Novel predictors of early atherosclerosis in nonalcoholic fatty liver disease.

Aim of the study: Non-alcoholic fatty liver disease (NAFLD) is regarded as the most relevant liver disease of the twenty-first century, affecting at least one third of the general population. NAFLD is associated with increased mortality due to cardiovascular disease (CVD) and cancer. The carotid intimal media thickness (CIMT), mean platelet volume (MPV) and endocan level could be markers for generalised atherosclerotic burden and endothelial dysfunction. The aims of the study were to evaluate the association between non-alcoholic fatty liver disease and early atherosclerosis by measuring CIMT, MPV and endocan level, as markers of endothelial dysfunction, in NAFLD patients. Material and methods: This cross-sectional study included 50 patients who were divided into two groups: group I included 25 subjects with NAFLD and group II included 25 healthy subjects. Complete blood count with MPV, liver profile, lipid profile, fasting blood glucose level, 2-hour postprandial kidney function test, and serum concentrations of endocan were measured for all patients. NAFLD fibrosis score (NFS) was calculated. Abdominal ultrasonography and carotid ultrasound scan for measurement of CIMT were performed. Results: Serum endocan levels, MPV and CIMT were significantly higher (p < 0.005) in NAFLD patients (0.6, 9.3 ±1.2 and 0.9 ±0.3 respectively) than healthy subjects (0.1, 8.1 ±0.6 and 0.6 ±0.1 respectively). The analysis of diagnostic performance of these factors revealed that they have good sensitivity and specificity in prediction of endothelial dysfunction with AUC (0.950, 0.844 and 0.849 respectively). Conclusions: Serum endocan levels, MPV and CIMT could be considered as good predictors of endothelial dysfunction and therefore early detection of subclinical atherosclerosis in NAFLD patients.

A combination of metformin and insulin improve cardiovascular and cerebrovascular risk factors in individuals with type 1 diabetes mellitus.

BACKGROUND: This study aims to further clarify whether the addition of metformin to insulin treatment improve cardiovascular and cerebrovascular risk factors in individuals with T1DM. METHODS: Electronic databases were searched for randomized controlled trials in which the efficacy and safety of metformin were compared with those of a placebo for risk factors of cardiovascular and cerebrovascular disease among individuals with T1DM, and a meta-analysis was conducted. RESULTS: Thirteen cardiovascular studies were identified. In the metformin group, mean carotid intimal media thickness was significantly reduced by 0.03 mm, ascending aortic pulse wave velocity by 6.3 m/s, descending aortic wall shear stress by 1.77 dyn/cm2 (P = 0.02), insulin daily dose by 0.05 U/kg/d, body weight by 2.27 kg, fat-free mass by 1.32 kg, body mass index by 0.58 kg/m2, hip circumference by 0.29 m, and low-density lipoprotein by 0.16 mmol/L, all above are P < 0.05. In the metformin group, flow-mediated dilation was increased by 1.29 %, glucose infusion rate/insulin by 18.22 mg/(kg⋅min)/µIU/µL, and waist-to-hip ratio by 0.02, all above are P < 0.00001. The metformin group showed no differences in blood pressure, reactive hyperemia index, waist circumference, triglyceride, total cholesterol, high-density lipoprotein cholesterol, or body mass index Z score. For cerebrovascular studies were identified. But none of them had a risk factor assessment. CONCLUSIONS: Metformin can ameliorate cardiovascular and cerebrovascular risk factors through non-hypoglycemic multiple pathways in individuals with T1DM.

Association between vascular endothelial dysfunction and the inflammatory marker neopterin in patients with classic congenital adrenal hyperplasia.

BACKGROUND AND AIMS: Patients with congenital adrenal hyperplasia (CAH) are at increased risk of cardiometabolic abnormalities. We aimed to evaluate vascular endothelial dysfunction and its association with serum neopterin (NP) levels in CAH patients. METHODS: The study included 40 patients, with a mean age of 14.8 ± 2.6 years; 28 (70%) subjects were females. They were compared with 40 healthy controls matched in anthropometric evaluation and measurement of fasting lipids, glucose, insulin, homeostasis model assessment for insulin resistance [HOMA-IR], and serum NP levels (nmol/L). Vascular ultrasound was used to measure brachial artery flow-mediated dilation (FMD%) and carotid intima-media thickness (CA-IMT). According to the degree of control on medical treatment, patients were classified into poor (n = 12) and good (n = 28) control groups. RESULTS: Compared to controls, CAH patients had lower brachial FMD% (4.60 ± 2.13 versus 9.31 ± 2.29, p = 0.001), similar CA-IMT (0.44 ± 0.08 versus 0.44 ± 0.06, p = nonsignificant) and higher NP (42.6 ± 11.6 versus 9.2 ± 3.8, p = 0.001). However, differences between poor and good control CAH patients were significant regarding FMD%, CA-IMT, and NP measurements. FMD% correlated significantly with NP (r = -0.54, p = 0.001), high-sensitivity CRP (r = -0.53, p = 0.001), HOMA-IR (r = -0.31, p = 0.01), CA-IMT (r = -0.22, p < 0.05), diastolic blood pressure (r = 0.32, p = 0.01) and systolic blood pressure (r = -0.022, p < 0.05). NP was the most significant independent predictor of FMD%, as determined by linear regression analysis (p = 0.001). CONCLUSIONS: Our study showed that CAH patients had endothelial dysfunction, which is an early process of vascular affection. This was significantly associated with NP levels, suggesting a crucial role of inflammation in the pathogenesis of vascular damage. Further studies are needed to confirm our findings and to investigate the exact role of NP, as either protective or proatherothrombotic.

Glycated apolipoprotein B-A surrogate marker of subclinical atherosclerosis.

AIMS: Sustained hyperglycemia is a causative factor for glycation of proteins. Glycated low-density lipoprotein (LDL) is strongly associated with an increased risk of CAD (Coronary Artery Disease) in diabetics. Hence, we planned to evaluate the association of glycated apo B with subclinical atherosclerosis. METHOD: Forty-five non obese and 45 obese diabetics were recruited. Glycated hemoglobin (HbA1c) levels were estimated by HPLC (High Pressure Liquid Chromatography) and small dense low-density lipoprotein (sdLDL) was calculated using standard formula. Plasma Insulin was done by RIA. Insulin resistance was calculated using homeostatic model assessment insulin resistance (HOMA-IR) model. Glycated apo B in serum was estimated using ELISA. Carotid intimal media thickness (CIMT) was estimated using B mode USG of carotid arteries. RESULTS: Glycated apo B levels were correlated significantly with fasting blood glucose (FBG) (p=0.001), post prandial glucose (PPG) (p=0.001), HbA1c (p=0.013). The percent glycated apo B levels correlated significantly with FBG (p=0.032), PPG (p=0.004) in obese diabetic group. Multivariate regression analysis of glycated apo B and percent glycated apo B, showed that glycated apo B (p=0.009) and percent glycated apo B (p=0.006) were significantly correlated to FPG in diabetic population. The percent glycated apo B was also significantly correlated to PPG (p=0.003) and sdLDL (p=0.009). CIMT levels were higher in obese diabetics with 2 plaques positive when compared to obese non diabetic controls; however levels were not statistically significant. CONCLUSION: Persistent hyperglycemia and sdLDL are independently associated with glycation of apo B. Presence of plaques and increased thickness of intima indicates that glycated apo B predisposes diabetics to atherosclerosis.

Avaliação da aterosclerose subclínica e de níveis plasmáticos de LDL minimamente modificada em pacientes com espondilite anquilosante e sua correlação com a atividade da doença / Evaluation of sub-clinical atherosclerosis and plasma levels of minimally modified LDL in patients with ankylosing spondylitis and its correlation with disease activity

INTRODUÇÃO: A aterosclerose acelerada foi demonstrada em algumas doenças autoimunes, principalmente lúpus eritematoso sistêmico e artrite reumatóide. Embora a alta prevalência do uso de corticosteróides possa ser um fator complicador, por causa de seus efeitos prejudiciais em diversos fatores de risco, acredita-se que, nesses pacientes, a inflamação sistêmica per se desempenhe papel importante na aterogênese. MÉTODOS: Avaliamos a aterosclerose subclínica e os níveis plasmáticos de LDL eletronegativa circulante em pacientes com espondilite anquilosante (EA). Catorze pacientes que atendiam aos critérios de Nova York modificados para EA foram comparados com 13 controles equiparados. Avaliamos a espessura da íntima-média (EIM) na carótida por ultrassonografia bilateral da artéria carótida comum, artéria carótida interna e na bifurcação. Os grupos foram homogêneos, no que tange a fatores de risco cardiovasculares. Apenas um paciente no grupo de EA estava sendo medicado com corticosteróide. RESULTADOS: A presença de inflamação ativa foi demonstrada por BASDAI elevado e níveis mais elevados de PCR em pacientes versus controles (12,36 vs. 3,45 mg/dl, P=0,002). Não observamos diferença na EIM da carótida entre os dois grupos, em qualquer local da artéria. A média de EIM (6 mensurações em 3 locais pré-especificados, bilateralmente) foi 0,72 ± 0,28 no grupo de EA e 0,70 ± 0,45 mm nos controles (P=0,91). Também não observamos diferença significativa na LDL minimamente modificada entre pacientes e controles (14,03 ± 17,40 vs. 13,21 ± 10,21; P=0,88). CONCLUSÕES: Pacientes com EA não demonstraram aumento na EIM da carótida, em comparação com controles. Do mesmo modo, os níveis plasmáticos circulantes de LDL(-) não diferiram significativamente nos dois grupos.

INTRODUCTION: Accelerated atherosclerosis has been shown in some autoimmune diseases, mainly in Systemic Lupus Erythematosus and Rheumatoid Arthritis. Although high prevalence of corticosteroids use may be a confounding factor due to their detrimental effects on several risk factors, systemic inflammation per se is supposed to play an important role in atherogenesis in these patients. METHODS: We have evaluated sub-clinical atherosclerosis and plasma levels of circulating electronegative LDL, which represents the fraction of LDL that is minimally modified, in patients with ankylosing spondylitis (AS). Fourteen patients who fulfilled the modified New York criteria for AS were compared with 13 paired controls. Carotid intimal-media thickness (IMT) was assessed by ultrasonography bilaterally in common carotid artery, internal carotid artery and in the bifurcation. Groups were homogeneous regarding cardiovascular risk factors. Only a single patient in AS group was in use of corticosteroid. RESULTS: The presence of active inflammation was demonstrated by elevated BASDAI and higher CRP levels and in patients versus controls (12.36 vs. 3.45 mg/dl, P = 0.002). No difference was found in carotid IMT between both groups, in any site of artery. Averaged IMT (6 measurements, at 3 pre-specified sites bilaterally) was 0.72 ± 0.28 in AS group and 0.70 ± 0.45 mm in controls (P = 0.91). Minimally modified LDL did not differ significantly either between patients and controls (14.03 ± 17.40 vs. 13.21 ± 10.21; P = 0.88). CONCLUSIONS: Patients with AS did not show increased carotid IMT in comparison to controls. In the same way, circulating plasma levels of LDL (-), did not differ significantly in both groups.