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The current guidelines of the European Society of Cardiology have up-dated and confirmed the role of a primary percutaneous coronary intervention (PCI) as the preferred reperfusion therapy in patients with acute coronary syndrome and ST-elevation. The establishment of regional network structures for implementation of this reperfusion strategy is recommended and described. Primary PCI should preferably be carried out via the transradial route and should include the implantation of modern drug-eluting stents. In most cases of coronary multivessel disease, primary PCI should be limited to the treatment of the infarcted artery. Routine mechanical thrombus aspiration during primary PCI is no longer recommended. Recommendations for a specific anti-thrombotic and secondary prophylactic medication after primary PCI are highlighted.

Background: Impaired renal function leads to dramatically increased risk for the development and progression of coronary artery disease (CAD). Therefore we aimed to assess the predictive value of different equations for estimated glomerular filtration rate (eGFR) in CAD-patients., Methods: From the AtheroGene study 2135 patients were included. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (4MDRD) equation for serum creatinine (sCr), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for sCr and cystatin C (CysC) each alone, and in combination (CysC/sCr). eGFR was assessed regarding the combined outcome of cardiovascular death and non-fatal myocardial infarction and regarding complex CAD represented by a SYNTAX score ≥23. Median follow-up was 4.3years., Results: Only the CKD-EPI equation using CysC could differentiate between eGFR >90ml/min/1.73m(2) vs. eGFR 60-90ml/min/1.73m(2) according to the occurrence of an endpoint event (log-rank test p=0.009). In the Cox regression analysis only eGFR calculated by CKD-EPI equation for CysC (Hazard ratio per 1 standard deviation (HR) 1.27 (95% CI 1.07-1.50); p=0.007) and for CysC/sCr (HR 1.22 (95% CI 1.02-1.46); p=0.026) were predictive regarding the outcome after adjustment for cardiovascular risk factors and Nt-proBNP. Furthermore, only eGFR calculated by CKD-EPI equation for CysC (odds ratio (OR) 1.57 (95% CI 1.36-1.78); p<0.001) and for CysC/sCr (OR 1.32 (95% CI 1.13-1.53); p<0.001) were significantly associated with a SYNTAX score ≥23., Conclusion: In patients with CAD the CKD-EPI equation for CysC and for CysC/sCr provided the best predictive value regarding the prognosis and the severity of CAD., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis. Results on the association between TAFI levels and the risk of coronary artery disease (CAD) are inconsistent., Objectives: We investigated the association between TAFI levels and the risk of cardiovascular events in CAD., Patients/methods: 1668 individuals with angiographically proven CAD at baseline were followed for a median of 2.3 years, as part of the prospective AtheroGene cohort. Fifty-six deaths from cardiovascular (CV) causes and 35 non-fatal CV events were observed., Results: At baseline, three TAFI measurements were available: one evaluating the total amount of TAFI (t-TAFI), one measuring the TAFIa/TAFIai amount, and the last the released activated peptide (TAFI-AP). TAFIa/TAFIai levels were associated with increased risk of CV death [hazard ratio (HR) for one tertile increase, 2.38 (1.56-3.63); P < 10(-4)]. This association remained significant after adjustment for conventional risk factors, CRP levels, white blood count and markers of thrombin generation and fibrinolysis [HR = 1.69 (1.07-2.67); P = 0.01]. In addition, CPB2 gene polymorphisms explained 12%, 6%, and 3% of t-TAFI, TAFIa/TAFIai and TAFI-AP levels, respectively, but none was associated with CV events., Conclusions: The amount of activated TAFI, measured by TAFIa/TAFIai ELISA, but not of the t-TAFI is independently associated with the risk of CV death.

Tumor necrosis factor (TNF) is a major cytokine involved in inflammatory reaction and a mortality predictor in patients with coronary artery disease (CAD). Plasma levels of soluble TNF (sTNF) depend on the rate of its synthesis but also on its shedding from cell surface, a mechanism mainly regulated by the TNF alpha converting enzyme (TACE or ADAM17). We investigated the relationship between ADAM17 and TNF polymorphisms, circulating levels of shed ADAM17 substrates (sTNF, sTNFR1 and sTNFR2), and cardiovascular risk in a prospective cohort of CAD patients. Five tag single-nucleotide polymorphisms (SNPs) of the ADAM17 gene as well as four previously described TNF SNPs were genotyped in the Atherogene Study composed of 1,400 CAD patients among which 136 died from a cardiovascular (CV) cause. sTNF, sTNFR1, and sTNFR2 concentrations were all significantly elevated in patients with future CV death, independently of other clinical/biological variables. While none of the studied TNF SNPs was associated with sTNF, sTNFR1, nor sTNFR2 levels, the ADAM17 -154A allele was found associated with a 14% increase of sTNF levels as compared to the -154C allele (p = 0.0066). Moreover, individuals carrying the 747Leu allele displayed a borderline increased risk of future cardiovascular death [odds ratio, 2.06 (1.05-4.04), p = 0.03]. These results suggest a role of ADAM17 in the regulation of sTNF plasma levels and identifies ADAM17 gene as a candidate for CAD. Tumor necrosis factor (TNF) is a major cytokine involved in inflammatory reaction and a mortality predictor in patients with coronary artery disease (CAD). We have studied the association of ADAM17 and TNF polymorphisms with circulating levels of shed ADAM17 substrates (sTNF, sTNFR1 and sTNFR2) and with cardiovascular risk in a large population of individuals with CAD (Atherogene Study, n = 1,400). Two newly identified polymorphisms, obtained by a systematic sequencing of the ADAM17 gene, C-154A and Ser747leu, slightly influence respectively sTNF plasma levels and the risk of cardiovascular death.

Objective: To get a better insight into the role of hemostasis in coronary artery disease (CAD), we assessed the impact of von Willebrand factor (vWF), fibrinogen, thrombin-antithrombin (TAT) complexes, D-dimers, and plasmin-antiplasmin (PAP) complexes on the risk of cardiovascular event in a prospective cohort of CAD patients., Methods and Results: The prospective Atherogene cohort includes 1057 individuals with an angiographically proven coronary artery disease at baseline. After a median follow-up of 6.6 years, 135 individuals died from a cardiovascular cause and 97 had a nonfatal cardiovascular event. Higher levels of all 5 hemostatic markers at baseline were associated with an increased risk of cardiovascular death, but not of nonfatal event. Except for vWF, these associations remained significant after adjustment for conventional cardiovascular risk factors and C-reactive protein (CRP) levels (P for trend according to increasing tertiles=0.20, 0.011, 0.026, 0.019, and 0.01 for vWF, fibrinogen, TAT, D-Dimer, and PAP, respectively). When including the 5 hemostatic markers in a stepwise Cox regression analysis where conventional risk factors and CRP were forced into the model, fibrinogen and D-dimers remained independently associated with the risk of cardiovascular death. Adjusted hazard ratios (95% CI) associated with one SD increase of fibrinogen and D-dimers were 1.27 (1.04 to 1.55) and 1.29 (1.09 to 1.53), respectively., Conclusions: In patients with coronary artery disease, fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death. Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease.

Carotid stenosis is frequent in patients with coronary artery disease (CAD). In the literature, 9-28% of patients with CAD have additional carotid artery stenosis, predictors of which are advanced age, smoking, diabetes mellitus, arterial hypertension, coronary multivessel disease, and peripheral arterial disease. Moreover, patients with unstable coronary syndromes and those with elevated inflammatory markers such as C-reactive protein or fibrinogen more often have concomitant CAD and carotid artery stenosis. The long-term prognosis of these patients is worse than with CAD only. Therefore, patients with CAD should be screened for additional carotid artery stenosis, especially if coronary artery bypass grafting is planned. Continuous wave Doppler sonography and color-coded duplex sonography are suitable methods to screen for carotid artery stenosis.

Background: Various functional polymorphisms of the cholesteryl ester transfer protein ( CETP) gene influence CETP activity and the concentration of high-density lipoprotein (HDL) cholesterol. Beside other functional variants mainly the promoter polymorphism CETP/C-629A is currently discussed as a risk factor of coronary artery disease (CAD). We evaluated in a large case-control study the impact of various CETP genotypes and haplotypes on HDL concentration and the prevalence of CAD., Methods and Results: In 1214 patients with documented CAD as well as 754 population controls we determined the CETP/C-629A, TaqIB, I405V, R451Q, and A373P polymorphisms. All genotypes have an impact on the HDL concentration; univariate genotype and haplotype analyses demonstrate a significant effect of A-allel carriers on the elevation of HDL concentration. In addition, among all genotypes determined, the C-629A polymorphism is associated with the prevalence of CAD in a codominant fashion. Homozygous A-allel carriers reveal a relative risk of 0.6 (95% CI 0.44-0.82; P = 0.005) compared to the wild type. Adjustment for classical risk factors did not alter this association significantly, whereas after controlling for HDL concentration no independent significance between CETP/C-629A genotype and prevalence of CAD was observed anymore., Conclusion: CETP genotypes have an significant but moderate impact on systemic HDL-cholesterol concentration. The A-allel of the CETP/C-629A polymorphism is associated with a reduced CAD risk. This risk reduction is probably mediated by elevated HDL-concentration. Whether genotyping of the CETP/C-629A polymorphism provides information over and above that obtained by HDL-cholesterol measurement has to be further investigated in various prospective studies.

P-selectin and P-selectin glycoprotein ligand (SELPLG, selectin P ligand) constitute a receptor/ligand complex that is likely to be involved in the development of atherosclerosis and its complications. While the genetic variability of P-selectin has already been investigated in depth, that of the SELPLG gene has not yet been extensively explored. The coding and regulatory sequences of the SELPLG were screened and nine polymorphisms were identified. The identified polymorphisms were genotyped in the AtheroGene study, a case-control study of coronary artery disease (CAD). Haplotype analysis revealed that two polymorphisms of SELPLG, the M62I and the VNTR, independently influenced plasma SELPLG levels. Conversely, haplotypes of SELPLG were not associated with CAD risk.

P-selectin is a cellular adhesion molecule that mediates the interaction of activated endothelial cells or platelets with leukocytes. Increased levels of soluble P-selectin have been reported in various cardiovascular disorders. We measured serum soluble P-selectin levels as well as 3 polymorphisms of the P-selectin gene (C-2123G, A-1969G, and Thr715Pro) in a large cohort of patients with documented coronary artery disease (n=869) and a healthy control group (n=334). The 3 P-selectin polymorphisms were strongly associated with P-selectin levels and altogether explained 7.3% and 18.6% of the P-selectin variability in patients and controls, respectively. Genotype distributions did not significantly differ between patients and controls. P-selectin levels were increased in patients younger than 55 years of age compared with controls (135.2 vs 114.3 ng/mL, P<0.01). On the contrary, patients older than 65 years of age had significantly lower P-selectin levels than did controls (121.5 vs 134.7 ng/mL, P<0.02). In intermediate age groups, P-selectin levels did not significantly differ between the 2 groups. In conclusion, this study revealed a strong association between P-selectin gene polymorphisms and serum P-selectin levels and a complex age-dependent relation between soluble P-selectin levels and coronary artery disease, which suggests that this molecule might have different roles in the atherothrombotic process.

Unlabelled: To determine which factors before percutaneous transluminal coronary angioplasty (PTCA) predict long-term outcome, we evaluated the clinical follow-up data from 535 patients 10 years after single-vessel PTCA. Events were defined as death, myocardial infarction, bypass surgery or repeat PTCA. During the follow-up period 79 patients (15%) died, 59 patients (11%) suffered a myocardial infarction, 107 patients (20%) had coronary artery bypass surgery and 141 patients (26%) underwent a redilatation. To determine the predictors of 10-year follow-up, 12 patient-related and 9 lesion parameters were analyzed by logistic regression analysis. Mortality was independently increased in patients with diabetes, with multi-vessel disease, after a previous myocardial infarction and in smokers. The presence of multi-vessel disease, symptoms of a higher angina class and younger age increased the risk for undergoing bypass surgery. In the statistical model with lesion parameters, the risk of bypass surgery was decreased if the stenosis was located in the distal segment of the coronary vessel and by a higher minimal luminal diameter before PTCA., Conclusion: Logistic regression analysis identified multi-vessel disease, diabetes, smoking and a previous myocardial infarction as independent clinical predictors of an adverse outcome 10 years after coronary angioplasty. Lesion parameters before PTCA seem to be less important with regard to the long-term outcome after PTCA.

Background: A substantial proportion of patients undergoing heart catheterization for suspected coronary artery disease have normal angiograms. Coronary morphology and blood flow velocity can be assessed very accurately with intracoronary ultrasound and Doppler. The purpose of this study was to use both methods to classify further patients with suspected coronary artery disease but with coronary angiograms adjudged normal at the time., Methods and Results: In forty-four patients with suspected coronary artery disease and normal coronary angiograms, intracoronary ultrasound and intracoronary Doppler were performed in the left anterior descending and left main coronary arteries. Coronary flow reserve was obtained by calculating the ratio of the maximal coronary flow mean velocity after the intracoronary administration of 10 mg papaverine to the coronary flow mean velocity at rest. Of 44 patients, 16 (36%) (group I) were found to have normal coronary morphology by intracoronary ultrasound and normal (> 3.0) coronary flow reserve (5.3 +/- 1.8). In seven patients (16%) (group II) there were normal intracoronary ultrasonic findings but a reduced coronary flow reserve (2.1 +/- 0.4). Plaque formation was found in a total of 21 (48%) of the 44 patients; mean plaque sizes were 3.6 +/- 1.6 mm2 for those in group III (normal coronary flow reserve) and 5.0 +/- 2.3 mm2 for those in group IV (reduced coronary flow reserve). Vessel area in both of these groups (16.3 +/- 8.0 mm2 and 19.2 +/- 6.1 mm2) was significantly larger than that of group I (14.6 +/- 5.7 mm2, P < 0.01). Plaque calcification was found in 25% of those in group III and 44% of those in group IV. Thus, only 36% of the patients with normal angiograms were true normal, 48% exhibited early stage of coronary atherosclerosis, and the other 16% might be considered as syndrome X., Conclusion: Intracoronary ultrasound and Doppler can be used to differentiate further heart disease in patients with normal coronary angiograms. Only a minority were true normal. Early signs of atherosclerosis cannot be detected by coronary angiography. This may have important therapeutic and prognostic implications.

This study used intravascular ultrasound (IU) to assess the incidence and extent of left main coronary artery (LMCA) disease and the effects of arterial remodeling. Sixty-nine patients undergoing cardiac catheterization were imaged with a 20 MHz rotational-tip IU device. Nine of the 69 studies (13%) could not be analyzed because of technical (n = 2) or anatomic (n = 7) reasons. Of the remaining 60 patients, 38 (63%) had at least 1 lesion in the left coronary artery perfusion territory by angiography; significant LMCA stenosis was present in 2 patients (3%). Intravascular ultrasonography demonstrated plaques in 27 of 60 LMCAs (45%), 6 of them in patients with normal angiograms. Twenty-four plaques (89%) were eccentric and calcium was present in 4 (15%). The mean minimal lumen diameter was 4.9 +/- 0.8 mm, the maximal lumen diameter was 5.6 +/- 0.8 mm, the planimetered lumen area was 22.6 +/- 6.0 mm2, the plaque area was 3.9 +/- 5.8 mm2, the vessel area was 26.5 +/- 5.9 mm2, and the area stenosis was 13 +/- 19%. In the 27 patients with plaque, plaque area was 8.7 +/- 5.7 mm2 and the area stenosis was 30 +/- 17%. The vessel area was significantly larger in diseased LMCAs (p < 0.001) and correlated with plaque area (r = 0.46). IU examination of the LMCA was feasible in 87% of patients and was more reliable for delineating plaques than angiography.

Percutaneous transluminal coronary angioplasty (PTCA) failed in 29 of 1,150 patients (2.5%) after successful passage of the guide wire. The reasons for failure were inability to pass the lesion with a balloon in 28 patients and inability to dilate the lesion in 1 patient. In these patients (15 stenoses and 14 chronic occlusions) rotational ablation was performed. We were able to pass the burr through the lesion in all of them, resulting in a reduction of diameter stenosis from 87 +/- 15 to 51 +/- 18%. Rotational ablation alone was initially successful (stenoses reduction > 20% and residual stenoses < 50%) in 15 of 29 (52%) patients. Additional PTCA was performed in 21 of 29 (72%) patients, in 8 to optimize the initially successful result and in 13 because the outcome was unsatisfactory. After dilatation the diameter stenosis was reduced to 41 +/- 14% immediately after the procedure and to 36 +/- 13% at 24 hr control. Overall success was achieved in 21 of 29 (72%) patients immediately after the procedure and in 26 of 29 (90%) patients at 24 hr control. No acute major complications occurred. We conclude that rotational ablation can be used as a safe and effective alternative when PTCA is not successful.

Percutaneous high frequency coronary rotational ablation (PTCR) was used in 10 patients with significant coronary artery disease. PTCR removes arteriosclerotic material from the vessel wall. A diamond-coated (60-80 micron) brass burr-drill, fastened to a flexible drive shaft rotating and tracking along a central coaxial guide wire, was used. The turbine rotates the drive shaft in excess of 150,000-190,000 revolutions per minute. PTCR was successful in all patients, but in three additional percutaneous transluminal coronary angioplasty (PTCA) was then successfully performed. Coronary dissection occurred only once, requiring surgery which was successful. No vessel perforation was observed. All vessels were open on the coronary angiograms performed after 24 hours. The main indication for PTCR seems to be a rigid and longer lesion which can not be dilated with the balloon catheter.

Tumor necrosis factor (TNF) is a major cytokine involved in inflammatory reaction and a mortality predictor in patients with coronary artery disease (CAD). Plasma levels of soluble TNF (sTNF) depend on the rate of its synthesis but also on its shedding from cell surface, a mechanism mainly regulated by the TNF alpha converting enzyme (TACE or ADAM17). We investigated the relationship between ADAM17 and TNF polymorphisms, circulating levels of shed ADAM17 substrates (sTNF, sTNFR1 and sTNFR2), and cardiovascular risk in a prospective cohort of CAD patients. Five tag single-nucleotide polymorphisms (SNPs) of the ADAM17 gene as well as four previously described TNF SNPs were genotyped in the Athero gene Study composed of 1,400 CAD patients among which 136 died from a cardiovascular (CV) cause. sTNF, sTNFR1, and sTNFR2 concentrations were all significantly elevated in patients with future CV death, independently of other clinical/biological variables. While none of the studied TNF SNPs was associated with sTNF, sTNFR1, nor sTNFR2 levels, the ADAM17 −154A allele was found associated with a 14% increase of sTNF levels as compared to the −154C allele ( p = 0.0066). Moreover, individuals carrying the 747Leu allele displayed a borderline increased risk of future cardiovascular death [odds ratio, 2.06 (1.05–4.04), p = 0.03]. These results suggest a role of ADAM17 in the regulation of sTNF plasma levels and identifies ADAM17 gene as a candidate for CAD. Tumor necrosis factor (TNF) is a major cytokine involved in inflammatory reaction and a mortality predictor in patients with coronary artery disease (CAD). We have studied the association of ADAM17 and TNF polymorphisms with circulating levels of shed ADAM17 substrates (sTNF, sTNFR1 and sTNFR2) and with cardiovascular risk in a large population of individuals with CAD (Athero gene Study, n = 1,400). Two newly identified polymorphisms, obtained by a systematic sequencing of the ADAM17 gene, C-154A and Ser747leu, slightly influence respectively sTNF plasma levels and the risk of cardiovascular death. [ABSTRACT FROM AUTHOR]

We evaluatedprospectively clinical and angiographic data in 400patients, 200 with unstable and200 with stable angina in order to determine which clinical markers could reliably predict unstable coronary artery lesions. Comparison of the angiogram of 200 patients with unstable and 200 with stable angina revealed a high-grade lesion (42% vs23%, P<0.0001), complex lesion morphology (49% vs20%, P<0.0001) and thrombus-containing lesions (7% vs 1%, P=0.006) as typical findings in patients with unstable angina. A high-grade lesion andlor complex lesion (including thrombotic lesions but excluding total occlusion) was found in 61% of unstable and 34% of stable patients (P<0.0001). Clinical features including the Braunwald classification of unstable angina were then evaluated by means of a multivariate approach with regard to their ability to predict the presence of unstable coronary artery lesions. Multivariate analysis revealed an abnormal ECG as the single most predictive clinical indicator of complex lesion morphology (P<0.0001, odds ratio 4, 2). The clinical presentation of recent onset of angina was highly predictive of a high grade lesion (P=0.00031 odds ratio 3, 2). The endpoint of a high-grade andlor a complex lesion was identified by an abnormal ECG (P=0.0015, odds ratio 3, 0) and recent onset angina (P=0.0119, odds ratio 2, 5). Thus, a high grade andlor complex lesion, typical of patients with unstable angina, was best identified by the clinical feature of recent onset angina andlor abnormal ECG changes. [ABSTRACT FROM PUBLISHER]