Chapter 87: Dyslipidaemia

Dyslipidaemia is the presence of an abnormal lipid/lipoprotein profile in the serum and can be classified as:

• predominant hypertriglyceridaemia

• predominant hypercholesterolaemia

• mixed pattern with elevation of both cholesterol and triglyceride (TG)

Modern epidemiological studies have established the facts that elevated plasma cholesterol causes pathological changes in the arterial wall leading to CAD, and that lipid-lowering therapy results in reduction of coronary and cerebrovascular events with improved survival.

A Cochrane systematic review² of 18 large RCTs found high quality evidence that statins reduce all-cause mortality and major vascular events. The number needed to treat (NNT) with statins varies markedly depending on the risk category the person falls into (see TABLE 87.1).

The main focus of treatment will be on primary dyslipidaemia but secondary causes (see TABLE 87.2) also need to be addressed. LDL-C is the lipid with the highest correlation with CHD and its level remains the primary target of lipid modifying therapy. The statins are the first-line therapy for a raised level. Like total cholesterol measurement, LDL-C should not be used in isolation.

• Major risk factors for CAD include:

  • – increased LDL cholesterol + reduced HDL cholesterol

  • – ratio LDL-C:HDL-C >4

• Risk increases with increasing cholesterol levels

• TG level >10 mmol/L increases risk of pancreatitis

• Management should be correlated with risk factors

• 10% reduction of total cholesterol gives 20% reduction in CAD after 3 years

• LDL-C reduction with statin therapy reduces heart attacks, stroke, the need for revascularisation and death

• Screening is recommended 5 yearly from age 45 years (Aboriginal and Torres Strait Islander people from 35 years)

The following fasting tests are recommended in patients every 5 years, starting at age 45 years:

• serum cholesterol level, HDL-C, LDL-C and triglyceride (TG)

Confirm an initial high result with a second test at 6–8 weeks. Those at moderate risk (5-year CV risk >10%) should have a screening test every two years. Commence testing at 35 years of age if Aboriginal or Torres Strait Islander.

All patients should receive advice and support regarding lifestyle risk management. Patients requiring pharmacological treatment are summarised in TABLE 87.3.

• Dietary measures:

  • – keep to ideal weight (as for cardiovascular disease, see CHAPTER 85)

  • – reduce saturated and trans fat intake, especially dairy products and meat

  • – avoid fast foods and deep-fried foods

  • – replace saturated fats with mono or polyunsaturated fats

  • – use approved cooking methods (e.g. steaming, grilling)

  • – trim fat off meat, remove skin from chicken

  • – avoid biscuits and cakes between meals

  • – high-fibre diet, especially fruit and vegetables (to increase soluble fibre)

  • – introduce plant sterol-enriched milk, margarine or cheeses

  • – alcohol intake 0–2 standard drinks/day

  • – drink more water

• Encourage physical activity: regular exercise program

• Cease smoking

• Cooperation of family is essential

• Exclude secondary causes (e.g. kidney disease, type 2 diabetes, hypothyroidism, obesity, alcohol excess—especially ↑ TG), specific diuretics

Checkpoints

• Diet therapy effective (TG ↓, LDL-C ↓) within 6–8 weeks

• Continue at least 6 months before considering drug therapy in all but the highest-risk category

The choice of the lipid-lowering agent depends on the pattern of the lipid disorder.^5,6 See TABLE 87.4. Use the following agents in addition to diet.

Treatment should commence with a statin. If LDL-C levels are not reduced to target levels or a maximally tolerated dose on a statin, add one of ezetimibe,^5,8 bile acid binding resin or nicotinic acid. These agents can be used as monotherapy if statins cannot be tolerated.

Hypercholesterolaemia especially ↑ LDL-C

Choose from the following.^6,9

First-line agent

1. HMG-CoA reductase inhibitors (statins—see TABLE 87.4): supported by evidence but be cautious in patients with muscle or hepatobiliary disease. Typical reduction is 30–50%.⁹

   • adverse effects: GIT side effects, myalgia, abnormal liver function (uncommon)

   • monitor: measure LFTs (ALT and CPK) and CK as baseline

   • repeat LFTs after 4–8 weeks. It is no longer recommended to continue to monitor these unless patient becomes symptomatic.⁵

   Additional drug therapy (options):

2. Ezetimibe 10 mg daily (especially if statin-intolerant). Reduces LDL by about 18%.⁹

3. Combination: ezetimibe + statin (consider if cholesterol above target)⁸

4. Bile acid binding resins (typically reduce LDL by 15–24%):

   • e.g. cholestyramine 4 g daily in fruit juice increasing to maximum tolerated dose (often poorly tolerated)

   • adverse effects: GIT side effects (e.g. constipation, offensive wind)

5. Fibrates: consider if above drugs not tolerated (e.g. fenofibrate 145 mg (o) daily—special care with renal impairment)

6. Nicotinic acid

   • nicotinic acid 250 mg (o) bd with food daily, increase gradually to max. 1000 mg tds if necessary (effective lipid reduction)

   • adverse effects: flushing (common), gastric irritation, gout

   • minimise side effects with gradual introduction; take with food

7. Evolocumab: a new monoclonal antibody agent for familial hypercholestoerolaemia and muscle-related statin intolerance¹⁰

Resistant LDL-C elevation

1. Combination statin + ezetimibe

2. Combined statin and resin

   • cholestyramine 4–8 g (o) mane

   • plus

   • a statin

Moderate to severe (isolated or predominant) TG elevation⁶

Fibrate:

• gemfibrozil 600 mg (o) bd

• or

• fenofibrate 145 mg (o) daily

Note: Slow response; monitor LFTs; predisposes to gallstones and myopathy

• and/or

• n-3 fish oil concentrate 6 g (o) daily in divided doses to max. 15 g/day

• add

• nicotinic acid if insufficient response

Note: Reduction in alcohol intake is important.

Massive hypertriglyceridaemia (TG) 10 mmol/L:

• fibrate plus fish oil plus (if necessary) nicotinic acid

Mixed hyperlipidaemia (↑ TG + ↑ LDL-C)

• If TG <4: a statin

• If TG >4: a fibrate

Consider combination therapy, e.g.:

• fish oil + statin

• fibrate + resin

Note: Statin + gemfibrozil increases risk of myopathy and should ideally be avoided.

Familial hypercholesterolaemia¹¹

This is a dominant inherited condition causing accelerated cardiovascular disease by 20–40 years. Diagnosis requires exclusion of secondary causes, e.g. nephrotic syndrome. Refer to Dutch lipid diagnostic criteria.¹¹

The decision to commence drug therapy should be based on at least two separate measurements at an accredited laboratory.

Be careful with beta blockers and diuretics affecting lipid levels.

Length of treatment

Possibly lifelong, although the need to consider deprescribing may become the priority with age over 75 years and increasing frailty or reduced life expectancy.

Follow-up investigations

• Serum lipids (overly frequent testing is widespread—for those on therapy, don’t monitor levels more often than 6–12 monthly without good reason)

• LFTs (ALT and CPK)

• Possibly CK

• Biochemical monitoring

Children

In general there is little justification for using lipid-regulating drugs in children, especially as the drugs have been shown to reduce heart disease within 2–5 years in adults.⁶ Initial dietary advice and avoidance of smoking is recommended. Bile acid binding resins are safe to use.

The elderly

The role of lipid therapy remains unclear. Generally, elderly patients with established CHD should receive standard lipid management unless their general medical status is poor or the potential harms start to outweigh potential benefits.

Pregnancy⁶

As a general rule the increase in cholesterol level associated with pregnancy subsides after delivery. Systemically absorbed lipid-lowering agents may be unsafe during pregnancy and should be avoided.

Claims have been made for the cholesterol-lowering properties of policosanol (derived from sugar cane), fish oils, plant sterols, vitamin E, garlic and lecithin. The evidence from RCTs to date indicates a modest benefit from policosanol, fish oils (consuming a fish-based meal at least twice a week is recommended) and plant sterols but there is insufficient evidence to recommend vitamin E, garlic and lecithin.¹²

Hand-out sheets from Murtagh’s Patient Education 7th edition:

• Cardiovascular (including coronary) risk factors

• Cholesterol: how to lower cholesterol