Cardiovascular Health and Life Expectancy Among Adults in the United States.

BACKGROUND: Cardiovascular disease may be the main reason for stagnant growth in life expectancy in the United States since 2010. The American Heart Association recently released an updated algorithm for evaluating cardiovascular health (CVH)-Life's Essential 8 (LE8) score. We aimed to quantify the associations of CVH levels, estimated by the LE8 score, with life expectancy in a nationally representative sample of US adults. METHODS: We included 23 003 nonpregnant, noninstitutionalized participants aged 20 to 79 years who participated in the National Health and Nutrition Examination Survey from 2005 to 2018 and whose mortality was identified through linkage to the National Death Index through December 31, 2019. The overall CVH was evaluated by the LE8 score (range, 0-100), as well as the score for each component of diet, physical activity, tobacco/nicotine exposure, sleep duration, body mass index, non-high-density lipoprotein cholesterol, blood glucose, and blood pressure. Life table method was used to estimate life expectancy by levels of the CVH. RESULTS: During a median of 7.8 years of follow-up, 1359 total deaths occurred. The estimated life expectancy at age 50 years was 27.3 years (95% CI, 26.1-28.4), 32.9 years (95% CI, 32.3-33.4), and 36.2 years (95% CI, 34.2-38.2) in participants with low (LE8 score <50), moderate (50≤ LE8 score <80), and high (LE8 score ≥80) CVH, respectively. Equivalently, participants with high CVH had an average 8.9 (95% CI, 6.2-11.5) more years of life expectancy at age 50 years compared with those with low CVH. On average, 42.6% of the gained life expectancy at age 50 years from adhering to high CVH was attributable to reduced cardiovascular disease death. Similarly significant associations of CVH with life expectancy were observed in men and women, respectively. Similarly significant associations of CVH with life expectancy were observed in White participants and Black participants but not in Mexican participants. CONCLUSIONS: Adhering to a high CVH, defined as the LE8 score, is related to a considerably increased life expectancy in US adults, but more research needs to be done in other races and ethnicities (eg, Hispanic and Asian).

Whole-exome sequencing of 14 389 individuals from the ESP and CHARGE consortia identifies novel rare variation associated with hemostatic factors.

Plasma levels of fibrinogen, coagulation factors VII and VIII and von Willebrand factor (vWF) are four intermediate phenotypes that are heritable and have been associated with the risk of clinical thrombotic events. To identify rare and low-frequency variants associated with these hemostatic factors, we conducted whole-exome sequencing in 10 860 individuals of European ancestry (EA) and 3529 African Americans (AAs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and the National Heart, Lung and Blood Institute's Exome Sequencing Project. Gene-based tests demonstrated significant associations with rare variation (minor allele frequency < 5%) in fibrinogen gamma chain (FGG) (with fibrinogen, P = 9.1 × 10-13), coagulation factor VII (F7) (with factor VII, P = 1.3 × 10-72; seven novel variants) and VWF (with factor VIII and vWF; P = 3.2 × 10-14; one novel variant). These eight novel rare variant associations were independent of the known common variants at these loci and tended to have much larger effect sizes. In addition, one of the rare novel variants in F7 was significantly associated with an increased risk of venous thromboembolism in AAs (Ile200Ser; rs141219108; P = 4.2 × 10-5). After restricting gene-based analyses to only loss-of-function variants, a novel significant association was detected and replicated between factor VIII levels and a stop-gain mutation exclusive to AAs (rs3211938) in CD36 molecule (CD36). This variant has previously been linked to dyslipidemia but not with the levels of a hemostatic factor. These efforts represent the largest integration of whole-exome sequence data from two national projects to identify genetic variation associated with plasma hemostatic factors.

Associations of carotid intima media thickness with gene expression in whole blood and genetically predicted gene expression across 48 tissues.

Carotid intima media thickness (cIMT) is a biomarker of subclinical atherosclerosis and a predictor of future cardiovascular events. Identifying associations between gene expression levels and cIMT may provide insight to atherosclerosis etiology. Here, we use two approaches to identify associations between mRNA levels and cIMT: differential gene expression analysis in whole blood and S-PrediXcan. We used microarrays to measure genome-wide whole blood mRNA levels of 5647 European individuals from four studies. We examined the association of mRNA levels with cIMT adjusted for various potential confounders. Significant associations were tested for replication in three studies totaling 3943 participants. Next, we applied S-PrediXcan to summary statistics from a cIMT genome-wide association study (GWAS) of 71 128 individuals to estimate the association between genetically determined mRNA levels and cIMT and replicated these analyses using S-PrediXcan on an independent GWAS on cIMT that included 22 179 individuals from the UK Biobank. mRNA levels of TNFAIP3, CEBPD and METRNL were inversely associated with cIMT, but these associations were not significant in the replication analysis. S-PrediXcan identified associations between cIMT and genetically determined mRNA levels for 36 genes, of which six were significant in the replication analysis, including TLN2, which had not been previously reported for cIMT. There was weak correlation between our results using differential gene expression analysis and S-PrediXcan. Differential expression analysis and S-PrediXcan represent complementary approaches for the discovery of associations between phenotypes and gene expression. Using these approaches, we prioritize TNFAIP3, CEBPD, METRNL and TLN2 as new candidate genes whose differential expression might modulate cIMT.

Ethnic Differences in Carotid Intima Media Thickness and Plaque Presence - The HELIUS study.

Introduction In the Netherlands, the prevalence of cardiovascular diseases (CVD) is higher among South-Asian Surinamese and lower among Moroccans compared to the Dutch. Traditional risk factors for atherosclerotic CVD do not fully explain these disparities. We aim to assess ethnic differences in plaque presence and intima media thickness (cIMT) and explore to which extent these differences are explained by traditional risk factors. Methods We used cross-sectional data from a subgroup of participants enrolled in the multi-ethnic population-based HEalthy Life In an Urban Setting (HELIUS) study who underwent carotid ultrasonography. Logistic and linear regression models were built to assess ethnic differences in plaque presence and cIMT with the Dutch population as reference. Additional models were created to adjust for socioeconomic status, body height and cardiovascular risk factors. Results Of the 3022 participants, 1183, 1051 and 790 individuals were of Dutch, South-Asian Surinamese and Moroccan descent. Mean age was 60.9 years (SD 8.0), 52.8% was female. Compared to the Dutch, we found lower odds for plaque presence in Moroccans (0.77, 95% CI 0.62; 0.95) and no significant differences between the South-Asian Surinamese and Dutch population (0.91, 95% CI 0.76; 1.10). After adjustment for CVD risk factors, we found a lower plaque presence in South-Asian Surinamese (0.63, 95% CI 0.48; 0.82). In both Moroccan and South-Asian Surinamese individuals, adjustment for socioeconomic status did not materially change the results. cIMT was lower in South-Asian Surinamese compared to the Dutch (-17.9 µm, 95% CI -27.9; -7.9) and partly explained by ethnic differences in body height as South-Asian Surinamese individuals were, on average, shorter than the Dutch population. No differences in cIMT between Moroccans and Dutch were found. Conclusions cIMT and plaque prevalence differ between ethnic groups independent of CVD risk. Lower plaque prevalence in Moroccans was partly attributable to a lower prevalence of traditional CVD risk factors, while body height was an important contributor to differences in cIMT in South-Asians. This study emphasizes the need for ethnic-specific cut-off values for plaque presence and cIMT.

Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity.

Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10-7, range P = 9.2 × 10-8 to 6.0 × 10-46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10-6, range P = 5.5 × 10-6 to 6.1 × 10-35, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10-54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.

Association between dietary phytochemical index, cardiometabolic risk factors and metabolic syndrome in Switzerland. The CoLaus study.

BACKGROUND AND AIMS: Plant-based diets are associated with reduced cardiometabolic risk factors (CRFs) and lower risk of metabolic syndrome (MetS), probably via phytochemicals acting synergistically. However, dietary phytochemical content estimation is challenging; therefore, the dietary phytochemical index (DPI) was proposed as a practical way to assess total dietary phytochemical content from phytochemical-rich foods (PRFs). We evaluated the association between DPI with CRFs and MetS and its components. METHODS AND RESULTS: Cross-sectional analysis of 2009-2012 data of Colaus cohort study (Lausanne, Switzerland), including 3879 participants (mean age 57.6 ± 10.4 years, 53.5% women). Dietary intake was assessed via a validated food frequency questionnaire. DPI was calculated as the total energy intake percentage obtained from PRFs consumption and assessed as quartiles. Associations were determined using multivariable linear and logistic regression for CRFs and MetS, respectively. Median DPI value was 25.5 (interquartile range: 17.7-34.6). After multivariable-adjusted analyses, significant inverse associations were observed between the last two highest DPI quartiles and waist circumference (WC), body mass index (BMI), insulin, leptin, and hs-CRP. No significant associations were observed for MetS or its components except for central obesity, as subjects in the highest DPI quartile had lower odds (OR: 0.78; 95% CI: 0.62, 0.97) than those in lowest quartile. CONCLUSION: A diet high in PRFs assessed via DPI is associated with lower WC, BMI, insulin, leptin, hs-CRP values, and lower odds of central obesity, indicating a potential protective effect of phytochemical intake on these CRFs and highlighting the importance of high PRFs intake in promoting cardiometabolic health.

Epidemiology and prevalence of tobacco use in Tehran; a report from the recruitment phase of Tehran cohort study.

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 < 0.001) and men compared to women (32.9% vs. 7.7% P < 0.001). The prevalence of tobacco use increased with more years of education (> 12 years: 19.3% vs. illiterate: 9.7%, P < 0.001), lower body mass index (< 20 kg/m2: 31.3% vs. ≥ 35 kg/m2: 13.8%, P < 0.001), higher physical activity (high: 23.0% vs. low: 16.4%, P < 0.001), opium (user: 66.6% vs. non-user: 16.5%, P < 0.001), and alcohol use (drinker: 57.5% vs. non-drinker: 15.4%, P < 0.001). Waterpipe users were younger (46.1 vs. 53.2 years) and had a narrower gender gap in prevalence than cigarette smokers (male/female ratio in waterpipe users: 2.39 vs. cigarette smokers: 5.47). Opium (OR = 5.557, P < 0.001) and alcohol consumption (OR = 4.737, P < 0.001) were strongly associated with tobacco use. Hypertension was negatively associated with tobacco use (OR = 0.774, P = 0.005). CONCLUSION: The concerning prevalence of tobacco use in Tehran and its large gender gap for cigarette and waterpipe use warrant tailored preventive policies.

Adding salt to foods and hazard of premature mortality.

AIMS: We analyzed whether the frequency of adding salt to foods was associated with the hazard of premature mortality and life expectancy. METHODS AND RESULTS: A total of 501 379 participants from UK biobank who completed the questionnaire on the frequency of adding salt to foods at baseline. The information on the frequency of adding salt to foods (do not include salt used in cooking) was collected through a touch-screen questionnaire at baseline. We found graded relationships between higher frequency of adding salt to foods and higher concentrations of spot urinary sodium or estimated 24-h sodium excretion. During a median of 9.0 years of follow-up, 18 474 premature deaths were documented. The multivariable hazard ratios [95% confidence interval (CI)] of all-cause premature mortality across the increasing frequency of adding salt to foods were 1.00 (reference), 1.02 (0.99, 1.06), 1.07 (1.02, 1.11), and 1.28 (1.20, 1.35) (P-trend < 0.001). We found that intakes of fruits and vegetables significantly modified the associations between the frequency of adding salt to foods and all-cause premature mortality, which were more pronounced in participants with low intakes than those with high intakes of these foods (P-interaction = 0.02). In addition, compared with the never/rarely group, always adding salt to foods was related to 1.50 (95% CI, 0.72-2.30) and 2.28 (95% CI, 1.66-2.90) years lower life expectancy at the age of 50 years in women and men, respectively. CONCLUSIONS: Our findings indicate that higher frequency of adding salt to foods is associated with a higher hazard of all-cause premature mortality and lower life expectancy.

Thoracic Aortic Diameter and Cardiovascular Events and Mortality among Women and Men.

Background Thoracic aortic diameter may have a role as a biomarker for major adverse cardiovascular events. Purpose To evaluate the sex-specific association of the diameters of the ascending (AA) and descending (DA) thoracic aorta with risk of stroke, coronary heart disease, heart failure, cardiovascular mortality, and all-cause mortality. Materials and Methods Study participants from the population-based Rotterdam Study who underwent multidetector-row CT between 2003 and 2006 were evaluated. Cox proportional hazard models were conducted to evaluate the associations of AA and DA diameters indexed and not indexed for body mass index (BMI) with cardiovascular events and mortality for men and women. Hazard ratios (HRs) were calculated per 1-unit greater SD of aortic diameters. Results A total of 2178 participants (mean age, 69 years; 55% women) were included. Mean follow-up was 9 years. Each 0.23-mm/(kg/m2) larger BMI-indexed AA diameter was associated with a 33% higher cardiovascular mortality risk in women (HR, 1.33; 95% CI: 1.03, 1.73). Each 0.16-mm/(kg/m2) larger BMI-indexed DA diameter was associated with a 38% higher risk of stroke (HR, 1.38; 95% CI: 1.07, 1.78) and with a 46% greater risk of cardiovascular mortality (HR, 1.46; 95% CI: 1.10, 1.94) in women. Larger BMI-indexed AA and DA diameters were associated with greater risk of all-cause mortality in both sexes. Conclusion Larger ascending and descending thoracic aortic diameters indexed by body mass index were associated with greater risk of adverse cardiovascular outcomes and mortality in women and men. Clinical trial registration no. NTR6831 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Williams in this issue.

Does reproductive stage impact cardiovascular disease risk factors? Results from a population-based cohort in Lausanne (CoLaus study).

CONTEXT: Menopause has been associated with adverse cardiovascular disease (CVD) risk profile, yet it is unclear whether the changes in CVD risk factors differ by reproductive stage independently of underlying ageing trajectories. DESIGN: The CoLaus study is a prospective population-based cohort study in Lausanne, Switzerland. PATIENTS: We used data from women at baseline and follow-up (mean: 5.6 ± 0.5 years) from 2003 to 2012 who did not use hormone therapy. We classified women into (i) premenopausal, (ii) menopausal transition, (iii) early (≤5 years) and (iv) late (>5 years) postmenopausal by comparing their menstruation status at baseline and follow-up. MEASUREMENTS: We measured fasting lipids, glucose and cardiovascular inflammatory markers. We used repeated measures (linear mixed models) for longitudinal analysis, using premenopausal women as a reference category. We adjusted analyses for age, medications and lifestyle factors. RESULTS: We used the data from 1710 women aged 35-75 years. Longitudinal analysis showed that the changes in CVD risk factors were not different in the other three menopausal categories compared to premenopausal women. When age was used as a predictor variable and adjusted for menopause status, most CVD risk factors increased, while interleukin-6 and interleukin-1ß decreased with advancing age. CONCLUSION: The current study suggests that women have a worsening cardiovascular risk profile as they age, and although menopausal women may have higher levels of cardiovascular risk factors compared to premenopausal women at any given time, the 5-year changes in cardiovascular risk factors may not depend on the reproductive stage.

Genomic analysis of diet composition finds novel loci and associations with health and lifestyle.

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10-8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10-5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15-0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1-0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈-0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction.

The European Academy of Neurology Brain Health Strategy: One brain, one life, one approach.

BACKGROUND AND PURPOSE: Brain health is essential for health, well-being, productivity and creativity across the entire life. Its definition goes beyond the absence of disease embracing all cognitive, emotional, behavioural and social functions which are necessary to cope with life situations. METHODS: The European Academy of Neurology (EAN) Brain Health Strategy responds to the high and increasing burden of neurological disorders. It aims to develop a non-disease-, non-age-centred holistic and positive approach ('one brain, one life, one approach') to prevent neurological disorders (e.g., Alzheimer's disease and other dementias, stroke, epilepsy, headache/migraine, Parkinson's disease, multiple sclerosis, sleep disorders, brain cancer) but also to preserve brain health and promote recovery after brain damage. RESULTS: The pillars of the EAN Brain Health Strategy are (1) to contribute to a global and international brain health approach (together with national and subspecialty societies, other medical societies, the World Health Organization, the World Federation of Neurology, patients' organizations, industry and other stakeholders); (2) to support the 47 European national neurological societies, healthcare and policymakers in the implementation of integrated and people-centred campaigns; (3) to foster research (e.g., on prevention of neurological disorders, determinants and assessments of brain health); (4) to promote education of students, neurologists, general practitioners, other medical specialists and health professionals, patients, caregivers and the general public; (5) to raise public awareness of neurological disorders and brain health. CONCLUSIONS: By adopting this 'one brain, one life, one approach' strategy in cooperation with partner societies, international organizations and policymakers, a significant number of neurological disorders may be prevented whilst the overall well-being of individuals is enhanced by maintaining brain health through the life course.

Physical activity and cardiometabolic risk factors in individuals with spinal cord injury: a systematic review and meta-analysis.

Physical inactivity in individuals with spinal cord injury (SCI) has been suggested to be an important determinant of increased cardiometabolic disease (CMD) risk. However, it remains unclear whether physically active SCI individuals as compared to inactive or less active individuals have truly better cardiometabolic risk profile. We aimed to systematically review and quantify the association between engagement in regular physical activity and/or exercise interventions and CMD risk factors in individuals with SCI. Four medical databases were searched and studies were included if they were clinical trials or observational studies conducted in adult individuals with SCI and provided information of interest. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the certainty of evidence. Of 5816 unique citations, 11 randomized clinical trials, 3 non-randomized trial and 32 cross-sectional studies comprising more than 5500 SCI individuals were included in the systematic review. In meta-analysis of RCTs and based on evidence of moderate certainty, physical activity in comparison to control intervention was associated with: (i) better glucose homeostasis profile [WMD of glucose, insulin and Assessment of Insulin Resistance (HOMA-IR) were - 3.26 mg/dl (95% CI - 5.12 to - 1.39), - 3.19 µU/ml (95% CI - 3.96 to - 2.43)] and - 0.47 (95% CI - 0.60 to - 0.35), respectively], and (ii) improved cardiorespiratory fitness [WMD of relative and absolute oxygen uptake relative (VO2) were 4.53 ml/kg/min (95% CI 3.11, 5.96) and 0.26 L/min (95% CI 0.21, 0.32) respectively]. No differences were observed in blood pressure, heart rate and lipids (based on evidence of low/moderate certainty). In meta-analysis of cross-sectional studies and based on the evidence of very low to low certainty, glucose [WMD - 3.25 mg/dl (95% CI - 5.36, - 1.14)], insulin [- 2.12 µU/ml (95% CI - 4.21 to - 0.03)] and total cholesterol [WMD - 6.72 mg/dl (95% CI - 13.09, - 0.34)] were lower and HDL [WMD 3.86 mg/dl (95% CI 0.66, 7.05)] and catalase [0.07 UgHb-1 (95% CI 0.03, 0.11)] were higher in physically active SCI individuals in comparison to reference groups. Based on limited number of cross-sectional studies, better parameters of systolic and diastolic cardiac function and lower carotid intima media thickness were found in physically active groups. Methodologically sound clinical trials and prospective observational studies are required to further elaborate the impact of different physical activity prescriptions alone or in combination with other life-style interventions on CMD risk factors in SCI individuals.

Gene-diet interactions and cardiovascular diseases: a systematic review of observational and clinical trials.

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.

COVID-19 in Health-Care Workers: A Living Systematic Review and Meta-Analysis of Prevalence, Risk Factors, Clinical Characteristics, and Outcomes.

Health-care workers (HCWs) are at the frontline of response to coronavirus disease 2019 (COVID-19), being at a higher risk of acquiring the disease and, subsequently, exposing patients and others. Searches of 8 bibliographic databases were performed to systematically review the evidence on the prevalence, risk factors, clinical characteristics, and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCWs. A total of 97 studies (all published in 2020) met the inclusion criteria. The estimated prevalence of SARS-CoV-2 infection from HCWs' samples, using reverse transcription-polymerase chain reaction and the presence of antibodies, was 11% (95% confidence interval (CI): 7, 15) and 7% (95% CI: 4, 11), respectively. The most frequently affected personnel were nurses (48%, 95% CI: 41, 56), whereas most of the COVID-19-positive medical personnel were working in hospital nonemergency wards during screening (43%, 95% CI: 28, 59). Anosmia, fever, and myalgia were the only symptoms associated with HCW SARS-CoV-2 positivity. Among HCWs positive for COVID-19 by reverse transcription-polymerase chain reaction, 40% (95% CI: 17, 65) were asymptomatic at time of diagnosis. Finally, severe clinical complications developed in 5% (95% CI: 3, 8) of the COVID-19-positive HCWs, and 0.5% (95% CI: 0.02, 1.3) died. Health-care workers suffer a significant burden from COVID-19, with those working in hospital nonemergency wards and nurses being the most commonly infected personnel.

Association of diabetes with atrial fibrillation types: a systematic review and meta-analysis.

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.

Menopausal Transition Is Not Associated with Dietary Change in Swiss Women.

BACKGROUND: Adherence to a healthy diet could contribute to maintaining adequate health throughout the menopausal transition, but data are scarce. OBJECTIVE: We evaluated the association between menopausal status and changes in dietary intake in Swiss adult women. METHODS: Cross-sectional (n = 2439) and prospective analyses (n = 1656) were conducted between 2009 and 2012 (first follow-up) among women (mean age ± SD, 58.2 ± 10.5 y) living in Lausanne, Switzerland. In both visits, dietary intake was assessed using a validated FFQ, and menopausal status was classified based on the presence or absence of menstruations. Multivariable linear and logistic regression models were used to investigate the cross-sectional association of menopausal status (postmenopausal compared with premenopausal) at the first follow-up with food intake and dietary recommendations. To examine whether menopausal status (premenopausal as reference group, menopausal transition, and postmenopausal) during 5 y of follow-up was associated with longitudinal changes in diet, including adherence to dietary Swiss recommendations, we applied multivariable linear and logistic mixed models adjusted for several covariates. RESULTS: At the first follow-up, postmenopausal women consumed less (P < 0.002) meat [median (IQR) 57.2 (35-86.2) compared with 62.5 (41.2-95.2) g/d], pasta [61.8 (37.5-89.2) compared with 85 (57.8-128) g/d], and added sugar [0.1 (0-4) compared with 0.7 (0-8) g/d] and more dairy products [126 (65.4-214) compared with 109 (64.5-182) g/d] and fruit [217 (115-390) compared with 174 (83.2-319) g/d] than premenopausal women. However, linear regression analysis adjusted for potential confounding factors showed no independent (cross-sectional) associations of menopausal status with total energy intake (TEI) and individual macro- or micronutrient intakes. In the prospective analysis, compared with women who remained premenopausal during follow-up (n = 244), no differences were found in changes in TEI, dietary intakes, or adherence to the Swiss dietary recommendations in women transitioning from premenopausal to postmenopausal (n = 229) and who remained postmenopausal (n = 1168). CONCLUSION: The menopausal transition is not associated with changes in dietary habits among Swiss women.

Egg consumption and cardiovascular risk: a dose-response meta-analysis of prospective cohort studies.

PURPOSE: Cardiovascular disease (CVD) is a leading cause of mortality globally and is strongly influenced by dietary risk factors. The aim was to assess the association between egg consumption and risk of CVD risk/mortality, including coronary heart disease (CHD), stroke, and heart failure. METHODS: MEDLINE, Embase, and Web of Science databases were searched through April 2020 for prospective studies. Two independent reviewers screened and extracted the data through standardized methods. Size effects were calculated as summary relative risks (SRRs) in a dose-response fashion through random-effects meta-analyses. RESULTS: Thirty-nine studies including nearly 2 million individuals and 85,053 CHD, 25,103 stroke, 7536 heart failure, and 147,124 CVD cases were included. The summary analysis including 17 datasets from 14 studies conducted on CVD (incidence and/or mortality) showed that intake of up to six eggs per week is inversely associated with CVD events, when compared to no consumption [for four eggs per week, SRR = 0.95 (95% CI: 0.90; 1.00)]; a decreased risk of CVD incidence was observed for consumption of up to one egg per day [SRR = 0.94 (95% CI: 0.89; 0.99)]. The summary analysis for CHD incidence/mortality including 24 datasets from 16 studies showed a decreased risk up to two eggs per week [(SRR = 0.96 (95% CI: 0.91; 1.00)]. No associations were retrieved with risk of stroke. The summary analysis for heart failure risk including six datasets from four studies showed that intake of one egg per day was associated with increased risk raising for higher intakes compared to no consumption [for 1 egg per day, SRR = 1.15 (95% CI:1.02; 1.30)]. After considering GRADE criteria for strength of the evidence, it was rated low for all outcomes but stroke, for which it was moderate (yet referring to no risk). CONCLUSION: There is no conclusive evidence on the role of egg in CVD risk, despite the fact that higher quality studies are warranted to obtain stronger evidence for a possible protection of CVD associated with moderate weekly egg consumption compared to no intake; equally, future studies may strengthen the evidence for increased heart failure risk associated with high regular egg consumption.

The neurological level of spinal cord injury and cardiovascular risk factors: a systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To determine the difference in cardiovascular risk factors (blood pressure, lipid profile, and markers of glucose metabolism and inflammation) according to the neurological level of spinal cord injury (SCI). METHODS: We searched 5 electronic databases from inception until July 4, 2020. Data were extracted by two independent reviewers using a pre-defined data collection form. The pooled effect estimate was computed using random-effects models, and heterogeneity was calculated using I2 statistic and chi-squared test (CRD42020166162). RESULTS: We screened 4863 abstracts, of which 47 studies with 3878 participants (3280 males, 526 females, 72 sex unknown) were included in the meta-analysis. Compared to paraplegia, individuals with tetraplegia had lower systolic and diastolic blood pressure (unadjusted weighted mean difference, -14.5 mmHg, 95% CI -19.2, -9.9; -7.0 mmHg 95% CI -9.2, -4.8, respectively), lower triglycerides (-10.9 mg/dL, 95% CI -19.7, -2.1), total cholesterol (-9.9 mg/dL, 95% CI -14.5, -5.4), high-density lipoprotein (-1.7 mg/dL, 95% CI -3.3, -0.2) and low-density lipoprotein (-5.8 mg/dL, 95% CI -9.0, -2.5). Comparing individuals with high- vs. low-thoracic SCI, persons with higher injury had lower systolic and diastolic blood pressure (-10.3 mmHg, 95% CI -13.4, -7.1; -5.3 mmHg 95% CI -7.5, -3.2, respectively), while no differences were found for low-density lipoprotein, serum glucose, insulin, and inflammation markers. High heterogeneity was partially explained by age, prevalent cardiovascular diseases and medication use, body mass index, sample size, and quality of studies. CONCLUSION: In SCI individuals, the level of injury may be an additional non-modifiable cardiovascular risk factor. Future well-designed longitudinal studies with sufficient follow-up and providing sex-stratified analyses should confirm our findings and explore the role of SCI level in cardiovascular health and overall prognosis and survival.

Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels.

BACKGROUND: Factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are associated with risk of arterial and venous thrombosis and with hemorrhagic disorders. We aimed to identify and functionally test novel genetic associations regulating plasma FVIII and VWF. METHODS: We meta-analyzed genome-wide association results from 46 354 individuals of European, African, East Asian, and Hispanic ancestry. All studies performed linear regression analysis using an additive genetic model and associated ≈35 million imputed variants with natural log-transformed phenotype levels. In vitro gene silencing in cultured endothelial cells was performed for candidate genes to provide additional evidence on association and function. Two-sample Mendelian randomization analyses were applied to test the causal role of FVIII and VWF plasma levels on the risk of arterial and venous thrombotic events. RESULTS: We identified 13 novel genome-wide significant ( P≤2.5×10-8) associations, 7 with FVIII levels ( FCHO2/TMEM171/TNPO1, HLA, SOX17/RP1, LINC00583/NFIB, RAB5C-KAT2A, RPL3/TAB1/SYNGR1, and ARSA) and 11 with VWF levels ( PDHB/PXK/KCTD6, SLC39A8, FCHO2/TMEM171/TNPO1, HLA, GIMAP7/GIMAP4, OR13C5/NIPSNAP, DAB2IP, C2CD4B, RAB5C-KAT2A, TAB1/SYNGR1, and ARSA), beyond 10 previously reported associations with these phenotypes. Functional validation provided further evidence of association for all loci on VWF except ARSA and DAB2IP. Mendelian randomization suggested causal effects of plasma FVIII activity levels on venous thrombosis and coronary artery disease risk and plasma VWF levels on ischemic stroke risk. CONCLUSIONS: The meta-analysis identified 13 novel genetic loci regulating FVIII and VWF plasma levels, 10 of which we validated functionally. We provide some evidence for a causal role of these proteins in thrombotic events.