Pitfall in Friedewald equation for ‘bad’ cholesterol
medwireNews: Using the Friedewald equation to estimate levels of low-density lipoprotein (LDL) cholesterol is the least accurate in patients for whom accuracy is most critical, shows the largest analysis to date.
The largest inaccuracies appeared when LDL cholesterol levels were relatively low but triglycerides were high, report Seth Martin (Johns Hopkins Hospital, Baltimore, Maryland, USA) and colleagues. They say their findings have "potentially far-reaching implications for patient care," given the ubiquity of lipid testing and the importance attached to the 70 mg/dL treatment target for LDL cholesterol in patients at high cardiovascular risk.
Almost 15% of the patients in the current study moved into a different treatment category based on their direct versus Friedewald equation LDL cholesterol measurements, with most of these being upward reclassifications requiring additional lipid lowering.
The team collected data on 1,340,614 patients who had direct lipid measurement using vertical spin density gradient ultracentrifugation. About 2% of these patients were excluded because they had triglyceride levels of 400 mg/dL or more, which is known to adversely affect the accuracy of the Friedewald equation.
Martin et al note that this exclusion is well known. "However, other potential limitations of the equation have received remarkably little scrutiny despite the equation's status as an important paradigm in medicine for over 40 years," they write in the Journal of the American College of Cardiology.
Among the remaining patients, LDL cholesterol levels estimated with the Friedewald equation tended to be lower than directly measured levels, particularly at LDL cholesterol levels below 100 mg/dL (the target for normal-risk patients). This was exacerbated by the presence of high triglyceride levels.
For example, if LDL cholesterol was below 70 mg/dL according to the Friedewald equation, directly measured levels were, on average, 9.0 mg/dL higher when triglyceride levels were 150-199 mg/dL but 18.4 mg/dL higher when they were 200-399 mg/dL.
Among patients with LDL cholesterol levels below 70 mg/dL according to the Friedewald equation, 23% had a directly measured level of 70 mg/dL or above, rising to 39% of those with triglyceride levels of 150-199 mg/dL and 59% of those with levels of 200-399 mg/dL.
"Based on these results, high-risk patients should have additional evaluation, especially if triglycerides are ≥150 mg/dL," says the team.
By Eleanor McDermid, Senior medwireNews Reporter