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  1. Article ; Online: Infection, inflammation, and cardiovascular risk: are we underestimating an old disease?

    Arnold, Natalie / Koenig, Wolfgang

    European heart journal

    2024  Volume 45, Issue 17, Page(s) 1521–1523

    MeSH term(s) Humans ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/etiology ; Inflammation ; Heart Disease Risk Factors
    Language English
    Publishing date 2024-04-09
    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/ehae104
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  2. Article ; Online: Lipid Lowering Drugs in Acute Coronary Syndromes (ACS).

    Arnold, Natalie / Koenig, Wolfgang

    Current atherosclerosis reports

    2023  Volume 25, Issue 12, Page(s) 939–946

    Abstract: Purpose of review: The purpose of this review is to critically discuss whether more aggressive lipid-lowering strategies are needed in patients with acute coronary syndromes (ACS).: Recent findings: Currently, available data on early (in-hospital/ ... ...

    Abstract Purpose of review: The purpose of this review is to critically discuss whether more aggressive lipid-lowering strategies are needed in patients with acute coronary syndromes (ACS).
    Recent findings: Currently, available data on early (in-hospital/discharge) administration of potent lipid-lowering drugs, such as proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in patients during the vulnerable post-ACS phase, have clearly demonstrated clinical efficacy of the "strike early and strike strong" approach not only for rapid reduction of low-density lipoprotein cholesterol (LDL-C) to unprecedentedly low levels, but also for associated favorable composition of coronary plaque. Intensive lipid-lowering therapy with rapid achievement of the LDL-C treatment goal in ACS patients seems reasonable. However, whether such profound LDL-C reduction would result in additional benefit on the reduction of future CV events still has to be established. Thus, data addressing CV outcomes in such vulnerable patients at extreme CV risk are urgently needed.
    MeSH term(s) Humans ; Proprotein Convertase 9 ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Acute Coronary Syndrome/drug therapy ; Cholesterol, LDL ; Hypolipidemic Agents/therapeutic use ; Anticholesteremic Agents/therapeutic use
    Chemical Substances PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-) ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Cholesterol, LDL ; Hypolipidemic Agents ; Anticholesteremic Agents
    Language English
    Publishing date 2023-11-28
    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/s11883-023-01163-6
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  3. Article ; Online: C-reactive protein, pharmacological treatments and diet: how to target your inflammatory burden.

    Bay, Benjamin / Arnold, Natalie / Waldeyer, Christoph

    Current opinion in lipidology

    2024  Volume 35, Issue 3, Page(s) 141–148

    Abstract: Purpose of review: This article focuses on pharmacological agents as well as dietary changes aimed at the reduction of the inflammatory burden measured by circulating C-reactive protein concentrations.: Recent findings: Over the last years, ... ...

    Abstract Purpose of review: This article focuses on pharmacological agents as well as dietary changes aimed at the reduction of the inflammatory burden measured by circulating C-reactive protein concentrations.
    Recent findings: Over the last years, repurposed as well as new anti-inflammatory agents have been investigated in outcome trials in the cardiovascular field. Currently, a specific inhibition of the inflammatory cascade via the interleukin-6 ligand antibody ziltivekimab is being explored in large-scale outcome trials, after the efficacy of this agent with regard to the reduction of inflammatory biomarkers was proven recently. Next to the investigated pharmacological agents, specific dietary patterns possess the ability to improve the inflammatory burden. This enables patients themselves to unlock a potential health benefit ahead of the initiation of a specific medication targeting the inflammatory pathway.
    Summary: Both pharmacological agents as well as diet provide the opportunity to improve the inflammatory profile and thereby lower C-reactive protein concentrations. Whilst advances in the field of specific anti-inflammatory treatments have been made over the last years, their broad implementation is currently limited. Therefore, optimization of diet (and other lifestyle factors) could provide a cost effective and side-effect free intervention to target low-grade vascular inflammation.
    MeSH term(s) Humans ; C-Reactive Protein/metabolism ; Inflammation/drug therapy ; Diet ; Anti-Inflammatory Agents/therapeutic use ; Anti-Inflammatory Agents/pharmacology
    Chemical Substances C-Reactive Protein (9007-41-4) ; Anti-Inflammatory Agents
    Language English
    Publishing date 2024-01-25
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1045394-5
    ISSN 1473-6535 ; 0957-9672
    ISSN (online) 1473-6535
    ISSN 0957-9672
    DOI 10.1097/MOL.0000000000000922
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  4. Article ; Online: PCSK9 Inhibitor Wars: How Does Inclisiran Fit in with Current Monoclonal Antibody Inhibitor Therapy? Considerations for Patient Selection.

    Arnold, Natalie / Koenig, Wolfgang

    Current cardiology reports

    2022  Volume 24, Issue 11, Page(s) 1657–1667

    Abstract: Purpose of review: Treatment of dyslipidemia represents one of the most crucial strategies to reduce risk of atherosclerotic cardiovascular (CV) disease (ASCVD). In this review, we critically summarize our knowledge on emerging cholesterol-lowering ... ...

    Abstract Purpose of review: Treatment of dyslipidemia represents one of the most crucial strategies to reduce risk of atherosclerotic cardiovascular (CV) disease (ASCVD). In this review, we critically summarize our knowledge on emerging cholesterol-lowering therapy, targeting PCSK9, paying particular attention on treatment allocation of two drug groups, currently available for clinical use, namely, anti-PCSK9 monoclonal antibodies (mAbs) and inclisiran, a first-in-class small interfering RNA against PCSK9.
    Recent findings: Although both drug classes show a pronounced, but fairly similar reduction in LDL-cholesterol, their long-term safety is still unknown. Compared to mAbs, inclisiran has a more favorable dosing regimen with biannual application that might improve therapeutic adherence significantly. However, a CV outcome trial (CVOT) for inclisiran is still missing. If inclisiran will be safe and effective in ongoing/future CVOTs, it has a huge potential to overcome medication non-compliance, thereby providing a powerful therapeutic option to decrease the burden of ASCVD.
    MeSH term(s) Humans ; Patient Selection ; Antibodies, Monoclonal/therapeutic use ; RNA, Small Interfering/therapeutic use ; Cholesterol ; Proprotein Convertase 9
    Chemical Substances Antibodies, Monoclonal ; RNA, Small Interfering ; Cholesterol (97C5T2UQ7J) ; PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-)
    Language English
    Publishing date 2022-09-10
    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/s11886-022-01782-6
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  5. Article ; Online: Persistent inflammatory residual risk despite aggressive cholesterol-lowering therapy: what is next?

    Arnold, Natalie / Koenig, Wolfgang

    Current opinion in cardiology

    2021  Volume 36, Issue 6, Page(s) 776–783

    Abstract: Purpose of review: To briefly summarize recently published evidence on the possible therapeutic modulation of inflammatory processes in atherosclerotic cardiovascular disease (ASCVD), focusing on the rationale for an additional randomized clinical trial, ...

    Abstract Purpose of review: To briefly summarize recently published evidence on the possible therapeutic modulation of inflammatory processes in atherosclerotic cardiovascular disease (ASCVD), focusing on the rationale for an additional randomized clinical trial, targeting both persistently elevated cholesterol and inflammatory residual risk and critically discuss still open issues and future perspectives with regard to treatment allocation.
    Recent findings: Several large-scale clinical trials over the past few years have advanced our understanding of the role of inflammation in atherosclerosis, demonstrating that targeting the NLRP3 inflammasome and the IL-1β pathway indeed represent a new avenue to reduce residual risk in patients with ASCVD. However, despite optimal lipid-lowering therapy and novel options to modulate residual inflammatory risk, there are still a large number of individuals, being at high risk for recurrent ASCVD events.
    Summary: The integration of a dual target strategy aimed at lowering the inflammatory burden in combination with aggressive lipid-modifying for those at high/very high ASCVD risk may hold potential to significantly improve patient care. However, a number of questions related to the design of such 2 × 2 factorial trial still needs to be answered.
    MeSH term(s) Atherosclerosis/drug therapy ; Atherosclerosis/prevention & control ; Cholesterol ; Humans ; Inflammation/drug therapy ; Randomized Controlled Trials as Topic
    Chemical Substances Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2021-09-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 645186-x
    ISSN 1531-7080 ; 0268-4705
    ISSN (online) 1531-7080
    ISSN 0268-4705
    DOI 10.1097/HCO.0000000000000909
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  6. Article ; Online: Kosten-Nutzen-Analyse neuer Lipidsenker.

    Blaum, Christopher / Arnold, Natalie / Waldeyer, Christoph

    Herz

    2022  Volume 47, Issue 3, Page(s) 236–243

    Abstract: Patients with atherosclerotic cardiovascular disease have a high risk for subsequent cardiovascular events despite optimal drug treatment including statins and ezetimibe. Dyslipidemia represents a central and direct cause of this, with a frequent failure ...

    Title translation Cost-benefit analysis of new lipid-lowering agents.
    Abstract Patients with atherosclerotic cardiovascular disease have a high risk for subsequent cardiovascular events despite optimal drug treatment including statins and ezetimibe. Dyslipidemia represents a central and direct cause of this, with a frequent failure to achieve the target values recommended in the guidelines. New lipid-lowering substances are increasingly becoming available for treatment of this residual risk. Due to their high cost, cost-effectiveness analyses are required in order to justify their use. Important variables when considering the cost-effectiveness of a drug are quality adjusted life years (QALY) and the incremental cost-effectiveness ratio (ICER). The lower bounds of the ICER determining the cost-effectiveness of a treatment vary between healthcare systems. The proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab are deemed to be cost-effective particularly in patients with high levels of low-density lipoprotein cholesterol (LDL-C) prior to treatment or with a high cardiovascular risk as determined by the presence of defined risk criteria. Similar considerations apply to the PCSK9 small interfering RNA (siRNA) inclisiran. Administration of bempedoic acid is deemed cost-effective especially in patients with statin intolerance. Eicosapentaenoic acid is deemed cost-effective overall, although the data with respect to the exact placebo-controlled efficacy are still inconclusive.
    MeSH term(s) Antibodies, Monoclonal/adverse effects ; Anticholesteremic Agents/pharmacology ; Anticholesteremic Agents/therapeutic use ; Cholesterol, LDL ; Cost-Benefit Analysis ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; PCSK9 Inhibitors ; Proprotein Convertase 9/metabolism
    Chemical Substances Antibodies, Monoclonal ; Anticholesteremic Agents ; Cholesterol, LDL ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; PCSK9 Inhibitors ; PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-)
    Language German
    Publishing date 2022-04-25
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 8262-4
    ISSN 1615-6692 ; 0340-9937 ; 0946-1299
    ISSN (online) 1615-6692
    ISSN 0340-9937 ; 0946-1299
    DOI 10.1007/s00059-022-05116-8
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  7. Article ; Online: Polygenic Risk Score: Clinically Useful Tool for Prediction of Cardiovascular Disease and Benefit from Lipid-Lowering Therapy?

    Arnold, Natalie / Koenig, Wolfgang

    Cardiovascular drugs and therapy

    2020  Volume 35, Issue 3, Page(s) 627–635

    Abstract: Improvement in risk prediction of atherosclerotic cardiovascular disease (ASCVD) using information on the genetic predisposition at an individual level might offer new possibilities for the successful management of such complex trait. Latest developments ...

    Abstract Improvement in risk prediction of atherosclerotic cardiovascular disease (ASCVD) using information on the genetic predisposition at an individual level might offer new possibilities for the successful management of such complex trait. Latest developments in genetic research with the conduction of genome-wide association studies have facilitated a broader utility of polygenic risk score (PRS) as a potent risk prognosticator, being strongly associated with future cardiovascular events. Although its discriminative ability beyond traditional risk factors is still a matter of controversy, PRS possesses at least comparable risk information to that provided by traditional risk tools. More importantly, increased genetic risk for ASCVD might be discovered at younger ages, much longer before conventional risk factors become manifest, thereby providing a potent instrument for aggressive primordial and primary prevention in those at high risk. Furthermore, there is strong evidence that inherited risk may be successfully modulated by a healthy lifestyle or medication use (e.g., statins or PCSK-9 inhibitors). Here, we provide a short overview of the current research related to the possible application of PRS in clinical routine and critically discuss existing pitfalls, which still limit a widespread utility of PRS outside a research setting.
    MeSH term(s) Atherosclerosis/genetics ; Atherosclerosis/prevention & control ; Biomarkers ; Cardiovascular Diseases/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Healthy Lifestyle ; Humans ; Hypolipidemic Agents/therapeutic use ; Multifactorial Inheritance ; Polymorphism, Single Nucleotide ; Precision Medicine ; Risk Assessment ; Risk Factors
    Chemical Substances Biomarkers ; Hypolipidemic Agents
    Language English
    Publishing date 2020-11-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 639068-7
    ISSN 1573-7241 ; 0920-3206
    ISSN (online) 1573-7241
    ISSN 0920-3206
    DOI 10.1007/s10557-020-07105-7
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  8. Article ; Online: Atherosklerose als inflammatorische Erkrankung – Pathophysiologie, klinische Relevanz und therapeutische Implikationen.

    Arnold, Natalie / Koenig, Wolfgang

    Deutsche medizinische Wochenschrift (1946)

    2019  Volume 144, Issue 5, Page(s) 315–321

    Abstract: Since the early 1990 s, both experimental and clinical data have clearly demonstrated that inflammatory processes accompany atherosclerotic disease from its initiation to the development of clinical complications. Numerous biomarkers involved at various ... ...

    Title translation Atherosclerosis as an Inflammatory Disease - Pathophysiology, Clinical Relevance and Therapeutic Implications.
    Abstract Since the early 1990 s, both experimental and clinical data have clearly demonstrated that inflammatory processes accompany atherosclerotic disease from its initiation to the development of clinical complications. Numerous biomarkers involved at various levels of the inflammation cascade have been shown to be associated with adverse cardiovascular outcomes. Among them, the classical acute phase reactant C-reactive protein (CRP) has been most intensively investigated. Recent research in this field has been driven by the observation that despite low LDL-cholesterol levels, a remarkably high number of patients are still at increased risk for recurrent cardiovascular events. This is argued to be attributable to the presence of a prolonged inflammatory response (reflected by a persistently elevated hsCRP), a concept, which is currently known as "residual inflammatory risk". The unequivocal proof that the inflammatory process is not only a simple bystander but is also causally involved in atherogenesis, came from the recent CANTOS trial, showing a 15 % reduction of primary MACE outcomes despite aggressive statin therapy and lower LDL-cholesterol levels. Thus, an anti-inflammatory treatment strategy might represent a promising tool to improve the outcome of this still deadly disease.
    MeSH term(s) Atherosclerosis ; Biomarkers/blood ; C-Reactive Protein/analysis ; Cholesterol, LDL/blood ; Humans ; Inflammation
    Chemical Substances Biomarkers ; Cholesterol, LDL ; C-Reactive Protein (9007-41-4)
    Language German
    Publishing date 2019-03-05
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 200446-x
    ISSN 1439-4413 ; 0012-0472
    ISSN (online) 1439-4413
    ISSN 0012-0472
    DOI 10.1055/a-0657-1595
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  9. Article ; Online: Is proteomics of value in cardiovascular risk assessment?

    Arnold, Natalie / Koenig, Wolfgang

    Current opinion in lipidology

    2019  Volume 30, Issue 6, Page(s) 452–461

    Abstract: Purpose of review: To briefly summarize recently published evidence in the field of cardiovascular proteomics, focusing on its ability to improve cardiovascular risk stratification and critically discussing still open and burning issues and future ... ...

    Abstract Purpose of review: To briefly summarize recently published evidence in the field of cardiovascular proteomics, focusing on its ability to improve cardiovascular risk stratification and critically discussing still open and burning issues and future perspectives of proteomics research.
    Recent findings: Several epidemiological studies have demonstrated an improvement in cardiovascular risk prediction beyond traditional risk factors by adding novel biomarkers, identified by both discovery and targeted proteomics. However, only a moderate improvement in risk discrimination over clinical variables was observed. Moreover, despite different outcomes there was also a strong overlap of identified candidates, with several of them being already well established cardiovascular risk markers such as growth differentiation factor 15, natriuretic peptides, C-reactive protein, interleukins, and metalloproteases.
    Summary: Although proteomics plays a crucial role in biomarker discovery, the modest discriminative ability of this technique raises the possibility that there are still hidden mechanisms in protein regulatory networks, which urgently need to be evaluated to improve a cardiovascular risk assessment to a clinically significant extent.
    MeSH term(s) Animals ; Biomarkers/metabolism ; C-Reactive Protein/metabolism ; Cardiovascular Diseases/metabolism ; Growth Differentiation Factor 15/metabolism ; Humans ; Interleukins/metabolism ; Metalloproteases/metabolism ; Natriuretic Peptides/metabolism ; Proteomics ; Risk Assessment ; Risk Factors
    Chemical Substances Biomarkers ; GDF15 protein, human ; Growth Differentiation Factor 15 ; Interleukins ; Natriuretic Peptides ; C-Reactive Protein (9007-41-4) ; Metalloproteases (EC 3.4.-)
    Language English
    Publishing date 2019-10-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1045394-5
    ISSN 1473-6535 ; 0957-9672
    ISSN (online) 1473-6535
    ISSN 0957-9672
    DOI 10.1097/MOL.0000000000000639
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  10. Article: Atherosklerose als inflammatorische Erkrankung – Pathophysiologie, klinische Relevanz und therapeutische Implikationen

    Arnold, Natalie / Koenig, Wolfgang

    DMW - Deutsche Medizinische Wochenschrift

    2019  Volume 144, Issue 05, Page(s) 315–321

    Abstract: Since the early 1990 s, both experimental and clinical data have clearly demonstrated that inflammatory processes accompany atherosclerotic disease from its initiation to the development of clinical complications. Numerous biomarkers involved at various ... ...

    Abstract Since the early 1990 s, both experimental and clinical data have clearly demonstrated that inflammatory processes accompany atherosclerotic disease from its initiation to the development of clinical complications. Numerous biomarkers involved at various levels of the inflammation cascade have been shown to be associated with adverse cardiovascular outcomes. Among them, the classical acute phase reactant C-reactive protein (CRP) has been most intensively investigated. Recent research in this field has been driven by the observation that despite low LDL-cholesterol levels, a remarkably high number of patients are still at increased risk for recurrent cardiovascular events. This is argued to be attributable to the presence of a prolonged inflammatory response (reflected by a persistently elevated hsCRP), a concept, which is currently known as “residual inflammatory risk”. The unequivocal proof that the inflammatory process is not only a simple bystander but is also causally involved in atherogenesis, came from the recent CANTOS trial, showing a 15 % reduction of primary MACE outcomes despite aggressive statin therapy and lower LDL-cholesterol levels. Thus, an anti-inflammatory treatment strategy might represent a promising tool to improve the outcome of this still deadly disease.
    Keywords Entzündung ; Atherosklerose ; C-reaktives Protein ; residuales kardiovaskuläres Risiko ; inflammation ; atherosclerosis ; C-reactive protein ; residual cardiovascular risk
    Language German
    Publishing date 2019-03-01
    Publisher © Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 200446-x
    ISSN 1439-4413 ; 0012-0472
    ISSN (online) 1439-4413
    ISSN 0012-0472
    DOI 10.1055/a-0657-1595
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