Adiposity and Smoking Mediate the Relationship Between Depression History and Inflammation Among Young Adults.

BACKGROUND: Depression is associated with inflammation, but the mechanisms underlying this association are unclear. We examined adiposity and smoking as potential pathways through which childhood depression may lead to an elevated inflammatory status among young adults. METHODS: The sample included 294 subjects with histories of depression (probands), 270 never-depressed siblings of probands (high-risk siblings), and 169 controls. C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM-1) were assessed in serum samples. An adiposity score was computed from body mass index and waist circumference. Smoking behavior was evaluated during an interview. Mixed-effects models were used to test whether adiposity and smoking mediate the relationship between depression and inflammation. RESULTS: Probands (p = .004), but not siblings (p = .071), had higher levels of sICAM-1 compared to controls. However, depression history and risk status had no direct effects on CRP (ps > .13) or IL-6 (ps > .16). Importantly, adiposity indirectly mediated the effect of group (probands vs. controls; siblings vs. controls) on all three inflammatory markers. Smoking indirectly mediated the effect of group (probands vs. controls; siblings vs. controls) on sICAM-1 only. CONCLUSIONS: Among young adults, the adverse inflammatory consequences of depression history are significant for sICAM-1. Adiposity and smoking are pathways through which depression can indirectly impact several inflammatory markers, suggesting possible preventive interventions to improve the immunologic and cardiovascular health of depression-prone individuals.

A Significant Positive Association of Vitamin D Deficiency with Coronary Artery Calcification among Middle-aged Men: For the ERA JUMP Study.

OBJECTIVE: Although a significant positive association of vitamin D deficiency with coronary heart disease has been demonstrated in cross-sectional as well as prospective studies, only a few studies have examined the association of vitamin D deficiency with subclinical atherosclerosis. We examined whether vitamin D deficiency is associated with subclinical atherosclerosis, as measured by coronary artery calcification (CAC) in asymptomatic adults. METHODS: In a population-based cross-sectional study, 195 men aged 40 to 49 years without cardiovascular disease were randomly selected (98 Caucasian and 97 Japanese American men). Liquid chromatography-tandem mass spectrometry was utilized to measure serum vitamin D. CAC was examined by electron beam computed tomography using standardized protocols and read centrally at the University of Pittsburgh using Agatston's methods. To investigate an association between vitamin D deficiency (defined as 25-hydroxyvitamin D [25(OH)D] < 20 ng/mL) and CAC (defined as Agatston score ≥ 10), we utilized multivariable logistic regression models. RESULTS: Prevalence of CAC and vitamin D deficiency was 27.2% and 10.3%, respectively. Participants with CAC were significantly older, had significantly higher body mass index (BMI), and had higher rates of smoking. Those with CAC were 3.31 times likely to be vitamin D deficient, after adjusting for traditional cardiovascular risk factors (odds ratio [OR] = 3.31, 95% confidence interval [CI], 1.12-9.77). CONCLUSIONS: In this population-based study of healthy middle-aged men, vitamin D deficiency had a significant positive association with the presence of CAC.

Comparison of HOMA-IR, HOMA-ß% and disposition index between US white men and Japanese men in Japan: the ERA JUMP study.

AIMS/HYPOTHESIS: At the same level of BMI, white people have less visceral adipose tissue (VAT) and are less susceptible to developing type 2 diabetes than Japanese people. No previous population-based studies have compared insulin resistance and insulin secretion between these two races in a standardised manner that accounts for VAT. We compared HOMA-IR, HOMA of beta cell function (HOMA-ß%) and disposition index (DI) in US white men and Japanese men in Japan. METHODS: We conducted a population-based, cross-sectional study, comprising 298 white men and 294 Japanese men aged 40-49 years without diabetes. Insulin, glucose, VAT and other measurements were performed at the University of Pittsburgh. We used ANCOVA to compare geometric means of HOMA-IR, HOMA-ß% and DI, adjusting for VAT and other covariates. RESULTS: White men had higher HOMA-IR, HOMA-ß% and DI than Japanese men, and the difference remained significant (p < 0.01) after adjusting for VAT (geometric mean [95% CI]): 3.1 (2.9, 3.2) vs 2.5 (2.4, 2.6), 130.8 (124.6, 137.3) vs 86.7 (82.5, 91.0), and 42.4 (41.0, 44.0) vs 34.8 (33.6, 36.0), respectively. Moreover, HOMA-IR, HOMA-ß% and DI were significantly higher in white men even after further adjustment for BMI, impaired fasting glucose and other risk factors. CONCLUSIONS/INTERPRETATION: The higher VAT-adjusted DI in white men than Japanese men may partly explain lower susceptibility of white people than Japanese people to developing type 2 diabetes. The results, however, should be interpreted with caution because the assessment of insulin indices was made using fasting samples and adjustment was not made for baseline glucose tolerance. Further studies using formal methods to evaluate insulin indices are warranted.

The association between maternal antioxidant levels in midpregnancy and preeclampsia.

OBJECTIVE: We sought to determine whether midpregnancy antioxidant levels are associated with preeclampsia, overall and by timing of onset. STUDY DESIGN: We carried out a case-control study, nested within a cohort of 5337 pregnant women in Montreal, Quebec, Canada. Blood samples obtained at 24-26 weeks were assayed for nonenzymatic antioxidant levels among cases of preeclampsia (n = 111) and unaffected controls (n = 441). We excluded women diagnosed with gestational hypertension only. We used logistic regression with the z-score of each antioxidant level as the main predictor variable for preeclampsia risk. We further stratified early-onset (<34 weeks) and late-onset preeclampsia and carried out multinomial logistic regression. Finally, we assessed associations between antioxidant biomarkers and timing of onset (in weeks) by Cox regression, with appropriate selection weights. We summed levels of correlated biomarkers (r(2) > 0.3) and log-transformed positively skewed distributions. We adjusted for body mass index, nulliparity, preexisting diabetes, hypertension, smoking, and proxies for ethnicity and socioeconomic status. RESULTS: The odds ratios for α-tocopherol, α-tocopherol:cholesterol, lycopene, lutein, and carotenoids (sum of α-carotene, ß-carotene, anhydrolutein, α-cryptoxanthin, and ß-cryptoxanthin) suggested an inverse association between antioxidant levels and overall preeclampsia risk; however, only lutein was significantly associated with overall preeclampsia in adjusted models (odds ratio, 0.60; 95% confidence interval, 0.46-0.77) per SD. In multinomial logistic models, the relative risk ratio (RRR) estimates for the early-onset subgroup were farther from the null than those for the late-onset subgroup. The ratio of α-tocopherol to cholesterol and retinol were significantly associated with early- but not late-onset preeclampsia: RRRs (95% confidence intervals) for early-onset preeclampsia 0.67 (0.46-0.99) and 1.61 (1.12-2.33), respectively. Lutein was significantly associated with both early- and late-onset subtypes in adjusted models; RRRs 0.53 (0.35-0.80) and 0.62 (0.47-0.82), respectively. Survival analyses confirmed these trends. CONCLUSION: Most antioxidants were more strongly associated with early-onset preeclampsia, suggesting that oxidative stress may play a greater role in the pathophysiology of early-onset preeclampsia. Alternatively, reverse causality may explain this pattern. Lutein was associated with both early- and late-onset preeclampsia and may be a promising nutrient to consider in preeclampsia prevention trials, if this finding is corroborated.

Maternal mid-pregnancy lipids and birthweight.

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 (< 25 kg/m(2) ) or overweight/obese (≥ 25 kg/m(2) ) pre-pregnancy BMI. MAIN OUTCOME MEASURES: Sex- and gestational-age-specific body weight z-score (BWz). RESULTS: Regression models examined associations among lipids (low: 1st quartile, referent: middle quartiles, high: 4th quartile) and BWz for the total sample and stratified by pre-pregnancy BMI. In adjusted analyses (n = 1207), low HDLc was associated with lower BWz (ß = -0.23, 95% CI -0.40 to -0.06), whereas high triglycerides were associated with higher BWz (ß = 0.23, 95% CI 0.06-0.41). Once stratified by pre-pregnancy BMI, low total cholesterol was associated with lower BWz in normal BMI women (ß = -0.25, 95% CI -0.47 to -0.03), whereas in overweight/obese BMI women, high HDLc was inversely (ß = -0.29, 95% CI -0.54 to -0.04) and high triglycerides were directly associated with BWz (ß = 0.32, 95% CI 0.07-0.54). Removing women with gestational diabetes/hypertensive disorders did not alter the results. CONCLUSIONS: The associations between maternal lipids and BWz vary by lipid measure and pre-pregnancy BMI. Future work should examine whether lipids and pre-pregnancy BMI make unique contributions to the fetal programming of disease.

Nonesterified fatty acids and spontaneous preterm birth: a factor analysis for identification of risk patterns.

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 (<37 weeks) and 222 women with births occurring at ≥37 weeks. C-reactive protein, total cholesterol, low-density lipoprotein and high-density lipoprotein (HDL) cholesterol, triglycerides, and uric acid were also measured. Polytomous logistic regression models were used to evaluate tertiles of NEFA levels and sPTB at <34 weeks and 34-36 weeks; factor analysis was used to characterize patterns of biomarkers. Women with NEFA levels in the highest tertile versus the lowest were 2.02 (95% confidence interval: 1.13, 3.48) times more likely to have sPTB, after adjustment for covariates. Risk of sPTB before 34 weeks was particularly high among women with high NEFA levels (odds ratio = 3.73, 95% confidence interval: 1.33, 10.44). Six biomarker patterns were identified, and 2 were associated with sPTB: 1) increasing NEFA and HDL cholesterol levels and 2) family history of gestational hypertension. NEFA levels early in pregnancy were independently associated with sPTB, particularly before 34 weeks. We also detected a novel risk pattern suggesting that NEFAs together with HDL cholesterol may be related to sPTB.

Regional pulse wave velocities and their cardiovascular risk factors among healthy middle-aged men: a cross-sectional population-based study.

BACKGROUND: Both carotid-femoral (cf) pulse wave velocity (PWV) and brachial-ankle (ba) PWV employ arterial sites that are not consistent with the path of blood flow. Few previous studies have reported the differential characteristics between cfPWV and baPWV by simultaneously comparing these with measures of pure central (aorta) and peripheral (leg) arterial stiffness, i.e., heart-femoral (hf) PWV and femoral-ankle (fa) PWV in healthy populations. We aimed to identify the degree to which these commonly used measures of cfPWV and baPWV correlate with hfPWV and faPWV, respectively, and to evaluate whether both cfPWV and baPWV are consistent with either hfPWV or faPWV in their associations with cardiovascular (CV) risk factors. METHODS: A population-based sample of healthy 784 men aged 40-49 (202 white Americans, 68 African Americans, 202 Japanese-Americans, and 282 Koreans) was examined in this cross-sectional study. Four regional PWVs were simultaneously measured by an automated tonometry/plethysmography system. RESULTS: cfPWV correlated strongly with hfPWV (r = .81, P < .001), but weakly with faPWV (r = .12, P = .001). baPWV correlated moderately with both hfPWV (r = .47, P < .001) and faPWV (r = .62, P < .001). After stepwise regression analyses with adjustments for race, cfPWV shared common significant correlates with both hfPWV and faPWV: systolic blood pressure (BP) and body mass index (BMI). However, BMI was positively associated with hfPWV and cfPWV, and negatively associated with faPWV. baPWV shared common significant correlates with hfPWV: age and systolic BP. baPWV also shared the following correlates with faPWV: systolic BP, triglycerides, and current smoking. CONCLUSIONS: Among healthy men aged 40 - 49, cfPWV correlated strongly with central PWV, and baPWV correlated with both central and peripheral PWVs. Of the CV risk factors, systolic BP was uniformly associated with all the regional PWVs. In the associations with factors other than systolic BP, cfPWV was consistent with central PWV, while baPWV was consistent with both central and peripheral PWVs.

Atherosclerotic renal artery stenosis as a cause for hypertension in an adolescent patient.

BACKGROUND: Atherosclerosis causing renal artery stenosis (RAS) is one of the most common secondary causes of hypertension in adults, but is rare in children. CASE-DIAGNOSIS/TREATMENT: RAS associated with coronary artery stenosis was diagnosed in a teenage patient who presented with intermittent chest pain and elevated blood pressures for 6 years. The diagnosis of RAS was suspected after physical examination revealed an abdominal bruit. Renal ultrasound with Doppler revealed normal appearing kidneys with high velocity in the aorta and renal arteries. Computed tomography angiography (CTA) of the chest and abdomen demonstrated generalized calcified atherosclerotic narrowing of the arteries including the renal, celiac, superior mesenteric and coronary arteries in the setting of hyperlipidemia. The lipid panel revealed hypercholesterolemia with elevated serum plant sterol concentrations, suggesting the diagnosis of sitosterolemia. Cardiac catheterization demonstrated left anterior descending artery and left circumflex artery stenosis, which required bypass of the left anterior descending artery and stenting of the left circumflex artery. Aggressive lipid control was recommended and he was treated medically with a beta-blocker, low-dose angiotensin-converting enzyme inhibitor, aspirin, statin, and clopidogrel. CONCLUSION: Although very rare, generalized atherosclerosis caused by genetic disorders should be considered an underlying cause for severe hypertension in children with hyperlipidemia.

Associations between arterial stiffness and platelet activation in normotensive overweight and obese young adults.

Obese individuals have elevated platelet activation and arterial stiffness, but the strength and temporality of the relationship between these factors remain unclear. We aimed to determine the effect of increased arterial stiffness on circulating platelet activity in overweight/obese young adults. This analysis included 92 participants (mean age 40 years, 60 women) in the Slow Adverse Vascular Effects of excess weight (SAVE) trial, a clinical trial examining the effects of a lifestyle intervention with or without sodium restriction on vascular health in normotensive overweight/obese young adults. Carotid-femoral (cf), brachial-ankle (ba) and femoral-ankle (fa) pulse wave velocity (PWV) served as measures of arterial stiffness and were measured at baseline and 6, 12 and 24 months follow-up. Platelet activity was measured as plasma ß-thromboglobulin (ß-TG) at 24 months. Higher plasma ß-TG was correlated with greater exposure to elevated cfPWV (p = 0.02) and baPWV (p = 0.04) during the preceding two years. After adjustment for serum leptin, greater exposure to elevated baPWV remained significant (p = 0.03) and exposure to elevated cfPWV marginally significant (p = 0.054) in predicting greater plasma ß-TG. Greater arterial stiffness, particularly central arterial stiffness, predicts greater platelet activation in overweight/obese individuals. This relationship might partly explain the association between increased arterial stiffness and incident atherothrombotic events.

Serum fatty acids and incidence of ischemic stroke among postmenopausal women.

BACKGROUND AND PURPOSE: Although studies have linked types of fatty acids with coronary heart disease, data on individual fatty acids and risk of ischemic stroke are limited. We aimed to examine the associations between serum fatty acid concentrations and incidence of ischemic stroke and its subtypes. METHODS: We conducted a prospective case-control study nested in the Women's Health Initiative Observational Study cohort of postmenopausal US women aged 50 to 79 years. Between 1993 and 2003, incident cases of ischemic stroke were matched 1:1 to controls on age, race, and length of follow-up (964 matched pairs). Conditional logistic regression was used to estimate odds ratios and 99.9% confidence intervals (CI) for ischemic stroke and its subtypes. RESULTS: The multivariable-adjusted odds ratios and 99.9% CI of ischemic stroke associated with a 1-SD increment in serum fatty acid concentration were 1.38 (99.9% CI, 1.05-1.83) for linoelaidic acid (18:2tt, SD=0.04%), 1.27 (99.9% CI, 1.06-1.51) for palmitic acid (16:0, SD=2.74%), 1.20 (99.9% CI, 1.01-1.43) for oleic acid (18:1n9, SD=2.32%), 0.72 (99.9% CI, 0.59-0.87) for docosapentaenoic acid (22:5n3, SD=0.18%), 0.72 (99.9% CI, 0.59-0.87) for docosahexaenoic acid (22:6n3, SD=0.91%), and 0.81 (99.9% CI, 0.67-0.98) for arachidonic acid (20:4n6, SD=2.02%). These associations were generally consistent for atherothrombotic and lacunar stroke but not cardioembolic stroke. CONCLUSIONS: These findings suggest that individual serum trans, saturated, and monounsaturated fatty acids are positively associated with particular ischemic stroke subtypes, whereas individual n3 and n6 polyunsaturated fatty acids are inversely associated.

Maternal lipids and small for gestational age birth at term.

OBJECTIVE: To compare maternal lipid and lipoprotein concentrations between small for gestational age (SGA) infants and infants with normal growth born at term. STUDY DESIGN: This was a case-control study nested within a large (n = 5337) prospective multicenter cohort of pregnant women followed to delivery. SGA cases (n = 323) were all term infants with birth weight below the 10th percentile for their gestational age and sex. Controls (n = 671) were selected at random from term infants with birth weight between the 25th and 75th percentiles. Plasma samples obtained at 24-26 weeks were analyzed for lipoproteins using a recently developed nuclear magnetic resonance-based procedure that distinguishes high-density lipoprotein (HDL) and low-density lipoprotein particles of different sizes. Apolipoprotein A-1 and C-II levels were analyzed using turbidimetric methods. RESULTS: Compared with controls, mothers of SGA cases had significantly higher mean concentrations of total HDL particles, medium and small HDL particles, and apolipoprotein A-1, with evidence of a dose-response relationship across quartiles of the control distribution. aORs for the highest quartiles were 2.8 (95% CI, 1.7-4.5) for total HDL particles and 3.1 (95% CI, 1.9-5.0) for apolipoprotein A-1. CONCLUSION: Our results suggest that the higher HDL particle and apolipoprotein A-1 concentrations in mothers of SGA cases may reflect defective placental transport of HDL, which could compromise cholesterol uptake by the developing fetus.

Mid-pregnancy maternal leptin levels, birthweight for gestational age and preterm delivery.

OBJECTIVE: Maternal blood leptin levels are positively associated with adiposity. Recent studies suggest that leptin is also abundantly produced by the placenta and may function as a regulator of foetal growth. Our goal was to examine mid-pregnancy levels of leptin in maternal blood in relation to birthweight for gestational age (BW/GA) and timing of delivery after accounting for maternal prepregnancy body mass index (prepreg-BMI) and pregnancy complications. PATIENTS: Data were from 1304 subcohort mother/infant pairs who participated in the Pregnancy Outcomes and Community Health (POUCH) Study (1998-2004). MEASUREMENTS: Leptin levels, measured at 16-27 weeks' gestation, were log-transformed. Geometric mean (GMean) leptin levels were estimated by weighted linear regression with gestational age at blood draw as a covariate. GMean was re-transformed to the original scale for reporting. RESULTS: Using the GMeans leptin in mothers of term appropriate-for-gestational age (AGA) neonates as the referent (25·2 µg/l), we observed lower levels in mothers of preterm-AGA (21·9 µg/l), term small-for-gestational age (SGA) (20·3 µg/l) and preterm-SGA neonates (21·7 µg/l). Results were largely unchanged after adjustment for prepreg-BMI. Leptin levels were higher in mothers who delivered large-for-gestational age (LGA) neonates, both preterm (33·6 µg/l) and term (29·1 µg/l), but the GMeans were markedly attenuated after adjustment for prepreg-BMI. CONCLUSION: The association between BW/GA and maternal leptin levels after adjustment for prepreg-BMI may represent: (i) a residual effect of maternal adiposity that is not fully captured by BMI; and/or (ii) variation in placental leptin levels entering the maternal circulation. In conclusion, mid-pregnancy maternal blood leptin levels may be an early indicator of foetal growth status.

Erythrocyte omega-6 and omega-3 fatty acids and mammographic breast density.

Diets low in omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and high in omega-3 (n-3) PUFAs may protect against breast cancer development. Associations of PUFA intake with mammographic density, an intermediate marker of breast cancer risk, have been inconsistent; however, prior studies have relied on self-reported dietary PUFA intake. We examined the association between circulating erythrocyte n-6 and n-3 PUFAs with mammographic density in 248 postmenopausal women who were not taking exogenous hormones. PUFAs in erythrocytes were measured by gas-liquid chromatography, and mammographic density was assessed quantitatively by planimetry. Spearman's correlation coefficients and generalized linear models were used to evaluate the relationships between PUFA measures and mammographic density. None of the erythrocyte n-6 or n-3 PUFA measures were associated with percent density or dense breast area.

Weight loss is more important than the diet type in improving adiponectin levels among overweight/obese adults.

OBJECTIVE: 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. DESIGN: This study is an ancillary study to a randomized clinical trial. SUBJECTS: Subjects included 143 overweight/obese adults (STD-D = 79; LOV-D = 64). INTERVENTION: 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. MEASURES: Weight, dietary intake with the 3-day food diary, and total and HMW adiponectin levels were measured. RESULTS: 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%; ps < 0.05) with no significant differences between the groups. We found significant associations between weight loss and increases in total (ß (SE) = -.071(.27); p = 0.003) and HMW adiponectin (ß (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 (p < 0.05). CONCLUSION: 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.

Pre-pregnancy obesity and maternal nutritional biomarker status during pregnancy: a factor analysis.

OBJECTIVE: Pre-pregnancy obesity has been associated with adverse birth outcomes. Poor essential fatty acid (EFA) and micronutrient status during pregnancy may contribute to these associations. We assessed the associations between pre-pregnancy BMI and nutritional patterns of maternal micronutrient and EFA status during mid-pregnancy. DESIGN: A cross-sectional analysis from a prospective cohort study. Women provided non-fasting blood samples at ≥ 20 weeks' gestation that were assayed for red cell EFA; plasma folate, homocysteine and ascorbic acid; and serum retinol, 25-hydroxyvitamin D, a-tocopherol, soluble transferrin receptors and carotenoids. These nutritional biomarkers were employed in a factor analysis and three patterns were derived: EFA, Micronutrients and Carotenoids. SETTING: The Antidepressant Use During Pregnancy Study, Pittsburgh, PA, USA. SUBJECTS: Pregnant women (n 129). RESULTS: After adjustment for parity, race/ethnicity and age, obese pregnant women were 3.0 (95% CI 1.1, 7.7) times more likely to be in the lowest tertile of the EFA pattern and 4.5 (95% CI 1.7, 12.3) times more likely to be in the lowest tertile of the Carotenoid pattern compared with their lean counterparts. We found no association between pre-pregnancy obesity and the Micronutrient pattern after confounder adjustment. CONCLUSIONS: Our results suggest that obese pregnant women have diminished EFA and carotenoid concentrations.

Circulating plasma phospholipid fatty acid levels as a biomarker of habitual dietary fat intake: The INTERMAP/INTERLIPID Study.

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.

Significant inverse associations of serum n-6 fatty acids with plasma plasminogen activator inhibitor-1.

Epidemiological studies suggested that n-6 fatty acids, especially linoleic acid (LA), have beneficial effects on CHD, whereas some in vitro studies have suggested that n-6 fatty acids, specifically arachidonic acid (AA), may have harmful effects. We examined the association of serum n-6 fatty acids with plasminogen activator inhibitor-1 (PAI-1). A population-based cross-sectional study recruited 926 randomly selected men aged 40-49 years without CVD during 2002-2006 (310 Caucasian, 313 Japanese and 303 Japanese-American men). Plasma PAI-1 was analysed in free form, both active and latent. Serum fatty acids were measured with gas-capillary liquid chromatography. To examine the association between total n-6 fatty acids (including LA and AA) and PAI-1, multivariate regression models were used. After adjusting for confounders, total n-6 fatty acids, LA and AA, were inversely and significantly associated with PAI-1 levels. These associations were consistent across three populations. Among 915 middle-aged men, serum n-6 fatty acids had significant inverse associations with PAI-1.

Maternal lipids at mid-pregnancy and the risk of preterm delivery.

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: <10(th) percentile, Referent: 10(th) -<70(th) percentile, High: ≥70(th) percentile), quartiles of TG (Referent: first quartile) and delivery outcome (Referent: term). RESULTS: Odds of medically indicated preterm delivery were increased among women with low TC (adjusted odds ratio (aOR)=2.04, 95% confidence interval (CI): 1.12, 3.72), low HDLc (aOR=1.89, 95%CI: 1.04, 3.42) or low LDLc (aOR=1.96, 95%CI: 1.09, 3.54). Odds of spontaneous preterm delivery were increased among women with high TC (aOR=1.51, 95%CI: 1.06, 2.15), high LDLc (aOR=1.42, 95%CI: 0.99, 2.04) or high TG (aOR=1.90, 95%CI: 1.21, 2.97 and aOR=1.72, 95%CI: 1.06, 2.78 for third and fourth quartiles, respectively). CONCLUSIONS: Extremely low TC, HDLc, and LDLc were associated with a modest increase in risk of medically indicated preterm delivery, whereas high TC, LDLc and TG modestly increased the risk of spontaneous preterm delivery. Further research is needed to uncover explanations for these associations and to identify optimal ranges for maternal lipids.

An exploratory factor analysis of nutritional biomarkers associated with major depression in pregnancy.

OBJECTIVE: Major 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. DESIGN: Prospective cohort study. SETTING: Pittsburgh, Pennsylvania, USA. SUBJECTS: Women 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. RESULTS: Three 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. CONCLUSIONS: While 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.

Fatty acid composition in the mature milk of Bolivian forager-horticulturalists: controlled comparisons with a US sample.

Breast milk fatty acid (FA) composition varies greatly among individual women, including in percentages of the long-chain polyunsaturated FAs (LCPUFA) 20:4n-6 (arachidonic acid, AA) and 22:6n-3 (docosahexaenoic acid, DHA), which are important for infant neurological development. It has been suggested that owing to wide variation in milk LCPUFA and low DHA in Western diets, standards of milk FA composition should be derived from populations consuming traditional diets. We collected breast milk samples from Tsimane women at varying lactational stages (6-82 weeks). The Tsimane are an indigenous, natural fertility, subsistence-level population living in Amazonia Bolivia. Tsimane samples were matched by lactational stage to samples from a US milk bank, and analysed concurrently for FA composition by gas-liquid chromatography. We compared milk FA composition between Tsimane (n = 35) and US (n = 35) mothers, focusing on differences in LCPUFA percentages that may be due to population-typical dietary patterns. Per total FAs, the percentages of AA, DHA, total n-3 and total n-6 LCPUFA were significantly higher among Tsimane mothers. Mean percentages of 18:2n-6 (linoleic acid) and trans FAs were significantly higher among US mothers. Tsimane mothers' higher milk n-3 and n-6 LCPUFA percentages may be due to their regular consumption of wild game and freshwater fish, as well as comparatively lower intakes of processed foods and oils that may interfere with LCPUFA synthesis.