BALTIMORE, MD — US researchers have devised and validated a novel method of estimating LDL-cholesterol levels[1]. The new method, which was tested and validated in more than 1.3 million individuals, uses an adjustable factor to estimate very low-density lipoprotein (VLDL) cholesterol to account for variance in triglyceride and non-HDL cholesterol levels used in the Friedewald equation.
To heartwire , lead investigator Dr Seth Martin (Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD) said, "The Friedewald equation works well for average patients, but an estimation of VLDL using an adjustable factor provides a more accurate and robust assessment of LDL cholesterol" from patient to patient, especially in high-risk patients with hypertriglyceridemia and low levels of LDL cholesterol.
The results of the study are published online November 17, 2013 in the Journal of the American Medical Association.
Large Sample of US Individuals
LDL cholesterol is estimated using the Friedewald equation. In the Friedewald equation, said Martin, there is an assumed fixed 5:1 ratio of triglyceride levels to VLDL cholesterol. However, the problem is assuming this fixed 5:1 ratio across a range of triglyceride and non-HDL-cholesterol levels. Other studies, for example, have shown evidence of variance in the ratio, ranging as high as 9:1 in one study.
To address the problems inherent in the Friedwald measurement, the group decided to take advantage of the large cohort of patients available to them in the Very Large Database of Lipids (VLDL-1B). Using VLDL-1B, the researchers took a sample of cholesterol measurements obtained directly after ultracentrifugation from 1 350 908 adults, adolescents, and children in the US between 2009 and 2011.
Instead of using the fixed ratio of triglycerides to VLDL cholesterol to estimate LDL, they used an adjustable ratio as determined from more than 900 000 patients in the derivation cohort. As expected, the derivation cohort showed wide interindividual variance in the triglyceride/VLDL ratio. In their analysis, triglyceride and non–HDL-cholesterol levels explained approximately two-thirds of the variance in the triglyceride/VLDL ratio.
The researchers then performed a regression analysis that accounted for lipids, age, and sex to determine strata-specific median triglyceride/VLDL-cholesterol ratios. Based on these values, a 180-cell table of median triglyceride and non-HDL cholesterol levels was devised. The adjusted ratio of triglycerides to VLDL cholesterol can be obtained in the table using the values of triglycerides and non-HDL cholesterol.
For those patients with triglycerides <400 mg/dL, the overall concordance of the novel method of measuring LDL was 91.7% when compared with the direct measurement of LDL cholesterol. In contrast, the Friedewald-estimated measurement of LDL using the fixed ratio had a concordance of just 85.4%.
"The greatest improvement in concordance occurred in classifying LDL cholesterol lower than 70 mg/dL, especially in patients with high triglyceride levels," Martin told heartwire . For example, in individuals with triglyceride levels ranging from 200 to 399 mg/dL and LDL cholesterol of less than 70 mg/dL, the estimated Friedewald measurement of LDL cholesterol had just a 40% concordance with the direct measurement of LDL cholesterol compared with 84.0% concordance using the adjustable ratio.
The researchers say the 180-cell table they devised for the adjustable ratio "could be could be coded into an online calculator, smartphone application, or automated laboratory reporting system." Compared with the Friedewald estimation, classifications based on US and European clinical practice guidelines using LDL-cholesterol estimates with this novel method are more concordant with LDL-cholesterol levels obtained using direct measurements, they conclude.
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Just this week, as reported by heartwire , new guidelines from the American College of Cardiology (ACC) and AHA, developed in conjunction with the National Heart, Lung, and Blood Institute (NHLBI), emphasized abandoning treating elevated LDL-cholesterol levels to a specific target, such as the older recommendations of <70 mg/dL or <100 mg/dL in secondary-prevention patients. Instead, the new guidelines emphasize treating risk, urging clinicians to treat patients with a moderate- or high-intensity statin depending on the patient's baseline risk for cardiovascular disease.
Martin said that despite the shift with the new guidelines, physicians still need to measure LDL cholesterol to determine baseline risk. In addition, they will need to recheck their patient's cholesterol levels even once treatment has started to make sure they are achieving the desired absolute reductions. In addition, European and Canadian guidelines still emphasize treating to target, so it is important to measure LDL-cholesterol levels accurately.
Martin reports no conflicts of interest. Disclosures for the coauthors are listed in the paper.
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