Nicola Cosentino

Severity of coronary atherosclerosis in patients with a first acute coronary event: a diabetes paradox

AIMS We aimed to compare coronary artery disease (CAD) at the time of a first acute coronary syndrome (ACS) in type II diabetic and non-diabetic patients by coronary angiography and by optical coherence tomography (OCT). METHODS AND RESULTS Two different patient populations with a first ACS were enrolled for the angiographic (167 patients) and the OCT (72 patients) substudy. Angiographic CAD severity was assessed by Bogaty, Gensini, and Sullivan scores, whereas collateral development towards the culprit vessel was assessed by the Rentrop score. Optical coherence tomography plaque features were evaluated at the site of the minimum lumen area (MLA) and of culprit segment. In the angiographic substudy, at multivariate analysis, diabetes was associated with both the stenosis score and the extent index (P = 0.001). Furthermore, well-developed collateral circulation (Rentrop 2-3) towards the culprit vessel was more frequent in diabetic than in non-diabetic patients (73% vs. 16%, P = 0.001). In the OCT substudy, at MLA site lipid quadrants were less and the lipid arc was smaller in diabetic than in non-diabetic patients (2.3 ± 1.3 vs. 3.0 ± 1.2; P = 0.03 and 198° ± 121° vs. 260° ± 118°; P = 0.03). Furthermore, the most calcified cross-section along the culprit segment had a greater number of calcified quadrants and a wider calcified arc in diabetic than in non-diabetic patients (1.7 ± 1.0 vs. 1.2 ± 0.9; P = 0.03 and 126° ± 95° vs. 81° ± 80°; P = 0.03). Superficial calcified nodules were more frequently found in diabetic than in non-diabetic patients (79 vs. 54%, P = 0.04). CONCLUSIONS In spite of potent pro-inflammatory, pro-oxidant and pro-thrombotic stimuli operating in type II diabetes, diabetic patients exhibit substantially more severe coronary atherosclerosis than non-diabetic patients at the time of a first acute coronary event. Better collateral development towards the culprit vessel, a predominantly calcific plaque phenotype and, probably, yet unknown protective factors operating in diabetic patients may explain these intriguing paradoxical findings.

Coronary atherosclerotic burden in patients with infection by CagA-positive strains of Helicobacter pylori

ObjectivesCytotoxic associated gene-A (CagA)-positive strains of Helicobacter pylori emerged as a possible atherosclerotic stimulus. Nevertheless, whether CagA-positivity is associated with more extensive or severe atherosclerotic coronary burden has never been studied. MethodsForty consecutive patients with coronary artery disease (CAD) and twenty consecutive patients with normal coronary arteries undergoing coronary angiography were enrolled. All patients underwent evaluation of classical atherogenic risk factors and assessment of anti-urease B and anti-CagA antibodies titer. Either the severity of coronary stenosis (stenosis score) or the extent of coronary atherosclerosis (extent score) was evaluated in CAD patients. ResultsThe anti-CagA antibody titer was significantly higher in patients with CAD as compared with normal coronary arteries patients [85 (10–108.75) vs. 47.3 (17–64) RU/ml, P=0.02], whereas there were no differences in anti-urease B titer between the two groups. A significant correlation was found between anti-CagA antibody titer and extent score (R=0.35, P=0.03), whereas stenosis score was similar (R=0.25, P=0.11). On the contrary, no significant correlation was found between anti-urease B antibody titer and either extent or stenosis score. Moreover, CagA-positive patients had a more extensive CAD (P=0.029) when compared with CagA-negative patients. Interestingly, whereas serum glucose, LDL levels, anti-urease B, and anti-CagA antibodies were predictors of extent score at univariate analysis, at multivariate analysis anti-CagA antibody titer only was an independent predictor of the extent of coronary atherosclerosis (B=0.051, standard error of B=0.042, P=0.04). ConclusionThese results support the association between CagA-positive H. pylori infection and coronary atherosclerotic burden. Further studies are needed to better elucidate the mechanism by which CagA-positive strains may promote atherosclerosis.

Pre-intervention eosinophil cationic protein serum levels predict clinical outcomes following implantation of drug-eluting stents

AIMS Eosinophils have been identified in post-mortem studies as important players of both restenosis and thrombosis after drug-eluting stent (DES) implantation. We aimed at assessing the association between baseline levels of eosinophil cationic protein (ECP), a marker of eosinophil activation, and recurrence of clinical events in a consecutive series of patients who underwent DES implantation. METHODS AND RESULTS Two hundred patients (age 63 +/- 10.4, males 75%) undergoing implantation of first-generation DES (Taxus or Cypher stents) were enrolled. We measured serum levels of ECP and total IgE by enzyme-linked immunosorbent assay and of C-reactive protein by high-sensitivity nephelometry prior to percutaneous coronary intervention. A clinical follow-up was planned 18 months after discharge. Major adverse cardiac events (MACEs), such as cardiac death, recurrent myocardial infarction, or clinically driven target lesion revascularization, were the endpoint of the study. Twenty-two patients (11%) had MACEs and showed higher serum levels of ECP compared with those without MACEs [30.5 (14.4-50) vs. 12.2 (4.4-31) microg/L, P = 0.004]. At simple Cox regression analysis, serum levels of ECP were a significant predictor of MACEs (hazard ratio 1.016, 95% confidence interval 1.003-1.03, P = 0.018). CONCLUSION This study shows for the first time an association between baseline ECP levels and the occurrence of MACEs in patients undergoing implantation of DES. Further studies are warranted to establish whether in this setting ECP is a risk marker or plays a contributory pathogenetic role.

Eosinophil cationic protein: A new biomarker of coronary atherosclerosis

AIMS Coronary atherosclerosis is a chronic inflammatory disease, but different inflammatory biomarkers may reflect different phases of atherosclerotic plaque evolution. We aimed at assessing the role of eosinophil cationic protein (ECP), a sensitive marker of eosinophil activation, and C-reactive protein (CRP) in coronary artery disease (CAD). METHODS AND RESULTS Consecutive anginal patients with angiographic evidence of CAD [stable angina (SA) or non-ST-elevation acute coronary syndrome (NSTE-ACS)], or with angiographically normal coronary arteries (NCA) were enrolled. The severity of CAD was graded according to Bogatys score and coronary lesion morphology was defined as smooth or complex. Baseline ECP and high sensitivity CRP were measured in all patients. Of 198 patients (64 + or - 10 years, male 74%), 91 had SA, 57 had NSTE-ACS and 50 had NCA. ECP levels were significantly higher in SA [30 microg/L (13.8-46.9), p<0.001] and NSTE-ACS [21.8 microg/L (5.5-46.3), p=0.016] compared to NCA [9.7 microg/L (6.1-13.6)], without significant difference between SA and NSTE-ACS (p=0.45). CRP levels were significantly higher in NSTE-ACS [2.38 mg/L (1.11-11.94)] compared to SA [1.48 mg/L (0.82-2.83), p=0.03], and NCA [1.09 mg/L (0.8-2.1), p<0.001], without significant difference between SA and NCA (p=0.20). The addition of ECP to main cardiovascular risk factors improved the area under the curve from 0.88 to 0.92, p=0.007 for the angiographic diagnosis of CAD; further addition of CRP increased the area to 0.94, p=0.014. At multiple linear regression analysis ECP levels independently predicted CAD severity (p=0.001), whereas CRP levels independently predicted lesion complexity (p=0.01). CONCLUSIONS Our study shows that ECP is a marker of CAD and that different inflammatory biomarkers reflect different phases of atherosclerotic plaque evolution.

A meta-analysis of randomized controlled trials on statins for the prevention of contrast-induced acute kidney injury in patients with and without acute coronary syndromes.

OBJECTIVES We assessed whether short-term, pre-procedural, intensive statin treatment may reduce contrast-induced acute kidney injury (CI-AKI) incidence in patients with and without acute coronary syndromes (ACS) undergoing coronary angiography (CA) and percutaneous coronary intervention (PCI). BACKGROUND Statins may exert renal-protective effects through their pleiotropic properties. However, there have been conflicting reports on the CI-AKI preventive effect of pre-procedural statin administration. METHODS Randomized controlled trials published between January 1st, 2003 and February 28th, 2014 comparing the preventive effects against CI-AKI of pre-procedural statins vs. control (lower statin dose, no statin, or placebo) in patients undergoing CA/PCI were included. RESULTS Data were combined from 9 clinical trials enrolling 5212 patients (age 65 ± 5 years, 63% males). Pooled analysis showed that intensive, short-term statin pre-treatment significantly reduced the risk of CI-AKI as compared to control (relative risk [RR] 0.50; 95% confidence interval [CI] 0.39 to 0.64; P<0.001). Pre-specified subgroup analysis showed that intensive statin pre-treatment significantly reduced CI-AKI risk in patients with ACS (RR 0.37; 95% CI 0.25 to 0.55; P<0.0001), with only a non-significant positive trend in patients without ACS (RR 0.65; 95% CI 0.41 to 1.03; P=0.07). No evidence of publication bias was detected. CONCLUSIONS Short-term, pre-procedural, intensive statin treatment significantly reduced CI-AKI incidence in ACS patients, and may contribute to the overall clinical benefit associated with the early use of these drugs in this clinical setting. Its role in non-ACS patients warrants further investigation.

Late (3 Years) Follow-Up of Successful Versus Unsuccessful Revascularization in Chronic Total Coronary Occlusions Treated by Drug Eluting Stent

The success rate of recanalization of coronary chronic total occlusion (CTO) has improved in recent years, but the clinical benefit associated with successful CTO recanalization in the drug-eluting stent (DES) era is not well known. A cohort of 317 consecutive patients (mean age 65 ± 10, 84% men) with CTOs (defined as Thrombolysis In Myocardial Infarction [TIMI] flow grade 0 and duration >3 months) of native coronary vessels in which percutaneous coronary intervention was attempted was enrolled from June 2005 to March 2009. All successful procedures (196 patients) were performed by DES implantation. The incidence of major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, and repeat revascularization) was assessed during a mean follow-up period of 3 years. MACE predictors were assessed in clinical, angiographic, and procedural data, including procedural success. Patients with successful percutaneous coronary intervention experienced a significantly lower MACE rate compared to those with failed procedures (17 [9%] vs 32 [26%], p = 0.008). Patients with multivessel disease experienced MACEs more frequently than those with single-vessel disease (45 [22%] vs 4 [4%], p = 0.002). On multiple Cox regression analysis, the presence of multivessel disease and CTO opening failure were independent predictors of MACEs (hazard ratio 2.31, 95% confidence interval 1.17 to 4.96, p = 0.01, and hazard ratio 1.81, 95% confidence interval 1.33 to 4.12, p = 0.02, respectively). The worst prognosis was confined to patients with multivessel disease and failed procedures (hazard ratio 2.73, 95% confidence interval 1.21 to 3.92, p = 0.03). In conclusion, successful recanalization of CTOs with DES translates into a reduction of the 3-year MACE rate compared to failed procedures, and the worst prognosis is observed in patients with failed procedures and multivessel disease, a notion that might be taken into account in the management of patients with coronary CTOs.

Eosinophil cationic protein and clinical outcome after bare metal stent implantation.

OBJECTIVE we assessed the association between baseline eosinophil cationic protein (ECP) levels, a sensitive marker of eosinophil activation, and clinical outcome in patients undergoing bare metal stent (BMS) implantation. METHODS basal ECP levels were measured in 110 patients (69±11 years, 88 men) undergoing BMS implantation. Major adverse cardiac events (MACEs), defined as cardiac death, non-fatal myocardial infarction, or clinically-driven target lesion revascularization, were registered at 24-month follow-up. RESULTS eighteen (16.4%) patients had MACEs and showed higher ECP levels compared with those without MACEs [20.1 (9.8-47.3) vs. 9.5 (5.0-27.2) g/L, p=0.02]. At follow-up, ECP level>11 g/L was the only significant predictor of MACEs (HR 3.5, 95% CI 1.1-10.4, p=0.03). CONCLUSION basal ECP levels are associated with MACEs after BMS implantation, suggesting that an allergic-mediated inflammation against the metal could explain some adverse reactions occurring after coronary stenting.

Effect of chronic Aspirin therapy on angiographic thrombotic burden in patients admitted for a first ST-elevation myocardial infarction.

Myocardial no-reflow may negate the benefit of urgent coronary revascularization in patients with acute ST-elevation myocardial infarction (STEMI). Among its pathogenetic mechanisms, distal embolization is of prominent importance and several studies have shown that a high coronary thrombotic burden is associated with distal embolization. We aimed at assessing predictors of angiographic thrombus grade in patients undergoing primary percutaneous coronary intervention. Ninety-one patients (62 +/- 12 years old, 79% men) presenting for a first STEMI and undergoing urgent coronary angiography within 12 hours from onset of symptoms were consecutively included in the study. Thrombus grade was evaluated by angiography according to the Gibson score and patients were allocated to the high thrombus grade (HTG; score 4 to 5) group or to the low thrombus grade (score 0 to 3) group. Variables predicting angiographic thrombus grade were assessed among clinical, angiographic, procedural, and laboratory data. Sixty-four patients (61 +/- 12 years old, 78% men) presented with HTG, whereas 27 patients (63 +/- 10 years old, 80% men) presented with low thrombus grade. Patients an HTG showed a significantly higher white blood cell count (12.5 +/- 4.8 vs 10.5 +/- 2.9, p = 0.015). Aspirin and beta-blocker therapy before admission were less frequently taken in the HTG group (5% vs 26% and 7% vs 23%, respectively, p = 0.01 and p = 0.03). At multivariate analysis, lack of previous therapy with aspirin was the only independent predictor of an HTG (odds ratio 6.14, 95% confidence interval 1.09 to 34.67, p = 0.04). In conclusion, previous aspirin therapy is associated with a decrease in angiographic thrombus grade in patients with STEMI treated with primary percutaneous coronary intervention, thus further priming efforts for appropriate use of aspirin in primary prevention of a first STEMI.

Vitamin D plasma levels and in-hospital and 1-year outcomes in acute coronary syndromes: a prospective study.

AbstractDeficiency in 25-hydroxyvitamin D (25[OH]D), the main circulating form of vitamin D in blood, could be involved in the pathogenesis of acute coronary syndromes (ACS). To date, however, the possible prognostic relevance of 25 (OH)D deficiency in ACS patients remains poorly defined. The purpose of this prospective study was to assess the association between 25 (OH)D levels, at hospital admission, with in-hospital and 1-year morbidity and mortality in an unselected cohort of ACS patients.We measured 25 (OH)D in 814 ACS patients at hospital presentation. Vitamin D serum levels >30 ng/mL were considered as normal; levels between 29 and 21 ng/mL were classified as insufficiency, and levels < 20 ng/mL as deficiency. In-hospital and 1-year outcomes were evaluated according to 25 (OH)D level quartiles, using the lowest quartile as a reference.Ninety-three (11%) patients had normal 25 (OH)D levels, whereas 155 (19%) and 566 (70%) had vitamin D insufficiency and deficiency, respectively. The median 25 (OH)D level was similar in ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) patients (14.1 [IQR 9.0–21.9] ng/mL and 14.05 [IQR 9.1–22.05] ng/mL, respectively; P = .88). The lowest quartile of 25 (OH)D was associated with a higher risk for several in-hospital complications, including mortality. At a median follow-up of 366 (IQR 364–379) days, the lowest quartile of 25 (OH)D, after adjustment for the main confounding factors, remained significantly associated to 1-year mortality (P < .01). Similar results were obtained when STEMI and NSTEMI patients were considered separately.In ACS patients, severe vitamin D deficiency is independently associated with poor in-hospital and 1-year outcomes. Whether low vitamin D levels represent a risk marker or a risk factor in ACS remains to be elucidated.

CD4+CD28null T lymphocytes are expanded in young women with polycystic ovary syndrome

Women affected by polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease. We demonstrated that women with PCOS showed an expansion of CD4(+)CD28(null) T cells, an aggressive population of T lymphocytes that has been recently associated with recurrent coronary instability and type 2 diabetes mellitus. This sheds new light on possible mechanisms responsible for the higher rate of cardiovascular disease among women with PCOS.