Kornel Chełstowski

Association between low-dose folic acid supplementation and blood lipids concentrations in male and female subjects with atherosclerosis risk factors.

Background Folic acid (FA) is one of the B complex vitamins. It is thought that FA deficiency promotes atherosclerosis formation in arterial endothelium. FA, acting through reducing homocysteine (Hcy) levels, may contribute to decreased cholesterol (Ch) synthesis. The aim of this study was to analyze the association of low-dose folic acid supplementation with blood lipids concentrations in subjects with atherosclerosis risk factors. Material/Methods The study enrolled 124 Caucasian individuals (60 M, ages 20–39; and 64 F, ages 19–39) with atherosclerosis risk factors (family history of premature ischemic stroke, arterial hypertension, dyslipidemia, overweight and obesity, cigarette smoking, and low level of physical activity). The participants were asked to take FA at a low dose of 0.4 mg/24 h for 12 weeks. Results FA levels increased in females (6.3 vs. 12.5 ng/dL; p=0.001) and males (6.4 vs. 11.4 ng/dL; p=0.001) and Hcy levels decreased (10.6 vs. 8.3 μmol/L; p=0.001 and 11.5 vs. 9.3; p=0.001, respectively). A significant reduction in mean concentration of total cholesterol in females (203.4 vs. 193.1 mg/dL; p=0.001) and in males (209.5 vs. 201.9; p=0.002) was observed. The low-density lipoprotein cholesterol (LDL-C) levels decreased in females and in males (107.4 vs. 99.9 mg/dL; p=0.001 and 121.5 vs. 115.1; p=0.002, respectively). The apoAI concentrations increased in smoking women and in men with BMI ≥25 kg/m2 (p=0.032 and p=0.024, respectively). Conclusions Low-dose FA supplementation has a beneficial effect on blood lipids through decreasing concentrations of total cholesterol and LDL-C and increasing concentrations of apoAI.

Is there an association between angiotensin-converting enzyme gene polymorphism and functional activation of monocytes and macrophage in young patients with essential hypertension?

Background This study was undertaken to determine whether the phenotype of monocytes and monocyte-derived macrophages is more proatherogenic in young persons with arterial hypertension and whether this phenotype is affected by smoking or polymorphism of the angiotensin-converting enzyme (ACE) gene. Methods We enrolled 40 young patients (24.1 ± 4.7 years) with previously untreated arterial hypertension and 40 age-matched healthy controls. There were 20 smokers and 20 non-smokers in each group. Results In the hypertensive group, we found enhanced monocyte expression of CD11a (P < 0.001), reduced expression of CD49d (P < 0.001) and CD62L (P < 0.005), greater oxidative stress in resting and phorbol-12-mistrate-13-acetate-stimulated monocytes (P < 0.001), enhanced adhesion of monocytes to endothelial cells (P < 0.001), greater expression of CD36 on monocyte-derived macrophages (P < 0.001), and enhanced production of reactive oxygen species by resting and phorbol-12-mistrate-13-acetate-stimulated macrophages (P < 0.001). Cigarette smoking by hypertensive patients was associated with enhanced (P < 0.002) CD11a expression. There were no associations of ACE gene polymorphism with cellular expression or reactive oxygen species production studied among hypertensive patients. Only CD62L expression in DD homozygote participants was higher (P < 0.039) than in II homozygote participants. Conclusions It is concluded that arterial hypertension affects the function of monocytes/macrophages in young persons. Polymorphism of the ACE gene is without effect on the functional activation of monocytes and macrophages.

Factors influencing multiplate whole blood impedance platelet aggregometry measurements, during aspirin treatment in acute ischemic stroke: a pilot study.

Among patients with stroke, the phenomenon of resistance to treatment with low-dose aspirin acetylsalicylic acid (ASA) is quite common. The study included 133 patients hospitalized with acute ischemic stroke. Impedance platelet aggregometry (IPA) and levels of vWF and thromboxane (TXB2) were assessed – with the efficacy of aspirin in daily clinical investigation. Responses to treatment with doses of 150 and 300 mg/day were measured. In addition, we analyzed the response of proinflammatory factors [fibrinogen, C-reactive protein (CRP), white blood corpuscles (WBC)], lipids and hemoglobin A1c, which may alter platelet aggregation response to treatment. After a week of treatment at 150 mg/day, ASA patients were classified as laboratory resistant (42%) or sensitive (58%). Values of IPA in the resistant group were significantly higher (472 ± 150 vs. 222 ± 59 AUC, P < 0.0001). In resistant patients were also found higher levels of fibrinogen (3.90 ± 0.89 vs. 3.46 ± 0.74 g/l, P = 0.0046), CRP (6.97 ± 5.66 vs. 4.17 ± 4.03 mg/l, P = 0.0011), WBC (9.2 ± 2.4 vs. 8.3 ± 2.2 × 109/l, P = 0.0207) and lower HDL cholesterol (46 ± 12 vs. 52 ± 15 mg/dl, P = 0.016). This research shows that aspirin resistance assessment by IPA well reflects the clinical status of patients and should be used routinely. Resistance generally fails to ‘break’ at higher doses, hence our suggestion that patients resistant to low doses of the drug immediately switch to a thienopyridine class antiplatelet agent, for example, clopidogrel.

Bone mineral density in girls with functional hypothalamic amenorrhea subjected to estroprogestagen treatment – a 4-year prospective study

The aim of this study was to evaluate the effects of 4-year estroprogestagen therapy (EP) on the bone mineral density (BMD) of 16- to 17-year-old girls with functional hypothalamic amenorrhea (FHA, n = 78). Baseline values of hormonal parameters, bone fraction of alkaline phosphatase (BALP), and cross-linked n-telopeptide of type I collagen (Ntx) were taken along with BMD measurements. Follow-up measurements of laboratory parameters were performed after 6 months of EP treatment. BMD was measured on a yearly basis. Six-month treatment resulted in a marked increase in estradiol levels and a significant decrease in BALP and Ntx. The relative increase in BMD was highest after the second year of treatment. Based on the dynamics of BMD changes during the first year of treatment, we identified a subgroup with no or insignificant reactions to the treatment. It was characterized by significantly higher baseline BMD and markedly lower baseline Ntx compared to the patients who responded to 1-year therapy well or extremely well. Further follow-up proved, however, that this subgroup did not differ significantly in terms of the long-term prognosis for BMD normalization. In conclusion, this study showed that EP therapy is effective in the treatment of BMD disorders associated with FHA.

Is there an effect of folic acid supplementation on the coagulation factors and C-reactive protein concentrations in subjects with atherosclerosis risk factors?

INTRODUCTION Folic acid (FA) may delay the formation of atherosclerotic lesions. Increased plasma levels of von Willebrand factor (VWF) are observed in cardiovascular disease, which leads to higher risk of thrombosis. Fibrinogen (Fb) is a well-documented risk factor of cardiovascular disease. The aim of this study was to analyze the effect of FA supplementation on the Fb, VWF and C-reactive protein (CRP) plasma concentrations in subjects with atherosclerosis risk factors. MATERIAL/METHODS The study enrolled 124 Caucasian individuals (60 M, 64 F) with atherosclerosis risk factors--family history of premature ischaemic stroke, arterial hypertension, dyslipidaemia, overweight and obesity, cigarette smoking and low physical activity. The participants were asked to take FA in the low dose of 0.4 mg/24 h for three months. RESULTS After FA supplementation a significant reduction of the VWF concentrations in females (76.6 vs 72.3%; p=0.028) and in males (75.5 vs 66.9%; p=0.001) was observed. Among women and men with dyslipidaemia concentrations of VWF decreased after FA supplementation (76.8% vs 69.6%; p=0.003 and 76.7% vs 67.8%; p=0.001 respectively). Among females and males with BMI ≥25 kg/m² concentrations of VWF decreased only in men (77.6% vs 66.5%; p=0.001). In female and male smokers supplementation of FA decreased VWF concentrations (82.5% vs 74.4%; p=0.012 and 76.6% vs 69.5%; p=0.036 respectively). DISCUSSION The results of our study suggest that there is an effect of FA supplementation on VWF concentrations in subjects with atherosclerosis risk factors.

PvuII and XbaI polymorphisms of estrogen receptor-α and the results of estroprogestagen therapy in girls with functional hypothalamic amenorrhea – preliminary study

Introduction The aim of this study was the long-term prospective evaluation of the effects of estroprogestagen (EP) therapy on the bone mineral density (BMD) of girls with functional hypothalamic amenorrhea (FHA) carrying various PvuII and XbaI polymorphisms of ER-α. Material and methods Prospective observation included 84 FHA girls and 50 controls. The FHA patients were subjected to 4-year sequential therapy with 17β estradiol (2 mg from the 2nd to 25th day of the menstrual cycle) and dydrogesterone (10 mg from the 16th to the 25th day). Hormonal parameters, serum concentration of the bone fraction of alkaline phosphatase (BALP), urine concentration of cross-linked n-telopeptide of type I collagen (Ntx) and BMD were determined before and after the treatment. Results Six-month treatment resulted in a marked increase in estradiol (p = 0.001), testosterone and prolactin levels (p = 0.01 both) and a significant decrease in BALP and Ntx (p = 0.001 both). Patients with the PP polymorphism had significantly lower baseline BMD compared to carriers of other polymorphic variants of PvuII (p = 0.003). A significant increase in BMD was observed throughout the entire therapy period, with no significant differences in the yearly dynamics of BMD changes observed amongst various polymorphic variants and haplotypes of ER-α. Conclusions The EP therapy is effective in the treatment of BMD disorders associated with FHA, and treatment results do not depend on PvuII and XbaI polymorphisms of ER-α.

Apnea testing using the oxygen insufflation method for diagnosis of brain death may compromise pulmonary function

Introduction: The aim of our study was to compare the reliability and safety of the classical I‐AT with the continuous positive airway pressure apnea test (CPAP‐AT). Material and methods: In the group of 48 patients (group O), an I‐AT was performed at the end of BD diagnostic procedures, and approximately 1–1.5 h later CPAP‐AT with 100% FiO2 and CPAP of 10 cm H2O, provided by ventilator in CPAP mode. After pre oxygenation with 100% FiO2 for 10 min, the PaO2/FiO2 ratio was recorded prior to I‐AT at time‐point one (T1) and prior to CPAP‐AT at time‐point two (T2). Group O was categorized into subgroup N‐H (non‐hypoxemic), consisting of 41 patients with good lung function, and subgroup H (hypoxemic) consisting of 7 patients with poor lung function. Within each subgroup PaO2/FiO2 at T1 and T2 were compared. Results: In Group O, PaO2/FiO2 decreased from 321 ± 128 mm Hg at T1 to 291 ± 119 mm Hg at T2 (p = 0.004). In subgroup N‐H, PaO2/FiO2 declined from 355 ± 103 to 321 ± 100 mm Hg (p = 0.008), and in subgroup H, PaO2/FiO2 remained almost unchanged. Additionally, in 4 patients from subgroup N‐H, PaO2/FiO2 decreased below 200 mm Hg at T2. Conclusions: Our study indicates that I‐AT may compromise pulmonary function and this may support the recommendation of safer CPAP‐AT alternative. HighlightsI‐AT may compromise pulmonary function in some patientsIn some non‐hypoxemic patients, PaO2/FiO2 ratio may decrease below the cutoff value of 200 mm Hg after I‐AT.This may justify considering the alternative, safer CPAP‐AT.

The character of haemostatic disorders and level of protein S-100 in acute ischaemic stroke can affect survival in the first week of follow-up: a pilot study.

Disorders of haemostasis which result in ischaemic stroke usually appear as thromboembolism in peripheral veins and the pulmonary circulation, and to a lesser extent as coagulopathy. The S-100 protein, a marker of stroke, correlates positively with the neurological deficit National Institutes of Health Stroke Scale (NIHSS). We adopted the hypothesis that early death of patients with acute ischaemic stroke can be explained by changes in blood coagulation and fibrinolysis. The study included 84 patients hospitalized with acute ischaemic stroke. Three groups were created: I (death between 1 and 2 days), II (death between 5 and 7 days) and III (with no deaths in hospital). We measured levels of fibrinogen, antithrombin, D-dimers, plasmin–antiplasmin complexes, plasminogen and clotting times (prothrombin time and activated partial thromboplastin time), platelet number, euglobulin clot lysis time (ECLTindex) and S-100 protein, C-reactive protein and white blood cells (WBCs). Group I had lower concentrations of fibrinogen compared to groups II (3.13 vs. 4.18, P < 0.01) and III (3.13 vs. 3.77, P < 0.02) and higher levels of D-dimers (3643 vs. 2278, P < 0.05), higher concentrations of plasmin–antiplasmin complexes (1410 vs. 882, P = 0.03) and a lower ECLTindex (152 vs. 219, P < 0.02) when compared with group III. Group I also had higher concentrations of protein S-100 (2.09 vs. 0.61, P < 0.001), higher NIHSS (18.0 vs. 13.2, P = 0.073) and number of WBC (14.1 vs. 11.1, P < 0.02) than in group III. The observed abnormalities in haemostasis, either found systemically or locally as cerebral microvascular thrombosis, may be factors potentially associated with death of patients with the shortest survival time.

Does the progeny of premature ischemic stroke sufferers need intensive interest of physicians oriented toward primary prevention? A pilot study

Background Few studies focus on the progeny of stroke patients with respect to the occurrence of other potential risk factors. Methods The study group covered 60 males and 62 females whose parents had suffered premature ischemic stroke (PIS); the control group comprised of 41 males and 47 females whose parents had no history of premature vascular event (mean age: 28.4 and 27.1 years, respectively). Examination of both the groups consisted of evaluation of their diet, measurement of arterial blood pressure and body mass index (BMI). Moreover, blood test was carried out and concentration of biochemical stroke risk factors was determined. Results The adult progeny of parents with a history of PIS followed a deficient, unbalanced, and nonvaried diet. Their average blood pressure and BMI reached higher values, compared with the results obtained in the control group (125.7 ± 16.06 vs. 122.64 ± 10.83 mmHg; 24.27 ± 3.98 vs. 22.54 ± 2.69 kg/m2, respectively; P<0.05). The same applies to average concentrations of the triglycerides 1.22 ± 0.76 vs. 1.06 ± 0.54 mmol/l; total cholesterol (5.34 ± 1.16 vs. 4.82 ± 0.89 mmol/l), low-density lipoprotein-cholesterol (2.95 ± 0.97 vs. 2.52 ± 0.73 mmol/l), total homocysteine (11.22 ± 4.22 vs. 10.18 ± 2.45 μmol/l), and fibrinogen (2.91 ± 0.68 vs. 2.78 ± 0.6 g/l) (P<0.05). Conclusion Adult children of PIS sufferers show different stroke risk factor profiles than the control group. It may indicate a need for preventive activities for this group in the future. Family occurrence of stroke requires further detailed studies on a larger cohort of patients from risk group.