Risk Factors and the Role of Lipids
The etiology of the disease remains not fully understood, but the disruption of lipid-protein metabolism plays a key role. Normally, a balance exists between lipoprotein fractions:
- Atherogenic (LDL, VLDL): transport cholesterol directly from the bloodstream into the vascular wall.
- Anti-atherogenic (HDL): responsible for the extraction (efflux) of excess cholesterol back out of the wall.
In atherosclerosis, this balance is shifted, and the level of atherogenic fractions in the blood rises sharply. Several groups of factors accelerate the development of the pathology. Non-modifiable factors include age and male sex (in women, the incidence rate catches up with men only after 70 years of age). Modifiable risk factors depend on lifestyle and concomitant diseases: arterial hypertension, diabetes mellitus, obesity, smoking, physical inactivity, and chronic stress.
Pathogenesis: How a Plaque Grows
Atherogenesis is based on a complex triad: lipid metabolism pathology, structural changes in the vascular wall, and platelet dysfunction. The leading hypothesis states that endothelial injury serves as the triggering mechanism, caused by pressure (in hypertension), adrenaline surges (during stress), or infections (chlamydia, cytomegalovirus).
The logic of atheromatous plaque formation:
- Inflammation: a chronic inflammatory reaction develops in the subendothelial layer, where mononuclear cells migrate and transform into macrophages.
- Lipid Accumulation: macrophages actively engulf the excess cholesterol circulating in the blood.
- Platelet Response: platelets adhere to the site of injury, releasing serotonin, thromboxane A2, and smooth muscle cell growth factor.
- Morphological Outcome: under the influence of growth factors, fibroblasts and smooth muscle cells proliferate, forming a dense fibrous plaque.
Clinical Manifestations by Vascular Beds
For many years, the process is asymptomatic. Clinical signs start with pronounced stenosis (greater than 50%) and depend on which arterial bed is most severely affected (locus minoris):
- Coronary arteries (often the anterior interventricular branch): various forms of coronary artery disease (CAD) develop, including angina pectoris and myocardial infarction.
- Aorta: in the thoracic section, it manifests with a systolic murmur, an accentuated second heart sound, and pulse differences in the upper limbs. An aneurysm may form in the abdominal section.
- Cerebral arteries (especially the carotid bifurcation): cause dyscirculatory encephalopathy.
- Renal arteries: ischemia of the renal tissue triggers the mechanism of renovascular hypertension.
- Mesenteric vessels: "abdominal angina" occurs—ischemic abdominal pain associated with increased intestinal peristalsis after eating. Critical stenosis threatens intestinal necrosis.
- Peripheral arteries of the lower limbs: intermittent claudication syndrome, leg weakness, and decreased pulsation on the dorsum of the foot (a. dorsalis pedis).
External Signs and Treatment Principles
Dyslipidemia can be suspected even before blood tests based on external stigmata: xanthomas, xanthelasmas (yellowish plaques on the eyelids), and corneal arcus senilis.
Therapy always begins with lifestyle modification. Patients are prescribed a diet with strict restriction of animal fats (no more than 40–50 g/day), easily digestible carbohydrates, and salt. Vegetable oils, fish, and vegetables are added to the diet. Quitting smoking and monitoring physical activity are mandatory. If non-pharmacological methods fail, medications are introduced:
- Statins (simvastatin, lovastatin)—the main group that blocks cholesterol synthesis in the body.
- Bile acid sequestrants (cholestyramine)—inhibit cholesterol absorption in the intestine.
- Nicotinic acid—used in high doses, but has a weaker evidence base compared to statins.
Briefly: answers to topical questions
Which atherosclerosis risk factors are classified as non-modifiable?
Non-modifiable (uncontrollable) risk factors for atherosclerosis include:
- Age—the frequency and severity of atherosclerosis increase with age.
- Sex—men develop the disease earlier; its course is more severe, and complications occur more frequently. In women, the incidence rate becomes comparable to that of men after the age of 70.
- Heredity—genetic forms exist associated with gene mutations/defects, including those for lipoprotein receptors; a burdened family history of cardiovascular disease is also significant.
What stages are distinguished in the morphogenesis of an atherosclerotic plaque?
Several successive stages of lesion development are distinguished in the patho- and morphogenesis of atherosclerosis. These include:
- Pre-lipid stage—microscopic, invisible damage to the intima and accumulation of lipoproteins.
- Lipoidosis—focal lipid infiltration with the formation of fatty spots and streaks.
- Liposclerosis—proliferation of connective tissue and formation of a fibrous plaque.
- Atheromatosis—breakdown of the central part of the plaque with the formation of detritus.
- Ulceration stage—formation of an atheromatous ulcer upon destruction of the fibrous cap.
- Atherocalcinosis—deposition of calcium salts into the masses and tissue of the plaque.
In a number of classifications, the last three processes are combined into a general stage of complicated lesions.
Which groups of pharmacological agents are used for lipid-lowering therapy in atherosclerosis?
Five main groups of drugs are used for medical lipid-lowering therapy of atherosclerosis. The classification according to mechanism of action includes:
- Statins—cholesterol synthesis inhibitors (HMG-CoA reductase inhibitors).
- Cholesterol absorption inhibitors—drugs that reduce cholesterol absorption in the intestine.
- Bile acid sequestrants—agents that inhibit absorption in the intestine.
- Fibrates—fibric acid derivatives acting as lipoprotein lipase activators.
- Nicotinic acid preparations — triglyceride lipase inhibitors.
To avoid confusing lipid fractions: LDL (Low Density) — Carries Pathology (into the vessel wall), HDL (High Density) — Clears the Problem (back to the liver).
Class and exam questions
What is "abdominal angina" in the context of atherosclerosis?
This is a figurative name for the symptom complex associated with lesions of the mesenteric vessels. It manifests as severe ischemic abdominal pain that occurs after eating due to the increased blood supply demand of the intestine.
At what percentage of stenosis do symptoms appear?
Clinical manifestation of atherosclerosis typically occurs when the vessel lumen is narrowed by more than 50%, and symptoms may be exacerbated by local spasm.
Which infections are considered triggers for atherosclerosis?
Among the infectious and immunological factors of vascular endothelial injury are the effects of chlamydia and cytomegalovirus, as well as circulating immune complexes.
What else to study on this topic
- Mechanism of action of statins and monitoring of their side effects
- Pathogenesis of renovascular arterial hypertension in renal artery stenosis
- Differences between stable and unstable atherosclerotic plaques
- Methods of surgical blood flow correction (stenting, bypass surgery)
- Stages of dyscirculatory encephalopathy in cerebral atherosclerosis
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