Increase of serum cyclophilin C levels in the follow-up of coronary artery disease: A biomarker and possible clinical predictor. / Aumento de niveles séricos de Ciclofilina C en el seguimiento de la enfermedad arterial coronaria: un biomarcador y posible predictor clínico

OBJECTIVE: This study is aimed at investigating the changes in serum CypC levels and their relationship with cardiovascular events at 12 months of follow-up in coronary artery disease (CAD) patients. METHODS: The study included a total of 125 subjects (40 patients with acute CAD, 40 patients with chronic CAD, and 45 control volunteers) and we analyzed plasma CypC levels from baseline to 6 and 12 months for a better understanding of its behavior in atherosclerosis. RESULTS: Serum CypC levels were shown to be gradually increased in CAD patients (30.63 pg/mL ± 3.77 at baseline, 38.70 pg/mL ± 6.41 at 6 months [p = 0.25], and 47.27 pg/mL ± 5.65 at 12 months [p = 0.007]). In addition, serum CypC levels during the follow-up were a significant predictor of CAD (c-statistic 0.76 at 6 months and 0.89 at 12 months; p < 0.001). Despite it, there was no significant association between CypC and cardiovascular events, but serum CypC levels tended to be higher in patients suffering cardiovascular events during the follow-up (29.02 pg/mL ± 6.39 vs. 79.96 pg/mL ± 22.18; p = 0.029). In this regard, plasma levels of high-sensitivity C-reactive protein (hsCRP) > 2.3 mg/L plus NT-proBNP > 300 pg/mL together were significant predictors of cardiovascular events during the follow-up in CAD patients with CypC levels >17.5 pg/mL (p = 0.048). CONCLUSIONS: Taken together, our results suggest that serum CypC levels increase during the follow-up in CAD patients and could be a novel biomarker with a possible prognostic value in combination with hsCRP and NT-proBNP.

OBJETIVO: Este estudio tiene como objetivo investigar los cambios en los niveles séricos de CypC y su relación con eventos cardiovasculares a los 12 meses de seguimiento en pacientes con EAC. MÉTODO: El estudio incluyó un total de 125 sujetos (40 pacientes con EAC aguda, 40 pacientes con EAC crónica y 45 voluntarios de control) y se analizaron los niveles ­plasmáticos de CypC desde el inicio hasta los 6 y 12 meses para comprender mejor su comportamiento en la aterosclerosis. RESULTADOS: Se demostró que los niveles séricos de CypC aumentaron gradualmente en pacientes con CAD [(30.63 pg/ml ± 3.77 al inicio del estudio, 38.70 pg/ml ± 6.41 a los 6 meses (p = 0.25) y 47.27 pg/ml ± 5.65 a los 12 meses (p = 0,007)]. Además, los niveles séricos de CypC durante el seguimiento fueron un predictor significativo de EAC (estadístico c 0.76 a los 6 meses y 0.89 a los 12 meses; p < 0.001). A pesar de ello, no hubo asociación significativa entre CypC y eventos cardiovasculares, pero los niveles séricos de CypC tendieron a ser más altos en los pacientes que sufrieron eventos cardiovasculares durante el seguimiento (29.02 pg/mL ± 6.39 vs. 79.96 pg/mL ± 22.18; p = 0.029). En este sentido, los niveles plasmáticos de hsCRP > 2.3 mg/L más NT-proBNP> 300 pg/ml juntos fueron predictores significativos de eventos cardiovasculares durante el seguimiento en pacientes con EAC con niveles de CypC > 17.5 pg/ml (p = 0.048). CONCLUSIONES: Tomados en conjunto, nuestros resultados sugieren que los niveles séricos de CypC aumentan durante el seguimiento en pacientes con EAC y podría ser un nuevo biomarcador con un posible valor pronóstico en combinación con hsCRP y NT-proBNP.

Cyclophilins in Ischemic Heart Disease: Differences Between Acute and Chronic Coronary Artery Disease Patients.

BACKGROUND: Cyclophilins (Cyps) are a family of peptidyl-prolyl cis/trans isomerases consistently involved in cardiovascular diseases through the inflammation pathway. This study aims to investigate the serum levels of Cyps (CypA, CypB, CypC and CypD) in patients with coronary artery disease (CAD) and the correlation with clinical characteristics and inflammation parameters. METHODS: We developed an observational prospective study with a total of 125 subjects: 40 patients with acute CAD, 40 patients with chronic CAD and 45 control volunteers, in whom serum levels of Cyps (CypA, CypB, CypC and CypD), interleukins and metalloproteinases were measured. RESULTS: CypA levels increased significantly in CAD patients compared with control subjects, but no differences were noted between acute CAD (7.80 ± 1.30 ng/mL) and chronic CAD (5.52 ± 0.76 ng/mL) patients (P = 0.13). No differences in CypB and CypD levels were showed between CAD patients and controls and between acute CAD and chronic CAD patients. In relation with CypC, the levels in CAD patients were significantly higher compared to controls (32.42 ± 3.71 pg/mL vs. 9.38 ± 1.51 pg/mL, P < 0.001), but no differences between acute and chronic CAD groups were obtained (P = 0.62). We analyzed the CypC > 17.5 pg/mL cut-off point, and it was significantly associated with older age, hypertension, dyslipidemia and more extensive CAD in acute and chronic CAD groups. CONCLUSIONS: CypA and CypC levels are increased in CAD patients. High CypC serum levels could be a novel biomarker in CAD patients correlating with a more severe disease.

Carotid plaque is a predictor of major adverse cardiac and cerebrovascular events in patients undergoing coronary angiography.

Background: Carotid disease, measured as carotid intima-media thickness (CIMT) and carotid plaque (CP), is associated with major adverse cardiac and cerebrovascular events (MACCE) in people without the previous atherosclerotic disease; however, there are few published data in patients undergoing coronary angiography. The aim of the study is to determinate if the carotid disease is associated with MACCE after coronary angiography. Methods: A total of 390 consecutive patients underwent coronary angiography after exercise echocardiography and carotid ultrasonography between 2002 and 2013. MACCE was defined as stroke, myocardial infarction due to atherosclerosis progression or death due to a stroke or cardiac event. Results: Two patients were lost (0.5%). During a mean follow-up of 6.0 years (standard deviation of 2.9), 52 patients (13.4%) suffered MACCE. 1, 5, and 10 years, event-free survival was 96.4% (1.0), 88.7% (1.7), and 81.4% (2.8), respectively. Event rates at 10 years were higher in the CP group (23.2% vs. 10.2%, p = 0.013) and in the CIMT > 0.9 mm group (25.9% vs. 13.3%, p = 0.023). Multivariate analysis showed smoking habit (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.36-4.62, p = 0.003), glomerular filtration rate (HR 0.98, 95% CI 0.98-0.99), aortic stenosis (HR 2.99, 95% CI 1.24-7.21, p = 0.014), incomplete/no coronary revascularization (HR 1.97, 95% CI 1.06-3.67, p = 0.033), insulin treatment (HR 2.63, 95% CI 1.30-5.31, p = 0.006), and CP (HR 2.36, 95% CI 1.02-5.44, p = 0.044) as predictors of MACCE. Conclusions: CP is an independent predictor of MACCE in patients undergoing coronary angiography.

Introducción: La enfermedad carotídea, definida como grosor de íntima media (GIMC) y placa (PC), se asocia con eventos adversos cardiacos y cerebrovasculares (EACC) en sujetos sin aterosclerosis previa; sin embargo hay pocos datos en pacientes sometidos a coronariografía. El objetivo del estudio es determinar si la enfermedad carotídea se asocia a EACC en pacientes remitidos a coronariografía. Métodos: Entre 2002 y 2013 390 pacientes fueron sometidos a coronariografía tras ecocardiograma de esfuerzo y ecografía carotídea. Se definió EACC como accidente cerebrovascular, infarto de miocardio por progresión aterosclerótica o muerte por accidente cerebrovascular o causa cardiaca. Resultados: Durante un seguimiento medio de 6 años (desviación estándar 2, 9) se registraron 2 pérdidas y 52 eventos (13,4%). La supervivencia media libre de eventos a uno, cinco y diez años fue 96.4% (1.0), 88.7% (1.7) y 81.4% (2.8). Hubo mayor número de eventos a 10 años en el grupo de PC (23.2% frente 10.2%, p = 0.013) y GIMC > 0.9 mm (25,9% frente 13.3%, p = 0.023). En el análisis multivariado los predictores de EACC fueron tabaquismo (hazard ratio [HR] 2.51, intervalo de confianza [IC] al 95% 1.36-4.62, p = 0.003), filtrado glomerular renal (HR 0.98 IC95% 0.98-0.99), estenosis aórtica (HR 2.99, IC 95% 1.24-7.21, p = 0.014), revascularización incompleta/no revascularización (HR 1.97, IC 95% 1.06-3.67, p = 0.033), tratamiento con insulina (HR 2.63, IC 95% 1.30-5.31, p = 0.006) y PC (HR 2.36, 95%CI 1.02-5.44, p = 0.044). Conclusiones: La PC es un predictor independiente de EACC en pacientes sometidos a coronariografía.

High Serum Cyclophilin C levels as a risk factor marker for Coronary Artery Disease.

Cyclophilins (Cyps) are ubiquitous proteins that belong to the immunophilins family consistently associated with inflammatory and cardiovascular diseases. While levels of CypA have been extensively studied, less data are available for other Cyps. The purpose of this case-control study was to determine the relationship of Cyps (A, B, C and D) with coronary artery disease (CAD) and eight inflammation markers. Serum levels of Cyps, interleukins and metalloproteinases were measured in serum collected from 84 subjects. Participants were divided into two sub-groups based on CAD diagnosis: 40 CAD patients and 44 control volunteers. Serum levels of CypA, CypB and CypC, IL-1ß and IL-6 were significantly higher in CAD patients. Bivariate correlation analysis revealed a significant positive correlation between Cyps and several blood and biochemical parameters. When the ability of Cyps levels for CAD diagnosis was evaluated, higher sensitivity and selectivity values were obtained with CypC (c-statistic 0.891, p < 0.001) indicating that it is a good marker of CAD disease, while less conclusive results were obtained with CypA (c-statistic 0.748, p < 0.001) and CypB (c-statistic 0.655, p < 0.014). In addition, significant correlations of traditional CAD risk factors and CypC were observed. In summary, high levels of CypC are a risk factor for CAD and therefore it can be proposed as a new biomarker for this disease.

Carotid plaque is a predictor of major adverse cardiac and cerebrovascular events in patients undergoing coronary angiography.

INTRODUCTION: Carotid disease, measured as carotid intima-media thickness (CIMT) and carotid plaque (CP), is associated with major adverse cardiac and cerebrovascular events (MACCE) in people without the previous atherosclerotic disease; however, there are few published data in patients undergoing coronary angiography. The aim of the study is to determinate if the carotid disease is associated with MACCE after coronary angiography. METHODS: A total of 390 consecutive patients underwent coronary angiography after exercise echocardiography and carotid ultrasonography between 2002 and 2013. MACCE was defined as stroke, myocardial infarction due to atherosclerosis progression or death due to a stroke or cardiac event. RESULTS: Two patients were lost (0.5%). During a mean follow-up of 6.0 years (standard deviation of 2.9), 52 patients (13.4%) suffered MACCE. 1, 5, and 10 years, event-free survival was 96.4% (1.0), 88.7% (1.7), and 81.4% (2.8), respectively. Event rates at 10 years were higher in the CP group (23.2% vs. 10.2%, p = 0.013) and in the CIMT > 0.9 mm group (25.9% vs. 13.3%, p = 0.023). Multivariate analysis showed smoking habit (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.36-4.62, p = 0.003), glomerular filtration rate (HR 0.98, 95% CI 0.98-0.99), aortic stenosis (HR 2.99, 95% CI 1.24-7.21, p = 0.014), incomplete/no coronary revascularization (HR 1.97, 95% CI 1.06-3.67, p = 0.033), insulin treatment (HR 2.63, 95% CI 1.30-5.31, p = 0.006), and CP (HR 2.36, 95% CI 1.02-5.44, p = 0.044) as predictors of MACCE. CONCLUSIONS: CP is an independent predictor of MACCE in patients undergoing coronary angiography.

INTRODUCCIÓN: La enfermedad carotídea, definida como grosor de íntima media (GIMC) y placa (PC), se asocia con eventos adversos cardiacos y cerebrovasculares (EACC) en sujetos sin aterosclerosis previa; sin embargo hay pocos datos en pacientes sometidos a coronariografía. El objetivo del estudio es determinar si la enfermedad carotídea se asocia a EACC en pacientes remitidos a coronariografía. MÉTODOS: Entre 2002 y 2013 390 pacientes fueron sometidos a coronariografía tras ecocardiograma de esfuerzo y ecografía carotídea. Se definió EACC como accidente cerebrovascular, infarto de miocardio por progresión aterosclerótica o muerte por accidente cerebrovascular o causa cardiaca. RESULTADOS: Durante un seguimiento medio de 6 años (desviación estándar 2, 9) se registraron 2 pérdidas y 52 eventos (13,4%). La supervivencia media libre de eventos a uno, cinco y diez años fue 96.4% (1.0), 88.7% (1.7) y 81.4% (2.8). Hubo mayor número de eventos a 10 años en el grupo de PC (23.2% frente 10.2%, p = 0.013) y GIMC > 0.9 mm (25,9% frente 13.3%, p = 0.023). En el análisis multivariado los predictores de EACC fueron tabaquismo (hazard ratio [HR] 2.51, intervalo de confianza [IC] al 95% 1.36-4.62, p = 0.003), filtrado glomerular renal (HR 0.98 IC95% 0.98-0.99), estenosis aórtica (HR 2.99, IC 95% 1.24-7.21, p = 0.014), revascularización incompleta/no revascularización (HR 1.97, IC 95% 1.06-3.67, p = 0.033), tratamiento con insulina (HR 2.63, IC 95% 1.30-5.31, p = 0.006) y PC (HR 2.36, 95%CI 1.02-5.44, p = 0.044). CONCLUSIONES: La PC es un predictor independiente de EACC en pacientes sometidos a coronariografía.

Carotid plaque is a predictor of major adverse cardiac and cerebrovascular events in patients undergoing coronary angiography / La presencia de placa carotídea es predictor de eventos adversos cardiacos y cerebrovasculares en sujetos sometidos a coronariografía

Abstract Introduction: Carotid disease, measured as carotid intima-media thickness (CIMT) and carotid plaque (CP), is associated with major adverse cardiac and cerebrovascular events (MACCE) in people without the previous atherosclerotic disease; however, there are few published data in patients undergoing coronary angiography. The aim of the study is to determinate if the carotid disease is associated with MACCE after coronary angiography. Methods: A total of 390 consecutive patients underwent coronary angiography after exercise echocardiography and carotid ultrasonography between 2002 and 2013. MACCE was defined as stroke, myocardial infarction due to atherosclerosis progression or death due to a stroke or cardiac event. Results: Two patients were lost (0.5%). During a mean follow-up of 6.0 years (standard deviation of 2.9), 52 patients (13.4%) suffered MACCE. 1, 5, and 10 years, event-free survival was 96.4% (1.0), 88.7% (1.7), and 81.4% (2.8), respectively. Event rates at 10 years were higher in the CP group (23.2% vs. 10.2%, p = 0.013) and in the CIMT > 0.9 mm group (25.9% vs. 13.3%, p = 0.023). Multivariate analysis showed smoking habit (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.36-4.62, p = 0.003), glomerular filtration rate (HR 0.98, 95% CI 0.98-0.99), aortic stenosis (HR 2.99, 95% CI 1.24-7.21, p = 0.014), incomplete/no coronary revascularization (HR 1.97, 95% CI 1.06-3.67, p = 0.033), insulin treatment (HR 2.63, 95% CI 1.30-5.31, p = 0.006), and CP (HR 2.36, 95% CI 1.02-5.44, p = 0.044) as predictors of MACCE. Conclusions: CP is an independent predictor of MACCE in patients undergoing coronary angiography.

Resumen La enfermedad carotídea, definida como grosor de íntima media (GIMC) y placa (PC), se asocia con eventos adversos cardiacos y cerebrovasculares (EACC) en sujetos sin aterosclerosis previa; sin embargo hay pocos datos en pacientes sometidos a coronariografía. El objetivo del estudio es determinar si la enfermedad carotídea se asocia a EACC en pacientes remitidos a coronariografía Métodos: Entre 2002 y 2013 390 pacientes fueron sometidos a coronariografía tras ecocardiograma de esfuerzo y ecografía carotídea. Se definió EACC como accidente cerebrovascular, infarto de miocardio por progresión aterosclerótica o muerte por accidente cerebrovascular o causa cardiaca. Resultados: Durante un seguimiento medio de 6 años (desviación estándar 2, 9) se registraron 2 pérdidas y 52 eventos (13,4%). La supervivencia media libre de eventos a uno, cinco y diez años fue 96.4% (1.0), 88.7% (1.7) y 81.4% (2.8). Hubo mayor número de eventos a 10 años en el grupo de PC (23.2% frente 10.2%, p = 0.013) y GIMC > 0.9 mm (25,9% frente 13.3%, p = 0.023). En el análisis multivariado los predictores de EACC fueron tabaquismo (hazard ratio [HR] 2.51, intervalo de confianza [IC] al 95% 1.36-4.62, p = 0.003), filtrado glomerular renal (HR 0.98 IC95% 0.98-0.99), estenosis aórtica (HR 2.99, IC 95% 1.24-7.21, p = 0.014), revascularización incompleta/no revascularización (HR 1.97, IC 95% 1.06-3.67, p = 0.033), tratamiento con insulina (HR 2.63, IC 95% 1.30-5.31, p = 0.006) y PC (HR 2.36, 95%CI 1.02-5.44, p = 0.044). Conclusiones: La PC es un predictor independiente de EACC en pacientes sometidos a coronariografía.

Subclinical carotid atherosclerosis predicts all-cause mortality and cardiovascular events in obese patients with negative exercise echocardiography.

BACKGROUND: Obesity is a major health problem due to its high prevalence. The relationship between obesity and cardiovascular disease is unclear. Some studies agree that certain conditions associated with obesity, such as physical inactivity or cardiovascular risk factors, are responsible for cardiovascular risk excess among obese people. Carotid intima-media thickness and carotid plaques (CP) have been associated with cardiovascular adverse events in healthy populations, and recent data suggest a higher prevalence of subclinical carotid atherosclerosis in obese and metabolically unhealthy patients. However, there are no studies correlating subclinical atherosclerosis and adverse events (AE) in obese subjects. AIM: To determine the association between carotid disease and AE in obese patients with negative exercise echocardiography (EE). METHODS: From January 1, 2006 to December 31, 2010, 2000 consecutive patients with a suspicion of coronary artery disease were submitted for EE and carotid ultrasonography. Exclusion criteria included previous vascular disease, left ventricular ejection fraction < 50%, positive EE, significant valvular heart disease and inferior to submaximal EE. An AE was defined as all-cause mortality, myocardial infarction and cerebrovascular accident. Subclinical atherosclerosis was defined as CP presence according to Manheim and the American Society of Echocardiography Consensus. RESULTS: Of the 652 patients who fulfilled the inclusion criteria, 226 (34.7%) had body mass indexes ≥ 30 kg/m2, and 76 of them (33.6%) had CP. During a mean follow-up time of 8.2 (2.1) years, 27 AE were found (11.9%). Mean event-free survival at 1, 5 and 10 years was 99.1% (0.6), 95.1% (1.4) and 86.5% (2.7), respectively. In univariate analysis, CP predicted AE [hazard ratio (HR) 2.52, 95% confidence interval (CI) 1.17-5.46; P = 0.019]. In multivariable analysis, the presence of CP remained a predictor of AE (HR 2.26, 95%CI 1.04-4.95, P = 0.041). Other predictors identified were glomerular filtration rate (HR 0.98, 95%CI 0.96-0.99; P = 0.023), peak metabolic equivalents (HR 0.83, 95%CI 0.70-0.99, P = 0.034) and moderate mitral regurgitation (HR 5.02, 95%CI 1.42-17.75, P = 0.012). CONCLUSION: Subclinical atherosclerosis defined by CP predicts AE in obese patients with negative EE. These patients could benefit from aggressive prevention measures.

Usefulness of carotid ultrasonography in the assessment of coronary artery disease extension in patients undergoing exercise echocardiography.

OBJECTIVES: To evaluate whether carotid disease is associated with coronary artery disease (CAD) extension in patients undergoing treadmill exercise stress echocardiography (EE). METHODS: We retrospectively studied 156 patients without previous vascular disease who underwent EE, carotid ultrasonography, and coronary angiography between 2002 and 2013. Low-, intermediate-, and high-risk EE were defined as negative, localized ischemia, and multivessel/extensive ischemia EE respectively; carotid disease according to Mannheim and American Society of Echocardiography Consensus and CAD extension from zero to three vessel disease as stenosis ≥50% by visual assessment. RESULTS: Of the 156 patients, 67 (42.9%), 43 (27.6%), 22 (14.1%), and 24 (15.4%) had zero, one, two, and three vessel disease respectively. Age (P = 0.047), male sex (P = 0.010), diabetes mellitus (P = 0.039), smoking habit (P = 0.015), fasting plasma glucose (P = 0.021), European Systematic COronary Risk Evaluation (P = 0.003), pretest CAD probability (P = 0.003), high-risk EE (P < 0.001), and carotid plaque presence (CP) (P < 0.001) were associated in univariate analysis with more extensive CAD. Predictors of CAD extension in multivariate analysis were high-risk EE (odds ratio [OR] 2.42, P < 0.001), CP presence (OR 1.75, P = 0.004), and pretest CAD probability >65% (OR 1.49, P = 0.023). CP was also associated with multivessel CAD in the 53 patients with low- or intermediate-risk EE (P = 0.001). CONCLUSIONS: CP is associated with CAD extension in patients with ischemic heart disease suspicion undergoing EE. Patients with CP could benefit from a more aggressive therapeutic strategy regarding patients without carotid disease and similar risk EE, especially in intermediate- and/or low-risk test where guidelines recommend initially optimal medical treatment.

Usefulness of carotid ultrasonography in the diagnosis of coronary artery disease in patients undergoing exercise echocardiography.

BACKGROUND: Relationship between carotid and coronary artery disease (CAD) in patients undergoing invasive and non-invasive test is unclear. The aim of the study is to evaluate whether carotid disease is associated with CAD in patients submitted to exercise echocardiography (EE) and if it improves the EE ability to predict CAD. METHODS: We retrospectively studied 156 subjects without previous vascular disease who underwent EE, carotid ultrasonography and coronary angiography between 2002 and 2013. Positive EE was defined as exercise induced wall motion abnormalities, carotid disease according to Manheim and American Society of Echocardiography Consensus and significant CAD as stenosis ≥50%. RESULTS: Eighty-nine (57.1%) subjects had significant CAD. Factors associated with CAD in multivariate analysis were fasting plasma glucose (odds ratio [OR] 1.02, p = 0.031), pre-test probability of CAD > 65% (OR 3.71, p < 0.001), positive EE (OR 10.51, p < 0.001) and carotid plaque (CP) presence (OR 2.95, p = 0.013). There was neither statistical significant difference in area under the curve after addition of CP to EE results (0.77 versus 0.81, p = 0.525) nor sensitivity, specificity, predictive values or efficiency. CP presence reclassified as very high-risk according to Systematic COronary Risk Evaluation 13 patients (34.2%) with negative EE and 22 (33.3%) without CAD. CONCLUSION: CP is associated with CAD in patients undergoing EE, however its addition to EE does not improve CAD prediction, probably due to insufficient statistical power. CP reclassified one third of patients to very high-risk category despite negative EE or CAD absence, these subjects benefit from aggressive primary prevention interventions.

Subclinical Carotid Atherosclerosis in COPD Cases and Control Smokers: Analysis in Relation with COPD Exacerbations and Exacerbation-like Episodes.

PURPOSE: It remains unclear whether there is a pathogenic link between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases. Subclinical carotid atherosclerosis is a predictor of future cardiovascular events. Exacerbations increase all-cause mortality in COPD, and exacerbation-like episodes have been described in subjects without COPD. Our objectives were as follows: (1) to confirm the independent association between COPD and carotid atherosclerosis and (2) to asses the possible relationship between COPD exacerbations or exacerbation-like episodes and a higher risk of atherosclerosis. METHODS: 127 COPD subjects and 80 control subjects with smoking history were studied. Carotid ultrasound examination was carried out in all subjects. Univariate and multivariate logistic regression analyses were performed in order to assess the relationship between both COPD diagnosis and previous COPD exacerbations (or exacerbation-like episodes in non-COPD subjects) and the presence of carotid atherosclerosis. RESULTS: The prevalence of carotid atherosclerosis was higher in COPD group (65.3 vs. 47.5%, p = 0.01; OR 2.18, 95% CI 1.23-3.88, p < 0.01). Diagnosis of COPD was not independently associated with atherosclerosis, after adjusting for potential confounders. Neither COPD exacerbations nor exacerbation-like episodes in control subjects were associated with a higher risk of atherosclerosis. CONCLUSION: There is a higher prevalence of carotid atherosclerosis in COPD than in control smokers or ex-smokers, but the differences seem to be related to shared risk factors. We have not found evidence for an increased risk of atherosclerosis associated with COPD exacerbations or exacerbation-like events. Further longitudinal studies should be carried out to confirm these findings.

Blood Pressure Profile and Hypertensive Organ Damage in COPD Patients and Matched Controls. The RETAPOC Study.

BACKGROUND: Several studies suggest that there is a pathogenic link between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases. On the other hand, increased sympathetic tone has been described in several respiratory diseases. Our objective was to determine whether hypertension mediated by sympathetic overactivity is a mechanism that explains the association between COPD and cardiovascular diseases. METHODS: Prospective nested case-control observational study; 67 COPD patients were matched 1:1 by sex and age to controls with smoking history. 24 hour-blood pressure monitoring, urinary catecholamines and their metabolites measurement, echocardiography, carotid ultrasound examination, nocturnal oximetry and retinography were performed. FINDINGS: classic cardiovascular risk factors and comorbidities were similarly distributed between cases and controls. No significant differences for blood pressure variables (difference for mean systolic blood pressure: -0·13 mmHg; 95% CI: -4·48,4·20; p = 0·94; similar results for all blood presssure variables) or catecholamines values were found between both groups. There was a tendency for lower left ventricle ejection fraction in the COPD cases, that approached statistical significance (64·8 ± 7·4 vs 67·1 ± 6·2, p = 0·05). There were no differences in the retinal arteriovenous ratio, the carotid intima-media thickness, or the number of carotid plaques, between cases and controls. Fibrinogen values were higher in the COPD group (378·4 ± 69·6 vs 352·2 ± 45·6 mg/dL, p = 0·01) and mean nocturnal oxygen saturation values were lower for COPD patients (89·0 ± 4·07 vs 92·3 ± 2·2%, p < 0·0001). INTERPRETATION: Hypertension induced by sympathetic overactivity does not seem to be a mechanism that could explain the association between COPD and cardiovascular disease.

Centenarians and their hearts: A prospective registry with comprehensive geriatric assessment, electrocardiogram, echocardiography, and follow-up.

BACKGROUND: Data on the cardiac characteristics of centenarians are scarce. Our aim was to describe electrocardiogram (ECG) and echocardiography in a cohort of centenarians and to correlate them with clinical data. METHODS: We used prospective multicenter registry of 118 centenarians (28 men) with a mean age of 101.5±1.7 years. Electrocardiogram was performed in 103 subjects (87.3%) and echocardiography in 100 (84.7%). All subjects underwent a follow-up for at least 6 months. RESULTS: Centenarians with abnormal ECG were less frequently females (72% vs 93%), had higher rates of previous consumption of tobacco (14% vs 0) and alcohol (24% vs 12%), and scored lower in the perception of health status (6.8±2.0 vs 8.3±6.8). Centenarians with significant abnormalities in echocardiography were less frequently able to walk 6 m (33% vs 54%). Atrial fibrillation/flutter was found in 27 subjects (26%). Mean left ventricular (LV) ejection fraction was 60.0±10.5%. Moderate or severe aortic valve stenosis was found in 16%, mitral valve regurgitation in 15%, and aortic valve regurgitation in 13%. Diastolic dysfunction was assessed in 79 subjects and was present in 55 (69.6%). Katz index and LV dilation were independently associated with the ability to walk 6 m. Age, Charlson and Katz indexes, and the presence of significant abnormalities in echocardiography were associated with mortality. CONCLUSIONS: Centenarians have frequent ECG alterations and abnormalities in echocardiography. More than one fifth has atrial fibrillation, and most have diastolic dysfunction. Left ventricular dilation was associated with the ability to walk 6 m. Significant abnormalities in echocardiography were associated with mortality.

Prognostic significance of six-minute walk test in non-group 1 pulmonary hypertension.

OBJECTIVE: To assess the value of the six-minute walk test (6MWT) to predict outcome in non-group 1 pulmonary hypertension (PH). BACKGROUND: Distance walked during 6MWT has been widely used as a prognostic test in pulmonary arterial hypertension (group 1 pulmonary hypertension); however, little is known regarding its prognostic value in other groups of PH. METHODS: This was a retrospective study of 60 patients diagnosed of PH, Dana Point classification groups 2-5. 6MWT and echocardiography were performed in all cases. RESULTS: Forty patients (66.6%) were females. Mean age was 70.8 ± 10.7 years (range: 32-85). Seven patients died after a mean follow-up of 23.2 ± 16.7 months. Distance <400 m during 6MWT was associated with a higher risk for death (RR: 4.39; 95% CI: 1.13-17.05; p = 0.03) and for clinical deterioration (death or need for hospitalization) (RR: 2.76; 95% CI: 1.18-6.42; p = 0.02). CONCLUSIONS: 6MWT is useful to predict outcome in non-group 1 PH.

Haemodynamic effects of non-invasive ventilation in patients with obesity-hypoventilation syndrome.

BACKGROUND AND OBJECTIVE: Although it has been reported that pulmonary hypertension is more frequent in patients with obesity-hypoventilation syndrome than in patients with 'pure' obstructive sleep apnoea syndrome, little is known about the haemodynamic repercussions of this entity. The aim was to describe the haemodynamic status, as assessed by echocardiography and 6-min walk test (6MWT), of patients with a newly diagnosed, most severe form of obesity-hypoventilation syndrome, and to evaluate the impact of non-invasive ventilation in these patients. METHODS: A prospective, descriptive, and single-centre follow-up study was conducted. At baseline, patients underwent echocardiography, spirometry, static lung volume measurement, 6MWT, overnight pulse-oximetry and polygraphic recording. Changes in echocardiography and 6MWT were assessed after 6 months of non-invasive ventilation. Right ventricular overload was defined on the basis of right ventricular dilatation, hypokinesis, paradoxical septal motion and/or pulmonary hypertension. RESULTS: Thirty patients (20 women; mean age 69 ± 11) were tested. The percentage of patients with right ventricular overload did not change significantly after non-invasive ventilation (43.3-41.6%; P = 0.24). In patients with right ventricular overload at diagnosis, pulmonary artery systolic pressure decreased significantly at six months (58 ± 11 to 44 ± 12 mm Hg; P = 0.014), and mean distance on 6MWT increased from 350 ± 110 to 426 ± 78 m (P = 0.006), without significant changes in body mass index. CONCLUSIONS: Right ventricular overload is a frequent finding in patients with the most severe form of obesity-hypoventilation syndrome. Treatment with non-invasive ventilation is associated with a decrease in pulmonary artery systolic pressure at six months and an increase in the distance covered during the 6MWT.

Electrocardiographic abnormalities in centenarians: impact on survival.

BACKGROUND: The centenarian population is gradually increasing, so it is becoming more common to see centenarians in clinical practice. Electrocardiogram abnormalities in the elderly have been reported, but several methodological biases have been detected that limit the validity of their results. The aim of this study is to analyse the ECG abnormalities in a prospective study of the centenarian population and to assess their impact on survival. METHOD: We performed a domiciliary visit, where a medical history, an ECG and blood analysis were obtained. Barthel index (BI), cognitive mini-exam (CME) and Charlson index (ChI) were all determined. Patients were followed up by telephone up until their death. RESULTS: A total of 80 centenarians were studied, 26 men and 64 women, mean age 100.8 (SD 1.3). Of these, 81% had been admitted to the hospital at least once in the past, 81.3% were taking drugs (mean 3.3, rank 0-11). ChI was 1.21 (SD 1.19). Men had higher scores both for BI (70 -SD 34.4- vs. 50.4 -SD 36.6-, P = .005) and CME (16.5 -SD 9.1- vs. 9.1 -SD 11.6-, P = .008); 40.3% of the centenarians had anaemia, 67.5% renal failure, 13% hyperglycaemia, 22.1% hypoalbuminaemia and 10.7% dyslipidaemia, without statistically significant differences regarding sex. Only 7% had a normal ECG; 21 (26.3%) had atrial fibrillation (AF), 30 (37.5%) conduction defects and 31 (38.8%) abnormalities suggestive of ischemia, without sex-related differences. A history of heart disease was significantly associated with the presence of AF (P = .002, OR 5.2, CI 95% 1.8 to 15.2) and changes suggestive of ischemia (P = .019, OR 3.2, CI 95% 1.2-8.7). Mean survival was 628 days (SD 578.5), median 481 days. Mortality risk was independently associated with the presence of AF (RR 2.0, P = .011), hyperglycaemia (RR 2.2, P = .032), hypoalbuminaemia (RR 3.5, P < .001) and functional dependence assessed by BI (RR 1.8, P = .024). CONCLUSION: Although ECG abnormalities are common in centenarians, they are not related to sex, functional capacity or cognitive impairment. The only abnormality that has an impact on survival is AF.

Long-term clinical outcome of patients with persistent right ventricle dysfunction or pulmonary hypertension after acute pulmonary embolism.

AIMS: Persistent, echocardiography-assessed right ventricle dysfunction (RVD) and/or pulmonary hypertension (PHT) are relatively frequent findings after an acute pulmonary embolism (PE). It has been suggested that echocardiography might predict long-term adverse events. Our objectives were to evaluate the prognostic value of RVD or isolated PHT 6 months after an acute PE with regard to all-cause mortality or venous thromboembolism (VTE) recurrence. METHODS AND RESULTS: In a previous study, echocardiography was used to assess RVD or PHT on admission and 6 months after an acute PE in 101 consecutive, haemodynamically stable pulmonary patients. We assessed the subsequent vital status and incidence of recurrent VTE in these patients. Six patients were lost for follow-up. The other 95 patients were categorized as those (i) with RVD or PHT 6 months after PE (17 cases, 17.8%) and (ii) patients with neither RVD nor PHT (78 cases, 82.1%). After a mean±SD of 2.8±1.06 years, there were 9 (9.4%) deaths and 12 (12.6%) VTE recurrences. At multivariate analysis, only age predicted all-cause mortality [hazard ratio (HR): 1.081, 95% confidence interval (CI): 1.003-1.166, P=0.004]. RVD or PHT persistence did not appear to increase the risk of mortality or recurrent VTE. CONCLUSION: Persistent echocardiographic signs of right ventricular pressure overload 6 months after an acute PE did not predict long-term adverse outcome events in this study.

"Giant R wave" electrocardiogram pattern during exercise treadmill test: A case report.

INTRODUCTION: The exercise treadmill test is widely used in the evaluation of patients with suspected or known coronary artery disease. The typical ischemic response used to be ST-segment depression. CASE PRESENTATION: We describe a case of a 51-year-old Caucasian man with an unusual ischemic response during the exercise treadmill test: a "giant R wave" electrocardiogram pattern as a manifestation of hyperacute ischemia that resolved with sublingual nitroglycerin. Coronary catheterization showed a severe stenosis in a proximal dominant circumflex coronary artery. We hypothesize that, in this case, the "giant R wave" pattern was related to severe hyperacute ischemia due to coronary spasm superimposed on the atherosclerotic lesion, which probably caused complete occlusion of the artery. The patient was successfully treated with coronary percutaneous revascularization. CONCLUSIONS: This is a dramatic and rare ischemic response during the exercise treadmill test, in which, a rapid administration of nitroglycerin can prevent life-threatening events.

Two coincidental neurological complications as a presenting form of infectious endocarditis.

A 46-year-old man with two consecutive neurological events (an ischemic stroke and an intracerebral hemorrhage) is presented. Streptococcus bovis biotype I was found in blood cultures and echocardiography showed native mitral valve mobile vegetations. The patient died due to the extension of intracerebral hemorrhage.

Isolated pulmonary native valve infectious endocarditis due to Enterococcus faecalis.

We report a case of isolated pulmonary native valve infectious endocarditis due to Enterococcus faecalis in a patient without predisposing factors. The early diagnostic suspicion plays a pivotal role in this entity. An individual clinical and echocardiographic management is mandatory in these patients.