Higher levels of apolipoprotein B–containing particles and lipoprotein(a) could be linked to a greater risk of coronary artery disease in a large prospective study of healthy adults.
Investigators followed 207,368 UK Biobank participants with no history of atherosclerotic disease, diabetes, or lipid-lowering therapy. Over a median follow-up of 13.7 years, 7,585 of the participants developed coronary artery disease (CAD).
A 1–standard deviation (SD) increase in nuclear magnetic resonance (NMR)-measured apolipoprotein B (apoB) particle (apoB-P) (370 nmol/L) was linked to a 34% higher risk of CAD (hazard ratio [HR] = 1.34, 95% confidence interval [CI] = 1.31–1.37). A similar association was seen with conventional apoB-P measurement (HR = 1.33, 95% CI = 1.30–1.36).
The investigators reported that total apoB-P count, rather than lipoprotein type or size, most accurately reflected lipid-related risk.
Although very low–density lipoprotein (VLDL) particles had a higher per-particle atherogenic risk compared with low-density lipoprotein (LDL) particles (HR per 100 nmol/L = 1.22 vs 1.07), LDL accounted for 91% of total apoB-P, making total particle count the stronger predictor overall.
"The lipid-related risk of CAD is most accurately reflected by the total count of apoB-P and is largely unaffected by major particle type (VLDL, [intermediate-density lipoprotein]/LDL), count, or size," said lead study author Jakub Morze, of SciLifeLab at the Chalmers University of Technology in Gothenburg, Sweden, and colleagues.
Lipoprotein size, including average VLDL and LDL diameters, showed no association with CAD after adjustment for apoB-P. Similarly, subclass analysis found no added predictive value from particle size once total count was considered.
In contrast, higher lipoprotein(a) [Lp(a)] levels independently increased CAD risk. A 1-SD increase (72 nmol/L) in Lp(a) was associated with a 20% higher risk (HR = 1.20, 95% CI = 1.18–1.22), and each 100 nmol/L increase conferred a 3.3-fold greater risk compared with an equivalent increase in apoB-P.
Adding apoB-P to clinical risk models improved 10-year prediction accuracy (area under the curve [AUC] = 0.758–0.769, P < .001). Including Lp(a) further raised the AUC to 0.774 (P < .001). By comparison, adding VLDL vs LDL type or particle size didn't significantly enhance model performance.
The findings were confirmed in an independent cohort of 10,857 participants from the Swedish SIMPLER study, which recorded 661 incident CAD cases.
The investigators concluded that for primary prevention, measuring apoB-P and Lp(a) may offer the most accurate lipid-related risk assessment. Particle type and size added limited value once apoB-P was accounted for.
“Adequate assessment of atherogenic risk from dyslipidemia is best accomplished by consideration of both apoB-P and Lp(a) concentrations,” the study authors concluded.
Full author disclosures are available in the published article.
Source: European Heart Journal
