Avaliação do perfil de metilação dos genes LDLR, PCSK9, LDLRAP1 em pacientes portadores de hipercolesterolemia familial / Evaluation of the methylation profile of LDLR, PCSK9, LDLRAP1 genes in patients with familial hypercholesterolemia

As variabilidades genotípicas que determinam algumas alterações fenotípicas e metabólicas podem ter seu diagnostico falho se baseado apenas nos dados genômicos. Na hipercolesterolemia familial (HF) pode-se observar que os dados de variantes nos genes da LDLR, PCSK9, APOB e LDLRAP1 sugeridos pelos consensos atuais para confirmar o diagnóstico, tem mostrado serem insuficientes, mostrando baixa porcentagem de confirmação, mesmo nos dos casos em que características fenotípicas apresentam dados sugestivos importantes. A complementação no auxílio diagnóstico com dados epigenéticos tem sido sugerida em muitas doenças, principalmente nas crônicos degenerativos. A metilação do DNA pode estar envolvida no mecanismo que regulam vários processos metabólicos, entre os quais os envolvidos na expressão de proteínas e neste estudo os que estão envolvidos no metabolismo do colesterol, que poderia explicar fenótipos hipercolesterolemicos sem demonstração clara de variantes nos genes de consenso. O objetivo do presente estudo foi comparar o perfil de metilação dos genes LDLR, PCSK9 e LDLRAP1 entre pacientes com diagnóstico de Hipercolesterolemia Familial confirmado através de variantes genéticas descritas na literatura e pacientes sem diagnóstico confirmado. Além da comparação com indíviduos normolipidêmicos. A seleção dos indivíduos foi realizada na Seção de Dislipidemia do Instituto Dante Pazzanese de Cardiologia (IDPC), do Departamento de Análises Clínicas e Toxicológicas da Universidade Federal do Rio Grande do Norte (UFRN), da Universidade Estadual de Campinas (UNICAMP) e da Faculdade de Medicina de São José do Rio Preto (FAMERP). Através dos critérios MEDPED foram selecionados 133 pacientes para a realização do sequenciamento de um painel de genes relacionados ao fenótipo de HF e a homeostasia do colesterol a fim de confirmar o diagnóstico. Todos os pacientes tiveram o DNA purificado, que foi submetido ao tratamento com bissulfito, amplificado, purificado, desnaturado e sequenciado no sistema PyroMark Q24. Avaliou-se o perfil de metilação, em sítio CpG dos genes da LDLR, PCSK9 e LDLR AP1. A análise estatística foi realizada utilizando o software SPSS v.19, GraphPad Prism, versão 1.03 e o e o software R. 4.1.0. Os pacientes foram classificados em Grupo I: Pacientes com diagnóstico molecular confirmado pelo estudo fenotípico e genotipico (n=40); Grupo II: Pacientes fenotipicamente determinados como hipercolesterolemico, mas sem diagnóstico molecular confirmado pelo estudo genomico (n=93); Grupo III: indivíduos fenotipicamente determinados normolipidêmicos de acordo com a V Diretriz Brasileira de Dislipidemia (n=23). A análise comparativa entre os grupos I x II e II x III, demonstrou diferença estatísta significativa em 13 sítios CpG do total de 28 sítios CpG analisados nos três genes. Além disso, foi possível concluir que alterações nos sítios CpG presentes no gene LDLR influenciaram na presença de xantomas e arco córneo. Houve correlação positiva entre a idade e perfil de metilação do gene PCSK9, assim como, alterações nos sítios CpG deste gene influenciaram na presença de arco córneo e IAM. Além disso, alterações no sítio CPG presente no gene LDLRAP1 influenciou no desenvolvimento de DAC, IAM e RM, além da presença de xantelasma

The genotypic variabilities that determine some phenotypic and metabolic alterations can be misdiagnosed if based only on genomic data. In familial hypercholesterolemia (FH) it can be observed that the data of variants in the genes of LDLR, PCSK9, APOB and LDLR AP1 suggested by the current consensus to confirm the diagnosis, has shown to be insufficient, showing a low percentage of confirmation, even in the cases in which phenotypic characteristics present important suggestive data. Complementing the diagnostic aid with epigenetic data has been suggested in many diseases, especially in chronic degenerative diseases. DNA methylation may be involved in the mechanisms that regulate several metabolic processes, including those involved in the expression of proteins that ,in this study, are involved in cholesterol metabolism, which could explain hypercholesterolemic phenotypes without a clear demonstration of variants in consensus genes. The aim of the present study was to compare the methylation profile of LDLR, PCSK9 and LDLRAP1 genes between patients with a diagnosis of Familial Hypercholesterolemia confirmed through genetic variants described in the literature and patients without a confirmed diagnosis. In addition to the comparison with normolipidemic individuals. The selection of individuals was carried out at the Dyslipidemia Section of the Instituto Dante Pazzanese de Cardiologia (IDPC), in the Department of Clinical and Toxicological Analyzes of the Federal University of Rio Grande do Norte (UFRN), in the State University of Campinas (UNICAMP) and in the Faculdade of Medicine of São José do Rio Preto (FAMERP). Through the MEDPED criteria, 133 patients were selected to perform the sequencing of a panel of genes related to the FH phenotype and cholesterol homeostasis in order to confirm the diagnosis. All patients had their DNA purified, which were subjected to bisulfite treatment, amplified, purified, denatured and sequenced on the PyroMark Q24 system. The methylation profile in the CpG site of the LDLR, PCSK9 and LDLRAP1 genes were evaluated. Statistical analysis were performed using SPSS v.19 software, GraphPad Prism, version 1.03 and R. 4.1.0 software. Patients were classified into Group I: Patients with a molecular diagnosis confirmed by phenotypic and genotypic studies (n=40); Group II: Patients phenotypically determined to be hypercholesterolemic, but without a molecular diagnosis confirmed by the genomic study (n=93); Group III: phenotypically determined normolipidemic individuals according to the V Brazilian Dyslipidemia Directive (n=23). The comparative analysis between groups I x II and II x III showed a statistically significant difference in 13 CpG sites of the total of 28 CpG sites analyzed in the three genes of the project. Furthermore, it was possible to conclude that alterations in the CpG sites present in the LDLR gene influenced the presence of xanthomas and arc corneum. There was a positive correlation between age and PCSK9 gene methylation profile, as well as changes in the CpG sites of this gene influenced the presence of arc corneum and AMI. In addition, alterations in the site present in the LDLRAP1 gene are influencing the development of CAD, AMI and MR, in addition to the presence of xanthelasma

The additive prognostic value of coronary calcium score (CCS) to single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI)-real world data from a single center.

AIMS: Single-photon emission computed tomography myocardial perfusion imaging [SPECT-MPI] is a functional test for coronary ischemia. We aimed to assess the additive prognostic value of coronary calcium score (CCS) to SPECT-MPI in stable patients. METHODS: This study is a retrospective analysis of 655 patients who underwent SPECT-MPI with CCS (2012 to 2017). Receiver operator characteristic (ROC) identified CCS cutoff value for all-cause mortality: CCS+ if > cutoff value and MPI+ if ≥ 5% total perfusion defect (TPD). Patients were divided into 1 MPI-/CCS-; 2 MPI+/CCS-; 3 MPI-/CCS+; 4 MPI+/CCS+ and compared. Cox proportional hazard analysis identified predictors of mortality. RESULTS: CCS cutoff for all-cause mortality was > 216 (C statistic 0.756, P < 0.0001). In MPI+ groups, mean TPD was similar (13.4% and 13.1% respectively) but mortality was higher in the CCS+ (12.5% vs. 4.8%, P = 0.22) as was the severe LV systolic dysfunction (8.0% vs. 0%, P = 0.095). In MPI- groups, mean TPD was similar (0.7% and 0.9% respectively) but all-cause mortality was higher in the CCS+ (10.7% vs. 1.6%, P < 0.0001) as was severe LVSD (2.9 % vs. 0.3% P = 0.016). Age, smoking, renal impairment ,and CCS > 216 were independent predictors of mortality. CONCLUSIONS: Patients with raised CCS on SPECT-MPI have increased mortality and poor LV function despite a negative MPI.

[Chronic coronary syndrome : New classification of stable coronary artery disease]. / Chronisches Koronarsyndrom : Neuklassifikation der stabilen koronaren Herzkrankheit.

In 2019 the European Society for Cardiology (ESC) published guidelines for the diagnosis and management of chronic coronary syndromes (CCS). Thus the term "stable coronary artery disease" is replaced by CCS. The newly introduced term is based on the current understanding of pathogenesis and clinical features of coronary artery disease (CAD) as well as therapeutic management. CCS defines CAD as a chronic process that can be influenced by lifestyle adjustments, pharmacological therapies and invasive interventions (percutaneous coronary intervention, coronary artery bypass grafting) with the aim of stabilization or regression. The present work provides an overview of various scenarios that involve CCS and diagnostic pathways to clarify potentially relevant CAD. It also highlights therapeutic management and secondary preventive procedures in accordance with the current recommendations of the ESC.

Association between cardiovascular risk factors and coronary artery disease assessed using CAD-RADS classification: a cross-sectional study in Romanian population.

OBJECTIVES: This study aimed to evaluate the association between cardiovascular risk factors and Coronary Artery Disease-Reporting and Data System (CAD-RADS) score in the Romanian population. CAD-RADS is a new, standardised method to assess coronary artery disease (CAD) using coronary CT angiography (CCTA). DESIGN: A cross-sectional observational, patient-based study. SETTING: Referred imaging centre for CAD in Transylvania, Romania. PARTICIPANTS: We retrospectively reviewed 674 patients who underwent CCTA between January 2017 and August 2018. The exclusion criteria included: previously known CAD, defined as prior myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft surgery (n=91), cardiac CT for other than evaluation of possible CAD (n=85), significant arrhythmias compromising imaging quality (n=23). Finally, 475 patients fulfilled the inclusion criteria. METHODS: Demographical, clinical and CCTA characteristics of the patients were obtained. CAD was evaluated using CAD-RADS score. Obstructive CAD was defined as ≥50% stenosis of ≥1 coronary segment on CCTA. RESULTS: We evaluated the association between risk factors and CAD-RADS score in univariate and multivariable analysis. We divided the patients into two groups according to the CAD-RADS system: group 1: CAD-RADS score between 0 and 2 (stenosis <50%) and group 2: CAD-RADS score ≥3 (stenosis ≥50%). On univariate analysis, male gender, age, hypertension, dyslipidaemia, smoking and diabetes mellitus were positively associated with a CAD-RADS score ≥3. The multivariate analysis showed that male sex, age, dyslipidaemia, hypertension and smoking were independently associated with obstructive CAD. CONCLUSION: This study demonstrated a significant association between multiple cardiovascular risk factors and a higher coronary atherosclerotic burden assessed using CAD-RADS system in the Romanian population.

Fallacies and Possible Remedies of the SYNTAX Score.

Quite a few studies have revealed the clinical values regarding the outcome predictions in the cohort of the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial and decision-making with the SYNTAX score. The Evaluation of Xience Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left-Main Revascularization (EXCEL) and Nordic-Baltic-British left main revascularization (NOBLE) studies are the largest international randomized studies so far, comparing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) in the treatment of left main coronary artery disease. Unfortunately, both studies failed to validate the value of the SYNTAX score in the selection of revascularization strategies for patients with coronary artery diseases (CAD).. This scenario prompted us to reconsider the inherent fallacies of the SYNTAX score in its derivation. We pointed out eight fallacies for the SYNTAX score in this paper. A recently developed Coronary Artery Tree description and Lesion EvaluaTion (CatLet) score, available at http://www.catletscore.com, a novel angiographic scoring system, could be the remedies for the SYNTAX score.

Prognostic significance of the Medina classification in bifurcation lesion percutaneous coronary intervention with second-generation drug-eluting stents.

The Medina classification is the most widespread method to describe bifurcation lesions. However, little is known regarding its prognostic impact. Therefore, the aim of this study is to assess the prognostic significance of the Medina classification following percutaneous coronary intervention (PCI). From a prospective registry of 738 consecutive patients undergoing PCI for bifurcation lesions, 505 were treated with second-generation drug-eluting stents (DES). Of these, 407 (80.6%) presented with "true bifurcation" (TB) lesions (Medina class 1.0.1, 1.1.1, 0.1.1) and 98 (19.4%) in all other categories ("non-true bifurcation" = NTB). We compared rates of death and major adverse cardiac events (MACE: cardiac death, myocardial infarction, or target vessel revascularization) at 12 months and 3 years. Patients with TB had lower rates of previous bypass surgery (7.4% vs. 11.2%, p = 0.043). TB lesions were more likely to be calcified (33.9% vs. 28.6%, p = 0.003) and ulcerated (8.8% vs. 4.1%, p < 0.01). At 12 months, mortality was numerically higher for TB PCI (4.1% vs. 2.1%, p = 0.052) and MACE rates were higher (19.2% vs. 10.2%, p < 0.001). At 3 years, both all-cause death (10.1% vs. 5.1%, p = 0.002) and rates of MACE (37.2% vs. 17.6%, p < 0.001) were higher for TB PCI. After performing regression analysis, TB remained an independent predictor for poor outcomes (OR-2.28 at 12 months, CI 1.45-9.50, p = 0.007, OR-3.75 at 3 years, CI 1.52-6.77, p = 0.001 for MACE). In conclusion, TB lesions, according to the Medina classification, portend worse prognosis for patients undergoing bifurcation PCI. This may guide prognostication and decision-making in treatment.

Comparative effectiveness analysis of percutaneous coronary intervention versus coronary artery bypass grafting in patients with chronic kidney disease and unprotected left main coronary artery disease.

AIMS: Outcomes according to the status of renal insufficiency have not been fully evaluated in left main coronary artery disease (LMCAD). In the present study therefore, we sought to evaluate clinical outcomes in patients with significant LMCAD stratified by the degree of renal insufficiency and the relative clinical outcomes after PCI and CABG stratified by the differential levels of renal function using data from the large multinational "all-comers" Interventional Research Incorporation Society-Left MAIN Revascularization (IRIS-MAIN) registry. METHODS AND RESULTS: Among 4,894 patients with LMCAD, renal insufficiency was graded according to the estimated glomerular filtration rate (eGFR). The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as death, myocardial infarction, stroke, or any revascularisation. The patients were stratified into three groups according to eGFR: 3,824 (78%) in group 1 (eGFR ≥60 ml·min-1·1.73 m2), 838 (17%) in group 2 (eGFR ≥30 and <60), and 232 (5%) in group 3 (eGFR <30). At two years, after adjustment, compared with group 1, the risk of MACCE was significantly higher in group 2 (hazard ratio [HR] 1.46, 95% confidence interval [CI]: 1.18-1.79) and in group 3 (HR 3.39, 95% CI: 2.61-4.40). The p interaction for MACCE across groups was 0.20. The adjusted risk of MACCE was similar between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in groups 1 and 2. However, PCI was associated with a significantly higher risk of MACCE compared to CABG (HR 1.88, 95% CI: 1.08-3.25) in group 3. CONCLUSIONS: The degree of renal insufficiency was proportionately associated with unfavourable outcomes in patients with LMCAD. In group 3, PCI was associated with a higher risk of MACCE compared with CABG. Also, the effect of PCI versus CABG on MACCE was consistent, with PCI being associated with less bleeding and CABG being associated with less repeat revascularisation.

A noninvasive and highly sensitive approach for the assessment of coronary collateral circulation by 192-slice third-generation dual-source computed tomography.

The coronary collateral circulation (CCC) is an alternative source of blood supply when the original vessels fail to provide sufficient blood. The accurate detection of CCC is critical for the treatment of ischemic heart disease, especially when the stent surgery is not an option. The assessment of minute vessels such as coronary collateral arteries is challenging. The objective of this study was to assess the feasibility of detection and classification of CCC using the192-slice third-generation dual-source computed tomography angiography (192-slice DSCT CTA).Eight hundred patients (450 men and 350 women, mean age: 56 ±â€Š11 years) with complete or subtotal occlusion of at least 1 major coronary artery were enrolled for our study. February 2016 and September 2018, the patient both 192-slice DSCT CTA and conventional coronary angiography (CAG) were performed in all enrolled patients. The interval between two approaches for a given patient was 6.1 ±â€Š3.7 days (Range: 1-15). The diagnostic accuracy of 192-slice DSCT CTA was evaluated by comparing it with that of CAG. The identified CCC was graded according to the Rentrop classification.The prevalence among patients of having at least 1 CCC was 43.8%. The sensitivity for detecting CCC by 192-slice DSCT was 91.7% (95% CI: 88.3% to 94.3%), specificity was 95.5% (95% CI: 93.1% to 97.2%), positive predictive value was 94.3% (95% CI: 91.5% to 96.2%), and negative predictive value was 93.3% (95% CI: 90.9% to 95.3%). Cohen-Kappa analysis showed that the consistency of the correct classification of CCC using CAG and 192-slice DSCT was very high with the kappa coefficient (κ) of 0.94 (95% CI: 0.91-0.96, P value = .01). Additionally, the radiation dose for 192-slice DSCT was as low as 0.42 ±â€Š0.04 mSv (range, 0.35-0.43 mSv).The 192-slice DSCT CTA is a reliable and sensitive non-invasive method for the evaluation of CCC with low radiation doses.

Long-term outcome of cardiac allograft vasculopathy: Importance of the International Society for Heart and Lung Transplantation angiographic grading scale.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major complication limiting long-term survival after heart transplantation (HTx). However, long-term outcome data of HTx recipients with detailed information on angiographic severity are scarce. METHODS: The study included 501 HTx recipients with angiographic follow-up up to 20 years post-transplant. All coronary angiograms were classified according to the International Society for Heart and Lung Transplantation (ISHLT) grading scale. RESULTS: CAV prevalence increased over time after transplantation, reaching 10% at 1 year, 44% at 10 years, and 59% at 20 years. Older donor age (hazard ratio [HR] 1.38 per 10 years, 1.20-1.59, p < 0.001), male donor sex (HR 1.86, 1.31-2.64, p < 0.001), stroke as donor cause of death (HR 1.47, 1.04-2.09, p = 0.03), recipient pre-transplant hemodynamic instability (HR 1.79, 1.15-2.77, p = 0.01), post-transplant smoking (HR 1.59, 1.06-2.39, p = 0.03), and first-year treated rejection episodes (HR 1.49, 1.01-2.20, p = 0.046) were independent risk factors for CAV. Baseline anti-metabolite drug use (HR 0.57, 0.34-0.95, p = 0.03) and more recent transplant date (HR 0.78 per 10 years, 0.62-0.99, p = 0.04) were protective factors. Compared with patients without CAV, the HR for death or retransplantation was 1.22 (0.85-1.76, p = 0.28) for CAV 1, 1.86 (1.08-3.22, p = 0.03) for CAV 2, and 5.71 (3.64-8.94, p < 0.001) for CAV 3. CONCLUSIONS: CAV is highly prevalent in HTx recipients and is explained by immunologic and non-immunologic factors. Higher ISHLT CAV grades are independently associated with worse graft survival.

[Correlation of lipoprotein(a) with clinical stability and severity of coronary artery lesions in patients with coronary artery disease].

OBJECTIVE: To analyze the correlation of lipoprotein(a) [Lp(a)] with the clinical stability and severity of coronary artery stenosis in patients with coronary artery disease (CAD). METHODS: A total of 531 patients undergoing coronary angiography in Nanfang Hospital between January, 2013 and December, 2016 were enrolled in this study. At the cutoff Lp(a) concentration of 300 mg/L, the patients were divided into high Lp(a) group (n=191) and low Lp(a) group (n=340). In each group, the patients with an established diagnosis of CAD based on coronary angiography findings were further divided into stable angina pectoris (SAP) group and acute coronary syndrome (ACS) group. The correlation between the severity of coronary artery stenosis and Lp(a) was evaluated. RESULTS: The patients in high and low Lp(a) groups showed no significant differences in age, gender, body mass index, smoking status, hypertension, or diabetes (P>0.05). Multivariate logistic regression analysis revealed that age, gender, and serum levels of low-density lipoprotein cholesterol (LDL-C) and Lp(a) were independent risk factors for CAD in these patients. A high Lp(a) level was associated with an increased risk of CAD (OR=2.443, 95%CI: 1.205-4.951, P=0.013). The patients with a high Lp(a) level were at a significantly higher risk of CAD than those with a low Lp(a) level irrespective of a low or high level of LDL-C (P=0.006 and 0.020). In the patients with CAD, the ACS group had a significantly higher Lp(a) level than the SAP group (P < 0.001); the proportion of the patients with high Gensini scores was significantly greater in high Lp(a) group than in low Lp(a) group (17.3% vs 5.6%, P=0.026), and a linear relationship was found between Lp(a) level and Gensini score (R=0.130, P=0.006). CONCLUSIONS: Serum level of Lp(a) is an independent risk factor for CAD, and an increased Lp(a) is the residual risk for CAD. In patients with CAD, a high Lp(a) level is associated with the clinical instability and severity of coronary artery stenosis.

High serum clusterin levels are associated with premature coronary artery disease in a Chinese population.

BACKGROUND: Clusterin plays an important role in the cardiovascular system, and serum levels of clusterin are higher in coronary artery disease patients. Here, we measured serum clusterin levels in premature coronary artery disease (PCAD) patients and explored the association of these levels with PCAD risk. METHODS: Serum samples and general clinical information were obtained from 672 subjects including 364 PCAD subjects, 126 non-PCAD subjects, and 182 controls. RESULTS: Serum clusterin levels were higher in PCAD patients than in controls, particularly in males with body mass index (BMI) < 25 kg/m2 (P < 0.0001). Compared with the lowest tertile of clusterin, the odds ratio of PCAD in the highest tertile was higher in both a univariate and three adjustment models, and it was 3.146-fold higher in Model 3. This association was especially significant in subgroups with BMI < 25 kg/m2 , total cholesterol < 5.7 mmol/L, high-density lipoprotein cholesterol ≥ 1.0 mmol/L, Urea < 7.14 mmol/L, and estimated glomerular filtration rate < 90 mL/min/1.73 m2 . Serum clusterin may be a potential diagnostic biomarker for PCAD (sensitivity 60.7%, specificity 51.6%, area under the curve 0.595 [95% CI, 0.544-0.647], P < 0.0001), and a combination of clusterin with clinical variables in Model 3 resulted in improved diagnostic accuracy (sensitivity 86.3%, specificity 64.2%, area under the curve 0.829 [95% CI, 0.782-0.877], P < 0.0001). CONCLUSIONS: Serum clusterin levels were increased in PCAD patients, especially for males with BMI < 25 kg/m2 . Higher clusterin levels were independently associated with the presence of PCAD, particularly in subjects with normal BMI, lower total cholesterol, urea, estimated glomerular filtration rate, and higher high-density lipoprotein cholesterol. Clusterin might be a potential diagnostic biomarker for PCAD patients, especially in combination with clinical variables.

Perioperative risk assessment with Euroscore and Euroscore II in patients with coronary artery or valvular disease.

Nowadays, both the European System for Cardiac Operative Risk Evaluation (EuroSCORE) logistic (ESL) and EuroSCORE II (ESII) models are used worldwide in predicting in-hospital mortality after cardiac operation. However, these scales are based on different populations and represent different medical approaches. The aim of the study was to assess the effectiveness of the ESL and the ESII risk scores in predicting in-hospital death and prolonged hospitalization in intensive care unit (ICU) after coronary artery bypass grafting (CABG), aortic valve replacement (AVR), and mitral valve replacement (MVR) by comparison of an estimated risk and a real-life observation at a reference cardiac surgery unit.This retrospective study was based on medical records of patients who underwent a CABG, AVR, or MVR at a reference cardiac surgery unit in a 2-year period. Primary endpoint was defined as in-hospital death. Secondary endpoint was a prolonged hospitalization at the ICU, defined as longer than 3 days.The study encompassed 586 patients [114 (23.1%) female, mean age 65.8 ±â€Š10.5 years], including 493 patients undergoing CABG, 66 patients undergoing AVR, and 27 patients undergoing MVR. The ESL and ESII risk scores were higher in MVR subgroup (31.7% ±â€Š30.5% and 15.3% ±â€Š19.4%) and AVR subgroup (9.7% ±â€Š11.6% and 3.2% ±â€Š4.2%) than in CABG subgroup (6.9% ±â€Š10.4% and 2.5% ±â€Š4.1%; P < .001). Subgroups of patients were significantly different in terms of clinical, biochemical, and echocardiography factors. Primary endpoint occurred in 36 (6.1%) patients: 21 (4.3%), 7 (10.6%), and 8 (29.7%) in CABG, AVR, and MVR subgroups, respectively. The ESII underestimated the risk of mortality. Secondary endpoint occurred in 210 (35.8%) patients: 172 (34.9%), 22 (33.4%), and 16 (59.3%) in CABG, AVR, and MVR subgroups, respectively.In the study, the perioperative risk estimated with the ESL and the ESII risk scores was compared with a real-life outcome among over 500 patients. Regardless of the type of surgery, result in the ESL was better correlated with the risk of in-hospital death.

Reclassification of Treatment Strategy With Instantaneous Wave-Free Ratio and Fractional Flow Reserve: A Substudy From the iFR-SWEDEHEART Trial.

OBJECTIVES: The authors sought to compare reclassification of treatment strategy following instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR). BACKGROUND: iFR was noninferior to FFR in 2 large randomized controlled trials in guiding coronary revascularization. Reclassification of treatment strategy by FFR is well-studied, but similar reports on iFR are lacking. METHODS: The iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome Trial) study randomized 2,037 participants with stable angina or acute coronary syndrome to treatment guided by iFR or FFR. Interventionalists entered the preferred treatment (optimal medical therapy [OMT], percutaneous coronary intervention [PCI], or coronary artery bypass grafting [CABG]) on the basis of coronary angiograms, and the final treatment decision was mandated by the iFR/FFR measurements. RESULTS: In the iFR/FFR (n = 1,009/n = 1,004) populations, angiogram-based treatment approaches were similar (p = 0.50) with respect to OMT (38%/35%), PCI of 1 (37%/39%), 2 (15%/16%), and 3 vessels (2%/2%) and CABG (8%/8%). iFR and FFR reclassified 40% and 41% of patients, respectively (p = 0.78). The majority of reclassifications were conversion of PCI to OMT in both the iFR/FFR groups (31.4%/29.0%). Reclassification increased with increasing number of lesions evaluated (odds ratio per evaluated lesion for FFR: 1.46 [95% confidence interval: 1.22 to 1.76] vs. iFR 1.37 [95% confidence interval: 1.18 to 1.59]). Reclassification rates for patients with 1, 2, and 3 assessed vessels were 36%, 52%, and 53% (p < 0.01). CONCLUSIONS: Reclassification of treatment strategy of intermediate lesions was common and occurred in 40% of patients with iFR or FFR. The most frequent reclassification was conversion from PCI to OMT regardless of physiology modality. Irrespective of the physiological index reclassification of angiogram-based treatment strategy increased with the number of lesions evaluated.

Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study.

OBJECTIVE: To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. DESIGN: Multicentre case-cohort study. SETTING: A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. PARTICIPANTS: 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. MAIN OUTCOME MEASURES: Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). RESULTS: There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. CONCLUSIONS: Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.

Qualidade de vida de pacientes em hemodiálise com doença coronariana versus sem doença coronariana / Quality of life of hemodialysis patients with coronary disease versus no coronary disease

A doença renal crônica (DRC) é um problema da saúde pública mundial e preditora para progressão da doença arterial coronariana (DAC), causando limitações e alterações na vida cotidiana dos pacientes e familiares e, consequentemente, na qualidade de vida. Nesse cenário, o Assistente Social, como integrante da equipe multiprofissional, propõe alternativas de enfrentamento às situações que comprometem o processo da saú - de-doença dos pacientes. O estudo tem como objetivos avaliar o impacto da presença da DAC na qualidade de vida dos pacientes em hemodiálise e identificar as diferenças no perfil sociodemográfico desses pacientes, conforme a presença da doença. Método: Estudo trans - versal e descritivo realizado com 51 pacientes em hemodiálise (30 com DAC e 21 sem DAC), em um hospital universitário de cardiologia de São Paulo, através de questionário de qualidade de vida para pacientes em tratamento dialítico KDQOL-SF TM 1.3, questionário socioeconômico e dados clínicos descritos em prontuário eletrônico. Resultados: No to - tal dos pacientes, houve predomínio do sexo masculino, da cor/raça autodeclarada par - da e preta, ensino fundamental incompleto e em benefício previdenciário/assistencial. Os pacientes sem DAC encontram-se aproximadamente dois anos a mais em tratamento dia - lítico. Entre as dimensões do KDQOL-SF TM 1.3, os pacientes com DAC apresentaram melhores índices de qualidade de vida. Conclusão: A qualidade de vida dos pacientes com DRC em hemodiálise que apresentam diagnóstico de DAC, apresentou-se relativamente melhor do que a dos pacientes sem DAC. Não houve diferenças sociodemográficas relevantes entre os grupo

Chronic kidney disease (CKD) is a worldwide public health problem and a predictor of the progression of coronary artery disease (CAD), causing limitations and changes in the daily lives of patients and their families and, therefore, in their quality of life. In this scenario, the Social Worker, as a member of a multiprofessional team, proposes alternatives for coping with situations that compromise patients' health-disease process. The aims of this study were to assess the impact of the presence of CAD on the quality of life of patients on hemodialysis, and to identify the differences in sociodemographic profile of these patients, according to the presence of CAD. Methods: A cross-sectional, descriptive study was conducted with 51 patients on hemodialysis treatment, (30 with CAD and 21 without CAD), at a university cardiology hospital in the city of São Paulo, using a quality of life questionnaire for patients on dialysis treatment KDQOL-SF TM 1.3, a socioeconomic questionnaire, and clinical data described in the electronic medical records. Results: Of the total patients, there was a predominance of males, with self-declared color/race Brown and Black, incomplete primary education, and receiving social security benefits. The patients without CAD had been in dialysis treatment for approximately two years more. Among the dimensions of the KDQOL-SF TM 1.3, patients with CAD had better quality of life indices. Conclusion: The quality of life of patients with CKD on hemodialysis and diagnosed with CAD was relatively better than that of patients without ut CAD. There were no relevant sociodemographic differences between the group

Fractional flow reserve derived from coronary computed tomography angiography reclassification rate using value distal to lesion compared to lowest value.

INTRODUCTION: A standardised approach to the interpretation of FFRCT data is currently lacking. We evaluated the rate of reclassification of FFRCT positivity using the FFRCT value distal to an anatomical stenoses compared to the lowest FFRCT value. METHOD: Patients who underwent coronary CTA and FFRCT analysis were eligible. FFRCT value of ≤ 0.80 was considered positive. Positive FFRCT distal to stenosis was defined as those with a stenoses of ≥ 25% with an associated FFRCT value of ≤ 0.80 within 2cm distal to the lesion. Outcome data on subsequent invasive coronary angiography (ICA) and coronary revascularisation were collected with a minimum follow-up of 60 days to account for delay between referral for invasive testing and/or revascularisation and receiving the procedure. RESULT: 192 patients (mean age 60.7 ± 10.6 years, 67.5% men) were included. FFRCT was positive for lowest FFRCT value in 55.7% of patients. Positive FFRCT value distal to stenosis was found in 31.3%. The overall reclassification rate of those positive for lowest FFRCT value to negative for FFRCT value distal to stenosis was 43.9% (p < 0.01). The reclassification rates were most pronounced for those with intermediate stenoses - 67% for those with < 50% stenoses, p < 0.01; 49% for 50-69% stenoses, p < 0.01. Amongst those who underwent ICA, the rate of revascularization was significant higher for those with positive FFRCT distal to stenosis compared to those positive for lowest FFRCT value (revascularization/ICA = 0.53 vs 0.44, p < 0.01). CONCLUSION: Using FFRCT values distal to a anatomical stenoses, 44% of patients positive for lowest FFRCT value were reclassified as negative for FFRCT value distal to stenosis. Those who underwent ICA, the rate of revascularisation was higher amongst those with positive FFRCT distal to stenosis compared to those positive for lowest FFRCT value.

The tense, the hostile and the distressed: multidimensional psychosocial risk profiles based on the ESC interview in coronary artery disease patients - the THORESCI study.

BACKGROUND: While single psychosocial factors have been associated with cardiovascular outcomes, it is still unclear how they cluster. Therefore, we examined whether latent multidimensional psychosocial risk profiles could be identified in the European Society of Cardiology (ESC) psychosocial screening interview. Additionally we examined whether these profiles were associated with specific sociodemographic, clinical, and psychosocial characteristics. METHOD: 681 coronary artery disease patients (age=64.9±10.6; 80% men) completed the ESC interview, comprising 15 items on 7 predefined components. Multiple self-report questionnaires focusing on demographics, mood symptoms, personality, coping, and life events were used. Clinical information was extracted from patients' medical records. RESULTS: Latent class analysis identified four psychological classes: 1. Low psychological distress (62%), 2. High hostility (19%), 3. High tension (11%), 4. High psychological distress (8%), and two social classes: Low chronic stress (81%), and High work stress (%19). Characteristics increasing the odds to belong to the "High hostility" class were male sex, negative affectivity, and psychiatric history. "High tension" membership was associated with female sex, being single, a sedentary lifestyle, seeking social support, NA, early adverse life-events, depression, anxiety, and psychiatric history. "High psychological stress" characteristics were younger age, smoking, a sedentary lifestyle, NA, depression, anxiety, early adverse life-events, psychiatric history. Being younger, alcohol use and avoidance-oriented coping increased the odds to be in the "High work stress" class. CONCLUSIONS: This study characterized four psychological and two social latent risk profiles. Results indicate the importance of a multidimensional psychosocial screening, potentially uncovering differential mechanistic pathways, which also may prove beneficial in clinical practice and in risk prevention strategies.

Avaliação de aspectos funcionais da lipoproteína de alta densidade (HDL) e suas subfrações em pacientes com doença arterial coronária / Evalution of functional aspects from high density lipoproteins (HDL) and their subfractions from coronary heart disease patients

Estudos clínicos e epidemiológicos indicam que baixas concentrações plasmáticas da lipoproteína de alta densidade (HDL) estão forte e independentemente associadas a uma maior incidência de doença arterial coronária (DAC). Entretanto, o insucesso dos agentes que são capazes de aumentar a concentração de HDL-C sugere que a funcionalidade da HDL pode representar um alvo terapêutico mais apropriado. Para a avaliação de um dos aspectos funcionais da HDL, o presente trabalho descreve o desenvolvimento de um método de grande praticidade que permite uma visão integrada de uma etapa fundamental do metabolismo que é a transferência de lípides entre as diferentes classes de lipoproteínas. A avaliação deste fenômeno nas subfrações de HDL, aspecto ainda não explorado, poderá fornecer novas informações a respeito da fisiopatologia da DAC. O método descrito no presente trabalho permite a avaliação da transferência simultânea das quatro principais classes lipídicas doadas por uma nanoemulsão semelhante à LDL para a HDL3. Foi realizada análise dos possíveis interferentes neste método. Verificou-se que a elevação da temperatura de 0 a 40 °C resultou em aumento progressivo na transferência de todos os lipídeos para a HDL3. A variação de pH entre 6,5 e 8,5 e o aumento na concentração de albumina não alteraram os valores de transferência. O aumento no tempo de incubação acima de 60 minutos promoveu diminuição na transferência de colesterol esterificado para a HDL3 e aumento na transferência de fosfolipídeos. O método apresentou boa precisão intra e inter-ensaio, sendo o coeficiente de variação menor que 5% para todos os lipídeos. A porcentagem média de transferência de colesterol livre, fosfolipídeos, triacilglicerol e colesterol em 45 invíduos saudáveis foi de respectivamente de 1,1±0,06; 13,5±0,15; 2±0,05 e 0,84±0,04% e em 45 portadores de doença arterial coronária foi respectimente 1,0±0,04; 15,8±0,44; 1,77±0,04 e 1,0±0,06%. Não houve diferença nos valores de idade, IMC, colesterol total, HDL-C, LDL-C, triacilglicerol, apo A-1, apo B, CETP, PLTP e LCAT, mas os indivíduos portadores de doença arterial coronária apresentaram valores maiores de colesterol livre e colesterol total em relação aos indivíduos saudáveis. O método desenvolvido no presente estudo é prático, preciso e de potencial relevância como ferramenta no estudo dos distúrbios de função da HDL

Clinical and epidemiological studies show that low concentrations of high density lipoproteins (HDL) are strongly and independently associated to an increased incidence of coronary artery disease (CAD). However, the lack of success of some drugs developed to increase HDL cholesterol concentrations (HDL-C) suggests that the functional aspects of HDL may represent a more appropriate therapeutic target. To study one of the functional aspects of HDL, the present work describes the development of a practical method that provides an integrated view of a fundamental step of lipid metabolism, namely, the lipid transfer among different lipoprotein classes. This phenomenon in the HDL subfractions is yet unexplored, and could provide new insights on the pathophysiology of CAD. The method described here allows the measurement of the ability of HDL3 to receive the major lipid classes from a radioactively labeled nanoparticle that resemble LDL. The possible interfering factors at the lipid transfer to HDL3 were studied. The increase in the assay temperature from 0 to 40 °C results in a progressive increase in the net transfer of all lipids to HDL3. The increase in incubation time above 60 minutes resulted in a reduced transfer of cholesterol esters to HDL3 with a concomitant increase in the transfer of phospholipids to the latter. The method presented adequate intra and inter-assay precision, with a coefficient of variation smaller than 5% for all lipids. The average percentage of free cholesterol, phospholipids, triacilglycerol an cholesterol transfer to HDL3 was respectively of 1,1±0,06; 13,5±0,15; 2±0,05 e 0,84±0,04% in 45 healthy individuals and 1,0±0,04; 15,8±0,44; 1,77±0,04 e 1,0±0,06% in 45 CAD patients. There was no difference in the age, BMI, total cholesterol, HDL-C, LDL-C, triacilglycerol, apo A-1, apo B, CETP, PLTP and LCAT but the CAD patients had higher levels of total cholesterol and free cholesterol. The method described here is practical, precise and potentially relevant as a tool to study HDL function

Left main coronary artery disease: importance, diagnosis, assessment, and management.

Left main coronary disease is seen in 4%-6% of patients undergoing coronary angiography for an ischemic evaluation and is a potentially fatal condition if not promptly identified and treated. Recent studies have increased our understanding of the complexity of left main coronary artery disease. This lesion subset offers numerous challenges in diagnosis and management. Fractional flow reserve and intravascular ultrasound are important adjuncts to angiography to determine the significance of ambiguous lesions of the left main coronary artery. Surgery is associated with much better outcomes than medical therapy and is considered by many to be the standard of care in patients who are surgical candidates. Recent studies comparing surgery with percutaneous coronary intervention (PCI) have defined subgroups with lesser extent of disease burden that may do just as well with PCI. Challenges remain in the management of bifurcation disease, and the interventional community anxiously awaits the results of the large-scale randomized trials comparing PCI with surgery.