TCT-251 Abnormal glucose metabolism and adverse event rates 12 months after treatment with contemporary drug-eluting stents:Insights from the BIO-RESORT Silent Diabetes study

BACKGROUND: Patients with abnormal glucose metabolism, including patients with undetected and thus untreated diabetes, may have higher event risks after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES). We assessed the prevalence and clinical impact of abnormal glucose metabolism in allcomer patients without previously known diabetes undergoing PCI. METHODS: The BIO-RESORT Silent Diabetes study, performed at Thoraxcentrum Twente, is a substudy of the randomized BIO-RESORT trial (NCT01674803). We performed an additional analysis identifying patients with an abnormal glucose metabolism by means of oral glucose tolerance testing (OGTT), and assessment of glycated hemoglobin A1c (HbA1c) with fasting plasma glucose (FPG) and clinical outcome at 12 months. RESULTS: Assessment of glucose metabolism revealed that of the 988 participants a total 330 (33.4%) patients had an abnormal metabolism, while 658 (66.6%) patients had a normal metabolism. Patients with abnormal glucose metabolism showed higher rates of the primary endpoint Target Vessel Failure (6.4% vs. 2.7%; p0.01), a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Multivariate analysis demonstrated that an abnormal glucose metabolism independently predicted adverse event risk (HR 2.2, 95%-CI:1.2-4.2). CONCLUSION: Abnormal glucose metabolism was detected in one out of three PCI all-comer patients and independently associated with a more than 2-fold higher event risk. Future intervention studies should determine whether meaningful benefits may accrue from routine glycaemia testing in such patients

TCT-819 Prediabetes and its Impact on 1-Year Clinical Outcome After Treatment with Newer-Generation Drug-eluting Stents in 2,986 All-Comer Patients

BACKGROUND Prediabetes (Pre-DM) is a risk factor state for developing diabetes mellitus (DM). Yet it is unclear whether detection of Pre-DM by routine assessment of glycated haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) among patients undergoing percutaneous coronary intervention (PCI) may help identify subjects with increased event risk. We assessed in all-comers who underwent PCI with contemporary drug-eluting stents (DES) the relation between glycaemia status and 1-year clinical outcome. METHODS HbA1c and FPG was determined in 2,362 non-DM participants in the multicenter, randomized, investigator-initiated TWENTE III trial, in order to identify Pre-DM (HbA1c 42-47mmol/mol; FPG 6.1- 6.9 mmol/L) and DM (HbA1c>=48mmol/mol; FPG >7 mmol/L). Another 624 patients had medically treated DM. The main clinical outcome parameter was a composite endpoint consisting of death, myocardial infarction, or revascularisation. RESULTS Glycaemic state was known in 2,986 trial participants: Pre- DM was present in 324 (11%), DM in 793 (27%), and normoglycaemia in 1,869 (63%) patients. Patients with Pre-DM and DM differed from normoglycemic patients in cardiovascular risk factors. The composite clinical endpoint in Pre-DM occurred in 11.1%, in DM in 10.5%, and in normoglycemic patients in 5.7% (

Endothelial Dysfunction After ST-segment Elevation Myocardial Infarction and Long-term Outcome: A Study With Reactive Hyperemia Peripheral Artery Tonometry

Introduction and objectives: Long-term data on the relationship between endothelial dysfunction after ST-segment elevation myocardial infarction and future adverse clinical events are scarce. The aim of this study was to noninvasively assess whether endothelial dysfunction 4 to 6 weeks after primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction predicts future clinical events. Methods: This prospective cohort study was performed in 70 patients of the RESPONSE randomized trial, who underwent noninvasive assessment of endothelial function 4 to 6 weeks after primary percutaneous coronary intervention. Endothelial function was measured by the reactive hyperemia peripheral artery tonometry method; an index < 1.67 identified endothelial dysfunction. Results: The reactive hyperemia peripheral artery tonometry index measured on average 1.90 ± 0.58. A total of 35 (50%) patients had endothelial dysfunction and 35 (50%) patients had normal endothelial function. Periprocedural “complications” (eg, cardiogenic shock, total atrioventricular block) were more common in patients with endothelial dysfunction than in those without (25.7% vs 2.9%; P < .01). During 4.0 ± 1.7 years of follow-up, 20 (28.6%) patients had major adverse cardiovascular events: events occurred in 9 (25.7%) patients with endothelial dysfunction and in 11 (31.5%) patients with normal endothelial function (P = .52). There was an association between the prevalence of diabetes mellitus at baseline and the occurrence of major adverse cardiovascular events during follow-up (univariate analysis: hazard ratio = 2.8; 95% confidence interval, 1.0-7.8; P < .05), and even in multivariate analyses the risk appeared to be increased, although not significantly (multivariate analysis: hazard ratio = 2.5; 95% confidence interval, 0.8-7.5). Conclusions: In this series of patients who survived an ST-segment elevation myocardial infarction, endothelial dysfunction, as assessed by reactive hyperemia peripheral artery tonometry 4 to 6 weeks after myocardial infarction, did not predict future clinical events during a mean follow-up of 4 years

Endothelial function after ST-elevation myocardial infarction in patients with high levels of high-sensitivity CRP and Lp-PLA2: A substudy of the RESPONSE randomized trial

The combination of high levels of high-sensitive C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase-A2 (Lp-PLA2) was recently shown to correlate with increased cardiovascular risk. Endothelial dysfunction is also known to be a risk factor for cardiovascular events. To test among patients with previous ST-elevation myocardial infarction (STEMI) the hypothesis that high levels of both hs-CRP and Lp-PLA2 may be associated with impaired endothelium-dependent vasodilatation. In this substudy of the RESPONSE randomized trial, we used reactive hyperemia peripheral artery tonometry (RH-PAT) 4 to 6weeks after STEMI and primary percutaneous coronary intervention (PPCI) to non-invasively assess endothelial function (RH-PAT index 239μg/L, respectively). Patients were 57.4±9.7years and 53 (77.9%) were men. 11 (16%) patients were classified as high-risk and 57 (84%) as low-to-intermediate-risk. The RH-PAT index was 1.68±0.22 in high-risk and 1.95±0.63 in low-to-intermediate-risk patients (p=0.17). Endothelial dysfunction was present in 8 (72.7%) high-risk and 26 (45.6%) low-to-intermediate-risk patients (p=0.09). Framingham risk score, NT-proBNP and fibrinogen levels were higher in high-risk patients (p≤0.03). In this population of patients with recent STEMI and PPCI, we observed between patients with high hs-CRP and Lp-PLA levels and all other patients no more than numerical differences in endothelial function that did not reach a statistical significance. Nevertheless, further research in larger study populations may be warrante

Endothelial Dysfunction After ST-segment Elevation Myocardial Infarction and Long-term Outcome: A Study With Reactive Hyperemia Peripheral Artery Tonometry

Long-term data on the relationship between endothelial dysfunction after ST-segment elevation myocardial infarction and future adverse clinical events are scarce. The aim of this study was to noninvasively assess whether endothelial dysfunction 4 weeks to 6 weeks after primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction predicts future clinical events. This prospective cohort study was performed in 70 patients of the RESPONSE randomized trial, who underwent noninvasive assessment of endothelial function 4 weeks to 6 weeks after primary percutaneous coronary intervention. Endothelial function was measured by the reactive hyperemia peripheral artery tonometry method; an index <1.67 identified endothelial dysfunction. The reactive hyperemia peripheral artery tonometry index measured on average 1.90±0.58. A total of 35 (50%) patients had endothelial dysfunction and 35 (50%) patients had normal endothelial function. Periprocedural "complications" (eg, cardiogenic shock, total atrioventricular block) were more common in patients with endothelial dysfunction than in those without (25.7% vs 2.9%; P <.01). During 4.0±1.7 years of follow-up, 20 (28.6%) patients had major adverse cardiovascular events: events occurred in 9 (25.7%) patients with endothelial dysfunction and in 11 (31.5%) patients with normal endothelial function (P=.52). There was an association between the prevalence of diabetes mellitus at baseline and the occurrence of major adverse cardiovascular events during follow-up (univariate analysis: hazard ratio=2.8; 95% confidence interval, 1.0-7.8; P <.05), and even in multivariate analyses the risk appeared to be increased, although not significantly (multivariate analysis: hazard ratio=2.5; 95% confidence interval, 0.8-7.5). In this series of patients who survived an ST-segment elevation myocardial infarction, endothelial dysfunction, as assessed by reactive hyperemia peripheral artery tonometry 4 weeks to 6 weeks after myocardial infarction, did not predict future clinical events during a mean follow-up of 4 year

Serial assessment of endothelial function 1, 6, and 12 months after ST-elevation myocardial infarction

Knowledge about the changes in endothelial function after ST-elevation myocardial infarction (STEMI) is of substantial interest, but serial data are scarce. The aim of the present study was to noninvasively evaluate whether endothelial function, as assessed shortly after primary percutaneous coronary intervention (PPCI) for STEMI, may improve until 12-month follow-up. This prospective observational cohort study was performed in patients in the RESPONSE randomized trial who participated in a substudy and underwent noninvasive assessment of endothelial function at 1 (baseline), 6, and 12-month follow-up after treatment of a STEMI by PPCI. The reactive hyperemia peripheral artery tonometry (RH-PAT) method was used to assess endothelial function (higher RH-PAT index signifies better function). Of the 70 study participants, who were 57.4 ± 9.7 years of age, 55 (78.6%) were male and 9 (13%) had diabetes. The endothelial function deteriorated significantly during follow-up: the RH-PAT index at baseline, 6, and 12-month follow-up was 1.90 ± 0.58, 1.81 ± 0.57, and 1.69 ± 0.49, respectively (p = 0.04). Although patients were carefully treated in outpatient clinics and adequate pharmacological therapy was prescribed, we noted an increase in total cholesterol (p = 0.001), LDL cholesterol (p = 0.002), HbA1C (p = 0.054), and diastolic blood pressure (p = 0.047) However, multivariate analysis revealed that this increase in cardiovascular risk factors could not explain the observed deterioration in endothelial function. In patients with STEMI, we observed a significant deterioration in endothelial function during 12 months after PPCI that could not be explained by changes in the traditional cardiovascular risk profile

Assessment of the relation between initial culprit vessel patency in acute ST-elevation myocardial infarction and endothelial function

To assess whether better endothelial function increases the likelihood of patients with acute ST-elevation myocardial infarction (STEMI) having initially patent culprit vessels. Clinical data on the relation between endothelial function and culprit vessel patency in STEMI patients are scarce. In this prospective cohort study in 71 patients with STEMI, endothelial function was non-invasively assessed by use of the reactive hyperaemia peripheral artery tonometry (RH-PAT) method at four to six weeks after the primary percutaneous coronary intervention (PPCI). The RH-PAT index measured on average 1.90±0.58. In patients with patent culprit vessels before PPCI (n=33, 46.5%), endothelial function was significantly better than in patients with occluded vessels (n=38, 53.5%) (RH-PAT index 2.08±0.34 vs. 1.75±0.35; p <0.007). Compared to patients with normal endothelial function, the patients with severe endothelial dysfunction had a fivefold higher risk of presenting with an occluded culprit vessel (OR 5.1, 95% CI: 1.8-14.2). Logistic regression analysis revealed that this relation between endothelial function and vessel patency became even stronger after adjustment for potential confounders (adjusted OR 7.1, 95% CI: 2.1-23.6). In this series of patients with acute STEMI, better endothelial function was independently associated with a higher likelihood of presenting with an initially patent culprit vesse

Three-year clinical outcome in all-comers with “silent” diabetes, prediabetes, or normoglycemia, treated with contemporary coronary drug-eluting stents: From the BIO-RESORT Silent Diabetes study

Background: Patients with coronary disease may have unknown diabetes or prediabetes. We evaluated 3-year outcomes after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES) in patients with silent diabetes, prediabetes, and normoglycemia. Methods: All BIO-RESORT trial (NCT01674803) participants without known diabetes, enrolled at our center, were invited for oral glucose tolerance testing (OGTT) and measurements of fasting plasma glucose and glycated hemoglobin (HbA1c). Results: OGTT detected silent diabetes in 68 (6.9%), prediabetes in 132 (13.4%), and normoglycemia in 788 (79.8%) of all 988 study participants. Follow-up was available in 986 (99.8%) patients. The main endpoint target vessel failure (TVF: cardiac death, target vessel-related myocardial infarction [MI], or target vessel revascularization) differed between groups (14.8, 9.9, and 5.6%; p =.002), driven by MI during the first 48 hr and by cardiac death (p <.001; p =.026). Between 48 hr and 3-years, there was no significant between-group difference in TVF, target vessel MI, and target vessel revascularization. Multivariable analysis demonstrated that silent diabetes was independently associated with TVF (adjusted HR: 2.52, 95%-CI: 1.26–5.03). An alternative diagnostic approach—HbA1c and fasting plasma glucose—detected silent diabetes and prediabetes in 33 (3.3%) and 217 (22.0%) patients, and normoglycemia in 738 (74.7%); TVF rates were 12.1, 7.9, and 6.0% (p =.23). Conclusion: In patients without known diabetes, abnormal glucose metabolism by OGTT was independently associated with higher 3-year TVF rates after PCI with contemporary DES. This difference was driven by periprocedural MI and cardiac death. After the first 48 hr, the rates of TVF, target vessel MI, and target vessel revascularization were low and did not differ significantly between metabolic groups

Prediabetes and its Impact on Clinical Outcome After Coronary Intervention in a Broad Patient Population

Aims: It is unclear whether detection of prediabetes (pre-DM) by routine assessment of glycated haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) among patients undergoing percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES) may help identify subjects with increased event risk. We assessed the relation between glycaemia status and one-year outcome after PCI. Methods and results: Glycaemia status was determined in 2,362 non-diabetic BIO-RESORT participants, treated at all four study sites, to identify pre-DM (HbA1c 42-47 mmol/mol; FPG 6.1-6.9 mmol/L) and unknown diabetes mellitus (DM) (HbA1c ≥48 mmol/mol; FPG ≥7.0 mmol/L). Another 624 patients had medically treated DM. The main composite endpoint consisted of death, myocardial infarction, or revascularisation. Glycaemic state was known in 2,986 participants: 324 (11%) patients had pre-DM, 793 (27%) had DM (known or new), and 1,869 (63%) patients had normoglycaemia. Pre-DM and DM patients differed from normoglycaemic patients in cardiovascular risk factors. The composite endpoint occurred in 11.1% in pre-DM, 10.5% in DM, and 5.7% in normoglycaemia (p<0.001). Pre-DM was associated with a twofold higher event risk compared to normoglycaemia (adj. HR 2.0, 95% CI: 1.4-3.0). Conclusions: Following PCI with contemporary DES, all-comers with pre-DM had significantly higher event risks than normoglycaemic patients. In non-DM patients requiring PCI, routine assessment of HbA1c and FPG appears to be of value to identify subjects with increased event risk