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Analysis of coagulation disorders and assessment of rebalanced hemostasis with the use of traditional coagulation assays is challenging in cirrhotic patients. Therefore, alternative tests are under investigation for the evaluation of coagulopathy in this specific setting. Aim of this study was to analyze the modifications of clot structure and function in cirrhotic patients with different degrees of severity. Cirrhotic patients referred to our Unit were consecutively enrolled. Global test measurements, including clot and lysis assays, clot lysis time, and determination of other fibrinolytic parameters, were performed. Analyses of clot formation, morphology, and lysis were performed with a turbidimetric clotting and lysis assay (EuroCLOT). Lysis of a tissue factor-induced clot by exogenous tissue plasminogen activator was analyzed by studying the modifications of turbidity during clot formation and the following lysis. We evaluated coagulative and fibrinolytic parameters in both plasma and ascites. Urokinase plasminogen activator (uPA) and gelatinase activity in ascites were also measured. We analyzed data from 33 cirrhotic patients (11 in Child-Pugh class A; 22 in class B or C and with ascites) and 21 healthy subjects (HS). In class B/C patients prolonged latency time, a decline in clotting absorbance, and decreased fibrin formation were observed in comparison with class A and HS. Generated curves and Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) progressively declined from HS to class C patients, whereas levels of plasminogen activator inhibitor-1 and tissue plasminogen activator increased. D-dimer levels were markedly increased in ascites, together with significantly smaller levels of TAFI, αlfa2-antiplasmin, and plasminogen. Caseinolytic activity was also present. Class C patients showed smaller amount of uPA and significantly lower levels of matrix metallopeptidases (MMP)2 in ascites in comparison with Class B subjects. Clot formation and lysis are altered in cirrhosis and fibrinolysis is activated in ascites. Ascitic levels of uPA and MMP2 are reduced and inversely related to the severity of liver disease.
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Ascite/sangue , Ascite/complicações , Biomarcadores/sangue , Coagulação Sanguínea/fisiologia , Fibrinólise/fisiologia , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Idoso , Testes de Coagulação Sanguínea , Feminino , Humanos , Masculino , PrognósticoRESUMO
Increasing evidence shows an association between high lipoprotein(a) [Lp(a)] levels and atherothrombotic diseases. Lp(a) trait is largely controlled by kringle-IV type 2 (KIV-2) size polymorphism in LPA gene, encoding for apo(a). Environmental factors are considered to determinate minor phenotypic variability in Lp(a) levels. In the present study, we investigated the possible gene-environment interaction between KIV-2 polymorphism and Mediterranean diet adherence or fish weekly intake in determining Lp(a) levels. We evaluated Lp(a), KIV-2 polymorphism, fish intake and Mediterranean diet adherence in 452 subjects [median age (range) 66 (46-80)years] from Montignoso Heart and Lung Project (MEHLP) population. In subjects with high KIV-2 repeats number, influence of Mediterranean diet adherence in reducing Lp(a) levels was observed (p = 0.049). No significant difference in subjects with low KIV-2 repeats according to diet was found. Moreover, in high-KIV-2-repeat subjects, we observed a trend towards influence of fish intake on reducing Lp(a) levels (p = 0.186). At multivariate linear regression analysis, high adherence to Mediterranean diet remains a significant and independent determinant of lower Lp(a) levels (ß = - 64.97, standard error = 26.55, p = 0.015). In conclusion, this study showed that only subjects with high KIV-2 repeats can take advantage to lower Lp(a) levels from correct nutritional habits and, in particular, from Mediterranean diet.
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Dieta Mediterrânea , Interação Gene-Ambiente , Lipoproteína(a)/genética , Lipoproteína(a)/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Peixes , Genótipo , Humanos , Itália , Kringles/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
INTRODUCTION: Although pathogenesis of small vessel disease is poorly understood, increasing evidence suggests that endothelial dysfunction may have a relevant role in development and progression of small vessel disease. In this cross-sectional study, we investigated the associations between imaging signs of small vessel disease and blood biomarkers of endothelial dysfunction at two different time points in a population of ischaemic stroke patients. PATIENTS AND METHODS: In stroke patients treated with intravenous thrombolysis, we analysed blood levels of von Willebrand factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and vascular endothelial growth factor. Three reviewers independently assessed small vessel disease features using computed tomography. At baseline and 90 days after the index stroke, we tested the associations between single and combined small vessel disease features and levels of blood biomarkers using linear regression analysis adjusting for age, sex, hypertension, diabetes, smoke. RESULTS: A total of 263 patients were available for the analysis. Mean age (±SD) was 69 (±13) years, 154 (59%) patients were male. We did not find any relation between small vessel disease and endothelial dysfunction at baseline. At 90 days, leukoaraiosis was independently associated with intercellular adhesion molecule-1 (ß = 0.21; p = 0.016) and vascular cell adhesion molecule-1 (ß = 0.22; p = 0.009), and lacunes were associated with vascular endothelial growth factor levels (ß = 0.21; p = 0.009) whereas global small vessel disease burden was associated with vascular endothelial growth factor (ß = 0.26; p = 0.006). DISCUSSION: Leukoaraiosis and lacunes were associated with endothelial dysfunction, which could play a key role in pathogenesis of small vessel disease. CONCLUSIONS: Small vessel disease features and total burden were associated with endothelial dysfunction 90 days after the stroke, whereas there was no relation during the acute phase. Our results suggest that endothelial dysfunction, particularly vascular endothelial growth factor, is involved in pathological process of small vessel disease.
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Small vessel disease (SVD) is frequent in aging and stroke patients. Inflammation and remodeling of extracellular matrix have been suggested as concurrent mechanisms of SVD. We investigated the relationship between imaging features of SVD and circulating metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in patients with ischaemic stroke. In patients treated with intravenous thrombolysis, we took blood samples before intravenous thrombolysis and 90 days after the acute stroke and analysed levels of MMPs and TIMPs. We assessed leukoaraiosis, number of lacunes and brain atrophy on pre-treatment CT scan and graded global SVD burden combining such features. We investigated associations between single features, global SVD and MMPs and TIMPs at baseline and at follow-up, retaining univariate statistically significant associations in multivariate linear regression analysis and adjusting for clinical confounders. A total of 255 patients [mean (±SD) = 68.6 (± 12.7) years, 154 (59%) males] were included, 107 (42%) had no signs of SVD; 47 (19%) had from moderate to severe SVD burden. A total of 107 (42%) patients had no signs of SVD; 47 (19%) had from moderate to severe SVD burden. After adjustment, only TIMP-4 proved associations with SVD features. Brain atrophy was associated with baseline TIMP-4 (ß = 0.20;p = 0.019) and leukoaraiosis with 90 days TIMP-4 (ß = 0.19; p = 0.013). Global SVD score was not associated with baseline TIMP-4 levels (ß = 0.10; p = 0.072), whereas was associated with 90 days TIMP-4 levels (ß = 0.21; p = 0.003). Total SVD burden was associated with higher TIMP-4 levels 90 days after stroke, whereas was not during the acute phase. Our results support a biological relationship between SVD grade and TIMP-4.
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Doenças de Pequenos Vasos Cerebrais/sangue , Doenças de Pequenos Vasos Cerebrais/etiologia , Acidente Vascular Cerebral/complicações , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidores Teciduais de Metaloproteinases/sangue , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Isquemia Encefálica/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Tomógrafos Computadorizados , Tomografia Computadorizada por Raios X , Inibidor Tecidual 4 de MetaloproteinaseRESUMO
BACKGROUND: The risk of developing red blood cell (RBC) transfusion-associated necrotizing enterocolitis (TANEC) in preterm infants has recently been emphasized. Our aim was to assess changes in cytokine serum levels after RBC transfusions in a cohort of very preterm infants to evaluate their possible proinflammatory effect. STUDY DESIGN AND METHODS: We carried out a prospective observational study. One transfusion event was studied in infants less than 32 weeks' gestation and more than 7 days old (n = 20) admitted to a tertiary neonatal intensive care unit. Interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor-α, interferon-γ (IFN-γ), IL-17, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule serum levels were measured in enrolled patients within 120 minutes before (T0 ) the RBC transfusion and then within 120 minutes (T1 ), 12 ± 3 hours (T2 ), 24 ± 6 hours (T3 ), and 48 ± 6 hours (T4 ) after the end of RBC transfusion. RESULTS: Infants received 19.8 ± 3.0 mL of RBCs at the mean age of 50 ± 18 days. Their hematocrit level increased from 24.1 ± 1.2% to 39.4 ± 2.9%. IL-1ß, IL-8, IFN-γ, IL-17, MCP-1, IP-10, and ICAM-1 increased significantly after RBC transfusions. CONCLUSION: Proinflammatory cytokines are increased after RBC transfusion. These findings may contribute to explaining the pathogenesis of TANEC and suggest the opportunity of adopting wise transfusion guidelines that would help to avoid detrimental risks of transfusion-related immunomodulation and of undertransfusion.
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Citocinas/sangue , Transfusão de Eritrócitos/efeitos adversos , Citocinas/genética , Enterocolite Necrosante/etiologia , Feminino , Idade Gestacional , Humanos , Imunomodulação , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Mediadores da Inflamação , Unidades de Terapia Intensiva Neonatal , Masculino , Estudos Prospectivos , Ativação TranscricionalRESUMO
Inflammatory mediators and metalloproteinases are altered in acute ischemic stroke (AIS) and play a detrimental effect on clinical severity and hemorrhagic transformation of the ischemic brain lesion. Using data from the Italian multicenter observational MAGIC (MArker bioloGici nell'Ictus Cerebrale) Study, we evaluated the effect of inflammatory and metalloproteinases profiles on three-month functional outcome, hemorrhagic transformation and mortality in 327 patients with AIS treated with intravenous thrombolys in according to SITS-MOST (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy) criteria. Circulating biomarkers were assessed at baseline and 24 h after thrombolysis. Adjusting for age, sex, baseline glycemia and National Institute of Health Stroke Scale, history of atrial fibrillation or congestive heart failure, and of inflammatory diseases or infections, baseline alpha-2macroglobulin (A2M), baseline serum amyloid protein (SAP) and pre-post tissue-plasminogen activator (tPA) variations (Δ) of metalloproteinase 9, remained significantly and independently associated with three-month death [OR (95% CI):A2M:2.99 (1.19-7.53); SAP:5.46 (1.64-18.74); Δmetalloproteinase 9:1.60 (1.12-2.27)]. The addition of baseline A2M and Δmetalloproteinase 9 or baseline SAP and Δmetalloproteinase 9 (model-2 or model-3) to clinical variables (model-1) significantly improved the area under curve for prediction of death [model-2 with A2M: p = 0.0205; model-3 with SAP: p = 0.001]. In conclusion, among AIS patients treated with thrombolysis, circulating A2M, SAP and Δmetalloproteinase 9 are independent markers of poor outcome. These results may prompt controlled clinical research about agents antagonizing their effect.
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Citocinas/sangue , Metaloproteases/sangue , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Idoso , Biomarcadores/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Valor Preditivo dos Testes , Curva ROC , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Beneficial effects of vegetarian and vegan diets on health outcomes have been supposed in previous studies. OBJECTIVES: Aim of this study was to clarify the association between vegetarian, vegan diets, risk factors for chronic diseases, risk of all-cause mortality, incidence, and mortality from cardio-cerebrovascular diseases, total cancer and specific type of cancer (colorectal, breast, prostate and lung), through meta-analysis. METHODS: A comprehensive search of Medline, EMBASE, Scopus, The Cochrane Library, and Google Scholar was conducted. RESULTS: Eighty-six cross-sectional and 10 cohort prospective studies were included. The overall analysis among cross-sectional studies reported significant reduced levels of body mass index, total cholesterol, LDL-cholesterol, and glucose levels in vegetarians and vegans versus omnivores. With regard to prospective cohort studies, the analysis showed a significant reduced risk of incidence and/or mortality from ischemic heart disease (RR 0.75; 95% CI, 0.68 to 0.82) and incidence of total cancer (RR 0.92; 95% CI 0.87 to 0.98) but not of total cardiovascular and cerebrovascular diseases, all-cause mortality and mortality from cancer. No significant association was evidenced when specific types of cancer were analyzed. The analysis conducted among vegans reported significant association with the risk of incidence from total cancer (RR 0.85; 95% CI, 0.75 to 0.95), despite obtained only in a limited number of studies. CONCLUSIONS: This comprehensive meta-analysis reports a significant protective effect of a vegetarian diet versus the incidence and/or mortality from ischemic heart disease (-25%) and incidence from total cancer (-8%). Vegan diet conferred a significant reduced risk (-15%) of incidence from total cancer.
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Doenças Cardiovasculares/mortalidade , Dieta Vegana , Dieta Vegetariana , Nível de Saúde , Neoplasias/mortalidade , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Humanos , Neoplasias/epidemiologia , Estudos Prospectivos , VegetarianosRESUMO
The left atrial appendage (LAA) is the main source of thromboembolism in patients with non-valvular atrial fibrillation (AF). As such, the LAA can be the target of specific occluding device therapies. Optimal management of patients with AF includes a comprehensive knowledge of the many aspects related to LAA structure and thrombosis. Here we provide baseline notions on the anatomy and function of the LAA, and then focus on current imaging tools for the identification of anatomical varieties. We also describe pathogenetic mechanisms of LAA thrombosis in AF patients, and examine the available evidence on treatment strategies for LAA thrombosis, including the use of non-vitamin K antagonist oral anticoagulants and interventional approaches.
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Tromboembolia/prevenção & controle , Apêndice Atrial/anatomia & histologia , Apêndice Atrial/embriologia , Apêndice Atrial/fisiologia , Fibrilação Atrial/complicações , Velocidade do Fluxo Sanguíneo/fisiologia , Ecocardiografia , Endotélio Vascular/fisiologia , Humanos , Angiografia por Ressonância Magnética , Dispositivo para Oclusão Septal , Acidente Vascular Cerebral/prevenção & controle , Oclusão Terapêutica/instrumentação , Oclusão Terapêutica/métodos , Tromboembolia/etiologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microangiopathy presenting with variable features, including migraine, psychiatric disorders, stroke, and cognitive decline and variable disability. On neuroimaging, CADASIL is characterized by leukoencephalopathy, multiple lacunar infarcts, and microbleeds. Previous studies suggest a possible role of endothelial impairment in the pathogenesis of the disease. METHODS: We assessed plasma levels of von Willebrand factor (vWF) and thrombomodulin (TM) and the blood levels of endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) in 49 CADASIL patients and 49 age-matched controls and their association with clinical/functional and neuroimaging features. RESULTS: In multivariate analysis, CADASIL patients had significantly higher vWF and lower EPC levels. TM levels were similar in the 2 groups. CADASIL patients with a more severe clinical phenotype (history of stroke or dementia) presented lower CPC levels in comparison with patients with a milder phenotype. On correlation analysis, lower CPC levels were associated with worse performances on neuropsychological, motor and functional tests, and with higher lesion load on brain magnetic resonance imaging (degree of leukoencephalopathy and number of lacunar infarcts). CONCLUSIONS: This is the first CADASIL series in which multiple circulating biomarkers have been studied. Our findings support previous studies on the presence and the possible modulating effect of endothelial impairment in the disease. Furthermore, our research data suggest that blood CPCs may be markers of disease severity.
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Biomarcadores/sangue , Encéfalo/patologia , CADASIL/sangue , CADASIL/patologia , Células Progenitoras Endoteliais/patologia , Adulto , Idoso , Antígenos CD/metabolismo , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Trombomodulina/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue , Fator de von Willebrand/metabolismoRESUMO
RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies. METHODS AND RESULTS: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. CONCLUSIONS: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Aneurisma da Aorta Abdominal/epidemiologia , Predisposição Genética para Doença/epidemiologia , Variação Genética/genética , Estudo de Associação Genômica Ampla/tendências , HumanosRESUMO
OBJECTIVE: To evaluate changes in residual platelet reactivity (RPR) over time, and bleeding and ischaemic events rate using 5 vs 10â mg maintenance dose (MD) regimens of prasugrel 1â month after acute coronary syndrome (ACS). BACKGROUND: The optimal level of RPR with prasugrel may change over time after an ACS. METHODS: After 60â mg loading dose of prasugrel (T0) followed by 10â mg/day for 1â month, patients were randomised to receive prasugrel 10â mg/day (n=95, group A) or 5â mg/day MD (n=98, group B) up to 1â year. RPR was assessed at T0, 37 (T1) and 180â days (T2). The primary end point was Bleeding Academic Research Consortium (BARC) bleeding events ≥2 between 1 and 12â months, and the secondary composite end point was cardiac death, myocardial infarction, stroke and definite/probable stent thrombosis. RESULTS: From T0 to T1, RPR significantly increased in both groups A and B and the increase was higher for group B (δ ADP 10â µmol: 13.8%±14.7% vs 23.5%±19.2%, p=0.001). At T2 a lower rate of high RPR patients were found in group A (2.6% vs13.3%; p=0.014). The BARC type ≥2 bleeding occurred in 12.6% of group A versus 4.1% of group B (OR 0.29, 95% CI 0.09 to 0.94) and secondary end point in 2.1% vs 1.0% (p=0.542), respectively, without stent thrombosis. CONCLUSIONS: RPR increases shifting from 60â mg loading dose to 10â mg/day prasugrel MD with a further increase of RPR reducing prasugrel MD to 5â mg 1â month after ACS. Clinical value of these pharmacodynamic findings should be proved in larger clinical trials. TRIAL REGISTRATION NUMBER: NCT01790854.
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INTRODUCTION: Thrombin generation (TG) is a central step of the coagulation system involved in hemostatic and thrombotic roles. Scarce data evaluating in the acute phase the association between TG and the risk of cardiovascular death of acute coronary syndrome (ACS) patients are available, in the era of percutaneous coronary intervention (PCI) and stenting with the use of dual antiplatelet treatment. MATERIALS AND METHODS: We investigated TG in 292 ACS patients undergoing PCI with stent implantation on dual antiplatelet treatment. Venous samples were obtained 12-24h after PCI. TG was assessed using the Calibrated Automated Thrombogram (CAT). RESULTS: At two years of follow-up, 57 out of 292 patients (19.5%) died from cardiovascular causes. Higher values of endogenous thrombin potential (ETP) [1115.9 (705-1441.3) vs 940.2 (666.0-1253.1), p=0.049], peak [176.1 (80.5-259.4) vs 107.3 (59.9-181.1), p=0.002] and velocity index [61.75 (21.03-97.88) vs 25.64 (11.95-50.90), p<0.001] were observed in relation to survival patients. At the multivariate model adjusted for the Global Registry of Acute Coronary Events risk score, the association between TG and cardiovascular death remained significant for ETP [OR (95% CI): 2.58 (1.10-6.03), p=0.029], peak [OR (95%CI): 3.27 (1.35-7.92), p=0.009] and velocity index [OR (95% CI): 3.06 (1.27-7.39), p=0.013]. This result was confirmed after adjustment for high on-treatment platelet reactivity [ETP: OR (95% CI) 2.35 (1.11-5.00), p=0.027; peak: OR (95% CI) 2.42 (1.13-5.15), p=0.022; velocity index: OR (95% CI) 2.43 (1.14-5.20), p=0.022]. CONCLUSIONS: ACS patients with a residual TG after PCI and stent implantation have a significantly higher risk of long-term cardiovascular death. These results might be useful in improving risk stratification for ACS patients and support the need of a tailored antithrombotic therapy.
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Síndrome Coronariana Aguda/terapia , Intervenção Coronária Percutânea , Trombina/análise , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/metabolismo , Síndrome Coronariana Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Risco , Stents/efeitos adversos , Trombina/metabolismo , Resultado do TratamentoRESUMO
Marfan syndrome (MFS) is a pleiotropic connective tissue disease inherited as an autosomal dominant trait, due to mutations in the FBN1 gene encoding fibrillin 1. It is an important protein of the extracellular matrix that contributes to the final structure of a microfibril. Few cases displaying an autosomal recessive transmission are reported in the world. The FBN1 gene, which is made of 66 exons, is located on chromosome 15q21.1. This review, after an introduction on the clinical manifestations that leads to the diagnosis of MFS, focuses on cardiovascular manifestations, pharmacological and surgical therapies of thoracic aortic aneurysm and/or dissection (TAAD), mechanisms underlying the progression of aneurysm or of acute dissection, and biomarkers associated with progression of TAADs. A Dutch group compared treatment with losartan, an angiotensin II receptor-1 blocker, vs no other additional treatment (COMPARE clinical trial). They observed that losartan reduces the aortic dilatation rate in patients with Marfan syndrome. Later on, they also reported that losartan exerts a beneficial effect on patients with Marfan syndrome carrying an FBN1 mutation that causes haploinsufficiency (quantitative mutation), while it has no significant effect on patients displaying dominant negative (qualitative) mutations. Moreover, a French group in a 3-year trial compared the administration of losartan vs placebo in patients with Marfan syndrome under treatment with beta-receptor blockers. They observed that losartan decreases blood pressure but has no effect on aortic diameter progression. Thus, beta-receptor blockers remain the gold standard therapy in patients with Marfan syndrome. Three potential biochemical markers are mentioned in this review: total homocysteine, serum transforming growth factor beta, and lysyl oxidase. Moreover, markers of oxidative stress measured in plasma, previously correlated with clinical features of Marfan syndrome, may be explored as potential biomarkers of clinical severity.
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Thoracic aortic aneurysm/dissection (TAAD) is a potential lethal condition with a rising incidence. This condition may occur sporadically; nevertheless, it displays familial clustering in >20% of the cases. Family history confers a six- to twentyfold increased risk of TAAD and has to be considered in the identification and evaluation of patients needing an adequate clinical follow-up. Familial TAAD recognizes a number of potential etiologies with a significant genetic heterogeneity, in either syndromic or nonsyndromic forms of the manifestation. The clinical impact and the management of patients with TAAD differ according to the syndromic and nonsyndromic forms of the manifestation. The clinical management of TAAD patients varies, depending on the different forms. Starting from the description of patient history, in this paper, we summarized the state of the art concerning assessment of clinical/genetic profile and therapeutic management of TAAD patients.
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Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/terapia , Dissecção Aórtica/genética , Dissecção Aórtica/terapia , Aconselhamento Genético/métodos , Testes Genéticos/métodos , Dissecção Aórtica/diagnóstico , Aneurisma da Aorta Torácica/diagnóstico , Estudos de Casos e Controles , Humanos , Itália , Anamnese/métodosRESUMO
BACKGROUND: Strong evidence supports an association between high levels of homocysteine (Hcy) and lipoprotein(a) [Lp(a)] and an increased rate of ischemic vascular events. METHODS: The study population comprised 162 patients (50 women [30.9%]; age, 66.71 ± 12.76 years) having a history of acute coronary syndrome within 1 year who underwent fasting blood sampling, measurement of intima-media thickness and pulse wave velocity at the common carotid and femoral arteries by Doppler ultrasound, and ankle-brachial index measurement. Cutoff values were considered 0.9 mm and 1.2 mm for carotid and femoral intima-media thickness, respectively; 12 m/s for pulse wave velocity; and <0.9 for ankle-brachial index. We included hypertension, dyslipidemia, diabetes, overweight/obesity, smoking, and family history of cardiovascular disease in the count of traditional risk factors (CRFs). Adding Hcy ≥15 µmol/L and Lp(a) ≥500 mg/L to CRFs, we obtained a new score, named TOTAL. RESULTS: On univariate analysis, Hcy and Lp(a) were significantly associated with presence of atherosclerotic extracoronary lesions (for Hcy: ß = .934; standard error = 0.178; P < .0001; for Lp(a): ß = .961; standard error = 0.177; P < .0001) and compliance alterations (for Hcy: odds ratio, 13.3; 95% confidence interval, 3.9-45.3; P < .0001; for Lp(a): odds ratio, 14.6; 95% confidence interval, 5.69-37.62; P < .0001). On multivariate analysis, Lp(a) and Hcy were significantly associated with extracoronary atherosclerosis, even after correction for CRFs. The area under the curve of the TOTAL score for both atherosclerosis and vascular compliance alterations was significantly higher than the area under the curve of traditional CRFs plus only Hcy ≥15 µmol/L or plus Lp(a) ≥500 mg/L, separately added. CONCLUSIONS: The addition of evaluation of Hcy ≥15 µmol/L and Lp(a) ≥500 mg/L to the traditional CRF count does improve detection of systemic atherosclerotic burden of patients with acute coronary syndrome and can offer a new opportunity to optimize secondary prevention.
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Síndrome Coronariana Aguda/sangue , Aterosclerose/sangue , Doenças das Artérias Carótidas/sangue , Doença da Artéria Coronariana/sangue , Homocisteína/sangue , Hiper-Homocisteinemia/sangue , Lipoproteína(a)/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Idoso , Índice Tornozelo-Braço , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Biomarcadores/sangue , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/epidemiologia , Espessura Intima-Media Carotídea , Distribuição de Qui-Quadrado , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/epidemiologia , Itália/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Análise de Onda de Pulso , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Ultrassonografia Doppler , Regulação para CimaRESUMO
Takotsubo cardiomyopathy (TTC) pathophysiology is still unclear. A transient intracoronary thrombosis dissolved at the time of angiography has been hypothesized. We aimed to evaluate the prevalence of thrombophilic disorders in TTC patients. In 75 TTC women, 75 age- and sex-matched acute coronary syndrome (ACS) patients, both enrolled during the acute phase, and in 75 control subjects, we compared the prevalence of congenital and acquired thrombophilic alterations and the values of clotting and endothelial activation biomarkers. Some parameters were re-assessed 1 month after the acute phase in TTC patients. No significant difference between the three groups was observed in factor II (G20210A) and V (G1691A) polymorphisms prevalence. Homocysteine levels were significantly higher in ACS patients vs. TTC and control subjects. Lipoprotein(a) values trended to be higher in TTC patients vs. control subjects, though not significantly. Other thrombophilic alterations in TTC patients were similar to that previously reported in healthy women. Von Willebrand factor and plasminogen activator inhibitor-1 were significantly higher in TTC and in ACS patients than controls. Clotting activation biomarkers were not statistically different between TTC patients and controls. During follow-up, in TTC patients, endothelial damage indices significantly decreased while clotting activation biomarkers remained unchanged. In conclusion, our results, showing a rate of thrombophilic alterations in TTC patients similar to control subjects, do not support the transient intracoronary thrombus hypothesis. However, several endothelial damage markers and lipoprotein(a) were higher in TTC patients vs. controls suggesting a role of endothelial dysfunction and of other factors concurring to hyperviscosity, as recently hypothesized.
Assuntos
Síndrome Coronariana Aguda/epidemiologia , Coagulação Sanguínea , Cardiomiopatia de Takotsubo/epidemiologia , Trombofilia/epidemiologia , Síndrome Coronariana Aguda/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Coagulação Sanguínea/genética , Testes de Coagulação Sanguínea , Viscosidade Sanguínea , Estudos de Casos e Controles , Endotélio Vascular/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Itália/epidemiologia , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo Genético , Prevalência , Fatores de Risco , Cardiomiopatia de Takotsubo/sangue , Cardiomiopatia de Takotsubo/diagnóstico , Trombofilia/sangue , Trombofilia/diagnóstico , Trombofilia/genéticaRESUMO
OBJECTIVE: To investigate lipoprotein(a) [Lp(a)], a well known cardiovascular risk factor, in women with history of placenta-mediated pregnancy complications (PMPC) compared with healthy uneventful-pregnancy women (HW), and the role of LPA gene functional polymorphisms in modulating both Lp(a) levels and PMPC risk. DESIGN: Retrospective observational study. SETTING: University hospital. PATIENT(S): A total of 360 women with history of PMPC (154 preeclampsia [PE], 121 stillbirth [SB], and 85 small for gestational age [SGA]) and 270 HW. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Lp(a) levels measurement and LPA +93C >T and +121G>A polymorphisms genotyping. RESULT(S): In PMPCs we observed higher Lp(a) levels than those found in HW and an association with PMPC risk, also after adjustment for age, familial history of cardiovascular disease, and traditional risk factors. By analyzing Lp(a) concentrations according to each pregnancy complication, we observed significantly higher Lp(a) levels in women with history of SB and PE, conferring 2.5-fold and 2-fold increased risks, respectively; no association with SGA was observed. Lp(a) concentrations progressively and significantly increased as LPA unfavorable allelic burden increased; unfavorable allelic burden influenced SB and PE risk. CONCLUSION(S): We evidenced, for the first time, an association between high Lp(a) concentrations and history of SB, and we confirmed the role of Lp(a) in PE risk; this well known atherothrombotic marker might represent one of the possible mechanisms shared by PMPC and cardiovascular disease.
Assuntos
Doenças Cardiovasculares/sangue , Lipoproteína(a)/sangue , Placenta/irrigação sanguínea , Placenta/metabolismo , Complicações na Gravidez/sangue , Adulto , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Pessoa de Meia-Idade , Insuficiência Placentária/sangue , Insuficiência Placentária/diagnóstico , Insuficiência Placentária/epidemiologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/epidemiologia , Estudos Retrospectivos , Natimorto/epidemiologia , Adulto JovemRESUMO
The involvement of the musculoskeletal system with other mild pleiotropic manifestations represents a clinical criterion, called "systemic features," to d iagnose Marfan's syndrome. We aimed to investigate the features of the hands and feet redressable contractures present in a group of Marfan patients. In 13 patients with previously diagnosed Marfan's syndrome, an accurate clinical examination was performed. In particular the characterization of the musculoskeletal system by visual analogic scale to measure muscle pain (VAS) and muscle strength (MRC system) was carried out; the Beighton scale score was used to evaluate the articular hypermobility. Ultrasound examination (US) was performed to detect deep-superficial flexor tendons and extensor tendons of both hands, and the short and long flexor and extensor tendons of the fingers and toes in static and dynamic positions. The ImageJ program was adopted to measure a profile of tendon echo-intensity. A reduction of the thickness of all tendons was detected by US in our patients; the VAS and Beighton scale scores were in normal ranges. The profile of tendon echo-intensity showed different textural details in all Marfan patients. This study provides evidence for other contractures' localization, and for altered findings of the tendons in patients with Marfan syndrome and finger/toe contractures. These changes may be associated with structural modifications in connective tissue.