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

Abstract

Background High blood cholesterol contributes to atherosclerosis, yet reliance on the lipid panel alone may mischaracterize individuals with elevated lipoprotein particle numbers. Objective Determine whether elevated lipoprotein or apolipoprotein measures are associated with carotid atherosclerosis and plaque progression independent of cardiovascular (CV) risk factors including standard lipids in a subcohort of 2,228 Multi-Ethnic Study of Atherosclerosis participants. Methods Ultrasonography assessed carotid artery plaque and common carotid intima media thickness (cIMT) at baseline and after a median period of 9.4 years. Nuclear magnetic resonance spectroscopy estimated lipoprotein particle concentrations. Apolipoprotein B (ApoB) and apolipoprotein A-I (ApoA-I) were measured using an automated immunoassay. Regression analysis determined associations of apolipoprotein and lipoprotein measurements with cIMT, and relative risk regression determined associations with carotid plaque progression. Results Following adjustment for typical CV risk factors, individuals in top quartiles of ApoB, ApoB/ApoA-I, LDL-P, small LDL-P, and total LDL-P/HDL-P showed similar risks of carotid plaque and cIMT progression as LDL-C non-HDL-C, total cholesterol (TC), and TC/HDL-C. A significant association with plaque progression remained in the top ApoB quartile following further adjustment for LDL-C (p=0.02) or TC+HDL-C (p=0.04), but was non-significant when adjusted for all lipid covariates (p=0.086). Those in the top quartile of small LDL-P concentrations showed greater cIMT progression than those in the referent following adjustment for LDL-C, but this was non-significant following adjustment for TC+HDL-C. Conclusion When coupled with evidence that apolipoprotein testing identifies lipid-lipoprotein discordance, these findings suggest that ApoB and small LDL-P provide atherosclerosis risk information that is not revealed by typical CV risk factors.

Apolipoprotein B discordance with low-density lipoprotein cholesterol and non–high-density lipoprotein cholesterol in relation to coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis (MESA)

“…The results of the present study are consistent with previous reports on the individual measures of apo B, LDL-C, and non-HDL-C, [7][8][9][10][11][12][13][14][15][16]39 but are generally smaller than associations reported in previous investigations of apo B discordance. 7,8,[10][11][12][13]15,16 This may be due to a number of differences between these studies, including differences in populations, outcome variables, or degree of concordance among markers.…”

“…1 Consistent with the findings in the present study, previous analyses in MESA observed that apo B did not improve CHD net reclassification when added to established CHD risk factors in the pooled cohort equation. 14,40…”

“…Alternatively, apolipoprotein B (apo B) may be a better, or a useful additional, marker for ASCVD risk assessment because it is present on atherogenic lipoproteins, and thus, is more reflective of particle numbers. [7][8][9][10][11][12][13][14][15] Importantly, apo B is highly correlated with LDL-C and non-HDL-C; therefore, the clinical utility of measuring apo B, in addition to cholesterol, is controversial. Most recently, the 2018 American College of Cardiology (ACC) American Heart Association/Multisociety Guidelines for the management of blood cholesterol has included apo B as a risk assessment enhancer that may be of value under certain circumstances.…”

Small Dense Low-Density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression

“…Elevated LDL-C levels are associated with CVD events 3 ) , and lowering LDL-C, along with lifestyle modifications and treatment modalities, has reduced CVD risk 41 ) . In addition, increased LDL-C levels are also associated with atherosclerosis development 25 – 27 ) . Recent recommendations indicate that LDL-C targets should be < 100 mg/dL in high risk subjects and < 70 mg/dL in CVD patients, similar to prior recommendations 42 – 44 ) .…”

Apolipoprotein B/apolipoprotein A1 ratio and mortality among incident peritoneal dialysis patients

“…Previous studies have suggested that a high apo B/apo A1 ratio strongly correlates with pathophysiological markers of atherosclerosis defined by coronary angiography [ 8 , 20 ], and calcium scores of the coronary arteries [ 21 ], and by ultrasound techniques such as the thickness of carotid arteries [ 16 , 22 , 23 ], endothelial dysfunction [ 24 ] and existence of femoral plaques [ 25 ]. In addition, a high apo B/apo A1 ratio can also be used to predict risk of carotid plaque development [ 26 ] and major adverse cardiovascular events [ 14 , 27 – 29 ]. Our findings are in agreement with these studies and show that the apo B/apo A1 ratio is independently associated with cardiovascular events.…”