Even Newer Cholesterol Guidelines

Summarized by Robert W. Griffith, MD
September 3, 2004

Introduction

The National Cholesterol Education Program issued guidelines in 2001 (the Adult Treatment Panel III Guidelines). Since that time five large important clinical trials have been completed, the results of which make a change in the guidelines necessary, according to members of the Panel.

The studies are the Heart Protection Study or HPS (20,500 adults in the UK), PROSPER (5,800 subjects in the USA), ALLHAT (10,000 subjects in the USA), ASCOT-LLA (20,000 subjects in UK and Scandinavia), and PROVE IT (4,000 hospitalized patients in the USA). All five studies employed a statin drug in one group of patients - simvastatin in one, atorvastatin in two, and pravastatin in three (one study used two statins in different groups).

The results confirmed the benefits of lowering cholesterol levels in high-risk patients, and supported the ATP III recommendation to bring the LDL-cholesterol to 100 mg/dL or below. (By high risk they meant older persons or those with diabetes.)

The major new recommendation (or option)

What's new, however, is evidence that very high-risk patients can benefit from even greater lowering of LDL-cholesterol levels. By 'very high risk' the Panel means:

• established cardiovascular disease, plus more than one major risk factor (especially diabetes), or
• severe and poorly controlled risk factors (e.g. continued smoking), or
• the metabolic syndrome, or
• acute coronary syndromes (angina, myocardial infarction)

The new 'option' the Panel offers is that, for very high-risk patients, LDL-cholesterol levels may be lowered to below 70 mg/dL. The Panel prefers to call this an option, or a 'reasonable therapeutic strategy', rather than a recommendation, as the concept has not been fully tested yet. However, they continue making a strong recommendation that LDL-cholesterol should be reduced in high-risk subjects to 100 mg/dL or less.

[100 mg/dL = 2.6 mmol/L, and 70 mg/dL = 1.8 mmol/L]

Risk of side effects from statins

There's no evidence that decreasing LDL-cholesterol to very low levels carries any significant risks, except those caused by drug toxicity. Statins have a well-characterized toxicity profile. In general, they are very well tolerated. However, in very rare cases, destruction of muscle tissue (rhabdomyolysis) leading to kidney failure can occur; patients on statins should promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Rhabdomyolysis is more likely at very high statin doses, and is slightly commoner with one or two particular statins. However, we must emphasize that it's a very rare event.

Occasionally there may be liver function upsets with statins. At one time regular liver function testing was recommended for all patients on statins, but this has been dropped except for those with existing liver problems at the time of prescribing. Study results have shown that statins given in low-to-moderate doses are not linked to a significant risk of lifer function test abnormalities.

The updated recommendations

In summary, the updated recommendations on cholesterol lowering are:

• High risk of coronary heart disease¹ , or risk equivalents²: recommended LDL goal is below 100 mg/dL
• Very high risk - see above - the LDL optional goal is below 70 mg/dL
• Moderately high risk (2 or more risk factors³): LDL goal is below 130 mg/dL
• Lower risk (0-1 risk factor): LDL goal is below 160 mg/dL.

[130 mg/dL = 3.4 mmol/L, and 160 mg/dL = 4.1 mmol/L]

Of course, implicit in these recommendations is the institution of all the necessary lifestyle changes - no smoking, weight control, plenty of physical activity, and a healthy diet. You can find ample help with these Therapeutic Lifestyle Changes (TLC) at other places on this website.

Source

• Implications of recent clinical trial for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. SM. Grundy, JI. Cleeman, CNB. Merz,  et al., Circulation, 2004, vol. 110, pp. 227--239

Footnotes
1. Coronary heart disease (CHD) includes history of MI, angina, or coronary artery procedures.
2. Risk equivalents include peripheral arterial disease, aortic aneurysm, carotid artery disease, TIA, or diabetes.
3. Risk factors include smoking, high blood pressure, HDL cholesterol below 40 mg/dL, family history of CHD, and age - men over 45, women over 55.

Related Links
Try a Little TLC
Do You Have the Metabolic Syndrome (Syndrome X)?
Lowering Cholesterol with Diet: It's Not Just About Fat
Should We Put Statins in the Drinking Water?

Please take a moment to give us your comments. For questions about Health matters you may check our "Questions & Answers" Portal and Service.