A longitudinal study of nutritional and inflammatory status in patients on dialysis.

OBJECTIVE: Several anthropometric, laboratory and bioelectrical impedance parameters of nutritional status and inflammation are often used as prognostic indices in patients on dialysis. Their longitudinal assessment is necessary for the estimation of their true prognostic value. We aim to estimate this prognostic value in better-nourished dialysis patients, which are commonly under-represented in pertinent studies. METHODS: The design is a prospective case series. Pertinent parameters were studied three times during a 20-month period in 47 haemodialysis (HD) and 27 peritoneal dialysis (PD) patients with a low malnutrition-inflammation score (MIS). Mortality rate was assessed three years after the initial evaluation. Correlation coefficients were calculated between mortality rate, the studied parameters and their alteration. RESULTS: Serum albumin of less than 40 g/l was strongly correlated with mortality risk. The alteration of studied parameters during a short period of time does not allow for long-term prediction of mortality risk. CONCLUSION: Serum albumin had the strongest predictive value of all the pertinent parameters in the study. Thus, better conjugate clinical and laboratory measurements should be developed for patients on PD, as well as for those with a relatively low MIS.

Subclinical hypothyroidism and vascular risk: an update.

Subclinical hypothyroidism (SCH), defined as elevated serum thyroid-stimulating hormone (TSH) in the presence of normal circulating free thyroxine (FT4) and triiodothyronine (T3), is a relatively common condition. Replacement treatment with levothyroxine is justified only for individuals with TSH levels >10 mIU/l. Serum lipid levels are influenced by thyroid status and there is evidence pointing to a link between SCH and an unfavorable lipid profile. Despite some conflicting data, most studies suggest that levothyroxine treatment may exert a beneficial effect on the lipid profile in SCH regarding mainly total cholesterol and low-density lipoprotein-cholesterol. Moreover, it appears that treatment may also improve some other markers associated with cardiovascular (CV) disease such as carotid intima media thickness (cIMT) indices of endothelial function and other predictors of vascular risk. The complex interaction between SCH and predictors of vascular disease may explain the variability of the results obtained from studies that assessed vascular events or even changes in some biochemical, functional or structural variables associated with an increased risk of vascular events. Further investigation is warranted by means of intervention studies to assess the clinical significance of levothyroxine treatment in SCH regarding CV risk.

Long-term impact of multifactorial treatment on new-onset diabetes and related cardiovascular events in metabolic syndrome: a post hoc ATTEMPT analysis.

This post hoc analysis of the Assessing The Treatment Effect in Metabolic Syndrome Without Perceptible diabeTes (ATTEMPT) study assesses the 3½ year incidence of new-onset diabetes (NOD) and related cardiovascular disease (CVD) events in patients with metabolic syndrome (MetS), after multifactorial (lifestyle and drug, including atorvastatin) intervention. Patients were randomized to group A (low-density lipoprotein cholesterol [LDL-C] target < 100 mg/dL) and group B (< 130 mg/dL). The incidence of NOD during the 42-month follow-up was very low, 0.83 to 1.00/100 patient-years in patients with MetS and MetS with impaired fasting glucose, respectively. Older age, increased waist circumference, and persistent MetS were determinants of NOD. One CVD nonfatal event occurred in the 28 patients with NOD. Our findings suggest that treating the characteristics of MetS is achievable and beneficial. New-onset diabetes incidence and CVD events were negligible and not different from what is expected in the general population.

Association between the changes in renal function and serum uric acid levels during multifactorial intervention and clinical outcome in patients with metabolic syndrome. A post hoc analysis of the ATTEMPT study.

AIM: To assess the effects of long-term multifactorial intervention on renal function and serum uric acid (SUA) levels and their association with estimated cardiovascular disease (eCVD) risk and actual CVD events. METHODS: This prospective, randomized, target-driven study included 1123 subjects (45.6% men, age 45-65 years) with metabolic syndrome (MetS) but without diabetes or CVD. Patients were randomized to multifactorial treatment. Atorvastatin was titrated from 10-80 mg/day aiming at a low density lipoprotein cholesterol (LDL-C) target of <100 mg/dl (group A) or an LDL-C target of <130 mg/dl (group B). Changes in estimated glomerular filtration rate (eGFR) and SUA levels were recorded in all patients and in the subgroup with stage 3 chronic kidney disease (CKD; eGFR = 30-59 ml/min/1.73 m(2); n = 349). We used ANOVA to compare changes within the same group, unpaired Student t-test to compare results between groups at specific time points, and log-rank test to compare event free survival. RESULTS: The eCVD-risk reduction was greater in group A. In the overall study population, eGFR increased by 3.5% (p < 0.001) and SUA levels fell by 5.6% (p < 0.001). In patients from group A with stage 3 CKD (group A1; n = 172), eGFR increased by 11.1% (p < 0.001) from baseline and by 7.5% (p < 0.001) in group B1 (n = 177; p < 0.001 vs. the change in group A1). The corresponding fall in SUA levels was 10.7% in group A1 (p < 0.001 vs. baseline) and 8.3% in group B1 (p < 0.001 vs. baseline and group A1). These changes were mainly attributed to atorvastatin treatment. Among the CKD stage 3 patients there were no CVD events in group A1, while 6 events occurred in group B1 (p = 0.014). CONCLUSIONS: Multifactorial intervention in patients with MetS without established CVD improved renal function and reduced SUA levels. These changes were more prominent in stage 3 CKD patients and might have contributed to the reduction in eCVD risk and clinical events. Original study registration number [ClinicalTrials.gov ID: NCT00416741].

Assessing the treatment effect in metabolic syndrome without perceptible diabetes (ATTEMPT): a prospective-randomized study in middle aged men and women.

AIM: To assess the reduction in estimated cardiovascular disease (e-CVD) risk after multifactorial treatment for 6 months and follow this change during the next 3-years. PATIENTS-METHODS: This prospective, randomized, target driven study included 1,123 subjects (512/611 men/women, aged 45-65 years) with metabolic syndrome (MetS) without diabetes or CVD referred to specialist outpatient clinics. Patients were randomized to two treatment groups: group A with low density lipoprotein cholesterol (LDL-C) target of < 100 mg/dl and group B with a target of < 130 mg/dl. Atorvastatin was used in both groups on top of optimal multifactorial treatment, (quinapril, amlodipine, hydrochlorothiazide for hypertension, metformin for impaired fasting glucose, and orlistat for obesity). The e-CVD risk was calculated using the Framingham, the PROCAM and Reynold's equations. RESULTS: Reductions in e-CVD risk at 6 months were > 50%in all patients, but were superior in group A and in women. Reductions were even greater during the next 3-years and were mainly attributed to changes in lipid profile. Actual CVD events were 1 in group A and 13 in group B; p=0.0012. CONCLUSIONS: Attaining the treatment target of LDL-C < 100 mg/dl within multifactorial treatment of MetS by expert clinics, is achievable and beneficial even in patients without diabetes or known CVD. This induces a considerable e-CVD risk reduction in MetS patients. Actual CVD events were negligible, suggesting that e-CVD risk overestimates actual CVD risk in MetS, at least in patients achieving LDL-C < 100 mg/dl [ClinicalTrials.gov ID: NCT00416741].

Safety and impact on cardiovascular events of long-term multifactorial treatment in patients with metabolic syndrome and abnormal liver function tests: a post hoc analysis of the randomised ATTEMPT study.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome (MetS), is common and accounts for 80% of cases of elevated liver function tests (LFTs). We assessed the long-term effects of multifactorial intervention on LFTs and their association with cardiovascular disease (CVD) events in patients with MetS without diabetes mellitus or CVD. MATERIAL AND METHODS: This prospective, randomized, open label study included 1,123 patients (aged 45-65 years). Patients received intensive lifestyle intervention and pharmacotherapy: atorvastatin in all patients (low density lipoprotein cholesterol [LDL-C] targets of<100 mg/dl [group A] or<130 mg/dl [group B]), inhibitors of the renin-angiotensin-aldosterone axis for hypertension, metformin for dysglycaemia and orlistat for obesity. RESULTS: Among participants, 326 had modestly elevated LFTs and ultrasonographic (US) evidence of NAFLD (165 patients in group A2 and 161 patients in group B2). The NAFLD resolved during the 42-month treatment period in 86% of patients in group A2 and in 74% of patients in group B2 (p<0.001). In both groups nearly 90% of patients attained lipid goals. Mean LDL-C and TG levels were higher in group B2 than in group A2 (p<0.001). There were no CVD events in group A2 whereas 5 non-fatal events occurred in group B2 (log-rank-p = 0.024). There were no major side-effects. CONCLUSIONS: Attaining multiple treatment targets is safe and beneficial in primary prevention patients with MetS and NAFLD. Lipid levels and LFTs normalized, US findings associated with NAFLD resolved and no CVD events occurred in patients with LDL-C levels<100 mg/dl (group A2). Resolution of NAFLD might have contributed to the prevention of CVD events.

Cardiovascular risk factors and estimated 10-year risk of fatal cardiovascular events using various equations in Greeks with metabolic syndrome.

We investigated cardiovascular disease (CVD) risk factors in 1501 Greeks (613 men and 888 women, aged 40-65 years) referred to outpatients with metabolic syndrome (MetS) and without diabetes mellitus or CVD. The 10-year risk of fatal CVD events was calculated using European Society of Cardiology Systematic Coronary Risk Estimation (ESC SCORE), Hellenic-SCORE, and Framingham equations. Raised blood pressure (BP) and hypertriglyceridemia were more common in men (89.6% vs 84.2% and 86.8% vs 74.2%, respectively; P < .001). Low high-density lipoprotein cholesterol (HDL-C) and abdominal obesity were more common in women (58.2% vs 66.2% and 85.8% vs 97.1%, respectively; P < .001). The 10-year risk of fatal CVD events using HellenicSCORE was higher in men (6.3% +/- 4.3% vs 2.7% +/- 2.1%; P < .001). European Society of Cardiology Systematic Coronary Risk Estimation and Framingham yielded similar results. The risk equations gave similar assessments in a European Mediterranean population except for HellenicSCORE that calculated more MetS women requiring risk modification. This might justify local risk engine evaluation in event-based studies. (Clinical-Trials.gov ID: NCT00416741).

Effects of tumor necrosis factor alpha inhibition with infliximab on lipid levels and insulin resistance in patients with inflammatory bowel disease.

INTRODUCTION: TNF-alpha is a critical mediator of inflammation with an important role in metabolic profile and insulin resistance. The regulation of these parameters by TNF-alpha in inflammatory bowel disease (IBD) is, however, poorly understood. The aim of this study was to assess the in-vivo TNF-alpha-mediated regulation of insulin resistance and of lipid levels in patients with IBD. METHODS: Twenty-two patients with IBD (eight females; 19 Crohn's disease) received infliximab according to treating physician's assessment at weeks 0, 2 and 6 from baseline and subsequently every 8 weeks and were prospectively followed for 14 weeks. Fasting insulin, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein A1 (apo-A1), apolipoprotein B100 and lipoprotein a were measured in serum at baseline and at week 14. Insulin resistance was calculated with the use of the Homeostasis Model Assessment index. RESULTS: Infliximab therapy induced clinical response or remission in 19 of the 22 patients. C-reactive protein levels were significantly decreased by week 14. Body mass index was increased in all patients. No difference was observed in insulin levels, Homeostasis Model Assessment index, triglycerides, LDL cholesterol, apolipoprotein B100 and lipoprotein a. In contrast, total cholesterol, HDL cholesterol and apo-A1 levels were significantly increased from baseline. CONCLUSION: TNF-alpha inhibition does not alter insulin resistance in IBD patients. In contrast, total cholesterol, HDL cholesterol and apo-A1 levels are significantly increased after infliximab treatment compared with baseline. The importance of these alterations needs to be clarified in future studies.

Effect of ciprofibrate on lipoproteins, fibrinogen, renal function, and hepatic enzymes.

AIM: The action of ciprofibrate in hypertriglyceridemic patients is well established. Not only is ciprofibrate able to alter the lipid profile, but it can also change the values of fibrinogen, C-reactive protein, creatinine, transaminases, gamma-glutamyl transpeptidase and serum alkaline phosphatase. However, previous studies focused on the effect of ciprofibrate in hypertriglyceridemic patients, leaving unanswered the question of whether ciprofibrate exerts the same effect on hyperlipidemic patients with normal triglyceride values. The aim of this study is to answer this question. METHODS: In this randomized clinical trial, 64 men and women with elevated cholesterol or triglyceride levels were included. Two subgroups were formed according to triglyceride levels: one (36 patients) with elevated triglyceride levels (> 200 mg/dL [2.26 mmol/L]) and another (28 patients) with normal triglyceride levels (< 200 mg/dL [2.26 mmol/l]). After a 6-week period of step 1 diet according to the National Cholesterol Education Program, ciprofibrate (100 mg once daily) was administered for 16 weeks. Primary efficacy points were the changes of lipid parameters (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, apoproteins A1, B, E and lipoprotein [a], high sensitivity C reactive protein, fibrinogen, glucose, insulin, aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase, urea and creatinine levels in a fasting blood sample before and after treatment with ciprofibrate. RESULTS: The subgroup with triglyceride < 200 mg/dL (2.26 mmol/L): After the administration of ciprofibrate total cholesterol and low-density lipoprotein cholesterol were reduced by 15% (P < 0.001), and 19% (P < 0.001), respectively, while high-density lipoprotein cholesterol increased by 9% (P = 0.02). Apoproteins B and E levels were reduced by 21% (P < 0.001) and 11% (P = 0.002), respectively. Subgroup with triglyceride > 200 mg/dL (2.26 mmol/L): After the administration of ciprofibrate, no significant change in LDL cholesterol levels was observed. Total cholesterol levels were reduced by 15% (P < 0.001) and high-density lipoprotein cholesterol levels were increased by 13% (P = 0.004). Apoprotein B and apoprotein E levels were reduced by 16% (P < 0.001) and 30% (P < 0.001), respectively. Apoprotein-A1 levels were increased by 5% (P = 0.024). In the whole group of patients, the fibrinogen levels fell by 7% (P = 0.043), and the serum creatinine level increased by 10% (P < 0.001). This rise in serum creatinine was more pronounced in patients with low triglyceride levels (15% vs 5%, P = 0.009). Ciprofibrate decreased C-reactive protein levels by 26% in 44 patients who had C-reactive protein measurements (P < 0.001). gamma-glutamyl transpeptidase activity was similarly decreased (by approximately 40%) in both groups of patients. Alkaline phosphatase activity decreased in both groups, a reduction which was greater in hypertriglyceridemics (20% vs 10%, P = 0.004). CONCLUSIONS: Ciprofibrate improved some of the vascular risk factors, such as total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apoproteins A1, B, and E, and fibrinogen levels in both hypertriglyceridemics and normotriglyceridemics. In addition, ciprofibrate raised the serum creatinine and improved the activity of the hepatic enzymes in the plasma in both patient subgroups.