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Chronic pulmonary thromboembolic disease is an important cause of severe pulmonary hypertension, and as such is associated with significant morbidity and mortality. The prognosis of this condition reflects the degree of associated right ventricular dysfunction, with predictable mortality related to the severity of the underlying pulmonary hypertension. Left untreated, the prognosis is poor. Pulmonary endarterectomy is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension and has been remarkably successful. Advances in surgical techniques along with the introduction of pulmonary hypertension-specific medication provide therapeutic options for the majority of patients afflicted with the disease. However, a substantial number of patients are not candidates for pulmonary endarterectomy due to either distal pulmonary vascular obstruction or significant comorbidities. Therefore, careful selection of surgical candidates in expert centres is paramount. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options.
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INTRODUCTION: Myocardial perfusion SPECT (MPS) is frequently used for cardiovascular risk stratification. The significance of MPS in patients with abnormal electrical ventricular activation is often questionable. This review assesses the value of MPS for risk stratification of patients with intrinsic left bundle branch block or that due to right ventricular apical pacing. METHODS: We reviewed the literature by a search of the MEDLINE database (January 1980 to September 2010). The terms prognosis or prognostic value were combined with SPECT and LBBB or pacing or pacemakers. MPS was categorised as low and high risk according to the original definitions. RESULTS: We identified 11 studies suitable for review. A low-risk MPS is associated with a low risk of cardiac events whereas high-risk MPS carries a 4.8-fold increased risk, 95% CI [3.2 - 7.2] (p < 0.0001). Despite secondary prevention and an improved medical and interventional care, these figures have hardly changed over time. CONCLUSION AND CLINICAL IMPLICATIONS: A low-risk MPS permits a policy of watchful waiting whereas a high-risk MPS requires further analysis and treatment. The persistent high cardiac death and acute myocardial infarction rate after a high-risk MPS suggest that the current management of these patients does not suffice and needs reconsideration.
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Pulmonary arteriovenous malformations (PAVMs) are associated with severe neurological complications in patients with hereditary haemorrhagic telangiectasia (HHT). The objective of the present study was to prospectively establish the diagnostic value of transthoracic contrast echocardiography (TTCE) as a screening technique for PAVM using chest high-resolution computed tomography (HRCT) as the gold standard for PAVMs. All consecutive adult patients referred for HHT screening underwent a chest HRCT (n = 299), TTCE (n = 281), arterial blood gas analysis (n = 291), shunt fraction measurement (n = 111) and chest radiography (n = 296). TTCE was positive in 87 (58.8%), 12 (16.7%) and four (6.7%) patients, and chest HRCT was positive in 54 (36.5%), three (4.2%) and zero (0%) patients with a definite, possible and negative clinical diagnosis of HHT, respectively. Two patients with a negative TTCE were diagnosed with PAVMs after computed tomography; in both cases the PAVMs were too small to be treated by embolotherapy. The sensitivity of TTCE was 97% (95% confidence interval (CI) 93.6-98.3) and negative predictive value 99% (95% CI 96.9-99.8). The other diagnostic tests showed a considerable lower diagnostic value. The present prospective study shows that transthoracic contrast echocardiography has an excellent diagnostic value and can be used as an initial screening procedure for pulmonary arteriovenous malformations. The high false-positive rate of transthoracic contrast echocardiography possibly represents microscopic pulmonary arteriovenous malformations.
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Malformações Arteriovenosas/diagnóstico por imagem , Ecocardiografia , Artéria Pulmonar/diagnóstico por imagem , Veias Pulmonares/diagnóstico por imagem , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/diagnóstico por imagem , Adulto , Malformações Arteriovenosas/etiologia , Meios de Contraste , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos ProspectivosRESUMO
Migraine with aura (MA) is associated with cardiac right-to-left shunt. We prospectively studied the association between pulmonary arteriovenous malformations (PAVMs) and MA in hereditary haemorrhagic telangiectasia (HHT). All 220 consecutive HHT patients who underwent high-resolution chest computed tomography for PAVM screening were included prospectively. Prior to screening, a structured validated headache questionnaire was completed by 196 patients (57% female; mean+/-sd age 44.6+/-15.2 yrs). Two neurologists diagnosed migraine according to the International Headache Society Criteria. A PAVM was present in 70 (36%) patients. The prevalence of MA was 24% in the presence of a PAVM compared with 6% in the absence of a PAVM (OR 4.6, 95% CI 1.84-11.2; p = 0.001), and MA was an independent predictor for the presence of PAVM using multivariate analysis (OR 3.6, 95% CI 1.21-10.5; p = 0.02). A PAVM was present in 68% of the patients with MA compared with 32% in the non-migraine controls (OR 4.6, 95% CI 1.84-11.2; p = 0.001), and a PAVM was an independent predictor for MA using multivariate analysis (OR 3.0, 95% CI 1.00-9.20; p = 0.05). In conclusion, PAVMs are associated with MA in HHT patients.
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Malformações Arteriovenosas/epidemiologia , Enxaqueca com Aura/epidemiologia , Enxaqueca sem Aura/epidemiologia , Telangiectasia Hemorrágica Hereditária/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Circulação Pulmonar , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: The purpose was to evaluate long-term outcome following balloon angioplasty for coarctation in adults. BACKGROUND: Long-term results of balloon angioplasty for native coarctation in adults remain incomplete, especially concerning the occurrence of aneurysm formation. METHODS: Long-term follow-up data were collected in consecutive patients retrospectively. Results of balloon angioplasty (29 patients, age 15-71 years, during 1995-2005) for discrete, native coarctation were evaluated, including MRI or CT. RESULTS: Mean follow-up ranged from 2.2 to 13 years (mean 8.5 +/- 3.2). Immediate success was obtained in all patients. Early mortality or complications were not encountered. Peak systolic pressure gradient decreased from 52 +/- 21 to 7.2 +/- 7.6 mm Hg (P < 0.001). Intima tear was detected in eight procedures angiographically, without signs of dissection. Three-month follow-up angiography in these patients showed unchanged (4/8 patients) or diminished abnormalities (4/8 patients). One asymptomatic patient, known with left ventricular dysfunction due to significant aortic valve insufficiency, died suddenly 5 years after balloon angioplasty. Recoarctation occurred in one patient (3%). Late aneurysm formation was excluded by MR in 24/29 and CT in remaining 5/29 patients during follow-up, including those patients in whom intima tear was encountered immediately postangioplasty. In three of seven patients an irregular aortic contour persisted, without indication of progression or aneurysm formation. Hypertension was completely relieved in 67% (14/21 patients) and improved in 33% (7/21 patients). CONCLUSIONS: Balloon angioplasty for native coarctation yields low reintervention probability in adult patients. Despite occurrence of angiographically established intimal tearing, aortic dissection and aneurysm formation were not encountered.
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Angioplastia com Balão/efeitos adversos , Aneurisma Aórtico/etiologia , Coartação Aórtica/terapia , Dissecção Aórtica/etiologia , Adolescente , Adulto , Idoso , Dissecção Aórtica/patologia , Angiografia Digital , Aneurisma Aórtico/patologia , Coartação Aórtica/complicações , Coartação Aórtica/patologia , Aortografia , Humanos , Hipertensão/etiologia , Hipertensão/terapia , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
We report a case of percutaneous mitral valve repair, using the Mitraclip device, in which we show that application of real-time three-dimensional transoesophageal echocardiography (3D-TEE) is extremely helpful for the guidance of this procedure. Because of its excellent visualization capacities, 3D-TEE simplifies the transseptal puncture, the positioning of the clip above the mitral valve orifice, the grasping of the mitral valve leaflets, and the evaluation of the final result. Therefore, we conclude that 3D-TEE has the potential to increase the safety and efficacy of this new technique to treat mitral regurgitation in patients who cannot undergo conventional valve surgery.
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Procedimentos Cirúrgicos Cardíacos/métodos , Ecocardiografia Tridimensional , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Idoso de 80 Anos ou mais , Feminino , HumanosRESUMO
Postprandial hyperlipidaemia has been associated with coronary artery disease (CAD). We investigated which of the generally used methods to test postprandial lipaemia differentiated best between patients with premature CAD (50+/-4 years, n=20) and healthy controls. Furthermore, the effects of rosuvastatin 40 mg/day on postprandial parameters were assessed. Standardised oral fat-loading tests (OFLT) and ambulant self-measurements of daylong capillary triglycerides (TGc) were performed. Total responses of individual lipoproteins, plasma TG (TGp) and remnant-like particle cholesterol (RLP-C) were estimated as area under the curve (AUC). Most AUCs were highest in untreated patients and reached control levels after rosuvastatin. From all AUCs, RLP-C-AUC was best associated to TGp-AUC in untreated patients and controls (adjusted R2=0.84, beta=0.92, p.
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Doença da Artéria Coronariana/diagnóstico , Hiperlipidemias/diagnóstico , Período Pós-Prandial , Área Sob a Curva , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/fisiopatologia , Feminino , Fluorbenzenos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/fisiopatologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Pirimidinas/uso terapêutico , Análise de Regressão , Rosuvastatina Cálcica , Sulfonamidas/uso terapêutico , Triglicerídeos/sangueRESUMO
Migraine is a common neurological disorder with a great impact on the quality of life and social activities. Pulmonary arteriovenous malformations (PAVMs) are mostly congenital, with a prevalence of 5-50% in patients with hereditary hemorrhagic telangiectasia (HHT). A high prevalence of PAVMs is found in patients with HHT and migraine. Embolization of PAVMs seems to decrease the prevalence of migraine. Different pathophysiological hypotheses have been proposed to explain the association between migraine and the different right-to-left shunts. This review article describes the association between a pulmonary right-to-left shunt and the occurrence of migraine.
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Malformações Arteriovenosas/complicações , Pneumopatias/complicações , Pulmão/anormalidades , Transtornos de Enxaqueca/etiologia , Humanos , Pulmão/irrigação sanguíneaRESUMO
Three men, aged 67 years, 80 years and 53 years, respectively, developed signs and symptoms of progressive right-sided heart failure following open heart surgery. They were diagnosed with constrictive pericarditis based on echocardiography, cardiac magnetic resonance and cardiac catheterisation. Following pericardiectomy, two of the patients fully recovered, while one, the 80-year-old man, died during convalescence. When signs and symptoms of progressive right-sided heart failure develop after open heart surgery, a diagnosis of constrictive pericarditis should be considered. Constrictive pericarditis after open heart surgery may be caused by inflammation of the pericardium; an old, fibrotic haemopericardium, which may be diffuse or loculated; pericardial adhesions; or a combination of these entities. Diagnosing constrictive pericarditis is difficult and may take a long time. However, it is important to recognise this disorder early before it has progressed to an advanced stage. Pericardiectomy is the only effective therapy. When performed too late, survival is significantly reduced.
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Cardiopatias/cirurgia , Insuficiência Cardíaca/diagnóstico , Pericardiectomia/métodos , Pericardite Constritiva/etiologia , Pericardite Constritiva/cirurgia , Idoso , Idoso de 80 Anos ou mais , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pericardiectomia/efeitos adversos , Pericardite Constritiva/diagnóstico , Pericardite Constritiva/mortalidade , Complicações Pós-Operatórias/diagnóstico , Análise de SobrevidaRESUMO
BACKGROUND: Percutaneous patent foramen ovale (PFO) closure seems to reduce the risk of recurrent thromboembolism. We report the safety and efficacy of percutaneous PFO closure in our centre. METHODS: All patients, >16 years of age, who underwent a percutaneous PFO closure in our centre were included. Reoccurrence of stroke, transient ischaemic attack (TIA) and peripheral thromboembolism were assessed. Periprocedural and midterm complications are reported. RESULTS: Eighty-three consecutive patients (mean age 49+/-13 years) were included. Indications for PFO closure were cryptogenic stroke (59.0%), TIA (33.7%), peripheral embolism (2.4%) and other (4.8%). For PFO closure, a Cardioseal/Starflex device was used in 63 patients and an Amplatzer PFO occluder device in 20 patients. Stroke recurred in 1.2%, TIA in 3.6%, peripheral embolism in 0% during a mean follow-up of 1.9+/-1.2 years. Major periprocedural complications occurred in 1.2%. The mid-term complication rate was 2.4% and only consisted of minor complications. During follow-up, a residual right-to-left shunt was present in 5.7% of the patients. No significant difference in outcome, complications or residual shunting could be documented between the two device types. CONCLUSION: In our centre, the percutaneous closure of a PFO seems to be a safe and effective procedure to prevent recurrence of paradoxical thrombo-embolic events. (Neth Heart J 2008;16:332-6.).
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A 57-year-old woman suffered from frequent flushes due to an ovarian carcinoid tumour.
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Tumor Carcinoide/diagnóstico , Neoplasias Ovarianas/diagnóstico , Tumor Carcinoide/cirurgia , Diagnóstico Diferencial , Feminino , Rubor/etiologia , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI, few data exist on the magnitude of platelet activation, aggregation and dosing of glycoprotein (GP) IIb/IIIa receptor inhibitors. METHODS: Sixty STEMI patients were randomised to abciximab, to high-dose tirofiban or to no additional GP IIb/IIIa inhibitor treatment. Platelet activation (P-selectin expression) was measured using flow cytometry and the level of inhibition of platelet aggregation was assessed using the Plateletworks assay. Additionally, the PFA-100 with the collagen/adenosine-diphosphate cartridge (CADP) was used to compare the levels of platelet inhibition. All measurements were performed at baseline (T(0)), immediately after (T(1)), 30 minutes (T(2)), 60 minutes (T(3)) and 120 minutes (T(4)) after primary PCI. RESULTS: The level of platelet activation in both GP IIb/IIIa receptor inhibitor treated groups was significantly lower compared with the control group at all time points after primary PCI (p=0.04). Also the administration of the currently recommended dose of abciximab resulted in significantly lower levels of inhibition of aggregation compared with high-dose tirofiban (p<0.0001). In addition, the CADP closure times were significantly prolonged in both GP IIb/IIIa inhibitor treated groups compared with the control group at time points T(1) (p=0.006) and T(4) (p<0.0001). CONCLUSION: The administration of high-dose tirofiban resulted in a significantly higher inhibition of platelet aggregation compared with the currently recommended dose of abciximab. Large clinical trials are needed to assess whether this laboratory superiority of high-dose tirofiban translates into higher clinical efficacy. (Neth Heart J 2007;15:375-81.).
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We investigated whether pro-inflammatory aspects of the postprandial phase can be modulated by rosuvastatin in premature coronary artery disease (CAD) patients. Herefore standardized 8 h oral fat loading tests were performed off-treatment and after rosuvastatin 40 mg/d in 20 male CAD patients (50 +/- 4 years). The expression of leukocyte activation markers CD11a, CD11b, CD62L and CD66b was studied using flowcytometry. Migration of isolated neutrophils towards chemoattractants was determined in a fluorescence-based assay. Rosuvastatin did not affect baseline leukocyte counts nor the postprandial neutrophil increment (maximum mean increase +10% pre- and +14% post-treatment, P < 0.01 for each). Rosuvastatin reduced baseline platelets (from 266 +/- 78 to 225 +/- 74 x 10(9) cells/L, P < 0.001) and blunted the postprandial platelet count change (maximum mean increase +6%, P = 0.01, and 0%, respectively). The baseline expression of CD11a, CD11b and CD62L increased on most types of leukocytes by rosuvastatin, whereas the postprandial responses were unaffected. Pretreatment, postprandial neutrophil migration increased dose-dependently, but there were no postprandial changes after rosuvastatin. The latter effect was unrelated to changes in lipoprotein concentrations. In conclusion, in CAD patients postprandial pro-inflammatory and pro-coagulant changes can be modified by rosuvastatin. These apparently lipid-lowering independent effects may render protection against atherosclerosis.
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Doença da Artéria Coronariana/sangue , Gorduras na Dieta/administração & dosagem , Fluorbenzenos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Leucócitos/efeitos dos fármacos , Período Pós-Prandial , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Antígenos CD/análise , Antígeno CD11a/análise , Antígeno CD11b/análise , Moléculas de Adesão Celular/análise , Quimiotaxia de Leucócito , Doença da Artéria Coronariana/complicações , Contagem de Eritrócitos , Proteínas Ligadas por GPI , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/complicações , Interleucina-8/sangue , Selectina L/análise , Leucócitos/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/fisiologia , Estresse Oxidativo , Contagem de Plaquetas , Rosuvastatina Cálcica , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
INTRODUCTION: The beneficial effects of ACE inhibitors are generally ascribed to blockade of neurohormonal activation. However, especially in chronic heart failure (CHF) patients plasma angiotensin II and aldosterone levels can be elevated despite ACE inhibition, the so-called ACE escape. In the present study, we aimed to identify the frequency and determinants of ACE escape in CHF patients. METHODS: We studied 99 stable chronic heart failure patients (NYHA class III and IV, 66% ischemic etiology) receiving long-term therapy with ACE inhibitors. In all patients, cardiac, renal, and neurohormonal parameters were measured. ACE escape was defined as plasma angiotensin level > or = 16 pmol/L. RESULTS: Mean (+/- SD) left ventricular ejection fraction of our 99 patients (79 men and 20 women, age 69 +/- 12 years) was 28 +/- 10%. In addition to an ACE inhibitor, 93% of patients received diuretics, 71% a beta-blocker, and 49% spironolactone. None of the patients used an angiotensin receptor blocker. In our population, 45% of the patients had an angiotensin II plasma concentration higher than 16 pmol/L (median concentration was 14.1 pmol/L). Spironolactone use was an independent predictor of elevated plasma angiotensin II levels. Furthermore, spironolactone users had significantly higher plasma active renin protein and aldosterone levels. Plasma angiotensin II concentration was positively correlated to active renin, plasma angiotensin I and plasma aldosterone. No correlation was found between plasma angiotensin II levels and serum ACE activity, dose of ACE inhibitor, or duration of use. CONCLUSION: In a group of severe chronic heart failure patients, 45% had elevated plasma angiotensin II levels independent of serum ACE activity despite long-term ACE inhibitor use. Although a causal link could not be proven, an association was found between spironolactone use and active renin protein, angiotensin II and aldosterone levels, suggesting that escape from ACE is mainly caused by a feedback mechanism.
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Angiotensina II/sangue , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Angiotensina I/sangue , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Retroalimentação Fisiológica/efeitos dos fármacos , Retroalimentação Fisiológica/fisiologia , Feminino , Insuficiência Cardíaca/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Peptidil Dipeptidase A/sangue , Renina/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Espironolactona/farmacologiaRESUMO
AIMS: Despite agreement on the need for screening for the presence of cardiovascular risk factors in first-degree family members of patients with premature coronary artery disease (CAD), this is not routinely carried out in relatives of normocholesterolaemic patients. We evaluated cardiovascular risk factors in family members of normocholesterolaemic patients with premature CAD. METHODS: Eligible index subjects were patients with premature CAD (<55 years in men and <65 years in women), who had undergone percutaneous transluminal coronary angioplasty. Patients with fasting total cholesterol levels >6.5 mmol/l were excluded. Sixteen index subjects were included with a mean age of 49±8 years and total cholesterol levels of 5.5±0.8 mmol/l. Sixty-four first-degree relatives from these 16 pedigrees were screened, namely 18 children, 42 siblings and four parents. National Cholesterol Education Program III guidelines were used to identify candidates for lipid-lowering treatment. Furthermore, the presence of four additional metabolic disorders was investigated: the metabolic syndrome, increased levels of lipoprotein(a) (Lp(a)), hyperhomocysteinaemia and postprandial hyperlipidaemia. RESULTS: Of 64 relatives free of CAD, 34 subjects (53%) fulfilled the criteria to receive therapeutic advice, 20 of whom (31% of the relatives) were candidates for drug therapy. Sixty-one relatives were available for a full assessment of metabolic disorders and in 37 relatives (61%) at least one metabolic abnormality was present. Twelve subjects had hyper-Lp(a), seven subjects had postprandial hyperlipidaemia and two had the metabolic syndrome. Furthermore, 16 subjects had a combination of at least two out of four metabolic disorders. CONCLUSION: Careful evaluation of coronary risk factors and metabolic variables in first-degree relatives of normocholesterolaemic CAD patients identifies a significant number of subjects at increased coronary risk in whom primary prevention measures should be initiated.
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Postprandial hyperlipidemia has been linked to premature coronary artery disease (CAD) in fasting normotriglyceridemic patients. We investigated the effects of increasing doses of simvastatin up to 80 mg/day on fasting and postprandial lipoprotein metabolism in 18 normotriglyceridemic patients with premature CAD. Fasting lipoprotein subfractions and cholesteryl ester transfer protein (CETP) activity were determined after each 5-week dose titration (0, 20, 40 and 80 mg/day). At baseline and after treatment with simvastatin 80 mg/day, standardised Vitamin A oral fat loading tests (50 g/m2; 10 h) were carried out. Ten normolipidemic healthy control subjects matched for gender, age and BMI underwent tests without medication. Treatment with simvastatin resulted in dose-dependent reductions of fasting LDL-cholesterol, without changing cholesterol levels in the VLDL-1, VLDL-2 and IDL fractions. In addition, simvastatin decreased CETP activity dose-dependently, although HDL-cholesterol remained unchanged. Simvastatin 80 mg/day decreased fasting plasma triglycerides (TG) by 26% (P < 0.05), but did not decrease significantly TG levels in any of the subfractions. The TG/cholesterol ratio increased in all subfractions. The plasma TG response to the oral fat loading test, estimated as area under the curve (TG-AUC), improved by 30% (from 21.5 +/- 2.5 to 15.1 +/- 1.9 mmol h/L; P < 0.01). Treatment with simvastatin 80 mg/day improved chylomicron remnant clearance (RE-AUC) by 36% from 30.0 +/- 2.6 to 19.2 +/- 3.3 mg h/L (P < 0.01). After therapy, remnant clearance in patients was similar to controls (19.2 +/- 3.3 and 20.3 +/- 2.7 mg h/L, respectively), suggesting a normalization of this potentially atherogenic process. In conclusion, high-dose simvastatin has beneficial effects in normotriglyceridemic patients with premature CAD, due to improved chylomicron remnant clearance, besides effective lowering of LDL-cholesterol. In addition, the lipoprotein subfractions became more cholesterol-poor, as reflected by the increased TG/cholesterol ratio, which potentially makes them less atherogenic.
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Quilomícrons/sangue , Doença da Artéria Coronariana/sangue , Jejum/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Lipoproteínas/sangue , Período Pós-Prandial , Sinvastatina/administração & dosagem , Triglicerídeos/sangue , Apolipoproteínas/sangue , Proteínas de Transporte/sangue , Proteínas de Transferência de Ésteres de Colesterol , Remanescentes de Quilomícrons , Relação Dose-Resposta a Droga , Feminino , Glicoproteínas/sangue , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Sinvastatina/farmacologiaRESUMO
OBJECTIVE: An increased hepatic flow of free fatty acids (FFAs) is associated with impaired peripheral FFA trapping by malfunctioning of the complement component 3 (C3)/acylation-stimulating protein system and overproduction of VLDL in familial combined hyperlipidemia (FCHL). Postprandial ketone bodies reflect FFA oxidation in the liver, but the postprandial changes in male and female patients separately have not been determined yet. Gender differences in postprandial ketone bodies and C3 changes were investigated in normolipidemic patients and patients with untreated FCHL. METHODS AND RESULTS: Thirty-two normolipidemic patients (16 female and 16 male) and 19 patients with untreated normolipidemia (9 female and 10 male) underwent an oral fat-loading test. Total and incremental areas under the curves (AUC and dAUC, respectively) after the oral fat load were calculated. Triglyceride AUC was similar between genders in each group. Normolipidemic female subjects showed a higher levels of dAUC-hydroxybutyric acid than male subjects (1.37+/-0.49 and 0.98+/-0.43 mmol x h/L). In FCHL, a similar trend was observed in female (1.92+/-0.38) compared with male (1.55+/-0.87) subjects. In contrast to normolipidemia, FCHL did not show a postprandial increase in C3, although C3 was higher in FCHL. CONCLUSIONS: Women have higher postprandial ketone bodies than men, probably reflecting enhanced postprandial hepatic FFA oxidation. In FCHL, both genders have higher postprandial ketone bodies and therefore higher hepatic FFA delivery. The higher fasting and postprandial C3 levels in FCHL may reflect resistance of the C3/acylation-stimulating protein system to promote peripheral fatty acid trapping.
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Ácidos Graxos não Esterificados/metabolismo , Hiperlipidemia Familiar Combinada/metabolismo , Corpos Cetônicos/metabolismo , Ácido 3-Hidroxibutírico/sangue , Adulto , Área Sob a Curva , Complemento C3/metabolismo , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/metabolismo , Ácidos Graxos não Esterificados/sangue , Feminino , Humanos , Hiperlipidemia Familiar Combinada/sangue , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Caracteres Sexuais , Triglicerídeos/sangueRESUMO
BACKGROUND: Several studies indicate that ACE-activity is related to atherosclerosis. We investigated the correlation between ACE-activity, in plasma as well as in the atherosclerotic plaque, and in-stent restenosis. METHODS AND RESULTS: ACE-activity was measured in blood samples from 178 patients who underwent a percutaneous coronary intervention with stent placement. During 8 months follow-up, 51 of these patients had an adverse clinical event. ACE-activity did not differ between patients with or without adverse events (21.5 vs. 23.1 nM/ml/min; P=0.36). Tissue samples were obtained with an atherectomy catheter before elective stent placement in another group of 13 patients with de novo stenosis. In this tissue, we determined the ACE-content immunohistologically. These patients were scheduled for follow-up quantitative coronary angiography after 12 months. In this group, the quantity of ACE was not correlated to the late luminal loss (0.31 vs. 0.38 mm; P=0.76). CONCLUSION: In this study, pre-procedural ACE-activity, in plasma as well as in the atherosclerotic plaque, does not predict the occurrence of in-stent restenosis.
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Angioplastia Coronária com Balão/instrumentação , Reestenose Coronária/enzimologia , Estenose Coronária/terapia , Vasos Coronários/enzimologia , Peptidil Dipeptidase A/metabolismo , Stents , Aterectomia Coronária , Biomarcadores/metabolismo , Biópsia , Reestenose Coronária/cirurgia , Estenose Coronária/enzimologia , Vasos Coronários/patologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Falha de Prótese , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de TempoRESUMO
Postprandial hyperlipidemia is associated with premature coronary sclerosis in fasting normolipidemic subjects. Self-determined daytime capillary triglyceride (cTG) profiles were compared between 26 fasting normotriglyceridemic patients with premature coronary artery disease (CAD) and 26 controls matched for gender, age and BMI. Daytime triglyceridemia was calculated as total area under the cTG-curve (cTG-AUC). Total and LDL cholesterol were not different between CAD patients (5.4+/-0.8 mmol/l and 3.6+/-0.7 mmol/l, respectively) and controls (5.0+/-0.9 mmol/l and 3.3+/-0.8 mmol/l, respectively). Patients with CAD were characterized by a 44% higher cTG-AUC than matched controls (P<0.01). Using logistic regression analysis, cTG-AUC was the strongest predictor of the presence of CAD (P<0.001). Adding apo AI to the model improved the predictive power from 71 to 77%. Sixteen patients were studied after increasing doses of simvastatin up to 80 mg/day. Although the target for LDL cholesterol was reached by simvastatin 20mg/day, significant effects on cTG-AUC were found only by higher doses of simvastatin. Simvastatin 40 mg/day decreased cTG-AUC by 28% (P<0.05 versus baseline), reaching comparable values as in controls, without further improvement with simvastatin 80 mg/day (26% reduction versus baseline; P<0.05). Daytime triglyceridemia is linked to premature coronary sclerosis in fasting normotriglyceridemic patients. A higher dose of simvastatin was needed to normalize daytime triglyceridemia than was required to "normalize" LDL cholesterol.
Assuntos
Ritmo Circadiano/fisiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Jejum/sangue , Hipertrigliceridemia/sangue , Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Sinvastatina/uso terapêutico , Triglicerídeos/sangue , Adulto , Idoso , Apolipoproteína A-I/sangue , Apolipoproteína A-I/efeitos dos fármacos , Apolipoproteínas B/sangue , Apolipoproteínas B/efeitos dos fármacos , Área Sob a Curva , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Doença da Artéria Coronariana/epidemiologia , Gorduras na Dieta/administração & dosagem , Relação Dose-Resposta a Droga , Ingestão de Energia/efeitos dos fármacos , Feminino , Humanos , Hipertrigliceridemia/epidemiologia , Hipolipemiantes/administração & dosagem , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Países Baixos , Valor Preditivo dos Testes , Fatores de Risco , Fatores Sexuais , Sinvastatina/administração & dosagem , Resultado do TratamentoRESUMO
Activation of leukocytes is obligatory for inflammation and atherogenesis by adhering to the endothelium via specific ligands. Although in vitro studies have shown that triglycerides (TG) can activate leukocytes, it is unknown whether this occurs in vivo. Using flowcytometry, we studied the expression of leukocyte activation markers CD11A, CD11B, CD62L (all involved in endothelium adhesion) and CD66B (a neutrophil degranulation marker) during a 6 h fat challenge (50 g/m2) and a water test in 10 healthy males (52 +/- 3 years). After fat, neutrophil counts were increased between t=1 and t =6 h, with a maximum at t=3 h (+32% versus t=0, P <0.05), while they remained unchanged after water. Both tests showed gradual lymphocyte count increments. The expression of activation markers on lymphocytes was low and showed comparable responses after both tests. After fat, a significant increase up to a maximum at t=6 h was seen for CD11B on monocytes and on neutrophils for CD11B, CD62L and CD66B. Postprandial activation of monocytes and neutrophils was higher after fat than after water. The maximal postprandial TG increment was significantly related to the increase of CD11B on monocytes (Pearson's R=0.64, P <0.05). In conclusion, postprandially there is a TG-specific increase of neutrophil counts and increased activation of monocytes and neutrophils. These results are suggestive of a pro-inflammatory situation that may correspond with increased adhesive capacity of these cells contributing to the inflammatory component of atherosclerosis.