Seasonal superoxide overproduction and endothelial activation in guinea-pig heart; seasonal oxidative stress in rats and humans.

Seasonality in endothelial dysfunction and oxidative stress was noted in humans and rats, suggesting it is a common phenomenon of a potential clinical relevance. We aimed at studying (i) seasonal variations in cardiac superoxide (O(2)(-)) production in rodents and in 8-isoprostane urinary excretion in humans, (ii) the mechanism of cardiac O(2)(-) overproduction occurring in late spring/summer months in rodents, (iii) whether this seasonal O(2)(-)-overproduction is associated with a pro-inflammatory endothelial activation, and (iv) how the summer-associated changes compare to those caused by diabetes, a classical cardiovascular risk factor. Langendorff-perfused guinea-pig and rat hearts generated ~100% more O(2)(-), and human subjects excreted 65% more 8-isoprostane in the summer vs. other seasons. Inhibitors of NADPH oxidase, xanthine oxidase, and NO synthase inhibited the seasonal O(2)(-)-overproduction. In the summer vs. other seasons, cardiac NADPH oxidase and xanthine oxidase activity, and protein expression were increased, the endothelial NO synthase and superoxide dismutases were downregulated, and, in guinea-pig hearts, adhesion molecules upregulation and the endothelial glycocalyx destruction associated these changes. In guinea-pig hearts, the summer and a streptozotocin-induced diabetes mediated similar changes, yet, more severe endothelial activation associated the diabetes. These findings suggest that the seasonal oxidative stress is a common phenomenon, associated, at least in guinea-pigs, with the endothelial activation. Nonetheless, its biological meaning (regulatory vs. deleterious) remains unclear. Upregulated NADPH oxidase and xanthine oxidase and uncoupled NO synthase are the sources of the seasonal O(2)(-)-overproduction.

A common variant in low-density lipoprotein receptor-related protein 6 gene (LRP6) is associated with LDL-cholesterol.

OBJECTIVE: A rare mutation in low-density lipoprotein receptor-related protein 6 gene (LRP6) was identified as the primary molecular defect underlying monogenic form of coronary artery disease. We hypothesized that common variants in LRP6 could predispose subjects to elevated LDL-cholesterol (LDL-C). METHODS AND RESULTS: Twelve common (minor allele frequency > or =0.1) single nucleotide polymorphisms in LRP6 were genotyped in 703 individuals from 213 Polish pedigrees (Silesian Cardiovascular Study families). The family-based analysis revealed that the minor allele of rs10845493 clustered with elevated LDL-C in offspring more frequently than expected by chance (P=0.0053). The quantitative analysis restricted to subjects free of lipid-lowering treatment confirmed the association between rs10845493 and age-, sex-, and BMI-adjusted circulating levels of LDL-C in families as well as 2 additional populations - 218 unrelated subjects from Silesian Cardiovascular Study replication panel and 1138 individuals from Young Men Cardiovascular Association cohort (P=0.0268, P=0.0476, and P=0.0472, respectively). In the inverse variance weighted meta-analysis of the 3 populations each extra minor allele copy of rs10845493 was associated with 0.14 mmol/L increase in age-, sex-, and BMI-adjusted LDL-C (SE=0.05, P=0.0038). CONCLUSIONS: Common polymorphism in the gene underlying monogenic form of coronary artery disease impacts on risk of LDL-C elevation.

How does the risk of cardiovascular death and cardiovascular risk factor profiles differ between socioeconomic classes in Poland: A country in transition.

BACKGROUND: Socioeconomic status (SES) is an important factor for cardiovascular diseases (CVD) development. A decline in death rate from CVD among subjects with high SES is observed in developed countries. The aim of this study was to assess differences in cardiovascular risk (CV) between socioeconomic classes in Poland, a country currently in transition. METHODS: A sample of 15,200 people was drawn. A three stage selection was performed. Eventually, 6170 patients were examined (2013/2014). Data was collected using a questionnaire in face-to-face interviews, anthropometric data and blood tests were also obtained. Education was categorized as incomplete secondary, secondary and higher than secondary school. Monthly income per person was categorized as low (≤ 1000 PLN), medium (1001-2000 PLN) and high (≥ 2001 PLN). Education and income groups were analyzed by prevalence of CVD risk factors and high CVD risk (SCORE ≥ 5%). RESULTS: Higher education was associated with lower prevalence of all analyzed CVD risk factors (p < 0.001), having the highest income with lower prevalence of hypertension, currently smoking, obesity and lower high density lipoprotein cholesterol. Multivariable analysis showed that frequency of high CVD risk decreased with increasing education level (OR 0.61; 95% CI 0.49-0.76; p < 0.01), a similar favorable impact of higher income on high CVD risk was demonstrated in the whole group (OR 0.81; 95% CI 0.67-0.99; p = 0.04). CONCLUSIONS: Socioeconomic status is an independent predictor of high CV risk of death. A favorable impact on the prevalence of high CV risk was demonstrated for education and partly for income in the whole group. It may reflect a transition being undergone in Poland, moreover, it predicts how socioeconomic factors may generate health inequalities in other transitioning countries.

[Acetylsalicylic acid hypersensitivity in a patient with coronary artery disease and insulin-dependent diabetes mellitus]. / Nadwrazliwosc na kwas acetylosalicylowy u pacjentki z choroba wiencowa i cukrzyca insulinozalezna.

A case of a patient with unstable coronary artery disease, insulin-dependent diabetes mellitus and acetylsalicylic acid hypersensitivity is presented. Acetylsalicylic acid desensitisation and coronary angioplasty with stent implantation were successfully performed. The patient continues to receive antiplatelet therapy and has stable angina. No late hypersensitivity reactions were seen after a follow-up of 16 months.

Correlation between serum low-density lipoprotein cholesterol concentration and arterial wall stiffness.

BACKGROUND: Elevated serum low-density lipoprotein cholesterol (LDL-C) concentration is a risk factor for atherosclerosis, which involves remodelling of the arterial walls with their subsequent stiffening. AIM: We sought to evaluate the relationship between serum lipid levels and the elastic properties of the arterial wall. METHODS: The study group comprised 315 men and women aged 55.84 ± 9.44 years. Serum glucose and lipid concentrations were determited. All subjects underwent blood pressure (BP) measurement, transthoracic echocardiography, and assessment of vascular compliance of large (C1) and small arteries (C2) using the HDI/Pulse Wave™ CR-2000 Research CardioVascular Profiling System (Hypertension Diagnostics Inc., Eagan, MN, USA). The subjects were divided into three groups: group I - LDL-C < 2.6 mmol/L, group II - LDL-C ≥ 2.6 mmol/L and < 4.0 mmol/L, and group III - LDL-C ≥ 4.0 mmol/L. RESULTS: There were no intergroup differences with regard to smoking status (p = 0.56), serum glucose concentration (p = 0.13), body mass index (p = 0.96), systolic (p = 0.17) and diastolic BP (p = 0.29), or C1 (p = 0.09). However, C2 was higher in groups I and II than in group III (5.12 ± 2.57 vs. 5.18 ± 2.75 vs. 4.20 ± 1.58 mL/mmHg × 100, respectively, p < 0.01). Multivariate regression analysis negated the independent associations between C1 and serum lipid levels. In contrast, C2 was independently inversely associated with serum LDL-C concentration (r = -0.15, p < 0.01). CONCLUSIONS: Higher serum LDL-C concentration seems to contribute independently to stiffening of small arterial vasculature in otherwise healthy adults. Screening for dyslipidaemia in the general population and its prompt treatment are highly recom-mended.

Socioeconomic status and cardiovascular risk SCORE.

BACKGROUND: Cardiovascular diseases (CVD) are one of the most frequent causes of morbidity and death both in men and women. The influence of the following factors on the occurrence and progression of atherosclerosis is well known: hyperten-sion, hypercholesterolaemia, tobacco smoking, obesity, diabetes, age, and sex. As well as the typical risk factors of CVD, there is also a significant association between the incidence of those diseases and socioeconomic status (SES). AIM: The aim of this study was to establish the correlation between SES status and CVD risk assessed according to the SCORE algorithm. METHODS: The study encompassed 516 participants (207 men and 309 women) aged 40-74 years, who had never been diagnosed with any CVD. The SES was calculated by multiplying the patient's education and net monthly income. The cor-relation between the SES and SCORE was established using linear and logistic regression analysis. RESULTS: After considering the influence of age, an inverse correlation between the SCORE risk value and the SES index was established, both in the entire group (p = 0.006) and in the men's group (p = 0.007). In the analysis of individual age subgroups, this correlation was demonstrated in the following groups: 55-59-year-olds (p = 0.011), 60-64-year-olds (p = 0.014), and 65-69-year olds (p = 0.034). A similar relationship was established in men aged 65-69 years (p = 0.038) and women aged 40-44 years (p = 0.003). The logistic regression analysis demonstrated that, after considering the influence of age, the odds of the SCORE risk value being ≥ 10% were becoming smaller along with the increase in the SES index value in the entire group (p = 0.048) and in the men's group (p = 0.011). The odds ratio (OR) for the SCORE risk value being ≥ 10% depending on the SES index value was OR = 0.978 (95% confidence interval [CI] 0.956-0.999) in the entire group and OR = 0.964 (95% CI 0.938-0.992) in men. Furthermore, we also established that the risk of SCORE ≥ 5% decreased with the increase in the SES index value in the women's group (OR = 0.970; 95% CI 0.941-0.999; p = 0.042). CONCLUSIONS: 1. We demonstrated a statistically significant correlation between the SES and the CVD risk assessed according to the SCORE algorithm. 2. The value of the CVD risk according to SCORE was inversely correlated with SES status.

Association between socioeconomic status and cardiovascular risk.

BACKGROUND: Cardiovascular disease (CVD) is one of the major health problems of the modern societies. Socioeconomic status (SES) is an important predictor of CVD and its risk factors. AIM: To examine whether SES is related to an increased cardiovascular (CV) risk in the population of southwestern Poland. METHODS: The study population comprised 2027 subjects, including 929 (45.8%) men and 1098 (54.2%) women participating in the WOBASZ study. From this population, we selected a subgroup of 1821 subjects free from CVD, including 816 men and 1005 women, all with defined SES. Their CV risk was estimated using the SCORE risk algorithm and an analysis of the relationship between SES indicators and the SCORE risk was performed. RESULTS: We found a negative correlation between the SCORE risk and SES (p = 0.0005). In the overall study group and among participating women, the SCORE risk was significantly lower among subjects with high SES (SES score > 12). This relation was also noted in men and women aged 30­39 years (p = 0.02), women aged 30­39 years (p = 0.0001) and 40­49 years (p = 0.04), and in men aged 70­74 years (p = 0.046). With an increase in SES, the proportion of high CVD risk subjects decreased significantly in the overall study population and in those aged 30­39 years (p = 0.01). Similar relations were observed in women in the entire age range and those aged 30­39 years (p = 0.01). We found that SES had a significant effect on the rate of high CVD risk in all study subgroups aged 30­39 years (odds ratio 0.57, 95% CI 0.39­0.85, p = 0.005 in men and women overall; odds ratio: 0.6, 95% CI 0.37­0.99, p = 0.045 in men; and odds ratio: 0.4, 95% CI 0.16­0.99, p = 0.01 in women). CONCLUSIONS: Socioeconomic status was found to be a predictor of high CVD mortality risk in men and women aged 30­39 years.

Outcomes of biodegradable polymer sirolimus-eluting PROLIM stent in patients with coronary artery disease. Results of 12-month follow-up of prospective registry.

BACKGROUND: Data from clinical trials suggested that biodegradable-polymer-based drug-eluting stents (DES) might improve long-term clinical outcomes. PROLIM (Balton, Warsaw, Poland) DES is based on a stainless steel platform with a closed cell design releasing sirolimus from biodegradable copolymer (lactic and glycolic acid) in eight weeks. AIM: In the present study the safety and the efficacy of a PROLIM stent was assessed in patients with de novo coronary lesions in 12-month clinical follow-up. METHODS: It was a single-centre, observational, prospective registry to assess the safety and efficacy of a PROLIM stent implantation in all consecutive patients with de novo coronary artery lesions treated with percutaneous coronary intervention (PCI). The primary study endpoint was a composite safety (cardiac death, non-fatal myocardial infarction), and the second study endpoint was the efficacy of PROLIM implantation-clinically driven target vessel revascularisation (TVR) assessed at 12-month follow-up. RESULTS: One hundred patients were enrolled into the study and 118 PROLIM stents were implanted. Thirty-two (32%) patients had diabetes, 46 (46%) patients were prior PCI, and 17 (17%) patients had coronary artery bypass grafting. 67% of stented lesions were complex ones (B2/C) and 17% were bifurcations. During the 12-month follow-up primary study endpoints occurred in five (5%) patients. Two (2%) cardiac deaths were reported and three (3%) TVRs were performed, of which one was related to in-PROLIM stent restenosis. CONCLUSIONS: PCI with biodegradable-polymer PROLIM DES seems to be safe and effective in 12-month follow-up. A larger trial is warranted to assess clinical outcomes post PROLIM stent implantation.

Changes in the prevalence, treatment, and control of hypercholesterolemia and other dyslipidemias over 10 years in Poland: the WOBASZ study.

INTRODUCTION Lowering exposure to dyslipidemias is one of the biggest challenges in cardiovascular disease prevention.  OBJECTIVES The aim of the study was to describe the prevalence of dyslipidemias and treatment of hypercholesterolemia in Poland, and to assess changes since the period of 2003-2005. PATIENTS AND METHODS Two cross-sectional surveys of the random samples of the Polish population were performed in the years 2003-2005 (WOBASZ) and 2013-2014 (WOBASZ II). Interviews were carried out according to a standard questionnaire. Blood lipid levels were determined in a single laboratory in frozen samples using the enzymatic colorimetric method. RESULTS The analysis included 14151 participants aged 20-74 years (WOBASZ) and 5947 participants aged 20-99 years (WOBASZ II). In the 2013-2014 survey, hypercholesterolemia was found in 70.3% of men and 64.3% of women. Isolated hypertriglyceridemia was found in 5.6% of men and 2.4% of women. Isolated low levels of high-density lipoprotein cholesterol (HDL-C) were found in 5.1% of men and in 7.3% of women. The prevalence of hypercholesterolemia did not change significantly with regards to the 2003-2005 survey. An increase in the prevalence of hypertriglyceridemia was found in men (relative ratio [RR], 1.26; 95% confidence interval [CI], 1.03-1.55), and an increase in the prevalence of low HDL-C levels was observed in both sexes (men: RR, 2.26; 95% CI, 1.77-2.88; women: RR, 1.94; 95% CI, 1.61-2.33). There was an increase in the proportion of persons receiving high- or moderate-intensity statin therapy. However, 60,6% of persons with hypercholesterolemia were not aware of their condition, and only 6% were treated and achieved the treatment target.  CONCLUSIONS There is an urgent need for more effective strategies for the prevention and management of dyslipidemias.

Exercise-induced mobilisation of endothelial progenitor cells in patients with premature coronary heart disease.

BACKGROUND: Endothelial progenitor cells (EPC) derive from bone marrow and participate in both endothelial regeneration and development of new blood vessels. EPC also play a role in the atherosclerotic process, and their number correlates negatively with the presence of classical risk factors. AIM: To evaluate circulating EPC count and their exercise-induced mobilisation in patients with premature coronary artery disease (CAD). METHODS: The study group included 60 patients with stable CAD diagnosed before 45 years of age. The control group consisted of 33 healthy age- and gender-matched volunteers. Venous blood was sampled 3 times in order to assess circulating EPC count immediately before an exercise test (EPC 0) and at 15 min (EPC 15) and 60 min (EPC 60) after the exercise test. RESULTS: Circulating EPC count in the study group at rest and at 15 min after exercise was comparable (2.1 vs. 2.1 cell/µL, p = 0.35) and increased significantly at 60 min after exercise in comparison to resting values (2.1 vs. 3.2 cell/µL, p < 0.00001). In the control group, circulating EPC count increased significantly at 15 min after exercise (2.0 vs. 3.5 cell/µL, p < 0.0001) but later decreased at 60 min after exercise, although it remained greater than at rest (2.7 vs. 2.0 cell/µL, p < 0.0002). Circulating EPC count at rest and at 60 min after exercise was comparable in the two groups (2.1 vs. 2.0 cell/µL, p = 0.96; and 3.2 vs. 2.7 cell/µL, p = 0.13, respectively) but it was significantly lower in the study group compared to the control group at 15 min after exercise (2.1 vs. 3.5 cell/µL, p < 0.00001). Circulating EPC count at rest and at 15 min after exercise did not correlate with the number of stenosed coronary arteries but at 60 min after exercise it was greater in patients with one-vessel disease compared to those with two- or three-vessel disease (4.2 vs. 3.4 cell/µL, p = 0.01; and 4.2 vs. 2.3 cell/µL, p = 0.00003). However, no difference in circulating EPC count was seen at 60 min after exercise between patients with two- or three-vessel disease (3.4 vs. 2.3 cell/µL, p = 0.3). CONCLUSIONS: 1. Circulating EPC count at rest is comparable between subjects with premature atherosclerosis and healthy volunteers. 2. A single bout of physical exercise causes a significant increase in circulating EPC count in both groups, but the dynamics of exercise-induced EPC mobilisation is different, with delayed exercise-induced EPC mobilisation in subjects with premature CAD. 3. The extent of atherosclerotic coronary lesions does not influence circulating EPC count at rest.

Effect of a significant asymptomatic unilateral carotid artery stenosis on outcomes in patients undergoing coronary artery bypass grafting.

BACKGROUND: Occurrence of a stroke is a major concern in patients undergoing coronary artery bypass grafting (CABG). It remains uncertain whether significant asymptomatic carotid artery stenosis (CAS) is associated with stroke incidence in such patients. AIM: To investigate the incidence of cerebrovascular events, myocardial infarction (MI), and death in patients with a significant asymptomatic CAS undergoing CABG. METHODS: We prospectively evaluated 123 consecutive patients with documented carotid artery duplex Doppler ultrasound examination who underwent isolated CABG. Patients with a significant (≥ 60%) asymptomatic unilateral CAS (n = 35) were compared with those without a significant CAS (n = 88) to assess the rates of stroke, MI and mortality after CABG. RESULTS: No significant differences between patients with a significant asymptomatic unilateral CAS and those without a significant CAS in regard to age (p = 0.5955), presence of hypertension (p = 0.2343), diabetes (p = 0.5495), smoking (p = 0.7891), serum creatinine (p = 0.47) and left ventricular systolic function as evaluated by ejection fraction (p = 0.3789). No cerebrovascular events, MI and deaths occurred during the first 30 days postoperatively. At 12 months, no differences were seen between the groups in the incidence of MI (p = 0.1005) and mortality (p = 0.3959). However, a trend towards higher stroke incidence was noted among patients with a significant asymptomatic unilateral CAS (p = 0.0692). The primary combined endpoint (stroke, MI, and mortality) occurred in 40% of patients with a significant asymptomatic unilateral CAS and 17.05% of patients without a significant CAS (p = 0.0097). Linear regression analysis showed an association between significant asymptomatic unilateral CAS and stroke (p = 0.0041), and between significant asymptomatic unilateral CAS and the primary end point (p = 0.0475). CONCLUSIONS: The presence of a significant asymptomatic unilateral CAS does not increase the risk of stroke, MI and mortality within 30 days after CABG but is was associated with an increased risk of cardiovascular events during the first 12 months postoperatively.

Does contrast agent injection during trans-catheter aortic valve implantation negatively affect kidney function?

BACKGROUND: Trans-catheter aortic valve implantation (TAVI) has recently emerged as an alternative to conventional surgery in high-risk surgical patients with haemodynamically significant aortic valve stenosis. However, patients referred for TAVI are usually elderly individuals (> 80 years) who frequently also suffer from renal impairment. Trans-catheter valve therapies require extensive use of contrast injections with a risk of nephrotoxicity. AIM: To evaluate post-TAVI renal function and to determine whether the exposure to contrast injections might cause reduced kidney function and contrast-induced nephropathy. METHODS: From January 2009 to September 2010, TAVI was performed in 39 patients (26 women and 13 men). The mean age of the patients was 81.43 ± 7.39 years, and the mean volume of contrast material administered was 187.95 ± 91.34 mL. Serum creatinine and glomerular filtration rate (GFR, acc. to the MDRD formula) were estimated in all patients prior to and 1, 2, and 5-8 days after TAVI. RESULTS: Two female patients died on postoperative day 1. Other patients did not show clinically significant reduction in renal function following the procedure (mean creatinine concentration 104.46 vs 99.77 vs 94.56 vs 93.64 mmol/L, NS and mean GFR 52.37 vs 56.63 vs 60.18 vs 61.34 mL/min/1.73 m², NS). CONCLUSIONS: 1. The TAVI procedure, which includes contrast injection does not seem to cause a clinically significant decrease of renal function. 2. None of our elderly patients with severe aortic valve stenosis, multiple co-morbidities, and pre- TAVI renal compromise developed contrast-induced nephropathy.