The third report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III) constituting the National Cholesterol Education Program's (NCEP) updated clinical guidelines for cholesterol testing and management was issued by the NIH (National Institutes of Health), USA in May 2001. While ATP III maintains that CHD patients should be treated intensively, its major new feature is a focus on primary prevention in persons with multiple risk factors. The report also calls for more intensive LDL (low density lipoprotein) lowering in certain groups of patients such as diabetics.

These aggressive new guidelines should triple the number of people taking drugs to lower their cholesterol. The major highlights of the updated guidelines are detailed below:

The new guidelines recommend a complete lipoprotein profile (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) as the preferred initial test, rather than screening for total cholesterol and HDL alone. The classification of LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides are as outlined in the table below.

LDL cholesterol
< 100 mg/dl	Optimal
100-129 mg/dl	Near optimal/above optimal
130-159 mg/dl	Borderline high
160-189 mg/dl	High
> 190 mg/dl	Very high
Total cholesterol
< 200 mg/dl	Desirable
200-239 mg/dl	Borderline high
> 240 mg/dl	High
HDL cholesterol
< 40 mg/dl	Low
> 60 mg/dl	Borderline high
Triglycerides
< 150 mg/dl	Normal
150-199 mg/dl	Borderline high
200-499 mg/dl	High
> 500 mg/dl	Very high

Thus, the new NCEP guidelines remain the same for total cholesterol, identifies LDL cholesterol < 100 mg/dl as optimal, raises low HDL cholesterol from < 35 mg/dl to < 40 mg/dl and lowers the desirable triglyceride levels from < 200 mg/dl to < 150 mg/dl.

ATP III continues to identify elevated LDL cholesterol as the primary target of therapy (Table).

CHD & CHD risk equivalents	< 100
Two or more risk factors	< 130 for CHD*
Zero to one risk factor	< 160 for CHD*

*Risk factors include cigarette smoking, hypertension (BP > 140/90 mmHg or on anti-hypertensive medication), low HDL cholesterol (< 40 mg/dl), family history of premature CHD, age (men > 45 years; women > 55 years). An HDL cholesterol > 60 mg/dl counts as a "negative" risk factor; its presence removes one risk factor from the total count

Thus the new guidelines have introduced a new concept called CHD risk equivalents. It includes those conditions, which carry a risk for major coronary events equivalent to that of established CHD and hence need more aggressive lipid lowering (i.e. LDL goal < 100 mg/dl). CHD risk equivalents comprise diabetes, other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm and symptomatic carotid artery disease) and multiple risk factors that confer a 10-year risk for CHD > 20% (as estimated from Framingham risk scores, a computer program that can predict the likelihood of a person having a myocardial infarction within the next 10 years).

Diabetes counts as a CHD risk equivalent because it confers a high risk of new CHD within 10 years. Hence even in these patients, the LDL goal is the same as in CHD patients, i.e., < 100 mg/dl.

The 'metabolic syndrome' represents a potential secondary target of risk reduction therapy. Management of the metabolic syndrome has a two-fold objective: to reduce underlying causes (i.e. obesity and physical inactivity), and to treat associated non-lipid and lipid risk factors.

MANAGEMENT OF HYPERTRIGLYCERIDEMIA
As per the new guidelines, for all persons with elevated triglycerides, the primary aim of therapy is to achieve the target goal for LDL cholesterol. When triglycerides are borderline high (150-199 mg/dl), emphasis should also be placed on weight reduction and increased physical activity. For high triglycerides (200-499 mg/dl), non-HDL cholesterol (total cholesterol minus HDL cholesterol) becomes a secondary target of therapy (Table).

Managing hypertriglyceridemia in patients with high triglycerides (200-499 mg/dl)

There are two approaches to drug therapy in these patients. First, the non-HDL cholesterol goal can be achieved by intensifying therapy with an LDL-lowering drug such as a statin. Alternatively, nicotinic acid or fibrate can be added, if used with appropriate caution, to achieve the non-HDL cholesterol goal by a further lowering of VLDL cholesterol. In rare cases in which triglycerides are very high (> 500 mg/dl), the initial aim of therapy is to prevent acute pancreatitis through triglyceride lowering. This approach requires very low fat diets (< 15% of calorie intake), weight reduction, increased physical activity, and usually a triglyceride-lowering drug (fibrate or nicotinic acid). Only after triglyceride levels have been lowered to < 500 mg/dl should attention turn to LDL lowering to reduce risk of CHD.

MANAGEMENT OF DIABETIC DYSLIPIDEMIA
The dyslipidemia exhibited by patients with type 2 diabetes essentially consists of high triglycerides, low HDL, and small, dense LDL. Though LDL levels may not be significantly elevated, diabetic patients have small dense LDL, which is highly atherogenic. Thus, every small increase in LDL leads to a much higher risk of CHD in diabetic patients compared to non-diabetic patients. Therefore the new guidelines support the identification of LDL cholesterol as the primary target of therapy, as it is in those without diabetes. Since diabetes is designated as a CHD risk equivalent in ATP III, the LDL cholesterol goal of therapy for most persons with diabetes will be < 100 mg/dl. When triglyceride levels are > 200 mg/dl, non-HDL cholesterol becomes a secondary target of cholesterol-lowering therapy.

NEW FEATURES OF
ATP III
Modifications of lipid and lipoprotein classification

• Identifies LDL cholesterol < 100 mg/dl as optimal
  
  
• Raises low HDL cholesterol from < 35 mg/dl to < 40 mg/dl
  
  
• Lowers the triglyceride classification cutpoints from < 200 mg/dl to < 150 mg/dl
  
  
• Recommends treatment beyond LDL lowering for persons with triglycerides > 200 mg/dl

Focus on multiple risk factors

• Raises persons with diabetes without CHD, most of whom display multiple risk factors, to the risk levels of CHD-risk equivalent
  
  
• Uses Framingham projections of 10-year absolute CHD risk (i.e. the percent probability of having a CHD event in 10 years) to identify certain patients with multiple (2+) risk factors for more intensive treatment Identifies persons with multiple risk factors (metabolic syndrome) as candidates for intensified therapeutic lifestyle changes

The fact that cardiovascular disease is assuming epidemic proportions in India has been recently confirmed in an Indian study published in the September issue of Journal of the American College of Cardiology.

The study called as the Chennai Urban Population Study (CUPS) conducted by Mohan et al, involved 1,262 subjects (aged 20 years or older) residing in two residential colonies in Chennai. The overall prevalence of coronary artery disease (CAD) was 11%. This is approximately 10 times the prevalence reported in urban India during the previous 40 years. Prevalence of CAD increased with an increase in total cholesterol, LDL cholesterol, triglycerides and total cholesterol/HDL ratio. Dr. Mohan also noted that the prevalence of diabetes, hyperlipidemia and obesity (particularly central obesity) has also been rising quite dramatically in the recent past. The study concluded that lifestyle changes and aggressive control of risk factors are urgently needed to reverse this trend.

Thus this study confirms that the urgent need of the hour is to recognize hyperlipidemia as a crucial CHD risk factor and take aggressive measures towards its control.

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