Classification of Hyperlipidemia

There are a number of classification systems available. In 1967, Fredrickson, Levy, and Lees introduced the first classification as a method of reporting that lipoproteins were raised. The World Health Organization adopted this classification (Table 3).

In 1987, the European Atherosclerosis Society recommended a five-group classification of primary hyperlipidemia (Table 4), and the National Cholesterol Education Program Adult Treatment Panel III published guidelines in 2002 for normal and elevated lipid levels (Table 5).

Clinically, the most important step is to determine if the lipid abnormality is primary or secondary to another condition. Table 6 shows the lipid changes seen in some common conditions. In practice, it is often easiest to classify lipid abnormalities into three

Table S Fredrickson/WHO classification of hyperlipoproteinemia

Type

Lipids increased

Lipoprotein increased

I

Triacylglycerol

Chylomicrons

II-a

Cholesterol

LDL

II-b

Cholesterol and

LDL and VLDL

triacylglycerol

III

Cholesterol and

Chylomicron remnants and IDL

triacylglycerol

IV

Triacylglycerol

VLDL

V

Cholesterol and

Chylomicrons and VLDL

triacylglycerol

Table 4 European Atherosclerosis Society classification of hyperlipoproteinemia

Group

Total

Triacylglycerols

cholesterol

(mmol/l)

(mmol/l)

Normal

<5.2

<2.3

A (mild hypercholesterolemia)

5.2-6.5

and <2.3

B (moderate

6.5-7.8

and <2.3

hypercholesterolemia)

C (isolated

<5.2

and 2.3-5.6

hypertriglyceridemia)

D (combined hyperlipidemia)

5.2-7.8

and 2.3-5.6

E (severe

>7.8

and/or >5.6

hypercholesterolemia and/or

hypertriglyceridemia)

Table 5 Adult Treatment Panel III levels for blood lipids

Classification

Total

LDL

Triacylglycerols

cholesterol

cholesterol

(mmol/l)

(mmol/l)

(mmol/l)

Normal

<5.2

<2.59

<1.7

Above optimal

2.6-3.3

Borderline high

5.2-6.2

3.4-4.1

1.8-2.2

High

>6.2

4.2-4.8

2.3-5.6

Very high

>4.9

>5.6

Table 6 Lipid changes in some common conditions

Condition

Total

HDL

Triacylglycerol

cholesterol

cholesterol

Diabetes

Normal or "

#

mellitus

Hypothyroidism

Î

Î

Can be "

Chronic renal

Normal or "

#

failure

Nephrotic

Î

Often #

Often "

syndrome

Cholestasis3

Î

Can be "

aAn abnormal lipoprotein called LpX is present.

aAn abnormal lipoprotein called LpX is present.

categories: raised total cholesterol, raised triacylglycerol, mixed hyperlipidemia.

It is becoming clear that certain lipoprotein patterns are particularly atherogenic. Elevated IDL with increased small, dense LDL particles and low HDL is one such pattern. Classifications based on these patterns may emerge.

Causes of Hypercholesterolemia

Serum cholesterol at birth does not exceed 2.5 mmol/l and is rarely above 4.0 mmol/l in children. The values for adults are given in Table 5. A raised cholesterol level, with little or no elevation of triacylglycerol, is usually a result of raised LDL

level. Occasionally, a raised HDL level is responsible for high cholesterol, as seen in the familial condition of primary hyper-a-lipoproteinemia. Secondary causes given in Table 6 include hypothyroidism, nephrotic syndrome, some cases of diabetes mellitus, and cholestasis. Primary causes include polygenic familial hypercholesterolemia, in which several gene abnormalities together with environmental effects serve to raise serum cholesterol. Several genetic loci contribute to increased plasma LDL levels, but there are five specific monogenic disorders that increase LDL: familial hypercholesterole-mia (LDL receptor gene), familial ligand-defective apoB-100 (apoB gene), autosomal recessive hypercholesterolemia (ARH gene), sitosterolen (ABCG5 or ABCG8 genes), and cholesterol 7a-hydroxylase deficiency (CYP7A1 gene).

Much less common, but more clearly defined, are the two autosomal conditions of familial combined hyperlipidemia (FCH) and monogenic familial hypercholesterolemia (FH). In FCH, there appears to be an increase in apoB production and thus an increase in serum LDL. Serum VLDL levels are raised in one-third of these subjects with an associated triacylglycerol increase, one-third show increases in LDL, and one-third show increases in LDL and VLDL. Monogenic FH is caused by a defect in the LDL receptor (LDLR). The consequent reduced LDL uptake by cells, particularly in the liver, results in raised LDL and cholesterol levels. There are 683 mutations in the LDLR gene. Of these, 58.9% are missense mutations, 21.1% are minor rearrangements, 13.5% are major rearrangements, and 6.6% are splice site mutations. The majority of mutations are found in two functional domains of the LDLR, the ligand binding domain (42%) and the epidermal growth factor precursorlike domain (47%).

Predominant hypertriglyceridemia may result from raised VLDL or chylomicron levels. Secondary causes include excess alcohol ingestion, obesity and excess carbohydrate intake, diabetes mellitus, renal failure, and pancreatitis. Primary hypertriglyceridemia can be a result of familial combined hypertriglyceridemia, familial endogenous hypertriglyceridemia, or hyperchylomicronemia.

Familial endogenous hypertriglyceridemia results from increased hepatic triacylglycerol production with increased VLDL production. It is associated with obesity, glucose intolerance, and hyperuricemia. Hyperchylomicronemia is a result of inherited or acquired impairment of lipoprotein lipase activity.

Reduced insulin levels in diabetes mellitus impair the activity of lipoprotein lipase, and hyperchylomicrone-mia can occur. Inherited deficiency of the lipase enzyme is rarely seen, as is deficiency of the apolipoprotein (apoC-II) required to activate the enzyme.

Mixed hyperlipidemia is often a secondary condition. Primary causes include familial combined hyperlipidemia and type III hyperlipidemia (dys-fi-lipoproteinemia or broad fi disease). Type III hyperlipidemia is associated with the apoE 2/2 phe-notype, resulting in impaired recognition of apoE by hepatic receptors and an accumulation of IDL.

Dyslipoproteinemia is a central feature of the metabolic syndrome, which is associated with accelerated atherosclerosis. Visceral obesity, dyslipi-demia, insulin resistance, hypertension, and a proin-flammatory and prothrombotic state are the main characteristics of this condition. It has been defined by the World Health Organization and the National Cholesterol Education Programme. The worldwide increase in levels of obesity in the developed world may presage an increase in CHD.

Dietary Effects Principles of Treatment

Treatment of hyperlipidemia is part of the management of CHD risk. This encompasses lifestyle changes, such as stopping smoking, increasing exercise, and modifying diet, as well as management of hypertension. Diet is the cornerstone of treating hyperlipidemia, best delivered by qualified dieticians, involving the whole family.

The main aims of diet are to correct excess calorie intake and to reduce the cholesterol and saturated fat content. Patients with hyperlipidemia can expect to see benefits from diet after 6 weeks and are reviewed every 4 months.

Diet can reduce total cholesterol 8-12%, with 60-80% of this change attributed to reductions in saturated fatty acid intake. The remaining change comes from reduced dietary cholesterol and changes in the intake of fiber and monounsaturated and polyunsaturated fatty acids. Dietary modification may not be successful in some primary hyperlipide-mias. The Diet and Reinfarction Trial and the Mediterranean Diet Study in postmyocardial infarction survivors showed that dietary modification, not necessarily accompanied by plasma cholesterol lowering, can improve short-term prognosis.

Fat Most of the saturated fats in the diet come from just four fatty acids: lauric acid (C12:0), myr-istic acid (C14:0), palmitic acid (C16:0), and stearic acid (C18:0). The first three fatty acids reduce LDL receptor activity, raising LDL and total cholesterol by approximately 0.25mmol/l per 10 g of saturated fat ingested. Watts and coworkers showed that total dietary fat (mainly saturated) increases hepatic VLDL-apoB secretion, so decreasing total fat intake should decrease hepatic apoB secretion.

Monounsaturates are being recommended more often. The most common is oleic acid (C18:1), found in the Mediterranean diet as olive oil. Animal fats are rich in monounsaturates but are also rich in saturated fats. The trans isomers of monounsatu-rates may raise total and LDL cholesterol and are best avoided.

In both type I and type V hyperlipidemia, the dietary management is to reduce fat intake to 20-40g/day. Medium-chain triacylglycerols are used and fish oils can be tried, but the mainstay of therapy is reduced fat intake. Dietary ^-sitosterol can block cholesterol absorption to a limited extent but is not used therapeutically.

Carbohydrate and calories Obesity is a common cause of hypertriglyceridemia due to raised VLDL levels in the obese subject. This may be because of an increase in insulin resistance resulting from obesity with concomitant hyperinsulinemia and elevation in hepatic VLDL synthesis. Some hypertrigly-ceridemic patients experience a further increase in triacylglycerol levels with an increase in carbohydrate intake, known as carbohydrate induction. This situation is accompanied by an increase in serum insulin levels. With weight reduction, the hypertryglyceridemia reduces and HDL cholesterol increases after 24 months.

Mild alcohol ingestion increases HDL cholesterol. Excess alcohol ingestion can precipitate hypertrigly-ceridemia of a type IV phenotype due to increased hepatic synthesis and secretion that, in subjects who cannot clear triacylglycerols efficiently, can progress to a type V phenotype. Serum LDL levels are usually low in alcoholics, although in some individuals they can be elevated.

Protein Changes in dietary protein intake have minimal effects on lipid levels. Vegetarians have lower serum lipids than nonvegetarians, but it is not clear how much of this is the result of a change from animal to vegetable protein.

Fiber Soluble fiber such as oat bran and guar lower cholesterol levels, perhaps by reducing bile acid absorption.

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Responses

  • FRANCESCA
    Who classification of hyperlipidemia?
    1 year ago
  • nicole kuhn
    What is classification and nutritional aspects of hyperlipidemia?
    12 months ago
  • jessica
    Who classification of hyperlipidaemia levels?
    11 months ago
  • rasmus
    How to classify someone as hyperlipidemia?
    9 months ago

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