The association between hypoalbuminemia and risk of death due to cancer and vascular disease in individuals aged 65 years and older: findings from the prospective Moli-sani cohort study.

Background: Serum albumin is inversely associated with overall mortality, but its association with specific causes of death remains uncertain. This study aims to investigate whether hypoalbuminemia, defined as serum albumin levels ≤35 g/L, is associated with mortality specifically attributed to cancer and/or vascular diseases. Methods: Serum albumin levels were measured in the population-based, prospective cohort of the Moli-sani study, established between 2005 and 2010. Hypoalbuminemia was defined as serum albumin levels ≤35 g/L. Cause-specific mortality was assessed using the validated Italian mortality registry and coded according to the International Classification of Diseases, Revision 9. Over a median follow-up period of 13.1 years, the relationship between serum albumin and mortality, adjusted for covariates, was investigated using competing-risk survival analysis. Findings: The analysed cohort comprised 17,930 individuals aged ≥35 years, of whom 8445 were men (47.1%). The mean age was 54 years (standard deviation (SD) = 11 years), with 3299 individuals (18.4%) aged older than 65 years. All participants had C-reactive protein levels <10 mg/L and no history of liver, renal, cardiovascular, or cancer disease. Hypoalbuminemia was found in 406 individuals (2.3%). The study documented a total of 1428 deaths, with 574 attributed to cancer and 464 to vascular causes. Hypoalbuminemia was independently associated with mortality when compared to serum albumin >40 g/L (Hazard Ratio (HR) = 1.61, 95% Confidence Interval: 1.21-2.13). A decrease of 1-SD in serum albumin levels corresponded to HR of 1.16 (1.09-1.22), 1.16 (1.05-1.28), and 1.13 (1.03-1.23) for total, vascular and cancer mortality, respectively. Upon stratifying by age, hypoalbuminemia was associated with total mortality solely in those aged ≥65 years (HR = 1.83; 1.33-2.50) but not in the <65 years group (HR = 1.03; 0.53-2.00; P < 0.0001 for difference). Similar age-related patterns emerged for vascular death (per 1-SD decrease HR = 1.19; 1.07-1.33 in individuals ≥65 years and HR = 1.05; 0.86-1.29 in individuals <65 years) and cancer mortality (HR = 1.15; 1.02-1.30; ≥65 years and HR = 1.08; 0.96-1.23; <65 years). Interpretation: Individuals ≥65 years old with serum albumin levels ≤35 g/L are at higher risk of total, cancer, and vascular mortality. Funding: This paper was developed within the project funded by Next Generation EU-"Age-It - Ageing well in an ageing society" project (PE0000015), National Recovery and Resilience Plan (NRRP)-PE8-Mission 4, C2, Intervention 1.3.

Olive oil consumption is associated with lower cancer, cardiovascular and all-cause mortality among Italian adults: prospective results from the Moli-sani Study and analysis of potential biological mechanisms.

BACKGROUND: Olive oil consumption has been reportedly associated with lower mortality rates, mostly from cardiovascular diseases, but its potential impact on cancer death remains controversial. Moreover, biological mechanisms possibly linking olive oil consumption to mortality outcomes remain unexplored. METHODS: We longitudinally analysed data on 22,892 men and women from the Moli-sani Study in Italy (follow-up 13.1 y), to examine the association of olive oil consumption with mortality. Dietary data were collected at baseline (2005-2010) through a 188-item FFQ, and olive oil consumption was standardised to a 10 g tablespoon (tbsp) size. Diet quality was assessed through a Mediterranean diet score. Multivariable-adjusted Cox proportional hazard models, also including diet quality, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The potential mediating role of inflammatory, metabolic, cardiovascular and renal biomarkers on the association between olive oil intake and mortality was evaluated on the basis of change-in-estimate and associated p values. RESULTS: Multivariable HRs for all-cause, cancer, cardiovascular and other cause mortality associated with high (>3 tbsp/d) versus low (≤1.5 tbsp/d) olive oil consumption were 0.80 (0.69-0.94), 0.77 (0.59-0.99), 0.75 (0.58-0.97) and 0.97 (0.73-1.29), respectively. Taken together, the investigated biomarkers attenuated the association of olive oil consumption with all-cause and cancer mortality by 21.2% and 13.7%, respectively. CONCLUSIONS: Higher olive oil consumption was associated with lower cancer, cardiovascular and all-cause mortality rates, independent of overall diet quality. Known risk factors for chronic diseases only in part mediated such associations suggesting that other biological pathways are potentially involved in this relationship.

Incremental monounsaturated to saturated fat ratio and fibre consumption is associated with a reduction in a composite score of modifiable cardiovascular risk factors: Prospective results from the Moli-sani study.

BACKGROUND/OBJECTIVES: Unsaturated fats, fibre-rich foods and polyphenols are distinctive features of a traditional Mediterranean diet and have pleiotropic properties possibly contributing to reduce the long-term risk of non-communicable diseases and mortality associated with this diet. We aimed to evaluate whether changes over time in dietary fats, fibre and polyphenols consumption are associated with modifications in cardiovascular disease (CVD) risk factors. METHODS: The analytic sample consists of a sub-cohort of 2023 men and women enrolled in the Moli-sani Study (n = 24,325). Dietary and health data were obtained both at baseline (2005-2010) and at re-examination (2017-2020). The exposures were changes in dietary fats, fibre and polyphenols consumption measured after 12.7 years (median), and the outcome was change in a composite score including 13 modifiable CVD risk factors (e.g., blood lipids, C-reactive protein), measured both at enrolment and after the 12.7 years period. RESULTS: In multivariable-adjusted analysis including lifestyles, sociodemographic and clinical factors, an incremental intake of the ratio of monounsaturated to saturated fats or of fibre was associated with a reduction in the composite score of CVD risk factors (ß = -0.086; 95%CI -0.150, -0.021 and ß = -0.051; 95%CI -0.091, -0.012, respectively). Change in polyphenol intake was not associated with a substantial variation in the CVD risk score (p = 0.15). CONCLUSIONS: An incremental consumption over time of monounsaturated versus saturated fats and of fibre was associated with an improvement in modifiable CVD risk factors as reflected by a composite score.

Mediterranean diet and other dietary patterns in association with biological aging in the Moli-sani Study cohort.

BACKGROUND & AIMS: Biological age (BA) is the hypothetical underlying age of an organism and has been proposed as a more powerful predictor of health than chronological age (CA). The difference between BA and CA (Δage) reflects the rate of biological aging, with lower values indicating slowed-down aging. We sought to compare the relationship of four a priori-defined dietary patterns, including a traditional Mediterranean diet (MD) and three non-Mediterranean diets, with biological aging (Δage) among Italian adults. We also examined distinctive nutritional traits of these diets as potential mediators of such associations. METHODS: Cross-sectional analysis on a sub-cohort of 4510 subjects (aged ≥35 y; 52.0% women) from the Moli-sani Study (enrolment, 2005-2010). Food intake was recorded by a 188-item semi-quantitative food-frequency questionnaire. A Mediterranean diet score (MDS) was used as exposure and compared with non-Mediterranean dietary patterns, i.e. DASH (Dietary Approaches to Stop Hypertension), Palaeolithic and the Nordic diets. A Deep Neural Network based on 36 blood biomarkers was used to compute BA and the resulting Δage (BA-CA), which was tested as outcome in multivariable linear regressions adjusted for clinical factors, lifestyles and sociodemographic factors. RESULTS: In a multivariable-adjusted model, 1 standard deviation increase in the MDS was inversely associated with Δage (ß = -0.23; 95%CI -0.40, -0.07), and similar findings were observed with the DASH diet (ß = -0.17; 95%CI -0.33, -0.01). High dietary polyphenol content explained 29.8% (p = 0.04) and 65.8% (p = 0.02) of these associations, respectively, while other nutritional factors analysed (e.g. dietary fibre) were unlikely to be on the pathway. No significant associations were found with either the Palaeolithic or the Nordic diets. CONCLUSIONS: Increasing adherence to either the traditional MD or the DASH diet was associated with delayed biological aging, possibly through their high polyphenol content.

Exploring domains, clinical implications and environmental associations of a deep learning marker of biological ageing.

Deep Neural Networks (DNN) have been recently developed for the estimation of Biological Age (BA), the hypothetical underlying age of an organism, which can differ from its chronological age (CA). Although promising, these population-specific algorithms warrant further characterization and validation, since their biological, clinical and environmental correlates remain largely unexplored. Here, an accurate DNN was trained to compute BA based on 36 circulating biomarkers in an Italian population (N = 23,858; age ≥ 35 years; 51.7% women). This estimate was heavily influenced by markers of metabolic, heart, kidney and liver function. The resulting Δage (BA-CA) significantly predicted mortality and hospitalization risk for all and specific causes. Slowed biological aging (Δage < 0) was associated with higher physical and mental wellbeing, healthy lifestyles (e.g. adherence to Mediterranean diet) and higher socioeconomic status (educational attainment, household income and occupational status), while accelerated aging (Δage > 0) was associated with smoking and obesity. Together, lifestyles and socioeconomic variables explained ~48% of the total variance in Δage, potentially suggesting the existence of a genetic basis. These findings validate blood-based biological aging as a marker of public health in adult Italians and provide a robust body of knowledge on its biological architecture, clinical implications and potential environmental influences.

Ultra-processed food intake and all-cause and cause-specific mortality in individuals with cardiovascular disease: the Moli-sani Study.

AIMS: To evaluate the association of ultra-processed food (UPF) intake and mortality among individuals with history of cardiovascular disease (CVD) and analyse some biological pathways possibly relating UPF intake to death. METHODS AND RESULTS: Longitudinal analysis on 1171 men and women (mean age: 67 ± 10 years) with history of CVD, recruited in the Moli-sani Study (2005-10, Italy) and followed for 10.6 years (median). Food intake was assessed using a food frequency questionnaire. UPF was defined using the NOVA classification according to degree of processing and categorized as quartiles of the ratio (%) between UPF (g/day) and total food consumed (g/day). The mediating effects of 18 inflammatory, metabolic, cardiovascular, and renal biomarkers were evaluated using a logistic regression model within a counterfactual framework. In multivariable-adjusted Cox analyses, higher intake of UPF (Q4, ≥11.3% of total food), as opposed to the lowest (Q1, UPF <4.7%), was associated with higher hazards of all-cause (hazard ratio [HR]: 1.38; 95% confidence interval (CI): 1.00-1.91) and CVD mortality (HR: 1.65; 95% CI: 1.07-2.55). A linear dose-response relationship of 1% increment in UPF intake with all-cause and CVD mortality was also observed. Altered levels of cystatin C explained 18.3% and 16.6% of the relation between UPF (1% increment in the diet) with all-cause and CVD mortality, respectively. CONCLUSION: A diet rich in UPF is associated with increased hazards of all-cause and CVD mortality among individuals with prior cardiovascular events, possibly through an altered renal function. Elevated UPF intake represents a major public health concern in secondary CVD prevention.

Dietary Polyphenol Intake Is Associated with Biological Aging, a Novel Predictor of Cardiovascular Disease: Cross-Sectional Findings from the Moli-Sani Study.

Biological aging, or the discrepancy between biological and chronological age of a subject (Δage), has been associated with a polyphenol-rich Mediterranean diet and represents a new, robust indicator of cardiovascular disease risk. We aimed to disentangle the relationship of dietary polyphenols and total antioxidant capacity with Δage in a cohort of Italians. A cross-sectional analysis was performed on a sub-cohort of 4592 subjects (aged ≥ 35 y; 51.8% women) from the Moli-sani Study (2005-2010). Food intake was recorded by a 188-item food-frequency questionnaire. The polyphenol antioxidant content (PAC)-score was constructed to assess the total dietary content of polyphenols. Total antioxidant capacity was measured in foods by these assays: trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) and ferric reducing-antioxidant power (FRAP). A deep neural network, based on 36 circulating biomarkers, was used to compute biological age and the resulting Δage, which was tested as outcome in multivariable-adjusted linear regressions. Δage was inversely associated with the PAC-score (ß = -0.31; 95%CI -0.39, -0.24) but not with total antioxidant capacity of the diet. A diet rich in polyphenols, by positively contributing to deceleration of the biological aging process, may exert beneficial effects on the long-term risk of cardiovascular disease and possibly of bone health.

Changes in the consumption of foods characterising the Mediterranean dietary pattern and major correlates during the COVID-19 confinement in Italy: results from two cohort studies.

We investigated the effect of confinement during the COVID-19 pandemic on the consumption of foods characterising the Mediterranean dietary pattern (MDP) and its major correlates in two Italian population-based cohorts comprising 3161 subjects (mean age 57.7 ± 15.4 y). At population level, 38.8% of participants reported an improvement of diet quality during the first nationwide lockdown. Healthful dietary changes were associated with older age (ß = 0.41; 95% confidence interval [CI] 0.08, 0.73 for 56-65 vs. 18-39 y), greater wealth (ß = 0.45; 0.01, 0.89 for >40,000 ≤ 60,000 vs. ≤ 10,000 EUR/y), increased physical activity (ß = 0.52; 0.22, 0.81) and reduced body weight (ß = 0.36; 0.11, 0.62). Switching to healthy eating was also related to increased consumption of organic (ß = 1.24; 0.88, 1.60) and locally-grown food (ß = 0.74; 0.51, 0.96). The first Italian lockdown led, in a substantial part of the population, to higher intake of foods characterising a MDP; this was also accompanied by healthier lifestyle and more sustainable food choices.

Egg consumption and risk of all-cause and cause-specific mortality in an Italian adult population.

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.

Daily Coffee Drinking Is Associated with Lower Risks of Cardiovascular and Total Mortality in a General Italian Population: Results from the Moli-sani Study.

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.

Tissue Plasminogen Activator Levels and Risk of Breast Cancer in a Case-Cohort Study on Italian Women: Results from the Moli-sani Study.

BACKGROUND: Elevated levels of key enzymes of the fibrinolytic system, such as tissue plasminogen activator (tPA), are reported as predictors of poor outcome in cancer patients. Limited information is available about their potential predictive value for breast cancer (BC) risk in the general population. AIM: We examined the association of tPA levels with BC risk in a case-cohort study including women from the prospective Moli-sani cohort. METHODS: A sample of 710 women (mean age: 54.6 ± 12.1 years) was selected as a subcohort and compared with 84 BC cases, in a median follow-up of 4.2 years. Incident cases of BC were validated through medical records. tPA plasma levels were measured using an enzyme-linked immunosorbent assay kit. Hazard ratio (HR) and 95% confidence interval (CI), adjusted for relevant covariates, were estimated by a Cox regression model using the Prentice method. RESULTS: Compared with the lowest quartile (<4.9 ng/mL), women in the highest quartile of tPA (>11.2 ng/mL) had increased risk of BC (HRIVvsI: 2.20, 95% CI: 1.13-4.28) after adjusted for age, smoking, education, menopause, and residence. Further adjustment for biochemical markers did not modify this association. The risk of BC increased by 34% for each increase in 1 standard deviation of log-transformed tPA levels (p = 0.046). Elevated levels of tPA were associated mainly with estrogen-receptor-positive BC (2.08, 95% CI: 1.18-3.66). CONCLUSION: Higher levels of tPA, reported to predict cardiovascular risk, are a potential biomarker for BC risk, supporting the hypothesis of a "common soil" linking the pathogenic mechanisms of hormone-dependent tumors and cardiovascular disease.

Chili Pepper Consumption and Mortality in Italian Adults.

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.

Alcohol consumption and hospitalization burden in an adult Italian population: prospective results from the Moli-sani study.

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.

Mediterranean diet and mortality in the elderly: a prospective cohort study and a meta-analysis.

The Mediterranean diet (MD) has been associated with prolonged survival in the general population, but no meta-analysis has apparently investigated the potential health benefits in relation to mortality in the elderly. We performed a longitudinal analysis on 5200 individuals aged ≥65 years identified within the general population recruited in the Moli-sani study cohort (2005-2010). Adherence to the MD was appraised by the a priori Mediterranean diet score (MDS; range 0-9). Survival estimates were derived using Cox regression and competing risk models. For the meta-analysis, PubMed and Scopus databases were searched from inception until April 2018 to identify prospective studies on the MD and death risk in the elderly. Over a median follow-up of 8·1 years, a total of 900 deaths were ascertained in the elderly sub-sample of the Moli-sani cohort. A one-point increase in the MDS was associated with lower risk of all-cause, coronary artery disease/cerebrovascular and non-cardiovascular/non-cancer mortality (multi-variable hazard ratio (HR)=0·94; 95 % CI 0·90, 0·98; HR=0·91; 95 % CI 0·83, 0·99 and HR=0·89; 95 % CI 0·81, 0·96, respectively). In a meta-analysis of seven prospective studies, including our results, for a total of 11 738 participants and 3874 deaths, one-point increment in MDS was associated with 5 % (4-7 %) lower risk of all-cause death. An inverse linear dose-response relationship was found from a meta-analysis including three studies. In conclusion, a prospective cohort study and a meta-analysis showed that closer adherence to the MD was associated with prolonged survival in elderly individuals, suggesting the appropriateness for older persons to adopt/preserve the MD to maximise their prospects for survival.

Favorable association of polyphenol-rich diets with lung function: Cross-sectional findings from the Moli-sani study.

BACKGROUND: The association of the polyphenol content of human diet with pulmonary function is not yet fully understood. This study aims at evaluating the association of polyphenol consumption with lung function in a novel holistic approach. METHODS: A cross-sectional analysis of 4551 women and 5108 men (age ≥35 years) from the Moli-sani study was performed. Participants were randomly recruited from the general population. The EPIC-FFQ was used for the dietary assessment. Polyphenol intakes were calculated using Eurofir-eBASIS, and a polyphenol antioxidant content (PAC) score was constructed to assess the total content of the diet in these nutrients. Pulmonary function maneuvers were performed, and the forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) were measured; FVC% predicted and FEV1% predicted were computed using the European Community of Coal and Steel prediction equations that included height and age. RESULTS: In both genders, in age, height, and energy intake adjusted models, the majority of classes of polyphenols (mg/day) showed a positive association with FEV1, FVC, FEV1% predicted, and FVC% predicted (ß-coef >0, P < .05). Associations remained significant after adjustment for confounding factors in most cases (ß-coef >0, P < .05). The PAC score was associated in both genders with an increase in pulmonary function parameters (ß-coef >0, P < .05). The inclusion of white blood cell (WBC) counts in the multivariate model reduced the association in men but not in women. . CONCLUSIONS: A higher overall polyphenol content of human diet was associated with better pulmonary function in a general population. The association might be partially mediated by WBC in men.

Reduced mortality risk by a polyphenol-rich diet: An analysis from the Moli-sani study.

OBJECTIVES: The effect of the polyphenol content of the human diet on mortality risk is not yet fully understood. The aim of this study was to evaluate the association of a polyphenol-rich diet with mortality rate and a possible mediation effect by inflammation, in what we believe to be a novel, holistic approach. METHODS: We analyzed 21 302 participants (10 980 women and 10 322 men, aged ≥35 y) from the Moli-sani cohort. The participants were followed up for a median of 8.3 y. The European Prospective Investigation into Cancer and Nutrition food frequency questionnaire (FFQ) was used for dietary assessment. Flavonol, flavone, flavanone, flavanol, anthocyanin, isoflavone, and lignan intakes were calculated using European Food Information Resource-Bioactive Substances in Food Information Systems and the polyphenol antioxidant content (PAC)-score was constructed to assess the total content of these nutrients in the diet. RESULTS: Participants included in the highest quintile of intake of various polyphenol classes and subclasses presented a significant lower all-cause mortality risk compared with those in the lowest group of consumption (hazard ratio [HR] < 1; P <0.05). Cox regression analyses adjusted for potential confounders indicated that participants in higher quintiles of PAC-score had lower all-cause mortality risk (HR <1; P <0.05). When cause-specific mortality rates were considered, similar effects were observed for cardiocerebrovascular and cancer mortality (HR <1; P <0.05). CONCLUSIONS: The polyphenol content of the diet was associated with reduced mortality risk in a Mediterranean population, possibly through an antiinflammatory mechanism.

High adherence to the Mediterranean diet is associated with cardiovascular protection in higher but not in lower socioeconomic groups: prospective findings from the Moli-sani study.

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.

Mean platelet volume is associated with lower risk of overall and non-vascular mortality in a general population. Results from the Moli-sani study.

Larger mean platelet volume (MPV) has been associated with adverse health outcomes in high-risk populations or patients with cardiovascular disease (CVD). We tested the association of MPV with mortality in a prospective cohort study including 17,402 subjects randomly recruited from an adult general population within the Moli-sani study (2005-2010). Two distinct subgroups (with or without CVD at baseline) were subsequently analysed. Hazard ratios (HR) were calculated using multivariable Cox-proportional hazard models. Over a median follow up of eight years (137,547 person-years), 925 all-cause deaths occurred (330 vascular, 351 cancer and 244 other deaths). In a multivariable model, the highest MPV quintile (mean MPV=10.0 fL), as compared to the lowest one, was associated with reduced risk of overall mortality (HR=0.79; 95 % confidence interval 0.64-0.98), cancer death (HR=0.70; 0.49-1.00) and death from other non- vascular/non cancer causes (HR=0.55; 0.36-0.84) but not with vascular mortality. The inverse association with overall death appeared even stronger in the subgroup without CVD at baseline (HR=0.64; 0.50-0.81). In contrast, within 920 subjects reporting a previous CVD event, larger MPV was associated with higher risk of total mortality (HR=1.69; 1.05-2.72; p for interaction=0.048) and with a trend of risk for other cause-specific deaths. In conclusion, larger MPV is associated with lower risk of overall and non-vascular death in subjects apparently free from CVD, but appears to be a predictive marker of death in patients with CVD history. The latter is a likely effect modifier of the association between MPV and death.

Relative contribution of health-related behaviours and chronic diseases to the socioeconomic patterning of low-grade inflammation.

OBJECTIVES: To test the association of low-grade inflammation with socioeconomic status (SES) and determine the relative contribution of prevalent chronic diseases and health-related behaviours in explaining such association. METHODS: Cross-sectional analysis on 19,867 subjects (age ≥35, 48.1% men) recruited within the Moli-sani study from 2005 to 2010 (Italy). A score of low-grade inflammation, including platelet and leukocyte counts, the granulocyte-to-lymphocyte ratio, and C-reactive protein was applied. SES was measured by education, household income, and occupational social class. RESULTS: Low SES was associated with elevated levels of low-grade inflammation. Health behaviours (including adiposity, smoking, physical activity, and Mediterranean diet adherence) explained 53.5, 53.9, and 84.9% of the association between social class, income, and education with low-grade inflammation, respectively. Adiposity and body mass index showed a prominent role, while prevalent chronic diseases and conditions only marginally attenuated SES inequalities in inflammation. CONCLUSIONS: Low-grade inflammation was socioeconomically patterned in a large Mediterranean population. Potentially modifiable behavioural factors explained the greatest part of this association with a leading contribution of adiposity, body mass index, and physical activity.