Medicine Lecture Note: Atherosclerosis

‭ATHEROSCLEROSIS‬ ‭INTRODUCTION‬ ‭ o fully understand how atherosclerosis works and what is at stake, you must first‬ T ‭understand how the system works and that atherosclerosis is a complex and‬ ‭partially known mechanism.‬ ‭Many gray areas still persist to this day.‬ ‭ ‬ ‭Atheroma: main etiology of cardiovascular conditions.‬ ■ ‭■‬ ‭Begins in childhood.‬ ‭■‬ ‭Evolution accelerated by CVX risk factors‬ ‭■‬ ‭Significant morbidity and mortality +++‬ ‭ ‬ ‭Major public health problem.‬ ■ ‭■‬ ‭Clinical polymorphism of atherosclerotic disease:‬ -‭ ‬ I‭schemic heart disease‬ ‭-‬ ‭Stroke – Arteriopathy obliterans – pathology of the Aorta‬ ‭GOALS‬‭:‬ ‭■‬ ‭Define atherosclerosis‬ ‭■‬ ‭Know the mechanisms of atherogenesis‬ ‭■‬ ‭Know the Cardiovascular risk factors‬ ‭‬ ■ ‭Know the evolving aspects and complications‬ ‭of atheromatous plaque‬ ‭■‬ ‭Know the Polyarterial‬ ‭■‬ ‭Describe the Principles of Management of FDCV and Polyarterial‬ ‭ATHEROSCLEROSIS‬ i‭s an association of various changes in the intermediate layer of large and‬ ‭medium-sized arteries.‬ i‭s a localized accumulation in the intima of lipids, inflammatory cells, extracellular‬ ‭matrix and possibly thrombosis, which will be accompanied by a qualitative‬ ‭modification of the arterial media.‬ ‭Cholesterol is the lipid involved in this pathology‬ -‭ ‬ a ‭ therosclerosis =lipid accumulation‬ ‭-‬ ‭arteriosclerosis: arterial sclerosis = cellular aging.‬ ‭DEFINITION‬ ‭According to the WHO, atheroma is:‬ ‭ earrangement of the Intima of large and medium caliber arteries consisting of a focal‬ R ‭accumulation of‬ ‭-‬‭Lipids‬ ‭-‬‭Complex carbohydrates‬ ‭-‬‭Blood‬ ‭-‬‭- Limestone deposits‬ ‭+‬ ‭Media shakeup‬ ‭Atherosclerosis = ATheroma + Sclerosis‬ ‭EPIDEMIOLOGICAL DATA‬ ‭■‬ ‭Geographic Variation: Northern and Eastern Europe/Southern Europe – Asia‬ ‭■‬ ‭Sex: 5 times more common in men than in women.‬ ‭■‬ ‭AGE: Prevalence increases with the age of the population - Aging ++‬ ‭■‬ ‭HYGIENE OF LIFESTYLE: Food Habits - Lifestyle‬ ‭ANATOMIC REVIEW OF THE VASCULAR WALL‬ ‭Histological reminder‬ ‭ he wall of a normal artery is made up of 3 coats: the intima, the media and the‬ T ‭adventitia.‬ ‭-‬‭The intima brings together the endothelium and the subendothelial space‬ ‭-‬‭the internal elastic L. separates the intima / media‬ ‭-‬‭The media is the thickest layer, it mainly includes Smooth Muscle Cells.‬ ‭General description‬ ‭■‬ ‭Atherosclerosis is a Chronic Inflammatory Arterial Pathology‬ ‭■‬ ‭linked to the interaction between modified Lipo-proteins‬ -‭ ‬‭inflammatory cells‬ ‭-‬‭the cellular elements of the arterial wall.‬ ‭-‬ ‭This chronic inflammation leads to a scarring reaction process of the wall art‬ ‭■‬ ‭Inflammatory “Plaque” Phenomena are stable becoming unstable lesions‬ ‭■‬ ‭Plaque complicated by plaque rupture or erosion and arterial thrombosis.‬ ‭Locations of atherosclerosis:‬ ‭Mechanical Stress Zones and Bifurcation Zones are the Preferred Zs‬ ‭Atherosclerosis affects the intima of large and medium-sized arteries‬ -‭ ‬ ‭-‬ ‭-‬ ‭-‬ ‭ orta, TABC, primary carotids,‬ A ‭Arteries of the (lower) limbs, primitive iliac Arteries‬ ‭of the viscera‬ ‭Cerebral and Coronary Arteries,‬ ‭PHYSIOPATHOLOGY‬ ‭Physiological Role of the Vascular Endothelium‬ ‭Vascular Endothelium‬ -‭ ‬ ‭-‬ ‭-‬ ‭-‬ ‭-‬ ‭Monocellular layer‬ I‭nternal surface of vessels‬ ‭Interface between blood and‬ ‭tissues. Thin = 10 u thick‬ ‭Considerable surface area = 280 and 350 m2‬ ‭Physiological function‬ ‭■‬ ‭Endothelium = Transducer‬ ‭■‬ ‭Captures information from the blood and translates it into a physiological response.‬ ‭‬ ■ ‭It is considered to be the largest endocrine organ, with endocrine, paracrine‬ ‭and autocrine functions‬ ‭■‬ ‭Very active exchange area allowing:‬ ‭-‬ R ‭ egulate hemodynamic functions by secretion of vasorelaxing and‬ ‭vasoconstrictor substances.‬ ‭ nder physiological conditions, the release of relaxation factors predominates‬ U ‭over that of contraction factors.‬ ‭Mechanisms of atheromatous disease‬ ‭Endothelial Dysfunction‬ ‭Effect of aging / FDRCVx‬ ‭Impaired endothelial function‬ -‭ Vascular homeostasis imbalance‬ ‭-Chronic inflammation‬ ‭-vasomotor disorder‬ ‭-Weakening of the arterial wall Acceleration‬ ‭of atherosclerosis,‬ -‭ ‬‭Meta-analysis (2411)‬ ‭-‬‭Link between endothelial dysfunction and the occurrence of CVX events.‬ -‭ ‬ ‭Patients with dysfunction: x2 to 3 risk of developing CVX disease‬ ‭within 5 to 10 years.‬ ‭-In other words Endothelial Dysfunction = Pathophysiology CVx Diseases‬ ‭ATHEROGENESIS‬ ‭1.‬‭Endothelial dysfunction and accumulation of LDLc in the intima:‬ ‭-‬‭Alteration of endothelial homeostasis‬‭by constraints‬ -‭ ‬ M ‭ echanical (HTA)‬ ‭-‬ ‭Biochemicals: Hypoxia, Free Radicals/Tobacco, vasoactive substances,‬ ‭ iabetes,.‬ d ‭-‬ ‭Infectious (CMV, Chlamydia pneumoniae)‬ ‭-‬‭Accumulation of low density lipoproteins‬ -‭ ‬ L ‭ DL; LDL-cholesterol) in the intima‬ ‭-‬ ‭Entry + more++ that the blood LDLc level is high)‬ ‭- Oxidation of LDLc becoming cytotoxic for the endothelium‬ ‭2.‬ ‭The injured endothelium promotes the recruitment of monocytes‬‭, which penetrate into the‬ ‭intima,‬ ‭-Monocytes capture oxidized LDLc and transform‬ ‭=>Macrophages then => Foam Cells.‬ -‭ The accumulation of foam cells (cells with lipid vacuoles) forms lipid streaks, the first‬ ‭visible sign of the formation of an atheroma.‬ -‭ Lipids, initially intracellular, will also accumulate in the extracellular environment‬ ‭and then group together within a lipid core.‬ ‭ .‬ 3 ‭Proliferation of the C. Smooth Muscles (SMC) and formation of a‬ ‭“Fibrous‬‭Cap”:‬ ‭ he SMCs: migrate from the media towards the intima, secrete collagen: formation of the fibrous‬ T ‭cap of the plaque.‬ ‭4.‬‭The Atheroma Plaque = the lesion constituted = Fibrino-Cruoric Nodule located in‬ ‭intimated him‬‭.‬ ‭It is made up of 2 parts:‬ -‭ ‬‭Lipid core: Lipid core‬ ‭-‬‭The Fibrous cap: Fibrous cap‬ ‭separates the lipid core from the rest of the intima.‬ ‭The plaque can become complicated‬ -‭ ‬‭calcifications,‬ ‭-‬‭ulcerations,‬ ‭-‬‭intra-plaque hemorrhage‬ ‭-‬‭intra-plaque thrombosis‬ ‭-‬‭rupture causing arterial thrombosis‬ ‭PROGRESS OF ATHEROSCLEROSIS‬ ‭The evolution of the lesions occurs in several stages‬ ‭-Early lesions (I, II, III) = Clinically Silent‬ ‭-Advanced lesions (IV, V, VI) = Reduction in arterial caliber‬ -‭ ‬‭Major disorganization of the intima‬ ‭-‬‭predisposition to complications‬ ‭The Natural Evolution of Atheroma Plaque‬ ‭1.‬ ‭Slow evolution:‬ ‭-‬‭Slow progression starting from early childhood‬ -‭ ‬ ‭Atherosclerotic plaque gradually reduces the arterial lumen despite the‬ ‭phenomenon of arterial remodeling.‬ -‭ ‬ ‭The lesions become symptomatic when 70% stenosis of the lumen‬ ‭(exertional angina, intermittent claudication, etc.)‬ -‭ ‬ ‭Atheroma can also destroy the extracellular matrix: This‬ ‭causes Aneurysmal dilations.‬ ‭2.‬ ‭Acute course‬‭: The Unstable Plate:‬ ‭The low stenosing plaque is considered at high risk of rupture‬ ‭Histologically‬ ‭This Plate is formed‬ -‭ ‬‭large lipid core‬ ‭-‬‭the fibrous layer is fine‬ ‭-‬‭significant macrophage infiltrate‬ ‭This plaque is complicated by a thrombus and obstructs the artery the phenomenon of‬ ‭ATHEROTHROMBOSIS‬ ‭ > an acute ischemic attack.‬ = ‭ THEROTHROMBOSIS‬ A ‭ he transformation of a Simple Plaque => Complicated Plaque is linked to local‬ T ‭inflammatory phenomena which will lead to Acute Thrombosis:‬ ‭-‬ ‭Plaque ulceration‬ ‭ ‬‭platelet adhesion‬‭→‬‭White Thrombus‬‭→‬‭Activation‬‭of Coagulation‬‭→‬‭Fibrinous‬ → ‭Bridges‬‭→‬‭Red Thrombus‬ ‭-‬ ‭Breakage or cracking of the plate‬ ‭-‬‭- > Main cause of acute thrombosis (ACS)‬ ‭-‬ ‭Intraplaque hemorrhage‬ ‭Factors favoring plaque rupture:‬ ‭•‬‭Extrinsic:‬ -‭ ‬ H ‭ igh blood pressure surge‬ ‭-‬ ‭Stress‬ ‭-‬ ‭Arterial spasm‬ ‭•‬‭Intrinsic: (vulnerability of the plaque)‬ -‭ ‬ I‭mportance of the lipid core in relation to the level of LDLcholesterol‬ ‭-‬ ‭Fragility of the fibrous shell by local inflammation‬ ‭The different stages of the evolution of atherosclerotic plaque:‬ ‭Risk Factors: FDR‬ ‭Non-Modifiable‬ ‭ DR:‬ F ‭■‬ ‭Age: the incidence of the disease increases with age, it mainly occurs as the‬ ‭duration of exposure to other risk factors.‬ ‭ ‬ ‭Sex: incidence is higher in men and postmenopausal women‬ ■ ‭■‬ ‭Genetics: some families have high risk regardless of other risk factors‬ ‭ his concerns the occurrence of cardiovascular accidents before the age of 50 in men and 60‬ T ‭years in women in the patient's family.‬ ‭FDR Editable:‬ ‭Major risk:‬ ‭-‬‭Dyslipidemia:‬‭↑LDLc‬‭,‬‭↓HDLc‬‭,‬‭↑TG‬ ‭-‬‭HTA: increases the shear force applied to the endothelium‬ ‭-‬ S ‭ moking (evaluated by number of packs/year): change in plasma‬ ‭viscosity,‬‭↓‬‭vasodilation‬ ‭-‬‭Diabetic: HyperTG,‬‭↓HDLc‬‭,‬‭↑‬‭fibrinogen and plasminogen‬‭activator inhibitor,‬‭↑‬ ‭Systolic blood pressure Minor‬ ‭Risk:‬ ‭-‬‭Sedentary lifestyle‬ -‭ ‬‭Obesity: especially android obesity‬ ‭-‬‭Stressful lifestyle‬ ‭-‬‭Chronic inflammation: CMV, Chlamydia Pneumoniae‬ ‭Clinical consequences depend on the stage of the atherosclerotic plaque‬ ‭■‬ ‭Stable plaque: arterial stenosis and ischemia‬ ‭ ‬‭Coronary: Angina pectoris‬ – ‭–‬‭Carotids: Lipothymia, dizziness‬ ‭–‬‭Lower limbs: Intermittent claudication‬ ‭–‬‭Mesenteric: intestinal angina‬ ‭■‬ ‭Ruptured plaque with arterial thrombosis: acute ischemic attacks‬ ‭ ‬‭Acute coronary syndromes‬ – ‭–‬‭Ischemic stroke‬ ‭–‬‭Critical limb ischemia‬ ‭–‬‭Mesenteric infarction‬ ‭EXPLORATION OF ATHEROSCLEROSIS‬ ‭1-‬ ‭GLOBAL CVX Risk Assessment‬ ‭Statistical evaluation of the probability of having atherosclerosis‬ ‭Taking into account the statistical association between atherosclerosis and age, sex, FDR‬ ‭2-‬ ‭Clinical evaluation‬ ‭-‬ ‭Functional symptoms of exercise,‬‭an advanced stage‬‭with arterial stenoses = Angina‬ ‭TIA, intermittent claudication‬ ‭-‬ ‭Physical Signs: pulse palpations, arterial murmurs, etc.‬ ‭ oncept of polyatheromatous patient = atheromatous disease must lead to the search‬ C ‭for other affected areas: Extension assessment‬ ‭Paraclinical Functional/Anatomical/Qualitative Explorations‬ ‭-‬ ‭Visualization of atheroma plaques and assessment of the stability/instability of the‬ ‭plaques‬ ‭-‬ ‭ isualization of atherosclerotic plaques and quantification of arterial stenoses and‬ V ‭the extent of lesions‬ ‭■‬ ‭Arterial opacification‬ ‭■‬ ‭Visualization of arterial light‬ ‭■‬ ‭Assessment of the impact and consequences of injuries‬ ‭INVASIVE EXPLORATIONS‬ ‭-‬ ‭Arteriography--coronrography‬ ‭-‬ ‭Luminographies‬ ‭Endocoronary ultrasound (IVUS)‬ ‭-‬ ‭Optical coherence tomography (OCT) (best resolution)‬ ‭NON-INVASIVE EXPLORATIONS‬ ‭-‬ ‭ECG – Simple Echocardiogram – Stress or Stress Echocardiogram‬ ‭-‬ ‭Myocardial Scintigraphy – Cardiac MRI‬ ‭-‬ ‭Arterial Doppler Ultrasound‬ ‭-‬ ‭AngioCT, arterial angio-MRI‬ ‭-‬ ‭BRAIN IMAGING‬ ‭Supported‬ ‭■‬ ‭Extensive support for all EDITABLE FDRs:‬ ‭–‬‭Tobacco +++, HTA, Diabetes, Dyslipidemia‬ ‭–‬‭Dietetics and therapeutic education‬ ‭–‬‭Regular and frequent physical activity, avoid being overweight.‬ ‭■‬ ‭Medicines to reduce morbidity and mortality‬ ‭–‬‭Aspirin (between 75 and 325 mg/day)‬ ‭ ‬‭Clopidogrel if intolerance to aspirin / Complicated Vx disorders.‬ – ‭–‬‭Systematic statins for secondary prevention.‬ ‭–‬ ‭To be discussed, according to the overall cardiovascular risk in primary‬ ‭prevention (asymptomatic polyvascular patients).‬ ‭–‬‭IEC (or ARA II)‬ ‭■‬ ‭Specific support for certain‬ ‭locations: coronary intervention, carotid artery, aneurysm, etc.‬ ‭CONCLUSION‬ ‭Atherosclerosis: the metaphor of the Brick Wall‬ ‭1-‬‭LDL cholesterol = BRICK‬ ‭2-‬ ‭Oxidation factors: Diabetes; HTA; Tobacco; Genetics‬ ‭-…. Ox LDL = Freshly cemented brick‬ ‭3-‬‭CEMENT = it is the Oxidation of LDLc‬ ‭4-‬‭Macon = INFLAMMATION‬ ‭LDL c alone is not enough to generate atherosclerotic plaque‬ ‭ he assistance of Oxidizing Factors is required: FDR CVX, Chronic‬ T ‭INFLAMMATORY Factors‬ ‭It should be understood that if we treat LDL c with Statins or Anti-PCSK-9 It's‬ ‭SIMPLY because it's the ONLY TARGET‬ ‭Physiology of Atherosclerotic Plaque = COMPLEX‬