Impact of high-dose statins on vitamin D levels and platelet function in patients with coronary artery disease.

BACKGROUND: Statins represent a pivotal treatment in coronary artery disease, offering a reduction in cardiovascular risk even beyond their lipid-lowering action. However, the mechanism of these "pleiotropic" benefits of statins is poorly understood. Vitamin D has been suggested as a potential mediator of the anti-inflammatory, anti-thrombotic and vascular protecting effects of statins. Aim of present study was to assess the impact of a high-intensity statin therapy on vitamin D levels and platelet function in patients with coronary artery disease. METHODS: Patients discharged on dual antiplatelet therapy and high-intensity statins after an ACS or elective PCI were scheduled for main chemistry and vitamin D levels assessment at 30-90days post-discharge. Vitamin D (25-OHD) dosing was performed by chemiluminescence method through the LIAISON® Vitamin D assay (Diasorin Inc). Platelet function was assessed by Multiplate® (multiple platelet function analyser; Roche Diagnostics AG). RESULTS: Among 246 patients included, 142 were discharged on a new statin therapy or with an increase in previous dose (Inc-S), while 104 were already receiving a high-dose statin at admission, that remained unchanged (Eq-S). Median follow-up was 75.5days. Patients in the Inc-S group were younger (p=0.01), smokers (p<0.001), with a less frequent history of hypercholesterolemia (p=0.05), diabetes (p=0.03), hypertension (p=0.02), or previous cardiovascular events (p<0.001). They were more often admitted for an acute coronary syndrome (p<0.001) and used less anti-hypertensive drugs or nitrates. Higher total circulating calcium was observed in the Inc-S group (p=0.004), while baseline vitamin D levels were similar in the 2 groups (p=0.30). A significant reduction in the circulating low-density lipoprotein (LDL) cholesterol was observed in the Inc-S group. Vitamin D levels increased in the Inc-S patients but not in the Eq-S group (delta-25OHD: 23.2±20.5% vs 3.1±4.7%, p=0.003), with a linear relationship between the magnitude of vitamin D elevation and the reduction of LDL cholesterol (r=-0.17, p=0.01). Platelet reactivity was significantly lower in the Inc-S patients, when evaluating aggregation with different platelet activating stimuli (arachidonic acid, p=0.02, collagen, p=0.004, thrombin-activating peptide, p=0.07, ADP, p=0.002). CONCLUSIONS: In patients with coronary artery disease, the addition of a high-intensity statin treatment, besides the lipid-lowering effects, is associated to a significant increase in vitamin D levels and lower platelet reactivity, potentially providing explanation of the "pleiotropic" benefits of statins therapy in cardiovascular disease.

Vitamin D levels and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor.

BACKGROUND: Suboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCIs). However, very few are known so far on the predictors of high-residual platelet reactivity (HRPR) despite antiplatelet strategies. Increasing attention has been paid in the last years to the role of vitamin D in atherothrombosis. Therefore, the aim of our study was to evaluate the impact of vitamin D levels on platelet function in patients treated with dual antiplatelet therapy (DAPT). Patients treated with DAPT (ASA and clopidogrel or ticagrelor) after a recent acute coronary syndrome (ACS) or elective PCI were scheduled for platelet function assessment at 30-90 days post-discharge. Platelet function was assessed by whole blood impedance aggregometry (Multiplate®-Roche Diagnostics AG), HRPR was considered for ASPI test values > 862 AU*min (for ASA) and adenosine diphosphate (ADP) test values ≥417 AU*min (for ADP-antagonists). Fasting samples were obtained for main chemistry parameters and vitamin D level assessment. Our population is represented by 503 patients, who were divided according to vitamin D quartiles (≤9.1; 9.2-14.4; 14.5-21.7; >21.7 ng/ml). Lower vitamin D levels related with age (p = 0.04), diabetic status (p = 0.05), and previous coronary surgery (p = 0.007), therapy with beta-blockers and statins (p = 0.01 and p = 0.02). Vitamin D inversely related to the levels of total cholesterol (p = 0.01), triglycerides (p < 0.001), hemoglobin (p = 0.05), and HbA1c (p < 0.001). Significantly higher platelet reactivity was observed after platelet stimulation with ADP (p = 0.01), but not with other platelet activators. The prevalence of HRPR for ASA was low (1.2%) and not conditioned by Vitamin D levels (adjusted OR[95%CI] = 1.56[0.71-3.5], p = 0.27). HRPR with ADP-antagonists was observed in 26% of patients, and the rate increased with lower vitamin D quartiles (37.3% vs 22.2% vs 24.4% vs 20.2%, p = 0.005, adjusted OR[95%CI] = 1.23[1.02-1.49], p = 0.04). An absolute increase in HRPR with lower vitamin D levels was similarly observed among patients receiving ticagrelor (adjusted OR[95% CI] = 1.40[0.95-2.06], p = 0.08), and those on clopidogrel (adjusted OR[95%CI] = 1.31[0.99-1.75], p = 0.06). Thus, lower vitamin D levels are associated with higher platelet reactivity and impaired effectiveness of ADP-antagonists, while not influencing the effectiveness of ASA. Future studies will tell whether vitamin D supplementation can reduce platelet reactivity, overcoming the phenomenon of resistance to antiplatelet agents.

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.

Analysis of electrical and mechanical left atrial properties in patients with persistent atrial fibrillation.

The study of left atrial (LA) mechanical function during atrial fibrillation (AFib) can provide valuable information, particularly if such profiling is related to the cavity electrical substrate and conveys prognostic information. To assess if there is any relation between LA mechanical and electrical asynchrony and if such evaluation can be of interest in stratifying AFib patients. 50 patients with persistent AFib who underwent electrical cardioversion (CV) were evaluated with pre-CV atrial electrograms (AEGs). Electrical asynchrony was classified according to Wells' patterns of AEGs, ranging from most organized (I) to most dispersed (III) one. LA mechanical asynchrony was addressed by transthoracic 2D-speckle-tracking echo and quantified according to time-to-peak standard deviation (TP-SD) of wall strains and their peak values (PS) before CV, after 24 h, at 1 month. Pre-CV a linear, inverse relation between TP-SD and PS (p < 0.001) and a direct linear relation between TP-SD and Wells' classes (p = 0.04) were observed. With sinus rhythm TP-SD decreased (p = 0.023) and PS increased (p < 0.001), suggesting improved LA mechanical milieu. A multivariate analysis, testing the effects of baseline variables in predicting post-CV recurrence of AFib, revealed that amount of TP-SD variation pre/24 h post-CV was the only independent predictor at 6 months (p = 0.046). Speckle tracking-derived LA parameters can describe LA wall forces during AFib, categorizing the asynchronous mechanistic profile of AFib that correlates with the degree of the dispersed LA electrical activity. The amount of changes in LA mechanical asynchrony pre/post-CV seems to have prognostic relevance in predicting SR maintenance.

Benefits from small molecule administration as compared with abciximab among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-analysis.

OBJECTIVES: The aim of the study was to perform a meta-analysis of randomized trials (RTs) comparing abciximab versus small molecules (eptifibatide and tirofiban) in primary angioplasty (PPCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Abciximab has been shown to provide significant benefits in PPCI for STEMI. However, small molecules represent an attractive strategy due to the reversibility of the inhibition of platelet aggregation and the lower costs. METHODS: We obtained results from RTs comparing abciximab versus small molecules in PPCI. The literature was scanned by searches of electronic databases (MEDLINE and CENTRAL) up to October 2008. The following key words were used: RT, myocardial infarction, reperfusion, primary angioplasty, glycoprotein IIb/IIIa inhibitors, abciximab, tirofiban, and eptifibatide. Concerning tirofiban, we only included trials or groups of patients with high-dose bolus and infusion. The primary end point was 30-day mortality. Secondary end points were 30-day reinfarction, post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow grade 3, and ST-segment resolution. RESULTS: A total of 6 RTs were included in the meta-analysis, involving 2,197 patients (1,082 randomized to abciximab and 1,115 to small molecules [high-dose tirofiban in 5 trials and eptifibatide in 1 trial]). Abciximab did not improve post-procedural TIMI flow grade 3 (89.8% vs. 89.1%, p = 0.72) or ST-segment resolution (67.8% vs. 68.2%, p = 0.66). Abciximab did not reduce 30-day mortality (2.2% vs. 2.0%, p = 0.66) or reinfarction (1.2% vs. 1.2%, p = 0.88), nor was there any difference in major bleeding complications (1.3% vs. 1.9%, p = 0.27). CONCLUSIONS: This meta-analysis shows among STEMI patients undergoing PPCI similar results between abciximab and small molecules in terms of angiographic, electrocardiographic, and clinical outcome.

Stapled transanal rectal resection for outlet obstruction syndrome: results and follow-up.

BACKGROUND: The objective of the present study was to assess safety, effectiveness, and long-term outcomes of stapled transanal rectal resection (STARR) for the cure of outlet obstruction syndrome (OOS). METHODS: Data were collected over a 3-year period (2004-2007), at the Department of Surgery of the University of Genoa, from 25 consecutive subjects (19 of them females) undergoing STARR because of OOS that had not responded to medical treatment,. RESULTS: Preoperatively, patients were submitted to clinical examination, defecography, colonoscopy, manometry, and recto-anal reflexes determination. All patients had mucosal prolapse, 15 rectal intussusception, 15 rectocele. Postoperatively no deaths were observed; one patient had a hemorrhage requiring reintervention. Mean time to resumption of normal activity was 8.5 +/- 4.5 days. Patients were followed for a mean of 24.7 +/- 10.9 months (range: 6-42 months). Late specific complications included 3 cases of urge to defecate, 8 of incontinence to flatus. Functional outcome was positive for 22 patients (excellent in 4 cases, good in 15, fairly good in 3). Six months postoperatively (25 s), patients had improvement of the mean Constipation Score (p = 0.0002), less pain during evacuation (p = 0.0003), and reduced use of digital assistance to defecate (p < 0.0001). Continence Grading Scale and enema use remained stable after intervention. Patients had increase in basal sphincter pressure (p = 0.0078) and maximal squeeze pressure (p = 0.0051). Recto-anal reflex study showed increase in abdominal pain threshold (p < 0.0001); anal sphincter relaxation threshold and desire to defecate threshold did not change. CONCLUSIONS: According to the present study, STARR seemed to be a safe and effective treatment for OOS associated with symptomatic rectocele and intussusception.

Inappropriate implantable cardioverter-defibrillator discharges unrelated to supraventricular tachyarrhythmias.

AIMS: The development of implantable cardioverter-defibrillators (ICDs) with QRS morphology discrimination and dual-chamber sensing capabilities has improved the differentiation of supraventricular from ventricular tachycardias (VTs). Inappropriate ICD discharges may result from extracardiac signals caused by electromagnetic interference (EMI), because of electric fields and leakage currents from domestic or medical electrical devices, damaged sensing leads, and various cardiac and extracardiac signals that mimic VT and/or ventricular fibrillation. The aim of our study was to determine retrospectively the incidence and clinical relevance of these ICD behaviours and offer possible therapeutic solutions. METHODS AND RESULTS: We have observed inappropriate discharges unrelated to supraventricular arrhythmias in 13 (3.9%) of the 336 patients implanted with ICDs in our centre from 1989 to 2005. Seven patients received inappropriate shocks following exposure to external EMI: improperly grounded electric stove, electrically powered watering system, hydro-massage bath, electrical pruner, electrocautery current during cardiac surgery, transcutaneous electric nerve stimulation. In four patients, spurious discharges were related to internal noise of the ICD system from inappropriate lead connections. In two cases, erroneous antitachycardia therapy was delivered following different body signals oversensing (T-wave oversensing, wide QRS double-counting and myopotentials). In nine patients, non-invasive solutions prevented further inappropriate therapies (avoidance of EMI, malfunctioning atrial lead exclusion, ventricular sensing reprogramming). In four patients, surgical revision of the system was required (lead connections or position revision). CONCLUSION: In our experience, inappropriate ICD discharges unrelated to supraventricular arrhythmias occurred in about 4% of ICD patients. A careful evaluation of clinical data and telemetric information (lead impedance, sensed R-wave, stored electrograms) is essential in order to understand the nature of inappropriate ICD discharges and to select the most appropriate solution.