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.

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.

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.

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.

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.

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.

Alcohol consumption, cardiac biomarkers, and risk of atrial fibrillation and adverse outcomes.

AIMS: There is inconsistent evidence on the relation of alcohol intake with incident atrial fibrillation (AF), in particular at lower doses. We assessed the association between alcohol consumption, biomarkers, and incident AF across the spectrum of alcohol intake in European cohorts. METHODS AND RESULTS: In a community-based pooled cohort, we followed 107 845 individuals for the association between alcohol consumption, including types of alcohol and drinking patterns, and incident AF. We collected information on classical cardiovascular risk factors and incident heart failure (HF) and measured the biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I. The median age of individuals was 47.8 years, 48.3% were men. The median alcohol consumption was 3 g/day. N = 5854 individuals developed AF (median follow-up time: 13.9 years). In a sex- and cohort-stratified Cox regression analysis alcohol consumption was non-linearly and positively associated with incident AF. The hazard ratio for one drink (12 g) per day was 1.16, 95% CI 1.11-1.22, P < 0.001. Associations were similar across types of alcohol. In contrast, alcohol consumption at lower doses was associated with reduced risk of incident HF. The association between alcohol consumption and incident AF was neither fully explained by cardiac biomarker concentrations nor by the occurrence of HF. CONCLUSIONS: In contrast to other cardiovascular diseases such as HF, even modest habitual alcohol intake of 1.2 drinks/day was associated with an increased risk of AF, which needs to be considered in AF prevention.

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.

Identification of dietary patterns in a general population of North Italian adults and their association with arterial stiffness. The RoCAV study.

BACKGROUND AND AIMS: The aims of this study were to identify dietary patterns in a general population of North Italian adults and to investigate the cross-sectional association between prevalent dietary patterns and arterial stiffness. METHODS AND RESULTS: Participants to the RoCAV study without chronic diseases at recruitment and with reliable dietary data were included. The food-frequency EPIC questionnaire was used to evaluate dietary habits. Dietary patterns were estimated using principal components analysis and Mediterranean diet adherence score (MedS). Carotid-femoral pulse wave velocity (cfPWV) was used as proxy of arterial stiffness. Basing on data from 2640 subjects (1608 men and 1032 women, mean ± SD 65.5 ± 6.7 years), four principal components (PC) were retained, explaining 24% of the overall variance. Considering 1284 subjects with cfPWV (mean ± SD 10.7 ± 2.5 m/s) data available, adherence to PC1 (Western-like dietary pattern) was associated with higher stiffness values (+0.29 m/s cfPWV for 1 SD increase of PC1, 95% CI:0.08,0.50; p = 0.007) in a multivariate model. Conversely, adherence to PC2 (Mediterranean-like) was not related to cfPWV values (-0.18, 95% CI: -0.36, 0.004; p = 0.06). Likewise, MedS and other PC patterns did not show any significant association with cfPWV. Mediation analysis showed that the association between Western-like dietary pattern and cfPWV is mediated by higher levels of leucocytes (9.2% of the effect, p = 0.047). CONCLUSIONS: Our study in a Southern European population identified a Western-like dietary pattern associated with an increased cfPWV, a proxy of arterial stiffness. The association with cfPWV was in part mediated by inflammatory status.

Occupational class differences in ankle-brachial index and pulse wave velocity measurements to detect subclinical vascular disease.

BACKGROUND: High pulse wave velocity (PWV) and low ankle brachial index (ABI) have been proposed as surrogate end-points for cardiovascular disease (CVD). OBJECTIVES: In a cross-sectional setting, we aimed at assessing the distributions of PWV and ABI among occupational classes (OC) in a population-based ever-employed salaried sample. METHODS: We enrolled 1388 salaried CVD-free workers attending a CVD population-based survey, the RoCAV study, and classified them into four OC, based on current or last job title: manager/director (MD), non-manual (NMW), skilled-manual (SMW) and (UMW) unskilled-manual workers. We derived brachial-ankle PWV and ABI from four-limb blood pressures measurements, then carotid-femoral PWV (cfPWV) was estimated. We estimated the OC gradients in cfPWV and ABI using linear and logistic regression models. RESULTS: Compared to MD (reference category), UMW had higher age- and BMI-adjusted cfPWV mean values both in men (0.63 m/s; 95%CI:0.11-1.16) and women (1.60 m/s; 0.43-2.77), only marginally reduced when adjusting for CVD risk factors. Decreased ABI mean values were also detected in lower OC. The overall detection rate of abnormal cfPWV (≥12 m/s) or ABI (≤0.9) values was 28%. Compared to MD, the prevalence of abnormal cfPWV or ABI was higher in NMW (OR=1.77; 95%CI:1.12-2.79), SMW (1.71; 1.05-2.78) and UMW (2.72; 1.65-4.50). Adjustment for CVD risk factors used in risk score equations did not change the results. DISCUSSION: We found a higher prevalence of abnormal values of arterial stiffness measures in lower OC, and these differences were not explained by traditional CVD risk factors. These may be presumably determined by additional work- and environmental-related risk factors.

Cardiac Troponin I and Incident Stroke in European Cohorts: Insights From the BiomarCaRE Project.

BACKGROUND AND PURPOSE: Stroke is a common cause of death and a leading cause of disability and morbidity. Stroke risk assessment remains a challenge, but circulating biomarkers may improve risk prediction. Controversial evidence is available on the predictive ability of troponin concentrations and the risk of stroke in the community. Furthermore, reports on the predictive value of troponin concentrations for different stroke subtypes are scarce. METHODS: High-sensitivity cardiac troponin I (hsTnI) concentrations were assessed in 82 881 individuals (median age, 50.7 years; 49.7% men) free of stroke or myocardial infarction at baseline from 9 prospective European community cohorts. We used Cox proportional hazards regression to determine relative risks, followed by measures of discrimination and reclassification using 10-fold cross-validation to control for overoptimism. Follow-up was based upon linkage with national hospitalization registries and causes of death registries. RESULTS: Over a median follow-up of 12.7 years, 3033 individuals were diagnosed with incident nonfatal or fatal stroke (n=1654 ischemic strokes, n=612 hemorrhagic strokes, and n=767 indeterminate strokes). In multivariable regression models, hsTnI concentrations were associated with overall stroke (hazard ratio per 1-SD increase, 1.15 [95% CI, 1.10-1.21]), ischemic stroke (hazard ratio, 1.14 [95% CI, 1.09-1.21]), and hemorrhagic stroke (hazard ratio, 1.10 [95% CI, 1.01-1.20]). Adding hsTnI concentrations to classical cardiovascular risk factors (C indices, 0.809, 0.840, and 0.736 for overall, ischemic, and hemorrhagic stroke, respectively) increased the C index significantly but modestly. In individuals with an intermediate 10-year risk (5%-20%), the net reclassification improvement for overall stroke was 0.038 (P=0.021). CONCLUSIONS: Elevated hsTnI concentrations are associated with an increased risk of incident stroke in the community, irrespective of stroke subtype. Adding hsTnI concentrations to classical risk factors only modestly improved estimation of 10-year risk of stroke in the overall cohort but might be of some value in individuals at an intermediate risk.

Temporal relations between atrial fibrillation and ischaemic stroke and their prognostic impact on mortality.

AIMS: Limited evidence is available on the temporal relationship between atrial fibrillation (AF) and ischaemic stroke and their impact on mortality in the community. We sought to understand the temporal relationship of AF and ischaemic stroke and to determine the sequence of disease onset in relation to mortality. METHODS AND RESULTS: Across five prospective community cohorts of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project we assessed baseline cardiovascular risk factors in 100 132 individuals, median age 46.1 (25th-75th percentile 35.8-57.5) years, 48.4% men. We followed them for incident ischaemic stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Over a median follow-up of 16.1 years, N = 4555 individuals were diagnosed solely with AF, N = 2269 had an ischaemic stroke but no AF diagnosed, and N = 898 developed both, ischaemic stroke and AF. Temporal relationships showed a clustering of diagnosis of both diseases within the years around the diagnosis of the other disease. In multivariable-adjusted Cox regression analyses with time-dependent covariates subsequent diagnosis of AF after ischaemic stroke was associated with increased mortality [hazard ratio (HR) 4.05, 95% confidence interval (CI) 2.17-7.54; P < 0.001] which was also apparent when ischaemic stroke followed after the diagnosis of AF (HR 3.08, 95% CI 1.90-5.00; P < 0.001). CONCLUSION: The temporal relations of ischaemic stroke and AF appear to be bidirectional. Ischaemic stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Future research needs to investigate the common underlying systemic disease processes.

Correction of QRS voltage for body mass index does not improve the prediction of fatal and nonfatal cardiovascular events. The Moli-sani study.

BACKGROUND AND AIMS: The diagnosis of LVH by ECG may particularly difficult in obese individuals. The aim of this study was to prospectively investigate whether the correction for body mass index (BMI) might improve the prognostic significance for cerebro and cardiovascular events of two electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) in a large cohort of Italian adults. METHODS AND RESULTS: In 18,330 adults (54 ± 11 years, 55% women) from the Moli-sani cohort, obesity was defined using the ATPIII criteria. The Sokolow-Lyon (SL) and Cornell Voltage (CV) criteria were used for ECG-LVH. In overweight and obese subjects, as compared with normal weight, the prevalence of ECG-LVH by the SL index was lower. During follow-up (median 4.3 yrs), 503 cerebro and cardiovascular events occurred. One standard deviation (1-SD) increment in uncorrected and in BMI-corrected SL index and CV was associated with an increased risk of events (HR 1.12, 95% CI 1.02-1.22 and HR 1.16, 95% CI 1.06-1.26 and HR 1.12, 95% CI 1.03-1.23 and HR 1.17, 95% CI 1.07-1.27, respectively for SL and CV). In obese subjects, 1-SD increment in uncorrected CV and in BMI-corrected CV was not associated to a significant risk of events (HR 1.05, 95% CI 0.910-1.22 and HR 1.08, 95% CI 0.95-1.23 respectively). Uncorrected SL index showed a significant association with events, which was marginally stronger with BMI-corrected SL voltage (HR 1.18, 95% CI 1.02-1.37 and HR 1.17, 95% CI 1.04-1.33 respectively, Akaike information criterion change from 3220 to 3218). CONCLUSIONS: BMI correction of ECG LVH voltage criteria does not significantly improve the prediction of cerebro and cardiovascular events in obese patients in a large cohort at low cardiovascular risk.

Association between variants of neuromedin U gene and taste thresholds and food preferences in European children: Results from the IDEFICS study.

AIM: The neuropeptide neuromedin U (NMU) known for its role in appetite, feeding and energy balance could be involved in the control of food choice and taste sensitivity. We examined the association between NMU polymorphisms/haplotypes and taste thresholds and food preferences in a population of European children. METHODS: A total of 578 subjects from the IDEFICS study (mean age 7.5 ±â€¯0.8 SD, boys 53.6%) with NMU genotype data and food preference (salty, fatty, sweet, flavour and umami food) and taste threshold (salt, fat, sweet, umami) tests available were analysed. Three single nucleotide polymorphisms (SNPs; rs6827359, T:C; rs12500837, T:C; rs9999653, C:T) of NMU gene were analyzed and five major haplotypes were inferred. The associations between genotypes and food preferences or taste thresholds were investigated (odds ratios -OR, adjusted for age, sex and country). A p < 0.05 after false discovery rate adjustment (pFDR) was considered statistically significant. RESULTS: The association between NMU genotypes and food preference showed two NMU SNPs associated with preference for food containing sodium glutamate (umami taste; rs6827359C, OR = 1.61, 95% confidence interval (CI):1.20-2.17; rs9999653T, OR = 1.59, 95%CI:1.18-2.13). In the haplotype analysis, the CTT haplotype showed an OR of 1.70 (95%CI:1.16-2.5) for the umami food preference, while CCT haplotype showed an OR of 1.63 (95%CI:1.11-2.40), compared to the most frequent haplotype (TTC). Carriers of CCT/CCT vs subjects with no CCT haplotype showed an OR of 4.78 (95%CI:1.86-12.30). Umami food preference was associated with low values of BMI z-score, arm circumferences, skinfolds and fat mass (pFDR<0.05). No association between NMU genetic variants and taste thresholds was found. CONCLUSIONS: This study shows for the first time in children an association between preference for umami food and a NMU haplotype, previously found associated with low BMI values.

Sex Differences and Similarities in Atrial Fibrillation Epidemiology, Risk Factors, and Mortality in Community Cohorts: Results From the BiomarCaRE Consortium (Biomarker for Cardiovascular Risk Assessment in Europe).

BACKGROUND: Atrial fibrillation (AF) is a common cardiac disease in aging populations with high comorbidity and mortality. Sex differences in AF epidemiology are insufficiently understood. METHODS: In N=79 793 individuals without AF diagnosis at baseline (median age, 49.6 years; age range, 24.1-97.6 years; 51.7% women) from 4 community-based European studies (FINRISK, DanMONICA, Moli-sani Northern Sweden) of the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), we examined AF incidence, its association with mortality, common risk factors, biomarkers, and prevalent cardiovascular disease, and their attributable risk by sex. Median follow-up time was 12.6 (to a maximum of 28.2) years. RESULTS: Fewer AF cases were observed in women (N=1796; 4.4%), than in men (N=2465; 6.4%). Cardiovascular risk factor distribution and lipid profile at baseline were less beneficial in men than in women, and cardiovascular disease was more prevalent in men. Cumulative incidence increased markedly after the age of 50 years in men and after 60 years in women. The lifetime risk was similar (>30%) for both sexes. Subjects with incident AF had a 3.5-fold risk of death in comparison with those without AF. Multivariable-adjusted models showed sex differences for the association of body mass index and AF (hazard ratio per standard deviation increase, 1.18; 95% confidence interval [CI], 1.12-1.23 in women versus 1.31; 95% CI 1.25-1.38 in men; interaction P value of 0.001). Total cholesterol was inversely associated with incident AF with a greater risk reduction in women (hazard ratio per SD, 0.86; 95% CI, 0.81-0.90 versus 0.92; 95% CI, 0.88-0.97 in men; interaction P value of 0.023). No sex differences were seen for C-reactive protein and N-terminal pro B-type natriuretic peptide. The population-attributable risk of all risk factors combined was 41.9% in women and 46.0% in men. About 20% of the risk was observed for body mass index. CONCLUSIONS: Lifetime risk of AF was high, and AF was strongly associated with increased mortality both in women and men. Body mass index explained the largest proportion of AF risk. Observed sex differences in the association of body mass index and total cholesterol with AF need to be evaluated for underlying pathophysiology and relevance to sex-specific prevention strategies.

Prevalence of Abdominal Aortic Aneurysms in the General Population and in Subgroups at High Cardiovascular Risk in Italy. Results of the RoCAV Population Based Study.

OBJECTIVES: Prevalence data on abdominal aortic aneurysm (AAA) in women, subjects younger than 65 years and in subgroups carrying specific risk factors are scarce. AAA prevalence was evaluated in an Italian population including women and younger subjects, stratifying for the presence of cardiovascular disease (CVD) risk factors and CVD risk score. MATERIALS AND METHODS: A population based cross-sectional study was conducted between 2013 and 2016. Men aged 50-75 and women aged 60-75 years, resident in the city of Varese (northern Italy), were randomly selected from the civil registry. A vascular surgeon performed an abdominal aortic ultrasound scan at four sites using the leading edge to leading edge method. CVD risk score was computed using the ESC-SCORE algorithm. The age and gender specific prevalence was estimated, stratifying by the presence of CVD and cardiovascular risk factors. RESULTS: Among the 3755 subjects with a valid ultrasound measurement, 63 subjects with an AAA were identified (5 referred for surgical intervention), among whom 34 were not previously known (30 men 1.3%, 95% CI 0.9-1.8; 4 women 0.3%, 95% CI 0.1-0.8). Considering age classes in men only, the highest prevalence of screen detected AAA was found in subjects aged 65-70 (1.2%; 95% CI 0.4-2.5) and 70-75 (2.5%; 95% CI 1.4-4.0) years. Among 65-75 year old men, the highest AAA prevalence was found in subjects with a previous myocardial infarction (MI 4.9%, 95% CI 2.0-9.9) and in ever-smokers reporting more than 15 pack years of smoking (4.1%, 95% CI 2.5-6.3). Among the younger subjects, those having an ESC-SCORE higher than 5% or a previous CVD (MI or stroke) showed a prevalence of 1.4% (95% CI 0.3-4.2; prevalence including subaneurysms 6.7%, 95% CI 3.7-11.0%). CONCLUSIONS: In the study population, both a general screening program in 65-75 year old men and an approach targeted to subgroups at higher risk merit evaluation in a cost-effectiveness study. In 50-64 year old men, strategies for population selection should consider CVD risk stratification tools.

Body Mass Index and Mortality in Elderly Subjects from the Moli-Sani Study: A Possible Mediation by Low-Grade Inflammation?

The association between obesity and mortality in the elderly remains controversial. To test the association between BMI and mortality, with the hypothesis of a mediation by low-grade inflammation (LGI), a prospective study design (median follow-up 7.8 years) was used on a sample of 4,970 elderly subjects (age ≥ 65 years) from the Moli-sani Study cohort. The association between BMI categories and overall or cause-specific mortality (hazard ratio, HR) was calculated by multivariable Cox regression. Dose-response relationship was tested using restricted cubic splines. Interaction between BMI and LGI, assessed through high-sensitivity C-reactive protein (hs-CRP) and INFLA-score, was also tested. In comparison with normal-weight, overweight was significantly associated with a 20% (adjusted HR = 0.80; 95%CI 0.67-0.95) reduced risk of total mortality, while severe obesity (BMI > 40) with an increased risk (HR = 1.81; 95%CI 1.13-2.93). Cubic spline curves showed a U-shaped relationship between BMI and total mortality (p value for nonlinear relationship = 0.001). Similar results were found for cardio-cerebrovascular and other causes mortality. Hs-CRP and INFLA-score were associated with an increased risk of total mortality in adjusted analyses. Mediation analysis did not show any effect of LGI on the association between BMI and mortality. However, after stratification for LGI under or below the population median, greater LGI increased the risk of mortality in obese elderly more than expected (p for interaction = 0.04). A U-shaped association between BMI and mortality was observed in Italian elderly subjects. While the association was independent of LGI levels, there was a significant interaction between BMI and LGI in increasing mortality risk in obese elderly individuals.

Monitoring quality of care in acute myocardial infarction patients using retrospective registry data.

BACKGROUND: Hospital-based registries provide a key contribution in assessing the quality of care in acute myocardial infarction (MI) patients, although some concern on selection bias of included cases has recently arisen. We investigated the feasibility of a retrospective, population-based registry of MIs in monitoring the quality of care. METHODS: We identified all the hospitalizations with a diagnosis of acute MI among 35-79 years old residents in the Varese province, Northern Italy, in 2007-2008. Information needed to define performance according to the American Heart Association set was extracted from hospital case histories. To characterize our approach, we focus on data completeness for critical event times and eligibility criteria, and on the analysis of ST-elevated MI (STEMI) patients according to received reperfusion treatment. RESULTS: Exact time of hospital admission and of percutaneous coronary angioplasty (PCI) procedure was available in 96% and 77% of MIs, with no difference between non-transferred (n = 1399) and inter-hospital transferred (n = 300) patients. Data completeness for eligibility to action/treatment criteria was >90% for each performance measure except statin prescription at discharge (76%). About 45% of STEMI experienced a delay in PCI-capable hospital arrival, and only one every three ST-elevated MI patients received primary PCI; these were more likely to be younger male cases with less comorbidities than un-treated patients. CONCLUSIONS: Complementary to clinical registries, the retrospective population-based is a feasible approach which allows monitoring the entire pattern of care of all hospitalized MI patients independent of their clinical characteristics.

From directive to practice: are pictorial warnings and plain packaging effective to reduce the tobacco addiction?

OBJECTIVES: Tobacco packaging represents an important form of promotion of tobacco products and for this reason plain packaging (PP) can be considered an additional tobacco control measure. In Italy the current tobacco packaging is branded with textual warnings. The study investigated the perception of PP with textual warnings (PPTWs) and pictorial warnings (PPPWs) in Italy. STUDY DESIGN: Cross-sectional. METHODS: The study was conducted on adults who were current, never and former smokers. The participants watched out three types of packages (current packaging, PPTWs and PPPWs) and eight pictorial warnings, and indicated which they considered the most effective ones to motivate smoking cessation or reduction and to prevent the onset. RESULTS: 1065 subjects were recruited. The PPPWs were considered the most effective in motivating to quit, reduce and prevent the smoking habits (ranged 83.4%-96.1%) in all tobacco users and age groups (≤40/>40 years) (P < 0.005). In general PP does not seem to be very effective in quitting for three-quarters of the smokers and 60% declared that they would have still started smoking with PP. The younger group believed less than the older one that PP gives a motivation to quit (29.4% vs 39.1%, P = 0.002). The pictures perceived as most effective in communicating the smoking effects were lung cancer and gangrene (about one-third of the sample). CONCLUSIONS: The textual warnings on tobacco products are a measure of control now outdated. Countries still using them should consider the idea of replace them with pictorial warnings that seem to be more effective. It is also desirable in the near future that these countries introduce the PPPWs.