Substances Anticholesteremic Agents ; Cholesterol, HDL ; Cholesterol, LDL ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Triglycerides ; Proprotein Convertase 9 (EC 3.4.21.-) ; Ezetimibe (EOR26LQQ24)
    Language English
    Publishing date 2018-06-14
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2055373-0
    ISSN 1534-3170 ; 1523-3782
    ISSN (online) 1534-3170
    ISSN 1523-3782
    DOI 10.1007/s11886-018-1003-x
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  8. Article ; Online: Keeping remnants in perspective.

    Borén, Jan / Packard, Chris J

    European heart journal

    2021  Volume 42, Issue 42, Page(s) 4333–4335

    Language English
    Publishing date 2021-08-05
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 603098-1
    ISSN 1522-9645 ; 0195-668X
    ISSN (online) 1522-9645
    ISSN 0195-668X
    DOI 10.1093/eurheartj/ehab531
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  9. Article ; Online: Exploring apolipoprotein C-III: pathophysiological and pharmacological relevance.

    Packard, Chris J / Pirillo, Angela / Tsimikas, Sotirios / Ference, Brian A / Catapano, Alberico L

    Cardiovascular research

    2024  Volume 119, Issue 18, Page(s) 2843–2857

    Abstract: The availability of pharmacological approaches able to effectively reduce circulating LDL cholesterol (LDL-C) has led to a substantial reduction in the risk of atherosclerosis-related cardiovascular disease (CVD). However, a residual cardiovascular (CV) ... ...

    Abstract The availability of pharmacological approaches able to effectively reduce circulating LDL cholesterol (LDL-C) has led to a substantial reduction in the risk of atherosclerosis-related cardiovascular disease (CVD). However, a residual cardiovascular (CV) risk persists in treated individuals with optimal levels of LDL-C. Additional risk factors beyond LDL-C are involved, and among these, elevated levels of triglycerides (TGs) and TG-rich lipoproteins are causally associated with an increased CV risk. Apolipoprotein C-III (apoC-III) is a key regulator of TG metabolism and hence circulating levels through several mechanisms including the inhibition of lipoprotein lipase activity and alterations in the affinity of apoC-III-containing lipoproteins for both the hepatic receptors involved in their removal and extracellular matrix in the arterial wall. Genetic studies have clarified the role of apoC-III in humans, establishing a causal link with CVD and showing that loss-of-function mutations in the APOC3 gene are associated with reduced TG levels and reduced risk of coronary heart disease. Currently available hypolipidaemic drugs can reduce TG levels, although to a limited extent. Substantial reductions in TG levels can be obtained with new drugs that target specifically apoC-III; these include two antisense oligonucleotides, one small interfering RNA and an antibody.
    MeSH term(s) Humans ; Apolipoprotein C-III/genetics ; Apolipoprotein C-III/metabolism ; Atherosclerosis/drug therapy ; Atherosclerosis/genetics ; Atherosclerosis/prevention & control ; Cholesterol, LDL ; Coronary Disease/genetics ; Lipoproteins/metabolism ; Triglycerides/metabolism
    Chemical Substances Apolipoprotein C-III ; Cholesterol, LDL ; Lipoproteins ; Triglycerides ; APOC3 protein, human
    Language English
    Publishing date 2024-03-20
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvad177
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    Zs.A 565: Show issues Location:
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  10. Article ; Online: Unpacking and Understanding the Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Apolipoprotein B Metabolism.

    Packard, Chris J

    Circulation

    2017  Volume 135, Issue 4, Page(s) 363–365

    MeSH term(s) Apolipoproteins B ; Cholesterol, LDL ; Proprotein Convertase 9 ; Proprotein Convertases ; Receptors, LDL ; Subtilisins
    Chemical Substances Apolipoproteins B ; Cholesterol, LDL ; Receptors, LDL ; Proprotein Convertase 9 (EC 3.4.21.-) ; Proprotein Convertases (EC 3.4.21.-) ; Subtilisins (EC 3.4.21.-)
    Language English
    Publishing date 2017-01-23
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.116.025897
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