Introduction

Most health professionals have now learned of the new guidelines for managing lipid profiles to prevent cardiovascular events that have been proposed in Adult Treatment Profile III issued by the US National Cholesterol Education Program (NCEP). They are more stringent than the earlier recommendations, with emphasis on risk factors other than low-density lipoprotein (LDL) cholesterol levels. While LDL-cholesterol is the primary target of therapy, the report has shifted emphasis to risk assessment and risk management, as being most likely to offer the maximum benefit in the long term.

The principal ATP III recommendations

• A fasting lipid profile every 5 years from age 20 onward
• The 5 major risk factors for setting target LDL levels are: smoking, hypertension (>140/90 mm Hg), low HDL (<40 mg/dL or <1.0 mmol/L), family history of premature coronary heart disease (CHD), age (men >45, women >55).
• Target LDL levels are: 0-1 risk factors: <160 mg/dL or <4.1 mmol/L; 2 or more risk factors: <130 mg/dL or <3.35 mmol/L; CHD and equivalent conditions (e.g. diabetes, aneurysm, carotid artery disease, peripheral artery disease): <100 mg/dL or <2.6 mmol/L.
• An HDL level >60 mg/dL or >1.5 mmol/L is a "negative" risk factor, i.e. it confers a degree of protection.
• Check high LDL patients for secondary dyslipidemias: diabetes, hypothyroidism, obstructive liver disease, chronic renal failure, steroid use.
• Therapeutic Lifestyle Changes (TLC) for LDL increases that are smaller than 30 mg/dL or 0.775 mmol/L above target level, otherwise add drug therapy (e.g. statins). ¹

The risk for CHD is influenced by other factors not included in the 5 major, independent risk factors listed above, together with a raised LDL cholesterol level. Perhaps the most important of these is a constellation of risk factors that represent many of the features which may be associated with the epidemic obesity seen today in the USA and emerging in other developed countries: the so-called metabolic syndrome, sometimes termed 'syndrome-X', or the insulin-resistance syndrome.

The Metabolic Syndrome

The easily-recognized features of this syndrome are:

• abdominal obesity: waist measurement >40 inches or >102 cm (men); >35 inches or >89 cm (women)
• atherogenic dyslipidemia: serum triglyceride >150 mg/dL or >1.7 mmol/L, HDL cholesterol <40 mg/dL or < 1.0 mmol/L (men) or <50 mg/dL or < 1.3 mmol/L (women)
• hypertension: >135/85 mm Hg
• fasting blood glucose >110 mg/dL or >6.1 mmol/L

The diagnosis is made when three or more of these features are present. While obesity is associated with insulin resistance, abdominal obesity is more closely associated with the metabolic syndrome than the Body Mass Index (BMI). There is probably a genetic component, based on studies in Scandinavia, where as many as 14% of Swedish men have the syndrome. ²

Treatment

After appropriate control of LDL cholesterol (with medication, if the level remains 30 mg/dL or more above the target level), subjects with the metabolic syndrome should be managed by energetic efforts at weight reduction and increased physical activity.

Loss of weight will enhance the lowering of LDL cholesterol, as well as reduce all the risk factors of the metabolic syndrome. Regular physical activity reduces very low-density lipoprotein (VLDL) levels, raises HDL cholesterol, and in some people lowers LDL cholesterol. It also lowers hypertension, reduces insulin resistance, and can improve cardiovascular function and coronary blood flow.

Comment

The ATP III contains important information on managing specific dyslipidemias, such as an 'isolated' increase in VLDL cholesterol. It also reviews the appropriate management of elevated LDL levels in different age groups for both sexes. The main conclusion is, however, that increased age is not an obvious discriminator - abnormal lipid levels require active treatment at any age.

Recent recognition of an 'obesity epidemic', together a startling earlier mean age of onset of type 2 diabetes, must force us to give the metabolic syndrome top priority. Although the benefits of weight control and physical activity are well-known and often reiterated ad nauseam, it is clear that efforts to improve the lifestyle of young adults (and children) must be reinforced, if we want to make a serious impact on cardiovascular disease. The relative safety of the statin drugs, and their widespread effectiveness beyond merely reducing LDL cholesterol levels, offer a way to help those that do not respond to 'therapeutic lifestyle changes'.