RESUMEN
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve endothelial dysfunction and reduce cardiovascular events in individuals with type 2 diabetes (T2D). Proprotein convertase subtilisin/kexin 9 (PCSK9i) inhibitors reduce cardiovascular events in high-risk patients. Whether the addition of PCSK9i to SGLT2i treatment adds benefits is not known. OBJECTIVES: To assess the PCSK9-i effect on the endothelial function of T2D individuals under treatment with SGLT2-i. METHODS: Individuals with T2D were randomized in a 1:1 ratio to a 16-week treatment with either empagliflozin (E) or empagliflozin plus evolocumab (EE). The primary endpoint was post-treatment change from baseline in flow-mediated dilation (FMD) at 1-min. Secondary outcomes included changes in plasma levels of nitric oxide metabolites and isoprostane. RESULTS: A total of 110 patients were enrolled, the mean age was 58 years, and 71% were men. The median post-treatment change in FMD at 1-min was 2.7% (interquartile range [IQR]: 0.9%) and 0.4% (IQR: 0.9%) in the EE and E groups, respectively (p < 0.001). There was a greater increase in plasma levels of nitrate [5.9 (16.5) vs. 2.6 (11.8); p = 0.001] and nitrite [0.14 (0.72) vs. 0.02 (0.74); p = 0.025] in the EE group than in the E group, respectively. Isoprostane reduction was more pronounced in the EE group when compared to the E group [-1.7 (5.9) vs. -1.1 (5.3); p < 0.001). CONCLUSIONS: In individuals with T2D, the addition of evolocumab on top of empagliflozin improves endothelial function.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Anticuerpos Monoclonales Humanizados , Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Glucósidos , Humanos , Isoprostanos , Masculino , Persona de Mediana Edad , Inhibidores de PCSK9 , Proproteína Convertasa 9/metabolismo , Resultado del TratamientoRESUMEN
Cardiovascular disease resulting from iron accumulation is still a major cause of death in patients with thalassemia major (TM). Voltage-gated calcium-channel blockade prevents iron entry into cardiomyocytes and may provide an adjuvant treatment to chelation, reducing myocardial iron uptake. We evaluated whether addition of amlodipine to chelation strategies would reduce myocardial iron overload in TM patients compared with placebo. In a multicenter, double-blind, randomized, placebo-controlled trial, 62 patients were allocated to receive oral amlodipine 5 mg/day or placebo in addition to their current chelation regimen. The main outcome was change in myocardial iron concentration (MIC) determined by magnetic resonance imaging at 12 months, with patients stratified into reduction or prevention groups according to their initial T2* below or above the normal human threshold of 35 ms (MIC, 0.59 mg/g dry weight). At 12 months, patients in the reduction group receiving amlodipine (n = 15) had a significant decrease in MIC compared with patients receiving placebo (n = 15) with a median of -0.26 mg/g (95% confidence interval, -1.02 to -0.01) vs 0.01 mg/g (95% confidence interval, -0.13 to 0.23), P = .02. No significant changes were observed in the prevention group (treatment-effect interaction with P = .005). The same findings were observed in the subgroup of patients with T2* <20 ms. Amlodipine treatment did not cause any serious adverse events. Thus, in TM patients with cardiac siderosis, amlodipine combined with chelation therapy reduced cardiac iron more effectively than chelation therapy alone. Because this conclusion is based on subgroup analyses, it needs to be confirmed in ad hoc clinical trials. This trial was registered at www.clinicaltrials.gov identifier as #NCT01395199.
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Amlodipino/uso terapéutico , Terapia por Quelación , Vasodilatadores/uso terapéutico , Talasemia beta/tratamiento farmacológico , Administración Oral , Adolescente , Adulto , Niño , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Hierro/metabolismo , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Pronóstico , Adulto JovenRESUMEN
The decrease in insulin sensitivity (IS) during myocardial infarction (MI) is recognized as a possible contributor to poor patient outcomes. Despite its potential relevance, a standardized and convenient IS assessment tool has yet to be established for said clinical scenarios. This study aimed to validate the accuracy of surrogate indexes in determining IS in acute MI patients by comparison with the gold standard reference method for measuring IS, the euglycemic-hyperinsulinemic clamp (EHC). We performed EHCs in 31 consecutive nondiabetic patients who were admitted within the first 24 h of symptoms of ST-segment elevation MI. Patients with prior diagnosis of diabetes, use of hypoglycemic agents, or a glycosylated hemoglobin ≥6.5% were excluded. EHCs were performed at the second day (D2) and sixth day (D6) post-MI. Basal (12-h fasting) blood samples from D2 and D6 were used to evaluate patient blood glucose and insulin levels. We then calculated the following surrogate indexes: homeostatic model assessment of insulin sensitivity (HOMA2S), homeostatic model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI). The IS index measured by EHC (ISiclamp) was correlated to HOMA2S, HOMA-IR, and QUICKI at D2 (r = 0.485, P = 0.009; r = -0.384, P = 0.048; r = 0.479, P = 0.01, respectively) and D6 (r = 0.621, P = 0.002; r = -0.576, P = 0.006; r = 0.626, P = 0.002, respectively). Receiver operator characteristic curves made for discrimination of ISiclamp above the median in D2 and D6 depicted areas under the curve of 0.740, 0.734, and 0.760 for HOMA2S, HOMA-IR, and QUICKI, respectively. Bland-Altman plots displayed no apparent systematic error for indexes, but a propensity for proportional error, particularly with HOMA-IR. Thus, based on EHC, these simple surrogate indexes are feasible for assessing IS during MI.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Resistencia a la Insulina/fisiología , Insulina , Infarto del Miocardio/sangre , Anciano , Diabetes Mellitus Tipo 2/sangre , Ayuno/sangre , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Insulina/sangre , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: Left ventricular hypertrophy and diastolic dysfunction (LVDD) remain highly frequent markers of cardiac damage and risk of progression to symptomatic heart failure, especially in resistant hypertension (RHTN). We have previously demonstrated that administration of sildenafil in hypertensive rats improves LVDD, restoring phosphodiesterase type 5 (PDE-5) inhibition in cardiac myocytes. METHODS: We hypothesized that the long-acting PDE-5 inhibitor tadalafil may be clinically useful in improving LVDD in RHTN independently of blood pressure (BP) reduction. A single blinded, placebo-controlled, crossover study enrolled 19 patients with both RHTN and LVDD. Firstly, subjects received tadalafil (20 mg) for 14 days and after a 2-week washout period, they received placebo orally for 14 days. Patients were evaluated by office BP and ambulatory BP monitoring (ABPM), endothelial function (FMD), echocardiography, plasma brain natriuretic peptide (BNP-32), cyclic guanosine monophosphate (cGMP) and nitrite levels. RESULTS: No significant differences were detected in BP measurements. Remarkably, at least four echocardiographic parameters related with diastolic function improved accompanied by decrease in BNP-32 in tadalafil use. Although increasing cGMP, tadalafil did not change endothelial function or nitrites. There were no changes in those parameters after placebo. CONCLUSION: The current findings suggest that tadalafil improves LV relaxation through direct effects PDE-5-mediated in the cardiomyocytes with potential benefit as an adjunct to treat symptomatic subjects with LVDD such as RHTN patients.
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Carbolinas/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Disfunción Ventricular Izquierda/tratamiento farmacológico , Anciano , Presión Sanguínea/efectos de los fármacos , Carbolinas/farmacología , Estudios Cruzados , GMP Cíclico/sangre , Diástole/efectos de los fármacos , Resistencia a Medicamentos , Femenino , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/sangre , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Nitritos/sangre , Inhibidores de Fosfodiesterasa 5/farmacología , Método Simple Ciego , Tadalafilo , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/fisiopatología , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
AIM OF THE STUDY: In contrast to the general population, individuals with primarily persistent elevation of inflammatory activity display a significant association between inflammatory biomarkers and atherosclerotic burden. In older individuals, immunosenescence upregulates the innate response and, by this way, may hypothetically favor the presence of this association. The aim of this study was to evaluate this hypothesis in healthy octogenarians. METHODS: Participants (n = 208) aged 80 years or older, asymptomatic and without medical and laboratory evidence of chronic diseases or use of anti-inflammatory treatments were included in the study. Lipid profile and plasma C-reactive protein (CRP) were measured at baseline and cardiac computed tomography was performed within 1-week interval for measuring coronary calcium score (CCS). RESULTS: The median plasma CRP was 1.9 mg/L (1.03.4) and 33 % of the participants had elevated CRP defined as C3 mg/L. Among those with high CRP, there was an increased frequency of high CCS (C100) as compared with their counterparts (71 vs 50 %, p = 0.001). The association between CRP and CCS persisted even after adjustment for age, sex, cardiovascular risk factors and statin therapy. The area under the receiver-operating curve for CRP was 0.606 using CCS C100 as a binary outcome. The sensitivities for CCS C100 were 40 and 74 % for the cutoff points of CRP C3 or 1 mg/L, respectively. CONCLUSION: The present study was able to confirm that in very elderly individuals, systemic inflammatory activity is independently associated with coronary atherosclerosis burden.
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Proteína C-Reactiva/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Factores de Edad , Anciano de 80 o más Años , Biomarcadores/sangre , Biomarcadores/metabolismo , Calcio/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Estudios Transversales , Femenino , Humanos , Inflamación/sangre , Inflamación/complicaciones , Inflamación/metabolismo , Lípidos/sangre , Masculino , Factores de Riesgo , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVES: To assess the level of agreement and interchangeability among different software programs for calculation of T2 values for iron overload. METHODS: T2 images were analysed in 60 patients with thalassaemia major using the truncation method in three software programs. Levels of agreement were assessed using Pearson correlation and Bland-Altman plots. Categorical classification for levels of iron concentration by each software program was also compared. RESULTS: For the heart, all correlation coefficients were significant among the software programs (P < 0.001 for all coefficients). The mean differences and 95% limits of agreement were 0.2 (-4.73 to 5.0); 0.1 (-4.0 to 3.9); and -0.1 (-4.3 to 4.8). For the liver all correlations were also significant with P < 0.001. Bland-Altman plots showed differences of -0.02 (-0.7 to 0.6); 0.01 (-0.4 to 0.4); and -0.02 (-0.6 to 0.6). There were no significant differences in clinical classification among the software programs. CONCLUSIONS: All tools used in this study provided very good agreement among heart and liver T2 values. The results indicate that interpretation of T2 data is interchangeable with any of the software programs tested. KEY POINTS: Magnetic resonance imaging in iron overload assessment has become an essential tool. Post processing options to establish T2 values have not been compared. No differences were found on T2 of the liver or heart using 3 different techniques. Availability of these methods should allow more widespread interpretation of iron overload by MRI.
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Sobrecarga de Hierro/diagnóstico , Hígado/patología , Imagen por Resonancia Magnética , Miocardio/patología , Programas Informáticos , Talasemia beta/diagnóstico , Adulto , Estudios Transversales , Femenino , Humanos , Hierro/metabolismo , Sobrecarga de Hierro/patología , Hígado/metabolismo , Masculino , Miocardio/metabolismo , Talasemia beta/patologíaRESUMEN
BACKGROUND: Manganese based agents are intracellular and accumulate inside myocytes allowing for different imaging strategies compared to gadolinium contrasts. While previous agents release manganese very slowly in the circulation, MnCl2 allows for rapid Mn2+ uptake in myocytes, creating a memory effect that can be potentially explored. Data on animal models are very encouraging but the safety and efficacy of this approach in humans has not yet been investigated. Therefore, our objectives were to study the safety and efficacy of a rapid infusion of manganese chloride (MnCl2) for cardiovascular magnetic resonance (CMR) in humans. METHODS: Fifteen healthy volunteers underwent a CMR scan on a 1.5 T scanner. Before the infusion, cardiac function was calculated and images of a short axis mid-ventricular slice were obtained using a 2D and 3D gradient-echo inversion recovery (GRE-IR) sequence, a phase-sensitive IR sequence and a single breath-hold segmented IR prepared steady-state precession acquisition for T1 calculations. MnCl2 was infused over three minutes at a total dose of 5 µMol/kg. Immediately after the infusion, and at 15 and 30 minutes later, new images were obtained and cardiac function re-evaluated. RESULTS: There was a significant decrease in T1 values compared to baseline, sustained up to 30 minutes after the MnCl2 infusion (pre,839 ± 281 ms; 0 min, 684 ± 99; 15 min, 714 ± 168; 30 min, 706 ± 172, P = 0.003). The 2D and 3D GRE-IR sequence showed the greatest increase in signal-to-noise ratio compared to the other sequences (baseline 6.6 ± 4.2 and 9.7 ± 5.3; 0 min, 11.3 ± 4.1 and 15.0 ± 8.7; 15 min, 10.8 ± 4.0 and 16.9 ± 10.2; 30 min, 10.6 ± 5.2 and 16.5 ± 8.3, P < 0.001 for both). There was a slight increase in systolic pressure and heart rate after three and four minutes of the infusion with normalization of these parameters thereafter. Patients showed good tolerance to MnCl2 with no major adverse events, despite all reporting transient facial flush. CONCLUSIONS: In the short term, MnCl2 appears safe for human use. It effectively decreases myocardium T1, maintaining this effect for a relatively long period of time and allowing for the development of new imaging strategies in CMR, especially in ischemia research.
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Cloruros , Medios de Contraste , Corazón/fisiología , Imagen por Resonancia Cinemagnética/métodos , Compuestos de Manganeso , Adulto , Presión Sanguínea , Brasil , Cloruros/administración & dosificación , Cloruros/efectos adversos , Medios de Contraste/administración & dosificación , Medios de Contraste/efectos adversos , Femenino , Corazón/anatomía & histología , Frecuencia Cardíaca , Humanos , Interpretación de Imagen Asistida por Computador , Infusiones Intravenosas , Imagen por Resonancia Cinemagnética/efectos adversos , Masculino , Compuestos de Manganeso/administración & dosificación , Compuestos de Manganeso/efectos adversos , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Volumen Sistólico , Factores de Tiempo , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Sodium glucose co-transporter 2 inhibitors (SGLT2is) prevent hospitalization resulting from heart failure (HHF). However, patients with type 2 diabetes mellitus use multiple antihyperglycemic drugs to achieve glycosylated hemoglobin (HbA1c) targets. In these drug combinations, the risk of HHF is unpredictable and so is the parallel effect of glucose-lowering. PURPOSE: To examine the impact of antihyperglycemic drugs and their association on HHF. DATA SOURCES: Forty randomized controlled trials (RCTs) reporting HHF. STUDY SELECTION: Published RCTs were the data source. DATA EXTRACTION: Incidence rates of HHF. DATA SYNTHESIS: Random additive-effects network meta-analysis showed that metformin (Pâ =â 0.55), sulfonylureas (Pâ =â 0.51), glucagon-like peptide-1 receptor-agonist (Pâ =â 0.16), and dipeptidyl peptidase 4 inhibitors (DPP4is; Pâ =â 0.54) were neutral on the risk of HHF. SGLT2is and SGLT2isâ +â DPP4is reduced the risk of HHF with a hazard ratio (HR) of 0.68 (95% CI, 0.60-0.76; Pâ <â 0.0001) and 0.70 (95% CI, 0.60-0.81; Pâ <â 0.0001), respectively. Increased risk of HHF was associated with thiazolidinediones (TZDs) as monotherapy or in combination with DPP4is (HR: 1.45; 95% CI, 1.18-1.78; Pâ =â 0.0004) and 1.49 (95% CI, 1.18-1.88; Pâ =â 0.0008), respectively. Regardless of the therapy, a 1% reduction in HbA1c reduced the risk of HHF by 31.3% (95% CI, 9-48; Pâ =â 0.009). LIMITATIONS: There are no data to verify drug combinations available for clinical use and to discriminate the effect of drugs within each of the therapeutic classes. CONCLUSIONS: The risk of HHF is reduced by SGLT2is as monotherapy or in combination with DPP4is and increased by TZDs as monotherapy or in combination. Glucose-lowering provides an additive effect of reducing HHF.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Cardiomiopatías Diabéticas/epidemiología , Insuficiencia Cardíaca/epidemiología , Hospitalización/estadística & datos numéricos , Hipoglucemiantes/administración & dosificación , Diabetes Mellitus Tipo 2/complicaciones , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/prevención & control , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Quimioterapia Combinada , Femenino , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/prevención & control , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Metaanálisis en Red , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores del Cotransportador de Sodio-Glucosa 2/administración & dosificación , Tiazolidinedionas/administración & dosificación , Resultado del TratamientoRESUMEN
RATIONALE, AIMS AND OBJECTIVES: Emergency short-stay unit (SSU) alleviates emergency department (ED) overcrowding, but may affect in-hospital indicators. Cardiology patients comprise a substantial part of patients admitted at SSU. This study evaluated whether SSU opening differentially modified in-hospital indicators at a whole general hospital and at its cardiology division (CARD). METHODS: We retrospectively analysed indicators based on 859 686 ED visits, and 171 547 hospital admissions, including 12 110 CARD admissions, from 2007 to 2018 at a general tertiary hospital, and compared global ED indicators and in-hospital indicators at the hospital and CARD before (2007-2011) and after (2011-2018) SSU opening. RESULTS: After SSU opening, monthly ED bed occupancy rate decreased (mean ± SD 200 ± 18% vs 187 ± 22%; P < .001) and in-hospital admissions from ED increased at the hospital (median [interquartile range] 460 [81] vs 524 [41], P < .001) and CARD (50 [12] vs 54 [12], P = .004). In parallel, monthly in-hospital elective admissions decreased at CARD (34 [18] vs 28 [17], P = .019), but not at the hospital (712 [73] vs 700 [104], P = .54). Average length of stay (LOS) increased at both hospital (8.5 ± 0.3 vs 8.7 ± 0.4 days, P < .001) and CARD (9.2 ± 1.5 vs 10.3 ± 2.3 days, P = .002) after SSU opening, but percent admissions at SSU showed a direct relationship with LOS solely at CARD. Furthermore, cardiology patients admitted at SSU had greater LOS, prevalence of coronary heart disease and age than those admitted at the conventional cardiology ward. CONCLUSIONS: SSU opening improved ED crowding, but was associated with changes in in-hospital indicators, particularly at CARD, and in the characteristics of hospitalized cardiology patients. These findings suggest that in-hospital cardiology services may need re-evaluation following SSU opening at a general hospital.
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Cardiología , Servicio de Urgencia en Hospital , Humanos , Tiempo de Internación , Admisión del Paciente , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
INTRODUCTION: In acute myocardial infarction (AMI), each 18 mg/dl (1 mmol/L) increment is associated with a 3% increase in mortality rates. All strategies applied for reducing blood glucose to this date, however, have not presented encouraging results. METHODOLOGY: We searched the Medline (PubMed) and Cochrane Library databases for randomized clinical trials (RCTs) from 1995 to 2017 that used the intensive strategy or GIK therapy for blood glucose control during the acute stage of the AMI. We included eight studies. In order to identify the effects of GIK or insulin therapy, we calculated a overall risk ratio (RR) with meta-analysis of fixed and random effects models. A two-tail p-value of < 0.05 was considered statistically significant. RESULTS: A total of 28,151 patients were included: 1,379 intensively treated with insulin, 13,031 in GIK group, and 13,741 in the control group. The total mortality was 10.5% (n=2,961) and the RR of 1.03 [95%CI 0.96-1.10]; I2 = 31%; p = 0.41 for the combined intensive insulin plus GIK groups in comparison with the control group. In meta-regression analyses, intense reductions in blood glucose (> 36 mg/dL) in relation to the estimated average blood glucose (estimated by HbA1c) were associated with higher mortality, whereas lower reductions in blood glucose (< 36 mg/dL) were not associated with mortality. The lowering of blood glucose in the acute phase of MI compared with the average blood glucose was more effective around 18 mg/dL. CONCLUSION: This meta-analysis suggests that there may be a tenuous line between the effectiveness and safety of reducing blood glucose in the acute phase of MI. The targets must not exceed a reduction greater than 36 mg/dL in relation to estimated average blood glucose.
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Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/mortalidad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Insulina/administración & dosificación , Infarto del Miocardio/metabolismo , Infarto del Miocardio/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVE: Diabetes is one of the leading causes of cardiovascular mortality. Over the last years, mortality has decreased significantly, more in individuals with diabetes than in healthy ones. That is mostly due to the control of other cardiovascular risk factors. The objective of our study was to analyze the dyslipidemia control in two diabetes cohorts. METHODS: Patients from two distinct cohorts were studied, 173 patients from the BHS (Brasília Heart Study) and 222 patients from the BDS (Brazilian Diabetes Study). The data on dyslipidemia control were studied in both different populations. All patients had diabetes. RESULTS: There are significant differences concerning comorbidities between the LDL-C and BDS groups. The average glycated hemoglobin is of 8.2 in the LDL-C > 100 group in comparison with 7.7 and 7.5 in the 70-100 and < 70 groups, respectively (p = 0.024). There is a higher percentage of hypertensive patients with LDL between 70-100 (63.9%), when comparing the < 70 and > 100 groups (54.3% and 54.9%, respectively; p = 0.005). Diastolic pressure is higher in the group with LDL > 100, with an average of 87 mmHg, in comparison with 82.6 mmHg and 81.9 mmHg in the 70-100 and < 70 groups, respectively (p = 0.019). The group with LDL > 100 has the greatest percentage of smokers (8.7%) in comparison with the groups with LDL between 70-100 and < 70 (5.6% and 4.3%, respectively; p = 0.015). There is also a difference in the previous incidence of coronaropathy. In the group with LDL < 70, 28.3% of patients had already experienced a previous infarction, compared with 11.1% and 10.6% in the 70-100 and > 100 groups, respectively (p < 0.001). CONCLUSIONS: The data in our study have shown that the dyslipidemia control in diabetic patients is inadequate and there is a tendency of direct association between lack of blood glucose control and lack of dyslipidemia control, in addition to the association with other cardiovascular risk factors, such as diastolic hypertension and smoking. This worsened control might be related to the plateau in the descending curve of mortality, and investments in this regard can improve the cardiovascular health in diabetic patients.
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Anticolesterolemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Dislipidemias/complicaciones , Simvastatina/uso terapéutico , Presión Sanguínea , Brasil/epidemiología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios de Cohortes , Comorbilidad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/mortalidad , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiología , Dislipidemias/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Triglicéridos/sangreRESUMEN
Atherosclerosis of peripheral arteries typically affects vessels of the lower limbs, suggesting that local hemodynamic stimuli play a role in this process. Our study evaluated the effects of body postural changes on carotid and popliteal blood pressure, circumferential wall tension (CWT) and arterial strain, and investigated the relationship between such hemodynamic parameters and intima-media thickness (IMT) of these arteries. One hundred seventeen nondiabetic, nonhypertensive, nonsmoker subjects (48 men and 69 women) were enrolled and had their blood pressure measured in the arm and calf in supine and orthostatic positions. Echo-doppler analysis evaluated the common carotid and popliteal arteries after blood pressure measurements, while CWT was calculated according to Laplace's law. The results showed that changing from supine to orthostatic posture increased blood pressure and CWT in popliteal but not in carotid arteries. Partial correlation analysis adjusted for age and body mass index revealed no major relationship between IMT of the studied vessels and local blood pressure or arterial strain. Conversely, supine and orthostatic CWT exhibited comparable correlation coefficients with carotid IMT, while orthostatic CWT displayed a stronger relationship with popliteal IMT than with supine CWT. These results were confirmed by multiple linear regression analysis that included age, sex, body mass index, lipid fractions and glucose as independent variables. Overall, our results indicate that orthostatic CWT is a stronger hemodynamic predictor of popliteal IMT than supine CWT, suggesting that erectile posture may be a potential risk factor for popliteal atherosclerosis because it increases the local hemodynamic burden. (Hypertens Res 2008; 31: 2059-2064).
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Aterosclerosis/etiología , Presión Sanguínea , Arteria Poplítea/patología , Postura , Adulto , Arterias Carótidas/fisiología , Femenino , Humanos , Masculino , Arteria Poplítea/fisiología , Túnica Íntima/patología , Túnica Media/patologíaRESUMEN
BACKGROUND: Although stress hyperglycemia after myocardial infarction (MI) is consistently associated with increased mortality, recent studies suggest that the addition of upstream markers of glucose metabolism may improve risk identification. Hence, our aim was to evaluate the association between insulin sensitivity changes during MI hospitalization and outcomes. METHODS: A prospective cohort of 331 consecutive ST-Elevation MI (STEMI) patients without insulin provision therapy was used for the analyses. Blood samples were collected upon admission (D1) and after 5days (D5) of the inciting event. We measured blood glucose and insulin to estimate insulin sensitivity using the updated Homeostasis Model Assessment (HOMA2S). Patients were assessed for intra-hospital death and major adverse cardiac events (MACE) during follow-up. RESULTS: HOMA2S was 62%±52% on D1 and 86%±57% on D5 (p<0.001). Total follow-up was a median of 2 (0.9-2.8) years and found a U-shaped relation between the change in HOMA2S from D1 to D5 (ΔHOMA2S) and major adverse cardiac events (MACE) (p=0.017). Fully adjusted cox-regression models showed that patients from T1 and T3 were about 2.5 times more prone to suffer from MACE than those in T2. Net Reclassification Index adding ΔHOMA2S as a categorical variable dichotomized as T2 and T1 or T3 to a model of GRACE risk score with glucose D1 yielded a better predictive model (0.184 [95% CI 0.124-0.264]; p=0.032). CONCLUSION: A U-shaped curve describes the relation between insulin sensitivity change and MACE during acute phase STEMI and, thus indicating that acute dysglycemia must be appreciated in light of a time spectrum and insulin levels.
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Resistencia a la Insulina/fisiología , Insulina/sangre , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
AIM/BACKGROUND: Abundant evidence shows that coronary artery calcification (CAC) is a strong marker of structural and functional changes within the artery wall. Thus far, the implications of CAC in patients with acute coronary syndromes remain unclear. We aimed to investigate whether the CAC score is associated with impaired reperfusion during the acute phase of ST-elevation myocardial infarction (STEMI). METHODS: We enrolled 60 consecutive STEMI patients to undergo cardiac computed tomography for assessment of the CAC score within 1 week after STEMI. Coronary thrombus burden, coronary blood flow (TIMI flow), and myocardial blush grade (MBG) were evaluated systematically. Patients with maximal TIMI flow and MBG were grouped as optimal reperfusion (n=27) and their counterparts as no-reflow (NR, n=33). RESULTS: There were no differences in the clinical characteristics between groups. Patients in the NR group had higher heart rate, coronary angiographic severity, and CAC score. CAC score greater than 100 was associated independently with the presence of NR (odds ratio 4.4, 95% confidence interval 1.17-16.3). The CAC score of nonculprit coronary arteries was higher in NR individuals than in their counterparts (P=0.04). In addition, the CAC score of the isnfarct-related artery correlated negatively with the TIMI-flow rate (r=-0.54, P<0.001) and with the MBG (r=-0.32, P=0.04). CONCLUSION: The CAC score is associated with the presence of the NR phenomenon in STEMI patients.
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Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Infarto del Miocardio/terapia , Fenómeno de no Reflujo/epidemiología , Intervención Coronaria Percutánea , Calcificación Vascular/diagnóstico por imagen , Anciano , Brasil/epidemiología , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos X , Calcificación Vascular/epidemiologíaRESUMEN
SUMMARY INTRODUCTION In acute myocardial infarction (AMI), each 18 mg/dl (1 mmol/L) increment is associated with a 3% increase in mortality rates. All strategies applied for reducing blood glucose to this date, however, have not presented encouraging results. METHODOLOGY We searched the Medline (PubMed) and Cochrane Library databases for randomized clinical trials (RCTs) from 1995 to 2017 that used the intensive strategy or GIK therapy for blood glucose control during the acute stage of the AMI. We included eight studies. In order to identify the effects of GIK or insulin therapy, we calculated a overall risk ratio (RR) with meta-analysis of fixed and random effects models. A two-tail p-value of < 0.05 was considered statistically significant. RESULTS A total of 28,151 patients were included: 1,379 intensively treated with insulin, 13,031 in GIK group, and 13,741 in the control group. The total mortality was 10.5% (n=2,961) and the RR of 1.03 [95%CI 0.96-1.10]; I2 = 31%; p = 0.41 for the combined intensive insulin plus GIK groups in comparison with the control group. In meta-regression analyses, intense reductions in blood glucose (> 36 mg/dL) in relation to the estimated average blood glucose (estimated by HbA1c) were associated with higher mortality, whereas lower reductions in blood glucose (< 36 mg/dL) were not associated with mortality. The lowering of blood glucose in the acute phase of MI compared with the average blood glucose was more effective around 18 mg/dL. CONCLUSION This meta-analysis suggests that there may be a tenuous line between the effectiveness and safety of reducing blood glucose in the acute phase of MI. The targets must not exceed a reduction greater than 36 mg/dL in relation to estimated average blood glucose.
RESUMO INTRODUÇÃO No infarto agudo do miocárdio (IAM), cada incremento de 18 mg/dl (1 mmol/L) se associa a um aumento de 3% na mortalidade. As estratégias de redução da glicemia tentadas até o momento, entretanto, não trouxeram resultados animadores. METODOLOGIA Foram pesquisadas nas bases de dados Medline (PubMed) e Cochrane Library os ensaios clínicos randomizados (ECRs) de 1995 a 2017 que utilizaram estratégia intensiva ou a terapia GIK no controle glicêmico durante a fase aguda do IAM. Foram incluídos oito estudos. Para identificar os efeitos da insulinoterapia ou da terapia GIK, calculamos um risco relativo geral (RR) com meta-análises de modelos de efeitos fixos e aleatórios. Um valor de p-bicaudal < 0,05 foi considerado estatisticamente significativo. RESULTADOS Foram incluídos 28.151 pacientes, sendo 1.379 no grupo de tratamento intensivo da glicemia, 13.031 no GIK e 13.741 no controle. A mortalidade total foi de 2.961 (10,5%), computando um risco relativo de 1,03 [95%CI 0,96-1,10]; I 2 = 31%; p = 0,41 para o grupo intensivo ou GIK contra o grupo conservador. Reduções intensas (> 36 mg/dL) em relação à glicemia estimada média se associaram à maior mortalidade, enquanto reduções menores não se associaram com seu incremento ou redução. A redução glicêmica na fase aguda em relação à glicemia estimada média foi mais efetiva e segura na faixa em torno de 18 mg/dL. CONCLUSÃO Esta meta-análise levanta a hipótese de haver um limite tênue entre efetividade e segurança para a redução glicêmica na fase aguda, sendo que os alvos não devem exceder uma redução maior do que 36 mg/dL de glicemia.
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Humanos , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Infarto del Miocardio/mortalidad , Infarto del Miocardio/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina/administración & dosificación , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/metabolismoRESUMEN
BACKGROUND: Reduced plasma concentration of high-density lipoprotein cholesterol (HDL-C) is associated with vulnerability to oxidative stress and propensity to endothelial dysfunction. Niacin directly activates both GPR-109A in leukocytes and the heme oxygenase-1 pathway, promoting strong anti-inflammatory and antioxidative effects, as well as induces immediate production of prostaglandin D2, leading to endothelial vasodilation. OBJECTIVE: This study investigated the short-term effects of extended-release niacin (ERN) administered with or without the prostaglandin D2 receptor antagonist laropiprant on endothelial function in patients with low HDL-C. METHODS: Asymptomatic men and women aged between 20 and 60 years who had plasma HDL-C levels <40 mg/dL were treated with ERN monotherapy 1 g/d or ERN/laropiprant 1 g/20 mg (ERN/LRP) in a crossover study design. The sequence of treatments was decided by simple randomization. Plasma samples and flow-mediated dilation (FMD) of the brachial artery were obtained at baseline, day 7 of treatment period 1, day 7 of washout, and day 7 of treatment period 2. RESULTS: Eighteen patients were enrolled (mean [SD] age, 42 [17] years; 11 men). Triglyceride levels decreased by 4% and 3%, and HDL size decreased by 5.8% and 6.2%, with ERN and ERN/LRP, respectively (both, P < 0.05). There were no changes in HDL-C levels or in cholesteryl esterase transfer protein activity with either treatment. The median increases in FMD were 4.5% and 4.1% with ERN and ERN/LRP, which receded after washout. On intergroup analysis, there were no differences with respect to variation in plasma HDL-C, triglycerides, C-reactive protein, direct bilirubin, or FMD. CONCLUSIONS: In these patients, the addition of laropiprant did not influence the effects of niacin on endothelial function. Based on these findings, short-term niacin treatment might improve endothelial function in patients with low HDL-C levels. ClinicalTrials.gov identifier: NCT01942291.
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Dislipidemias/tratamiento farmacológico , Endotelio Vascular/efectos de los fármacos , Indoles/uso terapéutico , Niacina/farmacología , Vasodilatadores/farmacología , Anciano , HDL-Colesterol/sangre , Estudios Cruzados , Preparaciones de Acción Retardada , Método Doble Ciego , Femenino , Humanos , Hipolipemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Niacina/administración & dosificación , Vasodilatación/efectos de los fármacos , Vasodilatadores/administración & dosificaciónRESUMEN
SUMMARY OBJECTIVE Diabetes is one of the leading causes of cardiovascular mortality. Over the last years, mortality has decreased significantly, more in individuals with diabetes than in healthy ones. That is mostly due to the control of other cardiovascular risk factors. The objective of our study was to analyze the dyslipidemia control in two diabetes cohorts. METHODS Patients from two distinct cohorts were studied, 173 patients from the BHS (Brasília Heart Study) and 222 patients from the BDS (Brazilian Diabetes Study). The data on dyslipidemia control were studied in both different populations. All patients had diabetes. RESULTS There are significant differences concerning comorbidities between the LDL-C and BDS groups. The average glycated hemoglobin is of 8.2 in the LDL-C > 100 group in comparison with 7.7 and 7.5 in the 70-100 and < 70 groups, respectively (p = 0.024). There is a higher percentage of hypertensive patients with LDL between 70-100 (63.9%), when comparing the < 70 and > 100 groups (54.3% and 54.9%, respectively; p = 0.005). Diastolic pressure is higher in the group with LDL > 100, with an average of 87 mmHg, in comparison with 82.6 mmHg and 81.9 mmHg in the 70-100 and < 70 groups, respectively (p = 0.019). The group with LDL > 100 has the greatest percentage of smokers (8.7%) in comparison with the groups with LDL between 70-100 and < 70 (5.6% and 4.3%, respectively; p = 0.015). There is also a difference in the previous incidence of coronaropathy. In the group with LDL < 70, 28.3% of patients had already experienced a previous infarction, compared with 11.1% and 10.6% in the 70-100 and > 100 groups, respectively (p < 0.001). CONCLUSIONS The data in our study have shown that the dyslipidemia control in diabetic patients is inadequate and there is a tendency of direct association between lack of blood glucose control and lack of dyslipidemia control, in addition to the association with other cardiovascular risk factors, such as diastolic hypertension and smoking. This worsened control might be related to the plateau in the descending curve of mortality, and investments in this regard can improve the cardiovascular health in diabetic patients.
RESUMO OBJETIVO O diabetes é importante causa de mortalidade cardiovascular. Nos últimos anos, a mortalidade diminuiu substancialmente, mais em diabéticos do que em não diabéticos, em grande parte devido ao controle de outros fatores de risco cardiovasculares. Nosso estudo tem como objetivo analisar o controle de dislipidemia em duas coortes de diabéticos. MÉTODOS Foram estudados pacientes de duas coortes distintas, sendo 173 pacientes do BHS (Brasília Heart Study) e 222 pacientes do BDS (Brazilian Diabetes Study). Os dados sobre controle de dislipidemia foram estudados nas duas populações diferentes. Todos os pacientes eram diabéticos. RESULTADOS Há diferenças significativas em relação às comorbidades entre os grupos de LDL-C no BDS. A média de hemoglobina glicada é de 8,2 no grupo com LDL-C > 100, comparado com 7,7 e 7,5 nos grupos 70-100 e < 70, respectivamente (p = 0,024). Há maior porcentagem de pacientes hipertensos com LDL entre 70-100 (63,9%), quando comparado aos grupos < 70 e > 100 (54,3% e 54,9%, respectivamente; p = 0,005). A pressão diastólica é mais elevada no grupo com LDL > 100, com média de 87 mmHg, comparado com 82,6 mmHg e 81,9 mmHg nos grupos 70-100 e < 70, respectivamente (p = 0,019). O grupo com LDL > 100 tem maior porcentagem de tabagistas (8,7%) quando comparado aos grupos com LDL entre 70-100 e < 70 (5,6% e 4,3%, respectivamente; p = 0,015). Há, também, diferença na incidência prévia de coronariopatia. No grupo com LDL < 70, 28,3% dos pacientes já apresentaram infarto prévio, comparados com 11,1% e 10,6% nos grupos 70-100 e > 100, respectivamente (p < 0,001). CONCLUSÃO Os dados do nosso estudo mostram que o controle de dislipidemia em diabéticos é inadequado, e há uma tendência de associação direta entre descontrole glicêmico e descontrole de dislipidemia, além de associação com outros fatores de risco cardiovascular, como hipertensão diastólica e tabagismo. Esse pior controle pode estar relacionado ao platô no descenso da curva de mortalidade, e o investimento nesse quesito pode melhorar a saúde cardiovascular dos diabéticos.
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Humanos , Masculino , Femenino , Simvastatina/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Dislipidemias/complicaciones , Anticolesterolemiantes/uso terapéutico , Triglicéridos/sangre , Presión Sanguínea , Brasil/epidemiología , Comorbilidad , Prevalencia , Factores de Riesgo , Estudios de Cohortes , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dislipidemias/prevención & control , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Persona de Mediana EdadRESUMEN
OBJECTIVE: Often, as diabetes mellitus type 2 (T2DM) evolves insidiously, prevention is commenced late and diagnosis is made when vascular damage has been set. Hence, our hypothesis is that T2DM awareness may influence the outcome of atherothrombotic events. METHODS: A consecutive cohort of patients manifesting ST-elevation myocardial infarction (MI) was classified according to the presence and awareness of the diagnosis of T2DM: known diabetes (kT2DM, n = 72), unknown diabetes (uT2DM, n = 80) and no diabetes (ND, n = 333). Medical history, laboratory data, and angiographic findings including myocardial blush grade (MBG) were prospectively obtained. The primary endpoint was in-hospital death and secondary endpoint was major adverse cardiac events (MACE) defined as sudden cardiac death, fatal MI and nonfatal MI that occurred from 30 days of study entry onwards. RESULTS: With the exception of glycated hemoglobin (p = 0.001) and triglycerides (p = 0.04), no differences were found between groups for all other biochemical, clinical or angiographic admission characteristics. Myocardial tissue reperfusion defined as MBG 3 was observed in 62% in the ND group, 50% in the kT2DM group and 23% in the uT2DM group (p = 0.01). All-cause in-hospital mortality was higher in uT2DM (16.7%) than in kT2DM (8.4%) and both groups had a higher mortality rate as compared with the ND group (3.8%, p = 0.01). During follow-up (653 ± 26 days), the incidence of MACE was higher in uT2DM than in kT2DM and in both compared to the ND group (p = 0.002). CONCLUSION: Unawareness of T2DM diagnosis is strongly associated with a poor short- and long-term outcome after MI.
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Diagnóstico Tardío/mortalidad , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Infarto del Miocardio/mortalidad , Estudios de Cohortes , Angiografía Coronaria , Creatina Quinasa/sangre , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Estudios Prospectivos , Resultado del Tratamiento , Triglicéridos/sangre , Troponina/sangreRESUMEN
Assessment of lipid profile parameters has been considered a cornerstone in classifying individuals and populations at risk for cardiovascular disease. Recently, however, preliminary data have raised the possibility of seasonal variations in these parameters, which may cause under- or overestimation. Biological rhythms and seasonal variation of lipid profile was investigated in 227 359 consecutive individuals who underwent health checkups in primary care centers between 2008 and 2010. Plasma low-density lipoprotein cholesterol (LDL-C) >130 mg/dL was 8% more prevalent during winter than summer, with a larger difference among women and middle-aged adults (p < 0.001). High-density lipoprotein cholesterol (HDL-C) <40 mg/dL and triglycerides (TG) >150 mg/dL were respectively 9% and 5% more prevalent during the summer (p < 0.001). Variation amplitude was 3.4 ± 0.3 mg/dL for HDL-C (p = 0.005), 7 ± 2 mg/dL for LDL-C (p = 0.047), and 12 ± 9 mg/dL for TG (p = 0.058). Based on a large population sample, this study confirms the existence of biological rhythms and seasonal variation in lipid profile. This finding must be particularly accounted for in cross-sectional analyses of relative risk, prevalence, or the rate of goal achievement for lipid parameters.
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Dislipidemias/epidemiología , Periodicidad , Estaciones del Año , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Brasil/epidemiología , Niño , Preescolar , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Dislipidemias/sangre , Dislipidemias/diagnóstico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Dinámicas no Lineales , Prevalencia , Factores de Riesgo , Distribución por Sexo , Factores Sexuales , Factores de Tiempo , Triglicéridos/sangre , Adulto JovenRESUMEN
OBJECTIVE: Lower limb arteries are exposed to higher hemodynamic burden in erectile posture. This study evaluated the effects of body posture on popliteal, carotid and brachial circumferential wall tension (CWT) and investigated the relationship between local CWT and atherosclerotic plaques in subjects with cardiovascular risk factors. METHODS: Two hundred and three subjects (118 women and 85 men) with cardiovascular risk factors (smoking, hypertension or diabetes mellitus) underwent clinical and laboratory analysis and had their blood pressure measured in the arm and calf in supine and orthostatic positions. Arteries were evaluated by ultrasound analysis, while CWT was calculated according to Laplace's law. RESULTS: Among the enrolled participants, 47%, 29% and none presented popliteal, carotid and brachial plaques, respectively. Carotid CWT measurements were not associated with local plaques after adjustment for potential confounders. Conversely, general linear model and logistic regression analyses adjusted for potential confounders demonstrated that peak orthostatic CWT was the only local hemodynamic parameter showing significant relationship with popliteal plaques in the whole sample. In gender-specific analyses, although positively correlated with popliteal plaques in both genders, local peak orthostatic CWT exhibited an independent association with popliteal plaques after adjustment for potential confounders only in women. CONCLUSION: Popliteal CWT measured in orthostatic posture, rather than in supine position, is associated with popliteal atherosclerotic plaques, particularly in women. These findings suggest that erectile posture might play a role in the atherogenesis of leg arteries by modifying local hemodynamic forces and that there may be gender differences in this regard.