Grzegorz Kopeć

Paraoxonase 2 Gene C311S Polymorphism Is Associated with a Risk of Large Vessel Disease Stroke in a Polish Population

Background: Oxidative stress plays a role in atherosclerosis. Human paraoxonase (PON) gene products exhibit antioxidant properties. We studied the significance of the Q192R and M55L polymorphisms of the PON1 gene and the C311S polymorphism of the PON2 gene in different etiologies of ischemic stroke. Methods: One hundred and thirty-six patients with large vessel disease (LVD) stroke, 140 with small vessel disease stroke, 272 with cardioembolic stroke, and their age- and sex-matched controls were included. PON genotypes were evaluated by PCR-RFLP analyses. Results: The distribution of PON1 polymorphisms was similar in each stroke group and in the respective controls. Genotypes with the C allele of the PON2 gene C311S polymorphism were overrepresented in LVD stroke patients as compared with their controls, both in univariate and multivariate (dominant model: OR = 1.58, 95% CI: 1.006–2.48) analyses. Conclusion: The genotype with the C allele of the PON2 gene is a risk factor for LVD stroke in a Polish population.

Atherosclerosis progression affects the relationship between endothelial function and aortic stiffness

Aortic stiffening is the most important determinant of elevated systolic blood pressure which in turn is the main contributor to the burden of disease attributable to hypertension. Endothelial function may affect arterial stiffening as has been shown for carotid-aorto-femoral segments in healthy humans or subjects with cardiovascular risk factors. We investigated whether this association is present selectively for aorta and whether it extends to patients with advanced atherosclerosis. Direct measurements of aortic pulse wave velocity (aPWV) to assess aortic stiffness and brachial artery flow-mediated dilatation (bFMD) tests to assess endothelial function were performed in 111 consecutive patients suspected of coronary artery disease. Progression of atherosclerosis was determined on the basis of the presence or absence of significant coronary artery stenosis, CAS (>or=50%) in angiography. bFMD was lower (P<0.001) and aPWV was higher (P<0.001) in a group of 72 patients with advanced atherosclerosis when compared with a group of 39 patients without significant CAS. bFMD was inversely associated with aPWV but only in patients without advanced atherosclerosis (r=-0.37, P=0.02), even after adjustment of confounding factors in a multivariate analysis model (R(2)=0.37, P<0.001). We concluded that endothelial function may influence aortic stiffness which is limited however by the progression of atherosclerosis.

The dynamic assessment of right-ventricular function and its relation to exercise capacity in heart failure

To evaluate right‐ventricular (RV) function during stress echocardiography (SE) and to assess its relationship with exercise capacity in heart failure (HF) patients.

Central Pulse Pressure: Is It Really an Independent Predictor of Cardiovascular Risk?

To the Editor: We read with interest the article by Jankowski et al1 about the cardiovascular risk associated with central aortic pulse pressure (aPP). Because the measurement of aPP by invasive methods is impractical for the risk stratification and as a means of monitoring the effectiveness of antihypertensive therapy, the authors highlighted in the discussion to the article that the important value of their findings seems to be “the understanding of the nature of relationship between pressure wave and atherosclerosis complications development.” However, it is a matter of debate whether the current study gives …

Markers of thrombogenesis and fibrinolysis and their relation to inflammation and endothelial activation in patients with idiopathic pulmonary arterial hypertension.

Background Chronic anticoagulation is a standard of care in idiopathic pulmonary arterial hypertension (IPAH). However, hemostatic abnormalities in this disease remain poorly understood. Therefore, we aimed to study markers of thrombogenesis and fibrinolysis in patients with IPAH. Methods We studied 27 consecutive patients (67% female) with IPAH aged 50.0 years (IQR: 41.0 - 65.0) and 16 controls without pulmonary hypertension. Prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin (TAT) complexes were measured to assess thrombogenesis; tissue-type plasminogen activator (tPA) antigen and plasmin-anti-plasmin complex to characterize activation of fibrinolysis; plasminogen activator inhibitor 1 (PAI-1) to measure inhibition of fibrinolysis; and endothelin-1 (ET-1) and interleukin-6 (IL-6) to assess endothelial activation and systemic inflammation, respectively. In addition, in treatment-naive IPAH patients these markers were assessed after 3 months of PAH-specific therapies. Results TPA (10.1[6.8-15.8] vs 5.2[3.3-7.3] ng/ml, p<0.001), plasmin-anti-plasmin (91.5[60.3-94.2] vs 55.8[51.1-64.9] ng/ml, p<0.001), IL-6 (4.9[2.5-7.9] vs 2.1[1.3-3.8] pg/ml, p=0.001) and ET-1 (3.7 [3.3-4.5] vs 3.4[3.1-3.5], p= 0.03) were higher in patients with IPAH than in controls. In IPAH patients plasmin-anti-plasmin and tPA correlated positively with IL-6 (r=0.39, p=0.04 and r=0.63, p<0.001, respectively) and ET-1 (r=0.55, p=0.003 and r=0.59, p=0.001, respectively). No correlation was found between tPA or plasmin-anti-plasmin and markers of thrombogenesis. Plasmin-anti-plasmin decreased after 3 months of PAH specific therapy while the other markers remained unchanged. Conclusions In the present study we showed that markers of fibrynolysis were elevated in patients with IPAH however we did not find a clear evidence for increased thrombogenesis in this group of patients. Fibrinolysis, inflammation, and endothelial activation were closely interrelated in IPAH.

Knowledge of a patient-dependant phase of acute myocardial infarction in Polish adults: the role of physician's advice.

BACKGROUND Effective management of acute myocardial infarction (AMI) is limited by patient delay in calling an ambulance. We aimed to assess knowledge related to a patient-dependant phase of AMI and its determinants in adults. METHODS Questionnaire survey was conducted among a random sample of 942 men (48%) and women (52%) aged 63.50 ± 6.50 selected from population registers in Cracow (Poland). Questions from the Behavioral Risk Factor Surveillance System were used to assess knowledge of AMI symptoms. The respondents were further asked about the first thing they would do in response to AMI symptoms, the emergency phone number and whether a doctor advised them about AMI. RESULTS All suggested AMI symptoms were recognized by 51 (5.4%) respondents. More persons would call an ambulance in response to AMI symptoms in another person than if they appear in themselves (87.4% vs. 74.4%, P = 0.02). Only 644 (68%) participants knew the emergency phone number and 104 (11%) were advised about AMI by their doctors. Such advice was associated with higher rates of knowledge of AMI symptoms and the emergency phone number but not with a declaration of the appropriate reaction to AMI symptoms. Participants after AMI did not represent better knowledge of a patient-dependant phase of AMI but paradoxically less frequently than other persons declared calling an ambulance in response to AMI symptoms. CONCLUSION Improvement in knowledge and attitudes related to a patient-dependant phase of AMI is needed in adults even if they experienced AMI before. A routine advice from a doctor may contribute significantly to this improvement.

Iron deficiency and hematological changes in adult patients after Fontan operation

BACKGROUND Growing evidence indicates that iron-deficiency anemia is common in patients with congenital heart diseases. The aim of this study was to characterize hematologic changes and iron metabolism in adult Fontan patients. We also searched for the associations between these parameters and physical performance in the study group. METHODS AND RESULTS Thirty-two white Fontan patients with a mean age of 25 ± 4.5 years and 30 healthy control subjects matched for age and sex were studied. Complete blood count together with iron-related parameters was determined in plasma of peripheral venous blood. The cardiopulmonary exercise test was performed. The Fontan patients had higher red blood cell counts (6.0 ± 2.1 × 10(9)/μl vs. 4.8 ± 0.4 × 10(9)/μl, p<0.001), hemoglobin (16.7 ± 1.4 g/dl vs. 14.2 ± 1.3g/dl, p<0.001), hematocrit (49 ± 3.4% vs. 42.1 ± 3.1%, p<0.001), red cell distribution width (RDW) (14.3 ± 2.4% vs. 12.8 ± 0.5%, p<0.001), while mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were similar in both the groups. Compared to the controls, the Fontan patients had higher unsaturated iron binding capacity (46.1 ± 12.6 μmol/l vs. 38.4 ± 11.9 μmol/l, p=0.02), total iron-binding capacity (62.8 ± 9.8 μmol/l vs. 57.8 ± 8.5 μmol/l, p=0.04), lower transferrin saturation (27.4 ± 11.4% vs. 34.6 ± 13.4%, p=0.03), and oxygen uptake, while iron and ferritin levels were comparable in both the groups. The multivariate model showed that SatO2 and cystatin C were independent predictors of RDW, and alanine aminotransferase was an independent predictor of ferritin level. Interestingly RDW was an independent predictor of oxygen uptake. CONCLUSION Adult patients after Fontan operation despite having increased hemoglobin, hematocrit, and red blood cells have insufficient iron stores. Red cell distribution width is an indicator of iron deficiency in adult Fontan patients and it correlates with lower exercise capacity. Elevated ferritin levels in adult patients after Fontan surgery are associated with liver failure.

Left ventricular mass is preserved in patients with idiopathic pulmonary arterial hypertension and Eisenmenger's syndrome.

BACKGROUND Left ventricular (LV) atrophic remodelling was described for chronic thromboembolic pulmonary hypertension (PH) but not in other forms of PH. We aimed to assess LV morphometric changes in idiopathic pulmonary arterial hypertension (IPAH) and Eisenmengers syndrome(ES). METHODS Fifteen patients with IPAH, 15 patients with ES and 15 healthy volunteers were included. Magnetic resonance was used to measure masses of LV, interventricular septum (IVS), LV free wall (LVFW), and LV end diastolic volume (LVEDV) indexed for body surface area. RESULTS Between patients with IPAH, ES and controls no differences in LVmassindex (54.4[45.2-63.3] vs 58.7[41.5-106.1] vs 52.8[46.5-59.3], p=0.50), IVSmassindex (21.6[18.2-21.9)] vs 27.4[18.0-32.9] vs 20.7[18.2-23.2], p=0.18), and LVFWmassindex ([32.4[27.1-40.0] vs 36.7[30.9-62.1] vs 32.5[26.9-36.1], p=0.29) were found. LVEDVindex was lower in IPAH patients than in controls and in ES patients (54.9[46.9-58.5] vs 75.2[62.4-88.9] vs 73.5[62.1-77.5], p<0.001). In IPAH LVEDV but not LV mass correlated with pulmonary vascular resistance (r=-0.56, p=0.03) and cardiac output (r=0.59, p=0.02). CONCLUSIONS LV mass is not reduced in patients with IPAH and with ES and is not affected by haemodynamic severity of PH. LVEDV is reduced in IPAH patients in proportion to reduced pulmonary flow but preserved in patients with ES, where reduced pulmonary flow to LV is compensated by right-to left shunt.

Low-density lipoprotein cholesterol and survival in pulmonary arterial hypertension

Low-density lipoprotein cholesterol(LDL-C) is a well established metabolic marker of cardiovascular risk, however, its role in pulmonary arterial hypertension (PAH) has not been determined. Therefore we assessed whether LDL-C levels are altered in PAH patients, if they are associated with survival in this group and whether pulmonary hypertension (PH) reversal can influence LDL-C levels. Consecutive 46 PAH males and 94 females were age matched with a representative sample of 1168 males and 1245 females, respectively. Cox regression models were used to assess the association between LDL-C and mortality. The effect of PH reversal on LDL-C levels was assessed in 34 patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing invasive treatment. LDL-C was lower in both PAH (2.6 ± 0.8 mmol/l) and CTEPH (2.7 ± 0.7 mmol/l) patients when compared to controls (3.2 ± 1.1 mmol/l, p < 0.001). In PAH patients lower LDL-C significantly predicted death (HR:0.44/1 mmol/l, 95%CI:0.26–0.74, p = 0.002) after a median follow-up time of 33(21–36) months. In the CTEPH group, LDL-C increased (from 2.6[2.1–3.2] to 4.0[2.8–4.9]mmol/l, p = 0.01) in patients with PH reversal but remained unchanged in other patients (2.4[2.2–2.7] vs 2.3[2.1–2.5]mmol/l, p = 0.51). We concluded that LDL-C level is low in patients with PAH and is associated with an increased risk of death. Reversal of PH increases LDL-C levels.

Mechanism and prognostic role of qR in V1 in patients with pulmonary arterial hypertension

BACKGROUND The presence of qR pattern in lead V1 of the 12-lead surface ECG has been proposed as a risk marker of death in patients with pulmonary arterial hypertension (PAH). We aimed to validate these findings in the modern era of PAH treatment and additionally to assess the relation of qR in V1 to PAH severity. We also investigated the possible mechanisms underlying this ECG sign. METHODS Consecutive patients with PAH excluding patients with congenital heart defect were recruited between February 2008 and January 2016. A 12-lead standard ECG was acquired and analyzed for the presence of qR in V1 and other potential prognostic patterns. Cardiac magnetic resonance and echocardiography were used for structural (masses and volumes) and functional (ejection fraction, eccentricity index) characterization of left (LV) and right (RV) ventricles. Standard markers of PAH severity were also assessed. RESULTS We enrolled 66 patients (19 males), aged 50.0±15.7years with idiopathic PAH (n=52) and PAH associated with connective tissue disease (n=14). qR in V1 was present in 26(39.4%) patients and was associated with worse functional capacity, hemodynamics and RV function. The main structural determinants of qR in V1 were RV to LV volume ratio (OR: 3.99; 95% CI: 1.47-10.8, p=0.007) and diastolic eccentricity index (OR: 15.0; 95% CI: 1.29-175.5, p=0.03). During observation time of 30.5±19.4months, 20 (30.3%) patient died, 13 (50%) patients with qR and 7 (17.5%) patients without qR pattern. Electrocardiographic determinants of survival were qR (HR: 3.06, 95% CI: 1.21-7.4; p=0.02) and QRS duration (HR: 1.02, 95% CI: 1.01-1.04; p=0.01). CONCLUSIONS Presence of qR in V1 reflects RV dilation and diastolic interventricular septum flattening. It is a sign of advanced PAH and predicts the risk of death in this population.