RESUMEN
BACKGROUND: A polypill comprising statins, multiple blood-pressure-lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease. METHODS: Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed. RESULTS: A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups. CONCLUSIONS: Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk. (Funded by the Wellcome Trust and others; TIPS-3 ClinicalTrials.gov number, NCT01646437.).
Asunto(s)
Anticolesterolemiantes/administración & dosificación , Antihipertensivos/administración & dosificación , Aspirina/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Anticolesterolemiantes/efectos adversos , Antihipertensivos/efectos adversos , Atenolol/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , LDL-Colesterol/sangre , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Hidroclorotiazida/administración & dosificación , Incidencia , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Factores de Riesgo , Simvastatina/administración & dosificaciónRESUMEN
Patients with chronic kidney disease (CKD) carry a high cardiovascular (CV) risk. Since whether this risk is reduced by aspirin is unclear, we examined if the effect of aspirin on cardiovascular outcomes varied by baseline kidney function in a primary cardiovascular disease prevention trial. The International Polycap Study-3 (TIPS-3) trial had randomized people without previous cardiovascular disease to aspirin (75 mg daily) or placebo. We now examined aspirin versus placebo on cardiovascular events in participants grouped by estimated glomerular filtration rate (eGFR), using a threshold of 60 ml/min/1.73 m2, and by using tertiles of eGFR. The primary outcome was a composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. A total of 5712 participants were randomized with a mean follow-up of 4.6 years. Of these, 983 (17.2%) had an eGFR under 60 ml/min/1.73 m2 (mean eGFR 49 ml/min/1.73 m2) and 4,729 over 60 ml/min/1.73 m2 (mean 84 ml/min/1.73 m2). In participants with an eGFR under 60 ml/min/1.73 m2 there were 26 primary outcomes in 502 participants on aspirin and 39/481 on placebo (hazard ratio 0.57; 95% confidence interval 0.34-0.94). In participants with an eGFR over 60 ml/min/1.73 m2 there were 90 primary outcomes in 2357 participants on aspirin and 95/2372 on placebo (0.95; 0.71-1.27). With tertiles of eGFR under 70, 70-90, and over 90 ml/min/1.73 m2, risk reductions with aspirin for the primary outcome were larger at lower eGFR levels (0.62; 0.43-0.91) for the lowest tertile, (0.96; 0.62-1.49) for the middle, and (1.30; 0.77-2.18) for the highest tertile. Thus, our findings support aspirin may reduce cardiovascular events in people with moderate to advanced stage CKD.
Asunto(s)
Enfermedades Cardiovasculares , Infarto del Miocardio , Insuficiencia Renal Crónica , Accidente Cerebrovascular , Humanos , Aspirina/efectos adversos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Insuficiencia Renal Crónica/tratamiento farmacológico , Tasa de Filtración Glomerular , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & controlRESUMEN
BACKGROUND: Cytokines play a potential role in atherosclerosis pathogenesis and progression. We investigated the association of interleukin-6 (IL-6) with the angiographic severity of coronary artery disease (CAD). METHODS: Three hundred ten angiografically diagnosed CAD patients and 210 controls were enrolled in this study. CAD patients were stratified according to IL-6 cut-off value into high levels IL-6 group (≥ 9.5 pg/mL) and low levels IL-6 group (< 9.5 pg/mL). The severity of CAD was assessed according to Gensini score (GS), artery stenosis degree and the number of vessels involved. The mean age was 60.3 ± 11.0 years. RESULTS: The level of IL-6 in patients was increased compared to controls and ranged from 1.5 to 3640.0 pg/mL. High levels of IL-6 were significantly associated with high levels of GS (> 40) but not with stenosis degree and vessel score. GS levels were significantly more elevated in patients with high levels of IL-6 group than in low IL6 levels patients (60.6 ± 39.5 vs 46.7 ± 37.2; p = 0.027). The analysis of the ROC curve performed in myocardial infarction patients showed that IL-6 (AUC: 0.941 (CI 95% 0.886, 0.997; p < 0.001) could be a powerful predictor marker in evaluating the infarct size after myocardial infarction when compared to myonecrosis biomarkers. CONCLUSIONS: IL-6 levels were associated with the severity of CAD assessed by the GS. Based on the highest levels of IL-6 measured in patients with STEMI, our study strongly suggests that IL-6 could be a powerful marker in evaluating the myocardial necrosis. TRIAL REGISTRATION: ClinicalTrials.gov Number: NCT03075566 (09/03/2017).
Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Intervención Coronaria Percutánea , Anciano , Humanos , Persona de Mediana Edad , Biomarcadores , Constricción Patológica , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Interleucina-6 , Intervención Coronaria Percutánea/efectos adversos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: In randomised controlled trials, fixed-dose combination treatments (or polypills) have been shown to reduce a composite of cardiovascular disease outcomes in primary prevention. However, whether or not aspirin should be included, effects on specific outcomes, and effects in key subgroups are unknown. METHODS: We did an individual participant data meta-analysis of large randomised controlled trials (each with ≥1000 participants and ≥2 years of follow-up) of a fixed-dose combination treatment strategy versus control in a primary cardiovascular disease prevention population. We included trials that evaluated a fixed-dose combination strategy of at least two blood pressure lowering agents plus a statin (with or without aspirin), compared with a control strategy (either placebo or usual care). The primary outcome was time to first occurrence of a composite of cardiovascular death, myocardial infarction, stroke, or arterial revascularisation. Additional outcomes included individual cardiovascular outcomes and death from any cause. Outcomes were also evaluated in groups stratified by the inclusion of aspirin in the fixed-dose treatment strategy, and effect sizes were estimated in prespecified subgroups based on risk factors. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to compare strategies. FINDINGS: Three large randomised trials were included in the analysis (TIPS-3, HOPE-3, and PolyIran), with a total of 18 162 participants. Mean age was 63·0 years (SD 7·1), and 9038 (49·8%) participants were female. Estimated 10-year cardiovascular disease risk for the population was 17·7% (8·7). During a median follow-up of 5 years, the primary outcome occurred in 276 (3·0%) participants in the fixed-dose combination strategy group compared with 445 (4·9%) in the control group (hazard ratio 0·62, 95% CI 0·53-0·73, p<0·0001). Reductions were also observed for the separate components of the primary outcome: myocardial infarction (0·52, 0·38-0·70), revascularisation (0·54, 0·36-0·80), stroke (0·59, 0·45-0·78), and cardiovascular death (0·65, 0·52-0·81). Significant reductions in the primary outcome and its components were observed in the analyses of fixed-dose combination strategies with and without aspirin, with greater reductions for strategies including aspirin. Treatment effects were similar at different lipid and blood pressure levels, and in the presence or absence of diabetes, smoking, or obesity. Gastrointestinal bleeding was uncommon but slightly more frequent in the fixed-dose combination strategy with aspirin group versus control (19 [0·4%] vs 11 [0·2%], p=0·15). The frequencies of haemorrhagic stroke (10 [0·2%] vs 15 [0·3%]), fatal bleeding (two [<0·1%] vs four [0·1%]), and peptic ulcer disease (32 [0·7%] vs 34 [0·8%]) were low and did not differ significantly between groups. Dizziness was more common with fixed-dose combination treatment (1060 [11·7%] vs 834 [9·2%], p<0·0001). INTERPRETATION: Fixed-dose combination treatment strategies substantially reduce cardiovascular disease, myocardial infarction, stroke, revascularisation, and cardiovascular death in primary cardiovascular disease prevention. These benefits are consistent irrespective of cardiometabolic risk factors. FUNDING: Population Health Research Institute.
Asunto(s)
Aspirina/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Quimioterapia Combinada , Metaanálisis como Asunto , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevención Primaria , Presión Sanguínea/efectos de los fármacos , Femenino , Hemorragia Gastrointestinal/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUND: Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis. METHODS: We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed. RESULTS: A total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P = 0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P = 0.03). CONCLUSIONS: Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo. (Funded by the Government of Quebec and others; COLCOT ClinicalTrials.gov number, NCT02551094.).
Asunto(s)
Antiinflamatorios/administración & dosificación , Colchicina/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Anciano , Angina de Pecho/epidemiología , Antiinflamatorios/efectos adversos , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Colchicina/efectos adversos , Método Doble Ciego , Femenino , Humanos , Incidencia , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea , Modelos de Riesgos Proporcionales , Recurrencia , Accidente Cerebrovascular/epidemiologíaRESUMEN
Matrix metalloproteinases (MMPs) are implicated in atherosclerotic plaque rupture and recondition. Specific tissue inhibitors (TIMPs) control MMP functions. Both MMPs and TIMPs are potential biomarkers of plaque instability. Elevated Apo-CII and CIII and Apo-E levels are recognized as cardiovascular disease risk factors. We aimed to establish the best blood biomarker panel to evaluate the coronary artery disease (CAD) severity. Plasma levels of MMP-3 and MMP-9, TIMP-1 and TIMP-2, Apo-CII, Apo-CIII and Apo-E were measured in 472 patients with CAD evaluated by coronary angiography and electrocardiography, and in 285 healthy controls. MMP-3 and MMP-9 plasma levels in CAD patients were significantly increased (P < 0.001) compared to controls (3.54- and 3.81-fold, respectively). Furthermore, these increments are modulated by CAD severity as well as for Apo-CII and Apo-CIII levels (P < 0.001). TIMPs levels were decreased in CAD versus controls (P < 0.001) and in inverse correlation to MMPs. Standard ROC curve approach showed the importance of panels of biomarkers, including MMP-3, MMP-9, TIMP-1, TIMP-2, Apo-CII and Apo-CIII, for disease aggravation diagnosis. A high area under curve (AUC) value (0.995) was reached for the association of MMP-9, TIMP-2 and Apo-CIII. The unbalance between MMPs and TIMPs in vascular wall and dyslipidaemia creates favourable conditions for plaque disruption. Our study suggests that the combination of MMP-9, TIMP-2 and Apo-CIII values ('CAD aggravation panel') characterizes the severity of CAD, that is electrophysiological state, number of involved vessels, stent disposal and type of stent.
Asunto(s)
Biomarcadores , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Biología Computacional , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/etiología , Susceptibilidad a Enfermedades , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
The 143 low- and middle-income countries (LMICs) of the world constitute 80% of the world's population or roughly 5.86 billion people with much variation in geography, culture, literacy, financial resources, access to health care, insurance penetration, and healthcare regulation. Unfortunately, their burden of cardiovascular disease in general and acute ST-segment-elevation myocardial infarction (STEMI) in particular is increasing at an unprecedented rate. Compounding the problem, outcomes remain suboptimal because of a lack of awareness and a severe paucity of resources. Guideline-based treatment has dramatically improved the outcomes of STEMI in high-income countries. However, no such focused recommendations exist for LMICs, and the unique challenges in LMICs make directly implementing Western guidelines unfeasible. Thus, structured solutions tailored to their individual, local needs, and resources are a vital need. With this in mind, a multicountry collaboration of investigators interested in LMIC STEMI care have tried to create a consensus document that extracts transferable elements from Western guidelines and couples them with local realities gathered from expert experience. It outlines general operating principles for LMICs focused best practices and is intended to create the broad outlines of implementable, resource-appropriate paradigms for management of STEMI in LMICs. Although this document is focused primarily on governments and organizations involved with improvement in STEMI care in LMICs, it also provides some specific targeted information for the frontline clinicians to allow standardized care pathways and improved outcomes.
Asunto(s)
Consenso , Países en Desarrollo/economía , Recursos en Salud/economía , Pobreza/economía , Infarto del Miocardio con Elevación del ST/economía , Infarto del Miocardio con Elevación del ST/epidemiología , Servicios Médicos de Urgencia/economía , Servicios Médicos de Urgencia/normas , Personal de Salud/economía , Personal de Salud/normas , Recursos en Salud/normas , Humanos , Intervención Coronaria Percutánea/economía , Intervención Coronaria Percutánea/normas , Guías de Práctica Clínica como Asunto/normas , Infarto del Miocardio con Elevación del ST/terapia , Terapia Trombolítica/economía , Terapia Trombolítica/normasRESUMEN
AIMS: The COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether time-to-treatment initiation (TTI) influences the beneficial impact of colchicine. METHODS AND RESULTS: In COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (<3, 4-7 and >8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated < Day 3 compared with placebo [hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32-0.84], in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53-1.75) or > Day 8 (HR = 0.82, 95% CI 0.61-1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P < 0.05). CONCLUSION: Patients benefit from early, in-hospital initiation of colchicine after MI. TRIAL REGISTRATION: COLCOT ClinicalTrials.gov number, NCT02551094.
Asunto(s)
Infarto del Miocardio , Accidente Cerebrovascular , Angina de Pecho , Colchicina/uso terapéutico , Humanos , Infarto del Miocardio/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: It is hypothesized that in individuals without clinical cardiovascular disease (CVD), but at increased CVD risk, a 50% to 60% reduction in CVD risk could be achieved using fixed dose combination (FDC) therapy (usually comprised of multiple blood-pressure agents and a statin [with or without aspirin]) in a single "polypill". However, the impact of a polypill in preventing clinical CV events has not been evaluated in a large randomized controlled trial. METHODS: TIPS-3 is a 2x2x2 factorial randomized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population. This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. Additional interventions in the factorial design of the study will compare the effect of (1) aspirin versus placebo on CV events (and cancer), (2) vitamin D versus placebo on the risk of fractures, and (3) the combined effect of aspirin and the Polycap on CV events. RESULTS: The study has randomized 5713 participants across 9 countries. Mean age of the study population is 63.9 years, and 53% are female. Mean INTERHEART risk score is 16.8, which is consistent with a study population at intermediate CVD risk. CONCLUSION: Results of the TIP-3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD.
Asunto(s)
Atenolol/administración & dosificación , Enfermedades Cardiovasculares/prevención & control , Hidroclorotiazida/administración & dosificación , Prevención Primaria/métodos , Ramipril/administración & dosificación , Simvastatina/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Diuréticos/administración & dosificación , Método Doble Ciego , Combinación de Medicamentos , Femenino , Salud Global , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Incidencia , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Nutritional choices, which include the source of dietary fatty acids (FA), have an important significant impact on coronary artery disease (CAD). We aimed to determine on patients with CAD the relationships between Trans fatty acids (Trans FA) and different CAD associated parameters such as inflammatory and oxidative stress parameters in addition to Gensini score as a vascular severity index. METHODS: Fatty acid profiles were established by gas chromatography from 111 CAD patients compared to 120 age-matched control group. Lipid peroxidation biomarkers, oxidative stress, inflammatory parameters and Gensini score were studied. RESULTS: Our study showed a significant decrease of the antioxidant parameters levels such as erythrocyte glutathione peroxydase (GPx) and superoxide dismutase (SOD) activities, plasma antioxidant status (FRAP) and thiol (SH) groups in CAD patients. On the other hand, catalase activity, conjugated dienes and malondialdehyde were increased. Plasmatic and erythrocyte Trans FA were also increased in CAD patients compared to controls. Furthermore, divergent associations of these Trans FA accumulations were observed with low-density lipoprotein-cholesterol/ high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratio, Apolipoprotein B (ApoB), lipid peroxidation parameters, high-sensitivity C Reactive Protein (hs-CRP), Interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and Gensini score. Especially, elaidic acid (C18:1 trans 9), trans C18:2 isomers and trans 11 eicosanoic acid are correlated with these parameters. Trans FA are also associated with oxidative stress, confirmed by a positive correlation between C20:1 trans 11 and GPx in erythrocytes. CONCLUSIONS: High level of Trans FA was highly associated with the induction of inflammation, oxidative stress and lipoperoxidation which appear to be based on the vascular severity and might be of interest to assess the stage and progression of atherosclerosis. The measurement of these Trans FA would be of great value for the screening of lipid metabolism disorders in CAD patients.
Asunto(s)
HDL-Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Ácidos Grasos trans/sangre , Adulto , Anciano , Antioxidantes/metabolismo , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/patología , Femenino , Humanos , Peroxidación de Lípido/genética , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Ácido Oléico/sangre , Ácido Oléico/genética , Ácidos Oléicos , Estrés Oxidativo/genética , Índice de Severidad de la Enfermedad , Ácidos Grasos trans/genética , Triglicéridos/sangre , Triglicéridos/genéticaRESUMEN
Long and very long chain fatty acids (LCFAs and VLCFAs) may play an active role in coronary artery diseases (CAD) etiology. Our aim was to evaluate the associations between LCPUFAs (C20:4n-6; C20:5n-3 and C22:6n-3) and VLCSFAs (C22:0, C24:0; and C26:0), as well as markers of peroxisomal integrity evaluated by phytanic acid and plasmalogen-C16:0 (PL-C16:0) in addition to the markers of lipid peroxidation (malondialdehyde [MDA] and conjugated dienes [CD]) and inflammation (high sensitivity C-reactive protein [hs-CRP]) with vascular severity evaluated by Gensini score in order to determine their possible effects on CAD in Tunisian population. Lipidomic strategy based on GC/MS-SIM was used to quantify LCPUFAs, VLCSFAs, and PL-C16:0 in red blood cells of CAD patients, non-CAD patients, and controls. We observed a significant increase in phytanic acid, PL-C16:0 and VLCFAs, particularly C26:0, in CAD group compared to controls. Further our findings showed positive correlations of C26:0 with MDA and with vascular severity score (Gensini score). In addition, a significant negative correlation was shown between hs-CRP and C22:6 n-3 (r=-0.297; p=0.002) and a significant positive association was observed between hs-CRP and C20:4 n-6 levels (r=0.196; p=0.039). Our results show changes in LCPUFAs and VLCSFAs concentrations in RBC among study groups, and suggest alterations in fatty acids metabolism regulated by elongase and desaturase enzymes. The positive correlations of C20:4n-6 and the negative correlations of C22:6n-3, simultaneously with Gensini score and hs-CRP, suggest a link of both inflammation and vascular severity complication of CAD with LCPUFAs and VLCSFAs. Induction of lipid oxidation, can be one of the outcomes of LCFAs and VLCFAs accumulation in vascular tissues and, thus, playing an important role in the pathogenesis of atherosclerosis. Quantification of LCPUFAs and VLCSFAs, phytanic acid and PL-C16:0 simultaneously, would be of great value for the screening of peroxisomal disorders in vascular tissue of CAD patients.
Asunto(s)
Enfermedad de la Arteria Coronaria/metabolismo , Ácidos Grasos/química , Ácidos Grasos/metabolismo , Ácido Fitánico/metabolismo , Plasmalógenos/metabolismo , Biomarcadores/metabolismo , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Humanos , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Túnez/epidemiologíaRESUMEN
BACKGROUND: Some factors related to diet are known to be involved in the progression of atherosclerosis in humans. METHODS: The relationship between plasma fatty acid (FA) levels and the severity of coronary artery disease (CAD), evaluated by Gensini score (GS), was investigated in CAD Tunisian patients compared to controls. Lipid profiles were analyzed, GS was calculated in CAD and non-CAD patients and compared to controls. RESULTS: CAD patients showed an alteration of conventional lipid parameters. In fact, a significant increase of plasmatic triglycerides (TG) level, atherogenic lipid ratios (TC/HDL-C,TG/HDL-C, LDL-C/HDL-C); and ApoB/ApoA1 was observed in the CAD group comparatively to controls (p < 0.001). Gensini score was showed to be a good indicator to evaluate cholesterol metabolism disorders associated with HDL-C since a negative association was found between HDL-C levels and GS for the two groups of patients. In addition, in the relation with FA and classes of FA, a negative association was found as expected, between Gensini score and total MUFA, PUFA n-3, total PUFA, GLA, DGLA and DHA. Furthermore, a positive association with stearic and erucic acid was found. Suggests that, GS is also a good indicator to evaluate FA metabolic disorders. Higher elongation index and modifications of desaturation index (D5D, D6D and D9D) were observed in patients compared to controls, supporting FA metabolism modifications. CONCLUSIONS: In conclusion, although that Tunisian population appears to follow the Mediterranean diet, variations of plasmatic FA levels and desaturase activities in CAD patients highlights an alteration of FA metabolism and suggests an important implication of certain FA in the development of atherosclerosis.
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Apolipoproteínas B/sangre , Enfermedad de la Arteria Coronaria/sangre , Ácidos Grasos/sangre , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , Triglicéridos/sangre , Anciano , Apolipoproteína A-I/sangre , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/fisiopatología , Ácidos Erucicos/sangre , Ácidos Grasos/clasificación , Femenino , Humanos , Lipoproteínas HDL/sangre , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Ácidos Esteáricos/sangre , TúnezRESUMEN
BACKGROUND: Patients with renal insufficiency experience worse prognosis after STEMI. The current guidelines do not clearly draw specific strategies for patients with renal dysfunction (RD). AIM: The aim of this study is to compare primary PCI (PPCI) and thrombolysis results as well as in-hospital mortality after successful reperfusion between the RD patients (RD+) and patients with normal renal function (RD-). METHODS: We retrospectively reviewed data for 1,388 patients admitted for STEMI between January 1995 and October 2011. Two groups were identified: PPCI (315 patients) and thrombolysis (379 patients). Ninety patients (13%) had RD defined by creatinine levels at admission > 130 micromol/l, they were equally treated by PPCI and thrombolysis. RESULTS: In the PPCI group, despite a similar pre-procedural TIMI flow (P = 0.82),TIMI III restoring was significantly lower in the RD+ group (78.6% vs. 91.8%, P = 0.013). Suboptimal result was also higher in the RD+ group (13.6% vs. 2.7%, P < 0.001), but ST regression after TIMI III achievement was similar in the 2 groups (P = 0.43), probably reflecting no microvascular damage. In the thrombolysis group, successful reperfusion was also significantly lower when RD exists (58% vs. 74%, P = 0.03). After successful reperfusion, RD+ patients experienced higher in-hospital mortality in the PPCI group (29% vs. 4.3%; P < 0.001), whereas mortality was similar in the thrombolysis group (3% vs. 0%, P = 0.42). CONCLUSION: RD reduces either PPCI or thrombolysis success, with no proven microvascular damage after PPCI. In-hospital prognosis, however, is worse in the RD group only after successful PPCI, but not after successful streptokinase thrombolysis.
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Angioplastia Coronaria con Balón , Infarto del Miocardio , Reperfusión Miocárdica , Insuficiencia Renal , Terapia Trombolítica , Anciano , Angioplastia Coronaria con Balón/efectos adversos , Angioplastia Coronaria con Balón/métodos , Angioplastia Coronaria con Balón/estadística & datos numéricos , Electrocardiografía , Femenino , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Mortalidad Hospitalaria , Humanos , Pruebas de Función Renal , Masculino , Microvasos/efectos de los fármacos , Microvasos/fisiopatología , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Infarto del Miocardio/fisiopatología , Reperfusión Miocárdica/efectos adversos , Reperfusión Miocárdica/métodos , Pronóstico , Insuficiencia Renal/complicaciones , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Terapia Trombolítica/estadística & datos numéricos , Resultado del Tratamiento , Túnez/epidemiologíaRESUMEN
Aims: Access to echocardiography is a significant barrier to heart failure (HF) care in many low- and middle-income countries. In this study, we hypothesized that an artificial intelligence (AI)-enhanced point-of-care ultrasound (POCUS) device could enable the detection of cardiac dysfunction by nurses in Tunisia. Methods and results: This CUMIN study was a prospective feasibility pilot assessing the diagnostic accuracy of home-based AI-POCUS for HF conducted by novice nurses compared with conventional clinic-based transthoracic echocardiography (TTE). Seven nurses underwent a one-day training program in AI-POCUS. A total of 94 patients without a previous HF diagnosis received home-based AI-POCUS, POC N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing, and clinic-based TTE. The primary outcome was the sensitivity of AI-POCUS in detecting a left ventricular ejection fraction (LVEF) <50% or left atrial volume index (LAVI) >34â mL/m2, using clinic-based TTE as the reference. Out of seven nurses, five achieved a minimum standard to participate in the study. Out of the 94 patients (60% women, median age 67), 16 (17%) had an LVEF < 50% or LAVI > 34â mL/m2. AI-POCUS provided an interpretable LVEF in 75 (80%) patients and LAVI in 64 (68%). The only significant predictor of an interpretable LVEF or LAVI proportion was the nurse operator. The sensitivity for the primary outcome was 92% [95% confidence interval (CI): 62-99] for AI-POCUS compared with 87% (95% CI: 60-98) for NT-proBNP > 125â pg/mL, with AI-POCUS having a significantly higher area under the curve (P = 0.040). Conclusion: The study demonstrated the feasibility of novice nurse-led home-based detection of cardiac dysfunction using AI-POCUS in HF patients, which could alleviate the burden on under-resourced healthcare systems.
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Background: Cardiovascular disease (CVD) continues to impart a large burden on the global population, especially in lower income countries where affordability limits the use of cardiovascular medicines. A fixed dose combination strategy of at least 2 blood pressure lowering medications and a statin with aspirin in a single pill has been shown to reduce the risk of incident CVD by 38% in primary prevention in a recent meta-analysis. We report the in-trial (median follow-up: 5 years) cost-effectiveness of a fixed dose combination (FDC) pill in different income groups based on data from that meta-analysis. Methods: Countries were categorized using World Bank economic groups: Lower Middle Income Countries (LMIC), Upper Middle Income Countries (UMIC) and High Income Countries (HIC). Country specific costs were obtained for hospitalized events, procedures, and non-study medications (2020 USD). FDC price was based on the cheapest equivalent substitute (CES) for each component. Findings: For the CES-FDC pill versus control the difference in cost was $346 (95% CI: $294-$398) per participant in Lower Middle Income Countries, $838 (95% CI: $781-$895) in Upper Middle Income Countries and $42 (95% CI: -$155 to $239) (cost-neutral) in High Income Countries. During the study period the CES-FDC pill was associated with incremental gain in quality-adjusted life years of 0.06 (95% CI: 0.04-0.08) resulting in an incremental cost-effectiveness ratio (ICER) of $5767 (95% CI: 5735-$5799), $13,937 (95% CI: $13,893-$14,041) and $700 (95% CI: $662-$738) respectively. In subgroups analyses, the highest 10 years CVD risk subgroup had ICERs of $2033, $7322 and -$6000/QALY. Interpretation: A FDC pill produced at CES costs is cost-neutral in HIC. Governments of LMI and UMI countries should assess these results based on the ICER threshold accepted in their own country and own specific health care priorities but should consider prioritizing this strategy for patients with high 10 years CVD risk as a first step. Funding: Population Health Research Institute.
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OBJECTIVE: The cardiovascular benefits of low-dose colchicine have been demonstrated in patients with coronary disease. Its effects were evaluated in this prespecified analysis in patients with type 2 diabetes (T2D) from the Colchicine Cardiovascular Outcomes Trial (COLCOT). RESEARCH DESIGN AND METHODS: COLCOT was a randomized, double-blinded trial of colchicine, 0.5 mg daily, versus placebo initiated within 30 days after a myocardial infarction. RESULTS: There were 959 patients with T2D enrolled and monitored for a median of 22.6 months. A primary end point event occurred in 8.7% of patients in the colchicine group and in 13.1% in the placebo group (hazard ratio 0.65; 95% CI 0.44-0.96; P = 0.03). Nausea was reported in 2.7% and 0.8% in the study groups (P = 0.03), and pneumonia occurred in 2.4% and 0.4% (P = 0.008). CONCLUSIONS: Among patients with T2D and a recent myocardial infarction, colchicine, 0.5 mg daily, leads to a large reduction of cardiovascular events. These results support the conduct of the COLCOT-T2D trial in primary prevention.
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Sistema Cardiovascular , Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Infarto del Miocardio , Humanos , Colchicina/uso terapéutico , Colchicina/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inducido químicamente , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/prevención & control , Enfermedad de la Arteria Coronaria/tratamiento farmacológicoRESUMEN
BACKGROUND: The Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa (PEACE MENA) is a prospective registry program in Arabian countries that involves in patients with acute myocardial infarction (AMI) or acute heart failure (AHF). METHODS: This prospective, multi-center, multi-country study is the first report of the baseline characteristics and outcomes of inpatients with AMI who were enrolled during the first 14-month recruitment phase. We report the clinical characteristics, socioeconomic, educational levels, and management, in-hospital, one month and one-year outcomes. RESULTS: Between April 2019 and June 2020, 1377 patients with AMI were enrolled (79.1% males) from 16 Arabian countries. The mean age (± SD) was 58 ± 12 years. Almost half of the population had a net income < $500/month, and 40% had limited education. Nearly half of the cohort had a history of diabetes mellitus, hypertension, or hypercholesterolemia; 53% had STEMI, and almost half (49.7%) underwent a primary percutaneous intervention (PCI) (lowest 4.5% and highest 100%). Thrombolytics were used by 36.2%. (Lowest 6.45% and highest (90.9%). No reperfusion occurred in 13.8% of patients (lowest was 0% and highest 72.7%).Primary PCI was performed less frequently in the lower income group vs. high income group (26.3% vs. 54.7%; P<0.001). Recurrent ischemia occurred more frequently in the low-income group (10.9% vs. 7%; P = 0.018). Re-admission occurred in 9% at 1 month and 30% at 1 year, whereas 1-month mortality was 0.7% and 1-year mortality 4.7%. CONCLUSION: In the MENA region, patients with AMI present at a young age and have a high burden of cardiac risk factors. Most of the patients in the registry have a low income and low educational status. There is heterogeneity among key performance indicators of AMI management among various Arabian countries.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/terapia , Estudios Prospectivos , Sistema de Registros , Clase Social , Resultado del TratamientoRESUMEN
BACKGROUND: In Tunisia, the number of cardiac implantable electronic devices (CIEDs) is increasing, owing to the increase in patient life expectancy and expanding indications. Despite their life-saving potential and a significant reduction in population morbidity and mortality, their increased numbers have been associated with the development of multiple early and late complications related to vascular access, pockets, leads, or patient characteristics. OBJECTIVE: The study aims to identify the rate, type, and predictors of complications occurring within the first year after CIED implantation. It also aims to describe the demographic and epidemiological characteristics of a nationwide sample of patients with CIED in Tunisia. Additionally, the study will evaluate the extent to which Tunisian electrophysiologists follow international guidelines for cardiac pacing and sudden cardiac death prevention. METHODS: The Tunisian National Study of Cardiac Implantable Electronic Devices (NATURE-CIED) is a national, multicenter, prospectively monitored study that includes consecutive patients who underwent primary CIED implantation, generator replacement, and upgrade procedure. Patients were enrolled between January 18, 2021, and February 18, 2022, at all Tunisian public and private CIED implantation centers that agreed to participate in the study. All enrolled patients entered a 1-year follow-up period, with 4 consecutive visits at 1, 3, 6, and 12 months after CIED implantation. The collected data are recorded electronically on the clinical suite platform (DACIMA Clinical Suite). RESULTS: The study started on January 18, 2021, and concluded on February 18, 2023. In total, 27 cardiologists actively participated in data collection. Over this period, 1500 patients were enrolled in the study consecutively. The mean age of the patients was 70.1 (SD 15.2) years, with a sex ratio of 1:15. Nine hundred (60%) patients were from the public sector, while 600 (40%) patients were from the private sector. A total of 1298 (86.3%) patients received a conventional pacemaker and 75 (5%) patients received a biventricular pacemaker (CRT-P). Implantable cardioverter defibrillators were implanted in 127 (8.5%) patients. Of these patients, 45 (3%) underwent CRT-D implantation. CONCLUSIONS: This study will establish the most extensive contemporary longitudinal cohort of patients undergoing CIED implantation in Tunisia, presenting a significant opportunity for real-world clinical epidemiology. It will address a crucial gap in the management of patients during the perioperative phase and follow-up, enabling the identification of individuals at particularly high risk of complications for optimal care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05361759; https://classic.clinicaltrials.gov/ct2/show/NCT05361759. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/47525.