Simone M. Fischer

High circulating autoantibodies against human oxidized low-density lipoprotein are related to stable and lower titers to unstable clinical situation

BACKGROUND Oxidized lipoproteins and antibodies anti-oxidized low-density lipoprotein (anti-oxLDL) have been detected in human plasma and in atherosclerotic lesions. However, the role of these autoantibodies in the maintenance of vascular health or in the pathogenesis of acute vascular insults remains unclear. We examined the relationship of human immunoglobulin G (IgG) anti-oxLDL antibodies with cardiovascular disease risk markers in stable subjects and in patients after an acute coronary syndrome (ACS). METHODS Titers of human anti-oxLDL antibodies were measured in hypertensive subjects in primary prevention (n=94), without other risk factors, and in individuals after a recent ACS event who also had metabolic syndrome (n=116). Autoantibodies against copper ion oxidized LDL were measured by enzyme-linked-immunosorbent assay. RESULTS Anti-oxLDL titers were higher in hypertensive patients and these subjects presented lower high sensitivity C-reactive protein (hs-CRP) than those with ACS (p<0.0001). We found significant correlations between anti-oxLDL and hs-CRP (r=-0.284), body mass index (r=-0.256), waist circumference (r=-0.368), apolipoprotein B (r=-0.191), glucose (r=-0.303), systolic blood pressure (r=0.319), diastolic blood pressure (r=0.167), high-density lipoprotein cholesterol (r=0.224) and apolipoprotein A1 (r=0.257) (p<0.02 for all). After multiple linear regression hs-CRP, fasting glucose and waist circumference remained independently and inversely associated with anti-oxLDL. CONCLUSIONS Acute inflammatory and metabolic conditions decrease titers of human antibodies of IgG class against oxidized LDL, and that circulating anti-oxLDL antibodies could be associated with a protective role in atherosclerosis.

Early increase in autoantibodies against human oxidized low-density lipoprotein in hypertensive patients after blood pressure control.

BACKGROUND Oxidized lipoproteins and antioxidized low-density lipoprotein (anti-oxLDL) antibodies (Abs) have been detected in plasma in response to blood pressure (BP) elevation, suggesting the participation of the adaptive immune system. Therefore, treatment of hypertension may act on the immune response by decreasing oxidation stimuli. However, this issue has not been addressed. Thus, we have here analyzed anti-oxLDL Abs in untreated (naive) hypertensive patients shortly after initiation of antihypertensive therapeutic regimens. METHODS Titers of anti-oxLDL Abs were measured in subjects with recently diagnosed hypertension on stage 1 (n = 94), in primary prevention of coronary disease, with no other risk factors, and naive of antihypertensive medication at entry. Subjects were randomly assigned to receive perindopril, hydrochlorothiazide (HCTZ), or indapamide (INDA) for 12 weeks, with additional perindopril if necessary to achieve BP control. Abs against copper-oxidized LDL were measured by enzyme-linked immunosorbent assay. RESULTS Twelve-week antihypertensive treatment reduced both office-based and 24-h ambulatory BP measurements (P < 0.0005). The decrease in BP was accompanied by reduction in thiobarbituric acid-reactive substances (TBARS) (P < 0.05), increase in anti-oxLDL Ab titers (P < 0.005), and improvement in flow-mediated dilation (FMD) (P < 0.0005), independently of treatment. Although BP was reduced, we observed favorable changes in anti-oxLDL titers and FMD. CONCLUSIONS We observed that anti-oxLDL Ab titers increase after antihypertensive therapy in primary prevention when achieving BP targets. Our results are in agreement with the concept that propensity to oxidation is increased by essential hypertension and anti-oxLDL Abs may be protective and potential biomarkers for the follow-up of hypertension treatment.

Highly sensitive C-reactive protein and male gender are independently related to the severity of coronary disease in patients with metabolic syndrome and an acute coronary event

Patients with metabolic syndrome are at high-risk for development of atherosclerosis and cardiovascular events. The objective of this study was to examine the major determinants of coronary disease severity, including those coronary risk factors associated with metabolic syndrome, during the early period after an acute coronary episode. We tested the hypothesis that inflammatory markers, especially highly sensitive C-reactive protein (hsCRP), are related to coronary atherosclerosis, in addition to traditional coronary risk factors. Subjects of both genders aged 30 to 75 years (N = 116) were prospectively included if they had suffered a recent acute coronary syndrome (acute myocardial infarction or unstable angina pectoris requiring hospitalization) and if they had metabolic syndrome diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III. Patients were submitted to a coronary angiography and the burden of atherosclerosis was estimated by the Gensini score. The severity of coronary disease was correlated (Spearmans or Pearsons coefficient) with gender (r = 0.291, P = 0.008), age (r = 0.218, P = 0.048), hsCRP (r = 0.256, P = 0.020), ApoB/ApoA ratio (r = 0.233, P = 0.041), and carotid intima-media thickness (r = 0.236, P = 0.041). After multiple linear regression, only male gender (P = 0.046) and hsCRP (P = 0.012) remained independently associated with the Gensini score. In this high-risk population, male gender and high levels of hsCRP, two variables that can be easily obtained, were associated with more extensive coronary disease, identifying patients with the highest potential of developing new coronary events.

Perfil glicometabólico inicial em pacientes com síndrome coronariana aguda e síndrome metabólica

FUNDAMENTO: Pacientes con sindrome metabolico (SM) tienen alto riesgo coronario y la disfuncion de la celula beta o la resistencia a la insulina puede prever un riesgo adicional de eventos cardiovasculares precoces. OBJETIVO: Evaluar las alteraciones glucometabolicas precoces en pacientes con SM, pero sin diagnostico de diabetes tipo 2, tras el sindrome coronario agudo. METODOS: Un total de 114 pacientes fue sometido a la prueba oral de tolerancia a la glucosa (POTG), de un a tres dias tras el alta hospitalaria, y luego de infarto agudo de miocardio o angina inestable. Basado en el POTG, definimos tres grupos de pacientes: tolerancia normal a la glucosa (TNG; n=26), tolerancia alterada a la glucosa (TAG; n=39) o diabetes mellitus (DM; n=49). Se utilizo el Modelo de Evaluacion de la Homeostasis (HOMA-IR) para estimarse la resistencia a la insulina; se evaluo la responsividad de la celula beta a traves del indice insulinogenico de 30 minutos (ΔI30/ΔG30). RESULTADOS: Basado en el HOMA-IR, los pacientes con DM se mostraban mas insulinoresistentes que los individuos con TNG o TAG (p<0,001). De acuerdo con el indice insulinogenico, la responsividad de la celula beta tambien estaba alterada en individuos con DM (p<0,001 vs. TNG o TAG). CONCLUSIONES: Se encontraron altas tasas de alteraciones glucometabolicas tras el sindrome coronario agudo en pacientes con SM. Como esas anormalidades incrementan acentuadamente el riesgo de desenlaces adversos, el POTG precoz se puede utilizar en pacientes con SM para identificar a los que presentan mayor riesgo coronario.BACKGROUND Patients with metabolic syndrome (MetS) are at high coronary risk and beta-cell dysfunction or insulin resistance might predict an additional risk for early cardiovascular events. OBJECTIVE This study aimed to evaluate early glucometabolic alterations in patients with MetS, but without previously known type 2 diabetes, after acute coronary syndrome. METHODS A total of 114 patients were submitted to an oral glucose tolerance test (OGTT) 1-3 days after hospital discharge due to myocardial infarction or unstable angina. Based on the OGTT, we defined three groups of patients: normal glucose tolerance (NGT; n=26), impaired glucose tolerance (IGT; n=39), or diabetes (DM; n=49). The homeostasis model assessment (HOMA-IR) was used to measure insulin resistance; beta-cell responsiveness was assessed by the insulinogenic index at 30 min (DeltaI30/DeltaG30). RESULTS Based on the HOMA-IR, patients with DM were more insulin-resistant than those with NGT or IGT (p<0.001). According to the insulinogenic index, the beta-cell responsiveness was also impaired in subjects with DM (p<0.001 vs NGT or IGT). CONCLUSION High rates of glucometabolic alterations were found after acute coronary syndrome in patients with MetS. As these abnormalities markedly increase the risk for adverse outcomes, early OGTT among MetS patients might be used to identify those at the highest coronary risk.

Early glucometabolic profile in patients with acute coronary syndromes and metabolic syndrome

FUNDAMENTO: Pacientes con sindrome metabolico (SM) tienen alto riesgo coronario y la disfuncion de la celula beta o la resistencia a la insulina puede prever un riesgo adicional de eventos cardiovasculares precoces. OBJETIVO: Evaluar las alteraciones glucometabolicas precoces en pacientes con SM, pero sin diagnostico de diabetes tipo 2, tras el sindrome coronario agudo. METODOS: Un total de 114 pacientes fue sometido a la prueba oral de tolerancia a la glucosa (POTG), de un a tres dias tras el alta hospitalaria, y luego de infarto agudo de miocardio o angina inestable. Basado en el POTG, definimos tres grupos de pacientes: tolerancia normal a la glucosa (TNG; n=26), tolerancia alterada a la glucosa (TAG; n=39) o diabetes mellitus (DM; n=49). Se utilizo el Modelo de Evaluacion de la Homeostasis (HOMA-IR) para estimarse la resistencia a la insulina; se evaluo la responsividad de la celula beta a traves del indice insulinogenico de 30 minutos (ΔI30/ΔG30). RESULTADOS: Basado en el HOMA-IR, los pacientes con DM se mostraban mas insulinoresistentes que los individuos con TNG o TAG (p<0,001). De acuerdo con el indice insulinogenico, la responsividad de la celula beta tambien estaba alterada en individuos con DM (p<0,001 vs. TNG o TAG). CONCLUSIONES: Se encontraron altas tasas de alteraciones glucometabolicas tras el sindrome coronario agudo en pacientes con SM. Como esas anormalidades incrementan acentuadamente el riesgo de desenlaces adversos, el POTG precoz se puede utilizar en pacientes con SM para identificar a los que presentan mayor riesgo coronario.BACKGROUND Patients with metabolic syndrome (MetS) are at high coronary risk and beta-cell dysfunction or insulin resistance might predict an additional risk for early cardiovascular events. OBJECTIVE This study aimed to evaluate early glucometabolic alterations in patients with MetS, but without previously known type 2 diabetes, after acute coronary syndrome. METHODS A total of 114 patients were submitted to an oral glucose tolerance test (OGTT) 1-3 days after hospital discharge due to myocardial infarction or unstable angina. Based on the OGTT, we defined three groups of patients: normal glucose tolerance (NGT; n=26), impaired glucose tolerance (IGT; n=39), or diabetes (DM; n=49). The homeostasis model assessment (HOMA-IR) was used to measure insulin resistance; beta-cell responsiveness was assessed by the insulinogenic index at 30 min (DeltaI30/DeltaG30). RESULTS Based on the HOMA-IR, patients with DM were more insulin-resistant than those with NGT or IGT (p<0.001). According to the insulinogenic index, the beta-cell responsiveness was also impaired in subjects with DM (p<0.001 vs NGT or IGT). CONCLUSION High rates of glucometabolic alterations were found after acute coronary syndrome in patients with MetS. As these abnormalities markedly increase the risk for adverse outcomes, early OGTT among MetS patients might be used to identify those at the highest coronary risk.

Association of Multiple Genetic Variants with the Extension and Severity of Coronary Artery Disease

Background Metabolic syndrome (MS) is a condition that, when associated with ischemic heart disease and cardiovascular events, can be influenced by genetic variants and determine more severe coronary atherosclerosis. Objectives To examine the contribution of genetic polymorphisms to the extension and severity of coronary disease in subjects with MS and recent acute coronary syndrome (ACS). Methods Patients (n = 116, 68% males) aged 56 (9) years, with criteria for MS, were prospectively enrolled to the study during the hospitalization period after an ACS. Clinical and laboratory parameters, high-sensitivity C-reactive protein, thiobarbituric acid reactive substances, adiponectin, endothelial function, and the Gensini score were assessed. Polymorphisms of paraoxonase-1 (PON-1), methylenotetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (ENOS), angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL) were analysed by polymerase chain reaction (PCR) technique, followed by the identification of restriction fragment length polymorphisms (RFLP, and a genetic score was calculated. Parametric and non-parametric tests were used, as appropriate. Significance was set at p < 0.05. Results Polymorphisms of PON-1, MTHFR and ENOS were not in the Hardy-Weinberg equilibrium. The DD genotype of LPL was associated with higher severity and greater extension of coronary lesions. Genetic score tended to be higher in patients with Gensini score < P50 (13.7 ± 1.5 vs. 13.0 ± 1.6, p = 0.066), with an inverse correlation between genetic and Gensini scores (R = -0.194, p = 0.078). Conclusions The LPL polymorphism contributed to the severity of coronary disease in patients with MS and recent ACS. Combined polymorphisms were associated with the extension of coronary disease, and the lower the genetic score the more severe the disease.

Efeitos da terapia combinada atorvastatina e clopidogrel na biodisponibilidade da estatina e na função plaquetária em pacientes com doença coronária estável

ABSTRACT Effects of the Atorvastatin and ClopidogrelCombination Therapy on Statin Bioavailabilityand Platelet Function of Patients withStable Coronary Disease Background: Atorvastatin 80 mg is recommended in patientswith coronary artery disease to reduce cardiovascularevents, however, there is controversy regarding the phar-macokinetic interactions between high doses of statinsand the concomitant use of clopidogrel, since they share thesame biotransformation pathway. This study evaluated theeffects of the atorvastatin/clopidogrel combination therapyon the pharmacokinetics of statins and on platelet function ofpatients with stable coronary artery disease receivingchronic statins. Method: Patients were admitted four times(V1 to V4) to a day-clinic. Statin was discontinued sevendays (D) before the first admission. Patients then receivedatorvastatin 80 mg (D1 to D22) and clopidogrel 75 mg/day(D8 to D29). Fasting blood samples were obtained at alltime points for lipid measurements, platelet function tests(cone and plate technique), and quantification of atorvastatinplasma levels (liquid chromatography and mass spectrome-try).

Perfil glucometabólico inicial en pacientes con síndrome coronario agudo y síndrome metabólico

FUNDAMENTO: Pacientes con sindrome metabolico (SM) tienen alto riesgo coronario y la disfuncion de la celula beta o la resistencia a la insulina puede prever un riesgo adicional de eventos cardiovasculares precoces. OBJETIVO: Evaluar las alteraciones glucometabolicas precoces en pacientes con SM, pero sin diagnostico de diabetes tipo 2, tras el sindrome coronario agudo. METODOS: Un total de 114 pacientes fue sometido a la prueba oral de tolerancia a la glucosa (POTG), de un a tres dias tras el alta hospitalaria, y luego de infarto agudo de miocardio o angina inestable. Basado en el POTG, definimos tres grupos de pacientes: tolerancia normal a la glucosa (TNG; n=26), tolerancia alterada a la glucosa (TAG; n=39) o diabetes mellitus (DM; n=49). Se utilizo el Modelo de Evaluacion de la Homeostasis (HOMA-IR) para estimarse la resistencia a la insulina; se evaluo la responsividad de la celula beta a traves del indice insulinogenico de 30 minutos (ΔI30/ΔG30). RESULTADOS: Basado en el HOMA-IR, los pacientes con DM se mostraban mas insulinoresistentes que los individuos con TNG o TAG (p<0,001). De acuerdo con el indice insulinogenico, la responsividad de la celula beta tambien estaba alterada en individuos con DM (p<0,001 vs. TNG o TAG). CONCLUSIONES: Se encontraron altas tasas de alteraciones glucometabolicas tras el sindrome coronario agudo en pacientes con SM. Como esas anormalidades incrementan acentuadamente el riesgo de desenlaces adversos, el POTG precoz se puede utilizar en pacientes con SM para identificar a los que presentan mayor riesgo coronario.BACKGROUND Patients with metabolic syndrome (MetS) are at high coronary risk and beta-cell dysfunction or insulin resistance might predict an additional risk for early cardiovascular events. OBJECTIVE This study aimed to evaluate early glucometabolic alterations in patients with MetS, but without previously known type 2 diabetes, after acute coronary syndrome. METHODS A total of 114 patients were submitted to an oral glucose tolerance test (OGTT) 1-3 days after hospital discharge due to myocardial infarction or unstable angina. Based on the OGTT, we defined three groups of patients: normal glucose tolerance (NGT; n=26), impaired glucose tolerance (IGT; n=39), or diabetes (DM; n=49). The homeostasis model assessment (HOMA-IR) was used to measure insulin resistance; beta-cell responsiveness was assessed by the insulinogenic index at 30 min (DeltaI30/DeltaG30). RESULTS Based on the HOMA-IR, patients with DM were more insulin-resistant than those with NGT or IGT (p<0.001). According to the insulinogenic index, the beta-cell responsiveness was also impaired in subjects with DM (p<0.001 vs NGT or IGT). CONCLUSION High rates of glucometabolic alterations were found after acute coronary syndrome in patients with MetS. As these abnormalities markedly increase the risk for adverse outcomes, early OGTT among MetS patients might be used to identify those at the highest coronary risk.