Role of Inflammation in the Pathogenesis of Frailty in the Elderly: Studies on the Contribution of Blood Platelets- PIPAF Platelets in the Pathogenesis of Ageing Associated Frailty
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Coronary Artery Disease
- Sponsor
- Azienda Ospedaliera di Perugia
- Enrollment
- 200
- Locations
- 2
- Primary Endpoint
- Rate of platelet activation
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a prospective observational study aimed at testing the existence of an association between frailty, inflammatory status, and degree of platelet activation and reactivity in elderly subjects with type 2 diabetes or coronary artery disease or Alzheimer's disease.
Detailed Description
Frailty in the elderly is a syndrome that strongly affects quality of life and represents a major social and economic challenge. Frailty often, and more frequently, occurs in individuals with aging-related diseases including type 2 diabetes, cardiovascular disease, and Alzheimer's disease. All of these diseases are associated with a state of weak chronic inflammation. Studies in recent years have pointed out that platelets can directly contribute to inflammatory processes. Due to of this ability to act as proinflammatory cells and of their strong involvement in various metabolic, cardiovascular, and neurodegenerative disorders, platelets appear to have key roles in the physio-pathological mechanisms that predispose to frailty. In the present study, it is planned to recruit 4 cohorts of elderly patients, each of 40 patients, divided by pathology ( frail elderly, diabetic elderly, elderly with stable atherosclerotic coronary artery disease, elderly with early-stage Alzheimer's disease) and a cohort of 40 healthy elderly subjects. All subjects will perform a blood draw at enrollment and after 24 months of follow up in order to evaluate: the state of platelet activation; the aggregating response of platelets to stimuli such as thrombin, Adenosine DiPhosphate (ADP), and collagen; the state of chronic inflammation and oxidative stress; the procoagulant profile of platelets; presence of platelet subpopulations characterized by RNA, microRNA and/or protein profiling. Each subject will also be given a questionnaire to assess frailty status (according to Fried's criteria) and urine samples will be collected to perform the assay of metabolites such as 11dh-TXB, 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-epiPGF2a (8-isoprostane).
Investigators
Paolo Gresele
Clinical Professor
Azienda Ospedaliera di Perugia
Eligibility Criteria
Inclusion Criteria
- •age \> 65 years
- •low-dose aspirin therapy (100 mg)
- •belonging to each of the cohorts indicated
Exclusion Criteria
- •Lack of inclusion criteria and/or consent to the study
Outcomes
Primary Outcomes
Rate of platelet activation
Time Frame: 3 years
Platelet activation will be assessed in vivo, on circulating platelets, by flowcytometry measurement of p-selectin, integrin αIIbβ3, and tissue factor expression, and in vitro, on isolated platelets, by studying the response to agonists (thrombin, ADP, collagen) with lumiaggregometry and ATP secretion
Secondary Outcomes
- Rate of systemic inflammation and oxidative stress(3 years)
- Procoagulant platelet activity(3 years)
- Rate of platelet heterogeneity(3 years)
- Rate of proinflammatory platelet activity(3 years)