Recurrent Cardiovascular Events in Survivors of Myocardial Infarction With ST-Segment Elevation (from the AMI-QUEBEC Study).

The characteristics and predictors of long-term recurrent ischemic cardiovascular events (RICEs) after myocardial infarction with ST-segment elevation (STEMI) have not yet been clarified. We aimed to characterize the 10-year incidence, types, and predictors of RICE. We obtained 10-year follow-up of STEMI survivors at 17 Quebec hospitals in Canada (the AMI-QUEBEC Study) in 2003. There were 858 patients; mean age was 60 years and 73% were male. The majority of patients receive reperfusion therapy; 53.3% and 39.2% of patients received primary percutaneous coronary intervention (PCI) and fibrinolytic therapy, respectively. Seventy-five percent of patients underwent in-hospital PCI (elective, rescue, and primary). At 10 years, 42% of patients suffered a RICE, with most RICEs (88%) caused by recurrent cardiac ischemia. The risk of RICE was the highest during the first year (23.5 per patient-year). At 10 years, the all-cause mortality was 19.3%, with 1/3 of deaths being RICE-related. Previous cardiovascular event, heart failure during the index STEMI hospitalization, discharge prescription of calcium blocker increased the risk of RICE by almost twofold. Each point increase in TIMI (Thrombolysis In Myocardial Infarction) score augmented the risk of RICE by 6%, whereas discharge prescription of dual antiplatelets reduced the risk of RICE by 23%. Our findings suggested that survivors of STEMI remain at high long-term risk of RICE despite high rate of reperfusion therapy and in-hospital PCI. Patients with previous cardiovascular event, in-hospital heart failure, and high TIMI score were particularly susceptible to RICE. Future studies are needed to confirm the impacts of calcium blocker and dual antiplatelets on long-term risk of RICE.

Pregnancy after heart transplantation: a well-thought-out decision? The Quebec provincial experience - a multi-centre cohort study.

Despite reports of successful pregnancies in heart transplant (HTx) recipients, many centers recommend their patients against maternity. We reviewed our provincial experience of pregnancy in HTx recipients by performing charts review of all known gestations following HTx in the province of Quebec (Canada), stratified between planned and unplanned pregnancies. Long-term survival was compared to HTx recipient women of childbearing age who did not become pregnant. Eighteen pregnancies, 56% unplanned, occurred in eight patients, 10.1 (2.6-27.0) years after HTx. Immunosuppression was CNI-based, with a mean dose increase of 48.3% (tacrolimus) and 26.5% (cyclosporine), without rejection. Cardiometabolic complications were high compared to the general Canadian population, including preeclampsia (15.4% vs. 5.5%), hypertension (38.5% vs. 4.6%), and diabetes (15.4% vs. 5.6%). Mean gestational age was 35.1 (23.4-39.6) weeks (72.2% live births; 53.8% prematurity). Mean birthweight was 2418 (660-3612) g. Serum creatinine increased during pregnancy, becoming significant after delivery (P = 0.0239), and returning to preconception level in all but three patients within a year. After 4.6 (1.2-17.2) years of follow-up, two rejection episodes occurred in one patient. Long-term mortality was similar to overall HTx women (Kaplan-Meier; P = 0.8071). Pregnancy in HTx carries high cardiometabolic complications and decreased kidney function, but is feasible with acceptable outcomes and no impact on mother's survival.

Cardiac signaling molecules and plasma biomarkers after cardiac transplantation: impact of tacrolimus versus cyclosporine.

BACKGROUND: We investigated cardiac proinflammatory, mitogenic, and apoptotic signaling events, and plasma biomarkers of inflammation and oxidative stress in de novo adult cardiac transplant (CTX) patients receiving tacrolimus (TAC) or cyclosporine A (CsA). METHODS: One hundred CTX recipients were randomized 1:1 to TAC/CsA in a prospective, randomized open-label multicenter study. Biomarkers of inflammation, immunity, oxidative stress, and cardiac signaling underlying growth and inflammation (extracellular signal-related kinase 1/2, p38 mitogen-activated protein kinase, mitogen-activated protein kinase kinases [MEK] 1/2 and 3/6, c-Src), and apoptosis and survival (c-Jun NH2-terminal kinases [JNK], Bax/Bcl2, Akt) were assessed at 2, 4, 12, 26, and 52 weeks post-CTX. Plasma from healthy controls (n = 30) and tissue from explanted non-failing hearts (n = 6) were used as controls. RESULTS: Biomarkers of inflammation/immunity (interleukin -6 and -18, soluble intercellular adhesion molecule, E-selectin, monocyte chemoattractant protein-1, osteopontin, fibrinogen, N-terminal prohormone brain natriuretic peptide, high-sensitive C-reactive protein) and oxidative stress (thiobarbituric acid reactive substances, nitrotyrosine) were increased, and antioxidant capacity was (glutathione/glutathione disulfide) decreased in patients vs healthy controls (p < 0.05). Phosphorylation of mitogen-activated protein kinases and Akt was increased, and Bax/Bcl was decreased in transplanted vs non-transplanted hearts. Except for plasma fibrinogen, which was lower in TAC vs. CsA, (p = 0.01), there were no significant differences in parameters studied between TAC vs CsA immunoprophylaxis. CONCLUSIONS: De novo CTX recipients exhibit significant sub-clinical inflammation and oxidative stress that persists 12 months after transplantation. Associated with this is activation of myocardial growth and inflammatory signaling and decreased apoptosis. Our findings suggest that CTX is an inflammatory condition associated with oxidative stress and myocardial growth regardless of CsA or TAC immunoprophylaxis and independently of rejection status.

Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) IMAGE HF Project I-A: study protocol for a randomized controlled trial.

BACKGROUND: Ischemic heart disease (IHD) is the most common cause of heart failure (HF); however, the role of revascularization in these patients is still unclear. Consensus on proper use of cardiac imaging to help determine which candidates should be considered for revascularization has been hindered by the absence of clinical studies that objectively and prospectively compare the prognostic information of each test obtained using both standard and advanced imaging. METHODS/DESIGN: This paper describes the design and methods to be used in the Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) multi-center trial. The primary objective is to compare the effect of HF imaging strategies on the composite clinical endpoint of cardiac death, myocardial infarction (MI), cardiac arrest and re-hospitalization for cardiac causes.In AIMI-HF, patients with HF of ischemic etiology (n = 1,261) will follow HF imaging strategy algorithms according to the question(s) asked by the physicians (for example, Is there ischemia and/or viability?), in agreement with local practices. Patients will be randomized to either standard (SPECT, Single photon emission computed tomography) imaging modalities for ischemia and/or viability or advanced imaging modalities: cardiac magnetic resonance imaging (CMR) or positron emission tomography (PET). In addition, eligible and consenting patients who could not be randomized, but were allocated to standard or advanced imaging based on clinical decisions, will be included in a registry. DISCUSSION: AIMI-HF will be the largest randomized trial evaluating the role of standard and advanced imaging modalities in the management of ischemic cardiomyopathy and heart failure. This trial will complement the results of the Surgical Treatment for Ischemic Heart Failure (STICH) viability substudy and the PET and Recovery Following Revascularization (PARR-2) trial. The results will provide policy makers with data to support (or not) further investment in and wider dissemination of alternative 'advanced' imaging technologies. TRIAL REGISTRATION: NCT01288560.

Cardiac allograft vasculopathy by intravascular ultrasound in heart transplant patients: substudy from the Everolimus versus mycophenolate mofetil randomized, multicenter trial.

OBJECTIVES: A pre-planned substudy of a larger multicenter randomized trial was undertaken to compare the efficacy of everolimus with reduced-dose cyclosporine in the prevention of cardiac allograft vasculopathy (CAV) after heart transplantation to that of mycophenolate mofetil (MMF) with standard-dose cyclosporine. BACKGROUND: CAV is a major cause of long-term mortality following heart transplantation. Everolimus has been shown to reduce the severity and incidence of CAV as measured by first year intravascular ultrasound (IVUS). MMF, in combination with cyclosporine, has also been shown to have a beneficial effect in slowing the progression of CAV. METHODS: Study patients were a pre-specified subgroup of the 553-patient Everolimus versus mycophenolate mofetil in heart transplantation: a randomized, multicenter trial who underwent heart transplantation and were randomized to everolimus 1.5 mg or MMF 3 g/day. IVUS was performed at baseline and at 12 months. Evaluable IVUS data were available in 189 patients (34.6%). RESULTS: Increase in average maximal intimal thickness (MIT) from baseline to month 12 was significantly smaller in the everolimus 1.5 mg group compared with the MMF group (0.03 mm vs. 0.07 mm, p < 0.001). The incidence of CAV, defined as an increase in MIT from baseline to month 12 of greater than 0.5 mm, was 12.5% with everolimus versus 26.7% with MMF (p = 0.018). These findings remained irrespective of sex, age, diabetic status, donor disease, and across lipid categories. CONCLUSIONS: Everolimus was significantly more efficacious than MMF in preventing CAV as measured by IVUS among heart-transplant recipients after 1 year, a finding, which was maintained in a range of patient subpopulations. CV surgery: transplantation, ventricular assistance, cardiomyopathy.

Effects of chronic sildenafil use on pulmonary hemodynamics and clinical outcomes in heart transplantation.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) in heart transplant (HT) candidates is associated with poor survival after HT. This study assessed the effect of peri-operative sildenafil administration on pulmonary hemodynamics and clinical outcomes in patients with advanced heart failure who were considered high-risk for HT because of elevated PVR and transpulmonary gradient (TPG). METHODS: The study included 119 consecutive patients who underwent HT between 2004 and 2011. Fifteen patients (Group A) had severe pulmonary hypertension (PH), defined as mean pulmonary pressure (MPAP)>25 mm Hg and PVR>2.5 Wood units (WU), and/or TPG>12 mm Hg after vasodilator test or the continuous administration of inotropics drugs, and 104 patients (Group B) were without severe PH. Group A received sildenafil therapy. Pulmonary hemodynamics were evaluated before HT with and without sildenafil therapy. Right catheterization was performed early after HT with sildenafil therapy and late after HT without sildenafil. Survival after HT was compared between the groups. RESULTS: The sildenafil dosage was 109±42 mg/day during 163±116 days before HT. After sildenafil therapy MPAP, PVR, and TPG decreased from 43.9±12.5 to 33.4±5.8 mm Hg, 5.0±1.1 to 3.0±1.6 WU, and 17.3±3.2 to 10.2±4.1 mm Hg, respectively (p<.01). All patients underwent successful HT. Sildenafil dosage was 140±70 mg/day for 43±45 days after HT. There were no differences in PVR and TPG with sildenafil therapy early after HT and without sildenafil 6 months after HT. Survival after HT was similar between the groups. CONCLUSION: Sildenafil therapy before and after HT in patients with severe PH is associated with improved pulmonary hemodynamics and successful HT, without an increase in post-HT mortality.

Usefulness and limitations of rituximab in managing patients with lymphoproliferative disorder after heart transplantation.

Posttransplant lymphoproliferative disorders remain an uncommon complication of heart transplant with a high mortality rate reported after conventional therapies. Four patients with posttransplant lymphoproliferative disorders, of whom 3 were CD20 positive, received intravenous dosages of rituximab, 375 mg/m(2), weekly, for 6 ± 2 weeks. The overall response rate was 75% with 3 complete responses (CD20 positive) and 1 case of progressive disease (CD20 negative). Rituximab should be considered as a first-line therapy for patients with CD20 positive posttransplant lymphoproliferative disorders.

Generation of priority research questions to inform conservation policy and management at a national level.

Integrating knowledge from across the natural and social sciences is necessary to effectively address societal tradeoffs between human use of biological diversity and its preservation. Collaborative processes can change the ways decision makers think about scientific evidence, enhance levels of mutual trust and credibility, and advance the conservation policy discourse. Canada has responsibility for a large fraction of some major ecosystems, such as boreal forests, Arctic tundra, wetlands, and temperate and Arctic oceans. Stressors to biological diversity within these ecosystems arise from activities of the country's resource-based economy, as well as external drivers of environmental change. Effective management is complicated by incongruence between ecological and political boundaries and conflicting perspectives on social and economic goals. Many knowledge gaps about stressors and their management might be reduced through targeted, timely research. We identify 40 questions that, if addressed or answered, would advance research that has a high probability of supporting development of effective policies and management strategies for species, ecosystems, and ecological processes in Canada. A total of 396 candidate questions drawn from natural and social science disciplines were contributed by individuals with diverse organizational affiliations. These were collaboratively winnowed to 40 by our team of collaborators. The questions emphasize understanding ecosystems, the effects and mitigation of climate change, coordinating governance and management efforts across multiple jurisdictions, and examining relations between conservation policy and the social and economic well-being of Aboriginal peoples. The questions we identified provide potential links between evidence from the conservation sciences and formulation of policies for conservation and resource management. Our collaborative process of communication and engagement between scientists and decision makers for generating and prioritizing research questions at a national level could be a model for similar efforts beyond Canada.

Epstein-Barr virus polymerase chain reaction-negative stage IV post-transplant lymphoproliferative disorder in a heart transplant patient treated with rituximab.

Post-transplant lymphoproliferative disorder (PTLD) is often associated with Epstein-Barr virus (EBV). However, in this report, we describe a heart transplant recipient with pathologically proven EBV-positive PTLD with undetectable virus by polymerase chain reaction. The patient had remission after anti-CD20 antibody treatment early after transplantation.

Hypertriglyceridemic waist: a useful screening phenotype in preventive cardiology?

The worldwide increase in the prevalence and incidence of type 2 diabetes represents a tremendous challenge for the Canadian health care system, especially if we consider that this phenomenon may largely be explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting the importance of intra-abdominal adipose tissue (visceral adipose tissue) as the fat depot conveying the greatest risk of metabolic complications. In this regard, body fat distribution, especially visceral adipose tissue accumulation, has been found to be a key correlate of a cluster of diabetogenic, atherogenic, prothrombotic and inflammatory metabolic abnormalities now often referred to as the metabolic syndrome. This dysmetabolic profile is predictive of a substantially increased risk of coronary artery disease (CAD) even in the absence of hyperglycemia, elevated low-density lipoprotein cholesterol or hypertension. For instance, some features of the metabolic syndrome (hyperinsulinemia, elevated apolipoprotein B and small low-density lipoprotein particles--the so-called atherogenic metabolic triad) have been associated with a more than 20-fold increase in the risk of ischemic heart disease in middle-aged men enrolled in the Quebec Cardiovascular Study. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of CAD beyond the presence of traditional risk factors. These results emphasize the importance of taking into account in daily clinical practice the presence of metabolic complications associated with abdominal obesity together with traditional risk factors to properly evaluate the cardiovascular risk profile of patients. From a risk assessment standpoint, on the basis of additional work conducted by several groups, there is now evidence that the simultaneous presence of an elevated waist circumference and fasting triglyceride levels (a condition that has been described as hypertriglyceridemic waist) may represent a relevant first-step approach to identify a subgroup of individuals at higher risk of being carriers of the features of the metabolic syndrome. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of CAD and type 2 diabetes. In conclusion, hypertriglyceridemic waist as a marker of visceral obesity and related metabolic abnormalities is a useful and practical clinical phenotype to screen persons at risk for CAD and type 2 diabetes.

Delays to reperfusion therapy in acute ST-segment elevation myocardial infarction: results from the AMI-QUEBEC Study.

BACKGROUND: Through the AMI-QUEBEC Study we sought to describe delays to reperfusion therapy for ST-segment elevation myocardial infarction (STEMI) and to identify factors associated with prolonged delays. METHODS: We reviewed the charts of all consecutive patients with STEMI admitted to 17 hospitals in the province of Quebec in 2003 to obtain data on the time from presentation to reperfusion therapy. Data were available for 1189 (83.0%) of 1432 patients. RESULTS: The median delay to reperfusion therapy was 32 minutes (first and third quartile [Q1, Q3] 20, 49) for 535 patients who received fibrinolytic therapy, 109 minutes (Q1, Q3 79, 150) for 455 patients who underwent primary percutaneous coronary intervention (PCI) at the initial hospital of presentation and 142 minutes (Q1, Q3 115, 194) for 199 patients who underwent primary PCI after an interhospital transfer. Patients who presented outside daytime working hours, those who received primary PCI and those who required interhospital transfer for primary PCI were less likely to receive reperfusion therapy within current recommended times (odds ratios [ORs] 0.49, 0.56 and 0.15, respectively). Increased age was associated with prolonged delays only among patients who received fibrinolytic therapy (OR for each 10-year increase in age 0.95, 95% credible interval [CrI] 0.93-0.99 for fibrinolytic therapy and 0.99, 95% CrI 0.95-1.05, for primary PCI). INTERPRETATION: In 2003, many patients with STEMI in Quebec were not treated within the recommended times. Delays may be reduced by reorganizing pre-and in-hospital care for patients with STEMI to expedite delivery of reperfusion therapy.

Moderate alcohol consumption is more cardioprotective in men with the metabolic syndrome.

The aim of the present study was to evaluate the relation among alcohol consumption, the metabolic syndrome, and the risk of ischemic heart disease (IHD). The study was conducted in a cohort of 1966 men from the Quebec Cardiovascular Study. All men were initially free of IHD and, during the follow-up period of 13 y, 219 first cases of IHD were diagnosed. Alcohol consumption was determined by calculating the g/d intake based on standard portions of beer, wine, and spirits. Metabolic syndrome was diagnosed according to a modification of the National Cholesterol Education Program Adult Treatment Panel III definition. Men who consumed >or=15.2 g of alcohol/d (4th quartile of the distribution) were younger (P < 0.001), had elevated plasma HDL-C concentrations (P < 0.001), and lower plasma concentrations of insulin (P = 0.01), CRP (P = 0.01), and fibrinogen (P < 0.001) than men in the 1st quartile (<1.3 g of alcohol/d). After adjustment for a series of coronary risk factors, alcohol consumption >or=15.2 g/d was associated with a 39% reduction in the 13-y risk of IHD [relative risk (RR) of IHD = 0.61, P = 0.02]. Finally, an alcohol consumption <15.2 g/d was associated with an increase of the risk of IHD in men with the metabolic syndrome (RR = 2.24, P < 0.001) but not in men without the metabolic syndrome (RR = 1.31, P = 0.22). These results confirm that moderate daily alcohol consumption has cardioprotective properties and suggest that the effects may be more important in subjects with a deteriorated risk profile, such as those with the metabolic syndrome.

Apolipoprotein-B, low-density lipoprotein cholesterol, and the long-term risk of coronary heart disease in men.

We examined whether plasma apolipoprotein-B (apo-B) levels add further information on the risk of coronary heart disease (CHD) after taking into account low-density lipoprotein (LDL) cholesterol concentrations and other traditional risk factors. Among 2,072 CHD-free men from the Québec Cardiovascular Study at entry and followed for 13 years, 230 had a first CHD event (CHD death or nonfatal myocardial infarction). Increased apo-B (tertile 1 vs 3) levels were associated with a significant increased risk of CHD after adjustment for nonlipid and lipid risk factors other than LDL cholesterol levels (relative risk 1.89, 95% confidence interval 1.31 to 2.73). High plasma LDL cholesterol concentrations (tertile 1 vs 3) were also associated with an increased risk of CHD independently of nonlipid and lipid risk factors (relative risk 2.02, 95% confidence interval 1.44 to 2.84). However, apo-B levels modulated to a significant extent the risk of CHD associated with increased concentrations of LDL cholesterol (>/=4.3 mmol/L). For instance, among men with high LDL cholesterol levels, those with an apo-B level <128 mg/dl were not at increased risk for CHD (relative risk 1.53, 95% confidence interval 0.89 to 2.62). In contrast, high levels of apo-B and LDL cholesterol were associated with a significant twofold increased risk of CHD (p <0.001). Receiver-operating curve analysis also indicated that plasma apo-B levels improved the ability to discriminate incident CHD cases among patients with high LDL cholesterol levels compared with a model based on LDL cholesterol levels (p = 0.04). In conclusion, plasma apo-B levels modulated the risk of CHD associated with LDL cholesterol over a 13-year follow-up.

Inflammatory markers and long-term risk of ischemic heart disease in men A 13-year follow-up of the Quebec Cardiovascular Study.

We tested the hypothesis that elevated plasma interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen concentrations are independent risk factors and interact in increasing the long-term risk of ischemic heart disease (IHD) in men. A total of 1982 IHD-free men from the Quebec Cardiovascular Study were followed over a period of 13 years during which 210 first fatal IHD events and non-fatal myocardial infarctions were recorded. Increased CRP levels (4th versus 1st quartile) were not associated with an increased risk of IHD after adjustment for non-lipid risk factors (age, body mass index, systolic blood pressure, diabetes, smoking and medication use at baseline), lipid risk factors (LDL and HDL cholesterol and triglyceride levels) and for IL-6 and fibrinogen (RR=0.70, 95% CI=0.43-1.13). High plasma IL-6 levels (4th versus 1st quartile) were associated with a 70% greater risk of IHD independent of confounding risk factors and of the other 2 inflammatory markers (RR=1.71, 95% CI=1.07-2.75). The relationship between high fibrinogen levels (4th versus 1st quartile) and IHD risk was borderline significant in multivariate analyses (RR=1.53, 95% CI=0.97-2.43). An inflammation score based on plasma IL-6 and fibrinogen levels improved the IHD risk predictive value of a multivariate model of traditional risk factors (p=0.03). Including plasma CRP levels into the inflammatory score provided no additional predictive value. In conclusion, elevated plasma IL-6 concentrations are more strongly related to IHD risk than CRP and fibrinogen. An inflammation score based on high plasma IL-6 and fibrinogen levels used in combination with traditional risk factors may improve our ability to adequately identify high risk individuals.

Insulin resistance syndrome, body mass index and the risk of ischemic heart disease.

BACKGROUND: Many people who are not obese according to standard height and weight criteria may still display features of insulin resistance syndrome and thus be at high risk of ischemic heart disease. We sought to investigate the effect of cumulative features of insulin resistance syndrome on the risk of ischemic heart disease associated with variations in body mass index (BMI) among men who participated in the Quebec Cardiovascular Study. METHODS: A cohort of 1824 nondiabetic men free of ischemic heart disease was evaluated at the 1985 baseline evaluation and followed for a period of 13 years, during which 284 first ischemic heart disease events were recorded. Relative hazards (RHs) of ischemic heart disease in 3 BMI groups (normal weight, overweight and obese) were estimated using Cox proportional hazards regression. RESULTS: Although obese men (BMI > or = 30 kg/m2) were the most likely to accumulate features of insulin resistance syndrome, the univariate risk of ischemic heart disease in this group was not significantly increased compared with normal-weight men (BMI < 25 kg/m2) (RH 1.26, 95% confidence interval [CI] 0.88-1.80). However, obese men who accumulated more than 4 features of insulin resistance syndrome were at increased risk of ischemic heart disease (RH 1.81, 95% CI 1.02-3.19) compared with normal-weight men who had fewer than 3 features of the syndrome. Conversely, having more than 4 features of insulin resistance syndrome was associated with a 3-fold increase in the risk of ischemic heart disease among normal-weight men (RH 3.01, 95% CI 1.70-5.32). INTERPRETATION: Although obesity is an important risk factor for ischemic heart disease, variations in BMI alone poorly reflect the risk of ischemic heart disease associated with features of insulin resistance syndrome.

Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Québec Cardiovascular Study.

OBJECTIVE: The objective of the present study was to investigate the association between large and small low-density lipoprotein (LDL) and long-term ischemic heart disease (IHD) risk in men of the Quebec Cardiovascular Study. METHODS AND RESULTS: Cholesterol levels in the large and small LDL subfractions (termed LDL-C> or =260A and LDL-C<255A, respectively) were estimated from polyacrylamide gradient gel electrophoresis of whole plasma in the cohort of 2072 men of the population-based Quebec Cardiovascular Study. All men were free of IHD at the baseline examination and followed-up for a period of 13 years, during which 262 first IHD events (coronary death, nonfatal myocardial infarction, and unstable angina pectoris) were recorded. Our study confirmed the strong and independent association between LDL-C<255A levels as a proxy of the small dense LDL phenotype and the risk of IHD in men, particularly over the first 7 years of follow-up. However, elevated LDL-C> or =260A levels (third versus first tertile) were not associated with an increased risk of IHD over the 13-year follow-up (RR=0.76; P=0.07). CONCLUSIONS: These results indicated that estimated cholesterol levels in the large LDL subfraction were not associated with an increased risk of IHD in men and that the cardiovascular risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles.

The triglyceride/high-density lipoprotein cholesterol ratio, the small dense low-density lipoprotein phenotype, and ischemic heart disease risk.

This study investigated the relevance of using the plasma triglyceride to high-density lipoprotein cholesterol ratio (Log TG/HDL-C) for the prediction of the small dense lowdensity lipoprotein (LDL) phenotype and the risk of ischemic heart disease (IHD). Analyses were based on data from the Quebec Cardiovascular Study in a cohort of 2072 men free of IHD at baseline, among whom 262 had a first IHD event (coronary death, non fatal myocardial infarction and unstable angina) during a 13-year follow-up period. LDL particle size phenotype was characterized using 2-16% polyacrylamide gradient gel electrophoresis (PAGGE) of whole plasma. There were significant associations between the Log TG/HDL-C ratio and features of LDL size phenotype such as the proportion of LDL with a diameter <255A (r = 0.43, p < 0.001) and LDL peak particle size (r = -20.55, p < 0.001). However, the Log TG/HDL-C ratio brought no additional value (p â yen 0.1) in predicting the small dense LDL phenotype (area under the receiver operating curve (AUROC = 71.9%) compared to TG alone (AUROC = 71.2%) or to a combination of Log TG and HDL-C (AUROC = 72.4%) after multivariate adjustment for non lipid risk factors. Finally, elevations in the Log TG/HDL-C ratio did not improve the discrimination of incident IHD cases from non IHD cases compared to the use of plasma TG levels alone (p = 0.5) or a combination of the individual TG and HDL-C values (p = 0.5). The Log TG/HDL-C ratio does not improve our ability to identify individuals with the small dense LDL phenotype compared to plasma TG levels alone. The Log TG/HDLC is also not superior to plasma TG levels alone in predicting IHD risk in men of the QuA(c)bec Cardiovascular Study.

The impact of brain death on survival after heart transplantation: time is of the essence.

BACKGROUND: It has been suggested that the modality of brain death and time from brain death until harvest impact survival and rejection after heart transplantation. METHODS: Donor files from 475 adult heart-transplant recipients were examined. From these files, a total management time (time from incident leading to brain death until aortic cross clamp) was determined, and the cause of brain death was noted. Recipient characteristics, details of postoperative course, as well as survival were obtained from the Stanford University Medical Center Heart Transplantation Database. RESULTS: Two hundred and thirty (48.4%) donors sustained traumatic injuries, 112 (23.6%) suffered a subarachnoid hemorrhage, and 102 (21.4%) died of a gunshot wound to the head. The modality of brain death did not influence medium and long-term survival. A management time longer than 72 hours was associated with poorer outcome of the heart-transplant recipients. There were significantly more treated rejection episodes in recipients whose donor sustained traumatic injuries. CONCLUSION: Modality of brain death does not impact survival but appears to influence rejection. Increased management time is associated with adverse survival trends in heart-transplant recipients.

Post-operative conversion from cyclosporine to tacrolimus in heart transplantation: a single-center experience.

BACKGROUND: Tacrolimus is a potent calcineurin inhibitor that was introduced to heart transplantation in the early 1990s. The side-effect profile of tacrolimus is more favorable than that of cyclosporine and some reports have suggested an advantage of tacrolimus in the treatment of rejection. The present study was undertaken to determine whether a late conversion to tacrolimus affords these benefits to heart transplant recipients. METHODS: Charts from 109 patients who underwent conversion from cyclosporine to tacrolimus for recurrent rejection or adverse effects were retrospectively reviewed. RESULTS: During the year after conversion to tacrolimus, there was a significant decrease in treated rejection episodes. Conversion to tacrolimus rapidly resulted in an improved lipid profile. Two years after conversion blood pressure was significantly reduced. Apart from rejection, these benefits were found mainly among individuals converted to tacrolimus within 1 year of heart transplantation. CONCLUSIONS: Conversion from cyclosporine to tacrolimus is safe and results in a more favorable risk factor profile. However, most of the benefits are seen in individuals converted within 1 year of transplantation.