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1.  A systematic review and meta-analysis of the effect of statins on plasma asymmetric dimethylarginine concentrations 
Scientific Reports  2015;5:9902.
The impact of statin therapy on plasma asymmetric dimethylarginine (ADMA) levels has not been conclusively studied. Therefore the aim of the meta-analysis was to assess the effect of statins on circulating ADMA levels. We searched selected databases (up to August 2014) to identify randomized controlled trials (RCTs) that investigate the effect of statins on plasma ADMA concentrations. A weighted meta-regression (WMD) using unrestricted maximum likelihood model was performed to assess the impact of statin dose, duration of statin therapy and baseline ADMA concentrations as potential variables on the WMD between statin and placebo group. In total, 1134 participants in 9 selected RCTs were randomized; 568 were allocated to statin treatment and 566 were controls. There was a significant reduction in plasma ADMA concentrations following statin therapy compared with placebo (WMD: − 0.104 μM, 95% confidence interval: − 0.131 to − 0.077, Z = − 7.577, p < 0.0001). Subgroups analysis has shown a significant impact of hydrophilic statins (WMD: − 0.207 μM, 95%CI: − 0.427 to + 0.013, Z = − 7.250, p < .0001) and a non-significant effect of hydrophobic statins (WMD: − 0.101 μM, 95%CI: − 0.128 to − 0.074, Z = − 1.845, p = 0.065). In conclusion, this meta-analysis of available RCTs showed a significant reduction in plasma ADMA concentrations following therapy with hydrophilic statins.
PMCID: PMC4429557  PMID: 25970700
2.  The Multi-Biomarker Approach for Heart Failure in Patients with Hypertension 
We assessed the predictive ability of selected biomarkers using N-terminal pro-brain natriuretic peptide (NT-proBNP) as the benchmark and tried to establish a multi-biomarker approach to heart failure (HF) in hypertensive patients. In 120 hypertensive patients with or without overt heart failure, the incremental predictive value of the following biomarkers was investigated: Collagen III N-terminal propeptide (PIIINP), cystatin C (CysC), lipocalin-2/NGAL, syndecan-4, tumor necrosis factor-α (TNF-α), interleukin 1 receptor type I (IL1R1), galectin-3, cardiotrophin-1 (CT-1), transforming growth factor β (TGF-β) and N-terminal pro-brain natriuretic peptide (NT-proBNP). The highest discriminative value for HF was observed for NT-proBNP (area under the receiver operating characteristic curve (AUC) = 0.873) and TGF-β (AUC = 0.878). On the basis of ROC curve analysis we found that CT-1 > 152 pg/mL, TGF-β < 7.7 ng/mL, syndecan > 2.3 ng/mL, NT-proBNP > 332.5 pg/mL, CysC > 1 mg/L and NGAL > 39.9 ng/mL were significant predictors of overt HF. There was only a small improvement in predictive ability of the multi-biomarker panel including the four biomarkers with the best performance in the detection of HF—NT-proBNP, TGF-β, CT-1, CysC—compared to the panel with NT-proBNP, TGF-β and CT-1 only. Biomarkers with different pathophysiological backgrounds (NT-proBNP, TGF-β, CT-1, CysC) give additive prognostic value for incident HF in hypertensive patients compared to NT-proBNP alone.
PMCID: PMC4463672  PMID: 25984599
hypertension; biomarkers; heart failure
3.  Lipid profile and glucose changes after supplementation with astaxanthin: a systematic review and meta-analysis of randomized controlled trials 
Archives of Medical Science : AMS  2015;11(2):253-266.
Many studies have shown that oral supplementation with astaxanthin may be a novel potential treatment for inflammation and oxidative stress in cardiovascular diseases, but evidence of the effects on lipid profile and glucose is still inconclusive. Therefore, we performed a meta-analysis to evaluate the efficacy of astaxanthin supplementation on plasma lipid and glucose concentrations.
Material and methods
The search included PubMed, Cochrane Library, Scopus, and EMBASE (up to November 27, 2014) to identify randomized controlled trials (RCTs) investigating the effects of astaxanthin supplementation on lipid profile and glucose levels. Two independent reviewers extracted data on study characteristics, methods and outcomes.
Seven studies meeting inclusion criteria with 280 participants were selected for this meta-analysis; 163 participants were allocated to the astaxanthin supplementation group and 117 to the control group. A random-effect meta-analysis of data from 7 RCTs (10 treatment arms) did not show any significant effect of supplementation with astaxanthin on plasma concentrations of total cholesterol (weighted mean difference (WMD): –1.52 mg/dl, 95% CI: –8.69 to –5.66, p = 0.679), LDL-C (WMD: +1.25 mg/dl, 95% CI: –6.70 to +9.21, p = 0.758), HDL-C (WMD: +1.75 mg/dl, 95% CI: –0.92 to +4.42, p = 0.199), triglycerides (WMD: –4.76 mg/dl, 95% CI: –21.52 to +12.00, p = 0.578), or glucose (WMD: –2.65 mg/dl, 95% CI: –5.84 to +0.54, p = 0.103). All these effect sizes were robust, and omission of any of the included studies did not significantly change the overall estimate.
This meta-analysis of data from 10 RCT arms did not indicate a significant effect of supplementation with astaxanthin on plasma lipid profile, but a slight glucose-lowering effect was observed. Further, well-designed trials are necessary to validate these results.
PMCID: PMC4424245  PMID: 25995739
astaxanthin; lipids; antioxidants; glucose
4.  Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel 
Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term ‘statin intolerance’. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10–15% of patients. In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented.
PMCID: PMC4379380  PMID: 25861286
definition; muscle symptoms; risk factors; statin intolerance
6.  Assessment of the Relationship between Lipid Parameters and Obesity Indices in Non-Diabetic Obese Patients: A Preliminary Report 
The aim of this cross-sectional study was to examine the relationship between obesity and lipid markers.
We divided 66 non-diabetic adult obese patients (mean age: 55.8±11.6 years) into 3 groups according to body mass index (BMI). All patients were measured for waist circumference (WC), hip circumference (HC), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body adiposity index (BAI), and visceral adiposity index (VAI). Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were determined, and lipid indices TC/HDL, LDL/HDL, and TG/HDL were also estimated.
TC and LDL-C in Group III were lower than in Group I (5.0±1.0 vs. 6.0±1.0 mmol/L, and 2.9±0.9 vs. 3.8±1.2 mmol/L; p<0.05 for both). Negative correlations were found between: BMI and TC, LDL, and HDL (r=−0.291; r=−0.310, r=−0.240, respectively); and WC, WHR, VAI, and HDL (r=−0.371, r=−0.296, r=−0.376, respectively). Positive correlations were found between WC, WHR, and TG/HDL (r=0.279, r=0.244, respectively) and between VAI and: TC (r=0.327), TG (r=0.885), TC/HDL (r=0.618), LDL/HDL (r=0.480), and TG/HDL (r=0.927).
Obesity is associated with lipid disturbances, especially with HDL-C reduction, in obese non-diabetic patients. VAI is strongly related to lipid profile and thus may be the most valuable obesity index in obese patients with dyslipidemias.
PMCID: PMC4271804  PMID: 25512170
Dyslipidemias; Obesity; Therapeutics
7.  Prevention of heart failure in older adults may require higher levels of physical activity than needed for other cardiovascular events 
International journal of cardiology  2013;168(3):1905-1909.
Little is known if the levels of physical activity required for the prevention of incident heart failure (HF) and other cardiovascular events vary in community-dwelling older adults.
We studied 5503 Cardiovascular Health Study (CHS) participants, age ≥65 years, free of baseline HF. Weekly metabolic equivalent task-minutes (MET-minutes), estimated using baseline total leisure-time energy expenditure, were used to categorize participants into four physical activity groups: inactive (0 MET-minutes; n=489; reference), low (1–499; n=1458), medium (500–999; n=1086) and high (≥1000; n=2470).
Participants had a mean (±SD) age of 73 (±6) years, 58% were women, and 15% African American. During 13 years of follow-up, centrally-adjudicated incident HF occurred in 26%, 23%, 20%, and 19% of participants with no, low, medium and high physical activity, respectively (trend p <0.001). Compared with inactive older adults, age-sex-race-adjusted hazard ratios (95% confidence intervals) for incident HF associated with low, medium and high physical activity were 0.87 (0.71–1.06; p=0.170), 0.68 (0.54–0.85; p=0.001) and 0.60 (0.49–0.74; p<0.001), respectively (trend p <0.001). Only high physical activity had significant independent association with lower risk of incident HF (HR, 0.79; 95% CI, 0.64–0.97; p=0.026). All levels of physical activity had significant independent association with lower risk of incident acute myocardial infarction (AMI), stroke and cardiovascular mortality.
In community-dwelling older adults, high level of physical activity was associated with lower risk of incident HF, but all levels of physical activity were associated with lower risk of incident AMI, stroke, and cardiovascular mortality.
PMCID: PMC4142221  PMID: 23380700
Physical activity; MET-minutes; Incident heart failure; Older adults
8.  Rate-Control versus Rhythm-Control Strategies and Outcomes in Septuagenarian Patients with Atrial Fibrillation 
The American journal of medicine  2013;126(10):10.1016/j.amjmed.2013.04.021.
The prevalence of atrial fibrillation substantially increases after 70 years of age. However, the effect of rate-control versus rhythm-control strategies on outcomes in these patients remains unclear.
In the randomized Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 4060 patients (mean age, 70, range, 49–80 years) with paroxysmal and persistent atrial fibrillation were randomized to rate-control versus rhythm-control strategies. Of these, 2248 were 70–80 years, of whom 1118 were in the rate-control group. Propensity scores for rate-control strategy were estimated for each of the 2248 patients and were used to assemble a cohort of 937 pairs of patients receiving rate-control versus rhythm-control strategies, balanced on 45 baseline characteristics.
Matched patients had a mean age of 75 years, 45% were women, 7% were non-white, and 47% had prior hospitalizations due to arrhythmias. During 3.4 years of mean follow-up, all-cause mortality occurred in 18% and 23% of matched patients in the rate-control and rhythm-control groups, respectively (hazard ratio {HR} associated with rate-control, 0.77; 95% confidence interval {CI}, 0.63–0.94; p=0.010). HRs (95% CIs) for cardiovascular and non-cardiovascular mortality associated with rate-control were 0.88 (0.65–1.18) and 0.62 (0.46–0.84), respectively. All-cause hospitalization occurred in 61% and 68% of rate-control and rhythm-control patients, respectively (HR, 0.76; 95% CI, 0.68–0.86). HRs (95% CIs) for cardiovascular and non-cardiovascular hospitalization were 0.66 (0.56–0.77) and 1.07 (0.91–1.27).
In septuagenarian patients with atrial fibrillation, compared with rhythm-control, a rate-control strategy was associated with significantly lower mortality and hospitalization.
PMCID: PMC3818786  PMID: 24054956
atrial fibrillation; rate control; rhythm control; hospitalization; mortality; propensity score; older adults
9.  Markers of increased cardiovascular risk in patients with chronic kidney disease 
Epidemiological studies have shown that chronic kidney disease (CKD) is an important risk factor for atherosclerosis and cardiovascular disease (CAD). The aim of the study was to determine markers of increased risk of CAD and to achieve a better understanding of agents implicated in the process of atherosclerosis in CKD patients.
The study group consisted of a total of 139 patients with CKD while the control group comprised 45 healthy volunteers. Concentrations of osteoprotegerin, osteopontin, osteocalcin, matrix γ-carboxyglutamic acid (Gla) protein (MGP), fetuin A, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), ATP binding cassette transporter A1 (ABCA1), ATP binding cassette transporter G1 (ABCG1) and renalase were measured by the ELISA method.
We observed decreased levels of fetuin A (control vs. CKD group: 37.5 vs. 33.2 ng/ml, p = 0.018), and increased concentrations of osteocalcin (control vs. CKD group: 9.1 ± 6.0 vs. 13.6 ± 10.3 ng/ml, p = 0.05), MMP-2 (113.1 ± 75.0 vs. 166.0 ± 129.9 ng/ml, p = 0.045), TIMP-2 (22.1 ± 5.1 vs. 25.4 ± 7,0 ng/ml, p = 0.005) and renalase (251.0 ± 157 vs. 316.1 ± 155.3 ng/ml, p = 0.026). In patients with CKD (in comparison to control group), left ventricle ejection fraction: 53.0 ± 3,5% vs. 48.5%, p = 0.012) and calcification of the aortic valve (9.5% vs. 39.8%, p = 0.008) were observed more frequently.
Decreased levels of fetuin A and increased concentration of osteocalcin, renalase, MMP-2 and TIMP-2 suggest that these factors may be involved in the pathogenesis of CAD in patients with CKD. Significantly increased indices of cardiac hypertrophy and its dysfunction in patients with CKD are indicators of pathological mechanisms occurring in cardiovascular system in this group of patients.
PMCID: PMC4246537  PMID: 25145866
Atherosclerosis; Chronic kidney disease; Calcification; CAD risk
10.  Defining the Role of Trimetazidine in the Treatment of Cardiovascular Disorders: Some Insights on Its Role in Heart Failure and Peripheral Artery Disease 
Drugs  2014;74(9):971-980.
Trimetazidine is a cytoprotective drug whose cardiovascular effectiveness, especially in patients with stable ischemic heart disease, has been the source of much controversy in recent years; some have gone so far as to treat the medication as a ‘placebo drug’ whose new side effects, such as Parkinsonian symptoms, outweigh its benefits. This article is an attempt to present the recent key studies, including meta-analyses, on the use of trimetazidine in chronic heart failure, also in patients with diabetes mellitus and arrhythmia, as well as in peripheral artery disease. This paper also includes the most recent European Society of Cardiology guidelines, including those of 2013, on the use of trimetazidine in cardiovascular disease.
PMCID: PMC4061463  PMID: 24902800
11.  Bedside Tool for Predicting the Risk of Postoperative Atrial Fibrillation After Cardiac Surgery: The POAF Score 
Atrial fibrillation (AF) remains the most common complication after cardiac surgery. The present study aim was to derive an effective bedside tool to predict postoperative AF and its related complications.
Methods and Results
Data of 17 262 patients undergoing adult cardiac surgery were retrieved at 3 European university hospitals. A risk score for postoperative AF (POAF score) was derived and validated. In the overall series, 4561 patients (26.4%) developed postoperative AF. In the derivation cohort age, chronic obstructive pulmonary disease, emergency operation, preoperative intra‐aortic balloon pump, left ventricular ejection fraction <30%, estimated glomerular filtration rate <15 mL/min per m2 or dialysis, and any heart valve surgery were independent AF predictors. POAF score was calculated by summing weighting points for each independent AF predictor. According to the prediction model, the incidences of postoperative AF in the derivation cohort were 0, 11.1%; 1, 20.1%; 2, 28.7%; and ≥3, 40.9% (P<0.001), and in the validation cohort they were 0, 13.2%; 1, 19.5%; 2, 29.9%; and ≥3, 42.5% (P<0.001). Patients with a POAF score ≥3, compared with those without arrhythmia, revealed an increased risk of hospital mortality (5.5% versus 3.2%, P=0.001), death after the first postoperative day (5.1% versus 2.6%, P<0.001), cerebrovascular accident (7.8% versus 4.2%, P<0.001), acute kidney injury (15.1% versus 7.1%, P<0.001), renal replacement therapy (3.8% versus 1.4%, P<0.001), and length of hospital stay (mean 13.2 versus 10.2 days, P<0.001).
The POAF score is a simple, accurate bedside tool to predict postoperative AF and its related or accompanying complications.
PMCID: PMC4187480  PMID: 24663335
antiarrhythmic prevention; atrial fibrillation; cardiac surgery; risk stratification
12.  Lipid, blood pressure and kidney update 2013 
The year 2013 proved to be very exciting as far as landmark trials and new guidelines in the field of lipid disorders, blood pressure and kidney diseases. Among these are the International Atherosclerosis Society Global Recommendations for the Management of Dyslipidemia, European Society of Cardiology (ESC)/European Society of Hypertension Guidelines for the Management of Arterial Hypertension, American Diabetes Association Clinical Practice Recommendations, the Kidney Disease: Improving Global Outcomes Clinical Practice Guidelines for Managing Dyslipidemias in Chronic Kidney Disease (CKD) Patients, the American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, the Joint National Committee Expert Panel (JNC 8) Evidence-Based Guideline for the Management of High Blood Pressure in Adults, the American Society of Hypertension/International Society of Hypertension Clinical Practice Guidelines for the Management of Hypertension in the Community, the American College of Physicians Clinical Practice Guideline on Screening, Monitoring, and Treatment of Stage 1–3 CKD and many important trials presented among others during the ESC Annual Congress in Amsterdam and the American Society of Nephrology Annual Meeting—Kidney Week in Atlanta, GA. The paper is an attempt to summarize the most important events and reports in the mentioned areas in the passing year.
PMCID: PMC4012155  PMID: 24573394
Anemia; Blood pressure; Cholesterol; Dyslipidemia; Hypertension; Lipids; Renal disease; Transplantation
13.  Less but better: cardioprotective lipid profile of patients with GCK-MODY despite lower HDL cholesterol level 
Acta Diabetologica  2014;51(4):625-632.
Patients with diabetes caused by single-gene mutations generally exhibit an altered course of diabetes. Those with mutations of the glucokinase gene (GCK-MODY) show good metabolic control and low risk of cardiovascular complications despite paradoxically lowered high-density lipoprotein (HDL) cholesterol levels. In order to investigate the matter, we analyzed the composition of low-density lipoprotein (LDL) and HDL subpopulations in such individuals. The LipoPrint© system (Quantimetrix, USA) based on non-denaturing, linear polyacrylamide gel electrophoresis was used to separate and measure LDL and HDL subclasses in fresh-frozen serum samples from patients with mutations of glucokinase or HNF1A, type 1 diabetes (T1DM) and healthy controls. Fresh serum samples from a total of 37 monogenic diabetes patients (21 from GCK-MODY and 16 from HNF1A-MODY), 22 T1DM patients and 15 healthy individuals were measured in this study. Concentrations of the small, highly atherogenic LDL subpopulation were similar among the compared groups. Large HDL percentage was significantly higher in GCK-MODY than in control (p = 0.0003), T1DM (p = 0.0006) and HNF1A-MODY groups (p = 0.0246). Patients with GCK-MODY were characterized by significantly lower intermediate HDL levels than controls (p = 0.0003) and T1DM (p = 0.0005). Small, potentially atherogenic HDL content differed significantly with the GCK-MODY group showing concentrations of that subfraction from control (p = 0.0096), T1DM (p = 0.0193) and HNF1A-MODY (p = 0.0057) groups. Within-group heterogeneity suggested the existence of potential gene–gene or gene–environment interactions. GCK-MODY is characterized by a strongly protective profile of HDL cholesterol subpopulations. A degree of heterogeneity within the groups suggests the existence of interactions with other genetic or clinical factors.
PMCID: PMC4127439  PMID: 24549415
MODY; Monogenic diabetes; Lipid subpopulations
14.  Obesity indices and inflammatory markers in obese non-diabetic normo- and hypertensive patients: a comparative pilot study 
The aim of this study was to estimate associations between inflammatory markers and obesity indices in normo- and hypertensive subjects.
65 obese adult subjects were divided into two groups: (A) of hypertensives (n = 54) and (B) of normotensives (n = 11). Waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), visceral adiposity index (VAI), body adiposity index (BAI) and tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and high sensitivity C-reactive protein (hsCRP) serum concentrations were estimated.
In group A WHtR was higher (0.69 ± 0.07 vs 0.63 ± 0.06; p < 0.01), hsCRP correlated with BMI and WHtR (r = 0.343; p = 0.011 and r = 0.363; p < 0.01, respectively). BAI correlated with hsCRP in group A and B (r = 0.329; p < 0.05 and r = 0.642; p < 0.05; respectively) and in females and males (r = 0.305; p = 0.05 and r = 0.44; p < 0.05, respectively). In females hsCRP was higher (3.2 ± 2.2 mg/l vs 2.1 ± 1.5 mg/l; p < 0.05). In patients without lipid lowering treatment hsCRP and IL-6 were higher (3.2 ± 1.7 mg/l vs 2.4 ±2.2 mg/l; p = 0.01 and 15.9 ± 7.2 pg/ml vs 13.6 ± 9.9 pg/ml; p < 0.01, respectively).
WHtR is a sensitive index associated with chronic inflammation in obese hypertensive subjects. BAI correlates with hsCRP independently of hypertension and sex. hsCRP is more sensitive marker associated with obesity than IL-6 and TNF-α. Lipid lowering treatment influence chronic inflammation.
PMCID: PMC3921991  PMID: 24507240
Obesity; Hypertension; Chronic inflammation; Obesity indices
15.  Treatment of non-ST-elevation myocardial infarction and ST-elevation myocardial infarction in patients with chronic kidney disease 
Archives of Medical Science : AMS  2013;9(6):1019-1027.
Renal dysfunction is frequent in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Chronic kidney disease (CKD) is associated with very poor prognosis and is an independent predictor of early and late mortality and major bleeding in patients with NSTE-ACS. Patients with NSTE-ACS and CKD are still rarely treated according to guidelines. Medical registers reveal that patients with CKD are usually treated with too high doses of antithrombotics, especially anticoagulants and inhibitors of platelet glycoprotein (GP) IIb/IIIa receptors, and therefore they are more prone to bleeding. Drugs which are excreted mainly or exclusively by the kidney should be administered in a reduced dose or discontinued in patients with CKD. These drugs include enoxaparin, fondaparinux, bivalirudin, and small molecule inhibitors of GP IIb/IIIa inhibitors. In long-term treatment of patients after myocardial infarction, anti-platelet therapy, lipid-lowering therapy and β-blockers are used. Chronic kidney disease patients before qualification for coronary interventions should be carefully selected in order to avoid their use in the group of patients who could not benefit from such procedures. This paper presents schemes of non-ST and ST-segment elevation myocardial infarction treatment in CKD patients in accordance with the current recommendations of the European Society of Cardiology (ESC).
PMCID: PMC3902722  PMID: 24482645
bleeding; chronic kidney disease; management; myocardial infarction; treatment
16.  Obesity indices and adipokines in non-diabetic obese patients with early stages of chronic kidney disease 
The aim of this study was to estimate obesity parameters: waist circumference (WC), waist-to-hip ratio (WHR), weight-to-height ratio (WHtR), visceral adiposity index (VAI), body adiposity index (BAI), and serum adipokines (leptin, adiponectin, resistin) and their associations with estimated glomerular filtration rate (eGFR), serum creatinine, and microalbuminuria (MA) in patients with early stages of CKD and in non-CKD obese patients.
67 non-diabetic obese (BMI ≥30 mg/kg2) out-clinic patients (25 males, 42 females), aged from 36.5 to 64 years were divided into 2 groups: Group A (n=15) – patients with early stages of CKD (eGFR between 30 and 60 ml/min/1.73 m2 or with MA >20 mg/l in morning urine sample independently from GFR) and Group B – patients without chronic CKD (n=52).
In Group A compared to Group B, BAI and leptin were higher (42.2±7.1 vs. 37.5±7.0; p<0.05 and 51.8±26.7 ng/mL vs. 35.3±24.9 ng/mL; p<0.05; respectively) and negative correlations occurred between eGFR and BAI (r=−0.709; p=0.003), leptin (r=−0.68; p=0.005), and resistin (r=−0.528; p<0.05). In Group B, negative correlations occurred between creatinine and VAI (r=−0.332; p<0.05), BAI (r=−0.619; p<0.0001), leptin (r=−0.676; p<0.0001), and adiponectin (r=−0.423; p=0.002), and between eGFR and resistin (r=−0.276; p<0.05).
BAI may be a valuable obesity parameter as a predictor of early stages of CKD in patients with obesity. Leptin may be an important pathogenic factor in obese patients with early stages of CKD. Resistin is associated with eGFR in obese patients, independently of CKD.
PMCID: PMC3852621  PMID: 24280776
adipokines; chronic kidney disease; obesity
17.  Effect of methoxy polyethylene glycol-epoetin beta on oxidative stress in predialysis patients with chronic kidney disease 
There is data in the literature indicating increased oxidative stress in chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs), which are commonly used to treat anemia in patients with CKD, seem to have an antioxidant action, which could be a part of nephroprotection. The aim of the current study was to investigate the effect of a long half-life ESA, methoxy polyethylene glycol-epoetin beta (Mircera), on some markers of oxidative stress in predialysis patients with CKD.
Peripheral blood was collected from 28 predialysis CKD patients 2 times, before Mircera treatment and after achieving target hemoglobin (Hb), and 15 healthy subjects (control group). Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activity in erythrocytes were measured according to commonly used methods as a function of the antioxidant defense system. To assess reactive oxygen species (ROS) production, malondialdehyde (MDA) concentration in erythrocytes and in plasma was measured according to a commonly used method.
SOD, GSH-Px, and CAT activity were similar, but plasma and erythrocyte MDA concentrations were significantly higher in CKD patients before ESA treatment in comparison to the control group. SOD, GSH-Px, and CAT activity was significantly higher, but plasma and erythrocyte MDA concentrations were significantly lower, in CKD patients after ESA treatment in comparison to these patients before treatment. We did not find a significant correlation between Hb concentration and SOD, GSH-Px, and CAT activity and plasma, as well as erythrocyte MDA concentrations. Analysis of all investigated groups showed a significant negative correlation between Hb concentration and plasma MDA concentration.
Our results suggest that treatment of anemia with methoxy polyethylene glycol-epoetin beta may inhibit oxidative stress in predialysis patients with CKD by enhancing the antioxidant defense system and reducing ROS production.
PMCID: PMC3829740  PMID: 24201565
chronic kidney disease (CKD); erythropoiesis-stimulating agents; oxidative stress; anemia
18.  Blood Pressure Levels and Stroke: J-curve Phenomenon? 
Current Hypertension Reports  2013;15(6):575-581.
The blood pressure J-curve discussion has been ongoing for more than 30 years, yet there are still questions in need of definitive answers. On one hand, existing antihypertensive therapy studies provide strong evidence for J-curve-shaped relationships between both diastolic and systolic blood pressure and primary outcomes in the general hypertensive patient population, as well as in high-risk populations, including subjects with coronary artery disease, diabetes mellitus, left ventricular hypertrophy, and the elderly. On the other hand, we have very limited data on the relationship between systolic and diastolic blood pressure and stroke prevention. Moreover, it seems that this outcome is more a case of “the lower the better.” Further large, well-designed studies are necessary in order to clarify this issue, especially as existing available studies are observational, and randomized trials either did not have or lost statistical power and were thus inconclusive.
PMCID: PMC3838583  PMID: 24158455
Blood pressure; Cerebrovascular event; Hypertension; J-curve relationship; Stroke
19.  Statin treatment in the elderly: how much do we know? 
PMCID: PMC3776192  PMID: 24049514
20.  Current perspectives on treatment of hypertensive patients with chronic obstructive pulmonary disease 
Systemic hypertension and chronic obstructive pulmonary disease (COPD) frequently coexist in the same patient, especially in the elderly. Today, a wide variety of antihypertensive drugs with different mechanisms of action are available to the prescribing physician. In addition, combination drugs for hypertension are becoming increasingly popular. Certain antihypertensive drugs can affect pulmonary function. Therefore the management of such patients can present therapeutic challenges. We have examined the literature pertaining to the use of antihypertensive drugs in patients with systemic hypertension and coexisting COPD. Although data are often limited or of poor quality, we have attempted to review and then provide recommendations regarding the use of all the specific classes of antihypertensive drug therapies including combination drugs in patients with COPD. The antihypertensive agents reviewed include diuretics, aldosterone receptor blockers, beta blockers, combined alpha and beta blockers, angiotensin-converting enzyme inhibitors, angiotensin II antagonists, calcium channel blockers, alpha-1 blockers, centrally acting drugs, direct vasodilators, and combinations of these drugs. Of these classes, calcium channel blockers and angiotensin II antagonists appear to be the best initial choices if hypertension is the only indication for treatment. However, the limited data available on many of these drugs suggest that additional studies are needed to more precisely determine the best treatment choices in this widely prevalent patient group.
PMCID: PMC3724277  PMID: 23901294
blood pressure; hypertension; COPD; treatment; antihypertensive drugs
21.  The influence of atorvastatin on parameters of inflammation left ventricular function, hospitalizations and mortality in patients with dilated cardiomyopathy – 5-year follow-up 
We assessed the influence of atorvastatin on selected indicators of an inflammatory condition, left ventricular function, hospitalizations and mortality in patients with dilated cardiomyopathy (DCM).
We included 68 DCM patients with left ventricular ejection fraction (LVEF) ≤40% treated optimally in a prospective, randomized study. They were observed for 5 years. Patients were divided into two groups: patients who were commenced on atorvastatin 40 mg daily for two months followed by an individually matched dose of 10 or 20 mg/day (group A), and patients who were treated according to current recommendations without statin therapy (group B).
After 5-year follow-up we assessed 45 patients of mean age 59 ± 11 years - 22 patients in group A (77% male) and 23 patients in group B (82% male). Interleukin-6, tumor necrosis factor alpha, and uric acid concentrations were significantly lower in the statin group than in group B (14.96 ± 4.76 vs. 19.02 ± 3.94 pg/ml, p = 0.012; 19.10 ± 6.39 vs. 27.53 ± 7.39 pg/ml, p = 0.001, and 5.28 ± 0.48 vs. 6.53 ± 0.46 mg/dl, p = 0.001, respectively). In patients on statin therapy a reduction of N-terminal pro-brain natriuretic peptide concentration (from 1425.28 ± 1264.48 to 1098.01 ± 1483.86 pg/ml, p = 0.045), decrease in left ventricular diastolic (from 7.15 ± 0.90 to 6.67 ± 0.88 cm, p = 0.001) and systolic diameters (from 5.87 ± 0.92 to 5.17 ± 0.97, p = 0.001) in comparison to initial values were observed. We also showed the significant increase of LVEF in patients after statin therapy (from 32.0 ± 6.4 to 38.8 ± 8.8%, p = 0.016). Based on a comparison of curves using the log-rank test, the probability of survival to 5 years was significantly higher in patients receiving statins (p = 0.005).
Atorvastatin in a small dose significantly reduce levels of inflammatory cytokines and uric acid, improve hemodynamic parameters and improve 5-year survival in patients with DCM.
PMCID: PMC3641983  PMID: 23566246
Atorvastatin; Dilated cardiomyopathy; Heart failure; Inflammation
22.  The risk of atherosclerosis in patients with chronic kidney disease 
International Urology and Nephrology  2013;45(6):1605-1612.
Chronic kidney disease (CKD) is becoming a serious health problem; the number of people with impaired renal function is rapidly rising, especially in industrialized countries. A major complication of CKD is cardiovascular disease. Accelerated atherosclerosis has been observed in early stages of renal dysfunction. The purpose of this study was to examine the relationship between the degree of renal insufficiency and both the prevalence and intensity of coronary artery disease (assessed on the basis of number of vessels with stenosis).
446 individuals with both serum creatinine >120 μmol/l (men) or >96 μmol/l (women) and acute coronary syndrome were included in the study. All patients included in this analysis underwent urgent coronarography. Data concerning glomerular filtration rate (GFR), number of vessels with stenosis, hypertension, lipid disorders, creatinine concentration, C-reactive protein, glucose and lipid profile were analyzed.
This study confirmed that moderate to severe renal impairment is associated with accelerated atherosclerosis. Moreover, patients with GFR values below 60 ml/min/1.73 m2 are predisposed to accelerated, multivessel cardiovascular disease.
GFR seems to be an independent risk factor for multivessel cardiovascular disease. Due to the fact that patients with renal dysfunction are at high risk of cardiovascular events, they should obtain optimal treatment resulting not only in kidney protection but also in the elimination of cardiovascular risk factors.
PMCID: PMC3844144  PMID: 23483304
Atherosclerosis; Chronic kidney disease; Comorbidities
23.  Highlights of mechanistic and therapeutic cachexia and sarcopenia research 2010 to 2012 and their relevance for cardiology 
Sarcopenia and cachexia are significant medical problems with a high disease-related burden in cardiovascular illness. Muscle wasting and weight loss are very frequent particularly in chronic heart failure and they relate to poor prognosis. Although clinically largely underestimated, the fields of cachexia and sarcopenia are of great relevance to cardiologists. In cachexia and sarcopenia a significant number of research publications related to basic science questions of muscle wasting and lipolysis were published between 2010 and 2012. Recently, the two processes of muscle wasting and lipolysis were found to be closely linked. Treatment research in pre-clinical models involves studies on a number of different therapeutic entities, including ghrelin, selective androgen receptor modulators (SARMs), as well as drugs targeting myostatin or melanocortin-4. In the human setting, studies using enobosarm (a SARM) and anamorelin (ghrelin) are in phase III. The last 3 years have seen significant efforts to define the field using consensus statements. In the future, these definitions should also be considered for guidelines and treatment trials in cardiovascular medicine. The current review aims to summarize important information and development in the fields of muscle wasting, sarcopenia and cachexia, focusing on findings in cardiovascular research, in order for cardiologists to have a better understanding of the progress in this still insufficiently known field.
PMCID: PMC3598129  PMID: 23515589
cachexia; sarcopenia; muscle wasting; mechanism; therapy; cardiovascular illness; heart failure
24.  Prevention of sudden cardiac death in patients with chronic kidney disease 
BMC Nephrology  2012;13:162.
Cardiovascular deaths account for about 40% of all deaths of patients with chronic kidney disease (CKD), particularly those on dialysis, while sudden cardiac death (SCD) might be responsible for as many as 60% of SCD in patients undergoing dialysis. Studies have demonstrated a number of factors occurring in hemodialysis (HD) that could lead to cardiac arrhythmias. Patients with CKD undergoing HD are at high risk of ventricular arrhythmia and SCD since changes associated with renal failure and hemodialysis-related disorders overlap. Antiarrhythmic therapy is much more difficult in patients with CKD, but the general principles are similar to those in patients with normal renal function - at first, the cause of arrhythmias should be found and eliminated. Also the choice of therapy is narrowed due to the altered pharmacokinetics of many drugs resulting from renal failure, neurotoxicity of certain drugs and their complex interactions. Cardiac pacing in elderly patients is a common method of treatment. Assessment of patients’ prognosis is important when deciding whether to implant complex devices. There are reports concerning greater risk of surgical complications, which depends also on the extent of the surgical site. The decision concerning implantation of a pacing system in patients with CKD should be made on the basis of individual assessment of the patient.
PMCID: PMC3519551  PMID: 23206758
Arrhythmias; Chronic kidney disease; Renal failure; Sudden cardiac death
25.  Blood Pressure J-Curve: Current Concepts 
Current Hypertension Reports  2012;14(6):556-566.
The blood pressure (BP) J-curve debate started in 1979, and we still cannot definitively answer all the questions. However, available studies of antihypertensive treatment provide strong evidence for J-shaped relationships between both diastolic and systolic BP and main outcomes in the general population of hypertensive patients, as well as in high-risk populations, including subjects with coronary artery disease, diabetes mellitus, left ventricular hypertrophy, and elderly patients. However, further studies are still necessary in order to clarify this issue. This is connected to the fact that most available studies were observational, and randomized trials did not have or lost their statistical power and were inconclusive. Perhaps only the Systolic Blood Pressure Intervention Trial (SPRINT) and Optimal Blood Pressure and Cholesterol Targets for Preventing Recurrent Stroke in Hypertensives (ESH-CHL-SHOT) will be able to finally answer all the questions. According to the current state of knowledge, it seems reasonable to suggest lowering BP to values within the 130–139/80–85 mmHg range, possibly close to the lower values in this range, in all hypertensive patients and to be very careful with further BP level reductions, especially in high-risk hypertensive patients.
PMCID: PMC3490060  PMID: 23054894
Blood pressure; J-curve; High-risk populations; Cardiovascular risk; Diabetes; Coronary artery disease; CAD; Elderly; Left ventricle hypertrophy; LVH; Hypertension; Hypotensive therapy; Antihypertensive treatment

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