LDL-particles (LDL-P) can better predict atherosclerotic risk and cardiovascular disease (CVD) risk when LDL-P and LDL-cholesterol (LDL-C) were discordant, according to a study published in the March-April issue of the Journal of Clinical Lipidology.
“The amount of cholesterol per low-density lipoprotein (LDL) particle is variable and related in part to particle size, with smaller particles carrying less cholesterol. This variability causes concentrations of LDL-C and LDL-P to be discordant in many individuals,” the authors wrote.
James D. Otvos, PhD, of LipoScience in Raleigh, N.C., and colleagues used MESA (Multi-Ethnic Study of Atherosclerosis), a cohort of 6,814 people free of CVD, to evaluate LDL-P measured by MR spectroscopy, to calculate LDL-C and carotid intima-media thickness (CIMT) and report the incidence rates of CVD events at baseline and during the 5.5-year follow-up.
Of the study cohort, 39 percent were white, 13 percent were Chinese American, 25 percent were African-American and 23 percent were Hispanic. The patients had a mean age of 62 and 51 percent were women.
Otvos and colleagues reported that LDL-C and LDL-P levels were correlated but often discordant. “Although many individuals had concordant levels of LDL-C and LDL-P, many others with low LDL-C percentile rank had much higher LDL-P, and vice versa,” the authors noted.
The researchers separately evaluated concordant and discordant subgroups and defined discordance as a difference of at least 12 percentile units to make half the population ‘‘concordant.’’
The results showed that 319 CVD events occurred during the follow-up period of 5.5 years, and that both LDL-C and LDL-P levels were associated with future CVD events. Between the concordant and discordant subgroups, 160 CVD events were experienced by patients with concordant LDL-C and LDL-P. In comparison, these numbers were 101 and 58 for patients with “LDL-P > LDL-C and LDL-P < LDL-C discordance.”
While the authors reported that mean levels of LDL-P in the three subgroups tracked positively for risk, however, LDL-C levels were inversely related to risk. Of the 1,631 patients with LDL-C, 1,115 patients had low levels of LDL-P.
In addition, of the 516 patients with low LDL-C but with discordantly greater LDL-P, 33 events occurred, compared with only 18 events in patients with low levels of LDL-P and discordantly higher levels of LDL-C.
Lastly, the researchers found that both LDL-C and LDL-P were associated with increased CIMT.
“The results indicate that when the cholesterol and particle measures of LDL disagree, the clinical and subclinical outcomes track with LDL-P more so than with LDL-C,” the authors wrote.
“It remains uncertain whether the mechanism(s) responsible for this risk are related primarily to elevations of LDL-P or whether other variables are associated with LDL-P. LDL-C discordance is more relevant than LDL-P from an etiologic perspective,” the authors wrote.
“The results of this study support the speculation that this risk is not as independent of LDL as studies equating LDL- C with 'LDL’ have suggested.”
Additionally, Otvos and colleagues suggested that the elevated LDL-P concentrations could identify patients who are likely to benefit from LDL lowering treatment strategies.
The FDA only considers LDL-C levels as a surrogate endpoint, suggesting that a clinical benefit can be recognized from LDL-C lowering; however, the authors noted that a flaw to this could be the fact that LDL-C changes can result from either LDL-P or cholesterol content. Therefore, the authors noted that future studies should assess whether LDL-P could be a better surrogate CVD endpoint than LDL-C.
The authors concluded: “When LDL-P and LDL-C were discordant, LDL-P was more strongly associated with risk of CVD events and with [increased] CIMT than was LDL-C. This finding has potentially important implications regarding our understanding of the etiology of atherosclerotic cardiovascular disease.”