Omega-3 Polyunsaturated Fatty Acids are not associated with Peripheral Artery Disease in a Meta-Analysis from the Multi-Ethnic Study of Atherosclerosis and Atherosclerosis Risk in Communities Study Cohorts.

BACKGROUND: Research suggests omega-3 polyunsaturated fatty acids (PUFAs) exert favorable effects on several biological processes involved in the development and progression of atherosclerotic cardiovascular disease (ASCVD). However, studies examining the relationship between omega-3 PUFAs and peripheral artery disease (PAD) are scarce. OBJECTIVES: We evaluated the associations between omega-3 PUFAs and incident PAD in a meta-analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerosis Risk in Communities (ARIC) study cohorts. METHODS: Omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured at baseline for all MESA (n = 6495) and Minnesota ARIC participants (n = 3612). Incident clinical PAD events (MESA n = 106; ARIC n = 149) identified primarily through ICD discharge codes were assessed through follow-up of each cohort. Associations between omega-3 PUFAs (EPA, DHA, and EPA+DHA) and incident PAD were modeled in MESA and ARIC as quartiles and continuously using Cox proportional hazards regression, respectively. A fixed-effects meta-analysis was conducted to evaluate associations in the 2 cohorts combined. RESULTS: In the fully adjusted model, in 10,107 participants, no significant associations were observed between EPA, DHA, or EPA+DHA, and incident PAD modeled as quartiles or continuously for either MESA or ARIC cohorts separately or in the meta-analysis after a follow-up of approximately 15 y. CONCLUSION: This study is consistent with previous literature indicating that the beneficial effects of omega-3 PUFAs on the markers of ASCVD may not translate to a clinically meaningful decrease in PAD risk.

n-6 fatty acid biomarkers and incident atrial fibrillation: an individual participant-level pooled analysis of 11 international prospective studies.

BACKGROUND: The presence of atrial fibrillation (AF) is associated with an over 2-fold increased risk of stroke, heart failure, and cardiovascular mortality. Long chain n-6 PUFAs have been suggested to have a variety of beneficial biologic effects that may reduce AF development; however, prior studies evaluating this relationship are limited. OBJECTIVES: We prospectively evaluated the association between circulating levels of linoleic acid (LA) and arachidonic acid (AA) with incident AF. METHODS: We used participant-level data from a global consortium of 11 prospective cohort studies with measurements of LA and AA in adults (aged ≥18 y). Participating studies conducted de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcomes, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS: Among 41,335 participants, 6173 incident cases of AF were ascertained, with median follow-up time of 14 y. In multivariable analysis, per interquintile range (difference between the 10th and 90th percentiles for each fatty acid), circulating n-6 levels were not associated with incident AF. For LA, the hazard ratio per interquintile range was 0.96 (95% confidence interval [CI]: 0.89, 1.04), and for AA, 1.02 (95% CI: 0.94, 1.10), with little evidence of heterogeneity between cohorts. Associations were similarly nonsignificant across subgroups of age, race, and biomarker fraction. CONCLUSIONS: Biomarkers of n-6 fatty acids including LA and AA are not associated with incident AF. These findings suggest that overall effects of n-6 PUFAs on influencing AF development are neutral.

Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation.

BACKGROUND: The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial. OBJECTIVES: This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF. METHODS: We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS: Among 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively. CONCLUSIONS: In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.

Furan Metabolites Are Elevated in Users of Various Tobacco Products and Cannabis.

Humans are exposed to furan, a toxicant and possible human carcinogen, through multiple sources including diet and tobacco smoke. The urinary metabolites of furan are derived from the reaction of its toxic metabolite with protein nucleophiles and are biomarkers of exposure and potential harm. An established isotopic dilution liquid-chromatography mass spectrometry method was used to measure these biomarkers in urine from users of e-cigarettes, cannabis, and/or combustible tobacco with/without reduced nicotine levels. Amounts of furan mercapturic acid metabolites were higher in these individuals relative to nonsmokers, indicating that they may be at risk for potential furan-derived toxicities.

Small dense low-density lipoprotein cholesterol compared to other lipoprotein biomarkers for predicting coronary heart disease among individuals with normal fasting glucose: The Multi-Ethnic Study of Atherosclerosis.

Objective: This study compared small dense low-density lipoprotein cholesterol (sdLDL-C) with apolipoprotein B (apo B), and low-density lipoprotein particles (LDL-P) in predicting CHD risk in generally healthy adults with normal fasting glucose (NFG). Methods: This study was conducted among participants with NFG in the Multi-Ethnic Study of Atherosclerosis (MESA) prospective cohort with measurements of sdLDL-C, LDL-P, and apo B available at baseline (2000-2002) and follow-up CHD data (through 2015) (N = 3,258). Biomarkers were evaluated as quartiles, and in categories using clinically and 75th percentile-defined cut-points. Discordance/concordance of sdLDL-C relative to other biomarkers was calculated using 75th percentile cut-points and linear regression residuals. Associations between individual biomarkers, sdLDL-C discordance and CHD incidence were evaluated using Cox proportional hazards regression. Results: There were 241 incident CHD events in this population through 2015. Higher sdLDL-C, apo B, LDL-P were similarly associated with increased CHD in individuals with NFG. Discordance of sdLDL-C with apo B or LDL-P by 75th percentiles was not significantly associated with CHD. Residuals discordantly higher/lower sdLDL-C relative to apo B (discordant high HR=1.26, 95% CI: 0.89, 1.78; discordant low HR=0.94, 95% CI: 0.68, 1.29) and LDL-P (discordant high HR=1.25, 95% CI: 0.88, 1.75; discordant low HR=0.84, 95% CI:0.60, 1.16), compared to those with concordant measures, had non-statistically significant higher/lower risk of CHD. Conclusions: Results suggest sdLDL-C, apo B and LDL-P are generally comparable for predicting CHD events in normoglycemic individuals. Larger studies are needed to confirm findings and to investigate whether measurement of sdLDL-C may be beneficial to evaluate as an additional risk-enhancing factor.

Associations of plasma omega-3 and omega-6 pufa levels with arterial elasticity: the multi-ethnic study of atherosclerosis.

BACKGROUND: Literature examining the relationship of circulating omega-3 and omega-6 polyunsaturated fatty acids [n-3(ω-3) and n-6 (ω-6) PUFAs] and arterial elasticity in large cohort-based populations are lacking. We investigated the association of circulating ω-3and ω-6 PUFAs with large artery elasticity (LAE) and small artery elasticity (SAE) in participants from the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: A total of 6124 participants (mean age 61.9; 52% female; 38% White, 27% Black, 22% Hispanic, and 13% Chinese-American) with plasma phospholipid PUFAs and arterial elasticity measured at baseline were included. LAE and SAE were derived from pulse contour analysis of the radial artery in all subjects in a supine position using tonometry. Linear regression models were used to determine associations for levels of (1) each circulating fatty acid, (2) total ω-3PUFAs, and (3) total ω-6 PUFAs with log-transformed LAE and SAE. RESULTS: Each standard deviation (SD) increment in circulating levels of total ω-3 PUFAs, eicosapentaenoic acid, and docosahexaenoic acid were associated with a 0.017 ml/mmHg, 0.017 ml/mmHg, and 0.015 ml/mmHg higher LAE respectively (p values all <0.01). No significant trends were observed for ω-3 PUFAs levels with SAE.22 Similarly, no significant trends were observed for ω-6 PUFA levels with either LAE or SAE. CONCLUSIONS: In a multi-ethnic cohort of individuals free of baseline cardiovascular disease, higher plasma levels of total and individual ω-3 PUFAs were associated with an increased LAE. Further understanding into differential associations of ω-6 PUFAs with LAE and SAE is needed.

ASSOCIATION OF PLASMA ω-3 FATTY ACIDS WITH EARLY AGE-RELATED MACULAR DEGENERATION IN THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS.

PURPOSE: To examine the association between omega-3 polyunsaturated fatty acids, docosahexaenoic acid, and eicosapentaenoic acid and age-related macular degeneration (AMD) in the Multi-Ethnic Study of Atherosclerosis cohort. METHODS: Multi-Ethnic Study of Atherosclerosis is a multicenter, prospective cohort study designed to identify risk factors for cardiovascular disease in four ethnic groups. Six thousand eight hundred and fourteen participants of White, African American, Hispanic/Latino, and Chinese descent, aged 45-84 years, were recruited, with those found to have cardiovascular disease excluded. Our study population included all Multi-Ethnic Study of Atherosclerosis participants with baseline polyunsaturated fatty acid measurements and retinal photography at Examination 5 (n = 3,772). Fundus photographs were assessed for AMD using a standard grading protocol. Relative risk regression (log link) determined associations between polyunsaturated fatty acid levels and AMD. RESULTS: There was a significant association between increasing docosahexaenoic acid levels and increasing docosahexaenoic acid + eicosapentaenoic acid levels with reduced risk for early AMD (n = 214 participants with early AMD, of which n = 99 (46.3%) are non-White). Eicosapentaenoic acid levels alone were not significantly associated with AMD. CONCLUSION: Our analysis suggests increasing levels of docosahexaenoic acid are associated with reduced risk for early AMD in a multiethnic cohort. This represents the first racially diverse study demonstrating an association between omega-3 polyunsaturated fatty acids and AMD risk.

Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study.

AIMS: Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD. METHODS AND RESULTS: We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45-1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08-1.34). Similar results were shown when examining discordance across clinical cutpoints. CONCLUSIONS: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.

Free fatty acids and heart failure in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Free fatty acids (FFAs) may be associated with heart failure (HF) risk, but prospective research is lacking. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Plasma ω-3 and ω-6 PUFA Concentrations and Risk of Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis.

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.

Plasma omega-3 and saturated fatty acids are differentially related to pericardial adipose tissue volume across race/ethnicity: the Multi-ethnic Study of Atherosclerosis.

BACKGROUND: Pericardial adipose tissue (PAT) is a cardiometabolic risk factor influenced by race/ethnicity, inflammation, and metabolic dysfunction. Omega-3 fatty acids (FAs) and saturated FAs (SFAs) are known to affect these latter phenomena and may influence PAT accumulation. We aimed to determine whether plasma levels of these FAs are related to PAT volume and its rate of change over a median 3-year follow-up. METHODS: Cardiac computed tomography assessed PAT in 6785 Multi-Ethnic Study of Atherosclerosis participants. Gas chromatography flame-ionization estimated plasma phospholipid FAs. Regression analyses estimated associations of FAs with PAT volume and its rate of change with adjustments for other risk factors. Race-interactions were tested. RESULTS: In cross-section, top tertiles of omega-3 FAs and odd-chained SFAs were associated with 2.8 and 4.93 cm3 lower PAT volumes, respectively; race/ethnicity was a significant modifying variable (p < 0.002). Even-chained SFAs were associated with 3.5 cm3 greater PAT volume. With stratification by race/ethnicity, Chinese Americans in the top tertile of omega-3 FAs showed 10.5 cm3 greater PAT volume than those in the referent tertile. Black individuals in the top tertile of odd-chained SFAs showed 5.0 cm3 lower PAT compared to referents. Black and Chinese Americans in top tertiles of even-chained SFAs showed respective 3.7 and 5.9 cm3 greater PAT volumes compared to referents. Two associations were observed in prospective analyses among Caucasians; race interactions were non-significant. CONCLUSIONS: Cross-sectional and prospective findings provide inconclusive evidence as to whether plasma FAs are related to PAT in healthy individuals. Cohort studies with longer follow-up periods are warranted.

Free fatty acids, cardiovascular disease, and mortality in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Physical activity, health-related quality of life, and adjuvant endocrine therapy-related symptoms in women with hormone receptor-positive breast cancer.

BACKGROUND: Physical activity (PA) is recommended for women with breast cancer (BC); however, data are sparse on the association of PA with quality of life (QOL) and patient-reported symptoms for women on adjuvant endocrine therapy (AET). METHODS: Women with hormone receptor-positive BC who were taking AET completed standardized surveys about their health-related QOL, AET-related symptoms, and levels of PA using validated measures. A Wald chi-square test and an analysis of variance were used to assess associations with PA and independent variables. Generalized linear regression analyses assessed associations between PA, QOL, and AET-related symptoms. RESULTS: The analytic cohort included 485 Black and White women. Black race, a high body mass index (BMI), and being on aromatase inhibitors (vs tamoxifen) were associated with lower PA in a bivariate analysis. In a multivariate analysis, lower self-reported PA was associated with a high BMI (P = .02) and chemotherapy uptake (P = .006). Better health-related QOL (P = .01), less severe overall AET-related symptoms (P = .02), and less severe gynecological symptoms (P = .03) were associated with increasing levels of moderate PA. CONCLUSIONS: Among women taking AET, moderate levels of PA may be associated with fewer medication-related symptoms and overall better ratings of health-related QOL. Because of the low levels of PA observed in the sample overall and particularly for Black women, identifying successful strategies to promote PA are needed.

Obesity is an initiator of colon adenomas but not a promoter of colorectal cancer in the Black Women's Health Study.

PURPOSE: Evidence for the association of anthropometrics with colorectal neoplasms is limited for African Americans. METHODS: We examined anthropometric measures with both colorectal adenoma and colorectal cancer (CRC) risk in the ongoing Black Women's Health Study. In a nested case-control analysis, 954 cases of colorectal adenoma were compared with 3,816 polyp-free controls, matched on age and follow-up time. For the CRC analyses, 413 incident CRC cases were identified over a 16-year follow-up (802,783 person-years). Adenoma cases and CRC were verified by medical record review. We used multivariable conditional logistic regression analyses (for adenoma) and Cox proportional hazards analyses (for CRC) that included anthropometric exposures and selected confounders. RESULTS: Overall body mass index (BMI) and other anthropometric factors were not associated with colorectal adenoma or cancer risk in Black women. However, increased risk of adenoma (but not CRC) was observed among especially related to adenomas in the proximal colon. Among women ≥ 50 years of age, risk of proximal adenoma increased 14% (95% CI 1.00, 1.31), 35% (95% CI 1.12, 1.63), and 25% (0.93, 1.68) with each standard deviation increase in BMI, waist circumference, and waist-to-hip ratio, respectively. None of the anthropometric factors were associated with young onset CRC or adenoma risk. CONCLUSION: Our results suggest that obesity might be an initiator for colon adenomas but not a promoter for colorectal cancer among Black women.

Associations between omega-6 polyunsaturated fatty acids, hyperinsulinemia and incident diabetes by race/ethnicity: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Association Between Homocysteine and Vascular Calcification Incidence, Prevalence, and Progression in the MESA Cohort.

Background While elevated homocysteine has been associated with calcification in several studies, its importance as a cardiovascular risk factor remains unclear. This study examines the relationship between homocysteine and vascular and valve calcification in the MESA (Multi-ethnic Study of Atherosclerosis) cohort. Methods and Results MESA participants with baseline homocysteine measurements and cardiac computed tomography scans were included (N=6789). Baseline and follow-up assessment of vascular (coronary artery [CAC], descending thoracic aorta [DTAC]) and valve (aortic valve [AVC], mitral annular [MAC]) calcification was performed. Prevalence ratio/relative risk regression was used to assess the relationship of homocysteine with prevalent and incident calcification, and multivariable logistic regression was used to assess associations between homocysteine and calcification progression. Elevated homocysteine was associated with greater relative risk of prevalent and incident CAC and incident DTAC. We also identified a strong association between elevated homocysteine and CAC and DTAC progression. Elevated homocysteine was found to confer a >2-fold increased risk of severe CAC progression (defined as ΔCAC ≥100/year) and an ≈1.5-fold increased risk for severe DTAC progression (defined as ΔDTAC ≥100/year). Conclusions To our knowledge, this is the first study demonstrating an association between elevated homocysteine and both incidence and progression of coronary and extra-coronary vascular calcification. Our findings suggest a potential role for elevated homocysteine as a risk factor for severe vascular calcification progression. Future studies are warranted to further assess the utility of homocysteine as a biomarker for vascular calcification incidence and progression. Clinical Trial Registration https://www.clinicaltrials.gov/. Unique identifier: NCT00005487.

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).

BACKGROUND: Discordant levels of apolipoprotein B (apo B) relative to low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) may be associated with subclinical atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE: The present study investigated whether discordance between apo B and LDL-C or non-HDL-C levels was associated with subclinical ASCVD measured by coronary artery calcium (CAC). METHODS: This study was conducted in a subpopulation of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, aged 45 to 84 years, free of ASCVD, and not taking lipid-lowering medications at the baseline (2000-2002) (prevalence analytic N = 4623; incidence analytic N = 2216; progression analytic N = 3947). Apo B discordance relative to LDL-C and non-HDL-C was defined using residuals and percentile rankings (>5/10/15 percentile). Associations with prevalent and incident CAC (CAC > 0 vs CAC = 0) were assessed using prevalence ratio/relative risk regression and CAC progression (absolute increase/year) using multinomial logistic regression. RESULTS: Higher apo B levels were associated with CAC prevalence, incidence, and progression. Apo B discordance relative to LDL-C or non-HDL-C was inconsistently associated with CAC prevalence and progression. Discordantly high apo B relative to LDL-C and non-HDL-C was associated with CAC progression. Associations for apo B discordance with non-HDL-C remained after further adjustment for metabolic syndrome components. CONCLUSION: Apo B was associated with CAC among adults aged ≥45 years not taking statins, but provided only modest additional predictive value of apo B for CAC prevalence, incidence, or progression beyond LDL-C or non-HDL-C. Apo B discordance may still be important for ASCVD risk assessment and further research is needed to confirm findings.

Fruit and VegeTable Intake and Lung Cancer Incidence Among Black Women According to Cigarette Smoking Status.

This project evaluated associations between fruit and vegetable intake, cigarette smoking and lung cancer incidence among U.S. Black women. The Black Women's Health Study is a prospective cohort study (analytic cohort = 46,889) among Black women between the ages 21 and 69 at baseline (1995). Fruit and vegetable intake and smoking history were ascertained via questionnaires at baseline and during follow-up. Associations between fruit and vegetable intake, smoking and lung cancer incidence (N = 306 incident cases through 2013) were evaluated using Cox proportional hazards regression. Among women in this cohort, 6.1% and 5.6% reported consuming at least three servings/d of fruit or vegetables, respectively. Smoking history was associated with increased lung cancer incidence. Being a current smoker of ≥15 cigarettes/d was associated with higher lung cancer incidence compared to never smokers (HR = 17.4, 95% CI: 11.5, 26.4). Fruit and vegetable was not associated with lung cancer incidence intake (≥5 vs. <3 servings/d, adjusted HR: 0.86, 95% CI: 0.54, 1.36). Associations between fruit and vegetable intake and lung cancer incidence did not differ by smoking history. Fruit and vegetable intake was low in this study population, but results do not support an association between fruit and vegetable intake and lung cancer incidence, regardless of smoking history.

Correction to: Dietary intake of soy and cruciferous vegetables and treatment-related symptoms in Chinese-American and non-Hispanic White breast cancer survivors.

In the original publication, the values provided for the isoflavone and glucosinolate intake variables were incorrectly labeled in Table 1. The correct values of 6.3 mg/day for isoflavone intake, and 20.4 mg/day and 50.1 mg/day for glucosinolate intake are provided in this erratum.

Dietary intake of soy and cruciferous vegetables and treatment-related symptoms in Chinese-American and non-Hispanic White breast cancer survivors.

PURPOSE: This project was undertaken to examine the association between dietary intake of soy or cruciferous vegetables and breast cancer treatment-related symptoms among Chinese-American (CA) and Non-Hispanic White (NHW) breast cancer survivors. METHODS: This cross-sectional study included 192 CA and 173 NHW female breast cancer survivors (stages 0-III, diagnosed between 2006 and 2012) recruited from two California cancer registries, who had completed primary treatment. Patient-reported data on treatment-related symptoms and potential covariates were collected via telephone interviews. Dietary data were ascertained by mailed questionnaires. The outcomes evaluated were menopausal symptoms (hot flashes, night sweats, vaginal dryness, vaginal discharge), joint problems, fatigue, hair thinning/loss, and memory problems. Associations between soy and cruciferous vegetables and symptoms were assessed using logistic regression. Analyses were further stratified by race/ethnicity and endocrine therapy usage (non-user, tamoxifen, aromatase inhibitors). RESULTS: Soy food and cruciferous vegetable intake ranged from no intake to 431 and 865 g/day, respectively, and was higher in CA survivors. Higher soy food intake was associated with lower odds of menopausal symptoms (≥ 24.0 vs. 0 g/day, OR 0.51, 95% CI 0.25, 1.03), and fatigue (≥ 24.0 vs. 0 g/day, OR 0.43, 95% CI 0.22, 0.84). However, when stratified by race/ethnicity, associations were statistically significant in NHW survivors only. Compared with low intake, higher cruciferous vegetable intake was associated with lower odds of experiencing menopausal symptoms (≥ 70.8 vs. < 33.0 g/day, OR 0.50, 95% CI 0.25, 0.97) in the overall population. CONCLUSIONS: In this population of breast cancer survivors, higher soy and cruciferous vegetable intake was associated with less treatment-related menopausal symptoms and fatigue.