Tatiana Helfenstein

The role of soluble fiber intake in patients under highly effective lipid-lowering therapy

BackgroundIt has been demonstrated that statins can increase intestinal sterol absorption. Augments in phytosterolemia seems related to cardiovascular disease.ObjectiveWe examined the role of soluble fiber intake in endogenous cholesterol synthesis and in sterol absorption among subjects under highly effective lipid-lowering therapy.DesignIn an open label, randomized, parallel-design study with blinded endpoints, subjects with primary hypercholesterolemia (n = 116) were assigned to receive during 12 weeks, a daily dose of 25 g of fiber (corresponding to 6 g of soluble fibers) plus rosuvastatin 40 mg (n = 28), rosuvastatin 40 mg alone (n = 30), sinvastatin 40 mg plus ezetimibe 10 mg plus 25 g of fiber (n = 28), or sinvastatin 40 mg plus ezetimibe 10 mg (n = 30) alone.ResultsThe four assigned therapies produced similar changes in total cholesterol, LDL-cholesterol, and triglycerides (p < 0.001 vs. baseline) and did not change HDL-cholesterol. Fiber intake decreased plasma campesterol (p < 0.001 vs. baseline), particularly among those patients receiving ezetimibe (p < 0.05 vs. other groups), and β-sitosterol (p = 0.03 vs. baseline), with a trend for lower levels in the group receiving fiber plus ezetimibe (p = 0.07). Treatment with rosuvastatin alone or combined with soluble fiber was associated with decreased levels of desmosterol (p = 0.003 vs. other groups). Compared to non-fiber supplemented individuals, those treated with fibers had weight loss (p = 0.04), reduced body mass index (p = 0.002) and blood glucose (p = 0.047).ConclusionAmong subjects treated with highly effective lipid-lowering therapy, the intake of 25 g of fibers added favorable effects, mainly by reducing phytosterolemia. Additional benefits include improvement in blood glucose and anthropometric parameters.

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.

Impaired glucose tolerance plus hyperlipidaemia induced by diet promotes retina microaneurysms in New Zealand rabbits

With the increasing prevalence of diabetes mellitus and metabolic syndrome worldwide, experimental models are required to better understand the pathophysiology and therapeutic approaches to preserve pancreatic beta cells, attenuate atherosclerosis and protect target organs. The aims of this study were to develop an experimental model of impaired glucose tolerance combined with hypercholesterolaemia induced by diet and assess metabolic alterations and target organ lesions. New Zealand male rabbits were fed high‐fat/high‐sucrose (10/40%) and cholesterol‐enriched diet for 24 weeks, when they were sacrificed. Biochemistry, fundus photographs with fluorescein angiography and pathological analyses were performed. Cholesterol‐fed and normal animals of same age were compared. Results: The animals with diet‐induced impaired glucose tolerance combined with hypercholesterolaemia gained weight, increased blood glucose, total cholesterol, LDL‐C and triglycerides and decreased HDL‐C (P < 0.05 vs. baseline). Fructosamine levels and the homeostasis model assessment of insulin resistance (HOMA‐IR) index were increased, while there was a reduction in the HOMA‐β (P < 0.05 for all vs. baseline). Histomorphologic findings of this model were aortic atherosclerosis, hepatic steatofibrosis and glomerular macrophage infiltration. Early clinical features of diabetic retinopathy with hyperfluorescent dots consistent with presence of retina microaneurysms were seen since week 12, progressing up to the end of the experiment (P < 0.0005 vs. baseline and 12 weeks). Our model reproduced several metabolic characteristics of human diabetes mellitus and promoted early signs of retinopathy. This non‐expensive model is suitable for studying mechanistic pathways and allowing novel strategic approaches.

Effects of two lipid lowering therapies on immune responses in hyperlipidemic subjects

AIMS To compare the effects of two of the most effective lipid-lowering therapies with similar LDL-cholesterol reduction capacity on the innate and adaptive immune responses through the evaluation of autoantibodies anti-oxidized LDL (anti-oxLDL Abs) and electronegative LDL [LDL(-)] levels. MAIN METHODS We performed a prospective, randomized, open label study, with parallel arms and blinded endpoints. One hundred and twelve subjects completed the study protocol and received rosuvastatin 40 mg or ezetimibe/simvastatin 10/40 mg for 12 weeks. Lipids, apolipoproteins, LDL(-), and anti-oxLDL Abs (IgG) were assayed at baseline and end of study. KEY FINDINGS Main clinical and laboratory characteristics were comparable at baseline. Lipid modifications were similar in both treatment arms, however, a significant raise in anti-oxLDL Abs levels was observed in subjects treated with rosuvastatin (p=0.026 vs. baseline), but not in those receiving simvastatin/ezetimibe. (p=0.233 vs. baseline), thus suggesting modulation of adaptive immunity by a potent statin. Titers of LDL(-) were not modified by the treatments. SIGNIFICANCE Considering atherosclerosis as an immune disease, this study adds new information, showing that under similar LDL-cholesterol reduction, the choice of lipid-lowering therapy can differently modulate adaptive immune responses.

Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies

Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies.

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.

Dietary Hyperlipidemia and Retinal Microaneurysms

Cardiovascular risk factors have a close relationship with vascular damage and inflammatory status and are mainly related to lifestyle, with diet playing a pivotal role. Experimental and clinical data support a link between diet, risk factors, and retinal vascular abnormalities. Diabetes, obesity, hypertension, dyslipidemia, and metabolic syndrome are associated with venular dilatation, arteriolar narrowing, arteriovenous ratio, retinal artery emboli, vein occlusion, hard exudates, and macular edema in humans. Inflammation and endothelial dysfunction are the underlying mechanisms of the retinal vascular abnormalities. Hemorrhages and microaneurysms are signs of diabetic retinopathy, whereas in hypertension, generalized and focal arteriolar narrowing, flame- and blot-shaped retinal hemorrhages, arteriovenous nicking, optic disc swelling, and cotton-wool spots can be seen. Angiotensin II type 1 receptor overexpression, endothelial dysfunction, and decreased glucose uptake on hyperinsulinemic state contribute to arterial damage. These aspects highlight the importance of a well-balanced diet for controlling modifiable risk factors and preventing target organ lesions.

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.