Achieving Secondary Prevention Low-Density Lipoprotein Particle Concentration Goals Using Lipoprotein Cholesterol-Based Data

Background: Epidemiologic studies suggest that LDL particle concentration (LDL-P) may remain elevated at guideline recommended LDL cholesterol goals, representing a source of residual risk. We examined the following seven separate lipid parameters in achieving the LDL-P goal of < 1000 nmol/L goal for very high risk secondary prevention: total cholesterol to HDL cholesterol ratio, TC/HDL, < 3; a composite of ATP-III very high risk targets, LDL-C < 70 mg/dL, non-HDL-C < 100 mg/dL and TG < 150 mg/dL; a composite of standard secondary risk targets, LDL-C < 100, non-HDL-C < 130, TG < 150; LDL phenotype; HDL-C >= 40; TG < 150; and TG/HDL-C < 3. Methods: We measured ApoB, ApoAI, ultracentrifugation lipoprotein cholesterol and NMR lipoprotein particle concentration in 148 unselected primary and secondary prevention patients. Results: TC/ HDL- C < 3 effectively discriminated subjects by LDL-P goal (F = 84.1, p < 10(-6)). The ATP- III very high risk composite target (LDL-C < 70, nonHDL-C < 100, TG < 150) was also effective (F = 42.8, p < 10(-5)). However, the standard secondary prevention composite (LDL-C < 100, non-HDL-C < 130, TG < 150) was also effective but yielded higher LDL-P than the very high risk composite (F = 42.0, p < 10(-5)) with upper 95% confidence interval of LDL-P less than 1000 nmol/ L. TG < 150 and TG/HDL-C < 3 cutpoints both significantly discriminated subjects but the LDL-P upper 95% confidence intervals fell above goal of 1000 nmol/ L (F = 15.8, p = 0.0001 and F = 9.7, p = 0.002 respectively). LDL density phenotype neared significance ( F = 2.85, p = 0.094) and the HDL-C cutpoint of 40 mg/dL did not discriminate (F = 0.53, p = 0.47) alone or add discriminatory power to ATP-III targets. Conclusions: A simple composite of ATP-III very high risk lipoprotein cholesterol based treatment targets or TC/HDL-C ratio < 3 most effectively identified subjects meeting the secondary prevention target level of LDL- P < 1000 nmol/L, providing a potential alternative to advanced lipid testing in many clinical circumstances.