Probucol therapy improves long-term (>10-year) survival after complete revascularization: a propensity analysis

ObjectiveProbucol has anti-atherosclerotic properties and has been shown to reduce post-angioplasty coronary restenosis. However, the effect of probucol therapy on long-term (>10 years) outcome following coronary revascularization is less well established. Accordingly, we sought to determine if probucol therapy at the time of complete coronary revascularization reduces mortality in patients with coronary artery disease (CAD).MethodsWe collected data from 1694 consecutive patients who underwent complete revascularization (PCI and/or bypass surgery). Mortality data were compared between patients administered probucol and those not administered probucol at the time of revascularization. A propensity score (PS) was calculated to evaluate the effects of variables related to decisions regarding probucol administration. The association of probucol use and mortality was assessed using 3 Cox regression models, namely, conventional adjustment, covariate adjustment using PS, and matching patients in the probucol and no-probucol groups using PS.ResultsIn the pre-match patients, 231 patients were administered probucol (13.6%). During follow-up [10.2 (SD, 3.2) years], 352 patients died (including 113 patients who died of cardiac-related issues). Probucol use was associated with significant decrease in all-cause death (hazard ratio [HR], 0.65; P = 0.036 [conventional adjustment model] and HR, 0.57; P = 0.008 [PS adjusted model]). In post-match patients (N = 450, 225 matched pair), the risk of all-cause mortality was significantly lower in the probucol group than in the no-probucol group (HR, 0.45; P = 0.002).ConclusionIn CAD patients who had undergone complete revascularization, probucol therapy was associated with a significantly reduced risk of all-cause mortality.     

Adiponectin is associated with increased mortality and heart failure in patients with stable ischemic heart disease: data from the Heart and Soul Study

ObjectiveSerum adiponectin protects against incident ischemic heart disease (IHD). However, in patients with existing IHD, higher adiponectin levels are paradoxically associated with worse outcomes. We investigated this paradox by evaluating the relationship between adiponectin and cardiovascular events in patients with existing IHD.MethodsWe measured total serum adiponectin and cardiac disease severity by stress echocardiography in 981 outpatients with stable IHD who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent heart failure hospitalizations, myocardial infarction, and death were recorded.ResultsDuring an average of 7.1 years of follow-up, patients with adiponectin levels in the highest quartile were more likely than those in the lowest quartile to be hospitalized for heart failure (23% vs. 13%; demographics-adjusted hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.04–2.56, p = 0.03) or die (49% vs. 31%; HR 1.67, 95% CI 1.24–2.26, p < 0.008), but not more likely to have a myocardial infarction (12% vs. 17%; HR 0.64, 95% CI 0.38–1.06, p = 0.08). The combined outcome of myocardial infarction, heart failure, or death occurred in 56% (136/245) of participants in the highest quartile of adiponectin vs. 38% (94/246) of participants in the lowest quartile (HR 1.54, 95% CI 1.31–2.21, p < 0.002). Adjustment for left ventricular ejection fraction, diastolic dysfunction, inducible ischemia, C-reactive protein, and NT-proBNP attenuated the association between higher adiponectin and increased risk of subsequent events (HR 1.43, 95% CI 0.98–2.09, p = 0.06).ConclusionsHigher concentrations of adiponectin were associated with heart failure and mortality among patients with existing IHD.     

Predictive value of white blood cell subtypes for long-term outcome following myocardial infarction

IntroductionElevation of total white blood cells (WBC) count is associated with higher mortality in patients with acute coronary syndromes. However, it is unknown which specific subset of leukocytes best correlates with increased risk of adverse outcome.Methods and resultsWe prospectively studied the predictive value of WBC subtypes for long-term outcome in 1037 patients with acute myocardial infarction (AMI). Total WBC, neutrophil, monocyte and lymphocyte counts, and high-sensitivity C-reactive protein (CRP) were obtained in each patient. The median duration of follow up was 23 months (range, 6–42 months). Analyzed separately, baseline total WBC (HR 2.2, 95% CI 1.5–3.3; P < 0.0001), neutrophil (HR 2.7, 95% CI 1.8–4.1; P < 0.0001) and monocyte (HR 1.9, 95% CI 1.3–2.8; P = 0.001) counts in the upper quartile, and lymphocyte count in the lower quartile (HR 1.5, 95% CI 1.1–2.3; P = 0.03), were all independent predictors of mortality. Comparing nested models, adding other WBC data failed to improve model based on neutrophil count. In contrast, adding neutrophil count to the models based on total WBC (P = 0.01), on monocyte count (P < 0.0001) or on lymphocyte count (P < 0.0001) improved the prediction of the models. Neutrophil count in the upper quartile (≥9800 μL^?1) remained a strong independent predictor of mortality after adjustment for left ventricular systolic function and for CRP (HR 2.2, 95% CI 1.6–3.0; P < 0.0001).ConclusionOf all WBC subtypes, elevated neutrophil count best correlates with mortality in patients with AMI. Neutrophil count provides additive prognostic information when combined with CRP.     

Helicobacter pylori infection, chronic atrophic gastritis and major cardiovascular events: a population-based cohort study

ObjectiveThere is debate whether infection with Helicobacter (H.) pylori, the main inducer of chronic atrophic gastritis (CAG), is a risk factor for cardiovascular disease and premature mortality.MethodsSerological measurements of H. pylori infection and pepsinogen (PG) I and II were obtained in a population-based German cohort of 9953 older adults (50–74 years). Cox regression was employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for myocardial infarction, stroke, cardiovascular and all-cause mortality during five-year follow-up.ResultsAccording to serology, 4977 participants (51.9%) were infected with H. pylori (2604 with cytotoxin-associated gene A (cagA) strains) and 541 (5.7%) had CAG (PGI < 70 ng/mL and PGI/PGII < 3). During follow-up, 540 participants died (163 from cardiovascular causes), 170 experienced a primary myocardial infarction and 241 had a stroke. Neither cytotoxin-associated gene A (cagA) negative nor cagA positive H. pylori infections were associated with an increased risk for myocardial infarction, stroke or all-cause mortality. Intriguingly, infection with cagA positive H. pylori strains was inversely associated with cardiovascular mortality (HR, 0.62; CI: 0.41–0.94). No statistically significant associations were observed for the small group of participants with CAG, but point estimates of adjusted HRs for myocardial infarction, stroke and cardiovascular mortality were all below 1 (0.71, 0.59 and 0.65, respectively).ConclusionsOur results do not support the hypothesis that H. pylori infection or CAG are risk factors for cardiovascular disease or mortality and instead suggest an inverse relationship of cagA positive H. pylori infection with fatal cardiovascular events.     

Optimal strategy of coronary revascularization in chronic kidney disease patients: A meta-analysis

BackgroundPatients with chronic kidney disease (CKD) have high risks of coronary artery disease (CAD). Coronary revascularization is beneficial for long-term survival, but the optimal strategy remains still controversial.MethodsWe searched studies that have compared percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) for revascularization of the coronary arteries in CKD patients. Short-term (30 days or in-hospital) mortality, long-term (at least 12 months) all-cause mortality, cardiac mortality and the incidence of late myocardial infarction and recurrence of revascularization were estimated.Results28 studies with 38,740 patients were included. All were retrospective studies from 1977 to 2012. Meta-analysis showed that PCI group had lower short-term mortality (OR 0.55, 95% CI 0.41 to 0.73, P < 0.01), but had higher long-term all-cause mortality (OR 1.29, 95% CI 1.23 to 1.35, P < 0.01). Higher cardiac mortality (OR 1.08, 95% CI 1.01 to 1.15, P < 0.05), higher incidence of late myocardial infarction (OR 1.78, 95% CI 1.65 to 1.91, P < 0.01) and recurring revascularization rate (OR 2.94, 95%CI 2.15 to 4.01, P < 0.01) is found amongst PCI treated patients compared to CABG group.ConclusionsCKD patients with CAD received CABG had higher risk of short-term mortality but lower risks of long-term all-cause mortality, cardiac mortality and late myocardial infarction compared to PCI. This could be due to less probable repeated revascularization.     

Benefits from intracoronary as compared to intravenous abciximab administration for STEMI patients undergoing primary angioplasty: a meta-analysis of 8 randomized trials

BackgroundAdjunctive abciximab administration has been demonstrated to reduce mortality and reinfarction in patients with ST-elevation myocardial infarction (STEMI) referred to invasive management. Standard abciximab regimen consists of an intravenous (IV) bolus followed by a 12-h IV infusion. Experimental studies and small clinical trials suggest the superiority of intracoronary (IC) injection of abciximab over IV route. Therefore, the aim of the current study was to perform a meta-analysis of randomized trials (RCTs) to assess the clinical efficacy and safety of IC vs IV abciximab administration in STEMI patients undergoing primary angioplasty.MethodsWe obtained results from all RCTs enrolling STEMI patients undergoing primary percutaneous coronary intervention (PCI). The primary endpoint was mortality, while recurrent myocardial infarction, postprocedural epicardial (TIMI 3) and myocardial (MBG 2–3) perfusion were identified as secondary endpoints. The safety endpoint was the risk of major bleeding complications.ResultsA total of 8 randomized trials were finally included in the meta-analysis, enrolling a total of 3259 patients. As compared to IV route, IC abciximab was associated with a significant improvement in myocardial perfusion (OR [95% CI] = 1.76 [1.28–2.42], p < 0.001), without significant benefits in terms of mortality (OR [95% CI] = 0.85 [0.59–1.23], p = 0.39), reinfarction (OR [95% CI] = 0.79 [0.46–1.33], p = 0.37), or major bleeding complications (OR [95% CI] = 1.19 [0.76–1.87], p = 0.44). However, we observed a significant relationship between patient's risk profile and mortality benefits from IC abciximab administration (p = 0.011).ConclusionsThe present updated meta-analysis showed that IC administration of abciximab is associated with significant benefits in myocardial perfusion, but not in clinical outcome at short-term follow-up as compared to IV abciximab administration, without any excess of major bleedings in STEMI patients undergoing primary PCI. However, a significant relationship was observed between patient's risk profile and mortality benefits from IC abciximab administration. Therefore, waiting for long-term follow-up results and additional randomized trials, IC abciximab administration cannot be routinely recommended, but may be considered in high-risk patients.     

The relation of serum gamma-glutamyl transferase levels with coronary lesion complexity and long-term outcome in patients with stable coronary artery disease

BackgroundRelation of serum gamma-glutamyl transferase (GGT) levels with extent, severity, and complexity of coronary artery disease has not been adequately studied. Therefore, we evaluated the relationship between GGT levels and coronary complexity, severity and extent assessed by SYNTAX score and long-term adverse events.MethodsWe enrolled 442 consecutive patients with stable angina pectoris who underwent coronary angiography. Baseline serum GGT levels were measured and SYNTAX score was calculated from the study population. Median follow-up duration was 363 days. Endpoints were all cause mortality and any revascularization.ResultsGGT levels demonstrated an increase from low SYNTAX tertile to high tertile. In multivariate analysis serum GGT, diabetes mellitus, HDL-cholesterol, eGFR and ejection fraction were found to be independent predictors of high SYNTAX score. The survival analysis showed that long-term revascularization rates were comparable between the GGT groups (for 36 U/l cut point) of the overall population (7.7% vs 8.6% logrank, p = 0.577), whereas long-term all cause mortality rate was higher in the GGT ≥ 36 U/l group (3.6% vs 11.6% logrank, p = 0.001). In Cox proportional hazards regression model, GGT ≥ 36 U/l group was found to be an independent predictor of long-term all cause mortality in the unadjusted (HR 2.54, 95% CI 1.17–5.48, p = 0.018) and age- and gender-adjusted (HR 2.58, 95% CI 1.19–5.58, p = 0.016) models.ConclusionSerum GGT level was independently associated with coronary complexity and long-term mortality in patients with stable coronary artery disease.     

The prognostic association between resting heart rate and cardiac death--myocardial perfusion defects as a potential mechanism

ObjectiveElevated resting heart rate (RHR) is a robust risk factor for cardiac events, and recent clinical trial evidence suggests lowering RHR may reduce cardiac risk among individuals with elevated RHR and known coronary artery disease (CAD). This study sought to elucidate the extent to which myocardial perfusion defects explain the association between RHR and cardiac death among individuals with known or suspected CAD undergoing myocardial perfusion imaging (MPI).MethodsThis retrospective cohort study included 3708 individuals with known or suspected CAD who underwent clinically indicated MPI with positron emission tomography (PET MPI). Stress, rest, and stress-induced myocardial perfusion defect sizes were measured objectively by automated computer software as percent of left ventricular myocardium hypoperfused. RHR was measured by electrocardiography prior to rest PET MPI. Cardiac and non-cardiac death information was obtained through the National Death Index. All analyses were stratified by beta blocker (BB) use.ResultsRHR was consistently associated with the presence of significant myocardial perfusion defects, though associations were stronger among BB than non-BB users. Among BB users, RHR was strongly associated with an increased risk of cardiac death in adjusted models before (hazard ratio [HR] = 2.6 comparing RHR ≥ 80 bpm vs. RHR < 60, p < 0.05) and after (HR = 2.4, p < 0.05) including stress myocardial perfusion defect size in the model. Results were similarly strong among non-BB users.ConclusionsResting heart rate was independently associated with cardiac death, however there was little evidence suggesting this association was explained by the presence of myocardial perfusion defects.     

Effect of free fatty acid inhibition on silent and symptomatic myocardial ischemia in diabetic patients with coronary artery disease

ObjectiveFree fatty acid inhibition with trimetazidine (TMZ) improves myocardial metabolism and myocardial ischemia in patients with coronary artery disease (CAD). Because of its effect on myocardial glucose utilization TMZ may represent a therapeutic option in diabetic patients with CAD. Aim of the present study was to evaluate whether the metabolic effect of TMZ may improve episodes of myocardial ischemia in diabetic patients with CAD.Research design and methodsWe assessed the effect of TMZ on 24 h ambulatory ECG monitoring (AEM) in 30 patients (22 males and 8 females, mean (SE) age 67 ± 6.5 years) with NIDDM and ischemic cardiomyopathy. Patients were randomized to receive on top of standard therapy either TMZ (20 mg, tds) or placebo (tds) and were evaluated at baseline and after 6 months.ResultsPatients randomized to TMZ or placebo were comparable regarding demographic data, distribution of CAD, and glicated haemoglobin levels. TMZ significantly reduced the number of episodes of transient myocardial ischemia (− 24% compared to baseline, p < 0.01; − 27% compared to placebo, p < 0.01), and Total Ischemic Burden (− 28% compared to baseline, p < 0.01; − 29% compared to placebo, p < 0.01). TMZ also significantly reduced the number of silent episodes of myocardial ischemia (− 42% compared to baseline and − 39% compared to placebo, p < 0.01) and the time of silent myocardial ischemia/24 h (− 37% compared to baseline and − 35% compared to placebo, p < 0.01). No significant changes in heart rate were detected between baseline, placebo and TMZ evaluations.ConclusionsTMZ is effective in reducing silent and symptomatic episodes of transient myocardial ischemia in diabetic patients with CAD on standard anti-anginal therapy.     

Association of single measurement of estimated glomerular filtration rate and non-quantitative dipstick proteinuria with all-cause and cardiovascular mortality in the elderly. Results from the Progetto Veneto Anziani (Pro.V.A.) Study

ObjectiveTo explore the independent and combined clinical validity of estimated glomerular filtration rate (eGFR) and proteinuria on predicting all-cause and cardiovascular mortality in an Italian elderly population.MethodsBaseline eGFR and proteinuria, all-cause and cardiovascular mortality during a mean follow-up time of 4.4 years were evaluated in 3063 subjects aged 65 years and older of the Progetto Veneto Anziani (Pro.V.A.) Study.ResultsSubjects with eGFR < 60 ml/min/1.73 m² (n = 956) presented a higher prevalence of proteinuria in comparison with those with eGFR ≥ 60 ml/min/1.73 m² (33.8% vs 25.1%, p < 0.01). After multivariable adjustment including proteinuria and major diseases, eGFR < 60 ml/min/1.73 m² was not associated with increased all-cause mortality. After multivariable adjustment including eGFR and major diseases, proteinuria was associated with all-cause mortality in overall subjects (HR = 1.43, 95% CI 1.15–1.78, p < 0.01), and in both sexes. After multivariable adjustment both eGFR < 60 ml/min/1.73 m² (HR = 1.68, 95% CI 1.02–2.78, p = 0.04), and proteinuria (HR = 2.07, 95% CI 1.31–3.27, p < 0.01) were associated with increased cardiovascular mortality. Subjects with both impaired eGFR and presence of proteinuria showed a higher risk for both all-cause and cardiovascular mortality compared to those with normal eGFR and absence of proteinuria.ConclusionIn this general Italian elderly population proteinuria is an independent predictor of all-cause and cardiovascular mortality, while eGFR is not an independent predictor of all-cause mortality, and it is nominally significantly associated with cardiovascular mortality. However, mortality risk is higher in individuals with combined reduced eGFR and proteinuria.     

Fate of individuals with ischemic amputations in the REACH Registry: three-year cardiovascular and limb-related outcomes

ObjectiveTo evaluate systemic and limb ischemic event rates of PAD patients with prior leg amputation and determine predictors of adverse outcomes.MethodsThe REduction of Atherothrombosis for Continued Health (REACH) Registry provided a prospective multinational cohort of 7996 outpatients with PAD enrolled from primary medical clinics in 44 countries in 2003–2004. 1160 patients (14.5%) had a prior leg amputation at any level. Systemic (myocardial infarction [MI], stroke, cardiovascular death) and limb (angioplasty, surgery, amputation) ischemic event rates were determined in a 3-year follow-up.ResultsPAD patients with leg amputations on entry had a 5-fold higher rate of a subsequent amputation (12.4% vs. 2.4%, P < .001), lower rate of peripheral angioplasty (8.3% vs. 10.7%, P = .005), and similar rates of surgical revascularization procedures compared with PAD patients without amputation. A nearly 2-fold increase in rates of cardiovascular death (14.5% vs. 7.7%, P < .001) and all-cause mortality (21.8% vs. 12.6%, P < .001) and an increase in the composite outcome of MI, stroke, cardiovascular death, or hospitalization (48.7% vs. 40.0%, P < .001) were noted. Recent (≤1 year) amputation was associated with higher rates of worsening PAD, subsequent lower extremity surgical revascularization procedures, re-amputation, non-fatal MI, and the composite outcome, including hospitalization. Adverse systemic and limb ischemic outcomes were similar regardless of amputation level.ConclusionsIndividuals with a history of leg amputations have markedly elevated rates of systemic and limb-related outcomes. PAD patients with recent ischemic amputation have the highest risk of adverse events. A history of “minor” ischemic amputation may confer an identical systemic risk as “major” leg amputation.     

Independent prognostic value of C-reactive protein and coronary artery disease extent in patients affected by unstable angina

BackgroundPrevious studies have reported conflicting results on the association between C-reactive protein (CRP) and extent of atherosclerosis, suggesting that the association between CRP and outcome in patients with acute coronary syndromes is independent of coronary artery disease extent. We tested this hypothesis in a selected population of patients with unstable angina undergoing coronary angiography.MethodsNinety-seven consecutive patients with unstable angina were enrolled in this single-centre study. All patients underwent coronary angiography. CRP was measured by an ultrasensitive nephelometric method. We also measured serum levels of soluble CD40 ligand by ELISA and plasma fibrinogen levels by use of the Clauss method. Atherosclerotic disease severity and extent were assessed by angiography using the Bogaty score. The extent index refers to the proportion of the coronary tree affected by detectable atheroma on angiography. The primary end-point at 6 months was a composite of: (a) death, (b) myocardial infarction, and (c) recurrence of unstable angina requiring hospitalization. Cardiac death was the secondary end-point.ResultsNo significant correlation was found between baseline CRP serum levels and angiographic measures of atherosclerotic disease severity and extent, whereas a trend for a significant correlation was found between soluble CD40 ligand and extent index (p = 0.06). Diabetic patients exhibited a higher extent index compared to non-diabetic patients (0.94 ± 0.1 versus 0.7 ± 0.04, p = 0.04). Predictors of primary end-point at both univariate and multivariate analysis were: extent index (p = 0.04 and 0.04, respectively), CRP levels (p = 0.05 and 0.02, respectively), and lack of revascularization (p = 0.03 and 0.02, respectively). Fibrinogen levels were the only independent predictor of cardiac death at follow-up (p = 0.04).ConclusionIn this study we demonstrate that in patients with unstable angina, CRP serum levels and coronary atherosclerosis are not correlated, but both are independently associated with a worse outcome at 6-month follow-up.     

Dietary fats and dietary cholesterol and risk of stroke in women

ObjectiveThe interplay between oxidative stress and inflammation is crucial in the pathogenesis of atherosclerosis. The adaptor protein p66Shc is implicated in atherogenesis and oxidative stress related responses in animal models of diseases. However, its role in humans remains to be defined. In this study, we hypothesized that expression of p66Shc increases in peripheral blood monocytes of patients affected by acute coronary syndromes (ACS).MethodsMale subjects aged 59 ± 4 (mean ± SD) years admitted for cardiac catheterization were subdivided in three groups: (a) no local stenosis for the control group, (b) at least one stenosis ≥75% in either left, circumflex or right coronary artery for the coronary artery disease (CAD) group or (c) ST-elevation/non-ST-elevation myocardial infarction for the ACS group. Monocytes were isolated from whole blood and p66Shc RNA levels were determined by quantitative real time PCR.Resultsp66Shc RNA levels were increased in ACS patients as compared to CAD (p = 0.007) and controls (p = 0.0249). Furthermore, malondialdehyde (MDA) and C-reactive protein (CRP) were increased in plasma of ACS patients. Levels of MDA correlated positively to p66Shc (r = 0.376, p = 0.01). Our data demonstrate increased p66Shc levels in monocytes of ACS but not CAD patients.ConclusionThis study suggests an involvement of p66Shc in the transition of a stable CAD to an ACS patient. p66Shc was associated with states of increased oxidative stress. Further work is needed to understand whether p66Shc may represent a possible pharmacological target or whether it represents an interesting novel biomarker.     

CYP2C19*2/ABCB1-C3435T polymorphism and risk of cardiovascular events in coronary artery disease patients on clopidogrel: Is clinical testing helpful?

BackgroundStudies evaluating CYP2C19*2 and ABCB1-C3435T polymorphisms have shown conflicting results. We performed this meta-analysis to evaluate role of clinical testing for these polymorphisms in CAD patients on clopidogrel.Methods19,601 patients from 14 trials were analyzed. The endpoints were major adverse cardiovascular events (MACE), cardiovascular (CV) death, stent thrombosis (ST), myocardial infarction (MI), stroke and major bleeding. Combined relative risks (RR) with 95% confidence intervals (CI) were computed for each outcome by using standard methods of meta-analysis and test parameters were computed.ResultsCYP2C19*2 polymorphism was associated with higher risk of MACE [RR: 1.28, CI: 1.06–1.54; p = 0.009], CV death [RR: 3.21, CI: 1.65–6.23; p = 0.001], MI [RR: 1.36, CI: 1.12–1.65; p = 0.002], ST [RR: 2.41, CI: 1.69–3.41; p < 0.001]. No difference was seen in major bleeding events [RR: 1.02, CI: 0.86–1.20; p = 0.83]. Subgroup analysis showed similar results for elective PCI [RR: 1.34, CI: 1.01–1.76; p = 0.03], and PCI with DES [RR: 1.53, CI: 1.029–1.269; p = 0.03]. CYP2C19*2 polymorphism has very low sensitivity (28–58%), specificity (71–73%), positive predictive value (3–10%) but good negative predictive value (92–99%). ABCB1-C3435T polymorphism analysis revealed similar MACE [RR: 1.13, CI: 0.99–1.29; p = 0.06], ST [RR: 0.88, CI: 0.52–1.47; p = 0.63] and major bleeding [RR: 1.04, CI: 0.87–1.25; p = 0.62] in both groups.ConclusionIn CAD patients on clopidogrel therapy, CYP2C19*2 polymorphism is associated with significantly increased adverse cardiovascular events. However, due to the low positive predictive value, routine genetic testing cannot be recommended at present.     

Subclinical coronary atherosclerosis and resting ECG abnormalities in an unselected general population

ObjectivesExposure to cardiovascular (CV) risk factors may result in coronary atherosclerosis and myocardial disease, which is reflected in the extent of coronary artery calcification (CAC) and resting ECG abnormalities, respectively. We studied the association of CAC with ECG abnormalities in a general population without myocardial infarction or revascularization.MethodsThe total cohort of 4814 subjects (45–75 years) were randomly selected from the general population for the Heinz Nixdorf Recall Study, an ongoing study designed to assess the prognostic value of modern risk stratification methods. In addition to measuring standard risk factors, digitized resting ECGs and the EBT-based Agatston score were obtained. Subjects were separated into those without (n = 1929) and with CV disease (CVD) or treated risk factors (tRF) (n = 2558).ResultsIn both groups, a positive CAC-score was more frequent and CAC-scores were higher in men and women with ECG abnormalities as compared to those with normal ECGs (p < 0.05 each). In persons without CVD/tRF, a CAC ≥75th percentile was more frequent in those with LVH (42.4%) and QTc >440 ms (34.2%) as compared to normal ECGs (23.0%, p < 0.01 for both). In persons with CVD/tRF, a CAC-score ≥75th percentile was found in subjects with A-Fib (46.3%), borderline-LVH (39.1%), ECG signs of MI (40.5%) and major ECG abnormalities (40.3%) versus 31.2% in those with normal ECGs (p < 0.03 for all). In multivariate analysis, LVH (p = 0.025) and major ECG abnormalities (p = 0.04) remained independently associated with CAC in subjects without and with CVD/tRF, respectively.ConclusionsECG-based evidence of myocardial disease is often associated with an elevated CAC burden, suggesting a link between epicardial and myocardial manifestations of risk factor exposure. The association of CAC burden with different ECG abnormalities in different clinical groups may have implications for the interpretation of the resting ECG and CAC burden in risk stratification.     

Association between cytochrome P450 2C19 polymorphism and clinical outcomes in Chinese patients with coronary artery disease

BackgroundCytochrome P450 (CYP)2C19 is expressed in vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which play a key role in regulating vascular tone. The aim of this study was to investigate whether the genetic functional variant 681G > A (*2) of cytochrome CYP2C19 is associated with adverse cardiovascular outcomes in Chinese patients with coronary artery disease (CAD).MethodsBetween July 2008 and September 2009, 654 consecutive patients with CAD were enrolled in this study. All participants underwent CYP2C19 genotyping. The primary study endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Secondary endpoints included the components of the primary endpoint, death from any cause, and recurrent revascularization.ResultsThe baseline characteristics were well-balanced between carriers (heterozygous *1/*2, n = 291; homozygous *2/*2, n = 57) and non-carriers (n = 306) of the CYP2C19*2 variant. During the follow-up period (11.42 ± 4.23 months), the primary endpoint occurred more frequently in homozygous *2/*2 than in non-carriers (n = 306) of CYP2C19*2 variant (12.28% versus 3.27%; adjusted hazard ratio [HR] = 5.191; 95% confidence interval [CI] = 1.936–13.917; P = 0.001); however, no such increase was evident in heterozygous *1/*2 patients (4.12% versus 3.27%; adjusted HR = 1.208; 95% CI 0.517–2.822; P = 0.662).ConclusionsThe homozygous CYP2C19*2/*2 genotype is an independent determinant of adverse vascular events in Chinese patients with CAD.     

Epicardial fat volume and concurrent presence of both myocardial ischemia and obstructive coronary artery disease

ObjectiveEpicardial fat volume (EFV) is linked to cardiovascular event risk. The aim of this study was to evaluate whether EFV is independently related to concurrent presence of both myocardial ischemia and obstructive coronary stenosis.MethodsWe studied 92 consecutive patients without known coronary artery disease (CAD) who underwent Rb-82 PET, coronary calcium scoring (CCS) and invasive coronary angiography (ICA) within 6 months. EFV was computed from non-contrast CT by validated software and indexed to body surface-area (EFVi, cm³/m²). Ischemia was defined by ≥5% difference of total perfusion deficit (quantified by validated software) between stress and rest. Obstructive stenosis was defined ≥50% luminal diameter stenosis.ResultsFifty three patients had both ischemia and stenosis. Compared to those without, patients with both having ischemia and stenosis had significantly higher CCS (1125 ± 1230 vs. 626 ± 690, p = 0.02) and EFVi (64.6 ± 20.6 vs. 49.7 ± 14.2 cm³/m², p = 0.0002). On multivariable analysis after adjusting age, gender, cardiovascular risk factors, chest pain, and CCS (≥400), only elevated EFVi (>68.1 cm³/m²) significantly predicted concurrent presence of both ischemia and stenosis (odds ratio 6.18, 95% confidence interval 1.73–22.01, p = 0.005). Area under the receiver-operator-characteristic analysis demonstrated a trend towards improved incremental prediction of concurrent myocardial ischemia and obstructive stenosis over age, gender, chest pain, and high CCS (0.73 vs. 0.65, p = 0.09).ConclusionsOur study suggests that elevated EFVi measured using non-contrast CT may be related to concurrent presence of both ischemia and stenosis.     

Comparison of late mortality after transcatheter aortic valve implantation versus surgical aortic valve replacement: Insights from a meta-analysis

IntroductionTranscatheter aortic valve implantation (TAVI) has shown non-inferior late mortality in severe aortic stenosis (AS) patients in intermediate to inoperable risk for surgery compared to surgical aortic valve replacement (SAVR). Late outcome of TAVI compared to SAVR is crucial as the number of TAVI continues to increase over the last few years.MethodsA comprehensive literature search of PUBMED and EMBASE were conducted. Inclusion criteria were that [1] study design was a randomized controlled trial (RCT) or a propensity-score matched (PSM) study: [2] outcomes included > 2-year all-cause mortality in both TAVI and SAVR. The random-effects model was utilized to calculate an overall effect size of TAVI compared to SAVR in all-cause mortality. Publication bias was assessed quantitatively with Egger's test.ResultsA total of 14 studies with 6503 (3292 TAVI and 3211 SAVR, respectively) were included in the meta-analysis. There was no difference in late all-cause mortality between TAVI and SAVR (HR 1.17, 95%CI 0.98–1.41, p = 0.08, I² = 61%). The sub-group analysis of all-cause mortality of RCT (HR 0.93 95%CI 0.78–1.10, p = 0.38, I² = 40%) and PSM studies (HR 1.44 95%CI 1.15–1.80, p = 0.02, I² = 35%) differed significantly (p for subgroup differences = 0.002). Meta-regression implicated that increased age and co-existing CAD may be associated with more advantageous effects of TAVI relative to SAVR on reducing late mortality. There was no evidence of significant publication bias (p = 0.19 for Egger's test).ConclusionsTAVI conferred similar late all-cause mortality compared to SAVR in a meta-analysis of RCT but had worse outcomes in a meta-analysis of PSM.     

Implementation of a pre-hospital network favoring primary angioplasty in STEMI to reduce mortality: the Algarve Project

ObjectiveTo analyze the impact of reperfusion by either primary percutaneous coronary intervention (PPCI) or fibrinolysis, and mortality rates of a pre-hospital fast-track network for treating patients with ST-elevation myocardial infarction (STEMI).Methods and ResultsA pre-hospital network for STEMI patients, designated the Green Lane for Acute Myocardial Infarction (GL-AMI), has been implemented in the southern region of Portugal – the Algarve Project. We performed an observational study based on a prospective registry of 1338 patients admitted to Faro Hospital between 2004 and 2009, classified in two groups according to the method of admission: emergency department group (EDG) and GL-AMI group (GLG). More patients from GLG were reperfused (p < 0.0001). PPCI was the preferred method of reperfusion, 73.1% in GLG and 45.3% in EDG. Time delays were significantly shorter in GLG, except for pre-hospital delay: pre-hospital delay (p = 0.11); door-to-needle (p < 0.0001); door-to-balloon (p < 0.0001); and delay between symptoms and reperfusion (p < 0.0001). In-hospital mortality (4.3% vs 9.2%, p = 0.0007) and 6-month mortality (6.3% vs 13.8%, p < 0.0001) were significantly lower in GLG.ConclusionsThe Algarve Project significantly reduced the time delay between onset of symptoms and reperfusion, significantly increased the rate of reperfusion, and significantly reduced in-hospital and six-month mortality.