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INTRODUCTION: There are several potential causes of QRS-axis deviation in the ECG, but there is limited data on the prognostic significance of QRS-axis deviation in ACS patients. SUBJECTS AND METHODS: We evaluated the long-term prognostic significance of acute phase frontal plane QRS-axis deviation and its shift during hospital stay in ACS patients. A total of 1026 patients who met the inclusion criteria were divided into three categories: normal (n = 823), left (n = 166) and right/extreme axis (n = 37). RESULTS: The median survival time was 9.0 years (95% CI 7.9-10.0) in the normal, 3.6 years (95% CI 2.4-4.7) in the left and 1.3 years (95% CI 0.2-2.4) in the right/extreme axis category. Both short and long-term all-cause mortality was lowest in the normal axis category and highest in the right/extreme axis category. Compared to normal axis, both admission phase QRS-axis deviation groups were independently associated with a higher risk of all-cause mortality. When including left ventricular hypertrophy in the ECG, only the right/extreme axis retained its statistical significance (aHR 1.76; 95% CI 1.16-2.66, p = 0.007). Axis shift to another axis category had no effect on mortality. CONCLUSION: In ACS patients, acute phase QRS-axis deviation was associated with higher risk of all-cause mortality. Among the axis deviation groups, right/extreme QRS-axis deviation was the strongest predictor of mortality in the multivariable analysis. Further studies are required to investigate to what extent this association is caused by pre-existing or by ACS-induced axis deviations. QRS-axis shift during hospital stay had no effect on all-cause mortality.
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Síndrome Coronario Agudo , Síndrome Coronario Agudo/diagnóstico , Arritmias Cardíacas , Electrocardiografía , Humanos , Hipertrofia Ventricular Izquierda , PronósticoRESUMEN
INTRODUCTION: Atrial fibrillation (AF) is a frequent finding in acute coronary syndrome (ACS), but there is conflicting scientific evidence regarding its long-term impact on patient outcome. The aim of this study was to survey and compare the ≥10-year mortality of ACS patients with sinus rhythm (SR) and AF. METHODS: Patients were divided into 2 groups based on rhythm in their 12-lead ECGs: (1) SR (n = 788) at hospital admission and discharge (including sinus bradycardia, physiological sinus arrhythmia, and sinus tachycardia) and (2) AF/atrial flutter (n = 245) at both hospital admission and discharge, or SR and AF combination. Patients who failed to match the inclusion criteria were excluded from the final analysis. The main outcome surveyed was long-term all-cause mortality between AF and SR groups during the whole follow-up time. RESULTS: Consecutive ACS patients (n = 1,188, median age 73 years, male/female 58/42%) were included and followed up for ≥10 years. AF patients were older (median age 77 vs. 71 years, p < 0.001) and more often female than SR patients. AF patients more often presented with non-ST-elevation myocardial infarction (69.8 vs. 50.4%, p < 0.001), had a higher rate of diabetes (31.0 vs. 22.8%, p = 0.009), and were more often using warfarin (32.2 vs. 5.1%, p < 0.001) or diuretic medication (55.1 vs. 25.8%, p < 0.001) on admission than patients with SR. The use of warfarin at discharge was also more frequent in the AF group (55.5 vs. 14.8%, p < 0.001). The rates of all-cause and cardiovascular mortality were higher in the AF group (80.9 vs. 50.3%, p < 0.001, and 73.8 vs. 69.6%, p = 0.285, respectively). In multivariable analysis, AF was independently associated with higher mortality when compared to SR (adjusted HR 1.662; 95% CI: 1.387-1.992, p < 0.001). CONCLUSION: AF/atrial flutter at admission and/or discharge independently predicted poorer long-term outcome in ACS patients, with 66% higher mortality within the ≥10-year follow-up time when compared to patients with SR.
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Síndrome Coronario Agudo , Fibrilación Atrial , Aleteo Atrial , Síndrome Coronario Agudo/complicaciones , Anciano , Fibrilación Atrial/complicaciones , Electrocardiografía , Femenino , Hospitalización , Humanos , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: Long-term outcome of real-life acute coronary syndrome (ACS) patients with selected ECG patterns is not well known. PURPOSE: To survey the 10-year outcome of pre-specified ECG patterns in ACS patients admitted to a university hospital. METHODS: A total of 1184 consecutive acute coronary syndrome patients in 2002-2003 were included and followed up for 10 years. The patients were classified into nine pre-specified ECG categories: 1) ST elevation; 2) pathological Q waves without ST elevation; 3) left bundle branch block (LBBB); 4) right bundle branch block (RBBB) 5) left ventricular hypertrophy (LVH) without ST elevation except in leads aVR and/or V1; 6) global ischemia ECG (ST depression ≥0.5 mm in 6 leads, maximally in leads V4-5 with inverted T waves and ST elevation ≥0.5 mm in lead aVR); 7) other ST depression and/or T wave inversion; 8) other findings and 9) normal ECG. RESULTS: Any abnormality in the ECG, especially Q waves, LBBB, LVH and global ischemia, had negative effect on outcome. In age- and gender adjusted Cox regression analysis, pathological Q waves (HR 2.28, 95%CI 1.20-4.32, p = .012), LBBB (HR 3.25, 95%CI 1.65-6.40, p = .001), LVH (HR 2.53, 95%CI 1.29-4.97, p = .007), global ischemia (HR 2.22, 95%CI 1.14-4.31, p = .019) and the combined group of other findings (HR 3.01, 95%CI 1.56-6.09, p = .001) were independently associated with worse outcome. CONCLUSIONS: During long-term follow-up of ACS patients, LBBB, ECG-LVH, global ischemia, and Q waves were associated with worse outcome than a normal ECG, RBBB, ST elevation or ST depression with or without associated T-wave inversion. LBBB was associated with the highest mortality rates.
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Síndrome Coronario Agudo , Síndrome Coronario Agudo/diagnóstico , Bloqueo de Rama/diagnóstico , Electrocardiografía , Hospitalización , Humanos , Hipertrofia Ventricular IzquierdaRESUMEN
BACKGROUND: A positive T wave in lead aVR (aVRT+) is an independent prognostic predictor of cardiovascular mortality in the general population as well as in cardiovascular disease. SUBJECTS AND METHODS: We evaluated the prognostic impact of aVRT+ in an ECG recorded as close to hospital discharge as possible in acute coronary syndrome patients (n = 527). We divided the patients into three categories based on the findings in the admission ECG: ST elevation, global ischemia and other ST/T changes. RESULTS: In the whole study population, and in all the three ECG subgroups, the 10-year all-cause mortality rate was higher in the aVRT+ group than in the aVRT- group. In Cox regression analysis, the age and gender adjusted hazard ratio (HR) for aVRT+ to predict all-cause mortality in the whole study population was 1.43 (95% confidence interval [CI] 1.12-1.83; p = 0.004). To predict cardiovascular mortality, the age and gender adjusted HR for aVRT+ was 1.54 (95% CI 1.14-2.07; p = 0.005) in the whole study population and 2.07 (95% CI 1.07-4.03; p = 0.032) in the category with other ST/T changes. CONCLUSION: In ACS patients with or without ST elevation, but with ischemic ST/T changes in their presenting ECG, a positive or isoelectric T wave in lead aVR in an ECG recorded in the subacute in-hospital stage is associated with all-cause and cardiovascular mortality during long-term follow-up. Clinicians should pay attention to this simple ECG finding at hospital discharge.
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Síndrome Coronario Agudo , Síndrome Coronario Agudo/diagnóstico , Electrocardiografía , Estudios de Seguimiento , Humanos , Isquemia , PronósticoRESUMEN
OBJECTIVES: We explored the 12-month clinical outcome of the titanium-nitride-oxide-coated OPTIMAX stent based on cobalt-chromium platform. BACKGROUND: The OPTIMAX stent demonstrated a satisfactory 6-month clinical outcome in de novo coronary lesions. METHODS: We enrolled 224 consecutive symptomatic patients with significant (50%) stenosis in de novo coronary lesions, who were treated with OPTIMAX stent implantation. The primary endpoint was major adverse cardiac events at 12-month follow-up, defined as a composite of cardiac death, non-fatal myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR). Stent thrombosis was adjudicated according to the definition of the Academic Research Consortium. RESULTS: The mean age of the cohort was 67 ± 8 years (75% males). Patients presented with acute coronary syndrome in 62.1%. Radial access was used in 92%; complex (type B and C) lesions were treated in 79.9%. Both procedural and clinical success occurred in 100% of the cases. The mean follow-up period was 366 ± 22 days. At 12-month follow-up, the primary endpoint occurred in 14 (6.3%) patients. Cardiac death occurred in three (1.3%) patients, non-fatal MI in seven (3.1%) patients, and ischemia-driven TLR in seven (3.1%) patients. No definite stent thrombosis occurred. CONCLUSIONS: In the current prospective observational study, implantation of the OPTIMAX stent demonstrated an adequate 12-month clinical outcome, with a low rate of major adverse cardiac events, and no stent thrombosis.
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Aleaciones de Cromo , Materiales Biocompatibles Revestidos , Enfermedad de la Arteria Coronaria/terapia , Estenosis Coronaria/terapia , Óxidos , Intervención Coronaria Percutánea/instrumentación , Stents , Titanio , Anciano , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/mortalidad , Trombosis Coronaria/etiología , Trombosis Coronaria/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Estudios Prospectivos , Diseño de Prótesis , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIMS: Genome-wide association studies (GWAS) have identified many variants associating with an increased risk of coronary artery disease (CAD). We studied the possible association between these variants and the risk of sudden cardiac death (SCD). METHODS AND RESULTS: A weighted genetic risk score (GRSCAD) was formed from variants most strongly associating with CAD identified by the CARDIoGRAMplusC4D Consortium explaining 10.6% of the heritability of CAD [153 single-nucleotide polymorphisms with r(2) < 0.2]. The association between GRSCAD and the occurrence of SCD was studied in three independent autopsy series of consecutive cases combining altogether 1035 autopsies with 306 SCDs due to CAD (SCDCAD). The results were replicated in a prospective follow-up study of 2321 patients (mean follow-up time of 6.2 years with 48 incident SCDs of which 39 due to CAD) undergoing clinical exercise test at baseline. In a meta-analysis of the autopsy series, GRSCAD associated significantly with the risk of SCDCAD with age, body mass index, and sex adjusted odds ratio (OR) of 1.042 (1.023-1.061, P = 9.1 × 10(-6)) for one allele increase in GRSCAD. The same association was seen in both sexes. GRSCAD predicted significantly the risk of SCDCAD also in a prospective study setting (Cox regression analysis adjusted with all relevant clinical data): hazard ratio 1.049 (1.010-1.090, P = 0.014). In meta-analysis of all cohorts (adjusting further for other genetic markers related to traditional risk factors and QT-interval), the association was highly significant [OR 1.045 (1.028-1.063), P = 1.7 × 10(-7)]. CONCLUSION: Genetic risk estimate for CAD may also be used to predict SCD.
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Enfermedad de la Arteria Coronaria/genética , Muerte Súbita Cardíaca/prevención & control , Anciano , Autopsia , Muerte Súbita Cardíaca/etiología , Métodos Epidemiológicos , Femenino , Predisposición Genética a la Enfermedad/genética , Variación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
BACKGROUND: Patients at high bleeding risk would benefit from a shorter dual antiplatelet therapy after PCI. Compared to first-generation devices, the design of newer generation drug-eluting stents may facilitate more rapid anatomical and functional healing of stented vessel based on thinner stent platforms, biodegradable/biocompatible polymers and rapid drug elution. METHODS AND RESULTS: Forty-four non-diabetic patients with acute coronary syndrome (ACS) and culprit lesion in the LAD were randomized to receive either biodegradable polymer sirolimus-eluting stent (BP-SES) or durable polymer zotarolimus-eluting stent (DP-ZES). Neointimal strut coverage was examined using optical coherence tomography, and vasodilator response on invasive thermodilution-derived coronary flow reserve (CFR) at 3-month follow-up. The primary endpoints were percent uncovered struts and CFR. A total of 425 cross-sections (4,897 struts) were analyzed in the BP-SES group, and 425 cross-sections (5,467 struts) in the DP-ZES group. The percent uncovered struts was lower in the BP-SES group compared with the DP-ZES group, both at strut level (3.9% vs. 8.9%, respectively, P<0.001), and stent level (3.9 ± 3.2% vs. 8.9 ± 6.9%, respectively, P=0.019). No significant difference was found between the 2 groups regarding CFR (3.0 ± 1.3 vs. 3.2 ± 1.0, respectively, P>0.05). CONCLUSIONS: In non-diabetic patients with ACS, BP-SES provided slightly better stent strut coverage at 3 months compared with DP-ZES, but neither stent was fully covered. No difference in vasodilator response was seen.
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Implantes Absorbibles , Síndrome Coronario Agudo , Plásticos Biodegradables , Stents Liberadores de Fármacos , Neointima , Sirolimus/análogos & derivados , Vasodilatación/efectos de los fármacos , Síndrome Coronario Agudo/fisiopatología , Síndrome Coronario Agudo/cirugía , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Infectious agents, especially bacteria and their components originating from the oral cavity or respiratory tract, have been suggested to contribute to inflammation in the coronary plaque, leading to rupture and the subsequent development of coronary thrombus. We aimed to measure bacterial DNA in thrombus aspirates of patients with ST-segment-elevation myocardial infarction and to check for a possible association between bacteria findings and oral pathology in the same cohort. METHODS AND RESULTS: Thrombus aspirates and arterial blood from patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (n=101; 76% male; mean age, 63.3 years) were analyzed with real-time quantitative polymerase chain reaction with specific primers and probes to detect bacterial DNA from several oral species and Chlamydia pneumoniae. The median value for the total amount of bacterial DNA in thrombi was 16 times higher than that found in their blood samples. Bacterial DNA typical for endodontic infection, mainly oral viridans streptococci, was measured in 78.2% of thrombi, and periodontal pathogens were measured in 34.7%. Bacteria-like structures were detected by transmission electron microscopy in all 9 thrombus samples analyzed; whole bacteria were detected in 3 of 9 cases. Monocyte/macrophage markers for bacteria recognition (CD14) and inflammation (CD68) were detected in thrombi (8 of 8) by immunohistochemistry. Among the subgroup of 30 patients with myocardial infarction examined by panoramic tomography, a significant association between the presence of periapical abscesses and oral viridans streptococci DNA-positive thrombi was found (odds ratio, 13.2; 95% confidence interval, 2.11-82.5; P=0.004). CONCLUSIONS: Dental infection and oral bacteria, especially viridans streptococci, may be associated with the development of acute coronary thrombosis.
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Enfermedades de la Boca/complicaciones , Infarto del Miocardio/etiología , Enfermedades Estomatognáticas/complicaciones , Trombosis/microbiología , Trombosis/patología , Estreptococos Viridans/aislamiento & purificación , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biomarcadores/metabolismo , Biopsia con Aguja , ADN Bacteriano/metabolismo , Femenino , Humanos , Receptores de Lipopolisacáridos/metabolismo , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Enfermedades de la Boca/microbiología , Estudios Retrospectivos , Enfermedades Estomatognáticas/microbiología , Trombosis/complicaciones , Estreptococos Viridans/genéticaRESUMEN
BACKGROUND: Long-term outcome of the three categories of acute coronary syndrome (ACS) in real-life patient cohorts is not well known. The objective of this study was to survey the 10-year outcome of an ACS patient cohort admitted to a university hospital and to explore factors affecting the outcome. METHODS: A total of 1188 consecutive patients (median age 73 years) with ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI) or unstable angina pectoris (UA) in 2002-2003 were included and followed up for ≥ 10 years. RESULTS: Mortality for STEMI, NSTEMI and UA patients during the follow-up period was 52.5%, 69.9% and 41.0% (p < 0.001), respectively. In multivariable Cox regression analysis, only age and creatinine level at admission were independently associated with patient outcome in all the three ACS categories when analyzed separately. CONCLUSIONS: All the three ACS categories proved to have high mortality rates during long-term followup in a real-life patient cohort. NSTEMI patients had worse outcome than STEMI and UA patients during the whole follow-up period. Our study results indicate clear differences in the prognostic significance of various demographic and therapeutic parameters within the three ACS categories.
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Síndrome Coronario Agudo , Infarto del Miocardio , Infarto del Miocardio sin Elevación del ST/fisiopatología , Infarto del Miocardio con Elevación del ST/fisiopatología , Anciano , Angina Inestable/fisiopatología , Humanos , Infarto del Miocardio/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Disturbed cellular cholesterol homeostasis may lead to accumulation of cholesterol in human atheroma plaques. Cellular cholesterol homeostasis is controlled by the sterol regulatory element-binding transcription factor 2 (SREBF-2) and the SREBF cleavage-activating protein (SCAP). We investigated whole genome expression in a series of human atherosclerotic samples from different vascular territories and studied whether the non-synonymous coding variants in the interacting domains of two genes, SREBF-2 1784G>C (rs2228314) and SCAP 2386A>G, are related to the progression of coronary atherosclerosis and the risk of pre-hospital sudden cardiac death (SCD). METHODS: Whole genome expression profiling was completed in twenty vascular samples from carotid, aortic and femoral atherosclerotic plaques and six control samples from internal mammary arteries. Three hundred sudden pre-hospital deaths of middle-aged (33-69 years) Caucasian Finnish men were subjected to detailed autopsy in the Helsinki Sudden Death Study. Coronary narrowing and areas of coronary wall covered with fatty streaks or fibrotic, calcified or complicated lesions were measured and related to the SREBF-2 and SCAP genotypes. RESULTS: Whole genome expression profiling showed a significant (p = 0.02) down-regulation of SREBF-2 in atherosclerotic carotid plaques (types IV-V), but not in the aorta or femoral arteries (p = NS for both), as compared with the histologically confirmed non-atherosclerotic tissues. In logistic regression analysis, a significant interaction between the SREBF-2 1784G>C and the SCAP 2386A>G genotype was observed on the risk of SCD (p = 0.046). Men with the SREBF-2 C allele and the SCAP G allele had a significantly increased risk of SCD (OR 2.68, 95% CI 1.07-6.71), compared to SCAP AA homologous subjects carrying the SREBF-2 C allele. Furthermore, similar trends for having complicated lesions and for the occurrence of thrombosis were found, although the results were not statistically significant. CONCLUSION: The results suggest that the allelic variants (SREBF-2 1784G>C and SCAP 2386A>G) in the cholesterol homeostasis regulating SREBF-SCAP pathway may contribute to SCD in early middle-aged men.
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Cyclooxygenase (COX) catalyzes formation of prostaglandins that contribute to the inflammation in atherosclerosis. Our objective was to study whether the functional C variant of the -765G-->C polymorphism in the human COX-2 gene associates with the severity of coronary atherosclerosis measured at the coronary artery level. The Helsinki sudden death study autopsy material (n = 300) comprised of Finnish men who died suddenly. The area of atherosclerotic lesions in the coronary arteries was quantitated, and coronary narrowing was measured. The occurrence of myocardial infarction (MI) was assessed. Genotyping was by restriction endonuclease analysis. Men carrying the minor C allele had larger areas of complicated lesions (P = .024) and a higher number of coronary arteries that had over 50% stenosis (P = .036) compared to men representing the common GG genotype. The COX-2 polymorphism was not associated with MI. Our data suggest that COX-2 may be involved in plaque growth.
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Enfermedad de la Arteria Coronaria/genética , Ciclooxigenasa 2/genética , Polimorfismo Genético , Adulto , Anciano , Enfermedad de la Arteria Coronaria/enzimología , Muerte Súbita/etiología , Finlandia , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/genética , Regiones Promotoras Genéticas , Factores de RiesgoRESUMEN
BACKGROUND AND PURPOSE: Smoking, increased fibrinogen levels, and platelet activation are related to the risk of ischemic stroke. The platelet fibrinogen receptor glycoprotein (Gp) IIb/IIIa Pl(A1/A2) polymorphism affects the binding of platelets to fibrinogen and is suggested to interact with smoking. METHODS: We explored the association of smoking and the Pl(A1/A2) polymorphism with ischemic stroke and survival in the Stroke Aging Memory cohort, comprising 486 consecutive patients (55 to 85 years old) who were analyzed 3 months after an ischemic stroke and followed up for 15 months. Stroke subtype determined by magnetic resonance imaging and GpIIb/IIIa Pl(A1/A2) genotype data were available for 272 patients. RESULTS: In multivariate analysis, smoking was the only factor related to the risk of lacunar infarcts (odds ratio [OR]=1.87, 95% CI=1.05 to 3.31; P=0.033), and it was also a predictor of death (n=24, 8.8%) at 15 months (OR=5.13, 95% CI=1.61 to 16.36; P=0.006), along with age (OR=1.10, 95% CI=1.01 to 1.19; P=0.008). The GpIIb/IIIa Pl(A1/A2) polymorphism alone showed no association with stroke subtype or survival. However, there was a smoking-by-genotype association with the risk of lacunar infarcts (OR=2.10, 95% CI=0.90 to 4.89; P=0.087) and with survival (OR=2.78, 95% CI=0.89 to 8.61; P=0.077). Among younger (55 to 69 years) stroke patients, smokers carrying the Pl(A2) allele were at a higher (OR=5.81, 95% CI=1.26 to 26.80; P=0.024) risk of lacunar infarcts than noncarrier smokers (OR=3.12, 95% CI=1.06 to 9.24; P=0.039). The effect of Pl(A2) and smoking combined on survival was also stronger (OR=8.86, 95% CI=1.68 to 46.55; P=0.010) than the effect of smoking alone (OR=5.06, 95% CI=1.20 to 21.35; P=0.027). CONCLUSIONS: Our results indicate that prothrombotic genetic factors may interact with smoking by modifying the stroke phenotype and affecting midterm survival.
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Infarto Encefálico/genética , Infarto Encefálico/mortalidad , Predisposición Genética a la Enfermedad/genética , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/genética , Polimorfismo Genético/genética , Fumar/efectos adversos , Fumar/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Coagulación Sanguínea/genética , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Finlandia/epidemiología , Estudios de Seguimiento , Frecuencia de los Genes/genética , Pruebas Genéticas , Genotipo , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tasa de SupervivenciaRESUMEN
OBJECTIVE: We investigated the association between hepatic lipase (HL) C-480T polymorphism and the risk of acute myocardial infarction (AMI) as well as pre-hospital sudden cardiac death (SCD). METHODS: Seven hundred sudden or unnatural pre-hospital deaths of middle-aged (33-70 years, mean 53 years) Caucasian Finnish men were subjected to detailed autopsy (Helsinki Sudden Death Study). Genotype data were obtained for 682 men. RESULTS: In logistic regression analysis with age, body mass index, hypertension, diabetes, smoking and alcohol consumption as covariates, men with the TT genotype had an increased risk for SCD and AMI compared to CC carriers (OR=3.0, P=0.011; and OR=3.7, P=0.003). There was a significant age-by-genotype interaction (P<0.05) on the risk of SCD. Compared to CC genotype carriers, the association between the TT genotype and SCD was particularly strong (P=0.001) among men <53 years of age, but this association was non-significant among older men. This was mainly due to a strong association between the TT genotype and AMI due to severe coronary disease in the absence of thrombosis. Carriers of the TT genotype were more likely to have severe coronary stenoses (> or =50%) than men with the CT or CC genotype (P=0.019). CONCLUSIONS: The results suggest that HL C-480T polymorphism is a strong age-dependent risk factor of SCD in early middle-aged men.
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Muerte Súbita Cardíaca/etiología , Lipasa/genética , Adulto , Anciano , Autopsia , Muerte Súbita Cardíaca/epidemiología , Finlandia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/genética , Polimorfismo Genético , Factores de RiesgoRESUMEN
The antiplatelet effect of aspirin varies individually. This study evaluated whether the antiplatelet effect of aspirin associates with polymorphisms in the genes coding for cyclo-oxygenase-1 (COX-1) and several platelet glycoprotein (GP) receptors in patients with stable coronary artery disease (CAD). Blood samples were collected from 101 aspirin-treated (mean 100 mg/d) patients. Compliance to treatment was assessed by plasma salicylate measurement. Platelet functions were assessed by two methods: 1) Response to arachidonic acid (AA, 1.5 mmol/L in aggregometry, and 2) PFA-100, evaluating platelet activation under high shear stress in the presence of collagen and epinephrine (CEPI). Aspirin non-response was defined as: 1) slope steeper than 12%/min in AA-aggregations, and 2) by closure time shorter than 170 s in PFA-100. The methods used detected different individuals as being aspirin non-responders. Five and 21 patients, respectively, were non-responders according to AA-induced aggregation and PFA-100. Increased plasma thromboxane B2 levels correlated with poor aspirin-response measured with both AA-induced aggregations and PFA-100 (P = 0.02 and P = 0.003, respectively). Of the non-responders detected by AA, 3 of 5 (60%) carried the rare G allele for the -A842G polymorphism of COX-1 in contrast to 16 of 96 (17%) responders (P = 0.016). Diabetes was associated with poor response. Aspirin non-response detected by PFA-100 associated with C13254T polymorphism of GP VI and female gender (P = 0.012 and P = 0.019, respectively). Although two patients were possibly non-compliant, this did not effect present conclusions. Evaluation of aspirin efficacy by AA-induced aggregation and PFA-100 detected different individuals, with different genotypic profiles, as being aspirin non-responders.
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Aspirina/farmacología , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/genética , Ciclooxigenasa 1/genética , Glicoproteínas de Membrana Plaquetaria/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Ácido Araquidónico/farmacología , Aspirina/sangre , Ciclooxigenasa 1/fisiología , Diabetes Mellitus/tratamiento farmacológico , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Farmacogenética , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Pruebas de Función Plaquetaria , Glicoproteínas de Membrana Plaquetaria/fisiología , Factores Sexuales , Tromboxano B2/farmacologíaRESUMEN
BACKGROUND: Adequate antiplatelet therapy in patients with myocardial infarction with ST-elevation (STEMI) is vital in order to avoid ischemic complications. However, especially with the novel potent oral drugs, bleeding is a major concern. We aimed to investigate whether STEMI patients switched to novel ADP receptor inhibitors due to high platelet reactivity (HPR) on clopidogrel have similar outcomes compared to patients with adequate response to clopidogrel. METHODS: A prospective cohort of 175 STEMI patients (mean age 62.3 years) undergoing primary PCI were included in the PASTOR study. Patients were loaded with 600 mg clopidogrel before the index PCI procedure. Bedside VerifyNow P2Y12 platelet function testing was performed the following morning. RESULTS: 46 patients (26.3%) were found to have HPR on clopidogrel (PRU>235) and were switched to novel ADP receptor antagonists. The remaining 129 patients were treated with clopidogrel. The mean duration of dual antiplatelet therapy (DAPT) was 6.7 months. Duration of entire follow-up of patients was approximately 2 years. Major adverse cardiac events (MACE) while patients were on DAPT occurred in 7.0% in the clopidogrel group compared to 8.7% in the novel ADP receptor antagonist group (p=0.70). No differences were observed between groups off-DAPT either. CONCLUSIONS: Following primary PCI for STEMI, patients with adequate response to clopidogrel show similar outcomes compared to patients switched to novel ADP receptor antagonists due to HPR on clopidogrel. Platelet reactivity testing can be used to guide the choice of antiplatelet therapy in patients with STEMI treated by primary PCI.
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Infarto del Miocardio/sangre , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea/métodos , Medicina de Precisión/métodos , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Ticlopidina/análogos & derivados , Anciano , Antitrombinas/administración & dosificación , Clopidogrel , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/cirugía , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Prospectivos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Ticlopidina/administración & dosificación , Ticlopidina/efectos adversos , Resultado del TratamientoRESUMEN
Data on early vascular healing response of novel stent designs are scarce. In this randomized prospective trial, we sought to compare early neointimal coverage of cobalt-chromium-based titanium-nitride-oxide-coated bioactive stents (CoCr-BAS) versus platinum-chromium everolimus-eluting stents (PtCr-EES) at 2-month follow-up in patients with acute coronary syndrome (ACS). Forty patients with ACS were randomized to receive either CoCr-BAS (n = 19) or PtCr-EES (n = 21). Neointimal strut coverage and strut apposition were examined by optical coherence tomography; and coronary flow reserve (CFR), fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) were assessed using a coronary pressure wire at 2 months. Two patients in the PtCr-EES underwent OCT out of the time frame of the study, and were excluded from analysis. At 63 ± 8 days, 302 cross-sections (3412 struts) were analysed in the CoCr-BAS group, and 324 cross-sections (3460 struts) in the PtCr-EES group. Median [IQR] neointimal thickness was 203 [108] µm and 42.2 [41] µm for CoCr-BAS and PtCr-EES, respectively (p < 0.001). Median [IQR] percentage of uncovered struts was 1.2 [2.8] % versus 11.3 [17.7] %, respectively (p < 0.001). Flow measurements were comparable between the two groups (p > 0.05 for all). CoCr-BAS showed earlier and more adequate neointimal coverage of struts at 2 months, compared with PtCr-EES, but with more neointimal hyperplasia. Functional healing as assessed by CFR, FFR, and IMR was similar between the two stent arms.
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Síndrome Coronario Agudo/terapia , Cromo , Materiales Biocompatibles Revestidos , Vasos Coronarios/efectos de los fármacos , Stents Liberadores de Fármacos , Everolimus/administración & dosificación , Óxido Nítrico/administración & dosificación , Intervención Coronaria Percutánea/instrumentación , Platino (Metal) , Titanio , Vasodilatadores/administración & dosificación , Cicatrización de Heridas , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/patología , Síndrome Coronario Agudo/fisiopatología , Anciano , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Vasos Coronarios/fisiopatología , Femenino , Finlandia , Reserva del Flujo Fraccional Miocárdico , Humanos , Hiperplasia , Masculino , Microcirculación , Persona de Mediana Edad , Neointima , Intervención Coronaria Percutánea/efectos adversos , Estudios Prospectivos , Método Simple Ciego , Factores de Tiempo , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Resistencia VascularRESUMEN
OBJECTIVES: Our aim was to corroborate the observed association between the deletion/deletion (DD) genotype of the insertion/deletion polymorphism in the alpha(2B)-adrenoceptor (AR) and increased risk for acute myocardial infarction (AMI), and to study whether this genotype also confers an increased risk for sudden cardiac death (SCD). BACKGROUND: Vasospasm has been suggested to play a role in AMI. Alpha(2)-AR mediate coronary vasoconstriction in humans, and studies on mice suggest the involvement of the alpha(2)-AR subtype B in vasoconstriction. A deletion variant of the human alpha(2B)-AR has been associated with impaired receptor desensitization in vitro. In a population-based prospective study of 912 middle-aged men, the DD genotype of the alpha(2B)-AR conferred an increased risk for AMI. METHODS: A series of 700 unselected sudden out-of-hospital deaths of middle-aged white men subjected to medico-legal autopsy was analyzed. RESULTS: Genotype information was obtained for 683 men (DD = 22%, insertion/deletion = 51%, insertion/insertion = 27%). Carriers of the DD genotype had an increased risk for SCD (n = 278, odds ratio [OR] = 2.0, p = 0.01) and fatal AMI (n = 84, OR = 2.1, p = 0.04) compared with the other two genotypes combined. The risks for SCD and fatal AMI were higher in carriers of the DD genotype who died before the age of 55 years (OR = 4.5 and 5.0, p < 0.001 for both). CONCLUSIONS: Middle-aged white men carrying the DD genotype of the alpha(2B)-AR have a significantly increased risk for SCD and AMI, especially before the age of 55 years.
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Muerte Súbita Cardíaca/etiología , Infarto del Miocardio/genética , Polimorfismo Genético , Receptores Adrenérgicos alfa 2/genética , Adulto , Anciano , Causas de Muerte , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Factores de Riesgo , Vasoconstricción/genéticaRESUMEN
OBJECTIVE: Matrix metalloproteinases 3 and 9 (MMP3 and MMP9) are present in atherosclerotic plaques and co-operate in the degradation of the fibrous cap of the atheroma, leading to fissuring and ultimately to acute coronary thrombosis. The functional genetic polymorphisms in the promoters of MMP3 and MMP9, which lead to low- and high-transcription activity genotypes, have been shown to be associated with myocardial infarction and angiographically measured atherosclerosis individually, whereas their effects in combination are not yet known. In order to assess the two disease loci simultaneously, we investigated the association of combined low and high promoter activity genotypes with different types of coronary lesions in an autopsy cohort of 300 Caucasian males aged 33-69 years (Helsinki Sudden Death Study). METHODS: Genotyping at these loci was performed by PCR, restriction enzyme digestion and minisequencing, and areas of the coronary wall covered with atherosclerotic lesions were measured using computer-assisted morphometry. RESULTS: In analysis of covariance (ANCOVA) with age, body mass index, hypertension, diabetes, smoking and alcohol consumption as covariates, a significant interaction between the MMP3 and MMP9 genotypes was observed on area of complicated lesions (P=0.012). Men with high promoter activity genotypes for both loci had, on average, more than two times larger area of complicated lesions (250%) compared with those men who had low promoter activity genotypes (P=0.008), but these loci showed no association with myocardial infarction. CONCLUSIONS: The joint action of two susceptibility loci, rather than single MMP genes alone, and the particular combination of MMP3 and MMP9 genotypes present at these loci may contribute to heterogeneity in the presentation of atherosclerosis.
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Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/genética , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo Genético , Adulto , Anciano , Apoptosis , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/enzimología , Vasos Coronarios/patología , Predisposición Genética a la Enfermedad/epidemiología , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , Factores de RiesgoRESUMEN
Nitric oxide (NO), formed by endothelial constitutive nitric oxide synthase (eNOS) maintains endothelium-dependent vasodilatation and also mediates antithrombotic actions. The eNOS gene harbours a common polymorphism in intron 4 (4a/b), and some clinical studies have suggested an association of the rare a-allele with coronary artery disease (CAD) and myocardial infarction (MI). However, contradictory results have also been reported. We studied associations of eNOS polymorphism with CAD and MI in two prospective autopsy series comprising altogether 700 Caucasian Finnish men, who died suddenly. In ANCOVA, no significant differences in areas of atherosclerotic lesions and coronary stenosis percentages were found between men carrying the a-allele (ba+aa) compared with those homozygous for the b-allele. Subjects with the a-allele had significantly lower risk of MI (odds ratio 0.44, 95% confidence interval 0.25-0.77, P=0.004) compared with those carrying the bb genotype. Men with the a-allele also tended to have coronary thrombosis less often (odds ratio 0.43, 95% confidence interval 0.18-1.01, P=0.055). The eNOS gene 4a/b polymorphism was not associated with the extent of coronary atherosclerosis, but the a-allele of the variant seems to protect to some degree against the development of MI.