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.

Fibrilación auricular y cardiopatía isquémica: más allá de la prevención del ictus / Atrial fibrillation and ischemic heart disease: beyond stroke prevention

El objetivo principal en el abordaje del paciente con fibrilación auricular es la reducción del riesgo de ictus mediante el tratamiento antitrombótico adecuado. Sin embargo, a pesar de una adecuada anticoagulación, sigue habiendo un importante riesgo residual de eventos isquémicos, particularmente infarto de miocardio y muerte de origen cardiovascular, que exige una protección más completa. Por lo tanto, en el paciente con fibrilación auricular, el tratamiento anticoagulante debería perseguir este doble objetivo, la reducción tanto del riesgo de ictus como de las complicaciones isquémicas. Diferentes estudios han demostrado que los antagonistas de la vitamina K solo disminuyen el riesgo de ictus y de eventos isquémicos cuando el control de la anticoagulación es óptimo, cosa que ocurre en un pequeño número de pacientes. Con respecto a los anticoagulantes orales de acción directa, aunque en general muestran un perfil de eficacia y seguridad mejor que los antagonistas de la vitamina K, parece que no todos ofrecerían la misma protección en cuanto a la reducción de los eventos isquémicos. Está demostrado que el rivaroxabán reduce de manera significativa (18%) el riesgo de infarto de miocardio. De hecho, los estudios muestran que el rivaroxabán proporciona una protección vascular más completa en diferentes contextos clínicos, no solo en el paciente con fibrilación auricular, sino también en el paciente con enfermedad vascular ateroesclerótica

The main aim of management in patients with atrial fibrillation is to reduce the risk of stroke using appropriate antithrombotic treatment. However, despite adequate anticoagulation, there remains a substantial residual risk of ischemic events, particularly myocardial infarction and cardiovascular death. A more general approach is needed. Consequently, in patients with atrial fibrillation, anticoagulation treatment should seek to achieve the twin targets of reducing the risk of both stroke and ischemic events. Studies have demonstrated that vitamin K antagonists reduce the risk of stroke and ischemic events only when anticoagulation control is optimal, a situation that occurs in only a small number of patients. Direct oral anticoagulants are generally more effective and safer than vitamin K antagonists. However, not all direct oral anticoagulants appear to offer the same protection against ischemic events. It has been shown that rivaroxaban significantly reduces the risk of myocardial infarction (by 18%). In fact, studies demonstrate that rivaroxaban provides comprehensive vascular protection across a range of clinical scenarios, not only in patients with atrial fibrillation, but also in those with atherosclerotic vascular disease

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.

"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.

Peroxisome proliferator-activated receptor-gamma agonists for management and prevention of vascular disease in patients with and without diabetes mellitus.

Inflammation is known to have a pathogenic role in atherosclerosis and the genesis of acute coronary syndromes. The peroxisome proliferator-activated receptor (PPAR)-gamma, which is expressed in many constituent cells of atheromatous plaques, inhibits the activation of several proinflammatory genes responsible for atheromatous plaque development and maturation. Agonists of this receptor, such as rosiglitazone and pioglitazone, are currently available for the treatment of type 2 diabetes mellitus, and several lines of evidence have shown that these drugs have antiatherogenic effects. Insulin resistance is associated with inflammation and has a key role in atherogenesis. The antiatherogenic and insulin sensitizing effects of the thiazolidinediones in patients with type 2 diabetes mellitus may be associated with this action. However, in recent years there has been growing evidence that the antiatherogenic effects of PPAR-gamma agonists are not confined to patients with diabetes mellitus. PPAR-gamma agonists have been shown to downregulate the expression of endothelial activation markers, reduce circulating platelet activity, improve flow-mediated dilatation and attenuate atheromatous plaque progression in patients without diabetes mellitus. These effects of PPAR-gamma agonists appear to result from both insulin sensitization and a direct modulation of transcriptional activity in the vessel wall. This review summarizes the current understanding of the role of PPAR-gamma agonists in atherogenesis and discusses their potential role in the treatment of coronary artery disease in patients with type 2 diabetes mellitus and in nondiabetic patients.

Role of inflammation and endothelial dysfunction in the pathogenesis of cardiac syndrome X.

Chest pain with normal coronary arteriograms represents a major diagnostic and therapeutic challenge to contemporary cardiology. Cardiac syndrome X (CSX), defined as typical angina-like chest pain, a positive response to exercise stress testing and normal coronary arteriograms, encompasses patients with a variety of pathogenic mechanisms. Cardiac ischemia has been documented in approximately 25% of CSX patients and is associated with endothelial dysfunction and microvascular vasodilator abnormalities. Increased endothelin-1, a powerful vasoconstrictor, has been suggested to play a pathogenic role. There is a high prevalence of postmenopausal women with CSX and thus estrogen deficiency has also been proposed to represent a possible pathogenic mechanism. Inflammatory mechanisms and endothelial dysfunction at the coronary microvascular level appear to be important in the pathogenesis of CSX. Treatment with agents that have protective effects on the vasculature and also anti-inflammatory properties, such as statins and angiotensin-converting enzyme inhibitors have been effective in improving both symptoms and electrocardiographic signs of myocardial ischemia in patients with CSX. This review discusses the roles for endothelial dysfunction and inflammation in the pathogenesis of CSX, as well as the potential therapeutic implications of these mechanisms.