CARDIAC PATHOLOGIES
ATHEROMA
Arteries are like pipes that carry blood throughout the body. Sometimes, inside these pipes, there can be some kind of sticky material that builds up. It's a bit like when debris accumulates in the drain pipes at home and clogs them. In the arteries, this sticky material is called atheroma.
Atheroma is mainly made up of fats, cholesterol and other substances. As it builds up, it can harden and form plaques inside the arteries. This can gradually narrow the space through which blood can flow. It's as if the pipe is partially blocked.
​When the arteries are blocked by these atherosclerotic plaques, it can cause pathologies. For example, if an artery that supplies the heart is blocked, it can lead to chest pain or even myocardial infarction (heart attack). If an artery that supplies the brain is blocked, it can cause a stroke.
Mechanisms of atherosclerosis
A - Definition
Atheroma is a rearrangement of the intima of large and medium-sized arteries, consisting of focal accumulation of lipids, complex carbohydrates, blood and blood products, fibrous tissue, and calcareous deposits, all accompanied by changes in the media.
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B - Formation of an atherosclerotic plaque
It occurs through the following mechanisms:
​• accumulation of LDL (Low Density Lipoproteins) in the intima, oxidation of LDL by free radicals;
• expression of adhesion molecules, attraction and transfer in the arterial wall of monocytes transformed into macrophages and foam cells;
• role of scavenger receptors in capturing oxidized LDL;
• endothelial dysfunction, favoured by smoking and oxidised LDL: reduced vasodilator and antithrombotic capacities;
self-perpetuating inflammatory reaction aggravating endothelial dysfunction and secreting metalloproteinases destructive of the extracellular matrix;
• migration of smooth muscle cells from the media to the neo-intima;
• secretion of growth factors, collagen and the extracellular matrix;
• lipid centre: organisation in the intima of foam cells (lipid striations) within an inflammatory tissue;
• late, fibrous screed that acts as a covering of the lipid center;
• chronological sequence including lipid striations found at a young age (during autopsies), then constitution of a real atherosclerotic plaque with a lipid center and its fibrous screed.
A: transcytosis and subintimal fixation;
B: oxidation of LDL (Low Density Lipoproteins);
C: monocyte adhesion and diapedesis;
D: transformation of monocytes into macrophages;
E: accumulation of oxidized LDL in the macrophage which turns into foam cells;
F: smooth muscle cell recruitment, migration and dedifferentiation;
G: endothelial dysfunction and platelet adhesion.
​C - Evolution of atherosclerotic plaques
Atherosclerotic plaque can progress towards:
• a break-up:
– it is a sudden complication, at the origin of acute clinical accidents (acute coronary syndrome = infarction, stroke [cerebrovascular accident]),
– it occurs by erosion or tearing of the fibrous screed covering the atherosclerotic plaque,
– there is immediate formation of a thrombus leading to acute accidents by reduction or obstruction of the lumen of the artery,
– the thrombus can fragment and create embolisms,
– rupture is all the more likely if the plaque is "young", rich in lipids and inflammatory cells, and the thin the fibrous screed. It therefore often concerns atherosclerotic plaques that are not very stenosing,
– many plaque ruptures remain asymptomatic;
• a progression:
– reduction of the lumen of the vessel due to the increase in the volume of the plate,
–possible progressive increase, but especially in flare-ups, during acute accidents of plaque rupture, by incorporating thrombotic material,
– slow evolution towards fibrous and calcified tissue,
– intraplate haemorrhage: this leads to a sudden increase in the volume of the plaque that can rupture the fibrous screed,
– a regression observed experimentally in animals, but difficult to demonstrate in humans.
D - Evolution of arterial stenosis (remodeling)
The increase in the thickness of the wall, by increasing the volume of the plates, is associated with a change in the diameter of the vessel. There are 2 types of remodeling:
• Compensating remodeling which widens the diameter to preserve the arterial lumen;
• Constrictive remodeling, which reduces the diameter of the vessel and increases vascular stenosis in relation to the atheromatous lesion.
Stenosis can gradually worsen, but can also worsen suddenly by the rupture or erosion of plaque and the formation of thrombus responsible for reducing light, or even occlusion.
E - Risk Factors (RDFs) for Atheroma
A distinction is made between:
• the main RDFs: smoking, hypertension, dyslipidemia and diabetes;
• non-modifiable RDFs: age, male sex, family history;
• predisposing factors: obesity, sedentary lifestyle, stress and psychosocial conditions;
• risk markers: these are elements associated with an increase in CV (cardiovascular) risk, but without an established causal link, for example: inflammatory markers (CRP: C-reactive protein), or evidence of the development of atheroma before the clinical stage (e.g. carotid plaques on ultrasound as a risk marker for coronary events).
F - How to reduce your risk of atheroma and cardiovascular events
The target goal for LDL-C is based on cardiovascular risk To achieve these goals, the ESC recommends:
​• always give lifestyle advice;
• consider drug treatment if the LDL-C remains above the target depending on the risk category;
• to combine drug treatment if the LDL-C remains well above the objective depending on the risk category;
• to combine drug treatment from the outset if the LDL-C remains above the objective in a secondary prevention situation
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G - Therapeutic objectives
​• LDL-C remains currently the main therapeutic objective because the evidence of cardiovascular benefit is based on its lowering. Therapeutic objectives are proposed for LDL-C according to risk categories.
• These therapeutic objectives do not apply to familial hypercholesterolemia, which has a high cardiovascular risk (cf. Therapeutic management of heterozygous familial hypercholesterolemia).
Dietary treatment
​It is always indicated in the presence of any lipid abnormalities and risk factors. Drug treatment can be started after 3 months if LDL-C control remains far from the objective, or immediately if LDL-C is much higher than the objective, especially in secondary prevention.
In all cases, the dietary treatment is continued over the long term.
Dietary modifications include:
• limiting the intake of saturated fatty acids (animal fats) < 10–12% of calories, in favour of mono- or polyunsaturated fatty acids;
elimination of trans fatty acids ("partially hydrogenated" fatty acids);
• increased consumption of omega-3 polyunsaturated fatty acids (fish);
• increased consumption of fibre in fruits, vegetables and whole grains;
• moderate limitation of dietary cholesterol: eggs are not eliminated, they are proposed to be limited to about 3/week;
• Use of foods enriched with plant sterols discussed.
In addition, it is recommended to implement a Mediterranean-type diet, because of its cardiovascular benefit, including the consumption of olive oil, a high intake of fruit and vegetables (5 servings/day), as well as nuts (walnuts, hazelnuts, almonds: 30 g/day).
In addition to these recommendations, there is the need to limit alcohol consumption (especially for triglycerides), to control weight and to correct a sedentary lifestyle.
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Dietary measures specific to hypertriglyceridemia are as follows:
• For all moderate hypertriglyceridemia without hyperchylomicronemia, the three important factors to consider are:
– weight reduction in case of excess (in particular excess abdominal adiposity),
– reduction of alcohol,
– reduction of sugars;
• These nutritional measures constitute the bulk of the treatment of moderate hypertriglyceridemia, with drug treatments having only a minor impact in this context;
• Major hypertriglyceridemia (> 10 g/L) with hyperchylomicronemia are special cases:
– specialist opinion necessary to confirm the diagnosis and therapeutic orientations, particularly in terms of nutrition,
– necessary reduction in lipid intake << 30 g/day.
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Drug treatment: statins
Depending on your situation, the doctor may prescribe statins
ECHANISMS OF ACTION OF THE DIFFERENT MOLECULES:
HMG-CoA reductase inhibitors or statins competitively inhibit the activity of HMG-CoA reductase by substituting for its natural substrate, HMG CoA, at the catalytic site of the enzyme. HMG CoA reductase is the enzyme that allows the transformation of HMG CoA into mevalonate, a limiting step in cholesterol synthesis by cells.
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Statins cause a decrease in the intracellular concentration of cholesterol, especially in hepatocytes. This drop in the concentration of intra-hepatocyte free cholesterol activates the molecular mechanisms responsible for the over-expression of LDL receptors allowing the increase in the uptake of atherogenic lipoproteins (LDL, remnants, IDL) by hepatocytes. From a biological point of view, this results in a reduction in the plasma concentration of LDL cholesterol. The decrease in circulating LDL also contributes to the decrease in VLDL, probably due to the suppression of apolipoprotein B synthesis.
In addition to their beneficial effect on lowering cholesterol, statins act by decreasing inflammation and oxidative stress and by upregulating endothelial NO synthase activity. Thus, statins improve endothelial functions and stabilize atheromatous plaque.
In summary, statins decrease circulating LDL levels and decrease inflammation and oxidative stress, and thus stabilize the atheromatous plaque.
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