Indicators of the atherogenic lipoprotein phenotype measured with density gradient ultracentrifugation predict changes in carotid intima-media thickness in men and women

Abstract

ObjectiveProgression of carotid intima-media thickness (CIMT) is a surrogate indicator for the early stages of atherosclerosis.MethodsThe study investigated relationships between baseline lipoprotein cholesterol, triglyceride (TG), and apolipoprotein (Apo) B levels assessed with density gradient ultracentrifugation (DGU) and progression of posterior wall common CIMT in men (45–75 years of age) and women (55–74 years of age) in the control arm of a clinical trial. Participants had baseline posterior wall CIMT 0.7–2.0 mm, without significant stenosis. CIMT was assessed using B-mode ultrasound at baseline, and 12 and ~18 months. A DGU cholesterol panel that assessed the major lipoprotein classes and subclasses, plus triglycerides, lipoprotein (a) cholesterol, low-density lipoprotein (LDL) peak time (inversely related to LDL particle density), and Apo B were performed on fasting baseline samples. Apo B was also measured using an enzyme linked immunosorbent assay.ResultsBaseline CIMT was inversely associated (P < 0.001) with CIMT progression. After adjustment for baseline CIMT, significant predictors of posterior wall CIMT progression in linear regression analyses included LDL peak time (inverse, P = 0.045), total high-density lipoprotein cholesterol (HDL-C) (inverse, P = 0.001), HDL2-C (inverse, P = 0.005), HDL3-C (inverse, P = 0.003), very low-density lipoprotein (VLDL)-C (P = 0.037), and VLDL1+2-C (P = 0.016).ConclusionThese data indicate that DGU-derived indicators of the “atherogenic lipoprotein phenotype,” including increased TG-rich lipoprotein cholesterol, lower HDL-C and HDL-C subfractions, and a greater proportion of LDL-C carried by more dense LDL particles, are associated with CIMT progression in men and women at moderate risk for coronary heart disease.

Traditional Risk Factors are Causally Related to Carotid Intima-Media Thickness Progression: Inferences from Observational Cohort Studies and Interventional Trials

“…Similar direct associations with C-IMTp were reported for triglycerides [126,132], whereas HDL-C levels associated inversely with C-IMTp in population based cohorts [13,17,111,126,133], in patients with VRFs [82,130,134,135] or CAD [22].…”

“…Studies performed in different patient populations investigated also associations of C-IMTp with lipid ratios, lipoprotein species, apolipoproteins and modified lipoproteins. Significant direct associations were reported for TC/HDL-C [9,132], TG/HDL-C [132], ApoB/HDL-C [132], VLDL-C [135], VLDL1+2-C [135], ApoB levels [126] or ApoB/ApoA-I ratio [136].…”

Apolipoprotein B is associated with carotid atherosclerosis progression independent of individual cholesterol measures in a 9-year prospective study of Multi-Ethnic Study of Atherosclerosis participants

“…Finally, in a subcohort of 472 Cardiovascular Risk in Young Finns study participants, ApoB and the ApoB/ApoA-I ratio measured at baseline were associated with common cIMT after a 21-year follow up period (p<0.001) independent of gender, age, and smoking. [6] Contrary to the above findings, a more recent study by Maki et al[32] showed no association between ApoB and cIMT progression over 12 and 18 month time periods (p=0.06), but the abbreviated timelines may have contributed to the borderline result.…”

Matrix Metalloproteinases 2 and 9 are CAD More Relevant Biomarkers Than -1, -8, and -12 to Separate CAD from Non-CAD Patients

“…ADAMS, ADAMTS), gene expression control [9, 12] LDL particle size and HDL´s free cholesterol acceptance [15]. In addition, conditions such as dyslipidemia, hypertension and diabetes [16,32] may modulate MMP activity. However, we must realize that the MMP activity was not investigated in situ and it may not necessarily reflect the MMP circulating behavior [18].…”