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Vanessa Roldán

Publications and source records attributed to Vanessa Roldán.

At least 19 recordsLinked to original sources
PubMed2006

A nonsense polymorphism in the protein Z-dependent protease inhibitor increases the risk for venous thrombosis.

The protein Z-dependent protease inhibitor (ZPI) is a hemostatic serpin with anticoagulant activity. As for antithrombin, deficiency of ZPI could have relevant thrombotic consequences. We have studied 6 genetic modifications affecting the ZPI gene, identifying 5 haplotypes. Haplotype H5 is featured by a stop codon at position 67. The relevance of these genetic modifications and haplotypes in venous thrombosis was evaluated in a case-control study including 1018 patients and 1018 age- and sex-matched controls. Surprisingly, the H5 haplotype was found in 0.9% of controls, supporting that the Arg67Stop change is a low frequency nonsense polymorphism. The prevalence of this haplotype increased significantly in patients (3.0%), one of whom was in a homozygous state. Multivariate analysis confirms that carriers have a 3.3-fold risk of developing venous thrombosis (P = .002; 95% CI: 1.5-7.1). Moreover, we observed a significant association of this polymorphism with familial history of thrombosis (P < .001). Our study supports that the ZPI Arg67Stop nonsense polymorphism might be an independent genetic risk factor for venous thrombosis. This polymorphism has slightly lower prevalence but similar thrombotic risk than the FV Leiden or prothrombin 20210A. Although further studies are required, all available data support that the ZPI is a candidate to play a significant role in thrombosis and should be evaluated in thrombophilic studies.

Adult↗
PubMed2006

Does smoking status influence the effect of physical exercise on fibrinolytic function in healthy volunteers?

UNLABELLED: Exercise has been reported to simultaneously trigger and protect against sudden death, the so-called "The Paradox of Exercise". Differences in fibrinolytic function appear to exist between chronic and acute exercise. The aim of the present study was to assess the fibrinolytic system after strenuous exercise in healthy people and explored the influence of smoking habit. METHODS: 23 healthy male volunteers were studied (14 non-smokers; 9 current smokers). Citrated plasma blood samples were taken before and 30 minutes after a maximal exercise treadmill test, and levels of tissue type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI-1) antigen and lipoprotein-a, Lp(a), [all ELISA] were measured as indices of fibrinolytic function. RESULTS: Smokers had higher body mass index and higher heart rate at baseline than non smokers (p = 0.046 and p = 0.001, respectively). At baseline, smokers showed increased plasma Lp(a) levels than non smokers (p = 0.04), with no differences in t-PA and PAI-1 antigen levels. Following the exercise treadmill test, smokers had a shorter exercise duration and lower exercise capacity than non smokers (p = 0.008 and p = 0.004, respectively). This was associated with a reduction in t-PA antigen levels in the whole study population, (p = 0.048) without differences in PAI-1 levels, with no significant differences between smokers and non smokers. Lp(a) levels were also significantly reduced (p = 0.0001). CONCLUSIONS: Acute exercise alters plasma tPA antigen and Lp(a) levels, but there was no significant effect of smoking status in healthy subjects.

Adult↗
PubMed2005

Antiplatelet versus anticoagulant therapies in advanced age: an unfinished task.

We have read with great interest a retrospective cohort study recently published by Blich and Gross. In our opinion, this article renews the controversy of the best antithrombotic therapy in patients with AF. The use of anticoagulant treatment to prevent the occurrence of stroke in patients with AF is supported by several randomized controlled clinical trials. Aspirin is also effective in preventing stroke in AF, but both direct and indirect comparisons with oral anticoagulation suggest less effectiveness. However, very probably these patients are quite different than those seen in the clinical practice. The role of antiplatelet therapy is not completely established, and the selection between aspirin or warfarin in advanced age remains an unfinished task.

Aged↗
PubMed2005

Statins and postoperative risk of atrial fibrillation following coronary artery bypass grafting.

Atrial fibrillation (AF) is a common complication after coronary artery bypass grafting. Atrial remodeling has been observed in AF and has been associated with the development of this arrhythmia. Because 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) have been demonstrated to modify remodeling, we hypothesized a protective role of statins against postoperative AF. We also hypothesized that extracellular matrix turnover and brain natriuretic peptide (BNP) might be related to such atrial remodeling. We studied 234 consecutive patients who underwent coronary artery bypass grafting (173 men; 65 +/- 9 years of age) in whom the occurrence of postoperative AF was monitored. In a subgroup of 66 patients, we measured plasma levels of matrix metalloproteinase-1 (MMP-1), its inhibitor, tissue inhibitor matrix metalloproteinase-1 (TIMP-1; as indexes of extracellular matrix remodeling), and N-terminus pro-BNP (related to left ventricular function) at baseline and at 24 hours after surgery. Of 234 patients, 66 (28.2%) developed postoperative AF. In multivariate analysis, previous AF was related to an increase in the development of AF (odds ratio 11.92, 95% confidence interval 2.37 to 59.98, p = 0.026), whereas statin use was related to a decrease in arrhythmia (odds ratio 0.52, 95% confidence interval 0.28 to 0.96, p = 0.038). A higher TIMP-1/MMP-1 ratio at 24 hours after surgery was present in those who did not develop postoperative AF (p = 0.043). Statin use was associated with increased TIMP-1 levels and TIMP-1/MMP-1 ratio (p = 0.027 and 0.036, respectively). No significant relations to N-terminus pro-BNP were seen. In conclusion, previous AF and nonuse of statins are significantly associated with AF after coronary artery bypass grafting. Statin use may be protective against AF after coronary artery bypass grafting, possibly due to alterations in the extracellular matrix and remodeling after coronary artery bypass grafting.

Aged↗
PubMed2005

Are there ethnic differences in the circadian variation in onset of acute myocardial infarction? A comparison of 3 ethnic groups in Birmingham, UK and Alicante, Spain.

We hypothesised that ethnicity may influence the circadian pattern in acute myocardial infarction (MI), in view of the potential differences in genetic background, cardiovascular risk factors and cultural habits. To test our hypothesis, we studied 340 consecutive acute MI patients (268 males; mean age 61.6+/-12.3 years) from two different city-centre teaching hospitals in Birmingham (United Kingdom) and Alicante (Spain). A different circadian rhythm in MI onset was observed between the ethnic groups (p=0.001), with a significantly higher number of acute MI onset occurring between midnight and noon in British Caucasians and Indo-Asians. In contrast, Mediterranean Caucasians showed the converse circadian pattern, with most of the acute MI events happened between noon and midnight. Indo-Asian patients were the youngest patient group and showed the highest prevalence of diabetes and increased body mass index. Mediterranean patients had the highest prevalence of smokers but their mean serum cholesterol was the lowest. No differences in sex, blood pressure, height and weight were observed. In conclusion, this study has shown a different circadian rhythm in acute MI onset between 3 ethnic groups from two different city-centre teaching hospitals in Birmingham (United Kingdom) and Alicante (Spain) and, for the first time, provide data in the Indo-Asian population. Further studies are required to determine the pathophysiological mechanism(s) underlying these differences.

Aged↗
PubMed2005

Correlation of plasma von Willebrand factor levels, an index of endothelial damage/dysfunction, with two point-based stroke risk stratification scores in atrial fibrillation.

To test the hypothesis that the new CHADS2 and Framingham point-based risk stratification scores could be related to plasma vWf (a plasma index of endothelial damage/dysfunction) and soluble E-selectin (an index of endothelial activation) levels in a large cohort of AF patients, we studied 200 consecutive patients (101 male; 72+/-9 years) attending our anti-coagulation clinic for the initiation of anticoagulation treatment with acenocoumarol. AF patients had a median CHADS2 score of 2 (1-2) and a median Framingham point-based risk score of 14 (9-21). Results of research indices in our AF patients were as follows: vWf 142.8+/-41.8 IU/dL and sE-sel 44 (31-62) ng/mL. There were significant correlations between plasma vWf levels and both risk CHADS2 and Framingham risk scores (vWf-CHADS2 risk score: Spearman, r=0.249, p<0.001; vWf-Framingham risk score: r=0.294, p<0.001). sE-sel did not show any significant correlation with both risk scores (sE-sel-CHADS2 risk score: r=-0.054, p=0.460; sE-sel-Framingham risk score: r=0.062, p=0.460). There were no statistically significant correlations between vWf and sE-sel (r=-0.127, p=0.081). Both CHADS2 and Framingham risk scores were significantly correlated with each other, r=0.627, p<0.001. In conclusion, in a wide cohort of non-selected and consecutive AF patients, endothelial damage/dysfunction (assessed by plasma vWf levels) but not endothelial activation (sE-sel) correlated with two new risk stratification scores for stroke in AF. Further prospective studies are needed to assess the prognostic role of prothrombotic indices in AF in relation to stroke and thromboembolic events, and their role in complementing clinical risk stratification schemas.

Aged↗
PubMed2005

A pharmacogenetic effect of factor XIII valine 34 leucine polymorphism on fibrinolytic therapy for acute myocardial infarction.

OBJECTIVES: The aim of this study was to evaluate the pharmacogenetic role of the factor XIII (FXIII) valine 34 leucine (Val34Leu) polymorphism in the fibrinolytic therapy of acute myocardial infarction (MI). BACKGROUND: Fibrinolytic therapy is an established treatment for acute MI, but up to 40% of treated patients do not achieve optimal tissue reperfusion. The FXIII Val34Leu polymorphism is one of the most relevant functional polymorphisms described in the haemostatic system. The common Leu34 allele associates with an increased FXIII-transglutaminase activity, which results in an increased and faster rate of fibrin stabilization. METHODS: We genotyped this polymorphism in 293 consecutive MI patients (62 +/- 12 years; 231 males) from two different European populations. All patients were treated with standard doses of fibrinolytic drugs. Noninvasive assessment of the efficacy of coronary fibrinolysis was evaluated by serial electrocardiograms and creatine kinase time-activity curves. The clinical outcome was also re-evaluated at 24 h (death, reinfarction, or urgent revascularization). RESULTS: Multivariate analysis showed that Leu34 carriers displayed a significantly less efficient fibrinolysis than carriers of Val/Val genotype (p = 0.021; odds ratio [OR] 1.90, 95% confidence interval [CI] 1.10 to 3.28). At 24 h, Leu34 allele carriers had the worst outcome (p = 0.006; OR 2.14, 95% CI 1.25 to 3.68). Interestingly, the combination of the Leu34 allele and nonsmoking status increased the risk of non-reperfusion criteria (p = 0.003, OR 3.77), and worse outcomes at 24 h (p = 0.001, OR 4.55). CONCLUSIONS: In a large cohort of nonselected and consecutive acute MI patients from two different European populations, we show clinical evidence that the presence of the Leu34 allele reduces the efficacy of fibrinolytic therapy.

Aged↗
PubMed2005

Synergistic association between hypercholesterolemia and the C46T factor XII polymorphism for developing premature myocardial infarction.

Factor XII (FXII) plays a key role in both coagulation and fibrinolysis, thus its role in thrombotic processes is uncertain. Both genetic and environmental factors determine FXII plasma levels. A common C46T polymorphism in the Kozak region of F12 gene disturbs the translation of the protein leading to a significant reduction of FXII levels although its clinical significance is conflictive. We studied the F12 C46T polymorphism in 281 patients who had suffered from an acute myocardial infarction (MI) before 45-year-old and 550 control subjects from the same area. Serum levels of cholesterol, HDL, LDL, triglycerides and C reactive protein (CRP) were assayed in the MI group. The 46T allele slightly increased the risk to suffer from premature MI (OR: 1.64; 95% CI: 1.14-2.37; p = 0.008). Moreover, patients carrying the 46T allele showed increased levels of CRP (p = 0.002). Interestingly, we found that the simultaneous presence of the 46T allele and hypercholesterolemia increases the risk to develop premature MI 2.26 times. The F12 C46T polymorphism, associated with a reduction of plasma FXII levels, seems to play a deleterious effect, predisposing the development of premature MI, especially in hypercholesterolemic patients. This effect could be associated with an increased pro-inflammatory state, as the 46T allele associates with high levels of CRP.

Age Factors↗
PubMed2005

Pharmacogenetics in cardiovascular antithrombotic therapy.

Thrombosis is the most important underlying mechanism of coronary heart disease and embolic stroke. Therefore, antithrombotic therapy is commonly used in cardiovascular diseases. Unfortunately, the benefits are limited, and an important proportion of treated patients will suffer a new thrombotic event. Lack of clinical benefits may be related to heterogeneous response to antithrombotic treatment among individuals (inter-individual heterogeneity). Few factors have been identified to be involved in this inter-individual heterogeneity. Recently, pharmacogenetic has emerged as a new field in medicine that tries to identify gene variants able to explain the heterogeneity in patient's response to a drug. Polymorphisms affecting disposition, metabolism, transporters or targets of the drug could modify the individual response to one therapy, and probably its side effects. The present review article explores the genetic influence on antithrombotic drug efficacy, analysing the modulating role of different polymorphisms on individuals' response to drugs commonly used in current day practice.

Anticoagulants↗
PubMed2005

Five prothrombotic polymorphisms and the prevalence of premature myocardial infarction.

We studied 5 functional hemostatic polymorphisms in 281 patients with premature myocardial infarction and in 530 control subjects. The role of these polymorphisms when analyzed independently is small, if any. However, the simultaneous combination of factor XIII and prothrombin polymorphisms exacerbated the risk. (OR=12.12; p=0.028). Moreover, combinations of factor V Leiden with prothrombin, and factor XII with prothrombin polymorphisms were only identified in patients. Our results support the relevance of gene-gene interactions in myocardial infarction.

Adult↗
PubMed2005

[Effect of maximum dose of atorvastatin on inflammation, thrombogenesis and fibrinolysis in high-risk patients with ischemic heart disease].

INTRODUCTION AND OBJECTIVES: It has been suggested that high doses of statins can be more effective in reducing the incidence of new cardiovascular events than conventional doses. The present study analyzed the effect of increasing the atorvastatin dose to 80 mg/day on indices of inflammation (C-reactive protein or CRP), thrombogenesis (prothrombin fragment [F1+2]) and fibrinolysis (tissue-type plasminogen activator antigen, t-PA, and its inhibitor PAI-1) in high-risk patients with ischemic heart disease. PATIENTS AND METHOD: We studied 27 patients with high-risk coronary heart disease who had lipid levels above those recommended despite treatment with atorvastatin at 40 mg/day. At baseline, patients were compared with 21 normocholesterolemic subjects without arteriosclerotic disease. Twenty-four patients were reevaluated 3 months after the atorvastatin dose was increased to 80 mg/day. RESULTS: The CRP, F1+2, t-PA and PAI-1 levels were significantly higher in patients than control subjects (all P<.05). After the atorvastatin dose was increased, significant reductions in CRP, F1+2, and PAI-1 levels were observed (P<.05). There was a significant positive correlation between the reduction in cholesterol level and that in F1+2 (r=0.43; P=.023). No other significant correlations were found. CONCLUSIONS: In a group of patient with high-risk heart disease and elevated lipid levels, increasing the atorvastatin dose led to significant improvements in inflammatory, thrombogenic, and hypofibrinolytic states.

Aged↗
PubMed2004

Short alleles of P-selectin glycoprotein ligand-1 protect against premature myocardial infarction.

BACKGROUND: Atherosclerosis is an inflammatory disease resulting from an injury that leads to an increase in the adhesiveness and permeability of the endothelium to leukocytes or platelets. The selectin family plays a key role initiating the cascade of events. Recently, we have demonstrated the functional relevance of a variable number of tandem repeats polymorphism affecting the P-selectin glycoprotein ligand (PSGL-1). Neutrophils carrying short alleles exhibit a significantly lower capacity to bind activated platelets. These alleles consistently protect against transient ischemic attack. We sought to evaluate the role of this polymorphism in premature myocardial infarction because genetic risk factors have more relevance in the development of disease in young patients. METHODS: We genotyped 219 Caucasian patients who had suffered a premature myocardial infarction (MI) (aged < or =45 years) and 594 control subjects from our Mediterranean area. The role of the PSGL-1 polymorphism was also evaluated according to the additional risk factors of age, sex, smoking history, hypertension, hypercholesterolemia, and diabetes. RESULTS: The frequency of the short alleles (B and C) was significantly lower in patients than in controls (P =.012, odds ratio 0.62; 95% CI 0.42-0.92). Multiple regression analysis revealed that B and C alleles had an independent protective effect on the development of premature MI (P =.034, odds ratio 0.62 95%CI: 0.40-0.96). CONCLUSIONS: We found an interesting association between a functional polymorphism and the risk of MI at a younger age. According to our results, the short B and C PSGL-1 alleles might protect against premature MI, probably because of their lesser adhesive capacity.

Adult↗