Longitudinal Trends in Severe Dyslipidemia in the Czech Population: The Czech MONICA and Czech Post-MONICA Study.

Background: Severe hypercholesterolemia is associated with an increase in the risk of developing atherosclerotic cardiovascular disease. The aim of this analysis was to assess longitudinal trends in severe dyslipidemia (defined as total cholesterol > 8 mmol/L or LDL-cholesterol > 5 mmol/L) in a representative population sample of the Czech Republic and to analyze the longitudinal trends in the basic characteristics of individuals with severe dyslipidemia. Methods: Seven independent cross-sectional surveys were organized in the Czech Republic to screen for major cardiovascular risk factors (from 1985 to 2015-2018). A total of 20,443 randomly selected individuals aged 25-64 years were examined. Results: The overall prevalence of severe dyslipidemia was 6.6%, with a significant downward trend from the fifth survey onwards (2000/2001). Over the study period of 30+ years, the individuals with severe dyslipidemia became older, increased in BMI, and did not change their smoking habits. Total cholesterol and non-HDL-cholesterol decreased significantly in both sexes throughout the duration of the study. Conclusions: Despite a significant improvement in lipids in the Czech Republic from 1985, substantially contributing to the decline in cardiovascular mortality, the number of individuals with severe dyslipidemia remained high, and in most cases, they were newly detected during our screening examinations and were thus untreated.

Short-term trajectories of exercise-induced plasma lipid changes in overweight females, with a focus on HDL-cholesterol.

BACKGROUND: Increased levels of plasma lipoproteins are among some of the modifiable risk factors for cardiovascular disease (CVD). Dietary changes and increased physical activity are the most powerful non-pharmacological interventions for achieving optimal plasma lipid levels. OBJECTIVES: To investigate the effect of an intensive short-term lifestyle intervention on plasma lipid trajectories in overweight non-diabetic females. MATERIAL AND METHODS: A total of 202 healthy overweight (body mass index (BMI) >27.5 kg/m2) females underwent an intensive short-term (ten-week) intervention (at least 4 units of one-hour exercise activity weekly at optimal energy intake) aimed at lowering body weight. Plasma lipid (total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglycerides (TG)) levels were examined at baseline and every 2 weeks over the course of the ten-week intervention. RESULTS: There was a significant decrease in BMI (Δ -4.7%, p < 0.001) and body weight (Δ -4.9%, p < 0.001) after the intervention. Positive changes (decreases) in TC (Δ -8%, p < 0.001), TG (Δ -9%, p < 0.001) and LDL-C (Δ -11%, p < 0.001) were observed immediately after 2 weeks, but levels did not decrease further thereafter. In contrast, HDL-C did not increase as expected: after 2 weeks of intervention, we observed a significant decrease of about 6% (p < 0.001) followed by a slow return to baseline values. But even after 10 weeks of intervention, HDL-C values had not reached the values detected at baseline. CONCLUSIONS: In overweight females, HDL-C decreased after short-term intensive lifestyle intervention. To confirm the protective effect of increased physical activity, plasma lipids need to be examined over a longer time period.

30-year trends in major cardiovascular risk factors in the Czech population, Czech MONICA and Czech post-MONICA, 1985 - 2016/17.

BACKGROUND: Compared with Western Europe, the decline in cardiovascular (CV) mortality has been delayed in former communist countries in Europe, including the Czech Republic. We have assessed longitudinal trends in major CV risk factors in the Czech Republic from 1985 to 2016/17, covering the transition from the totalitarian regime to democracy. METHODS: There were 7 independent cross-sectional surveys for major CV risk factors conducted in the Czech Republic in the same 6 country districts within the WHO MONICA Project (1985, 1988, 1992) and the Czech post-MONICA study (1997/98, 2000/01, 2007/08 and 2016/2017), including a total of 7,606 males and 8,050 females. The population samples were randomly selected (1%, aged 25-64 years). RESULTS: Over the period of 31/32 years, there was a significant decrease in the prevalence of smoking in males (from 45.0% to 23.9%; p < 0.001) and no change in females. BMI increased only in males. Systolic and diastolic blood pressure decreased significantly in both genders, while the prevalence of hypertension declined only in females. Awareness of hypertension, the proportion of individuals treated by antihypertensive drugs and consequently hypertension control improved in both genders. A substantial decrease in total cholesterol was seen in both sexes (males: from 6.21 ± 1.29 to 5.30 ± 1.05 mmol/L; p < 0.001; females: from 6.18 ± 1.26 to 5.31 ± 1.00 mmol/L; p < 0.001). CONCLUSIONS: The significant improvement in most CV risk factors between 1985 and 2016/17 substantially contributed to the remarkable decrease in CV mortality in the Czech Republic.

Analysis of circulating miRNAs in patients with familial hypercholesterolaemia treated by LDL/Lp(a) apheresis.

BACKGROUND: LDL/Lp(a) apheresis therapy is a well-established method of aggressively lowering LDL and Lp(a). Recently, miRNAs have been discussed as markers of vascular status including atherosclerosis. MiRNAs inhibit post-transcriptional processes through RNA duplex formation resulting in gene silencing or regulation of gene expression. MATERIALS AND METHODS: We measured a profile of 175 plasma-circulating miRNAs using pre-defined Serum/Plasma Focus Human microRNA PCR Panels in pooled samples of 11 subjects with familial hypercholesterolaemia under long-term apheresis treatment. Subsequently we analysed expressions of ten pre-selected miRNAs potentially involved in lipid homeostasis in the same group of subjects. We compared plasma-circulating miRNA levels isolated from peripheral blood collected immediately before and after apheresis. RESULTS: The greatest differences in plasma levels were found in miR-451a, miR-16, miR-19a/b, miR-223 and miR-185. In subsequent individual miRNA assay we detected a significant increase in miR-33b levels after apheresis (P < 0.05). Additionally, correlations between plasma lipids and miR-33a (P < 0.04) and miR-122 (P < 0.01) have been determined. Moreover, miR-122 levels in LDLR homozygotes were higher compared to heterozygotes after, but not before, apheresis treatment (P < 0.04). CONCLUSIONS: LDL/Lp(a) apheresis has an impact on miRNAs associated with lipid homeostasis and vascular status.

Biphasic response in number of stem cells and endothelial progenitor cells after left ventricular assist device implantation: A 6month follow-up.

BACKGROUND: Continuous blood flow could have deleterious effects on endothelium and vascular health. This could have serious consequences in patients with heart failure treated with continuous flow left ventricular assist devices (LVAD). Therefore, we studied effect of LVAD on three circulating vascular biomarkers: stem cells (SC), endothelial progenitor cells (EPC) and microparticles (MP). METHODS: In 23 patients (5 women) with end-stage heart failure, SC, EPC and MP were measured before, and 3 and 6months after implantation of LVAD (HeartMate II). SC were defined using determination of surface antigen expression as mononuclear CD34+/CD45low+ cells and EPC as mononuclear CD34+/CD45low+/KDR+ cells. MP concentrations were determined by ELISA method. RESULTS: Three months after LVAD implantation numbers of SC and EPC significantly decreased (p=0.01 and p=0.001, respectively). On the contrary, between 3rd and 6th month after implantation they significantly increased (p=0.006 and p=0.003, respectively).MP did not change significantly during the study despite exerting similar trend as SC and EPC. CONCLUSIONS: Observed biphasic changes of SC and EPC might reflect two processes. First, shortly after LVAD implantation, improved tissue perfusion could lead to decrease in ischemic stimuli and ensuing decrease of SC and EPC. Second, continuous flow between 3rd and 6th month produced by LVAD could lead to increase of SC and EPC through activation of endothelium. This explanation could be supported also by similar trend in the changes of concentrations of MP.

FTO first intron rs1558902 variant and platelets count in white middle-aged women: prague pre- and post-menopausal females (3PMFs) study.

The polymorphisms within the FTO gene play an important role in the genetic determination of body weight and body mass index and have been associated with cardiovascular disease, but the causal mechanism is still a matter of debate. The possible effect on the platelet count as a marker of hemocoagulation status as a possible cardiovascular risk factor was suggested in Japanese population. We have analyzed both rs1558902 FTO polymorphism (T > A) and platelet counts in the Prague Pre and Post Menopausal Females (3PMFs) study, including those of 669 women (mean age, 55.7 ± 2.7 years). The frequencies of the FTO genotypes were similar to other populations (TT, 30.4%; TA, 48.1%; and AA, 21.5%). We have not detected a significant association between the FTO rs1558902 variant and platelet counts in white women (TT, 242 ± 55 × 10; TA, 246 ± 67 × 10; and AA, 247 ± 55 × 10; F[2.642] = 0.30, P = 0.75). At least in white persons, platelet count seems not to be a link between the FTO variation and risk of cardiovascular disease.

HDL and apolipoprotein A1 concentrations as markers of cholesterol efflux in middle-aged women: interaction with smoking.

OBJECTIVES: It has been demonstrated that the deleterious effect of smoking on the cardiovascular system is mediated through a decrease in protective HDL cholesterol. In addition, women are more sensitive to the negative effects of smoking, although the exact mechanism underlying this phenomenon is currently unknown. In this study, we evaluated whether smoking habits could modify the association of HDL cholesterol and apolipoprotein A1 (ApoA1) with reverse cholesterol transport (RCT), as measured by cholesterol efflux (CHE), in middle-aged women. DESIGN: The study group consisted of 39 healthy middle-aged women, 21 non-smokers (age 51.8±2.5 years, BMI 25.1±2.8 kg/m2) and 18 smokers (age 50.5±3.2 years, BMI 24.8±3.5 kg/m2). In addition to all traditional cardiovascular risk factors, CHE from macrophages, labelled during a 48-hour incubation in a medium containing [14C] cholesterol, to plasma acceptors in study subjects was established as a marker of reverse cholesterol transport. RESULTS: CHE was significantly higher in non-smokers than in smokers (14.22±1.75% vs. 13.17±1.33%; p<0.05). Smoking habit had no effect on the association of HDL with ApoA1 or HDL with CHE. However, in contrast to the strong association of ApoA1 with CHE in non-smokers (r=0.62; p<0.01), no such strong association was found in smokers (r=0.38; n.s.). Main findings and conclusion: Based on our results, smoking can alter ApoA1-mediated reverse cholesterol transport in women.

The impact of left ventricle assist device on circulating endothelial microparticles - pilot study.

OBJECTIVES: Recent technological breakthroughs in the design of reliable systems for long term non-pulsatile mechanical heart support offer the possibility to study the effect of continuous blood flow in the vascular system. Generally, it is assumed that the absence of physiological pulsatile flow leads to prothrombogenic and proatherogenic changes. We investigated the change in the circulating endothelial microparticle concentration as a marker of endothelial damage in patients implanted with a continuous-flow left ventricle assist device (LVAD). METHODS: Endothelial microparticles were measured in 8 males (mean age 54.1±11.5 years) with terminal heart failure before and 3 months after implantation of an LVAD. The group consisted of 3 patients with dilated cardiomyopathy, 3 patients with ischemic cardiomyopathy, 1 patient with both conditions and 1 patient with congenital valvular disease. The concentration of endothelial microparticles was determined by ELISA Zymutest MP activity test. RESULTS: We did not observe a significant change in the concentration of circulating endothelial microparticles measured before and 3 months after implantation (p=0.669). High inter-individual variability in response to implantation was found. However, no association between a change in endothelial microparticle concentration and heart failure aetiology or a significant clinical complication attributed to LVAD implantation was observed. CONCLUSION: Results from this preliminary pilot study do not indicate that LVADs contribute to short-term vascular damage as defined by an increase in circulating endothelial microparticles.

Which index best correlates with body fat mass: BAI, BMI, waist or WHR?

OBJECTIVES: The body mass index (BMI) has been the most commonly applied clinical measure to characterise body composition in individuals. However, the BMI has been criticised as being an inaccurate measure of body fatness. Recently, a new index reflecting body composition, the Body Adiposity Index (BAI) was proposed. The BAI was calculated using the equation BAI=((hip circumference)/ ((height)1.5) - 18). AIM: The aim of this study was to compare estimates of body fat content, i.e., body adiposity index (BAI), BMI, waist-hip ratio (WHR) and waist and hip circumferences, with respect to their ability to predict the percentage of body fat (PBF). RESULTS: To select an optimal surrogate for adiposity, we examined the correlation between body adiposity percentage as measured by BIA and several variables, including BAI, BMI and WHR. Correlations ranged from a high of 0.78 for BMI, 0.67 for BAI and 0.66 for waist circumference to a low value of 0.39 for the WHR index. The correlation between PBF and BAI (R=0.67, R2=0.45, p<0.001) and the correlation between PBF and BMI (R=0.78, R2=0.60, p<0.001) were of similar magnitude. CONCLUSION: Based on our results and those of other studies, we can say that the BAI index is not a universally valid index that could be used in the place of the BMI index in a Caucasian population; indeed, it would not accurately reflect body fat mass and thus could lead to an increased risk of obesity. Further, WHR index is not a suitable for an estimation of body fat.

Possible effect of DHA intake on body weight reduction and lipid metabolism in obese children.

OBJECTIVES: The aim of the study was to determine whether increased intake of DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) would affect the weight loss or the various biochemical parameters in the blood of obese children following dietary/physical intervention. There were 120 obese (BMIs≥30 kg/m(2); mean 33.5 ± 3.9) children included in this randomized crossover study; aged 8-12 years (10.0 ± 1.9). METHODS: The children consumed an extra 300 mg DHA and 42 mg EPA (Haliborange ®) daily for a period of 3 weeks. Anthropometric and biochemical parameters were measured and documented for each of the subjects at the beginning of the study, after three weeks of treatment and at the end of the study. RESULTS: The daily consumption of 300 mg DHA and 42 mg of EPA was associated with decreased body weight (with DHA: 86.4 ± 19.6 to 80.8 ± 20.4 kg vs. without DHA: 85.6 ± 20.8 to 80.9 ± 19.9 kg; p<0.005) and total cholesterol concentration (with DHA: 3.72 ± 0.78 to 3.32 ± 0.53 mmol/l vs. without DHA: 3.74 ± 0.78 to 3.56 ± 0.56 mmol/l; p<0.05 and respectively with DHA). CONCLUSION: Daily consumption of 300 mg DHA and 42 mg EPA (Haliborange®) for 3 weeks leads to an improvement of the anthropometric and lipid parameters in obese children following dietary physical intervention.

Longitudinal trends in major cardiovascular risk factors in the Czech population between 1985 and 2007/8. Czech MONICA and Czech post-MONICA.

OBJECTIVE: The aim of our study was to assess longitudinal trends in major CV risk factors in a representative population sample of the Czech Republic. METHODS: Three cross-sectional surveys of CV risk factors were conducted within the WHO MONICA project in six Czech districts in 1985 (n=2570), 1988 (n=2768), and 1992 (n=2343). In 1997/98, 2000/01, and 2007/08, another three screenings for CV risk factors (a 1% random sample, aged 25-64, mean age 45 years) were conducted in the six original districts (n=1990; 2055; and 2246, respectively). RESULTS: Over a period of 22/23 years, there was a significant decrease in the prevalence of smoking in males (from 45.0 to 30.5%; p<0.001) and no change in smoking habits in females. BMI increased in males and did not change in females. Both systolic and diastolic blood pressure decreased significantly in both genders, while the prevalence of hypertension declined only in females. Awareness of hypertension also rose as did the proportion of individuals treated by antihypertensive drugs in both genders. Hypertension control improved in either gender. A remarkable drop in total cholesterol was seen in both sexes (males: from 6.21 + or - 1.29 to 5.29 + or - 1.10 mmol/L; p<0.001; females: from 6.18 + or - 1.26 to 5.30 + or - 1.06 mmol/L; p<0.001). CONCLUSIONS: The striking improvement in CV risk factors documented between 1985 and 2007/8 most likely contributed to the decrease in CV mortality in the Czech Republic.

APOE polymorphism and its effect on plasma C-reactive protein levels in a large general population sample.

The published data remain inconsistent on association between apolipoprotein E (APOE) gene variations and plasma levels of C-reactive protein (CRP), mainly because of low statistical power of previous studies. To clarify this question, we analyzed data from large population sample of randomly selected individuals from seven Czech towns (2,886 males and 3,344 females, the HAPIEE [Health, Alcohol, and Psychosocial factors In Eastern Europe] study). In both males and females, the lowest levels of plasma hsCRP were observed in the carriers of the APOE epsilon 4 epsilon 4 and epsilon 4 epsilon 3 genotypes. The median (interquartile range, IQR) concentration of hsCRP in carriers of the most common APOE epsilon 3 epsilon 3 genotype (two-thirds of participants) was 1.13 mg/l (IQR, 0.56-2.33) in men and 1.23 mg/l (IQR, 0.61-2.65) in women, compared with 0.72 mg/l (IQR, 0.61-0.86) in male and 0.72 mg/l (IQR, 0.61-0.85) in female carriers of APOE epsilon 4 epsilon 3/epsilon 4 epsilon 4 genotypes; the differences were statistically significant (p < 0.001). The association between APOE and CRP was not materially affected by adjustment for age, sex, history of cardiovascular disease, or cardiovascular risk factors. This study, the largest to date, provides robust evidence of an association between plasma hsCRP and the APOE genotype, an association not explained by history of cardiovascular disease nor its risk factors.

High-sensitivity C-reactive protein concentration in patients with myocardial infarction-environmental factors, and polymorphisms in interleukin-10 and CD14 genes.

BACKGROUND: It has been shown that high-sensitivity C-reactive protein (hsCRP) concentrations are associated with elevated risk of myocardial infarction, but the mechanisms regulating hsCRP concentration are not completely elucidated yet. In our study, association of interleukin-10 (IL-10) and CD14 polymorphisms and environmental factors with the risk of myocardial infarction was studied. METHODS: The study group consisted of 284 male patients aged below 65 years, admitted to hospital for myocardial infarction. The controls were age-matched individuals selected from a 1% representative population sample of adult men. RESULTS: While there was no difference in body mass index (BMI), the patients more frequently had abdominal-type obesity. hsCRP concentration was higher in patients (2.12+/-2.31 mg/L) than in controls (1.40+/-1.56 mg/L; p=0.001), in spite of statin treatment in most of the patients. No significant difference in lipoprotein concentrations was found. There was no difference in IL-10 and CD14 genotype distributions between the patients and controls. In smoking patients carrying the CD14 C allele, hsCRP concentration was significantly higher (p=0.0012) than in a non-smoking patients with the same allele. According to linear regression analysis, statin treatment was the only variable with an influence that reached statistical significance in the patient group, while in the control group, age, smoking, education and BMI significantly influenced hsCRP concentration. CONCLUSIONS: There was no association between IL-10 and CD14 polymorphisms and myocardial infarction occurrence. Gene-environment interaction may play an important role in influencing hsCRP concentration.

The decrease in C-reactive protein concentration after diet and physical activity induced weight reduction is associated with changes in plasma lipids, but not interleukin-6 or adiponectin.

Subclinical inflammation is a risk factor for cardiovascular disease. The mechanisms underlying increased levels of inflammatory markers and their changes in response to weight loss are not fully understood yet. It has been proposed that elevated concentrations of C-reactive protein (CRP) are mediated by cytokines produced in adipose tissue. We investigated the changes in circulating CRP after weight reduction, in relation to parameters relevant to the metabolic syndrome. Forty 25- to 35-year-old obese female volunteers participated in an intervention program of dietary education and supervised physical activity for a period of 9 weeks. Anthropological parameters and biochemical measurements (high-sensitivity CRP [hsCRP], plasma lipoproteins, interleukin 6 [IL-6], adiponectin) were analyzed before and after the intervention. Body mass index decreased by more than 7% from 31.5 +/- 4.1 to 29.1 +/- 3.9. Plasma free fatty acid (FFA) concentrations decreased by 30%, high-density lipoprotein cholesterol increased by 8%, and fasting insulin concentrations decreased by 15%. There were no significant changes in either low-density lipoprotein cholesterol or triacylglycerol concentrations. Subcutaneous and visceral adipose tissue mass decreased by 12% and 18%. High-sensitivity CRP concentrations decreased by 30%; however, mean plasma IL-6 and adiponectin concentrations remained unchanged. In linear regression analysis, the changes in plasma hsCRP concentrations were associated with baseline hsCRP concentration, change in triacylglycerols and FFA concentrations, and in waist circumference. The decrease in hsCRP concentration after weight reduction does not appear to be mediated by decreases in circulating IL-6 or adiponectin concentrations; however, change in hsCRP concentration is related to changes in waist circumference and lipid metabolism, reflected by plasma triacylglycerol and FFA levels.

Comparison of the effects of atorvastatin or fenofibrate on nonlipid biochemical risk factors and the LDL particle size in subjects with combined hyperlipidemia.

BACKGROUND: Combined hyperlipidemia (CH) is an increasingly prevalent risk factor for premature heart disease, and its treatment is troublesome. The aim of this study was to compare the effects of atorvastatin and fenofibrate on nonlipid biochemical risk factors and the low-density lipoprotein (LDL) particle size in subjects with CH. METHODS: Twenty-nine middle-aged men with CH were randomly assigned to open-label therapy with atorvastatin (10 mg daily) or micronized fenofibrate (200 mg daily); they were sequentially treated with both drugs, with crossover of medication after 10 weeks. RESULTS: Atorvastatin was more efficient in the reduction of total cholesterol, whereas fenofibrate was more efficient in the reduction of triglycerides. Only atorvastatin led to a significant reduction of LDL cholesterol and apolipoprotein B. Only fenofibrate increased high-density lipoprotein cholesterol. Neither drug influenced lipoprotein(a). Mean LDL particle size increased both after fenofibrate (3.08%) and atorvastatin (1.77%). Fenofibrate increased serum homocysteine (HCY) by 36.5%. Atorvastatin had no effect on HCY. Only atorvastatin increased fibrinogen by 17.4%. Only fenofibrate reduced C-reactive protein by 51.7%. Neither drug influenced HOMA (homeostasis model assessment) index of insulin resistance. The plasma level of thiobarbituric acid reactive substances, an index of oxidative stress, decreased after both treatments. CONCLUSIONS: Both atorvastatin and fenofibrate had similar beneficial effects on LDL particle size and on oxidative stress. The effects of both drugs on other parameters such as triglycerides, total and high-density lipoprotein cholesterol, fibrinogen, or HCY differed significantly. These differences, together with the risk profile of a patient, should be considered during selection of a particular lipid-lowering modality.