Complement component 7 is associated with total- and cardiac death in chest-pain patients with suspected acute coronary syndrome.

BACKGROUND: Complement activation has been associated with atherosclerosis, atherosclerotic plaque destabilization and increased risk of cardiovascular events. Complement component 7 (CC7) binds to the C5bC6 complex which is part of the terminal complement complex (TCC/C5b-9). High-sensitivity C-reactive protein (hsCRP) is a sensitive marker of systemic inflammation and may reflect the increased inflammatory state associated with cardiovascular disease. AIM: To evaluate the associations between CC7 and total- and cardiac mortality in patients hospitalized with chest-pain of suspected coronary origin, and whether combining CC7 with hsCRP adds prognostic information. METHODS: Baseline levels of CC7 were related to 60-months survival in a prospective, observational study of 982 patients hospitalized with a suspected acute coronary syndrome (ACS) at 9 hospitals in Salta, Argentina. A cox regression model, adjusting for conventional cardiovascular risk factors, was fitted with all-cause mortality, cardiac death and sudden cardiac death (SCD) as the dependent variables. A similar Norwegian population of 871 patients was applied to test the reproducibility of results in relation to total death. RESULTS: At follow-up, 173 patients (17.7%) in the Argentinean cohort had died, of these 92 (9.4%) were classified as cardiac death and 59 (6.0%) as SCD. In the Norwegian population, a total of 254 patients (30%) died. In multivariable analysis, CC7 was significantly associated with 60-months all-cause mortality [hazard ratio (HR) 1.26 (95% confidence interval (CI), 1.07-1.47) and cardiac death [HR 1.28 (95% CI 1.02-1.60)], but not with SCD. CC7 was only weakly correlated with hsCRP (r = 0.10, p = 0.002), and there was no statistically significant interaction between the two biomarkers in relation to outcome. The significant association of CC7 with total death was reproduced in the Norwegian population. CONCLUSIONS: CC7 was significantly associated with all-cause mortality and cardiac death at 60-months follow-up in chest-pain patients with suspected ACS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01377402, NCT00521976.

[Fatal spotted fever in Salta province]. / Fiebre manchada de evolución fatal en la provincia de Salta.

We describe the case of a 17-year-old male patient living in Salta city who, 10 days after visiting a rural area in Salta province, was hospitalized for febrile seizures. Shortly after admission, he developed an exanthema followed by a multiple organ dysfunction that evolved to irreversible septic shock followed by death 48 hours after admission. Serological diagnosis -high IgM and IgG anti-Rickettsia spp. antibody titres as detected by indirect immunofluorescence- arrived post mortem. Spotted fever group rickettsioses are tick-borne diseases distributed worldwide and continue being under diagnosed in several countries mainly due to a low clinical suspicion. In the north-western provinces of Argentina there is also the limitation of not counting with a regional laboratory to perform the etiological diagnosis. This is crucial because the severe forms of the disease, which are commonly caused by R. rickettsii, have been already documented in the region. Given that spotted fevers have broadly unspecific febrile presentations and the components of the enzootic cycle are present even in geographic areas not yet considered to be endemic for tick borne diseases, their diagnosis should not be underestimated. If the adequate antibiotic treatment is administered timely, the prognosis of this group of life-threatening diseases improves drastically.

Fiebre manchada de evolución fatal en la provincia de Salta / Fatal spotted fever in Salta province

Describimos el caso de un varón de 17 años oriundo de la ciudad de Salta quien, 10 días después de visitar una zona rural de la provincia homónima, ingresó a nuestro hospital por convulsiones febriles. Durante la internación presentó exantema seguido de disfunción orgánica múltiple, la que evolucionó rápidamente hacia shock séptico irreversible y muerte a las 48 horas de su admisión. El diagnóstico serológico -altos títulos de IgM e IgG anti-Rickettsia spp. por inmunofluorescencia indirecta- arribó post mortem. Las rickettsiosis del grupo de las fiebres manchadas son transmitidas por garrapatas, tienen distribución global y en varios países continúan siendo subdiagnosticadas debido a una baja sospecha clínica. En las provincias del noroeste argentino se agrega la carencia de un laboratorio regional capacitado para efectuar el diagnóstico etiológico. Esta limitación es crítica porque en esa región del país ya ha sido documentada la presencia de las formas graves de la enfermedad, usualmente debidas a R. rickettsii. Dado que las fiebres manchadas se presentan como sindromes febriles inespecíficos y los componentes del ciclo enzoótico están presentes en vastas áreas geográficas, incluso en algunas aún no consideradas endémicas para rickettsiosis, su diagnóstico nunca debe ser subestimado. Con el tratamiento antibiótico adecuado instaurado en tiempo oportuno, el pronóstico de este grupo de enfermedades potencialmente mortales mejora en forma drástica.

We describe the case of a 17-year-old male patient living in Salta city who, 10 days after visiting a rural area in Salta province, was hospitalized for febrile seizures. Shortly after admission, he developed an exanthema followed by a multiple organ dysfunction that evolved to irreversible septic shock followed by death 48 hours after admission. Serological diagnosis -high IgM and IgG anti-Rickettsia spp. antibody titres as detected by indirect immunofluorescence- arrived post mortem. Spotted fever group rickettsioses are tick-borne diseases distributed worldwide and continue being under diagnosed in several countries mainly due to a low clinical suspicion. In the north-western provinces of Argentina there is also the limitation of not counting with a regional laboratory to perform the etiological diagnosis. This is crucial because the severe forms of the disease, which are commonly caused by R. rickettsii, have been already documented in the region. Given that spotted fevers have broadly unspecific febrile presentations and the components of the enzootic cycle are present even in geographic areas not yet considered to be endemic for tick borne diseases, their diagnosis should not be underestimated. If the adequate antibiotic treatment is administered timely, the prognosis of this group of life-threatening diseases improves drastically.

Fatal spotted fever rickettsiosis in Argentina.

We present a fatal case of a 17-year-old male patient who was hospitalized for febrile seizures and generalized skin rash.

Potential Utility of Protein Targets of Cysteine-S-Nitrosylation in Identifying Clinical Disease Status in Human Chagas Disease.

Trypanosoma cruzi (Tc) infection causes Chagas disease (ChD) presented by dilated cardiomyopathy and heart failure. During infection, oxidative and nitrosative stresses are elicited by the immune cells for control the pathogen; however, excess nitric oxide and superoxide production can result in cysteine S-nitrosylation (SNO) of host proteins that affects cellular homeostasis and may contribute to disease development. To identify the proteins with changes in SNO modification levels as a hallmark of ChD, we obtained peripheral blood mononuclear cells (PBMC) from seronegative, normal healthy (NH, n = 30) subjects, and from seropositive clinically asymptomatic (ChD CA, n = 25) or clinically symptomatic (ChD CS, n = 28) ChD patients. All samples were treated (Asc+) or not-treated (Asc-) with ascorbate (reduces nitrosylated thiols), labeled with the thiol-labeling BODIPY FL-maleimide dye, resolved by two-dimensional electrophoresis (total 166 gels), and the protein spots that yielded significant differences in abundance or SNO level at p-value of ≤ 0.05 t-test/Welch/BH were identified by MALDI-TOF/TOF MS or OrbiTrap LC-MS/MS. Targeted analysis of a new cohort of PBMC samples (n = 10-14/group) was conducted to verify the differential abundance/SNO levels of two of the proteins in ChD (vs. NH) subjects. The multivariate adaptive regression splines (MARS) modeling, comparing differences in relative SNO level (Asc-/Asc+ ratio) of the protein spots between any two groups yielded SNO biomarkers that exhibited ≥90% prediction success in classifying ChD CA (582-KRT1 and 884-TPM3) and ChD CS (426-PNP, 582-KRT1, 486-ALB, 662-ACTB) patients from NH controls. Ingenuity Pathway Analysis (IPA) of the SNO proteome dataset normalized to changes in protein abundance suggested the proteins belonging to the signaling networks of cell death and the recruitment and migration of immune cells were most affected in ChD CA and ChD CS (vs. NH) subjects. We propose that SNO modification of the select panel of proteins identified in this study have the potential to identify ChD severity in seropositive individuals exposed to Tc infection.

Suggested Cut-Off Values for Vitamin D as a Risk Marker for Total and Cardiac Death in Patients with Suspected Acute Coronary Syndrome.

BACKGROUND: Several studies have demonstrated an association between low vitamin D levels and cardiovascular risk. Vitamin D cut-off levels are still under debate. OBJECTIVES: To assess two cut-off levels, 40 and 70 nmol/L, respectively, for vitamin D measured as 25-hydroxyvitamin D in chest pain patients with suspected acute coronary syndrome. METHODS: We investigated 1853 patients from coastal-Norway and inland Northern-Argentina. A similar database was used for pooling of data. Two-year follow-up data including all-cause mortality, cardiac death, and sudden cardiac death in the total patient population were analyzed, applying univariate and multivariable analysis. RESULTS: Two hundred fifty-five patients with known vitamin D concentrations died. In the multivariable analysis, there was a decrease in total mortality above a cut-off level of 40 nmol/L and a decrease in cardiac death above a cut-off level of 70 nmol/L [HRs of 0.66 (95% CI, 0.50-0.88), p = 0.004 and 0.46 (95% CI, 0.22-0.94), p = 0.034, respectively]. CONCLUSION: Vitamin D cut-off levels of 40 and 70 nmol/L were related to total mortality and cardiac death, respectively.

Borderline Values of Troponin-T and High Sensitivity C-Reactive Protein Did Not Predict 2-Year Mortality in TnT Positive Chest-Pain Patients, Whereas Brain Natriuretic Peptide Did.

BACKGROUND: Troponin-T (TnT), high-sensitive C-reactive protein (hsCRP), and Brain Natriuretic Peptide (BNP) have been shown to be independent prognostic indicators of total and cardiac death during short- and long-term follow-up. METHODS: We investigated prospectively the prognostic value of admission samples of TnT, hsCRP, and BNP in 871 chest-pain patients from South-Western Norway and 982 patients from Northern Argentina, based on a similar protocol and database setup. Follow-up was 2 years for the pooled population. The prognostic value of the selected biomarkers was investigated in quartiles of 239 patients with TnT values greater than 0.01 and up to and including 0.1 ng/mL, with continuous TnT as a potential confounder. RESULTS: After 24 months, 69 patients had died, of whom 38 died from cardiac causes. In the selected range of TnT, this biomarker was not significantly different between patients who died and survived (mean 0.0452 and 0.0457, p = 0.887). The BNP levels were significantly higher among patients dying than in long-term survivors [340 (142-656) versus 157 (58-367) pg/mL (median, 25 and 75% percentiles), p < 0.001]. In a multivariable Cox regression model for death within 2 years, the hazard ratio (HR) for BNP in the highest quartile (Q4) as compared to the lowest (Q1) was significantly related to total mortality [HR 2.84 (95% confidence interval (CI), 1.13-7.17)], p = 0.027, in addition to age (p ≤ 0.001) and hypercholesterolemia (p = 0.043). For cardiac death, the HR for BNP was 5.18 (95% CI, 1.06-25.3), p = 0.042. Several other variables (age, congestive heart failure, ST elevation myocardial infarction, and study country) were also significantly related to cardiac death. In a multivariable Cox regression model, hsCRP rendered no significant prognostic information for all-cause mortality (p = 0.089) or for cardiac mortality (p = 0.524). CONCLUSION: In patients with borderline TnT values (greater than 0.01 and up to and including 0.1 ng/mL), this biomarker as well as hsCRP did not render prognostic information, whereas BNP was found to be a strong prognostic indicator of 2-year total and cardiac mortality.

Vitamin d predicts all-cause and cardiac mortality in females with suspected acute coronary syndrome: a comparison with brain natriuretic Peptide and high-sensitivity C-reactive protein.

Vitamin D may not only reflect disease but may also serve as a prognostic indicator. Our aim was to assess the gender-specific utility of vitamin D measured as 25-hydroxy-vitamin D [25(OH)D] to predict all-cause and cardiac death in patients with suspected acute coronary syndrome (ACS) and to compare its prognostic utility to brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hsCRP). Blood samples were harvested on admission in 982 patients. Forty percent were women (65.9 ± 12.6 years). Mortality was evaluated in quartiles of 25(OH)D, BNP, and hsCRP, respectively, during a 5-year follow-up, applying univariate and multivariate analyses. One hundred and seventy-three patients died; 78 were women. In 92 patients (37 women), death was defined as cardiac. In women, the univariate hazard ratio (HR) for total death of 25(OH)D in Quartile (Q) 2 versus Q1, Q3 versus Q1, and Q4 versus Q1 was 0.55 (95% CI 0.33-0.93), 0.29 (95% CI 0.15-0.55), and 0.13 (95% CI 0.06-0.32), respectively. In females, it was an independent predictor of total and cardiac death, whereas BNP and hsCRP were less gender-specific. No gender differences in 25(OH)D were noted in a reference material. Accordingly, vitamin D independently predicts mortality in females with suspected ACS.

Socioeconomic assessment and impact of social security on outcome in patients admitted with suspected coronary chest pain in the city of salta, Argentina.

Low socioeconomic status is associated with increased mortality from coronary heart disease. We assessed total mortality, cardiac death, and sudden cardiac death (SCD) in relation to socioeconomic class and social security in 982 patients consecutively admitted with suspected coronary chest pain, living in the city of Salta, northern Argentina. Patients were divided into three socioeconomic classes based on monthly income, residential area, and insurance coverage. Five-year follow-up data were analyzed accordingly, applying univariate and multivariate analyses. At follow-up, 173 patients (17.6%) had died. In 92 patients (9.4%) death was defined as cardiac, of whom 59 patients (6.0%) were characterized as SCD. In the multivariate analysis, the hazard ratios (HRs) for all-cause and cardiac mortality in the highest as compared to the lowest socioeconomic class were 0.42 (95% confidence interval (CI), 0.22-0.80), P = 0.008, and 0.39 (95% CI, 0.15-0.99), P = 0.047, respectively. Comparing patients in the upper socioeconomic class to patients without healthcare coverage, HRs were 0.46 (95% CI, 0.23-0.94), P = 0.032, and 0.37 (95% CI, 0.14-1.01), P = 0.054, respectively. In conclusion, survival was mainly tied to socioeconomic inequalities in this population, and the impact of a social security program needs further attention.

Serum 25(OH)D is a 2-year predictor of all-cause mortality, cardiac death and sudden cardiac death in chest pain patients from Northern Argentina.

BACKGROUND: Several studies have shown an association between vitamin D deficiency and cardiovascular risk. Vitamin D status is assessed by determination of 25-hydroxyvitamin D [25(OH)D] in serum. METHODS: We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome (ACS) from Salta, Northern Argentina. 2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D, applying univariate and multivariate analysis. RESULTS: There were statistically significant changes in seasonal 25(OH)D levels. At follow-up, 119 patients had died. The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors, both in the total population and in patients with a troponin T (TnT) release (n = 388). When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality, the hazard ratio (HR) for cardiac death and sudden cardiac death in the total population was 0.37 (95% CI, 0.19-0.73), p = 0.004, 0.23 (95% CI, 0.08-0.67), p = 0.007, and 0.32 (95% CI, 0.11-0.94), p = 0.038, respectively. In patients with TnT release, the respective HR was 0.24 (95% CI, 0.10-0.54), p = 0.001, 0.18 (95% CI, 0.05-0.60), p = 0.006 and 0.25 (95% CI, 0.07-0.89), p = 0.033. 25(OH)D had no prognostic value in patients with no TnT release. CONCLUSION: Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS. TRIAL REGISTRATION: ClinicalTrials.gov NCT01377402.

B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year all cause mortality in chest pain patients: a prospective observational study from Salta, Argentina.

BACKGROUND: Several mechanisms are involved in the pathophysiology of the Acute Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may improve risk stratification in chest pain patients with suspected ACS. METHODS: We included 982 patients consecutively admitted with chest pain and suspected ACS at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were recorded during a 2-year follow up period. Patients were divided into quartiles according to BNP and hsCRP levels, respectively, and inter quartile differences in mortality were statistically evaluated applying univariate and multivariate analyses. RESULTS: 119 patients died, and the BNP and hsCRP levels were significantly higher among these patients than in survivors. In a multivariable Cox regression model for total death and cardiac death in all patients, the hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and 3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p = 0.029, respectively.The HR for total death for hsCRP in Q4 as compared to Q1 was 1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac death (p = 0.21). No prognostic impact of these two biomarkers was found in the TnT negative patients. CONCLUSION: BNP and hsCRP may act as clinically useful biomarkers when obtained at admission in a population with suspected ACS.

Flu vaccination in acute coronary syndromes and planned percutaneous coronary interventions (FLUVACS) Study.

AIMS: We have previously reported a significant benefit of vaccination against flu on the incidence of a single and composite end-point of death, myocardial infarction or recurrent ischaemia in patients with myocardial necrosis and planned percutaneous coronary interventions. To determine whether the observed benefits of vaccination against flu were maintained beyond the winter season a 1-year follow-up was conducted. METHODS AND RESULTS: During the winter season, we enrolled prospectively 200 myocardial infarction patients admitted in the first 72 h, and 101 planned angioplasty/stent patients (PCI) without unstable coronary artery disease, prior by-pass surgery, angioplasty or tissue necrosis. Only four patients failed to meet the inclusion criteria. Participants were randomly allocated to receive flu vaccination or remain unvaccinated on top of standard medication (control group). The study was conducted in hospitalized patients with the aim to test the potential beneficial effect of flu vaccination in a secondary prevention scenario. Under intention to treat analysis the incidence of the primary end-point cardiovascular death at 1 year was significantly lower among patients receiving vaccination, 6% as compared with controls, 17% (relative risk with vaccine as compared with controls, 0.34; 95% confidence interval (CI), 0.17 to 0.71; P=0.002). The triple composite end-point occurred in 22% of the patients in the vaccine group vs 37% in controls, hazard ratio 0.59, 95% CI 0.4 to 0.86) P=0.004. The beneficial effect was mainly detected in acute myocardial infarction patients (four events in the active arm vs 21 in the control group, P=0.0002 [95% CI 0.19, 0.07-0.53]), and Cox regression analyses revealed that there was a greater benefit with flu vaccination in patients at high risk according with the TIMI score, and those with non-ST-segment deviation myocardial infarction (95% CI: 0.13 [0.03-0.52]) CONCLUSIONS: Influenza vaccination may reduce the risk of death and ischaemic events in patients suffering from infarction and post-angioplasty during flu season. This effect was significantly evident at 1-year follow-up. Larger confirmatory studies are needed to evaluate the real impact on flu vaccination on outcome after acute coronary syndromes.

[Flu vaccination in patients with acute coronary syndromes: treatment benefit in prespecified subgroups]. / Vacunación antigripal en pacientes con síndromes coronarios agudos: beneficio del tratamiento en diferentes subgrupos.

BACKGROUND: The first prospective clinical Flu Vaccination in Acute Coronary Syndromes (FLUVACS) Trial has provided some evidence that flu vaccination together with standard therapy may be useful during the winter season to reduce the risk of death and major cardiac events in patients with acute myocardial infarction. PATIENTS AND METHOD: Information available in the FLUVACS database was analyzed to evaluate the efficacy of flu vaccination in different subgroups. Logistic regression was used to identify features related with better therapeutic results. RESULTS: Flu vaccination was effective in reducing the incidence of the composite endpoint (death, nonfatal myocardial reinfarction or recurrent angina prompting urgent revascularization) in most subgroups at 6 months after inclusion. The regression model showed a greater benefit of flu vaccination in patients with no ST-segment elevation or older than 65 years, nonsmokers and patients with a TIMI risk score higher than 6. CONCLUSIONS: Our data suggest that vaccination for secondary prevention of flu during the acute phase of myocardial infarction may be effective in a broad range of patients with acute coronary artery disease, regardless of their initial clinical risk.

Vacunación antigripal en pacientes con síndromes coronarios agudos: beneficio del tratamiento en diferentes subgrupos / Flu vaccination in patients with acute coronary syndromes: treatment benefit in prespecified subgroups

Introducción. El primer ensayo prospectivo sobre vacunación antigripal en pacientes con síndromes coronarios agudos (estudio FLUVACS) demostró que su aplicación durante la época invernal, sumada a la medicación estándar, fue más efectiva para reducir el riesgo de muerte y episodios cardiovasculares mayores en pacientes con infarto agudo de miocardio. Pacientes y método. Se analizó la información disponible de la base de datos del estudio FLUVACS, para evaluar la eficacia de la vacunación antigripal en diferentes subgrupos de pacientes. Se empleó un método estadístico de regresión logística para determinar qué rasgos estaban relacionados con un mejor resultado terapéutico. Resultados. La vacunación antigripal fue efectiva para reducir la incidencia del punto final combinado (muerte, reinfarto no fatal o angina recurrente que requiriera revascularización urgente) en la mayoría de los subgrupos a los 6 meses de seguimiento después de la inclusión. El modelo estadístico de regresión reveló un mayor beneficio con la vacunación antigripal en pacientes sin elevación del segmento ST, en los enfermos mayores de 65 años de edad, en los no fumadores y en pacientes con calificación de riesgo TIMI > 6. Conclusiones. Los resultados obtenidos en este estudio indican que el uso de la vacunación antigripal como prevención secundaria en pacientes que cursan la fase aguda de un infarto de miocardio podría beneficiar a un amplio grupo de enfermos con este diagnóstico, independientemente del riesgo clínico basal (AU)