Hyperlipoproteinemia
Introduction
Introduction to hyperlipoproteinemia Hyperlipoproteinemia refers to elevated levels of cholesterol (TC) and/or triglyceride (TG) in plasma, which is actually a manifestation of elevated levels of certain or certain types of lipoproteins in plasma. It is actually an expression of elevated levels of certain or certain types of lipoproteins in plasma. In recent years, it has been gradually recognized that a decrease in plasma LDL-C (low-density lipoprotein cholesterol) is also a disorder of blood lipid metabolism. Therefore, it has been suggested to use lipid dyslipidemia (dyslipidemia), and believe that this name can more fully and accurately reflect the state of dyslipidemia. basic knowledge The proportion of illness: 1.2%, more common in the elderly over 50 years old Susceptible people: no specific population Mode of infection: non-infectious Complications: atherosclerosis, acute pancreatitis
Cause
Cause of hyperlipoproteinemia
Disease factors (25%):
All causes of elevated levels of CM and/or VLDL in one or a few types of lipoproteins in plasma can lead to hypertriglyceridemia. Many metabolic diseases, certain diseases, hormones and drugs can cause hypertriglyceridemia.
Nutritional factors (15%):
Many nutritional factors can cause elevated levels of plasma triacylglycerol. A large intake of monosaccharides can also cause elevated levels of plasma triglycerides. This may be related to concomitant insulin resistance; it may also be due to the fact that monosaccharides alter the structure of VLDL and affect its rate of clearance.
The structure of the diet also has an effect on elevated plasma triglyceride levels. The diet of our population is characterized by high sugar and low fat. According to the survey, sugar accounts for 76%~79% of total calories, fat only accounts for 8.4%~10.6%, and the incidence of hyperlipidemia is 11%. Endogenous high triglyceride plasma is the most common. Drinking alcohol also has a significant effect on plasma triacylglycerol levels.
Lifestyle (10%):
The concentration of plasma triglyceride in people who are accustomed to sitting down is higher than those who insist on physical exercise. Both long-term and short-term physical exercise can reduce plasma triglyceride levels. Exercise can increase LPL activity, increase HDL-C (high-density lipoprotein cholesterol) levels, especially HDL2-C levels, and reduce hepatic lipase (HL) activity. Long-term adherence to exercise can also increase exogenous triacylglycerol clearance from plasma.
Smoking also increases plasma triacylglycerol levels. Epidemiological studies have confirmed that smoking increases plasma triglyceride levels by 9.1% compared to normal human mean.
Gene abnormality (5%):
Increased plasma triacylglycerol levels due to genetic abnormalities have abnormalities in 1CM and VLDL assembly. 2LPL and Apo CII (apolipoprotein CII) gene abnormalities. 3Apo E (apolipoprotein E) gene is abnormal.
Prevention
Hyperlipoproteinemia prevention
Prevention: Extensive and repeated health education through a variety of ways, promoting scientific diet, balanced diet, regular physical exercise, prevention of obesity, smoking cessation, alcohol, and health education for prevention and treatment of chronic diseases such as cardiovascular disease, obesity, and diabetes Combined, the blood lipids in the crowd are kept at an appropriate level. In addition, regular health checks can also help early detection of abnormal bleeding and timely treatment.
Complication
Hyperlipoproteinemia complications Complications atherosclerosis acute pancreatitis
Complications of hyperlipoproteinemia are atherosclerosis, hypertriglyceridemia, chylomicronemia, acute pancreatitis, and the like.
Symptom
Symptoms of hyperlipoproteinemia Common symptoms Subcutaneous nodules Abdominal pain Papular Hypertension Lipid deposition Dementia Intermittent claudication Shock Anuria-free psychosis
The clinical manifestations of hyperlipidemia mainly include two aspects: on the one hand, the yellow tumor caused by lipid deposition in the dermis; on the other hand, the atherosclerosis caused by lipid deposition in the vascular endothelium, producing coronary heart disease and peripheral Vascular disease, etc., the incidence of xanthomas in hyperlipidemia is not very high, the occurrence and development of atherosclerosis takes a long time, so most patients with hyperlipidemia do not have any symptoms and abnormal signs found The patient's hyperlipidemia is often found when performing blood biochemical tests (measuring blood cholesterol and triacylglycerol).
1. Clinical determination of plasma (clear) total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL) concentrations increased, high-density lipoprotein cholesterol (HCL) is low.
2. The deposition of lipids throughout the body
(1) xanthoma (xanthoma): is an abnormal localized skin bulge, its color can be yellow, orange or brown red, mostly nodules, plaque or papule shape, the texture is generally soft, mainly Since macrophages (foam cells), which are phagocytic lipids accumulated in the dermis, are also called yellow tumor cells, according to the morphology of the yellow tumor, the occurrence sites are generally classified into the following six types:
1 tendon xanthoma (tendon xanthoma): is a special type of nodular yellow tumor, which occurs in the tendon, common in the Achilles tendon, the back of the hand or the back of the tendon, the rectus femoris and the deltoid tendon It is a round or oval-shaped hard subcutaneous nodule, which adheres to the skin and has a clear boundary. This yellow tumor is often a characteristic feature of familial hypercholesterolemia.
2 palmar creases xanthoma: is a linear flat yellow tumor that occurs in the palm of the hand. It is an orange-yellow bulge that is distributed in the palm and finger folds. This yellow tumor is for the diagnosis family. Sexual abnormality -lipoproteinemia has a certain value.
3 tuberous xanthoma (tuberous xanthoma): slow development, occurs in the extension of the body, such as elbows, knees, knuckles and hips, ankles, buttocks, etc., rounded nodules, the size of which is different The boundary is clear, the early texture is soft, and the texture is hardened due to fibrosis in the later stage. This yellow tumor is mainly found in familial abnormal -lipoproteinemia or familial hypercholesterolemia.
4 tuberous eruptive xanthoma (tuberous eruptive xanthoma): occurs in the elbows of the extremities and the buttocks, skin lesions often appear in a short period of time in batches, showing a nodular fusion trend, rash-like yellow tumor often surrounded Nodular yellow tumor, the skin of the tumor is orange-yellow, often accompanied by an inflammatory basal. This yellow tumor is mainly seen in familial abnormal -lipoproteinemia.
5 eruptive xanthoma (eruptive xanthoma): as a needle or match head size papules, orange or brown with an inflammatory basal, sometimes oral mucosa can also be affected, mainly seen in hypertriglyceridemia.
6 flat yellow tumor (xanthelasma): seen in the periorbital week, also known as jaundice, is a more common type of yellow tumor, which appears in the eye around the orange slightly higher than the skin surface of the flat papules or flaky tumor Clear border, soft texture, generalized surface, neck, trunk and limbs, flat yellowish or brownish yellow papules, several millimeters to several centimeters in size. These yellow tumors are common in various hyperlipidemias, but also Can be seen in normal blood lipids.
The different forms of xanthomas can be seen in different types of hyperlipidemia, and in the same type of hyperlipidemia, various forms of xanthomas can occur. After effective lipid-lowering therapy, most of the yellow tumors can gradually disappear.
(2) lipid keratome: cornealarcus (cornealarcus), also known as the elderly ring, if found in people under 40 years old, are often accompanied by hyperlipidemia, familial hypercholesterolemia is more common, but the specificity is not very Strong.
(3) hyperlipidemia retinal lipemia changes: due to triglyceride-rich large granular lipoprotein deposition caused by light scattering on the fundus arterioles, often severe hypertriglyceridemia accompanied by Characteristics of chylomicronemia.
In addition, severe hypercholesterolemia, especially homozygous familial hypercholesterolemia can occur migratory polyarthritis, but this is rare, and arthritis is mostly self-limiting.
Severe hypertriglyceridemia can also cause acute pancreatitis and should be noted.
3. Atherosclerotic lesions
(1) Aortic atherosclerosis: lesions are more common in the posterior wall of the aorta and its branch opening, with the abdominal aorta being the heaviest, the thoracic aorta followed, and the ascending aorta being the lightest. All the aforementioned lesions are visible. In contrast to aneurysms of syphilitic aortitis, aneurysms of aortic AS are mainly found in the abdominal aorta, which can touch a pulsating mass in the abdomen, hear murmurs, and can cause fatal bleeding due to rupture due to aortic wall. The elasticity is reduced, the patient's systolic blood pressure is increased, the pulse pressure is widened, and the radial artery palpation can be similar to the pulse.
(2) coronary atherosclerosis: see coronary heart disease.
(3) carotid and cerebral atherosclerosis: lesions are most common in the beginning of the internal carotid artery, basilar artery, middle cerebral artery and Willis ring, fibrous plaque and atheromatous plaque often lead to stenosis, and because of Complex lesions aggravate stenosis and even form occlusion. Aneurysms are more common in the Willis ring. Long-term blood supply can cause brain parenchymal atrophy, which is characterized by narrowing of the cerebral gyrus, thinning of the cortex, widening of the sulci and deepening of the brain, and reduction of brain weight. Injury and memory loss, mental metamorphosis, and even dementia, rapid blood supply interruption can cause cerebral infarction (brain softening), arterial and small aneurysm rupture can cause cerebral hemorrhage and corresponding clinical manifestations.
(4) renal atherosclerosis: lesions most often involve the opening of the renal artery and the proximal end of the trunk, may also involve the interlobular artery and the arcuate artery, often due to stenosis caused by stenosis caused by stenosis Hypertension; may also cause renal tissue infarction due to plaque with thrombosis, causing pain in the kidney area, no urine and fever, leaving a large scar after the infarction is machined, multiple scars can cause the kidney to shrink, called AS-solid Kidney.
(5) Atherosclerosis of the extremities: the lower extremity arteries are heavier. When the lumen of the larger arteries is obviously narrow, the oxygen consumption may increase due to insufficient blood supply (such as walking), which may cause pain, improve after rest, and then go again. There is a severe pain, the so-called intermittent claudication. When the arterial lumen completely blocks the collateral circulation and cannot compensate, it causes dry gangrene in the toes.
(6) mesenteric atherosclerosis: due to stenosis or even obstruction of the mesenteric artery, the patient has severe abdominal pain, abdominal distension and fever, such as causing intestinal infarction, may have blood in the stool, paralytic ileus and shock and other symptoms.
Hyperlipidemia is higher than the upper limit of normal blood lipids. There are many classification methods, mainly four.
Examine
Examination of hyperlipoproteinemia
1. Blood lipid test items
Serum TC, serum HDL-C, serum TG, serum LDL-C increased [calculated by Friedewald formula: LDL-C (mmol/L) = TC-HDL-C-TG/2.2 or LDL-C (mg/dl) = TC-HD LC-TG/5 is limited to TG < 4.5 mmol/L, and TG > 4.5 mmol/L requires direct detection].
2. Review
If the abnormality is detected for the first time, it is advisable to review the blood lipid level after fasting for 12 to 14 hours. The serum cholesterol level may be 10% within 1 to 2 weeks. The laboratory variation is allowed to be within 3%, and the presence of hyperlipemia is judged. There should be at least 2 records of the blood specimen examination before the disease or decision on prevention and treatment.
Diagnosis
Diagnosis and identification of hyperlipoproteinemia
Diagnostic criteria
1. Classification of hyperlipidemia
(1) Classification of hyperlipoproteinemia phenotypes:
At present, the internationally accepted classification system based on Fredrickson's work is revised based on the degree of various plasma lipoprotein elevations. This classification does not include etiology, so it is called phenotypic classification. Hyperlipoproteinemia can be divided into 5 types (including subtypes, which can be divided into 6 types).
(2) Clinical classification:
1 hypercholesterolemia: elevated serum TC levels.
2 hypertriglyceridemia: elevated serum TG levels.
3 mixed hyperlipidemia: serum TC and TG levels increased.
4 low-density lipoproteinemia: serum HDL-C levels are reduced.
(3) Classification of causes:
1 primary hyperlipidemia.
2 secondary hyperlipidemia: common diseases due to diabetes, hypothyroidism, nephrotic syndrome.
(4) Gene classification: With the development of molecular biotechnology, some patients with hyperlipidemia are found to have defects in single or multiple genetic genes, many have family gene aggregation, and have obvious genetic predisposition, which is clinically called familial. Hyperlipidemia (including familial hypercholesterolemia; familial apolipoprotein B100 deficiency; familial mixed hyperlipidemia; familial abnormal -lipoproteinemia, etc.).
2. Detection of lipid-lowering subjects should be subject to lipid testing: National Cholesterol Education Program (NCEP) Adult Treatment Group Guide III (ATPIII) recommends screening for lipid profiles in the population, including fasting total TC, LDL-C , HDL-C, TG, due to the limitations of human and material resources, it is difficult to take a blood lipid survey in the population. The following are the subjects that should be tested for blood lipids:
(1) Patients with coronary heart disease, cerebrovascular disease or peripheral atherosclerosis.
(2) Those with high blood pressure, diabetes, obesity, and smoking history.
(3) Those with a family history of coronary heart disease or atherosclerosis, especially those with immediate or early death.
(4) Those with xanthoma or jaundice.
(5) Those with familial hyperlipidemia, the following may be considered as subjects of blood lipid examination: men over 140 years old; 2 women after menopause.
3. Judgment of results At present, there is no uniform normal value in the world. The blood lipid levels of TC and TG in China are lower than those in Europe and America, and their normal values are different from those in Europe and America.
4. People who should receive lipid-lowering treatment
(1) People with dyslipidemia need to adjust fat from the point of view of preventing coronary heart disease.
(2) According to the causes of hyperlipidemia, it can be divided into primary hyperlipidemia and secondary hyperlipidemia. Secondary hyperlipidemia refers to dyslipidemia caused by systemic diseases. Systemic diseases that can cause elevated blood lipids include hypothyroidism, diabetes, nephrotic syndrome, renal failure, liver disease, systemic lupus erythematosus, glycogen storage disease, etc. Primary hyperlipidemia is not found. Systemic diseases cause dyslipidemia, often due to genetic factors or acquired environmental factors, resulting in poor lifestyle. Both types of dyslipidemia require lipid regulation, but secondary dyslipidemia requires not only lipid regulation but also treatment of the primary disease.
(3) The same risk factors for coronary heart disease and coronary heart disease are the key targets of lipid-lowering therapy. The condition with the same risk of coronary heart disease is called coronary heart disease and other dangerous diseases. There are 3 cases of coronary heart disease and other dangerous diseases:
1 There are other clinical manifestations of atherosclerosis (peripheral arterial disease, abdominal aortic aneurysm and symptomatic carotid artery disease, etc.).
2 diabetes.
3 There are a number of risk factors and the risk of coronary heart disease is expected to be >20% in 10 years. It is especially emphasized that ATPIII treats diabetes as a risk disorder such as coronary heart disease, and requires that LDL-C should be treated as well as diabetes for coronary heart disease. .
Differential diagnosis
1. Familial hypercholesterolemia (FH)
It is an autosomal dominant hereditary disease. The pathogenesis of this disease is the absence or abnormality of LDL receptors on the surface of the cell membrane, leading to abnormal LDL metabolism in the body, resulting in plasma total cholesterol (TC) levels and low-density lipoprotein-cholesterol ( LDL-C) levels are elevated, and there are often multiple sites of xanthoma and early onset coronary heart disease.
In male heterozygous FH patients, coronary heart disease can occur in 30 to 40 years old, males expect 23% of patients to die of coronary heart disease before the age of 50, and more than 50% of male patients have significant coronary heart disease symptoms at the age of 60 However, in women with heterozygous FH patients are also susceptible to coronary heart disease, but the age of coronary heart disease is about 10 years later than male patients.
Homozygous FH patients are caused by an abnormal LDL receptor gene obtained from their parents, and there is no or almost no functional LDL receptor in the patient, resulting in 6-8 times higher plasma cholesterol levels than normal people. Early atherosclerosis, clinical signs and symptoms of coronary heart disease at the age of 10, if not effective treatment, these patients are difficult to live to 30 years old.
A practical method for routine diagnosis of FH is to accurately measure plasma cholesterol and triglyceride concentrations. If it is simple hypercholesterolemia and the plasma cholesterol concentration exceeds 9.1 mmol/L (350 mg/dl), there is almost no difficulty in diagnosing FH. Other manifestations support the diagnosis of FH, including the presence of tendon xanthomas in patients or their first-degree relatives, and the presence of hypercholesterolemia in first-generation relatives. In patients with cholesterolemia, for heterozygous FH, the plasma cholesterol concentration is 6.5 to 9.1 mmol/L (250 to 350 mg/dl), and if one of the other characteristics is also present, the diagnosis of FH can be made.
2. Familial apolipoprotein B100 deficiency
Familial defective apolipoprotein B100 (FDB) is caused by the replacement of arginine (Arg) at 3500 in Apo B100 by glutamine (Gln) (Arg3500Gln). Lpo of Apo B100 binds to receptors. LDL particles in human plasma contain only one molecule. Apo B100 heterozygote FDB should have two LDL particles in the body. One LDL granule contains normal Apo B100 and the other LDL granule. Then, with the mutated Apo B100, the affinity of the LDL rich in defective Apo B100 from the plasma of the FBD heterozygotes was only 10% of the normal.
The available data does not determine the frequency of FDB in the general population, as the vast majority of reported FDB cases have been found in studies of patients with hypercholesterolemia. The incidence of FDB in the general population is estimated to be 1 /700 ~ 1 / 500.
The abnormal dyslipidemia in patients with FDB appears to be similar to that of heterozygous FH, mainly due to moderate or severe elevations in plasma total cholesterol and LDL cholesterol concentrations.
3. Familial mixed hyperlipidemia
Familial mixed hyperlipidemia (FCH) was first recognized as an independent disease in 1973. This type of dyslipidemia is the most common (accounting for 11.3%) in people under 60 years of age with coronary heart disease. The incidence of FCH in the general population is 1% to 2%. Other studies have shown that FCH is the most common type of dyslipidemia in patients with ischemic stroke of unknown age above 40 years.
The dyslipidemia of FCH is characterized by elevated plasma cholesterol and triglyceride, and its biochemical abnormality is similar to type IIb hyperlipoproteinemia. Therefore, some people have compared FCH with type IIb hyperlipoproteinemia in making FCH. In the diagnosis, we must first pay attention to the exclusion of secondary hyperlipidemia.
The most prominent feature of FCH is that in the same family, there are various types of patients with hyperlipoproteinemia and a positive family history of myocardial infarction under 60 years of age, due to current metabolic abnormalities and genetic defects in FCH. The genes are still unclear, and no genetic markers with diagnostic significance are found. Therefore, it is necessary to establish a diagnosis of FCH to understand family history. The clinical and biochemical characteristics of FCH and the key points of diagnosis are listed as follows: There were many types of patients with high lipoprotein disease in the first generation of relatives; 2 positive family history of early onset coronary heart disease; 3 increased plasma Apo B levels; 4 no yellow tumors detected in first generation relatives; Patients under 20 years of age have no hyperlipidemia; 6 manifest as IIa, IIb, IV or V hyperlipidemia; 7LDL-cholesterol/Apo B ratio is low; 8HDL2-cholesterol level is reduced, generally considered that as long as there is the first 2 and 3 points are enough to diagnose FCH.
4. Familial abnormal -lipoproteinemia
Familial dysbetalipoproteinemia (FD), also known as type III hyperlipoproteinemia, separates the patient's plasma lipoprotein by ultracentrifugation and performs agarose electrophoresis. Protein (VLDL) electrophoresis often moves to the position instead of the normal pre- position, so the VLDL is called -VLDL. The structural analysis of these -VLDL shows that the cholesterol content is very rich, due to - VLDL is the most prominent manifestation of type III hyperlipoproteinemia, and has obvious familial aggregation, so it is called familial abnormal -lipoproteinemia.
The change of blood lipids is accompanied by a simultaneous increase in plasma cholesterol and triglyceride concentrations. The plasma cholesterol concentration is usually higher than 7.77 mmol/L (300 mg/dl), which can be as high as 26.0 mmol/L, and the plasma triacylglycerol concentration is increased. The mg/dl unit is roughly equivalent to or higher than the plasma cholesterol level. It is generally considered that if the plasma cholesterol and the triacylglycerol concentration are simultaneously increased, and the two are equivalent, the possibility of type III hyperlipoproteinemia should be considered.
Plasma -VLDL is considered to be the most important basis for the diagnosis of type III hyperlipoproteinemia. VLDL in plasma is rich in cholesterol ester (more than 25%, normal is about 15%) is one of the characteristics of -VLDL. The degree of cholesterol-containing ester in VLDL can generally be measured by measuring two ratios: 1 VLDL-cholesterol/plasma triacylglycerol ratio, which is 0.3 (mg/mg) for the diagnosis of type III hyperlipoproteinemia. And the ratio 0.28 (mg/mg) suggests that it may be type III hyperlipoproteinemia, 2VLDL-cholesterol/VIDL-triacylglycerol ratio, the ratio 1.0 (mmol/mmol) for the diagnosis of type III hyperlipoproteinemia Very valuable.
The most reliable biochemical marker for the diagnosis of type III hyperlipoproteinemia is the determination of the Apo E phenotype or the Apo E genotype. ApoE2 is present at the same time as any of the above characteristics, and the diagnosis of type III hyperlipoproteinemia can be established. Apo E The phenotype or genotype does not change due to other factors.
