Publications by authors named "Simona Costanzo"

122 Publications

Association between body mass index, waist circumference, and relative fat mass with the risk of first unprovoked venous thromboembolism.

Nutr Metab Cardiovasc Dis 2021 Jul 30. Epub 2021 Jul 30.

Department of Medicine and Surgery, University of Insubria, Varese, Italy; Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy.

Background And Aims: Obesity defined by body mass index (BMI) is independently associated with venous thromboembolism (VTE). Abdominal obesity, defined by waist circumference, is a predictor of cardiovascular events. Recently, relative fat mass (RFM) was proposed as a marker of cardiovascular risk. We assessed the role of three different measures of obesity to predict unprovoked VTE in a longitudinal study.

Methods And Results: Moli-sani is a prospective cohort study carried out in the general population of the Molise region, Italy. A total of 23,538 individuals (48% men, age 55.4 years) enrolled between 2005 and 2010 were eligible. Patients on anticoagulant treatment were excluded. BMI ≥30 kg/m defined obesity, waist circumference >102 cm for men or 88 cm for women defined abdominal obesity, tertiles of RFM were compared. The long-term incidence of first unprovoked VTE during follow-up was assessed. Overall, 29.6% individuals were obese and 44.2% had abdominal obesity. A total of 66 first unprovoked VTE events were diagnosed during a median follow-up of 8.2 years. After multivariable Cox regression analysis, the risk of unprovoked VTE was significantly higher in obese participants (HR 1.89, 95% CI 1.16-3.07) than in participants with BMI <30; in subjects with abdominal obesity than with normal waist circumference (HR 2.19, 1.26-3.81); and in subjects with third vs first RFM tertile index (HR 2.46, 1.15-5.28). The areas under the curves for the models including the three obesity indexes were comparable.

Conclusions: Three indexes of obesity based on BMI, waist circumference or RFM similarly predict first occurrence of unprovoked VTE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2021.07.018DOI Listing
July 2021

Iduronate-2-sulfatase transport vehicle rescues behavioral and skeletal phenotypes in a mouse model of Hunter syndrome.

JCI Insight 2021 Oct 8;6(19). Epub 2021 Oct 8.

Denali Therapeutics Inc., South San Francisco, California, USA.

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder caused by deficiency of the iduronate-2-sulfatase (IDS) enzyme, resulting in cellular accumulation of glycosaminoglycans (GAGs) throughout the body. Treatment of MPS II remains a considerable challenge as current enzyme replacement therapies do not adequately control many aspects of the disease, including skeletal and neurological manifestations. We developed an IDS transport vehicle (ETV:IDS) that is engineered to bind to the transferrin receptor; this design facilitates receptor-mediated transcytosis of IDS across the blood-brain barrier and improves its distribution into the brain while maintaining distribution to peripheral tissues. Here we show that chronic systemic administration of ETV:IDS in a mouse model of MPS II reduced levels of peripheral and central nervous system GAGs, microgliosis, and neurofilament light chain, a biomarker of neuronal injury. Additionally, ETV:IDS rescued auricular and skeletal abnormalities when introduced in adult MPS II mice. These effects were accompanied by improvements in several neurobehavioral domains, including motor skills, sensorimotor gating, and learning and memory. Together, these results highlight the therapeutic potential of ETV:IDS for treating peripheral and central abnormalities in MPS II. DNL310, an investigational ETV:IDS molecule, is currently in clinical trials as a potential treatment for patients with MPS II.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.145445DOI Listing
October 2021

Diabetes status-related differences in risk factors and mediators of heart failure in the general population: results from the MORGAM/BiomarCaRE consortium.

Cardiovasc Diabetol 2021 Sep 28;20(1):195. Epub 2021 Sep 28.

Division of Medicine, University of Turku and Turku University Hospital, Kiinanmyllynkatu 2, 20521, Turku, Finland.

Background: The risk of heart failure among diabetic individuals is high, even under tight glycemic control. The correlates and mediators of heart failure risk in individuals with diabetes need more elucidation in large population-based cohorts with long follow-up times and a wide panel of biologically relevant biomarkers.

Methods: In a population-based sample of 3834 diabetic and 90,177 non-diabetic individuals, proportional hazards models and mediation analysis were used to assess the relation of conventional heart failure risk factors and biomarkers with incident heart failure.

Results: Over a median follow-up of 13.8 years, a total of 652 (17.0%) and 5524 (6.1%) cases of incident heart failure were observed in participants with and without diabetes, respectively. 51.4% were women and the mean age at baseline was 48.7 (standard deviation [SD] 12.5) years. The multivariable-adjusted hazard ratio (HR) for heart failure among diabetic individuals was 2.70 (95% confidence interval, 2.49-2.93) compared to non-diabetic participants. In the multivariable-adjusted Cox models, conventional cardiovascular disease risk factors, such as smoking (diabetes: HR 2.07 [1.59-2.69]; non-diabetes: HR 1.85 [1.68-2.02]), BMI (diabetes: HR 1.30 [1.18-1.42]; non-diabetes: HR 1.40 [1.35-1.47]), baseline myocardial infarction (diabetes: HR 2.06 [1.55-2.75]; non-diabetes: HR 2.86 [2.50-3.28]), and baseline atrial fibrillation (diabetes: HR 1.51 [0.82-2.80]; non-diabetes: HR 2.97 [2.21-4.00]) had the strongest associations with incident heart failure. In addition, biomarkers for cardiac strain (represented by nT-proBNP, diabetes: HR 1.26 [1.19-1.34]; non-diabetes: HR 1.43 [1.39-1.47]), myocardial injury (hs-TnI, diabetes: HR 1.10 [1.04-1.16]; non-diabetes: HR 1.13 [1.10-1.16]), and inflammation (hs-CRP, diabetes: HR 1.13 [1.03-1.24]; non-diabetes: HR 1.29 [1.25-1.34]) were also associated with incident heart failure. In general, all these associations were equally strong in non-diabetic and diabetic individuals. However, the strongest mediators of heart failure in diabetes were the direct effect of diabetes status itself (relative effect share 43.1% [33.9-52.3] and indirect effects (effect share 56.9% [47.7-66.1]) mediated by obesity (BMI, 13.2% [10.3-16.2]), cardiac strain/volume overload (nT-proBNP, 8.4% [-0.7-17.4]), and hyperglycemia (glucose, 12.0% [4.2-19.9]).

Conclusions: The findings suggest that the main mediators of heart failure in diabetes are obesity, hyperglycemia, and cardiac strain/volume overload. Conventional cardiovascular risk factors are strongly related to incident heart failure, but these associations are not stronger in diabetic than in non-diabetic individuals. Active measurement of relevant biomarkers could potentially be used to improve prevention and prediction of heart failure in high-risk diabetic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-021-01378-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479921PMC
September 2021

Natriuretic Peptides and Risk of Type 2 Diabetes: Results From the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium.

Diabetes Care 2021 Sep 14. Epub 2021 Sep 14.

Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.

Objective: Natriuretic peptide (NP) concentrations are increased in cardiovascular diseases (CVDs) but are associated with a lower diabetes risk. We investigated associations of N-terminal pro-B-type NP (NT-proBNP) and midregional proatrial NP (MR-proANP) with incident type 2 diabetes stratified by the presence of CVD.

Research Design And Methods: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium, we included 45,477 participants with NT-proBNP measurements (1,707 developed type 2 diabetes over 6.5 years of median follow-up; among these, 209 had CVD at baseline) and 11,537 participants with MR-proANP measurements (857 developed type 2 diabetes over 13.8 years of median follow-up; among these, 106 had CVD at baseline). The associations were estimated using multivariable Cox regression models.

Results: Both NPs were inversely associated with incident type 2 diabetes (hazard ratios [95% CI] per 1-SD increase of log NP: 0.84 [0.79; 0.89] for NT-proBNP and 0.77 [0.71; 0.83] for MR-proANP). The inverse association between NT-proBNP and type 2 diabetes was significant in individuals without CVD but not in individuals with CVD (0.81 [0.76; 0.86] vs. 1.04 [0.90; 1.19]; multiplicative interaction = 0.001). There was no significant difference in the association of MR-proANP with type 2 diabetes between individuals without and with CVD (0.75 [0.69; 0.82] vs. 0.81 [0.66; 0.99]; multiplicative interaction = 0.236).

Conclusions: NT-proBNP and MR-proANP are inversely associated with incident type 2 diabetes. However, the inverse association of NT-proBNP seems to be modified by the presence of CVD. Further investigations are warranted to confirm our findings and to investigate the underlying mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc21-0811DOI Listing
September 2021

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

Eur J Epidemiol 2021 Aug 28. Epub 2021 Aug 28.

Department of Epidemiology and Prevention, IRCCS Neuromed, Via dell´Elettronica, 86077, Pozzilli, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10654-021-00797-7DOI Listing
August 2021

Age-specific atrial fibrillation incidence, attributable risk factors and risk of stroke and mortality: results from the MORGAM Consortium.

Open Heart 2021 07;8(2)

Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany.

Background: The main aim was to examine age-specific risk factor associations with incident atrial fibrillation (AF) and their attributable fraction in a large European cohort. Additionally, we aimed to examine risk of stroke and mortality in relation to new-onset AF across age.

Methods: We used individual-level data (n=66 951, 49.1% men, age range 40-98 years at baseline) from five European cohorts of the MOnica Risk, Genetics, Archiving and Monograph Consortium. The participants were followed for incident AF for up to 10 years and the association with modifiable risk factors from the baseline examinations (body mass index (BMI), hypertension, diabetes, daily smoking, alcohol consumption and history of stroke and myocardial infarction (MI)) was examined. Additionally, the participants were followed up for incident stroke and all-cause mortality after new-onset AF.

Results: AF incidence increased from 0.9 per 1000 person-years at baseline age 40-49 years, to 17.7 at baseline age ≥70 years. Multivariable-adjusted Cox models showed that higher BMI, hypertension, high alcohol consumption and a history of stroke or MI were associated with increased risk of AF across age groups (p<0.05). Between 30% and 40% of the AF risk could be attributed to BMI, hypertension and a history of stroke or MI. New-onset AF was associated with a twofold increase in risk of stroke and death at ages≥70 years (p≤0.001).

Conclusion: In this large European cohort aged 40 years and above, risk of AF was largely attributed to BMI, high alcohol consumption and a history MI or stroke from middle age. Thus, preventive measures for AF should target risk factors such as obesity and hypertension from early age and continue throughout life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/openhrt-2021-001624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330568PMC
July 2021

Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering.

J Healthc Eng 2021 25;2021:5556207. Epub 2021 Jun 25.

UOC Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5556207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238578PMC
August 2021

Ultra-processed food consumption and its correlates among Italian children, adolescents and adults from the Italian Nutrition & Health Survey (INHES) cohort study.

Public Health Nutr 2021 Jun 24:1-14. Epub 2021 Jun 24.

Department of Epidemiology and Prevention, IRCCS NEUROMED, Via dell'Elettronica, 86077 Pozzilli (IS), Italy.

Objective: To assess ultra-processed food (UPF) consumption and its socio-demographic, psychosocial and behavioural correlates in a general population of Italian children, adolescents and adults.

Design: Cross-sectional telephone-based survey.

Setting: Italy, 2010-2013.

Participants: In total, 9078 participants (5-97 years) from the Italian Nutrition & Health Survey. Dietary intakes were collected by a 1-d 24-h dietary recall. UPF was defined by the NOVA classification and expressed as percentage of total energies.

Results: Average energy intake from UPF (95 % CI) was 17·3 % (17·1 %, 17·6 %) among adults and 25·9 % (24·8 %, 27·0 %) in children/adolescents. Top sources of UPF were processed meats (32·5 %) and bread substitutes (16·7 %). Among adults, age (β = -3·10; 95 % CI (-4·40, -1·80) for >65 years v. 20-40 years; βs are dimensionless) and residing in Southern Italy (β = -0·73; 95 % CI (-1·32, -0·14) v. Northern) inversely associated with UPF. Screen view during meals was directly linked to UPF, as well as poor self-rated health (β = 5·32; 95 % CI (2·66, 7·99)), adverse life events (β = 2·33; 95 % CI (1·48, 3·18)) and low sleep quality (β = 2·34; 95 % CI (1·45, 3·23)). Boys consumed two-point percent more UPF of the total energy than girls (β = 2·01; 95 % CI (0·20, 3·82)). For all ages, a Mediterranean diet was inversely associated with UPF (β = -4·86; 95 % CI (-5·53, -4·20) for good v. poor adherence in adults and (β = -5·08; 95 % CI (-8·38, -1·77) for kids).

Conclusions: UPF contributes a modest proportion of energy to the diets of Italian adults while being one-quarter of the total energies in children/adolescents. UPF was associated with several psychosocial factors and eating behaviours. Increased adherence to Mediterranean diet would possibly result in lower UPF consumption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1368980021002767DOI Listing
June 2021

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study.

Front Med (Lausanne) 2021 9;8:639970. Epub 2021 Jun 9.

Ospedale del Mare, ASL Napoli 1, Napoli, Italy.

Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.639970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221239PMC
June 2021

Hydroxychloroquine and mortality in COVID-19 patients: a systematic review and a meta-analysis of observational studies and randomized controlled trials.

Pathog Glob Health 2021 Jun 15:1-11. Epub 2021 Jun 15.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli (IS), Italy.

 Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19, but its association with mortality is unclear. We reviewed published literature for evidence of an association between HCQ (with or without azithromycin (AZM)) and total mortality in COVID-19 patients. Articles were retrieved until April 29, 2021 by searching in seven databases. Data were combined using the general-variance-based method. A total of 25 cohort studies (N=41,339 patients) and 11 randomized clinical trials (RCTs; N=8,709) were found. The use of HCQ was not associated with mortality in meta-analysis of RCTs (pooled risk ratio (PRR): 1.08, 95%CI: 0.97-1.20; I=0%), but it was associated with 20% lower mortality risk (PRR=0.80, 95%CI: 0.69-0.93; I=80%) in pooling of cohort studies. The negative association with mortality was mainly apparent by pooling cohort studies that used lower doses of HCQ (≤400 mg/day; PRR=0.69, 95%CI: 0.57-0.87). Use of HCQ+AZM (11 studies) was associated with 25% non-statistically significant lower mortality risk (PPR=0.75; 0.51-1.10; P=0.15). Use of HCQ was not associated with severe adverse events (PRR=1.12, 95%CI: 0.88-1.44; I=0%). HCQ use was not associated with mortality in COVID-19 patients in pooling results from RCTs (high level of certainty of evidence), but it was associated with 20% mortality reduction when findings from observational studies were combined (low level of certainty of evidence). The reduction of mortality was mainly apparent in observational studies where lower doses of HCQ were used. These findings might help disentangling the debate on HCQ use in COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/20477724.2021.1936818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220439PMC
June 2021

Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project: a population-based study.

Addiction 2021 Jun 9. Epub 2021 Jun 9.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/add.15593DOI Listing
June 2021

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

Nutrients 2021 May 17;13(5). Epub 2021 May 17.

Department of Epidemiology and Prevention, IRCCS Neuromed, via dell'Elettronica, 86077 Pozzilli, Italy.

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 (β = -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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13051701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157169PMC
May 2021

Reduced pulmonary function, low-grade inflammation and increased risk of total and cardiovascular mortality in a general adult population: Prospective results from the Moli-sani study.

Respir Med 2021 08 4;184:106441. Epub 2021 May 4.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy; Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria, Varese, Italy. Electronic address:

Aim: to investigate the relation of pulmonary function impairment with mortality and the possible mediation by low-grade inflammation in a general adult population.

Methods: A prospective investigation was conducted on 14,503 individuals from the Moli-sani study (apparently free from lung disease and acute inflammatory status at baseline; 2005-2010). The 2012 Global Lung Function Initiative percent predicted (% pred) value of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF25-75) and FEV1 quotient (FEV1Q) index were used. C-reactive protein and blood cell counts were measured and a score of subclinical inflammation (INFLA-score) was calculated.

Results: Over a median follow-up of 8.6y, 503 deaths (28.9% cardiovascular) were ascertained. Total mortality increased by 19% for each decrease in 1 standard deviation of FEV1% pred or FVC% pred (Hazard Ratio:1.19; 95% CI:1.11-1.28 and 1.19; 1.10-1.28, respectively). Comparable findings for FEV1Q (1.30; 1.15-1.47) were observed. A statistically significant increased risk in cardiovascular mortality of 23%, 32% and 49% was observed for 1 standard deviation decrease of FEV1% pred, FVC% pred and FEV1Q, respectively. INFLA-score mediated the association of FEV1% pred and FEV1Q with cardiovascular mortality by 22.3% and 20.1%, respectively. Subjects with FEV1, FVC lower than normal limit showed increased risk both in total and cardiovascular mortality. Abnormal FEF25-75 values were associated with 33% (1.33; 1.02-1.74) total mortality risk.

Conclusions: Obstructive lung function impairment was associated with decreased survival. Low-grade inflammation mainly mediated the association of FEV1 with cardiovascular mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmed.2021.106441DOI Listing
August 2021

Sodium Intake and Proteinuria/Albuminuria in the Population-Observational, Cross-Sectional Study.

Nutrients 2021 Apr 11;13(4). Epub 2021 Apr 11.

Department of Epidemiology and Prevention, IRCCS Neuromed, 86077 Pozzilli, Italy.

Sodium effects on proteinuria are debated. This observational, cross-sectional, population-based study investigated relationships to proteinuria and albuminuria of sodium intake assessed as urinary sodium/creatinine ratio (NaCR). In 482 men and 454 women aged 35-94 years from the Moli-sani study, data were collected for the following: urinary NaCR (independent variable); urinary total proteins/creatinine ratio (PCR, mg/g), urinary albumin/creatinine ratio (ACR, mg/g), and urinary non-albumin-proteins/creatinine ratio (calculated as PCR minus ACR) (dependent variables). High values were defined as PCR ≥ 150 mg/g, ACR ≥ 30 mg/g, and urinary non-albumin-proteins/creatinine ratio ≥ 120 mg/g. Urinary variables were measured in first-void morning urine. Skewed variables were log-transformed in analyses. The covariates list included sex, age, energy intake, body mass index, waist/hip ratio, estimated urinary creatinine excretion, smoking, systolic pressure, diastolic pressure, diabetes, history of cardiovascular disease, reported treatment with antihypertensive drug, inhibitor or blocker of the renin-angiotensin system, diuretic, and log-transformed data of total physical activity, leisure physical activity, alcohol intake, and urinary ratios of urea nitrogen, potassium, and phosphorus to creatinine. In multivariable linear regression, standardized beta coefficients of urinary NaCR were positive with PCR (women and men = 0.280 and 0.242, 95% confidence interval = 0.17/0.39 and 0.13/0.35, < 0.001), ACR (0.310 and 0.265, 0.20/0.42 and 0.16/0.38, < 0.001), and urinary non-albumin-proteins/creatinine ratio (0.247 and 0.209, 0.14/0.36 and 0.09/0.33, < 0.001). In multivariable logistic regression, higher quintile of urinary NaCR associated with odds ratio of 1.81 for high PCR (1.55/2.12, < 0.001), 0.51 of 1.62 for high ACR (1.35/1.95, < 0.001), and of 1.84 for high urinary non-albumin proteins/creatinine ratio (1.58/2.16, < 0.001). Findings were consistent in subgroups. Data indicate independent positive associations of an index of sodium intake with proteinuria and albuminuria in the population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13041255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068813PMC
April 2021

Dietary selenium intake and risk of hospitalization for type 2 diabetes in the Moli-sani study cohort.

Nutr Metab Cardiovasc Dis 2021 06 25;31(6):1738-1746. Epub 2021 Feb 25.

Department of Epidemiology and Prevention, IRCCS NEUROMED, Pozzilli, IS, Italy; Department of Medicine and Surgery, Research Center in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, Varese-Como, Italy.

Background And Aims: Experimental and non-experimental human studies have consistently shown a positive association between exposure to the trace element selenium, which occurs primarily through diet, and risk of type 2 diabetes mellitus. Plausible biological mechanisms include adverse effects of selenium and selenium-containing proteins on glucose metabolism. However, the levels of exposure above which risk increases are uncertain.

Methods And Results: We examined the association between selenium intake and first hospitalization for type 2 diabetes during a median follow-up period of 8.2 years among 21,335 diabetes-free participants in the Moli-sani cohort, Italy. Selenium intake was ascertained at baseline using a food frequency questionnaire, showing a median value of 59 μg/day. During follow-up, we identified 135 incident cases of hospitalization for diabetes, based on population-based hospital discharge data. We used a Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization for diabetes, adjusting for potential confounders. HRs (95% CIs) were 1.01 (0.60-1.70), 1.13 (0.66-1.96) and 1.75 (0.99-3.10) comparing the second, third, and fourth sex-specific quartiles with the first quartile, respectively. Risk was 64% greater in the fourth quartile as compared with the previous three. Spline regression analysis also indicated a steeper increase in risk occurring among men compared with women.

Conclusions: In a large population of Italian adults free of type 2 diabetes at cohort entry, high dietary selenium intake was associated with increased risk of hospitalization for diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2021.02.016DOI Listing
June 2021

Different Anticoagulant Regimens, Mortality, and Bleeding in Hospitalized Patients with COVID-19: A Systematic Review and an Updated Meta-Analysis.

Semin Thromb Hemost 2021 Jun 13;47(4):372-391. Epub 2021 Apr 13.

Department of Epidemiology and Prevention. IRCCS Neuromed, via dell'Elettronica, Pozzilli, Isernia, Italy.

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 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; : 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; : 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; : 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0041-1726034DOI Listing
June 2021

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.

Int J Food Sci Nutr 2021 Apr 6:1-13. Epub 2021 Apr 6.

Department of Epidemiology and Prevention, IRCCS NEUROMED, Pozzilli (IS), Italy.

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 ( = 0.41; 95% confidence interval [CI] 0.08, 0.73 for 56-65 18-39 y), greater wealth ( = 0.45; 0.01, 0.89 for >40,000 ≤ 60,000 ≤ 10,000 EUR/y), increased physical activity ( = 0.52; 0.22, 0.81) and reduced body weight ( = 0.36; 0.11, 0.62). Switching to healthy eating was also related to increased consumption of organic ( = 1.24; 0.88, 1.60) and locally-grown food ( = 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09637486.2021.1895726DOI Listing
April 2021

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

Eur J Nutr 2021 Oct 24;60(7):3691-3702. Epub 2021 Mar 24.

Department of Epidemiology and Prevention, IRCCS NEUROMED, Via dell'Elettronica, 86077, Pozzilli, IS, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00394-021-02536-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437843PMC
October 2021

Changes in ultra-processed food consumption during the first Italian lockdown following the COVID-19 pandemic and major correlates: results from two population-based cohorts.

Public Health Nutr 2021 08 5;24(12):3905-3915. Epub 2021 Mar 5.

Department of Epidemiology and Prevention, IRCCS Neuromed, Via dell'Elettronica, Pozzilli (IS) 86077, Italy.

Objective: To evaluate changes in ultra-processed food (UPF) intake and its major correlates during the first Italian lockdown (9 March-3 May 2020).

Design: Retrospective observational study.

Setting: Italy.

Participants: We analysed 2992 subjects (mean age 57·9 ± 15·3 years, 40·4 % men). Individual participant data were pooled from two retrospective cohorts: (1) The Moli-LOCK cohort consists of 1501 adults, a portion of the larger Moli-sani study (n 24 325; 2005-2010) who were administered a phone-based questionnaire to assess lifestyles and psychological factors during confinement and (2) the Analysis of Long Term Risk of Covid-19 Emergency is a web-based survey of 1491 individuals distributed throughout Italy who self-responded to the same questionnaire by using Google forms.UPF was defined according to NOVA classification based on degree of food processing. An UPF score was created by assigning 1 point to increased consumption, -1 to decreased and 0 point for unchanged intakes of nineteen food items, with higher values indicating an increase in UPF during confinement.

Results: Overall, 37·5 % of the population reported some increase in UPF (UPF score ≥1). Adults were more likely to decrease UPF (multivariable regression coefficient β = -1·94; 95 % CI -2·72, -1·17 for individuals aged >75 years as compared with 18-39 years) as did individuals from southern Italian regions as compared with Northern inhabitants (β = -1·32; 95 % CI -1·80, -0·84), while UPF lowering associated with increased exercise (β = -0·90; 95 % CI -1·46, -0·35) and weight loss (β = -1·05; 95 % CI -1·51, -0·59) during confinement.

Conclusions: During the first Italian lockdown, about 40 % of our population switched to unfavourable eating as reflected by increased UPF intake and this may have long-term effects for health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1368980021000999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207556PMC
August 2021

Life Course Socioeconomic Status and Risk of Hospitalization for Heart Failure or Atrial Fibrillation in The Moli-Sani Study Cohort.

Am J Epidemiol 2021 Feb 24. Epub 2021 Feb 24.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli (IS), Italy.

We investigated the association of cumulative socioeconomic disadvantage (CSD) and socioeconomic (SES) trajectories across life course with the risk of first hospitalization for heart failure (HF) or atrial fibrillation (AF) and tested some biological mechanisms in explaining such associations. Longitudinal analysis on 21,756 HF- and AF-free subjects recruited in the Moli-sani Study (2005-2010; Italy) and followed up for 8.2 years. CSD was computed using childhood SES, education and adulthood SES indicators, and the same were used to define overall trajectories. High disadvantage across life course (CSD≥8) posed subjects at increased risk of HF (Hazard ratio [HR]=2.58; 95%CI 1.78, 3.74) or AF (HR=1.57;1.05,2.33), as compared to low CSD. All explanatory factors accounted for 18.5% and 24% of the excess of HF and AF risks, respectively, associated with CSD. For subjects with low childhood SES, advancements in education lowered risk of HF (HR=0.70;0.48, 1.02) or AF (HR=0.50;0.28, 0.89), whereas achievements of adulthood SES were unlikely to contribute to disease reduction. In conclusion, a life-course disadvantaged SES is an important predictor of first hospitalization for HF and AF; known risk factors partially explained the SES-disease gradient. Upwardly mobile groups are likely to mitigate the effect of poor childhood circumstances especially through educational advancement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwab046DOI Listing
February 2021

The CASSIOPEA Study (Economic Crisis and Adherence to the Mediterranean diet: poSSIble impact on biOmarkers of inflammation and metabolic PhEnotypes in the cohort of the Moli-sAni Study): Rationale, design and characteristics of participants.

Nutr Metab Cardiovasc Dis 2021 04 13;31(4):1053-1062. Epub 2020 Dec 13.

Department of Epidemiology and Prevention, IRCCS Neuromed, via dell'Elettronica, 86077, Pozzilli, IS, Italy; Department of Medicine and Surgery, Research Center in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, 21100, Varese-Como, Italy.

Background And Aims: The CASSIOPEA Study was designed to evaluate whether the economic downturn during the late 2000s was a contributing factor to the observed decrease in adherence to Mediterranean diet (MD).

Methods And Results: The study protocol consists of two steps: A) recall of 7406 men and women who, between 2005 and 2006, had been randomly recruited in the Moli-sani Study from the general population of Molise, to assess possible economic hardship (EH) related to the economic crisis initiated in 2007; B) re-examination, between 2017 and 2020, of available subjects identified in Step 1 as poorly or harder hit by EH to test the hypothesis that EH is associated with a decrease in MD adherence, possibly resulting in increased inflammation. The results of Step 1 are reported here. From the initial sample of individuals re-examined after 12.6 years (median; IQR = 12.1-13.0 y), 3646 were finally analysed. An Economic Hardship Score (EHS; range 0-14) was obtained by scoring three domains: 1) change in employment status; 2) financial hardship and 3) financial hardship for health expenditures. Overall, 37.8% of the sample reported high EHS (≥3), whilst 32% scored 0 (no EH). Those with high EHS were prevalently women and younger, with low socioeconomic status.

Conclusions: High economic hardship was prevalently reported by weaker socioeconomic groups. Longitudinal analysis (step 2) will examine whether the economic crisis had an effect on adherence to Mediterranean diet with consequent potential impact on inflammation, one of the main biological pathways linking MD to health outcomes. CLINICALTRIALS.

Gov Identifier: NCT03119142.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2020.12.008DOI Listing
April 2021

Will guidelines on alcohol consumption be personalized by a genetic approach?

Genes Nutr 2021 Jan 25;16(1). Epub 2021 Jan 25.

Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12263-021-00682-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830050PMC
January 2021

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

Eur Heart J 2021 03;42(12):1170-1177

Department of Cardiology, University Heart & Vascular Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany.

Aims: There is inconsistent evidence on the relation of alcohol intake with incident atrial fibrillation (AF), in particular at lower doses. We assessed the association between alcohol consumption, biomarkers, and incident AF across the spectrum of alcohol intake in European cohorts.

Methods And Results: In a community-based pooled cohort, we followed 107 845 individuals for the association between alcohol consumption, including types of alcohol and drinking patterns, and incident AF. We collected information on classical cardiovascular risk factors and incident heart failure (HF) and measured the biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I. The median age of individuals was 47.8 years, 48.3% were men. The median alcohol consumption was 3 g/day. N = 5854 individuals developed AF (median follow-up time: 13.9 years). In a sex- and cohort-stratified Cox regression analysis alcohol consumption was non-linearly and positively associated with incident AF. The hazard ratio for one drink (12 g) per day was 1.16, 95% CI 1.11-1.22, P < 0.001. Associations were similar across types of alcohol. In contrast, alcohol consumption at lower doses was associated with reduced risk of incident HF. The association between alcohol consumption and incident AF was neither fully explained by cardiac biomarker concentrations nor by the occurrence of HF.

Conclusions: In contrast to other cardiovascular diseases such as HF, even modest habitual alcohol intake of 1.2 drinks/day was associated with an increased risk of AF, which needs to be considered in AF prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehaa953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982286PMC
March 2021

Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study.

Thromb Haemost 2021 Aug 7;121(8):1054-1065. Epub 2021 Jan 7.

Cardiovascular and Thoracic Department, Azienda Ospedaliero-Universitaria Pisana and University of Pisa, Pisa, Italy.

Introduction:  A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality.

Aim:  We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients.

Methods:  In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores.

Results:  Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation.

Conclusion:  In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1347-6070DOI Listing
August 2021

DNA methylation in blood is associated with metabolic and inflammatory indices: results from the Moli-sani study.

Epigenetics 2021 Jan 4:1-14. Epub 2021 Jan 4.

Mediterranea Cardiocentro, Napoli, Italy.

Neuromedin U (NMU) is a neuropeptide involved in gut-brain axis, energy balance and immune response. We aimed at analysing the association between epigenetic variability and metabolic indices and the potential mediating role of low-grade inflammation in a general population of Italian adults. Blood DNA methylation levels at two CpG islands ( and ) were analysed using pyrosequencing in a randomly selected sub-cohort of 1,160 subjects from the Moli-sani study (≥35years; 49.20% men). Multivariable regressions adjusted for age, sex, smoking, alcohol and vegetable consumption were performed to estimate the associations between methylation and metabolic phenotypes (BMI, waist-to-hip ratio, blood pressure, glucose, HOMA-IR, lipids, lipoprotein(a) and apolipoproteins). Mediation analysis was performed to identify the influence of low-grade inflammation in the association using a composite index based on C reactive protein, granulocyte-to-lymphocyte ratio (GLR), platelet and white blood cell counts (INFLA-score).Using principal component analysis four methylation factors were identified: and . was FDR significantly associated with total cholesterol (for 1 SD increase: β = 4.5 ± 1.4 mg/dL of, R = 10.8%, p = 0.001), ApoB (0.03 ± 0.01 g/L, 12.2%, p = 0.0004), with INFLA-score (1.05 ± 0.22, = 2.7E-6) and GLR (-0.27 ± 0.03, 30.4%, = 1.3E-20). GLR and lymphocyte numbers mediate the association of with cholesterol (24.0% of total effect, Sobel p = 0.013) and ApoB (42.6%, p = 9E-7), respectively.These findings suggest that promoter methylation patterns could mark a pathway linking lipids with haematopoiesis and systemic inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15592294.2020.1864167DOI Listing
January 2021

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

J Nutr 2021 02;151(2):395-404

Department of Epidemiology and Prevention, IRCCS NEUROMED, Pozzilli, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jn/nxaa365DOI Listing
February 2021

Reduced Kidney Function and Relative Hypocalciuria-Observational, Cross-Sectional, Population-Based Data.

J Clin Med 2020 Dec 21;9(12). Epub 2020 Dec 21.

Department of Epidemiology and Prevention, IRCCS Neuromed, 86077 Pozzilli (IS), Italy.

This observational, cross-sectional, epidemiological analysis investigated relationships of kidney function to urine calcium and other variables. The analyses targeted two population-based samples of adults (Gubbio study and Moli-sani study: = 3508 and 955, respectively). Kidney function was assessed as estimated glomerular filtration rate (eGFR). Calcium/creatinine ratio (Ca/Cr) was used as index of urinary calcium in timed overnight urine under fed condition (Gubbio study), morning urine after overnight fast (Gubbio study), and first-void morning urine (Moli-sani study). Moli-sani study included also data for glomerular filtered calcium load, tubular calcium handling, and serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, calcium, and 25-hydroxyvitamin D. eGFR positively and independently related to Ca/Cr ( < 0.001). In multivariate analyses, eGFR lower by 10 mL/min × 1.73 m related to overnight urine Ca/Cr lower by 14.0 mg/g in men and 17.8 mg/g in women, to morning urine Ca/Cr lower by 9.3 mg/g in men and 11.2 mg/g in women, and to first-void urine Ca/Cr lower by 7.7 mg/g in men and 9.6 mg/g in women ( < 0.001). eGFR independently related to glomerular filtered calcium load ( < 0.001) and did not relate to tubular calcium handling ( ≥ 0.35). In reduced eGFR only (<90 mL/min × 1.73 m), low urine Ca/Cr independently related to low serum 1,25-dihydroxyvitamin D ( = 0.002) and did not relate to hyperphosphatemia, high serum parathyroid hormone, or hypocalcemia ( ≥ 0.14). Population-based data indicated consistent associations of lower kidney function with lower urine calcium due to reduction in glomerular filtered calcium. In reduced kidney function, relative hypocalciuria associated with higher prevalence of low serum 1,25-dihydroxyvitamin D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9124133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767498PMC
December 2020

Ultra-processed food consumption is associated with increased risk of all-cause and cardiovascular mortality in the Moli-sani Study.

Am J Clin Nutr 2021 02;113(2):446-455

Department of Epidemiology and Prevention, IRCCS NEUROMED, Pozzilli, Italy.

Background: Consumption of ultra-processed food (UPF) is gaining growing attention in relation to disease/mortality risk, but less is known on the main nutritional factors or biological mechanisms potentially underlying such associations.

Objectives: We aimed to assess the association between UPF and mortality risk in a large sample of the Italian adult population and test which nutritional factors were on the pathway of this relation. Established risk factors for cardiovascular disease (CVD) were analyzed as potential biological mechanisms linking UPF to mortality.

Methods: Longitudinal analysis was conducted on 22,475 men and women (mean ± SD age: 55 ± 12 y) recruited in the Moli-sani Study (2005-2010, Italy) and followed for 8.2 y. Food intake was assessed using a semiquantitative FFQ. UPF was defined using the NOVA classification according to degree of processing, and UPF intakes were categorized as quartiles of the ratio (%) of UPF (g/d) to total food consumed (g/d).

Results: Individuals reporting the highest intake of UPF (Q4, >14.6% of total food), as opposed to the lowest (Q1, UPF < 6.6%), experienced increased risks of CVD mortality (HR: 1.58; 95% CI: 1.23, 2.03), death from ischemic heart disease (IHD)/cerebrovascular disease (HR: 1.52; 95% CI: 1.10, 2.09), and all-cause mortality (HR: 1.26; 95% CI: 1.09, 1.46). High sugar content explained 36.3% of the relation of UPF with IHD/cerebrovascular mortality, whereas other nutritional factors (e.g., saturated fats) were unlikely to be on the pathway. Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality, and 12.0% for that of UPF with CVD mortality.

Conclusions: A high proportion of UPF in the diet was associated with increased risk of CVD and all-cause mortality, partly through its high dietary content of sugar. Some established biomarkers of CVD risk were likely to be on the pathway of such associations. These findings should serve as an incentive for limiting consumption of UPF, and encouraging natural or minimally processed foods, as several national nutritional policies recommend.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqaa299DOI Listing
February 2021

Contribution of cystatin C- and creatinine-based definitions of chronic kidney disease to cardiovascular risk assessment in 20 population-based and 3 disease cohorts: the BiomarCaRE project.

BMC Med 2020 11 9;18(1):300. Epub 2020 Nov 9.

Institute of Epidemiology and Medical Biometry, Ulm University, Helmholtzstr. 22, 89081, Ulm, Germany.

Background: Chronic kidney disease has emerged as a strong cardiovascular risk factor, and in many current guidelines, it is already considered as a coronary heart disease (CHD) equivalent. Routinely, creatinine has been used as the main marker of renal function, but recently, cystatin C emerged as a more promising marker. The aim of this study was to assess the comparative cardiovascular and mortality risk of chronic kidney disease (CKD) using cystatin C-based and creatinine-based equations of the estimated glomerular filtration rate (eGFR) in participants of population-based and disease cohorts.

Methods: The present study has been conducted within the BiomarCaRE project, with harmonized data from 20 population-based cohorts (n = 76,954) from 6 European countries and 3 cardiovascular disease (CVD) cohorts (n = 4982) from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for the Systematic COronary Risk Evaluation (SCORE) variables and study center. Main outcome measures were cardiovascular diseases, cardiovascular death, and all-cause mortality.

Results: The overall prevalence of CKD stage 3-5 by creatinine- and cystatin C-based eGFR, respectively, was 3.3% and 7.4% in the population-based cohorts and 13.9% and 14.4% in the disease cohorts. CKD was an important independent risk factor for subsequent CVD events and mortality. For example, in the population-based cohorts, the HR for CVD mortality was 1.72 (95% CI 1.53 to 1.92) with creatinine-based CKD and it was 2.14 (95% CI 1.90 to 2.40) based on cystatin-based CKD compared to participants without CKD. In general, the HRs were higher for cystatin C-based CKD compared to creatinine-based CKD, for all three outcomes and risk increased clearly below the conventional threshold for CKD, also in older adults. Net reclassification indices were larger for a cystatin-C based CKD definition. Differences in HRs (between the two CKD measures) in the disease cohorts were less pronounced than in the population-based cohorts.

Conclusion: CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of creatinine- and cystatin C-based CKD differed considerably between low- and high-risk populations. Especially in low-risk settings, the use of cystatin C-based CKD may result in more accurate risk estimates and have better prognostic value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12916-020-01776-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650190PMC
November 2020

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

Thromb Haemost 2021 Apr 18;121(4):449-456. Epub 2020 Oct 18.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy.

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 (HR: 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 ( = 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1718531DOI Listing
April 2021
-->