The Association between Multi-Vessel Coronary Artery Disease and High On-Aspirin Platelet Reactivity.

BACKGROUND: Multi-vessel coronary artery disease (MV-CAD) is correlated with worse clinical outcomes compared with single-vessel CAD (SV-CAD). The aim of this study was to evaluate the association between MV-CAD and high on-aspirin platelet reactivity (HAPR) in patients with stable CAD treated with aspirin. METHODS: The current study is an analysis of prospectively enrolled randomly selected patients with known stable CAD, who were taking aspirin (75-100 mg qd) regularly for at least one month, and had undergone coronary angiography at least 3 months prior to the enrollment to the study. EXCLUSION CRITERIA: acute coronary syndrome at the time of platelet function testing, active malignancy, acute infection, active inflammatory/rheumatic disease, major surgery in the past 6 months, chronic liver failure, treatment with oral anticoagulation, non-adherence with Aspirin and thrombocytopenia (<100 K/micl). Blood was drawn from the participants and sent for platelet function testing (VerifyNow, Instrumentation Laboratory Company, Bedford, Massachusetts, United States). MV-CAD was defined as >50% stenosis in ≥2 separate major coronary territories per coronary angiography. HAPR was defined as aspirin reaction units (ARU) >550. RESULTS: Overall, 507 patients were analyzed; age 66.7 ± 11.2, 17.9% women, 223 (44%) had MV-CAD. The rate of HAPR was significantly higher among patients with MV-CAD vs. SV-CAD (14.8% vs. 3.5%, p < 0.001, respectively). Furthermore, a "dose response"-like association was found between the number of stenotic coronary arteries and the rate of HAPR (3.5%, 13.5 and 17.3% for SV-CAD, 2-vessel and 3-vessel disease, respectively). In a multivariate analysis adjusted for potential confounders, MV-CAD was found to be a strong independent predictor of HAPR [OR = 1.8 (95%CI: 1.05-4.7), p = 0.014]. CONCLUSIONS: A significant association between MV-CAD and HAPR was found. Additional studies designed to investigate the mechanisms of HAPR and different therapeutic options for this subset of patients are warranted.

Impact of Calcium Channel Blockers on Aspirin Reactivity in Patients with Coronary Artery Disease.

PURPOSE: Calcium channel blockers (CCBs) do not reduce the risk of initial or recurrent myocardial infarction (MI) in patients diagnosed with stable coronary artery disease (CAD). The aim of this current study was to evaluate the association between CCBs and aspirin resistance in patients with CAD. METHODS: Patients with stable CAD who were regularly taking aspirin (75-100 mg qd) for at least 1 month prior to enrollment in the study were included. The VerifyNow system was used for platelet function testing with high on-aspirin platelet reactivity (HAPR) defined as aspirin reaction units (ARU) >550. We compared patients treated with CCBs versus control group. RESULTS: Five hundred three patients with CAD were included in this study, and 88 were treated with CCBs. Mean age (67.9±9.7 in the CCB group vs. 66.5±11.4 in the control group), gender (77.3 male vs. 82.9%), rates of diabetes mellitus (34.7 vs. 36.9%), rates of CKD (23.5 vs. 23.5%), dyslipidemia (85.1 vs. 85.3%), and statin therapy (89.5 vs. 90.7%) were similar. The mean ARU was 465.4±70.0 for patients treated with CCBs versus 445.2±60.0 in controls (p=0.006). Similarly, 15.9% of CCB patients demonstrated HAPR compared to 7.0% (p=0.006). The administration of CCBs was independently associated with HAPR in a multivariate analysis (OR 1.72, 95% CI: 1.04-8.91, p=0.047) as well as in propensity score matched analysis (OR 1.56; CI: 1.22-1.93; p<0.001). CONCLUSIONS: Usage of CCBs is positively correlated with aspirin resistance. These findings may suggest an adverse pharmacologic effect of CCBs among patients with stable CAD treated with aspirin.

Prognostic significance of reticulated platelet levels in diabetic patients with stable coronary artery disease.

Levels of reticulated platelets (RP) increase during high platelet turnover conditions, and have been shown to correlate with diabetes mellitus (DM) status. Little is known regarding the prognostic significance of levels of RP among patients with stable coronary artery disease (SCAD). The study consisted of patients with SCAD and DM, who visited our cardiology outpatient clinic between June 2016 and February 2017. RP levels were measured at baseline as immature platelet fraction (IPF)%, using flow cytometry. Outcomes at 2 years consisted of bleeding events and major adverse cardiovascular events (MACE), which included death, myocardial infarction, cerebrovascular accident and urgent revascularization. The study included 104 patients (mean age - 71.2 ± 9.5 years, 76.9% were male, and 83.7% had hypertension). IPF was significantly higher at baseline among patients who had suffered from a MACE (4.57% vs. 2.53%, p < .001), and lower in patients who had suffered from bleeding events, compared with those who had not (1.57% vs. 3.00%, p = .004). There were higher rates of MACE at higher IPF quartiles (p < .001, AUC-0.770), and higher rates of bleeding at the lowest quartiles (p = .007, AUC-0.781). In SCAD patients with DM, levels of RP are associated with a higher risk of MACE, and inversely correlated with the risk of bleeding.

Relation of Hypoalbuminemia to Response to Aspirin in Patients With Stable Coronary Artery Disease.

Serum albumin (SA) level is a powerful cardiovascular prognostic marker, suggested to be involved in regulation of platelet function. High on-aspirin platelet reactivity (HAPR) is associated with increased risk for deleterious cardiovascular events. The aim of the present study was to evaluate the association between HAPR and albumin levels in patients with stable coronary artery disease (CAD) treated with aspirin. Patients with known stable CAD, who were taking aspirin (75 to 100 mg qd) regularly for at least 1 month, were screened for the present study. Exclusion criteria: cancer, sepsis or acute infection, active inflammatory/rheumatic disease, recent major surgery, chronic liver failure, the administration of other antiplatelet drugs, nonadherence with aspirin and thrombocytopenia. Blood was drawn from the participants and sent for SA level and platelet function test (VerifyNow). HAPR was defined as aspirin reaction units (ARU) >550. Overall 116 patients were analyzed; age 69 ± 10, 28% women. Twenty (17%) were hypoalbuminemic (≤3.5 g/dl). Hypoalbuminemic patients had similar characteristics to the normal albumin group except mildly higher creatinine in the former. SA levels were significantly lower in the hypoalbuminemic group (3.2 ± 0.2 g/dl vs 4.2 ± 0.4 g/dl, respectively, p <0.001) whereas mean ARU was significantly higher compared with the normal albumin group (548 ± 45 vs 444 ± 66 ARU, respectively, p <0.001). A significant inverse association was observed between SA and ARU with (R2 = 0.67, p <0.001). Multivariate analysis adjusted for potential confounders found that albumin ≤3.5 is the strongest predictor of HAPR in patients with stable CAD (hazards ratio 4.9, 95% confidence interval 2.2 to 32, p = 0.002). In conclusion, hypoalbuminemia is strongly associated with HAPR in patients with stable CAD.

Yield of left ventricular dyssynchrony by gated SPECT MPI in patients with heart failure prior to implantable cardioverter-defibrillator or cardiac resynchronization therapy with a defibrillator: Characteristics and prediction of cardiac outcome.

BACKGROUND: Mechanical left ventricular dyssynchrony (MLVD) might contribute in the therapeutic decision-making in patients with heart failure (HF) prior to cardiac resynchronization therapy (CRT). Our aim was to assess MLVD in patients with HF prior to implantable cardioverter-defibrillator (ICD) compared to patients with CRT-D. METHODS: In a prospective study, patients with LVEF ≤ 35% who were scheduled for ICD or CRT-D, underwent gated SPECT myocardial perfusion imaging with technetium 99m sestamibi within 3 months prior procedure. MLVD was measured by phase analysis. RESULTS: The study cohort consisted of 143 patients, 71 with ICD and 72 with CRT-D. Age 68.3 ± 11 and LVEF 24 ± 6%. Phase standard deviation (SD) was 62.5 ± 18 and 59.7 ± 20 (P = NS), respectively. During follow-up of 23.7 ± 12.1 months, there were 10 vs 14 cardiac death in ICD and CRT-D, respectively (P = NS), hospitalization for HF, in 34 vs 53 (P < .001). In multivariate analysis, Phase SD was the independent predictor for cardiac death [HR 2.66 (95% CI 1.046-6.768), P = .04]. Kaplan-Meier curves of phase SD of 60° significantly identified ICD patients with and without cardiac deaths and hospitalization for HF exacerbation. CONCLUSIONS: MLVD by phase SD can identify patients with cardiac events and predict cardiac death in patients treated with ICD.

Prevalence of Carotid Artery Disease among Ambulatory Patients with Coronary Artery Disease.

BACKGROUND: Concomitant carotid artery disease (CaAD) in patients with coronary artery disease (CAD) is associated with worse cardiac and neurologic outcomes. The reported prevalence and risk factors for concomitant CaAD in CAD patients varied among previous studies. OBJECTIVES: To examine these factors in ambulatory patients with CAD and well-documented cholesterol levels treated with cholesterol-lowering medications. METHODS: We retrospectively analyzed prospectively collected data from 325 unselected patients with CAD (89 women, mean age 68.8 ± 9.9 years) undergoing routine evaluation at the coronary clinic of our hospital. RESULTS: The low density lipoprotein-cholesterol (LDL-C) was < 100 mg/dl in 292 patients (90%). Age at onset of CAD symptoms was 59.4 ± 10.8 years. Carotid stenosis ≥ 50% was seen in 83 patients (25.5%) and between 30% and 49% in 55 patients (17%) (duplex method). Carotid stenosis was significantly associated with hypertension (P = 0.032), peripheral arterial disease (P = 0.002) and number of coronary arteries with ≥ 50% stenosis (P = 0.002), and showed a borderline association with age at CAD onset (P = 0.062) and diabetes mellitus (P = 0.053). On linear regression analysis, independent predictors of CaAD were peripheral vascular disease (OR 3.186, 95% CI 1.403-7.236, P = 0.006), number of coronary arteries with ≥ 50% stenosis (OR 1.543, 95% CI 1.136-2.095, P = 0.005), and age at CAD onset (OR 1.028, 95% CI 1.002-1.054, P = 0.003). None of the variables studied predicted freedom from CaAD. CONCLUSIONS: Carotid atherosclerosis is very common in stable ambulatory patients with CAD regularly taking statins. The risk is higher in patients with peripheral arterial disease, a greater number of involved coronary arteries, and older age at onset of CAD.

Association of Helicobacter pylori with coronary artery disease and myocardial infarction assessed by myocardial perfusion imaging.

BACKGROUND: The relationship between Helicobacter pylori infection and coronary artery disease (CAD) has as yet not been fully examined. The myocardial perfusion imaging (MPI) stress test has proven its efficacy as an integral part of diagnosing CAD. OBJECTIVES: To investigate the association between CAD and H. pylori infection using MPI. METHODS: This prospective study evaluated CAD positivity among consecutive patients referred to a tertiary medical center for a stress/rest MPI. All patients were tested for serum anti-H. pylori and CagA protein immunoglobulin G antibodies. The CAD positivity group included patients with ischemia and/or myocardial infarction (MA) on a stress MPI, coronary artery bypass graft surgery (CABG), or percutaneous coronary interventions (PCI). CAD-negative subjects were defined as participants with a normal MPI, no pathological Q waves in resting ECG tracing, and no history of CAD. Both groups were compared for H. pylori and CagA seropositivity. Patients' demographic data, risk factors for CAD, and childhood socioeconomic status were recorded. RESULTS: The study group consisted of 300 consecutive patients, 170 men and 130 women; 64% (110/173) CAD-positive patients and 47% (60/127) CAD-negative participants were found seropositive for H. pylori infection (P = 0.005). In the adjusted analysis, H. pylori infection was found to be associated with CAD positivity (odds ratio 1.83, 95% confidence interval 1.06-3.17, P = 0.031), and MI (fixed perfusion defects on MPI) (OR 3.36, 95% CI 1.44-7.84, P = 0.005). No association was noted with CagA positivity. CONCLUSIONS: In patients undergoing a stress MPI, serum anti-H. pylori antibodies positivity was found to be associated with CAD, independent of traditional cardiovascular risk factors.

Prognostic value of left ventricular dyssynchrony by myocardial perfusion-gated SPECT in patients with normal and abnormal left ventricular functions.

BACKGROUND: Left ventricular (LV) dyssynchrony by phase analysis has been studied by myocardial perfusion imaging (MPI)-gated SPECT in patients with LV dysfunction in various clinical settings. We aimed to investigate the routine use of phase analysis with gated SPECT for predicting cardiac outcome. METHODS: Patients referred to a tertiary medical center in 2010-2011 prospectively underwent a gated SPECT and phase analysis, and follow-up for cardiac events. The values of clinical variables, MPI, LV function, and LV dyssynchrony in predicting cardiac events were tested by univariate and multivariate analyses. RESULTS: The study group included 787 patients (66.5 ± 11 years, 81% men) followed for a mean duration of 18.3 ± 6.2 months. There were 45 (6%) cardiac events defined as composite endpoint; cardiac death occurred in 26 patients, and the rest had new-onset or worsening heart failure and life-threatening arrhythmias. In multivariate analysis, it was shown that NYHA class, diabetes mellitus, and LVEF <50% were the independent predictors for composite endpoint. However, the independent predictors for cardiac mortality were NYHA class (for each increment in class) and phase standard deviation (SD) (for each 10° increment). CONCLUSION: Gated SPECT with phase analysis for the assessment of LV dyssynchrony can successfully predict cardiac death together with NYHA class, in patients with LV dysfunction.

Angiographic correlation of myocardial perfusion imaging with half the radiation dose using ordered-subset expectation maximization with resolution recovery software.

BACKGROUND: We previously described the feasibility of performing myocardial perfusion imaging (MPI) with half the technetium (Tc-99m) activity using ordered-subset expectation maximization with resolution recovery (OSEM-RR) processing. This study sought to assess the accuracy of this technique by correlating the findings with coronary angiography. METHODS: Of 290 patients who underwent MPI-gated SPECT using a half dose of Tc-99m sestamibi and OSEM-RR software in 2010-2012 at a tertiary medical center, 62 were referred for invasive coronary angiography within 90 days and formed the study group. Ischemia was defined as a summed difference score (SDS) of >3 on the MPI scan. Luminal stenosis of ≥70% on invasive coronary angiography served as the reference. RESULTS: Mean Tc-99m activity per study was 23.9 ± 11.5 mCi and mean effective radiation dose was 7.2 ± 3.4 mSv. MPI revealed no abnormalities in 10 patients (16.2%), myocardial infarction only in 8 patients (12.9%), and ischemia in 44 patients (71.1%). Overall sensitivity, specificity, and positive and negative predictive values for MPI compared to invasive angiography were 89.1%, 75.0%, 91.1%, and 70.5%, respectively. CONCLUSIONS: MPI SPECT performed with a half dose of Tc-99m and OSEM-RR image processing correlates well with invasive angiography. (J Nucl Cardiol 2013).

Relation of aspirin response to age in patients with stable coronary artery disease.

Recent studies have suggested that clopidogrel response may vary significantly with age. Limited data are available exploring the age dependency of ex vivo aspirin response in young and old patients with stable coronary artery disease. Patients with stable coronary artery disease (n = 583) who had been treated with aspirin 75 to 325 mg/day for ≥1 week were recruited from a general cardiology practice. The study cohort was divided into 2 groups: patients aged <75 years (n = 438) and patients aged ≥75 years (n = 145). Aspirin response was determined using the VerifyNow Aspirin Test, and resistance was defined as ≥500 or 550 aspirin reaction units (ARU). The independent predictive value of age on VerifyNow score (as a continuous function) was determined using multivariate linear regression, adjusted for gender, body mass index, and diabetes mellitus. Younger and older patients had similar baseline clinical profiles, including relative doses of aspirin therapy. The mean VerifyNow Aspirin Test score was significantly higher in patients aged ≥75 years: 450 ± 54 versus 434 ± 53 ARU (p = 0.0007). After accounting for the primary covariates, age remained a predictor of VerifyNow score (p = 0.007). Aspirin resistance on the basis of the 500-ARU cutoff was higher in older patients (19% vs 11%, p = 0.009), but there was no difference when the 550-ARU cutoff was used (7% vs 5%, p = 0.40). In conclusion, aspirin response differs significantly by age in patients with stable CAD.

Feasibility of myocardial perfusion imaging with half the radiation dose in obese patients using ordered-subset expectation maximization with resolution recovery software.

BACKGROUND: We previously described the feasibility of myocardial perfusion imaging (MPI) with nearly half the radiation dose using ordered-subset expectation maximization with resolution recovery (OSEM-RR) processing. This study sought to determine if the findings can be expanded to obese patients. METHODS: Fifty obese patients (>100 kg) referred for MPI underwent stress-rest or rest-stress studies with a half dose of Tc-99m sestamibi in a 1-day protocol using OSEM-RR processing. Image quality and clinical results were compared with matched patients (by age, sex, weight, presence/probability of coronary artery disease) evaluated with standard "full-dose" Tc-99m sestamibi, mostly in a 2-day protocol. Dose activities were adjusted individually by weight. RESULTS: Mean Tc-99m activity was 33.4 ± 13.9 mCi in the half-dose group and 60 ± 10 mCi in the full-dose group (P < .0001). Respective mean effective doses per study were 10 ± 4 and 18 ± 3 mSv (P < .0001). Overall image quality was good-to-excellent in 94% of the half-dose group and 80% of the full-dose group (P < .045). There was no between-group difference in rate or size of ischemia or infarction, except for stress left ventricular ejection fraction. CONCLUSIONS: MPI with half the radiation dose is feasible in obese patients. Image quality is better than for full-dose MPI, and the procedure can be performed in 1 day.

Feasibility of myocardial perfusion imaging with half the radiation dose using ordered-subset expectation maximization with resolution recovery software.

OBJECTIVE: This study sought to assess the feasibility of performing myocardial perfusion imaging (MPI) with half the technetium activity using ordered-subset expectation maximization with resolution recovery (OSEM-RR), an iterative reconstruction software developed to improve count statistics and acquisition time. METHODS: Two hundred eighteen patients referred for MPI were randomly allocated to undergo stress-rest or rest-stress protocols with standard full-dose (FD) injections of technetium (Tc)-99m sestamibi or half-dose (HD) injections and OSEM-RR processing. Dose activities were adjusted individually by weight. The groups were compared for image quality and clinical results. RESULTS: The groups were similar for mean patient age, weight, and body mass index, sex distribution, pre-test probability of CAD and CAD prevalence. Mean Tc-99m activities for the low-dose and high-dose stages were as follows: FD group: 429 ± 85 MBq and 1132 ± 200 MBq; HD group: 263 ± 129 MBq and 629 ± 85 MBq (P < .0001 for both). Mean effective dose per study was 13.6 ± 1.4 mSv in the FD group and 7.7 ± 1.0 mSv in the HD group (P < .001). Over all image quality was good-to-excellent in 98% and 95% of the groups, respectively. However, when we analyzed the low-dose stage separately, image quality was slightly worse in the HD than the FD, though still within the good-to excellent range. CONCLUSIONS: MPI with nearly half the radiation dose is feasible with good image quality.

Yield of a novel ultra-low-dose computed tomography device mounted on a dedicated cardiac SPECT system in improving the accuracy of myocardial perfusion imaging and the detection of chest abnormalities.

BACKGROUND: To examine the yield of an ultra-low-dose computed tomography (CT) transmission module for attenuation-correction (AC) on a dedicated cardiac camera in evaluation of SPECT-myocardial perfusion imaging (MPI) in the diagnosis of CAD and for additional chest abnormalities. METHODS: The study group included 150 patients with known or suspected CAD referred for technetium sestamibi SPECT MPI. CT transmission scanning (effective radiation 0.17 mSv) was performed after each gated SPECT scan. AC and non-corrected (NC) SPECT scans were evaluated on a 5-point scale using a 17-segment model, and the sum stress score (SSS) and sum rest score (SRS) were calculated for each condition. Overall image quality, sensitivity and normalcy rate (51 patients) and processing of 28 CT slices were screened for chest findings. RESULTS: CT-based AC significantly improved image quality (P = .01). Mean SSS was 3.8 ± 5.8 with AC and 6.1 ± 7.1 with NC (P < .001); the respective SRS values were 2.6 ± 6.3 and 3.9 ± 7.7 (P < .001). The sensitivity of detecting ≥70% stenosis was 71% and 86% (P = NS) and the normalcy rate was 30% and 89% (P < .0001) in NC and AC SPECT MPI, respectively. Chest CT: lung abnormalities in 31%, aortic calcifications in 27%, and hiatus hernia in 5%. CONCLUSIONS: Ultra-low-dose CT for AC of SPECT-MPI improves image quality, diagnostic accuracy and suggests detection of chest findings.

Clopidogrel tapering as a strategy to attenuate platelet rebound phenomenon in patients with bare-metal stents.

Early clustering of adverse cardiovascular events after abrupt cessation of clopidogrel has been reported in patients with acute coronary syndromes. A platelet rebound phenomenon may contribute to this increased thrombotic risk and a gradual drug tapering may attenuate this proposed platelet effect. Accordingly, we aimed to assess the effect of clopidogrel tapering on platelet reactivity. Twenty patients who underwent elective percutaneous coronary interventions with bare metal stents receiving 3 months of clopidogrel therapy (75 mg daily) were randomized to either of two discontinuation strategies: (1) Off group-abrupt drug cessation or (2) Tapering group-receiving clopidogrel 75 mg every other day for 4 weeks duration. Light transmission aggregometry, induced by ADP (5 and 10 µM) and collagen, was measured at four time-points (at baseline and 2, 4 and 6 weeks after randomization). In the off group, there was an early rise in platelet reactivity at 2 weeks after abrupt drug cessation compared to baseline, as measured by ADP 5 µmol/l (39.6 ± 2.8 vs. 67.9 ± 6.0, P < 0.001). The tapering regimen suppressed this rebound platelet aggregation by ADP 5 µmol/l at 2 weeks (P = 0.001) and 4 weeks (P = 0.001). Similar results were found with ADP 10 µmol/l and collagen agonists. Abrupt cessation of clopidogrel results in an early rise in platelet aggregability in patients with BMS that is attenuated by a tapering regimen. Clopidogrel administration every other day may achieve similar levels of platelet inhibition as full dose therapy. Further investigations evaluating clopidogrel tapering strategies and their potential clinical impact are warranted.

Feasibility of myocardial perfusion SPECT with prone and half-time imaging.

BACKGROUND: Myocardial perfusion imaging with single-photon emission tomography (SPECT) is associated with reduced specificity due to tissue attenuation. This can be corrected by prone imaging while necessitating additional imaging time. Image processing with iterative reconstruction allows for a half-time (HT) acquisition. OBJECTIVE: To assess the feasibility of myocardial perfusion with SPECT using prone imaging with HT acquisition. METHODS: Ninety-one patients referred for SPECT myocardial perfusion imaging and weighing up to 90 kg were enrolled for HT supine and prone SPECT protocol. Patients with known myocardial infarction were excluded. HT prone imaging was performed when supine imaging was visually equivocal or abnormal. Image quality was compared for each patient between supine and prone imaging. RESULTS: Acquisition time was 17.9 ± 2.9 min in the HT group compared with 31.8 ± 5.8 min in patients imaged with full-time acquisition. Image quality was good or excellent in 85.7% of studies in a supine position and in 81.3% of studies in the prone position (P = 0.25). No study was considered as nondiagnostic. Prone imaging reduced the rate of equivocal scans from 40.7 to 15.4% and of ischemic studies from 34.1 to 7.7%. In the study population, 80% of inferior and septal defects were corrected by the prone position. CONCLUSION: In a selected population, HT prone and supine imaging is feasible and is associated with a good image quality in most studies whereas acquisition time is reduced almost by half.

Circulating endothelial progenitor cell levels and function in patients who experienced late coronary stent thrombosis.

AIMS: The pathogenesis of late coronary stent thrombosis may be related to impaired arterial healing. Endothelial progenitor cells (EPCs) have been shown to play an important role in repair and re-endothelialization following vascular injury. We hypothesized that patients who develop late stent thrombosis may have reduced or dysfunctional EPCs, and aimed to compare EPC level and function in patients who experienced stent thrombosis vs. matched controls. METHODS AND RESULTS: Patients who developed late (> 30 days) stent thrombosis within the past 3 years were compared with matched patients who underwent stenting and did not develop stent thrombosis. All patients had blood samples taken ≥ 3 months from the stent thrombosis or index procedure. The proportion of peripheral mononuclear cells (PMNCs) expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34 was evaluated by flow cytometry. Endothelial progenitor cell colony forming units (CFUs) were grown from PMNCs, characterized and counted following 7 days of culture. The two groups (n = 30 each) were well-matched (93.3% men, mean age 60-62 years, 33.3% diabetes, 73-80% DESs). The proportion of cells co-expressing VEGFR-2, CD133, and CD34 was lower in the stent thrombosis group compared with the control [VEGFR-2(+)CD133(+): 0.18% (0.03-0.41%) vs. 0.47% (0.16-0.66%), P = 0.01; VEGFR-2(+)CD34(+): 0.32% (0.22-0.70%) vs. 0.66% (0.24-1.1%), P = 0.03]. The number of EPC CFUs was also lower in the stent thrombosis group [3.9% (3.2-5.5%) vs. 8.3% (6.5-13.4%) colonies/well, respectively, P < 0.0001]. CONCLUSION: Patients who suffered late coronary stent thrombosis appear to have reduced levels of circulating EPCs and impaired functional properties of the cells. These findings require validation by further studies, but may contribute to understanding the pathogenesis of late stent thrombosis.

Treatment of aspirin-resistant patients with omega-3 fatty acids versus aspirin dose escalation.

OBJECTIVES: The aim of this study was to evaluate whether addition of omega-3 fatty acids or increase in aspirin dose improves response to low-dose aspirin among patients who are aspirin resistant. BACKGROUND: Low response to aspirin has been associated with adverse cardiovascular events. However, there is no established therapeutic approach to overcome aspirin resistance. Omega-3 fatty acids decrease the availability of platelet arachidonic acid (AA) and indirectly thromboxane A2 formation. METHODS: Patients (n = 485) with stable coronary artery disease taking low-dose aspirin (75 to 162 mg) for at least 1 week were screened for aspirin response with the VerifyNow Aspirin assay (Accumetrics, San Diego, California). Further testing was performed by platelet aggregation. Aspirin resistance was defined by > or =2 of 3 criteria: VerifyNow score > or =550, 0.5-mg/ml AA-induced aggregation > or =20%, and 10-micromol/l adenosine diphosphate (ADP)-induced aggregation > or =70%. Thirty patients (6.2%) were found to be aspirin resistant and randomized to receive either low-dose aspirin + omega-3 fatty acids (4 capsules daily) or aspirin 325 mg daily. After 30 days of treatment patients were re-tested. RESULTS: Both groups (n = 15 each) had similar clinical characteristics. After treatment significant reductions in AA- and ADP-induced aggregation and the VerifyNow score were observed in both groups. Plasma levels of thromboxane B2 were also reduced in both groups (56.8% reduction in the omega-3 fatty acids group, and 39.6% decrease in the aspirin group). Twelve patients (80%) who received omega-3 fatty acids and 11 patients (73%) who received aspirin 325 mg were no longer aspirin resistant after treatment. CONCLUSIONS: Treatment of aspirin-resistant patients by adding omega-3 fatty acids or increasing the aspirin dose seems to improve response to aspirin and effectively reduces platelet reactivity.

Myocardial perfusion profile in a young population with and without known coronary artery disease: comparison by gender.

BACKGROUND: More and more young people are being referred for evaluation or screening for coronary artery disease (CAD). However, the value of myocardial perfusion imaging (MPI) in this population is unclear, especially in the absence of symptoms. METHODS: The study sample included 1765 consecutive patients less than 51 years old who were referred to a major medical center for stress/rest MPI study. Clinical and MPI variables were compared between patients with and without known CAD, by gender. RESULTS: There were 1346 (76%) men and 419 (24%) women of mean age 44 +/- 6 years; 461 (26%) had known CAD. Stress-induced ischemia was detected in 321 patients (18.2%) and significant ischemia in 131 (7.4%); there was no difference in the rate or severity of ischemia by presence of symptoms. Among those without known CAD, the rate of stress-induced ischemia by MPI was significantly lower in women than men. On logistic regression analysis, the independent predictors of ischemia in men were high cholesterol, diabetes, angina during stress testing, ST depression, and smoking (P<.0001); and in women, the independent predictors were diabetes and high cholesterol. CONCLUSION: Known CAD and stress-induced ischemia are significantly more prevalent in young men than in young women, irrespective of risk factors. The independent predictors of ischemia differ between men and women.

The impact of renal insufficiency on patients' outcomes in emergent angioplasty for acute myocardial infarction.

BACKGROUND: Renal insufficiency (RF) was shown to be associated with a worsened prognosis following acute myocardial infarction (AMI). OBJECTIVES: The authors analyzed the outcomes of AMI patients with impaired renal function tests treated using primary percutaneous coronary intervention (PCI), to determine factors associated with increased mortality risk. METHODS: This study included 558 consecutive AMI patients treated using primary PCI between January 2001 and June 2005. The authors compared outcome results according to glomerular filtration rate (GFR). An abbreviated equation was used to calculate GFR. Patients were grouped as follow: normal (> or =90 mL/min/1.73 m(2)), mildly impaired (60-89 mL/min/1.73 m(2)), moderately impaired (30-59 mL/min/1.73 m(2)), and severely impaired GFR (< 30 mL/min/1.73 m(2)). RESULTS: There was a stepwise increase in 30-day mortality among patients with normal, mildly, moderately, and severely impaired RF: 2.1%, 3.7%, 8.2%, and 22.2%, respectively (P = 0.004). Seventeen out of the 324 with any degree of RF died within 1 month [5.3%] of these nine patients [53%] died because of cardiac cause. Univariate correlation analysis, factors associated with an increased risk of 1 month mortality included: age > 75 years, left ventricular ejection fraction < 35%, lower GFR, killip class > 1, multivessel coronary artery disease, failure to achieve TIMI flow grade = 3, the occurrence of no-reflow, IABP use, lack of administration of anti GP 2b/3a. The amount of contrast media used during the procedure [mL/Kg] as well as renal function deterioration were also associated with increased mortality. CONCLUSIONS: Clinical and angiographic parameters collected before and during PCI can be used to predict 30-day mortality among AMI patients with RF. Findings indicate that in the setting of contemporary catheter-based reperfusion strategy for AMI, the extent of coronary artery disease, measures of PCI complexity, and degree of renal impairment prior/following the procedure are altogether related to mortality.