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Some studies suggest that new and modified formulas, such as the new formula derived from multiple linear regression, the modified Friedewald formula, and the Martin-Hopkins formula, provide more accurate LDL-C estimates compared to the traditional Friedewald formula, while other studies indicate that the Friedewald formula remains reliable under certain conditions but may have limitations in specific scenarios like high triglyceride levels or low LDL-C concentrations.
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Low-density lipoprotein cholesterol (LDL-C) is a critical marker for cardiovascular risk assessment and management. Traditionally, the Friedewald formula (FF) has been widely used to estimate LDL-C levels due to its simplicity and practicality. However, recent studies have highlighted its limitations, particularly in patients with high triglyceride (TG) levels and low LDL-C concentrations. This article synthesizes recent research on various cholesterol formulas, comparing their accuracy and applicability.
The Friedewald formula has been shown to overestimate LDL-C levels in certain populations. For instance, in an Indian cohort, the FF slightly overestimated LDL-C compared to direct measurements, especially in patients with TG levels above 350 mg/dL. Conversely, the FF tends to underestimate LDL-C at low concentrations, particularly in patients undergoing LDL apheresis or those treated with lipid-lowering drugs, with biases as high as -18.5% at mean LDL-C levels of 1.58 mmol/L.
Hypertriglyceridemia significantly affects the accuracy of the FF. Studies have demonstrated that the FF's reliability diminishes as TG levels increase. For example, in diabetic patients, the FF showed a mean positive bias of 21.8% at TG levels ≥1.7 mmol/L, exceeding the recommended allowable limit. Similarly, another study found that the FF underestimated LDL-C levels in patients with TG levels between 4.51 and 8.82 mmol/L.
A new formula derived from multiple regression analysis in an Indian population showed improved accuracy over the FF, with a correlation coefficient of 0.97 between directly measured LDL-C and the new formula. This approach highlights the potential for population-specific formulas to enhance LDL-C estimation accuracy.
The MFF, which adjusts the FF by considering non-HDL-C and TG concentrations, has shown better agreement with direct measurements. In a study, the MFF had significantly lower deviation percentages compared to the FF, particularly in patients with TG levels between 200-400 mg/dL.
The Martin-Hopkins formula has been found to outperform the FF, especially at LDL-C treatment targets below 1.4 mmol/L. It demonstrated a lower mean positive bias in hypertriglyceridemic patients, making it a more reliable option in such cases.
A study from Brazil proposed a simple formula, LDL-c = 3/4 (TC - HDL-c), which showed a higher correlation with directly measured LDL-C (r = 0.93) compared to the FF (r = 0.87). This formula's simplicity and accuracy make it a promising alternative for clinical use.
Using data mining techniques, a new formula was developed that exhibited a high correlation (r = 0.9769) with directly measured LDL-C, even at TG levels up to 1000 mg/dL. This approach underscores the potential of advanced statistical methods in refining LDL-C estimation.
The Friedewald formula, while historically significant, has notable limitations, particularly in patients with high TG levels and low LDL-C concentrations. Recent research has introduced several new and modified formulas that offer improved accuracy and reliability. These advancements underscore the importance of continuous evaluation and adaptation of cholesterol estimation methods to enhance cardiovascular risk assessment and management.
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