Effect of anti TNFalpha therapy on arterial diameter and wall shear stress and HDL cholesterol

It has been recently hypothesized that both TNFalpha and anti TNFalpha treatment have a stimulating effect on nitric oxide synthesis and release. Moreover, an in vitro experiment has demonstrated that HDL-cholesterol binds TNFalpha. Aims of our study were to investigate wall shear stress of peripheral arteries and endothelial function of brachial artery in subjects with Rheumatoid Arthritis (RA) at baseline and after infliximab. Moreover, we evaluated the effect of anti TNFalpha therapy on lipid profile. Ten patients with RA received infliximab therapy at weeks 0, 2 and 6. Lipids and vascular parameters were measured before and the day after each infusion. After the first treatment, FMD increased (3.7 +/- 1.9% versus 17.5 +/- 2.9%, P < 0.01) and common carotid and brachial artery diameters decreased (5.9 +/- 0.2 turn versus 5.5 +/- 0.2 mm; 3.5 +/- 0.4 mm versus 3.1 +/- 0.4 mm, respectively, P < 0.005). Common carotid and brachial artery wall shear stress increased (21.1 +/- 1.1 dynes/cm(2) versus 23.9 +/- 1.4 dynes/cm(2); 42.0 +/- 4.7 dynes/cm(2) versus 51.6 +/- 5.7 dynes/cm(2), p < 0.01). Similar results were observed after the second and third infusion. All these parameters returned to pre-treatment level at the following infusion. HDL-cholesterol and apolipoprotein AI significantly decreased after each treatment (1st treatment: 1.4 +/- 0.05 mmol/L versus 1.2 +/- 0.06 mmol/L, P < 0.01; 1.73 +/- 0.05 g/L versus 1.57 +/- 0.02 g/L, P < 0.03). The present data show vasoconstriction and an increase of wall shear stress in studied arteries after infliximab. HDL cholesterol is reduced by treatment and does not seem to influence FMD. (C) 2004 Elsevier Ireland Ltd. All rights reserved

Components of the metabolic syndrome and carotid atherosclerosis role of elevated blood pressure

Elevated blood pressure is among the factors that contribute to the metabolic syndrome (MetS). It is not known whether subjects with MetS and elevated blood pressure are at the same cardiovascular risk as subjects with MetS but without elevated blood pressure. To clarify this point, we have evaluated the prevalence of carotid atherosclerosis in subjects with MetS with or without elevated blood pressure. A large population was examined ( 842 women and 1011 men). Blood pressure, lipids, glucose, and waist were measured by routine methods. Carotid atherosclerosis was evaluated by echo Doppler examination. The prevalence of MetS was 24.4% in women and 28.7% in men. The prevalence of carotid atherosclerosis was 35.1% in women and 37.3% in men (p=NS), and increased with increasing number of MetS components. Age, smoking, and systolic blood pressure (SBP) were associated with the presence of carotid atherosclerosis ( logistic model), whereas age, high-density lipoprotein cholesterol, and SBP were associated with the extent of atherosclerosis ( linear model). When comparing subjects with an equal number of MetS components, the prevalence of carotid atherosclerosis was significantly higher in subjects with elevated blood pressure than in those without. No difference in carotid atherosclerosis prevalence was found in subjects bearing or not bearing components of the syndrome other than elevated blood pressure. The present findings demonstrate that subjects with MetS and elevated blood pressure have increased carotid atherosclerosis compared with subjects with MetS but without elevated blood pressure. The diagnosis of MetS per se might not adequately identify subjects at elevated cardiovascular risk

Components of the metabolic syndrome and carotid atherosclerosis: role of elevated blood pressure.

Elevated blood pressure is among the factors that contribute to the metabolic syndrome (MetS). It is not known whether subjects with MetS and elevated blood pressure are at the same cardiovascular risk as subjects with MetS but without elevated blood pressure. To clarify this point, we have evaluated the prevalence of carotid atherosclerosis in subjects with MetS with or without elevated blood pressure. A large population was examined (842 women and 1011 men). Blood pressure, lipids, glucose, and waist were measured by routine methods. Carotid atherosclerosis was evaluated by echo Doppler examination. The prevalence of MetS was 24.4% in women and 28.7% in men. The prevalence of carotid atherosclerosis was 35.1% in women and 37.3% in men (p=NS), and increased with increasing number of MetS components. Age, smoking, and systolic blood pressure (SBP) were associated with the presence of carotid atherosclerosis (logistic model), whereas age, high-density lipoprotein cholesterol, and SBP were associated with the extent of atherosclerosis (linear model). When comparing subjects with an equal number of MetS components, the prevalence of carotid atherosclerosis was significantly higher in subjects with elevated blood pressure than in those without. No difference in carotid atherosclerosis prevalence was found in subjects bearing or not bearing components of the syndrome other than elevated blood pressure. The present findings demonstrate that subjects with MetS and elevated blood pressure have increased carotid atherosclerosis compared with subjects with MetS but without elevated blood pressure. The diagnosis of MetS per se might not adequately identify subjects at elevated cardiovascular risk

The influence of PON1 192 polymorphism on endothelial function in diabetic subjects with or without hypertension.

Hypertension and type 2 diabetes mellitus (T2DM) cause endothelial dysfunction probably through increased oxidant stress. Paraoxonase (PON1) is an high-density lipoprotein (HDL)-linked anti-oxidant enzyme whose capacity is influenced by a genetic polymorphism at codon 192. In the present study we have investigated the role of PON1 polymorphism on endothelial function in subjects with T2DM with or without hypertension. Three groups of male subjects were enrolled: 65 healthy control subjects without T2DM or hypertension (CON), 51 with only T2DM (DM), and 67 with both hypertension and T2DM (HYP+DM). The PON1 Gln192Arg polymorphism was determined by polymerase chain reaction (PCR) amplification and restriction analysis. Endothelial function was evaluated as flow-mediated vasodilatation (FMD) of the brachial artery after forearm ischemia. Data were analyzed according to the presence or absence of the Arg allele. Subjects with T2DM had markedly impaired FMD, compared with those of the CON group. In the CON and HYP+DM groups no difference was observed in FMD between subjects homozygous for the Gln allele and those carrying the Arg allele. In the DM group FMD was lower among those carrying the Arg allele compared with Gln/Gln homozygotes (2.1+/-2.4% vs. 6.2+/-5.2%, p=0.002). In conclusion, the present findings demonstrated that FMD was less impaired in normotensive diabetic subjects homozygous for the Gln allele, consistent with the notion that this isoform has a more effective antioxidant action that serves to protect circulating low-density lipoprotein (LDL). Hypertension seems to abolish the protective effect of the Gln isoform. These findings, however, warrant further investigation to clarify their clinical import

High GADA titer increases the risk of insulin requirement in LADA patients: A 7-year follow-up (NIRAD study 7)

Objective: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. Methods: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. Results: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes ( P2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (PIC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients

High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7).

OBJECTIVE: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. METHODS: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. RESULTS: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P&lt;0.0001 for both). A BMI of ≤25 kg/m2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P&lt;0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P&lt;0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P&lt;0.0001, OR=6.95). CONCLUSIONS: High GADA titer, BMI ≤ 25, ZnT8 and IA-2IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients