Hypertriglyceridaemia (without hypercholesterolaemia)
A serum triglyceride concentration below 2.0 mmol litre-I is normal. In the range 2.0-6.0 mmol litre-I no specific intervention will be needed unless there are many coincident cardiovascular risk factors, and in particular a strong family history of early cardiovascular death. In general, patients should be advised that they have a minor lipid problem, offered advice on weight reduction if obese, and advice on correcting other cardiovascular risk factors.
If the triglyceride concentration is above 6.0 mmol litre-I there is a risk of pancreatitis and retinal vein thrombosis. Patients should be advised to reduce their weight if overweight and start a formal lipid-lowering diet. A proportion of individuals with hypertriglyceridaemia have livers which respond to even moderate degrees of alcohol intake by allowing accumulation or excess production of VLDL particles. If hypertriglyceridaemiapersists lipid measurements should be repeated before and after a 6 week interval of complete abstinence from alcohol. If a considerable improvement results, lifelong abstinence may prove necessary. Other drugs, including thiazides, oestrogens and glucocorticoids, can have a similar effect to alcohol in susceptible patients. If the triglyceride concentration remains elevated above 6.0 mmol litre “, despite the above measures, drug therapy is warranted. A fibric acid derivative is the agent of first choice. icotinic acid may be used in addition but its side-effects are often a problem. Fish oil capsules (Maxepa) which contain w-3 (n-3) long-chain fatty acids are also effective in lowering triglyceride concentrations.
The severe hypertriglyceridaemia associated with the rare disorders of lipoprotein lipase deficiency and apoprotein C-IJ deficiency may require restriction of dietary fat to 10-20% of total energy intake and the introduction of medium-chain triglycerides, which are not absorbed via chylomicrons.
Hypercholesterolaemia (without hypertrig Iyceridaem ia)
Individuals with polygenic hypercholesterolaemia require a graded approach and most will not need drug therapy. Perimenopausal women with hypercholesterolaemia should be offered female hormone replacement therapy as the risk of cardiovascular disease rises sharply after the menopause and hormone replacement therapy reduces this risk even in normocholesterolaemic women. A small number of women respond adversely to exogenous oestrogens with a rise in lipids and, therefore, measurement of the fasting lipids is necessary shortly after starting treatment. Individuals with familial hypercholesterolaemia will require treatment with both diet and drugs. FIBRATES raise HDL concentrations (beneficial) and reduce LDL cholesterol concentrations by 10-15% and are useful in patients with modest hypercholesterolaemia. Gemfibrozil has been demonstrated to reduce the incidence of cardiovascular events in a carefully performed large randomized double-blind placebo-controlled trial (Helsinki Heart Study) of patients with moderate hypercholesterolaemia,
whereas the benefit of the other fibrates on outcome has not been investigated.
BILE ACID BINDING RESINS produce an 8-15% reduction in LDL cholesterol concentration. Cholestyramine has been shown to reduce the incidence of cardiovascular events in hypercholesterolaemic patients in a carefully performed randomized double-blind placebocontrolled trial (Lipid Research Clinics Trial). The safety profile of these drugs is good and their long-term safety is established. They are particularly useful when a lipidlowering agent needs to be given to women of childbearing age. They have a synergistic effect when given with an HMG-CoA reductase inhibitor. This combination can reduce LDL cholesterol concentrations by 50-60%.
HMG-CoA REDUCTASE INHIBITORS reduce LDL cholesterol concentrations by 30-40%. There are no trial data showing an influence on outcome. In severe hypercholesterolaemia it is often combined with a bile acid binding resin (see above). Concurrent therapy with HMG-CoA reductase inhibitors and fibrates is usually avoided, in view of their overlapping side-effects, but in very severe cases such mixed therapy has been undertaken under very close supervision.
PROBUCOL is now used only rarely as a fourth-line agent.
Combined hyperlipidaemia (hypercholesterolaemia and hypertrig Iyceridaem ia)
Treatment is the same for all varieties of combined hyperlipidaemia.
For any given cholesterol concentration the hypertriglyceridaemia found in the combined hyperlipidaemias increases the cardiovascular risk considerably. Treatment is aimed to reduce serum cholesterol below 6.5 mmol litre ” and triglycerides below 2.0 mmollitre-I. Therapy is with diet in the first instance and with drugs if an adequate response has not occurred. Fibric acid derivatives are the treatment of choice since these reduce both cholesterol and triglyceride concentrations, and also have the benefit of raising cardioprotective HDL concentrations. The combination of fibric acid derivative and bile acid binding resin is of considerable use when a fibrate alone produces an insufficient reduction in LDL cholesterol. Nicotinic acid can be used in addition, although its unwanted effects render it a third-line agent.
The lipid-lowering diet
Studies have shown that dietitians helping patients adjust their own diet to meet the nutritional targets set out below produce a better lipid-lowering effect than issuing of standard diet sheets and advice from a doctor. The main elements of a lipid-lowering diet are:
REDUCTION OF TOTAL FAT INTAKE. Dairy products and meat are the principal sources of saturated fat in the diet. Intake of these products should therefore be reduced, and fish and poultry should be substituted. Visible fat and skin should be removed before cooking and preparing meat dishes. Meat products including pates, sausages and reconstituted meats (such as luncheon meat) should be avoided since the concentration of fat is unknown and often high. Baking and grilling of meats reduces the fat content and is preferred to frying. Low-fat or cottage cheese and skimmed or semi-skimmed milk should be substituted for the standard full-fat varieties. Pastries and cakes contain large quantities of fat and should be avoided. The overall aim should be to decrease fat intake such that it is providing approximately 30% of the total energy intake in the diet. Further reduction in fat intake is unacceptable to many patients.
SUBSTITUTION OF MONOUNSATURATES AND POLYUNSATURATES. Monounsaturated oils, particularly olive oil, and polyunsaturated oils such as sunflower, safflower, corn and soya oil should be used in cooking instead of saturated fat-rich alternatives.
REDUCTION IN DIETARY CHOLESTEROL INTAKE.
Liver, offal and fish roes should be avoided. Although eggs and prawns are rich in cholesterol their total contribution to the body’s cholesterol pool is small and they can still be part of a balanced lipid-lowering diet.
INCREASE FIBRE (non-starch polysaccharides, NSPs) content. Food high in soluble fibre, such as pulses, legumes, root vegetables, leafy vegetables, and unprocessed cereals, help reduce circulating lipid concentrations, and should be substituted in the diet in the place of higher fat alternatives.
REDUCE ALCOHOL CONSUMPTION. Excess alcohol is an important cause of secondary hyperlipidaemia, and may worsen primary lipid disorders.
ACHIEVE IDEAL BODY WEIGHT. Treatment of obesity is particularly important in the management of hyperlipidaemia both because it will exacerbate the lipid disorder itself, and also because obesity is an independent cardiovascular risk factor.