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Biomedical subjects

Carlos Macaya

Publications and source records attributed to Carlos Macaya.

At least 19 recordsLinked to original sources
PubMed2007

Relocation of minimal luminal diameter after bare metal and drug-eluting stent implantation: incidence and impact on angiographic late loss.

Late loss (LL) has been a fundamental angiographic end-point in drug-eluting stents (DES) clinical trials. However, calculation of LL may be affected by a mismatch between post-procedure (PO) and follow-up (FU) sites of the minimal lumen diameter (MLD). Our aims were to investigate the incidence and methodological implications of the relocation of MLD after bare metal (BMS), sirolimus-eluting (SES), and paclitaxel-eluting (PES) stent implantation. Data from DIABETES I and II trials, which involved diabetic patients treated with BMS, SES, and PES, were analyzed. Angiographic data with matched projections between PO and 9-month angiographic FU were included. In-stent, in-lesion, and in-segment analyses included conventional and customized sub-segmental (5-mm/subsegment) methodology. MLD relocation was considered when the sites of MLD shifted a distance >> the intrinsic variability of the method. Conventional LL, site matched LL, maximal LL (MaxLL), and average LL (AvgLL) were calculated. Relationships between various LL and 1-year target lesion revascularization (TLR) were investigated. Post MLD was located distally, outside the stent, in > or =65% of the analyses. At FU, MLD relocation occurred in 70.5% (BMS), 40% (SES), and 35% (PES). MLD shifted > or =11 mm on average, mainly towards the stented segment. MLD relocation still occurred in 42.8% (BMS), 33.7% (SES), and 36.4% (PES), when analysis was restricted to in-stent segment. Among LL measurements, MaxLL showed the best association with TLR rates. Relocation of the MLD is a frequent phenomenon after both BMS and DES, and should be taken into account when calculating LL. Comprehensive LL analyses, including MaxLL and AvgLL, provides a better appraisal of the biological and clinical effectiveness of DES.

Aged↗
PubMed2006

Relation of heart rate turbulence to severity of heart failure.

The aim of this study was to evaluate the association between heart rate turbulence (HRT) parameters and clinical, biochemical, echocardiographic, and electrocardiographic measures of heart failure (HF) in a large, prospectively enrolled population of patients with HF to determine whether HRT could be considered a marker of HF advancement and progression, giving insight into hemodynamic changes as well as changes of the autonomic nervous system. In 487 patients with HF (mean age 63 years), the following tests were performed: 12-lead surface electrocardiography, echocardiography, chest x-rays, N-terminal-pro-brain natriuretic peptide levels, and 24-hour Holter monitoring for HRT and heart rate variability analyses. Most patients were in New York Heart Association class II (82%) and had a mean left ventricular (LV) ejection fraction of 37 +/- 14%. Both HRT parameters, but especially turbulence slope, were significantly correlated with clinical indexes of HF (the third heart sound, peripheral edemas, jugular distension, and pulmonary congestion). Patients in New York Heart Association class III had significantly lower turbulence slopes and greater turbulence onset values than those in class II. Significant correlations were found between HRT parameters and the LV ejection fraction as well as with LV diameters. HRT parameters were significantly correlated with N-terminal-pro-brain natriuretic peptide levels (r = -0.47, p <0.001 for turbulence slope). Multivariate analyses showed that abnormal HRT parameters were independent predictors of HF severity measured by New York Heart Association class III and a LV ejection fraction <40%. In conclusion, the findings indicate that in patients with HF, HRT reflects well the severity of HF and associated LV dysfunction, which were verified in this study by a series of established clinical, echocardiographic, and biochemical parameters.

Adolescent↗
PubMed2006

Case report of a Spanish patient with arrhythmogenic right ventricular cardiomyopathy and palmoplantar keratoderma without plakoglobin and desmoplakin gene modifications.

We report a case of a 43 year old man from Spain, who has been diagnosed with Naxos disease. It is a hereditary disorder characterized by palmoplantar keratoderma, woolly hair and cardiomyopathy, which has been associated with a mutation in plakoglobin encoding gene in chromosome 17q21. In the patient, the direct sequencing of the plakoglobin gene discarded TG deletion at 2157 characteristic of Naxos disease. Analysis of the reported desmoplakin mutations associated with Carvajal Syndrome, another ARVC disease, that it is also accompanied with a skin and hair disorder, also failed to reveal mutations in desmoplakin gene. These results suggest the existence of other causative genes and/or other putative sites in desmoplakin/plakoglobin encoding genes than those recently published.

Adult↗
PubMed2006

Prognostic significance of functional mitral regurgitation after a first non-ST-segment elevation acute coronary syndrome.

AIMS: The development of mitral regurgitation (MR) after an acute myocardial infarction (AMI) is a recognized and frequent complication and its negative impact on survival has been observed. However, few data exist regarding MR after non-ST-segment elevation acute coronary syndrome (NSTSEACS). Our aim was to investigate the incidence, clinical predictors, and prognostic implications of MR in the setting of NSTSEACS. METHODS AND RESULTS: We studied 300 consecutive patients (71.7% men, mean age 66.9+/-13 years) admitted to our coronary care unit for an NSTSEACS. Every patient underwent an echocardiographic study during the first week after the index NSTSEACS and was clinically followed up. MR was detected in 42% (126 patients; 88 men, mean age 71.3+/-11 years). Mean follow-up was 425.6+/-194.8 days. Only age and left ventricular (LV) ejection fraction (EF) were found as independent markers of the development of MR; no variable was found as an independent predictor of in-hospital mortality and only MR was found as an independent predictor of long-term outcome. CONCLUSION: MR is frequent after an NSTSEACS. Age and a low LV EF are factors associated to its development. The presence and degree of MR confer a worse long-term prognosis to patients after a first NSTSEACS. Thus, the presence of MR should be specifically assessed in every patient after an NSTSEACS.

Aged↗
PubMed2006

Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention.

BACKGROUND: Despite its limitations, unfractionated heparin has been the standard anticoagulant used during percutaneous coronary intervention (PCI). Several small studies have suggested that intravenous enoxaparin may be a safe and effective alternative. Our primary aim was to assess the safety of enoxaparin as compared with that of unfractionated heparin in elective PCI. METHODS: In this prospective, open-label, multicenter, randomized trial, we randomly assigned 3528 patients with PCI to receive enoxaparin (0.5 or 0.75 mg per kilogram of body weight) or unfractionated heparin adjusted for activated clotting time, stratified according to the use or nonuse of glycoprotein IIb/IIIa inhibitors. The primary end point was the incidence of major or minor bleeding that was not related to coronary-artery bypass grafting. The main secondary end point was the percentage of patients in whom the target anticoagulation levels were reached. RESULTS: Enoxaparin at a dose of 0.5 mg per kilogram was associated with a significant reduction in the rate of non-CABG-related bleeding in the first 48 hours, as compared with unfractionated heparin (5.9% vs. 8.5%; absolute difference, -2.6; 95% confidence interval [CI], -4.7 to -0.6; P=0.01), but the higher enoxaparin dose was not (6.5% vs. 8.5%; absolute difference, -2.0; 95% CI, -4.0 to 0.0; P=0.051). The incidence of major bleeding was significantly reduced in both enoxaparin groups, as compared with the unfractionated heparin group. Target anticoagulation levels were reached in significantly more patients who received enoxaparin (0.5-mg-per-kilogram dose, 79%; 0.75-mg-per-kilogram dose, 92%) than who received unfractionated heparin (20%, P<0.001). CONCLUSIONS: In elective PCI, a single intravenous bolus of 0.5 mg of enoxaparin per kilogram is associated with reduced rates of bleeding, and a dose of 0.75 mg per kilogram yields rates similar to those for unfractionated heparin, with more predictable anticoagulation levels. The trial was not large enough to provide a definitive comparison of efficacy in the prevention of ischemic events. (ClinicalTrials.gov number, NCT00077844 [ClinicalTrials.gov].).

Aged↗
PubMed2006

Influence of the CD14 C260T promoter polymorphism on C-reactive protein levels in patients with coronary artery disease.

The CD14 receptor is an important mediator of inflammatory reactions, and its expression is under genetic control. The allelic variant of the C260T polymorphism located in the promoter region of the CD14 gene is associated with receptor expression and ischemic risk. To date, most studies assessing the functional implications of the C260T polymorphism have been performed under proinflammatory conditions (e.g., acute coronary syndromes), and whether gene sequence variations of the CD14 receptor have any functional effect on systemic inflammation in patients in a stable phase of their atherosclerotic disease process is unknown. Eighty-two patients with stable coronary artery disease were studied. High-sensitivity C-reactive protein (hs-CRP) was used as a measurement of systemic inflammation. The genotype distribution of the C260T polymorphism of the CD14 gene was as follows: CC in 18 of 82 patients (22%), TC in 48 of 82 patients (58.5%), and TT in 16 of 82 patients (19.5%). TT subjects had increased hs-CRP levels compared with carriers of the C allele (p = 0.04). A higher percentage of T allele homozygotes had hs-CRP levels >0.3 mg/dl (p = 0.01). Homozygosis status of the T allele was independently associated with hs-CRP levels >0.3 mg/dl (p = 0.004). In conclusion, these observations may support the findings in large-scale studies that T homozygotes of this functional polymorphism are at increased ischemic risk.

Adult↗
PubMed2006

Characterization of plaque prolapse after drug-eluting stent implantation in diabetic patients: a three-dimensional volumetric intravascular ultrasound outcome study.

OBJECTIVES: The aim of this research was to evaluate the plaque prolapse (PP) phenomenon after bare-metal (BMS) and drug-eluting stent (DES) implantation in patients with diabetes mellitus using 3-dimensional volumetric intravascular ultrasound (IVUS). BACKGROUND: Plaque prolapse has been observed in up to 22% of patients treated with BMS. Diabetic patients have a larger atherothrombotic burden and may be more prone to have PP. However, the incidence of PP and its clinical impact after DES implantation is unknown. METHODS: Three-dimensional IVUS was performed after intervention and at 9-month follow-up in 168 patients with diabetes (205 lesions) treated with bare BX Velocity stents ((BX Velocity/Sonic, Cordis, Johnson & Johnson) (BMS, n = 65), sirolimus-eluting stents (Cypher, Cordis) (SES, n = 69), and paclitaxel-eluting stents (Taxus, Boston Scientific, Natick, Massachusetts) (PES, n = 71). Intravascular ultrasound data at the sites of PP were compared with stented segments without PP in each lesion. Outcomes were evaluated at 9- and 12-month follow-up. RESULTS: There were 42 sites of PP (BMS = 11, SES = 11, PES = 20, p = NS) in 34 stented segments of 205 (16.6%) lesions. Plaque prolapse was more frequent in the right coronary artery and in chronic total occlusion lesions. Post-procedure PP volume was 1.95 mm3 in BMS, 2.96 mm3 in SES, and 4.53 mm3 in PES. At follow-up, tissue volume increased at PP sites in both BMS and PES, but not after SES. Neointimal proliferation was similar between PP and non-PP sites. Stent thrombosis and restenosis rates were similar between PP and non-PP lesions. CONCLUSIONS: The incidence of PP after implantation of new generation tubular stents in patients with diabetes remains high. Drug-eluting stent implantation was not associated with increased risk of PP. Plaque prolapse was not associated with stent thrombosis or increased neointimal proliferation.

Aged↗
PubMed2006

Nitric oxide blocks hKv1.5 channels by S-nitrosylation and by a cyclic GMP-dependent mechanism.

OBJECTIVE: This study was undertaken to analyze whether nitric oxide (NO) modulates the human potassium channel hKv1.5, which generates the ultrarapid delayed rectifier current (IKur) that determines the height and duration of atrial action potentials. METHODS: Currents were recorded using the whole-cell patch-clamp in Ltk- cells expressing hKv1.5 channels. RESULTS: The NO donors (+/-)-S-Nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside, a NO solution, and l-Arginine inhibited hKv1.5 currents in a concentration-dependent manner. The NO concentration in the cell chamber was monitored using a sensor, and the IC50 for NO-induced hKv1.5 block was 340+/-70 nM. SNAP also inhibited the IKur recorded in mouse ventricular myocytes. The NO effects were partially mediated by the activation of the soluble guanylate cyclase (sGC)/cGMP/cGMP-dependent protein kinase (PKG) pathway. The biotin-switch assay demonstrated the presence of S-nitrosylated cysteines (Cys) on the hKv1.5 protein in SNAP-treated cells. Molecular modeling of hKv1.5 channel structure suggests that S-nitrosylation of Cys331 (segment 2, S2) and Cys346 (S2) would be stabilized by hydrogen bridge bonds with Ile262 (S1) and Arg342 (S2), respectively. CONCLUSIONS: NO inhibits the hKv1.5 current by a cGMP-dependent mechanism and by the S-nitrosylation of the hKv1.5 protein, an effect that contributes to shaping the human atrial action potentials.

Analysis of Variance↗
PubMed2006

Insulin therapy is associated with platelet dysfunction in patients with type 2 diabetes mellitus on dual oral antiplatelet treatment.

OBJECTIVES: This study sought to assess the influence of type 2 diabetes mellitus (T2DM) and the impact of hypoglycemic treatment (insulin vs. noninsulin) on platelet function profiles in patients treated with dual oral antiplatelet therapy. BACKGROUND: Insulin inhibits platelet aggregation by suppressing the P2Y12 pathway. However, T2DM patients have a loss of responsiveness to insulin that leads to upregulation of the P2Y12 pathway, increased platelet reactivity, and reduced responsiveness to antiplatelet agents. Patients with insulin-treated diabetes mellitus (ITDM) have a more advanced disease status and higher atherothrombotic risk compared with non-ITDM (NITDM). However, the impact of insulin therapy on platelet dysfunction in patients treated with P2Y12 antagonists is unknown. METHODS: A total of 201 T2DM and 65 nondiabetic patients with coronary artery disease in a steady phase of aspirin and clopidogrel treatment were studied. Platelet aggregation was assessed using agonists specific (6 and 20 microM adenosine diphosphate [ADP]) and nonspecific (6 microg/ml collagen and 20 microM epinephrine) for the P2Y12 pathway. High shear-induced platelet reactivity was assessed by means of the PFA-100 system (Dade-Behring International, Miami, Florida). RESULTS: The T2DM patients had platelet aggregation and shear-induced platelet function significantly increased compared with nondiabetic patients using all assays. Platelet aggregation was increased in ITDM (n = 68) compared with NITDM (n = 133) patients after P2Y12-specific stimuli. Insulin treatment was the strongest predictor of ADP-induced aggregation. Platelet function profiles were similar between ITDM and NITDM using assays nonspecific to the P2Y12 pathway. Platelet dysfunction was independent of glycemic control and inflammatory status. CONCLUSIONS: The P2Y12-dependent and -independent pathways of platelet reactivity are altered in T2DM compared with nondiabetic patients, and ITDM have greater ADP-induced platelet aggregation compared with NITDM.

Aged↗
PubMed2006

High resistance of atrioventricular node to cryoablation: a great safety margin targeting perinodal arrhythmic substrates.

BACKGROUND: Findings from animal studies and small series of patients support the greater safety of cryoenergy over radiofrequency in the ablation of arrhythmic substrates near the AV node. OBJECTIVES: The purpose of this study was to systematically evaluate the electrophysiologic effects of successive cryoenergy applications to the human AV node in order to better define the safety margin of cryothermal ablation. METHODS: In 15 patients referred for AV nodal ablation, 94 cryomapping and 105 cryoablation applications were delivered through a 6-mm-tip cryothermal ablation catheter (Freezor Xtra, CryoCath) at predefined sites of the triangle of Koch. RESULTS: Temporary effects on AV conduction were observed in 18 (19%) cryomapping and 38 (36%) cryoablation applications. Persistent effects were observed in 9 (9%) cryoablation applications. Persistent effects were associated with cryoablation at the superior third of the triangle of Koch (P = .05), nadir tip temperature < or = -79 degrees C (P = .007), and effect onset time < or =15 seconds (P = .03). Temperature and effect onset time remained statistically significant after multivariate adjustment (P = .01 and .02, respectively). Overall, persistent complete AV block was achieved with cryoenergy in only one patient. In two additional patients, AV conduction remained modified. In the remaining patients, persistent complete AV block was achieved with radiofrequency (median one application per patient). CONCLUSION: The low rate of persistent AV conduction impairment observed with attempts to cryoablate the AV node supports a great safety margin of perinodal cryothermal ablation.

Aged↗
PubMed2006

A randomized comparison of sirolimus-eluting stent with balloon angioplasty in patients with in-stent restenosis: results of the Restenosis Intrastent: Balloon Angioplasty Versus Elective Sirolimus-Eluting Stenting (RIBS-II) trial.

OBJECTIVES: We sought to assess the effectiveness of sirolimus-eluting stents (SES) in patients with in-stent restenosis (ISR). BACKGROUND: Treatment of patients with ISR remains a challenge. METHODS: The Restenosis Intrastent: Balloon Angioplasty Versus Elective Sirolimus-Eluting Stenting (RIBS-II) study is a multicenter randomized trial conducted in 150 patients with ISR (76 allocated to SES and 74 to balloon angioplasty [BA]). The primary end point was recurrent restenosis rate at nine months. Secondary end points included prespecified subgroup analysis, lumen volume on intravascular ultrasound (IVUS), and a composite of major clinical events at one year. RESULTS: Angiographic success was obtained in all patients. At 9-month angiographic follow-up (96% of eligible patients) minimal lumen diameter was larger (2.52 mm [interquartile range (IQR) 2.09 to 2.81] vs. 1.54 mm [IQR 0.91 to 2.05]; p < 0.001) and recurrent restenosis rate was lower (11% vs. 39%; p < 0.001) in the SES group. Prespecified subgroup analyses were consistent with the main outcome measure. Lumen volume on IVUS at 9 months was also larger (279 mm3 [IQR 227 to 300] vs. 197 mm3 [IQR 177 to 230]; p < 0.001) in the SES group. At one-year clinical follow-up (100% of patients), the event-free survival (freedom from death, myocardial infarction, and target vessel revascularization) was significantly improved in the SES group (88% vs. 69%; p < 0.004) as the result of a lower requirement for target vessel revascularization (11% vs. 30%; p < 0.003). CONCLUSIONS: In patients with ISR, the use of SES provides superior long-term clinical, angiographic, and IVUS outcome than BA treatment.

Aged↗
PubMed2006

Vascular effects of sirolimus-eluting versus bare-metal stents in diabetic patients: three-dimensional ultrasound results of the Diabetes and Sirolimus-Eluting Stent (DIABETES) Trial.

OBJECTIVES: A predefined intravascular ultrasound (IVUS) substudy was performed to evaluate the vascular effects of sirolimus-eluting stent (SES) versus bare-metal stent (BMS). BACKGROUND: The Diabetes and Sirolimus-Eluting Stent (DIABETES) trial is a prospective, multicenter, randomized, controlled trial aimed at demonstrating the efficacy of the SES compared with BMS in diabetic patients. METHODS: Serial intravascular ultrasound analyses were performed in 140 lesions (SES = 75; BMS = 65) immediately after stent implantation and at nine-month follow-up. Vessel, luminal, and stent mean areas and volumes were evaluated at both edges and within the stented segment. Qualitative assessment of residual dissections and stent apposition were also performed. RESULTS: Baseline clinical and angiographic characteristics were similar between groups. At 9 months, in-stent neointimal hyperplasia (NIH) mean area and volume were significantly reduced in the SES group (median NIH area 0.01 mm2 [0.0 to 0.1] vs. 2.0 mm2 [1.0 to 2.9] and median NIH volume 0.11 mm3 [0 to 2.1] vs. 35.3 mm3 [16.6 to 62.6]; both p < 0.0001). In the SES group, stent edges evidenced significant increase in lumen dimensions mainly due to significant increase in vessel volume, whereas those of the BMS group presented vessel shrinkage leading to significant lumen reduction. Late acquired incomplete stent apposition was observed in 11 lesions (14.7%) in the SES group and 0 in the BMS group (p = 0.001). At one year, no stent thromboses occurred in malapposed stents. CONCLUSIONS: The SES implantation effectively inhibits NIH in diabetic patients. The antirestenotic effect of SES is also appreciated at the stent edges. Late acquired stent malapposition is a frequent phenomenon in diabetic patients treated with SES.

Aged↗
PubMed2006

Contribution of gene sequence variations of the hepatic cytochrome P450 3A4 enzyme to variability in individual responsiveness to clopidogrel.

OBJECTIVE: Metabolic activity of cytochrome P450 (CYP) 3A4 has been associated with clopidogrel response variability. Because metabolic activity of CYP3A4 is genetically regulated, we hypothesized that genetic variations of this enzyme may contribute to clopidogrel response variability. METHODS AND RESULTS: The CYP3A4*1B, CYP3A4*3, IVS7+258A>G, IVS7+894C>T, and IVS10+12G>A polymorphisms of the CYP3A4 gene were assessed in 82 patients in a steady phase of clopidogrel therapy. Glycoprotein (platelet glycoprotein (GP) IIb/IIIa receptor activation and platelet aggregation were assessed. A cohort of 45 clopidogrel-naïve patients was studied to determine the modulating effects of these polymorphisms after loading dose (300 mg) administration. Only the IVS7+258A>G, IVS7+894C>T, and IVS10+12G>A polymorphisms were sufficiently polymorphic. During the steady phase of clopidogrel treatment, IVS10+12A allele carriers had reduced GP IIb/IIIa activation (P=0.025) and better responsiveness (P=0.02); similarly, clopidogrel-naïve patients carriers of the IVS10+12A allele had reduced GP IIb/IIIa activation during the first 24 hours after a loading dose (P=0.025), increased platelet inhibition (P=0.006), and a more optimal drug response (P=0.003). This polymorphism did not influence platelet aggregation profiles. No association was observed between the other polymorphisms and clopidogrel responsiveness. CONCLUSIONS: The IVS10+12G>A polymorphism of the CYP3A4 gene modulates platelet activation in patients treated with clopidogrel and may therefore contribute to clopidogrel response variability.

Adenine↗
PubMed2006

Value of the American College of Cardiology/American Heart Association angiographic classification of coronary lesion morphology in patients with in-stent restenosis. Insights from the Restenosis Intra-stent Balloon angioplasty versus elective Stenting (RIBS) randomized trial.

BACKGROUND: The implications of the American College of Cardiology/American Heart Association (ACC/AHA) lesion classification in patients with in-stent restenosis (ISR) are unknown. METHODS: Four hundred fifty patients included in the RIBS randomized study were analyzed. A centralized core laboratory assessed ISR classifications including ACC/AHA, the classification of Mehran et al (Circulation 1999;100:1872-8), diffuse/focal, and a new quantitative ISR index (lesion length/stent length). Logistic regression models were constructed for prespecified outcome measures including (1) unsatisfactory acute results and (2) recurrent restenosis rate. RESULTS: Complex (B2/C) lesions (78%) more frequently obtained unsatisfactory acute results (20% vs 8%, P = .007), smaller minimal lumen diameter after the procedure (2.45 +/- 0.5 vs 2.73 +/- 0.5 mm, P = .001) and at follow-up (1.48 +/- 0.8 vs 1.94 +/- 0.8 mm, P = .0001), and had a higher restenosis rate (43 vs 24%, P = .001) than simple (A/B1) lesions. On logistic regression analysis, all classification schemes were useful to predict unsatisfactory initial results (area under the curve: 0.63, 0.61, 0.59, and 0.62) and recurrent restenosis (area under the curve: 0.60, 0.64, 0.61, and 0.63). The predictive ability of these schemes persisted despite adjustment for potential confounders. Although the ACC/AHA classification was a better predictor of acute results, the classification of Mehran was superior to predict restenosis. CONCLUSIONS: The ACC/AHA classification provides a useful tool to determine acute procedural results and the long-term angiographic outcome of patients with ISR.

Aged↗
PubMed2006

Proteomic study of plasma from moderate hypercholesterolemic patients.

Proteomics is a technology to detect and identify several proteins and their isoforms in a single sample. We used proteomics to analyze modifications in the protein map of plasma after simvastatin treatment of moderate hypercholesterolemic patients. Plasma from hypercholesterolemic patients (n = 9) was compared before and after 12 weeks of simvastatin treatment (40 mg/day). Patients with similar cardiovascular risk factors were used as controls (CR group). By using two-dimensional electrophoresis and mass spectrometry, we identified the different protein isoforms. The plasma expression of three fibrinogen gamma chain isoforms (FGG) was enhanced, whereas the expression of two isoforms of the fibrinogen beta chain (FGB) was reduced in the hypercholesterolemic patients compared with the CR group. The expression of apolipoprotein A-IV and three haptoglobin isoforms was higher in hypercholesterolemic patients. Simvastatin treatment modified the plasma expression of FGG chain isoform 1, FGB chain isoforms 1 and 2, vitamin D binding protein isoform 3, apo A-IV, and haptoglobin isoform 2. The modification of FGG chain isoform 1 and FGB chain isoforms 1 and 2 was positively correlated with total plasma cholesterol level. Proteomic analysis of plasma may help to know more in depth the molecular mechanism modified by simvastatin treatment.

Amino Acid Sequence↗
PubMed2006

Lack of association between gene sequence variations of platelet membrane receptors and aspirin responsiveness detected by the PFA-100 system in patients with coronary artery disease.

Platelet membrane receptors play a pivotal role in thrombus formation. Expression of platelet membrane receptors are under genetic control and gene sequence variations of receptors pivotal to thrombotic formation have been hypothesized to contribute to different degrees of individual response to aspirin. The aim of the present study was to investigate the impact of functional genetic polymorphisms of platelet membrane receptors on aspirin sensitivity assessed by means of the PFA-100 system in patients with coronary artery disease. Gene sequence variations of three platelet membrane receptors (GPIa/IIa, P2Y12, GPIIb/IIIa) pivotal to thrombus formation were assessed in 76 patients with coronary artery disease on chronic aspirin treatment. Patients with reduced sensitivity to aspirin were defined when closure-times of collagen/epinephrine cartridges < or =193 seconds and coined as PFA-100 non-responders. PFA-100 non-responders were observed in 33% of patients. Patients with diabetes mellitus were more frequently PFA-100 non-responders. Closure times of collagen/ADP coated cartridges were reduced in PFA-100 non-responders. The genotype distribution was similar in PFA-100 responder and non-responder patients for all three genotypes and did not vary in contemporaneous carriers of allelic variants. In conclusion, in vitro determined sensitivity to aspirin assessed using PFA-100 is not associated with gene sequence variations of platelet membrane receptors key to thrombus formation.

Aged↗