Discordance LDL-c with alternative LDL-related measures impairs coronary risk prediction

Mora S, Buring JE, Ridker PM
Circulation. Originally published December 17, 2013. doi: 10.1161/CIRCULATIONAHA.113.005873

Background

While LDL-c is the traditional measure to base lipid lowering therapy on, non-HDL-cholesterol (NHDL-c) or apolipoprotein B (apoB) are now also considered in individuals with hypertriglyceridemia or cardiometabolic abnormalities.
Since some individuals with ‘normal’ or below average LDL-c levels experience coronary events [1-3], it has been postulated that their increased risk might be the consequence of higher levels of NHDL-c, apoB or LDL-particles (LDL-P), which may not be readily apparent from their LDL-c values [4]. In these individuals cardiovascular (CV) risk may be underestimated when only LDL-c is considered. On the other hand, when individuals have higher LDL-c but below average NHDL-c, apoB or LDL-P, their risk may be overestimated.
This study aimed to examine the prognosis of individuals with discordant values of new (NHDL-c, apoB or LDL-P) and old (LDL-c) tests. It has been suggested that CV risk in healthy individuals may be more closely related to NHDL-c, apoB or LDL-P, rather than to LDL-c [5-9], and that this difference is more clinically relevant when the levels are not in agreement. [10-12]. This study therefore determined the prevalence and long-term prognosis of discordant levels of directly measured LDL-c compared with NHDL-c, apoB and LDL-P in 27533 apparently healthy women (Women’s Health Study), who were followed for over 17 years. Discordance was defined as LDL-c>median while the alternative measure was <median, or the other way around.

Main results

• LDL-c was strongly correlated with NHDL-c (Spearman r: 0.910, 95%CI: 0.908-0.912), apoB (r: 0.785, 95%CI: 0.780-0.789) and LDL-P (r: 0.692, 95%CI: 0.686,0.698, all P<0.0001). Nevertheless, prevalence of LDL-c discordance was 11.6%, 18.9% and 24.3% for NHDL-C, apoB and LDL-P respectively.

• Among 13595 women with below median LDL-c, coronary risk was underestimated by three-fold in women whose level of NHDL-c was discordant (age-adjusted HR: 2.92, 95%CI: 2.33-3.67 vs. concordant levels). A similar underestimation was seen for discordant apoB levels (age-adjusted HR: 2.48, 95%CI: 2.01-3.07), or LDL-P (age-adjusted HR: 2.32, 95%CI: 1.88-2.85)(all P<0.0001). After fully adjusting for other known risk factors, coronary risk remained underestimated by ~30-50%.
• Conversely, for the 13938 women with above median LDL-c, coronary risk was overestimated by about three-fold when NHDL-c, apoB, or LDL-P were discordant. After full adjustment, coronary risk was still overestimated by ~20-40%, but this was only statistically significant for discordance of LDL-c with apoB.
• The under- or overestimation of coronary risk became more pronounced when the analysis was repeated for discordance of LDL-c with all three alternative LDL-related measures.
• When reversing the analysis to determine the clinical utility of LDL-c as a second lipid measure, the effect of discordance of either NHDL-c, apoB or LDL-P with LDL-c on coronary risk was negligible. 

Conclusion

Discordance of LDL-c levels with alternative LDL-related measures is quite common among apparently healthy women. In these individuals, coronary risk was either underestimated (when LDL-c was below the median, and the other measures above) or overestimated (vice versa) by LDL-c values. When LDL-c and alternative LDL-c measures were concordant, clinical utility of all measures is similar.  These results support the use of alternative lipid testing to assess coronary risk in women with discordant LDL-related measures.

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