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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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate in an Italian general population, the association with mortality of a traditional Mediterranean diet (MD) and non-Mediterranean dietary (non-MD) patterns, and their combined effect, and to test some biomarkers of cardiovascular (CVD) risk as potential mediators of such associations. Methods: Longitudinal analysis on 22,849 men and women aged ≥ 35 years, recruited in the Moli-sani Study (2005–2010), followed up for 8.2 years (median). The MD was assessed by the Mediterranean diet score (MDS). The Dietary Approaches to Stop Hypertension (DASH), the Palaeolithic diet, and the Nordic diet were chosen as reportedly healthy non-MD patterns. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated by multivariable Cox regression. Results: Participants reaching higher MDS or DASH diet score experienced lower risk of both all-cause (HR 0.77; 95% CI 0.66–0.90 and 0.81; 0.69–0.96, respectively, highest vs lowest quartile) and CVD (0.77; 0.59–1.00 and 0.81; 0.69–0.96, respectively) death risk; risk reduction associated with the Palaeolithic diet was limited to total and other cause death, whereas the Nordic diet did not alter risk of mortality. Increasing adherence to MD was associated with higher survival in each stratum of non-MD diets. Biomarkers of glucose metabolism accounted for 7% and 21.6% of the association between either MDS or DASH diet, respectively, with total mortality risk. Conclusions: Both the traditional MD and DASH diet may reduce risk of all-cause mortality among Italians, as well as risk of dying from cardiovascular causes. The Palaeolithic diet did not appear to reduce cardiovascular risk, while the Nordic eating pattern was unlikely to be associated with any substantial health advantage. [ABSTRACT FROM AUTHOR]

Background: An inverse relationship between coffee intake and mortality has been observed in several population cohorts, but rarely within Mediterranean countries. Moreover, the biological pathways mediating such an association remain unclear.Objectives: We assessed the associations between coffee consumption and total and cause-specific mortality and examined the mediating roles of N-terminal pro B-type natriuretic peptide (NTproBNP), high-sensitivity Troponin I, blood glucose, lipid metabolism, and selected biomarkers of inflammation and renal function.Methods: We longitudinally analyzed data on 20,487 men and women (35-94 years old at baseline) in the Moli-sani Study, a prospective cohort established in 2005-2010. Individuals were free from cardiovascular disease (CVD) and cancer and were followed-up for a median of 8.3 years. Dietary data were collected by a 188-item semi-quantitative FFQ. Coffee intake was standardized to a 30-mL Italian espresso cup size. HRs with 95% CIs were calculated by multivariable Cox regression.Results: In comparison with no/rare coffee consumption (up to 1 cup/d), HRs for all-cause mortality across categories of coffee consumption (>1 to ≤2, >2 to ≤3, >3 to ≤4 and >4 cups/d) were 0.79 (95% CI, 0.65-0.95), 0.84 (95% CI, 0.69-1.03), 0.72 (95% CI, 0.57-0.92), and 0.85 (95% CI, 0.62-1.12), respectively. For CVD mortality, a nonlinear (P for non-linearity = 0.021) J-shaped association was found (magnitude of the relative reduction = 37%; nadir at 3-4 cups/d). Circulating levels of NTproBNP explained up to 26.4% of the association between coffee and all-cause mortality, while systolic blood pressure was likely to be on the pathway between coffee and CVD mortality, although to a lesser extent.Conclusions: In this large cohort of Italian adults, moderate consumption (3-4 cups/d) of Italian-style coffee was associated with lower risks of all-cause and, specifically, of CVD mortality. Among the known biomarkers investigated here, NTproBNP likely mediates the relationship between coffee intake and all-cause mortality. [ABSTRACT FROM AUTHOR]

Background and objectives: The absence of obstructive coronary artery disease (CAD) in patients with angina is common, but its prognosis is debated. We investigated outcomes of such patients to identify predictors of cardiovascular events. Methods: We selected 1014 patients with angina, evidence of myocardial ischemia at the electrocardiogram (ECG) exercise test or imaging stress tests, and nonobstructive CAD (absence of lumen diameter reduction ≥50%) at coronary angiography between 1999 and 2015. Note that, 1905 age‐ and risk factors‐matched asymptomatic subjects served as "real‐world" comparators. The primary endpoint was the occurrence of all‐cause death or myocardial infarction. Results: At 6‐years median follow‐up (interquartile range, 3–9 years), the primary endpoint occurred in 53 patients (5.5%, 0.92/100 person‐years). Besides similar event rates compared with asymptomatic subjects (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.62–1.15, p = 0.28), the index population showed a very heterogeneous prognosis. Patients with nonobstructive CAD (HR 1.85, 95% CI 1.02–3.37, p = 0.04, compared with "normal" coronary arteries) and ischemia at imaging tests (HR 2.11, 95% CI 1.07–4.14, p = 0.03, compared with ischemia detected only at the ECG exercise test) were at higher risk and those with both these components showing even >10‐fold event rates as compared with the absence of both. Three‐hundred and twenty‐five patients (34%) continued to experience angina, 69 (7.2%) underwent repeat coronary angiography, and 14 (1.5%) had consequent coronary revascularization for atherosclerosis progression. Conclusion: Apart from the impaired quality of life, angina without obstructive CAD has an overall benign but very heterogeneous prognosis. Nonobstructive CAD and myocardial ischemia at imaging tests both confer a higher risk. [ABSTRACT FROM AUTHOR]

Aim: To test the association of alcohol consumption with total and cause‐specific mortality risk. Design Prospective observational multi‐centre population‐based study. Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. Participants: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). Measurements Average alcohol intake by food frequency questionnaire, total and cause‐specific mortality. Findings In comparison with life‐time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7–14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7–20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10–35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high‐density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. Conclusions: In comparison with life‐time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality. [ABSTRACT FROM AUTHOR]

Purpose: Dietary guidelines recommend to limit egg consumption to 4 servings per week but the relation between egg intake and health outcomes is still controversial. To evaluate the association of egg consumption and mortality risk in Italian adults and to investigate nutritional factors and serum lipids as potentially explaining such associations. Methods: Longitudinal analysis on 20,562 men and women aged ≥ 35y, free from cardiovascular disease (CVD) and cancer belonging to the Moli-sani Study cohort (enrolled 2005–2010) followed up for a median of 8.2 years. Results: In multivariable-adjusted analysis as compared to low intake (> 0 ≤ 1 egg/week), eating > 4 eggs/week led to an increased risk of all-cause (Hazard ratio [HR] = 1.50; 95%CI 1.13–1.99), CVD (HR = 1.75; 1.07–2.87) and cancer mortality (HR = 1.52; 0.99–2.33). Similarly, an intake of 2–4 eggs/week was associated with higher all-cause (HR = 1.22; 1.01–1.46) and CVD mortality risk (HR = 1.43; 1.03–1.97). An increase of 1 egg per week was associated with higher mortality risk among high-risk individuals, such as those with hypertension and hyperlipidaemia. Dietary cholesterol explained about 43.0% and 39.3% (p values < 0.0001) of the association of eggs with all-cause and CVD mortality, respectively, while serum lipids (e.g., total cholesterol) accounted for a small proportion of egg-mortality relation. Conclusions: Among Italian adults, high egg consumption leads to an increased risk of all-cause and CVD mortality, with the risk being evident even at the recommended intake of 2–4 eggs per week. A substantial part of this association was likely due to the egg contribution to dietary cholesterol. Our findings suggest limiting the consumption of eggs in the diet and these results should be considered in the development of dietary guidelines and updates. [ABSTRACT FROM AUTHOR]

Cardiovascular (CV) disease is preventable through interventions targeting modifiable factors. Most algorithms based on modifiable CV risk factors (CV-rf) have been developed in US populations and do not account for the role of diet. We aimed to assess an algorithm based on modifiable CV-rf including diet, using data from an Italian population. To derive the Moli-sani Risk Score (M RS), we used data on 16,656 men and women (age ≥ 35 y) from the population of the Moli-sani Study. The Risk-and-Prevention-Study, Italy (N = 8606) acted as external validation cohort and the Life's-Simple-7 score was used as benchmark. The M RS targeted at fatal or non-fatal CV events and included 9 common modifiable CV-rf. After 8.1 years (median) of follow-up, 816 events occurred in the derivation cohort. The M RS was calculated as a weighted sum of its 9 components, with weights reflecting the strength of the association. In comparison with individuals in the first, those in the fourth quartile of the score had hazard ratio (HR) for CV events equal to 3.18 (95%CI: 2.54–3.97). One more point in the score was associated with 7% (6%–8%) and 4% (3%–5%) higher hazard of events in the derivation and validation cohort, respectively. The M RS performed better than the Life's Simple-7 for discrimination. We propose the Moli-sani Risk Score, a validated, performing algorithm able to measure the combined impact that modifiable CV-rf have on CV risk. The score can be used to design preventive interventions, quantify the effectiveness of interventions, and compare different preventive strategies. • Vascular disease is preventable through interventions targeting modifiable factors. • A score of vascular modifiable risk factors is provided, based on European data. • The algorithm is able to measure the combined impact of modifiable risk factors. • The score can be used to quantify the effectiveness of preventive interventions. [ABSTRACT FROM AUTHOR]

Background: The link between systemic inflammation and depression has been deeply investigated, but relatively few studies explored symptom-specific associations, mostly focusing on common inflammatory biomarkers like C-reactive protein (CRP) levels.Methods: We investigated associations of low-grade inflammation with depressive symptoms assessed through a reduced version of Patient Health Questionnaire 9 (PHQ-9) in a large population-based cohort of adult Italians (N = 13 301). We built logistic regressions between each depressive symptom and composite index of systemic inflammation based on four circulating biomarkers, namely CRP, Plt, WBC, and GLR (INFLA)-score, a composite blood-based inflammation index, and with its component biomarkers, namely CRP, platelets count (Plt), white blood cells count (WBC), and granulocyte-to-lymphocyte ratio (GLR).Results: We observed a strong association of the altered appetite/eating symptom with standardized INFLA-score (OR [95% CI] = 1.19 [1.12-1.26]; corrected p = 3.0 × 10-7 ), CRP (1.28 [1.20-1.36]; p = 1.9 × 10-13 ), and WBC (1.13 [1.06-1.20]; p = 2.3 × 10-3 ), and of tiredness/low energy with GLR (1.11 [1.05-1.17]; p = 9.4 × 10-3 ). These associations remained stable within nondepressed participants (PHQ-9 < 10), and after adjustment for the use of antidepressants, main chronic conditions, and lifestyle factors; while they were notably attenuated within depressed participants (PHQ-9 ≥ 10) and-for altered appetite only-by adjustment for obesity.Conclusions: This study provides a robust replication of the association previously reported between CRP and altered appetite in a large US population cohort, and supports a link between systemic inflammation, altered appetite, and tiredness. Moreover, it extends this evidence to inflammatory markers other than CRP and suggests new targets for the treatment of atypical depression. [ABSTRACT FROM AUTHOR]

Background: Chili pepper is a usual part of a traditional Mediterranean diet. Yet epidemiological data on the association between chili pepper intake and mortality risk are scarce, with a lack of studies from Mediterranean populations.Objectives: This study sought to examine the association between chili pepper consumption and risk of death in a large sample of the adult Italian general population, and to account for biological mediators of the association.Methods: Longitudinal analysis was performed on 22,811 men and women enrolled in the Moli-sani Study cohort (2005 to 2010). Chili pepper intake was estimated by the EPIC (European Prospective Investigation Into Cancer) Food Frequency Questionnaire and categorized as none/rare consumption, up to 2 times/week, >2 to ≤4 times/week, and >4 times/week.Results: Over a median follow-up of 8.2 years, a total of 1,236 deaths were ascertained. Multivariable hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality among participants in the regular (>4 times/week) relative to none/rare intake were 0.77 (95% confidence interval [CI]: 0.66 to 0.90) and 0.66 (95% CI: 0.50 to 0.86), respectively. Regular intake was also inversely associated with ischemic heart disease (HR: 0.56; 95% CI: 0.35 to 0.87) and cerebrovascular (HR: 0.39; 95% CI: 0.20 to 0.75) death risks. The association of chili pepper consumption with total mortality appeared to be stronger in hypertension-free individuals (p for interaction = 0.021). Among known biomarkers of CVD, only serum vitamin D marginally accounted for such associations.Conclusions: In a large adult Mediterranean population, regular consumption of chili pepper is associated with a lower risk of total and CVD death independent of CVD risk factors or adherence to a Mediterranean diet. Known biomarkers of CVD risk only marginally mediate the association of chili pepper intake with mortality. [ABSTRACT FROM AUTHOR]

Background: Breakfast quality, together with regularity of breakfast, has been suggested to be associated with cardiometabolic health advantages. We aimed to evaluate the quality of breakfast and its socioeconomic and psychosocial correlates in a large sample of the Italian population. Methods: Cross-sectional analyses on 7,673 adult and 505 children/adolescent regular breakfast eaters from the Italian Nutrition & Health Survey (INHES; 2010-2013). Dietary data were collected through a single 24-h dietary recall. Breakfast quality was assessed through the Breakfast Quality Index (BQI) combining intake of ten food groups, energy, and nutrients of public health concern, and potentially ranging from 0 to 10. The association of sociodemographic and psychosocial factors with BQI were analyzed by multivariable-adjusted linear regression models. Results: The average BQI was 4.65 (SD ± 1.13) and 4.97 (SD ± 1.00) in adults and children/adolescents, respectively. Amongst adults, older age (β = 0.19; 95%CI 0.06 to 0.31 for > 65 vs. 20–40 years) and having a high educational level (β = 0.13; 0.03 to 0.23; for postsecondary vs. up to elementary) were independent predictors of better breakfast quality, while men reported lower BQI (β = -0.08; -0.14 to -0.02 vs. women). Perceived stress levels at home and work and financial stress were inversely associated with BQI. Children/adolescents living in Central and Southern Italian regions had lower BQI compared to residents in Northern Italy (β = -0.55; -0.91 to -0.19 and β = -0.24; -0.47 to -0.01, respectively). Conclusions: In adults, breakfast quality was associated with age, sex, and educational level. Perceived stress levels were inversely associated with the quality of breakfast. In children/adolescents, a north-south gradient in breakfast quality was observed. [ABSTRACT FROM AUTHOR]

Abstract Background Statins are prescribed for patients with cardiovascular disease (CVD), along with the recommendation of adopting healthy diets. We evaluated the independent and the combined effect of statins and Mediterranean diet (MD) towards mortality risk in patients with previous CVD by using real-life data from a population-based prospective cohort. Methods Longitudinal analysis on 1180 subjects (mean age 67.7 ± 10) with prior CVD at enrollment in the Moli-sani Study and followed up for 7.9 y (median). Adherence to MD was appraised by a Mediterranean diet score. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated by multivariable Cox regression and competing risk models. Results Multivariable risk estimates associated with a 2-point increase in MD score were 0.84 (95% CI 0.70–1.00), 0.77 (0.61–0.97) and 0.70 (0.52–0.93) for overall, cardiovascular and coronary artery disease (CAD)/cerebrovascular deaths, respectively. Statins were not associated with death risk. Subjects combining statins and average-high adherence to MD had much lower than expected risk of cardiovascular and CAD/cerebrovascular mortality (p for interaction = 0.045 and 0.0015, respectively) as compared to those neither using statins nor having average-high MD. The combination of average-high MD and statins was associated in a likely synergistic way with reduced low-grade inflammation, but not with blood cholesterol. Conclusions MD lowered the risk of all-cause, cardiovascular and CAD/cerebrovascular mortality CVD patients, net of statins. In the same population, statins reduced CVD death risk only in combination with MD. Low-grade inflammation, rather than lipids, is likely to be on the pathway of the interaction between MD and statins towards mortality risk. Highlights • Mediterranean diet (MD) is associated with lower risk of death in CVD patients. • Statins reduce CVD death risk only in combination with Mediterranean diet. • Inflammation is likely to be on the pathway of the interaction of MD and statins. • Combination of MD and statins may be an optimal option for secondary prevention. [ABSTRACT FROM AUTHOR]

Platelet count varies by age, sex and ethnicity. However, previous studies have adopted standard ranges to identify subjects with thrombocytopenia or thrombocytosis. The aim of this study was to test the predictive role of age-sex-based cut-offs of platelet count proposed by an Italian collaborative study, towards the risk of cause-specific death. We conducted a prospective analysis on 21,563 adult subjects (mean age 55.6 ± 11.8) randomised from the general population of the Moli-sani study. Hazard ratios (HR) were calculated by multivariable Cox-proportional hazard models with 95% confidence intervals. Over a median follow-up of 8.2 years (interquartile range: 7.3 to 9.2 years; 175,972 person-years), we ascertained and validated 1,130 deaths, 415 of which are from cardiovascular disease, 439 from cancer and 276 from non-vascular/non-cancer causes. As opposed to the normal ranges defined by age and sex (extreme values from 122 to 405 x109/L), lower platelet number (87.7% of values being higher than 100x109/L) was associated with increased risk of total (HR = 1.92; 95%CI 1.38-2.67), cancer (HR = 1.77; 95%CI 1.03-3.05), and non-cardiovascular/non-cancer mortality (HR = 3.16; 95%CI 1.84-5.42) but was unrelated to cardiovascular mortality. Higher platelet count was not associated with any death risk. In conclusion, age-sex-based low platelet count, well above the traditional lower normal range of <100 x109/L, is associated with increased total and specific mortality risk in a general population. [ABSTRACT FROM AUTHOR]

Background: It is uncertain whether the cardiovascular benefits associated with Mediterranean diet (MD) may differ across socioeconomic groups. Methods: Prospective analysis on 18991 men and women aged ≥35 years from the general population of the Moli-sani cohort (Italy). Adherence to MD was appraised by the Mediterranean diet score (MDS). Household income (euros/year) and educational level were used as indicators of socioeconomic status. Hazard ratios (HR) were calculated by multivariable Cox proportional hazard models. Results: Over 4.3 years of follow-up, 252 cardiovascular disease (CVD) events occurred. Overall, a two-point increase in MDS was associated with 15% reduced CVD risk (95% confidence interval: 1% to 27%). Such association was evident in highly (HR=0.43; 0.25- 0.72) but not in less (HR=0.94; 0.78-1.14) educated subjects (P for interaction=0.042). Similarly, CVD advantages associated with the MD were confined to the high household income group (HR=0.39; 0.23-0.66, and HR=1.01; 0.79-1.29 for high- and low-income groups, respectively; P for interaction=0.0098). In a subgroup of individuals of different socioeconomic status but sharing similar MDS, diet-related disparities were found as different intakes of antioxidants and polyphenols, fatty acids, micronutrients, dietary antioxidant capacity, dietary diversity, organic vegetables and whole grain bread consumption. Conclusions: MD is associated with lower CVD risk but this relationship is confined to higher socioeconomic groups. In groups sharing similar scores of adherence to MD, diet-related disparities across socioeconomic groups persisted. These nutritional gaps may reasonably explain at least in part the socioeconomic pattern of CVD protection from the MD. [ABSTRACT FROM AUTHOR]

Background and aims The orientation of the frontal plane T-wave axis (T axis) is a reliable measure of ventricular repolarisation. We investigated the association between T-axis and the risk of coronary heart disease (CHD), heart failure (HF), atrial fibrillation (AF), stroke and cardiovascular (CVD) mortality. Methods A sample of 21,287 Moli-sani participants randomly recruited from the general adult (≥35 y) Italian population, free of CVD disease, were followed for a median of 4.4 years. T-axis was measured from a standard 12-lead resting ECG. Results After adjusting for CVD risk factors, subjects with abnormal T-axis showed an increase in the risk of both CHD (Hazard Ratio (HR) = 2.65; 95% CI = 1.67–4.21), HF (HR = 2.56; 1.80–3.63), AF (HR = 2.48; 1.56–3.94) and CVD mortality (HR = 2.83; 1.50–5.32). The association with CHD and HF, but not with AF or CVD death, remained significant after further adjustment for ECG abnormalities. Subjects with abnormal T-axis showed higher levels of subclinical inflammation, hs-troponin I and hs-NT-proBNP ( p < 0.001 for all). However, further adjustment for troponin I and/or NT-proBNP determined a reduction of HRs ranging from 12.1 to 24.0% for CHD, while additional adjustment for inflammation markers did not change any association. Conclusions An abnormal T-axis orientation is associated with an increased risk of both CHD and HF, independently of common CVD risk factors and other ECG abnormalities. This association was partially explained by increased hs-troponin I and hs-NT-proBNP levels. [ABSTRACT FROM AUTHOR]

Background Angiotensin receptor blockers (ARBs) are a valuable option to reduce cardiovascular (CV) mortality and morbidity in cardiac patients in whom ACE-inhibitors (ACE-Is) cannot be used. However, clinical outcome data from direct comparisons between ACE-Is and ARBs are scarce, and some data have recently suggested superiority of ACE-Is over ARBs. Methods We performed a Bayesian network-meta-analysis, with data from both direct and indirect comparisons, from 27 randomized controlled trials (RCTs), including a total population of 125,330 patients, to assess the effects of ACE-Is and ARBs on the composite endpoint of CV death, myocardial infarction (MI) and stroke, and on all-cause death, new-onset heart failure (HF) and new-onset diabetes mellitus (DM) in high CV risk patients without HF. Results Using placebo as a common comparator, we found no significant differences between ACE-Is and ARBs in preventing the composite endpoint of CV death, MI and stroke (RR: 0.92; 95% CI 0.78–1.08). When components of the composite outcome were analysed separately, ACEi and ARBs were associated with a similar risk of CV death (RR: 0.92; 95% CI 0.73–1.10), MI (RR: 0.91; 95% CI 0.78–1.07) and stroke (RR: 0.97; 95% CI 0.79–1.19), as well as a similar incident risk of all-cause death (RR: 0.94; 95% CI 0.85–1.05), new-onset HF (RR: 0.92; 95% CI 0.77–1.15) and new-onset DM (RR: 99; 95% CI 0.81–1.21). Conclusions With the limitations of indirect comparisons, we found that in patients at high CV risk without HF, ARBs were similar to ACE-Is in preventing the composite endpoint of CV death, MI and stroke. Compared with ARBs, we found no evidence of statistical superiority for ACE-Is, as a class, in preventing incident risk of all-cause death, CV death, MI, stroke, new-onset DM and new-onset HF. [ABSTRACT FROM AUTHOR]

The results presently available from randomised clinical trials and their meta-analysis indicate that Hydroxychloroquine is not associated in COVID-19 patients with either decreased mortality or clinical worsening. Thus, the use of Hydroxychloroquine in COVID-19 patients cannot at present be encouraged. However, the hypothesis that Hydroxychloroquine might have a beneficial role in subgroups of patients at low risk and/or when used at low dosage (≤ 400 mg/day) deserves to be tested in large, well designed randomised clinical trials. [ABSTRACT FROM AUTHOR]

Objective: Folate status has been associated with neural tube defects and cerebrovascular disease. The aim of this study was to evaluate possible differences in folate status in two European Union countries and to assess their possible association with dietary patterns and/or other lifestyles. Methods: In the framework of the European Union-funded IMMIDIET Project, 1068 individuals (534 male-female pairs), ages 26 to 64 y, were enrolled in Italy and the United Kingdom. One-year-recall food frequency questionnaire was used to evaluate dietary intake. Reduced rank regression analysis was used to derive a dietary pattern better describing high dietary folate intake. Results: Of the total participants, 11.3% of the Italians and 45.1% of the British exceeded the optimal dietary folate intake of 400 µg/d (Recommended Dietary Allowance). Of the women, 66.7% and 22.1% of Italian and British women, respectively, all at childbearing age, had folate serum levels <6.62 ng/mL (P = 0.01). The percentage of total variance of dietary folate intake explained by food group consumption was 14.2% and 16.3% in Italy and the United Kingdom, respectively. Reduced rank regression analysis indicated a healthy pattern that was positively associated with folate serum levels in both countries (for all β-coefficients >0; P < 0.001): 100 mg/d increase in dietary folate intake was associated with 13.8% and 10.5% increase in folate serum levels in the Italian and British population, respectively (for 100 mg/d increase eβ-coef = 1.138 and 1.105; P < 0.001). Smoking habit was negatively but physical activity positively associated with folate serum levels (P < 0.05). Conclusions: An inadequate dietary folate intake and subsequent serum levels were observed in the Italian participants. High consumption of food sources of folate was positively associated with folate serum levels, explaining a good proportion of its variability. [ABSTRACT FROM AUTHOR]

Platelet (PLT) and white blood cell (WBC) counts are 2 markers of inflammation and have been linked to the risk for cerebrovascular and coronary heart disease. A Mediterranean diet (MD) has been associated with reduced inflammation and mortality for major chronic diseases. We aimed at evaluating the association between the MD and both PLT and WBC counts. This cross-sectional analysis in a population-based cohort study included 14?586 healthy Italian citizens enrolled within the Moli-sani study. Adherence to MD was appraised by either the MD Score (MDS) or the Italian Mediterranean Index (IMI). PLT and WBC counts were both inversely related to MD adherence (MDS: P < .0001 and P = .008, respectively). As compared with those with poorer MD adherence, subjects with greater adherence had both reduced odds of being in the highest PLT-count group (MDS: odds ratio = 0.50; 95% confidence interval, 0.31-0.80) and increased odds of being in the lowest WBC-count group (IMI: odds ratio = 1.41; 95% confidence interval, 1.07-1.86). The association between WBC count and MDS disappeared when further adjusted for PLT count, whereas the association between PLT count and the MD was not affected by adjustment for WBCs. Food antioxidant and dietary fiber content modified the inverse association between MDS and WBC count and partially accounted for the association with PLTs. [ABSTRACT FROM AUTHOR]

Highlights: [•] Role of nutrition knowledge in determining differences among dietary patterns. [•] Nutrition knowledge was associated with higher adherence to a Mediterranean dietary pattern. [•] The odds ratio of being obese significantly decreased with increasing nutrition knowledge levels. [ABSTRACT FROM AUTHOR]

Abstract: Aim: We aimed at investigating the association between T-wave axis deviation, metabolic syndrome (MetS), its components and estimated risk of cardiovascular disease (CVD) at 10 years in an adult Italian population. Methods: 11,143 women (54 ± 11 years) and 9742 men (55 ± 11 years) were analyzed from the Moli-sani cohort, randomly recruited from the general population. MetS was defined using the ATPIII criteria. T-wave axis deviation was measured from the standard 12-lead resting electrocardiogram. CVD risk in ten years was estimated by the CUORE score. Results: 29% of men and 27% of women with MetS showed borderline or abnormal T-wave as compared to 24% and 17% without MetS (p < 0.0001 for both genders). Among components of MetS, elevated waist and blood pressure were strongly associated with T-wave axis deviation, whereas glucose, HDL and triglycerides were only marginally. The odds of having borderline or abnormal T-wave axis deviation in multivariable regression analysis, was 1.38 (95% CI:1.25–1.53) in MetS men and 1.68 (95% CI:1.51–1.87) in MetS women compared to those without. Further adjustment for MetS components completely abolished the associations. Abnormal T-wave axis deviation was associated with an increased risk of CVD in 10 years in men (OR = 4.4; 95% CI:1.10–17.9). Conclusion: T-wave axis deviation is strongly associated with components of the MetS, in particular high waist circumference and blood pressure and with an increased CVD risk, particularly in men. ECG monitoring to identify T-wave axis deviation in obese, hypertensive or MetS subjects can be an early indicator of vascular disease and help in reducing cardiac events. [Copyright &y& Elsevier]

Abstract: Daily intake of an anti-thrombotic diet may offer a suitable and effective way of coronary artery disease (CAD) prevention. A diet rich in fruit, vegetables, complex carbohydrates, monounsaturated fat and fish, moderate alcohol consumption but poor in salt, saturated fat and simple sugars, plays an important role in protect against CAD. Chocolate, coffee and tea, unfairly not included in “traditional healthy food basket”, have received much attention over the past few years, if for no other reason than they are consumed worldwide and are important dietary sources of polyphenols (flavonols and cathechins). Several in vitro and in vivo studies have tried to elucidate the role of these foods and a large amount of experimental studies clearly indicated a beneficial effect of polyphenols in influencing CAD. However, data from epidemiological studies are not conclusive. The blood pressure lowering effects and the anti-inflammatory activity of dark chocolate suggests its use as potential prophylactic and therapeutic agent, in particular considering that epidemiological studies suggest that dark chocolate is inversely associated with CAD. Although regular consumption of moderate quantities of coffee and (green) tea seems to be associated with a small protection against CAD, results from randomized clinical trials about their beneficial effects are less evident. As for other diffuse consumption habits, such as that of alcohol, moderation is the key word. In fact, both for coffee and chocolate, the optimal healthy effects on CAD have been observed to be associated with a moderate intake, while healthy outcomes vanish at heavy consumption. [Copyright &y& Elsevier]

Moderate alcohol consumption by apparently healthy people or patients with cardiovascular disease is associated with lower vascular and all-cause mortality. These findings were extended by two new meta-analyses aimed at assessing the relationship of alcohol drinking with vascular and total mortality in a large series of patients, including not only patients with a history of CVD but also diabetic and hypertensive patients. Two meta-analyses were performed: the first one considered 17 studies reporting secondary risk of vascular mortality; the second one included 14 studies reporting total mortality. The meta-analysis on vascular mortality and alcohol intake showed as an ‘L-shaped’ curve, indicating a protective effect (average 38%) that was maximal at about 40 and remained still significant up to 60 grams/day. J-shaped pooled curves were observed in the meta-analysis on mortality from any cause and in subgroups defined according to different types of patients or characteristics of the studies. While confirming the hazards of excess drinking, our findings indicate that in patients at high cardiovascular risk, low to moderate alcohol consumption is significantly associated with a reduced incidence of secondary non-fatal and/or fatal vascular events and all-cause mortality. [ABSTRACT FROM PUBLISHER]

Objectives: The purpose of this study was to quantify the relation between alcohol consumption and cardiovascular and total mortality in patients with a history of cardiovascular events. Background: Regular, moderate alcohol consumption by healthy people is associated with lower cardiovascular and all-cause mortality. No extensive meta-analysis is presently available on the possible association of alcohol consumption with secondary events in patients with cardiovascular disease. Methods: Articles were retrieved through October 2009 by search in PubMed and EMBASE. Fifty-four publications were identified, but only 8 were selected for our analyses, including 16,351 patients with a history of cardiovascular disease. Secondary events were cardiovascular or all-cause mortality. All selected studies were prospective. Data were pooled with a weighted, least-squares regression analysis of second-order fractional polynomial models. Results: The meta-analysis on cardiovascular mortality showed a J-shaped pooled curve with a significant maximal protection (average 22%) by alcohol at approximately 26 g/day. In the meta-analysis on mortality for any cause, J-shaped pooled curves were observed in the overall analysis (average maximal protection of 18% in the range of 5 to 10 g/day) and in all subgroups according to either the type of patients or the characteristics of the studies. Conclusions: In patients with cardiovascular disease, light to moderate alcohol consumption (5 to 25 g/day) was significantly associated with a lower incidence of cardiovascular and all-cause mortality. [Copyright &y& Elsevier]

The article discusses the study on range of intervals on the age-sex specification of platelet counts that cause mortality. The epidemiologic analyses was based from the population of inhabitants from Italian areas with hepatitis and hematologic diseases. Clinical practice on platelet counts reduce that number of individuals unduly considered at high risk of mortality.

Abstract: Introduction: Moderate alcohol consumption is protective against cardiovascular disease (CAD). ADHs are major enzymes of alcohol metabolism. A polymorphism in the alcohol dehydrogenases 1C gene (ADH1C) was reportedly associated with the protective effect of alcohol consumption on CAD risk and risk factor levels. Aims: The aim of our study was to investigate whether the association of alcohol consumption with metabolic risk factors for CAD is related to ADH1C variants. Methods: IMMIDIET is a cross-sectional study of 974 healthy male–female pairs living together, randomly recruited in Belgium, Italy and England. The rs698 ADH1C polymorphism was genotyped. A 1-year recall food frequency questionnaire was used to estimate alcohol intake. Results: The intake of alcohol did not vary in relation to ADH1C genotypes. BMI, waist circumference (WC), waist-to-hip ratio, blood pressure, HDL or total cholesterol, triglycerides and FVII:ag levels were positively associated with alcohol intake in men (multivariate ANOVA). Regression coefficient for alcohol and BMI or WC was progressively higher in heterozygotes and gamma 2 homozygotes as compared to gamma 1 homozygotes (p =0.006 and p =0.03 for interaction, respectively). No interaction was found for other risk factors. In women, alcohol intake was positively associated with HDL, LDL and FVII:ag levels but no interaction was found between ADH1C polymorphism and any risk factor. Conclusion: Regulation of ADH1C genotype on the association between alcohol consumption, BMI and WC was found in men from different European countries. In men homozygous for the gamma 2 alleles, intake of alcohol was positively associated with both BMI and WC values. [Copyright &y& Elsevier]

Dark chocolate contains high concentrations of flavonoids and may have antiinflammatory properties. We evaluated the association of dark chocolate intake with serum C-reactive protein (CRP). The Moli-sani Project is an ongoing cohort study of men and women aged ⩾35 y randomly recruited from the general population. By July 2007, 10,994 subjects had been enrolled. Of 4849 subjects apparently free of any chronic disease, 1317 subjects who declared having eaten any chocolate during the past year (mean age 53 ± 12 y; 51 % men( and 824 subjects who ate chocolate regularly in the form of dark chocolate only (50 ± 10 y; 55% men( were selected. High sensitivity-CRP was measured by an immunoturbidimetric method. The European Prospective Investigation into Cancerand Nutrition FF0 was used to evaluate nutritional intake. After adjustment for age, sex, social status, physical activity, systolic blood pressure, BMI, waist:hip ratio, food groups, and total energy intake, dark chocolate consumption was inversely associated with CRP (P = 0.0381. When adjusted for nutrient intake, analyses showed similar results (P = 0.016). Serum CRP concentrations [geometric mean (95% Cl)) univariate concentrations were 1.32 (1.26-1.39 mg/LI in nonconsumers and 1.10 (1 .03-1.17 mg/L) in consumers (P< 0.0001). A J-shaped relationship between dark chocolate consumption and serum CAP was observed; consumers of up to 1 serving (20 g) of dark chocolate every 3 d had serum CRP concentrations that were significantly lower than nonconsumers or higher consumers. Our findings suggest that regular consumption of small doses of dark chocolate may reduce inflammation. [ABSTRACT FROM AUTHOR]

The article reports on the result of the study on alcohol dosing and total mortality in men and women. The research shows that low levels of alcohol intake are inversely associated with total mortality in both men and women. It indicated that potential windows of alcohol intake that may confer a net beneficial effect of moderate drinking, at least in terms of survival while confirming the hazards of excess drinking.

Membrane glycoprotein (GP) IIb/IIIa plays a major role in platelet function; indeed it enables stimulated platelets to bind fibrinogen and related adhesive proteins, a process that is considered key in the development of thrombosis. The gene encoding GPIIIa (ITGB3, also known as GP3A) shows a common platelet antigen polymorphism [PL(A1)/PL(A2); expressed by alleles ITGB3*001 and ITGB3*002] that was variably associated with vascular disease. In 1996, the presence of the PL(A2) allele (ITGB3*001) was first reported to increase the risk of coronary heart disease. Shortly after, the interest in this study was increased by the publication of a case report on the death from myocardial infarction of an Olympic athlete who was found to be homozygous for the PL(A2) allele. Overviews of the published studies on the PL(A1)/PL(A2) polymorphism and coronary risk suggest an influence of the PL(A2) allele on the clinical phenotype and the interaction with other environmental factors. In particular, the strongest effect of the ITGB3 PL(A2) allele was expressed on the risk of occlusion after revascularization procedures, mainly after stent implantation, a condition in which platelet activation is more important as compared with other stenotic mechanisms. In the future, the identification of patients who are particularly responsive to GPIIb/IIIa antagonist therapy (e.g. those with the PL(A2) allele) might help to improve the treatment efficacy in this relatively small population. In a mechanism possibly unrelated to its effect on platelet reactivity to aggregating stimuli, the presence of the PL(A2) allele might influence the antiaggregatory effect of platelet inhibitory drugs such as aspirin (acetylsalicylic acid), clopidogrel, and GPIIb/IIIa antagonists. Although interesting, current data does not yet have direct clinical implications for patient risk identification and drug therapy tailoring. Larger studies are necessary to define the role of the PL(A2) allele in more homogeneous groups where platelet GPIIb/IIIa activation might be particularly relevant. [ABSTRACT FROM AUTHOR]

An inverse association between moderate alcohol consumption and vascular disease has been shown in several studies and confirmed in recent meta-analyses. Important issues remain about the relationship between alcoholic beverages and vascular disease. Among these are the differences in types of beverages, the optimal amount of alcoholic beverage intake, the individual or environmental modulation of the alcohol-related effect, and the pattern of drinking. In particular, many studies have dealt with the question of whether wine might offer a greater protection, most likely related to its nonalcoholic components. This review discusses open questions about wine and vascular disease. [ABSTRACT FROM AUTHOR]

Background: The GLP-1 receptor agonist liraglutide is used to treat hyperglycemia in type 2 diabetes but is also known to induce weight loss, preserve the beta cell and reduce cardiovascular risk. The mechanisms underlying these effects are however still not completely known. Herein we explore the effect of liraglutide on markers of immune cell activity in a population of obese individuals with prediabetes or newly diagnosed type 2 diabetes mellitus. Method: Plasma levels of the monocyte/macrophage markers, soluble (s)CD163 and sCD14, the neutrophil markers myeloperoxidase (MPO) and neutrophil gelatinase‐associated lipocalin (NGAL),the T-cell markers sCD25 and T-cell immunoglobulin mucin domain-3 (sTIM-3) and the inflammatory marker TNF superfamily (TNFSF) member 14 (LIGHT/TNFSF14) were measured by enzyme-linked immunosorbent assays in obese individuals with prediabetes or diabetes diagnosed within the last 12 months, prior to and after comparable weight loss achieved with lifestyle changes (n = 20) or liraglutide treatment (n = 20), and in healthy subjects (n = 13). Results: At baseline, plasma levels of the macrophage marker sCD163, and the inflammatory marker LIGHT were higher in cases as compared to controls. Plasma levels of sCD14, NGAL, sTIM-3 and sCD25 did not differ at baseline between patients and controls. After weight reduction following lifestyle intervention or liraglutide treatment, sCD163 decreased significantly in the liraglutide group vs. lifestyle (between-group difference p = 0.023, adjusted for visceral adipose tissue and triglycerides basal values). MPO and LIGHT decreased significantly only in the liraglutide group (between group difference not significant). Plasma levels of MPO and in particular sCD163 correlated with markers of metabolic dysfunction and inflammation. After weight loss, only sCD163 showed a trend for decreased levels during OGTT, both in the whole cohort as in those of liraglutide vs lifestyle group. Conclusion: Weight loss following treatment with liraglutide was associated with reduced circulating levels of sCD163 when compared to the same extent of weight loss after lifestyle changes. This might contribute to reduced cardiometabolic risk in individuals receiving treatment with liraglutide. [ABSTRACT FROM AUTHOR]

α 2 -macroglobulin (α 2 M) is a versatile endopeptidase inhibitor that plays a role in cell growth, inflammation and coagulation. α 2 M is an inhibitor of key coagulation enzyme thrombin. Hypercoagulability due to an excess of thrombin production can cause thrombotic events. Therefore, we investigated the association of α 2 M levels and cardiovascular events in a subset of the general Italian population. We determined α 2 M levels in the baseline samples of a prospective cohort (n = 19,688; age: 55 ± 12 years; 47.8 % men) of the Moli-sani study and investigated the association with the cardiovascular events (n = 432, 2.2 %) in the median follow-up period of 4.3 years. Hazard ratios (HR) with 95 % confidence intervals (CI) were calculated by multivariable Cox regression and adjusted for a large panel of confounding factors. α 2 M levels above the 90th percentile were significantly associated with cardiovascular disease (CVD) events after full adjustment for age, sex, current smoking, BMI, oral contraceptive use, cardiovascular diseases, hypertension, hypercholesterolemia, diabetes and history of cancer (HR: 1.36; CI: 1.06–1.74). Moreover, high α 2 M was associated with coronary heart disease (CHD; HR: 1.47; CI: 1.12–1.91), but not stroke. Stratification for CVD at baseline showed that high α 2 M levels are associated with CHD events in subjects without CVD at baseline (HR: 1.40; CI: 1.00–1.95) and subjects with CVD at baseline (HR: 1.58; CI: 1.02–2.44). We show in a prospective cohort that high levels of α 2 M could be a risk factor for cardiovascular events, especially coronary heart disease events. • Alpha 2 -Macroglobulin and cardiovascular events are associated. • High α 2 M is a risk factor for coronary heart disease. • The association is independent of age, sex, and lifestyle. [ABSTRACT FROM AUTHOR]

We conducted a systematic review and a meta-analysis to assess the association of anticoagulants and their dosage with in-hospital all-cause mortality in COVID-19 patients. Articles were retrieved until January 8, 2021, by searching in seven electronic databases. The main outcome was all-cause mortality occurred during hospitalization. Data were combined using the general variance-based method on the effect estimate for each study. Separate meta-analyses according to type of COVID-19 patients (hospitalized or intensive care unit [ICU] patients), anticoagulants (mainly heparin), and regimens (therapeutic or prophylactic) were conducted. A total of 29 articles were selected, but 23 retrospective studies were eligible for quantitative meta-analyses. No clinical trial was retrieved. The majority of studies were of good quality; however, 34% did not distinguish heparin from other anticoagulants. Meta-analysis on 25,719 hospitalized COVID-19 patients showed that anticoagulant use was associated with 50% reduced in-hospital mortality risk (pooled risk ratio [RR]: 0.50, 95% confidence interval [CI]: 0.40–0.62; I 2 : 87%). Both anticoagulant regimens (therapeutic and prophylactic) reduced in-hospital all-cause mortality, compared with no anticoagulation. Particularly in ICU patients, the anticoagulant therapeutic regimen was associated with a reduced in-hospital mortality risk (RR: 0.30, 95% CI: 0.15–0.60; I 2 : 58%) compared with the prophylactic one. However, the former was also associated with a higher risk of bleeding (RR: 2.53, 95% CI: 1.60–4.00; I 2 : 65%). Anticoagulant use, mainly heparin, reduced all-cause mortality in COVID-19 patients during hospitalization. Due to the higher risk of bleeding at therapeutic doses, the use of prophylactic dosages of anticoagulant is probably to be preferred in noncritically ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

Introduction: There is lack of data on the association of socioeconomic (SES) disadvantage experienced across life course with the risk of heart failure (HF) or atrial fibrillation (AF). Moreover, little is known on the mechanisms through which SES inequalities shape disease risk. Hypothesis: We assessed the hypothesis of an association between cumulative socioeconomic disadvantage (CSD) with risk of first hospitalization for HF or AF in a large general population-based cohort of Italians, and tested several sets of potential mediators in explaining such associations. Methods: Longitudinal analysis on 21,756 HF- or AF-free men and women (aged≥35 y) recruited in the Moli-sani Study cohort, Italy (2005-2010). A score to estimate CSD over life-course was computed by using childhood SES factors (hot water, overcrowding, housing), 3-level educational attainment, and adulthood SES indicators (occupation, overcrowding, housing). Five sets of pathways were tested as potential mediators: baseline health conditions, lifestyles, and traditional, inflammatory and novel markers of CVD risk (listed in Table). First hospital admissions were recorded by direct linkage with hospital discharge forms. Hazard ratios with 95% confidence intervals (95% CIs) were calculated using multivariable Cox-proportional hazard models. Results: Over a median follow up of 8.2 years, we recorded 836 and 504 admissions to hospital for HF and AF, respectively. A 1-point increment in CSD was associated with 16% and 6% increased risk of HF and AF, respectively. Risk estimates associated with highest CSD, as compared to lowest CSD group, were 2.55 (1.76-3.70) and 1.60 (1.08-2.38) for risk of HF and AF, respectively. Part of such associations was explained by novel biomarkers of CVD risk and baseline lifestyles (Table). Conclusions: HF and AF risks are shaped by cumulative socioeconomic disadvantage across the life course in a large Mediterranean population. Lifestyles and novel markers of CVD risk account for the largest proportion of such associations. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Background: It is uncertain whether the cardiovascular benefits associated with Mediterranean diet (MD) may differ across socioeconomic groups.Methods: Prospective analysis on 18991 men and women aged ≥35 years from the general population of the Moli-sani cohort (Italy). Adherence to MD was appraised by the Mediterranean diet score (MDS). Household income (euros/year) and educational level were used as indicators of socioeconomic status. Hazard ratios (HR) were calculated by multivariable Cox proportional hazard models.Results: Over 4.3 years of follow-up, 252 cardiovascular disease (CVD) events occurred. Overall, a two-point increase in MDS was associated with 15% reduced CVD risk (95% confidence interval: 1% to 27%). Such association was evident in highly (HR = 0.43; 0.25-0.72) but not in less (HR = 0.94; 0.78-1.14) educated subjects (P for interaction = 0.042). Similarly, CVD advantages associated with the MD were confined to the high household income group (HR = 0.39; 0.23-0.66, and HR = 1.01; 0.79-1.29 for high- and low-income groups, respectively; P for interaction = 0.0098). In a subgroup of individuals of different socioeconomic status but sharing similar MDS, diet-related disparities were found as different intakes of antioxidants and polyphenols, fatty acids, micronutrients, dietary antioxidant capacity, dietary diversity, organic vegetables and whole grain bread consumption.Conclusions: MD is associated with lower CVD risk but this relationship is confined to higher socioeconomic groups. In groups sharing similar scores of adherence to MD, diet-related disparities across socioeconomic groups persisted. These nutritional gaps may reasonably explain at least in part the socioeconomic pattern of CVD protection from the MD. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Cardiovascular risk and events in 17 low-, middle-, and high-income countries" by S. Yusuf and colleagues in the August 28, 2014 issue.

Background: Several environmental/lifestyle factors have been individually investigated in previous Parkinson's disease (PD) studies with controversial results. No study has prospectively and simultaneously investigated potential risk/protective factors of PD using both classical statistical and novel machine learning analyses. The latter may reveal more complex associations and new factors that are undetected by merely linear models. To fill this gap, we simultaneously investigated potential risk/protective factors involved in PD in a large prospective population study using both approaches. Methods: Participants in the Moli-sani study were enrolled between 2005 and 2010 and followed up until December 2018. Incident PD cases were identified by individual-level record linkage to regional hospital discharge forms, the Italian death registry, and the regional prescription register. Exposure to potential risk/protective factors was assessed at baseline. Multivariable Cox Proportional Hazards (PH) regression models and survival random forests (SRF) were built to identify the most influential factors. Results: We identified 213 incident PD cases out of 23,901 subjects. Cox PH models revealed that age, sex, dysthyroidism and diabetes were associated with an increased risk of PD. Both hyper and hypothyroidism were independently associated with PD risk. SRF showed that age was the most influential factor in PD risk, followed by coffee intake, daily physical activity, and hypertension. Conclusion: This study sheds light on the role of dysthyroidism, diabetes and hypertension in PD onset, characterized to date by an uncertain relationship with PD, and also confirms the relevance of most factors (age, sex, coffee intake, daily physical activity) reportedly shown be associated with PD. Further methodological developments in SRF models will allow to untangle the nature of the potential non-linear relationships identified. [ABSTRACT FROM AUTHOR]

Introduction: Resilience is a measure of stress coping ability and has been favourably associated with cardiovascular health. Yet little is known on the likely association between diet and resilience. Hypothesis: We tested the hypothesis that diet quality is associated with resilience. Methods: Cross-sectional analysis on 10,812 subjects (mean age 52.7±10.8, 50.5% men) recruited within the cohort of the Moli-sani study from 2005 to 2010. Resilience was measured by the 25-item Connor-Davidson Resilience Scale ranging from 0-100 with the higher score reflecting greater resilience. Food intake was recorded by the EPIC food frequency questionnaire and adherence to the Mediterranean diet was appraised by both a Greek and an Italian dietary score. Empirically-derived dietary patterns were obtained by principal components analysis (PCA), while dietary polyphenol and antioxidant intakes and fruit and vegetables variety were assessed by specific holistic scoring. Multivariable linear regression analysis (95%CI) was used to test the association between dietary scores and resilience. Results: As compared to those below the median value of resilience (score=67), more resilient subjects had higher educational status (19.4% vs 13.5% for university or postgraduate education) and were more likely to report favourable health behaviours (leisure-time physical activity and less prevalence of smoking habit). In a multivariable model, greater adherence to Mediterranean-type diets or vegetables-based dietary pattern obtained from PCA, as well as dietary polyphenol or antioxidant intakes and greater variety in fruit and vegetables consumption were all positively associated with resilience (Table). No association with Western-like diets was found. Conclusions: Diet quality, as measured by a number of dietary scores, was positively associated with higher resilience, whereas western-type diets were not. Modulation of stress coping ability may be a factor in considering healthy effect of high quality diet. [ABSTRACT FROM AUTHOR]

Background: Deviation of frontal plane T-wave axis (TDev) is a reliable measure of ventricular repolarisation abnormality. Objectives: We investigated the associations and possible mediators between TDev and the risk of coronary artery disease (CHD), atrial fibrillation (AF), heart failure (HF), stroke and cardiovascular mortality. Methods: A large sample of 21,287 Moli-sani participants (54.0±10 years, 46% women), randomly recruited from the general adult population of Southern Italy and free of clinically and ECG recognized vascular disease (including HF), were followed for a median of 4.3 years. TDev was measured from a standard 12-lead resting electrocardiogram. ECG abnormalities were identified by the MINNESOTA codes. Results: After adjusting for a large panel of covariates (see the Table), subjects with abnormal TDev showed a significant increase in the risk of CHD, AF, HF and CVD mortality, but not with stroke (Table). Associations with CHD and HF (but not AF or CVD mortality) were slightly reduced but remained significant after further adjustment for other ECG abnormalities (Table). Subjects with abnormal TDev showed higher levels of subclinical inflammation (measured by C-reactive protein, WBC, platelet counts and ratio of granulocytes to lymphocytes), hs-troponin I and hs-NT-proBNP (p<0.001 for all). However, while additional adjustment for inflammation markers did not change the association of TDev with any clinical outcome, further adjustment for troponin I or NT-proBNP or both determined a reduction ranging from 7.9 to 23.7% for the association of TDev with HF and from 20.7 to 33.8% for the association of TDev with CHD. Conclusions: Deviation of TDev is associated with an increased risk of HF or CHD, independently from a large panel of covariates and other ECG abnormalities. The association was partially explained by the increase in hs-troponin I and hs-NT-proBNP levels. [ABSTRACT FROM AUTHOR]

Introduction: The association between socioeconomic status (SES) and the risk of cardiovascular disease and all-cause mortality is well-established, while the impact of SES on heart failure (HF) incidence is less explored. Hypothesis: We tested the hypothesis of a SES gradient in the risk of HF. Methods: Population-based cohort study on 22,395 individuals (mean age 55.3±11.7, 47.7% men) free from HF at baseline randomly recruited from the general population included in the Moli-sani study (Italy). The cohort was followed up for a median of 7.6 years (168,031 person-years). Annual household income (Euros) and educational level were used as SES indicators. Presence of risk factors at baseline and a panel of health behaviours were tested as possible mediators of the association between SES and incident HF. Incident HF at follow-up was defined by HF hospitalization or HF death, according to the International Classification of Diseases-Ninth Revision (ICD-9). Hazard ratios (HR) with 95% confidence intervals were calculated by Cox-proportional hazard models. Results: We identified 757 first HF events. Both lowest education (middle and secondary schools) and household income (<60,000 Euros/y) were separately associated with increased risk of HF as compared with the highest category (Table). After simultaneous adjustment, the association of income appeared to be largely explained by education. The inclusion of traditional risk factors, biomarkers of heart failure and health-behaviors into the model attenuated the association of low education with HF incidence by 12%, 3.8% and 11.5%, respectively. Overall, the full explanatory model accounted for 23.8% of the educational gradient in the risk of HF (Table). Conclusions: Educational level, rather than income, is an independent predictor of HF development. Excess risk associated with low education was partially explained by traditional health risk factors, biomarkers of subclinical damage and health-behaviors. [ABSTRACT FROM AUTHOR]

Background: Education and income have been reportedly associated with mortality but their combined impact has not been extensively investigated. This study aims at evaluating the combined impact of income and education on overall and cardiovascular mortality in men and women. Methods: A prospective cohort study on a large sample of individuals (N=20,600, age ≥35) free from cardiovascular or cancer disease randomly enrolled in the Molisani study. The cohort was followed-up for overall mortality for 6.8 years (median 4.3 years). Education was considered as low (≤8 years of study) or high (>8 years). Low income group was defined as gross income ≤25,000euros/year while high income category included subjects reporting >25,000euro/years. A four-level variable was constructed to account for the combination of the two measurements: a) low income and low education group (reference group); b) high income and low education; c) low income and high education; d) high income and high education group. Hazard ratios were calculated using Cox-proportional hazard models. Results: During follow-up, 354 all-cause deaths occurred, 61 from cardiovascular causes. In a fully adjusted model, income, but not education, was significantly associated with a reduction of overall mortality. However, the group having both high income and high education levels showed a reduced risk of 54%(HR=0.46; 95CI: 0.32-0.66) compared to the reference group. Cardiovascular mortality was also reduced by 63%. Analyses stratified by sex showed that the highest combination of income and education had a stronger impact on overall mortality among women (HR=0.27; 95CI: 0.10-0.79) than among men (HR=0.50; 95CI:0.34- 0.76). Conclusions: The combination of high education and high income is associated with a consistent significant reduction of either overall or cardiovascular mortality. The protective effect of the combination is apparent in both genders but is stronger in women than in men. [ABSTRACT FROM AUTHOR]

Background and aims: Epidemiological evidence on the impact of different alcohol drinking patterns on health‐care systems or hospitalizations is sparse. We investigated how the different average volumes of alcohol consumed relate to all‐cause and cause‐specific hospitalizations. Design Prospective cohort study (baseline 2005–10) linked to a registry of hospital discharge records to identify hospitalizations at follow‐up (December 2013). Setting: Molise region, Italy. Participants: A total of 20 682 individuals (48% men, age ≥ 35 years) who participated in the Moli‐sani Study and were free from cardiovascular disease or cancer at baseline. Measurements The alcohol volume consumed in the year before enrolment was classified as: life‐time abstainers, former drinkers, occasional drinkers and current drinkers who drank 1–12 (referent), 12.1–24, 24.1–48 and > 48 g/day of alcohol. Cause‐specific hospitalizations were assigned by Italian Diagnosis Related Groups classification or by ICD‐9 code of main admission diagnoses. Incidence rate ratios (IRR) of hospitalization were estimated by Poisson regression, taking into account the total number of admissions that occurred during the follow‐up per person. Findings During a median follow‐up of 6.3 years, 12 996 multiple hospital admissions occurred. In multivariable analyses, life‐time abstainers and former drinkers had higher rates of all‐cause [IRR = 1.11, 95% confidence interval (CI) = 1.05–1.17 and IRR = 1.19, 95% CI = 1.02–1.31, respectively] and vascular (IRR = 1.14, 95% CI = 1.02–1.27 and IRR = 1.48, 95% CI = 1.24–1.76, respectively) hospitalizations compared with light alcohol consumers. Alcohol consumption > 48 g/day was associated with a higher rate of hospitalization for both alcohol‐related diseases (IRR = 1.74, 95% CI = 1.32–2.29) and cancer (IRR = 1.36, 95% CI = 1.12–1.65). The magnitude of the association between heavier alcohol intake and hospitalization tended to be greater in smokers than non‐smokers. No associations were observed with hospitalization for trauma or neurodegenerative diseases. Conclusions: Moderate alcohol consumption appears to have a modest but complex impact on global hospitalization burden. Heavier drinkers have a higher rate of hospitalization for all causes, including alcohol‐related diseases and cancer, a risk that appears to be further magnified by concurrent smoking. [ABSTRACT FROM AUTHOR]

There is little knowledge on the association of changes over time in adherence to a Mediterranean diet (MD) with changes in modifiable cardiovascular disease (CVD) risk factors and of markers of low-grade inflammation. To evaluate the association between long-term changes in MD adherence and concurrent changes in established CVD risk factors and in markers of low-grade inflammation among adult Italians. A prospective cohort study was conducted. Dietary and health data were obtained both at baseline (2005-2010) and at follow-up (2017-2020). Adherence to the MD was estimated by a Mediterranean Diet Score ranging from zero to nine points, and the exposure was change in this score measured after a median 12.7-year period. This study included a subgroup of 897 men and 1,126 women aged ≥35 years at enrolment in the Moli-sani Study (n = 24,325). Changes in two composite z scores, including nine established CVD risk factors (eg, serum lipid levels and blood pressure) and four inflammatory markers (including C-reactive protein), respectively, were measured both at enrolment and after the same 12.7-year period. Multivariable-adjusted linear regression models were used. In a multivariable-adjusted analysis, an increased Mediterranean Diet Score over time was associated with decreased levels in the Inflammatory score (β = –0.372, 95% CI –0.720 to –0.025), but had little or no influence on the CVD risk score (β = –0.200, 95% CI –0.752 to 0.351), compared with individuals who had decreased their MD adherence. Among individual food groups/nutrients included in the Mediterranean Diet Score, an increased intake of monounsaturated over saturated fats over time was associated with lower CVD Risk Score, whereas increased consumption of cereals was inversely linked to the Inflammatory Score, compared with the reduced consumption group. An increased adherence to a traditional MD over time was associated with reduced low-grade inflammation. These findings suggest the potential of a traditional Mediterranean eating pattern to help reduce the long-term risk of inflammation-related chronic diseases in an ageing population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Epidemiological data on the association between fibrinogen levels and mortality are scarse and controversial. Longitudinal analyses were performed, separately by sex, on 17,689 individuals from the Moli-sani study [53% women, ≥35 years, free from cardiovascular disease (CVD) or cancer at enrolment], to evaluate the association between plasma fibrinogen and all-cause and cause-specific mortality. Over a median follow-up of 11.2 years, 1,058 deaths (34.7% CVD, 36.3% cancer) were ascertained. Both in the lowest (1.12-2.64 g/L) and highest (=3.62 g/L) fibrinogen quintiles, women had an increased all-cause mortality hazard, when compared with third quintile (2.97-3.23 g/L). Dose-response analyses showed a U-shaped relationship in women (P overall <0.0001; P non-linear association <0.0001), but a positive linear association for all-cause mortality in men (P overall 0.0038; P nonlinear association 0.76). Similar trends for a U-shaped association were observed for CVD mortality, while no association was observed with cancer deaths. A U-shaped association of fibrinogen levels with other-cause mortality was also found in both sexes. This study shows that not only higher but also lower fibrinogen levels represent hazard for mortality when compared to normal levels; U-shaped curves being prevalently observed in women. [ABSTRACT FROM AUTHOR]

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 (β (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 β (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. [ABSTRACT FROM AUTHOR]