Search

Background:Accurate assessment of fat intake is essential to examine relationships between diet and disease risk. However, estimating individual intakes of fat quantity by dietary assessment is difficult., Objective:We assessed the association of plasma phospholipid fatty acid levels with dietary intake of fatty acids in the INTERMAP/INTERLIPID study, conducted with a standardized protocol., Methods:The study participants were 1339 men and women ages 40-59 years from five Japanese populations one from Hawaii; four from Japan. Fatty acid intake was estimated from four standardized 24-hour dietary recalls. Plasma phospholipid fatty acid composition was analyzed by gas chromatography. We illustrated the relationship between intake and circulating fatty acid levels using Spearman's rank-correlation coefficients, mean, and median values., Results:Spearman's rank-correlation coefficients between intake (g/d) and circulating fatty acid levels (µg/ml) were -0.03 to 0.21 for saturated fatty acids and monounsaturated fatty acids and -0.04 to 0.32 for trans fatty acids. The coefficients for essential n-3 and n-6 fatty acids were moderate to high, especially for eicosapentaenoic acid (EPA), 0.60; docosahexaenoic acid (DHA), 0.41; and EPA+DHA, 0.51. The circulating levels and intake of marine-derived n-3 fatty acids showed a linear association, at least for the intake of EPA+DHA up to 2.1 g/d., Conclusion:We observed high correlation between intake and circulating levels of marine-derived n-3 fatty acids in participants from Japanese and Japanese-American populations with high and low fish intake. Plasma phospholipid marine-derived n-3 fatty acid measurements are a simple and reliable biomarker for assessing dietary intake.

Background High-sensitivity cardiac troponin (hs-cTn) elevations are associated with incident cardiovascular disease events in primary prevention samples. However, the mechanisms underlying this association remain unclear. Methods We studied 458 men without known cardiovascular disease who participated in the cardiovascular disease substudy of the Multicenter AIDS Cohort Study and had cardiac CT angiography. We used multivariable linear and logistic regression models to examine the cross-sectional associations between coronary artery stenosis, coronary artery plaque, indexed left ventricular mass (LVMi), and the outcome of hs-cTnI. We also evaluated the associations between HIV serostatus or use of highly active antiretroviral therapy (HAART) and hs-cTnI. Results The mean age was 54 years, 54% were white, and 61% were HIV infected. In multivariable-adjusted logistic models, comparing the highest quartile of LVMi with the lowest quartile, the odds ratio (OR) of hs-cTnI ≥75th percentile was 2.59 (95% CI, 1.20-5.75). There was no significant association between coronary stenosis severity or plaque type and hs-cTnI in linear models; however, in logistic regression models, coronary artery stenosis ≥70% (8% of sample) was marginally associated with a higher likelihood (OR, 2.75 [95% CI, 1.03, 7.27]) of having hs-cTnI ≥75th percentile. There were no associations between HIV serostatus or HAART use and hs-cTnI in either linear or logistic models. Conclusion Among primary prevention men with or at risk for HIV, hs-cTnI concentrations were strongly associated with LVMi but were not associated with HIV infection or treatment status or with coronary plaque type or stenosis until the extremes of severity (≥70% stenosis).

Haptoglobin's (Hp) main role is to bind free hemoglobin (Hb), reducing its oxidative potential. The Hp–Hb complex formed is cleared from the circulation by macrophage receptor CD163. In diabetes, impaired Hp 2-2–Hb CD163 clearance and abnormal glomerular permeability allow the large Hp 2-2–Hb complex to cross the barrier, where its redox active iron leads to cellular toxicity. Although Hp 2-2 predicts renal function decline, whether renal iron deposition differs by Hp is unknown. We used renal quantitative T2* magnetic resonance imaging to estimate iron level in the cortex and medullar of type 1 diabetes (T1D) adults [15 Hp 1-1 and 15 Hp 2-2 carriers of similar age (53 years), duration (45 years), and gender]. Total kidney iron level was estimated as the sum of the cortex and medullar iron. Albuminuria was defined as urinary albumin to creatinine ratio >30 mg/g in two of three samples. Total kidney iron did not differ by gender or Hp but was higher in those with albuminuria (p = 0.05), an associa...

ObjectiveThis cross-sectional study examined whether contrasting distributions of nuclear magnetic resonance (NMR)-measured lipoproteins contribute to differences in the prevalence of subclinical atherosclerosis measured using coronary artery calcium (CAC) between the two groups of middle-aged males: the US-residing Caucasian (US-White) and Japan-residing Japanese (Japanese).MethodsIn a population-based study of 570 randomly selected asymptomatic men aged 40–49 years (270 US-White and 300 Japanese), we examined the relationship between race/ethnicity, NMR-measured lipoproteins and CAC (measured by Electron Beam CT and quantified using the Agatston method) using multivariable robust Poisson regression adjusting for traditional and novel risk factors for coronary heart disease (CHD).ResultsThe US-White compared with the Japanese had significantly different NMR-measured lipoprotein particle distributions. The US-White had a significantly higher prevalence of CAC≥10 (CAC-prevalence) compared with the Japanese adjusting for CHD risk factors (prevalence ratio (PR)=2.10; 95% CI=1.24 to 3.48), and this difference was partially attenuated (~18%) with further adjustment for lipoprotein levels (PR=1.73; 95% CI=1.02 to 3.08). There was no reclassification improvement with further addition of lipoproteins particle concentrations/size to a model that already included traditionally measured lipids (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), cardiovascular risk factors, and inflammatory markers (net reclassification improvement index=−2% to 3%).ConclusionsVariations in the distribution of NMR-measured lipoprotein particles partially accounted for the difference in the CAC-prevalence between middle-aged US-White and Japanese men.

AIMS: The haptoglobin (Hp) 2-2 genotype has been shown to increase the risk of coronary artery disease, kidney dysfunction and mortality from cardiovascular and renal causes in type 1 diabetes (T1D). Similar associations, however, have not been observed in those without diabetes. As cardiac autonomic neuropathy (CAN) is a cardiovascular disease risk factor, we assessed the presence of an association between the Hp 2-2 genotype and CAN. METHODS: The study included 216 individuals with childhood-onset T1D and 200 individuals with normal glucose tolerance (NGT) of similar age and gender distribution to their counterparts with T1D. CAN was assessed using an electrocardiogram as an abnormal, age-specific, heart rate response to deep breathing. Multivariable logistic regression models were used to assess the association between the Hp 2-2 genotype and CAN. RESULTS: Compared with NGT, participants with T1D had a similar proportion of Hp 2-2 carriers (41.5% vs. 32.0%, p=0.05) but a greater CAN prevalence (28.2% vs. 5.0%, p

Objective:A few studies have examined the longitudinal association of blood pressure (BP) with arterial stiffness progression, and the results were inconsistent. The objective of this study was to investigate the roles of initial BP and its longitudinal change on the progression of arterial stiffnes

Arterial stiffness is established as an independent predictor of cardiovascular morbidity and mortality. The objective was to prospectively evaluate association of aortic calcification burden with progression of arterial stiffness in population-based samples of healthy middle-aged men from ERA JUMP cohort (Electron-Beam Computed Tomography and Risk Factor Assessment in Japanese and US Men in the Post-World War II Birth Cohort). Men (n=635) aged 40 to 49 years (207 white American, 45 black American, 142 Japanese American, and 241 Japanese in Japan) were examined at baseline and 4 to 7 years later. Aortic calcification was evaluated from level of aortic arch to iliac bifurcation. Arterial stiffness progression was measured as annual change in brachial-ankle pulse wave velocity. Multivariable-adjusted general linear models were applied to investigate associations of longitudinal change in aortic calcification with arterial stiffness progression in participants overall, as well as in subgroups without or with prevalent aortic calcification at baseline. Annual change in aortic calcification was positively and significantly associated with arterial stiffness progression. In participants with annual changes in aortic calcium score of ≤0, 1 to 10, 11 to 100, and >100, the adjusted means (SD) for the annual change in brachial-ankle pulse wave velocity were 3.8 (2.2), 7.2 (2.2), 12.2 (1.8), and 15.6 (2.6) cm/s, respectively ( P for trend

AIMS We aimed to assess whether the association of the haptoglobin 2 allele with coronary artery disease is modified by glycaemic control in a prospective cohort study of individuals with childhood-onset Type 1 diabetes. METHODS Coronary artery disease events (death from coronary artery disease, confirmed myocardial infarction, stenosis ≥50%, revascularization) were assessed between 1986 and 2013 among 480 individuals with Type 1 diabetes (baseline age 28 years; diabetes duration 19 years). Better glycaemic control was defined as an updated mean HbA1c during follow-up of

Background and aim Few studies have examined the association of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFAs) with the measures of atherosclerosis in the general population. This study aimed to examine the relationship of total LCn-3PUFAs, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) with aortic calcification. Methods and results In a multiethnic population-based cross-sectional study of 998 asymptomatic men aged 40–49 years (300 US-White, 101 US-Black, 287 Japanese American, and 310 Japanese in Japan), we examined the relationship of serum LCn-3PUFAs to aortic calcification (measured by electron-beam computed tomography and quantified using the Agatston method) using Tobit regression and ordinal logistic regression after adjusting for potential confounders. Overall 56.5% participants had an aortic calcification score (AoCaS) > 0. The means (SD) of total LCn-3PUFAs, EPA, and DHA were 5.8% (3.3%), 1.4% (1.3%), and 3.7% (2.1%), respectively. In multivariable-adjusted Tobit regression, a 1-SD increase in total LCn-3PUFAs, EPA, and DHA was associated with 29% (95% CI = 0.51, 1.00), 9% (95% CI = 0.68, 1.23), and 35% (95% CI = 0.46, 0.91) lower AoCaS, respectively. Results were similar in ordinal logistic regression analysis. There was no significant interaction between race/ethnicity and total LCn–3PUFAs, EPA or DHA on aortic calcification. Conclusions This study showed the significant inverse association of LCn-3PUFAs with aortic calcification independent of conventional cardiovascular risk factors among men in the general population. This association appeared to be driven by DHA but not EPA.

The haptoglobin (Hp) 2 allele directly predicts coronary artery disease in type 1 diabetes, potentially due to its decreased antioxidative/anti-inflammatory properties. We measured the concentrations of oxidative/inflammatory biomarkers (urinary 15-isoprostane F2t [IsoP], α- and γ-tocopherol, tumor necrosis factor α [TNF-α], high-sensitivity C-reactive protein [hsCRP], white blood cell [WBC] count, fibrinogen, and adiponectin) thrice during 20 years of follow-up among 454 individuals with childhood-onset type 1 diabetes (mean baseline age, 28 years and diabetes duration, 19 years). Differences in biomarkers by Hp were assessed both at baseline (i.e., the first time point of measurements) and over time (with mixed models). No differences by Hp were observed at baseline with the exception of a significant trend toward higher IsoP concentrations with the number of Hp 2 alleles (p=0.01). In multivariable mixed models, the concentrations of IsoP (β=0.05, p=0.01) and WBC count (β=0.20, p=0.06) overtime increased incrementally with the number of Hp 2 alleles. No other biomarker assessed related to Hp. Reported elevated IsoP and WBC count concentrations over time among Hp 2 allele carriers lead to the hypothesis that the antioxidative and anti-inflammatory capacity of the Hp 2 is inferior to that of the Hp 1 allele in type 1 diabetes. Antioxid. Redox Signal. 23, 1439–1444.

OBJECTIVE Cross-sectional studies suggest that lipopolysaccharide-binding protein (LBP) may be associated with obesity and metabolic disorders. However, prospective studies examining LBP are lacking. This prospective study investigated the association between LBP and metabolic abnormalities in 580 African ancestry men (mean age, 59.1 ± 10.5 years). RESEARCH DESIGN AND METHODS We measured fasting serum LBP at baseline. Changes in adiposity and glucose homeostasis as well as case subjects with new type 2 diabetes and impaired fasting glucose (IFG) were assessed at a follow-up visit ˜6 years later. Baseline LBP values were tested across quartiles for linear trend with metabolic measures. Multivariable logistic regression was used to determine the odds of new cases of IFG or diabetes per 1-SD greater baseline LBP. RESULTS LBP was significantly associated with baseline BMI, waist circumference, whole-body and trunk fat, skeletal muscle density, fasting serum insulin, and HOMA-insulin resistance (IR) (all P < 0.01). Greater baseline LBP was significantly associated with longitudinal increases in the percentage of trunk fat (P = 0.025) and HOMA-IR (P = 0.034), but only borderline so with a decrease in skeletal muscle density (P = 0.057). In men with normal glucose, baseline LBP was associated with increased odds of having IFG at follow-up after adjustment for age, baseline trunk fat, and lifestyle factors (odds ratio per 1-SD LBP: 1.51; 95% CI 1.02–2.21). This association was attenuated after additional adjustment for change in trunk fat (P = 0.067). CONCLUSIONS LBP may be a marker of prediabetes. Some of this association appears to be mediated through increased central and ectopic skeletal muscle adiposity.

We tested if serum lipid and lipoprotein cholesterol levels are associated with longitudinal measures of bone mineral density (BMD) in 1289 African ancestry men. After 6 years of mean follow-up, men with clinically optimal levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), or triglycerides at baseline experienced the greatest BMD loss, independent of potential confounding factors (all p

Poor renal function is associated with increased rates of bone loss and osteoporotic fractures in Caucasian men. The importance of kidney function for skeletal health in African ancestry men, who are a population segment with a high prevalence of chronic kidney disease as well as high peak bone mass, is not well known. We examined the relationship between estimated glomerular filtration rate (eGFR) and rates of bone loss in a large population cohort of otherwise healthy Afro-Caribbean men aged 40 years and older. Dual X-ray absorptiometry of the proximal femur and quantitative computed tomography of the proximal radius and tibia were obtained approximately 6 years apart. We calculated eGFR from serum creatinine that was measured in fasting samples in 1451 men. Impaired kidney function (IKF, eGFR

Haptoglobin (Hp) genotype 2-2 increases cardiovascular diabetes complications. In type 2 diabetes, α-tocopherol was shown to lower cardiovascular risk in Hp 2-2, potentially through HDL function improvements. Similar type 1 diabetes data are lacking. We conducted a randomized crossover pilot of α-tocopherol supplementation on HDL function [i.e., cholesterol efflux (CE) and HDL-associated lipid peroxides (LP)] and lipoprotein subfractions in type 1 diabetes. Hp genotype was assessed in members of two Allegheny County, PA, type 1 diabetes registries and the CACTI cohort; 30 were randomly selected within Hp genotype, and 28 Hp 1-1, 31 Hp 2-1 and 30 Hp 2-2 were allocated to daily α-tocopherol or placebo for 8 weeks with a 4-week washout. Baseline CE decreased with the number of Hp 2 alleles (p-trend = 0.003). There were no differences in LP or lipoprotein subfractions. In intention-to-treat analysis stratified by Hp, α-tocopherol increased CE in Hp 2-2 (β = 0.79, p = 0.03) and LP in Hp 1 allele carriers (β Hp 1-1 = 0.18, p = 0.05; β Hp 2-1 = 0.21, p = 0.07); reduced HDL particle size (β = −0.07, p = 0.03) in Hp 1-1 carriers; increased LDL particle concentration in Hp 1-1; and decreased it in Hp 2-2 carriers. However, no significant interactions were observed by Hp. In this type 1 diabetes study, HDL function worsened with the number of Hp 2 alleles. α-Tocopherol improved HDL function in Hp 2-2 carriers and appeared to adversely affect lipid peroxides and lipoprotein subfractions among Hp 1 allele carriers. As no significant interactions were observed, findings require replication in larger studies.

Objective To describe associations between maternal lipids and birthweight and to determine whether pre-pregnancy body mass index (BMI) modifies these associations. Design Cohort study. Setting Multiple communities in Michigan, USA. Population Participants were a sub-cohort of women from the multi-community Pregnancy Outcomes and Community Health (POUCH) study (1998–2004). Methods Maternal total cholesterol, high-density lipoprotein (HDLc), and low-density lipoprotein (LDLc) cholesterol, and triglycerides were assessed at 16–27 weeks' gestation. Women were classified as having normal (

The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage.

Background We hypothesized that higher concentrations of LDL particles (LDL-P) and leptin, and lower concentrations of HDL particles (HDL-P), and total and high molecular weight (HMW) adiponectin, would predict incident coronary heart disease (CHD) among severely obese postmenopausal women. Methods In a case–cohort study nested in the Women's Health Initiative Observational Study, we sampled 677 of the 1852 white or black women with body mass index (BMI) ≥ 40 kg/m2 and no prevalent cardiovascular disease (CVD), including all 124 cases of incident CHD over mean 5.0 year follow-up. Biomarkers were assayed on stored blood samples. Results In multivariable-adjusted weighted Cox models, higher baseline levels of total and small LDL-P, and lower levels of total and medium HDL-P, and smaller mean HDL-P size were significantly associated with incident CHD. In contrast, large HDL-P levels were inversely associated with CHD only for women without diabetes, and higher total and HMW adiponectin levels and lower leptin levels were associated with CHD only for women with diabetes. Higher total LDL-P and lower HDL-P were associated with CHD risk independently of confounders including CV risk factors and other lipoprotein measures, with adjusted HR (95% CIs) of 1.55 (1.28, 1.88) and 0.70 (0.57, 0.85), respectively, and similar results for medium HDL-P. Conclusions Higher CHD risk among severely obese postmenopausal women is strongly associated with modifiable concentrations of LDL-P and HDL-P, independent of diabetes, smoking, hypertension, physical activity, BMI and waist circumference. General significance Severely obese postmenopausal women should be considered high risk candidates for lipid lowering therapy., Highlights • CHD risk is ~ 2-fold higher for severely obese postmenopausal women (BMI ≥ 40 kg/m2). • Baseline risk factors were measured among 677 severely obese postmenopausal women. • 5-year CHD risk related to higher LDL particles, lower total, medium HDL particles. • Paradoxical or no relations of adiponectin (total, HMW) and leptin with CHD risk • Clinical implications: Statins reduce LDL particles and increase HDL particles.

Aim: To examine whether the inflammatory markers C-reactive protein (CRP) and fibrinogen are associated with biomarkers of atherosclerosis [carotid intima-media thickness (IMT) and coronary artery calcification (CAC)] in the general male population, including Asians.Methods: Population-based samples of 310 Japanese, 293 Japanese-American and 297 white men 40-49 years of age without clinical cardiovascular disease underwent measurement of IMT, CAC and the CRP and fibrinogen levels as well as other conventional risk factors using standardized methods. Statistical associations between the variables were evaluated using multiple linear or logistic regression models.Results: The Japanese group had significantly lower levels of inflammatory markers and subclinical atherosclerosis than the Japanese-American and white groups (P-values all ＜0.001). The mean level of CRP was 0.66 vs. 1.11 and 1.47 mg/L, while that of fibrinogen was 255.0 vs. 313.0 and 291.5 mg/dl, respectively. In addition, the mean carotid IMT was 0.61 vs. 0.73 and 0.68 mm, while the mean prevalence of CAC was 11.6% vs. 32.1% and 26.3%, respectively. Body mass index (BMI) showed significant positive associations with both the CRP and fibrinogen levels. Although CRP showed a significant positive association with IMT in the Japanese men, this association became non-significant following adjustment for traditional risk factors or BMI. In all three populations, CRP was not found to be significantly associated with the prevalence of CAC. Similarly, fibrinogen did not exhibit a significant association with either IMT or the prevalence of CAC.Conclusions: The associations between inflammatory markers and subclinical atherosclerosis may merely reflect the strong associations between BMI and the levels of inflammatory markers and incidence of subclinical atherosclerosis in both Eastern and Western populations.

Background and aims Several studies have reported a significant inverse association of light to moderate alcohol consumption with coronary heart disease (CHD). However, studies assessing the relationship between alcohol consumption and atherosclerosis have reported inconsistent results. The current study was conducted to determine the relationship between alcohol consumption and aortic calcification. Methods We addressed the research question using data from the population-based ERA-JUMP Study, comprising of 1006 healthy men aged 40–49 years, without clinical cardiovascular diseases, from four race/ethnicities: 301 Whites, 103 African American, 292 Japanese American, and 310 Japanese in Japan. Aortic calcification was assessed by electron-beam computed tomography and quantified using the Agatston method. Alcohol consumption was categorized into four groups: 0 (non-drinkers), ≤1 (light drinkers), >1 to ≤3 (moderate drinkers) and >3 drinks per day (heavy drinkers) (1 drink = 12.5 g of ethanol). Tobit conditional regression and ordinal logistic regression were used to investigate the association of alcohol consumption with aortic calcification after adjusting for cardiovascular risk factors and potential confounders. Results The study participants consisted of 25.6% nondrinkers, 35.3% light drinkers, 23.5% moderate drinkers, and 15.6% heavy drinkers. Heavy drinkers [Tobit ratio (95% CI) = 2.34 (1.10, 4.97); odds ratio (95% CI) = 1.67 (1.11, 2.52)] had significantly higher expected aortic calcification score compared to nondrinkers, after adjusting for socio-demographic and confounding variables. There was no significant interaction between alcohol consumption and race/ethnicity on aortic calcification. Conclusions Our findings suggest that heavy alcohol consumption may be an independent risk factor for atherosclerosis.

Background/Objectives Higher volumes of ectopic cardiovascular fat (ECF) are associated with greater risk of coronary heart disease (CHD). Identifying factors that are associated with ECF volumes may lead to new preventive efforts to reduce risk of CHD. Significant racial/ethnic differences exist for overall and central adiposity measures which are known to be associated with ECF volumes. Whether racial/ethnic differences also exist for ECF volumes and their associations with these adiposity measures remain unclear. Subjects/Methods Body-mass index (BMI), CT-measured ECF volumes (epicardial, pericardial and their summation), and visceral adipose tissue (VAT) were examined in a community-based sample of 1,199 middle-aged men (24.2% Caucasians, 7.0% African-Americans, 23.6% Japanese-Americans, 22.0% Japanese, 23.2% Koreans). Results Significant racial/ethnic differences existed in ECF volumes and their relationships with BMI and VAT. ECF volumes were highest among Japanese-Americans and lowest among African-Americans. The associations of BMI and VAT with ECF differed by racial/ethnic groups. Compared to Caucasians, for each 1-unit increase in BMI, African-Americans had lower whereas Koreans had higher increases in ECF volumes (P-values

We considered that accumulation of nonesterified (free) fatty acids (NEFAs) in the first trimester of pregnancy would mark women at excess risk of spontaneous preterm birth (sPTB) and examined the interplay between NEFAs, lipids, and other markers to explore pathways to sPTB. In a case-control study nested in the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997–2001), we assayed NEFA levels in nonfasting serum collected at a mean gestational week of 9.4 (range, 4–20 weeks) in 115 women with sPTB (

Objective To determine the short-term efficacy of oral glucosamine supplementation by evaluating structural lesions in the knee joints, as assessed using 3T magnetic resonance imaging (MRI). Methods This study was designed as a randomized, double-blind, placebo-controlled trial. Recruitment was performed via mass mailings and an arthritis registry in southwestern Pennsylvania. In total, 201 participants with mild-to-moderate pain in one or both knees, as defined by a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score ≥25 and ≤100, were enrolled. Of these subjects, 69.2% had a Kellgren/Lawrence grade ≥2 in at least 1 knee. Participants received 24 weeks of treatment with 1,500 mg glucosamine hydrochloride in beverage form or a placebo beverage. The primary outcome was decreased worsening of cartilage damage on 3T MRI of both knees, assessed according to a validated scoring system, the Whole-Organ MRI Score (WORMS). Secondary outcomes included change in bone marrow lesion (BML) scores in all knees and change in excretion of urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II). Results The adjusted odds ratio (OR) for the likelihood of decreased cartilage damage over 24 weeks in any WORMS-scored subregion of the knee in the glucosamine treatment group compared to the control group was 0.938 (95% confidence interval [95% CI] 0.528, 1.666). Compared to subjects treated with glucosamine, control subjects showed more improvement in BMLs (adjusted OR 0.537, 95% CI 0.291, 0.990) but no difference in worsening BMLs (adjusted OR 0.691, 95% CI 0.410, 1.166) over 24 weeks. There was no indication that treatment with glucosamine decreased the excretion of urinary CTX-II (β = −0.10, 95% CI −0.21, 0.002). Conclusion The results of this short-term study provide no evidence of structural benefits (i.e., improvements in MRI morphologic features or urinary CTX-II excretion) from glucosamine supplementation in individuals with chronic knee pain.

Background Atherosclerosis causing renal artery stenosis (RAS) is one of the most common secondary causes of hypertension in adults, but is rare in children.

To determine whether serum concentrations of long chain n-3 polyunsaturated fatty acids (LCn3PUFAs) contribute to the difference in the incidence rate of coronary artery calcification (CAC) between Japanese men in Japan and white men in the USA.In a population based, prospective cohort study, 214 Japanese men and 152 white men aged 40-49 years at baseline (2002-2006) with coronary calcium score (CCS)=0 were re-examined for CAC in 2007-2010. Among these, 175 Japanese men and 113 white men participated in the follow-up exam. Incident cases were defined as participants with CCS≥10 at follow-up. A relative risk regression analysis was used to model the incidence rate ratio between the Japanese and white men. The incidence rate ratio was first adjusted for potential confounders at baseline and then further adjusted for serum LCn3PUFAs at baseline.Mean (SD) serum percentage of LCn3PUFA was100% higher in Japanese men than in white men (9.08 (2.49) vs 3.84 (1.79), respectively, p0.01). Japanese men had a significantly lower incidence rate of CAC compared to white men (0.9 vs 2.9/100 person-years, respectively, p0.01). The incidence rate ratio of CAC taking follow-up time into account between Japanese and white men was 0.321 (95% CI 0.150 to 0.690; p0.01). After adjusting for age, systolic blood pressure, low density lipoprotein cholesterol, diabetes, and other potential confounders, the ratio remained significant (0.262, 95% CI 0.094 to 0.731; p=0.01). After further adjusting for LCn3PUFAs, however, the ratio was attenuated and became non-significant (0.376, 95% CI 0.090 to 1.572; p=0.18).LCn3PUFAs significantly contributed to the difference in the incidence of CAC between Japanese and white men.

The study objective was to compare the effect of a standard calorie- and fat-restricted diet (STD-D) and a calorie- and fat-restricted lacto-ovo-vegetarian diet (LOV-D) on total and high-molecular-weight (HMW) adiponectin levels after 6 months of behavioral intervention.This study is an ancillary study to a randomized clinical trial.Subjects included 143 overweight/obese adults (STD-D = 79; LOV-D = 64).Both groups received the same standard behavioral intervention; the only difference was that LOV-D participants were instructed to eliminate meat, poultry, and fish from their diet.Weight, dietary intake with the 3-day food diary, and total and HMW adiponectin levels were measured.Both groups significantly increased total (STD-D +7.2 ± 17.8%; LOV-D +9.4 ± 21.8%) and HMW adiponectin levels (STD-D +18.5 ± 32.9%; LOV-D +15.8 ± 34.5%; ps0.05) with no significant differences between the groups. We found significant associations between weight loss and increases in total (β (SE) = -.071(.27); p = 0.003) and HMW adiponectin (β (SE) = -1.37(.47); p = 0.001) levels independent of the diet type. Weight loss at the higher quartile was associated with improvements of adiponectin levels (p0.05).Weight loss was associated with increased total and HMW adiponectin levels regardless of the diet type. Enhancing weight loss may be a means to improve adiponectin levels.

Aortic stiffness is being recognized as a predictor of cardiovascular disease (CVD) and all-cause mortality independent of blood pressure (BP), age, and other CVD risk factors.1 Aortic stiffness can be measured noninvasively by carotid–femoral pulse wave velocity (cfPWV), which is considered the gold standard method. In fact, the European Society of Hypertension/European Society of Cardiology added cfPWV as a factor to assess future CVD risk in recently published guidelines for the management of arterial hypertension.2 A recent meta-analysis reported that supplementation of marine n-3 fatty acids (FAs) improved aortic stiffness.3 The randomized clinical trials (RCTs) in the meta-analysis4–12 and 1 more recent RCT13 have several characteristics. First, subjects in these RCTs were individuals with type 2 diabetes,5,9 metabolic syndrome,10 hyperlipidemia,11,12 or individuals who were obese or overweight.4,6–8 Thus, the result may not be extrapolated to the general population. Second, although the differential effect of 2 major marine n-3 FAs: eicosapentaenoic (EPA; 20:5 n-3) and docosahexaenoic acids (DHA; 22:6 n-3), on CVD risk factors is a current research topic,14 only 1 RCT11 reported the effect of each of DHA and EPA on aortic stiffness separately. Third, although cfPWV is regarded as the gold standard to evaluate aortic stiffness, these RCTs, except for one study,13 used other methods. Finally, most of these RCTs examined the effect of >1 gram of fish oil on aortic stiffness,4–7,9–11,15 as compared with

Aims:Conflicting evidence exists regarding whether obesity is independently associated with coronary artery calcium (CAC), a measure of coronary atherosclerosis. We examined an independent association of obesity with prevalent CAC among samples of multi-ethnic groups whose background populations have varying levels of obesity and coronary heart disease (CHD)., Methods and results:We analysed a population-based sample of 1212 men, aged 40-49 years free of clinical cardiovascular disease recruited in 2002-06; 310 Japanese in Japan (JJ), 294 Koreans in South Korea (KN), 300 Japanese Americans (JA), and 308 Whites in the USA (UW). We defined prevalent CAC as an Agatston score of ≥10. Prevalent CAC was calculated by tertile of the body mass index (BMI) in each ethnic group and was plotted against the corresponding median of tertile BMI. Additionally, logistic regression was conducted to examine whether an association of the BMI was independent of conventional risk factors. The median BMI and crude prevalence of CAC for JJ, KN, JA, and UW were 23.4, 24.4, 27.4, and 27.1 (kg/m2); 12, 11, 32, and 26 (%), respectively. Despite the absolute difference in levels of BMI and CAC across groups, higher BMI was generally associated with higher prevalent CAC in each group. After adjusting for age, smoking, alcohol, hypertension, lipids, and diabetes mellitus, the BMI was positively and independently associated with prevalent CAC in JJ, KN, UW, but not in JA., Conclusion:In this multi-ethnic study, obesity was independently associated with subclinical stage of coronary atherosclerosis among men aged 40-49 years regardless of the BMI level.

Objective: When compared with other ethnic groups, African ancestry individuals have lower triglycerides and higher High-density lipoprotein cholesterol (HDL-C) levels, although the mechanisms for these differences remain unclear. A comprehensive array of factors potentially related to fasting serum lipid and lipoprotein levels in African ancestry men was evaluated. Design and Methods: Men (1,821) underwent dual-energy X-ray absorptiometry measures of total body fat and quantitative computed tomography assessments of calf skeletal muscle adiposity [subcutaneous and intermuscular adipose tissue (AT), and muscle density as a measure of intra-muscular AT]. Results: Multivariable linear regression analysis identified age (−), total body fat (+), subcutaneous AT (−), fasting glucose (+), fasting insulin (+), diastolic blood pressure (+), and non-African ancestry (+) as independent correlates of triglycerides (all P < 0.05). Total body fat (+), intra-muscular AT (−), and diastolic blood pressure (+) were independent correlates of Low-density lipoprotein cholesterol (LDL-C) (all P < 0.001). Age (+), waist circumference (−), fasting insulin (−), physical activity (+), and alcohol intake (+) were independent correlates of HDL-C (all P < 0.05). Conclusions: A novel relationship between skeletal muscle adiposity and serum lipid and lipoprotein levels in African ancestry men, independent of total and central adiposity was illuminated. In African ancestry populations, genetic factors are likely a significant determinant of triglycerides levels.

Recent data suggest excess circulating aldosterone promotes cardiometabolic decline. Weight loss may lower aldosterone levels, but little longitudinal data is available in normotensive adults. We aimed to determine whether, independent of changes in sodium excretion, reductions in serum aldosterone are associated with favorable changes in obesity-related factors in normotensive overweight/obese young adults. We studied 285 overweight/obese young adult participants (body mass index ≥ 25 and

Objective. This study examined associations between maternal lipid levels at mid-pregnancy and preterm delivery, medically indicated or spontaneous. Design: Prospective cohort study. Setting. Women were recruited from 52 clinics in five Michigan, USA communities (1998–2004). Population. Pregnant women were enrolled at 15–27 weeks’ gestation and followed to delivery (n=3019). Methods. A single blood sample was obtained at study enrollment. Blood lipids, i.e. total cholesterol (TC), high-density lipoprotein (HDLc), low-density lipoprotein (LDLc) cholesterol, and triglycerides (TG), were measured on a sub-cohort (n=1309). Main outcome measures. There were 221 spontaneous, 100 medically indicated preterm deliveries and 988 term deliveries. Polytomous logistic regression models examined relationships among cholesterol levels (Low

ObjectiveMajor depressive disorder (MDD) during pregnancy increases the risk of adverse maternal and infant outcomes. Maternal nutritional status may be a modifiable risk factor for antenatal depression. We evaluated the association between patterns in mid-pregnancy nutritional biomarkers and MDD.DesignProspective cohort study.SettingPittsburgh, Pennsylvania, USA.SubjectsWomen who enrolled at ≤20 weeks’ gestation and had a diagnosis of MDD made with the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) at 20-, 30- and 36-week study visits. A total of 135 women contributed 345 person-visits. Non-fasting blood drawn at enrolment was assayed for red cell essential fatty acids, plasma folate, homocysteine and ascorbic acid; serum 25-hydroxyvitamin D, retinol, vitamin E, carotenoids, ferritin and soluble transferrin receptors. Nutritional biomarkers were entered into principal components analysis.ResultsThree factors emerged: Factor 1, Essential Fatty Acids; Factor 2, Micronutrients; and Factor 3, Carotenoids. MDD was prevalent in 21·5 % of women. In longitudinal multivariable logistic models, there was no association between the Essential Fatty Acids or Micronutrients pattern and MDD either before or after adjustment for employment, education or pre-pregnancy BMI. In unadjusted analysis, women with factor scores for Carotenoids in the middle and upper tertiles were 60 % less likely than women in the bottom tertile to have MDD during pregnancy, but after adjustment for confounders the associations were no longer statistically significant.ConclusionsWhile meaningful patterns were derived using nutritional biomarkers, significant associations with MDD were not observed in multivariable adjusted analyses. Larger, more diverse samples are needed to understand nutrition–depression relationships during pregnancy.

Background Numerous studies reported beneficial effects of marine n-3 fatty acids (n-3 FAs) on cardiovascular disease (CVD) and its risk factors. However, the association of marine n-3 FAs with plasma fibrinogen, a risk factor for CVD, remains uncertain. Methods In a population-based, cross-sectional study of 795 men aged 40-49 without CVD (262 whites in Allegheny County, Pennsylvania, US, 302 Japanese in Kusatsu, Japan, and 229 Japanese Americans in Honolulu, Hawaii, US), we examined the association of marine n-3 FAs with plasma fibrinogen. Serum FAs were measured by capillary gas-liquid chromatography. Marine n-3 FAs were defined as the sum of docosahexaenoic, eicosapentaenoic, and docosapentaenoic acids. Plasma fibrinogen was measured by an automated clot-rate assay. Multiple linear regression analyses were performed to assess the association. Results White, Japanese, and Japanese American men had mean marine n-3 FAs levels of 3.47%, 8.78%, and 4.46%, respectively. Japanese men had a significant inverse association of marine n-3 FAs with fibrinogen (standardized regression coefficient of -0.11, p=0.049), after adjusting for age, body-mass index, and current smoking. The significant inverse association remained after further adjusting for diabetes, C-reactive protein, triglycerides and other variables. White or Japanese American men did not show a significant association. Conclusion We observed the significant inverse association of marine n-3 FAs with fibrinogen in Japanese, but not in whites or Japanese Americans. The observation suggests that marine n-3 FAs at very high levels, as seen in the Japanese, may decrease plasma fibrinogen levels.

Background Recent data suggest that highly elevated high-density lipoprotein cholesterol (HDL-C) may not always protect against cardiovascular disease. To what degree this is true in type 1 diabetes is unknown, although cardiovascular risk is increased despite elevated mean HDL-C. Objective To reassess the association between HDL-C and its subfractions with coronary artery disease (CAD) in childhood-onset type 1 diabetes. Methods Epidemiology of Diabetes Complications study participants free of CAD at baseline (301 men, 298 women; mean age, 27.1 and diabetes duration, 18.9 years) were studied. CAD was defined as angina, ischemic electrocardiogram changes, confirmed myocardial infarction, angiographic stenosis ≥50%, revascularization, or CAD death. Cholesterol in the HDL fraction and HDL3 cholesterol subfraction was measured enzymatically after precipitation with heparin/manganese and dextran sulfate, respectively. Results During 18 years of follow-up, 29.5% of men and 25.5% of women developed CAD. Although a linear decrease in incidence was observed with increasing HDL-C concentration in men, incidence increased in women at less than 47 mg/dL and greater than 80 mg/dL. These patterns largely reflected the HDL3 cholesterol-CAD association. After multivariable adjustment, the linear, inverse, HDL-C/CAD association persisted in men (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.94–0.99); in women, the U-shaped relationship lost significance. HDL3 cholesterol remained multivariably associated with CAD in both men (linear association, P = .03) and women (HR 2.31 (95% CI 1.31–4.08) and HR 1.80 (95% CI 1.01–3.23) for the lowest and highest versus the middle quintiles, respectively). Conclusion The increased CAD risk in women for an HDL-C >80 mg/dL in type 1 diabetes merits further study. Gender specificity could not be determined as only two men had HDL-C >80 mg/dL.

We tested the hypothesis that low leptin and high adiponectin levels are associated with higher rates of bone mineral density (BMD) loss among 3,075 men and women, aged 70–79, from the Health Aging and Body Composition Study. Results suggest that adiponectin, but not leptin, is a risk factor for bone loss in women. Adiponectin and leptin are hormones secreted by adipose cells that may impact BMD. Few studies have evaluated the longitudinal association of leptin and adiponectin levels with rates of BMD change. Hip and whole-body areal BMD (aBMD) were measured five times using dual-energy X-ray absorptiometry over 10 years (average follow-up time, 7.95 ± 1.92 years). Trabecular lumbar spine volumetric BMD (vBMD) was measured using quantitative computed topography at baseline and year 6 in the Pittsburgh cohort only. Random slope and intercept models were used to account for within person correlation as a result of repeated measures of hip and whole-body aBMD. Linear regression was used to model changes in spine trabecular vBMD. Among women, the annualized rate of hip aBMD loss in the highest tertile of adiponectin was −0.67% (95% CI −0.77, −0.58) compared to [−0.43% (95% CI −0.51, −0.35)] in the lowest tertile (p trend = 0.019) after adjusting for age, race, BMI, diabetes, baseline hip aBMD, and weight change. In men, hip aBMD loss was greatest in the high adiponectin group (tertile 3), however this association was not significant (p trend = 0.148). After adjusting for weight change in women, the association between higher leptin and lower hip aBMD loss was attenuated and no longer significant (p trend = 0.134). Leptin and adiponectin levels were not associated with whole-body aBMD or trabecular lumbar spine vBMD loss. Adiponectin was associated with increased hip aBMD loss in women only, supporting evidence that adiponectin may have an important role in bone health.

Both sagittal abdominal diameter (SAD) and waist circumference (WC) highly correlate with visceral adipose tissue (VAT) being linked to an atherogenic lipoprotein profile. However, it is uncertain whether SAD is a better correlate of atherogenic lipoprotein subfractions than WC. We examined relative associations of SAD vs WC with lipoprotein subfractions for US white and Japanese men, concurrently examining the associations of VAT vs subcutaneous adipose tissue with lipoprotein subfractions. A population-based sample of 260 white and 282 Japanese men aged 40 to 49 years was examined for VAT and subcutaneous adipose tissue by computed tomography; SAD and WC by a portable sliding-beam caliper and a measuring tape, respectively; and lipoprotein subfractions by nuclear magnetic resonance spectroscopy. Both SAD and WC were significantly and positively associated with large very low-density lipoprotein and total and small low-density lipoprotein particle concentrations, and inversely associated with large high-density lipoprotein particle concentration for both white and Japanese men. In body mass index-adjusted regression models, the significant associations of SAD remained for both white and Japanese men, whereas those of WC became nonsignificant for white men. When SAD and WC were simultaneously included into the body mass index-adjusted models, the associations of SAD remained significant and statistically stronger than those of WC for both white and Japanese men. Furthermore, the pattern of the associations of SAD with those lipoprotein subfractions was comparable to that of the associations of VAT. Sagittal abdominal diameter was comparable to VAT and stronger than WC in the associations with atherogenic lipoprotein subfractions for middle-aged, nondiabetic, white and Japanese men.

We examined the association of serum 25-hydroxyvitamin D [25(OH)D] with indices of bone quality in older men. Positive associations for 25(OH)D and bone mineral density, content, cortical thickness, and axial and polar strength strain indices were observed among Caucasians; however, among men of African descent findings were either null or negative. There are limited data on serum 25(OH)D and bone measures in men of African ancestry. To better understand racial differences in vitamin D status and bone health, a cross-sectional study among 446 Caucasian men in the US and 496 men of African ancestry in Tobago (age ≥ 65 years) was conducted. Serum 25(OH)D (liquid chromatography and tandem mass spectrometry) was measured, and peripheral quantitative computed tomography scans were administered. Bone measures estimated included trabecular and cortical volumetric bone mineral density (vBMD), bone mineral content (BMC), bone geometry (cross-sectional area and cortical thickness), and polar and axial strength strain indices (SSIp and SSIx). Men of African ancestry had higher 25(OH)D than Caucasians (34.7 vs. 27.6 ng/ml, p < 0.01). Among Caucasians, 25(OH)D was positively (p trend < 0.05) associated with cortical vBMD, total BMC, cortical thickness, SSIp, and SSIx at the distal radius after adjustment for potential confounders. Similar patterns were observed at the distal tibia. In contrast, in men of African ancestry, there was an inverse association (p trend < 0.05) between 25(OH)D and the cross-sectional area, and SSIx. Race modified (p for interaction < 0.05) the association between 25(OH)D and total BMC, cross-sectional area, SSIp, SSIx, and trabecular vBMD of the radius. In men of African ancestry, there was evidence of a threshold effect (at approximately 18 ng/ml) for 25(OH)D on tibial total BMC and cortical thickness. More studies are needed to better comprehend these race differences for 25(OH)D and bone density, geometry, and indices of bone strength.

SUMMARY. In patients with chronic hepatitis C virus (HCV) infection, steatosis and fibrosis have been shown to be inversely associated with total cholesterol (TC) and low- density lipoprotein cholesterol. Steatosis and fibrosis have also been found to be associated with triglyceride (TG) levels; though, the direction of the relationship is inconsistent across studies. The objective of this study was to assess whether viral level and histological factors are associated with the serum lipid profile in a treatment-naive cohort with chronic HCV genotype 1 infection. Participants were from the prospective Study of Viral Resistance to Antiviral Ther- apy (Virahep-C). Fasting lipid profiles were analysed for 160 African Americans and 170 Caucasian Americans. Linear regression was used to evaluate associations of each lipid with viral load and liver disease. TG levels were significantly and directly associated with HCV levels (P = 0.0034) and steatosis (P < 0.0001). Other lipid parameters were signifi- cantly lower in those with fibrosis (HDLc (P = 0.001) and TC levels (P = 0.004)) than in those without fibrosis. In patients with HCV genotype 1 infection, more severe liver disease was associated with lower lipid levels, with the exception of TG levels that were directly related to steatosis. The direct relationship between viral load and TG levels is consistent with proposed the mechanisms of very low den- sity lipoprotein/HCV particle secretion. In contrast, the direct relationship between TG level and steatosis is inconsistent with posited mechanisms of HCV-induced steatosis, a possi- ble reflection of HCV genotype 1 infection and a metabolic aetiology of steatosis.

This study examines the differences in circulating levels of cytokines among Japanese in Japan (JJ), Japanese Americans (JA), and whites and their associations with obesity and marine n-3 fatty acids (FA) in a cross-sectional population-based study of 297 men aged 40-49 (100 JJ, 99 whites, and 98 JA). Experimental studies show that cytokines are associated with obesity positively and marine n-3 FA inversely. Serum interleukin-1alpha (IL-1alpha), IL-1 receptor agonist (IL-1ra), IL-4, IL-8, IL-10, inducible protein-10 (IP-10), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and marine n-3 FA were determined. Body mass index (BMI), waist circumference, and computed tomography-measured visceral and subcutaneous adipose tissues were determined. The JJ had significantly lower levels of IL-1alpha, IL-4, IL-8, MCP-1, and TNF-alpha than whites and JA. Whites and JA had similar levels of IL-1alpha, IL-4, and IL-8 whereas whites had significantly higher levels of MCP-1 and TNF-alpha than JA. The JJ were least obese (BMI (kg/m(2)), mean +/- standard deviation) 23.6 +/- 2.8, 27.9 +/- 4.6, and 27.9 +/- 4.5 for JJ, whites, and JA, respectively. The JJ had marine n-3 FA about 100% higher than whites and JA (serum marine n-3 FA (%), median (interquartile range) 8.79 (7.41, 11.16), 3.47 (2.63, 4.83), and 4.44 (3.33, 6.01) for JJ, whites, and JA, respectively). Generally cytokines had weak and nonsignificant associations with indices of obesity and nonsignificant associations with marine n-3 FA. BMI had significant inverse associations with IL-1alpha, IL-4, and IL-8 in JA (P0.05). Marine n-3 FA had marginally significant inverse associations with IL-8 in JJ (P = 0.055) and TNF-alpha in whites (P = 0.076). The JJ had lower levels of many cytokines than whites and JA. Generally cytokines had weak and nonsignificant associations with indices of obesity and marine n-3 FA. Further investigation is needed to determine why JJ had lower circulating levels of cytokines.

Approximately one half of patients who undergo antiviral therapy for chronic hepatitis C virus (HCV) genotype 1 infection do not respond to treatment. African Americans (AAs) are less responsive to treatment than Caucasian Americans (CAs), but the reasons for this disparity are largely unknown. Recent studies suggest that serum lipids may be associated with treatment response. The aims of this study were to evaluate baseline and changes in serum lipids during therapy, determine whether serum lipids are associated with virological response, and assess whether these measures explain the racial difference in efficacy. The study participants were from Virahep-C, a prospective study of treatment-naïve patients with genotype 1 HCV infection who received peginterferon (PEG-IN) alfa-2a plus ribavirin therapy for up to 48 weeks. Fasting serum lipids were analyzed at baseline and during and after therapy in 160 AAs and 170 CAs. A relative risk (RR) model was employed to evaluate characteristics associated with sustained virological response (SVR). Antiviral therapy was associated with changes in serum lipids during and after antiviral therapy, with the changes differing by race and the amount of PEG-IFN taken. Baseline lipid measures independently associated with higher rates of SVR were lower triglyceride and higher low-density lipoprotein cholesterol, with an interaction between high-density lipoprotein cholesterol (HDLc) and gender. Lipid measures did not contribute significantly to an explanation of the racial difference in SVR.Serum lipids are associated with SVR, although these paramaters did not explain the racial difference in treatment response. The results of this study are compatible with proposed biological mechanisms of HCV entry, replication, and secretion, and may underscore new potential therapeutic targets for HCV eradication.

Background: The associations of serum omega-6 (n−6) fatty acids with lipoprotein subclasses at the population level are uncertain. Objective: We aimed to examine associations between major n−6 fatty acids [ie, linoleic acid (LA, 18:2n−6) and arachidonic acid (AA, 20:4n−6)] and the lipoprotein subclasses VLDL, LDL, and HDL. Design: We conducted a cross-sectional study in 1098 participants using population-based data from US white, Japanese American, Japanese, and Korean men aged 40–49 y. Serum fatty acids were analyzed by capillary gas-liquid chromatography. Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy. Multiple linear regression models as a function of each fatty acid were used after adjustment for age, population, body mass index, pack-years of smoking, alcohol consumption, diabetes, hypertension, and omega-3 (n−3) and trans fatty acids. Results: Serum LA was inversely associated with large VLDL (β = −0.62, P < 0.001), total LDL (β = −22.08, P < 0.001), and small LDL (β = −31.89, P < 0.001) particle concentrations and VLDL size (β = −0.72, P < 0.001). Serum LA was positively associated with large HDL particle concentration (β = 0.21, P < 0.001) and HDL size (β = 0.03, P < 0.001). The patterns of association of AA with large VLDL and large HDL particle concentrations were comparable with those of LA. Conclusions: At the population level, higher serum concentrations of LA were significantly associated with lower concentrations of total LDL particles. Higher serum concentrations of LA and AA were significantly associated with a lower concentration of large VLDL particles and a higher concentration of large HDL particles. These associations were consistent across the population groups. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT00069797","term_id":"NCT00069797"}}NCT00069797.

Background Neither macro- nor micronutrient supplements have been clearly demonstrated to reduce the risk of preterm birth. However, there has been little attention to carotenoids, tocopherols, and long-chain fatty acids other than n-3 polyunsaturates. Methods We conducted a case-control study nested in a large (n = 5337) prospective, multicenter cohort. All cohort women had an interview, examination, and venipuncture at 24-26 weeks' gestation. Frozen plasma samples in spontaneous preterm births (n = 207) and approximately 2-term controls per case (n = 443) were analyzed for carotenoids, retinol, tocopherols, and long-chain fatty acids. Fresh placentas were fixed, stained, and assessed (without knowledge of pregnancy outcome) for histologic evidence of infection or inflammation, decidual vasculopathy, and infarction. Results High (above the median) plasma concentrations of alpha- and beta-carotene, alpha- and beta-cryptoxanthin, and lycopene were all associated with reductions in risk of spontaneous preterm birth, with evidence of dose-response effects across quartiles. Modest increases in risk were observed with elevated total monounsaturated, total polyunsaturated, and total n-6 polyunsaturated long-chain fatty acids concentrations. Paradoxically, a high gamma-tocopherol concentration was associated with increased preterm birth risk (adjusted odds ratio = 1.8 [95% confidence interval = 1.2-2.6]). Only one of the studied micronutrients (lutein) was independently associated with a reduced risk of decidual vasculopathy (0.5 [0.3-0.9]). Conclusions Carotenoids and long-chain fatty acids warrant further investigation in in vitro, animal, and human studies of preterm birth.

Among Asians, including Japanese, obesity is related to dyslipidemia and insulin resistance at a lower level of body mass index (BMI) compared with non-Hispanic whites (NHW). We hypothesize that this ethnic difference in the relationship between BMI and metabolic risks is partly associated with the ethnic difference in fat distribution, namely, liver fat as well as visceral adipose tissue. To compare liver fat content among Japanese vs NHW men, regional computed tomographic images were taken to measure liver computed tomographic density in population-based samples of 313 Japanese and 288 NHW men aged 40 to 49 years, along with the assessment of metabolic parameters. Liver fat content was higher in Japanese than NHW men (liver to spleen attenuation ratio [lower value means higher liver fat content]: 1.01 +/- 0.16 vs 1.07 +/- 0.15, respectively; P < .01), despite a lower mean BMI in Japanese men (BMI: 23.6 +/- 2.9 vs 27.8 +/- 4.2 kg/m(2), P < .01). Moreover, Japanese men had a greater disposition for fatty liver with a small increase in BMI than NHW (P < .01), whereas both groups had a similar relationship between visceral adipose tissue and BMI. In both groups, liver fat content correlated with triglycerides, homeostasis model assessment of insulin resistance, and C-reactive protein. Liver fat content is higher among Japanese than NHW; and this ethnic difference becomes more robust with a small increase in BMI, suggesting that fatty liver is a sensitive marker for the failure of the adipose tissue to expand to accommodate an increased energy influx, and is associated with similar metabolic risk in Japanese despite lower BMI compared with NHW men.

Background: The association of serum polyunsaturated fatty acids (PUFAs) with lipids in different populations is not known. Objective: Our aim was to examine the association of serum n−6 (omega-6) or n−3 (omega-3) PUFAs with triglycerides or HDL-cholesterol concentrations in 261 white, 285 Japanese, and 212 Japanese American men aged 40–49 y. Design: We used a population-based cross-sectional study. Of the original sample (n = 926), those taking lipid-lowering medications or who had diabetes (n = 168) were excluded. Serum fatty acids were analyzed by capillary gas-liquid chromatography. Multiple regression models as a function of tertile groups of each PUFA were used. Results: Serum n−6 PUFAs were significantly inversely associated with triglycerides across populations after adjustment for age, body mass index, pack-years of smoking, and ethanol consumption [β = −0.39 (P < 0.001), −0.38 (P < 0.001), and −0.33 (P < 0.001) in whites, Japanese, and Japanese Americans, respectively]. Marine n−3 PUFAs were significantly inversely associated with triglycerides across populations [β = −0.15 (P < 0.001), −0.22 (P < 0.001), and −0.13 (P < 0.001) in whites, Japanese, and Japanese Americans, respectively]. n−6 PUFAs were significantly positively associated with HDL cholesterol in whites (β = 4.49, P < 0.001) and Japanese (β = 3.73, P < 0.01). Marine n−3 PUFAs were significantly positively associated with HDL cholesterol in Japanese (β = 2.15, P < 0.05), and eicosapentaenoic acid was significantly positively associated with HDL cholesterol in whites (β = 2.68, P < 0.01). Conclusion: Serum n−6 and n−3 PUFAs are inversely associated with triglycerides across populations.

Adiponectin is reduced in obesity, and has been suggested to play an important role in modulation of atherosclerosis. We studied the relationship between visceral (VAT) and subcutaneous (SAT) adipose tissue and serum adiponectin concentrations in Japanese men. Participants were 304 randomly selected community-based Japanese men aged 40 to 49 without a prior history of cardiovascular disease. Participants were grouped according to tertiles of serum adiponectin. In multiple linear regression analysis including age, pack years of smoking, and alcohol intake as covariates, log-transformed adiponectin was inversely associated with both VAT and SAT when these two obesity measures were included separately in the models. However, log-transformed adiponectin was inversely associated with VAT (standardized β estimate= −0.465, P< 0.0001) and positively associated with SAT (standardized β estimate = 0.166, P=0.03), when these were included concomitantly in the model. In conclusion, VAT and SAT had differential associations with serum adiponectin concentrations.

Background In the general population, adiposity exhibits a J- or U-shaped relationship with mortality; however, in catabolic states this relationship is often inversely linear. We have recently documented an age-independent increase in overweight/obesity in the Pittsburgh Epidemiology of Diabetes Complications study (EDC) of type 1 diabetes (T1D). As intensified insulin therapy (IIT) may promote weight gain, the impact of weight gain in T1D is of importance. We therefore assessed the association of adiposity with mortality in 655 EDC participants during twenty years of follow-up. Methods Individuals were categorized as underweight (BMI

BACKGROUND: Mothers who give birth to preterm infants are at increased risk of mortality from coronary heart disease and stroke, but the biological pathways underlying these associations have not been explored. METHODS: We carried out a case-control study nested in a large (n = 5337) prospective, multicentre cohort. All cohort women had an interview, examination and venipuncture at 24-26 weeks. Frozen plasma samples in spontaneous preterm births (n = 207) and 444 term controls were analysed for plasma homocysteine, folate, cholesterol (total, low-density lipoprotein and high-density lipoprotein) and thrombin-antithrombin (TAT) complexes. DNA was extracted and analysed for seven gene polymorphisms involved in thrombophilia or folate or homocysteine metabolism. Fresh placentas were fixed, stained and blindly assessed for histologic evidence of infarction and decidual vasculopathy. RESULTS: High (above the median) plasma homocysteine and HDL cholesterol were significantly and independently associated with the risk of spontaneous preterm birth [adjusted odds ratios (OR)s = 1.9 (95% 1.1-3.3) and 0.5 (0.3-0.9), respectively]. A higher proportion of women with high homocysteine concentrations had decidual vasculopathy [(13.0 vs 6.8%; OR = 1.9 (1.1-3.5)], although the positive association between decidual vasculopathy and preterm birth did not achieve statistical significance [OR = 1.5 (0.9-2.7)]. No significant associations were observed with the DNA polymorphisms or with plasma TAT or folate levels. CONCLUSIONS: Similar vasculopathic risk factors may underlie preterm birth and adult coronary heart disease and stroke.

Objective: Increased fat infiltration in skeletal muscle has been associated with diabetes. Quantitative computed tomography (QCT) can be used to measure muscle density, which reflects the lipid content of skeletal muscle such that greater fat infiltration in skeletal muscle is associated with lower muscle density. The relative contribution of genetic and environmental factors to fat infiltration in skeletal muscle has not been assessed. Therefore, our aim is to determine genetic and environmental contributions to measures of skeletal muscle composition, and describe their associations with type 2 diabetes in multigenerational families of African ancestry. Methods and Procedures: Peripheral QCT (pQCT) measures of skeletal muscle density were obtained for the calf in 471 individuals (60% women; mean 43 years) belonging to eight large, multigenerational Afro-Caribbean families (mean family size 51 individuals; 3,535 relative pairs). Results: The proportion of variance in muscle density due to additive genetic effects (residual heritability) was 35.0% (P < 0.001) and significant covariates (age, gender, BMI, and parity) explained 55.0% of the total phenotypic variation in muscle density. Muscle density was lower (P < 0.001) in 62 diabetics (69.5 mg/cm3) than in 339 nondiabetics (74.3 mg/cm3) and remained significant after adjusting for age, gender, and BMI (P = 0.005) or age, gender, and waist circumference (P = 0.01). Discussion: Our results provide new evidence that ectopic lipid deposition in skeletal muscle is a heritable trait and is associated with diabetes, independent of overall and central obesity in families of African heritage. Genome-wide screens and candidate gene studies are warranted to identify the genetic factors contributing to ectopic deposition of skeletal muscle fat.

Laboratory and epidemiologic evidence suggest that nonsteroidal anti-inflammatory drug (NSAID) use may be inversely related to the risk of breast cancer; however, the mechanism by which NSAIDs may protect against the development of this disease is uncertain. The objective of this observational study was to assess the relationship between current NSAID use and endogenous estradiol levels, an established breast cancer risk factor. To evaluate this aim, we conducted a cross-sectional investigation among 260 postmenopausal women who were not recently exposed to exogenous hormones. Information on current NSAID use (aspirin, cyclooxygenase-2 inhibitors, and other NSAIDs combined) was collected using a questionnaire at the time of blood draw. Estradiol was quantified in serum by radioimmunoassay. General linear models were used to evaluate the association between NSAID use and serum total estradiol. The age-adjusted and body mass index–adjusted geometric mean serum estradiol concentration among NSAID users (n = 124) was significantly lower than nonusers of NSAIDs (n = 136; 17.8 versus 21.3 pmol/L; P = 0.03). Further adjustment for additional potential confounding factors did not substantially alter estimates (17.7 versus 21.2 pmol/L; P = 0.03). To our knowledge, this report is the first to examine the relationship between NSAID use and serum estradiol in postmenopausal women. These cross-sectional findings suggest that NSAID use may be associated with lower circulating estradiol levels, potentially representing one mechanism through which NSAIDs exert protective effects on breast cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(3):680–7)

In men in the post-World War II birth cohort, that is, men aged 40 to 49 years, whites in the United States had significantly higher levels of intima-media thickness of the carotid arteries (IMT) than the Japanese in Japan (Electron-Beam Tomography and Risk Assessment Among Japanese and US Men in the Post World War II Birth Cohort [ERA JUMP] study). The difference remained after adjusting for traditional risk factors. Primary genetic effects are unlikely, given the degree to which IMT is increased in the Japanese who migrated to the United States. We investigated whether the differences in the distributions of lipoprotein subclasses explain the difference in IMT between the 2 populations. We examined population-based samples of 466 randomly selected men aged 40 to 49 years (215 whites from Allegheny County, Pennsylvania, and 241 Japanese from Kusatsu, Shiga, Japan). Lipoprotein subclasses were determined by nuclear magnetic resonance (NMR) spectroscopy. The whites had significantly higher levels of large very low-density lipoprotein particles and significantly lower levels of large high-density lipoprotein particles than the Japanese, whereas the 2 populations had similar levels of small low-density lipoprotein particles. The 2 populations had similar associations of IMT with NMR lipoproteins. Adjusting for NMR lipoproteins did not attenuate the significant difference in IMT between the 2 populations (0.671 +/- 0.006 mm for the whites and 0.618 +/- 0.006 mm for the Japanese, P = .01, mean +/- SE). Differences in the distributions of NMR lipoproteins between the 2 populations did not explain the higher IMT in the whites.

Background: Coronary artery calcification (CAC) is an established biomarker of coronary atherosclerosis and predicts future cardiovascular (CV) events. Basic science shows that marine omega-3 fatty acids (OM3) have anti-atherogenic properties yet previous studies in Western countries reported that dietary intake of OM3 had no significant association with CAC. Dietary intake of OM3 in Japan is >10x higher than in the US. We hypothesize that blood levels of OM3 in Japanese have a significant inverse association with CAC. Methods: A population-based sample of 982 men in Kusatsu, Shiga, Japan without CV disease was examined for blood levels of OM3, CV risk factors, and CAC. CAC was assessed by electron-beam tomography and quantified using the Agatston method. OM3 was measured by gas-liquid chromatography. We analyzed the association of OM3 with CAC scores at 67th and 80th percentiles adjusting for CV risk factors using quantile regression as the distribution of CAC scores is highly skewed. Results: Mean (SD) age of the participants was 58.7 (10.9). Rates (%) of hypertension, diabetes, current smoker were 47.3, 16.3, and 38.4, respectively. Mean (SD) LDL-C and OM3 was 127.8 (33.6) mg/dL and 10.2 (3.2) %, respectively. CAC scores were 0, 2, 19, 83, and 476 at 33th, 50th, 67th, 80th, and 95th percentiles, respectively. Blood levels of OM3 had significant inverse associations with CAC both at 67th and 80th percentiles after adjusting for CV risk factors (Table). Conclusions: This cross sectional study of Japanese whose blood levels of OM3 are 2-fold higher compared to the US shows that OM3 had a significant inverse association with atherosclerosis, suggesting that high blood levels of OM3 may have anti-atherogenic properties.