Dr. Norris is Clinical Assistant Professor of Medicine, Pennsylvania Hospital Department of Cardiology, University of Pennsylvania School of Medicine, Philadelphia.

Robert B. Norris, MD

Case history: A 45-year-old woman asks her gynecologist to check her cholesterol because her 47-year-old brother recently had a coronary artery stent placed. The gynecologist is the only physician she has seen over the last 5 years, and she has not had her cholesterol checked during that period. Both of the patient's parents developed coronary heart disease while in their 70s. She does not smoke, has no other known cardiovascular risk factors, and has not entered menopause. Her blood pressure is 120/80. The patient already watches her diet closely because of her concerns about heart disease

Should this patient be started on a lipid-lowering agent?

Cholesterol levels: The basics of the good and the bad

While the total cholesterol level may be a useful screening test, it's more clinically useful to examine the entire lipid panel. Evaluating LDL, HDL, and triglycerides provides a better risk-assessment tool. 

In most laboratories, LDL is calculated from the other more easily measured parameters using the formula: 

LDL=Total Cholesterol–HDL–Triglycerides÷5 However, when triglyceride levels are greater than 200 mg/dL, it's more accurate to measure the LDL directly. 

 At present, the primary target in cholesterol management is LDL. Not only have higher LDL levels been found to correlate with a higher incidence of CVD, but lowering LDL with lifestyle modification or medication reduces this risk.

  Over the last 20 years, numerous studies using statins and other lipid-lowering drugs have evaluated the benefits of lower LDL levels in both primary and secondary prevention.

  Most studies have shown a 20% to 40% reduction in relative risk of cardiovascular events in patients receiving statins.

  These findings have led to more aggressive LDL goals.  

HDL levels correlate inversely with the risk of CVD.

  The average HDL is 55 mg/dL in women versus 45 mg/dL in men. Epidemiologic studies such as the Framingham Heart Study have shown low HDL to be a risk for CVD, independent of LDL levels.

Patients with low HDL levels benefit from statins, studies show, even though statins usually increase HDL levels only modestly.

  Small studies have shown that raising HDL with niacin in conjunction with a statin may further reduce cardiac events.

  However, the mechanism of how HDL is raised is crucially important. Torcetrapib (CP-529414), a cholesteryl ester transfer protein (CETP) inhibitor previously in development that increased HDL significantly, was shown in a large clinical trial to actually increase cardiovascular events.

 This agent is no longer in development, although other CETP inhibitors are in clinical trials. 

 Elevated triglycerides are also associated with CVD, although more prominently in univariate than in multivariate analysis.

  High triglyceride levels are linked to several other parameters that raise risk, including low HDL; small, dense LDL; and insulin resistance as seen in metabolic syndrome as well as in diabetes. Currently, triglycerides above 150 mg/dL are considered to be elevated.  

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Robert B. Norris, MD

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