SISANews

Un nuovo calcolo per la stima del colesterolo LDL

La formula di Friedewald è il metodo di riferimento per il calcolo della concentrazione plasmatica del colesterolo LDL. E' molto semplice e si basa sul fatto che il rapporto tra i trigliceridi totali ed il colesterolo nelle VLDL è mediamente uguale a 5, a patto che i trigliceridi plasmatici non superino i 400 mg/dL. Il metodo è stato validato più volte in confronto con metodi di riferimento quali l'ultracentrifugazione ed ha sempre dato una buona risposta, tanto che è stato adottato nella quasi totalità degli studi clinici. La stima del colesterolo LDL rimane tuttavia approssimativa, dato che il rapporto tra trigliceridi e colesterolo VLDL, fissato ad un valore di 5, è tutt'altro che costante. Nel loro studio, condotto su più di 1.350.000 campioni di siero in cui le lipoproteine erano state separate con ultracentrifugazione in gradiente di densità, Martin e coll. hanno rilevato che il rapporto tra trigliceridi del siero e colesterolo VLDL mostrava un'ampia variabilità. La mediana si collocava effettivamente intorno a 5, per la precisione 5,2, ma il rapporto variava da 3,7 a 7,8 nella gran parte dei sieri esaminati. Gli autori propongono un metodo di stima del colesterolo VLDL utilizzando un fattore di conversione non più fisso e uguale a 5, ma variabile in base al valore dei trigliceridi e del colesterolo non-HDL. Con questo metodo di calcolo, peraltro non semplicissimo, la concordanza tra la stima del colesterolo LDL e la determinazione dello stesso dopo ultracentrifugazione del siero migliora notevolmente. Viene da chiedersi perché allora non usare direttamente il colesterolo non-HDL che numerosi studi sostengono sia un indicatore del rischio cardiovascolare più sensibile del colesterolo LDL.

Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile

Martin SS, Blaha MJ, Elshazly MB, Toth PP, Kwiterovich PO, Blumenthal RS, Jones SR

JAMA 2013;310:2061-2068

IMPORTANCE: In clinical and research settings worldwide, low-density lipoprotein cholesterol (LDL-C) is typically estimated using the Friedewald equation. This equation assumes a fixed factor of 5 for the ratio of triglycerides to very low-density lipoprotein cholesterol (TG:VLDL-C); however, the actual TG:VLDL-C ratio varies significantly across the range of triglyceride and cholesterol levels.
OBJECTIVE: To derive and validate a more accurate method for LDL-C estimation from the standard lipid profile using an adjustable factor for the TG:VLDL-C ratio.
DESIGN, SETTING, AND PARTICIPANTS: We used a convenience sample of consecutive clinical lipid profiles obtained from 2009 through 2011 from 1,350,908 children, adolescents, and adults in the United States. Cholesterol concentrations were directly measured after vertical spin density-gradient ultracentrifugation, and triglycerides were directly measured. Lipid distributions closely matched the population-based National Health and Nutrition Examination Survey (NHANES). Samples were randomly assigned to derivation (n=900 605) and validation (n=450 303) data sets.
MAIN OUTCOMES AND MEASURES: Individual patient-level concordance in clinical practice guideline LDL-C risk classification using estimated vs directly measured LDL-C (LDL-CD).
RESULTS: In the derivation data set, the median TG:VLDL-C was 5.2 (IQR, 4.5-6.0). The triglyceride and non-high-density lipoprotein cholesterol (HDL-C) levels explained 65% of the variance in the TG:VLDL-C ratio. Based on strata of triglyceride and non-HDL-C values, a 180-cell table of median TG:VLDL-C values was derived and applied in the validation data set to estimate the novel LDL-C (LDL-CN). For patients with triglycerides lower than 400 mg/dL, overall concordance in guideline risk classification with LDL-CD was 91.7% (95% CI, 91.6%-91.8%) for LDL-CN vs 85.4% (95% CI, 85.3%-85.5%) for Friedewald LDL-C (LDL-CF) (P<.001). The greatest improvement in concordance occurred in classifying LDL-C lower than 70 mg/dL, especially in patients with high triglyceride levels. In patients with an estimated LDL-C lower than 70 mg/dL, LDL-CD was also lower than 70 mg/dL in 94.3% (95% CI, 93.9%-94.7%) for LDL-CN vs 79.9% (95% CI, 79.3%-80.4%) for LDL-CF in samples with triglyceride levels of 100 to 149 mg/dL; 92.4% (95% CI, 91.7%-93.1%) for LDL-CN vs 61.3% (95% CI, 60.3%-62.3%) for LDL-CF in samples with triglyceride levels of 150 to 199 mg/dL; and 84.0% (95% CI, 82.9%-85.1%) for LDL-CN vs 40.3% (95% CI, 39.4%-41.3%) for LDL-CF in samples with triglyceride levels of 200 to 399 mg/dL (P<.001 for each comparison).
CONCLUSIONS AND RELEVANCE: A novel method to estimate LDL-C using an adjustable factor for the TG:VLDL-C ratio provided more accurate guideline risk classification than the Friedewald equation. These findings require external validation, as well as assessment of their clinical importance. The implementation of these findings into clinical practice would be straightforward and at virtually no cost.

JAMA 2013;310:2061-2068