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Abstract Background Disturbed cellular cholesterol homeostasis may lead to accumulation of cholesterol in human atheroma plaques. Cellular cholesterol homeostasis is controlled by the sterol regulatory element-binding transcription factor 2 (SREBF-2) and the SREBF cleavage-activating protein (SCAP). We investigated whole genome expression in a series of human atherosclerotic samples from different vascular territories and studied whether the non-synonymous coding variants in the interacting domains of two genes, SREBF-2 1784G>C (rs2228314) and SCAP 2386A>G, are related to the progression of coronary atherosclerosis and the risk of pre-hospital sudden cardiac death (SCD). Methods Whole genome expression profiling was completed in twenty vascular samples from carotid, aortic and femoral atherosclerotic plaques and six control samples from internal mammary arteries. Three hundred sudden pre-hospital deaths of middle-aged (33–69 years) Caucasian Finnish men were subjected to detailed autopsy in the Helsinki Sudden Death Study. Coronary narrowing and areas of coronary wall covered with fatty streaks or fibrotic, calcified or complicated lesions were measured and related to the SREBF-2 and SCAP genotypes. Results Whole genome expression profiling showed a significant (p = 0.02) down-regulation of SREBF-2 in atherosclerotic carotid plaques (types IV-V), but not in the aorta or femoral arteries (p = NS for both), as compared with the histologically confirmed non-atherosclerotic tissues. In logistic regression analysis, a significant interaction between the SREBF-2 1784G>C and the SCAP 2386A>G genotype was observed on the risk of SCD (p = 0.046). Men with the SREBF-2 C allele and the SCAP G allele had a significantly increased risk of SCD (OR 2.68, 95% CI 1.07–6.71), compared to SCAP AA homologous subjects carrying the SREBF-2 C allele. Furthermore, similar trends for having complicated lesions and for the occurrence of thrombosis were found, although the results were not statistically significant. Conclusion The results suggest that the allelic variants (SREBF-2 1784G>C and SCAP 2386A>G) in the cholesterol homeostasis regulating SREBF-SCAP pathway may contribute to SCD in early middle-aged men.

OBJECTIVES Improvement in quality of life (QoL) and survival benefit are the primary objectives of coronary artery bypass graft (CABG) surgery. The profile of patients undergoing isolated CABG has altered towards higher age with more preoperative comorbidities. Thus, the importance of QoL over the quantity of life among elderly patients is getting more emphasized. In this study, our main goal was to evaluate the long-term changes in QoL, overall performance status and symptomatic status after the CABG. METHODS Comprehensive data of 508 patients who underwent isolated CABG in a single institution were prospectively collected. The RAND-36 Health Survey (RAND-36) was used as an indicator of QoL. Karnofsky dependency category was used to evaluate overall performance status, and symptomatic status was assessed using New York Heart Association (NYHA) class. All assessment were made preoperatively and repeated 1 year and 12 years later. The follow-up of the study cohort was complete in 95 and 84% of the alive patients at 1 year and 12 years, respectively. Analysis was based mainly on three age groups: ≤64 years (282 patients), 65–74 years (175 patients) and ≥75 years (51 patients). RESULTS Thirty-day, 1-year and 10-year survival rates were 98, 97 and 79%, respectively. Twelve years after the surgery significant improvement (P < 0.05) was seen in all but one RAND-36 dimensions of the QoL (general health, P = 0.76) as well as in functional capacity (P < 0.001) and NYHA class. All age groups showed improvements in RAND-36 physical component summary (PCS) and mental component summary (MCS) scores compared with the preoperative values. The youngest subgroup maintained their physical and mental health status best, whereas older subgroups had more pronounced decreases in their PCS and MCS scores. CONCLUSIONS Despite an ongoing deterioration 12 years after the CABG, there was significant improvement in most dimensions of the QoL and functional capacity in comparison with the preoperative values. The elderly gain less long-term benefit from CABG regarding the QoL and survival. [ABSTRACT FROM PUBLISHER]

Objective. We aimed to characterize the expression of indoleamine 2,3-dioxygenase (IDO) or IDO-induced tryptophan degradation-dependent pathways, which may lead to suppression of T cells and possible protection against atherosclerosis. Methods and results. Expression of IDO and IDO-related pathway components was analyzed in advanced human atherosclerotic plaques ( n = 24) and in non-atherosclerotic arteries ( n = 6). Up-regulation of IDO and genes related to the IDO pathway was found to be pronounced in atherosclerotic plaques. Immunohistochemistry demonstrated IDO protein in the atheromatous core and co-distribution with monocyte-macrophages (CD68-positive cells). In gene-set enrichment analysis, the IDO pathway revealed a significant (false discovery rate (FDR) = 0.07) regulatory T cell, fork-head box protein 3 (FoxP3)-initiated CD28-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-inducible T cell co-stimulator (ICOS)-driven pathway leading to activation of IDO expression in antigen-presenting cells (APCs). Expression of these IDO pathway genes varied between 2.1- and 16.8-fold as compared to control tissues ( P < 0.05 for all). Conclusions. IDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis offering new viable therapeutic targets for the development of antiatherogenic immunosuppressive therapies. [ABSTRACT FROM AUTHOR]

Objective: Perioperative myocardial infarction (PMI) is a well-described complication of coronary artery bypass grafting (CABG). Data on its effect on patients'' subsequent health-related quality of life (QOL) and on other related consequences is deficient. The aim here was to evaluate in a prospective follow-up design the risk factors for and consequences of PMI and especially its possible impact on health-related QOL. Methods: Comprehensive data, including preoperative risk profile, perioperative variables and postoperative morbidity up to discharge were collected of 501 CABG patients in the Heart Center of Tampere University Hospital and in all eighteen postoperative care hospitals. Eighty patients (16%) fulfilled ECG or cardiac enzyme criteria for PMI and they were compared to patients with no PMI. The RAND-36 Health Survey (RAND-36) was used as an indicator of QOL. The primary outcomes were change in physical component summary (PCS), mental component summary (MCS) and the eight dimensions of health-related QOL from the RAND-36. Symptomatic status was estimated according to New York Heart Association (NYHA) class. Assessments were made preoperatively and repeated 12 months later. Results: Multivariate logistic regression analysis identified long cardiopulmonary bypass time (P=0.006) and high age (P=0.049) as independent predictors for PMI. Thirty-day mortality was adversely affected by PMI (6.3 vs 1.0%, P=0.001). In discharged patients, the occurrence of PMI did not affect 1-year survival adversely (98.7 vs 98.6%). The PMI patients showed significant (P<0.05) improvements in six of the eight dimensions of RAND-36, but they presented with a negative change in their ‘general health’ scores at the follow-up. All QOL scores improved significantly (P<0.001) among the patients without PMI. A highly significant (P<0.001) pattern of change was seen in the RAND-36 PCS and MCS scores in both groups although PMI patients showed significantly (P=0.002) smaller change in their PCS scores. Both groups showed similar freedom from anginal symptoms at 1 year (89.6 vs 90.1%) but in the PMI group later readmissions due to cardiac-related causes were more common (23 vs 10%, P=0.002). Conclusions: PMI increases 30-day mortality and affects also adversely on later health-related QOL following CABG. [Copyright &y& Elsevier]

Objectives: The aim of the present study was to evaluate the performance of three different preoperative risk models in the prediction of postoperative morbidity and mortality in coronary artery bypass (CAB) surgery. Methods: Data on 1132 consecutive CAB patients were prospectively collected, including preoperative risk factors and postoperative morbidity and in-hospital mortality. The preoperative risk models CABDEAL, EuroSCORE and Cleveland model were used to predict morbidity and mortality. A C statistic (receiver operating characteristic (ROC) curve) was used to test the discrimination of these models. Results: The area under the ROC curve for morbidity was 0.772 for the CABDEAL, 0.694 for the EuroSCORE and 0.686 for the Cleveland model. Major morbidity due to postoperative complications occurred in 268 patients (23.6%). The mortality rate was 3.4% (n=38 patients). The ROC curve areas for prediction of mortality were 0.711 for the CABDEAL, 0.826 for the EuroSCORE and 0.858 for the Cleveland model. Conclusions: The CABDEAL model was initially developed for the prediction of major morbidity. Thus, it is not surprising that this model evinced the highest predictive value for increased morbidity in this database. Both the Cleveland and the EuroSCORE models were better predictive of mortality. These results have implications for the selection of risk indices for different purposes. The simple additive CABDEAL model can be used as a hand-held model for preoperative estimation of patients'' risk of postoperative morbidity, while the EuroSCORE and Cleveland models are to be preferred for the prediction of mortality in a large patient sample. [Copyright &y& Elsevier]

Objective: To investigate whether novel pharmacological preconditioning with diazoxide could protect the myocardial function and decrease myocardial injury in patients undergoing coronary artery bypass grafting (CABG). Methods: Forty patients with stable angina who were scheduled for isolated elective CABG operations were randomized into control group (n=20) and diazoxide (DZX) group (n=20). In the DZX group, 1.5 mg/kg diazoxide was infused intravenously within 5 min followed by a 5-min washout before commencing the cardiopulmonary bypass (CPB). In the control group, a time-matched period of placebo infusion was given. Hemodynamic data and biochemical markers of myocardial injury were measured perioperatively. Results: There were no adverse effects related to diazoxide. Cardiac index (CI) increased postoperatively as compared with baseline. In the DZX group, the improvement of CI was better than that in the control group (p=0.001). Left and right ventricular stroke work indexes decreased postoperatively, and recovered much faster in the DZX group (p=0.027 and p=0.049, respectively). There were no statistically significant differences in the other hemodynamic parameters. The creatine kinase cardiac isoenzyme (CK-MB) was highest in both groups on the first postoperative day (control 28.8±23.8 and DZX 27.3±19.4, N.S.). The cumulative release of CK-MB postoperatively was lower in the DZX patients as compared with the controls, but the difference remained not significant (p=0.09). Conclusions: Pharmacological preconditioning of the human heart with diazoxide is feasible; it confers additional myocardial protection beyond that provided by the cardioplegia alone by attenuating myocardial stunning after CABG operations. [Copyright &y& Elsevier]

A prevalence of diabetes is increasing among the patients undergoing coronary artery bypass grafting (CABG). Data on whether health-related quality of life improves similarly after CABG in diabetics and nondiabetics are limited. We assessed long-term mortality and changes in quality of life (RAND-36 Health Survey) after CABG. Seventy-four of the 508 patients (14.6%) operated on in a single institution had a history of diabetes and were compared with nondiabetics. The RAND-36 Health Survey was used as an indicator of quality of life. Assessments were made preoperatively and repeated 1 and 12 years later. Thirty-day mortality was 2.7 versus 1.6 ( p  = 0.511) in the diabetics and nondiabetics. One- and 10-year survival rates in the diabetics and nondiabetics were 94.6% versus 97.0% ( p  = 0.287) and 63.5% versus 81.6% ( p  < 0.001), respectively. After 1 year, diabetics improved significantly ( p  < 0.005) in seven, and nondiabetics ( p  < 0.001) in all eight RAND-36 dimensions. Despite an ongoing decline in quality of life over the 12-year follow-up, an improvement was maintained in four out of eight dimensions among diabetics and in seven dimensions among nondiabetics. Physical and mental component summary scores on the RAND-36 improved significantly ( p  < 0.001) in both groups after 1 year, and at least slight improvement was maintained during the 12-year follow-up time. Diabetics have inferior long-term survival after CABG as compared with nondiabetics. They gain similar improvement of quality of life in 1 year after surgery, but they have a stronger decline tendency over the years.