Lucia Barbieri

Vitamin D deficiency is independently associated with the extent of coronary artery disease

Vitamin D (25‐OH D3) deficiency represents a rising social and economic problem in Western countries. Vitamin D has been recently reported to modulate inflammatory processes, endothelium and smooth muscle cell proliferation and even platelet function, thus potentially modulating atherothrombosis. Great interest has been addressed on its impact on cardiovascular outcome, with contrasting results. The aim of current study was to evaluate the relationship between 25‐OH D3 and the extent of coronary artery disease (CAD) in a consecutive cohort of patients undergoing coronary angiography.

Neutrophil to Lymphocyte Ratio and the Extent of Coronary Artery Disease: Results From a Large Cohort Study.

The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, may be of predictive and prognostic value for cardiovascular (CV) events. We evaluated the relationship of NLR with the prevalence and extent of coronary artery disease (CAD) in consecutive patients undergoing elective or urgent coronary angiography. Our population (n = 3738 patients) was divided into NLR quartiles. Higher NLR was associated with aging and established CV risk factors, previous percutaneous coronary revascularization, acute presentation, and more complex pharmacological therapy. The NLR was related to platelet count, white blood cell count, creatinine, glycemia, uric acid, and C-reactive protein (all P = .001) levels but inversely related to hemoglobin (P < .001), total cholesterol (P = .005), and triglycerides (P < .001) levels. The NLR was associated with multivessel disease (P < .001), anterior descending, right coronary arteries (P < .001) or circumflex branch lesions (P = .01), percentage of stenosis (P < .001), coronary calcification (P < .001), and intracoronary thrombus (P < .001) but inversely with in-stent restenosis (P < .001) and thrombolysis in myocardial infarction flow (P = .04). The NLR was directly related to the prevalence of CAD (P = .001) and severe CAD (P < .001). In patients undergoing coronary angiography, the NLR is independently associated with the prevalence and severity of CAD.

Mean platelet volume and the risk of periprocedural myocardial infarction in patients undergoing coronary angioplasty.

BACKGROUND Periprocedural myocardial infarction (PMI) represents a relatively common complication of percutaneous coronary intervention (PCI). Mean platelet volume (MPV) has been proposed as a marker for platelet activation, as larger sized platelets have been associated with higher pro-thrombotic risk. Therefore, aim of the current study was to evaluate whether MPV is associated with increased risk of PMI after PCI. METHODS We included 1056 consecutive patients undergoing PCI. We measured myonecrosis biomarkers at intervals from 6 to 48 h after PCI. Periprocedural myonecrosis was defined for troponin I increase by 3 times the ULN or by 50% if elevated at the time of the procedure. PMI was defined as CK-MB increase by 3 times the ULN or 50% if elevated at the time of the procedure. RESULTS We grouped patients according to tertiles values of MPV (<10.4 fl; 10.5-11.3 fl; >11.4 fl). High MPV was associated with diabetes (p = 0.025) and higher prevalence of cerebrovascular events (p = 0.005). MPV significantly related with haemoglobin levels (p < 0.001), but inversely to platelet count (p < 0.001) and higher presence of thrombus (p = 0.03). Larger sized platelets did not increase risk of periprocedural myonecrosis (p = 0.91; OR[95% CI] = 1.04[0.90-1.2], p = 0.64) or PMI (p = 0.09; OR[95%IC] = 1.13[0.93-1.37]; p = 0.20). Subgroup analysis confirmed no impact of MPV on periprocedural MI also in high-risk subsets of patients, such as those with ACS at presentation (OR[95%CI] = 1.09 [0.87-1.38]; p = 0.44), diabetes (OR[95% CI] = 1.02[0.71-1.47], p = 0.91), female gender (OR [95% CI] = 1.15 [0.78-1.71], p = 0.48), elderly patients (age ≥ 75 years) (OR[95%CI] = 1.21[0.87-1.69], p = 0.25) or with renal failure (OR[95%CI] = 1.55[0.91-2.61], p = 0.1). CONCLUSIONS This study demonstrates that MPV does not predict the risk of PMI in patients undergoing PCI.

Bivalirudin as compared to unfractionated heparin in patients undergoing percutaneous coronary revascularization: A meta-analysis of 22 randomized trials

UNLABELLED Bivalirudin has gained ground against unfractionated heparin (UFH) in percutaneous coronary interventions (PCI), due to a reported better safety profile. However, whether bivalirudin may provide also advantages in clinical outcome beyond the known benefits in major bleedings, is still a debated matter and was, therefore, the aim of present meta-analysis of randomized trials, evaluating efficacy and safety of bivalirudin as compared with UFH in PCI. METHODS AND STUDY OUTCOMES Literature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions were scanned. Primary endpoint was overall mortality. Secondary endpoints were: 1) mortality within 30-days; 2) overall and within 30-days non fatal myocardial infarction; 3) overall and within 30-days stent thrombosis. Safety endpoints were major bleedings (per protocol definition or TIMI classification). A prespecified analysis was conducted according to clinical presentation (Elective, ACS, STEMI). RESULTS A total of 22 randomized clinical were finally included, involving 40156 patients randomized to bivalirudin (52.9%) or to UFH (47.1%). Death occurred in 1100 (2.8%) of patients, with no difference between bivalirudin and UFH (2.7% vs 2.8% OR[95%C]=0.94[0.83,-.06], p=0.32, phet=0.48). The results did not change according to clinical presentation. By meta-regression analysis, the effects on mortality were not related to patients risk profile (r=-0.38(-0.89-0.14), p=0.15) or the reduction in bleeding complications (r=-0.008(-0.86-0.85), p=0.98). A significant increase in short-term stent thrombosis was observed with bivalirudin (OR[95%CI]=1.42 [1.10-1.83], p=0.006). However, Bivalirudin significantly reduced bleedings according to both study protocol definition (OR[95%CI]=0.62[0.56-0.69],p<0.00001; phet=0.0003) or TIMI major criteria (OR[95%CI]=0.65[0.53-0.79],p<0.0001, phet=0.95). CONCLUSIONS In present meta-analysis, among patients undergoing PCI, bivalirudin, as compared with UFH, is associated with a significant reduction in major bleeding complications that, however, does not translate into mortality benefits. Furthermore, bivalirudin is associated with higher rate of 30-days stent thrombosis and recurrent MI among STEMI patients.

Glycosylated Hemoglobin and Coronary Artery Disease in Patients Without Diabetes Mellitus

BACKGROUND Abnormal glucose metabolism is a major determinant of coronary artery disease (CAD) and mortality in developed countries. Glycosylated hemoglobin (HbA1c) is a more stable, accurate parameter of glucose homeostasis than fasting glycemia, thus providing prognostic information in diabetics. However, its role and relationship with CAD remains unclear in non-diabetics. PURPOSE To evaluate the relationship between HbA1c and CAD in a consecutive cohort of patients without diabetes mellitus. METHODS Non-diabetic patients undergoing coronary angiography between April 2007 and October 2012 were included. Additionally carotid intima-media thickness (C-IMT) was evaluated during hospitalization in a consecutive cohort of patients. RESULTS 1,703 consecutive patients were included and divided according to HbA1c tertiles (<5.5%, 5.5%-5.79%, ≥5.8%). HbA1c was associated with aging (p<0.001); hypercholesterolemia (p=0.01); renal failure (p=0.006); hypertension (p=0.002); previous myocardial infarction (p=0.004); previous percutaneous coronary intervention (p=0.01); indication to angiography (p=0.01); use of angiotensin receptor blockers (p=0.01); beta-blockers (p=0.03); nitrates (p=0.02); statins (p=0.008); calcium antagonists (p=0.01); diuretics (p<0.001); acetylsalicylic acid (p<0.001); baseline glycemia (p<0.001); triglycerides (p=0.02); and uric acid (p=0.04). HbA1c, but not fasting glycemia, was significantly associated with the prevalence of CAD (adjusted OR=1.51, 95% CI=1.15, 1.97, p=0.002), with 5.8% identified by the receiver operating characteristic (ROC) curve as the best cut-off value for CAD prediction. HbA1c was significantly associated with C-IMT and carotid plaques prevalence. CONCLUSIONS Among non-diabetic patients, higher HbA1c even within the normal range is significantly associated with the risk of CAD. Future large studies are needed to evaluate whether more aggressive cardiovascular prevention can reduce the risk of CAD among patients with HbA1c ≥ 5.8%.

Prevalence and predictors of high-on treatment platelet reactivity with ticagrelor in ACS patients undergoing stent implantation.

BACKGROUND Residual high-on treatment platelet reactivity (HRPR) predicts outcomes and major cardiovascular events. Ticagrelor has provided pharmacological and clinical evidence of more predictable and more potent antiplatelet effect as compared to clopidogrel. However, so far, few data have investigated the prevalence and predictors of HRPR in unselected patients treated with ticagrelor, that is therefore the aim of the current study. METHODS AND RESULTS Our population is represented by 195 patients undergoing coronary stenting for ACS and receiving ASA and ticagrelor. Platelet function was assessed by multiplate impedance aggregometry (MEA) between 1 and 3months after stenting. Main clinical features and biochemistry parameters were collected. HRPR for ticagrelor was defined for aggregation>417 AUC after MEA-ADP stimulation. A total of 26 patients, (13.3%), displayed HRPR with ticagrelor. Older age (≥70years, p=0.002), hypertension (p=0.02) previous myocardial infarction (p=0.04), therapy with nitrates and beta-blockers (p=0.02), diuretics (p=0.03) and fasting glycaemia (p=0.05) were associated to HRPR with ticagrelor. By multivariate analysis, age≥70years (OR [95%CI]=4.6[1.55-13.8], p=0.006), concomitant therapy with beta-blockers (OR [95%CI]=3.2[1.06-9.6], p=0.04) and platelets count (OR[95%CI]=1.0007 [1-1.016], p=0.05) were identified as independent predictors of HRPR with ticagrelor. CONCLUSION The present study firstly demonstrates that the occurrence of HRPR in patients treated with ticagrelor is not so futile, as it was observed in 13% of patients treated with ticagrelor. Older age, beta-blockers administration and platelets count are independent predictors of HRPR with ticagrelor.

Optimal Duration of Dual Antiplatelet Therapy After DES Implantation A Meta-Analysis of 11 Randomized Trials

Despite new-generations of drug-eluting stents (DESs), the optimal duration of dual antiplatelet therapy (DAPT) remains controversial. We performed a meta-analysis of randomized trials (RTs) evaluating the effectiveness and safety of shorter versus longer DAPT duration strategies in patients undergoing percutaneous coronary interventions with DES. Literature and main scientific session abstracts were searched. The primary end point was mortality. Secondary end points were (1) cardiovascular mortality, (2) nonfatal myocardial infarction, (3) definite/probable stent thrombosis (ST), and (4) major bleedings. We included 11 RTs (n = 32 372 patients). Shorter DAPT duration reduced mortality (odds ratio, OR [95% confidence interval, CI] = 0.85 [0.71-1], P = .05; p heterogeneity = 0.91). Similar results were observed when comparing 3 to 6 versus 12 months DAPT, while a significant increase in recurrent ischemic events was found for 6 to 12 months DAPT versus extended treatment (myocardial infarction: OR [95%CI] = 1.66 [1.37-2], P < .00001; phet = 0.13 and ST: OR [95%CI] = 2.47 [1.72-3.45], P < .00001; phet = 0.12), however, counterbalanced by a significant reduction in major bleeding (OR [95%CI] = 0.60 [0.47-0.76], P < .0001; phet = 0.38) and a trend in lower mortality. Thus, among selected patients undergoing DES implantation, a shorter DAPT strategy is associated with reduction in mortality and major bleeding but a higher risk of myocardial infarction and ST. A short duration (3-6 months) of DAPT appears as the safest strategy, while a prolonged duration (24-36 months) reduces thrombotic complications but with an excess in major bleeding complications.

Impact of age on mean platelet volume and its relationship with coronary artery disease: a single-centre cohort study

UNLABELLED Elderly patients represent a high risk category among subjects with atherosclerosis, due to the presence of comorbidities and suboptimal response to antiplatelet drugs. Mean platelet volume (MPV) has been indicated as a marker of platelet reactivity, with contrasting data on its role on coronary artery disease. Aim of the present study was to evaluate the impact of age on the MPV and its role on the extent of coronary artery disease (CAD). METHODS Our population is represented by a cohort of 3750 patients undergoing coronary angiography. Elderly were defined according to age ≥ 75 years. MPV was measured at admission. Significant coronary artery disease was defined as a stenosis >50% in at least 1 coronary vessel, while severe CAD was defined as left main and/or three-vessel disease. RESULTS A total of 1170 out of 3750 (31.2%) patients were ≥ 75 years old. Advanced age was associated with female gender (p<0.001), hypertension (p<0.001), renal failure (p<0.001), previous myocardial infarction (p=0.03) coronary artery bypass grafting (p<0.001) indication to angiography (p<0.001), therapy with angiotension-receptor blockers, (p=0.003), nitrates, diuretics and calcium-antagonists (p<0.001), serum creatinine (p<0.001), fibrinogen (p<0.001) and C reactive protein (p=0.02), but inversely to percutaneous coronary interventions (p=0.02), dyslipidemia, family history of CAD and smoking (p<0.001, respectively), use of statins (p=0.02) and beta blockers (p=0.003), haemoglobin, total cholesterol and triglycerides (p<0.001, respectively), white blood cells (p=0.009) and platelet count (p=0.006). Elderly patients displayed a significantly larger platelet volume (p<0.001), with a direct linear relationship between age and the MPV (r=0.08, p<0.001), with age being confirmed as an independent predictor of larger MPV (≥10.85fl) at multivariate analysis (adjusted OR [95% CI]=1.18 [1.01-1.40], p=0.04). Among the elderly, MPV value above the median (≥10.85fl) was not associated with a higher prevalence of coronary artery disease (77.3 vs. 79.4%, p=0.39, adjusted OR [95% CI]=0.94 [0.66-1.33], p=0.71), or higher prevalence of severe CAD (35.2 vs. 32.4%, p=0.28, adjusted OR [95% CI]=1.34 [0.99-1.82], p=0.06). CONCLUSION Advanced age was directly associated with larger mean platelet volume that, however, did not contribute to explain the higher prevalence and extent of coronary artery disease observed in elderly patients.

Uric acid levels and the risk of Contrast Induced Nephropathy in patients undergoing coronary angiography or PCI

BACKGROUND AND AIM Contrast Induced Nephropathy (CIN) is a common complication of procedures that require the use of contrast media, and seems to be mediated by oxidative stress and reactive oxygen species generation. Hyperuricemia is characterized by inhibited nitric oxide system and enhanced synthesis of reactive oxygen species. However, few studies have so far investigated the association between hyperuricemia and CIN that is therefore the aim of the current study among patients undergoing coronary angiography or percutaneous intervention. METHODS AND RESULTS We analyzed a total of 1950 patients with Creatinine clearance <90 ml/min) undergoing elective or urgent coronary angiography and/or angioplasty. Patients were divided according to tertiles of baseline uric acid (Group 1, ≤ 5.5 mg/dL n = 653; Group 2, 5.6-7.0 mg/dL, n = 654; Group 3, ≥ 7.0 mg/dL, n = 643). CIN was defined as an absolute ≥ 0.5 mg/dl or a relative ≥ 25% increase in the serum creatinine level at 24 or 48 h after the procedure. Patients with higher uric acid levels were older, previous smokers, with higher prevalence of hypertension and diabetes, but with lower family history of CAD. They had more often history of a previous CABG and baseline renal dysfunction. Patients of the third Tertile had also higher levels of white blood cells, higher triglycerides and lower HDL-cholesterol and higher percentage of dilated cardiomyopathy/valvular disease as indication for angiography and consequently a lower prevalence of PCI. Patients with higher SUA were more often on therapy with ACE inhibitors and diuretics, but less often with statins, nitrate, ASA and Clopidogrel at admission. The occurrence of CIN was observed in 251 patients (12.9%), and was significantly associated with uric acid levels (12.3% in Group 1, 10.4% in Group 2 and 16.0% in Group 3; p = 0.04). Similar results were observed when the analysis was performed according to each tertiles values in both male and female gender. The association between elevated uric acid (≥ 7 mg/dl) and CIN was confirmed by multivariate analysis after correction for baseline confounding (Adjusted OR [95%CI] = 1.42 [1.04-1.93], p = 0.026). Similar results were observed across major subgroups of high-risk patients, such as patients with diabetes, female gender, renal failure, hypertension, and elderly. CONCLUSIONS This is the first large study showing that among patients undergoing coronary angiography or percutaneous interventions elevated uric acid level is independently associated with an increased risk of CIN.

Dual Versus Single Antiplatelet Regimen With or Without Anticoagulation in Transcatheter Aortic Valve Replacement: Indirect Comparison and Meta-analysis

INTRODUCTION AND OBJECTIVES There is uncertainty on the correct management of antithrombotic therapies after transcatheter aortic valve replacement (TAVR), with dual antiplatelet therapy (DAPT) being currently recommended on an empirical basis. The aim of the present meta-analysis was to assess the safety and effectiveness of DAPT in patients undergoing TAVR. METHODS Studies comparing different antithrombotic regimens after TAVR were included. The primary endpoint was 30-day overall mortality. RESULTS We included 9 studies, 5 comparing DAPT with aspirin monotherapy and 4 comparing DAPT with monoantiplatelet therapy (MAPT) + oral anticoagulation. Among 7991 patients, 72% were on DAPT. The median follow-up was 3.5 months. Mortality was significantly lower in the DAPT group (12.2% vs 14.4%; OR, 0.81; 95%CI, 0.70-0.93; P = .003; Phet = .93), with similar benefits compared with aspirin monotherapy (OR, 0.80; 95%CI, 0.69-0.93; P = .004; Phet = .60), which were not statistically significant when compared with MAPT + oral anticoagulation (OR, 0.86; 95%CI, 0.55-1.35; P = .51; Phet = .97). A similar trend for DAPT was observed for stroke (OR, 0.83 95%CI, 0.63-1.10; P = .20; Phet = .67), with no increase in the rate of major bleedings (OR, 1.69; 95%CI, 0.86-3.31; P = .13; Phet< .0001). On indirect comparison analysis, no benefit in survival, stroke, or bleedings was identified for additional oral anticoagulation. CONCLUSIONS The present meta-analysis supports the use of DAPT after TAVR, reducing mortality and offering slight benefits in stroke, with no increase in major bleedings compared with MAPT. The strategy of aspirin + oral anticoagulation did not provide significant benefits compared with MAPT or DAPT.