Association of Coronary Calcium, Carotid Wall Thickness, and Carotid Plaque Progression With Low-Density Lipoprotein and High-Density Lipoprotein Particle Concentration Measured by Ion Mobility (From Multiethnic Study of Atherosclerosis [MESA]).

Current risk stratification strategies do not fully explain cardiovascular disease (CVD) risk. We aimed to evaluate the association of low-density lipoprotein (LDL-P) and high-density lipoprotein (HDL-P) particles with progression of coronary artery calcium and carotid wall injury. All participants in the Multi-Ethnic Study Atherosclerosis (MESA) with LDL-P and HDL-P measured by ion mobility, coronary artery calcium score (CAC), carotid intima-media thickness (IMT), and carotid plaque data available at Exam 1 and 5 were included in the study. CAC progression was annualized and treated as a categorical or continuous variable. Carotid IMT and plaque progression were treated as continuous variables. Fully adjusted regression models included established CVD risk factors, as well as traditional lipids. Mean (±SD) follow-up duration was 9.6 ± 0.6 years. All LDL-P subclasses as well as large HDL-P at baseline were positively and significantly associated with annualized CAC progression, however, after adjustment for established risk factors and traditional lipids, only the association with medium and very small LDL-P remained significant (β -0.02, p = 0.019 and β 0.01, p = 0.003, per 1 nmol/l increase, respectively). Carotid plaque score progression was positively associated with small and very small LDL-P (p <0.01 for all) and non-HDL-P (p = 0.013). Only the association with very small LDL-P remained significant in a fully adjusted model (p = 0.035). Mean IMT progression was not associated with any of the lipid particles. In conclusion, in the MESA cohort, LDL-P measured by ion mobility was significantly associated with CAC progression as well as carotid plaque progression beyond the effect of traditional lipids.

Ceponiene I ，Li D ，El Khoudary SR ，Nakanishi R ，Stein JH ，Wong ND ，Nezarat N ，Kanisawa M ，Rahmani S ，Osawa K ，Tattersall MC ，Budoff MJ ... -  《-》

High-Density Lipoprotein Subspecies Defined by Apolipoprotein C-III and Subclinical Atherosclerosis Measures: MESA (The Multi-Ethnic Study of Atherosclerosis).

Apolipoprotein C-III (apoC-III), a small proinflammatory protein present on 6% to 7% of high-density lipoprotein (HDL) particles, defines a subspecies of HDL adversely associated with coronary heart disease in primarily white cohorts. In a multi-ethnic population free of clinical cardiovascular disease, we evaluated the relationship between apoC-III-defined HDL subspecies and subclinical markers of atherosclerotic pathology. We investigated cross-sectional associations between apolipoprotein A-I concentrations of apoC-III-defined HDL subspecies, measured via ELISA and imaging measures of subclinical atherosclerosis, among 4659 participants in the MESA (The Multi-Ethnic Study of Atherosclerosis) at baseline (2000-2002). HDL particles containing and lacking apoC-III were divergently associated with coronary artery calcification in women (P-heterogeneity=0.002) but not in men (P-heterogeneity=0.31) and with carotid plaque score (P-heterogeneity=0.02) and intima-media thickness (P-heterogeneity=0.06) in the overall study population. HDL lacking apoC-III was inversely associated with all outcome measures (coronary artery calcification, women: odds ratio per SD=0.81 [95% confidence interval [CI], 0.73-0.90]; carotid plaque, overall: odds ratio per SD=0.92 [95% CI, 0.84-1.00]; intima-media thickness, overall: mean difference per SD=-14.0 µm [95% CI, -21.1 to -6.7 μm]), whereas HDL containing apoC-III was positively associated (coronary artery calcification, women: odds ratio=1.10 [95% CI, 0.99-1.22]; plaque, overall: odds ratio=1.10 [95% CI, 1.01-1.19]) or unassociated. Neither total HDL nor HDL subspecies was associated with changes in subclinical atherosclerosis measures up to 10 years later. The presence of apoC-III defined a subspecies of HDL not inversely associated with baseline measures of subclinical atherosclerosis, supporting a role of apoC-III in the pathophysiology of cardiovascular disease.

Aroner SA ，Koch M ，Mukamal KJ ，Furtado JD ，Stein JH ，Tattersall MC ，McClelland RL ，Jensen MK ... -  《Journal of the American Heart Association》

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.

High blood cholesterol contributes to atherosclerosis, yet reliance on the lipid panel alone may mischaracterize individuals with elevated lipoprotein particle numbers. The aim of the article was to 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 2228 Multi-Ethnic Study of Atherosclerosis participants. 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 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. After adjustment for typical CV risk factors, individuals in top quartiles of ApoB, ApoB/apolipoprotein A-I, low-density lipoprotein particles (LDL-P), small LDL-P, and total LDL-P/high-density lipoprotein (HDL) particles showed similar risks of carotid plaque and cIMT progression as LDL-C, non-HDL cholesterol (HDL-C), total cholesterol (TC), and TC/HDL-C. A significant association with plaque progression remained in the top ApoB quartile after further adjustment for LDL-C (P = .02) or TC + HDL-C (P = .04), but was nonsignificant when adjusted for all lipid covariates (P = .086). Those in the top quartile of small LDL-P concentrations showed greater cIMT progression than those in the referent after adjustment for LDL-C, but this was nonsignificant after adjustment for TC + HDL-C. 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.

Steffen BT ，Guan W ，Remaley AT ，Stein JH ，Tattersall MC ，Kaufman J ，Tsai MY ... -  《-》

Comparison of coronary artery calcium presence, carotid plaque presence, and carotid intima-media thickness for cardiovascular disease prediction in the Multi-Ethnic Study of Atherosclerosis.

Presence of coronary artery calcium (CAC), carotid plaque, and increased carotid intima-media thickness (IMT) may indicate elevated cardiovascular disease (CVD) risk; however, no large studies have compared them directly. This study compares predictive uses of CAC presence, carotid artery plaque presence, and high IMT for incident CVD events. Participants were from the Multi-Ethnic Study of Atherosclerosis (MESA). Predictive values of carotid plaque, IMT, and CAC presence were compared using Cox proportional hazards models, c-statistics, and net reclassification indices. The 6779 participants were mean (SD) 62.2 (10.2) years old; 49.9% had CAC, and 46.7% had carotid plaque. The mean left and right IMT were 0.754 (0.210) mm and 0.751 (0.187) mm, respectively. After 9.5 years (mean), 538 CVD events, 388 coronary heart disease (CHD) events, and 196 stroke/transient ischemic attacks were observed. CAC presence was a stronger predictor of incident CVD and CHD than carotid ultrasound measures. Mean IMT≥75th percentile (for age, sex, and race) alone did not predict events. Compared with traditional risk factors, c-statistics for CVD (c=0.756) and CHD (c=0.752) increased the most by the addition of CAC presence (CVD, 0.776; CHD, 0.784; P<0.001) followed by carotid plaque presence (CVD, c=0.760; CHD, c=0.757; P<0.05). Compared with risk factors (c=0.782), carotid plaque presence (c=0.787; P=0.045) but not CAC (c=0.785; P=0.438) improved prediction of stroke/transient ischemic attacks. In adults without CVD, CAC presence improves prediction of CVD and CHD more than carotid plaque presence or high IMT. CAC and carotid ultrasound parameters performed similarly for stroke/transient ischemic attack event prediction.

Gepner AD ，Young R ，Delaney JA ，Tattersall MC ，Blaha MJ ，Post WS ，Gottesman RF ，Kronmal R ，Budoff MJ ，Burke GL ，Folsom AR ，Liu K ，Kaufman J ，Stein JH ... -  《-》

The prevalence and correlates of subclinical atherosclerosis among adults with low-density lipoprotein cholesterol <70 mg/dL: The Multi-Ethnic Study of Atherosclerosis (MESA) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

The prevalence and correlates of subclinical atherosclerosis when low-density lipoprotein cholesterol (LDL-C) levels are low remain unclear. Therefore, we examined the association of cardiovascular risk factors and subclinical atherosclerosis among individuals with untreated LDL-C <70 mg/dL. We included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohorts. To optimize accuracy, LDL-C was calculated by the validated Martin/Hopkins equation that uses an adjustable factor for the ratio of triglycerides to very low-density lipoprotein cholesterol. We defined subclinical atherosclerosis as a coronary artery calcium (CAC) score >0 in the combined cohort or common carotid intima media thickness (cIMT) in the 4th quartile, using cohort-specific cIMT distributions at baseline. Logistic regression models examined the cross-sectional associations of cardiovascular risk factors and subclinical atherosclerosis. Among 9411 participants not on lipid lowering therapy, 263 (3%) had LDL-C <70 mg/dL (MESA: 206, ELSA: 57). Mean age in this population was 58 (SD 12) years, with 43% men, and 41% Black. The prevalence of CAC >0 in those with untreated LDL-C<70 mg/dL was 30%, and 18% were in 4th quartile of cIMT. In demographically adjusted models, only ever smoking was significantly associated with both CAC and cIMT. Similar results were obtained in risk factor-adjusted models (smoking: OR, 2.29; 95% CI, 1.10-4.80 and OR, 3.44; 95% CI, 1.41-8.37 for CAC and cIMT, respectively). Among middle-aged to older individuals with untreated LDL-C <70 mg/dL, subclinical atherosclerosis remains moderately common and is associated with cigarette smoking.

Al Rifai M ，Martin SS ，McEvoy JW ，Nasir K ，Blankstein R ，Yeboah J ，Miedema M ，Shea SJ ，Polak JF ，Ouyang P ，Blumenthal RS ，Bittencourt M ，Bensenor I ，Santos RD ，Duncan BB ，Santos IS ，Lotufo PA ，Blaha MJ ... -  《-》