Impact of Lipoprotein(a) Level on Low-Density Lipoprotein Cholesterol- or Apolipoprotein B-Related Risk of Coronary Heart Disease.

BACKGROUND: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities. OBJECTIVES: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDLLp(a)corr) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events. METHODS: Among 68,748 CHD-free subjects at baseline LDLLp(a)corr was calculated as "LDL-C-Lp(a)-C," where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDLLp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile). RESULTS: Similar risk estimates for incident CHD were found for LDL-C and LDL-CLp(a)corr30 or LDL-CLp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; Pinteraction0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (Pinteraction0.49). CONCLUSIONS: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels.

The independent and interactive effects of changes in overtime and night shifts during the COVID-19 pandemic on burnout among nurses: a longitudinal study.

OBJECTIVES: This study aimed to evaluate the independent and interactive effects of changes in overtime and night shifts on burnout among nurses during the COVID-19 pandemic. METHODS: Nurses working in an Italian university hospital (N=317) completed the Maslach Burnout Inventory in September 2019 and again in December 2020. Based on hospital administrative data, changes in overtime and night shifts in the same years were categorized into three groups each. Linear regressions were used to estimate 2020 burnout differences between exposure groups, controlling for 2019 burnout levels, demographic and work-related characteristics, and to test the interaction between the two exposures. RESULTS: Nurses in the onset of high overtime group had higher emotional exhaustion [4.33, 95% confidence interval (CI) 1.74-6.92], depersonalization (2.10, 95% CI 0.49-3.71), and poor personal accomplishment (2.64, 95% CI 0.55-4.74) compared to stable low overtime nurses. Nurses in the increase in night shifts group had lower emotional exhaustion (-4.49, 95% CI -7.46- -1.52) compared to no night shift nurses. Interaction analyses revealed that this apparently paradoxical effect was limited to stable low overtime nurses only. Moreover, increases in night shifts were associated with higher depersonalization and poor personal accomplishment in nurses in the stable high overtime group. CONCLUSIONS: Increase in overtime is an independent risk factor for burnout among nurses, highlighting the need for specific regulations and actions to address it. Long-standing guidelines for the assignment of night shifts might have contributed to attenuate the impact of their increase on nurses' mental health.

Association of perceived mental health with mortality, and analysis of potential pathways in Italian men and women: Prospective results from the Moli-sani Study cohort.

BACKGROUND: Perceived mental health (PMH) was reportedly associated with mortality in general populations worldwide. However, little is known about sex differences and pathways potentially linking PMH to mortality. We explored the relationship between PMH and mortality in Italian men and women, and analysed potential explanatory factors. METHODS: We performed longitudinal analyses on 9045 men and 9467 women (population mean age 53.8 ± 11.2 years) from the Moli-sani Study. Baseline PMH was assessed through a self-administered Short Form 36-item questionnaire. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95 % confidence intervals (95%CI) of death across sex-specific quartiles of PMH, controlling for age, chronic health conditions, and perceived physical health. Socioeconomic, behavioural, and physiological factors were examined as potential explanatory factors of the association between PMH and mortality. RESULTS: In women, HRs for the highest (Q4) vs. bottom quartile (Q1) of PMH were 0.75 (95%CI 0.60-0.96) for all-cause mortality and 0.59 (0.40-0.88) for cardiovascular mortality. Part of these associations (25.8 % and 15.7 %, for all-cause and cardiovascular mortality, respectively) was explained by physiological factors. In men, higher PMH was associated with higher survival (HR = 0.82; 0.69-0.98, for Q4 vs. Q1) and reduced hazard of other cause mortality (HR = 0.67; 0.48-0.95). More than half of the association with all-cause mortality was explained by physiological factors. LIMITATIONS: PMH was measured at baseline only. CONCLUSIONS: PMH was independently associated with mortality in men and women. Public health policies aimed at reducing the burden of chronic diseases should prioritize perceived mental health assessment along with other interventions.

Perceived work stressors and the transition to burnout among nurses in response to the pandemic: implications for healthcare organizations.

OBJECTIVES: This study aimed to assess the associations of pre-pandemic perceived work stressors and work satisfaction among nurses, including nurse assistants, with burnout profiles and their transitions in response to the pandemic. METHODS: Three hundred and thirty-seven nurses working in an Italian University hospital participated in a longitudinal study including a survey in August 2019 investigating perceived work stressors (assessed using the HSE Indicator Tool), work satisfaction (Work Satisfaction Scale), and burnout (Maslach Burnout Inventory), and a second survey in December 2020 assessing burnout. Using latent transition analysis, we identified burnout profiles and then estimated the associations between work stressors and satisfaction on profiles and transitions. RESULTS: We identified three pre-pandemic profiles, namely engaged (67%), ineffective (15%), and burnout (18%); and three pandemic profiles, namely engaged (37%), exhausted (51%), and severe burnout (12%). The severe burnout profile consisted of 70% nurses classified in the burnout profile before the pandemic. Overall, work stressors and satisfaction were associated with both pre-pandemic and pandemic burnout profiles. Among nurses not in the burnout profile prior to COVID-19, pre-pandemic hostile relationships increased [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.05-1.34] and work satisfaction decreased (OR 0.82, 95% CI 0.68-0.98) the probability to transition to exhausted. Moreover, work satisfaction (OR 0.54, 95% CI 0.32-0.91) and participation in work organization (OR 0.69, 95% CI 0.51-0.93) protected from transitioning to severe burnout. The association between peer support and the transition to exhausted needs further investigation. CONCLUSIONS: Pre-pandemic work stressors and satisfaction were associated with pandemic burnout and burnout transitions. To enhance preparedness for future crises, healthcare managers should carefully assess and tackle work-related constraints affecting nurses.

C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project.

BACKGROUND AND AIMS: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population. METHODS: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L). RESULTS: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024). CONCLUSIONS: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.

Dietary indices underpinning front-of-pack nutrition labels and health outcomes: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Nutrient profiling systems are increasingly used to characterize the healthfulness of foods for front-of-package (FOP) labeling, which have been proposed as an effective public health strategy to help people make healthier food choices. OBJECTIVE: This study aimed to review available evidence from cohort studies that evaluated the association of dietary indices underpinning FOP nutrition labels with all-cause mortality and incidence of cardiovascular diseases (CVDs) or cancer. METHODS: PubMed, Web of Science, and Scopus were systematically searched up to October 2023. We included articles if they were prospective cohort studies, if the exposure was any dietary index underpinning FOP nutrition labels [e.g., the modified Food Standard Agency-Nutrient Profiling System (FSAm-NPS) and the Health Star Rating System], and if outcomes were all-cause mortality or incidence of or mortality due to CVD and cancer. Random-effects models were used to calculate the pooled hazard ratios (HRs) and 95% CIs. RESULTS: We identified 11 records (7 unique prospective studies), which were included in the systematic review. The meta-analysis comprised 8 studies analyzing the FSAm-NPS dietary index (DI) as exposure. The pooled HRs associated with a 2-unit increase in the FSAm-NPS DI of all-cause mortality, CVD, and cancer risk were 1.06 (95% confidence interval [CI]: 0.99, 1.13; I2: 80%), 1.08 (95% CI: 1.00, 1.18; I2: 70%), and 1.09 (95% CI: 1.00, 1.19; I2: 77%), respectively. The Chilean Warning Label score and the Health Star Rating systems were examined by 1 study each and were significantly associated with the outcomes. CONCLUSIONS: DIs underpinning most common FOP nutrition labels and reflecting nutrient-poor diets show a tendency toward an increased incidence of CVD and cancer, but the observed effects are quite modest in magnitude. Further studies at the population level are needed to support the widely shared hypothesis that FOP labels, possibly in conjunction with other interventions, may contribute to reduce noncommunicable disease risk. This meta-analysis was registered at PROSPERO as CRD42021292625.

Systematic Violence Monitoring to Reduce Underreporting and to Better Inform Workplace Violence Prevention Among Health Care Workers: Before-and-After Prospective Study.

BACKGROUND: Monitoring workplace violence (WPV) against health care workers (HCWs) through incident reporting is crucial to drive prevention, but the actual implementation is spotty and experiences underreporting. OBJECTIVE: This study aims to introduce a systematic WPV surveillance in 2 public referral hospitals in Italy and assess underreporting, WPV annual rates, and attributes "before" (2016-2020) and "after" its implementation (November 2021 to 2022). METHODS: During 2016-2020, incident reporting was based on procedures and data collection forms that were neither standardized between hospitals nor specific for aggressions. We planned and implemented a standardized WPV surveillance based on (1) an incident report form for immediate and systematic event notification, adopting international standards for violence definitions; (2) second-level root cause analysis with a dedicated psychologist, assessing violence determinants and impacts and offering psychological counseling; (3) a web-based platform for centralized data collection; and (4) periodic training for workforce coordinators and newly hired workers. We used data from incident reports to estimate underreporting, defined as an observed-to-expected (from literature and the "before" period) WPV ratio less than 1, and the 12-month WPV rates (per 100 HCWs) in the "before" and "after" periods. During the latter period, we separately estimated WPV rates for first and recurrent events. RESULTS: In the "before" period, the yearly observed-to-expected ratios were consistently below 1 and as low as 0.27, suggesting substantial violence underreporting of up to 73%. WPV annual rates declined in 1 hospital (from 1.92 in 2016 to 0.57 in 2020) and rose in the other (from 0.52 to 1.0), with the divergence being attributable to trends in underreporting. Available data were poorly informative to identify at-risk HCW subgroups. In the "after" period, the observed-to-expected ratio rose to 1.14 compared to literature and 1.91 compared to the "before" period, consistently in both hospitals. The 12-month WPV rate was 2.08 (95% CI 1.79-2.42; 1.52 and 2.35 in the 2 hospitals); one-fifth (0.41/2.08, 19.7%) was due to recurrences. Among HCWs, the youngest group (3.79; P<.001), nurses (3.19; P<.001), and male HCWs (2.62; P=.008) reported the highest rates. Emergency departments and psychiatric wards were the 2 areas at increased risk. Physical assaults were more likely in male than female HWCs (45/67, 67.2% vs 62/130, 47.7%; P=.01), but the latter experienced more mental health consequences (46/130, 35.4% vs 13/67, 19.4%; P=.02). Overall, 40.8% (53/130) of female HWCs recognized sociocultural (eg, linguistic or cultural) barriers as contributing factors for the aggression, and 30.8% (40/130) of WPV against female HCWs involved visitors as perpetrators. CONCLUSIONS: A systematic WPV surveillance reduced underreporting. The identification of high-risk workers and characterization of violence patterns and attributes can better inform priorities and contents of preventive policies. Our evaluation provides useful information for the large-scale implementation of standardized WPV-monitoring programs.

Pre-pandemic burnout and its changes during the COVID-19 outbreak as predictors of mental health of healthcare workers: A lesson to be learned.

The aim of this study was to identify how previously existing burnout and its changes during the pandemic contributed to PTSD symptoms and psychological distress in a cohort of 388 healthcare workers (HCWs). Each HCW was surveyed in Sep 2019 (before COVID-19) and again in Dec 2020-Jan 2021 (during the pandemic) to assess burnout (MBI); and in the second wave only to assess PTSD (PCL-5-SF), psychological distress (GHQ-12) and resilience (CD-RISC-10). Changes in emotional exhaustion (EE) and depersonalisation (DEP) were stronger in HCWs with lower EE and DEP baseline values. HCWs with higher baseline poor personal accomplishment (PPA) improved more than those with lower baseline values. In multivariable-adjusted models, pre-pandemic EE and its changes were equally associated to both outcomes: standardised-ßs of 0.52 and 0.54 for PTSD, respectively; and 0.55 and 0.53 for psychological distress. Changes in DEP were associated with PTSD only (0.10). Changes in PPA had a higher association with psychological distress (0.29) than pre-pandemic PPA (0.13). Resilience was associated with lower psychological distress (-0.25). Preventive actions aimed at reducing EE, e.g., addressing organisational dysfunctions, are needed to mitigate the impact of future crises, whereas improving personal accomplishment levels is a key target to protect HCWs from mental health disorders during a pandemic.

Habitual adherence to a traditional Mediterranean diet and risk of SARS-CoV-2 infection and Coronavirus disease 2019 (COVID-19): a longitudinal analysis.

Evidence on habitual Mediterranean diet (MD) and risk of SARS-CoV-2 infection, and COVID-19 is limited. 1,520 participants from the Moli-sani Study (2017-2020) were tested during January-September 2021 and adherence to MD was ascertained through the Mediterranean Diet Score (MDS). SARS-CoV-2 infection cases were determined through serology, and previous clinical diagnosis of COVID-19 disease was self-reported. Results were presented as odd ratios (OR) with 95% confidence intervals (CI). The MDS was not associated with the likelihood of SARS-CoV-2 infection (OR= 0.94; 95% CI: 0.83-1.06) and COVID-19 (OR= 0.82; 95% CI: 0.62-1.10) diagnosis. High consumption of cereals was associated with lower odds of SARS-CoV-2 infection (OR = 0.91; 95% CI: 0.83-1.00; for each 25 g/d increase). Likelihood of having being diagnosed with COVID-19 disease decreased in association with increasing olive oil intake (OR= 0.10; 95% CI: 0.01-0.79; for each additional 10 g/d), moderate alcohol consumption (OR= 0.18; 95% CI: 0.04-0.82) and higher intakes of fruits and nuts (OR = 0.89; 95% CI: 0.79-0.99). Our findings emphasise the adoption and maintenance of a balanced MD as a key strategy to reduce the risk of future SARS-CoV-2 infections and COVID-19.

Association between BMI, RFM and mortality and potential mediators: Prospective findings from the Moli-sani study.

BACKGROUND: Body mass index (BMI) is the most frequently used adiposity measure, yet it is unable to differentiate fat mass from lean mass. Relative fat mass (RFM) has been proposed as an alternative. This paper aims to study RFM and BMI association with mortality in a general Italian population and potential mediators of such association. METHODS: 20,587 individuals from the Moli-sani cohort were analysed (mean age = 54 ± 11, women = 52%, median follow up = 11.2 years, interquartile range = 1.96 years). Cox regressions were used to assess BMI, RFM, and their interactive association with mortality. Dose-response relationships were computed with spline regression, mediation analysis was performed. All analyses were separated for men and women. RESULTS: Men and women with BMI > 35 kg/m2 and men in the 4th quartile of RFM showed an independent association with mortality (HR = 1.71, 95% CI = 1.30-2.26 BMI in men, HR = 1.37, 95%CI = 1.01-1.85 BMI in women, HR = 1.37 CI 95% = 1.11-1.68 RFM in men), that was lost once adjusted for potential mediators. Cubic splines showed a U-shaped association for BMI in men and women, and for RFM in men. Mediation analysis showed that 46.5% of the association of BMI with mortality in men was mediated by glucose, C reactive protein, forced expiratory volume in 1 s (FEV1), and cystatin C; 82.9% of the association of BMI in women was mediated by HOMA index, cystatin C and FEV1; lastly, 55% of RFM association with mortality was mediated by glucose, FEV1 and cystatin C. Regression models including BMI and RFM showed that RFM drives most of the risk in men, but is not predictive in women. CONCLUSIONS: The association between anthropometric measures and mortality was U shaped and it was largely dependent on sex. Associations were mediated by glucose metabolism, renal and lung function. Public health interventions should mainly focus on people with severe obesity or impaired metabolic, renal, or respiratory function.

Mucosal immune response after the booster dose of the BNT162b2 COVID-19 vaccine.

BACKGROUND: To date, only a few studies reported data regarding the development of mucosal immune response after the BNT162b2-booster vaccination. METHODS: Samples of both serum and saliva of 50 healthcare workers were collected at the day of the booster dose (T3) and after two weeks (T4). Anti-S1-protein IgG and IgA antibody titres and the neutralizing antibodies against the Wuhan wild-type Receptor-Binding Domain in both serum and saliva were measured by quantitative and competitive ELISA, respectively. Data were compared with those recorded after the primary vaccination cycle (T2). Neutralizing antibodies against the variants of concern were measured in those individuals with anti-Wuhan neutralizing antibodies in their saliva. FINDINGS: After eight months from the second dose, IgG decreased in both serum (T2GMC: 23,838.5 ng/ml; T3GMC: 1473.8 ng/ml) and saliva (T2GMC: 12.9 ng/ml; T3GMC: 0.3 ng/ml). Consistently, serum IgA decreased (T2GMC: 48.6 ng/ml; T3GMC: 6.4 ng/ml); however, salivary IgA showed a different behaviour and increased (T2GMC: 0.06 ng/ml; T3GMC: 0.41 ng/ml), indicating a delayed activation of mucosal immunity. The booster elicited higher titres of both IgG and IgA when compared with the primary cycle, in both serum (IgG T4GMC: 98,493.9 ng/ml; IgA T4GMC: 187.5 ng/ml) and saliva (IgG T4GMC: 21.9 ng/ml; IgA T4GMC: 0.65 ng/ml). Moreover, the booster re-established the neutralizing activity in the serum of all individuals, not only against the Wuhan wild-type antigen (N = 50; INH: 91.6%) but also against the variants (Delta INH: 91.3%; Delta Plus INH: 89.8%; Omicron BA.1 INH: 85.1%). By contrast, the salivary neutralizing activity was high against the Wuhan antigen in 72% of individuals (N = 36, INH: 62.2%), but decreased against the variants, especially against the Omicron BA.1 variant (Delta N = 27, INH: 43.1%; Delta Plus N = 24, INH: 35.2%; Omicron BA.1 N = 4; INH: 4.7%). This was suggestive for a different behaviour of systemic immunity observed in serum with respect to mucosal immunity described in saliva (Wald chi-square test, 3 df of interaction between variants and sample type = 308.2, p < 0.0001). INTERPRETATION: The BNT162b2-booster vaccination elicits a strong systemic immune response but fails in activating an effective mucosal immunity against the Omicron BA.1 variant. FUNDING: This work was funded by the Department of Medicine and Surgery, University of Insubria, and supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020), Italy.

Risk prediction of atrial fibrillation and its complications in the community using hs troponin I.

AIMS: Atrial fibrillation (AF) is becoming increasingly common. Traditional cardiovascular risk factors (CVRF) do not explain all AF cases. Blood-based biomarkers reflecting cardiac injury such as high-sensitivity troponin I (hsTnI) may help close this gap. METHODS: We investigated the predictive ability of hsTnI for incident AF in 45,298 participants (median age 51.4 years, 45.0% men) across European community cohorts in comparison to CVRF and established biomarkers (C-reactive protein, N-terminal pro B-type natriuretic peptide). RESULTS: During a median follow-up of 7.7 years, 1734 (3.8%) participants developed AF. Those in the highest hsTnI quarter (≥4.2 ng/L) had a 3.91-fold (95% confidence interval (CI) 3.30, 4.63; p < .01) risk for developing AF compared to the lowest quarter (<1.4 ng/L). In multivariable-adjusted Cox proportional hazards models a statistically significant association was seen between hsTnI and AF (hazard ratio (HR) per 1 standard deviation (SD) increase in log10(hsTnI) 1.08; 95% CI 1.01, 1.16; p = .03). Inclusion of hsTnI did improve model discrimination (C-index CVRF 0.811 vs. C-index CVRF and hsTnI 0.813; p < .01). Higher hsTnI concentrations were associated with heart failure (HR per SD 1.37; 95% CI 1.12, 1.68; p < .01) and overall mortality (HR per SD 1.24; 95% CI 1.09, 1.41; p < .01). CONCLUSION: hsTnI as a biomarker of myocardial injury does not improve prediction of AF incidence beyond classical CVRF and NT-proBNP. However, it is associated with the AF-related disease heart failure and mortality likely reflecting underlying subclinical cardiovascular impairment.

Exploring the incremental utility of circulating biomarkers for robust risk prediction of incident atrial fibrillation in European cohorts using regressions and modern machine learning methods.

AIMS: To identify robust circulating predictors for incident atrial fibrillation (AF) using classical regressions and machine learning (ML) techniques within a broad spectrum of candidate variables. METHODS AND RESULTS: In pooled European community cohorts (n = 42 280 individuals), 14 routinely available biomarkers mirroring distinct pathophysiological pathways including lipids, inflammation, renal, and myocardium-specific markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI]) were examined in relation to incident AF using Cox regressions and distinct ML methods. Of 42 280 individuals (21 843 women [51.7%]; median [interquartile range, IQR] age, 52.2 [42.7, 62.0] years), 1496 (3.5%) developed AF during a median follow-up time of 5.7 years. In multivariable-adjusted Cox-regression analysis, NT-proBNP was the strongest circulating predictor of incident AF [hazard ratio (HR) per standard deviation (SD), 1.93 (95% CI, 1.82-2.04); P < 0.001]. Further, hsTnI [HR per SD, 1.18 (95% CI, 1.13-1.22); P < 0.001], cystatin C [HR per SD, 1.16 (95% CI, 1.10-1.23); P < 0.001], and C-reactive protein [HR per SD, 1.08 (95% CI, 1.02-1.14); P = 0.012] correlated positively with incident AF. Applying various ML techniques, a high inter-method consistency of selected candidate variables was observed. NT-proBNP was identified as the blood-based marker with the highest predictive value for incident AF. Relevant clinical predictors were age, the use of antihypertensive medication, and body mass index. CONCLUSION: Using different variable selection procedures including ML methods, NT-proBNP consistently remained the strongest blood-based predictor of incident AF and ranked before classical cardiovascular risk factors. The clinical benefit of these findings for identifying at-risk individuals for targeted AF screening needs to be elucidated and tested prospectively.

Association of nutritional glycaemic indices with global DNA methylation patterns: results from the Moli-sani cohort.

BACKGROUND: High dietary glycaemic index (GI) and load (GL) have been associated with increased risk of various cardiometabolic conditions. Among the molecular potential mechanisms underlying this relationship, DNA methylation has been studied, but a direct link between high GI and/or GL of diet and global DNA methylation levels has not been proved yet. We analyzed the associations between GI and GL and global DNA methylation patterns within an Italian population. RESULTS: Genomic DNA methylation (5mC) and hydroxymethylation (5hmC) levels were measured in 1080 buffy coat samples from participants of the Moli-sani study (mean(SD) = 54.9(11.5) years; 52% women) via ELISA. A 188-item Food Frequency Questionnaire was used to assess food intake and dietary GI and GL for each participant were calculated. Multiple linear regressions were used to investigate the associations between dietary GI and GL and global 5mC and 5hmC levels, as well as the proportion of effect explained by metabolic and inflammatory markers. We found negative associations of GI with both 5mC (ß (SE) = - 0.073 (0.027), p = 0.007) and 5hmC (- 0.084 (0.030), p = 0.006), and of GL with 5mC (- 0.14 (0.060), p = 0.014). Circulating biomarkers did not explain the above-mentioned associations. Gender interaction analyses revealed a significant association of the gender-x-GL interaction with 5mC levels, with men showing an inverse association three times as negative as in women (interaction ß (SE) = - 0.16 (0.06), p = 0.005). CONCLUSIONS: Our findings suggest that global DNA methylation and hydroxymethylation patterns represent a biomarker of carbohydrate intake. Based on the differential association of GL with 5mC between men and women, further gender-based separate approaches are warranted.

The North Italian Longitudinal Study Assessing the Mental Health Effects of SARS-CoV-2 Pandemic on Health Care Workers-Part I: Study Design and Psychometric Structural Validity of the HSE Indicator Tool and Work Satisfaction Scale.

Literature on the impact of the SARS-CoV-2 pandemic on the mental health of Health Care Workers (HCWs) is mostly based on cross-sectional surveys. We designed a longitudinal study to assess work-related stress and mental health before and after the pandemic onset in a university-hospital in Lombardia region, Italy. We report on sample representativeness and structural validity of questionnaires assessing work stress (HSE Indicator Tool, HSE-IT) and work satisfaction (WS), which were not validated in the HCWs population. n = 1287 HCWs from 67 hospital wards/offices were invited to an online survey in summer 2019 (pre-COVID-19 wave) and again during winter 2020 (COVID-19 wave). Selected hospital wards/offices did not differ from the remaining wards for turn-over and down-sizing rates, overload, sick leaves, and night shifts (Wilcoxon rank tests p-values > 0.05). Participation rates were 70% (n = 805) and 60% (n = 431) in the pre-COVID-19 and COVID-19 waves, respectively. Socio-demographic and work-related characteristics did not impact data completeness nor participation to the COVID-19 wave. While confirming a 7-component structure for HSE-IT, we identified a new factor related to participation in work organization. A one-factor model for WS had satisfactory fit. Our longitudinal study based on a representative sample and adopting validated questionnaires is well-suited to elucidate the role of work conditions on the development of mental health disorders in HCWs.

Correlates of bitter, sweet, salty and umami taste sensitivity in European children: Role of sex, age and weight status - The IDEFICS study.

We aimed to describe differences in taste sensitivity in children according to age across 7- to 11-year-old children from eight European countries. We further compared taste sensitivity between boys vs. girls and under-/normal weight vs. overweight/obese children. Within the European multicentre IDEFICS (Identification and prevention of dietary and lifestyle-induced health effects in children and infants) study, 1938 school children participated in sweet, bitter, salty and umami detection threshold tests between 2007 and 2010, using the paired comparison staircase method. The lowest concentration at which the child was able to detect a difference to water was determined as taste detection threshold as a proxy of taste sensitivity. Mean taste thresholds were calculated stratified for sex, age groups, weight groups and country. BMI was calculated using measured height and weight; socio-demographic information was collected using questionnaires. Ordinal logistic regressions were conducted to investigate the association between sex, weight status (as categorical exposure variable) and age (as continuous exposure variable) and the taste sensitivity for the four taste modalities (as outcome), separately. Older children were more taste sensitive for sweet and salty and less taste sensitive for umami and bitter than younger children. Girls were more sensitive to sweet taste than boys. Overweight or obese children were less sensitive to sweet and salty taste compared to normal weight children This was the first study comparing taste sensitivity by measuring taste thresholds in children across different European countries. We conclude that taste thresholds are associated with weight status, children become more sensitive to sweet and salty tastes with increasing age, and girls might be more sensitive to sweet than boys.

Changes in a Mediterranean lifestyle during the COVID-19 pandemic among elderly Italians: an analysis of gender and socioeconomic inequalities in the "LOST in Lombardia" study.

Little is known on potential socioeconomic and gender disparities in dietary changes during the COVID-19 pandemic. We conducted a telephone-based survey during fall 2020 on 4400 participants representative of the population aged 65-99 years living in Lombardy, Italy. Changes in a Mediterranean lifestyle were assessed retrospectively by scoring modifications in the consumption of nine food groups and five diet-related behaviours compared to 2019. A Mediterranean COVID-19 Pandemic Score (MedCovid-19 Score) was computed, reflecting changes during pandemic, with increasing values indicating improvements in line with a Mediterranean lifestyle. Predictors of favourable dietary changes (MedCovid-19 Score ≥ 1) were education (odds ratio [OR] = 1.52; 95% confidence interval 1.19-1.95 for postgraduate vs. lower), wealth (OR = 1.52; 1.14-2.02 for high vs. low) and skilled manual occupations (OR = 1.57; 1.28-1.92 vs. white collars). Women were more likely than men to move away from a Mediterranean lifestyle (OR = 1.86; 1.58-2.21). In conclusions, changes towards a Mediterranean lifestyle were disproportionately distributed across gender and socioeconomic strata.

Risk Factors, Subsequent Disease Onset, and Prognostic Impact of Myocardial Infarction and Atrial Fibrillation.

Background Although myocardial infarction (MI) and atrial fibrillation (AF) are frequent comorbidities and share common cardiovascular risk factors, the direction and strength of the association of the risk factors with disease onset, subsequent disease incidence, and mortality are not completely understood. Methods and Results In pooled multivariable Cox regression analyses, we examined temporal relations of disease onset and identified predictors of MI, AF, and all-cause mortality in 108 363 individuals (median age, 46.0 years; 48.2% men) free of MI and AF at baseline from 6 European population-based cohorts. During a maximum follow-up of 10.0 years, 3558 (3.3%) individuals were diagnosed exclusively with MI, 1922 (1.8%) with AF but no MI, and 491 (0.5%) individuals developed both MI and AF. Association of sex, systolic blood pressure, antihypertensive treatment, and diabetes appeared to be stronger with incident MI than with AF, whereas increasing age and body mass index showed a higher risk for incident AF. Total cholesterol and daily smoking were significantly related to incident MI but not AF. Combined population attributable fraction of cardiovascular risk factors was >70% for incident MI, whereas it was only 27% for AF. Subsequent MI after AF (hazard ratio [HR], 1.68; 95% CI, 1.03-2.74) and subsequent AF after MI (HR, 1.75; 95% CI, 1.31-2.34) both significantly increased overall mortality risk. Conclusions We observed different associations of cardiovascular risk factors with both diseases indicating distinct pathophysiological pathways. Subsequent diagnoses of MI and AF significantly increased mortality risk.

Psychological Resilience, Cardiovascular Disease, and Metabolic Disturbances: A Systematic Review.

Background: Positive psychosocial factors can play an important role in the development of cardiovascular disease (CVD). Among them, psychological resilience (PR) is defined as the capacity of responding positively to stressful events. Our aim was to assess whether PR is associated with CVD or metabolic disturbances through a systematic review. Methods: We gathered articles from PubMed, Web of Science, PsycInfo, and Google Scholar up to October 28, 2021. We included articles that were in English, were observational, and had PR examined as exposure. The CVD outcomes were either clinical or metabolic outcomes (i.e., dyslipidemia, obesity, metabolic syndrome, hypertension, and diabetes). Results: Our literature search identified 3,800 studies, of which 17 met the inclusion criteria. Of them, seven were longitudinal and 10 cross-sectional, and 13 were on adults and four on children. The exposure assessment was heterogeneous, i.e., 12 studies used different kinds of self-administered questionnaires and five used interviews with a psychologist. Regarding outcomes, five studies investigated CVD, seven obesity, one metabolic syndrome, two hypertension, four dyslipidemia, and four diabetes. In longitudinal studies, PR was found to have an inverse association with included outcomes in five studies from the Swedish military conscription cohort but had no association with CVD in a study on African-American women and was associated with slower progression of diabetes in a general population. The cross-sectional studies showed that the prevalence of disease was not associated with PR in many cases but the progression of disease was associated with PR. Conclusion: PR seems to have a possibly favorable association with CVD and metabolic disturbances that differs according to the type of outcome and population. Our study limitations are given by the small number of studies available and the heterogeneity in PR measurement. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=237109], identifier [CRD42021237109].

Fine-grained investigation of the relationship between human nutrition and global DNA methylation patterns.

PURPOSE: Nutrition is an important, modifiable, environmental factor affecting human health by modulating epigenetic processes, including DNA methylation (5mC). Numerous studies investigated the association of nutrition with global and gene-specific DNA methylation and evidences on animal models highlighted a role in DNA hydroxymethylation (5hmC) regulation. However, a more comprehensive analysis of different layers of nutrition in association with global levels of 5mC and 5hmC is lacking. We investigated the association between global levels of 5mC and 5hmC and human nutrition, through the stratification and analysis of dietary patterns into different nutritional layers: adherence to Mediterranean diet (MD), main food groups, macronutrients and micronutrients intake. METHODS: ELISA technique was used to measure global 5mC and 5hmC levels in 1080 subjects from the Moli-sani cohort. Food intake during the 12 months before enrolment was assessed using the semi-quantitative EPIC food frequency questionnaire. Complementary approaches involving both classical statistics and supervised machine learning analyses were used to investigate the associations between global 5mC and 5hmC levels and adherence to Mediterranean diet, main food groups, macronutrients and micronutrients intake. RESULTS: We found that global DNA methylation, but not hydroxymethylation, was associated with daily intake of zinc and vitamin B3. Random Forests algorithms predicting 5mC and 5hmC through intakes of food groups, macronutrients and micronutrients revealed a significant contribution of zinc, while vitamin B3 was reported among the most influential features. CONCLUSION: We found that nutrition may affect global DNA methylation, suggesting a contribution of micronutrients previously implicated as cofactors in methylation pathways.