Eduardo de Teresa

Increased Soluble Fas Plasma Levels in Subjects at High Cardiovascular Risk Atorvastatin on Inflammatory Markers (AIM) Study, a Substudy of ACTFAST

Objectives—Increasing evidence indicates that the Fas/Fas ligand interaction is involved in atherogenesis. We sought to analyze soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations in subjects at high cardiovascular risk and their modulation by atorvastatin treatment. Methods and Results—ACTFAST was a 12-week, prospective, multicenter, open-label trial which enrolled subjects (statin-free or statin-treated at baseline) with coronary heart disease (CHD), CHD-equivalent, or 10-year CHD risk >20%. Subjects with LDL-C between 100 to 220 mg/dL (2.6 to 5.7 mmol/L) and triglycerides ≤600 mg/dL (6.8 mmol/L) were assigned to a starting dose of atorvastatin (10 to 80 mg/d) based on LDL-C at screening. Of the 2117 subjects enrolled in ACTFAST, AIM sub-study included the 1078 statin-free patients. At study end, 85% of these subjects reached LDL-C target. Mean sFas levels were increased and sFasL were reduced in subjects at high cardiovascular risk compared with healthy subjects. Atorvastatin reduced sFas in the whole population as well as in patients with metabolic syndrome or diabetes. Minimal changes were observed in sFasL. Conclusions—sFas concentrations are increased and sFasL are decreased in subjects at high cardiovascular risk, suggesting that these proteins may be novel markers of vascular injury. Atorvastatin reduces sFas, indicating that short-term treatment with atorvastatin exhibits antiinflammatory effects in these subjects.

Preventing ventricular dysfunction in pacemaker patients without advanced heart failure: results from a multicentre international randomized trial (PREVENT-HF)

Previous experimental and clinical studies have consistently suggested that right ventricular (RV) apical pacing has important adverse effects. Ventricular pacing (VP), however, is required, and cannot be reduced in many patients with atrioventricular (AV) block. The PREVENT‐HF study was an international randomized trial that explored differences in left ventricular (LV) remodelling during RV apical vs. biventricular (BIV) pacing in patients with AV block.

Adiponectin plasma levels are increased by atorvastatin treatment in subjects at high cardiovascular risk

Adiponectin can suppress atherogenesis by inhibiting the adherence of monocytes, reducing their phagocytic activity, and suppressing the accumulation of modified lipoproteins in the vascular wall. Contradictory data have been reported about the effect of statins on adiponectin plasma levels. In this work, adiponectin plasma levels were measured in 102 statin-free subjects from the Spanish population of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study, a 12-week, prospective, multi-centre, open-label trial which enrolled subjects with coronary heart disease, coronary heart disease-equivalent or a 10-year coronary heart disease risk >20%. Subjects were assigned to atorvastatin (10-80 mg/day) based on low-density lipoprotein (LDL)-cholesterol concentration at screening. For comparison, age and gender-matched blood donors (N=40) were used as controls. Control subjects did not present hypertension, hypercholesterolemia, diabetes, metabolic syndrome and history of cardiovascular diseases. Adiponectin levels were diminished in patients at high cardiovascular risk compared with control subjects [4166 (3661-4740) vs 5806 (4764-7075) ng/ml respectively; geometric mean (95% CI); P<0.0001]. In the whole population, atorvastatin treatment increased adiponectin levels [9.7 (3.2-16.7);% Change (95% CI); P=0.003]. This increment was in a dose-dependent manner; maximal effect observed with atorvastatin 80 mg/d [24.7 (5.7-47.1); P=0.01]. Adiponectin concentrations were positively correlated with high-density lipoprotein-cholesterol both before and after atorvastatin treatment. No association was observed between adiponectin and LDL-cholesterol before and after atorvastatin treatment. In conclusion, atorvastatin increased adiponectin plasma levels in subjects at high cardiovascular risk, revealing a novel anti-inflammatory effect of this drug.

Atorvastatin decreases elevated soluble CD40L in subjects at high cardiovascular risk. Atorvastatin on inflammatory markers study: a substudy of ACTFAST

The CD40/CD40 ligand plays a role in the inflammatory and prothrombotic processes in atherosclerosis. We analyzed whether short-term treatment with atorvastatin affects soluble CD40 ligand (sCD40L) plasma levels in subjects at high cardiovascular risk. sCD40L plasma concentrations were measured in 852 subjects from the Atorvastatin on Inflammatory Markers (AIM) Study, a 12-week prospective multicenter, open-label trial which enrolled statin-free subjects with coronary heart disease (CHD), CHD-equivalent (diabetes, peripheral vascular disease, or cerebrovascular disease), or a 10-year CHD risk >20%. Subjects were assigned to atorvastatin (10-80 mg/day) based on LDL-C at screening. Overall, sCD40L levels were not different in patients at high cardiovascular risk compared with healthy subjects. When sCD40L levels were divided in quartiles, patients in the highest quartile (N=213) had higher sCD40L concentrations than age- and gender-matched healthy subjects (N=29) (P<0.0001). Interestingly, all doses of atorvastatin significantly diminished sCD40L levels in subjects at the highest quartile. Furthermore, atorvastatin treatment decreased sCD40L more markedly in subjects with metabolic syndrome compared with those without metabolic syndrome. In conclusion, atorvastatin diminishes sCD40L plasma levels, more markedly so in subjects with metabolic syndrome. Our results indicate that short-term treatment with atorvastatin exhibits anti-inflammatory and antithrombotic effects in subjects at high cardiovascular risk.

Geometría ventricular e insuficiencia cardíaca

El estudio de la geometria ventricular ha despertado cierto interes en los ultimos anos. Tras una etapa en la decada de los 60 y 70 en la que el interes se centro en la fisiologia cardiaca y el papel de la geometria ventricular sobre esta, disponemos de nuevos estudios sobre el valor clinico de la morfologia normal o distorsionada del ventriculo izquierdo. Por otro lado, se describen nuevos metodos de valoracion de la geometria ventricular. El uso de tecnicas sencillas para evaluar la geometria ventricular permite conocer el valor clinico de la distorsion geometrica en pacientes con insuficiencia cardiaca. La sospecha de que la transformacion en la forma del ventriculo izquierdo hacia la esfericidad tiene valor pronostico ha aumentado el interes sobre este tema. Si la geometria ventricular alterada es un mejor parametro que los indices de la funcion ventricular habitualmente utilizados es objeto de analisis. Asimismo nuevas terapeuticas quirurgicas que intentan mejorar esta geometria alterada y por tanto favorecer el pronostico clinico de los pacientes con insuficiencia cardiaca estan en desarrollo.

Low‐Density Lipoprotein Cholesterol and High‐Sensitivity C‐Reactive Protein Lowering With Atorvastatin in Patients of South Asian Compared With European Origin: Insights From the Achieve Cholesterol Targets Fast With Atorvastatin Stratified Titration (ACTFAST) Study

The aim of this study was to determine the effects of atorvastatin in patients of South Asian versus European origin who participated in the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study. ACTFAST was a 12‐week prospective, open‐label study in patients at high risk for atherosclerosis (European origin, n = 1978; South Asian origin, n = 64). Compared with patients of European origin, patients of South Asian origin were younger, were less likely to smoke, and had lower body mass index, systolic blood pressure, low‐density lipoprotein cholesterol (LDL‐C) and triglycerides. Because significant differences were observed in baseline characteristics between patient groups, case control propensity scores were used. In the unmatched analysis, South Asians had greater LDL‐C response to atorvastatin than patients of European origin. However, after propensity matching, atorvastatin lowered LDL‐C and high‐sensitivity C‐reactive protein (hs‐CRP) to a similar degree in both groups, with no differences in safety profile. The authors observed no correlation between change in hs‐CRP and LDL‐C concentrations in either population. In conclusion, atorvastatin lowered both LDL‐C and hs‐CRP to a similar degree in patients of South Asian or European origin, suggesting usual starting doses of atorvastatin (with appropriate monitoring), rather than lower starting doses as has been advocated by some, may be used in patients of South Asian origin.

Intracoronary platelet activation in ischemic heart disease: Effects of ticlopidine

Plasma levels of platelet factor 4 have been measured in the aortic and coronary sinus blood of 35 patients: group I (n = 12) with normal coronary arteriograms; group II (n = 15) with angiographically proven coronary artery disease; and group III (n = 8) composed of patients with ischemic heart disease who were being treated with the antiaggregant agent ticlopidine at the time of cardiac catheterization. The mean increase in platelet factor 4 levels through the coronary circulation was 27.4 +/- 21.9 ng/ml (mean +/- standard deviation) in group II, compared with -1 +/- 4.5 ng/ml in group I (p less than 0.01). In group III plasma levels of platelet factor 4 in aortic and coronary sinus samples were all within the normal range. Thus, we conclude that platelet activation constantly occurs in the coronary circulation of patients with stable coronary artery disease, and can be prevented with ticlopidine.

Cardiomyogenic differentiation potential of human endothelial progenitor cells isolated from patients with myocardial infarction

BACKGROUND AIMSnEndothelial progenitor cells (EPCs) are known to play a beneficial role by promoting postnatal vasculogenesis in pathological events, such as ischemic heart disease and peripheral artery disease. However, little is known about the potential of EPCs to restore heart damage tissue. We compared the cardiac differentiation capacity of EPCs isolated from peripheral blood of patients with acute myocardial infarction (AMI) with EPCs obtained from umbilical cord blood (UCB).nnnMETHODSnEPCs from both origins were isolated by density gradient centrifugation and characterized through the use of endothelial markers (UEA-1lectin, CD133 and KDR) and endothelial cell colony-forming unit assay. Cardiac differentiation capacity of EPCs was assessed by immunofluorescence and reverse transcriptase-polymerase chain reaction after 5-azacytidine (5-aza) induction.nnnRESULTSnNo significant differences were observed between the number of endothelial cell colony-forming units in peripheral blood of patients with AMI and samples from UCB. Moreover, 5-aza induced the appearance of myotube-like structures and the positive expression of sarcomeric α-actinin, cardiac troponin I and T and desmin in a similar pattern for both cell sources, which indicates a comparable acquisition of a cardiac-like phenotype.nnnCONCLUSIONSnFor the first time, we have compared, in vitro, the cardiomyogenic potential of EPCs derived from patients with AMI with UCB-derived EPCs. Our data indicate that EPCs obtained from both origins have similar plasticity and functions and suggest a potential therapeutic efficacy in cardiac cell therapy.

Tratamiento diurético de la insuficiencia cardiaca

Los diureticos constituyen una de las piedras angulares del tratamiento de la insuficiencia cardiaca. La correcta utilizacion de estos agentes exige conocer adecuadamente su farmacodinamica y farmacocinetica, sus interacciones y las posibles causas de ineficacia, asi como sus peligros potenciales. Para evitarlos deben mantenerse unas normas basicas que incluyen el empleo de las dosis mas bajas que consigan mantener al paciente libre de edema, el control periodico de la funcion renal y los electrolitos sericos, y la utilizacion amplia de asociaciones entre diureticos potentes (de asa) y antialdosteronicos. Actualmente no disponemos de datos sobre el impacto que estos farmacos pueden tener en la supervivencia de los pacientes con insuficiencia cardiaca. Posiblemente, pocos campos como este se presten a ejercer en toda su amplitud la ars medicae.

Effects of Bisoprolol on Left Ventricular Hypertrophy in Essential Hypertension

SummaryPrevious studies have shown that beta-adrenergic blocking drugs can reverse ventricular hypertrophy in patients with systemic hypertension. Thirty patients with essential hypertension and left ventricular hypertrophy were studied at baseline after withdrawing all previous treatments and after 6 months of treatment with 5–20 mg of bisoprolol, a new beta-selective agent, to assess its possible action on left ventricular mass. Three patients did not finish the study. Blood pressure was reduced to below 160/90 mmHg in 22 of the remaining 27 patients. At the end of follow-up, the left ventricular mass (echocardiography) was reduced from 308.1±89 g to 262.3±51 g (p<0.001) and left ventricular mass index from 165±47.4 g/m2 to 141.03±26.7 g/m2 (p<0.001). The ratio of E wave/A wave velocity of transmitral blood flow measured by Doppler increased from 0.86±0.44 to 1.07±0.45 (p=0.005). Peak filling rate, derived from nuclear ventriculography, changed from 2.05±0.4 EDV/sec before the treatment to 2.23±0.47 EDV/sec after it (p=0.0046). Serum lipids as well as other biochemical tests were unchanged. Left ventricular volumes and ejection fraction did not change, and treadmill exercise time increased from 343±125 seconds to 420±135 seconds (p=0.002). Maximal systolic blood pressure during exercise decreased from 197.2±19.7 mmHg to 182.9±25.8 mmHg (p=0.011). There were few side effects. We conclude that bisoprolol reduces left ventricular mass, preserves systolic function, and improves diastolic function of the left ventricle in hypertensive subjects with left ventricular hypertrophy.