Clinical implications of discordance between low-density lipoprotein cholesterol and particle number

Abstract

Background: 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 cholesterol (LDL-C) and LDL particles (LDL-P) to be discordant in many individuals.

Methods: LDL-P measured by nuclear magnetic resonance spectroscopy, calculated LDL-C, and carotid intima-media thickness (IMT) were assessed at baseline in the Multi-Ethnic Study of Atherosclerosis, a community-based cohort of 6814 persons free of clinical cardiovascular disease (CVD) at entry and followed for CVD events (n = 319 during 5.5-year follow-up). Discordance, defined as values of LDL-P and LDL-C differing by ≥ 12 percentile units to give equal-sized concordant and discordant subgroups, was related to CVD events and to carotid IMT in models predicting outcomes for a 1 SD difference in LDL-C or LDL-P, adjusted for age, gender, and race.

Results: LDL-C and LDL-P were associated with incident CVD overall: hazard ratios (HR 1.20, 95% CI [CI] 1.08-1.34; and 1.32, 95% CI 1.19-1.47, respectively, but for those with discordant levels, only LDL-P was associated with incident CVD (HR 1.45, 95% CI 1.19-1.78; LDL-C HR 1.07, 95% CI 0.88-1.30). IMT also tracked with LDL-P rather than LDL-C, ie, adjusted mean IMT of 958, 932, and 917 microm in the LDL-P > LDL-C discordant, concordant, and LDL-P < LDL-C discordant subgroups, respectively, with the difference persisting after adjustment for LDL-C (P = .002) but not LDL-P (P = .60).

Conclusions: For individuals with discordant LDL-C and LDL-P levels, the LDL-attributable atherosclerotic risk is better indicated by LDL-P.

Figure 1

Relations between LDL-C and LDL-P among 5598 MESA participants. (A) Relation of LDL-C and LDL-P concentrations. (B) Relation of LDL-C and LDL-P levels given in percentile units. The dashed lines bracket concordant LDL-C and LDL-P values defined as those within ±12 percentile units.

Figure 2

Cumulative incidence of cardiovascular events in subgroups with concordant or discordant levels of LDL-C and LDL-P, from proportional hazards models adjusted for age, gender, and race. The 3 subgroups are the same as in Table 1; mean levels of LDL-P and LDL-C are adjusted for age, gender, and race.

Figure 3

Cumulative incidence of cardiovascular events in subgroups with low LDL-C and/or low LDL-P, from proportional hazards models adjusted for age and gender. Low LDL-C and LDL-P values were defined as < 100 mg/dL and <1060 nmol/L, respectively (<30^th percentile).

Figure 4

Carotid IMT in μm by tertile of LDL-C (top) or LDL-P (bottom) in 3 subgroups with concordant or discordant LDL levels. Least squares mean IMT and 95% confidence intervals are from multiple linear regression models adjusted for age, gender, race, systolic blood pressure, hypertension treatment, smoking, body mass index, and diabetes status. Subgroups analyzed: LDL-P > LDL-C discordant; n=1126 (), concordant; n=2246 (), LDL-P < LDL-C discordant; n=1127 ().