Race-Based Differences in Lipoprotein(a)-Associated Risk of Carotid Atherosclerosis.

Objective- Lp(a) [lipoprotein(a)] is a well-described risk factor for atherosclerosis, but Lp(a)-associated risk may vary by race/ethnicity. We aimed to determine whether race/ethnicity modifies Lp(a)-related risk of carotid atherosclerotic plaque outcomes among black, white, Chinese, and Hispanic individuals. Approach and Results- Carotid plaque presence and score were assessed by ultrasonography at baseline (n=5155) and following a median 9.4 year period (n=3380) in MESA (Multi-Ethnic Study of Atherosclerosis) participants. Lp(a) concentrations were measured by immunoassay and examined as a continuous and categorical variable using clinically-based cutoffs, 30 and 50 mg/dL. Lp(a) was related to greater risk of prevalent carotid plaque at baseline in whites alone (all P<0.001): per log unit (relative risk, 1.05); Lp(a)≥30 mg/dL (relative risk, 1.16); and Lp(a)≥50 mg/dL (relative risk, 1.20). Lp(a) levels over 50 mg/dL were associated with a higher plaque score at baseline in whites (all P<0.001) and Hispanics ( P=0.04). In prospective analyses, whites with Lp(a) ≥50 mg/dL were found to have greater risk of plaque progression (relative risk, 1.12; P=0.03) and higher plaque scores (all P<0.001) over the 9.4-year follow-up. Race-based differences between whites and black participants were significant for cross-sectional associations and for carotid plaque score following the 9.4 year study period. Conclusions- Race was found to be a modifying variable in Lp(a)-related risk of carotid plaque, and Lp(a) levels may have greater influence on plaque burden in whites than in black individuals. Borderline results in Hispanics suggest that elevated Lp(a) may increase the risk of carotid plaque, but follow-up studies are needed.

Plasma n-3 and n-6 Fatty Acids Are Differentially Related to Carotid Plaque and Its Progression: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: ω-3 (n-3) fatty acids (FAs) have long been considered healthful dietary components, yet recent clinical trials have questioned their cardiovascular benefits. By contrast, the ω-6 (n-6) FAs have been considered harmful, proatherogenic macronutrients, despite an absence of empirical evidence supporting this hypothesis. We aimed to determine whether plasma n-3 and n-6 FAs are related to risk of carotid plaque and its progression in 3327 participants of MESA (Multi-Ethnic Study of Atherosclerosis). APPROACH AND RESULTS: Carotid plaque was assessed using ultrasonography at baseline and after a median period of 9.5 years. Plasma phospholipid n-3 and n-6 FAs were determined using gas chromatography-flame ionization detection. Relative risk regression analyses assessed the relations of FAs with the presence or progression of carotid plaque adjusted for typical cardiovascular disease risk factors. At baseline, it was found that participants in the fourth quartile of n-3 docosahexaenoic acid showed a 9% lower risk of carotid plaque (P=0.05), whereas those in the second quartile of n-3 α-linolenic acid showed an 11% greater risk compared with respective referent quartiles (P=0.02). In prospective analyses, individuals in the top quartile of docosahexaenoic acid showed a 12% lower risk of carotid plaque progression during 9.5 years compared with those in the referent quartile (P=0.002). No significant relations were observed among n-6 FAs and plaque outcomes. No significant race/ethnicity interactions were found. CONCLUSIONS: These findings support docosahexaenoic acid as an atheroprotective macronutrient, whereas null findings for n-6 FAs challenge the view that they promote atherosclerosis.

Race is a key variable in assigning lipoprotein(a) cutoff values for coronary heart disease risk assessment: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: We aimed to examine associations of lipoprotein(a) (Lp(a)) concentrations with coronary heart disease (CHD) and determine whether current Lp(a) clinical laboratory cut points identify risk of disease incidence in 4 races/ethnicities of the Multi-Ethnic Study of Atherosclerosis (MESA). APPROACH AND RESULTS: A subcohort of 1323 black, 1677 white, 548 Chinese American, and 1044 Hispanic MESA participants were followed up during a mean 8.5-year period in which 235 incident CHD events were recorded. Lp(a) mass concentrations were measured using a turbidimetric immunoassay. Cox regression analysis determined associations of Lp(a) with CHD risk with adjustments for lipid and nonlipid variables. Lp(a) concentrations were continuously associated with risk of CHD incidence in black (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.09-2.04] and white participants (HR, 1.22; 95% CI, 1.02-1.45). Examining Lp(a) risk by the 50 mg/dL cut point revealed higher risks of incident CHD in all races except Chinese Americans: blacks (HR, 1.69; 95% CI, 1.03-2.76), whites (HR, 1.82; 95% CI, 1.15-2.88); Hispanics (HR, 2.37; 95% CI, 1.17-4.78). The lower Lp(a) cut point of 30 mg/dL identified higher risk of CHD in black participants alone (HR, 1.87; 95% CI, 1.08-3.21). CONCLUSIONS: Our findings suggest that the 30 mg/dL cutoff for Lp(a) is not appropriate in white and Hispanic individuals, and the higher 50 mg/dL cutoff should be considered. In contrast, the 30 mg/dL cutoff remains suitable in black individuals. Further research is necessary to develop the most clinically useful Lp(a) cutoff values in individual races/ethnicities.

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.

BACKGROUND: High blood cholesterol contributes to atherosclerosis, yet reliance on the lipid panel alone may mischaracterize individuals with elevated lipoprotein particle numbers. OBJECTIVE: 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. 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 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: 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. 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.