Chronic renal impairment and DDAH2-1151 A/C polymorphism determine ADMA levels in type 2 diabetic subjects.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS). Increased levels of ADMA cause impaired vasodilation, leading to endothelial dysfunction and a higher risk for cardiovascular events. In patients with a chronic kidney disease, increased ADMA levels are reported to play a role in the pathogenesis of accelerated atherosclerosis and are an independent risk marker leading to end-stage renal disease and mortality. Circulating ADMA is metabolized by the action of dimethylarginine dimethylamino hydrolase (DDAH) and DDAH2 isoform is the most prevalent in tissues expressing endothelial NOS. DDAH and NOS are co-expressed in the same kidney regional sites supporting the hypothesis that a strict and specific regulation of intracellular ADMA levels is crucial for NO generation in the kidney. Starting from these findings, the study aims to investigate the role of DDAH2 gene promoter polymorphism at position -1151 A/C in determining the levels of ADMA in type 2 diabetic patients (T2DM) with chronic renal impairment. METHODS: Three groups of carefully selected subjects of both sexes were enrolled and compared. The first group (control subjects) comprised 286 non-diabetic subjects (mean age 55.8 ± 11.4 years), the second group (T2DM uncomplicated subjects) was made up of 322 T2DM subjects without complications (mean age 64.9 ± 9.6 years) whereas the third group (T2DM CRF subjects) included 110 T2DM patients with chronic renal impairment. The rs805304 DDAH2-1151 A/C promoter polymorphism was determined by a polymerase chain reaction-restriction fragment length polymorphism approach. Results T2DM CRF subjects showed significant increased plasma levels of ADMA with respect to those of T2DM uncomplicated subjects and control subjects (0.51 versus 0.39 versus 0.37 µmol/L, P = 0.002, respectively). Analysis of variance showed an interaction between DDAH2-1151 C carrier and groups on ADMA plasma levels (F = 4.36; P < 0.05). ADMA plasma levels were also dependent on groups (F = 4.96; P < 0.01). CONCLUSIONS: Our work demonstrates that rs805304 DDAH2-1151 polymorphism plays a central role in determining ADMA in diabetic renal impairment, where patients with DDAH2-1151 C carriers showed the highest ADMA levels. This unfavourable genetic profile is highlighted by pathological kidney conditions such as diabetic CRF. These findings could open new insights on the pathways involving ADMA/DDAH/NOS in the development and progression of chronic renal impairment and therefore of the other micro- macrovascular diabetic complications.

Combination of biomarkers to predict mortality in elderly patients with myocardial infarction.

OBJECTIVE: The elderly subjects affected by Acute Myocardial Infarction (AMI) have the highest risk of mortality. Our study was designed to improve the capability of mortality risk stratification in elderly AMI patients through the concurrent evaluations of different biomarkers, including genetic markers. METHODS AND RESULTS: One-year follow-up study was performed in 250 elderly AMI patients. The combination of high total Homocysteine (tHcy), low folate and vitamin B12 plasma levels (18.0+/-9.0 micromol/l; 4.4+/-1.2 ng/ml; 404.2+/-287.5 pg/ml, respectively) and elevated CRP plasma levels (> or =6 mg/dl) identify the highest-risk pathway of heart mortality (RR=4.20, IC 95% 1.62-10.89, P<0.002) with respect to the combination of low total tHcy, high folate and vitamin B12 plasma levels (12.4+/-5.2 micromol/l; 8.9+/-2.5 ng/ml; 546.9+/-379.8 pg/ml, respectively) and low CRP plasma levels (<6 mg/dl). CONCLUSION: In elderly AMI patients the concomitant elevation of CRP and tHcy, associated with folate and vitamin B12 low levels, could be considered a significant predictive heart mortality risk factor.

A study on the action of vitamin E supplementation on plasminogen activator inhibitor type 1 and platelet nitric oxide production in type 2 diabetic patients.

BACKGROUND AND AIM: Type 2 diabetic (T2DM) patients show decreased fibrinolysis, mainly linked to high plasminogen activator inhibitor type 1 (PAI-1) production, together with a reduced bioavailability of nitric oxide and an impairment in Na(+)/K(+)-ATPase activity possibly involved in increased cardiovascular risk. Vitamin E is the major natural lipid-soluble antioxidant in human plasma. The present work was conducted in order to measure PAI-1, ICAM and VCAM-1 plasma levels, platelet nitric oxide production and membrane Na(+)/K(+)-ATPase activity in type 2 diabetic subjects treated with vitamin E (500 IU/day) for 10 weeks and then followed for other 20 weeks. METHODS AND RESULTS: Thirty-seven T2DM patients (24 males and 13 females) were studied. None of them were affected by any other disease or diabetic complications. Significant differences were detected for PAI-1 antigen (p<0.001), PAI-1 activity (p<0.001), nitric oxide (NO) production (p<0.001), and Na(+)/K(+)-ATPase activity (p<0.001) among the 4 phases of the study. A significant decrease both in ICAM and VCAM-1 plasma levels was also found at the 10th week compared with baseline (respectively p<0.001 and p<0.05). CONCLUSION: Our data suggest that vitamin E counteracts endothelial activation in T2DM patients possibly representing a new tool for endothelial protection.

Platelet nitric oxide production and IR: relation with obesity and hypertriglyceridemia.

BACKGROUND AND AIM: Three NOS isoforms are responsible for nitric oxide production in various tissues. Endothelial constitutive NOS is expressed in vascular endothelium and in platelets, contributing to vascular tone regulation and platelet aggregation. The aim of the present work was to examine eNOS polymorphism, to find a correlation with platelet NO production and degree of insulin resistance (IR) in non-diabetic subjects and in patients affected by type 2 diabetes. METHODS AND RESULTS: Seventy-one non-diabetic subjects and 37 patients affected by Type 2 diabetes were recruited. The subjects were subdivided into 3 groups as cut-off for the definition of an insulin resistant state: IR non-diabetic subjects, insulin sensitive subjects, and insulin-resistant patients affected by Type 2 diabetes. Plasma glyco-metabolic parameters, platelet nitric oxide production, endothelial nitric oxide synthase (eNOS) gene polymorphism were measured in all subjects enrolled. Significant differences between groups were found in BMI, fasting glycaemia, fructosamine and HbA(1c), triglycerides and HDL cholesterol levels. Evaluating all the subjects, platelet NO production was significantly related with BMI, waist circumference, and triglycerides concentrations, thus suggesting an association between increased platelet NO production, obesity and hypertriglyceridemia, independent of the degree of insulin-resistance. CONCLUSION: The modified platelet NO synthesis does not seem to be due to eNOS Glu298Asp polymorphism, while it can be hypothesized that it is caused by an iNOS induction, present in obesity, hypertriglyceridemia and in type 2 diabetes.

The PON1192RR genotype is associated with a higher prevalence of arterial hypertension.

OBJECTIVE: To investigate whether genetic polymorphism of paraoxonase (PON1192), an enzyme which protects low density lipoprotein from oxidation, is related to the prevalence of arterial hypertension. METHODS: Two groups of carefully selected subjects of both sexes were enrolled and compared. The first group comprised 219 healthy controls (mean age 46.5 +/- 14.7 years) whereas the second comprised 119 hypertensive patients (mean age 47.9 +/- 10.5 years) with untreated essential arterial hypertension. Anthropometric and biochemical parameters were within the normal range in both groups. The PON1192 polymorphism was determined by a polymerase chain reaction-restriction fragment length polymorphism approach. RESULTS: In hypertensive patients, a significant increase of the frequency of PON1192RR genotype with respect to healthy controls (14.3 versus 5.0%, P = 0.003) was found. Logistic regression analyses also showed that the PON1192RR genotype was independently associated with a four-fold increase in susceptibility to arterial hypertension (odds ratio = 4.31; 95% confidence interval = 1.63-11.43, P = 0.003). CONCLUSIONS: The finding that PON1192RR genotype is associated with a higher prevalence of arterial hypertension may contribute to improving the stratification of cardiovascular risk within a population aged 30-60 years. Determination of the PON1192 polymorphism may help to identify those individuals who are prone to developing cardiovascular diseases at an early stage, suggesting the need for close monitoring of cardiovascular risk factors before the onset of cardiovascular disease.

[Bariatric pacing. A new frontier for the treatment of severe obesity]. / Pacing gastrico. Una nuova frontiera nel trattamento dell'obesità grave.

A new bariatric procedure, gastric myo-electrical stimulation, has been developed. The Implantable Gastric Stimulator (IGS) induces satiety while avoiding the morbidity and mortality of the common restrictive malabsorptive or combination restrictive or malabsorptive procedure. The procedure does not alter normal anatomy. Advantages of IGS therapy are simplicity, a more rapid procedure, a safer procedure and the absence of nutritional side effects associated with some bariatric operations. The devices consists of a stimulation lead implanted in the gastric wall, connected to an electronic pulse generator (Transcend IGS, Transneuronix Inc, Mt. Arlington, NJ, SA) implanted subcutaneously into the abdominal wall. The lead is implanted by laparoscopy into the muscular layer of the lesser curvature of the stomach at the end of the pes anserinus area. The generator is connected (proper connection, was confirmed via radio frequency programming), and implanted subcutaneously. The mechanism of action of the IGS therapy requires a concomitant program of diet and lifestyle modifications in order to optimise the results.

Psychological, neuroendocrine and immune measures in non spousal carers of disabled elderly in Italy.

OBJECTIVES: The purpose of this study was to determine whether psychological well being as well as metabolic, neuroendocrine and immune functions were different in non spousal primary caregivers of disabled elderly than in controls. SETTING AND DESIGN: We randomly recruited 38 primary family carers of over 65 year old recipients of health home care services and 37 controls stratified according to sex and age. METHOD: Data were collected on psychological wellbeing (including anxiety, depression and self-perceived quality of life), on neuroendocrine and immune conditions (haemanalysis and metabolic signs, plasma ACTH, cortisol, prolactin, intra-lymphocyte content of beta-endorphins, NK cell activity and number), as well as on the incidence and severity of influenza disease during previous winter. RESULTS: Caregivers showed greater anxiety, although mean scores did not reach pathological levels. Neither depression nor satisfaction on quality of life did differ significantly, nor differences in haemanalisis and metabolic signs were found, apart from leukocyte and lymphocyte number, which was significantly lower in carers. Plasma levels of ACTH, cortisol and prolactin, the intra-lymphocyte content of beta-endorphins as well as the NK cell number and cytotoxicity did not show significant differences. Incidence and severity of influenza episodes was also similar, whereas the duration of influenza disease showed to be significantly longer. CONCLUSIONS: Non spousal caregivers of disabled elderly suffer from only slight alterations of psychological, endocrine and immune parameters, and do not respond very differently to influenza disease. This does not support therefore any generic privilege for them in the allocation of public support or respite services.

The p53 codon 72 (Arg72Pro) polymorphism is associated with the degree of insulin resistance in type 2 diabetic subjects: a cross-sectional study.

Tumor suppressor protein p53 has been demonstrated to regulate genes involved in energy generating metabolic pathways and apoptosis. To date, a new field of research is the involvement of TP53 codon 72 (Arg72Pro) polymorphism in the diabetic disease. The aim of this study was to evaluate whether the genotype and the related genetic models of Arg72Pro polymorphism of TP53 (rs1042522) are associated with insulin resistance and its metabolic parameters in diabetic and non-diabetic subjects. We examined 335 type 2 diabetic patients (65.5 ± 8.4 years) and 367 non-diabetic subjects (60.5 ± 11.7 years). The results were validated in a validation sample consisting of 199 type 2 diabetic (66.2 ± 8.5 years) and 224 non-diabetic subjects (61.2 ± 12.7 years). In the study sample, the analysis of covariance, adjusted for the effects of age, gender and BMI, showed a significant genotype-diabetes effect on insulin resistance evaluated by HOMA-IR (p = 0.038). This result was mediated by variations in fasting plasma insulin (p = 0.027), as no TP53 genotype-diabetes effects were detected for fasting plasma glucose. In particular, in the diabetic subjects, Pro/Pro genotype was associated with lower values of HOMA-IR with respect to Arg/Arg (p = 0.013) and Arg/Pro (p = 0.006) carriers. No difference in HOMA-IR between diabetic and non-diabetic Pro/Pro carriers was found. Significant recessive model-diabetes interaction effects on fasting insulin and HOMA-IR adjusted for age, sex and BMI were found (p = 0.007 and p = 0.029, respectively). Linear regression analyses, based on the assumption of an additive genetic model adjusted for age, sex and BMI, highlight p53 gene-diabetes interaction effects on fasting insulin (ß = -1.27; p = 0.001) and HOMA-IR (ß = -0.22; p = 0.006). The results of statistical analyses on fasting insulin and HOMA-IR were all confirmed in the validation sample. Furthermore, the logistic regression models confirmed that the effect of HOMA-IR levels on diabetes was moderated by Pro/Pro genotype in both study and validation samples (OR = 0.29, p = 0.034, 95 % CI = 0.09-0.91, OR = 0.37, p = 0.035, 95 % CI = 0.15-0.93, respectively). Our findings suggest that p53 codon 72 (Arg72Pro) polymorphism influences insulin resistance in type 2 diabetic patients independently of body mass.

Remodelling of biological parameters during human ageing: evidence for complex regulation in longevity and in type 2 diabetes.

Factor structure analyses have revealed the presence of specific biological system markers in healthy humans and diseases. However, this type of approach in very old persons and in type 2 diabetes (T2DM) is lacking. A total sample of 2,137 Italians consisted of two groups: 1,604 healthy and 533 with T2DM. Age (years) was categorized as adults (≤65), old (66-85), oldest old (>85-98) and centenarians (≥99). Specific biomarkers of routine haematological and biochemical testing were tested across each age group. Exploratory factorial analysis (EFA) by principal component method with Varimax rotation was used to identify factors including related variables. Structural equation modelling (SEM) was applied to confirm factor solutions for each age group. EFA and SEM identified specific factor structures according to age in both groups. An age-associated reduction of factor structure was observed from adults to oldest old in the healthy group (explained variance 60.4% vs 50.3%) and from adults to old in the T2DM group (explained variance 57.4% vs 44.2%). Centenarians showed three-factor structure similar to those of adults (explained variance 58.4%). The inflammatory component became the major factor in old group and was the first one in T2DM. SEM analysis in healthy subjects suggested that the glucose levels had an important role in the oldest old. Factorial structure change during healthy ageing was associated with a decrease in complexity but showed an increase in variability and inflammation. Structural relationship changes observed in healthy subjects appeared earlier in diabetic patients and later in centenarians.

Social isolation risk factors in older hospitalized individuals.

BACKGROUND: Elderly people are particularly vulnerable to the effects of social reduction, so there is an urgent need to identify the risks associated with social isolation. The aim of this paper was to analyze associations between psychological, socio-demographic, functional aspects on the risk of social isolation, mortality and re-hospitalization in older persons. METHODS: This is a longitudinal study on 580 hospitalized elderly sample aged ≥70yrs recruited from 2005 to 2007 in the Geriatrics Operative Unit of INRCA in Fermo, Italy. The comprehensive geriatric assessment (CGA) was used. Outcome measures included 36-month mortality and re-hospitalization. RESULTS: In all patients, approximately 20% (n=112) of the subjects were socially isolated. Women perceived their social support significantly worse than men (77.7 vs. 22.3%; p<0.001). A multiple logistic regression analysis (goodness of fit χ(2)=102.86, p<0.001) with risk of social isolation as the dependent variable, showed that women were at a greater risk than men for social isolation (OR=1.99, 95% CI=1.13-3.50). Furthermore, patients with a higher number of family components (OR=0.72, 95% CI=0.59-0.88) and good parameters of quality of life (PCS-12: OR=0.94, 95% CI=0.91-0.98; MCS-12: OR=0.94, 95% CI=0.92-0.97) were less likely to be socially isolated. Cox regression models adjusted for gender, quality of life and number of family components, showed that the social isolation did not predict mortality (HR=1.44, 95% CI=0.84-2.46, p=0.19), but was associated with higher re-hospitalization rates (HR=1.28, 95% CI=1.02-1.59, p=0.03). CONCLUSIONS: Our findings highlight several aspects related to the risk of social isolation and re-hospitalization in a specific group of older persons.

Development and validation of the HOPE prognostic index on 24-month posthospital mortality and rehospitalization: Italian National Research Center on Aging (INRCA).

BACKGROUND: A fast and simple tool is needed to test for the risk of mortality and rehospitalization in older patients. OBJECTIVE: The aim of this study was to construct and validate a prognostic index using specific items from the Comprehensive Geriatric Assessment (CGA) in a large population of older hospitalized adults. METHOD: This was a prospective study of a 24-month follow-up period, between 2005 to 2008 in 3,043 elderly patients (mean age, 81 ± 6) discharged from three acute geriatric wards in the Marche region of Italy. Baseline predictors of demographics and 25 items from the CGA regarding functional and cognitive status, depression, co-morbidity, social isolation, and quality of life were used to build a summary score, the Hospitalized Older Patient Examination (HOPE) Index. The HOPE index was developed in 1,533 patients and validated in 1,510 consecutively hospitalized patients. Outcome measures were 24-month mortality and rehospitalization. RESULTS: Three risk categories of HOPE based on the best sensitivity and specificity for mortality and rehospitalization were: Low (≤4), moderate (4-8), and high (≥8). Categorizing data across the HOPE index, mortality ranged from 7.9% to 14.5% in the development cohort and 6.2% to 14.0% in the validation cohort, whereas rehospitalization ranged from 68.3% to 79.4% and 69.8% to 79.8%, respectively. Kaplan-Meier survival curves demonstrated that risk for mortality increased with a worsening across the HOPE index (p < 0.001). In the development and validation cohorts, a close agreement was found for HOPE on mortality and rehospitalization with a receiver operating characteristic (ROC) of 0.69 (95% confidence interval [CI] 0.61-0.74) vs. 0.67 (95% CI 0.57-0.70) and rehospitalization of 0.62 (95% CI 0.58-0.66) vs. 0.60 (95% CI 0.56-0.63), respectively. In the development and validation cohorts, Cox proportional hazard models showed that a high HOPE index predicted risks of 2.38 (1.34-4.23) and 2.86 (1.24-6.61) on mortality and 1.27 (1.09-1.44) and 1.37 (1.10-1.64) on rehospitalization, respectively. CONCLUSIONS: HOPE may be useful for long-term clinical planning, discharge, and follow-up.

Mitochondrial DNA backgrounds might modulate diabetes complications rather than T2DM as a whole.

Mitochondrial dysfunction has been implicated in rare and common forms of type 2 diabetes (T2DM). Additionally, rare mitochondrial DNA (mtDNA) mutations have been shown to be causal for T2DM pathogenesis. So far, many studies have investigated the possibility that mtDNA variation might affect the risk of T2DM, however, when found, haplogroup association has been rarely replicated, even in related populations, possibly due to an inadequate level of haplogroup resolution. Effects of mtDNA variation on diabetes complications have also been proposed. However, additional studies evaluating the mitochondrial role on both T2DM and related complications are badly needed. To test the hypothesis of a mitochondrial genome effect on diabetes and its complications, we genotyped the mtDNAs of 466 T2DM patients and 438 controls from a regional population of central Italy (Marche). Based on the most updated mtDNA phylogeny, all 904 samples were classified into 57 different mitochondrial sub-haplogroups, thus reaching an unprecedented level of resolution. We then evaluated whether the susceptibility of developing T2DM or its complications differed among the identified haplogroups, considering also the potential effects of phenotypical and clinical variables. MtDNA backgrounds, even when based on a refined haplogroup classification, do not appear to play a role in developing T2DM despite a possible protective effect for the common European haplogroup H1, which harbors the G3010A transition in the MTRNR2 gene. In contrast, our data indicate that different mitochondrial haplogroups are significantly associated with an increased risk of specific diabetes complications: H (the most frequent European haplogroup) with retinopathy, H3 with neuropathy, U3 with nephropathy, and V with renal failure.

Leukocyte telomere shortening in elderly Type2DM patients with previous myocardial infarction.

OBJECTIVE: We performed a cross-sectional study to examine the differences in leukocyte telomere length among three groups of subjects: patients with type 2 diabetes mellitus without history of previous myocardial infarction (Type2DM), patients with type 2 diabetes mellitus with evidence of previous myocardial infarction (Type2DM+MI), and healthy control subjects (CTR). The main objective of the present study is to investigate differences in telomere length between the studied groups of subjects, with the aim to clarify if telomere length could be a reliable marker associated with MI in Type2DM patients. Secondary end point is the identification of associations between leukocyte telomere length and selected variables related to glycemic control, pro-inflammatory status and lipidic profile. RESEARCH DESIGN AND METHODS: A total of 272 elderly subjects, 103 Type2DM (mean age 70+/-4 years, 59% males), 65 Type2DM+MI (mean age 68+/-7 years, 68% males), and 104 CTR (mean age 69+/-7 years, 50% males) were studied. Telomere length, defined as T/S (Telomere-Single copy gene ratio), was determined in leukocytes by quantitative real-time polymerase chain reaction (real-time PCR)-based assay. Moreover, we assessed: (1) high sensitive C reactive protein (hsCRP), fibrinogen and plasminogen-activator inibitor-1 (PAI-1) as inflammatory markers; (2) fasting glucose, insulin, glycated haemoglobin (HbA1C) and waist-to-hip ratio as markers of glycemic control; (3) total-cholesterol, HDL-cholesterol and triglycerides as markers of lipidic profile, in all sample population. The use of statins and sulfonylurea, as well as the presence of some relevant diabetes complications (nephropathy and retinopathy) were also assessed. CONCLUSION: Type2DM+MI elderly patients have leukocyte telomere lengths shorter than those of Type2DM (without MI) and healthy CTR. Moreover, glucose, HbA1C and waist-to-hip ratio, variables related to glycemic control, showed a significant inverse correlation with leukocyte telomeres length.

The Pro/Pro genotype of the p53 codon 72 polymorphism modulates PAI-1 plasma levels in ageing.

Plasminogen activator inhibitor 1 (PAI-1) is over-expressed during ageing and it has been linked to cellular senescence. Recently, PAI-1 has been also identified in vitro as a critical downstream target of p53. TP53, the p53 gene, has a common functional polymorphism at codon 72 which influences the capability to modulate both apoptosis and cell senescence. In the attempt to demonstrate an in vivo role of p53 in the relationship between PAI-1 and age, we studied PAI-1 on 570 healthy subjects (aged from 18 to 92yrs.). PAI-1 showed significant relationship with age (r=0.12, p=0.02). Stratifying by genotype, it became evident that the association between PAI-1 and age was mainly due to Pro/Pro subjects (partial r=0.75, p<0.01). These results have been confirmed by a validation study on an independent sample population of 496 subjects (aged from 18 to 94yrs.). This is the first demonstration of an in vivo role of TP53 polymorphism in PAI-1 regulation, supporting the hypothesis that the effects of this polymorphism are age-dependent. In particular, our results indicate that Pro/Pro genotype plays a pivotal role in determining PAI-1 levels in aged subjects, while in Arg carriers PAI-1 levels are associated to the known insulin related determinants.

Endovascular repair of thoracic aortic disease with the EndoFit stent-graft: short and midterm results from a single center.

PURPOSE: To analyze the outcomes of endovascular treatment of thoracic aortic pathologies performed at a single center with the EndoFit thoracic stent-graft system. METHODS: From January 2002 to January 2007, 41 patients (33 men; mean age 69.3+/-9.7 years, range 48-84) were treated for thoracic aortic disease with the EndoFit stent-graft system. Patient data were retrieved from a retrospective review of hospital records. Indications for treatment were progression of aneurysm size in atherosclerotic aneurysms (n = 24, mean aneurysm diameter 7.19+/-1.48 cm), acute contained aortic rupture (n = 5), aortic dissection (n = 6), penetrating atherosclerotic ulcers (n = 4), post-traumatic pseudoaneurysm (n = 1), and post coarctation repair aneurysm (n = 1). RESULTS: The EndoFit stent-graft was successfully deployed in all 41 patients. The in-hospital and 30-day mortality rate was 7.3% (3 patients). Three (7.3%) postoperative endoleaks were recorded: a proximal type Ia and a distal Ib both resolved spontaneously at 1 and 3 months, respectively. The third patient had a persistent type Ia endoleak; conversion was necessary after 1 year. There was only 1 case of spinal ischemia, with consequent lower extremity weakness; no paraplegia was observed. During a mean 24.8-month follow-up, 2 secondary type Ia endoleaks were treated with additional stent-grafts. There were 7 (17%) deaths during follow-up. At 2 years, overall patient survival by Kaplan-Meier analysis was 70%; aneurysm-related survival was 89%. CONCLUSION: Endovascular treatment of vascular disease involving the descending thoracic aorta can be safely performed with the EndoFit thoracic stent-graft system.

Asymptomatic Helicobacter pylori infection increases asymmetric dimethylarginine levels in healthy subjects.

BACKGROUND: Chronic infections have been demonstrated to be early factors of atherosclerosis and cardiovascular diseases, and their relevance increases when they are caused by agents with extremely broad spectrum of disease outcome such as Helicobacter pylori. The consequent endothelial impairment leads to a reduced bioavailability of nitric oxide. Increasing evidences have pointed out that the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine, defined as a risk factor for cardiovascular disease, may increase in infections and plays an important role impairing the vascular functions of the endothelium. Starting from these findings, we aim to investigate whether H. pylori may affect asymmetric dimethylarginine levels. MATERIALS AND METHODS: The study was carried out on a group of 186 subjects (age 46.2 +/- 14.9 years). We evaluated asymmetric dimethylarginine, symmetric dimethylarginine, L-arginine, presence of H. pylori by 13C-urea breath test, and the main parameters of glyco and lipo metabolic balance. RESULTS: Increased levels of asymmetric dimethylarginine were found in H. pylori-positive subjects with respect to H. pylori-negative subjects (0.46 x/ / 1.13 versus 0.42 x/ / 1.23 mol/l, p < .001, respectively). No differences were detected in L-arginine levels between the two groups. Multiple regression analysis performed in H. pylori-positive subjects and H. pylori-negative subjects showed profound differences in the variables related to asymmetric dimethylarginine (R2 = 66.9%, p < .01 versus 34.3%, p < .01, respectively) and symmetric dimethylarginine (R2 = 39.2%, p < .01 versus 20.6%, p = .09, respectively) levels. CONCLUSIONS: Our data clearly demonstrate that H. pylori infection increases asymmetric dimethylarginine levels. Moreover, this infection causes a profound metabolic modification that alters the role of the known determinants of asymmetric dimethylarginine levels. We conclude that H. pylori infection must be taken into account as a cause of increased asymmetric dimethylarginine levels and that the eradication of H. pylori may therefore lead to a decrease in asymmetric dimethylarginine levels, which is a further reason for the reduction of the risk for cardiovascular disease in this large portion of population.