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BackgroundAging clocks tag the actual underlying age of an organism and its discrepancy with chronological age and have been reported to predict incident disease risk in the general population. However, the relationship with neurodegenerative risk and in particular with Parkinson’s Disease (PD) remains unclear, with few discordant findings reporting associations with both incident and prevalent PD risk.ObjectiveTo clarify this relationship, we computed a common aging clock based on blood markers and tested the resulting discrepancy with chronological age (ΔPhenoAge) for association with both incident and prevalent PD risk.MethodsIn a large Italian population cohort - the Moli-sani study (N=23,437; age ≥ 35 years; 52% women) - we carried out both Cox Proportional Hazards regressions modelling ΔPhenoAge as exposure and incident PD as outcome, and linear models testing prevalent PD as exposure and ΔPhenoAge as outcome. All models were incrementally adjusted for age, sex, education level completed and other risk/protective factors previously associated with PD risk in the same cohort (prevalent dysthyroidism, hypertension, diabetes, use of oral contraceptives, exposure to paints, daily coffee intake and cigarette smoking).ResultsNo significant association between incident PD risk (209 cases, median (IQR) follow-up time 11.19 (2.03) years) and PhenoAging was observed (Hazard Ratio [95% Confidence Interval] = 0.98 [0.71; 1.37]). However, a small but significant increase of ΔPhenoAge was observed in prevalent PD cases vs healthy subjects (β (Standard Error) = 1.39 (0.70)). An analysis of each component biomarker of PhenoAge revealed a significant positive association of prevalent PD status with red cell distribution width (RDW; β (SE) = 0.46 (0.18)). All the remaining markers did not show any significant evidence of association.ConclusionThe reported evidence highlights systemic effects of prevalent PD status on biological aging and red cell distribution width. Further cohort and functional studies may help shedding a light on the related pathways altered at the organism level in prevalent PD, like red cells variability, inflammatory and oxidative stress mechanisms.

Epidemiological data on the association between fibrinogen levels and mortality are scarse and controversial. Longitudinal analyses were performed, separately by sex, on 17,689 individuals from the Moli-sani study [53% women, ≥35 years, free from cardiovascular disease (CVD) or cancer at enrolment], to evaluate the association between plasma fibrinogen and all-cause and cause-specific mortality. Over a median follow-up of 11.2 years, 1,058 deaths (34.7% CVD, 36.3% cancer) were ascertained. Both in the lowest (1.12-2.64 g/L) and highest (≥3.62 g/L) fibrinogen quintiles, women had an increased all-cause mortality hazard, when compared with third quintile (2.97-3.23 g/L). Dose-response analyses showed a U-shaped relationship in women (P overall

BackgroundPatients with cancer are commonly characterized by abnormalities in laboratory coagulation tests, underlying a subclinical hypercoagulable condition. Due to the involvement of the hemostatic system in cancer patients, some of its biomarkers, such as fibrinogen, could be a useful tool in predicting cancer risk. We performed a case-cohort study to evaluate the relationship among fibrinogen levels and colorectal cancer (CRC).MethodsIn the framework of Moli-sani Study (N = 24,325, enrolled 2005–2010) a subcohort of 1,290 individuals (55.0% women; mean age 55.0 ± 12.0 years) was selected and compared with 126 CRC cases identified during a follow-up of 4.3 years. Incident cases of colorectal cancer were ascertained by direct linkage with hospital discharge forms according to the International Classification of Disease (ICD-9-CM) codes: 153–154. Events were validated through medical records and confirmed by histological reports. Fibrinogen levels were measured in frozen citrated plasma samples. Hazard Ratio (HR) and 95% confidence interval (CI), adjusted by relevant covariates were estimated by a Cox regression model using Prentice method.ResultsIndividuals with levels of fibrinogen ≥400 mg/dL had a higher hazard to develop colorectal cancer when compared to those with lower levels after adjustment for sex and age (HR: 1.81; 95% CI 1.12–2.92). Additional adjustment for CRC family history, income, physical activity, diabetes medication and hypercholesterolemia did not modify the result (HR: 1.91; 95% CI 1.15–3.17). Analyses stratified by age and sex showed a most evident association in elderly (HR: 2.30; 95% CI: 1.10–4.81) and in women (HR: 2.28; 95% CI: 1.08–4.81). Sensitivity analyses confirmed the main findings, showing independence from a potential role of confounding by a large panel of biomarkers, including inflammation and hemostasis factors.ConclusionOur results, based on a case-cohort study from a general adult population apparently free from any cancer during the recruitment, showed that fibrinogen levels ≥400 mg/dL were positively and independently associated with CRC, suggesting that this glycoprotein could be a potential biomarker for this type of cancer and supporting the “common soil hypothesis” in the pathophysiology of cardiovascular disease and tumors.

BackgroundMajor depressive disorder is a mental illness associated with chronic conditions like cardiovascular disease (CVD). Circulating inflammation has been proposed as a potential mechanism underlying this link, although the role of specific biomarkers, gender, and symptom domains is not well elucidated.MethodsWe performed multivariable Cox regressions of first hospitalization/all-cause mortality and CVD, ischemic heart (IHD), and cerebrovascular disease (CeVD) causes vs. depression severity in an Italian population cohort (N = 13,191; age ≥ 35 years; 49.3% men; 4,856 hospitalizations and 471 deaths, median follow-up 7.28 and 8.24 years, respectively). In models adjusted for age, sex, and socioeconomic status, we estimated the proportion of association explained by C-reactive protein (CRP), platelet count, granulocyte-to-lymphocyte ratio (GLR), and white blood cell count (WBC). Gender-by-depression interaction and gender-stratified analyses were performed. Associations of polychoric factors tagging somatic and cognitive symptoms with incident clinical risks were also tested, as well as the proportion explained by a composite index of circulating inflammation (INFLA score).ResultsSignificant proportions of the influence of depression on clinical risks were explained by CRP (4.8% on IHD hospitalizations), GLR (11% on all-cause mortality), and WBC (24% on IHD/CeVD hospitalizations). Gender-by-depression interaction was significantly associated only with all-cause mortality (p = 0.03), with moderate depression showing a + 60% increased risk in women, but not in men. Stable associations of somatic, but not of cognitive, symptoms with increased hospitalization risk were observed (+ 16% for all causes, + 14% for CVD causes), with INFLA score explaining small but significant proportions of these associations (2.5% for all causes, 8.6% for IHD causes).ConclusionsThese findings highlight the importance of cellular components of inflammation, gender, and somatic depressive symptoms in the link between depression and clinical (especially CVD) risks, pointing to the existence of additional pathways through which depression may play a detrimental effect on the cardiovascular system.

Chronological age (CA) may not accurately reflect the health status of an individual. Rather, biological age (BA) or hypothetical underlying “functional” age has been proposed as a relevant indicator of healthy aging. Observational studies have found that decelerated biological aging or Δage (BA-CA) is associated with a lower risk of disease and mortality. In general, CA is associated with low-grade inflammation, a condition linked to the risk of the incidence of disease and overall cause-specific mortality, and is modulated by diet. To address the hypothesis that diet-related inflammation is associated with Δage, a cross-sectional analysis of data from a sub-cohort from the Moli-sani Study (2005–2010, Italy) was performed. The inflammatory potential of the diet was measured using the Energy-adjusted Dietary Inflammatory Index (E-DIITM) and a novel literature-based dietary inflammation score (DIS). A deep neural network approach based on circulating biomarkers was used to compute BA, and the resulting Δage was fit as the dependent variable. In 4510 participants (men 52.0%), the mean of CA (SD) was 55.6 y (±11.6), BA 54.8 y (±8.6), and Δage −0.77 (±7.7). In a multivariable-adjusted analysis, an increase in E-DIITM and DIS scores led to an increase in Δage (β = 0.22; 95%CI 0.05, 0.38; β = 0.27; 95%CI 0.10, 0.44, respectively). We found interaction for DIS by sex and for E-DIITM by BMI. In conclusion, a pro-inflammatory diet is associated with accelerated biological aging, which likely leads to an increased long-term risk of inflammation-related diseases and mortality.

The EU-supported ATHENA project stems from a previous study suggesting that moderate wine consumption reduced the side-effects of radiotherapy (RT) in breast cancer patients, an effect possibly due to non-alcoholic anthocyanin fractions of wine. To evaluate the role of anthocyanins on RT skin side effects in breast cancer patients. Randomized, controlled, double-blind clinical trial. Patients were assigned to an intensity modulated radiation therapy (IMRT) either for three or five weeks, then randomized to receive three times a day a water-soluble anthocyanin (125 mg)-rich extract of corn cob or a placebo. Supplementation started one week before till the end of RT. Skin characteristics were detected by a standardized, non-invasive Cutometer® dual-MPA580, providing quantitative indices of skin maximal distensibility (R0), elasticity (R2, R5, R7) and viscoelasticity (R6); a Mexameter® MX18 probe evaluated the skin erythema (Er) and melanin (M). Measures were performed before (T0), at the end of RT and of supplementation (T1), and 1, 6 and 12 months after RT (T2-T4). Acute and late skin toxicity were scored according to the RTOG/EORTG scale. Selected biomarkers were measured at T0 and T1. 193 patients previously assigned to 3- or 5-week RT schedules were randomized to either anthocyanin (97) or placebo (96) supplementation. RT induced changes in skin parameters: R0, R2, R5 and R7 decreased, while R6 increased; the changes in R0 and R6 continued in the same direction up to one year, while the others recovered towards basal values; Er and M peaked at T1 and T2, respectively, and returned to basal values at T4. Comparable skin changes were apparent in anthocyanin and placebo groups. A moderate RT-induced increase in total and HDL cholesterol and triglycerides was prevented by anthocyanins. Anthocyanin supplementation did not prevent RT-induced local skin toxicity. The supplementation was well tolerated and safe. [ABSTRACT FROM AUTHOR]

Background and Aims: Evidence indicates that Vitamin D deficiency may be associated with increased risk of cardiovascular disease, although findings on risk of heart failure (HF) are controversial. We investigated the relationship between serum Vitamin D and the incidence of hospitalization for HF in a large prospective cohort of Italian adults.Methods and Results: 19,092 (49% men, age range 35-99 years) HF-free individuals from the Moli-sani study, with complete data on serum Vitamin D (25-hydroxyvitamin) levels and incident hospitalized HF, were analysed. The cohort was followed up for a median of 6.2 years. Baseline serum Vitamin D levels were categorized in deficient (<10 ng/mL), insufficient (10-29 ng/mL), and normal (≥30 ng/mL) Incident cases of hospitalization for HF were identified by linkage with the regional hospital discharge registry. Hazard ratios (HRs) were calculated using Cox-proportional hazard models. The prevalence of normal, insufficient or deficient levels of Vitamin D was 12.2%, 79.6% and 8.2%, respectively. During follow-up, 562 admissions to hospital for HF were identified. The incidence of HF was 1.6%, 2.9% and 5.3%, respectively in subjects with normal, insufficient and deficient levels of Vitamin D. After multivariable analysis, individuals with deficiency of Vitamin D had a higher risk of hospitalization for HF (HR: 1.61, 95%CI: 1.06-2.43) than those with normal levels. Further adjustment for subclinical inflammation did not substantially change the association between Vitamin D deficiency and HF.Conclusion: Deficiency of Vitamin D was associated, independently of known HF risk factors, with an increased risk of hospitalization for HF in an Italian adult population. [ABSTRACT FROM AUTHOR]

Abstract: Blood coagulation and inflammation play a key role in atherosclerosis and thrombosis. Candidate gene and genome wide association studies have identified potential specific genes that might have a causal role in these pathogenic processes. The analysis of quantitative traits is more powerful as they are closer to direct gene action than disease phenotypes. Thus linkage-based studies on extended families might be useful both to estimate the heritability and to map the genetic loci responsible for the regulation of the trait. Family-based studies may estimate high heritability for thrombosis and quantitative traits regarding both platelet aggregation and blood coagulation. Some specific loci relevant to thrombosis have been identified, with some of them showing a direct pleiotropic effect on the risk of thrombosis. Haemostasis factors can be activated by inflammatory stimuli. Fibrinogen level is genetically correlated with C-reactive protein levels with a link for both traits on chromosomes 12 and 21. Genes related to prostanoid biosynthesis, involved both in inflammation and thrombosis, show high heritability levels in both enzyme expression and prostanoid production. Considering that few large family-based linkage studies have as yet been performed on haemostasis and inflammation-related traits, additional studies are highly needed. We are performing a family-based linkage study on large pedigrees (750 subjects from 23 families with juvenile myocardial infarction and 31 control families), to identify genes responsible for quantitative traits involved in the pathway progressively going from inflammation to haemostasis, cell activation, thrombus formation and cardiovascular events. [Copyright &y& Elsevier]