IDENTIFICATION OF A NOVEL LMF1 NONSENSE MUTATION RES- PONSIBLE FOR SEVERE HYPERTRIGLYCERIDEMIA BY TARGETED NEXT-GENERATION SEQUENCING R. Spina, A.B. Cefalu', D. Noto, V. Ingrassia, V. Valenti, A. Giammanco, F. Fayer, G. Misiano, C. Scrimali, G.I. Altieri, A. Ganci, C.M. Barbagallo, M.R. Averna. Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy E-mail address: rossella.spina@libero.it (R. Spina). Background: Severe hypertriglyceridemia (HTG) may result from mu- tations in genes affecting the intravascular lipolysis of triglyceride rich lipoproteins. Objective and methods: The aim of this study was to investigate monogenic causes of severe HTG by a targeted Next Generation Sequencing (NGS) approach to capture the coding exons and intron/ exon boundaries of 18 genes affecting the main pathways of triglyc- eride synthesis and metabolism. Results: The targeted resequencing of candidate genes of severe HTG led to the discovery of a novel homozygous nonsense mutation in one patient with severe hypertriglyceridemia. The mutation causes a C>G substitution in exon 9 (c.1380C>G), leading to a premature stop codon (W460X). The clinical and molecular familial cascade screening allowed the identification of two additional affected siblings and seven heterozygous carriers of the mutation. Homozygosity for the c.1380C>G mutation resulted in a severe HTG phenotype in the pro- band (II-2) while two other siblings (II-1 and II-4) showed mild to moderate HTG suggesting a different and variable pattern of pene- trance among carriers of the same mutation of the LMF1 gene. None of them have suffered of acute pancreatitis or recurrent abdominal pain. Conclusions: We describe the third novel nonsense mutation of LMF1 gene (c.1380C>G -p.Y460X) identified by a customized NGS panel for targeted gene sequencing of 18 genes involved in hypertriglyceridemia. More studies are needed to understand the reasons of the phenotypic variability of the same molecular defect in the same family. BICUSPID AORTIC VALVE AND LIPOPROTEIN (A) E. Sticchi 1 , A. Cordisco 2 , B. Giusti 3 , S. Nistri 4 , A. Sereni 3 , R. De Cario 3 , R. Di Carlo 2 , A. Kura 3 , A.M. Gori 3 , M.G. D'Alfonso 2 , V. Mecarocci 2 , N. Marchionni 2 , G. Pepe 5, 6 , F. Mori 2 , R. Marcucci 3 . 1 Department of NEUROFARBA, University of Florence, Italy; 2 AOU Careggi, Cardio-Toraco-Vascular Department, Italy; 3 Department of Experimental and Clinical Medicine, University of Florence, Italy; 4 Cardiology Service, CMSR Veneto Medica, Altavilla Vicentina, Italy; 5 DENOTHE Center, University of Florence, Italy; 6 Department of Heart and Vessels, Marfan Syndrome and Related Disorders Regional Referral Center, Careggi Hospital, Florence, Italy E-mail address: elenasticchi@hotmail.com (E. Sticchi). Background: In bicuspid aortic valve (BAV), the most frequent congenital cardiopathy, the presence of calcification and stenosis (SAo) predicts a worse prognosis. In our study, we investigated the associa- tion between Lp(a) levels, kringle IV type 2 (KIV2) repeat number polymorphism, and the presence of calcification in BAV patients. Methods: Sixty-nine patients [79.7% males; median age: 45(30-53) yrs],admitted at the Center for Cardiovascular Diagnosis or Referring Center for Marfan syndrome and related disorders, AOU Careggi-Uni- versity of Florence, from June to November 2014, were investigated. Blood withdrawal was performed in order to determine Lp(a) levels (Randox Immunoturbidimetric Assay) and KIV2 repeat number. Pa- tients were compared with 69 control subjects [78% males; median age:52(50-54) yrs]. Results: BAV type 1 was present in 86.9% of patients (n¼60), remaining patients showed BAV type 2. In 58.5% of patients, calcifications were not present; among remaining patients, mild calcifications in 27.7%, moderate in 9.2% and severe in 4.6% were detected. BAV patients did not show significantly different Lp(a) levels with respect to controls, with a trend towards lower values [108(58-190) mg/L vs 126(51-346), p¼0.487]; a significantly higher KIV2 repeat number (9 vs 6, p¼0.028) was documented. Lp(a) levels were significantly higher in patients with valvular calcifications [no-calcifications: 84(47-163) mg/L, mild or moderate: 138(75-192) mg/L; severe: 421(241-1782) mg/L, p¼0.019], with a lower KIV2 repeat number. Higher Lp(a) levels in patients with SAo (105 mg/L vs 187, p¼0.032) with lower KIV2 repeat number were documented. Conclusions: In this study, we demonstrated for the first time an as- sociation between calcifications in BAV patients, KIV2 repeat number and Lp(a) levels measurement. Based on these information, needing a confirmation on larger populations, Lp(a) levels and KIV2 repeat number represent possible risk markers useful to stratify, among BAV patients, those with higher chance to develop valvular calcifications and aortic stenosis. RELATIONSHIPS BETWEEN ARTERIAL STIFFNESS AND BONE MIN- ERAL DENSITY IN POSTMENOPAUSAL WOMEN A. Tafa, A. Giambelluca, C. Caffarelli, C. Pondrelli, S. Cappelli, S. Gonnelli. Department of Internal Medicine, Endocrine-Metabolic Science and Biochemistry, University of Siena, Italy E-mail address: afertafa@yahoo.com (A. Tafa). Background: Although osteoporosis and Cardiovascular disease have always been considered as separate entities, there is accumulated ev- idence that they have several pathological mechanisms in common. However, little research has been conducted to examine the relation- ship between arterial stiffness and bone mineral density (BMD) in post- menopausal women. Methods: This study aimed to evaluate if arterial stiffnes was correlated with bone mass density (BMD) in 35 post menopausal women (women age 64.3 ± 9.4 years). We measured Bone Mineral Density (BMD) at lumbar spine (BMD-LS), at femur (neck: BMD-FN; total: BMD-FT) and at total-body (BMD-WB) and arterial stiffnes during a routine ultra- sound examination of the carotid arteries applying a previously vali- dated RF-based tracking of arterial wall able to estimate in real time common carotid intima-media thickness (QIMT™) and distension (QAS™) with high spatial and temporal resolution. Results: As expected, in women with osteoporosis, a significant inverse correlation was found between BMT and arterial stiffnes, respectively BMD-FN and arterial stiffnes (r¼ -0.30; p¼ <0.05) and BMD-FT and arteria stiffnes (R¼-0.33; p<0.05). Conclusion: This preliminary study confirms a significant inverse as- sociation between arterial stiffness and bone metabolism in post- menopausal women. METABOLOMICS BY NUCLEAR MAGNETIC RESONANCE IDENTIFIES PATIENTS WITH HIGH RISK OF DEATH WITHIN TWO YEARS AFTER A CARDIOVASCULAR EVENT: THE CASE OF THE AMIFLORENCE II STUDY L. Tenori 1,2 , B. Giusti 1,2 , A. Vignoli 1,2 , A.M. Gori 1,2 , C. Luchinat 1,2 , E. Grifoni 1,2 , A. Barchielli 1,2 , D. Balzi 1,2 , N. Marchionni 1,2 , R. Marcucci 1,2 . 1 Universit a di Firenze, Firenze, Italy; 2 AOU Careggi, Firenze, Italy E-mail address: leonardo.tenori@unifi.it (L. Tenori). Background: Risk stratification and management of patients with acute coronary syndromes (ACS) is challenging. Aim of this study was to evaluate the possible role of metabolomics in the prognostic stratifi- cation of ACS patients. Methods: 918 patients (345 females, 633 males, median age 74) were enrolled; among these 146 died (negative outcome), whereas 832 showed a positive outcome within 2 years from the cardiovascular event. Patients serum samples were analyzed via high resolution Pro- ton Nuclear Magnetic Resonance and the obtained spectra were used to characterized the metabolic profiles of the two cohorts of patients. Multivariate statistics and a Random Forest classifier were used to create a prognostic model for the prediction of death within 2 years from the cardiovascular event. Abstracts the SISA e39