Lefflux de cholestrol Pr Johanne SILVAIN johanne.silvain@aphp.fr 1 - - PowerPoint PPT Presentation

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Lefflux de cholestrol Pr Johanne SILVAIN johanne.silvain@aphp.fr 1 - - PowerPoint PPT Presentation

Jul 13, 2023 208 likes •500 views

Lefflux de cholestrol Pr Johanne SILVAIN johanne.silvain@aphp.fr 1 Sorbonne Universit 2 ACTION Study Group 3 INSERM UMRS 1166 ICAN 4 Institut de Cardiologie (APHP) www.action- cur.org PITIE-SALPETRIERE UNIVERSITY HOSPITAL Disclosures

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L’efflux de cholestérol

Pr Johanne SILVAIN johanne.silvain@aphp.fr

1 Sorbonne Université 2 ACTION Study Group 3 INSERM UMRS 1166 ICAN 4 Institut de Cardiologie (APHP)

www.action-cœur.org

PITIE-SALPETRIERE UNIVERSITY HOSPITAL

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DISCLOSURE STATEMENT OF FINANCIAL INTEREST Johanne SILVAIN MD, PhD Consulting fees, Speaker honorariums or Travel support from from Algorythm, Amed, Astra-Zeneca , Bayer, Boeringher Ingelheim, CLS Bering, Gilead Science, Sanofi-Aventis, Web MD Amgen, Astra-Zeneca and Saint-Jude Medical

Disclosures

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Quel est l’impact du Choléstérol sur le risque de 1er Evenement Cardiovasculaire ?

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Combinaison polygénique

500 000 Anglais bien portants

Score Génétique composé de 1.7 millions de variants

Inouye M. J Am Coll Cardiol. 2018

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Prédiction de 75% du risque

Inouye M. J Am Coll Cardiol. 2018 Khera AV et al. N Engl J Med 2016 Pas de Tabac Pas de surpoids (IMC <30) Activité Physique une fois / semaine Alimentation équilibrée

4 FACTEURS

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Et le choléstérol alors ?

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« Le bon » HDL « La brute » LDL « Le truand » Triglycérides « Les oubliés »

Lp(a) Inflammation

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Sachdeva et al, Am Heart J 2009

LDL Levels in 136,905 Patients Hospitalized With CAD LDLC (mg/dL)

Taux de LDL choléstérol et Coronaires

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Non-HDL Choléstérol

Brunner F et al, Lancet 2019

LDL, TG , Lp(a)

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Brunner F et al, Lancet 2019

LDL, TG , Lp(a)

Non-HDL Choléstérol

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Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and Atherosclerosis

Khera AV et al. N Engl J Med 2011;364:127-35. n= 996 patients (case control study) OR for Coronary Artery Disease According to Efflux Capacity and Selected Risk Factors.

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What is Efflux Capacity ?

1) Global cholesterol efflux capacity, a biomarker that integrates contributors and modulators of the initial step of the reverse cholesterol transport, has been associated with atherosclerosis independently of HDL-Cholesterol level.

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Silvain J et al. JACC 218

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L’Efflux de choléstérol

A- Serum Cholesterol Efflux Capacity

= Nettoyage de nos vaisseaux

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HDL Cholesterol Efflux Capacity and Incident Cardiovascular Events

Rohatgi A et al. N Engl J Med 2014;371:2383-93. n= 2924 adults free from cardiovascular disease Dallas Heart Study,

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The failure of HDL

2) HDL raising drugs (niacin but mostly CETP inhibitors) failed to prevent cardiovascular events and decreased mortality despite an increase in HDL levels, demonstrating that steady state HDL-Cholesterol levels do not represent the most appropriate risk factor index

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HDL therapies

Rader DJ et al. Lancet 2014.

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Lincoff MA et al. ACCELERATE. N Engl J Med. 2017 NIACIN => Landray MJ et al. N Engl J Med. 2014 => Boden WE et al. N Engl J Med. 2011 TORCETRAPID => Barter PJ et al. ILLUMINATE Trial. N Engl J Med. 2007 DALCETRAPID => Schwartz GG et al. dal-OUTCOMES. N Engl J Med. 2012 HDL INFUSIONS => Tardif JC et al. Eur Heart J. 2014

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Limitations

1/ Failure to raise functional HDL => Cholesterol Efflux +++ 2/ Bad Timing ? = long-term pharmacotherapy was intitiated in the chronic phase and not in the post MI period. = target in primary prevention ? 3/ Patients with high modifiable risk 4/ Off-target toxicity ?

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Un bon efflux de cholestérol = 56% de moins de 1er Evènement Cardiovasculaire

Rohatgi A et al. N Engl J Med 2014

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Silvain J et al. JACC 218 *Drs. Guerin and Silvain are first authors

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n= 1609 STEMI patients Silvain J et al. JACC 218

Un bon efflux de cholestérol = 46% de mortalité en moins après un infarctus

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Serum cholesterol efflux capacity and mortality in STEMI patients

Silvain J et al. JACC 218

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Silvain J et al. JACC 218

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Nambi V et al. JACC 2018

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Essai Clinique AEGIS-2

= Infusion de HDL recombinant (CSL-112) ou “Bon Choléstérol“ chez des patients souffrants d’un infarctus et à risque de récidive pour booster leur Efflux de Cholestérol

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Conclusion

  • Non-HDL cholesterol and inflammation are probably

more important than LDL alone as risk factor for 1st CV events.

  • CETP activity and HDL cholesterol do not reflect the

cardiovascular risk of patients

  • “Reverse cholesterol transport” measured by global

cholesterol efflux capacity, is independently associated with atherosclerosis, 1st CV events and long term survival in post MI patients.

  • HDL function is a new biomarker to identify patients

at higher risk of CV events and mortality and should be a target for atheroprotection

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Merci

Pr Johanne SILVAIN johanne.silvain@aphp.fr

1 Sorbonne Université 2 ACTION Study Group 3 INSERM UMRS 1166 ICAN 4 Institut de Cardiologie (APHP)

www.action-cœur.org

PITIE-SALPETRIERE UNIVERSITY HOSPITAL