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ABSTRACT: The short-term effects of multifactorial intervention for cardiovascular disease (CVD) prevention on renal function and serum uric acid (SUA) levels in patients with stage 3 chronic kidney disease (CKD) and multiple CVD risk factors are unclear. The aim of the study was to prospectively assess these effects.
This post hoc analysis of 5 "best practice" studies involved patients with multiple CVD risk factors. Estimated glomerular filtration rate (eGFR) was assessed using the Modification of Diet in Renal Disease (MDRD) formula. Among the 4,153 patients, 1,235 (29.7%) had stage 3 CKD (eGFR between 30 and 59 ml/min/1.73 m(2)). A baseline visit was followed by a concerted effort from previously trained physicians to improve adherence to lifestyle advice and optimize drug treatment, including a statin, for all vascular risk factors. After 6 months eGFR and SUA levels were re-evaluated.
The intervention improved compliance to lifestyle measures and increased the use of evidence-based medication, including a statin. There was also a 5.6% increase in eGFR (p < 0.001) in patients with stage 3 CKD and a 6.1% reduction in SUA levels (p < 0.001). Among patients with stage 3 CKD, 127 (10.3%) improved to stage 2 CKD and 9 (0.7%) advanced to stage 4 CKD by the end of the 6-month study period. There were no major side-effects.
Multitargeted intervention, including a statin, may improve renal function and reduce SUA levels within 6 months, thus offsetting 2 potential CVD risk factors in high-risk patients.
Archives of medical science : AMS. 12/2011; 7(6):984-92.
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Vassilios G. Athyros,
Emmanouel Ganotakis,
Genovefa D. Kolovou,
Vassilios Nicolaou,
Apostolos Achimastos,
Eleni Bilianou,
Theodore Alexandrides,
Asterios Karagiannis,
Konstantinos Paletas,
Evangelos N. Liberopoulos,
Konstantinos Tziomalos,
Dimitrios Petridis, Anna Kakafika,
Moses S. Elisaf,
Dimitri P. Mikhailidis
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ABSTRACT: 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].
Current Vascular Pharmacology 10/2011; 9(6):647-657. · 2.90 Impact Factor
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Vassilios G Athyros,
Emmanouel Ganotakis,
Genovefa D Kolovou,
Vassilios Nicolaou,
Apostolos Achimastos,
Eleni Bilianou,
Theodore Alexandrides,
Asterios Karagiannis,
Konstantinos Paletas,
Evangelos N Liberopoulos,
Konstantinos Tziomalos,
Dimitrios Petridis, Anna Kakafika,
Moses S Elisaf,
Dimitri P Mikhailidis
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ABSTRACT: 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.
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.
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.
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].
Current Vascular Pharmacology 04/2011; 9(6):647-57. · 2.90 Impact Factor
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Themistoklis Vassiliadis,
Alexander Mpoumponaris,
Sofia Vakalopoulou,
Olga Giouleme,
Dimitrios Gkissakis,
Nikolaos Grammatikos,
Konstantinos Soufleris, Anna Kakafika,
Konstantinos Tziomalos,
Kaliopi Patsiaoura,
Vassilios Papanikolaou,
Nikolaos Evgenidis
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ABSTRACT: Aim: Spur cell anemia (SCA) is a form of acquired hemolytic anemia seen in patients with advanced cirrhosis and particularly in patients with alcoholic cirrhosis. The aim of the present study was to evaluate the incidence of spur cells and spur cell anemia in patients with advanced liver disease and to correlate the presence of spur cell anemia with survival.Methods: During a 33-month period, all patients with advanced cirrhosis (Child–Pugh–Turcott score [CPT]≥7] who were hospitalized in our department for various reasons were included in this study.Results: A total of 54 patients were included in the study; 26 patients had spur cells on peripheral blood smear (median 4, range 1–14). Patients with spur cells had more advanced liver disease compared with those without spur cells (CPT score, P < 0.0001 and MELD score, P < 0.0001), lower hemoglobin levels (P < 0.0001), higher bilirubin levels (total/unconjugated, P < 0.0001), higher reticulocyte count (P < 0.0001) and more prolonged international normalized ratio (INR; P < 0.0001). Patients with 5% spur cells or more had more advanced disease compared with patients with 1–4% spur cells (CPT score, P = 0.004 and MELD score, P = 0.003), lower hemoglobin levels (P = 0.033), more elevated bilirubin levels (total/unconjugated, P = 0.006) and more prolonged INR (P = 0.04). Three-month survival was lower in patients with spur cells compared with patients without spur cells (P = 0.017 and P = 0.104, respectively). Patients with 5% spur cells or more had lower 3-month survival compared with those with 1–4% spur cells (P = 0.014).Conclusion: Presence of spur cells in patients with advanced cirrhosis is not always accompanied by spur cell anemia. The presence of 5% spur cells or more and/or hemolytic anemia is associated with poor prognosis and these patients might have to be given priority for liver transplantation.
Hepatology Research 01/2010; 40(2):161 - 170. · 2.20 Impact Factor
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Angiology 10/2008; · 1.51 Impact Factor
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ABSTRACT: Primary aldosteronism (PA) and, in particular, its two commonest subtypes (i.e. idiopathic hyperaldosteronism (IHA) and aldosterone-producing adenoma (APA)) have been recognized as the most common cause of secondary hypertension. While 'conservative' medical treatment with aldosterone receptor antagonists is the therapeutic approach of choice in controlling blood pressure in patients with PA due to IHA, the more invasive (laparoscopic) adrenalectomy seems to be the most suitable therapy for patients with APA. In this review, we focus on the medical approach for the management of APA in cases where surgical excision of the adrenal is not possible.
Endocrine Related Cancer 07/2008; 15(3):693-700. · 4.36 Impact Factor
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ABSTRACT: The cardiorenal anemia syndrome in congestive heart failure (CHF) is an independent risk factor for vascular morbidity and mortality. Several factors play a role in the pathogenesis of anemia in CHF, including inflammation, impaired renal function, use of certain antihypertensive or cardioprotective agents, and gastrointestinal or urinary losses of essential hemopoietic factors. Several trials evaluated the effects of administering erythropoietin (EPO) and/or iron to patients with CHF. Even though most of them were uncontrolled studies, their results suggest that EPO treatment might be beneficial in CHF. Nevertheless, more studies are needed and certain issues should be resolved, particularly the optimal hemoglobin level, before EPO can become part of the treatment of patients with CHF.
Angiology 05/2008; 60(1):74-81. · 1.51 Impact Factor
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ABSTRACT: Statins effectively lower plasma low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of vascular events. However, this benefit might be improved by dealing with other vascular risk factors such as high-density lipoprotein cholesterol (HDL-C). It follows that there has been an interest in drugs that raise plasma HDL-C levels. Among these drugs are the cholesteryl ester transfer protein (CETP) inhibitors. The first CETP inhibitor to be evaluated in an event-based trial was torcetrapib. This drug can considerably elevate serum HDL-C levels (e.g., by 72%). However, a recently published trial (ILLUMINATE) showed that torcetrapib used in combination with atorvastatin was associated with significantly more vascular events and deaths than atorvastatin alone. This finding resulted in the discontinuation of the torcetrapib development programme. The cause(s) of the adverse outcome remain speculative. It has been suggested that a significant rise in systolic blood pressure and possibly the quality of the HDL produced may be relevant. Despite this disappointing outcome it seems to be too early to close the book on CETP inhibitors because two other members of this class are being evaluated. These drugs (JTT-705 and anacetrapib) may be devoid of the adverse effect on systolic blood pressure. Eventually only appropriately designed, event-based trials, will settle the issue of whether CETP inhibitors are clinically useful.
Expert Opinion on Investigational Drugs 05/2008; 17(4):445-9. · 5.27 Impact Factor
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ABSTRACT: Epidemiological studies show that high density lipoprotein cholesterol (HDL-C) levels are inversely related to the risk of vascular events. Statins are the most widely prescribed drugs for the treatment of dyslipidaemias and their use for the prevention of vascular events is evidence based. Statins raise HDL-C but this effect seems to vary considerably between studies. We searched the literature to assess the relationship between statin-induced increases in HDL-C levels and surrogate and/or clinical endpoints. Based on the existing evidence, it is difficult to determine how much reduction, if any, in vascular risk is attributable to a statin-induced increment in HDL-C levels. Whether a statin that beyond its LDL-C lowering effect also raises HDL-C has additional benefits in the prevention of vascular events remains to be established.
Current Medicinal Chemistry 02/2008; 15(22):2265-70. · 4.86 Impact Factor
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Asterios Karagiannis,
Dimitri P Mikhailidis,
Konstantinos Tziomalos,
Maria Sileli,
Savvas Savvatianos, Anna Kakafika,
Thomas Gossios,
Napoleon Krikis,
Irene Moschou,
Michael Xochellis,
Vassilios G Athyros
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ABSTRACT: The prognostic significance of uric acid (UA) levels in acute stroke is unclear, so the objective of this study was to determine the association between levels of serum UA (SUA) and mortality in acute stroke.
Consecutive patients (n=435) presenting with ischemic stroke and intracerebral hemorrhage were included in the study. The length of stay in hospital and the occurrence of death were recorded. On univariate analysis, the occurrence of death was associated with older age, smoking, presence of congestive heart failure or atrial fibrillation, absence of hyperlipidemia, and intracerebral hemorrhage as the index event. Furthermore, glucose, urea, creatinine and SUA at admission were significantly higher in patients who died, whereas total and high-density-lipoprotein cholesterol were significantly lower. On multiple logistic regression analysis, the independent relationship between higher SUA levels and death was confirmed (odds ratio (OR), 1.37; 95%confidence interval (CI), 1.13-1.67; p=0.001). The only other variables independently associated with the occurrence of death were urea concentration and presence of atrial fibrillation. If urate was >7.8 mg/dl (0.47 mmol/L), then there would be a high probability of early death (87%).
Elevated levels of SUA are independently associated with an increased risk of early death in acute stroke.
Circulation Journal 08/2007; 71(7):1120-7. · 3.77 Impact Factor
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JAMA The Journal of the American Medical Association 06/2007; 297(20):2197; author reply 2197. · 30.03 Impact Factor
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Nephrology Dialysis Transplantation 04/2007; 22(3):963-4; author reply 964. · 3.40 Impact Factor
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Nephrology Dialysis Transplantation 02/2007; 22(1):293. · 3.40 Impact Factor
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ABSTRACT: Acute pancreatitis generates a complex cascade of immunological events that affect the pathogenesis and the progression of this disease. Several inflammatory mediators seem to play a critical role in the pathogenesis of pancreatitis and the subsequent inflammatory response. In turn, these mediators can influence hemostasis. Coagulation abnormalities occur in acute pancreatitis and are related to its severity. The contribution of blood platelets in the disturbed hemostasis in acute pancreatitis, although extensively studied, remains obscure. This article reviews the local and systemic implications of hemostatic abnormalities during acute pancreatitis. Furthermore, we discuss the prognostic value and the potential therapeutic implications of platelet activation and other hemostatic variables.
Pancreas 02/2007; 34(1):15-20. · 2.39 Impact Factor
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ABSTRACT: Tumor lysis syndrome is characterized by multiple metabolic derangements resulting from the release of intracellular components into the bloodstream due to abrupt malignant cell death, spontaneously or following antineoplastic therapy. The syndrome is characterized by hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia, while deposition of uric acid and calcium phosphate crystals may result in acute renal failure, which is often exacerbated by concomitant intravascular volume depletion. A case of tumor lysis syndrome complicated by acute renal failure in a patient with non-Hodgkin's lymphoma is reported and the pathophysiology, the clinical features, and the treatment options are discussed.
Annals of Hematology 06/2005; 84(5):343-6. · 2.62 Impact Factor
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ABSTRACT: Am J Hypertens (2005) 18, 167A–167A; doi:10.1016/j.amjhyper.2005.03.462
P-444: Uric acid as a prognostic risk factor in patients with acute stroke
Asterios Karagiannis1, Konstantinos Tziomalos1, Anna Kakafika1, Maria Sileli1, Napoleon Krikis1, Euthimia Moschou1, Michael Xohellis1 and Chrysanthos Zamboulis11Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
American Journal of Hypertension 04/2005; · 3.18 Impact Factor
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Nephrology Dialysis Transplantation 10/2004; 19(9):2418-9. · 3.40 Impact Factor
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ABSTRACT: Atherosclerosis is the leading cause of death in developed countries. Although the mechanisms that underlie this process are not well defined, it has been proposed that atherosclerosis is mainly an inflammatory disease. In this context, a number of inflammatory markers have been studied for their ability to predict future cardiovascular events in asymptomatic individuals or patients with established atherosclerotic disease.
The aim of our study was to evaluate the effect of micronized fenofibrate on serum inflammatory markers, such as C-reactive protein, fibrinogen, and plasma platelet-activating factor acetylhydrolase (PAF-AH) in patients with high triglyceride values. An analysis of baseline values revealed that hypertriglyceridemic patients (n = 58) exhibit an atherogenic phenotype, characterized not only by elevated lipid values but also by high concentrations of serum inflammatory markers. Along with the improvement in serum lipid profile (reduction in triglycerides and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein-cholesterol, with a concomitant increase in high-density lipoprotein-cholesterol levels), fenofibrate administration significantly reduced the values of serum inflammatory markers by 34%, 9.5%, and 24.8% for C-reactive protein, fibrinogen, and plasma PAF-AH, respectively. However, with the exception of PAF-AH, these reductions in inflammatory markers were not correlated with the changes in lipid values.
In addition to its well-known hypolipidemic effects, fenofibrate may also possess significant anti-inflammatory properties that can contribute its antiatherogenic effect.
Journal of Cardiovascular Pharmacology and Therapeutics 04/2004; 9(1):27-33. · 1.75 Impact Factor
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ABSTRACT: Hyperhomocysteinemia is regarded as an independent risk factor for cardiovascular disease. Lipid-lowering agents, such as fibrates, can modify homocysteine levels. However, less is known about the effect of statin therapy on homocysteine. The authors compared the effects of atorvastatin (40 mg/day), simvastatin (40 mg/day), and micronized fenofibrate (200 mg/day) on the serum concentrations of total homocysteine, vitamin B12, and folic acid in patients with primary hyperlipidemia. A total of 128 patients with primary hyperlipidemia (total cholesterol > 240 mg/dL and triglycerides < 350 mg/dL) were assigned to atorvastatin, simvastatin, or fenofibrate. Serum lipid and metabolic parameters were measured at baseline and at 6 and 12 weeks of treatment. Homocysteine correlated positively with serum creatinine and uric acid levels and inversely with serum folic acid levels. All treatment modalities reduced total, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations. High-density lipoprotein (HDL) cholesterol levels significantly increased only in the fenofibrate-treated patients (47.9 +/- 12.5 vs. 50.7 +/- 12.6 vs. 51.2 +/- 12.8 mg/dL, p < 0.01). Atorvastatin and fenofibrate treatment resulted in a significant reduction of serum uric acid levels (5.3 +/- 1.6 vs. 4.9 +/- 1.4 vs. 4.8 +/- 1.4 mg/dL, p < 0.0001 for atorvastatin; 5.6 +/- 1.6 vs. 4.3 +/- 1.4 vs. 4.4 +/- 1.4 mg/dL, p < 0.0001 for fenofibrate). Homocysteine levels were significantly increased only by fenofibrate (10.3 +/- 3.3 vs. 14.1 +/- 3.8 vs. 14.2 +/- 3.6 microU/L, p < 0.001) but did not change from baseline following statin treatment. Neither statins nor fenofibrate had any effect on serum vitamin B12 and folic acid levels. In contrast to fenofibrate, therapeutic dosages of atorvastatin and simvastatin have a neutral effect on serum homocysteine levels, which is in favor of their "cardioprotective" properties.
The Journal of Clinical Pharmacology 08/2003; 43(8):825-30. · 2.91 Impact Factor
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ABSTRACT: Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme associated mainly with the apolipoprotein B (apoB)-containing lipoproteins and primarily with LDL. A small proportion of enzymatic activity is also associated with HDL. Plasma paraoxonase 1 (PON1) is an esterase exclusively associated with HDL. The effect of fenofibrate on PAF-AH and PON1 activities in patients with dyslipidemias of Types IIA, IIB, and IV were studied. Fenofibrate reduced plasma PAF-AH activity in all patient groups. In Type IIA patients, this reduction was mainly due to a fall in enzyme activity associated with the dense LDL subspecies, whereas in Type IIB and Type IV patients, it was due to the decrease in PAF-AH activity associated with both the VLDL+IDL and dense LDL subspecies. Drug therapy in Type IIB and Type IV patients significantly increased the HDL-associated PAF-AH activity due to the increase in enzyme activity associated with the HDL-3c subfraction. Fenofibrate did not affect serum PON1 activities toward paraoxon and phenylacetate in either patient group. The fenofibrate-induced elevation of HDL-associated PAF-AH activity in dyslipidemic patients of Type IIB and Type IV, as well as the reduction in enzyme activity associated with atherogenic apoB-containing lipoproteins in all patient groups, may represent a new and important antiatherogenic effect of this potent lipid-modulating agent.
The Journal of Lipid Research 06/2003; 44(5):927-34. · 5.56 Impact Factor
