Addressing Global Educational Needs Related to Lipoprotein(a)
PeerVoice
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96 slides
Feb 25, 2025
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About This Presentation
Steven E. Nissen, MD, MACC, Leslie Cho, MD, and Florian Kronenberg, MD, MAE, discuss ASCVD in this CE activity titled "Addressing Global Educational Needs Related to Lipoprotein(a)." For the full presentation, please visit us at www.peervoice.com/UTX870.
Slide Content
PeerVoice
Addressing Global Educational Needs Related to Lipoprotein(a)
Learning Objectives
Evaluate current evidence demonstrating the causal relationship between
elevated lipoprotein(a) and cardiovascular risk, including within specific
populations worldwide
Use lipoprotein(a) testing and levels to inform cardiovascular risk stratification
and subsequent management
Identify current and investigational strategies to reduce cardiovascular risk in
patients with elevated lipoprotein(a)
PeerVoice is an EBAC® accredited provider since 2022.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoic
Addressing Global Educational Needs Related to Lipoprotein(a)
Learning Objectives
Evaluate current evidence demonstrating the causal relationship between
elevated lipoprotein(a) and cardiovascular risk, including within specific
populations worldwide
Use lipoprotein(a) testing and levels to inform cardiovascular risk stratification
and subsequent management
Identify current and investigational strategies to reduce cardiovascular risk in
patients with elevated lipoprotein(a)
PeerVoice is an EBAC® accredited provider since 2022.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoic
PeerVoice
Part 1 of 7: Appreciating the Causal Relationship Between Lp(a) and CVD:
Why We Have to Look Beyond LDL
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical School
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of Institute
eb ane user This educational content is not intended for US- or UK-based
. physicians.
Copyright © 2010-2025, PeerVoice
Part 1 of 7: Appreciating the Causal Relationship Between Lp(a) and CVD:
Why We Have to Look Beyond LDL
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical School
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of Institute
eb ane user This educational content is not intended for US- or UK-based
. physicians.
Copyright © 2010-2025, PeerVoice
PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Lipoprotein(a) [Lp(a)] Components: Dual Mechanisms Of Harm
Proatherogenic
+ Oxidized PL
Foam cell
Formation
SMC
proliferation
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
Prothrombotic
Kıvıo
Ke ¥ Plasminogen
KIV7 Activation
KIV6
KIS Y TFPI
KIV4
KIV3
y Clot
permeability
4 Platelet
Kiva response
Copyright © 2010-2025, PeerVoice
Lipoprotein(a) [Lp(a)] Components: Dual Mechanisms Of Harm
Proatherogenic
+ Oxidized PL
Foam cell
Formation
SMC
proliferation
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
Prothrombotic
Kıvıo
Ke ¥ Plasminogen
KIV7 Activation
KIV6
KIS Y TFPI
KIV4
KIV3
y Clot
permeability
4 Platelet
Kiva response
Copyright © 2010-2025, PeerVoice
PeerVoice
Global Distribution of Lp(a) Levels
75 nmol/L
E
El
El
E
——> 21%
50 100 150 ' 200 0 350 400 450 500
Lipoprotein(a) nmol/L
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
Global Distribution of Lp(a) Levels
75 nmol/L
E
El
El
E
——> 21%
50 100 150 ' 200 0 350 400 450 500
Lipoprotein(a) nmol/L
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
PeerVoice
Prevalence of Elevated Lp(a): US and Globally
Prevalence Top 10% Top 5% Top 1%
AAA e EE
Lp(a) Level 220 nmol/L | 285 nmol/L | 440 nmol/L.
Number (USA) 30 million | 16 million | 3.2 million
Number (EU) 150 million | 75 million | 37.5 million | 7.5 million
Number Globally 700 million | 350 million | 7 million
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Prevalence of Elevated Lp(a): US and Globally
Prevalence Top 10% Top 5% Top 1%
AAA e EE
Lp(a) Level 220 nmol/L | 285 nmol/L | 440 nmol/L.
Number (USA) 30 million | 16 million | 3.2 million
Number (EU) 150 million | 75 million | 37.5 million | 7.5 million
Number Globally 700 million | 350 million | 7 million
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Genetic Elevation of Lp(a) and ASCVD Risk
Lipoprotein(a)
Multivariable Adjusted
Percentile mg/dL
>95th >117
90th-95th 77-117
67th-89th 30-76
22nd-66th 5-29
<22nd [Reference] <5
HR (95% Cl)
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Genetic Elevation of Lp(a) and ASCVD Risk
Lipoprotein(a)
Multivariable Adjusted
Percentile mg/dL
>95th >117
90th-95th 77-117
67th-89th 30-76
22nd-66th 5-29
<22nd [Reference] <5
HR (95% Cl)
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Data From UK Biobank: Lp(a) and CV Outcome
Linear relationship down to 50 nmol/L (about 20 mg/dL)
Events per 1000 person years Modeled Hazard Ratio
x
@
x
Adjusted Hazard Ratio
>» a
2
460,508 miéco-ages UK Biobank Parilpants
Events per 1000 Person-Years
2
e
© 50 100 150 200 250 300 350 400 0 50 100 150 200 250 300 350 400
Lipoprotein(a) (nmol/L) Lipoprotein(a) (nmol/L)
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Data From UK Biobank: Lp(a) and CV Outcome
Linear relationship down to 50 nmol/L (about 20 mg/dL)
Events per 1000 person years Modeled Hazard Ratio
x
@
x
Adjusted Hazard Ratio
>» a
2
460,508 miéco-ages UK Biobank Parilpants
Events per 1000 Person-Years
2
e
© 50 100 150 200 250 300 350 400 0 50 100 150 200 250 300 350 400
Lipoprotein(a) (nmol/L) Lipoprotein(a) (nmol/L)
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Equivalence of Lp(a) Elevation to FH in Risk of MI
3
=
E
10
mg/dL 0 25 50 75 100 125 150 175 200 225 250 275 300 325 350 375 400
Lipoprotein (a)
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Equivalence of Lp(a) Elevation to FH in Risk of MI
3
=
E
10
mg/dL 0 25 50 75 100 125 150 175 200 225 250 275 300 325 350 375 400
Lipoprotein (a)
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Lp(a) Levels and Risk of Ischaemic Stroke
Strong causal relationship in observational and genetic studies
Per 50 mg/dl (105 nmol/l) Higher Lipoprotein(a) for Risk of Ischemic Stroke
Observational analysis
EN
ON Genetic, causal analyses
e
\ El — Via kringle IV type 2 — 1.20
Via rs 10455872 > een), 1.27
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
Lp(a) Levels and Risk of Ischaemic Stroke
Strong causal relationship in observational and genetic studies
Per 50 mg/dl (105 nmol/l) Higher Lipoprotein(a) for Risk of Ischemic Stroke
Observational analysis
EN
ON Genetic, causal analyses
e
\ El — Via kringle IV type 2 — 1.20
Via rs 10455872 > een), 1.27
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
PeerVoice
Nurses Health Study: LDL-C and Lp(a) Interaction
32,826 women
Relative
Risk
Lp(a) <30 mgldL Lp(a)230 mg/dL
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
LOL 2160 mg/dL.
LOL <160 mg/dL.
Copyright © 2010-2025, PeerVoice
Nurses Health Study: LDL-C and Lp(a) Interaction
32,826 women
Relative
Risk
Lp(a) <30 mgldL Lp(a)230 mg/dL
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
LOL 2160 mg/dL.
LOL <160 mg/dL.
Copyright © 2010-2025, PeerVoice
PeerVoice
Both Genetic Alleles Contribute to Lp(a) Level
llapo(a)allele Allele 2: large apofa) allele
Isoform specific
Lp(a) concentration
To
central
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 2010-2025, PeerVoice
Both Genetic Alleles Contribute to Lp(a) Level
llapo(a)allele Allele 2: large apofa) allele
Isoform specific
Lp(a) concentration
To
central
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 2010-2025, PeerVoice
PeerVoice
Elevated Lp(a): Concordance Amongst Relatives
[i First-degree relatives
Tl second-degree relatives,
D unretated
E =
mmol
Firstdegree Second degree Unrelated
Relation to index participant
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
Elevated Lp(a): Concordance Amongst Relatives
[i First-degree relatives
Tl second-degree relatives,
D unretated
E =
mmol
Firstdegree Second degree Unrelated
Relation to index participant
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
PeerVoice
High Lp(a): Effect of Family History on MI Risk
Family History
Lipoprotein(a) Premature MI
—
—
Percentile mg/dL nmol/L HR (95% Cl)
No 1.00 (reference)
1.87 (1.59-2.19)
No 1.06 (0.98-1.14)
Yes 2.36 (1.97-2.82)
No 1.27 (1.14-1.42)
2.50 (1.85-3.37),
No 1.43 (1.24-1.64)
3.07 (2.21-4.27)
No 1.94 (1.71-2.20)
4.00 (3.05-5.25)
43-68 88-144
69-92 145-197
93-425 198-923
This presentation is the property of Steven E. Nissen, MD, MACC.
2010-2025, PeerVoice
High Lp(a): Effect of Family History on MI Risk
Family History
Lipoprotein(a) Premature MI
—
—
Percentile mg/dL nmol/L HR (95% Cl)
No 1.00 (reference)
1.87 (1.59-2.19)
No 1.06 (0.98-1.14)
Yes 2.36 (1.97-2.82)
No 1.27 (1.14-1.42)
2.50 (1.85-3.37),
No 1.43 (1.24-1.64)
3.07 (2.21-4.27)
No 1.94 (1.71-2.20)
4.00 (3.05-5.25)
43-68 88-144
69-92 145-197
93-425 198-923
This presentation is the property of Steven E. Nissen, MD, MACC.
2010-2025, PeerVoice
PeerVoice
Lp(a) 230 mg/dL LDL-C perSD BMI per SD Smoking (Y/N)
£
=
E
2
=
£
2
El
+2
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
Lp(a) 230 mg/dL LDL-C perSD BMI per SD Smoking (Y/N)
£
=
E
2
=
£
2
El
+2
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
PeerVoice
Critical Insight
Lp(a) Heritage Study: Amongst
48,135 ASCVD patients
at 949 sites in 48 countries
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright € 2010-2025, PeerVoice
Critical Insight
Lp(a) Heritage Study: Amongst
48,135 ASCVD patients
at 949 sites in 48 countries
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright € 2010-2025, PeerVoice
PeerVoice
Abbreviations and References
Lipoprotein(a) [Lp(a)] Components: Dual Mechanisms Of Harm
Abbreviation(s): Apo: apolipoprotein; LDL: low-density lipoprotein; PL: phospholipid; SMC: smooth muscle cell;
TFPI: tissue factor pathway inhibitor.
Reference(s): Gencer B et al. Eur Heart J. 2017;38:1553-1560.
Global Distribution of Lp(a) Levels
Reference(s): Nissen SE et al. Open Heart. 2022;9(2):e002060.
Prevalence of Elevated Lp(a): US and Globally
Reference(s): Adapted from Tsimikas S. J Am Coll Cardiol. 2017:69:692-711.
Varvel S et al. Arterioscler Thromb Vasc Biol. 2016;36:2239-2245.
Genetic Elevation of Lp(a) and ASCVD Risk
Abbreviation(s): ASCVD: atherosclerotic cardiovascular disease (CVD).
Reference(s): Adapted from Kamstrup PR et al. JAMA. 2009;301:2331-2339.
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Abbreviations and References
Lipoprotein(a) [Lp(a)] Components: Dual Mechanisms Of Harm
Abbreviation(s): Apo: apolipoprotein; LDL: low-density lipoprotein; PL: phospholipid; SMC: smooth muscle cell;
TFPI: tissue factor pathway inhibitor.
Reference(s): Gencer B et al. Eur Heart J. 2017;38:1553-1560.
Global Distribution of Lp(a) Levels
Reference(s): Nissen SE et al. Open Heart. 2022;9(2):e002060.
Prevalence of Elevated Lp(a): US and Globally
Reference(s): Adapted from Tsimikas S. J Am Coll Cardiol. 2017:69:692-711.
Varvel S et al. Arterioscler Thromb Vasc Biol. 2016;36:2239-2245.
Genetic Elevation of Lp(a) and ASCVD Risk
Abbreviation(s): ASCVD: atherosclerotic cardiovascular disease (CVD).
Reference(s): Adapted from Kamstrup PR et al. JAMA. 2009;301:2331-2339.
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Abbreviations and References (Cont'd)
Data From UK Biobank: Lp(a) and CV Outcome
Reference(s): Adapted from Patel AP et al. Arterioscler Thromb Vasc Biol. 2021;41:465-474.
Equivalence of Lp(a) Elevation to FH in Risk of MI
Abbreviation(s): FH: familial hypercholesterolaemia; MI: myocardi
Reference(s): Hedegaard BS et al. J Am Coll Cardiol. 2022:80:1998-2010.
Lp(a) Levels and Risk of Ischaemic Stroke
Reference(s): Adapted from Langsted A et al. J Am Coll Cardiol. 2019;74:54-66.
Nurses Health Study: LDL-C and Lp(a) Interaction
Abbreviation(s): LDL-C: LDL-cholesterol.
Reference(s): Shai | et al. Eur Heart J. 2005;26:1633-1639.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Abbreviations and References (Cont'd)
Data From UK Biobank: Lp(a) and CV Outcome
Reference(s): Adapted from Patel AP et al. Arterioscler Thromb Vasc Biol. 2021;41:465-474.
Equivalence of Lp(a) Elevation to FH in Risk of MI
Abbreviation(s): FH: familial hypercholesterolaemia; MI: myocardi
Reference(s): Hedegaard BS et al. J Am Coll Cardiol. 2022:80:1998-2010.
Lp(a) Levels and Risk of Ischaemic Stroke
Reference(s): Adapted from Langsted A et al. J Am Coll Cardiol. 2019;74:54-66.
Nurses Health Study: LDL-C and Lp(a) Interaction
Abbreviation(s): LDL-C: LDL-cholesterol.
Reference(s): Shai | et al. Eur Heart J. 2005;26:1633-1639.
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PeerVoice
Abbreviations and References (Cont'd)
Both Genetic Alleles Contribute to Lp(a) Level
Reference(s): Konrad Schmidt K et al. J Lipid Res. 2016;57:1339-1359.
Elevated Lp(a): Concordance Amongst Relatives
Reference(s): Reeskamp LF et al. JAMA Cardiol. 2023;8:1M-M8.
High Lp(a): Effect of Family History on MI Risk
Reference(s): Hedegaard BS et al. J Am Coll Cardiol. 2022:80:1998-2010.
Lp(a) and Risk of Adult ASCVD in Finnish Youth (9-24 Y)
Abbreviation(s): BMI: body mass index; BP: blood pressure.
Reference(s): Raitakari O et al. Circulation. 2023;147:23-31.
Critical Insight
Reference(s): Nissen SE et al. Open Heart. 2022;9(2):e002060.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Abbreviations and References (Cont'd)
Both Genetic Alleles Contribute to Lp(a) Level
Reference(s): Konrad Schmidt K et al. J Lipid Res. 2016;57:1339-1359.
Elevated Lp(a): Concordance Amongst Relatives
Reference(s): Reeskamp LF et al. JAMA Cardiol. 2023;8:1M-M8.
High Lp(a): Effect of Family History on MI Risk
Reference(s): Hedegaard BS et al. J Am Coll Cardiol. 2022:80:1998-2010.
Lp(a) and Risk of Adult ASCVD in Finnish Youth (9-24 Y)
Abbreviation(s): BMI: body mass index; BP: blood pressure.
Reference(s): Raitakari O et al. Circulation. 2023;147:23-31.
Critical Insight
Reference(s): Nissen SE et al. Open Heart. 2022;9(2):e002060.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Part 2 of 7: Accepting the Causal Role of Lp(a) in Calcific Aortic Stenosis:
What Is the Path to Intervention
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic:
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical Schoo!
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of institute
Institute of Genetic Epidemiology
a This educational content is not intended for US- or UK-based
Innsbruck, Austria
physicians.
Copyright © 2010-2025, PeerVoice
Part 2 of 7: Accepting the Causal Role of Lp(a) in Calcific Aortic Stenosis:
What Is the Path to Intervention
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic:
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical Schoo!
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of institute
Institute of Genetic Epidemiology
a This educational content is not intended for US- or UK-based
Innsbruck, Austria
physicians.
Copyright © 2010-2025, PeerVoice
PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Valve Cal
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Valve Cal
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Evidence for Causal Role of Lp(a) for Calcific Aortic Stenosis
(CAS)
Large, Large,
Case-Control, Prospective, e-Wi Mendelian
‘Cross-Sectional Observational Association Randomisation
Studies Studies
LY
Studies
AS
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Evidence for Causal Role of Lp(a) for Calcific Aortic Stenosis
(CAS)
Large, Large,
Case-Control, Prospective, e-Wi Mendelian
‘Cross-Sectional Observational Association Randomisation
Studies Studies
LY
Studies
AS
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Absolute and Relative Risks of AS as a Function of Increasing
Plasma Lp(a) Concentration
Copenhagen General Population Study
Plasma Lp(a)
nmol/L mg/dl Percentiles ñ L
0-60 0-29 1-74 3 Aortic Valve Stenosis E
61-100 30-49 75-81
101-143 50-69 82-89
144-208 70-99 90-95
SO | mm 2209 2100 298
Absolute Risk/10,000 Person-Years
Aortic Valve Stenosis
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Absolute and Relative Risks of AS as a Function of Increasing
Plasma Lp(a) Concentration
Copenhagen General Population Study
Plasma Lp(a)
nmol/L mg/dl Percentiles ñ L
0-60 0-29 1-74 3 Aortic Valve Stenosis E
61-100 30-49 75-81
101-143 50-69 82-89
144-208 70-99 90-95
SO | mm 2209 2100 298
Absolute Risk/10,000 Person-Years
Aortic Valve Stenosis
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Lp(a) Is Causal Risk Factor for Aortic-Valve Calcification
SNP Associations With
Aortic-Valve Calcium
Mendelian Randomisation
Analysis: Lp(a) and Aortic
Valve Calcification
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Pvalue, logo
Chromosome Position
Association of | Association of Genetically
Meta-Analysis rs10455872 With | rs10455872 With Determined Lp(a)
Plasma Lp(a) Aortic-Valve Ca Levels
‘coefficient for linear 1.58 (121-194) _ .
regression (95% CI) P«.001
Odds ratio (95% CI) = a | | ee)
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Lp(a) Is Causal Risk Factor for Aortic-Valve Calcification
SNP Associations With
Aortic-Valve Calcium
Mendelian Randomisation
Analysis: Lp(a) and Aortic
Valve Calcification
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Pvalue, logo
Chromosome Position
Association of | Association of Genetically
Meta-Analysis rs10455872 With | rs10455872 With Determined Lp(a)
Plasma Lp(a) Aortic-Valve Ca Levels
‘coefficient for linear 1.58 (121-194) _ .
regression (95% CI) P«.001
Odds ratio (95% CI) = a | | ee)
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Lp(a) and Progression of Peak Velocity in CAS
ASTRONOMER Trial
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030
0.20
Vocak M/s/y
Progression Rate
o
©
P=.005
0.26 + 0.03
(n=73)
0.17 + 0.02
(n = 147)
Tertiles 1 and 2 Tertiles 3
Lp(a) <58.5 mg/dL Lp(a) >58.5 mg/dL
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Lp(a) and Progression of Peak Velocity in CAS
ASTRONOMER Trial
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030
0.20
Vocak M/s/y
Progression Rate
o
©
P=.005
0.26 + 0.03
(n=73)
0.17 + 0.02
(n = 147)
Tertiles 1 and 2 Tertiles 3
Lp(a) <58.5 mg/dL Lp(a) >58.5 mg/dL
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Survival W Aortic Valve Replaceme
ASTRONOMER Trial
100 Lp(a) <58.5
œ
°
Lp(a) >58.5
o
°
Adjusted EFS, %
a
°
HR, 2.0 (95% Cl, 11-3.7)
P=.02
D
ko]
o
Follow-Up Time, y
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Survival W Aortic Valve Replaceme
ASTRONOMER Trial
100 Lp(a) <58.5
œ
°
Lp(a) >58.5
o
°
Adjusted EFS, %
a
°
HR, 2.0 (95% Cl, 11-3.7)
P=.02
D
ko]
o
Follow-Up Time, y
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Pathophysiologic Role of Lp(a) in CAS
Vascular Lumen
INx2 >
ZAS factors
©
À PAI-1 ego
= ce
Plesmin efficac AN CA a -
a r Aortic Valve Tissue
D Tri Platelet activation we AN
and thrombosis Osteoblast-like cell
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Pathophysiologic Role of Lp(a) in CAS
Vascular Lumen
INx2 >
ZAS factors
©
À PAI-1 ego
= ce
Plesmin efficac AN CA a -
a r Aortic Valve Tissue
D Tri Platelet activation we AN
and thrombosis Osteoblast-like cell
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Lp(a) and OxPL Drive Valve Calcification and Disease
Progression in Patients With AS
Lp(a)
Pro-Osteogenic
Lom
Elevated Lp(a) and OxPL levels: J
Increased calcification activity 3
Higher risk of aortic valve replacement and
‚death
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Lp(a) and OxPL Drive Valve Calcification and Disease
Progression in Patients With AS
Lp(a)
Pro-Osteogenic
Lom
Elevated Lp(a) and OxPL levels: J
Increased calcification activity 3
Higher risk of aortic valve replacement and
‚death
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Abbreviations and References
Valve Calcification in Aortic Stenosis
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
Evidence for Causal Role of Lp(a) for Calci
Abbreviation(s): Lp(a): lipoprotein a.
Reference(s): Thanassoulis G et al. N Engl J Med. 2013;368:503-512.
Arsenault BJ et al. Circ Cardiovasc Genet. 2014;7:304-310.
Vongpromek R et al. J Intern Med. 2015;278:166-173.
Capoulade R et al. J Am Coll Cardiol. 2015;66:1236-1246.
Cairns BJ et al. Circulation. 2017;135:1181-1183.
Perrot N et al. JAMA Cardiol. 2019;4:620-627.
Steffen BT et al. Arterioscler Thromb Vasc Biol. 2019;39:523-529.
Aortic Stenosis (CAS)
Absolute and Relative Risks of AS as a Function of Increasing Plasma Lp(a) Concentration
Reference(s): Kronenberg F et al. Eur Heart J. 2022;43:3925-3946.
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Abbreviations and References
Valve Calcification in Aortic Stenosis
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
Evidence for Causal Role of Lp(a) for Calci
Abbreviation(s): Lp(a): lipoprotein a.
Reference(s): Thanassoulis G et al. N Engl J Med. 2013;368:503-512.
Arsenault BJ et al. Circ Cardiovasc Genet. 2014;7:304-310.
Vongpromek R et al. J Intern Med. 2015;278:166-173.
Capoulade R et al. J Am Coll Cardiol. 2015;66:1236-1246.
Cairns BJ et al. Circulation. 2017;135:1181-1183.
Perrot N et al. JAMA Cardiol. 2019;4:620-627.
Steffen BT et al. Arterioscler Thromb Vasc Biol. 2019;39:523-529.
Aortic Stenosis (CAS)
Absolute and Relative Risks of AS as a Function of Increasing Plasma Lp(a) Concentration
Reference(s): Kronenberg F et al. Eur Heart J. 2022;43:3925-3946.
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Abbreviations and References (Cont'd)
Lp(a) Is Causal Risk Factor for Aortic-Valve Calcification
Abbreviation(s): Ca: calcium; SNP: single nucleotide polymorphism.
Reference(s): Thanassoulis G et al. N Engl J Med. 2013;368:503-512.
Lp(a) and Progression of Peak Velocit CAS
Reference(s): Capoulade R et al. J Am Coll Cardiol. 2015;66:1236-1246.
Survival Without Aortic Valve Replacement
Abbreviation(s): EFS: event-free survival.
Reference(s): Capoulade R et al. J Am Coll Cardiol. 2015;66:1236-1246.
Tsimikas S. J Am Coll Cardiol. 2017:69:692-71l
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Abbreviations and References (Cont'd)
Lp(a) Is Causal Risk Factor for Aortic-Valve Calcification
Abbreviation(s): Ca: calcium; SNP: single nucleotide polymorphism.
Reference(s): Thanassoulis G et al. N Engl J Med. 2013;368:503-512.
Lp(a) and Progression of Peak Velocit CAS
Reference(s): Capoulade R et al. J Am Coll Cardiol. 2015;66:1236-1246.
Survival Without Aortic Valve Replacement
Abbreviation(s): EFS: event-free survival.
Reference(s): Capoulade R et al. J Am Coll Cardiol. 2015;66:1236-1246.
Tsimikas S. J Am Coll Cardiol. 2017:69:692-71l
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Abbreviations and References (Cont'd)
Pathophysiologic Role of Lp(a) in CAS
Abbreviation(s): ALP: alkaline phosphatase; ATX: autotaxin; BMP2: bone morphogenetic protein 2; IL: interleukin;
Ip-PLA2: lipoprotein-associated phospholipase A2; LPC: Iysophosphatidylcholine; LysoPA: lysophosphatidic acid;
OxPL: oxidised phospholipid; PAI-I: plasminogen activator inhibitor-1; RUNX2: runt-related transcription factor 2;
TFPI: tissue factor pathwa it IC: valvular interstitial cell.
Reference(s): Santangelo G et al. Nutr Metab Cardiovasc Dis. 2022;32:309-317.
Lp(a) and OxPL Drive Valve Calcification and Disease Progression in Patients With AS
Reference(s): Zheng KH et al. J Am Coll Cardiol. 2019;73:2150-2162.
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Abbreviations and References (Cont'd)
Pathophysiologic Role of Lp(a) in CAS
Abbreviation(s): ALP: alkaline phosphatase; ATX: autotaxin; BMP2: bone morphogenetic protein 2; IL: interleukin;
Ip-PLA2: lipoprotein-associated phospholipase A2; LPC: Iysophosphatidylcholine; LysoPA: lysophosphatidic acid;
OxPL: oxidised phospholipid; PAI-I: plasminogen activator inhibitor-1; RUNX2: runt-related transcription factor 2;
TFPI: tissue factor pathwa it IC: valvular interstitial cell.
Reference(s): Santangelo G et al. Nutr Metab Cardiovasc Dis. 2022;32:309-317.
Lp(a) and OxPL Drive Valve Calcification and Disease Progression in Patients With AS
Reference(s): Zheng KH et al. J Am Coll Cardiol. 2019;73:2150-2162.
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Part 3 of 7: Exploring Global Variations in Vulnerability:
How They Impact Lp(a)-Associated Risk
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic:
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical Schoo!
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of institute
Institute of Genetic Epidemiology
a This educational content is not intended for US- or UK-based
Innsbruck, Austria
physicians.
Copyright © 2010-2025, PeerVoice
Part 3 of 7: Exploring Global Variations in Vulnerability:
How They Impact Lp(a)-Associated Risk
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic:
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical Schoo!
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of institute
Institute of Genetic Epidemiology
a This educational content is not intended for US- or UK-based
Innsbruck, Austria
physicians.
Copyright © 2010-2025, PeerVoice
PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
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Influence of Sex and Age on Lp(a) Concentrations
Copenhagen General Population Study
(Women n = 37,545; Men n = 32,497)
17% higher Lp(a) after
30 Women n = 33,770 62 menopause
2 = ES Explanations .
Elser 2 » Lower oestradiol levels in
3 E women
e = + 12% lower Lp(a) during HRT
E 3 + Lower kidney function with
& ño à age explains large part of
eS the small Lp(a) increase
e with age
P for age by sex interaction = 8 + 107
o > o
40 50 60 70 80
Age, y
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Influence of Sex and Age on Lp(a) Concentrations
Copenhagen General Population Study
(Women n = 37,545; Men n = 32,497)
17% higher Lp(a) after
30 Women n = 33,770 62 menopause
2 = ES Explanations .
Elser 2 » Lower oestradiol levels in
3 E women
e = + 12% lower Lp(a) during HRT
E 3 + Lower kidney function with
& ño à age explains large part of
eS the small Lp(a) increase
e with age
P for age by sex interaction = 8 + 107
o > o
40 50 60 70 80
Age, y
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Lp(a) Concentrations and MI: No Sex Interaction
Lp(a) >40 mg/dL
(83 nmol/L)
MI N
=
E Al 8,080
S <50y 1998
= 250y 6082
5 fl 6,147
<2Q y 1,467
= 250y 4680
0.5
>40 mg/dL (>83 nmol/L) vs
<10 mg/dL (<18 nmol/L)
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Events
252
24
228
386
48
338
HR for Lp(a)
HR (95% Cl)
.44
1.78
LAT(
1.56 (138-177)
.80 ea)
53 (1.34-1.74,
1.23-1.69)
1.06-2.98)
19-166)
P Lp(a) by
Sex Interaction
60
81
Copyright © 2010-2025, PeerVoice
Lp(a) Concentrations and MI: No Sex Interaction
Lp(a) >40 mg/dL
(83 nmol/L)
MI N
=
E Al 8,080
S <50y 1998
= 250y 6082
5 fl 6,147
<2Q y 1,467
= 250y 4680
0.5
>40 mg/dL (>83 nmol/L) vs
<10 mg/dL (<18 nmol/L)
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Events
252
24
228
386
48
338
HR for Lp(a)
HR (95% Cl)
.44
1.78
LAT(
1.56 (138-177)
.80 ea)
53 (1.34-1.74,
1.23-1.69)
1.06-2.98)
19-166)
P Lp(a) by
Sex Interaction
60
81
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he UK Biobank
250
200
150
100
Lp(a), nmol/L
50
White South Black Chinese
Asian
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he UK Biobank
250
200
150
100
Lp(a), nmol/L
50
White South Black Chinese
Asian
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Association Between Lp(a) and Major CVD Outcomes
White Population Black Population
(n = 415,274) (n = 7,135)
% 4
3 3
3 HR #231 3 HR 21
515 at 300 nmol/L ae at 300 nmol/L
8 ? ma 2 2] 21200 mo
2 at 200 nmol/L =
ES E Tite 14
5] anata 154 at 100 nmol
at 100 nmol/L
1 1
920 9 10 10 200 250 300 330 400 0% so mo wo 200 250 300 330 400
Lp(a), nmol/L Lpla), nmol/L
Risk is very similar between black and white individuals at different concentrations:
Association is continuous and independent of ethnicity
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Association Between Lp(a) and Major CVD Outcomes
White Population Black Population
(n = 415,274) (n = 7,135)
% 4
3 3
3 HR #231 3 HR 21
515 at 300 nmol/L ae at 300 nmol/L
8 ? ma 2 2] 21200 mo
2 at 200 nmol/L =
ES E Tite 14
5] anata 154 at 100 nmol
at 100 nmol/L
1 1
920 9 10 10 200 250 300 330 400 0% so mo wo 200 250 300 330 400
Lp(a), nmol/L Lpla), nmol/L
Risk is very similar between black and white individuals at different concentrations:
Association is continuous and independent of ethnicity
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Abbreviations and References
Influence of Sex and Age on Lp(a) Concentrations
Abbreviation(s): HRT: hormone replacement therapy; Lp(a): lipoprotein a.
Reference(s): Nordestgaard BG, Langsted A. Lancet. 2024;404: 1255-1264,
Simony SB et al. Atherosclerosis. 2022;355.76-82.
Lp(a) Concentrations and MI: No Sex Interaction
Abbreviation(s): MI: myocardial infarction.
Reference(s): Simony SB et al. Atherosclerosis. 2022;355:76-82.
Ethnic Differences in Lp(a) Concentrations in the UK Biobank
Reference(s): Patel AP et al. Arterioscler Thromb Vasc Biol. 2021;41:465-474,
Association Between Lp(a) and Major CVD Outcomes
Abbreviation(s): CVD: cardiovascular disease.
Reference(s): Kronenberg F et al. Eur Heart J. 2022;43:3925-3946.
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Abbreviations and References
Influence of Sex and Age on Lp(a) Concentrations
Abbreviation(s): HRT: hormone replacement therapy; Lp(a): lipoprotein a.
Reference(s): Nordestgaard BG, Langsted A. Lancet. 2024;404: 1255-1264,
Simony SB et al. Atherosclerosis. 2022;355.76-82.
Lp(a) Concentrations and MI: No Sex Interaction
Abbreviation(s): MI: myocardial infarction.
Reference(s): Simony SB et al. Atherosclerosis. 2022;355:76-82.
Ethnic Differences in Lp(a) Concentrations in the UK Biobank
Reference(s): Patel AP et al. Arterioscler Thromb Vasc Biol. 2021;41:465-474,
Association Between Lp(a) and Major CVD Outcomes
Abbreviation(s): CVD: cardiovascular disease.
Reference(s): Kronenberg F et al. Eur Heart J. 2022;43:3925-3946.
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Part 4 of 7: Identifying Patients With Excess Risk Due to Elevated Lp(a):
Who to Test and When
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical Schoo!
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of Institute
Feb le dl This educational content is not intended for US- or UK-based
. physicians.
Copyright © 2010-2025, PeerVoice
Part 4 of 7: Identifying Patients With Excess Risk Due to Elevated Lp(a):
Who to Test and When
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical Schoo!
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of Institute
Feb le dl This educational content is not intended for US- or UK-based
. physicians.
Copyright © 2010-2025, PeerVoice
PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
EAS Consensus Panel Recommendations for Lp(a) Test
index patient since Lp(a)
Check the family in case of high Lp(a) of
concentration is genetically determined
Genetic testing is not required
Screening is also recommended in youth with a history of ischaemic stroke
or a family history of premature ASCVD or high Lp(a) and no other
identifiable risk factors
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EAS Consensus Panel Recommendations for Lp(a) Test
index patient since Lp(a)
Check the family in case of high Lp(a) of
concentration is genetically determined
Genetic testing is not required
Screening is also recommended in youth with a history of ischaemic stroke
or a family history of premature ASCVD or high Lp(a) and no other
identifiable risk factors
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What Do Current Guidelines/Statements Say About Lp(a)
Testing?
EAS/EFLM 2018 Family history of premature CVD
ESC/EAS 2019 Personal history of premature CVD
India 2020 Family history of high Lp(a)
Canada and Poland 2021 Familial hypercholesterolaemia
EAS Consensus 2022 Moderate to high ASCVD risk
China 2022 Patients with aortic valve stenosis
NLA 2024 UK and France
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What Do Current Guidelines/Statements Say About Lp(a)
Testing?
EAS/EFLM 2018 Family history of premature CVD
ESC/EAS 2019 Personal history of premature CVD
India 2020 Family history of high Lp(a)
Canada and Poland 2021 Familial hypercholesterolaemia
EAS Consensus 2022 Moderate to high ASCVD risk
China 2022 Patients with aortic valve stenosis
NLA 2024 UK and France
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What to Know About Lp(a) Testing
+ Done by a routine, non-fasting blood collection
+ Once in a lifetime is usually enough: low remains low; high remains high
. Lp(a) levels are reported in molar concentrations (nmol/L)
or in mass units (mg/dL): no number without the unit!
EAS Consensus Statement on Risk Thresholds
Rule Out [MGrey "Zone. Ruleln [Scania
The higher the
<30 mg/dL or 30=50'mg/dL or] >50 mg/dL or concentration,
<75 nmol/L | 75-125 nmol/L >125 nmol/L the higher the risk
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What to Know About Lp(a) Testing
+ Done by a routine, non-fasting blood collection
+ Once in a lifetime is usually enough: low remains low; high remains high
. Lp(a) levels are reported in molar concentrations (nmol/L)
or in mass units (mg/dL): no number without the unit!
EAS Consensus Statement on Risk Thresholds
Rule Out [MGrey "Zone. Ruleln [Scania
The higher the
<30 mg/dL or 30=50'mg/dL or] >50 mg/dL or concentration,
<75 nmol/L | 75-125 nmol/L >125 nmol/L the higher the risk
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Identifying Patients With Excess Risk: Never See Lp(a) Alone
Data are derived from the EAS Lp(a) Consensus statement based on data from
>400,000 study participants from the UK Biobank
mg/dL nmol/L
Additional risk
caused by Lp(a)
Absolute Lifetime Risk for
CV Events, %
Low Middle High
Number of Traditional Risk Factors
Traditional risk factors are age, sex, blood cholesterol, BP, smoking, diabetes, a family
history of heart attacks in early life and BMI
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Identifying Patients With Excess Risk: Never See Lp(a) Alone
Data are derived from the EAS Lp(a) Consensus statement based on data from
>400,000 study participants from the UK Biobank
mg/dL nmol/L
Additional risk
caused by Lp(a)
Absolute Lifetime Risk for
CV Events, %
Low Middle High
Number of Traditional Risk Factors
Traditional risk factors are age, sex, blood cholesterol, BP, smoking, diabetes, a family
history of heart attacks in early life and BMI
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Young Woman Without Symptoms But Positive Family History
All have Lp(a) =400 nmol/L.
Sudden Stent at
cardiac age <60
death
lea!
at age <50
3 stents at age 59
Lp(a), 387 nmol/L.
Elevated
LDL-C
7,
Age 33 Age 31
Lp(a), 305 nmol/L. Lp(a), 83 nmol/L
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+ A reason why family
members should be invited
to get Lp(a) tested
+ Start treatment of available
risk factors as early as
possible > prevention
Copyright © 2010-2025, PeerVoice
Young Woman Without Symptoms But Positive Family History
All have Lp(a) =400 nmol/L.
Sudden Stent at
cardiac age <60
death
lea!
at age <50
3 stents at age 59
Lp(a), 387 nmol/L.
Elevated
LDL-C
7,
Age 33 Age 31
Lp(a), 305 nmol/L. Lp(a), 83 nmol/L
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+ A reason why family
members should be invited
to get Lp(a) tested
+ Start treatment of available
risk factors as early as
possible > prevention
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Abbreviations and References
EAS Consensus Panel Recommendations for Lp(a) Testing
Abbreviation(s): ASCVD: atherosclerotic cardiovascular disease (CVD); EAS: European Atherosclerosis Society;
Lp(a): lipoprotein a.
Reference(s): Kronenberg F et al. Eur Heart J. 2022:43:3925-3946.
What Do Current Guidelines/Statements Say About Lp(a) Testing?
Abbreviation(s): EFLM: European Federation of Clinical Chemistry and Laboratory Medicine; ESC: European Society of
Cardiology; NLA: National Lipid Association.
Reference(s): Kamstrup PR et al. Eur J Prev Cardiol. 2024;31:903-914.
Kronenberg F et al. Curr Opin Lipidol. 2022;33:342-352.
What to Know About Lp(a) Testing
Reference(s): Kronenberg F et al. Eur Heart J. 2022;43:3925-3946.
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Abbreviations and References
EAS Consensus Panel Recommendations for Lp(a) Testing
Abbreviation(s): ASCVD: atherosclerotic cardiovascular disease (CVD); EAS: European Atherosclerosis Society;
Lp(a): lipoprotein a.
Reference(s): Kronenberg F et al. Eur Heart J. 2022:43:3925-3946.
What Do Current Guidelines/Statements Say About Lp(a) Testing?
Abbreviation(s): EFLM: European Federation of Clinical Chemistry and Laboratory Medicine; ESC: European Society of
Cardiology; NLA: National Lipid Association.
Reference(s): Kamstrup PR et al. Eur J Prev Cardiol. 2024;31:903-914.
Kronenberg F et al. Curr Opin Lipidol. 2022;33:342-352.
What to Know About Lp(a) Testing
Reference(s): Kronenberg F et al. Eur Heart J. 2022;43:3925-3946.
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Abbreviations and References (Cont'd)
Identifying Patients With Excess Risk: Never See Lp(a) Alone
Abbreviation(s): BMI: body mass index; BP: blood pressure.
Reference(s): Kronenberg F. Curr Atheroscler Rep. 2024:2675-82.
Young Woman Without Symptoms But Positive Family History
Abbreviation(s): LDL-C: low-density lipoprotein cholesterol.
Reference(s): Courtesy of Florian Kronenberg, MD, MAE; January 2025.
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Abbreviations and References (Cont'd)
Identifying Patients With Excess Risk: Never See Lp(a) Alone
Abbreviation(s): BMI: body mass index; BP: blood pressure.
Reference(s): Kronenberg F. Curr Atheroscler Rep. 2024:2675-82.
Young Woman Without Symptoms But Positive Family History
Abbreviation(s): LDL-C: low-density lipoprotein cholesterol.
Reference(s): Courtesy of Florian Kronenberg, MD, MAE; January 2025.
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Part 5 of 7: Incorporating Lp(a) Levels Into CV Risk Assessment:
How to Put Test Results to Use
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical School
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of institute
Institute of Genetic Epidemiology
a This educational content is not intended for US- or UK-based
Innsbruck, Austria
physicians.
Copyright © 2010-2025, PeerVoice
Part 5 of 7: Incorporating Lp(a) Levels Into CV Risk Assessment:
How to Put Test Results to Use
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical School
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of institute
Institute of Genetic Epidemiology
a This educational content is not intended for US- or UK-based
Innsbruck, Austria
physicians.
Copyright © 2010-2025, PeerVoice
PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
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Patient Information and Medical History
Age/Gender: 41-year-old male
Ethnicity: South East Asian
Chief Complaint: Dyspnoea on exertion (DOE) and chest pressure for past 3 months
Family History Physical Examination
+ Father: Ml at age 40 - BP:108/60 mmHg * Weight: 200 Ib (90 kg)
* Uncles: CAD with stents + Pulse: 68 bpm + BMI: 26.9 kg/m?
+ Brother PCI at age 48 + Height: 6'0°(183m) * WC: 37 inches (93 cm)
Past Medical History Cardiovascular and Respiratory Examination
+ Hypertension; receiving + Heart: RRR; normal Sl and $2; no murmur
amlodipine » Lungs: Clear
Extremities
+ No oedema
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Patient Information and Medical History
Age/Gender: 41-year-old male
Ethnicity: South East Asian
Chief Complaint: Dyspnoea on exertion (DOE) and chest pressure for past 3 months
Family History Physical Examination
+ Father: Ml at age 40 - BP:108/60 mmHg * Weight: 200 Ib (90 kg)
* Uncles: CAD with stents + Pulse: 68 bpm + BMI: 26.9 kg/m?
+ Brother PCI at age 48 + Height: 6'0°(183m) * WC: 37 inches (93 cm)
Past Medical History Cardiovascular and Respiratory Examination
+ Hypertension; receiving + Heart: RRR; normal Sl and $2; no murmur
amlodipine » Lungs: Clear
Extremities
+ No oedema
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Laboratory Results
CMP:Normal Lipid Profile Inflammatory Marker(s)
CBC:Normal *TC:197 mg/dL + hsCRP: 1.3 mg/L
HbAlc: 5.8% + HDL-C: 45 mg/dL
+ LDL-C: 136 mg/dL
+ TG: 82 mg/dL
+ Non-HDL-C: 152 mg/dL
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Laboratory Results
CMP:Normal Lipid Profile Inflammatory Marker(s)
CBC:Normal *TC:197 mg/dL + hsCRP: 1.3 mg/L
HbAlc: 5.8% + HDL-C: 45 mg/dL
+ LDL-C: 136 mg/dL
+ TG: 82 mg/dL
+ Non-HDL-C: 152 mg/dL
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Diagnostic Test Results
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SPECT With CT Attenuation
Protocol: Bruce protocol,
Stage 2 only
Max Heart Rate
94% PMHR
ECG Findings
Abnormal at rest
Borderline ST-T changes
Positive for chest pain (CP)
during stress
Peak BP: 164/100 mmHg
Imaging Findings
Anterior ischaemia
Transient ischaemic dilation (TID)
Severe calcification noted
Echocardiogram (Echo)
LV: Normal size; EF, 40%-45%
Regional wall motion: Mild inferior
hypokinesis
Valvular findings: Mild MR
Copyright © 2010-2025, PeerVoice
Diagnostic Test Results
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SPECT With CT Attenuation
Protocol: Bruce protocol,
Stage 2 only
Max Heart Rate
94% PMHR
ECG Findings
Abnormal at rest
Borderline ST-T changes
Positive for chest pain (CP)
during stress
Peak BP: 164/100 mmHg
Imaging Findings
Anterior ischaemia
Transient ischaemic dilation (TID)
Severe calcification noted
Echocardiogram (Echo)
LV: Normal size; EF, 40%-45%
Regional wall motion: Mild inferior
hypokinesis
Valvular findings: Mild MR
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Diagnostic Test Results (Cont'd)
+ Cardiac catheterisation showed severe 3V CAD
+ Referred for CCF for further evaluation:
Why does he have such severe CAD?
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Diagnostic Test Results (Cont'd)
+ Cardiac catheterisation showed severe 3V CAD
+ Referred for CCF for further evaluation:
Why does he have such severe CAD?
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Laboratory Results Revisited
CMP: Normal Lipid Profile Inflammatory Marker(s)
CBC:Normal *TC:197 mg/dL + hsCRP: 1.3 mg/L
HbAlc: 5.8% + HDL-C: 45 mg/dL
+ LDL-C: 136 mg/dL
+ TG: 82 mg/dL
+ Non-HDL-C: 152 mg/dL
Lp(a) 327.9 nmol/L (152 mg/dL)
UNL 75 nmol/L (30 mg/dL)
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Laboratory Results Revisited
CMP: Normal Lipid Profile Inflammatory Marker(s)
CBC:Normal *TC:197 mg/dL + hsCRP: 1.3 mg/L
HbAlc: 5.8% + HDL-C: 45 mg/dL
+ LDL-C: 136 mg/dL
+ TG: 82 mg/dL
+ Non-HDL-C: 152 mg/dL
Lp(a) 327.9 nmol/L (152 mg/dL)
UNL 75 nmol/L (30 mg/dL)
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Guideline Recommendations
7 2
Y, Y,
7 Y,
Y Y
Y Y
Y Y,
7 Y
Y. YE
zz Y
Y 2
7 72
‘AAS (2023) O Y Y
BHS(2022% © Y
EAS (2022)? 0 Y
FAS (2021)4 D Y
ccs (2021)5 0 Y
LAI (2020)° = Y Y Y
AACE/ACE (2020) Y
Y Y
NLA (2019, 2024) =
HEART UK (2019)? gy
ESC/EAS (2019) @
ACC/AHA (2018)" =
Established ASCVD (secondary prevention) Includes primary
Lp(a)-HERITAGE: only 14% of Lp(a) measurements in prevention patients
patients with established ASCVD prior to study enrolment
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Guideline Recommendations
7 2
Y, Y,
7 Y,
Y Y
Y Y
Y Y,
7 Y
Y. YE
zz Y
Y 2
7 72
‘AAS (2023) O Y Y
BHS(2022% © Y
EAS (2022)? 0 Y
FAS (2021)4 D Y
ccs (2021)5 0 Y
LAI (2020)° = Y Y Y
AACE/ACE (2020) Y
Y Y
NLA (2019, 2024) =
HEART UK (2019)? gy
ESC/EAS (2019) @
ACC/AHA (2018)" =
Established ASCVD (secondary prevention) Includes primary
Lp(a)-HERITAGE: only 14% of Lp(a) measurements in prevention patients
patients with established ASCVD prior to study enrolment
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and Traditional Risk Factors
mg/dL nmol/L
Absolute Lifetime Risk for
CV Events, %
Low Middle High
Number of Traditional Risk Factors
Traditional risk factors are age, sex, blood cholesterol, BP, smoking, diabetes, a family
history of heart attacks in early life and BMI
Data are derived from the EAS Lp(a) Consensus statement based on data from >400,000 study participants from the UK Biobank
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and Traditional Risk Factors
mg/dL nmol/L
Absolute Lifetime Risk for
CV Events, %
Low Middle High
Number of Traditional Risk Factors
Traditional risk factors are age, sex, blood cholesterol, BP, smoking, diabetes, a family
history of heart attacks in early life and BMI
Data are derived from the EAS Lp(a) Consensus statement based on data from >400,000 study participants from the UK Biobank
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Lp(a) and Cardiovascular Risk Progression
Primary
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Lp(a) and Cardiovascular Risk Progression
Primary
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Lp(a)-Mediated Calcific Atherosclerosis
|
a lit HF
ri
BE
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Lp(a)-Mediated Calcific Atherosclerosis
|
a lit HF
ri
BE
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Abbreviations and References
Patient Information and Medical History
Abbreviation(s): BMI: body mass index; BP: blood pressure; CAD: coronary artery disease; MI: myocardial infarction;
PCI: percutaneous coronary intervention; RRR: regular rate and rhythm; WC: wait circumference.
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
Laboratory Results
Abbreviation(s): CBC: complete blood count; CMP: comprehensive metabolic panel; hsCRP: high-sensitivity C-reactive
protein; HbAlc: glycated haemoglobin; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein
cholesterol; TC: total cholesterol; TG: triglycerides.
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
Diagnostic Test Results
Abbreviation(s): EF: ejection fraction; LV: left ventricular; MR: mitral regurgitation; PMHR: predicted maximum heart
rate; SPECT: single-photon emission computed tomography (CT).
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
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Abbreviations and References
Patient Information and Medical History
Abbreviation(s): BMI: body mass index; BP: blood pressure; CAD: coronary artery disease; MI: myocardial infarction;
PCI: percutaneous coronary intervention; RRR: regular rate and rhythm; WC: wait circumference.
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
Laboratory Results
Abbreviation(s): CBC: complete blood count; CMP: comprehensive metabolic panel; hsCRP: high-sensitivity C-reactive
protein; HbAlc: glycated haemoglobin; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein
cholesterol; TC: total cholesterol; TG: triglycerides.
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
Diagnostic Test Results
Abbreviation(s): EF: ejection fraction; LV: left ventricular; MR: mitral regurgitation; PMHR: predicted maximum heart
rate; SPECT: single-photon emission computed tomography (CT).
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
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Abbreviations and References (Cont'd)
Diagnostic Test Results (Cont'd)
Abbreviation(s): CCF: Cleveland Clinic Foundation.
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
Laboratory Results Revisited
Abbreviation(s): Lp(a): lipoprotein a.
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
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Abbreviations and References (Cont'd)
Diagnostic Test Results (Cont'd)
Abbreviation(s): CCF: Cleveland Clinic Foundation.
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
Laboratory Results Revisited
Abbreviation(s): Lp(a): lipoprotein a.
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
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Abbreviations and References (Cont'd)
Guideline Recommendations
Abbreviation(s): AACE/ACE: American Association of Clinical Endocrinologists/American College of Endocrinology;
AAS: Australian Atherosclerosis Society; ACC/AHA: American College of Cardiology/American Heart Association;
ASCVD: atherosclerotic cardiovascular disease (CVD); BHS: Beijing Heart Society; CCS: Canadian Cardiovascular
Society; EAS: European Atherosclerosis Society; ESC: European Society of Cardiology; FAS: French Atherosclerotic
Society; LAI: Lipid Association of India; NLA: National Lipid Association.
Reference(s): 1. Ward NC et al. Heart Lung Circ. 2023;32:287-296.
2. Li JJ et al. JACC Asia. 2022;2:653-665.
3. Kronenberg F et al. Eur Heart J. 2022;43:3925-3946.
4. Durlach V et al. Arch Cardiovasc Dis. 2021;114:828-847.
5. Pearson GJ et al. Can J Cardiol. 2021;37:129-1150.
6. Puri R et al. J Assoc Physicians India. 2020;68(11[Special]):8-9.
7. Handelsman Y et al. Endocr Pract. 2020;26:1196-1224.
8. Wilson DP et al. J Clin Lipidol. 2019;13:374-392.
9. Cegla J et al. Atherosclerosis. 2019;291:62-70.
10. Mach F et al. Eur Heart J. 2020;41111-188,
11. Grundy SM et al. Circulation. 2019;139(25):e1082-e1143.
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Abbreviations and References (Cont'd)
Guideline Recommendations
Abbreviation(s): AACE/ACE: American Association of Clinical Endocrinologists/American College of Endocrinology;
AAS: Australian Atherosclerosis Society; ACC/AHA: American College of Cardiology/American Heart Association;
ASCVD: atherosclerotic cardiovascular disease (CVD); BHS: Beijing Heart Society; CCS: Canadian Cardiovascular
Society; EAS: European Atherosclerosis Society; ESC: European Society of Cardiology; FAS: French Atherosclerotic
Society; LAI: Lipid Association of India; NLA: National Lipid Association.
Reference(s): 1. Ward NC et al. Heart Lung Circ. 2023;32:287-296.
2. Li JJ et al. JACC Asia. 2022;2:653-665.
3. Kronenberg F et al. Eur Heart J. 2022;43:3925-3946.
4. Durlach V et al. Arch Cardiovasc Dis. 2021;114:828-847.
5. Pearson GJ et al. Can J Cardiol. 2021;37:129-1150.
6. Puri R et al. J Assoc Physicians India. 2020;68(11[Special]):8-9.
7. Handelsman Y et al. Endocr Pract. 2020;26:1196-1224.
8. Wilson DP et al. J Clin Lipidol. 2019;13:374-392.
9. Cegla J et al. Atherosclerosis. 2019;291:62-70.
10. Mach F et al. Eur Heart J. 2020;41111-188,
11. Grundy SM et al. Circulation. 2019;139(25):e1082-e1143.
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Abbreviations and References (Cont'd)
Lp(a) and Traditional Risk Factors
Reference(s): Kronenberg F. Curr Atheroscler Rep. 2024;26:75-82.
Kronenberg F et al. Eur Heart J. 2022;43:3925-3946.
Lp(a) and Cardiovascular Risk Progression
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
Lp(a)-Mediated Calcific Atherosclerosis
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
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Abbreviations and References (Cont'd)
Lp(a) and Traditional Risk Factors
Reference(s): Kronenberg F. Curr Atheroscler Rep. 2024;26:75-82.
Kronenberg F et al. Eur Heart J. 2022;43:3925-3946.
Lp(a) and Cardiovascular Risk Progression
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
Lp(a)-Mediated Calcific Atherosclerosis
Reference(s): Courtesy of Leslie Cho, MD; January 2025.
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Part 6 of 7: Taking Action Against CV Risk in Patients With Elevated Lp(a):
What You Can Do Right Now
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical School
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of institute
Institute of Genetic Epidemiology
a This educational content is not intended for US- or UK-based
Innsbruck, Austria
physicians.
Copyright © 2010-2025, PeerVoice
Part 6 of 7: Taking Action Against CV Risk in Patients With Elevated Lp(a):
What You Can Do Right Now
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical School
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of institute
Institute of Genetic Epidemiology
a This educational content is not intended for US- or UK-based
Innsbruck, Austria
physicians.
Copyright © 2010-2025, PeerVoice
PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
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Statins Slightly Increase Lp(a) Levels: Meta-Analysis
Statin Study
_Kyetal 2008 (n=29)
‘Yoshida etal 2012 (n=21)
Tsimikas et al (MIRACL) 2004 — (n=1 da
Atorvastatin 80mg Ky et al 2008
Choi et al (REVERSAL) 2008 oe)
y = Rodenberg et al 2006 — (n=90)
Pravastatin 40mg Choi et al (REVERSAL) 2008 i
- Kyetal 2008
Pitivastatin 2mg Yoshida et al 2012
Atorvastatin 10mg
Rosuvastatin40mg Capoulade et al (ASTRONOMER) 2015
Simvastatin/Ezetimibe Yeangetal 2016
9%
+0 0 50
Mean % Change with Statins/Ezetimibe
This presentation is the property of Steven E. Nissen, MD, MACC.
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Statins Slightly Increase Lp(a) Levels: Meta-Analysis
Statin Study
_Kyetal 2008 (n=29)
‘Yoshida etal 2012 (n=21)
Tsimikas et al (MIRACL) 2004 — (n=1 da
Atorvastatin 80mg Ky et al 2008
Choi et al (REVERSAL) 2008 oe)
y = Rodenberg et al 2006 — (n=90)
Pravastatin 40mg Choi et al (REVERSAL) 2008 i
- Kyetal 2008
Pitivastatin 2mg Yoshida et al 2012
Atorvastatin 10mg
Rosuvastatin40mg Capoulade et al (ASTRONOMER) 2015
Simvastatin/Ezetimibe Yeangetal 2016
9%
+0 0 50
Mean % Change with Statins/Ezetimibe
This presentation is the property of Steven E. Nissen, MD, MACC.
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Statins Lower CV Risk Despite Increasing Lp(a)
Primary Endpoint
Lp(a) < Median —
,———
0.25 0.5
Rosuvastatin Superior
1.0
2.0
Placebo Superior
This presentation is the property of Steven E. Nissen, MD, MACC.
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Copyright © 2010-2025, PeerVoice
Statins Lower CV Risk Despite Increasing Lp(a)
Primary Endpoint
Lp(a) < Median —
,———
0.25 0.5
Rosuvastatin Superior
1.0
2.0
Placebo Superior
This presentation is the property of Steven E. Nissen, MD, MACC.
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Copyright © 2010-2025, PeerVoice
PeerVoice
Does a Low LDL-C Reduce Risk of Elevated Lp(a)?
Probability of Survival Free From CHD
LDL-C $100 mg/dL, Lp(a) < 50 mg/dL
— LDL-C >100 mg/dL, Lp(a) < 50 mg/dL.
LDL-C >100 mg/dL, Lp(a) 2 50 mg/dL.
MESA data
7 7 é
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is the property of Steven E. Nissen, MD, MACC.
70
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Does a Low LDL-C Reduce Risk of Elevated Lp(a)?
Probability of Survival Free From CHD
LDL-C $100 mg/dL, Lp(a) < 50 mg/dL
— LDL-C >100 mg/dL, Lp(a) < 50 mg/dL.
LDL-C >100 mg/dL, Lp(a) 2 50 mg/dL.
MESA data
7 7 é
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is the property of Steven E. Nissen, MD, MACC.
70
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Risk and Benefit of Aspirin in Treatment of Elevated Lp(a)
mMACE Benefit Aspree Trial
Bleeding Risk
Interaction
P=0,049 Interaction
P=NS
$
2
é
E
E
E
5
#
2
All Participants Rs3798220-C Genotype High Genotype Risk Quintile
This presentation is the property of Steven E. Nissen, MD, MACC.
ht © 2010-2025, PeerVoice
Risk and Benefit of Aspirin in Treatment of Elevated Lp(a)
mMACE Benefit Aspree Trial
Bleeding Risk
Interaction
P=0,049 Interaction
P=NS
$
2
é
E
E
E
5
#
2
All Participants Rs3798220-C Genotype High Genotype Risk Quintile
This presentation is the property of Steven E. Nissen, MD, MACC.
ht © 2010-2025, PeerVoice
PeerVoice
Fourier: Effect of Evolocumab on Lp(a)
Diminished Percent Change for Highest Quartile of Lipoprotein(a)
Q1(S13nmoVL) Q2(13-37 nmolL) Q3 (37-165 nmol/L) Q4 (>165 nmol/L)
0%
pproximately
! 86 MOL
(15 mg/dL) |
€
à
3
E
5
2
5
E
ö
13
5
2
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
Fourier: Effect of Evolocumab on Lp(a)
Diminished Percent Change for Highest Quartile of Lipoprotein(a)
Q1(S13nmoVL) Q2(13-37 nmolL) Q3 (37-165 nmol/L) Q4 (>165 nmol/L)
0%
pproximately
! 86 MOL
(15 mg/dL) |
€
à
3
E
5
2
5
E
ö
13
5
2
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
PeerVoice
Effect of Evolocumab on MACE by Baseline Lp(a)
Lp(a) < median Lp(a) > median
CV Death, MI or Stroke
2
a
5
=
£
3
&
3
3
Evolocumab Placebo Evolocumab
Interaction P = 0.07
This presentation is the property of Steven E. Nissen, MD, MACC.
ht © 2010-2025, PeerVoice
Effect of Evolocumab on MACE by Baseline Lp(a)
Lp(a) < median Lp(a) > median
CV Death, MI or Stroke
2
a
5
=
£
3
&
3
3
Evolocumab Placebo Evolocumab
Interaction P = 0.07
This presentation is the property of Steven E. Nissen, MD, MACC.
ht © 2010-2025, PeerVoice
PeerVoice
Apheresis: Effect on Major Cardiovascular Events
Events in
Apheresis
Treated
Patients
83882388
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.
12 Years Pre-Apheresis
m2 Years Post-Apheresis |
Copyright © 2010-2025, PeerVoice
Apheresis: Effect on Major Cardiovascular Events
Events in
Apheresis
Treated
Patients
83882388
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.
12 Years Pre-Apheresis
m2 Years Post-Apheresis |
Copyright © 2010-2025, PeerVoice
PeerVoice
Aphere:
+ Time-consuming
+ Expensive (Up to $4,000/session)
+ Not widely available
This presentation is the property of Steven E. Nissen, MD, MACC.
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Aphere:
+ Time-consuming
+ Expensive (Up to $4,000/session)
+ Not widely available
This presentation is the property of Steven E. Nissen, MD, MACC.
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PeerVoice
Best Current Management Strategy: Intensively Treat Every
Other Risk Factor
Target a very low LDL-cholesterol with statins and ezetimibe
Meticulously control blood pressure
Optimize body weight
Recommend a heart-healthy diet
Encourage regular physical activity
Avoid smoking
Monitor for progression of aortic valve calcification
PCSKS9 inhibitors may provide value (weak evidence)
Consider aspirin addition when there is no high risk of bleeding
In most severe cases, consider lipoprotein apheresis
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
Best Current Management Strategy: Intensively Treat Every
Other Risk Factor
Target a very low LDL-cholesterol with statins and ezetimibe
Meticulously control blood pressure
Optimize body weight
Recommend a heart-healthy diet
Encourage regular physical activity
Avoid smoking
Monitor for progression of aortic valve calcification
PCSKS9 inhibitors may provide value (weak evidence)
Consider aspirin addition when there is no high risk of bleeding
In most severe cases, consider lipoprotein apheresis
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
PeerVoice
Abbreviations and References
Statins Slightly Increase Lp(a) Levels: Meta-Analysis
Abbreviation(s): Lp(a): lipoprotein a.
Reference(s): Adapted from Tsimikas S. J Am Coll Cardiol. 2017;
9:692-711.
Statins Lower CV Risk Despite Increasing Lp(a)
Abbreviation(s): CV: cardiovascular.
Reference(s): Khera AV et al. Circulation. 2014129:635-642.
Does a Low LDL-C Reduce Risk of Elevated Lp(a)?
Abbreviation(s): CHD: coronary heart disease; LDL-C: low-density lipoprotein cholesterol.
Reference(s): Rikhi R et al. Atherosclerosis. 202: 2-108,
Risk and Benefit of Aspirin in Treatment of Elevated Lp(a)
Abbreviation(s): MACE: major adverse CV events; NS: not sigt
Reference(s): Raitakari O et al. Circulation. 2023;147:23-31.
icant.
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Abbreviations and References
Statins Slightly Increase Lp(a) Levels: Meta-Analysis
Abbreviation(s): Lp(a): lipoprotein a.
Reference(s): Adapted from Tsimikas S. J Am Coll Cardiol. 2017;
9:692-711.
Statins Lower CV Risk Despite Increasing Lp(a)
Abbreviation(s): CV: cardiovascular.
Reference(s): Khera AV et al. Circulation. 2014129:635-642.
Does a Low LDL-C Reduce Risk of Elevated Lp(a)?
Abbreviation(s): CHD: coronary heart disease; LDL-C: low-density lipoprotein cholesterol.
Reference(s): Rikhi R et al. Atherosclerosis. 202: 2-108,
Risk and Benefit of Aspirin in Treatment of Elevated Lp(a)
Abbreviation(s): MACE: major adverse CV events; NS: not sigt
Reference(s): Raitakari O et al. Circulation. 2023;147:23-31.
icant.
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Abbreviations and References (Cont'd)
Fourier: Effect of Evolocumab on Lp(a)
Reference(s): O'Donoghue ML et al. Circulation. 2019;139:1483-1492.
Effect of Evolocumab on MACE by Baseline Lp(a)
Abbreviation(s): MI: myocardial infarction.
Reference(s): O'Donoghue ML et al. Circulation. 2019,139:1483-1492.
Apheresis: Effect on Major Cardiovascular Events
Abbreviation(s): CABG: coronary artery bypass grafting; PCI: percutaneous coronary intervention.
Reference(s): Leebmann J et al. Circulation. 2013;128:2567-2576.
Apheresis Impractical for Most Patients
Reference(s): Courtesy of Steven E. Nissen, MD, MACC; January 2025.
Best Current Management Strategy: Intensively Treat Every Other Risk Factor
Abbreviation(s): PCSK9: proprotein convertase subtilisin/kexin type 9.
Reference(s): Courtesy of Steven E. Nissen, MD, MACC; January 2025.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Abbreviations and References (Cont'd)
Fourier: Effect of Evolocumab on Lp(a)
Reference(s): O'Donoghue ML et al. Circulation. 2019;139:1483-1492.
Effect of Evolocumab on MACE by Baseline Lp(a)
Abbreviation(s): MI: myocardial infarction.
Reference(s): O'Donoghue ML et al. Circulation. 2019,139:1483-1492.
Apheresis: Effect on Major Cardiovascular Events
Abbreviation(s): CABG: coronary artery bypass grafting; PCI: percutaneous coronary intervention.
Reference(s): Leebmann J et al. Circulation. 2013;128:2567-2576.
Apheresis Impractical for Most Patients
Reference(s): Courtesy of Steven E. Nissen, MD, MACC; January 2025.
Best Current Management Strategy: Intensively Treat Every Other Risk Factor
Abbreviation(s): PCSK9: proprotein convertase subtilisin/kexin type 9.
Reference(s): Courtesy of Steven E. Nissen, MD, MACC; January 2025.
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PeerVoice
Part 7 of 7: Uncovering Direct Approaches to Address Elevated Lp(a):
What We've Learned
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical School
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of institute
Institute of Genetic Epidemiology
a This educational content is not intended for US- or UK-based
Innsbruck, Austria
physicians.
Copyright © 2010-2025, PeerVoice
Part 7 of 7: Uncovering Direct Approaches to Address Elevated Lp(a):
What We've Learned
Steven E. Nissen, MD, MACC
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University at Cleveland Clinic
Chief Academic Officer
Cleveland Clinic
Cleveland, Ohio, USA
Leslie Cho, MD
Professor of Medicine
Cleveland Clinic Lerner College of Medicine, Case Western Medical School
Vice Chair of the Heart Vascular Thoracic Institute and Section Head of Preventative Cardiology and Cardiac Rehabilitation
Cleveland Clinic
Cleveland, Ohio, USA
Florian Kronenberg, MD, MAE
Professor of Genetic Epidemiology
Medical University of Innsbruck
Head of institute
Institute of Genetic Epidemiology
a This educational content is not intended for US- or UK-based
Innsbruck, Austria
physicians.
Copyright © 2010-2025, PeerVoice
PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Steven E. Nissen, MD, MACC, has a financial interest/reiationship or affiliation in the form of:
Grant/Research Support from AbbVie Inc.; Amgen Inc.; Arrowhead Pharmaceuticals; AstraZeneca: Bristol Myers Squibb
Company; Eli Lilly and Company; Esperion Therapeutics, Inc; Medtronic, Inc; MyoKardia, Inc.; NewAmsterdam Pharma
BV: Novartis AG; Pfizer Inc. and Silence Therapeutics.
Leslie Cho, MD, has a financial interest/relationship or affiliation in the form of:
Grant/Research Support from Esperion Therapeutics, Inc. and Novartis AG.
‘Speaker or participant in accredited CME/CPD for Daiichi Sankyo Company, Limited.
7] Florian Kronenberg, MD, MAE, has a financial interest/relationship or affiliation in the form of:
Consultant for CRISPR Therapeutics; F. Hoffmann-La Roche Ltd; and Silence Therapeutics.
Advisory Board for Novartis AG.
Speaker or participant in accredited CME/CPD for Amgen Inc. and Novartis AG.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Development
* Injectables
— Pelacarsen - Phase 3
— Olpasiran - Phase 3
— Zerlasiran - Phase 2
— Lepodisiran - Phase 3
Oral
— Muvalaplin (oral) — Phase 2
CRSPR-based gene editing
This presentation is the property of Steven E. Nissen, MD, MACC.
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Development
* Injectables
— Pelacarsen - Phase 3
— Olpasiran - Phase 3
— Zerlasiran - Phase 2
— Lepodisiran - Phase 3
Oral
— Muvalaplin (oral) — Phase 2
CRSPR-based gene editing
This presentation is the property of Steven E. Nissen, MD, MACC.
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PeerVoice
Current Approaches Involve Gene Silencing
Antiser
Antisense DNA Strand
Single-Strand Phosphorothioate (PS) AP yA
Multiple Mechanisms — 2'-MOE, 2'-OMe, cEt, LNA
Antisense
siRNA RNA ae
Double-strand Phosphodiester {DD (IL
RISC Mechanism 2-OMe, 2-F
Aliphatic substituents ‘Strand
‘Sense
Target
Protein
Aptamer DNA or RNA
Structured Mixed modifications
Pegylation
(REG! anticoagulation system)
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
Copyright © 2010-2025, PeerVoice
Current Approaches Involve Gene Silencing
Antiser
Antisense DNA Strand
Single-Strand Phosphorothioate (PS) AP yA
Multiple Mechanisms — 2'-MOE, 2'-OMe, cEt, LNA
Antisense
siRNA RNA ae
Double-strand Phosphodiester {DD (IL
RISC Mechanism 2-OMe, 2-F
Aliphatic substituents ‘Strand
‘Sense
Target
Protein
Aptamer DNA or RNA
Structured Mixed modifications
Pegylation
(REG! anticoagulation system)
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
Copyright © 2010-2025, PeerVoice
PeerVoice
Structure of Lipoprotein(a)
Apolipoprotein(a) Apolipoprotein B
This presentation is the property of Steven E. Nissen, MD, MACC.
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Structure of Lipoprotein(a)
Apolipoprotein(a) Apolipoprotein B
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
PeerVoice
RNA Interference: Nucleic Acid-Based Therapies
Degrade mRNA
for
Apolipoprotein(a)
Anti-Sense
Oligonucleotide
or siRNA
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
No Lp(a) produced
2010-2025, PeerVoice
RNA Interference: Nucleic Acid-Based Therapies
Degrade mRNA
for
Apolipoprotein(a)
Anti-Sense
Oligonucleotide
or siRNA
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
No Lp(a) produced
2010-2025, PeerVoice
PeerVoice
GalNAc Conjugation Enhances Drug Delivery and Improves Both
Safety and Efficacy
N-Acetyl-galactosamine (GalNAc), a highly efficient
ligand for the hepatic asialoglycoprotein receptor
GalNAc, derived from galactose is cleaved and cleared
rapidly
GalNAc conjugation results in rapid uptake by
hepatocytes and rapid clearance from serum
This presentation is the property of Steven E. Nissen, MD, MACC.
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GalNAc Conjugation Enhances Drug Delivery and Improves Both
Safety and Efficacy
N-Acetyl-galactosamine (GalNAc), a highly efficient
ligand for the hepatic asialoglycoprotein receptor
GalNAc, derived from galactose is cleaved and cleared
rapidly
GalNAc conjugation results in rapid uptake by
hepatocytes and rapid clearance from serum
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Phase 2: Effect of Pelacarsen (ASO) on Lp(a) Levels
Placebo 20mg/Q4W 40mg/Q4W 20mg/Q2W 6OmgiQ4W 20mg/Qw
E
E
3
Es
E
E
[3]
€
8
2
=
5
3
=
E
a
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeorVoice
Phase 2: Effect of Pelacarsen (ASO) on Lp(a) Levels
Placebo 20mg/Q4W 40mg/Q4W 20mg/Q2W 6OmgiQ4W 20mg/Qw
E
E
3
Es
E
E
[3]
€
8
2
=
5
3
=
E
a
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeorVoice
PeerVoice
An Alternative to an ASO: Small-Interfering RNA
Sense strand GalNAc
-
Anti-sense strand
Anti-sense strand
Nucleotides chemically modified for resistance to degradation by ribonudeases
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
An Alternative to an ASO: Small-Interfering RNA
Sense strand GalNAc
-
Anti-sense strand
Anti-sense strand
Nucleotides chemically modified for resistance to degradation by ribonudeases
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
PeerVoice
Olpasiran siRNA: Phase 2 Dose-Finding Study
‘Mean Percent Change
Trial Week
This presentation is the property of Steven E. Nissen, MD, MACC.
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Olpasiran siRNA: Phase 2 Dose-Finding Study
‘Mean Percent Change
Trial Week
This presentation is the property of Steven E. Nissen, MD, MACC.
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PeerVoice
Zerlasiran Phase 1: Multiple Ascending Doses
Treatment Group 200 mg 300 mg m450mg Placebo
Second
300 and 450 mg
Dose
y
Percent Change in Lipoprotein (a) (%)
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
Copyright © 2010-2025, PeerVoice
Zerlasiran Phase 1: Multiple Ascending Doses
Treatment Group 200 mg 300 mg m450mg Placebo
Second
300 and 450 mg
Dose
y
Percent Change in Lipoprotein (a) (%)
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
Copyright © 2010-2025, PeerVoice
PeerVoice
GalNAc: Lepodisiran Plasma Levels Following Dosing
Lepodisiran Plasma Concent
Time Post Dose (h)
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
GalNAc: Lepodisiran Plasma Levels Following Dosing
Lepodisiran Plasma Concent
Time Post Dose (h)
This presentation is the property of Steven E. Nissen, MD, MACC.
Copyright © 2010-2025, PeerVoice
PeerVoice
Effect of Lepodisiran on Lp(a) Over Time
2
E
3
Fe
6.
$
E
2 15 29 43 57 71 85 113
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
Effect of Lepodisiran on Lp(a) Over Time
2
E
3
Fe
6.
$
E
2 15 29 43 57 71 85 113
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870
PeerVoice
Oral Muvalaplin Binds Apo(a) Preventing Interaction With Apo B
Lipoy otein (a)
This presentation is the property of Steven E. Nissen, MD, MACC.
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Oral Muvalaplin Binds Apo(a) Preventing Interaction With Apo B
Lipoy otein (a)
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 2010-2025, Peer Voice
PeerVoice
4
8
Lipoprotel
This presentation is the property of Steven E. MD, MACC.
Copyright © 2010-2025,
4
8
Lipoprotel
This presentation is the property of Steven E. MD, MACC.
Copyright © 2010-2025,
PeerVoice
Lp(a) Lowering Required for 22% Risk Reduction
Absolute lowering in Lp(a)
40 60 80 100 120 140
nn i
—— —
dL SN Burgess et al
reduction 2018
rg
=
2
&
=
=
©
©
=
3
©
e
Masden et al
2019
Masden et al
~ 2019
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Lp(a) Lowering Required for 22% Risk Reduction
Absolute lowering in Lp(a)
40 60 80 100 120 140
nn i
—— —
dL SN Burgess et al
reduction 2018
rg
=
2
&
=
=
©
©
=
3
©
e
Masden et al
2019
Masden et al
~ 2019
This presentation is the property of Steven E. Nissen, MD, MACC.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Abbreviations and References
Help Is on the Way: Lp(a) Drugs in Development
Abbreviation(s): CRSPR: clustered regularly interspaced short palindromic repeats; Lp(a): lipoprotein a.
Reference(s): Courtesy of Steven E. Nissen, MD, MACC; January 2025.
Current Approaches Involve Gene Silencing
Abbreviation(s): REGI: regnase-1; RISC: RNA-induced silencing complex; siRNA: small-interfering RNA.
Reference(s): Courtesy of Steven E. Nissen, MD, MACC; January 2025.
Structure of Lipoprotein(a)
Abbreviation(s): LDL: low-density lipoprotein.
Reference(s): Courtesy of Steven E. Nissen, MD, MACC; January 2025.
RNA Interference: Nucleic Acid-Based Therapies
Reference(s): Adapted from Tsimikas S. Lancet. 2015;386:1472-1483.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Abbreviations and References
Help Is on the Way: Lp(a) Drugs in Development
Abbreviation(s): CRSPR: clustered regularly interspaced short palindromic repeats; Lp(a): lipoprotein a.
Reference(s): Courtesy of Steven E. Nissen, MD, MACC; January 2025.
Current Approaches Involve Gene Silencing
Abbreviation(s): REGI: regnase-1; RISC: RNA-induced silencing complex; siRNA: small-interfering RNA.
Reference(s): Courtesy of Steven E. Nissen, MD, MACC; January 2025.
Structure of Lipoprotein(a)
Abbreviation(s): LDL: low-density lipoprotein.
Reference(s): Courtesy of Steven E. Nissen, MD, MACC; January 2025.
RNA Interference: Nucleic Acid-Based Therapies
Reference(s): Adapted from Tsimikas S. Lancet. 2015;386:1472-1483.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Abbreviations and References (Cont'd)
GalNAc Conjugation Enhances Drug Delivery and Improves Both Safety and Efficacy
Reference(s): Prakash TP et al. Nucleic Acids Res. 2014;42:8796-8807.
Phase 2: Effect of Pelacarsen (ASO) on Lp(a) Levels
Abbreviation(s): ASO: antisense oligonucleotide; LS: least-squares.
Reference(s): Tsimikas S et al. N Engl J Med. 2020;382:244-255.
An Alternative to an ASO: Small-Interfering RNA
Reference(s): Courtesy of Steven E. Nissen, MD, MACC; January 2025.
Olpasiran siRNA: Phase 2 Dose-Finding Study
Reference(s): O'Donoghue ML et al. N Engl J Med. 2022;387:1855-1864.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Abbreviations and References (Cont'd)
GalNAc Conjugation Enhances Drug Delivery and Improves Both Safety and Efficacy
Reference(s): Prakash TP et al. Nucleic Acids Res. 2014;42:8796-8807.
Phase 2: Effect of Pelacarsen (ASO) on Lp(a) Levels
Abbreviation(s): ASO: antisense oligonucleotide; LS: least-squares.
Reference(s): Tsimikas S et al. N Engl J Med. 2020;382:244-255.
An Alternative to an ASO: Small-Interfering RNA
Reference(s): Courtesy of Steven E. Nissen, MD, MACC; January 2025.
Olpasiran siRNA: Phase 2 Dose-Finding Study
Reference(s): O'Donoghue ML et al. N Engl J Med. 2022;387:1855-1864.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Abbreviations and References (Cont'd)
Zerlasiran Phase 1: Multiple Ascending Doses
Reference(s): Nissen SE et al. JAMA. 2024;331:1534-1543.
GalNAc: Lepodisiran Plasma Levels Following Dosing
Reference(s): Nissen SE et al. JAMA. 2023;330:2075-2083.
Effect of Lepodisiran on Lp(a) Over Time
Reference(s): Nissen SE et al. JAMA. 2023;330:2075-2083.
Oral Muvalaplin Binds Apo(a) Preventing Interaction With Apo B
Abbreviation(s): Apo: apolipoprotein
Reference(s): Nicholls SJ et al. JAMA, 2023:330:1042-1053.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
Abbreviations and References (Cont'd)
Zerlasiran Phase 1: Multiple Ascending Doses
Reference(s): Nissen SE et al. JAMA. 2024;331:1534-1543.
GalNAc: Lepodisiran Plasma Levels Following Dosing
Reference(s): Nissen SE et al. JAMA. 2023;330:2075-2083.
Effect of Lepodisiran on Lp(a) Over Time
Reference(s): Nissen SE et al. JAMA. 2023;330:2075-2083.
Oral Muvalaplin Binds Apo(a) Preventing Interaction With Apo B
Abbreviation(s): Apo: apolipoprotein
Reference(s): Nicholls SJ et al. JAMA, 2023:330:1042-1053.
www.peervoice.com/UTX870 Copyright © 2010-2025, PeerVoice
PeerVoice
Abbreviations and References (Cont'd)
Effect of Muvalaplin on Lp(a) Over Time
Reference(s): Nicholls SJ et al. JAMA. 2024;332:367-368.
Lp(a) Lowering Required for 22% Risk Reduction
Reference(s): Adapted from Masden CM et al. Arterioscler Thromb Vase Biol. 2020;40:255-266.
Copyright © 2010-2025, PeerVoice
www.peervoice.com/UTX870
Abbreviations and References (Cont'd)
Effect of Muvalaplin on Lp(a) Over Time
Reference(s): Nicholls SJ et al. JAMA. 2024;332:367-368.
Lp(a) Lowering Required for 22% Risk Reduction
Reference(s): Adapted from Masden CM et al. Arterioscler Thromb Vase Biol. 2020;40:255-266.
Copyright © 2010-2025, PeerVoice
www.peervoice.com/UTX870
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