Tesi etd-11302016-153726
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Tipo di tesi
Perfezionamento
Autore
SAPONARO, FEDERICA
URN
etd-11302016-153726
Titolo
NEW PERSPECTIVES FOR VITAMIN D AND HEART: ROLE IN HEART FAILURE PATHOGENESIS AND PROGNOSIS.
Settore scientifico disciplinare
MED/13
Corso di studi
SCIENZE MEDICHE - Translational Medicine
Commissione
relatore Prof. RECCHIA, FABIO ANASTASIO
Parole chiave
- Vitamin D
- Heart Failure
Data inizio appello
28/02/2017;
Disponibilità
completa
Riassunto analitico
Chronic Heart failure (HF) is a major cause of morbidity and mortality in all industrialized countries. HF is a progressive condition and, once it has ensued, may require hospitalization because of worsening, arrhythmias or myocardial infarction occurrence. The prognosis of HF remains poor, even if the treatment of this condition has made remarkable progress in the past decades. Indeed, novel targets, biomarkers and therapies are needed. Among different biomarkers proposed for cardiovascular risk evaluation in HF, Vitamin D could be an emerging tool.
Vitamin D is classically involved in bone homeostasis. However, recent studies strongly suggest other extraskeletal functions for vitamin D, including pleiotropic effects on cardiovascular system. Twenty-five hydroxy-vitamin D (25OHD) represents the biomarker of vitamin D status, but it is still controversial which is the optimal level in the adult. There are evidences that low serum 25OHD levels are associated with increased risk of cardiovascular disease (CVD)including hypertension, coronary artery disease, ischemic heart disease, stroke and type 2 diabetes.
Moreover, there are data supporting the hypothesis that vitamin D could exerts some modulatory effects in the pathophysiology of Heart Failure, namely downregulation of the renin–angiotensin system, enhancement of insulin secretion and sensitivity, protection against angiogenesis and modulation of inflammatory processes.
Growing data about the condition of poor vitamin D status in patients with HF have been recently published, with main limitations due to 25OHD levels evaluation or a variety of approaches, difficult to be compared. Indeed, in the majority of studies, Vitamin D levels were measured with traditional immunoassay, that often show an unsatisfactory accuracy and a remarkable intra- and inter-assay variability around the cut off limits. Higher specificity and sensitivity can be obtained by High Performances Liquid Chromatography coupled to mass spectrometry (HPLC-MS/MS), that is frequently referred as the new “gold standard” method. However, data regarding vitamin D and HF functional capacity and prognosis markers are still scanty and required. The aims of this thesis are:
1)to investigated the relationship between 25OHD levels, measured using HPLC-MS/MS, and functional parameters derived from the cardiopulmonary test (CPET), that is a good, routinely used tool of risk stratification in HF patients. Furthermore, we analysed the prognostic value of serum 25OHD levels, using an emerging score of mortality risk for HF: the Metabolic Exercise Cardiac Kidney Index or MECKI score
2)To evaluate the effects of vitamin D supplementation on HF outcomes in a prospective, placebo-controlled study, comparing HF biochemical and instrumental markers at baseline and after supplementation.
3)To evaluate the vitamin D metabolites levels and distribution in tissues, in rat model.
Vitamin D is classically involved in bone homeostasis. However, recent studies strongly suggest other extraskeletal functions for vitamin D, including pleiotropic effects on cardiovascular system. Twenty-five hydroxy-vitamin D (25OHD) represents the biomarker of vitamin D status, but it is still controversial which is the optimal level in the adult. There are evidences that low serum 25OHD levels are associated with increased risk of cardiovascular disease (CVD)including hypertension, coronary artery disease, ischemic heart disease, stroke and type 2 diabetes.
Moreover, there are data supporting the hypothesis that vitamin D could exerts some modulatory effects in the pathophysiology of Heart Failure, namely downregulation of the renin–angiotensin system, enhancement of insulin secretion and sensitivity, protection against angiogenesis and modulation of inflammatory processes.
Growing data about the condition of poor vitamin D status in patients with HF have been recently published, with main limitations due to 25OHD levels evaluation or a variety of approaches, difficult to be compared. Indeed, in the majority of studies, Vitamin D levels were measured with traditional immunoassay, that often show an unsatisfactory accuracy and a remarkable intra- and inter-assay variability around the cut off limits. Higher specificity and sensitivity can be obtained by High Performances Liquid Chromatography coupled to mass spectrometry (HPLC-MS/MS), that is frequently referred as the new “gold standard” method. However, data regarding vitamin D and HF functional capacity and prognosis markers are still scanty and required. The aims of this thesis are:
1)to investigated the relationship between 25OHD levels, measured using HPLC-MS/MS, and functional parameters derived from the cardiopulmonary test (CPET), that is a good, routinely used tool of risk stratification in HF patients. Furthermore, we analysed the prognostic value of serum 25OHD levels, using an emerging score of mortality risk for HF: the Metabolic Exercise Cardiac Kidney Index or MECKI score
2)To evaluate the effects of vitamin D supplementation on HF outcomes in a prospective, placebo-controlled study, comparing HF biochemical and instrumental markers at baseline and after supplementation.
3)To evaluate the vitamin D metabolites levels and distribution in tissues, in rat model.
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