Risk Of Major Cardiac Events Research Articles

Immunosuppression in Renal Transplantation and Dyslipidemia, Which Factors Should Be Considered?

Dear Editor, Secondary dyslipidemia is the most common form of lipid metabolism derangement, due to the fact that primitive dyslipidemia represent only 0.5-2% of cases (1). Transplantation is a common cause of dyslipidemia, it has been shown that it defines metabolic syndrome, a common finding in renal transplant recipients (RTR) (2), and statins are within the top 15 drugs used by these patients (3). Moreover the increasing prescription of statins in this population is related to the frequent screening for dyslipidemia in transplanted patients (3). Immunosuppression could cause hypercholesterolemia and Cyclosporine (CsA) is widely used as immunosuppressive drug even if in the recent years physicians prescribe more frequently Tacrolimus than CsA (3). Moreover renal function in RTR is reduced and in many causes they are long-term treated with steroids. An additional risk factor for dyslipidemia should be taken into account in RTR such as chronic kidney disease, a condition in which triglycerides are increased and HDL-cholesterol is reduced. The main causes of these alterations are increased plasma levels of VLDL, IDL, LDL, Lp(a) and reduced activity of hepatic triglyceride lipase and peripheral lipoprotein lipase (4). Hypercholesterolemia secondary to steroids is due to hyperinsulinemia and peripheral insulin resistance increases hepatic synthesis of VLDL, moreover steroids reduce the release of ACTH with up-regulation of LDL-cholesterol hepatic receptors (5). On the contrary, the mechanism responsible for hypercholesterolemia during CsA treatment is still a matter of debate. CsA is a lipophilic drug and is carried by HDL and LDL cholesterol; it has been suggested that the drug impairs hepatic clearance of LDL (6). Moreover hepatic sterol regulatory element binding protein-2 is activated leading to increased VLDL synthesis, and secretion of bile and bile salts is impaired causing reduced cholesterol elimination (7). Hosseini et al. (8) study evaluated the relationship between CsA and dyslipidemia in RTR; they showed that plasma levels of cholesterol and triglycerides started increasing 4-12 months after beginning of immunosuppressive therapy, while subsequently HDL-cholesterol decreased and LDL-cholesterol increased. Logistic regression analysis showed that female gender and serum creatinine were the major risk factors for hypercholesterolemia and hypertriglyceridemia; on the contrary, CsA was not related to them. Similar results were shown by Laufer et al. (9) in heart transplant recipients. In their study the main risk factors were the history of cardiac disease leading to transplantation and steroids therapy. Hricik et al. (10) evaluated RTR and showed that reduction of steroid’s dose caused decreasing total plasma cholesterol levels. Cardiovascular disease is a major problem in RTR due to its relationship with morbidity and mortality and graft loss. Statins seem to have a protective effect in RTR, especially on risk of major cardiac events and they need to be considered during patients follow-up (4).

Efficacy and safety of sirolimus-eluting stents versus bare-metal stents in coronary artery disease patients with diabetes: a meta-analysis.

To compare by meta-analysis the efficacy and safety of sirolimus-eluting and bare-metal stents in coronary artery disease (CAD) patients with diabetes. PubMed, MEDLINE and EMBASE were searched from 1971 to 2012. Data on the efficacy and safety of sirolimus-eluting and bare-metal stents in patients with diabetes were collected. A meta-analysis was then performed on a total of 1 259 CAD patients with diabetes from six studies. The odds ratio (OR) was used for comparison. Subgroup analysis was performed according to the sample size, year of study, subjects' geographic area and study method. Compared with those in the bare-metal stent group (BMS), the subjects in the sirolimus-eluting stent (SES) group had a reduced risk for major cardiac events [OR 0.42, 95% confidence interval (CI): 024-0.74, p < 0.01] and target-lesion revascularisation (OR 0.26, 95% CI: 0.11 - 0.59, p < 0.01). There was no difference for myocardial infarction (OR 0.92, 95% CI: 0.61-1.40, p > 0.05) or mortality (OR 1.19, 95% CI: 0.74-1.92, p > 0.05). Subgroup analysis showed a significant difference for overall risk of major cardiac events between SES and BMS when the sample size was ≤ 90 (OR 0.28, 95% CI: 0.16-0.48, p < 0.01), when it was a randomised control trial (RCT) (OR 0.28, 95% CI: 0.19-0.42, p < 0.01), or when it was performed on European subjects (OR 0.45, 95% CI: 0.27-0.77, p < 0.01). The sensitivity was not different when one study was removed at a time. Our study confirmed that SES are safer and more effective than BMS in CAD patients with diabetes, as far as major cardiac events are concerned.

Warfarin use among older atrial fibrillation patients with non–ST-segment elevation myocardial infarction managed with coronary stenting and dual antiplatelet therapy

We sought to determine the risk of readmission for bleeding and major cardiac events in stented non-ST-segment elevation myocardial infarction (NSTEMI) atrial fibrillation (AF) patients. For this patient population, selection of an antithrombotic strategy poses a unique challenge in clinical practice, and comparative outcome data are sparse. We linked NSTEMI patients aged ≥ 65 years in the CRUSADE Registry (2003-2006) to Medicare claims data. We examined patients with AF who received coronary stenting and either dual antiplatelet therapy (DAPT, aspirin + clopidogrel) or triple therapy (DAPT + warfarin) upon discharge. Multivariable Cox analysis was used to compare the 1-year risks of major cardiac events and readmission for bleeding. We identified 1,648 stented NSTEMI AF patients. Of these, 1,200 (73%) received DAPT, and 448 (27%) received triple therapy at hospital discharge. Predicted thromboembolic and bleeding risks did not appear to influence the decision to receive DAPT or triple therapy. At 1 year, 20.4% had a major cardiac event, and 13.5% were admitted for bleeding. Use of triple therapy relative to DAPT at discharge was associated with a similar adjusted risk of major cardiac events (adjusted hazard ratio 0.94, CI 0.73-1.21) but a trend toward increased risk of readmission for bleeding (hazard ratio 1.29, CI 0.96-1.74, P = .09). In routine practice and in contrast with practice recommendations, most elderly NSTEMI patients with AF who undergo percutaneous coronary intervention with stent placement receive DAPT rather than triple therapy at discharge. Those receiving triple therapy versus DAPT had a similar risk of an ischemic event but a trend toward increased bleeding.

Modifiable Risk Factors and Major Cardiac Events Among Adult Survivors of Childhood Cancer

To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer. Among 10,724 5-year survivors (median age, 33.7 years) and 3,159 siblings in the Childhood Cancer Survivor Study, the prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity was determined, along with the incidence and severity of major cardiac events such as coronary artery disease, heart failure, valvular disease, and arrhythmia. On longitudinal follow-up, rate ratios (RRs) of subsequent cardiac events associated with cardiovascular risk factors and cardiotoxic therapy were assessed in multivariable Poisson regression models. Among survivors, the cumulative incidence of coronary artery disease, heart failure, valvular disease, and arrhythmia by 45 years of age was 5.3%, 4.8%, 1.5%, and 1.3%, respectively. Two or more cardiovascular risk factors were reported by 10.3% of survivors and 7.9% of siblings. The risk for each cardiac event increased with increasing number of cardiovascular risk factors (all P(trend) < .001). Hypertension significantly increased risk for coronary artery disease (RR, 6.1), heart failure (RR, 19.4), valvular disease (RR, 13.6), and arrhythmia (RR, 6.0; all P values < .01). The combined effect of chest-directed radiotherapy plus hypertension resulted in potentiation of risk for each of the major cardiac events beyond that anticipated on the basis of an additive expectation. Hypertension was independently associated with risk of cardiac death (RR, 5.6; 95% CI, 3.2 to 9.7). Modifiable cardiovascular risk factors, particularly hypertension, potentiate therapy-associated risk for major cardiac events in this population and should be the focus of future interventional studies.

Clopidogrel before PCI lowers risk of major cardiac events

Clopidogrel before PCI lowers risk of major cardiac events

Association of Clopidogrel Pretreatment With Mortality, Cardiovascular Events, and Major Bleeding Among Patients Undergoing Percutaneous Coronary Intervention

Clopidogrel pretreatment is recommended for patients with acute coronary syndromes (ACS) and stable coronary artery disease who are scheduled for percutaneous coronary intervention (PCI), but whether using clopidogrel as a pretreatment for PCI is associated with positive clinical outcomes has not been established. To evaluate the association of clopidogrel pretreatment vs no treatment with mortality and major bleeding after PCI. MEDLINE, EMBASE, Cochrane Controlled Trials Register databases, and reference lists of qualifying articles. STUDY SELECTION Studies reporting clinical data on mortality and major bleeding were included. Of the 392 titles identified, 15 articles published between August 2001 and September 2012 met the inclusion criteria: 6 randomized controlled trials (RCTs), 2 observational analyses of RCTs, and 7 observational studies. Quality of studies was assessed with the Ottawa Scale and the Jadad Score as appropriate. Results were independently extracted by 2 reviewers. A random-effect model was applied. Pretreatment was defined as the administration of clopidogrel before PCI or catheterization. The main analysis was performed on RCTs and confirmed by observational analyses and observational studies. Prespecified subgroups--clinical presentation and clopidogrel loading dose--were analyzed. The primary efficacy and safety end points were all-cause mortality and major bleeding. Secondary end points included major cardiac events. Of the 37 814 patients included in the meta-analysis, 8608 patients had participated in RCTs; 10,945, in observational analyses of RCTs; and 18,261, in observational studies. Analysis of RCTs showed that clopidogrel pretreatment was not associated with a reduction of death (absolute risk, 1.54% vs 1.97%; OR, 0.80; 95% CI, 0.57-1.11; P = .17) but was associated with a lower risk of major cardiac events (9.83% vs 12.35%; OR, 0 .77; 95% CI, 0.66-0.89; P < .001). There was no significant association between pretreatment and major bleeding overall (3 .57% vs 3.08%; OR, 1.18; 95% CI, 0.93-1.50; P = .18). Analyses from observational analyses of RCTs and observational studies were consistent for all results. Among patients scheduled for PCI, clopidogrel pretreatment was not associated with a lower risk of mortality but was associated with a lower risk of major coronary events.

Mo1924 Metabolic Syndrome in Liver Transplant Recipients and Their Risk of Major Cardiac Events

Mo1924 Metabolic Syndrome in Liver Transplant Recipients and Their Risk of Major Cardiac Events

Stearidonic Acid–Enhanced Soybean Oil: A Plant-Based Source of (n-3) Fatty Acids for Foods

Omega-3 (n-3) fatty acids have been reported to have a variety of cardiovascular and neuropsychiatric benefits. Although obtaining the preformed fatty acids EPA and DHA from their traditional source (fish) is optimal, such an approach may not be realistic for meeting the world’s growing demand for (n-3) fatty acids; therefore, a more sustainable and dependable source is needed. Stearidonic acid (SDA) is a metabolic precursor of EPA that can be provided by SDA-enhanced soybean oil. Such a product can provide a sustainable source of (n-3) fatty acids that does not endanger fish stocks. Two clinical trials have demonstrated that SDA-enhanced soybean oil can significantly improve an emerging marker of cardiovascular health, the omega-3 index (RBC EPA+DHA). The increase in the Index seen in these trials was used to estimate the potential clinical benefit of SDA consumption based on prior prospective cohort studies. In this analysis, risk for sudden cardiac death and the rate of cellular aging would both theoretically be reduced. The lower risk for major cardiac events seen in the Japan EPA Lipid Intervention Study (which used EPA supplementation) suggests that raising EPA tissue levels, independent of changes in DHA, can have clinical benefit. Thus, the consumption of foods containing SDA-enhanced soybean oil may be both a practical and sustainable approach to enriching tissues with beneficial (n-3) fatty acids.

Cardiac Event Risk in Japanese Subjects Estimated Using Gated Myocardial Perfusion Imaging, in Conjunction With Diabetes Mellitus and Chronic Kidney Disease

Cardiac event risk is estimated using quantitative gated myocardial perfusion imaging (MPI) and clinical background in patients with ischemic heart disease. The aim of the present study was to calculate major cardiac event risk and tabulate it in the Heart Risk Table for clinical use of risk stratification. Multivariate logistic regression was performed based on a multicenter prognostic database (Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated Single-photon emission computed tomography [J-ACCESS investigation]) using MPI (n=2,395). The risk of major cardiac events (cardiac death, non-fatal myocardial infarction and heart failure requiring hospitalization) was estimated using age, ejection fraction (EF), estimated glomerular filtration rate (eGFR) and presence of diabetes mellitus (DM). Age-matched standard eGFR was determined in 77 subjects. Major cardiac event risk was calculated using the equation: risk (%/3 years)=1/(1+Exp(-(-4.699-0.0151×eGFR+0.7998×DM+0.0582×age+0.697×SSS-0.0359×EF))×100, where SSS refers to summed stress scores. Risk was determined without eGFR (the initial version) and using the present formula with eGFR (revised version), with consistent results. DM and chronic kidney disease were major determinants of cardiac events. Cardiac event risk was estimated using MPI defect score and left ventricular EF in conjunction with eGFR and the presence of DM. The risk table might be used for risk evaluation in Japanese patients undergoing MPI.

Treating Cardiac Arrhythmias Detected With an Implantable Cardiac Monitor in Patients After an Acute Myocardial Infarction

Using an implantable cardiac monitor (ICM) in patients with acute myocardial infarction (MI) allows continuous electrocardiogram monitoring and provides a much more detailed picture of the incidence of brady- and tachyarrhythmias than conventional follow-up. The CARISMA study was the first to use the ICM in post-MI patients with moderate to severe left ventricular systolic dysfunction. Atrial fibrillation (AF) events lasting longer than 30s were associated with an almost threefold increase in the risk of major cardiac events. This confirms the current definition of clinically significant AF episodes, as patients with episodes of shorter duration were not at increased risk. The association of AF to progressive heart failure, reinfarction, and cardiovascular death underlines the need for an intensive follow-up of post-MI patients with new-onset AF in order to reveal underlying causes of AF such as progressive left ventricular dysfunction or myocardial ischemia. Asymptomatic, especially nightly, bradycardia episodes including high-degree 2°-3° atrioventricular (AV) block, sinus bradycardia, and sinus arrest were frequently documented by ICM in the CARISMA study. Ten percent of patients experienced high-degree 2°-3° AV block, of which the main part was nightly and asymptomatic, and 50% of all cardiovascular deaths occurred in this group, most from severe heart failure. Therefore, in post-MI patients with paroxysmal high-degree AV block, pacemaker implantation should be done, and in the case of left ventricular dysfunction (LVEF ≤ 35%), an implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator (ICD/CRT-D) may be indicated. Nonsustained ventricular tachycardia (VT) is very frequent in post-MI patients, and in the CARISMA study, high-risk patients with nonsustained VT were implanted with an ICD. Furthermore, in 10% of the patients, the ICM recorded nonsustained VT episodes of ≥ 16 beats per minute, resulting in a twofold increase in the risk for cardiac death. Thus, patients with nonsustained VT should undergo careful investigation, and we recommend a repeat echocardiography and electrophysiological stimulation in these patients. Patients with sustained VT or VF should receive an ICD.

Efficacy and Safety of Abciximab in Diabetic Patients Who Underwent Percutaneous Coronary Intervention with Thienopyridines Loading: A Meta-Analysis

BackgroundIt has been controversial whether abciximab offered additional benefits for diabetic patients who underwent percutaneous coronary intervention (PCI) with thienopyridines loading.MethodsMEDLINE, EMBASE, the Cochrane library clinical trials registry, ISI Science Citation Index, ISI Web of Knowledge and China National Knowledge Infrastructure (CNKI) were searched, supplemented with manual-screening for relevant publications. Quantitative meta-analyses were performed to assess differences between abciximab groups and controls with respect to post-PCI risk of major cardiac events (MACEs), angiographic restenosis and bleeding complications.Results9 trials were identified, involving 2,607 diabetic patients receiving PCI for coronary artery diseases. Among those patients who underwent elective PCI or primary PCI, pooling results showed that abciximab did not significantly reduce risks of MACEs (for elective-PCI patients: RR1-month: 0.93, 95% CI: 0.60–1.44; RR1-year: 0.95, 95% CI: 0.81–1.11; for primary-PCI patients: RR1-month: 1.05, 95% CI: 0.70–1.57; RR1-year: 0.98, 95% CI: 0.80–1.21), nor all-cause mortality, re-infarction and angiographic restenosis in either group. The only beneficial effect by abciximab appeared to be a decrease 1-year TLR (target lesion revascularization) risk in elective-PCI patients (RR1-year: 0.83, 95% CI: 0.70–0.99). Moreover, occurrence of minor bleeding complications increased in elective-PCI patients treated with abciximab (RR: 2.94, 95% CI: 1.68–5.13, P<0.001), whereas major bleedings rate was similar (RR: 0.83, 95% CI: 0.27–2.57).ConclusionsConcomitant dosing of abciximab and thienopyridines provides no additional benefit among diabetic patients who underwent PCI; this conclusion, though, needs further confirmation in larger studies.

Long-term outcome after sirolimus-eluting stents versus bare metal stents in patients with Diabetes mellitus: a patient-level meta-analysis of randomized trials

Although it is widely believed that patients with diabetes mellitus obtain the greatest benefit from drug-eluting stents, convincing evidence on long-term efficacy and safety of these stents is lacking. We performed a meta-analysis of individual patient data from four randomized trials including 583 patients comparing sirolimus eluting with bare metal stents (median follow-up of 4.2years). These were the only specific trials reporting on drug-eluting stents in diabetic patients. The primary endpoint was the incidence of major cardiac events. The secondary endpoints were all-cause mortality and myocardial infarction as a safety endpoint and target lesion re-intervention as an efficacy endpoint. Stent thrombosis was also evaluated. There was a significant reduction in the overall hazard of major cardiac events (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.36-0.63, P<0.001) with sirolimus-eluting stents. This was mostly due to a significant reduction in the overall hazard of repeat revascularization (HR 0.27, 95% CI 0.18-0.41, P<0.001) in favor of sirolimus-eluting stents. However, the overall hazard of death (HR 0.91, 95% CI 0.59-1.41, P=0.68) as well as death or myocardial infarction (HR 0.77, 95% CI 0.54-1.09, P=0.14) were not significantly different between the groups. No significant differences were observed regarding stent thrombosis (HR 0.50, 95% CI 0.15-1.69, P=0.26). Sirolimus-eluting stents are highly effective in reducing the risk for major cardiac events and safe in diabetic patients with coronary artery disease.

Adenosine-stress cardiac magnetic resonance imaging in the assessment of coronary artery disease: A net cost analysis and reimbursement implications

Methods 218 patients from a registry on 605 consecutive CMR patients were matched to a prior sample in which CMR was demonstrated to reliably stratify patients regarding their risk of major cardiac events [1]. Propensity scoring methods were used to match on comorbidity profiles, demographics, CAD-related clinical presentation, and CAD risk as measured by their Morise scores. The matched sample included adult subjects with suspected CAD who were evaluated by stress CMR. We identified the proportion of patients who were able to avoid cardiac catheterization based upon the results of their CMR tests. Given this information, and data on the costs of cardiac catheterization and CMR tests, a net cost analysis was performed. Results CMR use substantially reduces the need for cardiac catheterization by 62.4%. Assuming catheterization costs of EUR 619 based on Diagnosis Related Groups (DRG) reimbursement rates in Germany, use of CMR leads to cost savings of EUR 90 on average. The breakeven-level for CMR costs at which it is cost neutral is EUR 386. These results were robust in sensitivity analysis. Cost savings are greatest for patients with lowest risk of CAD as measured by their baseline Morise scores. However, cost savings are likely for all Morise sub groups examined, with the exception of patients at the highest risk of CAD as measured by their Morise score.

Depressive symptoms in persons with acute coronary syndrome: Specific symptom scales and prognosis

ObjectiveTo determine which particular depressive symptom scales, derived from three scales, predicted poorer prognosis in persons with acute coronary syndrome (ACS). MethodsHospitalized ACS patients (n=408) completed questionnaires (depression, vital exhaustion). Mokken scaling derived unidimensional scales. Major cardiac events (cardiac mortality, ACS, unplanned revascularization) were assessed at median 67 weeks post event. ResultsOnly depressive symptoms of fatigue-sadness predicted prognosis in univariate (hazard ratio [HR]=1.8, 95% CI 1.1–3.0, P=.025) and multivariate analysis (HR=1.8, 95% CI 1.1–2.9, P=.025). Symptoms of anhedonia (HR=1.6, 95% CI 0.9–2.8, P=.102) and depressive cognitions (HR=1.3, 95% CI 0.7–2.2, P=.402) did not. ConclusionSymptoms of fatigue-sadness, but not other symptoms, were associated with increased risk of major cardiac events. Depression should be considered as a multidimensional, rather than a unidimensional, entity when designing interventions.

Effect of fluvastatin on cardiac outcomes in kidney transplant patients with systemic lupus erythematosus: A randomized placebo‐controlled study

Patients with systemic lupus erythematosus (SLE), with or without end-stage renal failure, are at increased risk of premature cardiovascular disease. Although statin therapy has been found to reduce cardiovascular risk in the general population, its effectiveness in kidney transplant recipients with SLE has not been examined. This study was undertaken to investigate the effect of fluvastatin on cardiac end points in a randomized controlled trial of renal transplant patients with SLE. Patients with SLE were identified from among participants in the Assessment of Lescol in Renal Transplantation trial, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40-80 mg/day) on cardiovascular outcomes in renal transplant recipients. Patients were randomized to either a group receiving fluvastatin or a placebo group for the duration of the 5-6-year trial, and then invited to continue in a 2-year open-label extension during which all participants, regardless of original group, received fluvastatin. Patients were followed up for a total of 7-8 years for assessment of the primary end point of major cardiac events, comprising nonfatal myocardial infarction, cardiac death, and coronary intervention procedures. Fluvastatin reduced low-density lipoprotein cholesterol levels by 29.2% (95% confidence interval [95% CI] 18.3-40%), from a mean +/- SD of 4.0 +/- 0.9 mmoles/liter to 2.8 +/- 1.1 mmoles/liter, and total cholesterol by 19.6% (95% CI 11.7-27.5%), from 6.4 +/- 0.9 mmoles/liter to 5.1 +/- 1.1 mmoles/liter. Compared with placebo-treated patients, patients randomized to receive fluvastatin exhibited a 73.4% reduction in the risk of major cardiac events (relative risk 26.6 [95% CI 5.9-119.4], P = 0.064). Our results indicate that the effect of fluvastatin on cardiac events in renal transplant recipients with SLE is similar to that observed with statin therapy in the renal transplant population as a whole.

Risk factors for non-fatal myocardial infarction and cardiac death in incident dialysis patients

The risks of major cardiac events in patients initiating long-term dialysis related to prior coronary disease and various other factors are not well known. We used United States Renal Data System data to analyse the outcomes of non-fatal myocardial infarction (MI) and cardiac death in incident dialysis patients from years 1997 through 2001 (n = 214 890). The presence of established coronary artery disease was determined from the Medical Evidence form, non-fatal MI events were determined from Medicare claims' data and cause of death was determined from the Death Notification form. Multivariable analyses were performed employing Cox proportional hazards models using demographics, co-morbidities, laboratory variables, prior erythropoietin use, body mass index and type of dialysis. In patients with prior coronary disease as compared to those without, the adjusted relative risk of non-fatal MI was 1.57 (95% CI, 1.5-1.65) and cardiac death was 1.16 (95% CI, 1.14-1.18). The 5-year cumulative incidence of non-fatal MI was 8.1 and 6% and cardiac death was 48.3 and 40.2%, in patients with and without prior coronary disease, respectively. Amongst important factors, blacks had a lower risk of non-fatal MI and cardiac death as compared to whites. A history of hypertension conferred a lower independent risk of cardiac death events. Lower haemoglobin, higher albumin and higher creatinine values each conferred a lower independent risk of non-fatal MI and cardiac death. Incident dialysis subjects with prior coronary disease have a risk of non-fatal MI greater by 57% and cardiac death by 16% as compared to subjects without prior coronary disease. In both populations, the competing risk of cardiac death is several-fold greater than that of non-fatal MI. There are several factors suggesting reverse epidemiology phenomena with respect to major cardiac events in the dialysis population.

Quilty in biopsy is associated with poor prognosis after heart transplantation

We tested if Quilty (endocardial infiltration of lymphocytes) in routinely processed endomyocardial biopsy is associated with poor outcome after heart transplantation (HTx). Biopsies ( n = 9829) harvested within the first post-transplant year from 938 patients (778 men, mean age 49 years) were evaluated for Quilty and acute cellular rejection (according to the International Society for Heart and Lung Transplantation, ISHLT, classification). Transplant vasculopathy was evaluated by coronary angiography, and severe stenosis was found in 19% of patients. Survival was tested by Kaplan–Meier and Cox regression analyses for all-cause mortality and major cardiac events (lethal acute cellular rejection, graft loss or myocardial infarction). We found 1840 (19%) Quilty-positive biopsies in 487 Quilty-positive patients (52%). Quilty was more prevalent in women ( p = 0.038) and younger men ( p = 0.001), and was correlated with ISHLT grade 1R (OR 1.45, 95% CI 1.36–1.55; p < 0.001) and ISHLT grade 2R (OR 2.48, 95% CI 2.21–3.41; p < 0.001). Quilty in any biopsy was associated with a higher all-cause mortality (log rank p = 0.045) due to a higher risk for major cardiac event ( p = 0.0001). Multivariate regression analysis showed Quilty (RR 1.69, 95%CI 1.05–2.73) and transplant vasculopathy (RR 2.78, 95%CI 1.68–4.61) as risk factors for major cardiac events and treated hyperlipidemia as lowering the risk for major cardiac events (RR 0.47, 95%CI 0.28–0.77). Quilty is associated with graft loss and poor outcome post HTx. Index biopsy during the first post-transplant year is a useful tool to identify patients at risk and is recommended during routine post-transplant management.

Stimulants Show Little Risk of Major Cardiac Events

Stimulants Show Little Risk of Major Cardiac Events

High-Density Lipoprotein Cholesterol, High-Density Lipoprotein Particle Size, and Apolipoprotein A-I: Significance for Cardiovascular Risk: The IDEAL and EPIC-Norfolk Studies

This study was designed to assess the relationship of high-density-lipoprotein cholesterol (HDL-C), HDL particle size, and apolipoprotein A-I (apoA-I) with the occurrence of coronary artery disease (CAD), with a focus on the effect of very high values of these parameters. High plasma levels of HDL-C and apoA-I are inversely related to the risk of CAD. However, recent data suggest that this relationship does not hold true for very high HDL-C levels, particularly when a preponderance of large HDL particles is observed. We conducted a post-hoc analysis of 2 prospective studies: the IDEAL (Incremental Decrease in End Points through Aggressive Lipid Lowering; n = 8,888) trial comparing the efficacy of high-dose to usual-dose statin treatment for the secondary prevention of cardiovascular events, and the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk case-control study, including apparently healthy individuals who did (cases, n = 858) or did not (control patients, n = 1,491) develop CAD during follow-up. In IDEAL, only HDL-C and apoA-I were available; in EPIC-Norfolk, nuclear magnetic resonance spectroscopy-determined HDL particle sizes were also available. In the IDEAL study, higher HDL-C proved a significant major cardiac event risk factor following adjustment for age, gender, smoking, apoA-I, and apoB. A similar association was observed for HDL particle size in EPIC-Norfolk. Increased risk estimates were particularly present in the high ends of the distributions. In contrast, apoA-I remained negatively associated across the major part of its distribution in both studies. When apoA-I and apoB are kept constant, HDL-C and HDL particle size may confer risk at very high values. This does not hold true for very high levels of apoA-I at fixed levels of HDL-C and apoB. These findings may have important consequences for assessment and treatment of CAD risk.

TIMI risk score underestimates prognosis in unstable angina/non‐ST segment elevation myocardial infarction

To determine the value of the TIMI risk score in the individual risk stratification of patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). TIMI risk score is a validated tool to identify groups of patients at high risk for major cardiac events. Its prognostic value in individual patients with current diagnostic tools and therapy is unknown. TIMI risk score was assessed in patients with UA/NSTEMI admitted to six Belgian hospitals and related to clinical outcome at 30 days. Of the 500 patients enrolled, 49.4% were placed in the low TIMI risk group (score = 0-3) and 50.6% in the high-risk group (score = 4-7). Multivariate analysis identified raised cardiac markers and invasive strategy, but not high TIMI risk score as independent predictors of death and new myocardial infarction (MI). Moreover, the incidence of death and MI in the low TIMI risk group with positive cardiac markers was not lower than in the high TIMI risk group with positive markers: 15.1% versus 17.8% (P = 0.7). TIMI risk score is of limited value for individual risk stratification. The presence of positive cardiac markers (troponin) appears to be a more powerful prognostic marker.