Differential effect by chronic disease risk: A secondary analysis of the ChooseWell 365 randomized controlled trial.

Objective: Whether employees' health status is associated with the effectiveness of workplace health promotion programs is unknown. The objective of this study was to determine if the effect of a workplace healthy eating intervention differed by baseline chronic disease status. Methods: This was a secondary analysis of a randomized controlled trial conducted September 2016 to February 2018 among US hospital employees to test the effect of a 12-month behavioral intervention (personalized feedback, peer comparisons, and financial incentives) on diet and weight. Participants were classified as having chronic disease (yes/no) based on self-reported hypertension, hyperlipidemia, heart disease, stroke, pre-diabetes, diabetes, cancer or another serious illness. BMI was measured at study visits and calories purchased were measured from cafeteria sales data over 24 months. Mixed models with random effects assessed heterogeneity of treatment effects by chronic disease. Results: Participants (N = 548) were mostly female (79.7 %) and white (81.2 %); 224 (40.9 %) had chronic disease. Among those with chronic disease, intervention participants reduced caloric intake by 74.4 [22.3] kcal more than control, with a smaller difference between intervention and control (-1.9 [18.7] kcal) (three-way p-interaction = 0.02). The effect on BMI for those with chronic disease (0.47 [0.21] kg/m2) indicated weight stability among intervention participants and weight gain among controls while the effect (-0.56 [0.18] kg/m2) for those without chronic disease was the opposite (three-way p-interaction < 0.01). Conclusions: Those with chronic diseases had greater reductions in calories purchased and gained less weight. Employers with limited resources for health promotion might consider tailoring programs to employees at highest risk.

Implementation of a 2-for-1 Price Incentive for Fruits and Vegetables in a Grocery Retail Setting.

BACKGROUND AND PURPOSE: There is growing interest in expanding healthy eating interventions in the retail setting. The purpose of this study was to evaluate the implementation of a successful 2-for-1 price incentive for fruits and vegetables (F&V), including frozen and canned, that took place in partnership with a large chain grocery retailer in Maine. Intervention Approach. A randomized controlled trial (RCT) pilot study was conducted in 2015-2016, followed by a larger RCT in 2016-2017, to assess whether a supermarket double-dollar F&V incentive increased purchases of these items. EVALUATION METHODS: A convergent, parallel mixed-methods design was used to examine barriers and facilitators to implementing the interventions, using six implementation outcomes: acceptability, adoption, appropriateness, feasibility, implementation fidelity, and perceived cost. RESULTS: The intervention was deemed highly acceptable, appropriate, and feasible by shoppers, retailers, and researchers. The F&V discount had a high rate of initial adoption. There was a moderate degree of fidelity, which improved over time based on lessons learned from the pilot and applied to the subsequent RCT. Specific costs associated with implementation from the research perspective are reported. Implications for Practice, Policy, and Research. Partnerships between academic researchers and retailers can be an effective model for improving healthful purchases among shoppers. These findings are relevant for investigators, public health advocates, and retailers interested in implementing similar grocery retail-based interventions.

Early or late pregnancy loss and development of clinical cardiovascular disease risk factors: a prospective cohort study.

OBJECTIVE: To assess the association between the outcome of a woman's first pregnancy and risk of clinical cardiovascular disease risk factors. DESIGN: Prospective cohort study. SETTING AND POPULATION: Nurses' Health Study II. METHODS: Multivariable-adjusted Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between first pregnancy outcome and hypertension, type 2 diabetes, and hypercholesterolemia. MAIN OUTCOME MEASURES: Hypertension, type 2 diabetes, and hypercholesterolemia. RESULTS: Compared to women who reported a singleton live first birth, women with early spontaneous abortion (<12 weeks) had a greater rate of type 2 diabetes (HR: 1.20; 95% CI: 1.07-1.34) and hypercholesterolemia (HR: 1.06; 95% CI: 1.02-1.10), and a marginally increased rate of hypertension (HR: 1.05, 95% CI: 1.00-1.11). Late spontaneous abortion (12-19 weeks) was associated with an increased rate of type 2 diabetes (HR: 1.38; 95% CI: 1.14-1.65), hypercholesterolemia (HR: 1.11; 95% CI: 1.03-1.19), and hypertension (HR: 1.15; 95% CI: 1.05-1.25). The rates of type 2 diabetes (HR: 1.45; 95% CI: 1.13-1.87) and hypertension (HR: 1.15; 95% CI: 1.01-1.30) were higher in women who delivered stillbirth. In contrast, women whose first pregnancy ended in an induced abortion had lower rates of hypertension (HR: 0.87; 95% CI: 0.84-0.91) and type 2 diabetes (HR: 0.89; 95% CI: 0.79-0.99) than women with a singleton live birth. CONCLUSIONS: Several types of pregnancy loss were associated with an increased rate of hypertension, type 2 diabetes, and hypercholesterolemia, which may provide novel insight into the pathways through which pregnancy outcomes and CVD are linked. TWEETABLE ABSTRACT: Pregnancy loss is associated with later maternal risk of hypertension, type 2 diabetes, and hypercholesterolemia.

Alcohol consumption and the risk of incident pulmonary embolism in US women and men.

Essentials The association of moderate alcohol consumption with pulmonary embolism (PE) risk remains unclear. In three large US cohorts, we evaluated the association of alcohol consumption with PE risk. We found no evidence of an association of alcohol consumption amount or frequency with PE risk. Secondary analyses of type and heavy episodic drinking also yielded null findings. SUMMARY: Background Moderate alcohol consumption has been variably associated with hemostatic and fibrinolytic factor levels, but the association between alcohol consumption and the risk of incident pulmonary embolism (PE) remains uncertain. Objective To evaluate alcohol consumption amount and frequency in relation to PE risk. Methods Nurses' Health Study (NHS), NHS II and Health Professionals Follow-Up Study participants free of venous thromboembolism (VTE) at baseline (n = 217 442) reported alcohol consumption by type, quantity and frequency, every 2-4 years. Incident PE cases were identified by self-report and confirmed for participants without cancer. In this cohort study, we used Cox proportional hazards models to estimate multivariable-adjusted hazard ratios (HRs) for PE associated with alcohol consumption amount and, separately, frequency. Secondary analyses evaluated alcohol type and heavy episodic drinking in relation to PE risk, and amount and frequency in relation to medical record-confirmed idiopathic PE and any self-reported VTE risk. Cohort-specific analyses were pooled using random-effects meta-analysis. Results During ≥ 20 years of follow-up, we identified 1939 PE events. We found no strong evidence of an association between PE risk and alcohol consumption amount (pooled HRadj for 5.0-14.9 g day-1 vs. abstention = 0.97 [95% CI, 0.79, 1.20]) or frequency (pooled HRadj for 5-7 drinking days per week vs. abstention = 1.04 [95% CI, 0.88, 1.23]). Secondary analyses of type, heavy episodic drinking, idiopathic PE and VTE also yielded null findings. Conclusions Among three large prospective cohorts of US men and women, we found no evidence of an association between the amount or frequency of alcohol consumption and PE risk.

Reduction in physical function in women after venous thromboembolism.

Essentials The association of venous thromboembolism (VTE) with subsequent physical function remains unclear. We prospectively evaluated this relationship among women from the Nurses' Health Studies. We found a decline in physical function over four years in women with incident VTE. This decline was somewhat greater among women specifically reporting a pulmonary embolism. SUMMARY: Background Physical function is integral to healthy aging; however, limited research has examined the association of venous thromboembolism(VTE) with subsequent physical function. Objectives To prospectively evaluate the relationship between VTE and decline in physical function among 80 836 women from the Nurses' Health Study(NHS), ages 46-72 in 1992, and 84 304 women from the Nurses' Health Study II(NHS II), ages 29-48 in 1993. Methods Physical function was measured by the Medical Outcomes Short Form-36 physical function scale, administered every 4 years. We compared change in physical function for women with vs. without an incident VTE in each 4-year follow-up period using multivariable linear regression. Results We observed a decline in physical function over 4 years when comparing women with vs. those without incident VTE in both older (NHS) and younger (NHS II) women (multivariable-adjusted mean difference NHS, -6.5 points [95% CI -7.4, -5.6] per 4 years; NHS II, -3.8 [95% CI -5.6, -2.0]). This difference appeared greater among women specifically reporting a pulmonary embolism (NHS, -7.4 [95% CI -8.7, -6.1]; NHS II, -4.8 [95% CI -6.8, -2.8]), and was equivalent to 6.2 years of aging. Whereas longer-term slopes of physical function decline following a VTE were not different from the slopes of decline in women without a VTE, the absolute level of physical function of women with VTE was worse at the end of follow-up compared to women without VTE. Conclusions In this prospective cohort, incident VTE was strongly associated with an acute decline in physical function. These results suggest it may be clinically important to consider approaches to ameliorating functional deficits shortly after VTE diagnosis.

Post-traumatic stress disorder symptom duration and remission in relation to cardiovascular disease risk among a large cohort of women.

BACKGROUND: Prior studies suggest that post-traumatic stress disorder (PTSD) is associated with elevated cardiovascular disease (CVD) risk, but effects of duration and remission of PTSD symptoms have rarely been evaluated. METHOD: We examined the association of time-updated PTSD symptom severity, remission and duration with incident CVD risk (552 confirmed myocardial infarctions or strokes) over 20 years in 49 859 women in the Nurses' Health Study II. Among women who reported trauma on the Brief Trauma Questionnaire, PTSD symptoms, assessed by a screener, were classified by symptom severity and chronicity: (a) no symptoms, (b) 1-3 ongoing, (c) 4-5 ongoing, (d) 6-7 ongoing, (e) 1-3 remitted, (f) 4-7 remitted symptoms. Inverse probability weighting was used to estimate marginal structural logistic regression models, adjusting for time-varying and time-invariant confounders. RESULTS: Compared with women with no trauma exposure, women with trauma/no PTSD [odds ratio (OR) 1.30, 95% confidence interval (CI) 1.03-1.65] and women with trauma/6-7 symptoms (OR 1.69, 95% CI 1.08-2.63) had elevated risk of CVD; women with remitted symptoms did not have elevated CVD risk. Among women exposed to trauma, every 5 additional years of PTSD symptomology was associated with 9% higher CVD incidence compared with women with trauma/no PTSD. CONCLUSIONS: The findings suggest that alleviating PTSD symptoms shortly after onset may attenuate CVD risk.

Post-traumatic stress disorder and cardiometabolic disease: improving causal inference to inform practice.

Post-traumatic stress disorder (PTSD) has been declared 'a life sentence' based on evidence that the disorder leads to a host of physical health problems. Some of the strongest empirical research - in terms of methodology and findings - has shown that PTSD predicts higher risk of cardiometabolic diseases, specifically cardiovascular disease (CVD) and type 2 diabetes (T2D). Despite mounting evidence, PTSD is not currently acknowledged as a risk factor by cardiovascular or endocrinological medicine. This view is unlikely to change absent compelling evidence that PTSD causally contributes to cardiometabolic disease. This review suggests that with developments in methods for epidemiological research and the rapidly expanding knowledge of the behavioral and biological effects of PTSD the field is poised to provide more definitive answers to questions of causality. First, we discuss methods to improve causal inference using the observational data most often used in studies of PTSD and health, with particular reference to issues of temporality and confounding. Second, we consider recent work linking PTSD with specific behaviors and biological processes, and evaluate whether these may plausibly serve as mechanisms by which PTSD leads to cardiometabolic disease. Third, we evaluate how looking more comprehensively into the PTSD phenotype provides insight into whether specific aspects of PTSD phenomenology are particularly relevant to cardiometabolic disease. Finally, we discuss new areas of research that are feasible and could enhance understanding of the PTSD-cardiometabolic relationship, such as testing whether treatment of PTSD can halt or even reverse the cardiometabolic risk factors causally related to CVD and T2D.

The effect of healthy dietary consumption on executive cognitive functioning in children and adolescents: a systematic review.

A systematic review was conducted to evaluate whether healthier dietary consumption among children and adolescents impacts executive functioning. PubMed, Education Resources Information Center, PsychINFO and Thomson Reuters' Web of Science databases were searched, and studies of executive functioning among children or adolescents aged 6-18 years, which examined food quality, macronutrients and/or foods, were included. Study quality was also assessed. In all, twenty-one studies met inclusion criteria. Among the twelve studies examining food quality (n 9) or macronutrient intakes (n 4), studies examining longer-term diet (n 6) showed positive associations between healthier overall diet quality and executive functioning, whereas the studies examining the acute impact of diet (n 6) were inconsistent but suggestive of improvements in executive functioning with better food quality. Among the ten studies examining foods, overall, there was a positive association between healthier foods (e.g. whole grains, fish, fruits and/or vegetables) and executive function, whereas less-healthy snack foods, sugar-sweetened beverages and red/processed meats were inversely associated with executive functioning. Taken together, evidence suggests a positive association between healthy dietary consumption and executive functioning. Additional studies examining the effects of healthier food consumption, as well as macronutrients, on executive functioning are warranted. These studies should ideally be conducted in controlled environments and use validated cognitive tests.

Post-traumatic stress disorder symptoms and risk of hypertension over 22 years in a large cohort of younger and middle-aged women.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been linked to hypertension, but most research on PTSD and hypertension is cross-sectional, and potential mediators have not been clearly identified. Moreover, PTSD is twice as common in women as in men, but understanding of the PTSD-hypertension relationship in women is limited. We examined trauma exposure and PTSD symptoms in relation to incident hypertension over 22 years in 47 514 civilian women in the Nurses' Health Study II. METHOD: We used proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for new-onset hypertension (N = 15 837). RESULTS: PTSD symptoms assessed with a screen were modestly associated with incident hypertension in a dose-response fashion after adjusting for potential confounders. Compared to women with no trauma exposure, women with 6-7 PTSD symptoms had the highest risk of developing hypertension (HR 1.20, 95% CI 1.12-1.30), followed by women with 4-5 symptoms (HR 1.17, 95% CI 1.10-1.25), women with 1-3 symptoms (HR 1.12, 95% CI 1.06-1.18), and trauma-exposed women with no symptoms (HR 1.04, 95% CI 1.00-1.09). Findings were maintained, although attenuated, adjusting for hypertension-relevant medications, medical risk factors, and health behaviors. Higher body mass index and antidepressant use accounted for 30% and 21% of the PTSD symptom-hypertension association, respectively. CONCLUSIONS: Screening for hypertension and reducing unhealthy lifestyle factors, particularly obesity, in women with PTSD may hold promise for offsetting cardiovascular risk.

Bidirectional associations between alcohol consumption and health-related quality of life amongst young and middle-aged women.

BACKGROUND: Evidence from cross-sectional studies has suggested a positive association between moderate alcohol consumption and health-related quality of life but prospective data remain scarce. OBJECTIVES: To examine the bidirectional relationships between alcohol consumption and health-related quality of life using a longitudinal study design. METHODS: A total of 92 448 participants of the Nurses' Health Study II reported their alcohol consumption (in 1991, 1995, 1999 and 2003) and health-related quality of life (in 1993, 1997 and 2001). Using generalized estimating equations, we modelled the physical and mental component summary (PCS and MCS) scores as a function of alcohol consumption 2 years earlier (n = 88 363) and vice versa (n = 84 621). RESULTS: Greater alcohol consumption was associated with better PCS scores 2 years later in a dose-response manner up to ~1 serving daily [mean difference (ß) = 0.67 ± 0.06 PCS units, for moderate versus infrequent drinkers]. After adjustment for previous PCS, a similar but attenuated pattern was observed (ß = 0.33 ± 0.07). Moderate alcohol consumption was not related to MCS, whereas moderate-to-heavy alcohol consumption was associated with lower MCS scores (ß = -0.34 ± 0.15). Higher PCS scores were associated with greater alcohol consumption 2 years later, also after adjustment for previous alcohol consumption (ß = 0.53 ± 0.05 g day(-1) ). MCS was not associated with alcohol consumption 2 years later. CONCLUSION: Amongst young and middle-aged women, moderate alcohol intake was associated with a small improvement in physical health-related quality of life 2 years later and vice versa. Moderate alcohol consumption was not associated with mental health-related quality of life in either direction.

Do genetic risk scores for body mass index predict risk of phobic anxiety? Evidence for a shared genetic risk factor.

BACKGROUND: Obesity and anxiety are often linked but the direction of effects is not clear. METHOD: Using genetic instrumental variable (IV) analyses in 5911 female participants from the Nurses' Health Study (NHS, initiated 1976) and 3697 male participants from the Health Professional Follow-up Study (HPFS, initiated 1986), we aimed to determine whether obesity increases symptoms of phobic anxiety. As instrumental variables we used the fat mass and obesity-associated (FTO) gene, the melanocortin 4 receptor (MC4R) gene and a genetic risk score (GRS) based on 32 single nucleotide polymorphisms (SNPs) that significantly predict body mass index (BMI). 'Functional' GRSs corresponding with specific biological pathways that shape BMI (adipogenesis, appetite and cardiopulmonary) were considered. The main outcome was phobic anxiety measured by the Crown Crisp Index (CCI) in 2004 in the NHS and in 2000 in the HPFS. RESULTS: In observational analysis, a 1-unit higher BMI was associated with higher phobic anxiety symptoms [women: ß = 0.05, 95% confidence interval (CI) 0.030-0.068; men: ß = 0.04, 95% CI 0.016-0.071). IV analyses showed that BMI was associated with higher phobic anxiety symptoms in the FTO-instrumented analysis (p = 0.005) but not in the GRS-instrumented analysis (p = 0.256). Functional GRSs showed heterogeneous, non-significant effects of BMI on phobic anxiety symptoms. CONCLUSIONS: Our findings do not provide conclusive evidence in favor of the hypothesis that higher BMI leads to higher levels of phobic anxiety, but rather suggest that genes that influence obesity, in particular FTO, may have direct effects on phobic anxiety, and hence that obesity and phobic anxiety may share common genetic determinants.

Calcium supplement intake and risk of cardiovascular disease in women.

UNLABELLED: Some recent reports suggest that calcium supplement use may increase risk of cardiovascular disease. In a prospective cohort study of 74,245 women in the Nurses' Health Study with 24 years of follow-up, we found no independent associations between supplemental calcium intake and risk of incident coronary heart disease (CHD) and stroke. INTRODUCTION: Some recent reports suggest that calcium supplements may increase cardiovascular disease (CVD) risk. The objective was to examine the independent associations between calcium supplement use and risk of CVD. METHODS: We conducted a prospective cohort study of supplemental calcium use and incident CVD in 74,245 women in the Nurses' Health Study (1984-2008) free of CVD and cancer at baseline. Calcium supplement intake was assessed every 4 years. Outcomes were incident CHD (nonfatal or fatal MI) and stroke (ischemic or hemorrhagic), confirmed by medical record review. RESULTS: During 24 years of follow-up, 4,565 cardiovascular events occurred (2,709 CHD and 1,856 strokes). At baseline, women who took calcium supplements had higher levels of physical activity, smoked less, and had lower trans fat intake compared with those who did not take calcium supplements. After multivariable adjustment for age, body mass index, dietary calcium, vitamin D intake, and other CVD risk factors, the relative risk of CVD for women taking >1,000 mg/day of calcium supplements compared with none was 0.82 (95% confidence interval [CI] 0.74 to 0.92; p for trend <0.001). For women taking >1,000 mg/day of calcium supplements compared with none, the multivariable-adjusted relative risk for CHD was 0.71 (0.61 to 0.83; p for trend < 0.001) and for stroke was 1.03 (0.87 to 1.21; p for trend = 0.61). The relative risks were similar in analyses limited to non-smokers, women without hypertension, and women who had regular physical exams. CONCLUSIONS: Our findings do not support the hypothesis that calcium supplement intake increases CVD risk in women.

Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study.

BACKGROUND AND AIMS: Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study. METHODS AND RESULTS: The present work is an observational study within the PREDIMED trial. Over an average of 4.3 years of follow-up, there were 273 confirmed cases of CVD among the 7172 participants (96.3%) who completed a validated 137-item food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the Phenol-Explorer database on polyphenol content of each reported food. After multivariate adjustment, a 46% reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake (HR = 0.54; 95% confidence interval [CI] = 0.33-0.91; P-trend = 0.04). The polyphenols with the strongest inverse associations were flavanols (HR = 0.40; CI 0.23-0.72; P-trend = 0.003), lignans (HR = 0.51; CI 0.30-0.86; P-trend = 0.007), and hydroxybenzoic acids (HR = 0.47; CI 0.26-0.86; P-trend 0.02). CONCLUSION: Greater intake of polyphenols, especially from lignans, flavanols, and hydroxybenzoic acids, was associated with decreased CVD risk. Clinical trials are needed to confirm this effect and establish accurate dietary recommendations.

Fatty Acid desaturase gene variants, cardiovascular risk factors, and myocardial infarction in the costa rica study.

Genetic variation in fatty acid desaturases (FADS) has previously been linked to long-chain polyunsaturated fatty acids (PUFAs) in adipose tissue and cardiovascular risk. The goal of our study was to test associations between six common FADS polymorphisms (rs174556, rs3834458, rs174570, rs2524299, rs174589, rs174627), intermediate cardiovascular risk factors, and non-fatal myocardial infarction (MI) in a matched population based case-control study of Costa Rican adults (n = 1756). Generalized linear models and multiple conditional logistic regression models were used to assess the associations of interest. Analyses involving intermediate cardiovascular risk factors and MI were also conducted in two replication cohorts, The Nurses' Health Study (n = 1200) and The Health Professionals Follow-Up Study (n = 1295). In the Costa Rica Study, genetic variation in the FADS cluster was associated with a robust linear decrease in adipose gamma-linolenic, arachidonic, and eicosapentaenoic fatty acids, and significant or borderline significant increases in the eicosadienoic, eicosatrienoic, and dihomo-gamma-linolenic fatty acids. However, the associations with adipose tissue fatty acids did not translate into changes in inflammatory biomarkers, blood lipids, or the risk of MI in the discovery or the replication cohorts. In conclusion, fatty acid desaturase polymorphisms impact long-chain PUFA biosynthesis, but their overall effect on cardiovascular health likely involves multiple pathways and merits further investigation.

Habitual intake of dietary flavonoids and risk of Parkinson disease.

OBJECTIVE: To prospectively examine whether higher intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, and polymers) were associated with a lower risk of developing Parkinson disease (PD). METHODS: In the current analysis, we included 49,281 men in the Health Professional Follow-up Study and 80,336 women from the Nurses' Health Study. Five major sources of flavonoid-rich foods (tea, berry fruits, apples, red wine, and orange/orange juice) were also examined. Flavonoid intake was assessed using an updated food composition database and a validated food frequency questionnaire. RESULTS: We identified 805 participants (438 men and 367 women) who developed PD during 20-22 years of follow-up. In men, after adjusting for multiple confounders, participants in the highest quintile of total flavonoids had a 40%lower PD risk than those in the lowest quintile (hazard ratio [HR] = 0.60; 95% confidence interval 0.43, 0.83; p trend = 0.001). No significant relationship was observed in women (p trend = 0.62) or in pooled analyses (p trend = 0.23). In the pooled analyses for the subclasses, intakes of anthocyanins and a rich dietary source, berries, were significantly associated with a lower PD risk (HR comparing 2 extreme intake quintiles were 0.76 for anthocyanins and 0.77 for berries, respectively; p trend < 0.02 for both). CONCLUSIONS: Our findings suggest that intake of some flavonoids may reduce PD risk, particularly in men, but a protective effect of other constituents of plant foods cannot be excluded.

Genetic variation in fatty acid elongases is not associated with intermediate cardiovascular phenotypes or myocardial infarction.

BACKGROUND/OBJECTIVES: Elongases 2, 4 and 5, encoded by genes ELOVL2, ELOVL4 and ELOVL5, have a key role in the biosynthesis of very long chain polyunsaturated fatty acids (PUFAs). To date, few studies have investigated the associations between elongase polymorphisms and cardiovascular health. We investigated whether ELOVL polymorphisms are associated with adipose tissue fatty acids, serum lipids, inflammation and ultimately with nonfatal myocardial infarction (MI) in a Costa Rican population. SUBJECTS/METHODS: MI cases (n=1650) were matched to population-based controls (n=1650) on age, sex and area of residence. Generalized linear and multiple conditional logistic regression models were used to assess the associations between seven common ELOVL polymorphisms and cardiometabolic outcomes. Analyses were replicated in The Nurses' Health Study (n=1200) and The Health Professionals Follow-Up Study (n=1295). RESULTS: Variation in ELOVL2, ELOVL4 and ELOVL5 was not associated with adipose tissue fatty acids, intermediate cardiovascular risk factors or MI. In the Costa Rica study, the number of the minor allele copies at rs2294867, located in the ELOVL5 gene, was associated with an increase in total and LDL cholesterol (adjusted P-values=0.001 and <0.0001 respectively). Additionally, the number of the minor allele copies at rs761179, also located in the ELOVL5 gene, was significantly associated with an increase in total cholesterol (adjusted P-value=0.04). However, the observed associations were not replicated in independent populations. CONCLUSION: Common genetic variants in elongases are not associated with adipose tissue fatty acids, serum lipids, biomarkers of systemic inflammation, or the risk of MI.

Psoriasis and risk of nonfatal cardiovascular disease in U.S. women: a cohort study.

BACKGROUND: Psoriasis has been linked to cardiovascular comorbidities in cross-sectional studies, but evidence regarding the association between psoriasis and incident cardiovascular disease (CVD) is limited. OBJECTIVES: To make a prospective evaluation of the association between psoriasis and risk of incident nonfatal CVD. METHODS: Participants (n = 96, 008) were included from the Nurses' Health Study II, and followed for 18 years. Information on physician-diagnosed psoriasis was obtained by self-report and diagnosis was confirmed by supplementary questionnaires. We included 2463 individuals with self-reported psoriasis and a subsample of 1242 with validated psoriasis. The main outcome was incident nonfatal CVD events [nonfatal myocardial infarction (MI) and nonfatal stroke], ascertained by biennial questionnaires and confirmed. RESULTS: During 1 709 069 person-years of follow-up, 713 incident nonfatal CVD events were confirmed. Psoriasis was associated with a significantly increased multivariate-adjusted hazard ratio (HR) of nonfatal CVD, 1·55 [95% confidence interval (CI): 1·04-2·31]. HRs for nonfatal MI and stroke were 1·70 (95% CI: 1·01-2·84) and 1·45 (95% CI: 0·80-2·65), respectively. The association remained consistent in a sensitivity analysis of confirmed psoriasis (HR: 2·06, 95% CI: 1·31-3·26). For individuals with concomitant psoriatic arthritis, the risk of nonfatal CVD was even higher (HR: 3·47; 95% CI: 1·85-6·51). Women diagnosed with psoriasis at < 40 years of age or with duration of psoriasis ≥ 9 years had substantial elevations in CVD risk: HR: 3·26 (95% CI: 1·21-8·75) and 3·09 (95% CI: 1·15-8·29), respectively. CONCLUSIONS: Psoriasis is an independent predictor for nonfatal CVD among women, with particularly high risk for those with longer duration of psoriasis and concomitant psoriatic arthritis.

Exposure to alcohol, drugs and tobacco and the risk of subsequent suicidality: findings from the Mexican Adolescent Mental Health Survey.

AIMS: To examine whether the association between prevalence measures of suicidality and substance abuse/dependence among adolescents (1) is attenuated when temporal priority of exposure and outcome are taken into account, (2) extends to substance use (i.e. without disorder), (3) applies to tobacco use and dependence independent of illicit drugs and alcohol use/disorder, and (4) is confounded by comorbid mental illness. DESIGN: Discrete-time survival models were applied to retrospectively reported age of onset of first suicidal ideation, plan and attempt and age of onset of first substance use and disorder. PARTICIPANTS: 3005 adolescents aged 12-17 residing in the Mexico City Metropolitan Area in 2005. MEASUREMENTS: The World Mental Health computer-assisted adolescent version of the Composite International Diagnostic Interview was used to assess suicidal outcomes and psychiatric disorders including substance dependence/abuse. FINDINGS: Use of and dependence on tobacco is as strong a predictor of subsequent suicidality as is use of and dependence with abuse of alcohol and drugs. The association between substance use and subsequent suicidality is not fully accounted for by comorbid mental illness. CONCLUSION: Efforts to reduce the use as well as the abuse of alcohol, drugs and tobacco may help reduce the risk of subsequent suicidal behaviors among adolescents in Mexico.

Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables.

Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes.