1. Age, sex, and race of onset Although familial hypercholesterolemia is rare, it develops at an early age, with clinical signs and symptoms of coronary artery disease appearing before the age of 10. Without prompt and effective treatment, patients often die of myocardial infarction in their early 20s. Lipoprotein lipase deficiency can manifest as chylomicronemiasyndrome from infancy or childhood.
Familial apolipoprotein B100 deficiency is seen mainly in Caucasian ethnic groups, and only in 1993 was a patient of Chinese ancestry identified. Their LDL-cholesterol levels begin to rise in childhood or adolescence. Plasma total cholesterol and LDL-cholesterol levels continue to rise with age.
Not all primary hyperlipidemia begins at an early age. Most patients with familial mixed hyperlipidemia do not develop hyperlipidemia until adulthood, except for a few who may develop it in childhood. With the exception of dominantly inherited apolipoprotein E mutations, type III hyperlipoproteinemia is rare in children and adolescents under 20 years of age and is more common in males than in females, with onset in males occurring earlier than in females, and in females, onset usually occurs after menopause. Familial hypertriglyceridemia also develops in adulthood.
2. Early-onset cardiovascular disease often has a family history of early-onset coronary artery disease. The incidence of early-onset coronary heart disease in familial apolipoprotein B100-deficiency is similar to that of heterozygotes with familial hypercholesterolemia. coronary artery disease occurs in about one-third of those who develop coronary artery disease before the age of 60 years. peripheral vascular lesions occur, often in combination with hypertension. carotid atherosclerosis is present in 48% of patients.
Early-onset vascular lesions are more common in type III hyperlipoproteinemia. In addition to early-onset coronary artery disease, peripheral vascular lesions of the lower extremities are also frequent. Early-onset coronary artery disease is rare in familial lipoprotein lipase deficiency.
3. In patients with familial lipoprotein lipase deficiency, recurrent pancreatitis can occur because of limited pancreatic cell necrosis due to obstruction of pancreatic capillaries by celiac emboli. Acute pancreatitis can occur in 1/3 to 1/2 of patients. It often occurs after eating a high-fat diet or a full meal, and the degree of abdominal pain is positively correlated with plasma triacylglycerol levels. In addition, the manifestation of abdominal pain often varies from person to person, and a lack of careful diagnosis can lead to surgical errors.
Pancreatitis also occurs in patients with familial apolipoprotein C II deficiency. However, they have relatively high plasma VLDL-cholesterol levels and low concentrations of celiac disease, so the disease is relatively mild, and symptoms are usually not apparent before the age of 20.
4. Yellow tumor
(1)Flat yellow tumor: mainly seen around the eyelid, so it is also called eyelid yellow tumor, which is more common in the clinic. Generally manifested as a flat papule at the inner canthus of the upper eyelid, orange, rice grain to soybean size, oval, clear border, soft texture. Usually develop slowly, the number can gradually increase. A few may involve the face, neck, trunk and limbs. It is mainly seen in familial hypercholesterolemia, familial apolipoprotein B100 deficiency, and type III hyperlipoproteinemia; it can also be seen in people with normal blood lipids, and may be due to excessive uptake of oxidized or modified lipoproteins by macrophages in the tissues.
(2)Palm wrinkles yellow tumor: distributed in the palm and finger wrinkles, orange lines of flat mildly raised. This is a characteristic manifestation of type III hyperlipoproteinemia, and about 50% of patients may have palm wrinkle yellow tumors.
(3)Nodular xanthomas: they occur in the elbows, knees, knuckles and other extensor sides as well as ankles, hips, buttocks and other parts of the body, and are scattered in the early stage of distribution, and they are round nodules with the size of a soybean to an egg, and they are yellow, orange, or brownish-red in color, with clear borders and soft texture. Generally, the progress is slow. In the later stage, the nodules increase and merge into lobulated plaques of different sizes. Due to the formation of fibrosis, the texture of the nodules gradually becomes hard and is not easy to subside. If there is injury or infection, ulcers may be formed. This kind of yellow tumor is mainly seen in type III hyperlipoproteinemia, which is also characteristic.
(4) Rash yellow tumors: manifested as orange or brownish-yellow papules with whitish centers and inflammatory bases, similar to acne, occurring on the abdominal wall, the back, the buttocks, and other parts of the body susceptible to pressure, and sometimes oral mucous membranes can also be involved. It is mainly seen in severe hypertriglyceridemia due to familial lipoprotein lipase deficiency and familial apolipoprotein C II deficiency.
(5) Nodular rash yellow tumors: most common in the extensor side of the limbs, such as elbows and buttocks, in the form of orange-yellow nodules, can appear in batches in a short period of time, with a tendency to merge, surrounded by a rash-like yellow tumor encircled, often accompanied by inflammatory substrate. It is mainly seen in type III hyperlipoproteinemia.
(6) Tendon xanthoma: this is a special type of nodular xanthoma, which occurs in the tendon area, commonly found in the Achilles tendon, dorsal extensor tendon of the hand or foot, rectus femoris muscle of the knee and deltoid tendon of the shoulder, etc. It is round or ovoid in shape. It is a round or ovoid, hard, subcutaneous nodule that is adherent to the skin and has clear borders. Tendon xanthomas can occur in about 58% of patients with familial hypercholesterolemia, in 38% of patients with familial apolipoprotein B100 deficiency, and in some patients with type III hyperlipoproteinemia. Small tendon xanthomas can be easily missed if not examined carefully, and x-rays can show Achilles tendon xanthomas.
The above types of xanthomas can be seen in different types of hyperlipidemia, and multiple forms of xanthomas can be seen in people with the same type of hyperlipidemia. However, yellow tumors are rare in familial mixed hyperlipidemia. Usually, with effective lipid-lowering therapy, most yellow tumors can gradually subside.
5. Clinical manifestations of various primary hyperlipidemias.
6. Other manifestations of corneal arches, also known as senile rings, are most often associated with hyperlipidemia if they appear in people under 40 years of age. Early-onset corneal bowing is most often seen in familial hypercholesterolemia, but is not very specific. Approximately 28% of patients with familial apolipoprotein B100 deficiency may have corneal bowing. It is also seen in familial hypertriglyceridemia. Corneal clouding can occur in familial LCAT deficiency.
Severe hypertriglyceridemia (>22.6 mmol/L or 2000 mg/dl) produces a hyperlipidemic fundus by deposition of triacylglycerol-rich large-particle lipoproteins in small arteries in the fundus; triacylglycerol deposition in the reticuloendothelial cells can also cause hepatosplenomegaly; celiac spruemia can also lead to respiratory distress and neurologic symptoms. Pure familial hypercholesterolemia may present with wandering polyarthritis, which is self-limiting. Patients with familial mixed hyperlipidemia and familial hypertriglyceridemia tend to be obese. Type III hyperlipoproteinemia is often associated with other metabolic disorders such as obesity, diabetes mellitus, and hypothyroidism, and these conditions can further elevate the patient's lipid levels. Patients with secondary hyperlipidemia may have clinical manifestations of various primary diseases.
There is currently no international or national standardized approach to the diagnostic criteria for hyperlipidemia. In order to prevent and control atherosclerosis and coronary heart disease, the appropriate plasma cholesterol level is 5.17mmol/L (200mg/dl) or less. the diagnostic criteria for hyperlipidemia set by the Adult Treatment Panel (ATP) of the American Council for Cholesterol Education Program in 2001.
The new criteria recommend initiating drug therapy at an LDL-C concentration of >130mg/dl, with an LDL-C concentration of <100mg/dl as the treatment goal. Greater emphasis was placed on low HDL-C concentration as a risk factor for coronary heart disease, and the original value of <35mg/dl was revised to offset a risk factor for coronary heart disease at <40mgdl="">60mg/dl. Reduced the criteria for the classification of triacylglycerol, focusing more on its moderate elevation. 40mg
Most scholars in China believe that plasma total cholesterol concentration >5.17mmol/L (200mg/dl) can be designated as hypercholesterolemia, plasma triacylglycerol concentration >2.3mmol/L (200mg/dl) for hypertriacylglycerolemia. The diagnostic criteria for hyperlipidemia vary from place to place due to factors such as the different populations tested and differences in the testing methods used.
1. Classification of hyperlipidemiaThe usual classification of hyperlipidemia is not an etiologic diagnosis, and it can often be altered by changes in diet, medications, or other environmental factors. The simple classification of hyperlipidemia has included the types of hyperlipoproteinemia that are common and are more associated with the development of coronary heart disease.
(1) Clinically, it can be simply divided into the following four categories:
①Hypercholesterolemia: increased plasma TC levels.
②Mixed hyperlipidemia: increased plasma TC and TG levels.
③Hypertriacylglycerolemia: increased plasma TG level.
④Low high-density lipoproteinemia: decreased plasma HDL-C levels.
(2) According to the etiology, it can be divided into:
①Primary hyperlipidemia: it is an abnormality of lipid metabolism caused by genetic defects or gene mutations, dietary habits, lifestyle and other natural environmental factors.
②Secondary hyperlipidemia: caused by a clear underlying disease. Common underlying diseases that can cause secondary hyperlipidemia are diabetes mellitus, hypothyroidism, chronic kidney disease and nephrotic syndrome, obstructive hepatic and biliary diseases, hepatic glycogen storage disease, pancreatitis, ethanol intoxication, idiopathic hypercalcemia, multiple myeloma, macroglobulinemia and lupus erythematosus, anorexia nervosa and so on. Certain medications such as thiazide diuretics, oral contraceptives containing female hormones, thyroxine, anabolic steroid hormones, and certain beta-blockers can also cause secondary hyperlipidemia. Secondary hyperlipidemia can be expected to be corrected when these underlying conditions are cured or controlled, or when the drugs in question are discontinued.
2. Define the risk factors and risk states of coronary heart disease other than high cholesterol
(1) Positive risk factors:
1) Sex: the incidence rate of men is higher than that of women, and it is 3-4 times higher in the middle age, and the incidence rate of women increases after menopause, but the ratio of men to women is still around 1.
②Age: the incidence of coronary heart disease increases with age.
③High blood pressure: no matter systolic or diastolic blood pressure increases for a long time, will make the risk of coronary heart disease increases.
④Smoking: the degree of risk is related to the amount of smoking, the risk of smokers than non-smokers can be one times higher.
⑤Family history of coronary heart disease: the risk of coronary heart disease increases when there is a history of coronary heart disease in the immediate family, especially when there is an early onset of coronary heart disease (before the age of 55 for men and before the age of 65 for women).
6 Diabetes mellitus and impaired glucose tolerance: the risk is two times higher in men and three to four times higher in women, and the risk is equally increased regardless of insulin dependence.
7 premature menopause: women who have premature menopause and are not treated with estrogen replacement therapy have an increased risk of coronary heart disease.
8 obesity: the distribution and degree of obesity is very important, excessive increase in trunk and abdominal organ fat, is certainly a risk factor for coronary heart disease. Other relevant risk factors are still less active lifestyle. The importance of increased blood fibrinogen, blood insulin resistance, increased blood lipoprotein (a) or homocysteinemia as risk factors for coronary heart disease is being studied.
(2) Negative risk factors: 1 risk factor can be subtracted if the serum HDL-C level >1.6 mmol/L (60 mg/dl), because high levels of HDL-C can lead to a reduction in coronary heart disease risk factors.