Luciano Consuegra-Sánchez

Elevated serum neopterin levels and adverse cardiac events at 6 months follow-up in Mediterranean patients with non-ST-segment elevation acute coronary syndrome

BACKGROUND Little information exists regarding the prognostic role of biomarkers of inflammation in Mediterranean patients. High C-reactive protein and neopterin levels - a marker of macrophage activation - predict cardiovascular events in stable angina patients and patients with acute coronary syndromes (ACS). We sought to assess whether plasma neopterin levels predict adverse clinical outcomes in Mediterranean patients with non-ST elevation (NSTE) ACS, i.e. unstable angina (UA) and NSTE myocardial infarction (MI). METHODS We prospectively assessed 397 patients (74% men) admitted with NSTEACS, 147 (37%) had unstable angina and 250 (63%) NSTEMI. Blood samples for neopterin and CRP assessment were obtained at admission. The study endpoint was the composite of cardiac death, acute myocardial infarction and unstable angina at 180 days. RESULTS Baseline neopterin concentrations (nmol/L) were similar in unstable angina and NSTEMI patients (8.3 [6.6-10.7] vs. 7.9 [6.2-10.9]; p=0.4). Fifty-nine patients (14.9%) had events during follow-up. Twenty-nine (21.5%) patients with neopterin levels in the highest third experienced the combined endpoint, compared to 30 (11.5%) patients with neopterin levels in the second and the lowest thirds (log-rank 7.435, p=0.024). On multivariable hazard Cox regression, neopterin (highest vs. 1st and 2nd thirds, HR 1.762, 95% CI [1.023-3.036]) was independently associated with the combined endpoint. CONCLUSION Increased neopterin levels are an independent predictor of 180-day adverse cardiac events in Mediterranean patients with NSTEACS.

A comparative study of biomarkers for risk prediction in acute coronary syndrome—Results of the SIESTA (Systemic Inflammation Evaluation in non-ST-elevation Acute coronary syndrome) study

OBJECTIVE We compared the 1-year predictive value of several inflammatory and non-inflammatory biomarkers in ACS patients. METHODS In 610 patients (73.0% male)--36.0% unstable angina (UA) and 64.0% NSTEMI--we assessed high-sensitivity C-reactive protein (hs-CRP), interleukins 6, 10 and 18, soluble CD40 ligand, P- and E-selectin, NT-proBNP, fibrinogen and cystatin C at hospital admission. Two outcomes at 1-year follow up were selected for analysis: (1) all-cause death, MI, UA, or coronary revascularization, and (2) all-cause death, and non-fatal MI. The effect of biomarker levels on endpoints was examined by the Cox proportional hazards model, and their discrimination ability with the C statistic (AUC). RESULTS Of 549 patients (90.0%) who completed the 1-year follow up, 206 (37.5%) and 54 (8.9%) reached the first and second composite endpoints, respectively. None of the biomarkers studied improved prediction of the first endpoint. However, considered as continuous variables, and in combination, NT-proBNP and fibrinogen, increased the AUC from 0.64 (95% CI 0.55-0.72) to 0.73 (95% CI 0.64-0.81; p=0.02) for prediction of the second endpoint. Cut-off values for NT-proBNP and fibrinogen, regarding best sensitivity and specificity for prediction of the secondary endpoint were 1043.9 ng/L and 4.47 mg/dL, respectively. For these cut-off points, sensitivity, specificity, positive predictive value and negative predictive value were 40.5% vs 59.5%, 83.3% vs 67.1%, 18.8% vs 14.9% and 93.5% vs 94.4% for NT-proBNP and fibrinogen, respectively. CONCLUSION In ACS patients, inflammatory biomarkers offer modest incremental information to that provided by clinical risk markers. Fibrinogen and NT-proBNP measurements, however, improve cardiovascular risk prediction.

Effect of intravenous and intracoronary melatonin as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: Results of the Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty trial

The MARIA randomized trial evaluated the efficacy and safety of melatonin for the reduction of reperfusion injury in patients undergoing revascularization for ST‐elevation myocardial infarction (STEMI). This was a prespecified interim analysis. A total of 146 patients presenting with STEMI within 6 hours of chest pain onset were randomized to receive intravenous and intracoronary melatonin (n=73) or placebo (n=73) during primary percutaneous coronary intervention (PPCI). Primary endpoint was myocardial infarct size as assessed by magnetic resonance imaging (MRI) at 6 ± 2 days. Secondary endpoints were changes in left ventricular volumes and ejection fraction (LVEF) at 130 ± 10 days post‐PPCI and adverse events during the first year. No significant differences in baseline characteristics were observed between groups. MRI was performed in 108 patients (86.4%). Myocardial infarct size by MRI evaluated 6 ± 2 days post‐PPCI, did not differ between melatonin and placebo groups (P=.63). Infarct size assessed by MRI at 130 ± 10 days post‐PPCI, performed in 91 patients (72.8%), did not show statistically significant differences between groups (P=.27). The recovery of LVEF from 6 ± 2 to 130 ± 10 days post‐PPCI was greater in the placebo group (60.0 ± 10.4% vs 53.1 ± 12.5%, P=.008). Both left ventricular end‐diastolic and end‐systolic volumes were lower in the placebo group (P=.01). The incidence of adverse events at 1 year was comparable in both groups (P=.150). Thus, in a nonrestricted STEMI population, intravenous and intracoronary melatonin was not associated with a reduction in infarct size and has an unfavourable effect on the ventricular volumes and LVEF evolution. Likewise, there is lack of toxicity of melatonin with the doses used.

High-sensitivity versus conventional troponin for management and prognosis assessment of patients with acute chest pain

Objectives High-sensitivity troponin (hs-cTn) is substituting conventional cTn for evaluation of chest pain. Our aim was to assess the impact on patient management and outcome. Methods A total of 1372 consecutive patients presenting at the emergency department with non-ST-elevation acute chest pain were divided into two periods according to the cTn assay used, conventional (n=699, March 2008 to July 2010) or hs-cTn (n=673, November 2010 to March 2013). Management policies were similar and according to guidelines. The primary endpoint was major adverse cardiac events (MACE) at 6 months (death, myocardial infarction, readmission by unstable angina or postdischarge revascularisation). Results There were minor differences in baseline characteristics. In the hs-cTn period, more patients elevated cTn (73% vs 37%, p=0.0001) leading to more coronary angiograms (77% vs 55%, p=0.0001) and revascularisations (45% vs 31%, p=0.0001); conversely, fewer patients were initially assigned to exercise testing (14% vs 36%, p=0.0001) and, therefore, discharged early after a negative result (7% vs 22%, p=0.0001). At 6 months, 135 patients suffered MACE, including 54 deaths. After adjusting for a Propensity Score, hs-cTn use was not significantly associated with MACE (HR=0.99; 95% CI 0.70 to 1.41; p=0.98) or mortality (HR=1.02; 95% CI 0.59 to 1.77; p=0.95), though the risk of longer hospitalisation stay increased at the index episode (OR=1.35, 95% CI 1.07 to 1.71, p=0.02). Conclusions hs-cTn simplified chest pain triage on avoiding a more complex evaluation with non-invasive tests in the chest pain unit, but prompted longer hospitalisations and more invasive procedures without impacting on the 6-month outcomes.

Randomised, Double-Blind, Placebo-Controlled Trial of Ivabradine in Patients with Acute Coronary Syndrome: Effects of the If Current Inhibitor Ivabradine on Reduction of Inflammation Markers in Patients with Acute Coronary Syndrome—RIVIERA Trial Study Design and Rationale

PurposeElevated levels of serum inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) represent independent risk factors for further cardiovascular events. In an atherosclerosis model, selective heart rate (HR) reduction with ivabradine has been shown to decrease markers of vascular oxidative stress, to improve endothelial function, and to reduce atherosclerotic plaque formation. We hypothesized that the addition of ivabradine to standard medical therapy has a beneficial effect on markers of inflammatory stress in acute coronary syndromes (ACS) patients.MethodsRIVIERA is a unicenter, randomized, double-blind, placebo-controlled trial involving 1,270 patients of either gender admitted to hospital with non ST elevation ACS. The primary study aim is to evaluate the effects of ivabradine therapy, initiated at the time of hospital admission, on hs-CRP levels. There is also a combined secondary endpoint i.e. to assess the effects of ivabradine on the occurrence of death, nonfatal myocardial infarction, recurrent symptomatic ischemia, urgent revascularization, and cardiac arrest at 30-days and 1-year follow up.ConclusionWe hypothesize that ivabradine therapy, when started immediately after hospital admission for ACS, will result in the reduction of hs-CRP levels and the improvement of cardiovascular outcome.

Evaluation of ASPIRE trial: a Phase III pivotal registration trial, using intracoronary administration of Generx (Ad5FGF4) to treat patients with recurrent angina pectoris.

The ASPIRE study (a randomized, controlled, parallel group, multicenter study to evaluate the efficacy and safety of Ad5FGF-4 using adenosine single-photon emission computed tomography (SPECT) myocardial perfusion imaging in patients with stable angina pectoris) (ClinicalTrials.gov Identifier: NCT01550614) is a 100-patient, controlled, randomized, multicenter study conducted in six centers in Russia. This trial will assess the therapeutic efficacy of Generx (Ad5-FGF4) using rest and stress SPECT following a one-time, catheter-based administration. Adenovirus-based antianginal therapy represents an interesting option but the difficulties observed in the various trials carried out to date illustrate the complexity of the issue. Large and well-designed studies should be encouraged to provide definitive answers to this important research question.

Metabolic and Inflammatory Profiles of Biomarkers in Obesity, Metabolic Syndrome, and Diabetes in a Mediterranean Population. DARIOS Inflammatory Study

INTRODUCTION AND OBJECTIVES There is a paucity of data regarding the differences in the biomarker profiles of patients with obesity, metabolic syndrome, and diabetes mellitus as compared to a healthy, normal weight population. We aimed to study the biomarker profile of the metabolic risk continuum defined by the transition from normal weight to obesity, metabolic syndrome, and diabetes mellitus. METHODS We performed a pooled analysis of data from 7 cross-sectional Spanish population-based surveys. An extensive panel comprising 20 biomarkers related to carbohydrate metabolism, lipids, inflammation, coagulation, oxidation, hemodynamics, and myocardial damage was analyzed. We employed age- and sex-adjusted multinomial logistic regression models for the identification of those biomarkers associated with the metabolic risk continuum phenotypes: obesity, metabolic syndrome, and diabetes mellitus. RESULTS A total of 2851 subjects were included for analyses. The mean age was 57.4 (8.8) years, 1269 were men (44.5%), and 464 participants were obese, 443 had metabolic syndrome, 473 had diabetes mellitus, and 1471 had a normal weight (healthy individuals). High-sensitivity C-reactive protein, apolipoprotein B100, leptin, and insulin were positively associated with at least one of the phenotypes of interest. Apolipoprotein A1 and adiponectin were negatively associated. CONCLUSIONS There are differences between the population with normal weight and that having metabolic syndrome or diabetes with respect to certain biomarkers related to the metabolic, inflammatory, and lipid profiles. The results of this study support the relevance of these mechanisms in the metabolic risk continuum. When metabolic syndrome and diabetes mellitus are compared, these differences are less marked.

Short- and long-term prognosis of previous and new-onset atrial fibrillation in ST-segment elevation acute myocardial infarction.

INTRODUCTION AND OBJECTIVES The impact of atrial fibrillation on the prognosis of myocardial infarction is still the subject of debate. We analyzed the influence of previous and new-onset atrial fibrillation on in-hospital and long-term prognosis in patients with acute myocardial infarction. METHODS Prospective study of 4284 patients with ST-segment elevation acute myocardial infarction. We studied all-cause in-hospital and long-term mortality (median, 7.2 years) using adjusted models. RESULTS In total, 3.2% of patients had previous atrial fibrillation and 9.8% had new-onset atrial fibrillation. In general, both groups of patients had a high baseline risk profile and an increased likelihood of in-hospital complications. The crude in-hospital mortality rate was higher in patients with previous atrial fibrillation than in those with new-onset atrial fibrillation (22% vs 12%; P<.001; 30% vs 10%; P<.001). The long-term mortality rate was 11.11/100 patient-years in patients with previous atrial fibrillation and 5.35/100 patient years in those with new-onset atrial fibrillation (both groups, P<.001). New-onset fibrillation alone (odds ratio=1.55; 95% confidence interval, 1.08-2.22) was an independent predictor of in-hospital mortality. Previous atrial fibrillation (hazard ratio=1.24; 95% confidence interval, 0.94-1.64) and new-onset atrial fibrillation (hazard ratio=0.98; 95% confidence interval, 0.80-1.21) were not independent predictors of long-term mortality. CONCLUSIONS New-onset atrial fibrillation during hospitalization is an independent risk factor for in-hospital mortality in acute myocardial infarction.

Usefulness of delta troponin for diagnosis and prognosis assessment of non-ST-segment elevation acute chest pain

Background: The additional diagnostic and prognostic information provided by delta high-sensitivity troponin T (hs-cTnT) in patients with acute chest pain and hs-cTnT elevation remains unclear. Methods: The study group consisted of 601 patients presenting at the emergency department with non-ST-segment elevation acute chest pain and hs-cTnT elevation after two determinations (admission and within the first six hours). Maximum hs-cTnT and delta hs-cTnT (absolute or percentage change between the two measurements) were considered. Cutoff values were optimized using the quartile distribution for the endpoints. The endpoints were diagnostic (significant stenosis in the coronary angiogram) and prognostic (death or recurrent myocardial infarction at one year). Results: Regarding the diagnostic endpoint, 114 patients showed a normal angiogram. Both maximum hs-cTnT ⩾80 ng/ml (OR 2.5, 95% CI 1.3–4.8, P=0.005) and delta hs-cTnT ⩾20 ng/l (OR 2.1, 95% CI 1.1–4.0, P=0.02) median value cutoffs were related to significant coronary stenosis. Furthermore, the combination of hs-cTn <80 ng/l and delta hs-cTn <20 ng/l showed the lowest probability of significant coronary stenosis (OR 0.3, 95% CI 0.1–0.4, P=0.001). During follow-up, 86 patients experienced the prognostic endpoint. After full adjustment for clinical data, maximum hs-cTnT ⩾30 ng/l, first quartile cutoff, was related to the outcome (HR 1.8, 95% CI 1.0–3.4, P=0.05), while delta hs-cTnT, either absolute or percentage change, lacked prognostic value. Conclusions: Maximum hs-cTnT captures all the prognostic information provided by hs-cTnT in non-ST-segment elevation acute chest pain. Low maximum and low delta hs-cTnT are associated with a normal coronary angiogram, which could make the final diagnosis challenging in some cases.

Aumento de mortalidad asociado a olmesartán en pacientes diabéticos para la prevención o retraso de microalbuminuria: ¿es una causa de preocupación?

Microalbuminuria cannot be ignored by cardiologists because it is considered a predictor of coronary artery disease in patients with type 2 diabetes. Angiotensin II receptor blockers (ARB-II) have been accepted nephroprotective agents in patients with type 2 diabetes with microalbuminuria since publication of the Irbesartan Patients with Diabetes and Microalbuminuria (IRMA-2) study. In patients with macroalbuminuria, the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan (RENAAL) and Irbesartan in Diabetic Nephropathy Trial (IDNT) studies showed a slowing of progression to terminal kidney disease. However, in patients with diabetes with microalbuminuria, the Diabetic Retinopathy Candesartan Trial (DIRECT) showed no significant reduction in microalbuminuria. Recently, the Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study has been published. Interestingly, it found that the use of olmesartan vs placebo to be associated with a significantly reduced incidence of microalbuminuria (23% relative reduction). However, it also showed increased incidence of cardiovascular death with olmesartan