Moli-sani Study Research Articles

Socioeconomic trajectories and risk of hospitalization in the Moli-sani Study cohort

Abstract Background A life course approach was used to explore the impact of socioeconomic status (SES) on risk of hospitalizations for all-cause and for cardiovascular disease (CVD). Methods Longitudinal analyses on 19,999 subjects apparently free from CVD and cancer, recruited in the Moli-sani Study, Italy (2005-2010). Low and high SES in childhood, educational attainment (low/high) and SES during adulthood (measured by a score including material resources and dichotomized as low/high) defined the trajectories over life course. First hospital admissions were recorded by direct linkage with hospital discharge form registry. Hazard ratios (HR) with 95% confidence interval (95%CI) were calculated by multivariable Cox-regression. Results Over a median follow up of 7.3 y, we ascertained a total of 7,594 all-cause and 2,539 CVD hospitalizations. Poor childhood SES was associated with 11% and 17% increased risk of all-cause and CVD hospitalizations, respectively. Among subjects with poor childhood SES, an upward trajectory in education was associated with lower risk of hospital admission for all-cause (HR = 0.85; 95%CI 0.76-0.94) and CVD (HR = 0.78; 0.64-0.95), as opposed to subjects remained stably low (low education and adulthood SES). Individuals with high childhood SES, but not educational achievement, were at 26% increased risk of hospitalization for any cause, as compared to the stably high SES group, while failure to achieve both educational and material advancements was associated with 37% higher risk of CVD hospitalization. Conclusions In a large sample of healthy adults, social mobility (educational and/or material upward trajectories) was associated with lower incidence of hospital admissions for all-cause and CVD. Key messages Social mobility may counterbalance the negative health burden associated with low early-life SES. High SES in childhood poorly affects hospitalization risk if no additional achievements across life course occur.

Mediterranean diet and risk of first hospitalization for heart failure and atrial fibrillation

Abstract Background We aimed to explore the association of a traditional Mediterranean diet (MD) with risk of first hospitalization for heart failure (HF) or atrial fibrillation (AF) in a population-based cohort from a southern Italian region. Methods Longitudinal analysis on 20,598 men and women (aged≥35 y) free from HF, AF and cardiovascular disease recruited in the Moli-sani Study (2005-2010). First hospital admissions for HF or AF were recorded by direct linkage with hospital discharge form registry. Dietary data were collected by the EPIC food frequency questionnaire, adherence to MD was appraised by the Greek Mediterranean diet score (MDS ranging 0-9). Hazard ratios (HR) with 95% confidence interval (95%CI) were calculated by multivariable Cox-regression. Results Over a median follow up of 8.2 y, we ascertained 661 HF events and 337 AF cases. A 2-point increase in the MDS was associated with a downward trend in the risk of developing HF (HR = 0.94;0.85-1.04) after adjustment for potential confounders, while no association was found with risk of AF (HR = 1.07;0.94-1.21). Analyses run separately by gender revealed that higher adherence to an MD was associated with lower risk of HF among women (HF = 0.83;0.72-0.95 for 2-point increase in the MDS) but not in men (HR = 1.07;0.93-1.22; p for interaction=0.011). No gender-related difference was observed for AF risk (p for interaction=0.62). Among women, higher intake of monounsaturated over saturated fats was associated with 38% (20% to 52%) lower risk of HF, while in men moderate alcohol intake was likely to reduce HF risk (HR = 0.87;0.70-1.08). Conclusions Closer adherence to a traditional MD is associated with lower risk of first hospitalization for HF among women but not in men. No association was found with risk of AF. Key messages A traditional MD reduces the risk of HF in women but not in men. Minor dietary changes inspired to a traditional MD could be valuable primary prevention measures for risk of HF.

Health-related quality of life and risk of hospitalization in a healthy general population

Abstract Background The association of health-related quality of life (HRQL) with total and cardiovascular (CVD) hospitalization was assessed in a population-based cohort of apparently healthy subjects; several pathways possibly accounting for such associations were also tested. Methods Longitudinal analysis on 16,849 subjects free from CVD and cancer from the Moli-sani Study, Italy (2005-2010). HRQL was performed by the 36-Item Short Form Health Survey including both mental and physical domains. First hospital admissions were recorded by direct linkage with hospital discharge form registry. Hazard ratios (HR) with 95% confidence interval (95%CI) were calculated by multivariable Cox-regression. Results Over a median follow-up of 7.3 y, 6,061 all-cause, 1907 CVD, 431 IHD and 294 stroke hospital admissions were ascertained. The highest quintile of mental HRQL was associated with 23% (95%CI: 17% to 29%), 26% (15% to 36%) and 30% (5% to 48%) lower risk of total, CVD and IHD admissions to hospital, respectively, as compared to the lowest. Risk estimates for physical health were 0.60 (0.56-0.65 for Q5 vs Q1), 0.57 (0.50-0.65) and 0.73 (0.55-0.97) for total, CVD and IHD hospital admissions, respectively. A downward trend with stroke hospitalizations was found for both mental and physical HRQL. Healthy behaviours explained up to 13% of the association between mental HRQL and IHD risk; inflammatory markers (i.e. C-reactive protein and white blood cell count)) accounted for a significant proportion (34%) of the association of physical HRQL with IHD hospitalizations. Conclusions In a large sample of disease-free subjects, not only physical, but also higher mental HRQL is associated with lower risk of total and CVD hospitalizations. Key messages HRQL adds meaningful information beyond traditional risk factors to the prediction of hospitalization. HRQL assessment may be useful in stratifying hospitalization risk among a general population of healthy adults.

Variants in Neuromedin U pathway genes and risk of cardiovascular disease in an Italian population

Abstract Background Neuromedin U (NMU) is a hypothalamic neuropeptide with several functions, considered to be a potential therapeutic target for diabetes mellitus. The aim of this study was to analyse the association between genetic variants in NMU pathway genes and cardiovascular risk, in Italian adults from the general population recruited for the Moli-sani study. Methods A total of 4,039 participants (mean age 55.8±12.1 SD; men 46.1%) were randomly selected from the whole study population (N = 24,325; recruitment years 2005-2010). DNA from blood samples stored in the Moli-sani biobank were genotyped for 14 single nucleotide polymorphisms (SNPs) in the genes encoding for NMU, Neuromedin S (NMS) and their receptors NMUR1 and NMUR2. Cox regression analysis (age, sex, BMI, blood pressure, glucose and lipid levels as covariates) was performed to estimate the associations between SNPs and fatal or non-fatal CVD events (validated myocardial infarction or stroke), identified from death certificates and electronic records during a median follow-up of 4.5 years. A genetic score was then computed. Results CVD events (N = 93) were associated with mutant alleles in the NMU SNP rs55796004 (HR = 1.94; 95%CI:1.08-3.48) and rs4856020 (HR = 0.52; 95%CI: 0.29-0.94) and in the NMS SNP rs12474526 (HR = 0.48, 95%CI:0.28-0.81), independently from CVD risk factors. A SNP in NMUR1 showed a borderline association (rs6754952, HR = 0.74; 95%CI:0.54-1.00). The derived genetic score was associated with CVD incidence with a HR of 1.57 (95%CI:1.25-1.96, per 1 score SD). A HR of 7.33 (95%CI:1.68-32.01) was found comparing the last vs the 1st decile of the genetic score. Conclusions Italian adults carrying variants in NMU pathway genes are at increased CVD risk. Intermediate phenotypes, mediating this association independent of classical risk factors, are unknown and should be investigated. Once confirmed, these results could be useful to improve CVD risk assessment and to plan cost-effective interventions. Key messages Polymorphisms in NMU pathway genes are associated with CVD risk independently of classical CVD risk factors, suggesting a potential clinical utility in CVD prediction when added to CVD risk algorithms. The unknown phenotype mediating the association between NMU genes polymorphisms and CVD development could be the neglected CVD risk factor potentially explaining the unpredicted CVD fraction.

Vitamin D Status and Indices of Mineral Homeostasis in the Population: Differences Between 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D.

Opinions are conflicting about the epidemiology of vitamin D deficiency. This population-based study investigated cross-sectionally the associations of 25-hydroxyvitamin D (calcidiol) and 1,25-dihydroxyvitamin D (calcitriol) with indices of mineral homeostasis. Study cohort consisted of 979 persons of the Moli-Sani study, both sexes, ages ≥35 years. Data collection included serum calcidiol by different assays, serum calcitriol, serum parathyroid hormone, serum and urine calcium, and phosphorus. Prevalence of mild-to-moderate calcidiol deficiency (10–19 ng/mL) was 36.4% and did not associate with hypocalcemia or hyperparathyroidism. Prevalence of severe calcidiol deficiency (<10 ng/mL) was 16.8% and associated with hyperparathyroidism only (odds ratio = 8.81, 95% confidence interval = 2.4/32.9). Prevalence of calcitriol deficiency (<18 pg/mL) was 3.1% and associated with hypocalcemia (29.1, 7.4/114.5) but not hyperparathyroidism. In ANOVA along concentration strata, lower calcidiol associated with higher parathyroid hormone only (p < 0.001). Lower calcitriol associated with lower serum and urine calcium (p < 0.001) but not with parathyroid hormone. Calcidiol findings were consistent with different calcidiol assays. In the population, mild-to-moderate calcidiol deficiency did not associate with abnormal mineral homeostasis. Severe calcidiol deficiency and calcitriol deficiency associated with different disorders: lower calcidiol associated with hyperparathyroidism whereas lower calcitriol associated with hypocalcemia and low urine calcium.

Interaction between Mediterranean diet and statins on mortality risk in patients with cardiovascular disease: Prospective findings from the Moli-sani Study

Introduction: Statins are prescribed for patients with cardiovascular disease (CVD), along with the recommendation of adopting healthy diets. This stufy aimed to evaluate the independent and the combined effect of statins and Mediterranean diet (MD) towards mortality risk in subjects with previous CVD by using real-life data from a population-based prospective cohort. We performed a longitudinal analysis on 1,180 subjects (mean age 67.7 ± 10) with prior CVD at enrollment in the Moli-sani study and followed up for 7.9 years (median). Adherence to MD was appraised by a Mediterranean diet score (MDS). Hazard ratios (HR) with 95% confidence intervals (95%CI) calculated by multivariable Cox regression and competing risk models. Low-grade inflammation was measured by an INFLA-score including C-reactive protein, leukocyte and platelet counts, and the ratio of granulocyte to lymphocyte number.

Association of traditional Mediterranean diet and non-Mediterranean dietary scores with all-cause and cause-specific mortality: Prospective findings from the Moli-sani study

Association of traditional Mediterranean diet and non-Mediterranean dietary scores with all-cause and cause-specific mortality: Prospective findings from the Moli-sani study

Chili pepper consumption and risk of total and cause-specific mortality in a Mediterranean population: Prospective findings from the Moli-sani study

Chili pepper consumption and risk of total and cause-specific mortality in a Mediterranean population: Prospective findings from the Moli-sani study

Machine Learning Approaches for the Estimation of Biological Aging: The Road Ahead for Population Studies.

In recent years, different machine learning algorithms have been developed for the estimation of Biological Age (BA), defined as the hypothetical underlying age of an organism. BA can be computed based on different circulating and non-circulating biomarkers. In this perspective, identifying biomarkers with a prominent influence on BA and developing reliable models for its estimation is of fundamental importance for monitoring healthy aging, and could provide new tools to screen health status and the risk of clinical events in the general population. Here, we briefly review the different machine learning (ML) approaches used for BA estimation, focusing on those methods with potential application to the Moli-sani study, a prospective population-based cohort study of 24,325 subjects (35–99 years). In particular, we discuss the potential of BA estimation based on blood biomarkers, which likely represents the easiest and most immediate way to compute organismal BA. Similarly, we describe ML methods for the estimation of brain age based on structural neuroimaging features. For each method, we discuss the relation with epidemiological variables (e.g., mortality), genetic and environmental factors, and common age-related diseases (e.g., Alzheimer disease), to examine the potential as aging biomarker in the general population. Finally, we hypothesize new approaches for BA estimation, both at the single organ and at the whole organism level. Overall, here we trace the road ahead in the Big Data era for our and other prospective general population cohorts, presenting ways to exploit the notable amount of data available nowadays.

Impact of combined healthy lifestyle factors on survival in an adult general population and in high-risk groups: prospective results from the Moli-sani Study.

There is poor knowledge on the association between combined lifestyles with mortality risk among individuals at high risk, and little is known on the biological mechanisms that could be on the pathway. Longitudinal analysis on 22839 individuals from the Moli-sani Study (Italy, 2005-2010). Among them, we identified 5200 elderly individuals (≥65year), 2127 subjects with diabetes and 1180 with cardiovascular disease (CVD) at baseline. A healthy lifestyle score (HLS) was calculated, allocating 1 point for each of the following: abstention from smoking; adherence to Mediterranean diet; physical activity; absence of abdominal obesity. Hazard ratios (HR) with 95% confidence intervals (95%CI) were calculated by multivariable Cox regression and competing risk models. During 8.2years of follow-up, 1237 deaths occurred. In the general population, adherence to all four healthy lifestyles, compared with none or 1, was associated with lower risk of all-cause (HR=0.53; 95%CI:0.39-0.72), CVD (HR=0.54; 0.32-0.91), cancer (HR=0.62; 0.39-1.00) and mortality from other causes (HR=0.39; 0.19-0.81). A 1-point increase in HLS was associated with 20%, 22% and 24% lower risk of total mortality among the elderly, in subjects with diabetes or CVD, respectively. Traditional (e.g. blood lipids), inflammatory (e.g. C-reactive protein) and novel biomarkers (e.g. markers of cardiac damage) accounted for up to 24% of the association of HLSwith all-cause mortality risk in the general population. The impact of combined four healthy lifestyles on survival was considerable, both in the general population and among high-risk subgroups. Inflammatory and novel biomarkers of CVD risk explained a substantial proportion of this association.

Socioeconomic trajectories across the life course and risk of total and cause-specific mortality: prospective findings from the Moli-sani Study

BackgroundA life course approach has been suggested as the most appropriate to establish the total impact of socioeconomic status (SES) on adult health outcomes; however, such an approach has been...

Abstract P224: Chili Pepper Intake and Risk of Total and Cardiovascular Mortality in Italian Adults: Prospective Findings From the Moli-Sani Study

Introduction: Chili pepper, along with other spices, is an integral part of a traditional Mediterranean diet (MD). Yet there is paucity of epidemiological data on the association between chili pepper intake and mortality risk, with lack of studies from Mediterranean populations. Hypothesis: We assessed the hypothesis of an association between chili pepper consumption and total and cardiovascular (CVD) risk of death in a large sample of the Italian general population, and tested different biological mediators of the association. Methods: Longitudinal analysis on 22,811 men and women aged≥35 years enrolled in the Moli-sani Study cohort, Italy (2005-2010). Chili pepper intake was estimated by the EPIC food frequency questionnaire and categorized as none/rare consumption, up to 2 times/week, 2-4 and &gt; 4 times/week. Multivariable hazard ratios (HR) with 95% confidence intervals (95%CI) were calculated by multivariable Cox regression and competing risk models. Results: Over a median follow up of 8.2 years, a total of 1,236 deaths were ascertained, of which 444 from CVD. Multivariable risk estimates for all-cause and CVD mortality among participants in the regular (&gt;4 times/week) relative to the none-rare intake were, respectively, 0.77 (0.66-0.90) and 0.66 (0.50-0.86). Regular intake also lowered ischemic heart disease (0.55;0.35-0.87) and cerebrovascular death risks (0.39;0.20-0.76). Traditional CVD risk factors (e.g. blood cholesterol, triglycerides) only marginally account for such associations (Table). Conclusions: In a large Mediterranean population, regular consumption of chili pepper is associated with lower risk of total and CVD death independent of adherence to MD. Known biomarkers only marginally accounted for the association of chili pepper intake with total mortality.

Abstract P353: Health-Related Quality of Life and Risk of All-cause and Cardiovascular Hospitalization in a Healthy General Population: Prospective Findings From the Moli-Sani Study

Introduction: There is paucity of data on the longitudinal association of health-related quality of life (HRQL) with health outcomes from the general population, and little is known on the pathways of such associations. Hypothesis: We assessed the hypothesis that HRQL would predict risk of total and cardiovascular (CVD) hospitalization in a population-based cohort of healthy subjects, and tested four pathways possibly accounting for such associations. Methods: Longitudinal analysis on 16,097 subjects from the general population of the Moli-sani study, Italy (2005-2010), free from CVD, cancer and diabetes. HRQL was assessed by the 36-Item Short Form Health Survey including both mental and physical domains. Behavioural, traditional, inflammatory and novel markers of CVD risk (listed in table) were tested as explanatory factors. First hospital admissions were recorded by direct linkage with hospital discharge forms. Hazard ratios (HR) with 95% confidence interval (95%CI) were calculated by multivariable Cox-regression. Results: Over a median follow-up of 7.4 years, 5644 all-cause and 1724 CVD hospital admissions were ascertained. The highest quintile of mental HRQL was associated with 23% (95%CI: 17% to 29%) and 27% (15% to 37%; Table) lower risk of total and CVD hospitalization, respectively, as compared to the lowest. Risk estimates for physical health were 0.59 (0.54-0.63 for Q5 vs Q1) and 0.56 (0.48-0.64) for total and CVD risk of hospital admissions, respectively. Novel biomarkers (listed in table) accounted for the largest, although modest, proportion of the association of HRQL with risk of CVD hospitalization. Conclusions: In a large sample of disease-free subjects, not only higher physical, but also higher mental HRQL is associated with lower risk of total and CVD hospitalizations. Differences in baseline novel biomarkers slightly explain such associations. Our results suggest that HRQL assessment may be useful in stratifying hospitalization risk among a general population of adults.

Abstract 013: Cumulative Socioeconomic Disadvantage Across Life Course and Risk of Hospitalization for Heart Failure or Atrial Fibrillation and Mediating Pathways: Prospective Findings From the Moli-Sani Study

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 P079: Prediction of All-Cause Mortality in Diabetic Patients

Introduction: Diabetics people have an increased risk of developing health problems, including macro-vascular complications, and have more than double risk of death for any causes. Early identification of high-risk diabetic patients is therefore important so that appropriate interventions can be provided to help reduce the risk of premature mortality. Hypothesis: The purpose of this study was to investigate factors associated with all-cause mortality in diabetic patients and create a mortality risk calculator to aid in treatment decisions. Methods: Longitudinal analysis on 2,286 patients with type 2 diabetes individuated in the general population of the Moli-sani study, a population-based cohort study that recruited 24,325 men and women aged≥35 yr of Southern Italy, 2005-2010. Diabetes was defined as use of antidiabetic treatment or fasting blood glucose ≥126 mg/dl at baseline. The cohort was followed up until December 31 st 2015. Overall mortality was assessed by the Italian mortality registry (ReNCaM registry) and validated by Italian death certificates. Association of risk factors with mortality was assessed by multivariable Cox-regression survival analysis. A global score for mortality was obtained summing up scores (σ) obtained as rescaled beta coefficients of the Cox regression for each conditions. Results: Over a median follow-up of 7.8 years (17,652 person-years), 318 all-cause deaths were ascertained. Starting from a large panel of potential risk factors, we settled a final multivariable model including conditions independently associated with all-cause mortality, specifically: age (σ=0, 2 or 7 for age&lt;55 yr, 55-70 yr or ≥70 yr, respectively), sex (σ=0 or 2 for women or men), diabetic drugs in use (σ=0, 1 or 2 for none, yes but not insulin, insulin, respectively), history of cardiovascular disease (σ=0 or 2 for no or yes), cigarette smoking (σ=0, 2 or 3 for no, former or current), C-reactive protein (CRP) (σ=0, 1 or 3 for CRP≤1 mg/L, 1-2.99 mg/L or 3-10 mg/L), estimated glomerular filtration rate (eGFR, ml/min/1.73m 2 ) (σ=0, 1 or 3 for eGFR≥90, 60-90 or &lt;60) and adhesion to Mediterranean Diet (σ=0, -1 or -2 for low (0-3 points), intermediate or high adhesion (≥6 points)). C-statistic for the final model was 0.74. Diabetic patients stratified according to global score clearly were discriminated as mortality risk; specifically hazard ratio and predicted risk of death at 10 years were 1.0 (referent) and 4.5%, 2.80 (95%CI: 2.00 to 3.93) and 12.1% and 8.47 (6.14 to 11.68) and 32.2% for values of the global score 0 to 5 (prevalence 15.7%), 8 to10 (19.9%) and 14 to 24 (16.8%), respectively (P for difference in Kaplan-Meier curves &lt;0.0001). Conclusions: A global score of risk for all-cause mortality in diabetic patients has been developed, easy to use in clinical practice which include classical CVD risk factors and indicators of nephropathy, low grade inflammation and adherence to Mediterranean Diet.

Commentary on Costanzo et al. (2019): The need for secondary analyses of prospective cohort studies—creating a better understanding of alcohol consumption and hospitalization

The risk relationsip between alcohol consumption and disease occurrence often differs depending on whether the end-point used is mortality or morbidity. More studies using morbidity as an end-point are required to avoid incorrect results when estimating the burden of alcohol-related harm. Cohort study networks offer opportunities for conducting such studies. Alcohol consumption is a leading risk factor for the burden of disease 1, 2, and a large proportion of the alcohol-attributable burden is due to disability and impaired functioning 1-3. However, the majority of cohort studies which examine the risk relationship (RR) between alcohol consumption and disease occurrence use mortality as an end-point 4 because mortality is easier to assess as its recording is often mandated by law, while the measurement of non-fatal end-points are more resource-intensive to collect and often are not mandated by law 4, 5. For example, studies using hospitalization as an end-point require a central collection and collation of hospitalization records, and for these records to be linked to a unique personal identifier. However, in many countries and regions, hospitalization services are administered by multiple companies with different data access and data organization policies. Under such circumstances, the resources needed to collect and harmonize hospitalization data from multiple sources are often cost- and resource-prohibitive. Consequently, for meta-analyses, data on the effects of alcohol on morbidity alone are not sufficiently available to produce accurate and precise RR estimates. Accordingly, for most disease conditions, meta-analyses combine studies which use mortality and morbidity as end-points 3, 4. Previous studies have found evidence that the alcohol RRs for various chronic diseases 6-9 may differ depending on whether mortality or morbidity is used as the end-point. In line with this, the Moli-sani study differs from mortality-based studies 3, 19 in that heavy alcohol consumers were found not to be at an increased risk of hospitalization from ischaemic heart disease and cerebrovascular accidents. These differences in the RRs by disease end-point are due to potentially confounding factors (e.g. the stage at which the diseases are diagnosed and treated, access to health care, heavy drinkers avoiding hospitals due to stigmatization by health-care workers 10-14 and/or factors affected by alcohol consumption (e.g. adherence to treatment regimens 15. Therefore, the combining of mortality and morbidity RRs may lead to incorrect results in studies which utilize both these RRs, such as the 2018 Global Status Report on Alcohol and Health 1, the 2017 Global Burden of Disease study 2 and other studies which have estimated hospitalizations and hospitalization costs attributable to alcohol 16-18. The data analysis of the Moli-sani study by Costanzo and colleagues 19 demonstrates the availability of opportunities to perform analyses of cohort studies which are linked to hospital discharge registries. As a result of the observation that there are different alcohol RRs for morbidity and mortality, there is a need for additional analyses of cohort studies linked to hospitalization records to examine the association of alcohol with specific alcohol-related diseases. Such analyses could take advantage of existing cohort study networks. An example of a large cohort study network is the European Prospective Investigation into Cancer and Nutrition (of which the Moli-sani study is a participant). Although this cohort study network was originally designed to examine the RRs for various risk factor exposures and the development of cancer, such a network can be used for the secondary purpose of assessing the RR for alcohol consumption and hospitalization. These sorts of analyses will lead to improvements in our understanding of how alcohol consumption leads to disease occurrence and, further, will improve the evidence base for studies which model how best to reduce morbidity, hospitalizations and hospital costs due to alcohol consumption. None. K.D.S. receives funding from the 2018 Canadian Institutes of Health Research - Institute of Population and Public Health Trailblazer Award in Population and Public Health Research.

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

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. Prospective cohort study (baseline 2005-10) linked to a registry of hospital discharge records to identify hospitalizations at follow-up (December 2013). Molise region, Italy. A total of 20 682 individuals (48% men, age≥35years) who participated in the Moli-sani Study and were free from cardiovascular disease or cancer at baseline. 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. During a median follow-up of 6.3years, 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. 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.

Interaction between Mediterranean diet and statins on mortality risk in patients with cardiovascular disease: Findings from the Moli-sani Study

BackgroundStatins 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. MethodsLongitudinal 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. ResultsMultivariable 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. ConclusionsMD 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.

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

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

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.