Hyperlipidemia


Hyperlipidemia is abnormally high levels of any or all lipids or lipoproteins in the blood. The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding. Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing medication to control blood lipid levels.
Lipids are transported in a protein capsule. The size of that capsule, or lipoprotein, determines its density. The lipoprotein density and type of apolipoproteins it contains determines the fate of the particle and its influence on metabolism.
Hyperlipidemias are divided into primary and secondary subtypes. Primary hyperlipidemia is usually due to genetic causes, while secondary hyperlipidemia arises due to other underlying causes such as diabetes. Lipid and lipoprotein abnormalities are common in the general population and are regarded as modifiable risk factors for cardiovascular disease due to their influence on atherosclerosis. In addition, some forms may predispose to acute pancreatitis.

Signs and symptoms

Hyperlipidemia, on its own, is typically asymptomatic. However, it can predispose one to more serious medical problems via lipid buildup, such as atherosclerosis, heart attack, or stroke.
Some indicators of hyperlipidemia are xanthomas, which are yellow "bumps" on the arms, legs, or trunk, or xanthelasmas, which are yellowish deposits of fat on the eyelids.

Causes

The major causes of hyperlipidemia are either genetic or lifestyle causes. Individuals with a genetic predisposition for hyperlipidemia or a family history are more at risk for this disease. However, unhealthy habits can lead to secondary hyperlipidemia: A diet heavy in trans fats or saturated fats, contained in red meats and dairy, can lead to secondary hyperlipidemia. Not getting enough exercise can also be a risk factor. Stress and alcohol can lead to elevated levels of cholesterol. Smoking damages blood vessels, contributing to atherosclerosis and lowers HDL levels. An increase in age also increases the risk of hyperlipidemia.

Classification

Hyperlipidemias may basically be classified as either familial when caused by specific genetic abnormalities or acquired when resulting from another underlying disorder that leads to alterations in plasma lipid and lipoprotein metabolism. Also, hyperlipidemia may be idiopathic, that is, without a known cause.
Hyperlipidemias are also classified according to which types of lipids are elevated, that is hypercholesterolemia, hypertriglyceridemia or both in combined hyperlipidemia. Elevated levels of Lipoprotein may also be classified as a form of hyperlipidemia.

Familial (primary)

Familial hyperlipidemias are classified according to the Fredrickson classification, which is based on the pattern of lipoproteins on electrophoresis or ultracentrifugation. It was later adopted by the World Health Organization. It does not directly account for HDL, and it does not distinguish among the different genes that may be partially responsible for some of these conditions.

Type I

Type I hyperlipoproteinemia exists in several forms:
Type I hyperlipoproteinemia usually presents in childhood with eruptive xanthomata and abdominal colic. Complications include retinal vein occlusion, acute pancreatitis, steatosis, and organomegaly, and lipemia retinalis.

Type II

Hyperlipoproteinemia type II is further classified into types IIa and IIb, depending mainly on whether elevation in the triglyceride level occurs in addition to LDL cholesterol.
Type IIa
This may be sporadic, polygenic, or truly familial as a result of a mutation either in the LDL receptor gene on chromosome 19 or the ApoB gene. The familial form is characterized by tendon xanthoma, xanthelasma, and premature cardiovascular disease. The incidence of this disease is about one in 500 for heterozygotes, and one in 1,000,000 for homozygotes.
HLPIIa is a rare genetic disorder characterized by increased levels of LDL cholesterol in the blood due to the lack of uptake of LDL particles. This pathology, however, is the second-most common disorder of the various hyperlipoproteinemias, with individuals with a heterozygotic predisposition of one in every 500 and individuals with homozygotic predisposition of one in every million. These individuals may present with a unique set of physical characteristics such as xanthelasmas, tendon and tuberous xanthomas, arcus juvenilis, arterial bruits, claudication, and of course atherosclerosis. Laboratory findings for these individuals are significant for total serum cholesterol levels two to three times greater than normal, as well as increased LDL cholesterol, but their triglycerides and VLDL values fall in the normal ranges.
To manage persons with HLPIIa, drastic measures may need to be taken, especially if their HDL cholesterol levels are less than 30 mg/dL and their LDL levels are greater than 160 mg/dL. A proper diet for these individuals requires a decrease in total fat to less than 30% of total calories with a ratio of monounsaturated:polyunsaturated:saturated fat of 1:1:1. Cholesterol should be reduced to less than 300 mg/day, thus the avoidance of animal products and to increase fiber intake to more than 20 g/day with 6g of soluble fiber/day. Exercise should be promoted, as it can increase HDL. The overall prognosis for these individuals is in the worst-case scenario if uncontrolled and untreated individuals may die before the age of 20, but if one seeks a prudent diet with correct medical intervention, the individual may see an increased incidence of xanthomas with each decade, and Achilles tendinitis and accelerated atherosclerosis will occur.
Type IIb
The high VLDL levels are due to overproduction of substrates, including triglycerides, acetyl-CoA, and an increase in B-100 synthesis. They may also be caused by the decreased clearance of LDL. Prevalence in the population is 10%.
This form is due to high chylomicrons and IDL. Also known as broad beta disease or dysbetalipoproteinemia, the most common cause for this form is the presence of ApoE E2/E2 genotype. It is due to cholesterol-rich VLDL. Its prevalence has been estimated to be approximately 1 in 10,000.
It is associated with hypercholesterolemia, hypertriglyceridemia, a normal ApoB concentration, and two types of skin signs. It is characterized by the early onset of cardiovascular disease and peripheral vascular disease. Remnant hyperlipidemia occurs as a result of abnormal function of the ApoE receptor, which is normally required for clearance of chylomicron remnants and IDL from the circulation. The receptor defect causes levels of chylomicron remnants and IDL to be higher than normal in the blood stream. The receptor defect is an autosomal recessive mutation or polymorphism.

Type IV

is an autosomal dominant condition occurring in approximately 1% of the population. This form is due to high triglyceride level. Other lipoprotein levels are typically within the normal reference range or slightly increased. Treatment include diet control, fibrates and niacins. Although statins are typically the first line treatment for hyperlipidemias, fibrates are actually better at reducing elevated triglyceride levels and are considered first line.

Type V

Hyperlipoproteinemia type V, also known as mixed hyperlipoproteinemia familial or mixed hyperlipidemia, is very similar to type I, but with high VLDL in addition to chylomicrons.
It is also associated with glucose intolerance and hyperuricemia.
In medicine, combined hyperlipidemia is a commonly occurring form of hypercholesterolemia characterized by increased LDL and triglyceride concentrations, often accompanied by decreased HDL. On lipoprotein electrophoresis it shows as a hyperlipoproteinemia type IIB. It is the most common inherited lipid disorder, occurring in about one in 200 persons. In fact, almost one in five individuals who develop coronary heart disease before the age of 60 has this disorder. The elevated triglyceride levels are generally due to an increase in very low density lipoprotein, a class of lipoprotein prone to cause atherosclerosis.
Both conditions are treated with fibrate drugs, which act on the peroxisome proliferator-activated receptors, specifically PPARα, to decrease free fatty acid production.
Statin drugs, especially the synthetic statins can decrease LDL levels by increasing hepatic reuptake of LDL due to increased LDL-receptor expression.

Unclassified familial forms

These unclassified forms are extremely rare:
Acquired hyperlipidemias often mimic primary forms of hyperlipidemia and can have similar consequences. They may result in increased risk of premature atherosclerosis or, when associated with marked hypertriglyceridemia, may lead to pancreatitis and other complications of the chylomicronemia syndrome. The most common causes of acquired hyperlipidemia are:
Other conditions leading to acquired hyperlipidemia include:
Treatment of the underlying condition, when possible, or discontinuation of the offending drugs usually leads to an improvement in the hyperlipidemia.
Another acquired cause of hyperlipidemia, although not always included in this category, is postprandial hyperlipidemia, a normal increase following ingestion of food.