Farmakoterapia zaburzeń lipidowych w praktyce. Wybrane aspekty z wytycznych European Society of Cardiology i European Atherosclerosis Society.

Choroby układu sercowo-naczyniowego to niezmiennie główna przyczyna chorobowości i śmiertelności. Wpływ na patogenezę tych chorób ma wiele czynników ryzyka, a jednym z nich są zaburzenia lipidowe. Leczenie jest wielokierunkowe i obejmuje ocenę całkowitego ryzyka sercowo-naczyniowego z określeniem celów terapeutycznych, modyfikację stylu życia (leczenie niefarmakologiczne) oraz farmakoterapię. Niniejsze opracowanie ma celu praktyczne podejście do leczenia zaburzeń lipidowych i zawiera wybrane elementy dotyczące głównie aktualnych standardów leczenia farmakologicznego.Choroby układu sercowo-naczyniowego to niezmiennie główna przyczyna chorobowości i śmiertelności. Wpływ na patogenezę tych chorób ma wiele czynników ryzyka, a jednym z nich są zaburzenia lipidowe. Leczenie jest wielokierunkowe i obejmuje ocenę całkowitego ryzyka sercowo-naczyniowego z określeniem celów terapeutycznych, modyfikację stylu życia (leczenie niefarmakologiczne) oraz farmakoterapię. Niniejsze opracowanie ma celu praktyczne podejście do leczenia zaburzeń lipidowych i zawiera wybrane elementy dotyczące głównie aktualnych standardów leczenia farmakologicznego

Hiperurykemia w chorobach układu sercowo-naczyniowego

Hyperuricemia is a very common phenomenon in everyday medical practice and according tothe latest epidemiological studies, it affects 57.6 million people worldwide. We recognize itwhen the concentration of uric acid in blood exceeds 6.8 mg/dl. The etiology of hyperuricemiais multifactorial and results, inter alia, from excessive purine production, excessive supplyand absorption, and impaired excretion of uric acid. Hyperuricemia leads to the developmentof gout. In addition, it has been proven that hyperuricemia is associated with an increasedrisk of cardiovascular disease. The hyperuricemia therapy requires comprehensive activities.One of the available methods of pharmacological treatment of hyperuricemia is theuse of allopurinol. This drug significantly reduces serum uric acid levels and reduces therisk of heart disease with a reduction in the total risk of death.Hiperurykemia jest bardzo częstym zjawiskiem w codziennej praktyce lekarskiej i według najnowszych badań epidemiologicznych dotyczy 57,6 milionów ludzi na całym świecie. Rozpoznajemy ją, gdy stężenie kwasu moczowego we krwi przekracza 6,8 mg/dl. Etiologia hiperurykemii jest wieloczynnikowa i wynika między innymi z nadmiernej produkcji puryn, nadmiernej ich podaży i wchłaniania oraz upośledzonego wydalania kwasu moczowego. Hiperurykemia prowadzi do rozwoju dny moczanowej. Ponadto udowodniono powiązanie hiperurykemii ze zwiększonym ryzykiem występowania chorób układu sercowo-naczyniowego. Terapia hiperurykemii wymaga kompleksowych działań. Jedną z dostępnych metod leczenia farmakologicznego hiperurykemii jest stosowanie allopurynolu. Lek ten w sposób istotny redukuje stężenie kwasu moczowego w surowicy oraz zmniejsza ryzyko wystąpienia chorób serca ze zmniejszeniem całkowitego ryzyka zgonu

A case of a patient treated with percutaneous edge-to-edge mitral valve repair, percutaneous left atrial appendage occlusion and implantable cardioverter-defibrillator

The article presents the case of a 55-year-old woman who suffered from anterior myocardial infarction andchronic complications of the underlying disease, heart failure with reduced left ventricular ejection fraction,severe secondary mitral regurgitation, and paroxysmal atrial fibrillation. Due to the severity of symptoms,which persisted despite the optimal pharmacotherapy, after exclusion of reversible causes, the patient wasqualified for different advanced percutaneous treatment methods. Within two years from the onset of thedisease, three percutaneous procedures were performed: mitral valve correction with the MitraClip system,left atrial appendage occlusion using the Watchman system, and implantation of cardioverter-defibrillator

Validation of the Functioning in Chronic Illness Scale (FCIS)

Diagnosis of deficient areas in the functioning of patient with chronic disease is necessary to undertake the adequate therapeutic actions. The aim of the study was to validate a new self-reported questionnaire for patients with chronic disease assessing the impact of the disease on the patient, the patient’s impact on the disease and the impact of the disease on patient’s attitudes. Results: The internal consistency of the questionnaire expressed by a-Cronbach coefficient = 0.855, indicates its high reliability and homogeneity. The set of 24 items fulfilled the assumption of factor analysis: the determinant of correlation matrix was 0.001, Kaiser-Mayer-Olkin (K-M-O) statistic was 0.843 and the Bartlett’ test of sphericity was statistically significant. The factor analysis was conducted using the principal component analysis with Varimax rotation. The scale and subscale levels were determined based on the percentiles scale. Conclusion: The validation procedure revealed that FCIS is a reliable and homogeneous tool to measure patient’s physical and mental functioning in the chronic illness. The set of items divided into 3 subscales allows evaluation of: the impact of the disease on the patient, the patient’s impact on the disease and the impact of the disease on the patient’s attitudes

Tlenek azotu jako przyczyna i potencjalne miejsce ingerencji terapeutycznej w hiporeaktywności naczyń we wczesnym okresie posocznicy

Kliniczny zespół rozwijający się w konsekwencji uogólnionej reakcji zapalnej w następstwie zakażenia określa się mianem posocznicy. W ciężkiej postaci posocznicy dochodzi do niewydolności wielonarządowej. Podstawowy mechanizm redukcji odpowiedzi mięśniówki gładkiej naczyń przez lipopolisacharydy wiąże się z aktywacją odpowiedzi zapalnej z uwalnianiem cytokin i chemokin o działaniu prozapalnym, jak interleukina (IL) 1, IL-6, IL-12, IL-15, IL-18, czynnik martwicy nowotworów a. Kolejnym etapem jest uwalnianie następnych mediatorów reakcji zapalnej, takich jak prostaglandyny, leukotrieny, białka ostrej fazy czy aktywacja indukowalnej syntazy tlenku azotu, a także wolnych rodników tlenowych. Nasilenie produkcji tlenku azotu jest w początkowym okresie posocznicy podstawowym mechanizmem powstawania hiporeaktywności naczyń i wtórnie objawów wstrząsu. W związku z tym pojawia się pytanie, czy efekt działania tlenku azotu jest istotny klinicznie, a wobec tego, czy hamowanie syntezy tlenku azotu we wczesnym okresie posocznicy może poprawiać rokowanie. Wyniki prowadzonych badań wykazały jednak, że produkcja tlenku azotu, zwłaszcza w pierwszym okresie posocznicy, wydaje się zjawiskiem istotnym nie tylko ze względu na skutki hemodynamiczne, ale również z powodu aktywacji procesu zapalnego. Zważywszy na wieloczynnikową etiologię posocznicy i wtórnej hiporeaktywności mięśniówki gładkiej, terapia związana z hamowaniem syntezy tlenku azotu nie ma zastosowania klinicznego, tym bardziej że zwykle leczenie rozpoczyna się znacznie później niż interwencję terapeutyczną w doświadczalnych modelach wstrząsu septycznego. (Folia Cardiologica Excerpta 2011; 6, 1: 36–43

The Adherence Scale in Chronic Diseases (ASCD). The power of knowledge: the key to successful patient — health care provider cooperation

Introduction. Patients’ adherence to long-term therapies is low. It translates into reduced quality of life and significant deterioration of health economics. Identification of potential barriers of medication-related adherence is a starting point allowing implementation of more advanced interventions directed to adherence improvement. Aim. The purpose of our study was to create and validate a simple instrument used to assess patients’ adherence to recommended medications. Material and methods. The Adherence Scale in Chronic Diseases is a self-reported questionnaire with 8 items and with proposed 5 sets of answers. The total score in the Adherence Scale in Chronic Diseases ranges from 0 to 32 points. Three levels of adherence were considered (low: scores of 0 to 20; medium 21 to 25; high > 26). The validation of the questionnaire was conducted in accordance with the validation procedure. Assessment of the internal consistency was performed using a-Cronbach coefficient. In order to conduct the factor analysis, we assessed: the determinant of correlation matrix, Kaiser-Mayer-Olkin (K-M-O) statistic and the Bartlett’s test of sphericity. Factor analysis was conducted using principal component analysis with Oblimin rotation. The Kaiser criterion and scree plot were used in order to determine components of the questionnaire. Adherence levels were determined based on the percentiles. Results. Grand total of 413 patients with a cardiovascular disease were included in the study. The reliability and homogeneity of the questionnaire were confirmed by a-Cronbach coefficient (0.739). Factor analysis showed that in this questionnaire we can extract two components. The analysis of factor loadings indicated excluding item 2 from the questionnaire. After exclusion of the mentioned item, we repeated the validation procedure. For such a new dataset, according to the Kaiser criterion, only one component was extracted. Conclusions. The Adherence Scale in Chronic Diseases is a practical, reliable, consistent and well validated instrument for identifying specific obstacles to medication adherence. Its simplicity causes that it can be successfully applied in daily practice by health care professionals. Our survey has the potential to improve patient — health care professional communication and relationship.

Impact of prior statin therapy on evaluation of the inflammatory process and cortisol concentration in patients with the first ST-segment elevation myocardial infarction undergoing coronary angioplasty with bare metal stent implantation

Introduction. The aim of the current study was to verify the impact of statin therapy on evaluation of the inflammatory process and cortisol concentration in patients with the first episode of ST-segment elevation myocardial infarction undergoing coronary angioplasty with bare metal stent implantation. Material and methods. The study was designed as a prospective, single-center cohort study, with a total number of 200 patients enrolled between 2005 and 2008. Results. Seventeen patients with ongoing statin therapy and 167 patients without those agents underwent pPCI with BMS implantation. The cortisol concentration on admission was significantly lower in statin therapy subgroup — median 14.9 μg/dL (9.5–23.3 IQR) vs. 28,1 μg/dL (17.2–39.9 IQR) for patients without lipid lowering drug, p = 0.01. The level of cortisol after 23h was also significantly lower in statin receiving subgroup: 10.4 μg/dL (8.3–19 IQR) vs. 17.3 μg/dL (10.1–25.9 IQR) adequately, p = 0.021. Those two groups did not differ significantly in relation to CRP, IL-6, IL-10 concentrations and to anti-inflammatory cytokine ratio [IL-6/IL-10] on admission, after 24h and at discharge. Significant differences were observed in the concentrations of cTnI and activities of CK and CK-MB. Conclusions. Ongoing statin therapy before an episode of myocardial infarction has an influence on cortisol concentration and cardiac markers. No significant effect on serum levels of cytokines has been observed.

The influence of genetic polymorphisms of CYP2C19 and ABCB1 on ADP-induced platelet aggregation in clopidogrel-treated patients: A comparison between the index hospitalization for myocardial infarction and the 3-month follow-up visit

Background. Recent studies suggest that polymorphisms of genes involved in the clopidogrel metabolism may be associated with an impaired drug bioactivation and possibly with unfavourable clinical outcomes. The aim of this study was to assess the effect of selected genetic polymorphisms on adenosine diphosphate-induced platelet aggregation (ADP-PA) during the index hospitalization and after 3 months of clopidogrel therapy in patients presenting with myocardial infarction (MI). Materials and methods. The study was designed as a single-center cohort trial with the 3-month follow-up. Genotyping for CYP2C19*2, CYP2C19*17, ABCB1 alleles and platelet reactivity assessment using the Multiplate Analyzer were performed in 157 patients. Results. ADP-PA during the index hospitalization was significantly higher than at the 3-month follow-up visit regardless of the genotyp e [CYP2C19*1/*1 alleles (24.0 v. 15.5 U; p < 0.00001), CYP2C19*17 allele (CT: 25.0 v. 15.0 U; p = 0.000 2; TT: 35.0 v. 22.0 U; p = 0.02) and ABCB1 allele (CC: 27.0 v. 15.0 U; p < 0.0002; CT 24.0 v. 17.0 U; p < 0.0005)]. In univariate analysis we failed to demonstrate any impact of the analyzed genetic variants on both in-hospital and 3-month ADP-PA, except for CYP2C19*17/*17 homozygotes. Significantly higher values of ADP-PA were found in CYP2C19*17/*17 (TT homozygotes) allele carriers when compared with carriers of two wild alleles during the index hospitalization (CC: 20.0 U v. TT: 35.0 U; p = 0.02), but not at the 3-month follow-up visit. Multivariate regression analysis revealed increased mean platelet volume (β = 7.2), elevated platelet count (β = 0.2) and the presence of heart failure at discharge (β = 6.9), but not genetic polymorphisms, to be independent determinants of high ADP-PA during the index hospitalization. Similarly, elderly age (β = 3.3), high white blood cell count (β = 1.4), elevated platelet count (β = 0.4) and increased mean platelet volume (β = 0.1), but not genetic polymorphisms, were independently associated with the higher values of ADP-PA after 3 months of clopidogrel therapy. Conclusions. On-clopidogrel platelet reactivity significantly decreases beyond the acute phase of MI regardless of the genotype. Additionally, our study indicates that in clopidogrel-treated MI patients genetic polymorphisms are not the major determinants of the interindividual variability in platelet reactivity. However, due to a limited sample size, their minor contribution cannot be excluded

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up

Background: The aim of this study was to assess antiplatelet effect of prasugrel in acute coronary syndrome (ACS) patients with high on-treatment platelet reactivity (HTPR) on clopidogrel, undergoing percutaneous coronary intervention (PCI).Methods: A prospective, platelet reactivity-guided, parallel-group, open-label study including 71 patients pretreated with clopidogrel 600 mg and assigned either to prasugrel (30 mg loading dose, 10 mg maintenance dose; n = 46) or clopidogrel (150 mg maintenance dose for 6 days and thereafter 75 mg maintenance dose; n = 25) regimen, based on vasodilator-stimulated phosphoprotein (VASP)-assessed platelet reactivity index (PRI; > 50% vs. ≤ 50%) measured next morning post-PCI.Results: Median PRI value after switch to prasugrel sharply declined at 24 h (70.0 [61.3–75.6] vs. 11.9 [6.8–25.7]%; p < 0.000001) and slightly but significantly rose between 24 h and 30 days (27.9 [15.5–46.8]%; p < 0.0006). In contrast, median PRI values in the clopidogrel group were similar at baseline and at 24 h (25.1 [13.7–40.2] vs. 22.0 [18.4–36.8]%; p = NS) and then modestly rose at 30 days (30.3 [20.4–45.7]%; p < 0.03). The prevalence of HTPR decreased in the prasugrel group between baseline and 24 h measurements (100.0 vs. 4.3%; p < 0.0001). Rates of patients with HTPR at 24 h and 30 days were similar in both groups, so were the tendencies in patterns of platelet inhibition evaluated with multiple electrode aggregometry as compared with the VASP assay.Conclusions: Our study indicates that prasugrel overcomes HTPR on clopidogrel in the acute phase of interventionally treated ACS and maintains its antiplatelet potency in 30-day follow-up. Potential clinical benefits of personalized antiplatelet prasugrel-based therapy warrant further investigation in clinical ACS trials.

Diurnal variation in platelet inhibition by clopidogrel

Morning increase in the occurrence of myocardial infarction, stroke and sudden cardiac death is a well-recognized phenomenon, which is in line with a morning enhancement of platelet aggregation. We investigated whether platelet inhibition during clopidogrel and aspirin therapy varies during the day. Fifty-nine consecutive patients (45 men and 14 women) with first ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary interventions (pPCI) on dual antiplatelet therapy were prospectively enrolled into the study. Blood samples were collected 4 days after start of clopidogrel treatment at 6.00 a.m., 10.00 a.m., 2.00 p.m. and 7.00 p.m. Arachidonic acid and adenosine diphosphate (ADP)-induced platelet aggregation were assessed by impedance aggregometry. Platelet inhibition by clopidogrel was lowest in the midmorning: median ADP-induced platelet aggregation was 55%, 17% and 27% higher at 10.00 a.m. compared to 6.00 a.m., 2.00 p.m. and 7.00 p.m., respectively ( p<0.002). Nonresponsiveness to clopidogrel defined according to the device manufacturer was 2.4-fold more frequent in the midmorning than in the early morning. We observed a more pronounced midmorning increase in ADP-induced platelet aggregation in diabetic patients when compared to non-diabetics. In contrast, no diurnal variation in the antiplatelet effect of aspirin was observed. In conclusion, in patients presenting with STEMI undergoing pPCI, platelet inhibition by clopidogrel is less strong in the midmorning hours. This periodicity in platelet aggregation in patients on dual antiplatelet therapy should be taken into consideration when assessing platelet function in clinical studies