Low lymphocyte count and cardiovascular diseases.

Inflammation plays a crucial pathophysiological role in the entire continuum of the atherosclerotic process, from its initiation, progression, and plaque destabilization leading ultimately to an acute coronary event. Furthermore, once the clinical event has occurred, inflammation also influences the left ventricular remodelling process. Under the same paradigm, there is evidence that lymphocytes play an important role in the modulation of the inflammatory response at every level of the atherosclerotic process. Low lymphocyte count (LLC) is a common finding during the systemic inflammatory response, and clinical and animal studies suggest that LCC plays a putative role in accelerated atherosclerosis. For instance, there is recent evidence that LLC is associated with worse outcomes in patients with heart failure, chronic ischemic heart disease and acute coronary syndromes. Further indirect evidence supports the pathologic role of LLC related to the fact that 1) lymphopenia--due to a decreased count of lymphocyte T cells--normally occurs as a part of the human ageing process, and 2) increased incidence of cardiovascular events has been reported in conditions where lymphopenia is common, such as renal transplant recipients, human immunodeficiency virus infection, survivors of nuclear disasters and autoimmune diseases. The aim of the present article is to review: a) the pathophysiological mechanisms that have been proposed for the observed association between LLC and cardiovascular diseases (CVD), b) the available evidence regarding the diagnostic and prognostic role attributable to LLC in patients with CVD, and; c) the potential therapeutic implications of these findings.

Prognostic and therapeutic implications of dipyridamole stress cardiovascular magnetic resonance on the basis of the ischaemic cascade.

OBJECTIVE: To determine the prognostic and therapeutic implications of stress perfusion cardiovascular magnetic resonance (CMR) on the basis of the ischaemic cascade. SETTING: Single centre study in a teaching hospital in Spain. PATIENTS: Dipyridamole stress CMR was performed on 601 patients with ischaemic chest pain and known or suspected coronary artery disease. On the basis of the ischaemic cascade, patients were categorised in C1 (no evidence of ischaemia, n = 354), C2 (isolated perfusion deficit at stress first-pass perfusion imaging, n = 181) and C3 (simultaneous perfusion deficit and inducible wall motion abnormalities, n = 66). CMR-related revascularisation (n = 102, 17%) was defined as the procedure prompted by the CMR results and carried out within the next three months. RESULTS: During a median follow-up of 553 days, 69 major adverse cardiac events (MACE), including 21 cardiac deaths, 14 non-fatal myocardial infarctions and 34 admissions for unstable angina with documented abnormal angiography were detected. In non-revascularised patients (n = 499), the MACE rate was 4% (14/340) in C1, 20% (26/128) in C2 and 39% (12/31) in C3 (adjusted p value = 0.004 vs C2 and <0.001 vs C1). CMR-related revascularisation had neutral effects in C2 (20% vs 19%, 1.1 (0.5 to 2.4), p = 0.7) but independently reduced the risk of MACE in C3 (39% vs 11%, 0.2 (0.1 to 0.7), p = 0.01). CONCLUSIONS: Dypiridamole stress CMR is able to stratify risk on the basis of the ischaemic cascade. A small group of patients with severe ischaemia-simultaneous perfusion deficit and inducible wall motion abnormalities-are at the highest risk and benefit most from MACE reduction due to revascularisation.

Trombocitopenia en un paciente en diálisis peritoneal / No disponible

Las reacciones adversas a fármacos ocurren hasta en un6% de los pacientes hospitalizados y son una causa importante de morbi-mortalidad. Los antibióticos, clásicamente los beta-lactámicos y las sulfamidas son los más frecuentemente asociados a reacciones adversas y de hipersensibilidad. La vancomicina es un antibiótico glucopéptido cuyo uso está dirigido a infecciones por Staphylococcus aureus resistente a meticilina (SARM) y St. coagulasa negativo. En las Unidades de Nefrología, la vancomicina es, en muchos protocolos, el antibiótico de primera elección para el tratamiento de infecciones estafilocócicas en relación con catéteres centrales de hemodiálisis y el tratamiento de las peritonitis en pacientes en diálisis peritoneal. La toxicidad secundaria a vancomicina incluye «síndrome del hombre rojo», ototoxicidad y toxicidad hematológica. Dentro de esta última, la más frecuente es la neutropenia leve; menos frecuentes son la leucocitosis, eosinofilia, agranulocitosis y la trombopenia. Presentamos un paciente con ERC 5 en programa de diálisis peritoneal continua ambulatoria(DPCA), que presentó una trombopenia secundaria a la administración intraperitoneal de vancomicina. La ausencia de mejoría en la cifra de plaquetas con tratamientos clásicos obligó a la utilización del anticuerpo monoclonalanti-CD20, el rituximab, con recuperación rápida tras cuatro dosis de la cifra de plaquetas (AU)

Adverse reactions to drugs occur in up to 6% of hospitalized patients and are an important cause of increment in morbimortality. The widely-prescribed antibiotics beta-lactams and sulfamides are the most frequently associated to adverse reactions and hypersensitivity. Vancomyc in is a glycopeptidic antibiotic used to treat infections caused by Staph. coagulasa positive (S. aureus)and Staph. coagulasa negative. Nowadays its extensive use is a consequence of bacterial resistance to classical antibiotics such as beta-lactams. In Nephrology Units, vancomycin is the antibiotic of first choice to treat staphylococcal infections related to central venous catheters for hemodialysis, as well as for the treatment of peritonitis in patients undergoing peritoneal dialysis. Toxicity due to vancomycin includes the «red man syndrome», ototoxicity and hematological toxicity. The most common sign of haematological toxicity is mild neutropenia; less frecuent are leukocytosis, eosinophilia, agranulocytosis and thrombocytopenia (AU)

Combination of clinical risk profile, early exercise testing and circulating biomarkers for evaluation of patients with acute chest pain without ST-segment deviation or troponin elevation.

OBJECTIVE: To investigate the combination of clinical data, exercise testing and biomarkers for the evaluation of patients with chest pain without ST-segment deviation or troponin elevation. DESIGN: Prospective cohort design. SETTTING: Two teaching hospitals in Spain. PATIENTS: 422 patients presenting to the emergency department were studied. Leukocyte count, C-reactive protein (CRP), pregnancy-associated plasma protein A (PAPP-A) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were determined. A validated clinical risk score (number of points according to pain characteristics and risk factors) was used for clinical evaluation and early exercise testing was performed. MAIN OUTCOME MEASURES: Adverse events (death, myocardial infarction or revascularisation) during a median 60 weeks follow-up. RESULTS: By receiver operating characteristic curve analysis, the association between death or myocardial infarction and adverse events was not significant with leukocyte count (p = 0.3, p = 0.3) or CRP (p = 0.5, p = 0.8), was borderline significant with PAPP-A (p = 0.07, p = 0.04) and strongly significant with NT-pro-BNP (p = 0.0001, p = 0.0001). By Cox regression including clinical risk score, exercise testing result and biomarkers, exercise testing was the independent predictor of revascularisation (p = 0.0001), whereas risk score (p = 0.03) and NT-proBNP (p = 0.0004) predicted death or myocardial infarction. The inclusion of NT-proBNP improved the accuracy of the model for death or myocardial infarction (C-statistic 0.84 versus 0.76, p = 0.01). The combination of clinical score and NT-proBNP afforded the stratification in high (17.2%, p = 0.0001), intermediate (5.3%) and low (1.1%) risk categories of death or myocardial infarction. CONCLUSIONS: NT-proBNP provides incremental prognostic information above that given by clinical history and exercise testing in patients with chest pain without ST-segment deviation and negative troponin.

Prognostic value of leukocytosis in acute coronary syndromes: the cinderella of the inflammatory markers.

In recent years, numerous studies have validated the role of inflammation in the pathogenesis of atherosclerosis. Several of such studies have produced compelling evidence that inflammation participates in both, the initiation and perpetuation of the atherosclerotic process. Furthermore, epidemiological observations have found basal white blood cell (WBC) count is strongly associated with future cardiovascular disease (CVD), highlighting the participation of leukocytes in the pathogenesis of the ischemic damage that occurred during an acute coronary event, in particularly during the acute myocardial infarction (MI). Fundamentally, an acute MI triggers a systemic response to a necrotic insult characterized by leukocytosis and acute-phase protein synthesis. In this setting, elevated WBC count plays a central role in the reparative process that takes place to replace the necrotic tissue for collagen. In addition to be a proxy for the intensity of the peri-infarction inflammatory response, recent evidence has also shown that an elevated WBC counts, measured during the acute phase of MI, to be associated with adverse outcomes. This relationship holds true even when adjusting for classical prognostic variables some of which are surrogates for the extension of the infarcted-area. WBC count prognostic value in absence of necrosis marker elevation (like unstable angina), however, remains unclear and controversial. Additionally, and essentially due to its simplicity, cost-effectiveness and wide availability, WBC count has drawn the attention of researchers as a potential stratification tool in acute coronary syndromes (ACS). However, a formal comparison is needed between WBC count with other inflammatory markers such high-sensitive C-reactive protein to fully characterize its diagnostic accuracy.

[Glucose levels in non-diabetic patients. Is it a prognostic factor in acute coronary syndrome?]. / Niveles de glucemia en pacientes no diabéticos. 'Es un factor pronóstico en el síndrome coronario agudo?

INTRODUCTION: The role of glucose elevation above levels considered normal in non- diabetic patients with acute coronary syndromes (ACS) is not adequately defined. The aim of this study was to determine the association between serum glucose at admission and 1-year mortality in this type of patients. METHODS: We studied 648 non diabetic patients admitted consecutively with ACS. Serum glucose was determined at admission, together with classical risk factors, biochemical and inflammatory markers. The primary endpoint was all cause mortality at one year follow-up. RESULTS: Patients with normal glucose had lower mortality than patients with impaired fasting glucose (14.1% vs 5.7% 1-year mortality) or with glucose levels in diabetic range (24.7% vs 5.7% 1-year mortality). CONCLUSIONS: In non-ST elevation acute coronary syndromes, elevated levels of glucose in non-diabetic patients are strong predictors of all cause death at one year follow-up. This prognostic value is independent of other risk factors biochemical and inflammatory markers.

Microvascular perfusion 1 week and 6 months after myocardial infarction by first-pass perfusion cardiovascular magnetic resonance imaging.

OBJECTIVE: To characterise the evolution of myocardial perfusion during the first 6 months after myocardial infarction by first-pass perfusion cardiovascular magnetic resonance imaging (CMR) and determine its significance. DESIGN: Prospective cohort design. SETTING: Single-centre study in a teaching hospital in Spain. PATIENTS: 40 patients with a first ST-elevation myocardial infarction, single-vessel disease and thrombolysis in myocardial infarction (TIMI) grade 3 flow (stent in 33 patients) underwent rest and low-dose dobutamine CMR 7 (SD 1) and 184 (SD 11) days after infarction. Microvascular perfusion was assessed at rest by visual assessment and quantitative analysis of first-pass perfusion CMR. Of the 640 segments, 290 segments subtended by the infarct-related artery (IRA) were focused on. RESULTS: Both 1 week and 6 months after infarction, segments with normal perfusion showed more wall thickening, contractile reserve and wall thickness, and less transmural necrosis, p <0.05 in all cases. Of 76 hypoperfused segments at the first week, 47 (62%) normalised perfusion at the sixth month. However, 42 segments (14% of the whole group) showed chronic abnormal perfusion; these segments showed worse CMR indices in the late phase (p<0.05 in all cases). CONCLUSIONS: In patients with an open IRA, more than half of the segments with abnormal perfusion at the first week are normally perfused after six months. First-pass perfusion CMR shows that in a small percentage of segments, abnormal perfusion may become a chronic phenomenon-these areas have a more severe deterioration of systolic function, wall thickness, contractile reserve and the transmural extent of necrosis.

Risk stratification of patients with acute chest pain and normal troponin concentrations.

OBJECTIVE: To investigate the outcome of patients with acute chest pain and normal troponin concentrations. DESIGN: Prospective cohort design. SETTING: Single centre study in a teaching hospital in Spain. PATIENTS: 609 consecutive patients with chest pain evaluated in the emergency department by clinical history (risk factors and a chest pain score according to pain characteristics), ECG, and early (< 24 hours) exercise testing for low risk patients with physical capacity (n = 283, 46%). All had normal troponin concentrations after serial determination. MAIN OUTCOME MEASURES: Myocardial infarction or cardiac death during six months of follow up. RESULTS: 29 events were detected (4.8%). No patient with a negative early exercise test (n = 161) had events versus the 6.9% event rate in the remaining patients (p = 0.0001). Four independent predictors were found: chest pain score > or = 11 points (odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1 to 5.5, p = 0.04), diabetes mellitus (OR 2.3, 95% CI 1.1 to 4.7, p = 0.03), previous coronary surgery (OR 3.1, 95% CI 1.3 to 7.6, p = 0.01), and ST segment depression (OR 2.8, 95% CI 1.3 to 6.3, p = 0.003). A risk score proved useful for patient stratification according to the presence of 0-1 (2.7% event rate), 2 (10.2%, p = 0.008), and 3-4 predictors (29.2%, p = 0.0001). CONCLUSIONS: A negative troponin result does not assure a good prognosis for patients coming to the emergency room with chest pain. Early exercise testing and clinical data should be carefully evaluated for risk stratification.

Valsalva sinus pseudoaneurysm causes acute myocardial infarction and stroke simultaneously.

Spontaneous Valsalva sinus pseudoaneurysm is a rare and highly lethal condition. Below we present a clinical case of a young woman with spontaneous Valsalva sinus pseudoaneurysm diagnosed presenting with acute myocardial infarction (AMI) and ischemic stroke.

QT dispersion within the first 6 months after an acute myocardial infarction: relationship with systolic function, left ventricular volumes, infarct related artery status and clinical outcome.

INTRODUCTION: We analysed QT dispersion within the first 6 months postinfarction, its relationship with the main established risk stratifiers and its clinical value. METHODS AND RESULTS: In 55 patients with a first Q-wave myocardial infarction the 12-lead electrocardiogram was scanned and digitised for analysis of QT dispersion (QT maximum-QT minimum) at first day (72 [61-96] ms), first week (69 [47-90] ms), first month (67 [46-88] ms) and sixth month (47 [40-74] ms; P<0.0001 vs. first day). Cardiac catheterization was performed at first week and at sixth month; QT dispersion was not related to ejection fraction, left ventricular volumes, infarct related artery status or contractile reserve (improvement of the infarcted area with low-dose dobutamine); no relation was found between QT dispersion decrease from first week to sixth month with regional systolic function improvement. Finally, during a mean follow-up period of 35+/-22 months QT dispersion was not independently related to clinical events. CONCLUSION: QT dispersion decreases progressively during the first months after myocardial infarction. These changes should be taken into account to define cut-off values of clinical interest in this phase. This variable does not seem related to the classic prognosis predictors. In a nonselected postinfarction population it has a low clinical value.

Relationships between heart rate variability, functional capacity, and left ventricular function following myocardial infarction: an evaluation after one week and six months.

BACKGROUND: Relationships between heart rate (HR) variability and different prognostic markers such as ejection fraction, functional capacity, and patency of the infarct-related artery, as well as the comparison of their time courses are not fully elucidated. HYPOTHESIS: The aim of study was to assess prospectively the early postinfarction changes in HR variability and its evolution over a period of 6 months: the relationships between HR variability and functional capacity in exercise testing; left ventricular function in cardiac catheterization: status of the infarct-related artery; and the comparison of their time courses. METHODS: In 42 patients with anterior myocardial infarction, a study was made of the early changes in HR variability analyzed by the complex demodulation method, its evolution over a period of 6 months. and the relationships between HR variability and (1) functional capacity in exercise testing, (2) left ventricular function in cardiac catheterization, and (3) status of the infarct-related artery. RESULTS: At 1 week HR variability parameters correlated directly with functional capacity indicators such as METS, percent change in HR from rest to peak exercise (%deltaHR), difference between initial and peak HR (HR range), percent peak theoretical HR (% peak HR), left ventricular ejection fraction (EF), and, inversely, with end-systolic volume (ESV). Stepwise multiple regression analysis to establish HR variability parameters (recorded at 1 week) as related to functional capacity and left ventricular function at 1 week and 6 months postinfarction established the following variables: (1) At 1 week: standard deviation (SD) of the RR cycles in relation to %deltaHR (r = 0.60, p <0.0001), HR range (r = 0.43, p < 0.01), and EF (r = 0.79, p < 0.0001). (2) At 6 months, the sole accepted HR variability parameter was the SD in relation to %deltaHR (r = 0.38, p < 0.05) and HR range (r = 0.45, p < 0.01). No variability parameter was accepted in relation to METS, % peak HR, or ESV. Relationship between EF or ESV and HR variability parameters was not significant when both were evaluated at 6 months. At that time, there was a significant increase in all HR variability parameters among all surviving patients (n = 39), with the exception of the LF/HF ratio and mean RR cycle. The percent increase in HR variability between the first week and 6 months was greater among those patients with the lowest basal EF. No relation was established between HR variability and patency of the infarct-related artery. CONCLUSION: The decrease in HR variability observed following myocardial infarction is associated with a diminished functional capacity and an increased alteration of the EF. This does not affect the recovery of HR variability, which was observed in all surviving patients.

ST-segment elevation on Q-leads during exercise in patients with ST-segment elevation at rest after myocardial infarction.

INTRODUCTION: ST-segment elevation on Q-leads after an acute myocardial infarction is related to a greater infarct size. The meaning of a further exercise-induced ST-segment elevation in these patients has not been analyzed. METHOD: Thirty-six patients with ST-segment elevation on Q-leads were studied after a first acute myocardial infarction. Exercise testing and cardiac catheterization were performed at the first week. Left ventricular volumes (ml/m(2)); the extent of abnormal wall motion (AWM: chords); contractile reserve (AWM improvement with low dose dobutamine) and coronary patency in the culprit artery were analyzed. Cardiac catheterization was repeated at the sixth month in 20 patients; systolic recovery (AWM improvement), left ventricular volumes and coronary patency were again evaluated. RESULTS: Patients with exercise-induced ST-segment elevation in two or more Q-leads (n=21) showed lesser contractile reserve (6+/-6 vs. 12+/-7 chords, P=0.01) than patients without exercise-induced ST-segment elevation (n=13). AWM (F=8.1) and absence of exercise-induced ST-segment elevation (F=9.5; positive predictive value: 80%; negative predictive value: 68%) were the only independent predictors of contractile reserve. Nevertheless, this electrocardiographic sign was not related to left ventricular volumes, coronary patency or systolic function and it did not predicted late systolic recovery. CONCLUSIONS: In patients with baseline ST-segment elevation on Q-leads an exercise-induced ST-segment elevation is independently related to a lesser contractile reserve but not to the evolution of volumes or regional dysfunction during the first 6 months post-infarction. Therefore, the clinical value of this sign seems to be limited to the non-invasive detection of myocardial viability during the early post-infarction phase.

[Risk factors related to infections during the first year of highly active antiretroviral therapy]. / Factores de riesgo asociados a la aparición de infecciones durante el primer año de tratamiento antirretroviral de alta eficacia.

BACKGROUND: To evaluate the immunological, virological and clinical response of HIV-infected patients who start combined therapy with protease inhibitors (PI) in a community hospital. To identify risk factors related with infections. PATIENTS AND METHOD: Clinical review of patients with combined therapy, assessing CD4+ cell counts, viral load (Amplicor) and development of infections during the first year on PI (group A) and comparative study with the same patients during the previous year with PI (group B). RESULTS: 134 patients were included in group A and 84 in Group B. Nadir of CD4+ was 169 X 10(6)/l. After 6 months of PI therapy, the mean CD4 increased from 217 to 355 X 10(6)/l and the median viral load decreased from 88,000 copies/ml (14,000-485,000) to less than 400 copies /ml (< 400-9,000), 60% of patients had less than 400 copies/ml. The incidence of non-opportunistic infections was similar in both groups (36 vs 43%; p = NS). However, the rate of opportunistic infections decreased from 30 to 15% (RR: 0.41 [CI 0.21-0.81]; p = 0.007) in the group with PI, particularly Pneumocystis carinii pneumonia and toxoplasmosis. Multivariated analysis including CD4+ cell count, nadir of CD4+, viral load and risk behavior only nadir of CD4 < 100 X 10(6)/l was associated with a lower risk of developing opportunistic infections (RR: 0.2 [CI: 0.1-0.7]; p = 0.001). CONCLUSIONS: Combined therapy with PI improved immunological and virological markers and decreased the rate of opportunistic infections. A CD4+ cell count nadir higher than 100 X 10(6)/l was a marker of good prognosis during the first year with PI irrespective of response to therapy.

[Determinants of contractile reserve in the infarction area. A quantitative study using dobutamine in contrast left ventriculography]. / Determinantes de la reserva contráctil en la zona del infarto. Estudio cuantitativo mediante ventriculografía de contraste con dobutamina.

AIM: The aim of this study was to relate the contractile reserve in infarction segments to the dysfunction at rest and to the residual coronary stenosis. METHODS: The study group consisted of 95 patients with a first myocardial infarction. Contrast left ventricular at baseline and after dobutamine infusion at 7.5 microg/kg/min and coronary angiograms were performed. The centerline method was used to quantify the extent of dysfunction (percentage of chords with dysfunction in the territory of the infarction artery) and its maximum severity (maximum units of standard deviation [SD] below the normal wall motion reference). Reduction of dysfunction extent with dobutamine was measured. RESULTS: On increasing baseline dysfunction severity, both the magnitude of the response to dobutamine ( 2 SD 3 SD 4 SD +/- 5 SD [n = 15] = 9+/-13%, > 5 SD [n = 13] = 3+/-4%, p = 0,0001), and the number of patients with a significant (> or =15%) positive response ( 2 SD 3 SD 4 SD 5 SD = 0%, p<0,0001) decreased. There were no differences in dobutamine improvement among the subgroups with (n = 84) or without (n = 11) significant stenosis in the infarction artery (18+/-15 vs. 16 +/-18%), or between the subgroups with a patent (n = 76, 18+/-19%) or occluded (n = 19, 11+/-11%) artery. CONCLUSIONS: Dobutamine response is related to dysfunction severity in the infarction area: when the severity is 5 (high negative response prevalence), dobutamine testing does not seem indicate. The existence of residual coronary stenosis does not attenuate contractile reserve at low dobutamine doses.