Alejandro Recio-Mayoral

Endothelial dysfunction, inflammation and atherosclerosis in chronic kidney disease – a cross-sectional study of predialysis, dialysis and kidney-transplantation patients

BACKGROUNDnCardiovascular morbidity and mortality are high in chronic kidney disease (CKD) patients compared to the general population. Systemic inflammation may contribute to endothelial dysfunction and accelerated atherosclerosis in CKD patients. We assessed the relationship among, endothelial dysfunction, early atherosclerosis and inflammation in predialysis, dialysis and post kidney-transplantation CKD patients.nnnMETHODS AND RESULTSnWe studied 76 consecutive CKD patients; 38 predialysis, 18 haemodialysis and 22 kidney-transplant patients. A group of 65 age and gender matched controls were also studied. In both patients and controls, high-sensitivity C-reactive protein (CRP) levels, systemic endothelial function (brachial artery flow mediated dilation, FMD,%) and carotid artery intima-media thickness (IMT, mm) were measured. CKD patients had increased CRP levels (3.7 [1.0-6.0]mg/L vs 1.0 [0.5-2.1]mg/L; p<0.001), reduced FMD (2.2 [1.0-4.0] vs 5.6 [4.4-7.1]; p<0.001) and increased IMT (0.82±0.21 vs 0.67±0.16; p<0.001) values compared to controls. In CKD patients, a significant negative correlation was found between CRP levels and FMD responses (r=-0.51; p<0.001) while a significant positive correlation was found between CRP and IMT values (r=0.50; p<0.001). Increased CRP levels were an independent predictor of both abnormal FMD and IMT after adjusting for age, systolic and diastolic BP and total cholesterol. Compared with predialysis and kidney-transplant patients, haemodialysis subjects had significantly lower FMD and higher CRP and IMT values.nnnCONCLUSIONSnCKD patients taken together have a higher inflammatory status compared to controls. Abnormal FMD responses and IMT values are more commonly found in dialysis patients. Our findings suggest that endothelial dysfunction and atherosclerotic changes correlate with inflammation.

Vitamin D deficiency and endothelial dysfunction in non-dialysis chronic kidney disease patients

BACKGROUNDnCardiovascular (CV) events are common in patients with chronic kidney disease (CKD) but inadequately explained by traditional risk factors. Vitamin D deficiency is highly prevalent in CKD and has been proposed to be a non-traditional risk factor, but its relationship with vascular function is unknown.nnnMETHODS AND RESULTSnThe aim of this study was to investigate the relationship between vitamin D levels and endothelial function in non-diabetes patients with mild to moderate CKD. Endothelial function was measured non-invasively using brachial artery flow mediated dilation (FMD). 25 hydroxy vitamin D levels were measured using electrochemiluminescence immunoassay. In 50 CKD patients (age 56±11 years, BMI 25±4kg/m(2), 46% females, 14% smokers, 86% hypertensives, 52% with dyslipidaemia) the mean vitamin D level was 53±33nmol/L (21±13ng/L). The mean FMD was 3.8±2.4%. Decreasing 25 hydroxy vitamin D levels were associated with decreasing FMD [r=0.44, p=0.001]. In multivariate analysis the association remained independent after adjustment with traditional risk factors (adjusted beta 0.451; t=3.46; p<0.002). Patients with low vitamin D (≤37.5nmol/L) demonstrated low FMD compared to patients with vitamin D values >37.5nmol/L (4.4±2.5% vs. 2.5±1.6%; p=0.007); however the traditional risk factors were similar between the two groups.nnnCONCLUSIONnThis is the first demonstration of an association of vitamin D deficiency with abnormal vascular endothelial function in non-dialysis CKD patients. Further studies with intervention and exploration of the mechanism are needed to establish a cause effect relationship.

Insulin Resistance, Inflammation, and Vascular Disease in Nondiabetic Predialysis Chronic Kidney Disease Patients

Chronic kidney disease (CKD) is associated with high cardiovascular morbidity and mortality, which is not fully explained by traditional risk factors; hence, the interest in nontraditional risk factors such as inflammation and insulin resistance (IR). Though IR is shown in nondiabetic CKD, its association with vascular disease and inflammation in this population is unknown, and is what this study aims to investigate.

Frailty predicts major bleeding within 30 days in elderly patients with Acute Coronary Syndrome

OBJECTIVEnBleeding in ACS patients is an independent marker of adverse outcomes. Its prognostic impact is even worse in elderly population. Current bleeding risk scores include chronological age but do not consider biologic vulnerability. No studies have assessed the effect of frailty on major bleeding. The aim of this study is to determine whether frailty status increases bleeding risk in patients with ACS.nnnMETHODSnThis prospective and observational study included patients aged ≥75years admitted due to type 1 myocardial infarction. Exclusion criteria were severe cognitive impairment, impossibility to measure handgrip strength, cardiogenic shock and limited life expectancy due to oncologic diseases. The primary endpoint was 30-day major bleeding defined as a decrease of ≥3g/dl of haemoglobin or need of transfusion.nnnRESULTSnA total of 190 patients were included. Frail patients (72, 37.9%) were older, with higher comorbidity features and with a higher CRUSADE score at admission. On univariate analysis, frailty predicted major bleeding during 30-day follow-up despite less frequent use of a P2Y12 inhibitor (66.2% vs 83.6%, p=0.007) and decreased catheterisation rate (69.4% vs 94.1%, p<0.001). Major bleeding was associated with increased all-cause mortality at day 30 (18.2% vs 2.5%, p<0.001). On multivariate analysis, frailty was an independent predictor for major bleeding.nnnCONCLUSIONnFrailty phenotype, as a marker of biological vulnerability, is an independent predictor of major bleeding in elderly patients with ACS. Frailty can play an important role in bleeding risk stratification and objective indices should be integrated into routine initial evaluation of these patients.

Neopterin levels and left ventricular dysfunction in patients with chronic stable angina pectoris

BACKGROUNDnLeft ventricular ejection fraction (LVEF) is the strongest predictor of survival in patients with chronic stable angina (CSA). Inflammation plays a key role in the pathogenesis of atherosclerosis and an enhanced inflammatory status has a negative impact on patient outcome. It is not known whether a relationship exists between inflammation and LV function in patients with CSA. We therefore sought to investigate whether C reactive protein (CRP) and neopterin correlate with LV dysfunction in patients with CSA.nnnMETHODSnWe assessed 181 patients with CSA who underwent diagnostic coronary angiography in our institution. High-sensitivity CRP and neopterin serum concentrations were measured immediately before angiography.nnnRESULTSnBaseline neopterin levels - but not CRP - showed a significant inverse correlation with LVEF (r=-0.222; p=0.003 and r=-0.097; p=0.194, respectively). After adjustment for relevant confounders which included, among others, the extent and severity of coronary disease, neopterin was found to be independently associated with LVEF (B -2.36, CI 95% -4.560 to -0.176, p=0.034). Moreover, high neopterin levels were an independent predictor of LV dysfunction (LVEF <45%) (OR, 8.52, CI 95% 1.10-65.64; p=0.040). Receiver operating characteristic analysis for neopterin showed an area under the curve of 0.736 (CI 95% 0.59-0.87, p<0.009) for prediction of LV dysfunction.nnnCONCLUSIONnIncreased serum neopterin concentrations inversely correlate with LVEF values and high neopterin levels are a predictor of LV dysfunction in patients with CSA, irrespective of the extent and severity of coronary artery disease. Neopterin may thus be clinically useful for patient risk stratification.

The role of levosimendan in acute heart failure complicating acute coronary syndrome: A review and expert consensus opinion

Acute heart failure and/or cardiogenic shock are frequently triggered by ischemic coronary events. Yet, there is a paucity of randomized data on the management of patients with heart failure complicating acute coronary syndrome, as acute coronary syndrome and cardiogenic shock have frequently been defined as exclusion criteria in trials and registries. As a consequence, guideline recommendations are mostly driven by observational studies, even though these patients have a particularly poor prognosis compared to heart failure patients without signs of coronary artery disease. In acute heart failure, and especially in cardiogenic shock related to ischemic conditions, vasopressors and inotropes are used. However, both pathophysiological considerations and available clinical data suggest that these treatments may have disadvantageous effects. The inodilator levosimendan offers potential benefits due to a range of distinct effects including positive inotropy, restoration of ventriculo-arterial coupling, increases in tissue perfusion, and anti-stunning and anti-inflammatory effects. In clinical trials levosimendan improves symptoms, cardiac function, hemodynamics, and end-organ function. Adverse effects are generally less common than with other inotropic and vasoactive therapies, with the notable exception of hypotension. The decision to use levosimendan, in terms of timing and dosing, is influenced by the presence of pulmonary congestion, and blood pressure measurements. Levosimendan should be preferred over adrenergic inotropes as a first line therapy for all ACS-AHF patients who are under beta-blockade and/or when urinary output is insufficient after diuretics. Levosimendan can be used alone or in combination with other inotropic or vasopressor agents, but requires monitoring due to the risk of hypotension.

Left ventricular hypertrophy and endothelial dysfunction in chronic kidney disease

UNLABELLEDnAim Mortality, predominantly due to cardiovascular events, is high in patients with chronic kidney disease (CKD) and left ventricular hypertrophy (LVH) is a strong risk factor. Vascular endothelial dysfunction (ED) is common in CKD, but its potential contribution to LVH in non-dialysis CKD is unknown. This study investigated the association of ED with LVH in non-dialysis CKD patients.nnnMETHODS AND RESULTSnWe studied 30 CKD patients (17 pre-dialysis and 13 renal transplant recipients) and 29 age-gender-matched controls. In both groups, high-sensitivity C-reactive protein (hsCRP) levels, systemic ED (brachial artery flow-mediated dilatation, FMD), and LVH using two-dimensional echocardiography were measured. LV mass index (LVMI) was calculated using Penn formula and indexed by height. CKD patients had higher CRP levels (3.9 ± 2.8 vs. 1.0 ± 0.7 mg/L; P < 0.001), reduced FMD (3.2 ± 2.1 vs. 6.1 ± 1.9%; P < 0.001), and increased LVMI (146.1 ± 40.2 vs. 105.3 ± 26.2 g/m; P < 0.001), compared with controls. In CKD patients, LVMI increased with decreasing FMD (r = -0.371; P = 0.043) and FMD decreased with increasing CRP (r = -0.741; P < 0.001). Patients with low FMD <2.3% had higher CRP and LVMI (161.9 ± 48.9 vs. 130.4 ± 20.7 g/m; P = 0.033), compared with CKD patients with FMD ≥2.3%. There was no significant difference in age, blood pressure, cholesterol, FMD, and LVMI between pre-dialysis and post-renal transplant CKD patients. In multivariate regression, the relationship between LVMI and FMD remained significant after adjusting for age, diabetes, and smoking (adjacent beta = -0.396; P = 0.004).nnnCONCLUSIONnThis pilot study demonstrates for the first time a relationship of ED with LVH in non-dialysis CKD patients; suggesting but not proving a cause-effect relationship.

Frailty is an independent prognostic marker in elderly patients with myocardial infarction

Acute coronary syndrome (ACS) patients are increasingly older. Conventional prognostic scales include chronological age but do not consider vulnerability. In elderly patients, a frail phenotype represents a better reflection of biological age.

Myocardial stunning identified by using strain/strain rate imaging during dobutamine stress echocardiography in a rare late recurrence of Tako-Tsubo syndrome.

Tako-Tsubo cardiomyopathy affects postmenopausal women and is often associated to emotional or physical stress. It is typically characterized by transient left ventricular apical ballooning with chest pain and, electrocardiographic changes and biochemical markers suggestive of acute coronary syndrome, despite angiographically normal coronary arteriograms. The pathogenesis of the condition is still unknown, but increased catecholamine levels have been postulated as a pathogenic mechanism. Little data exist in the medical literature regarding recurrent events in this disorder. We present here a case of a 62 year-old woman who had a recurrent episode of Tako-Tsubo syndrome 6 years after initial presentation with typical features of the condition. An underlying cause could not be found that could explain the recurrence of this late episode.

Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy

Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminal-prohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.