Subclinical markers of cardiovascular disease predict adverse outcomes in chronic kidney disease patients with normal left ventricular ejection fraction.

Emerging cardiovascular biomarkers, such as speckle tracking echocardiography (STE) and aortic pulse wave velocity (aPWV), have recently demonstrated the presence of subclinical left ventricular dysfunction and arterial stiffening in patients with chronic kidney disease (CKD) and no previous cardiovascular history. However, limited information exists on the prognostic impact of these biomarkers. We aimed to investigate whether STE and aPWV predict major adverse cardiac events (MACE) in this patient population. In this cohort study we prospectively analysed 106 CKD patients with no overt cardiovascular disease (CVD) and normal left ventricular ejection fraction. Cardiac deformation was measured using STE while aPWV was measured using arterial tonometry. The primary end-point was the composite of all-cause mortality, acute coronary syndrome, stable angina requiring revascularization (either using percutaneous coronary intervention or coronary artery bypass surgery), hospitalization for heart failure and stroke. Over a median follow up period of 49 months (interquartile range 11-63 months), 26 patients (24.5%) reached the primary endpoint. In a multivariable Cox hazards model, global longitudinal strain (GLS) (HR 1.12, 95% CI 1.02-1.29, p = 0.041) and aPWV (HR 1.31, 95% CI 1.05-1.41, p = 0.021) were significant, independent predictors of MACE. GLS and aPWV independently predict MACE in CKD patients with normal EF and no clinically overt CVD.

Early detection of subclinical left ventricular myocardial dysfunction in patients with chronic kidney disease.

AIMS: To identify subclinical left ventricular (LV) myocardial dysfunction using speckle tracking echocardiography (STE) in patients with chronic kidney disease (CKD), preserved LV ejection fraction (LVEF), and no cardiovascular history or symptoms. METHODS AND RESULTS: Cross-sectional comparisons of conventional and STE parameters were performed between controls and patients with different stages of CKD. CKD patients were followed up for major adverse cardiovascular events (MACEs). We recruited 106 CKD patients and 38 controls. Mean age was 54.4 ± 15.1 and 36.9 ± 11.5 years, respectively (P < 0.001), with 49.1 vs. 52.6% being female (P = 0.705). There were 29 (27.4%) patients with CKD stages 1/2, 38 (35.8%) with stage 3, and 39 (36.8%) with stages 4/5. Global longitudinal strain (GLS) was more impaired when moving from controls to CKD stages 4/5 (-20.67 ± 3.06, -20.39 ± 2.29, -18.33 ± 3.81, -18.01 ± 2.64, controls vs. CKD stages 1/2, vs. CKD stage 3, vs. CKD stages 4/5, respectively, Padjusted = 0.016), whereas LV twist (16.2 ± 4.8, 18.51 ± 4.36, 19.91 ± 5.35, 24.6 ± 5.35, Padjusted < 0.001) and LV twist rate (101.7 ± 30.3, 110.4 ± 30.1, 121 ± 31.4, 154.8 ± 36.7, Padjusted < 0.001) increased. Risk factor-adjusted GLS (standardized beta ß = -0.245, P = 0.025), strain rate (SR) [global longitudinal strain rates (GLSRs); ß = -0.236, P = 0.019], and early diastolic longitudinal strain rate (GLSRe; ß = 0.247, P = 0.019) were significantly associated with estimated glomerular filtration rate (eGFR), whereas LV twist (ß = -0.432, P < 0.001), LV twist rate (ß = -0.433, P < 0.001), and number of segments with diastolic dysfunction (ß = -340, P < 0.001) were inversely and independently associated with eGFR. Impaired GLS (more than -16%) was observed in almost a quarter of CKD patients and associated with a reduced estimated MACE-free survival at 12-month follow-up (88.5 vs 93.7%, Plogrank = 0.038). CONCLUSION: In CKD patients with no cardiovascular symptoms or history and preserved LVEF, STE can identify subclinical abnormalities of both systolic (decreased GLS and GLSR, increased LV twist, and twist rate) and diastolic (decreased GLSRe and increased number of segments with diastolic dysfunction) LV function.

Pericardial effusion in a young patient with newly diagnosed systemic lupus erythematosus and a mediastinal mass.

We present the case of a 32-year-old-woman who was admitted to the hospital for evaluation of pericardial effusion. The subsequent diagnostic workup revealed the presence of a mediastinal mass along with systemic lupus erythematosus (SLE). The patient underwent thymectomy, and histological evaluation of the resected mass revealed thymic follicular hyperplasia without evidence of malignancy. SLE disease activity was promptly controlled by corticoids. Clinicians should be aware of the occasional association of autoimmune disorders with focal thymic hyperplasia, which might be confused with thymomas or thymocarcinomas.

Amino-terminal pro-C-type natriuretic peptide is associated with arterial stiffness, endothelial function and early atherosclerosis.

OBJECTIVE: C-type natriuretic peptide (CNP) is a paracrine molecule with effects on endothelial integrity, vascular tone and atherosclerotic process. Arterial stiffness, wave reflections, endothelial dysfunction and carotid intima-media thickness (IMT) are predictors of cardiovascular events. We investigated whether CNP is related to arterial structure and function in men. METHODS: We evaluated arterial structural and functional characteristics in 117 consecutive men (mean age 57.3 + or - 9.2 years), with and without cardiovascular risk factors, who had no established cardiovascular disease. Arterial elastic properties were evaluated with carotid-femoral pulse wave velocity (PWV), wave reflections with augmentation index (AIx), endothelial function with flow-mediated dilatation of the brachial artery (FMD) and early atherosclerosis with carotid IMT. Amino-terminal proCNP (NT-proCNP) was assessed in venous blood. RESULTS: The number of cardiovascular risk factors was inversely related to levels of NT-proCNP (P<0.01) and there was a progressive increase in Framingham risk score according to decreasing tertiles of NT-proCNP (P<0.001). In multivariable regression analysis NT-proCNP exhibited significant negative associations with PWV and IMT and positive association with FMD (all P<0.05) that were independent of age, blood pressure, smoking habits, body mass index, blood glucose, total triglycerides, low-density lipoprotein and endothelin-1 or high-sensitivity C-reactive protein. There was no relation between NT-proCNP and AIx. CONCLUSION: The present study is the first to demonstrate in a global arterial approach relationship between CNP and functional and early structural arterial changes. These findings elucidate pathophysiological links and may have important clinical implications for the estimation of cardiovascular risk in men.

Relationship of fibrinogen with arterial stiffness and wave reflections.

INTRODUCTION: Increased levels of fibrinogen have been related to target organ damage and cardiovascular outcomes. Arterial elastic properties are important determinants of cardiovascular performance and predictors of the corresponding risk. This study investigated whether the fibrinogen level is associated with arterial stiffness and wave reflections. METHODS: We studied 229 consecutive, non-diabetic patients with uncomplicated, never-treated essential hypertension (mean age 51 years, 149 men) and an age-matched control group of 159 normotensive individuals (mean age 50 years, 83 men). Carotid-femoral and carotid-radial pulse wave velocity (PWVc-f and PWVc-r) were measured as indices of elastic-type, aortic stiffness and muscular type, medium-sized arterial stiffness, respectively. The heart rate-corrected augmentation index (AIx75) was estimated as a composite marker of wave reflections and arterial stiffness. Plasma fibrinogen was measured using immunonephelometry. RESULTS: The fibrinogen level and arterial function indices (PWVc-f, PWVc-r, AIx75) were significantly higher in hypertensive patients than controls. In the whole population, fibrinogen level correlated with PWVc-f and AIx75 in univariable analysis, but not with PWVc-r. In multivariable analysis, an independent association was established between fibrinogen level and PWVc-f after adjusting for age, sex, mean pressure, heart rate, height, body mass index, smoking status, and total cholesterol. In contrast, no significant relationship was observed between fibrinogen and AIx75 after adjusting for confounders. CONCLUSION: The plasma fibrinogen level is independently associated with aortic stiffening. This finding underlines the important role of fibrinogen as a marker of arterial damage, and implies a possible contribution of this compound to the pathophysiology of cardiovascular disease.