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.

Roma coronary heart disease patients have more medical risk factors and greater severity of coronary heart disease than non-Roma.

OBJECTIVES: Coronary heart disease (CHD) is the most common cause of mortality and morbidity world-wide. Evidence on ethnic differences between the Roma and non-Roma regarding medical risk factors is scarce. The aim of this study was to assess differences in medical risk factors and the severity of CHD in Roma compared with non-Roma CHD patients, adjusted for gender, age and education. METHODS: Six hundred seventy four patients were included in this cross-sectional study (132 Roma, 542 non-Roma). Data on medical risk factors, symptoms, medication and severity of CHD were obtained from medical records. After matching Roma and non-Roma according to education, linear and logistic regression analyses with adjustments for gender and age were used. RESULTS: Compared with non-Roma, Roma patients had significantly more risk factors and more severe types of CHD. They were treated less frequently with statins and beta-blockers, were more frequently left on pharmacotherapy and surgically revascularised. These differences remained after controlling for education, gender and age. CONCLUSIONS: Roma CHD patients have a worse risk profile at entry of care and seem to be undertreated compared with non-Roma CHD patients.

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.

Variants within the ghrelin gene--association with HDL-cholesterol, but not with body mass index.

Ghrelin is a hormone which influences eating habits, the amount of food ingested and the body's energy balance. We examined whether genetic variants in the ghrelin gene are associated with BMI, WHR and plasma lipid levels. We have evaluated the influence of ghrelin polymorphisms (Arg51>Gln, Leu72>Met and Gln90>Leu) on BMI, WHR, and plasma lipid levels in 1,191 males and 1,368 females representatively selected from the Czech population. Anthropometrical and biochemical parameters were analysed in two different years. In the entire population, we have detected 4.8% of carriers of the Gln51 allele, 14.2% carriers of the Met72 allele, and 10.9% of the Leu90 allele. Frequencies did not differ between males and females and alleles were not in linkage disequilibrium. BMI or WHR were not influenced by variants in the ghrelin gene. The ghrelin variant Leu72>Met was associated with elevated levels of plasma HDL-cholesterol. Compared to Leu/ Leu homozygotes, the Met carriers had lower HDL-cholesterol concentrations in males (1.18 +/- 0.29 mmol/l vs. 1.24 +/- 0.35 mmol/l, P = 0.01) as well as in females (1.45 +/- 0.35 mmol/l vs. 1.51 +/- 0.38 mmol/l, P = 0.01). The other lipid parameters (total cholesterol and triglycerides) were not associated with this variant. There were no associations between other ghrelin variants (Arg51>Gln and Gln90>Leu) and analysed biochemical parameters. We conclude that in the Caucasian population, variations in the ghrelin gene could play a role in genetic determination of plasma levels of HDL-cholesterol, but they have no effect on BMI or WHR.

APOA5 variant Ser19Trp influences a decrease of the total cholesterol in a male 8 year cohort.

OBJECTIVES: To evaluate whether the relationship between dietary composition and plasma lipid levels is genetically determined. DESIGN AND METHODS: We have evaluated the influence of common apolipoprotein A5 (APOA5) variants (T-1131 > C, Ser19 > Trp and Val153 > Met) on plasma lipid concentrations in 117 males for whom dietary composition markedly changed and total cholesterol decreased (from 6.21 +/- 1.31 mmol/L in 1988 to 5.43 +/- 1.06 mmol/L in 1996) over an 8 year follow-up study. RESULTS: APOA5 T-1131 > C and Val153 > Met variants did not influence the change in lipid measures over time. In Ser/Ser19 homozygotes, the plasma cholesterol was relatively stable over the years (6.1 +/- 1.2 mmol/L in 1988 and 5.6 +/- 1.0 mmol/L in 1996, -8%, P < 0.01). In contrast, in the Trp19 carriers, the decrease of the plasma cholesterol was more than 20% (6.5 +/- 1.6 mmol/L in 1988 and 5.1 +/- 1.0 mmol/L in 1996) (P < 0.001). The difference of the changes is significant (8% vs. 20%, P < 0.005). Changes in other analyzed lipid parameters have not been significantly associated with APOA5 variants. CONCLUSIONS: Ser19 > Trp variant in the APOA5 gene may play an important role in an individual's sensitivity to dietary composition.

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.

Rare variant of apolipoprotein E (Arg136 -->Ser) in two normolipidemic individuals.

Through the analysis of the common apolipoprotein (apo) E gene polymorphism in large Caucasian population study with the PCR and subsequent restriction analysis, we have identified carriers of mutant allele Arg136-->Ser. Both of them (71-years-old female and her 43-years-old son) have normal lipid parameters. We suggest that Arg136-->Ser mutation in apoE is not necessarily connected with elevated lipid levels in all cases. Furthermore, so far unidentified factors (environmental and/or genetic) are important for the development of lipid metabolism disorders in apoE Arg136-->Ser mutation carriers.

No relation between angiotensin-converting enzyme gene polymorphism and smoking dependence.

BACKGROUND: Smoking as a major risk factor for development of cancer and cardiovascular disease is thought to be partially genetically determined. The aim of this study was to investigate whether there is an association between insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme (ACE) and smoking status and the number of cigarettes smoked per week. METHODS: Using polymerase chain reaction, I/D polymorphism was evaluated in the ACE gene in 1204 male and 1375 female representative Caucasians. Information about smoking status and number of cigarettes smoked per week was collected via a questionnaire. RESULTS: Frequencies of the alleles and genotypes of ACE I/D polymorphism did not differ between smokers, past smokers and individuals who had never smoked. No association was found between ACE I/D polymorphism and the number of cigarettes smoked per week, either in males or in females. CONCLUSION: I/D polymorphism in the ACE gene does not play any role in genetic determination of predisposition to smoking.

Polymorphisms in ABCG5 and ABCG8 transporters and plasma cholesterol levels.

ABCG5 and ABCG8 transporters play an important role in the absorption and excretion of sterols. Missence polymorphisms (Gln604Glu in the ABCG5 and Asp19His, Tyr54Cys, Thr400Lys, and Ala632Val in the ABCG8) in these genes have been described. In 131 males and 154 females whose dietary composition markedly changed and lipid parameters decreased over an 8-year follow-up study (total cholesterol decreased from 6.21+/-1.31 mmol/l in 1988 to 5.43+/-1.06 mmol/l in 1996), these polymorphisms were investigated using PCR. Plasma lipid levels and changes in plasma lipid levels were independent of the Gln604Glu polymorphism in ABCG5 and Asp19His and the Ala632Val polymorphisms in ABCG8. The Tyr54Cys polymorphism influenced the degree of reduction in total plasma cholesterol (delta -0.49 mmol/l in Tyr54 homozygotes vs. delta +0.12 mmol/l in Cys54 homozygotes, p<0.04) and LDL-cholesterol (delta -0.57 mmol/l in Tyr54 homozygotes vs. delta +0.04 mmol/l in Cys54 homozygotes, p<0.03) levels between 1988 and 1996 in females, but not in males. Male Thr400 homozygotes exhibited a greater decrease in total cholesterol (delta -0.90 mmol/l vs. delta -0.30 mmol/l, p<0.02) and LDL-cholesterol (delta -0.62 mmol/l vs. delta -0.19 mmol/l, p<0.04) than Lys400 carriers. No such association was observed in females. We conclude that Tyr54Cys and Thr400Lys variations in the ABCG8 gene may play a role in the genetic determination of plasma cholesterol levels and could possibly influence the gender-specific response of plasma cholesterol levels after dietary changes. These polymorphisms are of potential interest as genetic variants that may influence the lipid profile.

[Longitudinal trends in major cardiovascular disease risk factors in the Czech population]. / Dlouhodobé trendy hlavních rizikových faktoru kardiovaskulárních onemocnení v ceské populaci.

BACKGROUND: Cardiovascular disease (CVD) is the main cause of death in the Czech Republic. The decline in CVD mortality observed in our country since 1985 may be due to a decrease in its incidence or case fatality. Case fatality is mostly related to the standard of health care whereas the incidence of CVD is associated with the risk profile of the population. The aim of this study is to monitor longitudinal trends in major CVD risk factors in the Czech population. Assessment of longitudinal trends in the population risk profile may help in analyzing the trends in CVD morbidity and mortality. METHODS AND RESULTS: In the years 1985, 1988, 1992, 1997/98 and 2000/01, five independent cross-sectional surveys of CVD risk factors were conducted in a 1% population random sample, aged 25-64 years, selected from six districts of the Czech Republic (with a total of 5,736 males and 6,027 females examined). Over the study period of 15/16 years, there is a significant increase in BMI in males (from 27.0 +/- 4.0 to 28.1 +/- 4.4 kg/m2, p < 0.001) while the changes in BMI in females are of borderline significance. The proportion of male smokers is decreasing (from 49.2% to 37.8%, p < 0.001) whereas there is no change in the prevalence of smoking in the female population. Mean systolic and diastolic blood pressure as well as the prevalence of hypertension are decreasing in both sexes since 1985 (from 51.9% to 45.6% in males, p < 0.001; from 42.5% to 33.0% in females, p < 0.001). There is an increase in awareness of hypertension (from 41.4% to 62.1% in males, p < 0.001; from 58.9% to 73.8% in females, p < 0.001). The proportion of individuals treated by antihypertensive drugs is increasing (from 21.1% to 41.8%, p < 0.001 in males; from 38.9% to 59.1% in females, p < 0.001). Hypertension control has improved in either sex (males: from 2.8% to 13.1%, p < 0.001; females: from 5.2% to 22.2%, p < 0.001). Over the study period, there is a clear significant downward trend in total cholesterol levels in both sexes (males: from 6.21 +/- 1.29 to 5.88 +/- 1.08 mmol/l, p < 0.001; females: from 6.18 +/- 1.26 to 5.82 +/- 1.13 mmol/l, p < 0.001). CONCLUSIONS: In a representative Czech population sample, a favorable trend in most major CVD risk factors was observed in the 1985-2000/01 period. This plays most likely a role in the decrease in CVD mortality.

[Antagonistic effect of the insertion/deletion (HpaI) polymorphism in the regulatory part of the gene for apolipoprotein CI in children with high and low levels of cholesterol]. / Protichudný efekt inzercního/delecního (HpaI) polymorfizmu v regulacní cásti genu pro apolipoprotein CI u detí s vysokou a nízkou hladinou cholesterolu.

BACKGROUND: High plasma lipids are one of the risk factor of atherosclerosis. Both environmental (diet, physic activity) and genetic factors have been implicated in the development of hyperlipidaemia. Apolipoprotein (apo) CI plays an important role in plasma cholesterol and triglycerides transport by VLDL particles. The aim of the study was to establish the role of the insertion/deletion polymorphism in apoCI gene in the determination of plasma lipids in children. METHODS AND RESULTS: Using PCR and restriction analysis (HpaI) we have measured I/D polymorphism in APOCI gene in two groups of children selected from opposite ends of the cholesterol distribution curve of 2000 children. Eighty-two children in high-(HCG) and eighty-six children in low-(LCG) cholesterolemic groups participated on the study. No significant difference was found in the frequencies of the APOCI genotypes or alleles between HCG vs. LCG. Association between LDL cholesterol and genotypes within the LCG was found--the D/D homozygotes have higher lipid level compared to the others (p < 0.05). In LCG opposite, but insignificant (p = 0.09) trend was observed. CONCLUSIONS: The widespread I/D polymorphism in the gene for APOCI determines the plasma lipid levels in childhood and it could become another important genetic marker that plays a role in the genetic determination of cholesterolemia.

Prevalence, awareness, treatment, and control of hypertension in the Czech Republic. Results of two nationwide cross-sectional surveys in 1997/1998 and 2000/2001, Czech Post-MONICA Study.

Hypertension is an easily diagnosed and eminently modifiable risk factor for the development of all clinical manifestations of atherosclerosis. Despite the availability of a simple, non-invasive, and rather accurate method of measuring blood pressure (BP), and overwhelming evidence that reducing BP effectively prevents cardiovascular events, hypertension at the population level is not managed optimally. In 1997/1998 and 2000/2001, two surveys for cardiovascular risk factors were conducted in nine districts of the Czech Republic, involving a 1% population random sample aged 25-64 years in each district. In concordance with the MONICA Project, the present study confirms a high prevalence of hypertension in the Czech population, detecting an increase in prevalence for the male population over a period of 3 years (males from 38.8 in 1997/1998 to 42.3 in 2000/2001; P<0.05). Within the same period, there is also a significant increase in the awareness of hypertension in males (from 57.3 in 1997/1998 to 60.0 in 2000/2001; P<0.05), and an increase in the number of male hypertensives being treated by antihypertensive drugs (from 30.9 to 44.3; P<0.05). Control of hypertension did not change in either sex, being still suboptimal (males 16.4%, females 25.4% in the last survey in 2000/2001).

The influence of APOAV polymorphisms (T-1131>C and S19>W) on plasma triglyceride levels and risk of myocardial infarction.

The importance of an APOAV gene for plasma triglyceride level determination has been shown on transgenic and knockout mice. We examined whether APOAV variants are associated with plasma triglyceride levels and risk of myocardial infarction (MI). We have evaluated the influence of APOAV polymorphisms (T-1131>C and S19>W) on plasma triglycerides in 1191 males and 1368 females representatively selected from the Czech population. Triglycerides have been analysed in 1997 and 2001. Subsequently, we have analysed the genotype frequencies of the APOAV polymorphism in 435 patients with MI. T-1131>C variation in the APOAV gene affects the plasma triglyceride showing a higher level in C-1131 carriers than in T/T-1131 homozygotes. This association has been observed both in males and females (p < 0.001). Similarly, plasma triglycerides were also significantly influenced by the S19>W APOAV genotypes. In both males and females, the W19 carriers have triglycerides significantly (p < 0.001) higher compared to the S19 homozygotes. In a group of MI patients, the frequency of the rare homozygotes for at least one APOAV polymorphism (C/C-1131 and/or W/W19) was significantly higher than that in the population sample (7.4 vs 2.0%, p < 0.00001). We conclude that variations in the APOAV gene not only play a role in genetic determination of triglyceride levels but also could influence risk of MI.

[Polymorphism in the regulatory part of the cholesterol 7 alpha hydroxylase gene in children with high and low levels of cholesterol]. / Polymorfizmus v regulacní cásti genu pro cholesterol 7 alpha hydroxylázu u detí s vysokou a nízkou hladinou cholesterolu.

BACKGROUND: High plasma cholesterol is one of the risk factors of atherosclerosis. Both environmental (diet, physic activity) and genetic factors have been concerned in the development of hypercholesterolemia. Cholesterol 7 alpha hydroxylase (CYP-7A1) is a key enzyme in the bile acid synthesis and it plays an important role in cholesterol catabolism. The aim of the study was to establish the role of A-204-->C polymorphism in CYP-7A1 gene in plasma lipid determination in children. METHODS AND RESULTS: Using PCR and restriction analysis (BsaI) we have measured A-204-->C polymorphism in CYP-7A1 gene in two groups of children selected from opposite ends of the cholesterol distribution curve of 2000 children. Eighty-two children in high- (HCG) and eighty-six children in low- (LCG) cholesterolemic groups participated in the study. No significant difference was found in the frequencies of the genotypes or alleles of the A-204-->C polymorphism in the CYP-7A1 gene between HCG and LCG. In HCG, C/C-204 homozygotes have the highest and A/A homozygotes the lowest levels of LDL-cholesterol (4.21 +/- 0.68 mmol/l vers. 3.69 +/- 0.60 mmol/l, p < 0.05). No associations between lipid parameters and genotypes within the LCG group were found. CONCLUSIONS: The A-204-->C polymorphism in the gene for CYP-7A1 is not the major determinant of plasma lipid levels in childhood. Its impact is expressed only on high cholesterol background.

Beer and obesity: a cross-sectional study.

OBJECTIVE: There is a common notion that beer drinkers are, on average, more 'obese' than either nondrinkers or drinkers of wine or spirits. This is reflected, for example, by the expression 'beer belly'. However, the few studies on the association between consumption of beer and abdominal obesity produced inconsistent results. We examined the relation between beer intake and waist-hip ratio (WHR) and body mass index (BMI) in a beer-drinking population. DESIGN: A cross-sectional study. SETTINGS: General population of six districts of the Czech Republic. SUBJECTS: A random sample of 1141 men and 1212 women aged 25-64 y (response rate 76%) completed a questionnaire and underwent a short examination in a clinic. Intake of beer, wine and spirits during a typical week, frequency of drinking, and a number of other factors were measured by a questionnaire. The present analyses are based on 891 men and 1098 women who where either nondrinkers or 'exclusive' beer drinkers (ie they did not drink any wine or spirits in a typical week). RESULTS: The mean weekly beer intake was 3.1 l in men and 0.3 l in women. In men, beer intake was positively related to WHR in age-adjusted analyses, but the association was attenuated and became nonsignificant after controlling for other risk factors. There appeared to be an interaction with smoking: the relation between beer intake and WHR was seen only among nonsmokers. Beer intake was not related to BMI in men. In women, beer intake was not related to WHR, but there was a weak inverse association with BMI. CONCLUSION: It is unlikely that beer intake is associated with a largely increased WHR or BMI.

[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.

Apolipoprotein E and apolipoprotein CI polymorphisms in the Czech population: almost complete linkage disequilibrium of the less frequent alleles of both polymorphisms.

Apolipoproteins E and CI are the predominant components of triglyceride-rich lipoproteins. The genes are located in one gene cluster and both are polymorphic. Three allelic (epsilon2, epsilon3 and epsilon4) polymorphisms of the APOE gene influence plasma cholesterol levels. The distribution of these alleles differ between ethnic groups. PCR genotyping was used to determine the APOE and APOCI allele incidence in a representative group of 653 probands (302 men and 351 women) of Czech origin. The observed relative frequencies for the epsilon2, epsilon3 and epsilon4 alleles were 7.1 %, 82.0 % and 10.9 %, respectively, and are similar to other middle European populations. APO epsilon4 carriers have the highest and APO epsilon2 carriers the lowest levels of plasma total cholesterol (p<0.0001) and LDL cholesterol (p<0.0001). The frequency of the insertion (I) allele (HpaI restriction site present) of the APOCI polymorphism was 18.5 %. APOCI I/I homozygotes have the highest level of triglycerides (p<0.003). An almost complete linkage disequilibrium of the insertion allele of APOCI with the APOE alleles epsilon2 and epsilon4 has been detected and suggests that the deletion in the APOCI gene probably follows the deriving of all three APOE alleles on the APO epsilon3 allele background.

Rare variant of apolipoprotein E (Arg136-->Cys) in a subject with normal lipid values.

During the screening of apolipoprotein (apo) E gene polymorphism with PCR and subsequent restriction analysis, we have identified a female carrier with a mutant allele Arg136-->Cys. This proband had normal lipid parameters and no history of coronary artery disease (CAD). We did not confirm the previously described connection between apo E Arg136-->Cys mutation and elevated lipid levels. In the case of this mutation, other factors (environmental and/or genetic) are important for the development of lipid metabolism disorders.