Changes in nutrition, cholesterol concentration, and cardiovascular disease mortality in the Czech population in the past decade.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
R Poledne
Publications and source records attributed to R Poledne.
Evaluation of the effects of fixed combinations of sustained-release verapamil/trandolapril versus captopril/hydrochlorothiazide on metabolic and electrolyte parameters in patients with essential hypertension.
The objective of this randomised open, active controlled, cross-over study was to evaluate the effect of a fixed combination of verapamil SR/trandolapril compared to captopril/hydrochlorothiazide on serum lipids, lipoproteins, and other metabolic and electrolyte parameters in patients with essential hypertension. Another objective was to assess the efficacy and safety of both combinations. One hundred hypertensives with systolic blood pressure 140-209 mm Hg and diastolic blood pressure 90-119 mm Hg were evaluated after 16 weeks receiving a fixed combination of verapamil SR 180 mg/ trandolapril 2 mg (VT) or captopril 50 mg/hydro- chlorothiazide 25 mg (CH) both given once daily. Lipids and lipoproteins were assessed in duplicate on 2 consecutive days. The study was completed by 80 patients. There was no statistically significant difference between the two combined regimens with respect to low-density lipoprotein (LDL)-cholesterol for the 'intention-to-treat' population measured at the end of each treatment period (3.44 +/- 0.87 mmol/L with VT, and 3.46 +/- 0.86 mmol/L with CH). No differences were found for other lipid parameters like total cholesterol, triglycerides, apolipoproteins A1 and B, Lp(a). High-density lipoprotein (HDL)-cholesterol was significantly higher with VT (1.39 +/- 0.01 vs 1.35 +/- 0.01, P < 0. 03). Serum potassium declined while uric acid and glucose increased on CH. In conclusion, no significant differences were found in LDL-cholesterol and in other lipid parameters with the exception of HDL-cholesterol which was significantly higher on VT. Serum potassium declined while uric acid and glucose increased on CH (all significantly). Both fixed combinations were well tolerated. The incidence of adverse events was higher on CH. Both fixed combinations significantly lowered BP. Journal of Human Hypertension (2000) 14, 347-354
Adolescent↗
Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a history of the polycystic ovary syndrome.
The aim of the study was to determine the prevalence of non-insulin dependent diabetes mellitus (NIDDM), arterial hypertension, coronary artery disease and the risk factors for these diseases in perimenopausal women with a history of polycystic ovary syndrome (PCOS) treatment. A group of 28 women was selected from a large group of patients who had undergone wedge ovarian resection. A total of 752 controls was selected by age (45-59 years) from a random female population sample. There was no difference between the two groups in body mass index, waist circumference or waist-hip ratio. Both groups were found to have identical family histories of NIDDM, hypertension, and coronary artery disease and identical smoking habits. We did not find a difference between the mean concentrations of lipids and fasting glucose. The two groups did not differ in the proportions of women with elevated lipid concentrations. The prevalence of NIDDM and coronary artery disease was significantly higher in PCOS women. In conclusion, women in the general population have the same level of risk factors at perimenopausal age as PCOS women. Patients with markedly expressed clinical symptoms of PCOS made up a subgroup in the general population at high risk for developing NIDDM and coronary artery disease.
Coronary Disease↗
Serum ferritin levels in subjects at high risk of atherosclerosis.
Serum ferritin levels were determined in a group of 148 subjects drawn from a community study who were found to be at high risk of atherosclerosis (evaluated on the basis of the following data: levels of non-HDL cholesterol, arterial pressure, smoking status, cardiovascular or cerebrovascular disease in a subject's history, diabetes mellitus, a positive family predisposition to, or accumulation of the above factors) and compared with the levels obtained in a control group of 148 examined age- and sex-matched subjects from the same community with non-significant risk factors. Mean serum ferritin levels were higher in the whole risk group and in the subgroups of risk men and postmenopausal women than in the corresponding controls (the whole risk group: 263.4 +/- 218.5 micrograms/l vs. 198.3 +/- 179.5 micrograms/l, p < 0.05; the subgroup of men 361.8 +/- 235.7 micrograms/l vs. 286.4 +/- 194.6 micrograms/l, p < 0.05 and the subgroup of postmenopausal women 184.1 +/- 143.1 vs. 126.7 +/- 108.4 micrograms/l, p < 0.05).
Adult↗
Plasma levels of remnant particles are determined in part by variation in the APOC3 gene insulin response element and the APOCI-APOE cluster.
Remnant particles of triglyceride-rich lipoproteins (RLP) are known to be a strong predictor of atherogenicity. The serum concentrations of remnant-like particle triglyceride (RLPTG) and remnant-like particle cholesterol (RLPC) have been determined in a representative sample of the Czech MONICA study (n = 285). The relationship was investigated between remnant particle triglyceride/cholesterol concentrations and polymorphisms in the genes APOC3 (-482C-->T/3238C-->G), APOE (epsilon2/epsilon3/epsilon4), APOCI (-317-321ins), APOB (signal peptide), hepatic lipase (LIPE, -480C-->T), and lipoprotein lipase (LPL, S447X). Univariate analysis showed significant effects on RLPTG associated only with the APOE genotype (P = 0.009), the APOC3 -482C-->T genotype (P = 0.018), and the APOCI -317-321ins (P = 0.014) genotype and significant effects on RLPC with APOE (P = 0.01) and APOCI -317-321ins (P = 0.021). The raising effect of the APOE genotype for both remnant cholesterol and triglyceride was confined to the epsilon2/4 (n = 6) and varepsilon4/4 (n = 3) groups, and thus when the epsilon2/4 group was omitted in order to analyze by allele (epsilon2+/epsilon3+/epsilon4+), significance was lost (P = 0.6). There was strong linkage disequilibrium between the APOE and APOCI alleles (chi(2), P < 0.001) and a multivariate ANOVA of RLPTG with all three significantly associated variants as factors demonstrated that while the APOC3 -482C-->T effect was independent of the others (P = 0.003), the APOCI -317-321ins and APOE effects were not. This was also true for the APOCI -317-321ins and APOE effects on RLPC. To assess whether APOE-CI effects on RLPC were independent of their effects on total cholesterol and triglyceride levels, multiple linear regression was used. Using multiple linear regression, it appeared that the APOE-CI effects on RLPC were independent of their effects on plasma cholesterol, but the effects of APOC3 and APOE-CI on RLPTG could not be separated from their effects on plasma Tg levels. Further characterization of this remnant particle phenotype and its genetic determinants may lead to a better understanding of its metabolism and contribution to atherosclerosis.
Adult↗
Sex differences in the response of postprandial lipemia to a change from a low-fat low-cholesterol diet to a high-fat high-cholesterol diet.
To determine whether a short-term change in dietary habits affects postprandial lipemia in men and women in the same way, postprandial triglyceridemia was measured in age- and BMI-matched young healthy men and women after two weeks on the self-selected low-fat low-cholesterol (LF) diet and after another two weeks on the self-selected high-fat high-cholesterol (HF) diet. After a standardized challenge meal (1.4 g fat/kg of body weight), men had higher postprandial triglyceridemia than women on the HF diet but no such difference was observed on the LF diet. The results of this preliminary study suggest that there may be important sex differences in the mechanisms regulating the postprandial lipemia response to different diets, women being able to adapt better to the HF diet with respect to postprandial lipemia.
Adult↗
Variable expression of hypercholesterolemia in Apolipoprotein E2* (Arg136 --> Cys) heterozygotes.
In the process of population screening for apo E gene polymorphism with the PCR and subsequent restriction analysis, we identified a female who demonstrated heterozygosity for an unusual restriction fragment caused by the loss of a CfoI restriction site. Sequence analysis of the apo E gene was performed and a carrier of the mutant allele with C --> T substitution at cDNA position 3817 was identified, which caused an Arg136 --> Cys change. The first-line relatives have been screened for this rare mutation with PCR and restriction analysis of PCR products. The complete lipoprotein parameters have been determined in the probands family. In the family, only one child had the same mutant allele as his mother had. The proband (7.49 mmol/l) with her siblings had hypercholesterolemia and a high body mass index (BMI 31.6 kg/m2). By contrast, her son had a normal lipid spectrum with normal BMI. We described the mutation apo E2* (Arg136 --> Cys) in a family with elevated lipid levels, but there was no confirmation of the connection between this mutation and type III hyperlipoproteinemia or hyperlipoproteinemia at all. In the case of this mutation, other factors (mainly genetic) are important for the development of lipid metabolism disorders.
Apolipoproteins B↗
Influence of intrauterine undernutrition on the development of hypercholesterolemia in an animal model.
A low birth weight is a new risk factor for the development of premature atherosclerosis. The effect of intrauterine undernutrition on hypercholesterolemia in later life was studied in an experimental model using the Prague Hereditary Hypercholesterolemic (PHHC) rat. Compared to animals in the control group (Wistar rats), animals with an increased sensitivity to high-cholesterol diet (PHHC rats) display hypercholesterolemia. Only in PHHC animals, individuals undernourished in their intrauterine life (hypotrophic group, HG) had a significantly higher total cholesterol, compared with individuals without food restriction in pregnancy (eutrophic group, EG). Restricted food intake in pregnancy led to smaller nests and a decreased number of pups in each litter. We found no significant diferences in birth weight between HG and EG. In spite of similar birth weights in PHHC and Wistar rats, intrauterine undernutrition caused an increase in cholesterolemia in the HG group of the PHHC rats. The effect of intrauterine undernutrition on the development of hypercholesterolemia will most likely play a role in individuals with geneticaly determined increased susceptibility to a high-cholesterol diet. The use of this model of intrauterine undernutrition for the study of hypercholesterolemia has proved to be feasible.
Animals↗
[Longitudinal trends of total and HDL cholesterol in a representative population sample in the Czech Republic].
Cardiovascular diseases are the main cause of death in the Czech Republic. Since 1984 there is a decline of the total and cardiovascular mortality in the CR which is due to a decline of the mortality from IHD and cerebrovascular disease. Within the framework of the MONICA project in 1985, 1988 and 1992 in six districts of the CR screening examinations of cardiovascular disease risk factors were made. For examination always 1% of the population aged 25-64 years (random sampling) was invited. In 1997 and 1998 a similar cross-sectional surmy was made in nine districts of the CR. A total of 3,209 subjects were examined. In 1985-1997/98 in the representative population samples of six districts of the CR there was a significant decline of total cholesterol (men from 6.21 +/- 1.29 to 5.65 +/- 1.15 mmol/l, p < 0.001, women from 6.18 +/- 1.26 to 5.53 +/- 1.21 mmol/l, p < 0.001 and the total cholesterol/HDL ratio (men from 4.94 +/- 1.83 mmol/l to 4.66 +/- 1.46, p < 0.001, women from 4.14 +/- 1.32 to 3.89 +/- 1.30 mmol/l p < 0.001).
Adult↗
[Frequency of occurrence of apolipoprotein E isoforms in patients with various types of hyperlipoproteinemias].
BACKGROUND: Apolipoprotein E is a polymorphic protein playing a crucial role in the metabolism of plasma lipoproteins. Three alleles referred to as epsilon 2, epsilon 3 and epsilon 4 code for three common isoforms of apoE. The most frequent allele in the population at large is epsilon 3 allele. epsilon 2 and epsilon 4 alleles are connected with lipoprotein disorders as well as with other diseases. The aim of our study was to establish frequencies of apoE coding alleles in patients with different types of hyperlipidaemia (HLP) and to reveal differences in their distribution in comparison with the general population. METHODS AND RESULTS: Therefore apoE genotype was assayed in 752 patients with primary HLP and 291 subjects randomly selected from the general Czech population. Allele frequencies were determined separately in a group of patients with familial hypercholesterolaemia (FH), polygenic hypercholesterolaemia (PHC), familial combined hyperlipidaemia (FCH) and in patients with type III. hyperlipidaemia (III). In patients with HLP a significantly higher frequency of epsilon 4 allele than in control subjects was found. In the group of FH patients frequency of the epsilon 2 allele was higher than in control subjects. In patients with PHC a significantly higher frequency of the epsilon 4 allele and lower frequency of the epsilon 2 allele were observed. In the group of FCH patients distribution of epsilon alleles did not differ from the control group. Frequency of the epsilon 2 allele in patients with type III. hyperlipidaemia was significantly higher than in controls. CONCLUSIONS: We conclude that there exist significant differences in frequencies of apoE coding alleles between patients with primary hyperlipidaemia and a randomly selected population sample. The revealed differences in allelic distribution suggest that the impact of apoE polymorphism is not uniform in all types of hyperlipidaemia.
Alleles↗
C(-260)-->T polymorphism in the promoter of the CD14 monocyte receptor gene as a risk factor for myocardial infarction.
BACKGROUND: The CD14 receptor of monocytes is an important mediator for the activation of monocytes/macrophages by endotoxins from the envelope of Gram-negative bacteria (lipopolysaccharides). We identified a polymorphism in the CD14 receptor and examined whether this genetic marker influenced the expression of the CD14 receptor on monocytes and affected the predisposition to myocardial infarction. METHODS AND RESULTS: We identified a C(-260)-->T nucleotide change, creating a HaeIII polymorphism in the promoter of the CD14 gene. The polymorphism was determined in 178 male patients <65 years old (cases; average age, 55.9+/-6.3 years) at the time of their first myocardial infarction and in 135 representative selected male control subjects (controls; average age, 55.2+/-11.5 years). The frequency of the T allele (absence of the cutting site) was 0.49 in cases and 0.35 in controls (P=0.0005; OR, 1.781; 95% CI, 1.286 to 2.465). Subsequently, we measured the expression of monocyte CD14 by flow cytometry in 18 volunteers with different CD14 genotypes. A significantly higher density of the CD14 receptor was shown in the T/T homozygotes than in the others (P=0.0028). CONCLUSIONS: A higher frequency of allele T(-260) in the promoter of the CD14 receptor gene was found in myocardial infarction survivors than in controls. At the same time, this variation was associated with a higher density of CD14 receptors in healthy volunteers. Therefore, we can conclude that in addition to the well-established risk factors, a genetically determined reaction of monocytes/macrophages to infectious stimuli could play an important role in the process of atherosclerosis.
Aged↗
[Age and changes in dietary habits affect hyperlipoproteinemia after kidney transplantation].
BACKGROUND: Atherosclerosis of the blood vessels is the most frequent cause of morbidity and mortality of patients after transplantation of the kidneys with a long-term function of the graft. It is assumed that the most significant risk factor for its development is secondary hyperlipoproteinaemia (HLP). In the development of HLP a number of factors may participate (chronic renal insufficiency, proteinuria, immunosuppressive treatment, diet, increment of body weight, age, genetic factors). The objective of the investigation was to follow changes of the lipid spectrum after renal transplantation and evaluate the impact of different factors which participate in these changes. METHODS AND RESULTS: The authors investigated in a retrospective metabolic study for a period of 18 months a total of 348 patients after the first cadaverous kidney transplantation. They compared the findings in 34 patients (group I) who had throughout the investigation period a total cholesterol of < or = 5.2 and triacylglycerols < or = 2.3 and group II (314 patients) who had elevated values of these factors. The mean values of different parameters differed highly significantly (group I vs. group II): cholesterol 4.6 +/- 0.4 vs 6.8 +/- 1.5 (p < 0.001), triacylglycerols 1.8 +/- 0.8 vs 3.6 +/- 1.6 (p < 0.001), LDL-cholesterol 2.6 +/- 0.6 vs 4.0 +/- 1.1 (p < 0.001), (all in mmol/l) and HDL/total cholesterol 0.28 +/- 0.07 vs 0.20 +/- 0.09 (p < 0.01). The authors did not detect a difference in the incidence of isoforms of apo E. There were no differences in the mean cyclosporin A levels: 394 +/- 114 vs. 489 +/- 202 (ng/ml) and renal function CCr 1.0 +/- 0.6 vs 0.9 +/- 0.3 (ml/s). In group I there was a significantly higher intake of energy 150 +/- 20 vs. 125 +/- 25 (kJ), of fat 1.6 +/- 0.3 vs. 1.0 +/- 0.2 (g/kg) and disaccharides (by 50%). With this corresponded also a significantly higher increment of BMI 27.4 +/- 4.6 vs. 23.8 +/- 3.3 (p < 0.01). Patients in group II were also significantly older (44.5 +/- 14.1 vs 49.4 +/- 12.5, p < 0.01). CONCLUSIONS: It is assumed that one of the main causes of the development of HLP after transplantation are poor dietary habits of the patients associated with an excessive intake of energy, fats and disaccharides and an increase of body weight. The patient's age is significantly higher. Standard lower doses of immunosuppressive drugs have obviously only a supportive effect.
Adult↗
Does angiotensin-converting enzyme polymorphism influence the clinical manifestation and progression of heart failure in patients with dilated cardiomyopathy?
To evaluate the role of angiotensin-converting enzyme (ACE) polymorphism on the development of end-stage dilated cardiomyopathy, the ACE gene polymorphism of 90 patients after heart transplantation because of this disease was compared with the population sample. No difference in gene frequencies was found, but when compared with the population sample there were fewer ID heterozygotes detected; no significant influence of ACE polymorphism on the course of the disease before transplantation was found.
Adult↗
European Lipoprotein Club: report of the 21st Annual Conference, Tutzing, September 28-October 1, 1998.
Molecular biology and genetics were the hallmarks of the conference. Attendees from 20 European countries participated in lively discussions with international speakers. The opening round table session entitled 'Genetic approach to complex diseases' was chaired by Harald Funke. Steve Humphries (London) presented association studies and Harald Funke (Munster) presented multiparameter analyses, as models of genetic epidemiological approaches to atherosclerosis. Gerd Utermann (Innsbruck) showed, through sib pair linkage analysis, how apo (a) gene polymorphism determines plasma levels of Lp(a). Klaus Lindpainter (Basel) described novel genetic strategies heading for a more targeted medicine, through the identification of genetic mechanisms of disease and therapeutic responses. Session I, chaired by Richard James (Geneva) and Guido Franceschini (Milano), on 'Basic mechanisms of action of drugs' highlighted molecular and cellular actions by which present (fibrates, statins) or future (ACAT or MTP inhibitors) drugs or hormones may modulate lipoprotein metabolism. Marten Hofker (Leiden) and Philippa Talmud (London) chaired Session II on 'Regulation of gene expression', which reported cellular regulations by nuclear receptors (PPARs), or the regulation of lipid trafficking by membrane receptors (SR-BI, Megalin, Apo-E receptor, scavenger receptors) or by intracellular (IFN gamma signalling pathways) or extracellular proteins (lipases). Beyond gene expression, Session III, 1st part, entitled 'Lipoprotein modifying enzymes' was chaired by Katriina Aalto-Setälä (Tampere). Roles of lipases (HL, LPL) and transfer proteins (CETP, PLTP), as well as structures of lipid binding molecules (LCAT, apolipoproteins), were further explored. The 'Gene interactions' session chaired by Rudolph Poledne (Prague), and 'Novelties' chaired by Hans Dieplinger (Innsbruck), reported elegant models of cross-bred, tissue specific knock-out or YAC-transgenic mice for lipoprotein metabolism, and descriptions of gene interactions in polygenic disorders or new loci for familial lipid disorders (familial combined hyperlipidemia, metabolic syndrome and Tangier disease) in humans.
Animals↗
(TTA)n repeat polymorphism in the HMG-CoA reductase gene and cholesterolaemia.
BACKGROUND: Hypercholesterolaemia is one of the main risk factors of atherosclerosis. Both environmental and genetic factors have been implicated in the development of hypercholesterolaemia. The enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase plays an important role in cholesterol synthesis. Thus we supposed that polymorphisms in this gene could influence cholesterolaemia. PATIENTS AND METHODS: Using PCR, we measured the (TTA)n repeat polymorphism near the Alu sequence of the gene for HMG-CoA reductase in two groups of children selected from opposite ends of the cholesterolaemia distribution curve obtained from measuring cholesterolaemia in 2000 children. Eighty-two children in high- and eighty-six children in low-cholesterolaemic groups participated on the study. RESULTS: A significant difference was found in the frequencies of the genotypes of the 10+ add alleles (43.9% in high-cholesterolaemic children vs 24.4% in low-cholesterolaemic children p < 0.025). No differences were demonstrated in the frequencies of other genotypes (allele 10+ even and without allele 10). No associations between lipid parameters and genotypes or genotype subgroups within the group of high- and low-cholesterolaemic children were found. CONCLUSION: The (TTA)n repeat polymorphism in the gene for HMG-CoA reductase could be another genetic marker that plays a role in the genetic determination of cholesterolaemia.
Child↗
Intima-media thickness of carotid arteries in borderline hypertensives.
The purpose of this study was to assess the effect of the main risk factors for cardiovascular disease on the process of subclinical atherosclerosis in originally borderline hypertensives. The relation of far wall common carotid artery intima-media thickness (IMT CCA) measured by B-mode ultrasound to smoking, body mass index (BMI), blood pressure, lipids, and angiotensin-converting enzyme (ACE) gene polymorphism was analyzed. In 48 subjects examined (mean age, 61.9 +/- 2.54 years), median IMT CCA was 0.708 mm. Statistically significant differences in BMI (26.5 vs. 29.2 kg/m2, p < 0.025) and HDL-cholesterol level (1.42 vs. 1.1 mmol/l, p < 0.025) between the first and third tertile of IMT CCA were found. No differences were observed between "controls" and "cases" in blood pressure, total cholesterol, and triacylglycerols. No significant differences in IMT CCA were found between smokers and nonsmokers and among different alleles of the ACE gene. These data reflect the importance of HDL-cholesterol and BMI on the process of atherosclerosis within an otherwise homogeneous group of patients.
Adult↗
The common cDNA and amino acid sequences of the CD14 (myeloid cell-specific leucine-rich glycoprotein) receptor.
The CD14 receptor is a myeloid cell specific receptor, which plays a role in the recognition of lipopolysaccharides (endotoxins of gram-negative bacteria) and cell stimulation. To date, several sequences of the cDNA of the CD14 receptor have been described. We sought to establish whether the substitutions C(230)-->G, and G(560)-->A are polymorphic or if they result from a PCR or sequencing error. Using two mismatched PCRs, we confirmed (on 75 unrelated probands) that the substitutions are not due to common polymorphisms. The common cDNA sequence has the C in position 230 and G in position 560. This corresponds to the amino acids Ala and Cys in positions 77 and 187, respectively.
Amino Acid Sequence↗
A genetic and correlation analysis of liver cholesterol concentration in rat recombinant inbred strains fed a high cholesterol diet.
Liver cholesterol concentration in rats fed a high cholesterol diet, is under genetic control which is supported by significant differences observed among inbred strains. For instance, the Brown Norway (BN-Lx/Cub) rat developed a twofold higher liver cholesterol concentration than the spontaneously hypertensive rat (SHR/Ola). In the current study, we used 30 recombinant inbred (RI) strains, derived from BN-Lx and SHR progenitors, to locate quantitative trait loci (QTL) that are responsible for differences in liver cholesterol concentrations between the BN-Lx and SHR strains. The heritability of liver cholesterol was estimated to be 0.55 and a significant association was detected between concentration of liver cholesterol and the D10Cebrp1016s2 marker on chromosome 10 (lod score = 3.3); this putative QTL was responsible for nearly 64% of additive genetic variability and thus represents a major genetic determinant of liver cholesterol concentration. Liver cholesterol concentrations significantly correlated with intermediate density lipoprotein (IDL) cholesterol levels.
Animals↗