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Biomedical subjects

René A Tio

Publications and source records attributed to René A Tio.

At least 19 recordsLinked to original sources
PubMed2006

C-reactive protein and angiographic characteristics of stable and unstable coronary artery disease: data from the prospective PREVEND cohort.

AIMS: High sensitive-C-reactive protein (hs-CRP) is associated with coronary risk, which may be explained by an association with (unstable) coronary artery disease (CAD). Until now, histopathological and angiographic studies have failed to consistently demonstrate a strong relationship. However, most of these studies were limited by a cross-sectional design. Our aim was to prospectively evaluate the association between hs-CRP and plaque instability. Therefore, firstly, we investigated the relation between hs-CRP measured long before coronary angiography (CAG) and angiographic characteristics of stable and unstable CAD. In addition, we investigated the association with coronary events during follow up in the total PREVEND population. METHODS AND RESULTS: Of the population based Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 8139 subjects without previous documented CAD were followed for the incidence of CAG and coronary events from 1997 to 2003. For the qualitative angiographic analysis, 216 CAGs were available. Mean time to CAG was 37+/-19 months. The 864 coronary vessels were graded as follows: 436 coronary vessels as normal, 175 as non-obstructive CAD, 179 as stable obstructive CAD and 74 as unstable obstructive CAD. Multilevel ordinal regression analysis was performed to study associations between baseline clinical variables and angiographic findings. Hs-CRP contributed significantly to the multivariate model after adjustment for age, gender, smoking, lipids and blood pressure. In 8139 subjects, 201 (2.5%) first coronary events occurred during follow up. Cox survival analysis showed age- and sex-adjusted hazard ratios for hs-CRP 1-3 and >3mg/L of, respectively, 1.26 (95% CI 0.67-2.40) and 3.16 (95% CI 1.26-3.16), relative to hs-CRP <1mg/L. CONCLUSION: In the prospective PREVEND study of subjects without previous documented CAD, hs-CRP levels at baseline were associated with angiographic characteristics and clinical consequences of plaque instability during follow up. This observation supports the concept that hs-CRP significantly contributes to coronary atherogenesis.

Aged↗
PubMed2006

Systemic VEGF levels after coronary artery bypass graft surgery reflects the extent of inflammatory response.

BACKGROUND: Circulating vascular endothelial growth factor (VEGF) was studied as a substitute endpoint for treatment response after VEGF plasmid therapy. The effect of coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB) on systemic VEGF levels are however largely unknown, therefore, we studied the effect of this procedure to measure VEGF levels after surgery alone. METHODS: Fourteen patients requiring CABG were included. VEGF165 levels, ischemic markers, and hematology were measured before, directly after six days after surgery. RESULTS: VEGF165 in serum and whole blood levels were increased up to six days after CABG, respectively 249.6+/-50.4 to 451.7+/-56.4 (day 6) and 581.9+/-105.1 to 783.4+/-97.7 (day six). There was a close correlation of circulating VEGF165 with leukocyte counts and platelets and not with ischemic markers. CONCLUSION: Following surgery and in case of activated leukocyte and platelet counts care must be taken in the interpretation of systemic VEGF165 levels.

Adult↗
PubMed2006

Restenosis after percutaneous coronary intervention is associated with the angiotensin-II type-1 receptor 1166A/C polymorphism but not with polymorphisms of angiotensin-converting enzyme, angiotensin-II receptor, angiotensinogen or heme oxygenase-1.

OBJECTIVES: The renin-angiotensin system (RAS) is thought to play a major role in the pathophysiology of de-novo restenotic lesions and in-stent restenosis after percutaneous coronary intervention (PCI). Heme oxygenase-1 (HO-1), is thought to beneficially influence these processes. We examined the effect of pharmacologic as well as genetic RAS interactions on restenosis in a large population of consecutive patients undergoing PCI, and evaluated possible gene-gene interactions in both systems. METHODS: The GENDER project is a multicenter prospective follow-up study, including 3146 patients after successful PCI. Genotyping in these patients was performed for the ACE gene insertion/deletion, the angiotensinogen 235Met/Thr, T174M and A(-6)G, the angiotensin-II type 1 receptor (AT1R) 1166A/C and T810A, the angiotensin-II type 2 receptor (AT2R) 1675G/A and 3123A polymorphisms and the length polymorphism in the HO-1 promoter region. RESULTS: A total of 3104 patients were followed for 10 months. In 2975 patients at least one of the nine genotypes could be determined. The AT1R 1166 CC genotype showed a significant association with TVR; the other polymorphisms did not. RAS-inhibitory drugs were not associated with the incidence of TVR, nor did they interact with any of the investigated polymorphisms. Patients with the ACE I/I polymorphism showed a trend towards a better outcome if they had a short number of repeats in the HO-1 promoter. This relationship was inversely present in carriers of the ACE D/D polymorphism. CONCLUSION: We could only establish a role for the AT1R 1166A/C polymorphism in restenosis after PCI. However, significant gene-gene interaction was suggested for the ACE gene and the HO-1 promotor. The RAS and HO-1 relation in restenosis merits further investigation.

Alleles↗
PubMed2006

Inflammation and apoptosis genes and the risk of restenosis after percutaneous coronary intervention.

OBJECTIVES: Genetic factors appear to be important in the development of restenosis after percutaneous coronary intervention, as well as in the process of inflammation, a pivotal factor in restenosis. Caspase-1, interleukin-1-receptor and protein tyrosine phosphatase nonreceptor type 22 are important mediators in the inflammatory response and caspase-1 also in apoptosis. Therefore, we examined whether polymorphisms in these candidate genes are related to the risk of developing restenosis after percutaneous coronary intervention. METHODS: The GENetic DEterminants of Restenosis-project is a multicenter prospective follow-up study. The 5352G/A (L235L) caspase-1-polymorphism, the 7464C/G (A124G) interleukin-1r-polymorphism and the 1858C/T (R620W) protein tyrosine phosphatase nonreceptor type 22-polymorphism were genotyped. To examine the functional effect of the caspase-1 polymorphism, mature plasma interleukin-1beta levels were measured by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated whole blood from a subpopulation of patients. RESULTS: A total of 3104 patients, age 62.1+/-10.7 years, were included after successful percutaneous coronary intervention. A significant association between the 5352AA genotype of the caspase-1 gene and target vessel revascularization (relative risk 2.2, 95% confidence interval 1.32-3.76) was observed after correcting for clinical variables. Angiographic analysis of a subgroup of patients (N=478) also showed an increased risk for developing restenosis for patients having the 5352GA/AA genotype (P=0.001). The results were corroborated, although they were not statistically significant, by somewhat higher mature interleukin-1beta levels in patients with the 5352AA genotype. CONCLUSIONS: The present study shows that patients with the 5352AA genotype in the caspase-1 gene are at increased risk of developing restenosis. If confirmed by other studies, screening patients for this genotype can lead to better risk stratification and provide indications for improving individual treatment; for instance, by providing a new target for drug-eluting stents.

Aged↗
PubMed2005

Genetic inflammatory factors predict restenosis after percutaneous coronary interventions.

BACKGROUND: Restenosis is a negative effect of percutaneous coronary intervention (PCI). No clinical factors are available that allow good risk stratification. However, evidence exists that genetic factors are important in the restenotic process as well as in the process of inflammation, a pivotal factor in restenosis. Association studies have identified genes that may predispose to restenosis, but confirmation by large prospective studies is lacking. Our aim was to identify polymorphisms and haplotypes in genes involved in inflammatory pathways that predispose to restenosis. METHODS AND RESULTS: The GENetic DEterminants of Restenosis (GENDER) project is a multicenter prospective study, including 3104 consecutive patients after successful PCI. Forty-eight polymorphisms in 34 genes in pathways possibly involved in the inflammatory process were analyzed. The 16Gly variant of the beta2-adrenergic receptor gave an increased risk of target vessel revascularization (TVR). The rare alleles of the CD14 gene (-260T/T), colony-stimulating factor 2 gene (117Thr/Thr), and eotaxin gene (-1328A/A) were associated with decreased risk of TVR. However, through the use of multiple testing corrections with permutation analysis, the probability of finding 4 significant markers by chance was 12%. CONCLUSIONS: Polymorphisms in 4 genes considered involved in the inflammatory reaction showed an association with TVR after PCI. Our results may contribute to the unraveling of the restenotic process. Given the explorative nature of this analysis, our results need to be replicated in other studies.

Amino Acid Substitution↗
PubMed2005

Lipoprotein lipase gene polymorphisms and the risk of target vessel revascularization after percutaneous coronary intervention.

OBJECTIVES: We sought to identify polymorphisms in genes that predispose to restenosis. BACKGROUND: Variations in the lipoprotein lipase (LPL) gene have been implicated in a number of pathophysiologic conditions associated with coronary heart disease. The present study examines the impact of polymorphisms in the LPL gene on restenosis (defined by target vessel revascularization [TVR]) in a large patient population undergoing percutaneous coronary intervention (PCI). A mouse model for restenosis was used to further investigate LPL's role in restenosis. METHODS: The GENetic DEterminants of Restenosis (GENDER) project is a multicenter, prospective study design that enrolled 3,104 consecutive patients after successful PCI. These patients were genotyped for four different LPL gene polymorphisms. In apolipoprotein E (ApoE)*3-Leiden transgenic mice, arterial messenger ribonucleic acid (mRNA) was used to assess LPL expression during a cuff-induced restenotic process. RESULTS: Using multivariable analysis, carriers of the 447Ter allele of the LPL enzyme showed a lower risk of TVR compared with 447Ser homozygotes (p = 0.005). In the mouse model, LPL mRNA levels were increased 40-fold compared with control arteries at 6 h after cuff placement. CONCLUSIONS: The LPL C/G polymorphism (Ser447Ter), resulting in a truncation of the two C-terminal amino acids of the mature LPL protein, appears to be an important protective factor for TVR in humans. The role of LPL in this process was further established in a mouse model, where LPL expression was very strongly up-regulated in the target arterial wall, suggesting a contribution of this lipolytic enzyme to restenosis. Possibly, LPL Ser447Ter genotyping may lead to better risk stratification and tailored therapy in the prevention of restenosis after PCI.

Angioplasty, Balloon, Coronary↗
PubMed2005

Clinical impact of vasomotor function assessment and the role of ACE-inhibitors and statins.

Impaired endothelial function is recognised as one of the earliest events of atherogenesis. Endothelium-dependent vasomotion has been the principal method to assess endothelial function. In this article, we will discuss the clinical value of the different techniques to evaluate endothelium-dependent vasomotion. To date, there seems not to be a simple and reliably endothelial function test to identify asymptomatic subjects at increased risk for cardiovascular disease in clinical practice. Recent studies indicate that pharmacological interventions, in particular with ACE-inhibitors and statins, might improve endothelial function. However, there is no solid evidence that improvement of endothelial function is a necessity for the observed reduction in cardiovascular events by these compounds. Overall, at this moment, there is no place in clinical practice for the use of endothelial function as a method for risk assessment or target of pharmacological interventions.

Animals↗
PubMed2005

Tumor necrosis factor-alpha plays an important role in restenosis development.

Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNFalpha, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER) project included 3104 patients who underwent a successful PCI. Systematic genotyping for six polymorphisms in the TNFalpha gene was performed. The role of TNFalpha in restenosis was also assessed in ApoE*3-Leiden mice, TNFalpha knockout mice, and by local delivery of a TNFalpha biosynthesis inhibitor, thalidomide. The -238G-1031T haplotype of the TNFalpha gene increased clinical and angiographic risk of restenosis (P=0.02 and P=0.002, respectively). In a mouse model of reactive stenosis, arterial TNFalpha mRNA was significantly time-dependently up-regulated. Mice lacking TNFalpha or treated locally with thalidomide showed a reduction in reactive stenosis (P=0.01 and P=0.005, respectively). Clinical and preclinical data indicate that TNFalpha plays an important role in restenosis. Therefore, TNFalpha genotype may be used as a risk marker for restenosis and may contribute to individual patient screening prior to PCI in clinical practice. Inhibition of TNFalpha may be an anti-restenotic target strategy.

Aged↗
PubMed2005

The feasibility of repeated left ventricular ejection fraction analysis with sequential single-dose radionuclide ventriculography.

OBJECTIVE: Repeated left ventricular ejection fraction (LVEF) analyses with sequential single-dose radionuclide ventriculography might be an interesting technique for monitoring the effect of positive inotropic interventions. The aim of the study was to assess the reproducibility of LVEF measurement with planar radionuclide ventriculography within 3 h, using a standard single dose of radioactive tracer. METHODS: Sixteen patients underwent routine planar radionuclide ventriculography with a standard dose of 500 MBq of [Tc]pertechnetate and returned after 3 h for a repeat planar radionuclide ventriculography without administration of additional tracer. RESULTS: The average initial LVEF was 35.1+/-18.6%-point (range, 12%-point to 68%-point). The mean difference of the LVEF between the initial planar radionuclide ventriculography and the repeat planar radionuclide ventriculography was 2.8%+/-6.3% (range, -11.8% to 13.3%, P=NS). The correlation between both measurements was significant with a correlation coefficient of 0.995 (P<0.01). Bland-Altman analysis revealed a mean LVEF difference of 0.94%-point between the baseline planar radionuclide ventriculography and the repeat planar radionuclide ventriculography (95% confidence interval: -2.7%-point to 4.5%-point). The visual wall motion assessment showed excellent reproducibility, with a kappa-statistic of 0.98. CONCLUSION: Repeated radionuclide ventriculography with a 3 h interval using a single standard dose of 500 MBq of [Tc]pertechnetate is highly reproducible and will be useful for monitoring the effect of positive inotropic interventions.

Feasibility Studies↗
PubMed2005

-455G/A polymorphism and preprocedural plasma levels of fibrinogen show no association with the risk of clinical restenosis in patients with coronary stent placement.

The effect of preprocedural fibrinogen levels on in-stent restenosis is largely unknown. The -455G/A polymorphism of the fibrinogen beta-gene is associated with baseline plasma level or acute phase increase of fibrinogen. Therefore, we hypothesized that there is a relationship between this polymorphism and preprocedural fibrinogen level and clinical restenosis at follow-up among patients with coronary stent placement. The GENetic DEterminants of Restenosis (GENDER) project is a multicenter follow-up study that enrolled 3,146 consecutive patients after successful percutaneous coronary intervention. A coronary stent was placed in 2,309 patients. Of these, 2,257 (97.7%) patients were successfully genotyped for the -455G/A polymorphism. Plasma fibrinogen levels were measured at baseline in a subpopulation of 623 stented patients with the von Clauss method and patients were grouped into tertiles according to fibrinogen levels. Primary endpoint was target vessel revascularization (TVR); secondary combined endpoint was defined as death presumably from cardiac causes, MI not attributable to another coronary artery than the target vessel, and TVR. No association was observed between the -455G/A polymorphism and TVR or combined endpoint (p=0.99, p=0.97, respectively). Multivariate regression analysis revealed that the risk of TVR and combined endpoint was not higher for patients in the highest tertile for fibrinogen versus the lowest tertile (RR=0.60, 95% CI: 0.26-1.37 for TVR, RR=0.64, 95% CI: 0.29-1.44 for combined endpoint). In conclusion, the presence of -455G/A polymorphism in the fibrinogen beta-gene and preprocedural fibrinogen level is not associated with an increased risk of TVR or combined endpoint in a patient population with coronary stent placement. Therefore, these parameters are not worthwhile for stratifying patients at risk for restenosis pre-stenting.

Aged↗
PubMed2005

Long-term safety of intracoronary haemodynamic assessment for deferral of angioplasty in intermediate coronary stenoses: a 5-year follow-up.

BACKGROUND: Intracoronary flow and pressure measurements can be used for evaluating intermediate lesions. Studies focussing on short- and medium-term results demonstrated its safety. Long-term results are, however, not available. OBJECTIVE: The goal of this study was to assess the long-term safety and clinical implications of decision making for intermediate coronary stenosis based on intra-coronary haemodynamic measurements. METHODS AND RESULTS: In this prospective study, 61 patients with an intermediate coronary stenosis were included between January 1994 and December 1998. In these patients either coronary flow reserve or fractional flow reserve was measured. Death, target vessel revascularization, myocardial infarction, unstable angina and cerebrovascular accident were considered as major adverse cardiac events. The patients were followed during 5.5 (1.8) years for the occurrence of major adverse cardiac events (MACE). Although many patients presented with complaints, only 19.7% experienced a MACE in the follow-up period. CONCLUSION: Intracoronary measurements of CFR and FFR can be routinely used for objective clinical decision making in intermediate coronary stenoses. The low 5-year event rate supports conservative treatment strategy when cut-off values are implemented.

Aged↗
PubMed2005

Metabolic syndrome and risk of restenosis in patients undergoing percutaneous coronary intervention.

OBJECTIVE: Patients with metabolic syndrome have increased risk of cardiovascular events. The number of patients with metabolic syndrome is rapidly increasing, and these patients often need revascularization. However, only limited data are available on the effect of metabolic syndrome on restenosis in patients undergoing percutaneous coronary intervention (PCI). RESEARCH DESIGN AND METHODS: To assess the role of metabolic syndrome in the development of restenosis, we performed an analysis in a population of patients from the GENetic DEterminants of Restenosis (GENDER) study. The GENDER project, a multicenter prospective study, included consecutive patients after successful PCI and was designed to study the predictive value of various genetic and other risk factors for subsequent clinical restenosis, defined as target vessel revascularization (TVR) or combined end point of death, myocardial infarction, and TVR. This subpopulation of GENDER consisted of 901 patients, 448 of whom (49.7%) had metabolic syndrome. RESULTS: On multivariable Cox regression analysis, controlling for age, sex, previous myocardial infarction, stent length, current smoking, and statin therapy, there was no association between increased risk of TVR (hazard ratio 1.03 [95% CI 0.68-1.57]) or the combined end point (1.05 [0.71-1.55]) and the presence of metabolic syndrome. CONCLUSIONS: This study demonstrates that metabolic syndrome is not associated with TVR or the combined end point after PCI. Furthermore, accumulating characteristics of metabolic syndrome were neither associated with increased risk of TVR nor with the combined end point. Therefore, PCI has equal beneficial results in patients with or without metabolic syndrome. This is important information in light of the pandemic proportion of metabolic syndrome that the medical community will face.

Angioplasty, Balloon, Coronary↗
PubMed2004

Determination of vessel size: a putative framework to assess clinical outcome.

BACKGROUND: Unknown is the predictive value of the coronary artery diameter without the administration of vasomotor stimuli. A small reference diameter of the target vessel has been demonstrated to be an adverse prognostic factor in patients undergoing revascularisation. The present study investigated the prognostic value of the proximal non-stenotic left anterior descending coronary artery (LAD) diameter in patients referred for a first diagnostic angiogram without a previous revascularisation. METHODS: A total of 277 patients (mean age 57 year, 61% male) were eligible for analysis. The proximal non-stenotic diameter of the LAD was measured by quantitative coronary angiography without prior nitrate infusion. We defined a small LAD as a diameter < or =2.5 mm. Cardiovascular events were defined as cardiac death, myocardial infarction, and hospitalizations for unstable angina. RESULTS: During a median follow-up of 47 months, 24 major cardiac events occurred. The cumulative survival for patients with a small LAD was significantly lower, than for patients with a large LAD (hazard ratio 2.51; 95% confidence interval 1.11-5.66, p=0.03). In the multivariate analysis, a LAD diameter < or =2.5 mm remained a significant predictor of cardiovascular events after adjustment for age, gender, and the presence of significant coronary artery disease (hazard ratio 2.32; 95% confidence interval 1.01-5.34, p=0.048). CONCLUSION: In patients referred for a first diagnostic angiogram without a previous revascularisation, the diameter of the proximal non-stenotic LAD is an independent predictor of cardiovascular events.

Aged↗
PubMed2004

Angiotensin-(1-7) attenuates neointimal formation after stent implantation in the rat.

Angiotensin-(1-7) is an endogenous, biologically active peptide of the renin-angiotensin system with vasodilatory, antithrombotic, and antiproliferative properties. This study examined the effects of angiotensin-(1-7) infusion on neointimal formation after stent placement in the rat. Male Wistar rats underwent stent implantation in the abdominal aorta or sham surgery. Subsequently, an osmotic minipump was placed for angiotensin-(1-7) (24 microg/kg per hour) or saline administration. After 4 weeks, histomorphometric and histological analyses were performed, and the endothelial function was measured in isolated thoracic aortic rings. Stent implantation resulted in equal mean injury scores within the groups. The angiotensin-(1-7)-treated group displayed a significant reduction in neointimal thickness (112+/-8 versus 141+/-11 microm; P<0.05), neointimal area (0.51+/-0.05 versus 0.70+/-0.07 mm2; P<0.05), and percentage stenosis (10.4+/-1.0 versus 14.0+/-1.3%; P<0.05) compared with the saline-treated group. Furthermore, angiotensin-(1-7) infusion attenuated the stenting-induced impairment in endothelium-dependent relaxation (42.6+/-3.0 versus 64.5+/-6.0% of phenylephrine maximal contraction; P<0.001). In conclusion, angiotensin-(1-7) treatment attenuates neointimal formation after stent implantation in the rat, combined with an improvement of endothelial function.

Angiotensin I↗
PubMed2004

Assessing the prognostic value of coronary endothelial function in patients referred for a first coronary angiogram.

At present, the value of endothelial function as a prognostic tool has been evaluated only in selected groups of patients with mild or minor coronary artery disease, not in the complete spectrum of patients presenting with angina. The objective of this study was to evaluate whether endothelium-dependent vasodilation of the coronary arteries in response to acetylcholine infusion as a marker of endothelial function would have prognostic value in patients referred for a first coronary angiogram. The data suggest that endothelial function assessment does not contribute to the prediction of outcomes in patients referred for a first coronary angiogram.

Adolescent↗