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Assessment of Risk Factors and Biomarkers Associated With Risk of Cardiovascular Disease Among Women Consuming a Mediterranean Diet.

ABSTRACT: Importance:Higher Mediterranean diet (MED) intake has been associated with lower risk of cardiovascular disease (CVD), but limited data are available about the underlying molecular mechanisms of this inverse disease association in human populations. Objective:To better characterize the relative contribution of traditional and novel factors to the MED-related risk reduction in CVD events in a US population. Design, Setting, and Participants:Using a prospective cohort design, baseline MED intake was assessed in 25?994 initially healthy US women in the Women's Health Study who were followed up to 12 years. Potential mediating effects of a panel of 40 biomarkers were evaluated, including lipids, lipoproteins, apolipoproteins, inflammation, glucose metabolism and insulin resistance, branched-chain amino acids, small-molecule metabolites, and clinical factors. Baseline study information and samples were collected between April 30, 1993, and January 24, 1996. Analyses were conducted between August 1, 2017, and October 30, 2018. Exposures:Intake of MED is a 9-category measure of adherence to a Mediterranean dietary pattern. Participants were categorized into 3 levels based on their adherence to the MED. Main Outcomes and Measures:Incident CVD confirmed through medical records and the proportion of CVD risk reduction explained by mediators. Results:Among 25?994 women (mean [SD] age, 54.7 [7.1] years), those with low, middle, and upper MED intakes composed 39.0%, 36.2%, and 24.8% of the study population and experienced 428 (4.2%), 356 (3.8%), and 246 (3.8%) incident CVD events, respectively. Compared with the reference group who had low MED intake, CVD risk reductions were observed for the middle and upper groups, with respective HRs of 0.77 (95% CI, 0.67-0.90) and 0.72 (95% CI, 0.61-0.86) (P for trend?

SUBMITTER: Ahmad S

PROVIDER: S-EPMC6324327 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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Assessment of Risk Factors and Biomarkers Associated With Risk of Cardiovascular Disease Among Women Consuming a Mediterranean Diet.

Ahmad Shafqat S Moorthy M Vinayaga MV Demler Olga V OV Hu Frank B FB Ridker Paul M PM Chasman Daniel I DI Mora Samia S

JAMA network open 20181207 8

<h4>Importance</h4>Higher Mediterranean diet (MED) intake has been associated with lower risk of cardiovascular disease (CVD), but limited data are available about the underlying molecular mechanisms of this inverse disease association in human populations.<h4>Objective</h4>To better characterize the relative contribution of traditional and novel factors to the MED-related risk reduction in CVD events in a US population.<h4>Design, setting, and participants</h4>Using a prospective cohort design, ...[more]

PMID: 30646282

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Project description:Biotin functions as a cofactor for several carboxylase enzymes with key roles in metabolism. At present, the dietary requirement for biotin is unknown and intake recommendations are provided as Adequate Intakes (AIs). The biotin AI for adults and pregnant women is 30 ?g/d, whereas 35 ?g/d is recommended for lactating women. However, pregnant and lactating women may require more biotin to meet the demands of these reproductive states.The current study sought to quantify the impact of reproductive state on biotin status response to a known dietary intake of biotin.To achieve this aim, we measured a panel of biotin biomarkers among pregnant (gestational week 27 at study entry; n = 26), lactating (postnatal week 5 at study entry; n = 28), and control (n = 21) women who participated in a 10- to 12-wk feeding study providing 57 ?g of dietary biotin/d as part of a mixed diet.Over the course of the study, pregnant women excreted 69% more (vs. control; P < 0.001) 3-hydroxyisovaleric acid (3-HIA), a metabolite that accumulates during the catabolism of leucine when the activity of biotin-dependent methylcrotonyl-coenzyme A carboxylase is impaired. Interestingly, urinary excretion of 3-hydroxyisovaleryl-carnitine (3-HIA-carnitine), a downstream metabolite of 3-HIA, was 27% lower (P = 0.05) among pregnant (vs. control) women, a finding that may arise from carnitine inadequacy during gestation. No differences (P > 0.05) were detected in plasma biotin, urinary biotin, or urinary bisnorbiotin between pregnant and control women. Lactating women excreted 76% more (vs. control; P = 0.001) of the biotin catabolite bisnorbiotin, indicating that lactation accelerates biotin turnover and loss. Notably, with respect to control women, lactating women excreted 23% less (P = 0.04) urinary 3-HIA and 26% less (P = 0.05) urinary 3-HIA-carnitine, suggesting that lactation reduces leucine catabolism and that these metabolites may not be useful indicators of biotin status during lactation.Overall, these data demonstrate significant alterations in markers of biotin metabolism during pregnancy and lactation and suggest that biotin intakes exceeding current recommendations are needed to meet the demands of these reproductive states. This trial was registered at clinicaltrials.gov as NCT01127022.

Project description:AimsTo investigate whether metabolic signature composed of multiple plasma metabolites can be used to characterize adherence and metabolic response to the Mediterranean diet and whether such a metabolic signature is associated with cardiovascular disease (CVD) risk.Methods and resultsOur primary study cohort included 1859 participants from the Spanish PREDIMED trial, and validation cohorts included 6868 participants from the US Nurses' Health Studies I and II, and Health Professionals Follow-up Study (NHS/HPFS). Adherence to the Mediterranean diet was assessed using a validated Mediterranean Diet Adherence Screener (MEDAS), and plasma metabolome was profiled by liquid chromatography-tandem mass spectrometry. We observed substantial metabolomic variation with respect to Mediterranean diet adherence, with nearly one-third of the assayed metabolites significantly associated with MEDAS (false discovery rate < 0.05). Using elastic net regularized regressions, we identified a metabolic signature, comprised of 67 metabolites, robustly correlated with Mediterranean diet adherence in both PREDIMED and NHS/HPFS (r = 0.28-0.37 between the signature and MEDAS; P = 3 × 10-35 to 4 × 10-118). In multivariable Cox regressions, the metabolic signature showed a significant inverse association with CVD incidence after adjusting for known risk factors (PREDIMED: hazard ratio [HR] per standard deviation increment in the signature = 0.71, P < 0.001; NHS/HPFS: HR = 0.85, P = 0.001), and the association persisted after further adjustment for MEDAS scores (PREDIMED: HR = 0.73, P = 0.004; NHS/HPFS: HR = 0.85, P = 0.004). Further genome-wide association analysis revealed that the metabolic signature was significantly associated with genetic loci involved in fatty acids and amino acids metabolism. Mendelian randomization analyses showed that the genetically inferred metabolic signature was significantly associated with risk of coronary heart disease (CHD) and stroke (odds ratios per SD increment in the genetically inferred metabolic signature = 0.92 for CHD and 0.91 for stroke; P < 0.001).ConclusionsWe identified a metabolic signature that robustly reflects adherence and metabolic response to a Mediterranean diet, and predicts future CVD risk independent of traditional risk factors, in Spanish and US cohorts.

Project description:Evidence for the cardioprotective effects of a Mediterranean-style (Med-style) diet is strong, however few Med-style dietary interventions have been developed for and tested among Hispanic Americans (HAs), especially younger HAs of reproductive age whose dietary habits may strongly influence dietary intake for all family members.We adapted a previously tested and evidence-informed lifestyle intervention to reduce CVD risk and evaluated its feasibility, acceptability, and effects on self-reported lifestyle behaviors in this study enrolling low-income HA women attending a Title X family planning clinic in eastern North Carolina. The 3-month long intervention, given to all participants, promoted a Med-style dietary pattern with a focus on increasing consumption of foods commonly consumed by HA that have high quality dietary fats (polyunsaturated and monounsaturated fats primarily from plant sources and fish) and carbohydrates (fruits, vegetables, and whole grains). The intervention also recommended increasing physical activity and was given during 2 face-to-face counseling sessions and 2 telephone counseling sessions. Major outcomes were engagement with study activities and intervention acceptability; lifestyle behavior change at 3-month follow-up is also reported.Baseline characteristics (n?=?36) were: mean age 33 years, 35 (97%) without health insurance, 32 (89%) born in Mexico, and mean BMI 30?kg/m2. Engagement was high among the 36 participants with 33 (92%) completing the intervention and follow-up measures. At follow-up, most participants thought the intervention was helpful (range: 85-100%) and acceptable (100% agreed 'I would recommend the program to others'). The mean dietary fat quality score improved by 0.5 units (95% CI: 0.0-1.1) and the mean fruit-vegetable servings/day improved by 0.7/day (95% CI: 0.1-1.3).Intervention engagement and acceptability were high and there was improvement in self-reported dietary behaviors. This type of Med-style dietary pattern intervention should be evaluated in randomized trials enrolling HAs at risk for CVD.

Project description:BACKGROUND:Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in high-risk women. METHODS AND FINDINGS:We conducted a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016. We randomised inner-city pregnant women with metabolic risk factors (obesity, chronic hypertension, or hypertriglyceridaemia) to a Mediterranean-style diet with high intake of nuts, extra virgin olive oil, fruits, vegetables, nonrefined grains, and legumes; moderate to high consumption of fish; low to moderate intake of poultry and dairy products; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat versus usual care. Participants received individualised dietary advice at 18, 20, and 28 weeks' gestation. The primary endpoints were composite maternal (gestational diabetes or preeclampsia) and composite offspring (stillbirth, small for gestational age, or admission to neonatal care unit) outcomes prioritised by a Delphi survey. We used an intention-to-treat (ITT) analysis with multivariable models and identified the stratification variables and prognostic factors a priori. We screened 7,950 and randomised 1,252 women. Baseline data were available for 593 women in the intervention (93.3% follow-up, 553/593) and 612 in the control (95.6% follow-up, 585/612) groups. Over a quarter of randomised women were primigravida (330/1,205; 27%), 60% (729/1,205) were of Black or Asian ethnicity, and 69% (836/1,205) were obese. Women in the intervention arm consumed more nuts (70.1% versus 22.9%; adjusted odds ratio [aOR] 6.8, 95% confidence interval [CI] 4.3-10.6, p ? 0.001) and extra virgin olive oil (93.2% versus 49.0%; aOR 32.2, 95% CI 16.0-64.6, p ? 0.001) than controls; increased their intake of fish (p < 0.001), white meat (p < 0.001), and pulses (p = 0.05); and reduced their intake of red meat (p < 0.001), butter, margarine, and cream (p < 0.001). There was no significant reduction in the composite maternal (22.8% versus 28.6%; aOR 0.76, 95% CI 0.56-1.03, p = 0.08) or composite offspring (17.3% versus 20.9%; aOR 0.79, 95% CI 0.58-1.08, p = 0.14) outcomes. There was an apparent reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47-0.91, p = 0.01) but not in other individual components of the composite outcomes. Mothers gained less gestational weight (mean 6.8 versus 8.3 kg; adjusted difference -1.2 Kg, 95% CI -2.2 to -0.2, p = 0.03) with intervention versus control. There was no difference in any of the other maternal and offspring complications between both groups. When we pooled findings from the Effect of Simple, Targeted Diet in Pregnant Women With Metabolic Risk Factors on Pregnancy Outcomes (ESTEEM) trial with similar trials using random effects meta-analysis, we observed a significant reduction in gestational diabetes (odds ratio [OR] 0.67, 95% CI 0.53-0.84, I2 = 0%), with no heterogeneity (2 trials, 2,397 women). The study's limitations include the use of participant reported tools for adherence to the intervention instead of objective biomarkers. CONCLUSIONS:A simple, individualised, Mediterranean-style diet in pregnancy did not reduce the overall risk of adverse maternal and offspring complications but has the potential to reduce gestational weight gain and the risk of gestational diabetes. TRIAL REGISTRATION:ClinicalTrials.gov NCT02218931.

Project description:IntroductionGreater adherence to a Mediterranean diet is linked to lower risk for cardiovascular morbidity/mortality in studies of Mediterranean cohorts, older subjects, and/or those with existing health conditions. No studies have examined the effects of this dietary pattern in younger working populations in the United States. We investigated the effects of Mediterranean diet adherence on cardiovascular disease (CVD) biomarkers, metabolic syndrome and body composition in an occupationally active, non-Mediterranean cohort.MethodsA cross-sectional study in a cohort of 780 career male firefighters, ages 18 years or older, from the United States Midwest. No dietary intervention was performed. A modified Mediterranean diet score (mMDS) was developed for assessment of adherence to a Mediterranean dietary pattern from a previously administered life-style questionnaire that examined pre-existing dietary habits. Clinical data from fire department medical examinations were extracted and analyzed.ResultsObese subjects had significantly lower mMDS, and they reported greater fast/take-out food consumption (p<0.001) and intake of sweetened drinks during meals (p = 0.002). After multivariate adjustment, higher mMDS was inversely related to risk of weight gain over the past 5 years (odds ratio [OR]: 0.57, 95% confidence interval [CI]: 0.39-0.84, p for trend across score quartiles: 0.01); as well as the presence of metabolic syndrome components (OR: 0.65, 95% CI: 0.44-0.94, p for trend across score quartiles: 0.04). Higher HDL-cholesterol (p = 0.008) and lower LDL-cholesterol (p = 0.04) were observed in those with higher mMDS in linear regression after multivariate adjustment for age, BMI and physical activity.ConclusionsIn a cohort of young and active US adults, greater adherence to a Mediterranean-style dietary pattern had significant inverse associations with metabolic syndrome, LDL-cholesterol and reported weight gain, and was significantly and independently associated with higher HDL-cholesterol. Our results support the potential effectiveness of this diet in young, non-Mediterranean working cohorts, and justify future intervention studies.

Dataset Information

Assessment of Risk Factors and Biomarkers Associated With Risk of Cardiovascular Disease Among Women Consuming a Mediterranean Diet.

Publications

Assessment of Risk Factors and Biomarkers Associated With Risk of Cardiovascular Disease Among Women Consuming a Mediterranean Diet.

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