Vitamin D Deficiency in Patients with Diabetes in French Guiana: Epidemiology and Relation with Microvascular and Macrovascular Complications.

Vitamin D (VD) insufficiency is common among patients with diabetes in French Guiana. The study aimed to evaluate the prevalence of VD deficiency in the different type of diabetes encountered and to analyze the relationship between VD deficiency and diabetes complications. METHODS: An observational study was conducted between May 2019 and May 2020 in French Guiana, based on data from the CODIAM study (Diabetes Cohort in French Amazonia), describing the characteristics of patients with diabetes mellitus. Among 600 patients enrolled with diabetes, 361 had an available VD assay. RESULTS: The mean 25(OH)VD (hydroxycalciferol) level was 27.9 ng/mL. The level of VD was inversely proportional to the HbA1c (glycated hemoglobin) level. Patients with angina pectoris had a greater proportion of deficiencies VD < 20 ng/mL than those without angina. By contrast, patients with retinopathy had higher vitamin D concentrations than those without retinopathy. There was no association between vitamin D and arteriopathy, stroke, nephropathy and polyneuropathy. VD deficiency was more frequent in women, and in patients with a high school education. CONCLUSION: The prevalence of VD deficiency was high in patients with diabetes in French Guiana, emphasizing the importance of VD supplementation.

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.

A prospective study of patients with refractory angina: outcomes and the role of high-sensitivity troponin T.

BACKGROUND: The predictors of cardiovascular events in patients with chronic refractory angina are limited. High-sensitivity cardiac troponin T (hs-cTnT) assays are biomarkers that may be used to determine the prognosis of patients with stable coronary artery disease. HYPOTHESIS: Hs-cTnT is a predictor of death and nonfatal myocardial infarction (MI) in patients with refractory angina. METHODS: We prospectively enrolled 117 consecutive patients in this study. A heart team ruled out myocardial revascularization feasibility after assessing recent coronary angiograms; evidence of myocardial ischemia served as an inclusion criterion. Optimal medical therapy was encouraged via outpatient visits every 6 months; plasma hs-cTnT levels were determined at baseline. The primary endpoint was the composite incidence of death and nonfatal MI. RESULTS: During a median follow-up period of 28.0 months (interquartile range, 18.0-47.5 months), an estimated 28.0-month cumulative event rate of 13.4% was determined via the Kaplan-Meier method. Univariate predictors of the composite endpoint were hs-cTnT levels and LV dysfunction. Following a multivariate analysis, only hs-cTnT was independently associated with the events in question, either as a continuous variable (hazard ratio per unit increase in the natural logarithm: 2.83, 95% confidence interval: 1.62-4.92, P < 0.001) or as a categorical variable (hazard ratio for concentrations above the 99th percentile: 5.14, 95% confidence interval: 2.05-12.91, P < 0.001). CONCLUSIONS: In patients with chronic refractory angina, plasma concentration of hs-cTnT is the strongest predictor of death and nonfatal MI. Notably, none of the outcomes in question occurred in patients with baseline plasma levels <5.0 ng/L.

Obstructive sleep apnoea is associated with myocardial injury in patients with refractory angina.

OBJECTIVE: To investigate the association between obstructive sleep apnoea (OSA) severity with markers of overnight myocardial injury in patients with refractory angina. METHODS: Patients with refractory angina were characterised clinically and they underwent ischaemia imaging stress tests by single-photon emission computed tomography (SPECT) and/or cardiac MRI. The patients were admitted to the hospital, remained under resting conditions for blood determination of high-sensitivity cardiac troponin T (hs-cTnT) at 14:00, 22:00 and after overnight polysomnography at 7:00. RESULTS: We studied 80 consecutive patients (age: 62±10 years; male: 66%; body mass index (BMI): 29.5±4 kg/m(2)) with well-established diagnosis of refractory angina. The mean apnoea-hypopnoea index (AHI) was 37±29 events/h and OSA (AHI >15 events/h) was present in 75% of the population. Morning detectable hs-cTnT and above 99th percentile was present in 88% and 36% of the population, respectively. Patients in the first to third quartiles of OSA severity did not have circadian variation of hs-cTnT. In contrast, patients in the fourth quartile (AHI ≥51 events/h) had a circadian variation of hs-cTnT with a morning peak of hs-cTnT that was two times higher than that in the remaining population (p=0.02). The highest quartile of OSA severity remained associated with the highest quartile of hs-cTnT (p=0.028) in multivariate analysis. CONCLUSION: Very severe OSA is common and independently associated with overnight myocardial injury in patients with refractory angina.

Níveis NT-Pro-BNP e resposta ao exercício em pacientes com fluxo lento coronariano / NT-Pro-BNP levels and their response to exercise in patients with slow coronary flow

FUNDAMENTO: Os peptídeos natriuréticos são liberados pelo coração em resposta ao estresse da parede. OBJETIVO: As concentrações de NT-Pro-BNP em pacientes com Fluxo Lento Coronariano (FLC) foram avaliadas antes e depois do teste de exercício e comparados com os valores dos controles saudáveis. MÉTODOS: A população do estudo foi de 34 pacientes com FLC [22 homens (64,7%), com idade 51,0 ± 6,2 anos], e 34 indivíduos normais com artérias coronarianas normais [21 homens (61,8%), com idade 53,2 ± 6,6 anos]. As taxas de fluxo coronariano dos pacientes e controles foram determinadas pelo escore TIMI Trombólise no Infarto do Miocárdio (Thrombolysis in Myocardial Infarction). As amostras de sangue foram coletadas em repouso e após o teste ergométrico. RESULTADOS: As concentrações basais de NT-Pro-BNP nos pacientes com FLC foram superiores às dos indivíduos-controle (NT-Pro-BNP: 49,7 ± 14,2 pg/mL vs. 25,3 ± 4,6 pg/mL p <0,0001, respectivamente), e essa diferença entre os grupos aumentou após o teste de exercício (NT-Pro-BNP: 69,5 ± 18,6 pg/mL vs. 30,9 ± 6,4 pg/mL, p <0,0001). No grupo FLC após o exercício, a concentração de NT-Pro-BNP em 15 pacientes com angina foi maior do que aqueles sem angina (76,8 ± 17,8 pg/mL vs. 63,8 ± 17,5 pg/mL, p = 0,041).A concentração de NT-Pro-BNP em 11 pacientes com infradesnivelamento do segmento ST foi também maior do que aqueles sem infradesnivelamento do segmento ST (82,4 ± 17,3 pg/mL vs. 63,3 ± 16,1 pg/mL, p = 0,004). Os aumentos na mediana pós-exercício no NT-Pro-BNP (Δ NT-Pro-BNP) foram maiores no grupo FLC do que no grupo de controle (Δ NT-Pro-BNP: 19,8 ± 7,7 pg/mL vs. 5,7 ± 4,5 pg/mL, p < 0,0001). CONCLUSÃO: Os resultados deste estudo sugerem que pode haver uma ligação fisiopatológica importante entre a gravidade do FLC (microvascular ou disfunção da artéria coronária epicárdica) e o nível de circulação de NT-Pro-BNP em pacientes com FLC.

BACKGROUND: Natriuretic peptides are released by the heart in response to wall stress. OBJECTIVE: The NT-Pro-BNP concentrations in slow coronary flow (SCF) patients were assessed before and after the exercise test and compared with the values of healthy controls. METHODS: The study population was 34 patients with SCF [22 males (64.7%), aged 51.0±6.2 years], and 34 normal subjects with normal coronary arteries [21 males (61.8%), aged 53.2±6.6 years]. Coronary flow rates of all patients and control subjects were documented as Thrombolysis in Myocardial Infarction (TIMI) frame count. Blood samples were drawn at rest and after the exercise testing. RESULTS: The baseline NT-Pro-BNP concentrations of the SCF patients were higher than those of the control subjects (NT-Pro-BNP: 49.7±14.2 pg/mL vs. 25.3±4.6 pg/mL p<0.0001, respectively), and this difference increased after exercise test between the groups (NT-Pro-BNP: 69.5±18.6 pg/mL vs. 30.9±6.4 pg/mL p<0.0001). In SCF group after exercise, NT-Pro-BNP concentration in 15 patients with angina was higher than those without angina (76.8 ± 17.8 pg/mL vs. 63.8±17.5 pg/mL p=0.041). NT-Pro-BNP concentration in 11 patients with ST depression was also higher than those without ST depression (82.4 ± 17.3 pg/mL vs. 63.3 ± 16.1 pg/mL p=0.004). Median post-exercise increases in NT-Pro-BNP (Δ NT-Pro-BNP) were higher in the SCF group than in the control group (Δ NT-Pro-BNP: 19.8±7.7 pg/mL vs. 5.7±4.5 pg/mL p<0.0001). CONCLUSION: The results of this study suggest that there may be an important pathophysiologic link between the severity of SCF (microvascular or epicardial coronary artery dysfunction) and the level of circulating NT-Pro-BNP in SCF patients.

NT-Pro-BNP levels and their response to exercise in patients with slow coronary flow.

BACKGROUND: Natriuretic peptides are released by the heart in response to wall stress. OBJECTIVE: The NT-Pro-BNP concentrations in slow coronary flow (SCF) patients were assessed before and after the exercise test and compared with the values of healthy controls. METHODS: The study population was 34 patients with SCF [22 males (64.7%), aged 51.0 ± 6.2 years], and 34 normal subjects with normal coronary arteries [21 males (61.8%), aged 53.2 ± 6.6 years]. Coronary flow rates of all patients and control subjects were documented as Thrombolysis in Myocardial Infarction (TIMI) frame count. Blood samples were drawn at rest and after the exercise testing. RESULTS: The baseline NT-Pro-BNP concentrations of the SCF patients were higher than those of the control subjects (NT-Pro-BNP: 49.7 ± 14.2 pg/mL vs. 25.3 ± 4.6 pg/mL p<0.0001, respectively), and this difference increased after exercise test between the groups (NT-Pro-BNP: 69.5 ± 18.6 pg/mL vs. 30.9 ± 6.4 pg/mL p<0.0001). In SCF group after exercise, NT-Pro-BNP concentration in 15 patients with angina was higher than those without angina (76.8 ± 17.8 pg/mL vs. 63.8 ± 17.5 pg/mL p=0.041). NT-Pro-BNP concentration in 11 patients with ST depression was also higher than those without ST depression (82.4 ± 17.3 pg/mL vs. 63.3 ± 16.1 pg/mL p=0.004). Median post-exercise increases in NT-Pro-BNP (Δ NT-Pro-BNP) were higher in the SCF group than in the control group (Δ NT-Pro-BNP: 19.8 ± 7.7 pg/mL vs. 5.7 ± 4.5 pg/mL p<0.0001). CONCLUSION: The results of this study suggest that there may be an important pathophysiologic link between the severity of SCF (microvascular or epicardial coronary artery dysfunction) and the level of circulating NT-Pro-BNP in SCF patients.

Improving RBC K transport and hemoglobin-O2 binding by amiloride: A novel therapeutic approach for reversion of angina and myocardial ischemia in coronary heart diseases.

UNLABELLED: Coronary heart disease (CHD) is the leading cause of morbidity and mortality across the entire world, in which reversion of angina or improvement of ECG remains an unrealistic therapeutic option for most patients, suggesting that microvascular dysfunction or impaired oxygen delivery might be critical factors in CHD. This research article, thus presents the rationale basis, clinical and experimental, for the first therapeutic innovation addressing the role of red blood cell (RBC) H/K and O2/CO2 exchanges in CHD. It is followed by a randomized single-blind trial of Amiloride and Optimal Medical Therapy (OMT, n=35 cases) vs OMT alone (n=35 cases) in patients having angina, ST-T alteration and a defective RBC-K transport. All patients had serial clinical evaluation, Ion Transport Studies, ECGs and non-invasive aortic waveform and cardiovascular hemodynamic recordings. Statistical analysis was performed by SAS. RESULTS: Amiloride rapidly improved RBC-K (93.5 ±4 vs 84.5 ±4 mmol/lc, p= < 0.001), angina (80% of cases, 1.5 ±0.3 weeks, CI:1.72 to 1.45), CCS Class (1.3 ±0.5 vs 3.1 ±0.8, p < 0.001) vs patients with OMT alone CCS Class (3.2 ± 0.4 vs 3.3 ± 0.5, p =0.21). Reversion of angina was sustained through the next 6-months (87% vs 26 % in OMT, RR 2.1, odds ratio 6.31, Pearson x2 34.6,p < 0.0001 at 95% CI) and 1-year (85% vs 37% OMT). At 6-months of amiloride, ECG became normal (29% vs 0%, RR ∞ uncalculated-time, odds ratio ∞, Pearson x2 42.4 at 95% CI, p < 0.0001), improved (55% vs 29%; RR2.1, odds ratio 3.16, 95% CI, p < 0.0001) or unchanged (15% vs 67% OMT). At 1-year, seven patients on amiloride (18%) exhibited evidence of electrical regeneration of the heart, not observed with placebo. IN CONCLUSION: This therapeutical innovation of amiloride improves RBC H/K and O2/CO2 function, and reverses angina, ST-T alterations while inducing electrical regeneration of the heart, in patients receiving optimal medical treatment for angina. The article has short discussion on the relevant patents to the topic.

[Leukocyte count as a risk factor for coronary adverse events among patients admitted for an acute coronary syndrome]. / Recuento leucocitario y riesgo cardiovascular tras un síndrome coronario agudo.

BACKGROUND: Leukocytosis occurs as a response to a variety of inflammatory processes. AIM: To determine if white blood cell count (WBCC) at admission among patients who suffer an acute coronary syndrome (ACS) has an independent prognostic value for the occurrence of new cardiovascular adverse events (CAE). PATIENTS AND METHODS: Prospective study of 558 patients aged 68 +/- 13 years (122 women) admitted to the hospital for an acute coronary syndrome. WBCC was measured at admission. A logistic regression model was used to assess the association of WBCC with the occurrence of CAE during the next six months after admission (post infarction angina, re-infarction, cardiac failure and mortality). RESULTS: An univariate analysis showed that patients with a WBCC > 15.000 cell/mm(3) had a significantly higher mortality and occurrence of CAE. The multivariate analysis showed that subjects with WBCC < 10.000 cell/mm(3) experienced fewer CAE than subjects with a WBCC > 15.000 cell/mm(3), with an odds ratio of 0.46 (95% confidence intervals = 0.21-0.97, p = 0,042). CONCLUSIONS: An elevated WBCC at admission among patients with an ACS is associated with a higher incidence of CAE in the ensuing six months.

Recuento leucocitario y riesgo cardiovascular tras un síndrome coronario agudo / Leukocyte count as a risk factor for coronary adverse events among patients admitted for an acute coronary syndrome

Background: Leukocytosis occurs as a response to a variety of infammatory processes. Aim: To determine if white blood cell count (WBCC) at admission among patients who suffer an acute coronary syndrome (ACS) has an independent prog-nostic value for the occurrence of new cardiovascular adverse events (CAE). Patients and Methods: Prospective study of 558 patients aged 68 ± 13 years (122 women) admitted to the hospital for an acute coronary syndrome. WBCC was measured at admission. A logistic regression model was used to assess the association of WBCC with the occurrence of CAE during the next six months after admission (post infarction angina, re-infarction, cardiac failure and mortality). Results: An univariate analysis showed that patients with a WBCC > 15.000 cell/mm³ had a signifcantly higher mortality and occurrence of CAE. The multivariate analysis showed that subjects with WBCC < 10.000 cell/mm³ experienced fewer CAE than subjects with a WBCC > 15.000 cell/mm³, with an odds ratio of 0.46 (95 percent confdence intervals = 0.21-0.97, p = 0,042). Conclusions: An elevated WBCC at admission among patients with an ACS is associated with a higher incidence of CAE in the ensuing six months.

B-type natriuretic peptide: a strong predictor of early and late mortality in patients with acute chest pain without ST-segment elevation in the emergency department.

BACKGROUND: The prognostic importance of early measurement of B-type natriuretic peptide (BNP) in patients with acute chest pain while the diagnosis is still uncertain is unknown. We determined the prognostic value of BNP in these patients immediately after presenting to the emergency department. METHODS: Seven hundred and twenty-three consecutive individuals with suspicious ischemic acute chest pain and no ST-segment elevation were prospectively evaluated using a systematic diagnostic strategy and followed for 1 year. Acute coronary syndrome was diagnosed in 326 patients during their hospital stay. RESULTS: In the follow-up, 15 (2.1%) patients of the whole cohort died of cardiac cause at 1 month and 51 (7.1%) at 1 year. Patients who died had significantly higher admission BNP levels than survivors and this correlation proved linear according to quartile levels. Patients with BNP greater than 101 pg/ml had 13 times higher rate of 1-month mortality (P<0.0001) and 5.3 times higher rate of 1-year mortality (P<0.0001) than patients with BNP of 101 pg/ml or less. Multiple logistic regression analysis disclosed BNP as a strong independent predictor of 1-month and 1-year mortality adding significant prognostic information over traditional risk markers. CONCLUSION: Admission BNP is an independent and powerful marker of early and late cardiac mortality in patients with acute chest pain without ST-segment elevation. These results suggest that BNP should be measured upon arrival at the emergency department for risk stratification in all these patients.

Enhanced inflammatory response to coronary stenting marks the development of clinically relevant restenosis.

OBJECTIVES: The aims of this study were to investigate the effect of coronary stenting on the release of cytokines and cell-mediated immunity factors and to evaluate the association between inflammation and clinical outcomes at 6 months. BACKGROUND: Circulating levels of inflammatory markers and cytokines are elevated in patients with acute coronary syndromes and are related to an unfavorable outcome. The aims of this study were to investigate the effect of coronary stenting on the release of cytokines and cell-mediated immunity factors and to evaluate the association between inflammation and clinical outcomes at 6 months. METHODS: Forty patients with single native coronary artery disease treated with stenting were enrolled. Peripheral venous blood samples were collected before and 6 h, 48 h, and 12 weeks after stenting. Serum concentrations of high-sensitivity C-reactive protein, interleukin-6, interleukin-8, tumor necrosis factor-alpha (markers of inflammation) and serum-soluble interleukin-2 receptor for T-lymphocyte activation (sIL2-R, marker of cell-mediated immunity) were measured. Patients also were evaluated clinically one, 3, and 6 months post-stenting or when they presented with cardiovascular symptoms to identify major adverse cardiac events (cardiac death, MI, revascularization). RESULTS: Concentrations of interleukins 6 and 8 and tumor necrosis factor-alpha peaked at 6 h (11.0, 12.6, and 5.3 pg/ml, respectively). The peak level of high-sensitivity C-reactive protein (2.77 mg/dL) occurred 48 h post stenting, while sIL2-R peaked (495 U/ml) at 12 weeks. Patients who experienced restenosis had higher levels of C-reactive protein at 48 h (4.94 vs. 1.84 mg/dl; P = 0.043) and of IL-8 at 6 h (26.75 vs. 13.55 pg/mL; P = 0.048) than those without restenosis. CONCLUSIONS: Proinflammatory cytokines and inflammatory markers are released into the peripheral circulation early after coronary stenting, and increased levels of some are associated with clinically relevant restenosis.

Enhanced inflammatory response following coronary stent implantation in stable angina patients.

BACKGROUND: Percutaneous coronary intervention (PCI) is associated with an increase in inflammatory activity. However, little is known about the association between the inflammatory response post-PCI and plaque morphology. The objective of this study was to characterize the inflammatory response following coronary stent implantation (CSI) of stable atherosclerotic plaques, according to plaque morphology. METHODS: The study population consisted of 62 patients with stable angina that had an elective indication of CSI. Immediately before CSI, the patients underwent intravascular ultrasound (IVUS) for determination of the predominant plaque morphology of the target lesion: calcified (C, n=15), fibrocalcified (FC, n=16), fibrolipidic (FL, n=16), or lipidic (L, n=15). Angiographic lesion types were also determined. Coronary sinus samples were collected at baseline (BL) and 15 min after CSI for measuring inflammatory mediators (IM): interleukin-6 (IL-6, in pg/ml), tumoral necrosis factor-alpha (TNF, in pg/ml), interferon-gamma (IFN, in IU/ml), and neopterin (N, in ng/ml). RESULTS: BL IL-6, TNF, IFN, and N were, respectively, for C plaques (mean+/-S.D.): 1.3+/-3.0, 8.0+/-3.5, 0.1+/-0.2, and 3.2+/-0.8; for FC plaques: 6.7+/-3.3, 1.9+/-2.0, 0.1+/-0.1, and 3.8+/-2.0; for FL plaques: 0.7+/-0.9, 8.7+/-4.3, 0.1+/-0.2, and 4.0+/-2.4; and, for L plaques: 1.9+/-2.8, 0.9+/-1.4, 0.0+/-0.1, and 5.2+/-3.3. After 15 min of CSI, percentual changes of IL-6, TNF, IFN, and N, respectively, were for C plaques: 43.8+/-19.6%, 7.7+/-5.5%, -7.5+/-5.3%, and -20.0+/-11.2%; for FC plaques: 7.7+/-5.5%, 168.4+/-56.9%, 311.1+/-159.9%, and 0%; for FL plaques: 147.5+/-16.1%*, 714.3+/-34.4%*, 116.1+/-9.9%*, and 3000.0+/-230.0%*; and, for L plaques: 147.7+/-14.4%*, 140.3+/-15.0%*, 131.6+/-11.9%*, and 2300.0+/-25.9%*. Moreover, B1 (n=28) and B2 (n=32) predominated and resulted in significant changes only for IL-6 and IFN, respectively. *P<0.05: 15 min vs BL. CONCLUSIONS: These data suggest that stable angina patients with predominant lipidic (L and FL) plaques present a greater inflammatory response after CSI in than those with predominant calcified (C and FC) plaques.

Platelet activation in different clinical forms of the coronary artery disease (role of P-selectin and others platelet markers in stable and unstable angina).

OBJECTIVE: Markers of platelet activation are elevated in coronary artery disease. We sought to identify the presence and the potential associations of different markers of platelet activation. METHODS: We studied patients with unstable angina (n=28), patients with stable angina (n=36) and patients without coronary artery disease (n=30); sex and age matched. Blood levels of the adhesion molecule P-selectin, Thromboxane B2 and Serotonin were measured by enzyme immunoassays. RESULTS: When we compared the groups the results were: sP-selectin, thromboxane B2 and serotonin levels were significantly higher in patients with unstable angina than in patients with stable angina. CONCLUSION: These markers of platelet activation were able to identify unstable forms of coronary artery disease.

Influence of gender on the prognostic value of troponin I after elective percutaneous coronary interventions.

OBJECTIVE: To evaluate the association between troponin I concentrations (TnI) in patients submitted to elective percutaneous coronary interventions (PCI) and adverse coronary events (ACE) during a six month follow-up period. METHODS: One hundred and eleven patients who had been submitted to an elective PCI were consecutively selected during a one year timeframe. The patients had stable angina (SA), unstable angina (UA) or silent ischemia (SI) and were asymptomatic for at least 72 hours before the procedure. TnI concentrations were measured between 8 and 24 hours after the PCI. Each patient was contacted by telephone six months later and interviewed regarding ACE which were defined as death, myocardial infarction, new revascularization and recurrent ischemia. RESULTS: Twenty-four patients showed elevated concentrations of TnI (21.6%) after the PCI regardless of clinical characteristics or procedure complications. Those who presented elevated TnI concentrations had higher event rates: 66.7 vs. 42.5% (RR=1.57; CI 95%=1.08-2.28). This risk seems to be higher in the subgroups of females and patients with a previous diagnosis of unstable angina. Multivariate analysis confirmed that gender was the only effect modifying co-variable associated with ACE risk, which is higher for females with elevated TnI concentrations (OR=7.22; CI 95%=1.4 -36.9) and unaltered for males (OR=1.26; CI 95%=0.35-4.55). CONCLUSION: Elevated TnI concentrations were a common occurrence after PCI and is a factor related to the development of ACE in the mid term. However, when adjusted for other variables, this effect is only maintained in female patients.

Ativação plaquetária em formas clínicas distintas da doença arterial coronariana (papel da P-selectina e de outros marcadores nas anginas estável e instável) / Platelet activation in different clinical forms of the coronary artery disease (roll of P-selectin and others platelet markers in the stable and unstable angina) / Platelet activation in different clinical forms of the coronary artery disease (roll of P-selectin and others platelet markers in the stable and unstable angina)

OBJETIVO: Os marcadores da ativação plaquetária em geral se apresentam elevados na doença arterial coronariana. Desse modo, procuramos identificar a presença e as potenciais associações de diferentes marcadores da ativação plaquetária. MÉTODOS: Estudamos pacientes com angina instável (n=28), pacientes com angina estável (n=36) e pacientes sem doença arterial coronariana (n=30); sexo e idade foram estratificados. Os níveis sangüíneos da molécula de adesão P-selectina, do thromboxane B2 e de serotonina foram medidos por imunoensaios enzimáticos. RESULTADOS: Quando comparamos os grupos, os resultados foram: a P-selectina, o thromboxane B2 e os níveis do serotonina apresentaram-se significativamente mais elevados nos pacientes com angina instável do que nos pacientes com angina estável. CONCLUSÃO: Estes marcadores da ativação plaquetária podem, portanto, identificar formas instáveis de doença arterial coronariana.

OBJECTIVE: Markers of platelet activation are elevated in coronary artery disease. We sought to identify the presence and the potential associations of different markers of platelet activation. METHODS: We studied patients with unstable angina (n=28), patients with stable angina (n=36) and patients without coronary artery disease (n=30); sex and age matched. Blood levels of the adhesion molecule P-selectin, Thromboxane B2 and Serotonin were measured by enzyme immunoassays. RESULTS: When we compared the groups the results were: sP-selectin, thromboxane B2 and serotonin levels were significantly higher in patients with unstable angina than in patients with stable angina. CONCLUSION: These markers of platelet activation were able to identify unstable forms of coronary artery disease.

Influência do gênero no valor prognóstico da troponina I após angioplastia coronariana eletiva / Influence of gender on the prognostic value of troponin I after elective percutaneous coronary interventions

OBJETIVO: Avaliar a associação entre níveis de troponina I (TnI) em pacientes submetidos, eletivamente, a intervenções coronárias percutâneas (ICP) com ocorrência de eventos cardíacos adversos (ECA) no seguimento de 6 meses. MÉTODOS: No período de um ano, foram selecionados consecutivamente 111 pacientes submetidos a ICP eletiva, com angina estável (AE), instável (AI) ou isquemia silenciosa (IS), assintomáticos por mais de 72 horas antes do procedimento. As dosagens de TnI foram realizadas entre 8 e 24 horas após a ICP. Cada paciente foi contatado por telefone, após seis meses, e questionado quanto à ocorrência de ECA, definidos como morte, infarto do miocárdio, nova revascularização e recorrência de isquemia. RESULTADOS: Ocorreu elevação de TnI em 24 (21,6 por cento) pacientes após a ICP, independente de características clínicas e complicações do procedimento. O surgimento de eventos foi mais freqüente em quem apresentou elevação de TnI: 66,7 vs. 42,5 por cento (RR=1,57; IC95 por cento=1,08-2,28). Este risco parece ser maior nos subgrupos de gênero feminino e naqueles com diagnóstico prévio de AI. Após análise multivariada, apenas gênero se confirmou como co-variável modificadora de efeito com risco de ECA maior em mulheres com elevação de TnI (OR=7,22. IC95 por cento=1,4 -36,9) e similar em homens (OR=1,26. IC95 por cento=0,35-4,55). CONCLUSÃO: Elevação de TnI foi freqüentemente encontrada após ICP e é um fator associado ao surgimento de ECA a médio prazo. Entretanto, quando ajustada para outras variáveis, este efeito só se manteve em pacientes do gênero feminino.

OBJECTIVE: To evaluate the association between troponin I concentrations (TnI) in patients submitted to elective percutaneous coronary interventions (PCI) and adverse coronary events (ACE) during a six month follow-up period. METHODS: One hundred and eleven patients who had been submitted to an elective PCI were consecutively selected during a one year timeframe. The patients had stable angina (SA), unstable angina (UA) or silent ischemia (SI) and were asymptomatic for at least 72 hours before the procedure. TnI concentrations were measured between 8 and 24 hours after the PCI. Each patient was contacted by telephone six months later and interviewed regarding ACE which were defined as death, myocardial infarction, new revascularization and recurrent ischemia. RESULTS: Twenty-four patients showed elevated concentrations of TnI (21.6 percent) after the PCI regardless of clinical characteristics or procedure complications. Those who presented elevated TnI concentrations had higher event rates: 66.7 vs. 42.5 percent (RR=1.57; CI 95 percent=1.08-2.28). This risk seems to be higher in the subgroups of females and patients with a previous diagnosis of unstable angina. Multivariate analysis confirmed that gender was the only effect modifying co-variable associated with ACE risk, which is higher for females with elevated TnI concentrations (OR=7.22; CI 95 percent=1.4 -36.9) and unaltered for males (OR=1.26; CI 95 percent=0.35-4.55). CONCLUSION: Elevated TnI concentrations were a common occurrence after PCI and is a factor related to the development of ACE in the mid term. However, when adjusted for other variables, this effect is only maintained in female patients.

Serial changes in plasma levels of cytokines in patients with coronary artery disease.

OBJECTIVES: Inflammation is known to be a major determinant of the progression of coronary artery disease (CAD). In the present study we have evaluated the plasma levels of cytokines-tumor necrosis factor-alpha (TNF), interleukin- 1 alpha (IL-1), interleukin-6 (IL-6), interferon-gamma (IFN), and interleukin-10 (IL-10)- to examine the association between these cytokines and C-reactive protein (CRP) in patients with CAD. METHODS: Patients with acute coronary syndromes (ACS; n = 20) were compared with patients with stable angina (SA; n= 20) and with control volunteers (C; n= 20). Blood samples were collected at the time of admission from all patients and 15 and 30 days thereafter. RESULTS: CRP levels (20.8+/-8.8 mg/L) (mean+/-SEM) were higher at baseline in ACS than SA patients (4.1+/-0.8mg/L) or the control subjects (5.1+/-1.8mg/L) (p<0.05). At admission, IL-6 was detected in 50% of the ACS patients and 5% of the SA patients or control subjects, while TNF was detected in 35% of the ACS and SA patients but only in 5% of control subjects. Subsequently, IL-6 levels declined and were no longer detectable, while TNF levels increased among ACS patients at all time periods tested when compared with other patients. The presence of IL-1 and IL-10 were not detectable in the blood samples examined, and IFN could only be detected in the ACS group. A significant correlation was observed between IL-6 and CRP levels (r=0.4; p<0.01) in all groups. There were no correlations among any of the other cytokines and CRP levels. CONCLUSIONS: Our study demonstrates raised levels of TNF, IL-6, IFN, and CRP in patients with ACS and a positive correlation between IL-6 and CRP but not with the other cytokines.

The pre-existence of an acute coronary event predicts differences in biological parameters and clinical evolution among patients with longstanding stable angina.

BACKGROUND: To date, patients displaying stable angina with or without a previous acute coronary event have been grouped together and are offered nowadays, similar clinical approach. However, from clinical experience, increasing doubt exists whether they behave clinically in the same way. In the current study, we investigated whether differences might exist in the clinical, angiographic and biological parameters between these two distinct clinical presentations. METHODS: The cardiovascular risk factor profile, clinical evolution, angiographic data, white blood cell (WBC) count and plasma concentrations of lipids and fibrinogen were compared between two groups of patients with longstanding stable angina. The first group consisted of 160 subjects who had undergone myocardial infarction (MI) as the first manifestation of coronary artery disease (CAD) and had no further coronary event. The second group was composed of 226 subjects who had effort-induced angina but never experienced an acute coronary event. The mean period between the first CAD manifestation and entry into the study was 7+/-6 years for MI group and 7+/-4 years for patients with uneventful angina. RESULTS: MI patients displayed 8% higher WBC count (P=0.038), 20% higher fibrinogen (P=0.001), 12% lower HDL cholesterol (P=0.02), 8% lower apoA1 (P=0.005) and 46% higher lipoprotein (a) (P=0.005) than patients who presented an uneventful clinical course. Upon multivariate logistic regression analysis, fibrinogen (OR=1.14; 95% CI=1.08-1.28; P=0.033), lipoprotein (a) (OR=1.19; 95% CI=1.05-1.34; P=0.0036) and HDL cholesterol levels (OR=0.97; 95% CI=0.94-0.99; P=0.0095) remained independently associated with the pre-existence of MI. Patients with prior MI evolved more frequently towards clinically refractory angina (P=0.04). In addition, fibrinogen levels were independently associated with evolution to clinically refractory angina (OR=1.03; 95% CI=1.005-1.550; P=0.0448). CONCLUSIONS: Stable CAD patients with a prior MI differ from those who display an uneventful effort-induced angina in their biological profile and their evolution towards clinically refractory angina.

Valor del test de troponina T en el Departamento de Emergencia en el paciente con angor sin sobreelevación del ST / Value of troponin T testing in an emergency unit in patients with angor and non ST-segment elevation

Se realizó un estudio para evaluar la utilidad de la troponina T cardíaca (TnT) en la decisión de ingreso o alta del hospital y el impacto de su empleo en los costos de internación en 90 pacientes que consultaron por angor en el Departamento de Emergencia, con al menos un factor de riesgo coronario y que no tenían sobreelevación del ST en el ECG. De acuerdo a la clínica, el ECG y la fracción CK-MB del ingreso, se planteó la internación o el alta, pero el paciente permaneció en observación. A las seis horas del ingreso se dosificó la TnT y si el valor era <0,01 ng/ml, el paciente era dado de alta; si era mayor, ingresaba al hospital. En los 20 pacientes para quienes se había planteado el alta inicial, la TnT fue negativa. Entre los 70 pacientes para quienes se planteó el ingreso, 10 tuvieron TnT positiva, por lo que fueron ingresados. Otros 24 pacientes de este grupo también fueron ingresados por el médico tratante, a pesar del resultado negativo del test. En los 30 días siguientes nueve pacientes presentaron eventos isquémicos agudos (dos muerte y siete angor recurrente) entre los 10 pacientes con TnT positiva, y tres pacientes presentaron angor recurrente entre los 78 con TnT negativa. El valor predictivo negativo del test fue de 96,2 por ciento y el valor predictivo positivo fue de 90,O por ciento. El empleo del test de TnT significó un ahorro de U$S 105.304, que podría haber llegado a U$S 137.280 si todos los pacientes con TnT negativa hubieran sido dados de alta. El test de TnT es una herramienta de diagnóstico altamente efectiva en el Departamento de Emergencia en pacientes con angor sin sobreelevación de ST, pues permite optimizar su manejo y reducir los costos de internación, por lo que debería ser el marcador estándar en los servicios de emergencia. (AU)

Increased plasma levels of soluble vascular cellular adhesion molecule-1 in patients with chest pain and angiographically normal coronary arteries.

AIMS: To assess plasma levels of vascular cellular adhesion molecule-1, a marker of endothelial dysfunction, in patients presenting with coronary syndromes submitted to coronary angiography. METHODS AND RESULTS: Plasma levels of soluble vascular cellular adhesion molecule-1 were measured by enzymatic immunoabsorbent assay in eight patients with angina-like chest pain and angiographically normal coronary arteries; in 14 patients with stable angina and in 18 patients with unstable angina, both with coronary lesions by angiography, and in 10 healthy volunteers. Levels of soluble vascular cellular adhesion molecule-1 were higher in unstable angina patients (1777+/-161 SE pg ml(-1)) compared to patients with stable angina (1178+/-206 SE pg ml(-1), P<0.05). Moreover, patients with angina-like chest pain and normal coronary arteries had significantly higher soluble vascular cellular adhesion molecule-1 levels (2307+/-295 SE pg ml(-1)) compared to stable angina patients (P<0.05), but similar levels compared to unstable angina patients. Patient groups had higher values of soluble vascular cellular adhesion molecule-1 compared to the control group (734+/-97 SE pg ml(-1)). CONCLUSIONS: Increased levels of soluble vascular cellular adhesion molecule-1 are associated with coronary artery disease in patients with anatomically established lesions. In patients free of flow-limiting lesions and angina-like chest pain, high levels of this marker may indicate endothelial dysfunction.