Marcin Barylski

Lipids, blood pressure, kidney - what was new in 2011?

The year 2011 was very interesting regarding new studies, trials and guidelines in the field of lipidology, hypertensiology and nephrology. Suffice it to mention the new European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines on the management of dyslipidaemias, American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines on hypertension in the elderly, and many important trials presented among others during the American Society of Nephrology (ASN) Annual Congress in Philadelphia and the AHA Annual Congress in Orlando. The paper is an attempt to summarize the most important events and reports in the mentioned areas in the passing year.

Statins decrease all-cause mortality only in CKD patients not requiring dialysis therapy—A meta-analysis of 11 randomized controlled trials involving 21,295 participants

The available studies have reported the benefits of statins on all-cause and cardiovascular mortality in chronic kidney disease (CKD) patients. However studies in end-stage renal disease patients on dialysis yielded conflicting results. Therefore, we performed a meta-analysis and provide the most reliable trial data to date on the impact of statin therapy on cardiovascular events and death from all causes in CKD patients. Data from PubMed, Web of Science, Cochrane Library, and Scopus for the years 1966 to October 2012 were searched. The final meta-analysis included 11 randomized controlled trials involving 21,295 participants with CKD. Among them 6857 were on dialysis. The use of statins in subjects with non-dialysis-dependent CKD resulted in a marked reduction in death from all causes (relative risk [RR]: 0.66; 95% confidence interval [CI]: 0.55-0.79; p<0.0001), cardiac causes (RR: 0.69; 95%CI: 0.55-0.68; p=0.0012), cardiovascular events (RR: 0.55; 95%CI: 0.4-0.75; p=0.0001) and stroke (RR: 0.66; 95%CI: 0.5-0.88; p=0.0022). The use of statins in dialysis-dependent CKD patients resulted in a non-significant effect on death from all causes (RR: 0.99; 95%CI: 0.88-1.11; p=0.85) and stroke (RR: 1.31; 95%CI: 0.9-1.89; p>0.05), but had the effect of reducing death from cardiac causes (RR: 0.79; 95%CI: 0.64-0.98; p<0.05) and cardiovascular events (RR: 0.81; 95%CI: 0.7-0.94; p<0.05). In conclusion, the use of statins should be indicated in cardiovascular disease prevention especially in patients with non-dialysis-dependent CKD. According to the very limited data the obtained results suggest caution in expecting a reduction in cardiovascular events in patients on dialysis.

HSP 70 and atherosclerosis – protector or activator?

Background: Atherosclerosis and its complications represent the leading cause of morbidity and mortality. Heat shock protein 70 (HSP70) protects cellular elements from injury by reducing oxidation, inflammation and apoptosis and by refolding damaged proteins. HSP70 improves viability of stressed vascular smooth muscle cells, possibly via its chaperone functions. It has been proposed that the response mounted against bacterial HSPs results in an autoimmune reaction, which has the potential to cause complement-mediated endothelial injury, and hence accelerate atherogenesis. Objective: to examine the roles of HSPs in atherosclerosis. Methods: A literature review. Results/Conclusions: The role of HSPs in atherosclerosis is controversial. HSP60 probably acts as an autoantigen, and may trigger both cell- and antibody-mediated immune responses, while HSP70 is likely to be involved in cytoprotection. The significance of this inverse relation between HSP70 and atherosclerosis has not yet been elucidated. Whether HSPs will become therapeutic targets remains to be established.

Emerging therapies for raising high-density lipoprotein cholesterol (HDL-C) and augmenting HDL particle functionality

High-density lipoprotein (HDL) particles are highly complex polymolecular aggregates capable of performing a remarkable range of atheroprotective functions. Considerable research is being performed throughout the world to develop novel pharmacologic approaches to: (1) promote apoprotein A-I and HDL particle biosynthesis; (2) augment capacity for reverse cholesterol transport so as to reduce risk for the development and progression of atherosclerotic disease; and (3) modulate the functionality of HDL particles in order to increase their capacity to antagonize oxidation, inflammation, thrombosis, endothelial dysfunction, insulin resistance, and other processes that participate in arterial wall injury. HDL metabolism and the molecular constitution of HDL particles are highly complex and can change in response to both acute and chronic alterations in the metabolic milieu. To date, some of these interventions have been shown to positively impact rates of coronary artery disease progression. However, none of them have as yet been shown to significantly reduce risk for cardiovascular events. In the next 3-5 years a variety of pharmacologic interventions for modulating HDL metabolism and functionality will be tested in large, randomized, prospective outcomes trials. It is hoped that one or more of these therapeutic approaches will result in the ability to further reduce risk for cardiovascular events once low-density lipoprotein cholesterol and non-HDL-cholesterol targets have been attained.

Neutrophil Superoxide Anion Generation During Atorvastatin and Fluvastatin Therapy Used in Coronary Heart Disease Primary Prevention

Neutrophil superoxide anion generation was measured during atorvastatin and fluvastatin therapy in patients with coronary heart disease (CHD) risk. The patients were randomly allotted into three groups. The atorvastatin group comprised 17 patients who were administered the drug orally 10 mg a day at bed time. The fluvastatin group consisted of 18 patients on an oral dose of 40 mg once daily at bed time. The control group comprised 12 healthy subjects with no drug administration. Blood samples were collected from cubital vein before and after 6-week therapy with these drugs and once in the control group. Neutrophil superoxide anion generation in whole blood without and with opsonized zymosan (OZ) stimulation was determined using superoxide dismutase from bovine erythrocytes. In the atorvastatin group, statistically significant (P < 0.05) decrease in superoxide anion generation by nonstimulated and OZ-stimulated neutrophils was observed after 6 weeks of therapy. In fluvastatin group, no changes in neutrophil superoxide anion generation were observed after the 6-week treatment period. Our study has shown an additional nonlipid mechanism of atorvastatin used in CHD primary prevention.

Plasma Endothelin-1 Levels in Septic Patients

Dysfunction of the vascular endothelium (ET) causes an increase in serum ET-1 concentration, as observed in septic patients. It was assumed that in this patient population the ET-1 level correlates with the degree of sepsis severity, including the level of organ dysfunction and, in particular, the level of circulatory dysfunction. The aim of the present study was to assess the relationship between levels of ET-1 and levels of N-terminal brain natriuretic propeptide (NT-proBNP), procalcitonin (PCT), and C-reactive protein (CRP), as well as the Sepsis-related Organ Failure Assessment (SOFA) score in septic patients. PCT and CRP were used to estimate the level of sepsis severity; the SOFA score was used to estimate multiorgan dysfunction; and NT-proBNP was used as a marker of cardiac dysfunction. Twenty patients with sepsis and severe sepsis were included in the study. Blood serum ET-1, NT-proBNP, PCT, and CRP concentrations were determined at specific time intervals, and the SOFA score was calculated. Mean ET-1, NT-proBNP, PCT, and CRP concentrations were 8.39 pg/ml ± 6.39 pg/mL, 140.80 pg/mL ± 84.65 pg/mL, 22.32 ng/mL ± 97.41 ng/mL, and 128.51 mg/L ± 79.05 mg/L, respectively. Correlation between ET-1 levels and levels of NT-proBNP, PCT, and CRP was .3879 (P < .001), .358 (P < .001), and .225 (P = .011), respectively. Mean SOFA score was 6.31 pts ± 3.75 pts. Correlation between the ET-1 levels and SOFA score was .470 (P < .001). Six patients (30%) died during the observation period of 28 days. ET-1 levels correlate with levels of NT-proBNP, PCT, and CRP, as well as the SOFA score in septic patients.

Combined Dyslipidemia: Should the Focus be LDL Cholesterol or Atherogenic Dyslipidemia?

As the population becomes more obese and the prevalence of diabetes and the metabolic syndrome increases, low-density lipoprotein-cholesterol (LDL-C) may lose its value as a sole predictor for cardiovascular risk among lipids. Combined dyslipidemia is typically characterized by elevations in LDL-C and triglyceride levels, often accompanied by decreased high-density lipoproteincholesterol (HDL-C) concentrations and increased levels of small, dense LDL. This common disorder results from overproduction of hepatically synthesized apolipoprotein B in very low-density lipoproteins. In the last few years most of the international scientific guidelines as well as several expert panels have confirmed that LDL-C represents the primary or even the only target of treatment. Yet, increasing evidence suggests moving away from a LDL-C target-based approach to a more tailored treatment approach. For example, non- HDL-C has been introduced in the last few years as a target of treatment.

Plasma Total Antioxidant Activity in Comparison With Plasma NO and VEGF Levels in Patients With Metabolic Syndrome

Introduction: The aim of our study was to estimate plasma antioxidant activity as well as plasma nitric oxide (NO) and vascular endothelial growth factor levels in patients with metabolic syndrome compared with healthy participants. Material and Methods: Fifty patients (24 women and 26 men, mean age 55.9 + 11.8 years) with metabolic syndrome were compared with 25 healthy participants (12 women and 13 men, mean age 54.2 + 12.8 years). Plasma total antioxidant activity and plasma levels of NO and VEGF were determined in all participants. Results: In the patients with metabolic syndrome, plasma total antioxidant activity, nitric oxide, and vascular endothelial growth factor were significantly lower (P < .001) than that observed in healthy participants (3.2 + 1.6 vs 6.4 + 2.1 mM/L), (6.3 + 2.2 vs 9.8 + 2.7 μM/L), and 71.0 + 16.9 vs 137.5 + 12.6 pg/mL), respectively. Conclusions: Decreased plasma total antioxidant activity, NO, and VEGF levels in patients with metabolic syndrome reflect significant endothelial dysfunction. This suggests that oxidation—reduction balance disorders might play an important role in this process

Atrial and brain natriuretic peptide and endothelin-1 concentration in patients with idiopathic arterial hypertension: The dependence on the selected morphological parameters

Introduction. The aim of the work was to study the maintenance of atrial and brain natriuretic peptide (ANP, BNP) and endothelin-1 (ET-1) in patients with idiopathic arterial hypertension and the relationships between cardiac morphological parameters and concentrations of examined peptides in group of patients with left ventricular hypertrophy (LVH). Methods. Seventy-six patients were enrolled in the study: 21 patients with confirmed idiopathic arterial hypertension (group 1), 18 with idiopathic hypertension and eccentric hypertrophy (group 1a), 14 with idiopathic hypertension and concentric hypertrophy (group 1b), and 23 patients without arterial hypertension, organic heart disease, or chronic respiratory tract diseases (group 2—control group). All subjects were submitted for echocardiographic evaluation. Posterior wall thickness (PWT), interventricular septum thickness (IVST), left ventricular end-diastolic diameter (LVEDd), left atrium diameter (LAD), left ventricular mass index (LVMI), ejection fraction (EF), fractional shortening (FS), midwall shortening fraction (MWS), and relative wall thickness index (RWT) were studied. Concentrations of ANP(1-28), BNP, and ET-1 were determined with the use of radioimmunological kits (RIA). The obtained results were subjected to statistical analysis. Results. A considerable increase of ANP and BNP was observed in all patients with hypertension (group 1) in comparison to patients without hypertension (group 2). Significant increases of ANP were found in groups 1a and 1b in comparison to group 1 and 2, as well as considerably increase of BNP in group 1b compared to groups 1, 1a, and 2. In the group of patients with hypertension (group 1), a significant increase in the concentration of ET-1 compared to group 2 was found. However, the concentrations of ET-1 in groups 1 and 2 were not statistically different. Significant differences in concentrations of ET-1 between groups 1a, 1b, and 1 and 2 were seen. Significant correlations were found between concentrations of ANP, BNP, ET-1 and morphological parameters: PWT, IVST, LVMI and RWT. In group 1b, a correlation between concentrations of ANP, BNP, MWS, and LAD was found. The multiple regression analysis showed that RWT independently correlates with concentrations of ANP and BNP, and the concentration of BNP is in closer relation to RWT than ANP. In the case of ET-1, the multiple regression analysis did not show that LVMI or RWT had any independent influence on secretion of ET-1 in patients with idiopathic hypertension and LVH. Conclusions. Increased concentration of ANP in patients with idiopathic hypertension may point to the coexistence of complications with type of LVH. High concentration of BNP may specifically suggest concentric LVH. This is important—especially if there are difficulties in interpretations of results of other clinical examinations. However, increased concentrations of ET-1 in the plasma of patients with hypertension and LVH should not be treated as an indicator of LVH degree.

Use of Montelukast Alone or in Combination with Desloratadine or Levocetirizine in Patients with Persistent Allergic Rhinitis

Background We assessed the course of treatment in patients with persistent allergic rhinitis (AR) treated with montelukast, levocetirizine, or desloratadine alone or combinations of antihistamine and montelukast. Methods A 32-week randomized, double-blind, placebo-controlled, crossover, double-armed study in 40 adult patients with history of persistent AR, clinical allergy to house-dust mites, and a total nasal symptom score of at least 5 (congestion of at least 2) has been performed. Patients with asthma, chronic obstructive pulmonary disease, nonallergic rhinitis with clinical allergy associated with seasonal allergens, and other serious diseases were excluded. There were four 6-week treatment periods separated by 2-week washout periods. Twenty patients received either montelukast or antihistamine, a combination of montelukast and antihistamine, or placebo. The sequence of treatment was randomly assigned. Nasal symptoms were assessed using a 4-point scale at baseline, daily during the 1st week and on days 14, 21, 28, 35, and 42 of treatment. Results Montelukast alone, levocetirizine alone, desloratadine alone, and the montelukast/antihistamine combinations significantly improved nasal symptoms during the first 24 hours. Improvement gradually increased during the 6 weeks of treatment, especially in patients receiving montelukast alone or in combination therapy with the antihistamine in both arms. Improvement at 42 days of treatment was significantly greater than that achieved on the 1st day of therapy in patients treated with the combination of montelukast and levocetirizine. Conclusion Montelukast alone or in combination with antihistamines gave a gradual increase in nasal symptom improvement within 6 weeks of treatment in patients with persistent AR.