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• Lp(a) was not associated with baseline/progression of CAC volume/density. • Lp(a) associated modestly with CAC volume progression. • At younger ages Lp(a) associated modestly with CAC baseline and volume progression. • Lp(a) was not as robustly associated with CAC as other lipid biomarkers. Coronary artery calcium (CAC) scoring is often used for atherosclerotic cardiovascular disease (ASCVD) risk stratification in individuals with elevated lipoprotein(a) [Lp(a)]. To evaluate associations between Lp(a) and baseline CAC (volume/density) and CAC progression compared to other lipid biomarkers. We utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of individuals without clinical ASCVD, excluding statin users. We evaluated the associations between Lp(a), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides, total cholesterol, apolipoprotein B, and non-HDL-C with baseline CAC and annual CAC progression using multivariable ordinal regression with adjustment for ASCVD risk factors. Analyses were also stratified by median age. In 5,597 participants (2,726 at median 9.5-year follow-up), Lp(a) was not associated with baseline CAC volume or density and was modestly associated with volume progression (OR 1.11, 95% CI 1.03-1.21). However, other biomarkers were positively associated with baseline volume and volume progression (LDL-C: OR 1.26, 95% CI: 1.19-1.33 and OR 1.22, 95% CI: 1.15-1.30, respectively), except HDL-C which was inversely associated. LDL-C, total cholesterol and non-HDL-C were inversely associated with baseline density. In participants <62 years of age, Lp(a) was modestly associated with baseline CAC volume (OR 1.10, 95% CI: 1.00-1.20) and volume progression (OR 1.16 95% CI: 1.04-1.30). In contrast to other lipid biomarkers, Lp(a) was not associated with baseline CAC volume or density and was only modestly associated with volume progression. Our findings suggest that Lp(a) is not as robustly associated with CAC as other lipid biomarkers. [ABSTRACT FROM AUTHOR]

Background Circulating individual SFAs in pregnant females are critical for maternal and fetal health. However, research on identifying their modifiable factors is limited. Objectives We aimed to examine the associations of total physical activity (PA) and types of PA with circulating individual SFAs during pregnancy in a multiracial/multiethnic cohort of pregnant females in the United States. Methods The study included participants in a nested case–control study (n  = 321) from the Eunice Kennedy Shriver NICHD Fetal Growth Studies–Singleton Cohort. Sampling weights were applied, so the results represented the entire Fetal Growth Cohort. Plasma phospholipid SFAs were measured at 4 visits [10–14 (visit 1), 15–26 (visit 2), 23–31 (visit 3), and 33–39 (visit 4) weeks of gestation] throughout pregnancy. PA of the previous year at visit 1 and since the previous visit at the subsequent visits was assessed using the validated Pregnancy PA Questionnaire. Time-specific and longitudinal associations were examined using multivariable linear and generalized estimating equation models. Results Total PA (metabolic equivalent of task-h/wk) was positively associated with circulating heptadecanoic acid (17:0) at visit 1 (β × 103: 0.07; 95% CI: 0.02, 0.11) and pentadecanoic acid (15:0) at visit 3 (β × 103: 0.09; 95% CI: 0.03, 0.14) independent of sociodemographic, reproductive, pregnancy, and dietary factors. Across the 4 visits, the positive associations with total PA were consistent for pentadecanoic acid (β × 103: 0.06; 95% CI: 0.02, 0.10) and heptadecanoic acid (β × 103: 0.10; 95% CI: 0.06, 0.14). Out of the 4 PA types (i.e. sports/exercise, household/caregiving, transportation, and occupational PA) considered, the magnitude of positive associations was the largest for sports/exercise PA. Conclusions Our findings suggest that maternal PA is positively associated with circulating pentadecanoic and heptadecanoic acids. The findings warrant confirmation by future studies. This trial was registered at clinicaltrials.gov as NCT00912132. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2010.03.023 Byline: Karine Sahakyan (a), Barbara E.K. Klein (a), Chelsea E. Myers (a), Michael Y. Tsai (b), Ronald Klein (a) Abstract: Data from longitudinal studies suggest that biomarkers of inflammation and endothelial dysfunction are associated with development of hypertension. None of these studies have examined the association of these markers with hypertension risk in persons with diabetes. We examined the associations of inflammatory and endothelial dysfunction markers with long-term hypertension incidence in persons with type 1 diabetes mellitus. Author Affiliation: (a) Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI (b) Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN Article History: Received 27 January 2010; Accepted 18 March 2010

Background n-3 and n-6 PUFAs have physiologic roles in sleep processes, but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters. Objectives We sought to assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Research Consortium. Methods Harmonized, de novo, individual-level analyses were performed and pooled across 12 cohorts. Participants were 35–96 y old and from 5 nations. Circulating measures included α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA), DHA, EPA + DPA + DHA, linoleic acid, and arachidonic acid. Sleep duration (10 cohorts, n  = 18,791) was categorized as short (≤6 h), 7–8 h (reference), or long (≥9 h). Difficulty falling asleep (8 cohorts, n  = 12,500) was categorized as yes or no. Associations between PUFAs, sleep duration, and difficulty falling sleeping were assessed by cross-sectional multinomial logistic regression using standardized protocols and covariates. Cohort-specific multivariable-adjusted ORs per quintile of PUFAs were pooled with inverse–variance weighted meta-analysis. Results In pooled analysis adjusted for sociodemographic characteristics and health status, participants with higher very long-chain n-3 PUFAs were less likely to have long sleep duration. In the top compared with the bottom quintiles, the multivariable-adjusted ORs (95% CIs) for long sleep were 0.78 (95% CI: 0.65, 0.95) for DHA and 0.76 (95% CI: 0.63, 0.93) for EPA + DPA + DHA. Significant associations for ALA and n-6 PUFA with short sleep duration or difficulty falling sleeping were not identified. Conclusions Participants with higher concentrations of very long-chain n-3 PUFAs were less likely to have long sleep duration. While objective biomarkers reduce recall bias and misclassification, the cross-sectional design limits assessment of the temporal nature of this relation. These novel findings across 12 cohorts highlight the need for experimental and biological assessments of very long-chain n-3 PUFAs and sleep duration. [ABSTRACT FROM AUTHOR]

Prospective and longitudinal data on the association between acylcarnitines and gestational diabetes (GDM) are lacking. This study aims to prospectively investigate 28 acylcarnitines in relation to subsequent GDM risk. Within the NICHD Fetal Growth Studies-Singleton Cohort, plasma levels of acylcarnitines and cardiometabolic biomarkers were measured at gestational week (GW) 10–14, 15–26, 23–31, and 33–39 among 107 GDM cases and 214 controls. At GW 10–14, per standard deviation (SD) increased level of C14:1-OH was associated with a 55% increased risk of GDM after adjusting for major risk factors for GDM [OR (95% CI): 1.55 (1.05–2.29)]. At GW 15–26, C4, C8:1 and C16:1-OH were associated with an increased risk of GDM [OR (95% CI) for per SD increase: 1.42 (1.01–2.00), 1.41 (1.02–1.96), and 1.77 (1.10–2.84), respectively]. Whereas increased C10 and C18 were related to lower risk of GDM [OR (95% CI) for per SD increase: 0.74 (0.55–1.00), and 0.69 (0.49–0.97), respectively]. Moreover, we observed correlations of individual acylcarnitine with multiple clinical markers implicated in glucose homeostasis and cardiometabolic function among non-GDM women. Our results demonstrate that several plasma acylcarnitine species are differentially associated with GDM risk by chain length. Future studies are warranted to investigate the distinct roles of individual acylcarnitine in glucose homeostasis in pregnancy. [ABSTRACT FROM AUTHOR]

• Free Fatty Acids (FFA) were not associated with heart failure (HF) overall. • FFA were not associated with reduced ejection HF. • Higher FFA were associated with preserved ejection fraction HF among females only. • FFA were not associated with NT-proBNP. • FFA were inversely associated with LV mass index and LV hypertrophy. Free fatty acids (FFAs) may be associated with heart failure (HF) risk, but prospective research is lacking. This study investigated associations between fasting FFAs and HF incidence overall and by ejection fraction (EF) subtypes [HF with preserved EF (HFpEF) and HF with reduced EF (HFrEF)] to evaluate FFAs as a potential biomarker for HF risk prediction. This study was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA) prospective cohort among 6,667 participants with complete baseline (2000-2002) FFAs and HF follow-up (through 2015). Associations between FFAs and HF incidence were evaluated with Cox proportional hazards regression. Cross-sectional associations between FFAs and HF risk markers were also evaluated using linear regression [N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular (LV) mass index] and logistic regression [LV hypertrophy (LVH)]. Stratification and cross-product terms were utilized to evaluate differences by age, sex, race/ethnicity and diabetes. FFAs were not associated with HF overall or with HFrEF. FFAs were not associated with HFpEF in the overall population or among males, but were borderline positively associated with risk among females (fully-adjusted tertile 3 vs. 1 HR=2.17, 95% CI: 1.06, 4.42) (sex P-interaction=0.05). FFAs were not associated with NT-proBNP, but were inversely associated with LV mass index and LVH with stronger associations among females (P-interaction≥0.10). Associations did not differ by age, race/ethnicity or diabetes status. FFAs generally do not appear to be an independent predictor for HF risk. Additional research is needed to confirm findings particularly studies evaluating associations by sex and EF subtypes. [ABSTRACT FROM AUTHOR]

Background: Current literature examining the prospective relation of circulating omega-3 (n-3) and omega-6 (n-6) PUFAs and atrial fibrillation (AF) is limited to predominantly white populations.Objectives: We investigated the association of circulating n-3 and n-6 PUFAs with incident AF in participants from the Multi-Ethnic Study of Atherosclerosis.Methods: A total of 6229 participants (mean age = 62 y; 53% female; 39% white, 27% black, 22% Hispanic, and 12% Chinese) who were free of baseline AF and with plasma phospholipid PUFAs measured at baseline using GC were prospectively followed for the development of AF. Incident AF was ascertained using International Classification of Diseases-9 codes from hospital discharge records and Medicare claims data with follow-up through 2014. Multivariable Cox proportional hazards regression analysis was performed to determine the risk of incident AF.Results: During a median follow-up of 12.9 y, 813 (13%) participants developed AF. Each higher SD increment in arachidonic acid (AA; 20:4n-6) concentrations was associated with an 11% decreased risk of incident AF (HR: 0.89; 95% CI: 0.82, 0.96). Similarly, higher overall n-6 PUFA concentrations were also associated with a reduced AF risk (HR per SD increment: 0.93; 95% CI: 0.87, 1.00). Although no significant overall associations were observed for any individual n-3 PUFAs, higher circulating concentrations of DHA (22:6n-3) and EPA (20:5n-3) were associated with a decreased AF risk in blacks and Hispanics (DHA only) but not whites or Chinese Americans.Conclusions: In a multiethnic cohort of individuals free of baseline cardiovascular disease, higher plasma concentrations of n-6 PUFAs, particularly AA, were associated with a reduced risk of incident AF. Important differences in AF risk were also noted across race/ethnicity for the n-3 PUFAs DHA and EPA. [ABSTRACT FROM AUTHOR]

Lipoprotein (a) [Lp(a)] is a risk factor for coronary heart disease and calcific aortic valve disease. We determined the relationships of Lp(a) with prevalence and progression of coronary artery calcification (CAC), mitral annular calcification (MAC), and thoracic aortic calcification (TAC) in a multi-ethnic cohort of middle to older-aged adults. This analysis included 6705 Multi-Ethnic Study of Atherosclerosis participants. Lp(a) was measured with a turbidimetric immunoassay. CAC, MAC, and TAC were assessed by cardiac computed tomography both at baseline and once during follow-up. In adjusted relative risk regression cross-sectional analysis, a Lp(a) level ≥50 ​mg/dL was associated with a 22% higher prevalence of MAC (relative risk (RR) ​= ​1.22, 95% confidence interval (CI) 1.00, 1.49). No significant associations were observed for prevalent CAC or TAC. In adjusted prospective analyses, participants with Lp(a) ≥50 ​mg/dL were at significantly higher risk for rapid CAC progression (median follow-up ​= ​8.9 years), defined as ≥100 units/year, compared to those with lower Lp(a) levels (RR ​= ​1.67, 95% CI ​= ​1.23, 2.27). The association between higher Lp(a) levels and incident CHD was no longer significant after adjusting for CAC progression. No significant associations were observed for MAC or TAC progression (median follow-up ​= ​2.6 years). Higher Lp(a) levels are associated with more rapid CAC progression. Additional study is needed to better understand how this relationship can further improve the ability of Lp(a) to enhance cardiovascular disease risk prediction. [ABSTRACT FROM AUTHOR]

Omega-6 polyunsaturated fatty acids (PUFAs) have been shown to relate to insulin resistance and type 2 diabetes (T2D), but influence of race/ethnicity has not been investigated. The aim of this study was to determine whether omega-6 PUFAs, and estimated desaturase enzyme activity, are associated with fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and incident T2D, and whether associations differ by race/ethnicity. This study was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA) (N = 6282). Associations between baseline plasma phospholipid fatty acids (LA, Linoleic Acid; GLA, γ-linoleic acid; DGLA, Dihomo-γ-linolenic acid; AA, arachidonic acid; D5D, delta-5 desaturase; D6D, delta-6 desaturase), fasting glucose, insulin, and HOMA-IR [(fasting insulin – fasting glucose)/22.5] were evaluated using linear regression. Associations between omega-6 PUFAs (N = 5508 after excluding diabetics at baseline) and T2D incidence were assessed using Cox proportional hazards regression. Analyses were replicated/stratified by race/ethnicity (White, Black, Chinese, Hispanic) and tests for interaction were assessed by inclusion of a cross-product term in models. In fully adjusted models, insulin and HOMA-IR were positively associated with LA (insulin: 0.213 per SD, p = 0.01; HOMA-IR: 0.252 per SD, p < 0.001), GLA (insulin: 0.010 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), DGLA (insulin: 0.279 per SD, p < 0.001; HOMA-IR: 0.175 per SD, p < 0.001) and D6D activity (insulin: 0.001 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), and inversely associated with AA (insulin −0.272 per SD, p < 0.001; HOMA-IR: −0.125 per SD, p = 0.03) and D5D activity (insulin: −0.530 per SD, p < 0.001; HOMA-IR: −0.322 per SD, p < 0.001), while weak or no associations were observed with fasting glucose, and associations appeared to differ by race/ethnicity. After accounting for HOMA-IR at baseline, LA was inversely (HR: 0.87, p = 0.003) and DGLA (HR: 1.17, p < 0.001) and AA (HR: 1.15, p = 0.001) were positively associated with T2D in the overall population, but associations were attenuated or no longer present when stratified by race/ethnicity (P-interaction >0.05). Results confirm previous reports that omega-6 PUFAs are associated with hyperinsulinemia. Findings suggest omega-6 PUFAs are more likely markers of hyperinsulinemia rather than a protective/risk factor for T2D and indicate racial/ethnic differences in associations, but further research is needed to confirm findings. [ABSTRACT FROM AUTHOR]

Fasting free fatty acid (FFA) levels may be associated with cardiovascular disease (CVD) and mortality, but research among generally healthy adults, females, and racially/ethnically diverse populations is lacking. The primary aim of this project was to investigate prospective associations between fasting FFAs and coronary heart disease (CHD) and CVD incidence and CVD-specific and all-cause mortality in a generally healthy age, sex, and racially/ethnically heterogeneous population. This study was conducted in the Multi-Ethnic Study of Atherosclerosis cohort using baseline (2000–2002) fasting FFAs and outcome data through 2015 (N = 6678). Cox proportional hazards regression was used to calculate hazard ratios for associations between FFAs and CHD, CVD, CVD-specific mortality, and all-cause mortality. Interactions by age, sex, race/ethnicity, and metabolic syndrome were evaluated by stratification and cross-product terms. A secondary analysis was conducted to evaluate associations between FFAs, and inflammatory and endothelial activation biomarkers were evaluated using linear regression (analytic N range: 964–6662). FFA levels were not associated with CHD or CVD incidence. Higher FFAs were associated with CVD-specific and all-cause mortality, but associations were attenuated in fully adjusted models with a borderline significant association remaining only for all-cause mortality (fully adjusted, per standard deviation increase hazard ratio = 1.07, 95% confidence interval: 1.00–1.14). Associations did not differ by age, sex, race/ethnicity, or metabolic syndrome. Fasting FFAs were not associated with CHD, CVD, or CVD-specific mortality and were modestly associated with all-cause mortality, regardless of age, sex, race/ethnicity, or metabolic syndrome status. • Free fatty acids (FFAs) were not associated with coronary heart disease or cardiovascular disease incidence. • FFA were positively, but nonsignificantly, associated with cardiovascular disease–specific mortality. • FFA were modestly, positively associated with all-cause mortality. • Findings did not differ by age, sex, race/ethnicity, or metabolic syndrome status. • FFA were associated with several inflammatory and endothelial activation biomarkers. [ABSTRACT FROM AUTHOR]

Background Very-long-chain SFAs (VLSFAs) have recently gained considerable attention as having beneficial effects on health and aging. Objectives The objective of this study was to assess the associations of plasma phospholipid VLSFAs [arachidic acid (20:0), behenic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0)] with 20-y cognitive decline in the Atherosclerosis Risk in Communities (ARIC) participants. Furthermore, this study compared the associations of plasma phospholipid VLSFAs with 5 common groups of fatty acids [i.e., total SFAs, total MUFAs, total ω-3 (n–3) PUFAs, total marine-derived ω-3 PUFAs, total ω-6 PUFAs]. Methods This study used a cohort study design of 3229 ARIC participants enrolled at the Minnesota field center. Fatty acids were measured at visit 1 (1987–1989); and cognition was assessed at visits 2 (1990–1992), 4 (1996–1998), and 5 (2011–2013) using 3 tests: the Delayed Word Recall Test (DWRT), the Digit-Symbol Substitution Test (DSST), and the Word Fluency Test (WFT). Results Higher proportions of plasma phospholipid total VLSFAs and each individual VLSFA were associated with less decline in WFT, a test of verbal fluency. For example, 1 SD higher in total VLSFAs at baseline was associated with 0.057 SD (95% CI: 0.018, 0.096, P  = 0.004) less cognitive decline over 20 y as measured by WFT score. None of the 5 common fatty acid groups were associated with change in WFT, but a higher proportion of plasma phospholipid total MUFAs was associated with greater decline in DWRT; higher total ω-6 PUFAs with less decline in DWRT; and higher total ω-3 and total marine-derived ω-3 PUFAs with less decline in DSST. Conclusions This study suggests that higher proportions of plasma phospholipid VLSFAs in midlife may be associated with less 20-y cognitive decline. [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor (HGF) is associated with subclinical and clinical atherosclerosis. However, the significance of change in HGF and development of atherosclerotic disease is unknown. In a large and diverse population-based cohort, we report that change in the biomarker HGF is an independent predictor of incident CHD. [ABSTRACT FROM AUTHOR]

Background Limited evidence has suggested that circulating levels of the omega-9 fatty acid, oleic acid, may be related to greater risks of adverse cardiovascular outcomes. Objective We aimed to determine whether plasma oleic acid may be independently associated with clinical and subclinical cardiovascular disease (CVD) and all-cause mortality in a large multiethnic cohort. Methods Plasma fatty acids were measured by gas chromatography–flame ionization in 6568 participants of the Multi-Ethnic Study of Atherosclerosis. The presence of coronary artery calcium (CAC) and aortic valve calcification (AVC) was determined by computed tomography, and carotid plaque was assessed by ultrasound. Incident CVD was defined as myocardial infarction, fatal coronary heart disease, resuscitated cardiac arrest, stroke, or stroke death. Heart failure (HF) was adjudicated from clinical records. Relative risk regression estimated plasma oleic acid-related rate ratios for prevalent CAC, AVC, and carotid plaque. Cox regression estimated hazard ratios (HRs) for CVD, HF, and all-cause mortality over a median 13-year follow-up. Results Individuals in top quartiles of oleic acid showed greater rate ratios of CAC, AVC, and carotid plaque (all P <.001), but associations were rendered nonsignificant after adjustment for other risk factors. By contrast, those in top quartiles of plasma oleic acid showed significantly greater risks of incident HF (HR: 2.03; P <.001), CVD (HR: 1.41; P =.008), and all-cause mortality (HR: 1.55; P <.001) than those in referent quartiles independent of typical risk factors as well as plasma omega-3 fatty acid levels. Conclusions Plasma oleic acid appears to be a risk factor for CVD events and all-cause mortality independent of typical risk factors and plasma omega-3 fatty acids. Additional studies are warranted for confirmation and to further examine whether plasma oleic acid directly contributes to, or serves as a marker of, disease pathogenesis. These findings should not be extrapolated to dietary oleic acid intake. Highlights • Plasma oleic acid levels are related to cardiovascular disease events and all-cause mortality. • Associations were independent of typical cardiovascular disease risk factors and plasma omega-3 levels. • High plasma oleic acid may be pathogenic or a marker of stearoyl-coenzyme CoA desaturase-1 activity. • These results should not be extrapolated to dietary oleic acid intake. [ABSTRACT FROM AUTHOR]

Background: Data on saturated fatty acids (SFAs) in relation to metabolic function and glucose homeostasis remain controversial. Such data are lacking among pregnant women. Objective:We prospectively investigated objectively measured individual and subclasses of plasma phospholipid SFAs throughout pregnancy in relation to cardiometabolic markers and gestational diabetes mellitus (GDM) risk. Design: Within the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort of 2802 singleton pregnancies, 107 GDM cases were ascertained via medical record review and matched to 214 non-GDM controls on age, race/ethnicity, and gestational week (GW) at blood collection. Individual plasma phospholipid SFA concentrations were repeatedly measured throughout pregnancy at GWs 10-14, 15-26, 23-31, and 33-39 and also grouped into subclasses of even- or odd-chain SFAs. Results: From GW 10, even-chain SFA concentrations were significantly higher among women who later developed GDM, whereas odd-chain SFAs were significantly lower among GDM cases compared with controls. At GWs 10-14, the SFA palmitic acid (16:0) was positively associated with impaired insulin resistance and cardiometabolic markers and the risk of GDM [adjusted OR comparing the highest with the lowest quartile (aORQ4-Q1): 4.76; 95% CI: 1.72, 13.10; P-trend = 0.001]. In contrast, odd-chain SFAs were inversely related to the previously mentioned markers and GDM risk [aORQ4-Q1 for pentadecanoic acid (15:0): 0.32; 95% CI: 0.11, 0.92; P-trend = 0.025; for heptadecanoic acid (17:0): 0.20; 95% CI: 0.07, 0.58; P-trend = 0.003]. Women with high (median or greater) evenchain SFAconcentrations and low(less than median) odd-chain SFAs had a 9.43-fold (95%: CI 3.26-, 27.30-fold) increased risk compared with women with low even-chain and high odd-chain SFA concentrations. Similar results were observed at GWs 15-26. Conclusions: The study provided one of the first lines of evidence suggesting that circulating concentrations of SFAs varying by SFA chain length, as early as GWs 10-14, were significantly and differentially associated with subsequent risk of GDM. Our findings highlight the importance of assessing objectively measured, individual, and subclasses of SFAs to investigate their distinct biological and pathophysiologic roles in glucose homeostasis and cardiometabolic outcomes. This study was registered at www.clinicaltrials.gov as NCT00912132. [ABSTRACT FROM AUTHOR]

Background Apolipoprotein B-100 (ApoB) is a well-researched lipoprotein marker used in assessing the risk of coronary heart disease (CHD) development. Despite its continued use at the bedside, ApoB methodologies have not been thoroughly compared and may differentially discriminate CHD risk, resulting in patient misclassification. Objective This study compared 3 ApoB immunoassays and their associations with incident CHD risk over a 12-year follow-up period in the Multi-Ethnic Study of Atherosclerosis. Methods Plasma ApoB concentrations were measured in 4679 participants of Multi-Ethnic Study of Atherosclerosis at baseline, using 3 immunoturbidimetric methods. Roche and Kamiya reagent-based methods were analyzed on a Roche modular P analyzer, and the Diazyme reagent-based method was analyzed on a Siemens Dimension analyzer. Cox proportional analysis estimated ApoB-related risk of incident CHD over a median follow-up period of 12.5 years with adjustments for nonlipid CHD risk factors. ApoB concentrations were examined as continuous variables but were also dichotomized based on clinical designations of borderline (100 mg/dL), high (120 mg/dL), and very high ApoB levels (140 mg/dL). Results Moderate to strong correlations among ApoB methods were observed (r = 0.79–0.98). ApoB concentrations (per standard deviation) were similarly associated with CHD risk and hazard ratio (95% confidence interval): Roche: 1.16 (1.03–1.30); Kamiya: 1.14 (1.02–1.28); and Diazyme: 1.14 (1.02–1.28). Conclusion Although all 3 ApoB were similarly associated with risk of incident CHD over the study period regardless of the reagent type, the bias between methods suggests that these reagents are not fungible, and assay harmonization may be warranted. [ABSTRACT FROM AUTHOR]

T-helper type 1 (Th1) cells are pro-inflammatory and provide signals to immune cells. Animal models and in vitro human cell culture experiments have indicated that long chain n-3 polyunsaturated fatty acids (LCn3PUFAs) reduce Th1 cell levels; however, the association is unknown in healthy humans. We hypothesized that circulating levels and dietary intake of LCn3PUFAs have an inverse association with circulating levels of Th1 cells and studied 895 participants in the Multi-Ethnic Study of Atherosclerosis (age 61 ± 10 years at exam 1, 52% women, 44% white, 21% African-American, 24% Hispanic-American, 11% Chinese-American). Phospholipid LCn3PUFAs (% of total fatty acids), measured by gas chromatography, and intake of LCn3PUFAs, evaluated by food frequency questionnaire, were evaluated at exam 1 (2000-02) and defined as the sum of eicosapentaenoic and docosahexaenoic acids. Th1 cells were measured by flow cytometry at exam 4 (2005-07), expressed as a percentage of CD4 + lymphocytes that were interferon-γ + (%Th1: CD4 + IFN-γ + ). Median (interquartile range) plasma LCn3PUFA, dietary LCn3PUFA, and %Th1 levels were 4.31% (3.40–5.82%), 0.09 (0.05–0.16) g/day, and 14.4% (9.8–20.0%), respectively. When the association of LCn3PUFA-quartiles with %Th1 was analyzed using general linear models, neither plasma nor dietary LCn3PUFAs were significantly associated with %Th1 ( P -trend = 0.58 and 0.80, respectively), which remained even after adjusting for demographics, lifestyle factors, lipids, season, and cytomegalovirus titers. In this multi-ethnic U.S. population, circulating levels and dietary intake of LCn3PUFAs were not significantly associated with Th1 cell levels. Further research is needed to assess potential benefits of supplementation and much higher dietary consumption of LCn3PUFAs on Th1 cells. [ABSTRACT FROM AUTHOR]

Background Previous studies have suggested that for clinical purposes, subjects with fasting triglycerides (TGs) between 89–180 mg/dl (1–2 mmol/l) would benefit from postprandial TGs testing. Objective To determine the postprandial TG response in 2 independent studies and validate who should benefit diagnostically from an oral-fat tolerance test (OFTT) in clinical practice. Methods A population of 1002 patients with coronary heart disease (CHD) from the CORDIOPREV clinical trial and 1115 white US subjects from the GOLDN study underwent OFTTs. Subjects were classified into 3 groups according to fasting cut points of TGs to predict the usefulness of OFTT: (1) TG < 89 mg/dl (<1 mmol/l); (2) TG, 89–180 mg/dl (1–2 mmol/l); and (3) TG > 180 mg/dl (>2 mmol/l). Postprandial TG concentration at any point > 220 mg/dl (>2.5 mmol/l) has been pre-established as an undesirable postprandial response. Results Of the total, 49% patients with CHD and 42% from the general population showed an undesirable response after the OFTT. The prevalence of undesirable postprandial TG in the CORDIOPREV clinical trial was 12.8, 50.3, and 89.7%, in group 1, 2, and 3, respectively ( P < .001) and 11.2, 58.1, and 97.5% in group 1, 2, and 3, respectively ( P < .001) in the GOLDN study. Conclusions These two studies validate the predictive values reported in a previous consensus. Moreover, the findings of the CORDIOPREV and GOLDN studies show that an OFTT is useful to identify postprandial hyperlipidemia in subjects with fasting TG between 1–2 mmol/l (89–180 mg/dL), because approximately half of them have hidden postprandial hyperlipidemia, which may influence treatment. An OFTT does not provide additional information regarding postprandial hyperlipidemia in subjects with low TG (<1 mmol/l, <89 mg/dL) or increased TG (>2 mmol/l, >180 mg/dl). [ABSTRACT FROM AUTHOR]

Objective Higher lipoprotein(a) [Lp(a)] has been linked with peripheral arterial disease (PAD). Also, elevated Lp(a) serum levels have been observed in women and African Americans (AAs). It remains uncertain if sex and ethnicity modify the association between Lp(a) and PAD. Methods Lp(a) mass concentration was measured with a latex-enhanced turbidimetric immunoassay, from blood collected at baseline clinic visits after a 12-hour fast, in a multiethnic cohort. Also at baseline, the ankle-brachial index was measured. PAD was defined as an ankle-brachial index <1.0. Multivariable logistic regression was used to determine sex and ethnic differences in associations of log-transformed Lp(a) and the presence of PAD. Results In 4618 participants, the mean age was 62 ± 10 years; Lp(a) mean was 30 ± 32 mg/dL and median (interquartile range) was 18 (8-40 mg/dL); 48% were male; 36% were European American, 29% were AA, 23% were Hispanic American (HA), and 12% were Chinese American; and 11% had PAD. Across all ethnic groups, serum Lp(a) was higher among women compared with men and highest among AAs compared with other ethnicities. After adjustments for traditional cardiovascular disease risk factors (age, sex, ethnicity, hypertension, diabetes, smoking, total cholesterol, and high-density lipoprotein cholesterol) as well as interleukin-6, fibrinogen, D-dimer, and homocysteine levels, one log unit increase in Lp(a) was associated with greater odds for PAD (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.01-1.25). In fully adjusted models, significant gender ∗ ln [Lp(a)] and ethnicity ∗ ln [Lp(a)] interactions were observed ( P = .08 for both). The association between higher Lp(a) and PAD was strongest in HA men (OR, 1.73; 95% CI, 1.07-2.80) and HA women (OR, 1.49; 95% CI, 1.07-2.08). Nonsignificant associations were observed for European American, AA, and Chinese American men and women. Conclusions We observed a significant and independent association between elevated Lp(a) and PAD only among HA women and men, despite higher serum Lp(a) levels among AAs. Future studies are needed to determine the role that lowering of Lp(a) may have on the burden of PAD in HAs. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: Although an inverse association of red blood cell cis-vaccenic acid and risk of myocardial infarction has been reported, it is unclear whether cis-vaccenic acid might lower the risk of heart failure (HF) with antecedent coronary heart disease (CHD). We sought to examine the relation of plasma cis-vaccenic acid with HF with antecedent CHD. Methods: This nested case-control study was based on 788 incident HF cases (of whom 258 cases had antecedent CHD) and 788 controls. Each control was selected using a risk set sampling technique at the time of the occurrence of the index case and matched on year of birth, age at blood collection, and race. Fatty acids were measured using gas chromatography and incident HF was self-reported on annual questionnaires and validation in a subsample using medical records. Results: In a multivariable conditional logistic regression, the odds ratio (95% confidence interval) for HF with prior CHD were 1.0 (ref), 0.72 (0.33–1.57), 0.28 (0.12–0.67), and 0.23 (0.09–0.58) across consecutive quartiles of cis-vaccenic acid (p_trend 0.0004). Each standard deviation of cis-vaccenic acid was associated with a 41% lower risk of HF with antecedent CHD (95% CI: 17%–59%) in a multivariable adjusted model. Conclusions: Our data suggest that higher plasma levels of plasma cis-vaccenic acid may be associated with a lower risk of HF with antecedent CHD. Confirmation of these results in the general population including women and other ethnic groups is warranted. [Copyright &y& Elsevier]

L-selectin has been suggested to play a role in atherosclerosis. Previous studies on cardiovascular disease (CVD) and serum or plasma L-selectin are inconsistent. The association of serum L-selectin (sL-selectin) with carotid intima-media thickness, coronary artery calcium, ankle-brachial index (subclinical CVD), and incident CVD was assessed in 2403 participants in the Multiethnic Study of Atherosclerosis. Regression analysis and the Tobit model were used to study subclinical disease; Cox proportional hazards regression, for incident CVD. Mean age was 63 ± 10 years and 47% were male. Mean sL-selectin was significantly different across ethnicities. Within each race/ethnicity, sL-selectin was associated with age and sex; among non-Hispanic whites and African Americans, it was associated with smoking status and current alcohol use. sL-selectin levels did not predict subclinical or clinical CVD after correction for multiple comparisons. Conditional logistic regression models were used to study the association of plasma L-selectin and CVD in 154 incident CVD cases, and 306 age-, sex-, and ethnicity-matched control subjects. The median follow-up time was 8.5 years. L-selectin levels in plasma were significantly lower than in serum and the overall concordance was low. Plasma levels were not associated with CVD. In conclusion, in this large, multiethnic population, soluble L-selectin levels did not predict clinical or subclinical CVD. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: Previous studies have suggested that some plasma phospholipid saturated fatty acids (SFA) are associated with an increased risk of coronary heart disease and hypertension, major risk factors for heart failure (HF). However, little is known about the association between SFA and HF. This study examines associations of individual plasma phospholipid SFA with HF risk in US male physicians. Methods: The current ancillary study used a prospective nested matched case–control design to select 788 cases of incident HF and 788 controls. Plasma phospholipid SFAs were measured using gas chromatography. HF was self-reported on follow-up questionnaires and validated by review of medical records in a subsample. We used conditional logistic regression to estimate relative risks. Results: Mean age was 58.7 ± 8.0 years. One standard deviation higher plasma phospholipid 16:0 was associated with an odds ratio (95% CI) of 1.20 (1.04, 1.38) controlling for established HF risk factors and other SFAs (p = 0.042). However, this association was not significant after Bonferroni correction (p > 0.008). We did not observe associations between other SFAs (14:0, 15:0, 18:0, 20:0, or 22:0) and HF risk (all p for trend > 0.05). Conclusions: Our data suggested no association between plasma phospholipid SFAs and HF in US male physicians. [Copyright &y& Elsevier]

Background: Dairy consumption is linked to a lower risk of type 2 diabetes, but constituents responsible for this relation are not established. Emerging evidence suggests that trans-palmitoleate (trans 16:1n-7), a fatty acid in dairy and also partially hydrogenated oils, may be associated with a more favorable metabolic profile and less incident diabetes. Objective: We investigated the association of trans-palmitoleate with metabolic risk and incident diabetes in a multiethnic US cohort. Design: Phospholipid fatty acids and metabolic risk factors were measured in 2000-2002 among 2617 adults in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort of white, black, Hispanic, and Chinese Americans. In 2281 participants free of baseline diabetes, we also prospectively assessed the risk of new-onset diabetes (205 cases) from baseline to 2005-2007. Results: trans-Palmitoleate concentrations correlated positively with self-reported consumption of whole-fat dairy, butter, margarine, and baked desserts and with other circulating biomarkers of both dairy fat and partially hydrogenated oil consumption, which suggested mixed dietary sources. After multivariable adjustment, trans-palmitoleate concentrations were associated with higher LDL cholesterol (quintile 5 compared with quintile 1: +6.4%; P-trend = 0.005), lower triglycerides (-19.1%; P-trend < 0.001), lower fasting insulin (-9.1%; P-trend = 0.002), and lower systolic blood pressure (-2.4 mm Hg; P-trend = 0.01). In prospective analyses, trans-palmitoleate was independently associated with lower incident diabetes (P-trend = 0.02), including a 48% lower risk in quintile 5 compared with quintile 1 (HR: 0.52; 95% CI: 0.32, 0.85). All findings were similar between men and women and between different race-ethnic subgroups. Conclusions: Circulating trans-palmitoleate is associated with higher LDL cholesterol but also with lower triglycerides, fasting insulin, blood pressure, and incident diabetes in a multiethnic US cohort. Our findings support the need for further experimental and dietary intervention studies that target circulating trans-palmitoleate. [ABSTRACT FROM AUTHOR]

Background: Although trans fatty acids (TFAs) may increase the risk of dyslipidemia and coronary artery disease (CAD), limited data are available on their association with heart failure (HF). Objective: Our goal was to assess associations of plasma and dietary TFAs with HF and CAD. Design: We used a prospective, nested case-control design to select 788 incident HF cases and 788 matched controls from the Physicians' Health Study for biomarker analyses and a prospective cohort for the dietary analyses. Plasma fatty acids were assessed by using gas chromatography, and dietary intake was estimated by using a food-frequency questionnaire. Self-reported HF was ascertained by using annual follow-up questionnaires with validation in a subsample. We used conditional logistic (or Cox) regression to estimate multivariable-adjusted ORs (or HRs) for HF and CAD. Results: Multivariable-adjusted ORs (95% CIs) for HF across consecutive quintiles of plasma trans 18:2 (linoleic acid) fatty acids were 1.0 (reference), 1.10 (0.79, 1.54), 0.88 (0.62, 1.25), 0.71 (0.49, 1.02), and 0.67 (0.45, 0.98) (P-trend = 0.01). Each SD of plasma trans 18:2 was associated with a 22% lower risk of HF (95% CI: 6%, 36%). Plasma trans 16:1 and 18:1 were not associated with risk of HF (P > 0.05). Dietary trans fats were not associated with incident HF or CAD. Conclusions: Our data are consistent with a lower risk of HF with higher concentrations of plasma trans 18:2 but not with trans 16:1 or trans 18:1 fatty acids in male physicians. Dietary TFAs were not related to incident HF or CAD. [ABSTRACT FROM AUTHOR]

Background: Although 1 in 5 adults will develop heart failure (HF) in their lifetime, data on the effect of plasma omega-6 (n-3) PUFAs on risk of HF are currently sparse. Objectives: We investigated whether plasma phospholipid omega-6 concentrations are associated with risk of HF in US male physicians. In a secondary analysis, we evaluated whether such an association differs between HF with and without previous myocardial infarction (MI). Design: With the use of a nested case-control design, this ancillary study comprised 788 cases and 788 matched controls from the Physicians' Health Study. Plasma omega-6 PUFAs were measured by using gas chromatography. Results: The mean age of subjects was 58.7 y with a mean follow-up time of 17.1 y. We did not show any evidence of a statistically significant relation between total omega-6 PUFAs and HF [OR (95% CI): 1.00; 0.85 (0.63, 1.14); 0.84 (0.63, 1.13); and 0.87 (0.63, 1.20) across consecutive quartiles of omega-6 PUFAs; P-linear trend = 0.39]. Results were similar for HF with and without previous MI. Conclusion: Our data showed no significant association between total plasma omega-6 PUFAs and risk of developing HF. [ABSTRACT FROM AUTHOR]

Background: Data on the relation of plasma and dietary omega-3 (n-3) fatty acids (FAs) with heart failure (HF) risk have been inconsistent. . Objective: We evaluated the relation of n-3 FAs with HF in US male physicians. Design: We used nested case-control (n = 1572) and prospective cohort study designs (n = 19,097). Plasma phospholipid n-3 FAs were measured by using gas chromatography, and food-frequency questionnaires were used to assess dietary n-3 FAs and fish intake. Incident HF was ascertained via annual follow-up questionnaires and validated in a subsample. Results: The mean age was 58.7 y at blood collection. In a multi- variable model, plasma a-linolenic acid (ALA) was associated with a lower risk of HF in a nonlinear fashion (P-quadratic trend = 0.02), and the lowest OR was observed in quintile 4 (0.66; 95% CI: 0.47, 0.94). Plasma EPA and DHA were not associated with HF, whereas plasma docosapentaenoic acid (DPA) showed a nonlinear inverse relation with HF for quintile 2 (OR: 0.55; 95% CI: 0.39, 0.79). Dietary marine n-3 FAs showed a trend toward a lower risk of HF in quintile 4 (HR: 0.81; 95% CI: 0.64, 1.02) and a nonlinear pattern across quintiles. Fish intake was associated with a lower risk of HF, with RRs of ~0.70 for all categories of fish consumption greater than one serving per month. Conclusions: Our data are consistent with an inverse and nonlinear relation of plasma phospholipid ALA and DPA, but not EPA or DHA, with HF risk. Fish consumption greater than once per month was associated with a lower HF risk. [ABSTRACT FROM AUTHOR]

High levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) are associated with inflammation, atherosclerosis, and coronary heart disease events. In addition, Lp-PLA2 has been linked to classical markers of endothelial activation, including soluble vascular cell adhesion molecule-1 (sVCAM-1). Although treatment with fenofibrate reduces Lp-PLA2 mass, it is unclear whether fenofibrate reduces sVCAM-1 levels or whether an association exists between any changes observed in Lp-PLA2 and sVCAM-1. Concentrations of Lp-PLA2 mass and sVCAM-1 levels were measured in plasma at baseline and after 3 weeks of fenofibrate treatment (160 mg/d) in 96 hypertriglyceridemic participants of the Genetics of Lipid-lowering Drugs and Diet Network study. Lp-PLA2 and sVCAM-1 were stratified by tertiles as determined by baseline levels of the respective target. Fenofibrate treatment resulted in a 30.1% mean increase in Lp-PLA2 mass (P = 0.0003) and a 14.7% mean increase in sVCAM-1 levels (P = 0.0096) but only in tertile1 of either target. In contrast, Lp-PLA2 mass was reduced by 35.3% (P < 0.0001) in tertile 3. Soluble VCAM-1 levels were significantly reduced by 7.74% (P = 0.0109) and 17.2% (P < 0.0001) in tertiles 2 and 3, respectively. No associations were observed between Lp-PLA2 and sVCAM-1 at baseline or post-treatment. In conclusion, fenofibrate treatment in hypertriglyceridemic subjects reduced the levels of Lp-PLA2 mass and sVCAM-1, but only in those with elevated baseline levels of these biomarkers. The greatest reductions in Lp-PLA2 levels were observed in individuals with Lp-PLA2 concentrations indicative of increased cardiovascular disease risk (>200 ng/mL). [ABSTRACT FROM AUTHOR]

The scaffolding protein PDZ domain containing 1 (PDZK1) regulates the HDL receptor scavenger receptor class B type I. However, the effect of PDZKI genetic variants on lipids and metabolic syndrome lMetSl traits remains unknown. This study evaluated the association of 3 PDZK1 single nucleotide polymorphisms (SNP) (i33968C > T, i15371G > A, and i19738C > T) with lipids and risk of MetS and their potential interactions with diet. PDZK1 SNP were genotyped in 1000 participants (481 men, 519 women) included in the Genetics of Lipid Lowering Drugs and Diet Network study. Lipoprotein subfractions were measured by proton NMR spectroscopy and dietary intake was estimated using a validated questionnaire. The PDZK1_i33968C > T polymorphism was associated with MetS (P = 0.034), mainly driven by the association of the minor T allele with higher plasma triglycerides IP = 0.004) and VLDL (P= 0.021), and lower adiponectin concentrations (P = 0.022) than in participants homozygous for the major allele (C). We found a significant gene × BMI × diet interaction, in which the deleterious association of the i33968T allele with MetS was observed in obese participants with high PUFA and carbohydrate (P-values ranging from 0.004 to 0.020) intakes. Conversely, a there was a protective effect in nonobese participants with high PUFA intake (P< 0.05). These findings suggest that PDZK1_133968C >T genetic variants may be associated with a higher risk of exhibiting MetS. This gene × BMI × diet interaction offers the potential to identify dietary and other lifestyle changes that may obviate the onset of MetS in individuals with a specific genetic background. [ABSTRACT FROM AUTHOR]

The transcription factor 7-like 2 (TCF7L2) has been recently associated with diabetes risk, and it may exert its effect through metabolic syndrome (MetS)-related traits and be subjected to modification by environmental factors. We investigated the effect of single nucleotide polymorphisms (SNP), rs7903146 and rs12255372, within the TCF7L2 locus on postprandial lipemia and other MetS-related traits and their modulation by dietary fat. Data were collected from 1083 European Americans participating in the Genetics of Lipid Lowering Drugs and Diet Network Study. Carriers of the minor T allele at the CIT rs79031 46 SNP had higher fasting plasma glucose (P = 0.012), lower homeostasis model assessment of β cell function (P = 0.041), higher plasma VLDL (P = 0.035), and lower large LDL particle (P = 0.0071 concentrations and higher risk of MetS (P = 0.011) than CC individuals. Moreover, we identified significant interactions between this SNP and PUFA intake modulating fasting VLDL particle concentrations (P = 0.016) and postprandial triglycerides (TG) (P = 0.028), chylomicrons (P = 0.025), total VLDL (P = 0.026), and large VLDL (P= 0.018) concentrations. Thus, only T allele carriers with a PUFA intake ⩾7.36% of energy had elevated fasting plasma VLDL concentrations and postprandial TG-rich lipoproteins. These variables did not differ in I allele carriers and noncarriers in the low-PUFA intake group. Moreover, these significant interactions were due exclusively to (n-6) PUFA intake. In summary, high (n-6) PUFA intakes (⩾6.62% of energy intake) were associated with atherogenic dyslipidemia in carriers of the minor T allele at the TCF7L2 rs7903146 SNP and may predispose them to MetS, diabetes, and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Abstract: We have asked whether the prevalence of combined hyperlipidemia (CHL) differs by race/ethnicity, obesity, and insulin resistance in a contemporary, multiethnic, US cohort. We determined the prevalence and adjusted odds of CHL in a cohort of 5923 men and women free of clinically recognized cardiovascular disease and diabetes according to race/ethnicity (white, Chinese, African American, and Hispanic), obesity, and insulin resistance. Untreated lipid values were imputed for those on lipid-lowering therapy. Combined hyperlipidemia was defined using age- and sex-specific greater than or equal to 75th percentile cut points for low-density lipoprotein cholesterol and triglycerides obtained from a predominantly white North American population study. Compared with whites, adjusted odds ratios for CHL were 0.48 in African Americans (95% confidence interval [CI], 0.30-0.75), 1.33 in Hispanics (95% CI, 0.93-1.91), and 1.06 in Asians (95% CI, 0.62-1.82). Within the entire population, the adjusted odds of CHL were over 2-fold higher in overweight and obese participants compared with normal-weight participants and more than 4-fold higher in quartiles 2 through 4 of insulin resistance compared with quartile 1. African Americans had lower odds for CHL than whites despite higher body mass index and abdominal adiposity. Hispanics had a nonsignificantly higher trend, and Asians had no significantly different odds than whites. Modest increases in weight and insulin resistance were associated with significantly higher odds of CHL in a multiethnic US population. Further research is needed to determine the most efficacious diet, exercise, and drug management to decrease the risk of CHL and coronary heart disease among racial/ethnic groups in the United States. [Copyright &y& Elsevier]

Moderate hyperhomocysteinemia is associated with many diseases. Major factors affecting plasma total homocysteine (tHcy) concentrations include fotate concentrations and polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene. Because U.S-mandated fortification of grain products with folic acid has improved folate and tHcy status in Americans, we investigated the effect of the MTHFR 677C>T variant before and after fortification. We determined tHcy and folate concentrations in sera from 844 Caucasian and 587 African American participants in the Coronary Artery Risk Development in Young Adults study before and after fortification and we genotyped the MTHFIR 677C>T variant. MTHFR 6771T homozygotes had higher (P < 0.011 tHcy concentrations both before and after fortification compared with MTHFR 677CC homozygotes. However, the difference between these 2 genotypes decreased from 2.5 μmoI/L before fortification to <0.7 μmol/L postfortification (P < 0.01). In addition, the prevalence of moderate hyperhomocysteinemia (tHcy > 13 μmol/L) in 677TT homozygotes decreased from 33% before fortification to 12% postfortification IP < 0.011. Using a cutoff value of 13 μmoI/L to define moderate hyperhomocysteinemia, the sensitivity of the MTHFR 67711 genotype to predict elevations in homocysteine was low H30%) both before and after folic acid fortification. Increasing the cutoff from 13 to 19 μmol/L increased the sensitivity of the assay before fortification to 62% but decreased the sensitivity to 17% postfortification. We conclude that after folic acid fortification in the US, measurement of tHcy rather than genotyping of MTHFR 67711 should be used as the primary assay for the diagnosis and monitoring of moderate hyperhomocysteinemia. J. Nutr. 139: 33-37, 2009. [ABSTRACT FROM AUTHOR]

Few studies have adequately considered the type of seafood and background dietary factors when evaluating diet-biomarker and diet-disease associations. The objective of this paper is to evaluate the relationship between different seafood meals and long-chain (n-3) fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] biomarkers in the Multi-Ethnic Study of Atherosclerosis (MESA) with white, Chinese-American, black, and Hispanic participants. Dietary intake from a FFQ and plasma phospholipid fatty acids were assessed in 900 MESA participants who here not taking fish oil supplements. When simultaneously adjusting for all seafood groups, concentrations of EPA and DHA in plasma phospholipids were positively correlated with nonfried fish consumption in all 4 ethnic groups (r = 0.24-6.46; P < 0.01) but not with nonfried shellfish, fried fish, or fish in mixed dishes. The magnitude of this correlation was attenuated by up to 67% when type of seafood was not taken into account. After further adjusting for demographic characteristics and other dietary characteristics in multivariate regression models, the association of nonfried fish consumption remained significant (P-trend < 0.001). Data were suggestive of a plateau effect at a nonfried fish intake of about twice weekly. The association of nonfried fish consumption was not modified by intake of (n-6) PUFA or α-linolenic acid. This study highlights the importance of cooking methods (nonfried vs. fried fish), types of seafood (fish vs. shellfish), and the overall seafood consumption when assessing health effects of long-chain (n-3) fatty acids of seafood consumption. [ABSTRACT FROM AUTHOR]

Abstract: The cholesteryl ester transfer protein (CETP) plays a key role in high-density lipoprotein (HDL) metabolism. Genetic variants that alter CETP activity and concentration may cause significant alterations in HDL-cholesterol (HDL-C) concentration; however, controversies remain about whether these genetic variants are associated with atherosclerosis. We genotyped the CETP R451Q, A373P, −629C/A, Taq1B, and −2505C/A polymorphisms in a cohort of Caucasian, Chinese, African-American, and Hispanic individuals within the Multi-Ethnic Study of Atherosclerosis. Genotypes were examined in relationship to HDL-C, CETP activity, CETP concentration, and three measures of subclinical cardiovascular disease (CVD): coronary artery calcium (CAC) measured by fast CT scanning, carotid intimal-medial thickness (IMT), and carotid artery plaque measured by ultrasonography. Carriers of the 451Q and 373P alleles have a significantly higher CETP concentration (22.4% and 19.5%, respectively; p <0.001) and activity (13.1% and 9.4%, respectively; p <0.01) and lower HDL-C (5.6% and 6.0%, respectively; p <0.05). The minor alleles of the R451Q and A373P polymorphisms are associated with the presence of CAC, even after adjusting for CVD risk factors and HDL-C (p =0.006 and p =0.01, respectively). The R451Q polymorphism is also associated with presence of carotid artery plaque (p =0.036). Polymorphism is associated with neither common nor internal carotid IMT. We confirmed that the −629A, Taq1B B2, and −2505A alleles are significantly associated with lower CETP concentration (20.8%, 25.0%, and 23.7%, respectively; p <0.001) and activity (14.8%, 19.8%, and 18.4%, respectively; p <0.001) and higher HDL-C concentration (9.7%, 11.5%, and 10.4%, respectively; p <0.01). However, we did not find any associations between these non-coding polymorphisms and subclinical CVD. [Copyright &y& Elsevier]

Chronic inflammation has been identified as an important component of the metabolic syndrome (MetS). Therefore, environmental and genetic factors contributing to the variation of inflammatory responses could affect individuals' susceptibility to MetS. We investigated the association between common IL β genetic polymorphisms, inflammation, and the MetS, and the modulation of diet-related variables (i.e., erythrocyte membrane fatty acid composition) in a white U.S. population. ILβ single nucleotide polymorphisms (SNP) )-1473G > C, -511G > A, -31T> C, 3966C > T, 6054G > AL clinical and biochemical measurements were characterized in a total of 1120 subjects 1540 males and 580 females) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. The 6054 G > A SNP was significantly associated with plasma C-reactive protein (P = 0.054), adiponectin (P = 0.021), and the prevalence of MetS IP = 0.0041. Moreover, there was a significant interaction between the 6054G > A SNP and erythrocyte membrane (n-3) PUFA (P = 0.019). Among subjects with low (n-3) PUFA content (below the median), the 6054 G allele was associated with increased risk of the MetS (OR = 3.29, 95%Cl = 1.49-7.26 for GG and OR = 1.95, 95%C) = 0.85-4.46 for GA, P< 0.001) compared with the AA genotype, but there were no significant genotype associations among subjects with high (n-3) PUFA content (above the medianl. Furtheranalyses supported a significant haplotype global effect on the MetS (P= 0.017) among subjects with low (n-3) PUFA content. These results suggested that IL β genetic variants were associated with measures of chronic inflammation and the MetS risk, and that genetic influences were more evident among subjects with low (n-3) PUFA intake. [ABSTRACT FROM AUTHOR]

Despite wide use of the influenza vaccine, relatively little is known about its effect on the measurement of inflammatory markers. Because inflammatory markers such as C-reactive protein (CRP) are increasingly being used in conjunction with lipids for the clinical assessment of cardiovascular disease and in epidemiologic studies, we evaluated the effect of influenza vaccination on markers of inflammation and plasma lipid concentrations. We drew blood from 22 healthy individuals 1 to 6 hours before they were given an influenza vaccination and 1, 3, and 7 days after the vaccination. Plasma CRP, interleukin (IL)-6, monocyte chemotactic protein 1, tumor necrosis factor ?, IL-2 soluble receptor ?, and serum amyloid A were measured, and differences in mean concentrations of absolute and normalized values on days 1, 3, and 7 were compared with mean baseline values. There was a significant increase in mean IL-6 (P < .01 absolute values, P < .001 normalized values) on day 1 after receiving the influenza vaccine. The mean increases in normalized high sensitivity CRP values were significant on day 1 (P < .01) and day 3 (P = .05), whereas the mean increase in normalized serum amyloid A was significant only on day 1 (P < .05). No significant changes were seen in mean concentrations of IL-2 soluble receptor ?, monocyte chemotactic protein-1, or tumor necrosis factor-?. Of the lipids, significant decreases in mean concentrations of normalized triglyceride values were seen on days 1 (P < .05), 3 (P < .001), and 7 (P < .05) after vaccination. Our findings show that the influenza vaccination causes transient changes in select markers of inflammation and lipids. Consequently, clinical and epidemiologic interpretation of the biomarkers affected should take into account the possible effects of influenza vaccination. [Copyright &y& Elsevier]