Current cholesterol cutpoints may be inaccurate in high-risk patients, study finds

Current guideline-based treatment cutpoints using non-high-density lipoprotein cholesterol (non-HDL-C) may not be accurate for risk stratification and lipid-lowering therapy, especially in high-risk patients, according to a new study.

Low-density lipoprotein cholesterol (LDL-C) levels are the most commonly used treatment target for dyslipidemia management. LDL-C is usually estimated using the Friedewald equation, as follows: LDL-C=total cholesterol minus HDL-C minus (triglycerides/5) when measurements are in mg/dL. However, some guidelines base treatment cutpoints on non-HDL-C levels, which are calculated differently (non-HDL-C=total cholesterol minus HDL-C) and measure the cholesterol content in all of the atherogenic lipoproteins. Treatment goals for non-HDL-C have generally been considered to be approximately 30 mg/dL above established LDL-C levels, although this relationship had not previously been evaluated as in this study.

Researchers used data from the Very Large Database of Lipids to determine whether population percentiles of non-HDL-C and low-density lipoprotein cholesterol (LDL-C) varied within patients and could affect risk stratification. Friedewald-estimated LDL-C and non-HDL-C were calculated and population percentiles were assigned. The authors then determined which percentiles corresponded to current LDL-C cutpoints in clinical guidelines and whether patients would be reclassified to a higher treatment category based on non-HDL-C versus LDL-C. Guideline-based non-HDL-C cutpoints (30 mg/dL higher than LDL-C cutpoints) and percentile-based non-HDL-C cutpoints (equivalent percentiles to LDL-C cutpoints) were both examined. The study results were published online Aug. 21 by the Journal of the American College of Cardiology.

The study population included 1,310,440 U.S. adults who had triglyceride levels below 400 mg/dL. Their mean age was 59 years, and 52% were women. The authors found that LDL-C cutpoints of 70 mg/dL, 100 mg/dL, 130 mg/dL, 160 mg/dL and 190 mg/dL corresponded to the same population percentiles as non-HDL-C levels of 93 mg/dL, 125 mg/dL, 157 mg/dL, 190 mg/dL and 223 mg/dL, respectively. When patients were reclassified by non-HDL-C, a significant proportion moved to a higher treatment category compared with LDL-C, especially high-risk patients and patients with a triglyceride level of 150 mg/dL or greater.

Fifteen percent of patients with an LDL-C level below 70 mg/dL had a non-HDL-C level of 100 mg/dL, the guideline-based cutpoint, while 25% had a non-HDL-C of 93 mg/dL or greater, the percentile-based cutpoint. When triglyceride levels between 150 and 199 mg/dL were also considered, 22% of patients with an LDL-C level below 70 mg/dL had a non-HDL-C level of 100 mg/dL and 50% had a non-HDL-C of 93 mg/dL or greater.

The authors acknowledged that clinical and demographic data were limited and that they could not determine the effect of reclassification on clinical outcomes, among other limitations. However, they concluded that patient-level discordance exists between non-HDL-C and LDL-C percentiles, especially at lower LDL-C and higher triglyceride levels, when they said accuracy is most critical.

“Lowering conventional non-HDL-C cutpoints for high-risk patients to match percentiles of LDL-C cutpoints as well as wider adoption of non-HDL-C in clinical practice may potentially improve secondary prevention outcomes and residual risk assessment and treatment,” the authors wrote.