Perspective

Friedewald equation may underestimate LDL levels

The Friedewald equation appears to underestimate LDL levels, particularly at low cholesterol levels in the setting of high triglycerides, researchers reported in a new study.

“We found that in nearly one out of four patients in the ‘desirable’ LDL cholesterol range for people with a higher heart disease risk, the Friedewald equation had it wrong,” Seth S. Martin, MD, clinical fellow at the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, said. “As a result, many patients may think they achieved their LDL cholesterol target when, in fact, they may need more aggressive treatment to reduce their heart disease risk.”

Seth S. Martin, MD 

Seth S. Martin

To examine differences in Friedewald-estimated and directly measured LDL values, researchers examined lipid profiles of more than 1.3 million US adults (mean age, 59 years; 52% women) after cholesterol vertical spin density gradient ultracentrifugation from 2009 to 2011. Those data were compared with samples using the Friedewald equation. Adult lipid distribution was comparable to National Health and Nutrition Examination Survey participants.

Overall, greater differences in Friedewald- estimated vs. directly measured LDL occurred at lower LDL and higher triglyceride levels.

When Friedewald LDL level was <70 mg/dL, median direct LDL was 9 mg/dL higher (5th to 95th percentile, 1.8 to 15.4 mg/dL) when triglycerides were 150 mg/dL to 199 mg/dL and 18.4 mg/dL higher (5th to 95th percentile, 6.6 to 36 mg/dL) when triglycerides were 200 mg/dL to 399 mg/dL. When patients had Friedewald results of <70 mg/dL, 23% had a direct LDL ≥70 mg/dL (39% when triglycerides were the same at 150 mg/dL and 59% if triglycerides were 200 mg/dL to 399 mg/dL), according to the data.

“When the triglyceride level is elevated, especially if it is ≥150 mg/dL as it is in many patients with obesity and insulin resistance, then the estimate is too far off in too many patients,” Martin told Cardiology Today.

“The most important finding from our study is that the Friedewald equation tends to underestimate LDL most when accuracy is most crucial,” the researchers concluded. – by Deb Dellapena and Katie Kalvaitis

For more information:

Martin SS. JAm Coll Cardiol. 2013;doi:10.1016/j.jacc.2013.01.079.

Disclosure: See the full study for a list of the researchers’ relevant financial disclosures.

The Friedewald equation appears to underestimate LDL levels, particularly at low cholesterol levels in the setting of high triglycerides, researchers reported in a new study.

“We found that in nearly one out of four patients in the ‘desirable’ LDL cholesterol range for people with a higher heart disease risk, the Friedewald equation had it wrong,” Seth S. Martin, MD, clinical fellow at the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, said. “As a result, many patients may think they achieved their LDL cholesterol target when, in fact, they may need more aggressive treatment to reduce their heart disease risk.”

Seth S. Martin, MD 

Seth S. Martin

To examine differences in Friedewald-estimated and directly measured LDL values, researchers examined lipid profiles of more than 1.3 million US adults (mean age, 59 years; 52% women) after cholesterol vertical spin density gradient ultracentrifugation from 2009 to 2011. Those data were compared with samples using the Friedewald equation. Adult lipid distribution was comparable to National Health and Nutrition Examination Survey participants.

Overall, greater differences in Friedewald- estimated vs. directly measured LDL occurred at lower LDL and higher triglyceride levels.

When Friedewald LDL level was <70 mg/dL, median direct LDL was 9 mg/dL higher (5th to 95th percentile, 1.8 to 15.4 mg/dL) when triglycerides were 150 mg/dL to 199 mg/dL and 18.4 mg/dL higher (5th to 95th percentile, 6.6 to 36 mg/dL) when triglycerides were 200 mg/dL to 399 mg/dL. When patients had Friedewald results of <70 mg/dL, 23% had a direct LDL ≥70 mg/dL (39% when triglycerides were the same at 150 mg/dL and 59% if triglycerides were 200 mg/dL to 399 mg/dL), according to the data.

“When the triglyceride level is elevated, especially if it is ≥150 mg/dL as it is in many patients with obesity and insulin resistance, then the estimate is too far off in too many patients,” Martin told Cardiology Today.

“The most important finding from our study is that the Friedewald equation tends to underestimate LDL most when accuracy is most crucial,” the researchers concluded. – by Deb Dellapena and Katie Kalvaitis

For more information:

Martin SS. JAm Coll Cardiol. 2013;doi:10.1016/j.jacc.2013.01.079.

Disclosure: See the full study for a list of the researchers’ relevant financial disclosures.

    Perspective
    Karol Watson

    Karol Watson

    The direct measurement of LDL is more expensive and requires specialized testing equipment; therefore, LDL is usually ‘estimated’ from quantitative measurements of HDL and total cholesterol and plasma triglycerides using the Friedewald equation.

    The Friedewald equation is known to be inaccurate when triglycerides are above 400 mg/dL; however, many lipid specialists realize that the calculated LDL begins to differ from the measured LDL as soon as triglycerides are above 200 mg/dL. The good news is, from our standpoint, it does not usually alter treatment decisions. When we order an LDL level, most lipid panels give us an LDL that was calculated from the Friedewald equation, which is different from a directly measured LDL. When you directly measure LDL, you are actually measuring the cholesterol content present in LDL. When you calculate it, you are saying: ‘If the triglycerides are normal, then this is what the LDL must be.’ But as we know, in many patients the triglycerides are not normal.

    This study should alert physicians to the fact that they need to get a directly measured LDL for patients with higher triglycerides. It is good to raise the issue; health care professionals need to be aware of underestimation or overestimation of cholesterol levels. Going forward, it shouldn’t be too expensive to directly measure LDL; we need insurance companies to pay for it.

    • Karol Watson, MD, PhD, FACC
    • Associate Professor of Medicine/Cardiology Co-director, UCLA Cholesterol and Lipid Management Center

    Disclosures: Watson reports no relevant financial disclosures.