Association of intima-media thickness of carotid arteries with remnant lipoproteins in men and women.

The subclass of triglyceride-rich lipoproteins - remnant-like particles (RLP) seems to be strong and independent risk factor for cardiovascular disease. We evaluated the role of RLP and other risk factors (RF) with sonographically measured intima-media thickness of carotid arteries (IMT CCA) in a cohort of Czech population including women defined according to the time after menopause. We investigated relation of IMT CCA to age, weight, central obesity, plasma lipids including remnant-like particles cholesterol (RLP-C) and triglycerides (RLP-TG) in 136 men and 160 women. Using multiple linear regression analysis, significant association between IMT CCA and RLP-C was found in women 1-7 years after menopause. In the whole group of women, only age and fasting blood glucose were independently associated with IMT CCA. In men only age significantly correlated with IMT CCA. Significant decrease of all plasma lipids between 1988 and 1996 in men was detected, while in women significant increase in triglycerides and no change in non-HDL cholesterol was observed. RLP-C was the strongest independent RF for atherosclerosis in postmenopausal women but its association with IMT CCA was limited to several years after menopause. In conclusion, women changing reproductive status could be more sensitive to atherogenic impact of remnant lipoproteins.

Effect of exercise on markers of vascular health in renal transplant recipients.

The cornerstone of cardiovascular risk management is lifestyle intervention including exercise which could exert favorable impact also in renal transplant recipients. Nevertheless, reliable assessment of the effect of lifestyle interventions is complicated and the available data in this population are not consistent. The aim of the study was to evaluate the effect of physical activity on selected laboratory markers of vascular health including circulating stem cells, endothelial progenitor cells, microparticles, and plasma asymmetric dimethyl arginine in renal transplant recipients. Nineteen men and 7 women were recruited in 6-month program of standardized and supervised exercise. Control group consisted of 23 men and 13 women of similar age and body mass index not included into the program. One year after the transplantation, the main difference between intervention and control group was found in the change of endothelial progenitor cells (p=0.006). Surprisingly, more favorable change was seen in the control group in which endothelial progenitor cells significantly increased compared to the intervention group. The explanation of this finding might be a chronic activation of reparative mechanisms of vascular system in the population exposed to multiple risk factors which is expressed as relatively increased number of endothelial progenitor cells. Therefore, their decrease induced by exercise might reflect stabilization of these processes.

Endothelial dysfunction expressed as endothelial microparticles in patients with end-stage heart failure.

Left ventricular assist devices (LVAD), currently used in treatment of terminal heart failure, are working on principle of rotary pump, which generates continuous blood flow. Non-pulsatile flow is supposed to expose endothelial cells to high stress and potential damage. Therefore, we investigated longitudinal changes in concentration of circulating endothelial microparticles (EMP) as a possible marker of endothelial damage before and after implantation of LVAD. Study population comprised 30 patients with end-stage heart failure indicated for implantation of the Heart Mate II LVAD. Concentrations of microparticles were measured as nanomoles per liter relative to phosphatidylserine before and 3 months after implantation. At 3 months after implantation we observed significant decrease in concentration of EMP [5.89 (95 % CI 4.31-8.03) vs. 3.69 (95 % CI 2.70-5.03), p=0.03] in the whole group; there was no difference observed between patients with ischemic etiology of heart failure (n=18) and with heart failure of non-ischemic etiology (n=12). In addition, heart failure etiology had no effect on the rate of EMP concentration decrease with time. These results indicate possibility that LVAD do not cause vascular damage 3 months after implantation. Whether these results suggest improvement of vascular wall function and of endothelium is to be proved in long-term studies.

The association between subclinical atherosclerosis in carotid arteries and Connexin 37 gene polymorphism (1019C>T; Pro319Ser) in women.

AIM: The aim of our study was to evaluate a possible association between subclinical atherosclerosis in carotid arteries and the connexin 37 gene polymorphism (1019C>T; Pro319Ser) in a population of urban and rural women. METHODS: A 5% population sample of urban women aged 45-54 years (N.=896) and a 1% representative sample of rural women aged 33-72 years (N.=152) were examined using an identical protocol and genotyped for Cx37 gene polymorphism. The association between the Cx37 polymorphism and intima-media thickness in common carotid arteries measured by ultrasound (CIMT) was studied. RESULTS: We have found a different pattern of the effect of the Cx37 gene on CIMT with regard to fasting glycemia with significant interaction between fasting glycemia and Cx37 gene on CIMT (test for equality of slopes P<0.0001). In addition, we also detected potential threshold effect of fasting glycemia at the concentration of 5.5 mmol/L (ANCOVA; P=0.026). Carriers of TT genotype showed protection against subclinical atherosclerosis if their fasting glycemia was above 5.5 mmol/L. CONCLUSION: In women with higher fasting glycemia TT genotype of Cx37 polymorphism was protective against subclinical atherosclerosis. Therefore, the Cx37 gene may exert completely different effects in the artery wall, depending on glycemia.

May alcohol-induced increase of HDL be considered as atheroprotective?

It is well known that the consumption of moderate doses of alcohol leads to the increase of HDL-cholesterol (HDL-C). Atheroprotectivity of HDL particles is based primarily on their role in reverse cholesterol transport (RCT). In the study with a cross-over design 13 male volunteers were studied in two different regimens: i) drinking of 36 g alcohol daily and ii) drinking only non-alcoholic beverages, to test whether alcohol-induced increase of HDL cholesterol can affect cholesterol efflux (CHE) from cell culture of labeled human macrophages. Alcohol consumption induced significant (p < 0.05) increases of HDL cholesterol from 1.25 +/- 0.32 to 1.34 +/- 0.38 mmol/l and Apo A1 from 1.34 +/- 0.16 to 1.44 +/- 0.19 g/l. These changes were combined with a slight increase of cholesterol efflux from 13.8 +/- 2.15 to 14.9 +/- 1.85 % (p = 0.059). There were significant correlations between individual changes of HDL-C and Apo A1 concentrations and individual changes of CHE (0.51 and 0.60, respectively). In conclusion, moderate alcohol consumption changes the capacity of plasma to induce CHE only at a border line significance.

Proinflammatory status, genetics and atherosclerosis.

Over the last decade, C-reactive protein concentration analyzed by the high sensitivity method (hsCRP) has been proven as a marker of premature atherosclerosis. Concentration exceeding 2 mg/l represents an increased individual risk of myocardial infarction and stroke but strict application of this borderline is complicated by relations of CRP concentrations to other risk factors of cardiovascular diseases. In a large 1 % representative sample of the Czech population, a positive relation of hsCRP to BMI, a waist circumference and triglyceride concentration was documented. Substantial sex differences were found in its relationship to age. Whereas it is continuously increasing in men, this increase appears in women only after menopause. A substantial decrease of body weight and visceral fat volume by increased physical activity is accompanied by significant decrease of hsCRP in young obese women. This decrease was not related to a change of interleukin-6 concentration, although it is supposed to regulate CRP production. CRP concentration is partly under genetic control as a higher concentration in young siblings of probands with proved coronary atherosclerosis was documented. The participation of genes related to lipoprotein metabolism (genes for apolipoprotein CI and apolipoprotein E) influence hsCRP concentrations. We hypothesized that an increased concentration of hsCRP represents a certain marker of proinflammatory status related to central obesity and triglyceride metabolism and it might be related to individual properties of monocytes in atherogenesis.

Replacement of dietary saturated FAs by PUFAs in diet and reverse cholesterol transport.

Dietary intervention is the first and usually successful approach in the treatment of high LDL cholesterol (LDL-C) concentration, but it is frequently accompanied by a decrease in HDL concentration. We studied 14 male volunteers on two different diets, high saturated fatty acid (SFA) and high PUFA, in a crossover design to test whether a decrease in HDL can affect reverse cholesterol transport from relabeled macrophages. A significant decrease of LDL-C (in mmol/l) after a PUFA diet compared with an SFA diet from 3.15 +/- 0.65 to 2.80 +/- 0.56 (P < 0.01) was accompanied by a significant decrease of HDL cholesterol (HDL-C) (in mmol/l) from 1.21 +/- 0.30 to 1.10 +/- 0.32 (P < 0.05). These changes did not affect cholesterol efflux (CHE) from macrophages (9.74 +/- 1.46% vs. 9.53 +/- 1.41%). There was no correlation between individual changes of HDL-C and changes of CHE. It is concluded that the decrease of HDL-C after successful dietary intervention of LDL-C is not accompanied by a decrease of CHE.

Apolipoprotein AV variants do not affect C-reactive protein levels in Caucasian males.

The important role of APOAV gene variants in determination of plasma triglyceride levels has been shown in many population studies. Recently, an influence of APOAV T-1131>C polymorphism on C-reactive protein (CRP) in young Korean males has been reported. We have therefore analyzed a putative association between T-1131>C, Ser19>Trp and Val153>Met APOAV variants (PCR and restriction analysis) and CRP concentrations in 1119 Caucasian males, aged between 28 and 67 years (49.2+/-10.8 years). The frequency of C allele carriers was lower in Caucasians than in Koreans (15.5% vs. 46.2%). CRP levels did not differ between T/T homozygotes (n=946, 1.61+/-2.05 mg/l) and carriers of the C allele (n=173, 1.67+/-1.95 mg/l). Thus, in contrast to Korean males, T-1131>C APOAV variant has no effect on plasma concentrations of CRP in a large group of Caucasian males. Other APOAV variants (Ser19>Trp and Val153>Met) did not also influence plasma concentrations of CRP. APOAV variants are unlikely to be an important genetic determinant of plasma CRP concentrations in Caucasian males.

[A new method to estimate glomerular filtration rate based on serum concentration of creatinine, urea and albumin (MDRD, Modification of Diet in Renal Disease)]. / Nová metoda stanovení glomerulární filtrace na podklade sérové koncentrace kreatininu, mocoviny a albuminu (MDRD).

The equation developed from the MDRD (Modification of Diet in Renal Disease) study provides more accurate estimate of GFR than other commonly used equations. The aim of this study was to compare prediction of GFR based on MDRD and Cockcrof-Gault (CG) method. The study was performed in 111 patients (mean age 42 +/- 5 years) with chronic renal impairment (Scr = 281 +/- 83 micromol/l). The mean of MDRD was 0.480 +/- 0.345 ml/s/1.73 m2 and that of CG 0.608 +/- 0.336 ml/s/1.73 m2. The difference is highly significant (p < 0.0001). The mean of CG/MDRD ratio was 1.24 +/- 0.17. This ratio was significantly higher (p < 0.01) in obese patients (1.59 +/- 0.14 vs 1.22 +/- 0.09). The CG/MDRD ratio did not show relation to Scr. The results are in keeping with the assumption that the difference between MDRD and CG method cannot be explained by increased tubular secretion of creatinine in residual nephrons. Obesity seems to be on of the factors responsible for the difference between CG and MDRD values.

[CD14 (C-159-->T) polymorphism and levels of C-reactive protein]. / CD14 (C-159-->T) polymorfizmus a hladina C-reaktivního proteinu.

BACKGROUND: High plasma levels of C-reactive protein (involved in unspecific host defence) have been described as independent risk factor of atherosclerosis. The possible association has been analysed between the CD14C-159-->T polymorphism and plasma level of CRP. METHODS AND RESULTS: With the PCR and subsequent restriction analysis we have evaluated C-159-->T polymorphism in the CD14 gene of 166 representatively selected male Caucasians with known plasma level of CRP. The CRP was measured immunologically. A significantly higher (p < 0.01) frequency of the CD14-159TT homozygotes between the individuals with the plasma level of CRP > 2.19 mg/l (31.9%, 15 out of 47) has been detected when compared to the group with plasma level of CRP lower than 2.18 mg/l (11.9%, 5 out of 42). CONCLUSIONS: CD14 C-159-->T polymorphism could be the first described genetic marker associated with plasma level of C-reactive protein.

[Plasma level of Lp(a) in patients with myocardial infarct is not controlled by the apolipoprotein E gene polymorphism]. / Plazmatická koncentrace Lp(a) u pacientu s infarktem myokardu není ovlivnena polymorfizmem genu pro apolipoprotein E.

BACKGROUND: We evaluated a two risk factors of atherosclerosis development, apolipoprotein E genotype and plasma level of Lp(a), and their association in Czech population. PATIENTS AND CONTROLS: Apo E and Lp(a) have been determined in the group of 109 men with premature myocardial infarction and compared with the population samples (301 men for apo E polymorphism and 112 men for Lp(a) evaluation). METHODS AND RESULTS: Apo E gene polymorphism was analysed by PCR with subsequent restriction analysis of the PCR product. Lp(a) concentration was measured enzymatically using the IMMUNO set. The frequency of alleles of apo E genotype in myocardial infarction patients did not significantly differ from that found in the control group. The distribution of the Lp(a) concentrations in MI patients was shifted to higher levels than in population sample (p < 0.0001). CONCLUSIONS: We have not found correlation between this two risk factors of myocardial infarction. High concentration of Lp(a) is on apo E polymorphism independent risk factor of development of myocardial infarction.

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.

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

[Development of smoking habits in the population of the Czech Republic from 1985 to 1997/98]. / Vývoj kuráckých zvyklostí obyvatelstva Ceské republiky v období 1985-1997/98.

BACKGROUND: Tobacco smoking belongs to high risk factors for the circulation diseases. Aim of the present study is to identify and describe smoking habits of the population in nine districts in Czech republic in years 1997/98 and in six of these districts to analyze smoking trends during the period of 1985-1997/98. METHODS AND RESULTS: Information on the smoking habits were collected in years 1985, 1988, and 1992 in six districts which took part in the international project WHO MONICA. In 1997/98 data collection was extended into three other districts. New randomly selected samples of 1% of the population were explored each time. 5293 males and 5610 females 25-64 years old were questioned during a controlled talk with a health-officer. In 1997/98 in nine districts the prevalence of actual smokers was 38%, that of former smokers was 24% and 38% of non-smokers. The group of females consisted of 27% of actual smokers, 10% of former smokers, and 63% of non-smokers. The average daily consumption was 16.4% (+/- 8.6) cigarettes per day in males and 11.3 (+/- 7.0) cigarettes per day in females. In 1985-1997/98 the smoking prevalence of males aged 25-64 years decreased in six districts from 49% to 37% (p < 0.001). No changes were detected in females of the same age group (28% in 1985, 26% in 1997/98). Decreasing tendency was observed in both males and females up to 45 years old, in males also in the age group 55-64 years. In females older than 45 years the smoking prevalence increased. Significant changes in the smoking prevalence were found when samples were analyzed according to the education level. In males with basic education and among skilled workers the smoking prevalence decreased in years 1985-1997 from 53% to 42% (p < 0.05), among males with secondary education smoking prevalence decreased from 45% to 33% (p < 0.01) and in graduates from 34% to 23% (p < 0.01). In females with basic education the smoking prevalence increased from 25% to 31% (p < 0.05), among females with secondary education it decreased from 34% to 21% (p < 0.001), in graduate females it decreased from 31% to 18% (p < 0.05). CONCLUSIONS: Present situation and 13 years long development of smoking habits differs in males and females. Higher prevalence was found in males as well as the daily consumption of cigarettes. Since 1985 the male smoking prevalence has decreased in age groups 25-64 years and in age and education level subgroups. Only partial decrease of the female smoking prevalence was observed in age group till 45 years and in subgroups with secondary education and graduates. Significant increase in the smoking prevalence among females with basic education as well as the finding that women do not quit smoking with increasing age my become an important information for preventive programmes.

[Longitudinal trends of total and HDL cholesterol in a representative population sample in the Czech Republic]. / Longitudinální trendy celkového a HDL-cholesterolu u reprezentativního vzorku populace Ceské republiky.

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).

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.