When and who to test for lipids?

The whole area of lipid testing – interpretation of abnormal results, prescribing of statins, primary and secondary prevention, use of alternative treatments – is often a daily issue for GPs, however, it is not without its controversies and dilemmas.

When should a GP screen for lipid levels?

 Often a GP will screen because of risk factors, but at other times it is patient-driven. Many GPs have on-site testing in their practices. This can be convenient for patients to use as they do not have to travel to hospitals. However, costing must be to the fore in such a setting. Machines are expensive to buy, have to be regularly serviced and each testing strip costs around €25.

The area of lipid testing is getting enormous attention nowadays, not least because of the inherent cost and time taken. A recent article in the British Journal of General Practice¹ stated that there has been a tenfold increase in lipid testing over the past 20 years.

Alarmingly, in the article it says that the proportion of lipid testing for monitoring has risen from 28-61% in the past 10 years. This puts an extraordinary strain on laboratory services and GPs really need solid guidelines to know when to retest in terms of monitoring.

Ideally, GPs should be putting more emphasis on lipid testing for case-finding or cardiovascular risk assessment rather than for monitoring purposes. Some experts indeed add that there may be measurement error if monitoring is too frequent.

The most recent guidelines² for use of statins in primary prevention state that:

• Statins may benefit patients who have a greater than 2% per year risk of cardiovascular disease
• Statins should be considered in men with diabetes aged over 50 years
• Statins should be considered in women with diabetes aged over 60 years
• Statins should be considered for men with multiple risk factors when they reach 55 years 
• Statins should be considered for women with multiple risk factors when they reach 65 years  
• A low-dose statin may be sufficient in elderly patients.

Elderly people with hypertension may benefit from additional anti-hypertensive treatment because of the risk of stroke and heart failure and this should be a prime consideration.

So therefore, GPs must be cautious when prescribing statins for primary prevention. They should only prescribe for those who have a 20% 10-year risk of developing a cardiovascular event (or an annual cardiovascular disease risk rate of 2%).

Lifestyle

Lifestyle advice is the cornerstone of lipid management. This includes dietary advice; stopping smoking if this is an issue; and advice on alcohol intake and the promotion of exercise on a daily basis if possible. 

Exercise alone can increase HDL by up to 30%. An unsaturated fat diet can raise HDL versus other diets. Replacing carbohydrates with a protein or monosaturated fat diet can improve CHD risk. If lipid testing shows a mild increase in cholesterol, all the above should be addressed initially. 

If there is no cardiovascular risk present, a trial of dietary change and exercise alone may be prudent. There are excellent diet sheets available which patients can put on the door of their fridge as a constant reminder! Lifestyle changes alone may be sufficient to get cholesterol into the normal range for some patients.

Statins

Statins are the main group of lipid-regulating drugs.  There are five statin types, all of which decrease LDL cholesterol and have a modest effect on reducing triglycerides. They are atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin. Atorvastatin and rosuvastatin are the newer, more potent types.

Many patients will get their lipid levels into the normal range with a lower dose of a statin type. However, there are some patients that need more aggressive therapy with the newer, more potent types. These include acute coronary syndromes, severe hypercholesterolaemia and patients with diabetes.

Side-effects of statins

When prescribing statins, patients must be warned of certain side-effects including CNS, auditory, gastrointestinal, psychiatric, musculoskeletal, metabolic, hepatic, reproductive, immunological and rarely, interstitial lung disease with high doses. The notion that some or any of these side-effects might occur may push people into an aggressive look at lifestyle changes to see if they can get within normal range without statins.

Two statin types are more water-soluble and so less likely to cross the blood-brain barrier. These include pravastatin and rosuvastatin and are less likely to cause neuropsychiatric side-effects, eg. depression, sleep disturbance, memory loss, headache, peripheral neuropathy, dizziness and hypoesthesia. Very rarely, statins may cause interstitial lung disease, but watch out for symptoms of dyspnoea, non-productive cough and deterioration in general health.  

Because of the known increased risk of myopathy seen with high-dose simvastatin, it may be best to use the newer, more potent statins, eg. atorvastatin or rosuvastatin if high doses are indicated.

Drug interactions occur with statins and those on warfarin and statins need careful monitoring of their INR. All patients on statins should avoid grapefruit. Both simvastatin and atorvastatin affect metabolism via cytochrome p450 and probably should be avoided with patients taking itraconazole, ketoconazole, erythromycin and clarithromycin.  

If patients are taking verapamil, amiodarone or diltiazem, then lower doses of simvastatin or atorvastatin should be prescribed. Statins are contraindicated in pregnancy and lactation. Statins are also contraindicated in active liver disease, impaired liver function, myopathy and cholestasis. Statins may be prescribed in the presence of abnormal liver function tests provided the LFTs are less than three times the normal values.

In all patients on lipids, LFT monitoring should be done as a baseline within three months and again at 12 months.  If they are normal at 12 months they do not need repeating unless indicated (according to NICE guidelines³).

Hypercholesterolaemia

Familial hypercholesterolaemia (FH) is the most common cause of premature coronary heart disease. It is under-diagnosed in primary care. Statins are highly effective in treatment. FH is autosomal-dominant so siblings and children of an affected person have a 50% chance of being affected. One in 500 people are affected. DNA testing is particularly good in younger patients. We should be on the alert if we get a cholesterol level > 7.5, but firstly, rule out secondary causes, eg. hypothyroid, diabetes and drug therapy.

Criteria for diagnosis of FH: cholesterol > 7.5; LDL > 4.9 in adult (> 6.7 and > 4 in child). Positive family history of MI < 50 years in second-degree relative or MI < 60 years in first degree relative.

It is important to refer suspected cases of familial hypercholesterolaemia to a lipid clinic to confirm diagnosis, do family tracing, genetic screening and start aggressive treatment. The target is a 5% reduction in LDL levels using high-dose statin +/- ezetimibe.

Other lipid-lowering drugs

Apart from statins, the other group of lipid-lowering drugs includes fibrates, niacin, omega-3 fatty acids and ion-exchange resins, all of which may play an added role in achieving lipid goals.  

Fibrates reduce triglycerides. Fibrates may also reduce LDL and increase HDL. It may be best to separate taking the two drugs, eg. fibrate mane and statin nocte, as they compete at the same site in the liver and the risk of drug interactions are higher. Gemfibrozil is an example of a fibrate.

Nicotinic acid is a water-soluble B-complex vitamin which inhibits the release of free fatty acids from adipose tissue (less free fatty acids presented to the liver). Thus, it reduces LDL and triglycerides and raises HDL. It may also reduce ApoB which is thought to be a very atherogenic lipoprotein. Side-effects to its use include facial flushing. This may be lessened by taking aspirin 30 minutes beforehand. Nicotinic acid is not used first-line in diabetes as it may impair glucose tolerance.

Omega-3-acid ethyl esthers may help to lower triglyceride levels. They may be used as monotherapy if dietary measures are insufficient. They may also be combined with statins when there is insufficient control of triglycerides. They are also used as an adjuvant in secondary prevention post-myocardial infarction.

Ezetimibe is an ion-exchange resin. It localises at the brush border of the small intestine thus selectively inhibiting intestinal absorption of cholesterol and plant sterols. As mentioned earlier, it is now available in combination with simvastatin. Its use may be considered in familial hypercholesterolaemia.

As mentioned earlier, the whole area of lipids and statins is a challenge to GPs on a regular basis. There is often fine-tuning needed for best control. New research and new drugs are inevitable. Hopefully we can keep abreast and offer up best standards for our patients.