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Background: The PlA2 allele of the gene encoding for GPIIIa subunit of the platelet membrane receptor glycoprotein (GP) IIb/IIIa has been suggested as a significant risk factor for thrombotic complications of coronary artery disease (CAD). The aim of the current investigation was to investigate the association between PlA GPIIIa polymorphism and the extent of angiographically confirmed CAD in patients from the north region of Poland. Methods: The study was performed in 397 male Caucasian patients. All subjects had significant coronary artery stenosis confirmed by elective coronary angiography. Screening for the PlA GPIIIa genotypes was performed by polymerase chain reaction of genomic DNA, followed by NciI digestion and agarose gel electrophoresis. Results: The genotype distribution of the PlA GPIIIa polymorphism in our study group was PlA1/A1—75%, PlA1/A2—24% and PlA2/A2—1% with PlA1 and PlA2 allele frequencies of 0.87 and 0.13, respectively. The prevalence of the homozygous PlA1/A1 genotype among subjects with multiple-vessel CAD (two or three vessels with at least 50% stenosis) was significantly higher than in patients with single-vessel disease; the odds ratio of PlA2/A2 or PlA1/A2 patients for having multiple-vessel CAD was 0.46 (95% CI 0.27–0.77, P<0.01). The mean CAD score for PlA1/A1 patients was significantly higher in comparison to PlA2/A2 and PlA1/A2 patients (7.58±2.20 and 6.98±2.37, respectively, P<0.05). Conclusions: Our results suggest, that the PlA1/A1 genotype of PlA GPIIIa polymorphism is associated with more severe CAD in male Caucasian patients from the north region of Poland. [Copyright &y& Elsevier]

Background: The aim was to assess the influence of menstrual cycle on results of exercise echocardiography and electrocardiography. Methods: Premenopausal women (n = 28) with regular monthly menses, presented typical angina, positive electrocardiogram (ECG) exercise stress test, and normal coronary angiogram were recruited. Exercise supine bicycle echocardiography with simultaneous recording of 12-lead ECG was performed once a week for 4 consecutive weeks. Occurrence of angina, time to angina, time to significant ST deviation, and segmental myocardial contractility were analyzed. Blood samples were drawn to estimate follicle-stimulating hormone, luteinizing hormone, β-estradiol, progesterone concentration and confirm the position in menstrual cycle. In correlation analysis, linear and logistic regression were used as appropriate. Qualitative variables were categorized into quartiles in logistic regression analysis. Results: Exercise ST depression was more frequently observed in both luteal phases (early luteal 78%, late luteal 86%) compared to the late follicular phase (50%, P < .05). Time to ST depression was significantly longer in late follicular phase compared to other phases. The rate of segmental exercise left ventricular hypokinesis was low and not significantly related to menstrual cycle. Using linear regression, significant positive correlation was found between estradiol-progesterone ratio and time to ST depression. Using multiple logistic regression, we confirmed that progesterone level is independent factor influencing the presence of ST depression. Conclusion: In women with typical angina and normal coronary angiogram, the position in menstrual cycle influences the ST depression but not myocardial contractility during exercise echocardiography. [Copyright &y& Elsevier]

Background and Aims Familial hypercholesterolemia (FH), which leads to premature cardiovascular events, still remains underrecognized and undertreated in most countries. Untreated FH individuals aged 20–39 years are at 100-fold higher risk of mortality from coronary heart disease compared to those of a general population. Therefore, special efforts should be implemented to diagnose FH patients at early stages of life. The aim of this study was to evaluate the efficacy of the revised Dutch Lipid Clinic Network (DLCN) criteria proposed by the Polish Lipid Experts Forum to select index FH patients for DNA mutational analysis in Poland. Methods The study included 193 unrelated adult patients (mean age 48 ± 13 years) with clinical diagnosis of FH based on the revised DLCN score, tested sequentially for mutations in LDLR and APOB genes using bidirectional Sanger sequencing and MLPA techniques. The cut-off points of the clinical FH criteria score were assessed by ROC statistics to identify patients with the highest probability of carrying an FH-causing mutation. Results The causal heterozygous LDLR or APOB mutation was identified in 41% (80/193) of probands. Adults aged <40 years were more likely to carry an FH-causing mutation compared to subjects aged ≥40 years (65% vs. 33%; p < 0.001). LDL-C thresholds for the molecular diagnosis of FH were 5.79 mmol/l for individuals aged<40 and 6.7 mmol/l for subjects ≥40 years old. The threshold values of the clinical diagnostic score for efficient selection of patients for genetic testing were 5 and 7 points for individuals aged <40 and ≥40 years, respectively. Conclusions The study validated the efficacy of proposed clinical FH criteria for the disease diagnosis in Poland. The clinical criteria score thresholds for positive FH molecular diagnosis differ depending on age (<40 and ≥40 years). We propose that in the healthcare systems with limited genetic testing resources individuals younger than 40 years, who fulfill the clinical criteria for possible, probable or definite FH should qualify for the FH mutation testing. The index patients aged ≥40 years with clinical diagnosis of probable or definite FH should also qualify for the genetic testing. [ABSTRACT FROM AUTHOR]

Abstract: Postangioplasty restenosis is a multifactorial process and involves mechanisms such as inflammation and stimulation of the expression of growth factors. Lipoprotein-associated phospholipase A2 (Lp-PLA2) can modify inflammatory responses by hydrolyzing phospholipids with shortened and/or oxidized sn-2 residues. In this study, we tested a hypothesis that adenovirus-mediated Lp-PLA2 gene transfer can reduce restenosis in rabbits. Aortas of cholesterol-fed NZW rabbits were balloon-denuded and intra-arterial gene transfer was performed using Dispatch catheter with Lp-PLA2 or LacZ adenoviruses (1.15×1010 pfu). Intima/media ratio (I/M), histology and cell proliferation were analyzed. Two weeks after the gene transfer I/M in the LacZ-transduced control group was 0.45±0.05 but Lp-PLA2 gene transfer reduced I/M to 0.25±0.03. At four weeks time point I/M in the Lp-PLA2 group (0.34±0.05) was also lower than in the LacZ group (0.53±0.06). Plasma Lp-PLA2 activity was increased in the Lp-PLA2 group (48.2±4.2) as compared to the LacZ group (33.6±3.51) at two weeks time point. Transgene expression was detected in the arterial wall two and four weeks after the procedure. Apoptosis was higher in the control vessels than in the Lp-PLA2 group at two weeks time point. In conclusion, local adenovirus-mediated Lp-PLA2 gene transfer resulted in a significant reduction in neointima formation in balloon-denuded rabbit aorta and may be useful for the prevention of restenosis after arterial manipulations. [Copyright &y& Elsevier]