The Proinflammatory Soluble CD40 Ligand Is Associated with the Systemic Extent of Stable Atherosclerosis.

Background and objectives: Polyvascular atherosclerosis is frequent and associated with a high cardiovascular risk, although the mechanisms regulating the atherosclerosis extent to single or multiple arterial territories are still poorly understood. Inflammation regulates atherogenesis and soluble CD40 ligand (sCD40L) is an inflammatory mediator associated with the presence of single-territorial atherosclerosis. We assessed whether the sCD40L expression is associated with the atherosclerosis extent to single or multiple arterial territories and with the atherosclerosis severity in different territories. Materials and Methods: We prospectively enrolled 94 participants with no atherosclerosis (controls, n = 26); isolated coronary atherosclerosis (group 1, n = 20); coronary and lower extremity (LE) atherosclerosis (group 2, n = 18); coronary and carotid atherosclerosis (group 3, n = 12); and coronary, LE, and carotid atherosclerosis (group 4, n = 18). Serum sCD40L levels were quantified. Results: The sCD40L levels (ng/mL, mean (standard deviation)) were 4.0 (1.5), 5.6 (2.6), 7.2 (4.2), 5.9 (3.7), and 5.1 (2.4) in controls and groups 1 to 4, respectively (ANOVA p = 0.012). In nonrevascularized patients, the sCD40L levels were significantly higher in group 2 than in group 1 and were correlated with the number of LE diseased segments. Prior LE bypass surgery was associated with lower sCD40L levels. Coexistence of coronary and LE atherosclerosis was independently associated with the sCD40L levels. Conclusions: The sCD40L levels were increased in stable atherosclerosis, particularly in polyvascular coronary and LE atherosclerosis. The number of LE diseased segments and prior LE revascularization were associated with sCD40L expression. To our knowledge, these are novel data, which provide insights into the mechanisms underlying multi-territorial atherosclerosis expression. sCD40L may be a promising noninvasive tool for refining the stratification of the systemic atherosclerotic burden.

Prognostic effect and modulation of cardiac sympathetic function in heart failure patients treated with cardiac resynchronization therapy.

BACKGROUND: Cardiac autonomic dysfunction as assessed by 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy is associated with poor prognosis in heart failure (HF) patients. Although cardiac resynchronization therapy (CRT) has emerged as an effective therapy in improving outcomes on HF patients, its effect on cardiac sympathetic nervous function is still not fully understood. We aimed to study the value of pre-implantation 123I-mIBG late heart-to-mediastinum ratio (HMR) as a predictor of response and outcomes after CRT and to correlate modification in this parameter with CRT response and functional improvement. METHODS AND RESULTS: BETTER-HF (Benefit of exercise training therapy and cardiac resynchronization in HF patients) is a prospective randomized clinical trial including HF patients submitted CRT (mean LVEF 24 ± 8%, 74% NYHA class ≥ III) who underwent a clinical, echocardiographic, and scintigraphic assessment before and 6 months after CRT. One-hundred and twenty-one patients were included. Echocardiographic response was observed in 54% and composite outcome of cardiac mortality, cardiac transplant or heart failure hospitalization in 24% of patients. Baseline late HMR was an independent predictor of CRT response (regression coefficient 2.906, 95% CI 0.293-3.903, P .029) and outcomes (HR 0.066 95% CI 0.005-0.880, P .040). At follow-up, 123I-mIBG imaging showed positive changes in cardiac sympathetic nerve activity only in responders to CRT (1.36 ± 0.14 prior vs. 1.42 ± 0.16 after CRT, P .039). There was a significant correlation between improvement in late HMR and improvement in peak oxygen consumption (r 0.547, P < .001). CONCLUSION: In our study, baseline cardiac denervation predicted response and clinical outcomes after CRT implantation. Cardiac sympathetic function was improved only in patients who responded to CRT and these positive changes were correlated with improvement in functional capacity.

High-intensity interval training in cardiac resynchronization therapy: a randomized control trial.

AIMS: To determine the effects of high-intensity interval training (HIIT) following cardiac resynchronization therapy (CRT) implantation in patients with chronic heart failure (CHF), on noninvasive estimates of systolic ventricular function, exercise performance, severity of symptoms and quality of life. METHODS: Cardiopulmonary exercise testing, resting transthoracic echocardiogram and health-related quality of life assessment were obtained before and at 6 months after CRT implantation in 37 patients with moderate-to-severe CHF. Patients were randomized after CRT to either a 24-week HIIT group (90-95% peak heart rate, 2 days per week) or to a usual care group (CON). Mixed design 2 × 2 repeated measures ANOVA were used to test for differences within and in-between groups. RESULTS: Improvements in health-related quality of life (HIIT = 98.54%, CON = 123.47%), NYHA class (HIIT = 43.44%, CON = 38.30%) HR recovery at minute 1 (HIIT = 32.32%, CON = 42.94%), pulse pressure at peak effort (HIIT = 14.06%, CON = 9.52%, LVEF (HIIT = 42.17%, CON = 51.10%) and LV Mass (HIIT = 13.26%, CON = 11.88%) were similar in both groups (p > 0.05). Significant increases in CPET duration in the HIIT group (25.94%), and increases in peak VO2 (HIIT = 8.64%, CON = 4.85%) and percent-predicted VO2 (HIIT = 10.57%, CON = 4.26%) in both groups, were observed in the intention-to-treat analysis. CONCLUSION: Six months of HIIT in patients in CRT did not further improved indices of functional capacity and health-related quality of life, and LV structure and function, compared to CRT alone. However, HIIT led to further improvements in exercise performance. It remains unclear whether HIIT benefits patients in CRT to a similar degree as more conventional forms of exercise training previously shown to maximize benefits in CRT. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov . Unique identifier: NCT02413151.

[Anomalous origin of left coronary artery: a malignant interarterial variant with a benign clinical course]. / Origem anómala da coronária esquerda: variante interarterial maligna com evolução clínica benigna.

Anomalous origin of coronary arteries represents a clinical challenge not only because of the anatomical variability, but also the possible functional consequences, pathophysiological mechanisms involved and the absence of large series in the literature that would provide evidence for clinical and therapeutic orientation. The authors describe the case of a 55-year-old male patient with a long history of atypical chest pain who was considered to have a low to intermediate likelihood of coronary artery disease. Therefore, and also bearing in mind his physical limitations (congenital left leg atrophy), he was referred for cardiac CT to rule out coronary artery disease. The exam showed a left coronary artery arising from the right coronary cusp and with an interarterial course, between the aorta and pulmonary trunk. Although this is a potentially malignant anatomical variant with surgical indication, a conservative approach was chosen, considering the late diagnosis and particular risk-benefit profile.

Blunted coronary flow velocity reserve is associated with impairment in systolic function and functional capacity in hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction constitutes an important pathophysiological feature in hypertrophic cardiomyopathy (HCM). We aimed to assess the association between impaired coronary flow velocity reserve (CFVR) and ventricular systolic function and functional capacity. METHODS: Eighty-three patients with HCM were enrolled in this prospective cohort study. Patients underwent echocardiogram to evaluate ventricular performance and CFVR in the left anterior descending artery (LAD) and posterior descending artery (PD). Diastolic coronary flow velocity was measured in basal conditions and in hyperemia. CFVR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). The link between CFVR and biventricular systolic function and peak VO2 was studied. RESULTS: Age was 55.0(14.4)years, 50 patients (60%) were male; 59 patients (71%) had nonobstructive HCM. Mean CFVR LAD was 1.81(0.49) and CFVR PD was 1.73(0.55). Lower CFVR PD was associated with impaired global longitudinal strain (GLS) 2D (ß-estimate:-3.240,95%CI:-4.634;-1.846, p < 0.001), GLS 3D (ß-estimate:-2.559,95%CI:-3.932;-1.186, p < 0.001) and area strain (ß-estimate:-3.044,95%CI:-5.373;-0.716, p = 0.011). Lower values of CFVR PD related to worse global work index (ß-estimate:267.824,95%CI:75.964;459.683, p = 0.007), global constructive work (ß-estimate:217.300,95%CI:38.750;395.850, p = 0.018) and global work efficiency (ß-estimate:5.656,95%CI:2.229;9.084, p = 0.002). Impaired CFVR LAD (ß-estimate:2.826, 95%CI:0.913;4.739, p = 0.004) and CFVR PD (ß-estimate:2.801,95%CI:0.657;4.945, p = 0.011) were associated with lower TAPSE. Lower values of CFVR LAD (ß-estimate:2.580, 95%CI:0.169;4.991, p = 0.036) and CFVR PD (ß-estimate:3.163, 95%CI: 0.721;5.606, p = 0.012) were associated with worse peak VO2. CONCLUSION: Lower CFVR was associated with impairment in biventricular systolic function parameters and functional capacity assessed by pVO2.

Soluble CD40 ligand expression in stable atherosclerosis: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The role of inflammation in atherosclerosis development and expression in different arterial territories is unclear. Soluble CD40 ligand (sCD40L) mediates inflammation and atherogenesis. Through a systematic review and meta-analysis, we assessed whether sCD40L was dysregulated in stable atherosclerosis, irrespective of the diseased arterial territory, and whether this dysregulation differed according to the specific territory. METHODS: Systematic literature searches were performed in MEDLINE, Cochrane Library, Web of Science, and Embase for studies reporting circulating sCD40L levels in individuals with and without stable atherosclerosis. sCD40L levels were compared using random-effects meta-analysis, weighted by the inverse variance method (study protocol: PROSPERO CRD42020181392). RESULTS: Fifty-four studies (59 estimates) including 7705 patients and 7841 controls were analyzed. sCD40L levels were found to be increased in patients with atherosclerosis, irrespective of the territory (standardized mean difference [SMD] 0.43, 95% CI 0.29-0.57; 59 estimates; χ2 heterogeneity p < 0.001; I2 = 92%). SMD was greatest in carotid atherosclerosis (SMD 0.58, 95% CI 0.30-0.86; 17 estimates), followed by coronary (SMD 0.43, 95% CI 0.24-0.62; 33 estimates), lower extremity (SMD 0.26, 95% CI -0.02-0.54; 7 estimates), and renal atherosclerosis (SMD -0.07, 95% CI -2.77-2.64; 2 estimates) (χ2 heterogeneity p < 0.001; I2 ≥ 80% for all). Subgroup analysis revealed that sCD40L levels were increased in clinical, but not subclinical, atherosclerosis. CONCLUSIONS: sCD40L levels were increased in stable atherosclerosis, particularly in the carotid and coronary territories. These novel data support sCD40L as a marker of systemic atherosclerosis, possibly with differential roles in specific territories.

Cigarette Smoking, miR-27b Downregulation, and Peripheral Artery Disease: Insights into the Mechanisms of Smoking Toxicity.

Cigarette smoking is a risk factor for the development of peripheral artery disease (PAD), although the proatherosclerotic mediators of cigarette smoking are not entirely known. We explored whether circulating microRNAs (miRNAs) are dysregulated in cigarette smokers and associated with the presence of PAD. Ninety-four participants were recruited, including 58 individuals without and 36 with PAD, 51 never smokers, 28 prior smokers, and 15 active smokers. The relative expression of six circulating miRNAs with distinct biological roles (miR-21, miR-27b, miR-29a, miR-126, miR-146, and miR-218) was assessed. Cigarette smoking was associated with the presence of PAD in multivariate analysis. Active smokers, but not prior smokers, presented miR-27b downregulation and higher leukocyte, neutrophil, and lymphocyte counts; miR-27b expression levels were independently associated with active smoking. Considering the metabolic and/or inflammatory abnormalities induced by cigarette smoking, miR-27b was independently associated with the presence of PAD and downregulated in patients with more extensive PAD. In conclusion, the atheroprotective miR-27b was downregulated in active smokers, but not in prior smokers, and miR-27b expression was independently associated with the presence of PAD. These unreported data suggest that the proatherogenic properties of cigarette smoking are mediated by a downregulation of miR-27b, which may be attenuated by smoking cessation.

Circulating miRNAs Are Associated with the Systemic Extent of Atherosclerosis: Novel Observations for miR-27b and miR-146.

The mechanisms that regulate the systemic extent of atherosclerosis are not fully understood. We investigated whether the expression of circulating miRNAs is associated with the extent of stable atherosclerosis to a single territory or multiple territories (polyvascular) and with the severity of atherosclerosis in each territory. Ninety-four participants were prospectively recruited and divided into five age- and sex-matched groups: presenting no atherosclerosis, isolated coronary atherosclerosis, coronary and lower extremity atherosclerosis, coronary and carotid atherosclerosis, and atherosclerosis of the coronary, lower extremity, and carotid territories. The expression of six circulating miRNAs with distinct biological roles was assessed. The expression of miR-27b and miR-146 differed across groups (p < 0.05), showing a decrease in the presence of atherosclerosis, particularly in the three territories. miR-27b and miR-146 expression decreased in association with a higher severity of coronary, lower extremity, and carotid atherosclerosis. Polyvascular atherosclerosis involving the three territories was independently associated with a decreased miR-27b and miR-146 expression. Both miRNAs presented an area under the curve of ≥0.75 for predicting polyvascular atherosclerosis involving the three territories. To conclude, miR-27b and miR-146 were associated with the presence of severe polyvascular atherosclerosis and with the atherosclerosis severity in each territory. Both are potential biomarkers of severe systemic atherosclerosis.

Myocardial work is associated with significant left ventricular myocardial fibrosis in patients with hypertrophic cardiomyopathy.

Late gadolinium enhancement on cardiac magnetic resonance adds prognostic information in patients with hypertrophic cardiomyopathy. Whether Myocardial work, a new parameter on transthoracic echocardiographic, can be associated with significant fibrosis in hypertrophic cardiomyopathy patients is unknown. In a single-centre prospective evaluation of hypertrophic cardiomyopathy patients in whom transthoracic echocardiographic and cardiac magnetic resonance were performed, Myocardial work and related indices were calculated from global longitudinal strain and from estimated left ventricular pressure curves. The extent of late gadolinium enhancement was quantitatively assessed. Late gadolinium enhancement ≥ 15% was chosen to define significant fibrosis. Logistic regression analysis was used to find the variables associated with late gadolinium enhancement ≥ 15% and cut-off values were determined. Among the forty-six patients analysed mean age was 56 ± 15 years, 28 (61%) were male patients and the mean left ventricular ejection fraction by transthoracic echocardiographic was 67 ± 8%. Global constructive work and global work index were significantly related to late gadolinium enhancement ≥ 15%, while global longitudinal strain nearly reached statistical significance. A cut-off ≤ 1550 mmHg% of global constructive work was associated with significant fibrosis with a sensitivity of 91% and a specificity of 84%, while the best cut-off for global longitudinal strain (> - 15%) had a sensitivity of 67% and a specificity of 76%. In our study cohort, global constructive work was associated with significant left ventricular myocardial fibrosis in cardiac magnetic resonance, suggesting its utility in patients who may not be able to have a cardiac magnetic resonance study.

Inflammation is associated with the presence and severity of chronic coronary syndrome through soluble CD40 ligand.

INTRODUCTION: Inflammation contributes to the initiation and progression of atherosclerosis, although the underlying inflammatory pathways are not entirely known. Specifically, the role of the proinflammatory soluble CD40 ligand (sCD40L) on the expression of chronic coronary syndrome (CCS) is not completely understood. We evaluated whether sCD40L expression is associated with the presence of CCS and with the clinical and anatomical severity of CCS. METHODS: We prospectively recruited 94 participants, assigned to two groups matched by age and sex, without coronary artery disease (n=26) and with CCS (n=68). Clinical, laboratory and anatomical data were prospectively collected, and serum levels of sCD40L were measured. RESULTS: In patients with CCS, classic cardiovascular risk factors were more prevalent, and the sCD40L levels, leukocyte and neutrophil counts, and neutrophil/lymphocyte ratio, but not the C-reactive protein levels, were significantly higher than those in controls. sCD40L was independently associated with the presence of obstructive coronary artery disease in multivariate analysis. Regarding CCS severity, sCD40L levels showed a significant stepwise increase with increasing angina severity (ANOVA P=0.001). In addition, sCD40L was independently associated with the anatomical severity of coronary artery disease, as assessed by the Gensini score. Among patients with CCS, those with previous coronary artery bypass grafting (n=23) had lower sCD40L levels than patients waiting for revascularization (n=45) [4.3 (2.1) ng/mL vs. 6.8 (3.5) ng/mL, P=0.001]. CONCLUSIONS: The expression of the proinflammatory sCD40L was associated with the presence of CCS and reflected the clinical and anatomical severity of CCS. In addition, we describe for the first time the association between prior CABG and reduced sCD40L levels in patients with CCS.

Stratification of ST-elevation myocardial infarction patients based on soluble CD40L longitudinal changes.

Involvement of soluble CD40 ligand (sCD40L) in thrombosis and inflammation on the context of coronary artery disease is currently being revised. In that perspective, we had studied the association of sCD40L with markers of platelet activation and markers of endothelial and vascular function. On that cohort, a stratification of patients with acute myocardial infarction (AMI) 1 month after percutaneous coronary intervention (PCI) was observed based on concentrations of sCD40L. The study intended to identify the groups of AMI patients with different profiles of sCD40L concentrations and verify how medication, clinical evolution, biochemical data, and markers of regulation of endothelial function at genetic (endothelial nitric oxide synthase polymorphisms) and post-transcriptional levels (circulating microRNAs) affect sCD40L serum levels. Lower quartiles of sCD40L (<2.3 ng/mL) were associated with higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high frequency of G894T polymorphism, and altered expression of a set of microRNAs assumed to be involved in the regulation of endothelial and cardiac function and myocardium hypertrophy, relative to patients in sCD40L upper quartiles. A characteristic sCD40L variation pattern in STEMI patients was identified. Low levels of sCD40L 1 month after PCI distinguish STEMI patients with worse prognosis, a compromised cardiac healing, and a persistent endothelial dysfunction, as given by the association between sCD40L, NT-proBNP, G894T polymorphism, and specific profile of miRNA expression. These results suggest sCD40L could have a prognostic value in STEMI patients.

Non-invasive coronary artery evaluation with multidetector computed tomography.

OBJECTIVES: To evaluate the diagnostic accuracy of 16-slice multidetector spiral computed tomography in the non-invasive detection of coronary artery disease compared to invasive coronary angiography. DESIGN: Prospective study. PATIENTS: We studied 35 patients, 21 men and 14 women, mean age 63.6+/-13.8 years, who underwent elective invasive coronary angiography one week prior to undergoing 16-slice multidetector computed tomography. METHODS: We used a Toshiba Aquilion 16-slice system. Helical acquisition was performed with breath holding after injection of 140 ml of a contrast agent into a peripheral vein. Cross-sectional images were reconstructed with a slice thickness of 0.5 mm or 1 mm. We set 15 anatomical segments for the coronary tree and the evaluation was performed independently for both techniques. Coronary artery lesions with over 50% reduction in diameter were considered significant. Findings from both techniques were evaluated using ROC curve analysis. RESULTS: It was possible to evaluate 87.7% of the coronary tree segments; heavy calcification, enability to perform breath holding, motion artefacts and stents made evaluation of the other segments impossible. Overall sensitivity and specificity were 85.9% and 98.2% respectively with a 95 % confidence interval; positive predictive value was 87% and negative predictive value 97% For the different anatomical segments, sensitivity and specificity were: proximal 88.9% and 97.8%; medial 90.9% and 95.8%; distal 86.7% and 99.1% respectively. CONCLUSIONS: Multidetector computed tomography is a promising non-invasive technique for detecting or ruling out significant coronary lesions.

Changes of soluble CD40 ligand in the progression of acute myocardial infarction associate to endothelial nitric oxide synthase polymorphisms and vascular endothelial growth factor but not to platelet CD62P expression.

Reported in vitro data implicated soluble CD40 ligand (sCD40L) in endothelial dysfunction and angiogenesis. However, whether sCD40L could exert that influence in endothelial dysfunction and angiogenesis after injury in acute myocardial infarction (AMI) patients remains unclear. In the present study, we evaluated the association of sCD40L with markers of platelet activation, endothelial, and vascular function during a recovery period early after AMI. To achieve this goal, the time changes of soluble, platelet-bound, and microparticle-bound CD40L levels over 1 month were assessed in AMI patients and correlated with endothelial nitric oxide synthase (eNOS) polymorphisms, vascular endothelial growth factor (VEGF) concentrations, and platelet expression of P-selectin (CD62P). The association of soluble form, platelet-bound, and microparticle-bound CD40L with CD62P expression on platelets, a marker of platelet activation, was also assessed to evaluate the role of CD40L in the thrombosis, whereas the association with eNOS and VEGF was to evaluate the role of CD40L in vascular dysfunction. This work shows for the first time that time changes of sCD40L over 1 month after myocardial infarct onset were associated with G894T eNOS polymorphism and with the VEGF concentrations, but not to the platelet CD62P expression. These results indicate that, in terms of AMI pathophysiology, the sCD40L cannot be consider just as being involved in thrombosis and inflammation but also as having a relevant role in vascular and endothelial dysfunction.

Optimal cut-off value for homeostasis model assessment (HOMA) index of insulin-resistance in a population of patients admitted electively in a Portuguese cardiology ward.

INTRODUCTION: Insulin resistance is the pathophysiological key to explain metabolic syndrome. Although clearly useful, the Homeostasis Model Assessment index (an insulin resistance measurement) has not been systematically applied in clinical practice. One of the main reasons is the discrepancy in cut-off values reported in different populations. We sought to evaluate in a Portuguese population the ideal cut-off for Homeostasis Model Assessment index and assess its relationship with metabolic syndrome. MATERIAL AND METHODS: We selected a cohort of individuals admitted electively in a Cardiology ward with a BMI < 25 Kg/m2 and no abnormalities in glucose metabolism (fasting plasma glucose < 100 mg/dL and no diabetes). The 90th percentile of the Homeostasis Model Assessment index distribution was used to obtain the ideal cut-off for insulin resistance. We also selected a validation cohort of 300 individuals (no exclusion criteria applied). RESULTS: From 7 000 individuals, and after the exclusion criteria, there were left 1 784 individuals. The 90th percentile for Homeostasis Model Assessment index was 2.33. In the validation cohort, applying that cut-off, we have 49.3% of individuals with insulin resistance. However, only 69.9% of the metabolic syndrome patients had insulin resistance according to that cut-off. By ROC curve analysis, the ideal cut-off for metabolic syndrome is 2.41. Homeostasis Model Assessment index correlated with BMI (r = 0.371, p < 0.001) and is an independent predictor of the presence of metabolic syndrome (OR 19.4, 95% CI 6.6 - 57.2, p < 0.001). DISCUSSION: Our study showed that in a Portuguese population of patients admitted electively in a Cardiology ward, 2.33 is the Homeostasis Model Assessment index cut-off for insulin resistance and 2.41 for metabolic syndrome. CONCLUSION: Homeostasis Model Assessment index is directly correlated with BMI and is an independent predictor of metabolic syndrome.

Introdução: A resistência à insulina é a chave fisiopatológica de explicação da Síndrome Metabólica. Apesar de claramente útil, o índice Homeostasis Model Assessment (uma medição da resistência à insulina) não tem sido aplicado sistematicamente na prática clínica. Uma das principais razões relaciona-se com a discrepância de valores limiares reportados em diferentes populações. Procurámos avaliar uma população portuguesa o valor limiar ideal e avaliar a sua relação com a Síndrome Metabólica. Material e Métodos: Selecionámos uma coorte de indivíduos admitidos eletivamente numa enfermaria de cardiologia com um IMC < 25 Kg/m2 e sem anomalias do metabolismo da glicose (glicémia em jejum < 100 mg/dL e sem diabetes). Utilizámos o percentil 90 da distribuição do índice Homeostasis Model Assessment para seleção do limiar adequado para resistência à insulina. Selecionouse também uma coorte de validação composta por 300 indivíduos, sem aplicação dos critérios de exclusão referidos anteriormente. Resultados: De uma população de 7 000 indivíduos e após aplicação dos critérios de exclusão, ficámos com 1 784 indivíduos para análise. O percentil 90 do índice foi 2,33. Na coorte de validação, aplicando esse limiar, 49,3% dos indivíduos apresentam resistência à insulina. Contudo, apenas 69,9% dos doentes com síndrome metabólica apresentam resistência à insulina com esse limiar. Por análise das curvas ROC, o limiar ideal para síndrome metabólica é 2,41. O índice Homeostasis Model Assessment correlacionou-se com o IMC (r = 0,371, p < 0,001) e é um preditor independente de presença de síndrome metabólica (OR 19,4, IC 95% 6,6 ­ 57,2, p < 0,001). Discussão: O nosso estudo mostrou que numa população portuguesa de doentes admitidos eletivamente numa enfermaria de cardiologia, o limiar pelo índice Homeostasis Model Assessment para resistência à insulina é 2,33 e para síndrome metabólica é 2,41. Conclusão: O índice Homeostasis Model Assessment correlacionou-se com o IMC e é um preditor independente de síndrome metabólica.

Body mass index as a predictor of the presence but not the severity of coronary artery disease evaluated by cardiac computed tomography.

BACKGROUND: The relation between body mass index (BMI) and coronary artery disease (CAD) extension remains controversial. The aim of this study was to evaluate the correlation between BMI and CAD extension documented by coronary computed tomography angiography (CCTA). METHODS AND RESULTS: Prospective registry including 1706 consecutive stable patients that performed CCTA (dual source scanner) for the evaluation of CAD. The population was stratified by BMI: normal 530 (31.1%), overweight 802 (47.0%) and obesity 374 (21.9%). BMI was significantly higher in patients with CAD (27.7 ± 4.3 vs 26.8 ± 4.3 kg/m(2), p < 0.001); these patients were also older, more often male and had higher prevalence of diabetes, hypertension and dyslipidemia. By multivariate analysis (logistic regression) BMI remains an independent predictor of CAD (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.06; p = 0.012). Regarding the severity of CAD, BMI was not significantly different among patients with and without obstructive CAD (27.7 ± 4.3 vs 27.2 ± 4.3 kg/m(2), p = 0.120). In 319 patients (4516 segments; 4077 evaluable), a detailed atherosclerotic burden was evaluated and compared among BMI classes, defined according to the presence of plaque and the degree of stenosis. Obstructive CAD was identified in 16.9% of the patients and 45.1% had non-obstructive CAD. The discriminative threshold for high burden, established by the segment involvement score (SIS), was >5 segments with plaque (15.4% patients). The prevalence of SIS >5 among the BMI classes was: 18.7%, 13.7% and 13.6% for normal, overweight and obesity respectively (p values for the specific classes versus all other patients: 0.241, 0.450 and 0.663). CONCLUSIONS: In this population of stable patients undergoing CCTA for suspected CAD, BMI was an independent predictor of its presence, but was not correlated with the coronary disease severity.

Carotid intima-media thickness and carotid plaques improves prediction of obstructive angiographic coronary artery disease in women.

Does carotid intima-media thickness (cIMT), a surrogate marker of cardiovascular events, have predictive incremental value over established risk factors for stable coronary artery disease (CAD)? Prospective study of 300 patients, with suspected stable CAD, admitted for an elective coronary angiography and carotid ultrasound. The CAD patients had a higher cIMT, which showed a modest predictive accuracy for CAD (area under the receiver-operating characteristic curve 0.638, 95% confidence interval 0.576-0.701, P < .001). The cIMT was an independent predictor of CAD, together with age, gender, and diabetes. C-statistic for CAD prediction by traditional risk factors was not significantly different from a model that included cIMT, carotid plaque presence, or both. However, in women, it was significantly increased by the addition of cIMT or carotid plaque presence. Although cIMT cannot be used as a sole indicator of CAD, it should be considered in the panel of investigations that is requested, particularly in women who are candidates for coronary angiography.

T lymphocytes alterations are associated with oxidized LDL, troponin T, white blood cells and C-reactive protein during acute myocardial infarction.

BACKGROUND: Auto-immune responses are associated with oxidized LDL (ox-LDL) release, a key factor in plaque destabilization. Data on the relationship between ox-LDL and T lymphocytes in human populations remains scarce. T cells also react with other molecules from the lesion and/or damage the myocardium. OBJECTIVE: The objective of the present study was to examine the relationship between circulating T lymphocytes, ox-LDL, markers of myocardial necrosis (cTnT), myocardial dysfunction (N-terminal pro-brain natriuretic peptide - NT-proBNP) and inflammation (C-reactive protein - CRP) in the setting of acute myocardial infarction. METHODS: A longitudinal study of 55 patients with ST-elevation myocardial infarction (STEMI) were evaluated at three time points: admission, 2 and 40 days following admission, together with 30 patients with stable angina (SA) and 56 subjects without coronary artery disease serving as controls (CTR). RESULTS: STEMI patients had maximal ox-LDL values and minimal levels of CD3+ T lymphocytes at admission, which was normalized during the recovery period. The increasing trend of CD3+ T cells was positively associated with an ox-LDL decline over time. CRP and cTnT longitudinal variations were negatively associated with the CD3+ T-cell increasing trend. These associations were not found in SA patients or controls. CONCLUSIONS: The associations found between CD3+ T lymphocytes, ox-LDL and cTnT suggest a specificity of the immune response in AMI towards arterial and myocardial inflammation and remodelling.

Nonobstructive coronary disease leading to STEMI: assessment of residual stenosis after thrombus aspiration.

AIMS: Nonobstructive coronary atherosclerotic lesions can lead to ST-elevation myocardial infarction (STEMI). Thrombus aspiration during a primary percutaneous coronary intervention provides a setting to evaluate the degree of stenosis of culprit lesions leading to STEMI. The aim of this study was to assess the degree of culprit lesion residual stenosis after thrombus aspiration and to compare the demographic, clinical, and angiographic characteristics between patients with obstructive versus nonobstructive residual stenosis. METHODS AND RESULTS: From a single-center registry of 483 consecutive patients with STEMI undergoing a primary percutaneous coronary intervention, 172 patients underwent thrombus aspiration and were eligible for our study. We defined two groups according to the residual stenosis after thrombus aspiration: group A (n=119, 69%) with residual stenosis greater than or equal to 50%, and group B (n=53, 31%) with residual stenosis less than 50%.In terms of the baseline angiographic characteristics, patients with residual stenosis less than 50% had significantly lower prevalence of multivessel disease (15.1 vs. 46.2%, P<0.001). On multivariable analysis of the preprocedural variables, absence of vascular disease (odds ratio 4.99, 95% confidence interval 1.08-23.12, P=0.040) and age less than 59 years (odds ratio 2.67, 95% confidence interval 1.25-5.73, P=0.011) were independent predictors of culprit residual stenosis less than 50%. CONCLUSION: In this population, a significant proportion of patients with STEMI had nonobstructive residual stenosis after thrombus aspiration. These patients were younger, had a lower prevalence of vascular disease in other vascular territories, and less multivessel disease, suggesting an earlier stage of atherosclerosis.

Diabetes as an independent predictor of high atherosclerotic burden assessed by coronary computed tomography angiography: the coronary artery disease equivalent revisited.

(1) To study the prevalence and severity of coronary artery disease (CAD) in diabetic patients. (2) To provide a detailed characterization of the coronary atherosclerotic burden, including the localization, degree of stenosis and plaque composition by coronary computed tomography angiography (CCTA). Single center prospective registry including a total of 581 consecutive stable patients (April 2011-March 2012) undergoing CCTA (Dual-source CT) for the evaluation of suspected CAD without previous myocardial infarction or revascularization procedures. Different coronary plaque burden indexes and plaque type and distribution patterns were compared between patients with (n = 85) and without diabetes (n = 496). The prevalence of CAD (any plaque; 74.1 vs. 56%; p = 0.002) and obstructive CAD (≥50% stenosis; 31.8 vs. 10.3%; p < 0.001) were significantly higher in diabetic patients. The remaining coronary atherosclerotic burden indexes evaluated (plaque in LM-3v-2v with prox. LAD; SIS; SSS; CT-LeSc) were also significantly higher in diabetic patients. In the per segment analysis, diabetics had a higher percentage of segments with plaque in every vessel (2.6/13.1/7.5/10.5% for diabetics vs. 1.4/7.1/3.3/4.4% for nondiabetics for LM, LAD, LCx, RCA respectively; p < 0.001 for all) and of both calcified (19.3 vs. 9.2%, p < 0.001) and noncalcified or mixed types (14.4 vs. 7.0%; p < 0.001); the ratio of proximal-to-distal relative plaque distribution (calculated as LM/proximal vs. mid/distal/branches) was lower for diabetics (0.75 vs. 1.04; p = 0.009). Diabetes was an independent predictor of CAD and was also associated with more advanced CAD, evaluated by indexes of coronary atherosclerotic burden. Diabetics had a significantly higher prevalence of plaques in every anatomical subset and for the different plaque composition. In this report, the relative geographic distribution of the plaques within each subgroup, favored a more mid-to-distal localization in the diabetic patients.

Prevalence and predictors of coronary artery disease in patients with a calcium score of zero.

The absence of coronary calcification is associated with an excellent prognosis. However, a calcium score of zero does not exclude the presence of coronary artery disease (CAD) or the possibility of future cardiovascular events. Our aim was to study the prevalence and predictors of coronary artery disease in patients with a calcium score of zero. Prospective registry consisted of 3,012 consecutive patients that underwent cardiac CT (dual source CT). Stable patients referred for evaluation of possible CAD that had a calcium score of zero (n = 864) were selected for this analysis. The variables that were statistically significant were included in a multivariable logistic regression model. From 864 patients with a calcium score of zero, 107 (12.4%) had coronary plaques on the contrast CT (10.8%, n = 93 with nonobstructive CAD and 1.6%, n = 14 with obstructive CAD). By logistic regression analysis, the independent predictors of CAD in this population were age >55 years [odds ratio (OR) 1.63 (1.05-2.52)], hypertension [OR 1.64 (1.05-2.56)] and dyslipidemia [OR 1.54 (1.00-2.36)]. In the presence of these 3 variables, the probability of having coronary plaques was 21%. The absence of coronary artery calcification does not exclude the presence of coronary artery disease, but the prevalence of obstructive disease is very low. In this population, the independent predictors of CAD in the setting of a calcium score of zero were hypertension, dyslipidemia, and age above 55 years. In the presence of these 3 predictors, the probability of having CAD was almost 2 times higher than in the general population.