Treatment characteristics among patients with binge-eating disorder: an electronic health records analysis.

OBJECTIVES: Treatment for adults diagnosed with binge-eating disorder (BED) includes psychotherapy and/or pharmacotherapy and aims to reduce the frequency of binge-eating episodes and disordered eating, improve metabolic-related issues and reduce weight, and address mood symptoms. Data describing real-world treatment patterns are lacking; therefore, this study aims to characterize real-world treatment patterns among patients with BED. METHODS: This retrospective study identified adult patients with BED using natural language processing of clinical notes from the Optum electronic health record database from 2009 to 2015. Treatment patterns were examined during the 12 months preceding the BED recognition date and during a follow-up period after BED recognition (1-3 years for most patients). RESULTS: Among 1042 patients, 384 were categorized as the BED cohort and 658, who met less stringent criteria, were categorized as probable BED. In the BED cohort, mean ± SD age was 45.2 ± 13.4 years and 81.8% were women (probable BED, 45.9 ± 12.8 years, 80.2%). A greater percentage of patients in the BED cohort were prescribed pharmacotherapy (70.6% [probable BED, 66.9%]) than received/discussed psychotherapy (53.1% [probable BED, 39.2%]) at baseline. In the BED cohort, 54.4% of patients were prescribed antidepressants (probable BED, 52.4%), 25.3% stimulants (probable BED, 20.1%), and 34.4% nonspecific psychotherapy (probable BED, 24.6%) at baseline, with no substantive differences observed during follow-up. Low percentages of patients in the BED cohort received/discussed cognitive behavioral therapy at baseline (12.5% [probable BED, 9.0%) or during follow-up (13.0% [probable BED, 8.8%). Among patients with ≥1 psychotherapy visit, the mean ± SD number of visits in the BED cohort was 1.2 ± 5.9 at baseline (probable BED, 1.7 ± 7.3) and 2.2 ± 7.7 during follow-up (probable BED, 2.6 ± 7.7). CONCLUSION: This cohort of patients with BED was treated more frequently with pharmacotherapy than psychotherapy. These data may help inform strategies for reducing differences between real-world treatment patterns and evidence-based recommendations.

Delayed pregnancy detection and return to fertility with extended levonorgestrel-containing oral contraceptives: A real world setting cohort study.

PURPOSE: As part of the European risk management plan of a 91-day extended levonorgestrel-containing combined oral contraceptive (COCLNG ), a study was performed to assess its safety. This analysis was conducted to examine delayed pregnancy detection and return to fertility with extended combined oral contraceptives (COC). METHODS: We conducted a retrospective cohort study in new users of 91-day COCLNG or 28-day COCLNG within a US-based healthcare claims database from 2006 to 2017. Delayed pregnancy detection during current COCLNG exposure was defined as the time between estimated pregnancy start and first prenatal care encounter. Additionally, the time between estimated pregnancy start and COCLNG discontinuation was measured. To measure return to fertility, pregnancy rates were estimated among females who discontinued treatment. 91-day COCLNG users were propensity score-matched to 28-day COCLNG users. Hazard ratio for pregnancy was calculated using Cox proportional hazards models. RESULTS: The 91-day and 28-day COCLNG users had 25 593 and 76 586 treatment episodes, respectively. The median time to pregnancy detection was 64.5 and 61.0 days (p = 0.24) in users of 91-day COCLNG and 28-day COCLNG . The median exposure time to treatment after estimated pregnancy start was 54.0 and 38.0 days (p < 0.01). In the fertility analysis, pregnancy rates were 54.82 (95% CI, 50.05-59.93) and 69.30 (95% CI, 64.98-73.82) per 1000 person-years in extended COCLNG discontinuers and 28-day COCLNG discontinuers. The adjusted hazard ratio of pregnancy was 0.77 (95% CI, 0.69-0.85). CONCLUSIONS: Small differences were observed for pregnancy rates and delayed pregnancy detection between 91-day extended COCLNG and 28-day COCLNG , which may be related to the longer days' supply of extended COCLNG . Differences in the fertility analysis may be related to unmeasured residual confounding.

Identification of pregnancies and infants within a US commercial healthcare administrative claims database.

PURPOSE: Health care insurance claims databases are becoming a more common data source for studies of medication safety during pregnancy. While pregnancies have historically been identified in such databases by pregnancy outcomes, International Classification of Diseases, 10th revision Clinical Modification (ICD-10-CM) Z3A codes denoting weeks of gestation provide more granular information on pregnancies and pregnancy periods (i.e., start and end dates). The purpose of this study was to develop a process that uses Z3A codes to identify pregnancies, pregnancy periods, and links infants within a commercial health insurance claims database. METHODS: We identified pregnancies, gestation periods, pregnancy outcomes, and linked infants within the US-based Optum Research Database between 2015 and 2020 via a series of algorithms utilizing diagnosis and procedure codes on claims. The diagnosis and procedure codes included ICD-10-CM codes, Current Procedural Terminology (CPT) codes, and Healthcare Common Procedure Coding System (HCPCS) codes. RESULTS: We identified 1 030 874 pregnancies among 841 196 women of reproductive age. Of pregnancies with livebirth outcomes, 84% were successfully linked to infants. The prevalence of pregnancy outcomes (livebirth, stillbirth, ectopic, molar, and abortion) was similar to national estimates. CONCLUSIONS: This process provides an opportunity to study drug safety and care patterns during pregnancy and may be replicated in other claims databases containing ICD-10-CM, CPT, and HCPCS codes. Work is underway to validate and refine the various algorithms.

Long-term safety of extended levonorgestrel-containing oral contraceptives in the United States.

OBJECTIVES: To compare the safety profile of Seasonique, a 91-day levonorgestrel-containing combined oral contraceptive (COCLNG), to 28-day COCLNG regarding the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE). STUDY DESIGN: A new user cohort study was conducted in a US health care database from 2006 to 2017. Each 91-day COCLNG treatment episode in females was matched to up to four 28-day COCLNG treatment episodes by propensity score. We identified VTE cases in either (1) an inpatient setting with ICD-9 and ICD-10 diagnosis codes of PE and/or DVT in the primary position, or (2) an outpatient setting with ICD-9 or ICD-10 diagnosis codes of DVT in conjunction with an anticoagulant medication dispensing or alteplase (thrombolytic) during the 30-day period following the date of DVT diagnosis. VTE was validated using medical records. We assessed the study endpoints in the two cohorts using incidence rates and Cox proportional hazards models adjusted for potential confounders. RESULTS: Of the 25,593 treatment episodes in 91-day COCLNG and 76,586 treatment episodes in 28-day COCLNG, 35 and 68 patients had VTEs, respectively, corresponding to a hazard ratio (HR) of 1.40 (95% confidence interval [CI], 0.90-2.19). The VTE algorithm had a positive predictive value of 76.4% (95% CI, 66.2%-84.8%). ATEs were recorded in 13 and 28 episodes, respectively, with a corresponding HR of 1.21 (95% CI, 0.58-2.53). CONCLUSIONS: These results do not indicate a significant difference between 91-day COCLNG and 28-day COCLNG in terms of VTE or ATE risk. IMPLICATIONS: Compared to use of 28-day COCLNG, use of 91-day extended COCLNG was not associated with a significant difference in risk of venous and arterial thromboembolism.

Suicidality risk among adults with binge-eating disorder.

OBJECTIVE: To estimate relative suicidality risk associated with binge-eating disorder (BED). METHODS: Retrospective study of patients identified as having BED (N = 1042) and a matched general population cohort (N = 10,420) from the Optum electronic health record database between January 2009 and September 2015. Patients had ≥1 outpatient encounter with a provider who recognized BED during the 12-month baseline preceding entry date. Incidence and relative risk of suicidality were assessed. RESULTS: Incidence per 1000 person-years (95% CI) of suicidal ideation and suicide attempts, respectively, was 31.1 (23.1, 41.0) and 12.7 (7.9, 19.4) in the BED cohort and 5.8 (4.7, 7.1) and 1.4 (0.9, 2.2) in the comparator cohort. Risk of suicidal ideation and suicide attempts was greater in the BED cohort (HR [95% CIs], 6.43 [4.42, 9.37]) than in the comparator cohort (HR [95% CI], 9.47 [4.99, 17.98]) during follow-up. After adjusting for psychiatric comorbidities, associations of suicidal ideation and suicide attempts with BED remained elevated in patients with BED having histories of suicidality. CONCLUSIONS: Findings suggest that history of suicidality may result in an increased risk of suicidal ideation and suicide attempts in patients with BED relative to the general population. Psychiatric comorbidity burden may explain the elevated risk of these conditions in BED.

Replacing the consumption of red meat with other major dietary protein sources and risk of type 2 diabetes mellitus: a prospective cohort study.

BACKGROUND: Greater consumption of red meat has been associated with a higher risk of type 2 diabetes mellitus (T2DM). A decreased intake of red meat and simultaneous increased intake of other high-protein foods may be associated with a lower risk of T2DM. These analyses of specific food replacements for red meat may provide more accurate dietary advice. OBJECTIVE: We examined the association between a decrease in intake of red meat accompanied by an increase in other major dietary protein sources and risk of T2DM. METHODS: We prospectively followed 27,634 males in the Health Professionals Follow-up Study, 46,023 females in the Nurses' Health Study, and 75,196 females in the Nurses' Health Study II. Diet was assessed by a validated FFQ and updated every 4 y. Cox proportional hazards models adjusted for T2DM risk factors were used to model the food replacements. We calculated HRs and 95% CIs for the T2DM risk associated with replacements of 1 daily serving of red meat with another protein source. RESULTS: During 2,113,245 person-years of follow-up, we identified 8763 incident T2DM cases from 1990 to 2013. In the pooled analyses, a decrease in total red meat intake during a 4-y period replaced with another common protein food was associated with a lower risk of T2DM in the subsequent 4-y period. The HR (95% CI) per 1 serving/d was 0.82 (0.75, 0.90) for poultry, 0.87 (0.77, 0.98) for seafood, 0.82 (0.78, 0.86) for low-fat dairy, 0.82 (0.77, 0.86) for high-fat dairy, 0.90 (0.81, 0.99) for eggs, 0.89 (0.82, 0.98) for legumes, and 0.83 (0.78, 0.89) for nuts. The associations were present for both unprocessed and processed red meat, although stronger for the replacement of processed red meat. CONCLUSIONS: Replacing red meat consumption with other protein sources was associated with a lower risk of T2DM.

Exenatide use and incidence of pancreatic and thyroid cancer: A retrospective cohort study.

A retrospective cohort study, supplemented with a nested case-control study, was performed using two administrative databases from commercial health plans in the United States to compare the incidence of pancreatic and thyroid cancer among users of exenatide versus other antidiabetic drugs (OADs). Patients with type 2 diabetes who initiated exenatide or OADs between 1 June 2005 and 30 June 2015 were included. Pancreatic and thyroid cancers were identified using chart-validated algorithms in the cohort study. Cases in the nested case-control study were chart-confirmed pancreatic or thyroid cancers, and controls were sampled using risk-set sampling. The time-fixed analyses comparing 33 629 exenatide initiators with 49 317 propensity-score-matched OAD initiators yielded hazard ratios of 0.76 (95% confidence interval [CI] 0.47-1.21) for pancreatic cancer and 1.46 (95% CI 0.98-2.19) for thyroid cancer. Results in the time-dependent analyses by cumulative duration or dose were similar. Nested case-control analyses yielded rate ratios of 0.61 (95%CI, 0.37-1.00) for pancreatic cancer and 0.89 (95% CI, 0.64-1.24) for thyroid cancer. This observational study suggested exenatide use was not associated with an increased risk of pancreatic or thyroid cancer.

Change in Alcohol Intake in Relation to Weight Change in a Cohort of US Men with 24 Years of Follow-Up.

OBJECTIVE: The aim of this study was to prospectively investigate the potential effects of alcohol by subtype on reported long-term weight change. METHODS: This study examined changes in alcohol intake (total, wine, light beer, regular beer, and liquor) and simultaneous changes in reported body weight within 4-year periods from 1986 to 2010 from US men in the Health Professionals Follow-Up Study. The study adjusted for age, changes in lifestyle and dietary covariates, and cardiovascular risk factors. RESULTS: The study included observations of 44,603 four-year periods from 14,971 men. Total alcohol, total beer, regular beer, and liquor intakes, modeled as the increase in weight per increase in drinks per day, were each directly associated with moderate weight gain over the 4-year periods, in pounds: total alcohol: 0.23 (0.10 to 0.35); total beer: 0.29 (0.08 to 0.51); regular beer: 0.61 (0.22 to 1.00); and liquor: 0.28 (0.09 to 0.48). Results for wine and light beer were as follows: wine: 0.16 (-0.04 to 0.36) and light beer: -0.38 (-1.07 to 0.08). Results were strongest for men < 55 years old. CONCLUSIONS: Increased alcohol consumption was associated with minor reported weight gain at levels unlikely to be clinically meaningful. Beverage-specific differences were not substantial enough to make dietary recommendations for weight loss or maintenance by beverage type. The greatest risk of weight gain was among men who increased consumption to levels well above moderation.

Evidence for the vitamin D hypothesis: The NHANES III extended mortality follow-up.

BACKGROUND AND AIMS: Emerging evidence suggests that low levels of vitamin D may be an important risk factor for multiple chronic diseases and mortality, but the evidence is mixed. Vitamin D levels are associated with sun exposure, diet, and metabolic status. One potential explanation for the lack of consistent findings amongst various studies is that low vitamin levels may be associated with poor diets or other risk factors that we were not adequately controlled for in different analyses. METHODS: Prospective analysis of adults over the age of 35 in NHANES III data (1988-1994) with 20 year mortality follow-up. Sequential Cox proportional hazard models quartiles of 25OH vitamin D adjusted for age, season, geography, sociodemographic (SD), CVD risk factors (CVD) and nutritional factors (NF) were performed. RESULTS: Gender, race, diabetes, anti-hypertensive meds, income, taking vitamin D supplements, physical activity, alcohol consumption, region, body mass index, blood pressure, creatinine, albumin, CRP, thyroxine, iron, RBC folate, vitamin A, E, alpha-carotene, and lycopene were all associated with different quartiles of vitamin D and as well as CHD and all-cause mortality and thus are important potential confounders of this relationship. Adjusting for the confounding factors, higher levels of vitamin D demonstrate an inverse relationship with all-cause mortality, but only the top quartile of vitamin D shows an inverse relationship with CHD mortality. CONCLUSIONS: The highest quartile compared to the lowest quartile of 25OH vitamin D levels is inversely associated with CHD and all-cause mortality adjusting for multiple confounders. Whether supplementation of individuals with low vitamin D will result in similar benefits will require a randomized clinical trial.

Origin, Methods, and Evolution of the Three Nurses' Health Studies.

We have summarized the evolution of the Nurses' Health Study (NHS), a prospective cohort study of 121 700 married registered nurses launched in 1976; NHS II, which began in 1989 and enrolled 116 430 nurses; and NHS3, which began in 2010 and has ongoing enrollment. Over 40 years, these studies have generated long-term, multidimensional data, including lifestyle- and health-related information across the life course and an extensive repository of various biological specimens. We have described the questionnaire data collection, disease follow-up methods, biorepository resources, and data management and statistical procedures. Through integrative analyses, these studies have sustained a high level of scientific productivity and substantially influenced public health recommendations. We have highlighted recent interdisciplinary research projects and discussed future directions for collaboration and innovation.

Dietary flavonoid intake and weight maintenance: three prospective cohorts of 124,086 US men and women followed for up to 24 years.

OBJECTIVE: To examine whether dietary intake of specific flavonoid subclasses (including flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, and flavonoid polymers) is associated with weight change over time. DESIGN: Three prospective cohort studies. SETTING: Health professionals in the United States. PARTICIPANTS: 124,086 men and women participating in the Health Professionals Follow-up Study (HPFS), Nurses' Health Study (NHS), and Nurses' Health Study II (NHS II). MAIN OUTCOME MEASURE: Self reported change in weight over multiple four year time intervals between 1986 and 2011. RESULTS: Increased consumption of most flavonoid subclasses, including flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers, was inversely associated with weight change over four year time intervals, after adjustment for simultaneous changes in other lifestyle factors including other aspects of diet, smoking status, and physical activity. In the pooled results, the greatest magnitude of association was observed for anthocyanins (-0.23 (95% confidence interval -0.30 to -0.15) lbs per additional standard deviation/day, 10 mg), flavonoid polymers (-0.18 (-0.28 to -0.08) lbs per additional SD/day, 138 mg), and flavonols (-0.16 (-0.26 to -0.06) lbs per additional SD/day, 7 mg). After additional adjustment for fiber intake, associations remained significant for anthocyanins, proanthocyanidins, and total flavonoid polymers but were attenuated and no longer statistically significant for other subclasses. CONCLUSIONS: Higher intake of foods rich in flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers may contribute to weight maintenance in adulthood and may help to refine dietary recommendations for the prevention of obesity and its potential consequences.

New and emerging biomarkers in cardiovascular disease.

Cardiovascular disease (CVD) is the most common cause of death and disability worldwide. Therefore, great importance has been placed on the discovery of novel risk factors and metabolic pathways relevant in the prevention and management of CVD. Such research is ongoing and may continue to lead to better risk stratification of individuals and/or the development of new intervention targets and treatment options. This review highlights emerging biomarkers related to lipid metabolism, glycemia, inflammation, and cardiac damage, some of which show promising associations with CVD risk and provide further understanding of the underlying pathophysiology. However, their measurement methodology and assays will require validation and standardization, and it will take time to accumulate evidence of their role in CVD in various population settings in order to fully assess their clinical utility. Several of the novel biomarkers represent intriguing, potentially game-changing targets for therapy.

Changes in Intake of Fruits and Vegetables and Weight Change in United States Men and Women Followed for Up to 24 Years: Analysis from Three Prospective Cohort Studies.

BACKGROUND: Current dietary guidelines recommend eating a variety of fruits and vegetables. However, based on nutrient composition, some particular fruits and vegetables may be more or less beneficial for maintaining or achieving a healthy weight. We hypothesized that greater consumption of fruits and vegetables with a higher fiber content or lower glycemic load would be more strongly associated with a healthy weight. METHODS AND FINDINGS: We examined the association between change in intake of specific fruits and vegetables and change in weight in three large, prospective cohorts of 133,468 United States men and women. From 1986 to 2010, these associations were examined within multiple 4-y time intervals, adjusting for simultaneous changes in other lifestyle factors, including other aspects of diet, smoking status, and physical activity. Results were combined using a random effects meta-analysis. Increased intake of fruits was inversely associated with 4-y weight change: total fruits -0.53 lb per daily serving (95% CI -0.61, -0.44), berries -1.11 lb (95% CI -1.45, -0.78), and apples/pears -1.24 lb (95% CI -1.62, -0.86). Increased intake of several vegetables was also inversely associated with weight change: total vegetables -0.25 lb per daily serving (95% CI -0.35, -0.14), tofu/soy -2.47 lb (95% CI, -3.09 to -1.85 lb) and cauliflower -1.37 lb (95% CI -2.27, -0.47). On the other hand, increased intake of starchy vegetables, including corn, peas, and potatoes, was associated with weight gain. Vegetables having both higher fiber and lower glycemic load were more strongly inversely associated with weight change compared with lower-fiber, higher-glycemic-load vegetables (p < 0.0001). Despite the measurement of key confounders in our analyses, the potential for residual confounding cannot be ruled out, and although our food frequency questionnaire specified portion size, the assessment of diet using any method will have measurement error. CONCLUSIONS: Increased consumption of fruits and non-starchy vegetables is inversely associated with weight change, with important differences by type suggesting that other characteristics of these foods influence the magnitude of their association with weight change.

Reproducibility of Circulating MicroRNAs in Stored Plasma Samples.

BACKGROUND: Most studies of microRNA (miRNA) and disease have examined tissue-specific expression in limited numbers of samples. The presence of circulating miRNAs in plasma samples provides the opportunity to examine prospective associations between miRNA expression and disease in initially healthy individuals. However, little data exist on the reproducibility of miRNAs in stored plasma. METHODS: We used Real-Time PCR to measure 61 pre-selected microRNA candidates in stored plasma. Coefficients of variation (CVs) were used to assess inter-assay reliability (n = 15) and within-person stability over one year (n = 80). Intraclass correlation coefficients (ICCs) and polychoric correlation coefficients were used to assess within-person stability and delayed processing reproducibility (whole blood stored at 4°C for 0, 24 and 48 hours; n = 12 samples). RESULTS: Of 61 selected miRNAs, 23 were detected in at least 50% of samples and had average CVs below 20% for inter-assay reproducibility and 31 for delayed processing reproducibility. Ten miRNAs were detected in at least 50% of samples, had average CVs below 20% and had ICCs above 0.4 for within-person stability over 1-2 years, six of which satisfied criteria for both interassay reproducibility and short-term within-person stability (miR-17-5p, -191-5p, -26a-5p, -27b-3p, -320a, and -375) and two all three types of reproducibility (miR-27b-3p and -26a-5p). However, many miRNAs with acceptable average CVs had high maximum CVs, most had low expression levels, and several had low ICCs with delayed processing. CONCLUSIONS: About a tenth of miRNAs plausibly related to chronic disease were reliably detected in stored samples of healthy adults.

A randomized controlled trial of vitamin E and selenium on rate of decline in lung function.

BACKGROUND: The intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers. METHODS: The Respiratory Ancillary Study (RAS) tested the single and joint effects of selenium (200 µg/d L-selenomethionine) and vitamin E (400 IU/day all rac-α-tocopheryl acetate) in a randomized double-blind placebo-controlled trial. At the end of the intervention, 1,641 men had repeated pulmonary function tests separated by an average of 3 years. Linear mixed-effects regression models estimated the effect of intervention on annual rate of decline in lung function. RESULTS: Compared to placebo, intervention had no main effect on either forced expiratory volume in the first second (FEV1) or forced expiratory flow (FEF25-75). There was no evidence for a smoking by treatment interaction for FEV1, but selenium attenuated rate of decline in FEF25-75 in current smokers (P = 0.0219). For current smokers randomized to selenium, annual rate of decline in FEF25-75 was similar to the annual decline experienced by never smokers randomized to placebo, with consistent effects for selenium alone and combined with vitamin E. CONCLUSIONS: Among all men, there was no effect of selenium and/or vitamin E supplementation on rate of lung function decline. However, current smokers randomized to selenium had an attenuated rate of decline in FEF25-75, a marker of airflow. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00241865 .

Novel metabolic biomarkers of cardiovascular disease.

Coronary heart disease (CHD) accounts for one in every six deaths in US individuals. Great advances have been made in identifying important risk factors for CHD, such as hypertension, diabetes mellitus, smoking and hypercholesterolaemia, which have led to major developments in therapy. In particular, statins represent one of the greatest successes in the prevention of CHD. While these standard risk factors are important, an obvious opportunity exists to take advantage of ongoing scientific research to better risk-stratify individuals and to identify new treatment targets. In this Review, we summarize ongoing scientific research in a number of metabolic molecules or features, including lipoproteins, homocysteine, calcium metabolism and glycaemic markers. We evaluate the current state of the research and the strength of evidence supporting each emerging biomarker. We also discuss whether the associations with CHD are strong and consistent enough to improve current risk stratification metrics, and whether these markers enhance our understanding of the underlying biology of CHD and thus point towards new treatment options.

ß2-microglobulin, cystatin C, and creatinine and risk of symptomatic peripheral artery disease.

BACKGROUND: ß2-Microglobulin and cystatin C may have advantages over creatinine in assessing risk associated with kidney function. We therefore investigated whether emerging filtration markers, ß2-microglobulin and cystatin C, are prospectively associated with risk of the development of peripheral artery disease (PAD). METHODS AND RESULTS: We conducted nested case-control studies among women within the Nurses' Health Study (1990-2010) and among men within the Health Professionals Follow-up Study (1994-2008) with the use of archived blood samples collected before PAD diagnosis. During follow-up, symptomatic PAD was confirmed in 144 women and 143 men. Controls were matched 3:1 based on age, race, smoking status, fasting status, and date of blood sampling. Conditional logistic regression models were used to estimate relative risks (RRs) and were adjusted for plasma creatinine and cardiovascular risk factors. In women, the RRs (95% CI) per 1-SD) increment were 1.16 (0.85 to 1.58) for ß2-microglobulin and 0.94 (0.69 to 1.28) for cystatin C. Corresponding RRs in men were 1.50 (1.08 to 2.09) for ß2-microglobulin and 1.54 (1.07 to 2.22) for cystatin C. There was no association between creatinine and PAD risk in women, whereas the association in men (RR 1.41, 95% CI 1.10 to 1.81) disappeared after adjustment for either ß2-microglobulin or cystatin C. In pooled analyses of men and women, only ß2-microglobulin was associated with PAD risk (RR 1.31, 95% CI 1.04 to 1.64). CONCLUSIONS: In pooled analyses, ß2-microglobulin was associated with an increased risk of symptomatic PAD; a similar association with cystatin C was observed only in men. The findings suggest that ß2-microglobulin may capture the atherosclerosis-promoting or atherosclerosis-related elements of kidney dysfunction better than creatinine.

Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease.

OBJECTIVE: Few studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD. METHODS: We used two cohort studies of 72,348 women in the Nurses' Health Study (NHS, 1990-2010) and 44,504 men in the Health Professionals Follow-up Study (HPFS, 1986-2010). We measured plasma homocysteine in nested matched case-control studies of clinically recognized PAD within both cohorts, including 143 PAD cases and 424 controls within the NHS (1990-2010) and 143 PAD cases and 428 controls within the HPFS (1994-2008). We examined the association between diet and risk of incident PAD in the cohorts using a food frequency questionnaire and 790 cases of PAD over 3.1 million person-years of follow-up. RESULTS: Higher homocysteine levels were positively associated with risk of PAD in men (adjusted IRR 2.17; 95% CI, 1.08-4.38 for tertile 3 vs. 1). There was no evidence of an association in women (adjusted IRR 1.14; 95% CI, 0.61-2.12). Similarly, higher folate intake, including supplements, was inversely associated with risk of PAD in men (adjusted HR 0.90; 95% CI, 0.82-0.98 for each 250 µg increase) but not women (HR 1.01, 95% CI, 0.88-1.15). Intakes of the other B vitamins, betaine, and choline were not consistently associated with risk of PAD in men or women. CONCLUSION: Homocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women.

Mediterranean and Dietary Approaches to Stop Hypertension dietary patterns and risk of sudden cardiac death in postmenopausal women.

BACKGROUND: The Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets are characterized by higher intake of fruit, vegetables, whole grains, and unsaturated fatty acids. All of these foods and nutrients may affect cholesterol, inflammation, the development of atherosclerosis, and, therefore, risk of cardiac death. OBJECTIVE: Our objective was to examine the association between the Mediterranean and DASH dietary patterns and risk of sudden cardiac death (SCD) in women. DESIGN: We used a prospective cohort of 93,122 postmenopausal women enrolled in the Women's Health Initiative study between 1993 and 1998 and followed for an average of 10.5 y. Women completed a food-frequency questionnaire (FFQ) twice during follow-up. We scored their diets according to how closely the reported diet resembled each dietary pattern. SCD was defined as death that occurred within 1 h of symptom onset. RESULTS: A higher Mediterranean diet score was associated with lower risk of SCD (HR: 0.64; 95% CI: 0.43, 0.94) when women in the highest quintile were compared with women in the lowest quintile after adjustment for age, total energy, race, income, smoking, and physical activity. After adjustment for potential mediators, the association was similar (HR: 0.67; 95% CI: 0.46, 0.99). A higher DASH diet score was not associated with risk of SCD. However, sodium intake, which is a crucial component of the DASH dietary pattern, was not well characterized by the FFQ. CONCLUSION: The Mediterranean dietary pattern may be associated with lower risk of SCD in women. This trial was registered at clinicaltrials.gov as NCT00000611.