Higher spermidine intake is linked to lower mortality: a prospective population-based study.

Background: Spermidine administration is linked to increased survival in several animal models.

Objective: The aim of this study was to test the potential association between spermidine content in diet and mortality in humans.

Design: This prospective community-based cohort study included 829 participants aged 45-84 y, 49.

A Cytokine-Like Protein Dickkopf-Related Protein 3 Is Atheroprotective.

Background: Dickkopf-related protein 3 (DKK3) is a secreted protein that is involved in the regulation of cardiac remodeling and vascular smooth muscle cell differentiation, but little is known about its role in atherosclerosis.

Methods: We tested the hypothesis that DKK3 is atheroprotective using both epidemiological and experimental approaches. Blood DKK3 levels were measured in the Bruneck Study in 2000 (n=684) and then in 2005 (n=574).

Association Between Vascular Cell Adhesion Molecule 1 and Atrial Fibrillation.

Importance: Accumulating evidence links inflammation and atrial fibrillation (AF).

Objective: To assess whether markers of systemic and atrial inflammation are associated with incident AF in the general population.

Design, Setting, And Participants: The Bruneck Study is a prospective, population-based cohort study with a 20-year follow-up (n = 909).

Lipoprotein(a) and incident type-2 diabetes: results from the prospective Bruneck study and a meta-analysis of published literature.

Aims: We aimed to (1) assess the association between lipoprotein(a) [Lp(a)] concentration and incident type-2 diabetes in the Bruneck study, a prospective population-based study, and (2) combine findings with evidence from published studies in a literature-based meta-analysis.

Methods: We used Cox proportional hazards models to calculate hazard ratios (HR) for incident type-2 diabetes over 20 years of follow-up in 815 participants of the Bruneck study according to their long-term average Lp(a) concentration. For the meta-analysis, we searched Medline, Embase and Web of Science for relevant prospective cohort studies published up to October 2016.

Aberrant regulation of RANKL/OPG in women at high risk of developing breast cancer.

Breast cancer is the most common female cancer, affecting approximately one in eight women during their lifetime in North America and Europe. Receptor Activator of NF-kB Ligand (RANKL), its receptor RANK and the natural antagonist osteoprotegerin (OPG) are essential regulators of bone resorption. We have initially shown that RANKL/RANK are essential for hormone-driven mammary epithelial proliferation in pregnancy and RANKL/RANK have been implicated in mammary stem cell biology.

Correlates of serum hepcidin levels and its association with cardiovascular disease in an elderly general population.

Background: The expression of the key iron regulatory hormone hepcidin is regulated by iron availability, inflammation, hormones, hypoxia, and anaemia. Increased serum concentrations of hepcidin have recently been linked to atherosclerosis. We studied demographic, haematologic, biochemical, and dietary correlates of serum hepcidin levels and its associations with incident cardiovascular disease and with carotid atherosclerosis.

Leucocyte telomere length and risk of type 2 diabetes mellitus: new prospective cohort study and literature-based meta-analysis.

Background: Short telomeres have been linked to various age-related diseases. We aimed to assess the association of telomere length with incident type 2 diabetes mellitus (T2DM) in prospective cohort studies.

Methods: Leucocyte relative telomere length (RTL) was measured using quantitative polymerase chain reaction in 684 participants of the prospective population-based Bruneck Study (1995 baseline), with repeat RTL measurements performed in 2005 (n = 558) and 2010 (n = 479).

Haptoglobin 2-2 genotype is not associated with cardiovascular risk in subjects with elevated glycohemoglobin-results from the Bruneck Study.

Background: Haptoglobin (Hp) is an abundant plasma protein with antioxidant properties. The Hp 2-2 genotype has previously been linked to coronary heart disease risk in individuals with elevated glycosylated hemoglobin (HbA1c). We investigated the association of Hp and HbA1c with cardiovascular disease (CVD) in the longitudinal, population-based Bruneck Study.

Carotid atherosclerosis and incident atrial fibrillation.

Objective: Atrial fibrillation (AF) and atherosclerotic vascular disease are closely entangled disorders and often coexist. Whether atherosclerosis predisposes to the development of AF has not been fully elucidated.

Approach And Results: This study was performed within the framework of the Bruneck Study, a population-based survey with near-complete participation (932 of 1000), long-term follow-up (1990-2010), and thorough assessment of AF.

Prospective study on circulating MicroRNAs and risk of myocardial infarction.

Objectives: This study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005) in the Bruneck cohort and determine their cellular origin.

Background: Circulating miRNAs are emerging as potential biomarkers. We previously identified an miRNA signature for type 2 diabetes in the general population.

Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes.

Rationale: MicroRNAs (miRNAs) have been implicated in the epigenetic regulation of key metabolic, inflammatory, and antiangiogenic pathways in type 2 diabetes (DM) and may contribute to common disease complications.

Objective: In this study, we explore plasma miRNA profiles in patients with DM.

Methods And Results: Total RNA was extracted from plasma samples of the prospective population-based Bruneck study.

Telomere length and risk of incident cancer and cancer mortality.

Context: Telomeres are essential to preserve the integrity of the genome. Critically short telomeres lead to replicative cell senescence and chromosomal instability and may thereby increase cancer risk.

Objective: To determine the association between baseline telomere length and incident cancer and cancer mortality.

Cellular aging reflected by leukocyte telomere length predicts advanced atherosclerosis and cardiovascular disease risk.

Objective: To determine the association between leukocyte telomere length (TL) and atherosclerosis and its clinical sequelae stroke and myocardial infarction.

Methods And Results: Within the scope of the prospective population-based Bruneck Study, leukocyte TL was measured by quantitative polymerase chain reaction in 800 women and men aged 45 to 84 years (in 1995). The manifestation of cardiovascular disease (CVD) (1995-2005) and the progression of atherosclerosis (1995-2000) were carefully assessed.

Vascular cell adhesion molecule 1 as a predictor of severe osteoarthritis of the hip and knee joints.

Objective: Osteoarthritis (OA) is a leading cause of pain and physical disability in middle-aged and older individuals. We undertook this study to determine predictors of the development of severe OA, apart from age and overweight.

Methods: Joint replacement surgery due to severe hip or knee OA was recorded over a 15-year period in the prospective Bruneck cohort study.

Common CCR5-del32 frameshift mutation associated with serum levels of inflammatory markers and cardiovascular disease risk in the Bruneck population.

Background And Purpose: Atherosclerosis is a progressive inflammatory disease and can develop in large arteries such as carotid and femoral arteries or medium-sized muscular arteries of the heart. Previous predominantly experimental studies suggested an important role of chemokines in the development of atherosclerosis. The main aim of this study was to examine potential effect of the CCR5-del32 mutation on systemic inflammation, intima-media thickness in carotid and femoral arteries, and on the indices of cardiovascular disease.

Endothelial progenitor cells, cardiovascular risk factors, cytokine levels and atherosclerosis--results from a large population-based study.

Background: EPC number and functionality are assumed to reflect the endogenous vascular repair capacity with the EPC pool declining in higher ages and being exhausted by unfavorable life-style and risk factors. This intriguing and clinically highly relevant concept, however, has so far been derived from small case-control studies and patient series.

Methodology And Principle Findings: In the population-based Bruneck Study EPC number and EPC-colony forming units (EPC-CFU) were assessed as part of the fourth follow-up evaluation (2005) in 571 and 542 subjects, respectively.

High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study.

Background: Chronic inflammatory diseases are associated with bone loss and an enhanced fracture risk. It is unknown, however, whether low-grade inflammation in healthy individuals, as estimated by the high-sensitivity C-reactive protein (hs-CRP) level, interferes with bone metabolism and affects the risk of nontraumatic fractures.

Methods: Lifetime bone fractures were carefully recorded in the cohort of the population-based Bruneck Study (n = 919) along with information on the date of occurrence and associated circumstances.

Oxidized phospholipids predict the presence and progression of carotid and femoral atherosclerosis and symptomatic cardiovascular disease: five-year prospective results from the Bruneck study.

Objectives: The purpose of this work was to determine the predictive value of oxidized phospholipids (OxPLs) present on apolipoprotein B-100 particles (apoB) in carotid and femoral atherosclerosis.

Background: The OxPLs are pro-inflammatory and pro-atherogenic and may be detected using the antibody E06 (OxPL/apoB).

Methods: The Bruneck study is a prospective population-based survey of 40- to 79-year-old men and women initiated in 1990.

Urinary albumin excretion is independently associated with carotid and femoral artery atherosclerosis in the general population.

Aims: In diabetic patients, increased urinary albumin excretion (UAE), termed microalbuminuria when in the range between 30 and 300 mg/dL per day, is associated with a higher risk of atherosclerosis and its complications. Whether or not this notion applies to the general population is a matter of ongoing controversy because none of the few previous investigations among non-diabetics strictly represent the general community.

Methods And Results: Urinary albumin-to-creatinine ratio (uACR), a measure of UAE, was assessed from overnight spot urine samples in a population-based cohort of 684 individuals.

Soluble RANKL and risk of nontraumatic fracture.

Context: The receptor activator of nuclear factor kappaB ligand (RANKL) is essential for osteoclast and, possibly, osteoblast activation and may represent a key link between bone formation and resorption.

Objective: To determine the relationship between serum level of RANKL and the risk of nontraumatic fracture.

Design, Setting, And Participants: As part of a prospective population-based study conducted in Bruneck, Italy, we recorded all fractures that occurred between 1990 and 2000 in 906 participants and classified them as traumatic (n = 115) or nontraumatic (n = 31).