This article is based on USA recommendations. Consequently, the units employed for lipid levels are mg/dL. For readers from those countries more familiar with the mmol/L units, it's possible to convert mg/dL to mmol/L by multiplying by 0.02586. Alternately, to convert mmol/L to mg/dL, divide by 0.02586. For triglycerides, the corresponding conversion factor is 0.01129.

Introduction

In May 2001 the US National Heart, Lung, and Blood Institute issued new guidelines for managing high cholesterol levels. The vigorous approach that has been proposed almost triples the number of adults who should be receiving lipid-lowering drugs. Here is a summary of the new guidelines, slightly simplified. The first step is to determine the subject's likely risk of having coronary heart disease (CHD), followed by treatment dependent on the actual lipid profile.

Determine the risk level

All adults should have a fasting lipoprotein profile (total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride) done every 5 years. The cholesterol levels are now classified as follows, based on data from studies that assess the risk of coronary events:

LDL Cholesterol (mg/dL)	<100	Optimal
	100-129	Near optimal/above optimal
	130-159	Borderline high
	160-189	High
	>= 190	Very high
Total Cholesterol (mg/dL)	<200	Desirable
	200-239	Borderline high
	>= 240	High
HDL Cholesterol (mg/dL)	<40	Low
	>= 60	High

The major risk factors (excluding the actual LDL cholesterol level) to be used modifying for setting target LDL levels are:

• Cigarette smoking
• Hypertension (BP >=140/90 mmHg, or taking antihypertensive medication)
• Low HDL cholesterol - i.e. <40 mg/dL. (If the HDL cholesterol is over 60 mg/dL, this removes one risk factor from the total count.)
• Family history of premature CHD (CHD in male first degree relative <55 years; CHD in female first degree relative <65 years)
• Age: men >=45 years; women >=55 years

The target LDL cholesterol can now be individualized for the subject:

• No, or one, risk factor: <160 mg/dL
• More than one risk factor: <130 mg/dL
• Presence of diabetes, or CHD, or other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease): <100 mg/dL

The approach to treatment

Before deciding on a treatment plan, the physician should exclude the possibility of secondary hyperlipidemia. Any person with elevated LDL cholesterol or other form of hyperlipidemia should undergo clinical or laboratory assessment to rule out secondary dyslipidemia before initiation of lipid-lowering therapy. Causes of secondary dyslipidemia include: diabetes, hypothyroidism, obstructive liver disease, chronic renal failure, and some drugs (progestins, anabolic steroids, and corticosteroids). The appropriate tests to detect these conditions include: glycosylated hemoglobin serum TSH, serum liver enzymes, serum albumin, and urinalysis.

Roughly 50% of those who need to address their LDL cholesterol level can reach their target by lifestyle changes alone:

• Reduced intakes of saturated fats (<7% of total calories), trans fatty acids, and cholesterol (<200 mg per day)
• Enhanced LDL lowering with help from dietary plant stanols/sterols (2 g/day) and increased viscous (soluble) fiber (10-25 g/day)
• Weight reduction
• Increased physical activity (contributing approximately 200 Kcal per day).

At initiation of Therapeutic Lifestyle Changes (TLC) - Visit One - the patient is instructed to reduce saturated fat and dietary cholesterol, and take up moderate physical activity. Referral to a dietician can be discussed.

At Visit Two - 6 weeks later - the LDL cholesterol is estimated. If the LDL target is not reached, TLC is intensified: dietary advice is reinforced, along with possible referral to a dietician. Fiber intake should be increased, and plant stanols/sterols may be added.

At Visit Three - 6 weeks later - if the LDL target is still not achieved, and the patient has evidence of the metabolic syndrome¹, drug treatment should be started. In addition, weight management should be intensified, and physical activity supervised.

Depending on their response, patients can continue to be monitored at regular intervals (every 6 weeks), or have drug treatment added to the TLC regime. Of course, if the patient has established heart disease and is unlikely to achieve the LDL goal with TLC alone, drug treatment can be started at once. Otherwise, 6 months of TLC is reasonable before resorting to drug therapy for those patients still above their desired level.

Drug treatment

Once the decision is taken to initiate drug treatment - Visit One - a statin, a bile acid sequestrant or nicotinic acid may be given. Statins (HMG CoA reductase Inhibitors) are well tolerated², and have been shown to have benefits in addition to their lipid-lowering actions.³ They are usually the first choice for treatment.

At Visit Two 6 weeks later - if the LDL target has not been reached, one can increase the dose of the statin, or add a bile acid sequestrant or nicotinic acid.

At Visit Three - 6 weeks later - if the LDL target is still not achieved, the drug regime may be intensified, or the patient referred to a lipid specialist. Once the LDL target is reached, other lipid risk factors (hypertriglyceridemia, low HDL cholesterol) and non-lipid risk factors should be addressed.

One potential secondary target of therapy is the metabolic syndrome, which represents a constellation of lipid and nonlipid risk factors of metabolic origin. This is discussed more fully in a separate article - see the link below.

Hypertriglyceridemia should also be treated. Levels above 150 mg/dL are abnormal; 150-199 mg/dL is borderline high, 200-499 mg/dL high, and above 500 mg/dL very high. The primary aim of therapy is to reach the LDL goal, as outlined above. If the triglycerides are above 200 mg/dL after the LDL goal is reached, one should set a secondary goal for non-HDL cholesterol (i.e. total - HDL) at 30 mg/dL higher than LDL goal.

For both hypertriglyceridemia and low HDL cholesterol (<=40 mg/dL) continuing after LDL cholesterol control, weight management and physical activity measures should be stepped up, as well as increased lipid-lowering medication, with the addition of nicotinic acid or fibrates, as needed.

In the relatively near future, the role of homocysteine as a heart disease risk factor will become clearer (see link below); in the meantime, heart disease patients may possibly benefit from a multivitamin preparation containing 400 mcg of folate.

Conclusions

In spite of widespread public information about the risks associated with elevated lipid levels, control of serum cholesterol levels in the general population has not been good, by any criteria. Careful analyses of epidemiologic studies have now demonstrated the cardiac risks according to actual lipid levels, and resulted in the development of these new, aggressive, guidelines. It is hoped that the recommendations will lead to improved efforts to achieve better lipid control, with healthier lifestyles precluding the need for greater medical treatment.