Cas de Liaison Athérosclérose - 1ère Année de Médecine - PDF

1ère Année de Médecine Cas de liaison Athérosclérose #4 Prof. François Mach, MD, Service de Cardiologie Département de Médecine Hôpital Universitaire de Genève [email protected] www.cardiology-geneva.ch...

1ère Année de Médecine Cas de liaison Athérosclérose #4 Prof. François Mach, MD, Service de Cardiologie Département de Médecine Hôpital Universitaire de Genève [email protected] www.cardiology-geneva.ch Genève, le 4 décembre 2024  Conclusions/Messages Athérosclérose 11-11-2024 La prévention joue un rôle fondamentale, pas assez utilisée, dans la diminution des maladies CV. Les scores de risque permettent de mieux définir les individus et patients qui doivent être traités le plus agressivement. Les interventions médicamenteuses se basent sur l’estimation du risque cardiovasculaire. Conclusions/Messages Athérosclérose 11-11-2024 Le cholestérol n’est pas un poison, mais une substance vitale pour toutes les cellules de l’organisme. Conclusions/Messages Athérosclérose 11-11-2024 Plusieurs voies métabliques du cholestérol: - Exogène - Endogène - Reverse transport Conclusions/Messages Athérosclérose 11-11-2024 Le cholestérol est transporté dans la sang sous forme de lipoprotéines Conclusions/Messages Athérosclérose 11-11-2024 HDL cholestérol = le bon LDL cholestérol = le mauvais Circulation des lipoprotéines Structure des lipoprotéines Structure des lipoprotéines 2 patients à risque modéré en prévention primaire Même taux de LDL-C calculé (=2.6 mmol/L) Good Bad Cholesterol levels: Us versus them… JACC 2004;43:2142 Cholestérol et risque CV Mortality (Framingham) 100 95 90 Survival (%) 85 80 Cholesterol (mmol/L) ≤4.7 75 4.7 - 5.7 70 5.7 - 6.7 >6.7 65 0 5 10 15 20 25 30 Years What is a “normal” LDL-cholesterol ? We were all born with a LDL-c value around 1.2 mmol/l  Clear relationship between LDL-C and risk of CV events LDL-C is the main driver for atherosclerosis: 4 compelling lines of evidence Eur Heart J 2022;43:3198 Time-exposure to LDL-c JACC 2018;72:2890  Cholestérol & Athérosclérose Dyslipidémies Ø Disorder of lipid & lipoprotein metabolism Ø A common form of dyslipidemia is characterized by three lipid abnormalities: § Elevated triglycerides, § Elevated LDL and § Reduced HDL cholesterol Ø Important modifiable risk factor for CAD  Cholestérol & Athérosclérose Dyslipidémies Causes Primary Secondary Genetic Disorders Diabetes Nephrotic Syndrome Hypothyroidism Drug – Induced Hypertension Western “attitude”  Hypercholestérolémie Familiale Familial hypercholesterolemia (FH) is a genetically modulated clinical syndrome in which the phenotype is characterized by a high LDL-c level from birth, a propensity to tendon xanthomata, and early onset CHD. Its established causes are LDLR mutations (most common), gain-of-function PCSK9 mutations, familial defective apoB, and Lp(a) mutations. Eur Heart J 2013;34:3478 HoFH have normal organ development and behavior Hypercholestérolémie Familiale The most frequent of rare diseases… Eur Heart J 2013;34:3478 Hypercholestérolémie Familiale Clear relationship between LDL-C and risk of CV events Eur Heart J Case Rep 2020;4:1 Clear relationship between LDL-C and risk of CV events Cardiac CT-Scan Coronary angiography Eur Heart J Case Rep 2020;4:1  Estimated millions of individuals worldwide with familial hypercholesterolaemia by WHO regions and by income groups Eur Heart J 2013;34:3478 Frequency of Familial Hypercholesterolemia Clin Cardiol 2014;37:119  Diagnosis of Familial Hypercholesterolemia Dutch FH criterias Familial Hypercholesterolemia – cascade screening Eur Heart J 2013;34:3478 Familial Hypercholesterolemia – cascade screening Eur Heart J 2013;34:3478 Familial Hypercholesterolemia in Switzerland What is the prevalence of FH in ACS patients ? Eur Heart J 2015;36:2438  Familial Hypercholesterolemia in Switzerland Prognosis of Familial Hypercholesterolemia in Switzerland Incidence of recurrent coronary events after ACS, Incidence of recurrent coronary events in young patients by presence of FH (n=4’534) with premature ACS, by presence of FH (n=1’369) HR 3.71 (1.16 - 11.81) Circulation 2016;134:698  Treatment of Familial Hypercholesterolemia Kaplan–Meier curve estimates of cumulative CHD-free survival among individuals with familial hypercholesterolemia according to statin treatment Eur Heart J 2013;34:3478 Treatment of Familial Hypercholesterolemia Eur Heart J 2015;36:2425  The lower the better, but also the sooner the better LDL cholesterol burden in individuals with or without familial hypercholesterolemia as a function of the age of initiation of statin therapy Eur Heart J 2013;34:3478  The lower the better, but also the sooner the better Cummulative LDL-C and risk of heart attacks 12 - Cummulative LDL-c (gram/year) 9- MI threshold 9 gram-year of LDL-c 6- 0- - - - - - 20 40 60 80 100 Age (years) Typical MI in a 60 y.o. men with 150mg/dl = 9 gram-year of LDL-C A 30 y.o. FH men with 300mg/dl (9 gram-year of LDL-C at the age of 30 !!!) A 50 y.o. women with PCSK9-/+ and 70mg/dl (9 gram-year of LDL-C at the age of 100 !!!)  Treatment of Familial Hypercholesterolemia We recommend: children, adults, and families should be screened for FH if: Family member presents with FH Total cholesterol in adult ≥ juste 8mmol/L LDL plus grand que 5 Total cholesterol in child ≥ 6mmol/L Premature CHD Tendon xanthomas Sudden premature cardiac death Eur Heart J 2013;34:3478 Caractéristiques des lipoprotéines Characteristics of lipoproteins Lipoprotein(a)  Lp(a) - the next target to fight cardiovascular disease LDL-like Described by K. Berg in 1963 particle An independent risk factor for cardiovascular disease Shows only minor correlations with other lipoproteins (if any) Concentrations are mainly genetically determined One of the most important genetic risk factors for CVD Oxidized Apolipoprotein(a) Phospholipids Lipoprotein(a) and CV risk NEJM 2009;361:2518-28 Lp(a) and CV risk Eur Heart J 2010;31:2844  The association between Lp(a) and major CVD* outcomes is continuous independent of ethnicity → Lp(a) measurement is relevant globally White individuals (n=415,274) Black individuals (n=7,135) * defined as the composite of the first occurrence of fatal or non-fatal myocardial infarction, fatal or non-fatal ischemic stroke, or coronary revascularization [percutaneous coronary intervention or coronary artery bypass graft surgery] Eur Heart J 2022;43:3925 Lp(a) and arterial wall inflammation Eur Heart J 2020;41:2272 Eur Heart J 2020;41:2262 Pathophysiology of Lp(a) Suggested role of high plasma lipoprotein(a) concentrations in thrombus growth at sites of atherosclerotic plaque rupture Lancet September 12, 2024  Presented by Brian Ference http://www.lpaclinicalguidance.com/ Therosclerosis 2023: https://doi.org/10.1016/j.atherosclerosis.2023.04.012 http://www.lpaclinicalguidance.com/ Therosclerosis 2023: https://doi.org/10.1016/j.atherosclerosis.2023.04.012  Remember patient has: LDL-C 135 mg/dL Syst. BP 135 mmHG Often raised argument: "Why should I measure Lp(a) when I can't lower it?" 52.1%, http://www.lpaclinicalguidance.com/ Lipoprotein(a) – The perfect killer Lipoprotein(a) Lipoprotein(a) is a CV risk factor Eur Heart J 2022;43:3925 Alimentation & Cholestérol Alimentation & Cholestérol Alimentation & Cholestérol  Alimentation & Cholestérol Le métabolisme du cholestérol sera nettement amélioré si le niveau énergétique est augmenté d’au moins 1000 kcal, optimalement 2000 kcal/semaine, par l’activité physique régulière Quels sports, combien de calories brulées ? ► Nage (brasse): 458 kcal/ 30‘ ► High Intensity Interval Training: 444 kcal/ 30‘ ► Jogging: 394 kcal/ 30‘ ► Zumba: 271 kcal/ 30‘ ► Vélo de course: 300 kcal/ 30’ 458 kcal 244 kcal 52 kcal  Stratégie optimale pour perdre du poids: Combinaison de moins de calories et plus bouger Obesity 2012;20:1628 Bénéfices cardiovasculaires grace à l’activité physique (2020 WHO guidelines) Sédentarité - Intervention Conclusions/Messages Athérosclérose 4-12-2024 L’hypercholestérolémie Familiale (HF) est la plus fréquente des maladies rares, environ 1/250-300 habitants en Suisse. L’HF est très largement sous-diagnostiquée en prévention primaire, et en prévention secondaire. Conclusions/Messages Athérosclérose 4-12-2024 Le score Dutch lipid network permet de très bien documenter la présence d’une HF. Conclusions/Messages Athérosclérose 4-12-2024 Le diagnostique d’HF est un facteur de mauvais pronostique après une syndrome coronarien aigu (infarctus du myocarde). HR 3.71 (1.16 - 11.81) Conclusions/Messages Athérosclérose 4-12-2024 En présence d’une HF, un traitement hypolipémiant efficace permet de diminuer significativement la survenue de futurs événements CV. Conclusions/Messages Athérosclérose 4-12-2024 La Lipoprotéine(a) Lp(a) est une LDL-like lipoprotéine avec une addition de apo(a), ce qui lui confer un défaut de reconnaissance par le LDLR. La Lp(a) a de nombreuses propriétés augmentant l’athérogénèse et la thrombogénèse. Son augmentation dans le sang est principalement liée à des mutations génétiques.