Impact of Diabetes on Homocysteine Levels and Its Relationship with Coronary Artery Disease: A Single-Centre Cohort Study.

BACKGROUND/AIMS: Coronary artery disease (CAD) is a major cause of mortality worldwide. Hyperhomocysteinemia has been identified as a risk factor for CAD due to increased thrombogenicity, oxidative stress status and endothelial dysfunction. Few data have been provided on the impact of diabetes on homocysteine and its relationship with the prevalence and extent of CAD in this high-risk subset of patients and therefore, this is the aim of this study. METHODS: Our population is represented by a consecutive cohort of patients undergoing coronary angiography at Azienda Ospedaliera-Universitaria, 'Maggiore della Carità', Novara, Italy from March 2007 to October 2012. RESULTS: Diabetes was observed in a total of 1,125 out of 3,534 patients. Diabetes was associated with more advanced age, hypercholesterolemia, arterial hypertension, renal failure, previous myocardial infarction, coronary revascularization (p < 0.001, respectively) and smoking (p = 0.001). Patients with diabetes were more frequently on angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium-antagonists, diuretics, statins (p < 0.001, respectively), and acetylsalicylic acid (p = 0.004). Patients with diabetes displayed higher creatinine and triglycerides (p < 0.001), but lower total and high-density lipoprotein-cholesterol (p < 0.001) and haemoglobin (p < 0.001). Diabetes was associated with a significantly higher prevalence and extent of CAD and more complex lesions at angiography, including calcified lesion, total occlusions, in-stent restenosis. No significant difference was found in total homocysteine (tHcy) levels between diabetic and non-diabetic patients (p = 0.2). No difference in the percentage of patients with tHcy above the third tertile (≥18.2 nmol/ml) was observed between patients with or without diabetes (32.8 vs. 35%, p = 0.18; adjusted OR 0.88, 95% CI 0.73-1.05, p = 0.14). Among patients with diabetes, no significant association was found between tHcy, CAD (82.4 vs. 83.6 vs. 78.6%, p = 0.19) or severe CAD (33.2 vs. 33.1 vs. 36.9%, p = 0.18). Same results were observed after correction for baseline differences (adjusted OR 0.78, 95% CI 0.61-1.02, p = 0.11) for CAD and severe CAD (adjusted OR 0.92, 95% CI 0.76-1.13, p = 0.46). CONCLUSIONS: In our study, diabetes was not associated with higher tHcy levels. Furthermore, elevated tHcy is not a risk factor for CAD among patients with diabetes.

Effect of diabetes mellitus on periprocedural myocardial infarction in patients undergoing coronary stent implantation.

BACKGROUND: Diabetic patients undergoing percutaneous coronary interventions are still regarded as a very high risk category because of an increased platelet reactivity and risk of complications, especially in patients with inadequate glycaemic control. However, although its prognostic effect on long-term outcome is well-defined, still unclear is the effect of diabetes on the risk of periprocedural myocardial infarction in patients undergoing percutaneous coronary interventions, which was therefore the aim of our study. METHODS: Myonecrosis biomarkers were dosed at intervals from 6 to 48 h after nonemergent percutaneous coronary interventions. Periprocedural myocardial infarction was defined as creatine kinase-MB increase by three times the upper limit normal or by 50% of an elevated baseline value, whereas periprocedural myonecrosis as troponin I increase by three times the upper limit normal or 50% of baseline. RESULTS: Of 1311 patients, diabetes mellitus was found in 458 patients (34.9%) and associated with age (p = 0.03), hypertension (p < 0.001), renal failure (p = 0.01), previous MI (p = 0.03), previous coronary revascularization (p < 0.001), higher fasting glycaemia and lower haemoglobin (p < 0.001), more severe coronary disease (p < 0.001), multivessel percutaneous coronary interventions (p = 0.03), coronary calcification (p = 0.003) and in-stent restenosis (p < 0.001) but lower presence of thrombus (p = 0.03). Diabetic patients were receiving significantly more frequent specific pharmacological treatment at admission. Diabetic status did not influence the risk of periprocedural myocardial infarction or periprocedural myonecrosis [adjusted OR(95%CI) = 0.90(0.64-1.27), p = 0.57 and adjusted OR(95%CI) = 0.92(0.70-1.21), p = 0.55]. Amongst diabetic patients, we did not observe any effect of chronic glycaemic control on periprocedural myocardial infarction. CONCLUSIONS: Diabetic status, independent of chronic glycaemic control, is not associated with increased risk of periprocedural myocardial infarction and myonecrosis in patients undergoing percutaneous coronary interventions.

Impact of red blood cells count on the relationship between high density lipoproteins and the prevalence and extent of coronary artery disease: a single centre study [corrected].

We have hypothesized that high red blood cells (RBC) count can potentially play an atheroprotective role in patients with coronary atherosclerosis. We, therefore, have investigated the relationship between high density lipoproteins cholesterol (HDL-C) and RBC levels in patients undergoing coronary angiography. Coronary artery disease (CAD) is a major cause of mortality. Impaired lipid profile represents a major risk factor for atherosclerosis. High density lipoprotein (HDL) is a key factor in atherosclerosis disease development. RBC can mimic HDL's reverse cholesterol transportation with a potential atheroprotective role. Coronary angiography has been evaluated in 3,534 patients. Fasting samples were collected for haematology and lipids levels assessment. Coronary disease was defined for at least 1 vessel stenosis >50 %. Patients were divided according to HDL-C and RBC tertiles. Lower HDL-C was significantly associated to the prevalence of CAD (84.8 vs 78.5 vs 67.3 %, p ≤ 0.001; adjusted OR [95 % CI] = 1.55 [1.3-1.8], p < 0.001) and severe CAD (30 % vs 30 % vs 24.4 %, p = 0.002; adjusted OR [95 % CI] = 1.08 [1.01-1.16], p = 0.02), this relationship was maintained even dividing our population according to RBC tertiles (p < 0.001).In conclusion, HDL-C levels are directly related to RBC count and inversely to the prevalence and extent of coronary disease. Higher RBC levels can reduce the risk of CAD in patients with lower HDL-C levels, suggesting an important atheroprotective role.

Absolute eosinophils count and the extent of coronary artery disease: a single centre cohort study.

Leukocytes have been involved in the pathogenesis of atherosclerosis, and recent attention has been raised on eosinophils, that have been claimed for a wide number of cardiovascular pathologies, affecting endocardium, myocardium and vascular walls. However, few data have been reported so far on the relationship between absolute eosinophils count (AEC) and the prevalence and extent of coronary artery disease (CAD), that was the aim of present study. Consecutive patients undergoing non-urgent coronary angiography were included. Haematological parameters were measured at admission. Significant CAD was defined as at least 1 vessel stenosis >50 %, while severe CAD as left main and/or trivessel disease, as evaluated by Quantitative Coronary Angiography. Our population is represented by 3,742 patients, divided according to tertiles values of AEC (≤0.1; 0.1-0.2; >0.2 × 10(3)/µl). Higher eosinophils values were significantly associated to male gender, main established cardiovascular risk factors, previous percutaneous or surgical coronary revascularization, antihypertensive and antiplatelet therapy at admission but inversely with acute presentation. Higher AEC was directly related with platelets count (p < 0.001), haemoglobin levels (p = 0.02), white blood cells count (p = 0.02), higher serum creatinine (p < 0.001), triglycerides (p < 0.001) and glycosylated haemoglobin (p < 0.001), while inversely with HDL cholesterol (p < 0.001). AEC was associated with multivessel disease (p = 0.03), chronic occlusions (p = 0.01), in-stent restenosis (p = 0.002), while inversely with the presence of intracoronary thrombus (p < 0.001). A significant relationship was found between AEC and the prevalence of coronary artery disease (p = 0.049), but not for the extent of more severe LM/trivessel CAD (p = 0.31). At multivariate analysis no independent role of eosinophils was found for CAD (adjusted OR [95 % CI] = 1.02 [0.91-1.15], p = 0.70), or severe CAD (adjusted OR [95 % CI] = 0.99 [0.89-1.1], p = 0.9), even when considering separately acute and elective patients. In conclusion, among patients undergoing coronary angiography, higher eosinophils levels are not independently associated with the prevalence and extent of coronary artery disease, but appear confounded by their link with major cardiovascular risk factors.

Platelet glycoprotein IIIa Leu33Pro gene polymorphism and coronary artery disease: A meta-analysis of cohort studies.

Great interest has been focused in the last year on genetic predictors of cardiovascular risk. Glycoprotein IIb/IIIa (GP IIb/IIIa), fibrinogen receptor, is the final common pathway for aggregation and a key point for atherothrombosis. A single nucleotide polymorphism of IIIa subunit (Leu33Pro-PlA(1)/PlA(2) allele) has been suggested to increase aggregation and adhesion, however, contrasting reports have been reported so far on its effects on coronary artery disease (CAD). Aim of the current study was to perform a large meta-analysis including cohorts of patients undergoing coronary angiography in order to evaluate whether this polymorphism is associated with coronary artery disease. Literature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions abstracts were scanned for data of consecutive cohorts of patients undergoing coronary angiography, where PlA genotype was assessed. Primary endpoint was the prevalence of CAD. Secondary endpoint was severity of CAD defined as prevalence of multivessel disease (≥2 vessels). Data from seven studies were extracted, including a final number of 6700 patients. Among them 1893 (28.3%) carried the PlA(2) polymorphism, 163 of them in homozygosis. Angiographically defined CAD was present in 3573 (74.3%) PlA(1)/PlA(1) patients and in 1430 (75.5%) PlA(2) carriers. PlA(2) polymorphism was not associated with an increased prevalence of coronary artery disease, (OR [95% CI] = 1.07 [0.95-1.21], p = 0.28, pheterogeneity = 0.39). Similar results were obtained for multivessel disease (OR [95% CI] = 1.07[0.95-1.20], p = 0.27, pheterogeneity = 0.12). Meta-regression analysis demonstrated a significant inverse relationship between the risk of CAD among the PlA(2) carriers and ageing (r = -0.044, (-0.09, -0.0008), p = 0.046). Present meta-analysis demonstrates that 33Leu → Pro substitution of GPIIIa does not influence the prevalence and extent of angiographically defined coronary artery disease in general population, although apparently playing a role among younger patients.

Platelet-larger cell ratio and the risk of periprocedural myocardial infarction after percutaneous coronary revascularization.

Periprocedural myocardial infarction (PMI) represents a frequent complication in patients undergoing percutaneous coronary revascularization. Despite great attention focused on pharmacological prevention of periprocedural damage, very little is known about using biomarkers to potentially predict the risk of PMI. Larger platelets have been associated with enhanced reactivity, increased cardiovascular risk, and higher rates of complications after coronary stenting. The platelet-larger cell ratio (P-LCR) identifies the largest-sized fraction of platelets, the proportion potentially more closely related to thrombotic events. The present study evaluated the relationship between P-LCR and PMI. We included 1,285 patients undergoing PCI. Myonecrosis biomarkers were dosed at intervals from 6 to 48 h after PCI. Periprocedural myonecrosis was defined as troponin I increase by three times the upper limit of normal (ULN) or by 50 % of an elevated baseline value, whereas PMI was defined as an increase in creatine kinase MB by 3 × ULN or 50 % of baseline. We grouped patients according to tertile values of P-LCR (<27.5; ≥35.1). Higher P-LCR was associated with age (P = 0.01), diabetes (P = 0.001), previous cerebrovascular accidents (P = 0.007), therapy with statins (P < 0.001), angiotensin receptor blockers (P < 0.001), aspirin (P = 0.002), and nitrates (P = 0.01). P-LCR was related to hemoglobin levels (P < 0.001), and inversely related to platelet count (P < 0.001) and glycemia (P = 0.05). Patients with higher P-LCR had a lower presence of coronary thrombus (P = 0.003). Higher P-LCR values did not increase the risk of PMI (P = 0.10; adjusted odds ratio (OR) (95 % confidence interval (CI)) = 0.97 (0.69-1.38)), P = 0.89) or periprocedural myonecrosis (P = 0.96; adjusted OR (95 % CI) = 1.003 (0.76-1.32), P = 0.99). Results were confirmed even in higher-risk subgroups of patients. P-LCR does not increase the risk of periprocedural myocardial infarction and myonecrosis in patients undergoing coronary stenting.

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

BACKGROUND: 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. MATERIALS AND METHODS: Patients undergoing elective coronary angiography were included in a cross-sectional study. Fasting samples were collected for 25-OH D3 levels assessment. Significant CAD was defined as at least 1 vessel stenosis > 50%, while severe CAD as left main and/or trivessel disease, as evaluated by quantitative coronary angiography. RESULTS: Hypovitaminosis D was observed in 70·4% of 1484 patients. Patients were divided according to vitamin D tertiles (< 9·6; 9·6-18·4; ≥ 18·4). Lower vitamin D levels were associated with age, female gender (P < 0·001), renal failure (P = 0·05), active smoking (P = 0·001), acute coronary syndrome at presentation (P < 0·001), therapy with calcium antagonists (P = 0·02) and diuretics (P < 0·001), less beta-blockers (P = 0·02) and statins (P = 0·001) use. Vitamin D was directly related to haemoglobin (P < 0·001) and inversely with platelet count (P = 0·002), total and low-density-lipoprotein cholesterol (P = 0·002 and P < 0·001) and triglycerides (P = 0·01). Vitamin D did not influence angiographic features of coronary lesions, but was associated with higher prevalence of left main or right CAD (P = 0·03). Vitamin D deficiency was significantly associated with higher prevalence of CAD (adjusted OR [95%CI] = 1·32[1·1-1·6], P = 0·004) and severe CAD (adjusted OR [95%CI] = 1·18[1-1·39], P = 0·05). CONCLUSION: Hypovitaminosis D was observed in the vast majority of patients undergoing coronary angiography. Vitamin D deficiency is significantly associated with the prevalence and extent of CAD, especially for patients with values < 10 ng/mL. Therefore, future large studies are needed to evaluate whether vitamin D supplementation may prevent CAD and its progression.

Benefits from new ADP antagonists as compared with clopidogrel in patients with stable angina or acute coronary syndrome undergoing invasive management: a meta-analysis of randomized trials.

AIMS: New P2Y12 receptor inhibitors have provided new and more potent antiplatelet strategies, although raising several concerns on possible increase of bleedings. The aim of current meta-analysis was to evaluate the efficacy and safety of new adenosine diphosphate (ADP) receptor antagonists as compared with clopidogrel in elective or ACS patients managed invasively. METHODS AND RESULTS: Literature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions abstracts were scanned for randomized trials comparing new ADP antagonists with clopidogrel in patients with acute coronary syndromes or stable angina. Primary endpoint was mortality. Secondary endpoints were: (1) nonfatal myocardial infarction (MI), (2) recurrent ischemia symptoms or ischemia-driven revascularization (RI/IDR), (3) stent thrombosis (ST), and (4) safety endpoints, defined as for TIMI major bleeding criteria. A total of 8 randomized clinical trials were finally included, for a total population of 67,851 patients. Mean follow-up was 7.6 months, ranging from 48 hours to 30 months. New ADP antagonists significantly reduced mortality {3.1% vs. 3.6%, odds ratio [OR] [95% confidence interval (CI)], 0.86 [0.79-0.94], P = 0.0008, P(het) = 0.18}, with greater impact of oral drugs. Similar benefits were found for MI [6.1% vs. 7%; OR (95% CI) (random-effect model) = 0.88 (0.79-0.98), P = 0.01, P(het) = 0.02], RI [2.7% vs. 3.1%; OR (95% CI) = 0.85 (0.77-0.93), P = 0.0005, P(het) = 0.09], or ST [1.1% vs. 1.7%; OR (95% CI) = 0.60 (0.51-0.71), P < 0.00001, P(het) = 0.13]. By meta-regression analysis, no relationship was observed between benefits in mortality, new MI, RI, and ST with new ADP antagonists and patients' risk profile [beta (95% CI) = -0.01 [-0.30 to 0.27], P = 0.94; beta (95% CI) = -0.05 [-1.49 to 1.43], P = 0.96); beta (95% CI) = 0.19 (-0.18 to 0.57), P = 0.31, and beta (95% CI) = -0.08 (-0.86 to 0.70), P = 0.84, respectively]. CONCLUSIONS: Present meta-analysis shows that the new ADP antagonists prasugrel, ticagrelor, and cangrelor are associated to significant reduction of mortality, reinfarction, RI, and ST respect to clopidogrel alone, without significant increase in bleeding complications.

Platelet distribution width and the risk of periprocedural myocardial infarction in patients undergoing percutaneous coronary intervention.

Periprocedural myocardial infarction (PMI) still occurs in a large amount of percutaneous coronary interventions (PCI), mainly due to increased platelet activation. Platelet size has been suggested as an indicator of enhanced reactivity and platelet distribution width (PDW) could reflect morphologic changes in platelets, therefore affecting their function and potentially increasing the risk of complications after coronary stenting. Aim of the present study was to evaluate the relationship between PDW and PMI. We included 1,300 consecutive patients undergoing PCI. Myonecrosis biomarkers were dosed at intervals from 6 to 48 h after PCI. Periprocedural myonecrosis was defined as troponin I increase by three times the ULN or by 50 % of an elevated baseline value, whereas PMI as CKMB increase by three times the ULN or 50 % of baseline. We grouped patients according to tertiles values of PDW (<12.1; ≥13.9). Higher PDW was associated with age (p = 0.03), diabetes (p < 0.001), previous cerebrovascular accidents (p = 0.04), therapy with statins (p = 0.001) and ARBs (p < 0.001), ASA (p = 0.02), nitrates (p = 0.006), calcium antagonists (p = 0.05) and lower pre-procedural clopidogrel bolus (p = 0.005). PDW related with haemoglobin levels (p < 0.001), while inversely to platelet count (p < 0.001) and glycaemia (p = 0.003). Patients with larger PDW had lower presence of coronary thrombus (p < 0.001), higher rate of coronary calcifications (p = 0.02), higher stenting rate (p = 0.03) and lower rate of distal embolization (p = 0.03). Larger PDW did not increase risk of PMI (p = 0.11; adjusted OR [95 % CI] = 0.94 [0.78-1.1], p = 0.55) or periprocedural myonecrosis (p = 0.73; adjusted OR [95 % CI] = 0.95 [0.82-1.1], p = 0.51). Results were confirmed even in higher-risk subgroups of patients. In patients undergoing coronary stenting, PDW does not increase the risk of periprocedural MI and therefore should not be considered a risk factor for thrombotic periprocedural complications after PCI.

Platelet HPA-1 a/HPA-1 b polymorphism and the risk of periprocedural myocardial infarction in patients undergoing elective PCI.

Periprocedural myocardial infarction (PMI) represents a relatively common complication of percutaneous coronary intervention (PCI) and large interests have been focused on platelets in order to prevent such a complication. The single nucleotide polymorphism Leu33Pro of platelet glycoprotein IIIa has been related to an increased platelet reactivity, a lower response to antiplatelet agents and higher risk of stent restenosis. Therefore, aim of our study was to evaluate the impact of this polymorphism on PMI in elective patients undergoing PCI. Our population is represented by 422 consecutive patients with cardiac biomarkers within normality undergoing elective PCI. We measured cardiac biomarkers (CK-MB and Troponin I) at baseline, and 8, 24 and 48 hours after the procedure. For all subjects, we performed genetic analysis to assess the presence of Leu33Pro polymorphism. A total of 136 patients (32.2%) were polymorphic. Those patients were younger (p = 0.03) and more often dislypidemic (p = 0.01). Angiographic features did not differ according to genetic status. Pharmacological treatment pre and during angioplasty was similar. PCI-related complications did not differ according to genotype, with the only exception of higher rate of distal embolization in polymorphic patients. However, Leu33Pro polymorphism was not associated with increased risk of periprocedural myonecrosis and PMI even after correction for baseline differences, (respectively OR = 1.22 [0.81-1.84], p = 0.34 for myonecrosis and OR = 1.66 [0.85-3.23]; p = 0.14 for PMI). At subgroup analysis, the Leu33Pro substitution was associated with higher risk of PMI only among diabetics (adjusted OR = 4.46 [1.12-17.76], p = 0.03). Among patients undergoing elective PCI, the polymorphism Leu33Pro of platelet glycoprotein IIIa is associated with increased risk of PMI only in diabetic patients.

High fibrinogen level is an independent predictor of presence and extent of coronary artery disease among Italian population.

Few reports have so far investigated the relationship between fibrinogen levels and the extent of coronary artery disease (CAD) as evaluated by coronary angiography, that is therefore the aim of the current study. We measured fibrinogen in 2,121 consecutive patients undergoing coronary angiography. Patients were divided in 5 groups based on quintiles of fibrinogen levels. Significant CAD was defined as stenosis >50% in at least 1 coronary vessel. We additionally measured carotid intima-media thickness (CIMT) in a subgroup of 359 patients. Patients with elevated fibrinogen were older (P = 0.038), with larger prevalence of diabetes (P = 0.027), female gender (P < 0.0001), hypertension (P < 0.001), chronic renal failure (P < 0.0001), previous CVA (P = 0.036), less often with family history of CAD (P = 0.019) and previous PCI (P < 0.0001), more often presenting with ACS (P < 0.0001), more often on nitrates (P < 0.0001), clopidogrel (P = 0.009) and diuretics (P < 0.0001). Fibrinogen levels were linearly associated with baseline glycaemia (P < 0.017), WBC count (P < 0.0001), creatinine (P < 0.0001), and Platelet count (P < 0.0001) but inversely associated with RBC count (P < 0.0001). Fibrinogen levels were associated with CAD (P = 0.001), especially for extremely high levels (5th percentile, P < 0.0001). At multivariate analysis, after correction for baseline confounding factors, high fibrinogen level (5th percentile) was still associated with the prevalence of CAD (P = 0.034). Furthermore, fibrinogen levels were related with maximal CIMT (r = 0.12; P = 0.01), with larger prevalence of carotid plaques in patients with higher fibrinogen levels (5th quintile) as compared to remaining patients (P = 0.046). This study showed that high fibrinogen level is significantly associated with CAD and carotid atherosclerosis.

Platelet-large cell ratio and the extent of coronary artery disease: results from a large prospective study.

Even though platelet volume has been supposed to be indicator of platelet activation, contrasting results have been reported on its relationship with the extent of coronary artery disease (CAD). No data have been so far reported on Platelet-Large Cell Ratio (P-LCR). Thus, the aim of the current study was to investigate whether P-LCR is associated with CAD. We measured P-LCR in 1882 consecutive patients undergoing coronary angiography. Significant CAD was defined as stenosis >50% in at least 1 coronary vessel. We additionally measured Carotid Intima-Media Thickness (IMT) in 359 patients. The relationship between P-LCR and platelet aggregation was evaluated by PFA-100 and Multiplate. Patients with higher P-LCR were older (P = 0.038), with larger prevalence of diabetes (P < 0.0001), dilated cardiomyopathy or valvular heart disease (P = 0.004) and less often family history of CAD (P = 0.045), more often on statins (P = 0.002), and diuretics (P = 0.016). P-LCR was significantly associated with baseline glycaemia (P = 0.001) and RBC count (P < 0.001), but inversely related to platelet count (P < 0.0001). P-LCR was not associated with the prevalence of CAD (adjusted P = 0.3) or its severity. In addition, P-LCR was not related to Carotid IMT or platelet aggregation in patients with or without aspirin therapy. This study showed that P-LCR is not related to platelet aggregation, aspirin resistance, the extent of CAD and carotid IMT. Thus, P-LCR can not be considered as a marker of platelet reactivity or a risk factor for CAD.

Platelet distribution width and the extent of coronary artery disease: results from a large prospective study.

It has been postulated that large platelets may be an indicator of platelet activation, and thus be related to the extent of coronary artery disease (CAD). Platelet distribution width (PDW) directly measures the variability in platelet size. However, no data has been so far reported on this index and CAD. Thus, the aim of the current study was to investigate whether PDW is associated with the extent of CAD. We measured PDW in 1882 consecutive patients undergoing coronary angiography. Significant CAD was defined as stenosis >50% in at least one coronary vessel. We additionally measured Carotid Intima-Media Thickness (IMT) in 359 patients. Patients with higher PDW were older (p = 0.012), with higher weight (p < 0.0001) and waist (p < 0.0001), larger prevalence of diabetes (p = 0.014), dilated cardiomyopathy or valvular heart disease (p < 0.0001) and less often family history of CAD (p = 0.021), more often on statins (p = 0.005), and diuretics (p = 0.016). PDW was significantly associated with baseline glycaemia (p = 0.002) and Red Blood Cell count (p < 0.0001), but inversely related to platelet count (p < 0.0001). PDW was not associated with the prevalence of coronary artery disease (OR [95% CI] = 0.91 [0.81–1.04], p = 0.16; adjusted OR [95% CI] = 0.96 [0.82–1.12], p = 0.56). No relationship was observed between IMT and PDW as tertiles or as continuous variable (Mean IMT: r = 0.04; p = 0.46; Maximal IMT: r = 0.036, p = 0.49). This study showed that PDW is not related to the extent of CAD and carotid IMT. Thus, PDW can not be considered as a risk factor for CAD.

Thrombectomy during primary angioplasty: methods, devices, and clinical trial data.

Distal embolization is a relatively common complication in primary angioplasty and is associated with poor perfusion and higher mortality. The aim of this article is to critically review literature on thrombectomy devices to prevent distal embolization in patients undergoing primary angioplasty. Several manual and mechanical devices have been proposed. Although negative data have been observed with mechanical devices, significant impact on mortality has been observed with routine use of manual thrombectomy devices, due to an improvement in myocardial perfusion and reduction in distal embolization. Therefore, routine adjunctive manual thrombectomy devices should be recommended in the setting of ST-segment elevation myocardial infarction, whereas the use of larger manual thrombectomy devices (7F) or mechanical devices may be considered in patients with large thrombotic burden to provide more guarantees for complete thrombus removal.

Bivalirudin as compared to unfractionated heparin among patients undergoing coronary angioplasty: A meta-analyis of randomised trials.

It has been shown that bleeding complications are associated with higher mortality rates among patients undergoing coronary angioplasty. Due to its properties, bivalirudin may provide benefits in terms of bleeding and thrombotic complications as compared to unfractionated heparin (UFH). The aim of the current study was to perform a meta-analysis of randomised trials to evaluate whether bivalirudin might offer benefits in terms of mortality as compared to UFH. We obtained results from all randomised trials evaluating the benefits of adjunctive bivalirudin as compared to UFH with or without Gp IIb-IIIa inhibitors among patients undergoing coronary angioplasty. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL) from January 1990 to October 2008. The following keywords were used: randomised trial, coronary angioplasty, stent, reperfusion, primary angioplasty, bivalirudin, direct thrombin inhibitors, hirulog. Primary endpoint was mortality. Secondary endpoint was infarction. Safety endpoint was the risk of major bleeding complications. No language restriction was applied. A total of nine randomised trials were included in the meta-analysis, with 15655 patients randomised to bivalirudin and 13104 patients randomised to UFH. We did not observe any difference in mortality between bivalirudin and UFH (1.73% vs 1.67%, p = 0.15) without any relationship between the baseline risk of mortality (r = 0.17, p = 0.71) or the reduction in major bleeding complications (r = -0.29, p = 0.53) and the benefits in mortality with bivalirudin. A trend in higher risk of myocardial infarction was observed with bivalirudin (6.9% vs 5.9%, p = 0.07, p het = 0.65). Bivalirudin was associated with a significant reduction in major bleeding complications (1.7% vs 3.4%, p < 0.0001), as compared to UFH. This meta-analysis shows that among patients undergoing coronary angioplasty, bivalirudin is associated with significant reduction in major bleeding complications. However, these benefits did not translate into benefits in mortality, with even a trend in higher risk of myocardial infarction.

Impact of duration of clopidogrel prescription on outcome of DES as compared to BMS in primary angioplasty: a meta-regression analysis of randomized trials.

AIMS: Recent concerns have emerged on the potential higher risk of stent thrombosis after Drug-eluting stents (DES) implantation, that might be even more pronounced among ST-segment elevation myocardial infarction (STEMI) patients. The aim of the current study was to evaluate, by a meta-analytic approach, whether the benefits and safety of DES as compared to bare-metal stents (BMS) in patients undergoing primary angioplasty for STEMI may be influenced by the duration of prescription of dual oral antiplatelet therapy. METHODS: The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of DES for STEMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, stenting, DES, sirolimus-eluting stent (SES), Cypher, paclitaxel-eluting stent (PES), Taxus. Information on study design, type of stent, inclusion and exclusion criteria, primary endpoint, number of patients, angiographic and clinical outcome, were extracted by two investigators. Disagreements were resolved by consensus. RESULTS: A total of 12 trials were included in the meta-analysis, involving 4,351 patients (2,260 or 51.9% randomized to DES and 2,091 or 48.1% randomized to BMS). In five trials (involving 1690 patients) dual oral antiplatelet therapy was prescribed for at least 1 year. The outcome of DES as compared to BMS was not affected by the duration of dual antiplatelet therapy in terms of death (P interaction = 0.16), reinfarction (P interaction = 0.91) and in-stent thrombosis (P interaction = 0.26) and TVR (P interaction = 0.38). These data were confirmed by the use of a meta-regression analysis. CONCLUSIONS: This meta-analysis shows that among selected STEMI patients undergoing primary angioplasty, DES (SES and PES), as compared to BMS, are safe and their benefits are not affected by the duration of clopidogrel prescription.

Percutaneous coronary intervention-related time delay, patient's risk profile, and survival benefits of primary angioplasty vs lytic therapy in ST-segment elevation myocardial infarction.

BACKGROUND: Previous reports have suggested an impact of patient's risk profile and percutaneous coronary intervention (PCI)-related time delay on the benefits of primary angioplasty as compared with fibrinolysis. However, several factors, such as inappropriate interpretation and definition of delays, missing currently available trials, and arguable risk-benefit analysis, limit the value of these reports. Thus, the aim of the current review is to assess whether the prognostic impact of PCI-related time delay may vary according to patient's risk profile, presentation delay, and type of lytic therapy. METHODS: We obtained results from all randomized trials comparing fibrinolysis and primary angioplasty in ST-segment elevation myocardial infarction. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL) for papers published from January 1990 to April 2007. The following key words were used: randomized trial, myocardial infarction, reperfusion, primary angioplasty, rescue angioplasty, fibrinolysis, thrombolysis, duteplase, reteplase, tenecteplase, and alteplase. Major clinical end point assessed was mortality at 30-day follow-up. The relationship between mortality benefits from primary angioplasty, patient's risk profile, and PCI-related time delay was evaluated by using a weighted least-square regression in which results from each trial were weighted by the square root of the number of patients of each trial. RESULTS: A total of 27 trials were finally included, with 4399 patients randomized to primary angioplasty and 4474 patients randomized to fibrinolysis. The relationship between the benefits from primary angioplasty and PCI-related time changed according to risk profile. The higher the risk profile, the larger the reduction in mortality benefits from primary angioplasty as compared with fibrinolysis per each 10 minutes of PCI-related time delay (0.75%, 0.45%, and 0%, in high-, medium-, and low-risk patients, respectively). Furthermore, the impact was observed only in trials enrolling patients within the first 6 hours from symptom onset. CONCLUSIONS: When primary angioplasty is selected as reperfusion strategy, all efforts should be attempted to shorten time-to-treatment, particularly in medium- or high-risk patients and in early presenters, because in these patients, a larger loss of mortality benefits as compared with fibrinolysis is observed per each 10 minutes of PCI-related time delay.

Homocysteine and risk of periprocedural myocardial infarction in patients undergoing coronary stenting.

BACKGROUND: Despite improvements in pharmacological and mechanical devices, the risk of periprocedural myocardial infarction (PMI) is still high, particularly in prothrombotic conditions. Hyperhomocysteinemia has been associated with enhanced platelet function, impaired endothelial function and prothrombotic status, thus increasing the risk of cardiovascular events. No study has, so far, investigated the relationship between homocysteine levels and the risk of periprocedural MI in patients undergoing percutaneous coronary intervention (PCI), and this is therefore the aim of the current study. METHODS: In 1150 patients undergoing PCI, homocysteinemia was assessed at admission. Cardiac biomarkers were measured at intervals from 8 to 48 h after PCI. Periprocedural myonecrosis was defined by a troponin I increase to three times the upper limit of normal (ULN) or by 50% if elevated at the time of the procedure. PMI was defined as a CK-MB increase to three times the ULN or of 50% if elevated at the time of the procedure. RESULTS: We grouped patients according to tertile values of homocysteine. Higher homocysteine levels were associated with older age (P < 0.001), male sex (P = 0.02), arterial hypertension (P = 0.007), diabetes (P = 0.04), renal failure (P < 0.001), higher creatinine levels (P = 0.01), previous MI (P = 0.02), previous PCI (P = 0.04) and previous cerebrovascular accidents (P = 0.01). Homocysteine was associated with lower ejection fraction (P < 0.001), treatment with angiotensin-receptor blockers (P < 0.001), nitrates (P = 0.008) and diuretics (P < 0.001) and acetylsalicylic acid (P = 0.01). Homocysteine levels were directly related with the extent of coronary disease (P = 0.04) and coronary calcifications (P < 0.001) but inversely with type C lesions (P = 0.001), TIMI 3 flow pre-PCI (P = 0.02), stenosis severity (P = 0.01) and thrombus (P = 0.004). In addition, they are associated with higher rates of balloon predilatation (P = 0.02), lower use of thrombectomy (P = 0.01) and periprocedural administration of GPIIbIIIa inhibitors (P = 0.02). Ageing, male sex, diabetes, renal failure, creatinine levels, diuretics use, coronary calcifications and type C lesions were independently related to homocysteine. Homocysteine did not affect the risk of PMI [adjusted odds ratio (OR) 1.14 (0.91-1.42), P = 0.26], or periprocedural myonecrosis [adjusted OR 1.17 (0.98-1.39), P = 0.08]. Similar results were found after propensity score adjustment [adjusted OR 1.19 (0.95-1.48), P = 0.14 for PMI and adjusted OR 1.18 (0.99-1.4), P = 0.07 for myonecrosis] and at subgroup analysis in higher risk subsets of patients. CONCLUSION: In patients undergoing PCI, the risk of PMI is not influenced by hyperhomocysteinemia.

Relationship between glycoprotein IIIa platelet receptor gene polymorphism and coronary artery disease.

Glycoprotein IIb/IIIa (GP IIb/IIIa) is a key receptor for platelet aggregation and adhesion. We investigated whether a single-nucleotide polymorphism of GP IIIa subunit (Leu33Pro-PlA(1)/PlA(2) allele) is associated with the extent of coronary artery disease (CAD) in a consecutive cohort of 1518 patients undergoing coronary angiography. Significant CAD was defined as at least a stenosis >50% and severe CAD as left main disease and/or trivessel disease. Additionally, carotid intima-media thickness (cIMT) was evaluated in 339 patients. The PlA(2) allele was observed in 458 (30.2%) patients and associated with hypercholesterolemia (P = .03). No difference was observed in the prevalence of CAD (72.6% vs 70.1%, P = .29; adjusted odds ratio, OR [95% confidence interval, CI] = 0.85 [0.67-1.08], P = .19) and severe CAD (27.5% vs 26.5%, adjusted OR [95% CI] = 0.93 [0.72-1.19], P = .55). Furthermore, Leu33Pro polymorphism did not affect cIMT and the prevalence of carotid plaques. Therefore, this polymorphism cannot be regarded as a risk factor for coronary or carotid atherosclerosis.