Hypercholesterolemia

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Hypercholesterolemia , also called high cholesterol , is a high cholesterol level in the blood. This is a form of high blood lipids and hyperlipoproteinemia (increased lipoprotein levels in the blood).

Increased levels of non-HDL and LDL cholesterol in the blood may be a consequence of an unhealthy diet, obesity, inherited (genetic) disease (such as LDL receptor mutations in familial hypercholesterolaemia), or the presence of other diseases such as type 2 diabetes and underactive thyroid.

Cholesterol is one of the three major classes of lipids used by all animal cells to build up its membrane and thus produced by all animal cells. Plant cells do not produce cholesterol. It is also a precursor of steroid hormones and bile acids. Since cholesterol is not soluble in water, cholesterol is transported in the blood plasma in protein particles (lipoproteins). Lipoproteins are classified by their densities: very low density lipoprotein (VLDL), low density lipoprotein (LDL), medium density lipoprotein (IDL) and high density lipoprotein (HDL). All lipoproteins carry cholesterol, but elevated levels of lipoproteins in addition to HDL (called non-HDL cholesterol), especially LDL-cholesterol, are associated with an increased risk of atherosclerosis and coronary heart disease. In contrast, higher HDL cholesterol levels are protective.

Avoid trans fats and replace saturated fats in adult diets with polyunsaturated fat recommended dietary measures to reduce total blood cholesterol and LDL in adults. In people with very high cholesterol (eg, familial hypercholesterolaemia), diets are often insufficient to achieve the desired LDL degradation, and lipid-lowering drugs are usually necessary. If necessary, other treatments such as LDL aphthesis or even surgery (for the subtypes of familial hypercholesterolemia) are performed. Approximately 34 million adults in the United States have high blood cholesterol.

Video Hypercholesterolemia

Signs and symptoms

Although hypercholesterolemia itself is asymptomatic, elevated serum cholesterol levels can cause atherosclerosis (hardening of the arteries). For decades, elevated serum cholesterol contributes to the formation of atheromatous plaques in the arteries. This can lead to progressive narrowing of the involved arteries. Smaller plaques can rupture and cause clots to form and block blood flow. The sudden blockage of the coronary arteries can cause a heart attack. Blockage of the arteries that supply the brain can cause a stroke. If the development of stenosis or occlusion gradually, the blood supply to the tissues and organs slowly decreases until organ function becomes impaired. At this point, tissue ischemia (restriction of blood supply) may manifest as specific symptoms. For example, temporary brain ischemia (commonly referred to as transient ischemic attack) may manifest as temporary loss of vision, dizziness and impaired balance, speech impediment, weakness or numbness or tingling, usually on one side of the body. Inadequate blood supply to the heart can cause chest pain, and ischemia in the eye may manifest as temporary loss of vision in one eye. Inadequate blood supply to the leg can manifest as calf pain while walking, while in the gut it may appear as a stomachache after eating.

Some types of hypercholesterolaemia lead to certain physical findings. For example, familial hypercholesterolemia (Type IIa hyperlipoproteinemia) may be associated with xanthelasma palpebrarum (yellowish spots beneath the skin around the eyelids), senile arcus (white or gray coloration of the peripheral cornea), and xanthomata (yellowish cholesterol-rich material deposition). ) of the tendon, especially the radius. Type III hyperlipidemia may be associated with xanthomata in the palms of hands, knees, and elbows.

Maps Hypercholesterolemia

Cause

Hypercholesterolemia is usually due to a combination of environmental and genetic factors. Environmental factors include weight, diet, and stress.

A number of other conditions can also increase cholesterol levels including type 2 diabetes mellitus, obesity, alcohol use, monoclonal gammopathy, dialysis, nephrotic syndrome, hypothyroidism, Cushing's syndrome, anorexia nervosa, drugs (eg thiazide diuretics, ciclosporin, glucocorticoids, beta blockers, retinoic acid, antipsychotics).

Genetics

Genetic contributions are usually caused by the additional effects of some genes, although sometimes it may be caused by a single gene defect as in the case of familial hypercholesterolaemia.

Genetic abnormalities in some cases are entirely responsible for hypercholesterolemia, such as in familial hypercholesterolaemia, in which one or more genetic mutations in the autosomal dominant APOB gene, autosomal recessive gene LDLRAP1 , autosomal dominant familial hypercholesterolaemia ( HCHOLA3 ) variant of PCSK9 genes, or LDL receptor genes. Familial hypercholesterolemia affects about one in five hundred people.

Diet

Diet has an effect on blood cholesterol, but the size of this effect varies between individuals. In addition, when food cholesterol intake falls, production (especially by the liver) is usually elevated, resulting in changes in blood cholesterol can be low or even increase. This compensatory response may explain hypercholesterolemia in anorexia nervosa. A 2016 review found tentative evidence that dietary cholesterol was associated with higher blood cholesterol. Trans fats have been shown to reduce HDL levels while increasing LDL levels. LDL and total cholesterol also increase with a very high fructose intake.

Stress and hormones

Glucocorticoids increase the production of LDL cholesterol by increasing the production and activity of HMG-CoA reductase. These include stress hormones cortisol and physiological drugs commonly used for asthma, rheumatoid arthritis, or connective tissue disorders. Steroid hormones and other drugs are also involved. In contrast, thyroid hormones decrease cholesterol production. Therefore, hypothyroidism (thyroid hormone deficiency) causes hypercholesterolaemia.

Drugs

Hypercholesterolemia may be a side effect of a number of drugs, including blood pressure medications, antipsychotics, anticonvulsants, immunosuppressives, human immunodeficiency virus therapy, and interferon.

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Diagnosis

Cholesterol is measured in milligrams per deciliter (mg/dL) of blood in the United States and several other countries. In the UK, most European and Canadian countries, milimoles per liter of blood (mmol/Ll) are the size.

For healthy adults, the UK National Health Service recommends a upper total cholesterol limit of 5 mmol/L, and low-density lipoprotein (LDL) 3 mmol/L cholesterol. For people at high risk of cardiovascular disease, the recommended limit for total cholesterol is 4 mmol/L, and 2 mmol/L for LDL.

In the United States, the National Heart, Lung, and Blood Institute at the National Institutes of Health classify total cholesterol less than 200 mg/dL as "desired," 200-239 mg/dL as "high limit," and 240 mg/dL or more as "high".

There is no absolute cutoff between normal and abnormal cholesterol levels, and interpretation of the value should be made with respect to health conditions and other risk factors.

Higher total cholesterol levels increase the risk of cardiovascular disease, especially coronary heart disease. LDL or non-HDL cholesterol levels predict future coronary heart disease; which is a better predictor of debate. High levels of small solid LDL can be very detrimental, although small solid LDL measurements are not recommended for risk prediction. In the past, LDL and VLDL levels were rarely measured directly due to costs. Fasting triglyceride levels are taken as indicators of VLDL levels (generally about 45% of fasting triglycerides comprise VLDL), whereas LDL is usually estimated by the Friedewald formula:

LDL ${\ displaystyle \ approx}  ÂÂ$ kolesterol total - HDL - (0,2 x trigliserida puasa).

However, this equation does not apply to non-fasting blood samples or if fasting triglycerides increase & gt; 4.5 mmol/L (& gt; ~ 400 mg/dL). Therefore, the latest guidelines recommend the use of direct methods for the measurement of LDL if possible. It may be useful for measuring all lipoprotein subfractions (VLDL, IDL, LDL, and HDL) when assessing hypercholesterolemia and measuring apolipoprotein and lipoprotein (a) can also be valuable. Genetic screening is now recommended if a form of familial hypercholesterolaemia is suspected.

Classification

Classically, hypercholesterolemia is categorized by lipoprotein electrophoresis and Fredrickson classification. More recent methods, such as "lipoprotein subclass analysis", have offered significant improvements in understanding the association with the development of atherosclerosis and its clinical consequences. If hypercholesterolaemia is hereditary (familial hypercholesterolaemia), more often a premature family history, early onsetosclerosis is found.

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Screening

The US Preventive Services Task Force in 2008 strongly recommend routine checks for men aged 35 and older and women 45 years and over for lipid disorders and abnormal lipid treatment in people at high risk for coronary heart disease. They also recommend routinely screening men ages 20 to 35 and women aged 20 to 45 if they have other risk factors for coronary heart disease. In 2016 they concluded that testing a general population under the age of 40 without symptoms was an unclear benefit.

In Canada, screening is recommended for men aged 40 and older and women 50 and older. In those with normal cholesterol levels, screening is recommended every five years. After people use statins, further testing only provides few benefits unless it is possible to determine adherence to treatment.

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Treatment

For those at high risk, a combination of lifestyle modification and statins has been shown to reduce mortality.

Lifestyle

Recommended lifestyle changes for those with high cholesterol include: stopping smoking, limiting alcohol consumption, increasing physical activity, and maintaining a healthy weight.

Overweight or obese individuals can lower blood cholesterol by weight loss - an average of one kilogram of weight can lower LDL cholesterol by 0.8 mg/dl.

Diet

Eating a diet with a high proportion of vegetables, fruits, dietary fiber, and low fat lowers total cholesterol.

Eating a cholesterol diet causes a small increase in serum cholesterol. Limit diet for cholesterol is proposed in the United States, but not in Canada, the UK, and Australia. However, there is no conclusive evidence of the effects of a cholesterol diet on cardiovascular disease. As a result, by 2015 the Diet Guidebook Advisory Committee in the United States removes recommendations to limit cholesterol intake.

Cochrane Reviews of 2015 found replacing saturated fats with polyunsaturated fats results in a small decrease in cardiovascular disease by lowering blood cholesterol. Other reviews have not found the effects of saturated fats on cardiovascular disease. Trans fats are recognized as potential risk factors for cardiovascular diseases related to cholesterol, and avoiding them in adult diets is recommended.

The National Lipid Association recommends that people with family hypercholesterolemia limit total fat intake to 25-35% of energy intake, saturated fat to less than 7% of energy intake, and cholesterol to less than 200 mg per day. Changes in total fat intake in a low-calorie diet do not seem to affect blood cholesterol.

Increased consumption of soluble fiber has been shown to reduce LDL cholesterol levels, with each additional gram of soluble fiber reducing LDL by an average of 2.2 mg/dL (0.057 mmol/L). Increasing the consumption of whole grains also reduces LDL cholesterol, with wheat wheat being very effective. The inclusion of 2 g per day of phytosterol and phytostanol and 10 to 20 g of soluble fiber per day decreased dietary cholesterol absorption. A high-fructose diet can increase LDL cholesterol levels in the blood.

Medication

Statins (or HMG-CoA reductase inhibitors) are commonly used to treat hypercholesterolemia if the diet is ineffective. Other agents that may be used include: fibrates, nicotinic acid, and cholestyramine. This, however, is only recommended if statins are not tolerated or in pregnant women. Statins can lower total cholesterol by about 50% in most people; effects appear similar regardless of the statins used. While statins are effective in reducing mortality in those who have had previous cardiovascular disease, there is debate as to whether they are effective or not in those with high cholesterol but no other health problems. One review found no death benefit in those at high risk, but without prior cardiovascular disease. Other reviews concluded the benefits of death do exist. Statins can improve quality of life when used in people without existing cardiovascular disease (ie for primary prevention). Statins lower cholesterol in children with hypercholesterolaemia, but no studies in 2010 showed improved clinical outcomes and diet was the mainstay of therapy in childhood. Antibodies injected against PCSK9 protein (evolocumab, bococizumab, alirocumab) can lower LDL cholesterol and have been shown to reduce mortality.

Alternative medicine

According to a survey in 2002, alternative medicine was used in an attempt to treat cholesterol by 1.1% of US adults. Consistent with previous surveys, this one found the majority of individuals (55%) used it in conjunction with conventional treatment. A trial review of phytosterols and/or phytostanol, an average dose of 2.15 g/day, reported an average 9% reduction in LDL-cholesterol. In 2000, the Food and Drug Administration approved the labeling of foods containing certain amounts of phytosterol ester or phytostanol ester as a cholesterol-lowering; In 2003, the FDA Interim Health Claim Rule stated that label claims for dietary or dietary supplements gave more than 0.8 g/day of phytosterols or phytostanols. Some researchers, however, are concerned about dietary supplementation with sterol esters and draw attention to the lack of long-term safety data.

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Epidemiology

High total cholesterol levels in the United States in 2010 were more than 13%, down from 17% in 2000.

Average cholesterol in the UK is 5.9 mmol/L, whereas in rural China and Japan, total cholesterol averages 4 mmol/L. The rate of coronary artery disease is high in the UK, but low in rural China and Japan.

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Research

A variety of clinical practice guidelines have addressed the treatment of hypercholesterolaemia.

The National Cholesterol Education Program revised their guidelines; However, their 2004 revision has been criticized for using non-scrambled observation data.

In the UK, the National Institute for Health and Clinical Excellence has made recommendations for the treatment of high cholesterol levels, published in 2008.

The Task Force for the management of dyslipidaemia from the European Society of Cardiology and the European Atherosclerosis Society published guidelines for the management of dyslipidaemia in 2011.

Gene therapy is being studied as a potential treatment.

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Custom population

Among people whose life expectancy is relatively short, hypercholesterolemia is not a risk factor for death with any cause including coronary heart disease. Among people older than 70, hypercholesterolemia is not a risk factor for hospitalization with myocardial infarction or angina. There is also an increased risk in people older than 85 years in the use of statin drugs. Therefore, drugs that lower lipid levels should not be routinely used among people with limited life expectancy.

The American College of Physicians recommends for hypercholesterolaemia in diabetics:

1. Lipid-lowering therapy should be used for the secondary prevention of cardiovascular mortality and morbidity for all adults with known coronary artery disease and type 2 diabetes.
2. Statins should be used for primary prevention of macrovascular complications in adults with type 2 diabetes and other cardiovascular risk factors.
3. After lipid-lowering therapy begins, type 2 diabetes mellitus should consume at least moderate-dose statin.
4. For people with type 2 diabetes who consume statins, routine monitoring of liver function tests or muscle enzymes is not recommended except under certain circumstances.

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References

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External links

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