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Abstract Background The interaction between modelers and policymakers is becoming more common due to the increase in computing speed seen in recent decades. The recent pandemic caused by the SARS-CoV-2 virus was no exception. Thus, this study aims to identify and assess epidemiological mathematical models of SARS-CoV-2 applied to real-world data, including immunization for coronavirus 2019 (COVID-19). Methodology PubMed, JSTOR, medRxiv, LILACS, EconLit, and other databases were searched for studies employing epidemiological mathematical models of SARS-CoV-2 applied to real-world data. We summarized the information qualitatively, and each article included was assessed for bias risk using the Joanna Briggs Institute (JBI) and PROBAST checklist tool. The PROSPERO registration number is CRD42022344542. Findings In total, 5646 articles were retrieved, of which 411 were included. Most of the information was published in 2021. The countries with the highest number of studies were the United States, Canada, China, and the United Kingdom; no studies were found in low-income countries. The SEIR model (susceptible, exposed, infectious, and recovered) was the most frequently used approach, followed by agent-based modeling. Moreover, the most commonly used software were R, Matlab, and Python, with the most recurring health outcomes being death and recovery. According to the JBI assessment, 61.4% of articles were considered to have a low risk of bias. Interpretation The utilization of mathematical models increased following the onset of the SARS-CoV-2 pandemic. Stakeholders have begun to incorporate these analytical tools more extensively into public policy, enabling the construction of various scenarios for public health. This contribution adds value to informed decision-making. Therefore, understanding their advancements, strengths, and limitations is essential.

In 2019, the EAT-Lancet Commission proposed a Planetary Health Diet (PHD) to address challenges toward sustainable and healthy diets. However, its suitability within the Dutch context and a comparison with the Dutch Dietary Guidelines (DDG) needs investigation. Our study aimed to compare the PHD with DDG in terms of food groups, servings, nutritional content, and adequacy in adults. We modeled two theoretical diets, the PHD (PHD-NL) and another based on the DDG (DDG-NL), using the Dutch National Food Consumption Survey (FCS-2016) and Dutch Food Composition Database to calculate the nutritional content and compared it with the Dutch Dietary Reference Values (DRVs). The PHD included higher quantities of vegetables, fish, legumes, and nuts, while the DDG suggested more significant amounts of cereals, tubers, starchy vegetables, dairy, and red meat. We observed differences in macronutrient distribution; while both diets lacked sufficient vitamin D, calcium content was lower in the PHD-NL. The PHD-NL had higher levels of fiber, vegetable protein, unsaturated fats, and non-heme iron, while vitamins B2, B6, B12, and calcium were lower than the DDG-NL diet. The PHD-NL has nutritional adequacy in the Dutch context, except for vitamin D and calcium, although it is essential to be cautious with iron because of the bioavailability of non-heme iron in plant-based diets. These findings have implications for the adoption of a sustainable diet according to nutritional requirements, population health status, and sociocultural context, as well as compliance with specific dietary behaviors of populations.

Abstract Aims Prior research, largely focused on US male veterans, indicates an increased risk of cardiovascular disease among individuals with post-traumatic stress disorder (PTSD). Data from other settings and populations are scarce. The objective of this study is to examine PTSD as a risk factor for incident major adverse cardiovascular events (MACEs) in South Africa. Methods We analysed reimbursement claims (2011–2020) of a cohort of South African medical insurance scheme beneficiaries aged 18 years or older. We calculated adjusted hazard ratios (aHRs) for associations between PTSD and MACEs using Cox proportional hazard models and calculated the effect of PTSD on MACEs using longitudinal targeted maximum likelihood estimation. Results We followed 1,009,113 beneficiaries over a median of 3.0 years (IQR 1.1–6.0). During follow-up, 12,662 (1.3%) persons were diagnosed with PTSD and 39,255 (3.9%) had a MACE. After adjustment for sex, HIV status, age, population group, substance use disorders, psychotic disorders, major depressive disorder, sleep disorders and the use of antipsychotic medication, PTSD was associated with a 16% increase in the risk of MACEs (aHR 1.16, 95% confidence interval (CI) 1.05–1.28). The risk ratio for the effect of PTSD on MACEs decreased from 1.59 (95% CI 1.49–1.68) after 1 year of follow-up to 1.14 (95% CI 1.11–1.16) after 8 years of follow-up. Conclusion Our study provides empirical support for an increased risk of MACEs in males and females with PTSD from a general population sample in South Africa. These findings highlight the importance of monitoring cardiovascular risk among individuals diagnosed with PTSD.

Abstract Introduction The diagnosis of cardiac contusion, caused by blunt chest trauma, remains a challenge due to the non-specific symptoms it causes and the lack of ideal tests to diagnose myocardial damage. A cardiac contusion can be life-threatening if not diagnosed and treated promptly. Several diagnostic tests have been used to evaluate the risk of cardiac complications, but the challenge of identifying patients with contusions nevertheless remains. Aim of the study To evaluate the accuracy of diagnostic tests for detecting blunt cardiac injury (BCI) and its complications, in patients with severe chest injuries, who are assessed in an emergency department or by any front-line emergency physician. Methods A targeted search strategy was performed using Ovid MEDLINE and Embase databases from 1993 up to October 2022. Data on at least one of the following diagnostic tests: electrocardiogram (ECG), serum creatinine phosphokinase-MB level (CPK-MB), echocardiography (Echo), Cardiac troponin I (cTnI) or Cardiac troponin T (cTnT). Diagnostic tests for cardiac contusion were evaluated for their accuracy in meta-analysis. Heterogeneity was assessed using the I 2 and the QUADAS-2 tool was used to assess bias of the studies. Results This systematic review yielded 51 studies (n = 5,359). The weighted mean incidence of myocardial injuries after sustaining a blunt force trauma stood at 18.3% of cases. Overall weighted mean mortality among patients with blunt cardiac injury was 7.6% (1.4–36.4%). Initial ECG, cTnI, cTnT and transthoracic echocardiography TTE all showed high specificity (> 80%), but lower sensitivity (

Abstract Introduction Tobacco use is a major health concern worldwide, especially in low/middle-income countries. We aimed to assess the prevalence of cigarette smoking, waterpipe, and pipe use in Tehran, Iran. Methods We used data from 8272 participants of the Tehran Cohort Study recruitment phase. Tobacco use was defined as a positive answer to using cigarettes, waterpipes, or pipes. Participants who did not report tobacco use during the interview but had a previous smoking history were categorized as former users. Age- and sex-weighted prevalence rates were calculated based on the national census data, and characteristics of current and former tobacco users were analyzed. Results Age- and sex-weighted prevalence of current tobacco users, cigarette smokers, waterpipe, and pipe users in Tehran was 19.8%, 14.9%, 6.1%, and 0.5%, respectively. Current tobacco use was higher in younger individuals (35–45 years: 23.4% vs. ≥ 75 years: 10.4%, P 12 years: 19.3% vs. illiterate: 9.7%, P

Background Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways. Methods To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses. Results Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology. Conclusions Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries.

Abstract Several raw-data processing software for accelerometer-measured physical activity (PA) exist, but whether results agree has not been assessed. We examined the agreement between three different software for raw accelerometer data, and associated their results with cardiovascular risk. A cross-sectional analysis conducted between 2014 and 2017 in 2693 adults (53.4% female, 45–86 years) living in Lausanne, Switzerland was used. Participants wore the wrist-worn GENEActive accelerometer for 14 days. Data was processed with the GENEActiv manufacturer software, the Pampro package in Python and the GGIR package in R. For the latter, two sets of thresholds “White” and “MRC” defining levels of PA and two versions (1.5–9 and 1.11–1) for the “MRC” threshold were used. Cardiovascular risk was assessed using the SCORE risk score. Time spent (mins/day) in stationary, light, moderate and vigorous PA ranged from 633 (GGIR-MRC) to 1147 (Pampro); 93 (GGIR-White) to 196 (GGIR-MRC); 19 (GGIR-White) to 161 (GENEActiv) and 1 (GENEActiv) to 26 (Pampro), respectively. Spearman correlations between results ranged between 0.317 and 0.995, while concordance coefficients ranged between 0.035 and 0.968. With some exceptions, the line of perfect agreement was not in the 95% confidence interval of the Bland–Altman plots. Compliance to PA guidelines varied considerably: 99.8%, 98.7%, 76.3%, 72.6% and 50.2% for Pampro, GENEActiv, GGIR-MRC v.1.11–1, GGIR-MRC v.1.4–9 and GGIR-White, respectively. Cardiovascular risk decreased with increasing time spent in PA across most software packages. We found large differences in PA estimation between software and thresholds used, which makes comparability between studies challenging.

Abstract Background The prevalence of type 2 diabetes mellitus has increased in the past decades. We investigated the prevalence of diabetes and its awareness, treatment, and control among adult residents of Tehran. Methods We used the recruitment phase data of the Tehran Cohort study, enrolling a random sample of adult residents of Tehran aged ≥35 years. Diabetes was defined as self-report, current use of glucose-lowering medications, and/or fasting plasma glucose (FPG) ≥126mg/dl. Impaired fasting glucose (IFG) was defined as an FPG of 100-125mg/dl. Awareness was defined as diabetes self-report, treatment as receiving glucose-lowering medications, and glycemic control as FPG

Objectives: To identify the validated and reliable indicators and tools to assess good governance for population health, wellbeing, and equity in urban settings, and assess processes of multisectoral action and civic engagement as reported by peer-reviewed articles.Methods: We conducted a systematic review searching six databases for observational studies reporting strategies of either urban health, multisectoral action or civic engagement for wellbeing, health, or equity.Results: Out of 8,154 studies initially identified we included 17. From the included studies, 14 presented information about high-income countries. The general population was the main target in most studies. Multisectoral action was the most frequently reported strategy (14 studies). Three studies used Urban Health Equity Assessment and Response Tool (Urban HEART). Health indicators were the most frequently represented (6 studies). Barriers and facilitators for the implementation of participatory health governance strategies were reported in 12 studies.Conclusion: Data on the implementation of participatory health governance strategies has been mainly reported in high-income countries. Updated and reliable data, measured repeatedly, is needed to closely monitor these processes and further develop indicators to assess their impact on population health, wellbeing, and equity.

Abstract Background Creatinine is the most widely used test to estimate the glomerular filtration rate (GFR), but muscle mass as key determinant of creatinine next to renal function may confound such estimates. We explored effects of 24‐h height‐indexed creatinine excretion rate (CER index) on GFR estimated with creatinine (eGFRCr), muscle mass‐independent cystatin C (eGFRCys), and the combination of creatinine and cystatin C (eGFRCr‐Cys) and predicted probabilities of discordant classification given age, sex, and CER index. Methods We included 8076 adults enrolled in the PREVEND study. Discordant classification was defined as not having eGFRCr

Abstract Background Both genetic background and diet are important determinants of cardiovascular diseases (CVD). Understanding gene-diet interactions could help improve CVD prevention and prognosis. We aimed to summarise the evidence on gene-diet interactions and CVD outcomes systematically. Methods We searched MEDLINE® via Ovid, Embase, PubMed®, and The Cochrane Library for relevant studies published until June 6th 2022. We considered for inclusion cross-sectional, case–control, prospective cohort, nested case–control, and case-cohort studies as well as randomised controlled trials that evaluated the interaction between genetic variants and/or genetic risk scores and food or diet intake on the risk of related outcomes, including myocardial infarction, coronary heart disease (CHD), stroke and CVD as a composite outcome. The PROSPERO protocol registration code is CRD42019147031. Results and discussion We included 59 articles based on data from 29 studies; six articles involved multiple studies, and seven did not report details of their source population. The median sample size of the articles was 2562 participants. Of the 59 articles, 21 (35.6%) were qualified as high quality, while the rest were intermediate or poor. Eleven (18.6%) articles adjusted for multiple comparisons, four (7.0%) attempted to replicate the findings, 18 (30.5%) were based on Han-Chinese ethnicity, and 29 (49.2%) did not present Minor Allele Frequency. Fifty different dietary exposures and 52 different genetic factors were investigated, with alcohol intake and ADH1C variants being the most examined. Of 266 investigated diet-gene interaction tests, 50 (18.8%) were statistically significant, including CETP-TaqIB and ADH1C variants, which interacted with alcohol intake on CHD risk. However, interactions effects were significant only in some articles and did not agree on the direction of effects. Moreover, most of the studies that reported significant interactions lacked replication. Overall, the evidence on gene-diet interactions on CVD is limited, and lack correction for multiple testing, replication and sample size consideration.

Dietary phytochemical intake associations with cardiovascular health and mortality remain unknown. We studied the relations between total dietary phytochemical intake and cardiovascular health outcomes in a middle-aged Swiss population. We analyzed data spanning 2009 to 2021 from a prospective cohort study in Lausanne, Switzerland, including 3721 participants (54.8% women, 57.2 ± 10.3 years) without cardiovascular disease (CVD) history. Dietary intake was assessed using a validated self-reported food frequency questionnaire. The Dietary Phytochemical Index (DPI) and the healthy Dietary Phytochemical Index (hDPI) were calculated as the total energy intake percentage obtained from phytochemical-rich food consumption. The Healthy Plant-Based Diet Index (hPBD) was estimated by scoring healthy plant foods positively and less-healthy plant foods negatively. Indices tertiles and cardiometabolic outcome associations were determined using Cox proportional hazard models. Over 30,217 person-years of follow-up, 262 CVD events, and 178 deaths occurred. Unadjusted analyses found 36%, 33%, and 32% lower CVD risk for the highest hDPI, DPI, and hPBD tertiles, respectively. After adjustment, only the second hDPI tertile showed a 30% lower CVD risk (HR 0.70, 95% CI 0.51–0.95; P for trend 0.362). No other associations emerged. In this middle-aged Swiss cohort, no associations between dietary indices reflecting a phytochemical-rich dietary pattern and incident CVD, all-cause, or CVD mortality were observed.

Summary: Background: Healthy ageing (HA) has been defined using multiple approaches. We aim to produce a comprehensive overview and analysis of the theoretical models underpinning this concept and its associated normative terms and definitions. Methods: We conducted a systematic review of peer-reviewed HA models in Embase.com, Medline (Ovid), Cochrane CENTRAL, CINAHL, PsycINFO, and Web of Science until August 2022. Original theoretical papers, concept analyses, and reviews that proposed new models were included. Operational models/definitions, development psychology theories and mechanisms of ageing were excluded. We followed an iterative approach to extract the models’ characteristics and thematically analyze them based on the approach of Walker and Avant. The protocol was registered in PROSPERO (CRD42021238796). Findings: Out of 10,741 records, we included 59 papers comprising 65 models/definitions, published in English (1960–2022) from 16 countries in Europe, Asia, and America. Human ageing was described using 12 normative terms, mainly (models (%)): successful (34 (52%)), healthy (eight (12%)), well (five (8%)), and active (four (6%)). We identified intrinsic/extrinsic factors interacting throughout the life course, adaptive processes as attributes, and outcomes describing ageing patterns across objective and subjective dimensions (number of models/definitions): cognitive (62), psychological (53), physical (49), social (49), environmental (19), spiritual (16), economic (13), cultural (eight), political (six), and demographic (four) dimensions. Three types of models emerged: health-state outcomes (three), adaptations across the life course (31), or a combination of both (31). Two additional sub-classifications emphasized person-environment congruence and health promotion. Interpretation: HA conceptualizations highlight its multidimensionality and complexity that renders a monistic model/definition challenging. It has become evident that life long person-environment interactions, adaptations, environments, and health promotion/empowerment are essential for HA. Our model classification provides a basis for harmonizing terms and dimensions that can guide research and comparisons of empirical findings, and inform social and health policies enabling HA for various populations and contexts. Funding: MM, ZMRD, and OI are supported by the European Union’s Horizon 2020 Marie Skłodowska-Curie grant No 801076, and MM is also supported by the Swiss National Foundation grant No 189235.

Abstract Background Atrial fibrillation (AF) is a common arrhythmia classified as paroxysmal and non-paroxysmal. Non-paroxysmal AF is associated with an increased risk of complications. Diabetes contributes to AF initiation, yet its role in AF maintenance is unclear. We conducted a systematic review and meta-analysis to summarize the evidence regarding the association of diabetes with AF types. Methods We searched 5 databases for observational studies investigating the association of diabetes with the likelihood of an AF type (vs another type) in humans. Study quality was evaluated using the Newcastle–Ottawa Scale. Studies classifying AF types as paroxysmal (reference) and non-paroxysmal were pooled in a meta-analysis using random effects models. Results Of 1997 articles we identified, 20 were included in our systematic review. The population sample size ranged from 64 to 9816 participants with mean age ranging from 40 to 75 years and percentage of women from 24.8 to 100%. The quality of studies varied from poor (60%) to fair (5%) to good (35%). In the systematic review, 8 studies among patients with AF investigated the cross-sectional association of diabetes with non-paroxysmal AF (vs paroxysmal) of which 6 showed a positive association and 2 showed no association. Fourteen studies investigated the longitudinal association of diabetes with “more sustained” AF types (vs “less sustained”) of which 2 showed a positive association and 12 showed no association. In the meta-analysis of cross-sectional studies, patients with AF and diabetes were 1.31-times more likely to have non-paroxysmal AF than those without diabetes [8 studies; pooled OR (95% CI), 1.31 (1.13–1.51), I2 = 82.6%]. The meta-analysis of longitudinal studies showed that for patients with paroxysmal AF, diabetes is associated with 1.32-times increased likelihood of progression to non-paroxysmal AF [five studies; pooled OR (95% CI), 1.32 (1.07–1.62); I2 = 0%]. Conclusions Our findings suggest that diabetes is associated with an increased likelihood of non-paroxysmal AF rather than paroxysmal AF. However, further high quality studies are needed to replicate these findings, adjust for potential confounders, elucidate mechanisms linking diabetes to non-paroxysmal AF, and assess the impact of antidiabetic medications on AF types. These strategies could eventually help decrease the risk of non-paroxysmal AF among patients with diabetes.

BackgroundTailored recommendations for patients after percutaneous coronary interventions (PCI) need physical activity (PA) to be objectively measured and assessed for adherence to guidelines. The recent WHO guidelines removed the daily recommended bout duration, while the potential impact of this change on patients after PCI remains unclear.AimWe evaluated prevalence estimates of adherence to PA recommendations among patients after PCI across the 2010 [≥30 min moderate- to vigorous-intensity PA (MVPA) at ≥ 10-min bout duration] and 2020 WHO guidelines (≥30 min of MVPA of any bout duration), as well as 7,500 and 10,000 steps.MethodsWe conducted an observational longitudinal single-center study with patients after PCI for chronic or acute coronary syndrome (ACS); maximal age 80 years. Wrist-worn accelerometers recorded participants’ PA data from the evening of hospital discharge over the next 18 days.ResultsWe analyzed data from 282 participants with sufficient minimum wear time (7 days of ≥12 h), including 45 (16%) women; and 249 (88%) with ACS. Median wear time was 18 (17, 18) days. Median participant age was 62 (55, 69) years. Fifty-two participants (18.4%) fulfilled 2010 WHO guidelines and 226 (80.1%) fulfilled the 2020 WHO guidelines. Further, 209 (74.1%) participants achieved ≥7,500 steps/day and 155 (55.0%) performed ≥10,000 steps/day.ConclusionAmong participants after PCI, most MVPA was accumulated in bouts

IntroductionCurrent guidelines recommend wearable activity trackers to detect insufficient physical activity (PA) and help increase PA to prevent or ameliorate cardiovascular disease. However, there is a paucity of data regarding how objectively measured PA trajectories, patterns, and sedentary time, are associated with mortality and recurrent events after percutaneous coronary intervention (PCI) in patients with established coronary artery disease (CAD). Additionally, it remains unclear if early PA and sedentary time after PCI are associated with such outcomes. Therefore, in the present study (ClinicalTrials.gov Identifier: NCT04663373), we aim to establish the associations of objectively measured PA with major adverse cardiac events and mortality at one-year follow-up.Methods and analysisIn this single-centre observational study, patients with CAD will be prospectively recruited immediately after PCI. All the information from the clinical history, baseline characteristics, and outcomes during follow-up will be obtained from the CARDIOBASE registry. Accelerometer data will be collected for 18 days following hospital discharge and 14 days at one-year follow-up. PA trajectories will be identified by group-based trajectory modeling. Major adverse cardiac events and mortality will be prospectively monitored up to 1 year after PCI. All data will be collected using Research Electronic Data Capture.

Background Hyperphosphatemia has been associated with coronary artery calcification (CAC) mostly in chronic kidney disease, but the association between phosphate levels within the normal phosphate range and CAC is unclear. Our objectives were to evaluate associations between phosphate levels and CAC among men and women from the general population and assess causality through Mendelian randomization. Methods and Results CAC, measured by electron‐beam computed tomography, and serum phosphate levels were assessed in 1889 individuals from the RS (Rotterdam Study). Phenotypic associations were tested through linear models adjusted for age, body mass index, blood pressure, smoking, prevalent cardiovascular disease and diabetes, 25‐hydroxyvitamin D, total calcium, C‐reactive protein, glucose, and total cholesterol : high‐density lipoprotein cholesterol ratio. Mendelian randomization was implemented through an allele score including 8 phosphate‐related single‐nucleotide polymorphisms. In phenotypic analyses, serum phosphate (per 1 SD) was associated with CAC with evidence for sex interaction (Pinteraction=0.003) (men β, 0.44 [95% CI, 0.30–0.59]; P=3×10−9; n=878; women β, 0.24 [95% CI, 0.08–0.40]; P=0.003; n=1011). Exclusion of hyperphosphatemia, chronic kidney disease (estimated glomerular filtration rate

Background: Chagas disease (CD) is a neglected tropical disease, endemic in Latin America, but due to migration and environmental changes it has become a global public health issue. Objectives: To assess the global prevalence and disability-adjusted life years due to CD using findings from the Global Burden of Disease Study 2019. Methods: The Global Burden of Disease data was obtained from the Global Burden of Disease Collaborative Network; results were provided by the Institute for Health Metrics and Evaluation. The prevalence and disability-adjusted life-years (DALYs) were described at a global, regional, and national level, including data from 1990 to 2019. Results: Globally, CD prevalence decreased by 11.3% during the study period, from 7,292,889 cases estimated in 1990 to 6,469,283 in 2019. Moreover, the global DALY rate of CD decreased by 23.7% during the evaluated period, from 360,872 in 1990 to 275,377 in 2019. In addition, significant differences in the burden by sex, being men the most affected, age, with the elderly having the highest burden of the disease, and sociodemographic index (SDI), with countries with the lowest SDI values having the highest prevalence of the disease, were observed. Finally, the prevalence trends have followed different patterns according to the region, with a sustained decrease in Latin America, compared to an increasing trend in North America and Europe until 2010. Conclusion: The global burden of CD has changed in recent decades, with a sustained decline in the number of cases. Although the majority of cases remain concentrated in Latin America, the increase observed in countries in North America and Europe highlights the importance of screening at-risk populations and raising awareness of this neglected tropical disease.

Background: High levels of blood pressure (BP) remain undetected and poorly controlled in large segments of the population leading to an enormous burden in terms of disease and mortality. Objective: We aimed to assess the prevalence, awareness, treatment, and control of hypertension in Tehran. Methods: We used the data of 8,296 adults aged ≥35 years from the Tehran Cohort Study who were enrolled between May 2016 and February 2019. Hypertension was defined as systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg, self-report, and/or current antihypertensive medication use. The age- and sex-weighted prevalence of hypertension and high normal BP was calculated using the 2016 national census. Furthermore, awareness, treatment, and control of hypertension were analyzed. Results: The mean age of the participants was 53.8 ±12.75 years, and 54.0% were women. The weighted prevalence of hypertension and high normal BP were 36.5% and 12.2%, respectively. Among hypertensive individuals, 68.2% were aware of hypertension, 53.3% were receiving medication, and 40.4% had adequate BP control. The awareness, treatment, and control of hypertension were significantly higher in women (72.2% vs. 63.4% [P < 0.001], 55.1% vs 51.1% [P = 0.020], and 42.7% vs. 37.7% [P = 0.004], respectively) and this gap considerably increased with advancing age. Hypertension was more prevalent in northern Tehran but with a better treatment rate and control in the same regions. Conclusion: Despite the high prevalence of hypertension in the adult population of Tehran, the rates of awareness, treatment, and control of hypertension are unsatisfactory and demand comprehensive strategies to improve this situation, especially in younger men.

Background: Based on current evidence, it is not clear whether lone hypertension increases the risk for severe illness from COVID-19, or if increased risk is mainly associated with age, obesity and diabetes. The objective of the study was to evaluate whether lone hypertension is associated with increase mortality or a more severe course of COVID-19, and if treatment and control of hypertension mitigates this risk. Methods: This is a prospective multi-center observational cohort study with 30-day outcomes of 9,531 consecutive SARS-CoV-2 PCR-positive patients ≥ 18 years old (41.9 ± 9.7 years, 49.2% male), Uzbekistan, June 1-September 30, 2020. Patients were subclassified according to JNC8 criteria into six blood pressure stages. Univariable and multiple logistic regression was conducted to examine how variables predict outcomes. Results: The 30-days all-cause mortality was 1.18% (n = 112) in the whole cohort. After adjusting for age, sex, history of myocardial infarction (MI), type-2 diabetes, and obesity, none of six JNC8 groups showed any significant difference in all-cause mortality. However, age was associated with an increased risk of 30-days all-cause mortality (OR = 1.09, 95%CI [1.07–1.12], p < 0.001), obesity (OR = 7.18, 95% CI [4.18–12.44], p < 0.001), diabetes (OR 4.18, 95% CI [2.58–6.76], p < 0.001), and history of MI (OR = 2.68, 95% CI [1.67–4.31], p < 0.001). In the sensitivity test, being ≥ 65 years old increased mortality 10.56-fold (95% CI [5.89–18.92], p < 0.001). Hospital admission was 12.4% (n = 1,183), ICU admission 1.38% (n = 132). The odds of hospitalization increased having stage-2 untreated hypertension (OR = 4.51, 95%CI [3.21–6.32], p < 0.001), stage-1 untreated hypertension (OR = 1.97, 95%CI [1.52–2.56], p < 0.001), and elevated blood pressure (OR = 1.82, 95% CI [1.42–2.34], p < 0.001). Neither stage-1 nor stage-2 treated hypertension patients were at statistically significant increased risk for hospitalization after adjusting for confounders. Presenting with stage-2 untreated hypertension increased the odds of ICU admission (OR = 3.05, 95 %CI [1.57–5.93], p = 0.001). Conclusions: Lone hypertension did not increase COVID-19 mortality or in treated patients risk of hospitalization.

Abstract Background Since the placenta also has a sex, fetal sex–specific differences in the occurrence of placenta-mediated complications could exist. Objective To determine the association of fetal sex with multiple maternal pregnancy complications. Search strategy Six electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Web-of-Science, PubMed, and Google Scholar were systematically searched to identify eligible studies. Reference lists of the included studies and contact with experts were also used for identification of studies. Selection criteria Observational studies that assessed fetal sex and the presence of maternal pregnancy complications within singleton pregnancies. Data collection and analyses Data were extracted by 2 independent reviewers using a predesigned data collection form. Main results From 6522 original references, 74 studies were selected, including over 12,5 million women. Male fetal sex was associated with term pre-eclampsia (pooled OR 1.07 [95%CI 1.06 to 1.09]) and gestational diabetes (pooled OR 1.04 [1.02 to 1.07]). All other pregnancy complications (i.e., gestational hypertension, total pre-eclampsia, eclampsia, placental abruption, and post-partum hemorrhage) tended to be associated with male fetal sex, except for preterm pre-eclampsia, which was more associated with female fetal sex. Overall quality of the included studies was good. Between-study heterogeneity was high due to differences in study population and outcome definition. Conclusion This meta-analysis suggests that the occurrence of pregnancy complications differ according to fetal sex with a higher cardiovascular and metabolic load for the mother in the presence of a male fetus. Funding None.

Background Diabetes is a major risk factor for atrial fibrillation (AF). However, it remains unclear whether individual AF phenotype and related comorbidities differ between patients who have AF with and without diabetes. This study investigated the association of diabetes with AF phenotype and cardiac and neurological comorbidities in patients with documented AF. Methods and Results Participants in the multicenter Swiss‐AF (Swiss Atrial Fibrillation) study with data on diabetes and AF phenotype were eligible. Primary outcomes were parameters of AF phenotype, including AF type, AF symptoms, and quality of life (assessed by the European Quality of Life‐5 Dimensions Questionnaire [EQ‐5D]). Secondary outcomes were cardiac (ie, history of hypertension, myocardial infarction, and heart failure) and neurological (ie, history of stroke and cognitive impairment) comorbidities. The cross‐sectional association of diabetes with these outcomes was assessed using logistic and linear regression, adjusted for age, sex, and cardiovascular risk factors. We included 2411 patients with AF (27.4% women; median age, 73.6 years). Diabetes was not associated with nonparoxysmal AF (odds ratio [OR], 1.01; 95% CI, 0.81–1.27). Patients with diabetes less often perceived AF symptoms (OR, 0.74; 95% CI, 0.59–0.92) but had worse quality of life (β=−4.54; 95% CI, −6.40 to −2.68) than those without diabetes. Patients with diabetes were more likely to have cardiac (hypertension [OR, 3.04; 95% CI, 2.19–4.22], myocardial infarction [OR, 1.55; 95% CI, 1.18–2.03], heart failure [OR, 1.99; 95% CI, 1.57–2.51]) and neurological (stroke [OR, 1.39, 95% CI, 1.03–1.87], cognitive impairment [OR, 1.75, 95% CI, 1.39–2.21]) comorbidities. Conclusions Patients who have AF with diabetes less often perceive AF symptoms but have worse quality of life and more cardiac and neurological comorbidities than those without diabetes. This raises the question of whether patients with diabetes should be systematically screened for silent AF. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02105844.

Objectives: Global environmental challenges demand sustainable behaviours and policies to protect human and planetary health. We aimed to summarize the evidence about the factors related to Sustainable Food Consumption (SFC) behaviours of university students, and to propose an operational categorization of SFC behaviours.Methods: Seven databases were searched for observational studies evaluating Sustainable Food Consumption (SFC) among university students and that reported at least one behavioural outcome measure. Qualitative synthesis was conducted, and PRISMA guidelines for reporting were followed.Results: Out of 4,479 unique references identified, 40 studies were selected. All studies examined personal factors, while 11 out of 40 also measured social or situational factors. Except for food waste, females had higher levels of SFC behaviours, but situational factors moderated this association. Knowledge and attitudes showed mixed results. Overall, sustainable food consumers reported healthier lifestyles.Conclusions: Healthy lifestyle of sustainable food consumers suggests possible synergies between human health and sustainability in terms of motivations for food choice. Moderation effects of social and situational factors on personal factors reveal opportunities to design and examine the effects of choice architecture interventions.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

Our understanding of the functional link between differential DNA methylation and type 2 diabetes and obesity remains limited. Here the authors present a blood-based EWAS of fasting glucose and insulin among 4808 non-diabetic Europeans and identify nine CpGs not previously implicated in glucose, insulin homeostasis and diabetes.

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n = 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL—C), triglycerides (TG), diastolic, and systolic blood pressure (BP). Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P

Abstract New gridded climate datasets (GCDs) on spatially resolved modeled weather data have recently been released to explore the impacts of climate change. GCDs have been suggested as potential alternatives to weather station data in epidemiological assessments on health impacts of temperature and climate change. These can be particularly useful for assessment in regions that have remained understudied due to limited or low quality weather station data. However to date, no study has critically evaluated the application of GCDs of variable spatial resolution in temperature‐mortality assessments across regions of different orography, climate, and size. Here we explored the performance of population‐weighted daily mean temperature data from the global ERA5 reanalysis dataset in the 10 regions in the United Kingdom and the 26 cantons in Switzerland, combined with two local high‐resolution GCDs (HadUK‐grid UKPOC‐9 and MeteoSwiss‐grid‐product, respectively) and compared these to weather station data and unweighted homologous series. We applied quasi‐Poisson time series regression with distributed lag nonlinear models to obtain the GCD‐ and region‐specific temperature‐mortality associations and calculated the corresponding cold‐ and heat‐related excess mortality. Although the five exposure datasets yielded different average area‐level temperature estimates, these deviations did not result in substantial variations in the temperature‐mortality association or impacts. Moreover, local population‐weighted GCDs showed better overall performance, suggesting that they could be excellent alternatives to help advance knowledge on climate change impacts in remote regions with large climate and population distribution variability, which has remained largely unexplored in present literature due to the lack of reliable exposure data.

Sarcopenia is a heterogeneous skeletal muscle disorder involving the loss of muscle mass and function. However, the prevalence of sarcopenia based on the most recent definition remains to be determined in older people with chronic airway diseases. The aim was to evaluate sarcopenia prevalence and association with chronic airway diseases and its lung function in an older population, using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. We performed a cross-sectional analysis in 5082 participants (mean age 69.0±8.8 years, 56% females) from the Rotterdam Study. Participants with interpretable spirometry and an available assessment of sarcopenia were included. The appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS) were assessed using dual-energy X-ray absorptiometry (DXA) and a hydraulic hand dynamometer, respectively. We analysed the association between sarcopenia and chronic airway diseases by using regression models adjusted for age, sex, smoking status, total fat percentage and other relevant confounders. Participants with chronic airway diseases had higher prevalence of probable sarcopenia (12.0%, 95% CI 10.2–13.8) and confirmed sarcopenia (3.0%, 95% CI 2.1–3.9) than without. Chronic airway diseases were associated with “probable sarcopenia” (OR 1.28, 95% CI 1.02–1.60), “confirmed sarcopenia” (OR 2.13, 95% CI 1.33–3.43), reduced HGS (β −0.51 (−0.90–−0.11)) and reduced ASMI (β −0.19 (−0.25–−0.14)). Forced expiratory volume in 1 s

Background: Although it is well acknowledged that psychosocial risk factors (PSRF) such as low socio-economic status, stress, social isolation, negative emotions and negative personality patterns may contribute to the development and adverse outcome of cardiovascular disease (CVD), screening for PSRF in CVD patients is usually limited to anxiety and depression, mainly for feasibility reasons. We therefore aimed to develop a user-friendly screening battery for routine assessment of PSRFs and to evaluate this instrument regarding feasibility of application, PSRF results and attendance of psychological counselling if recommended to cardiac rehabilitation (CR) patients. Methods: This is a prospective single center cohort study including 609 consecutive CR patients. We first developed a screening instrument based on seven validated scales for the most relevant PSRFs with totally 90 questions presented in a uniform graphical design to facilitate completion called Psychocardiogram® (PCG) and applied the instrument in consecutive patients attending CR. Patients with positive screening results were invited to a psychological counseling session. Results: Six hundred and nine consecutive patients, aged 34 to 86 years (mean 60.7 years), 85% men, entering the CR program at the Bern University Hospital with ischemic heart failure (CHF), coronary artery disease (CAD) or peripheral artery disease, were included in this study. Eighty-three point three percent of the patients completed the PCG within 40 minutes. Vital exhaustion and Type-D personality were the most prevalent PSRFs (56.9% and 51.1%, respectively), whereas low social support (14.4%) and elevated depressive symptoms (15.9%), were the least prevalent ones. After screening, 120 patients (52.86%) with at least one PSRF made use of psychological counseling. Conclusions: We found the PCG to be a useful screening tool for PSRF in CR patients with the potential to get new insights into the prevalence of particular PSRF in specific populations and to better study their impact on occurrence and outcome of CVD.

Whilst current public health measures focused on good hygiene practices and limiting person-to-person transmission contribute effectively in managing the COVID-19 pandemic, they will not prevent all individuals from becoming infected. Thus, it is of importance to explore what individuals could do to mitigate adverse outcomes. The value of beneficial health behaviours and a healthy lifestyle to improve immune functioning and lower adverse consequences of COVID-19 are increasingly being emphasized. Here we discuss seven key health behaviours and corresponding recommendations that may assist in reducing unfavourable COVID-19 outcomes.

Abstract Background Researchers performing systematic reviews (SRs) must carefully consider the relevance of thousands of citations retrieved from bibliographic database searches, the majority of which will be excluded later on close inspection. Well-developed bibliographic searches are generally created with thesaurus or index terms in combination with keywords found in the title and/or abstract fields of citation records. Records in the bibliographic database Embase contain many more thesaurus terms than MEDLINE. Here, we aim to examine how limiting searches to major thesaurus terms (in MEDLINE called focus terms) in Embase and MEDLINE as well as limiting to words in the title and abstract fields of those databases affects the overall recall of SR searches. Methods To examine the impact of using search techniques aimed at higher precision, we analyzed previously completed SRs and focused our original searches to major thesaurus terms or terms in title and/or abstract only in Embase.com or in Embase.com and MEDLINE (Ovid) combined. We examined the total number of search results in both Embase and MEDLINE and checked whether included references were retrieved by these more focused approaches. Results For 73 SRs, we limited Embase searches to major terms only while keeping the search in MEDLINE and other databases such as Web of Science as they were. The overall search yield (or total number of search results) was reduced by 8%. Six reviews (9%) lost more than 5% of the relevant references. Limiting Embase and MEDLINE to major thesaurus terms, the number of references was 13% lower. For 15% of the reviews, the loss of relevant references was more than 5%. Searching Embase for title and abstract caused a loss of more than 5% in 16 reviews (22%), while limiting Embase and MEDLINE that way this happened in 24 reviews (33%). Conclusions Of the four search options, two options substantially reduced the overall search yield. However, this also resulted in a greater chance of losing relevant references, even though many references were still found in other databases such as Web of Science.

Abnormal PR interval duration is associated with risk for atrial fibrillation and heart block. Here, van Setten et al. identify 44 PR interval loci in a genome-wide association study of over 92,000 individuals and find genetic overlap with QRS duration, heart rate and atrial fibrillation.

Abstract Background Within systematic reviews, when searching for relevant references, it is advisable to use multiple databases. However, searching databases is laborious and time-consuming, as syntax of search strategies are database specific. We aimed to determine the optimal combination of databases needed to conduct efficient searches in systematic reviews and whether the current practice in published reviews is appropriate. While previous studies determined the coverage of databases, we analyzed the actual retrieval from the original searches for systematic reviews. Methods Since May 2013, the first author prospectively recorded results from systematic review searches that he performed at his institution. PubMed was used to identify systematic reviews published using our search strategy results. For each published systematic review, we extracted the references of the included studies. Using the prospectively recorded results and the studies included in the publications, we calculated recall, precision, and number needed to read for single databases and databases in combination. We assessed the frequency at which databases and combinations would achieve varying levels of recall (i.e., 95%). For a sample of 200 recently published systematic reviews, we calculated how many had used enough databases to ensure 95% recall. Results A total of 58 published systematic reviews were included, totaling 1746 relevant references identified by our database searches, while 84 included references had been retrieved by other search methods. Sixteen percent of the included references (291 articles) were only found in a single database; Embase produced the most unique references (n = 132). The combination of Embase, MEDLINE, Web of Science Core Collection, and Google Scholar performed best, achieving an overall recall of 98.3 and 100% recall in 72% of systematic reviews. We estimate that 60% of published systematic reviews do not retrieve 95% of all available relevant references as many fail to search important databases. Other specialized databases, such as CINAHL or PsycINFO, add unique references to some reviews where the topic of the review is related to the focus of the database. Conclusions Optimal searches in systematic reviews should search at least Embase, MEDLINE, Web of Science, and Google Scholar as a minimum requirement to guarantee adequate and efficient coverage.

Abstract Background It remains unclear into which level the systolic blood pressure (SBP) should be lowered in order to provide the best cardiovascular protection among older people. Hypertension guidelines recommendation on attaining SBP levels 33,600 participants) were included. Compared with attaining SBP levels ≥140 mmHg, levels of 130 to

Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.

Lipid concentrations are heritable traits. Recently, the number of known genetic loci associated with lipid levels in adults increased from 95 to 157. The effects of these 157 loci have not been tested in children. Considering that lipid levels track from childhood to adulthood, we studied to determine whether these variants already affected lipid concentrations in a large group of 2,645 children with a median age of 6.0 years (95% range 5.7–7.3 years) from the population-based Generation R Study. Twenty-eight SNPs associated with TGs, 39 SNPs associated with total cholesterol (TC), 28 SNPs associated with LDL cholesterol (LDL-C), and 56 SNPs associated with HDL cholesterol (HDL-C) were analyzed individually and combined into genetic risk scores (GRSs). All risk scores were associated with their specific outcomes. The differences in mean absolute lipid and lipoprotein values between the 10% of children with the highest lipid or lipoprotein GRS versus the 10% with the lowest score were 0.28, 0.25, 0.32, and 0.30 mmol/l for TGs, TC, LDL-C, and HDL-C, respectively. In conclusion, we show for the first time that GRSs based on 157 SNPs associated with adult lipid concentrations are associated with lipid levels in children. The genetic background of these phenotypes at least partly overlaps between children and adults.

COPD is associated with a progressive loss of muscle mass and function. However, there is an unmet need to define and standardise methods to estimate the prevalence of sarcopenia in COPD patients. We performed a systematic review and meta-analysis of the prevalence of this extrapulmonary manifestation in COPD patients. We searched Embase, Medline (Ovid), CINAHL (EBSCO), Web of Science, Scopus and Google Scholar for studies published up to January 17, 2019, assessing sarcopenia in COPD patients based on low muscle mass and decreased muscle function. Interventional studies, in vitro experiments, protocols or reviews and meta-analyses were excluded. We estimated heterogeneity (I2) and assessed significance (Q) using a Chi-squared test for estimates obtained from random-effects models. 4465 articles were initially identified. After removing the duplicates and applying the selection criteria, we reviewed 62 full-text articles. Finally, 10 articles (n=2565 COPD patients) were included in this systematic review and meta-analyses. Overall, the prevalence of sarcopenia in patients with COPD was 21.6% (95% CI 14.6–30.9%, I2=94%), ranging from 8% in population-based to 21% in clinic-based studies, and 63% in COPD patients residing in nursing homes. Sarcopenia is frequently observed in COPD patients, with varying prevalence across population settings. Sarcopenia in COPD should be assessed using standardised tests and cut-off points from sarcopenia consensus criteria for clinical practice and international comparisons.

Background The purpose of this study was to investigate the association between kidney function and arterial calcification in major vascular beds and to establish whether arterial calcification mediates the relation between kidney function measures and cardiovascular disease (CVD) incidence. Methods and Results In 2241 participants from the Rotterdam Study (mean age 69 years, 52% female), kidney function was assessed using the estimated glomerular filtration rate and urine albumin‐to‐creatinine ratio. All participants underwent noncontrast computed tomography to quantify the amount of arterial calcification in the coronary arteries, aortic arch, extracranial, and intracranial internal carotid arteries. We used linear regression models, adjusted for age, sex, and cardiovascular risk factors, to evaluate the association between kidney function and arterial calcification volume in the 4 vessel beds. Incidence rate of CVD was calculated in 3 groups of participants based on their kidney function and presence of arterial calcification. We conducted mediation analysis to evaluate whether arterial calcification mediates this association. We found that in age‐ and sex‐adjusted models, lower estimated glomerular filtration rate and higher albumin‐to‐creatinine ratio were associated with larger calcification volumes in all 4 vascular beds. Adjusting for cardiovascular risk factors attenuated the effect estimates. CVD incidence was higher in participants with estimated glomerular filtration rate 60 and no calcification. After adjusting for cardiovascular risk factors, arterial calcification did not mediate the association between kidney function measures and CVD incidence. Conclusions The association of impaired kidney function and larger volumes of arterial calcification is partly explained by cardiovascular risk factors. Arterial calcification does not mediate the association between kidney function and CVD beyond cardiovascular risk factors.

Epigenetic mechanisms have been suggested to play a role in the genetic regulation of pathways related to inflammation. Therefore, we aimed to systematically review studies investigating the association between DNA methylation and histone modifications with circulatory inflammation markers in blood. Five bibliographic databases were screened until 21 November of 2017. We included studies conducted on humans that examined the association between epigenetic marks (DNA methylation and/or histone modifications) and a comprehensive list of inflammatory markers. Of the 3,759 identified references, 24 articles were included, involving, 17,399 individuals. There was suggestive evidence for global hypomethylation but better-quality studies in the future have to confirm this. Epigenome-wide association studies (EWAS) (n=7) reported most of the identified differentially methylated genes to be hypomethylated in inflammatory processes. Candidate genes studies reported 18 differentially methylated genes related to several circulatory inflammation markers. There was no overlap in the methylated sites investigated in candidate gene studies and EWAS, except for TMEM49, which was found to be hypomethylated with higher inflammatory markers in both types of studies. The relation between histone modifications and inflammatory markers was assessed by one study only. This review supports an association between epigenetic marks and inflammation, suggesting hypomethylation of the genome. Important gaps in the quality of studies were reported such as inadequate sample size, lack of adjustment for relevant confounders, and failure to replicate the findings. While most of the studies have been focused on C-reactive protein, further efforts should investigate other inflammatory markers.

Patients with chronic obstructive pulmonary disease (COPD) commonly present with multimorbidity. We aimed to investigate the association between COPD and the development of peripheral arterial disease (PAD) in the general population, and how this might affect mortality among individuals with COPD. We included 3123 participants of the population-based Rotterdam Study without PAD at baseline (mean age 65 years; 57.4% female). The association between COPD at baseline and PAD during follow-up was studied using logistic regression (PAD being indicated by an ankle–brachial index (ABI) of 0.9 or less). Cox regression was used for mortality analysis and interaction terms were used to investigate mortality risk modification by PAD. The presence of COPD was associated with incident PAD (adjusted odds ratio 1.9, 95% CI 1.1–3.2). Mortality rates per 100 000 person-years were as follows: 10.0 in individuals without COPD or PAD, 18.4 in those with COPD only, 16.1 in those with PAD only and 30.1 in individuals with both COPD and PAD. No statistical interaction was found between PAD and COPD on risk of dying. Individuals with COPD have an almost doubled risk of developing PAD. Although PAD does not modify the association between COPD and mortality, people suffering from both diseases have substantially higher mortality rates.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

Folic acid is routinely recommended for women trying to conceive to ensure proper fetal development. Here, the authors perform a large epigenomics study to examine which fetal epigenetic changes are associated with varied maternal plasma folate levels.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Background High blood pressure levels and higher arterial stiffness have been shown to be associated with lower cognition during adulthood, possibly by accumulative changes over time. However, vascular factors may already affect the brain during early life. Methods and Results We examined the relation between cognition and vascular factors within 5853 children from the Generation R Study (mean age 6.2 years) and 5187 adults from the Rotterdam Study (mean age 61.8 years). Diastolic and systolic blood pressure and arterial stiffness were assessed, the latter by measuring pulse‐wave velocity and pulse pressure. For cognition, the Generation R Study relied on nonverbal intelligence, whereas the Rotterdam Study relied on a cognitive test battery to calculate the g‐factor, a measure of global cognition. In the Generation R Study, standardized diastolic blood pressure showed a significant association with standardized nonverbal intelligence (β=−0.030, 95% confidence interval=[−0.054; −0.005]) after full adjustment. This association held up after excluding the top diastolic blood pressure decile (β=−0.042 [−0.075; −0.009]), suggesting that the relation holds in normotensives. Within the Rotterdam Study, standardized cognition associated linearly with standardized systolic blood pressure (β=−0.036 [−0.060; −0.012]), standardized pulse‐wave velocity (β=−0.064 [−0.095; −0.033]), and standardized pulse pressure (β=−0.044 [−0.069; −0.020], and nonlinearly with standardized diastolic blood pressure (quadratic term β=−0.032 [−0.049; −0.015]) after full adjustment. Conclusions Blood pressure and cognition may already be related in the general population during early childhood, albeit differently than during adulthood.

Background Cardiovascular risk factors have differential effects on various manifestations of cardiovascular disease, but to date direct formal comparisons are scarce, have been conducted primarily in men, and include only traditional risk factors. Methods and Results Using data from the multi‐ethnic Women's Health Initiative Observational Study, we used a case–cohort design to compare 1731 women with incident cardiovascular disease during follow‐up to a cohort of 1914 women. The direction of effect of all 24 risk factors (including various apolipoproteins, hemoglobin A1c, high‐sensitivity C‐reactive protein, N‐terminal pro‐brain natriuretic peptide, and tissue plasminogen activator antigen) was concordant for coronary heart disease (CHD, defined as myocardial infarction and CHD death) and ischemic stroke; however, associations were generally stronger with CHD. Significant differences for multiple risk factors, including blood pressure, lipid levels, and measures of inflammation, were observed when comparing the effects on hemorrhagic stroke with those on ischemic outcomes. For instance, multivariable adjusted hazard ratios per standard deviation increase in non–high‐density lipoprotein cholesterol were 1.16 (95% confidence interval, 1.06–1.28) for CHD, 0.97 (0.88–1.07) for ischemic stroke, and 0.76 (0.63–0.91) for hemorrhagic stroke (P