Does inclusion of education and marital status improve SCORE performance in central and eastern europe and former soviet union? findings from MONICA and HAPIEE cohorts.

BACKGROUND AND OBJECTIVE: The SCORE scale predicts the 10-year risk of fatal atherosclerotic cardiovascular disease (CVD), based on conventional risk factors. The high-risk version of SCORE is recommended for Central and Eastern Europe and former Soviet Union (CEE/FSU), due to high CVD mortality rates in these countries. Given the pronounced social gradient in cardiovascular mortality in the region, it is important to consider social factors in the CVD risk prediction. We investigated whether adding education and marital status to SCORE benefits its prognostic performance in two sets of population-based CEE/FSU cohorts. METHODS: The WHO MONICA (MONItoring of trends and determinants in CArdiovascular disease) cohorts from the Czech Republic, Poland (Warsaw and Tarnobrzeg), Lithuania (Kaunas), and Russia (Novosibirsk) were followed from the mid-1980s (577 atherosclerotic CVD deaths among 14,969 participants with non-missing data). The HAPIEE (Health, Alcohol, and Psychosocial factors In Eastern Europe) study follows Czech, Polish (Krakow), and Russian (Novosibirsk) cohorts from 2002-05 (395 atherosclerotic CVD deaths in 19,900 individuals with non-missing data). RESULTS: In MONICA and HAPIEE, the high-risk SCORE ≥5% at baseline strongly and significantly predicted fatal CVD both before and after adjustment for education and marital status. After controlling for SCORE, lower education and non-married status were significantly associated with CVD mortality in some samples. SCORE extension by these additional risk factors only slightly improved indices of calibration and discrimination (integrated discrimination improvement <5% in men and ≤1% in women). CONCLUSION: Extending SCORE by education and marital status failed to substantially improve its prognostic performance in population-based CEE/FSU cohorts.

SCORE performance in Central and Eastern Europe and former Soviet Union: MONICA and HAPIEE results.

AIMS: The Systematic COronary Risk Evaluation (SCORE) scale assesses 10 year risk of fatal atherosclerotic cardiovascular disease (CVD), based on conventional risk factors. The high-risk SCORE version is recommended for Central and Eastern Europe and former Soviet Union (CEE/FSU), but its performance has never been systematically assessed in the region. We evaluated SCORE performance in two sets of population-based CEE/FSU cohorts. METHODS AND RESULTS: The cohorts based on the World Health Organization MONitoring of trends and determinants in CArdiovascular disease (MONICA) surveys in the Czech Republic, Poland (Warsaw and Tarnobrzeg), Lithuania (Kaunas), and Russia (Novosibirsk) were followed from the mid-1980s. The Health, Alcohol, and Psychosocial factors in Eastern Europe (HAPIEE) study follows Czech, Polish (Krakow), and Russian (Novosibirsk) cohorts from 2002-05. In Cox regression analyses, the high-risk SCORE ≥5% at baseline significantly predicted CVD mortality in both MONICA [n = 15 027; hazard ratios (HR), 1.7-6.3] and HAPIEE (n = 20 517; HR, 2.6-10.5) samples. While SCORE calibration was good in most MONICA samples (predicted and observed mortality were close), the risk was underestimated in Russia. In HAPIEE, the high-risk SCORE overpredicted the estimated 10 year mortality for Czech and Polish samples and adequately predicted it for Russia. SCORE discrimination was satisfactory in both MONICA and HAPIEE. CONCLUSION: The high-risk SCORE underestimated the fatal CVD risk in Russian MONICA but performed well in most MONICA samples and Russian HAPIEE. This SCORE version might overestimate the risk in contemporary Czech and Polish populations.

Number of children is associated with plasma CRP levels.

BACKGROUND: C-reactive protein (CRP) is an acute-phase serum protein produced by the liver. High plasma levels of CRP have been associated primarily with infection, but elevated CRP levels have also been found to be associated with more than one hundred conditions and factors, including social and economic factors. MATERIALS AND METHODS: To evaluate the possible association between individuals' number of children and plasma levels of C-reactive protein, we studied a representative population of 2,426 adults. CRP was analyzed using the high sensitivity method (hsCRP). Individuals were divided into five groups of zero, one, two, three and four and more children. RESULTS: We found that individuals with more children had significantly higher levels of plasma hsCRP than individuals without children or than individuals with a low number of children (p for trend <0.001). This association could reflect the known associations between CRP and higher economic stress, exhaustion, episodic stress and chronic stress. CONCLUSIONS: We found significantly elevated levels of plasma CRP in individuals with more children than in individuals without children or with a low number of children.

APOA5 Ala315>Val, identified in patients with severe hypertriglyceridemia, is a common mutation with no major effects on plasma lipid levels.

BACKGROUND: The importance of the apolipoprotein A5 (APOA5) gene in determining plasma triglyceride (TG) levels has been demonstrated in transgenic and knockout mice and confirmed by human association studies in different ethnic groups. METHODS: We screened for nonsynonymous APOA5 mutations in patients with plasma TG levels >10 mmol/L. The coding sequence and promoter region of the APOA5 gene were sequenced in 95 individuals with severe hypertriglyceridemia (HTG). A large population sample of 3,202 individuals was screened by PCR and restriction analysis for presence of detected mutation. RESULTS: In total, three heterozygous carriers of 944C>T (Ala315>Val) were identified in the severe HTG patients, while 22 carriers were identified in the population sample. The rare allele frequency of the Val315 was significantly higher in the HTG sample than in controls (0.016 vs. 0.003, p<0.01, respectively). Most of the control Ala315Val carriers, however, had plasma lipid levels (TGs, total cholesterol and high-density lipoprotein cholesterol) within the usual range detected in the population. CONCLUSIONS: APOA5 Ala315>Val does not play any dominant/important role in the genetic determination of plasma TG levels, but the increased frequency in HTG patients compared to controls suggests that it might interact with other gene variants to cause HTG.

Apolipoprotein A-V variant (T-1131>C) affects plasma levels of non-high-density lipoprotein cholesterol in Caucasians.

BACKGROUND: The importance of apolipoprotein A-V (APOAV) gene variants in the determination of plasma triglyceride levels in humans has been proven in several population studies. OBJECTIVES: To investigate whether APOAV gene variants are associated with the different plasma cholesterol fractions. METHODS: The influence of APOAV polymorphisms (T-1131>C, Ser19>Trp and Val153>Met) on plasma cholesterol fractions was evaluated in 1191 men and 1368 women representatively selected from the Czech population. Low-density lipoprotein cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and HDL cholesterol levels were analyzed. RESULTS: The T-1131>C variation in the APOAV gene was found to affect plasma non-HDL cholesterol, showing significantly higher levels in C-1131 carriers than in T/T-1131 homozygotes. This association was observed in both men (4.61+/-1.09 mmol/L in C-1131 carriers versus 4.47+/-1.07 mmol/L in T/T-1131 homozygotes; P<0.01) and women (4.46+/-1.22 mmol/L in C-1131 carriers versus 4.24+/-1.17 mmol/L in T/T-1131 homozygotes; P<0.01). Interestingly, when low-density lipoprotein cholesterol (obtained by the Friedewald formula) or HDL cholesterol levels were analyzed, no significant association was detected. CONCLUSION: The APOAV gene variant T-1131>C may play a role not just in the genetic determination of triglyceride levels but may also influence plasma levels of non-HDL cholesterol.

Sex-specific interaction between APOE and APOA5 variants and determination of plasma lipid levels.

The APOA5 and APOE genes play an important role in determination of plasma levels of triglycerides (TG) and total cholesterol (TC). We have analyzed APOA5 (T-1131>C and Ser19>Trp) and APOE (e2/e3/e4) variants in 2500 representatively selected Caucasians (1168 men, 1332 women). In female subjects (but not in male) an association between APOE polymorphism and TC was observed on the background of the common APOA5 haplotype (TT-1131/SerSer19) - APOE2 carriers have the lowest (5.12 (1.15) mmol/l) and the APOE4 carriers have the highest (6.05 (1.06) mmol/l) levels of plasma TC (P<0.001). If at least one APOA5 C-1131 or Trp19 allele was present, APOE exhibits no significant effect on plasma TC. APOA5 did not affect plasma TG levels, if APOE4 allele was present. In the presence of APOE2 or APOE3, carriers of the APOA5 alleles, C-1131 and/or Trp19, have higher TG levels (1.64 (1.05) mmol/l) than others (1.37 (0.75) mmol/l) (P<0.01). In male subjects, the same, but non-significant trend was observed. In female subjects, we have detected an interaction between APOE and APOA5 variants and plasma lipid levels.

Polymorphisms in the APOA1/C3/A4/A5 gene cluster and cholesterol responsiveness to dietary change.

BACKGROUND: The relationship between dietary composition and plasma lipids is to some extent genetically determined. It has been found that variants of some genes (e.g., apolipoprotein E and cholesterol 7-alpha hydroxylase) play an important role in changes in plasma lipid levels in response to dietary intervention. We analyzed the effect of variation in the apolipoprotein (APO) APOA1/C3/A4/A5 gene cluster on decreases in plasma cholesterol levels over an 8-year follow-up study. METHODS: Men (n=133) from the Czech population, for which dietary composition has markedly changed (red meat 80-->68 kg/person/year, animal fat 16-->9 kg/person/year, fruits and vegetables 133-->150 kg/person/year) were recruited. APOA1 (G-75>A and C83>T), APOC3 (C-482>T and C3238>G), APOA4 (Thr347>Ser and Gln360His) and APOA5 (T-1131>C, Ser19>Trp and Val153>Met) variants were analyzed by PCR and restriction analysis. Lipid levels were analyzed in 1988 and 1996. Dietary information was obtained from the Institute of Agricultural Economy. RESULTS: In APOA5 Ser19Ser homozygotes (n=105), plasma cholesterol was relatively stable over the years (6.1+/-1.3 and 5.6+/-1.0 mmol/L in 1988 and 1996), but the decrease was much higher in Trp19 carriers (n=27; 6.5+/-1.6 vs. 5.1+/-1.1 mmol/L). This difference in change is significant at p<0.005. Similarly, a better response to dietary changes was detected in carriers of the common APOA4 haplotypes Thr-347Thr/Gln360Gln and Thr347Ser/Gln360Gln (n=102; 6.3+/-1.3 and 5.5+/-1.1 mmol/L in 1988 and 1996, p<0.001). Total cholesterol was relatively stable over time in carriers (n=18) of at least one His360 allele and/or two Ser347 alleles (5.7+/-1.1 and 5.5+/-0.9 mmol/L in 1988 and 1996, n.s.). Other variants analyzed did not influence the change in lipid measurements over time. CONCLUSIONS: APOA4 and APOA5 variants may play an important role in the individual sensitivity of lipid parameters to dietary composition in men.

Genetic polymorphisms of TGF-beta, PAI-1, and COL1A-1, and determination of bone mineral density in Caucasian females.

OBJECTIVE: The aim of this study was to examine whether the variants in genes for transforming growth factor beta1 (TGF-beta1; Leu10>Pro and Arg25>Pro), plasminogen activator inhibitor 1 (PAI-1; 4G>5G variant) and collagen -1 (COL1A-1; Sp1 variant) may be useful in identifying individuals with increased susceptibility to early postmenopausal bone loss within the population of Czech women. METHODS: Polymorphisms were genotyped (by PCR and restriction analysis) in 1400 females representatively selected from the Czech population as well as in 218 postmenopausal osteoporotic women 40-70 years of age (mean age 58.7 years) and a 151 control group of postmenopausal females in the same age range (mean age 59.1 years) with normal BMD. RESULTS: We have not found any statistically significant differences in the frequency of the individual genotypes or alleles of analyzed variants between the groups of osteoporotic patients (OP), population group (PG) and control group (CG). The frequencies of the individual genotypes in the analyzed groups were as follows - 1) TGF-beta1 gene: Leu10Leu10 OP - 30.2%, PG - 35.6%, CG 35.1%; Leu10Pro10 OP - 52.1%, PG - 47.1%, CG 50.0%; Pro10Pro10 OP - 17.7%, PG - 17.3%, CG 14.9%; 2) TGF-beta1 gene Arg25 homozygotes OP - 83.8%, PG - 86.1%, CG - 89.3%, Pro25 carriers OP - 16.2%, PG - 13.9%, CG - 10.7%, 3) PAI-1 gene: 4G4G OP - 34.9%, PG - 31.8, CG - 28.5%, 5G4G OP - 43.6%, PG - 46.7%, CG - 50.3%, 5G5G OP - 21.5%, PG - 21.5%, CG - 21.2%, and 4) COL1A-1 ("SS" homozygotes, OP - 63.0%, PG - 63.7%, - CG 64.9%, "s" carriers OP - 37.0%, PG - 36.3%, CG - 35.1%). CONCLUSIONS: Variants in genes for TGF-beta1 (Leu10>Pro and Arg25>Pro), PAI-1 (4G>5G) and COL1A-1 (Sp1 variant) are not associated with low BMD in postmenopausal Czech Caucasian females.

No associations between genetic polymorphisms of TGF-beta, PAI-1, and COL1A1, and bone mineral density in Caucasian females.

OBJECTIVE: The aim of this study was to examine whether variants in genes for transforming growth factor beta1 (TGF-beta1; Leu10>Pro and Arg25>Pro), plasminogen activator inhibitor 1 (PAI-1; 4G>5G variant) and collagen 1 (COL1A1; Sp1 variant) may be useful in identifying individuals with increased susceptibility to early postmenopausal bone loss within the population of Czech women. METHODS: Polymorphisms were genotyped (by PCR and restriction analysis) in 1400 females representatively selected from the Czech population as well as in 218 postmenopausal osteoporotic women 40-70 years of age (mean age 58,7 years) and a 151 postmenopausal females within the same age range (mean age 59,1 years) with normal BMD. RESULTS: We have not found any statistically significant differences in the frequency of individual genotypes or alleles of analyzed variants between the groups of osteoporotic patients (OP), population group (PG) and control group (CG). The frequency of the individual genotypes in the analyzed groups was as follows 1) TGF-beta1 gene: Leu10Leu10 OP 30.2 %, PG 35.6 %, CG 35.1 %; Leu10Pro10 OP 52.1 %, PG 47.1 %, CG 50.0 %; Pro10Pro10 OP 17.7 %, PG 17.3 %, CG 14.9 %; 2) TGF-beta1 gene Arg25 homozygotes OP 83.8 %, PG 86.1%, CG 89.3 %, Pro25 carriers OP 16.2 %, PG 13.9 %, CG 10.7 %, 3) PAI-1 gene: 4G4G OP 34.9 %, PG 31.8, CG 28.5 %, 5G4G OP 43.6 %, PG 46.7 %, CG 50.3 %, 5G5G OP 21.5 %, PG 21.5%, CG 21.2%, and 4) COL1A-1 ("SS" homozygotes, OP 63.0%, PG 63.7%, CG 64.6 %, "s" carriers OP 37.0 %, PG 36.3 %, CG 35.1 %). CONCLUSIONS: Variants in genes for TGF-beta1 (Leu10>Pro and Arg25>Pro), PAI-1 (4G>5G) and COL1A1 (Sp1 variant) are not associated with low BMD in postmenopausal Czech Caucasian females.

Sex-specific effect of APOAV variant (Val153>Met) on plasma levels of high-density lipoprotein cholesterol.

The importance of the APOAV gene for the determination of plasma triglyceride levels has been suggested by creations of transgenic and knockout mice and confirmed in population studies. We examined whether the newly detected APOAV variant is associated with plasma lipid levels and risk of myocardial infarction (MI). APOAV polymorphism (Val153>Met) was genotyped in 1191 males and 1368 females representatively selected from the Czech population. Lipid levels were analyzed in 1997 and 2001 in all individuals. Subsequently, we have analyzed the genotype frequencies of APOAV polymorphism in 435 male patients with MI. Val153>Met variation in the APOAV gene affects the plasma high-density lipoprotein cholesterol levels showing a higher level in Val/Val homozygotes than in Met carriers in both years (1.51 +/- 0.36 and 1.52 +/- 0.37 mmol/L compared with 1.42 +/- 0.33 and 1.39 +/- 0.35 mmol/L, P < .01). This association has been observed in females but not in males. Other analyzed lipid parameters (total cholesterol, low-density lipoprotein cholesterol, and triglycerides) have not been associated with APOAV Val153>Met variant. In a group of patients with MI, the frequency of the Met153 carriers was not significantly different from the male population sample (6.5% vs 6.4%). Val153>Met variation in the APOAV gene plays a sex-specific role in genetic determination of plasma high-density lipoprotein cholesterol levels, but does not influence risk of MI in males.

Genetic analysis of APOAV polymorphisms (T-1131/C, Ser19/Trp and Val153/Met): no effect on plasma remnant particles concentrations.

BACKGROUND: APOAV is newly described protein, which plays a crucial role in the determination of plasma triglyceride (TG) levels. Remnant lipoproteins (RLPs) result from partial catabolised TG-rich particles. Elevated levels of RLP are associated with atherosclerosis, and they are a predictor of coronary events in patients with coronary artery disease. METHODS: We have evaluated the influence of APOAV polymorphisms (T-1131/C, Ser19/Trp and Val153/Met were measured by PCR and restriction analysis) on plasma levels of RLP-cholesterol and RLP-TG in 285 unrelated representative selected individuals (131 men and 154 women) aged 33-72 years. RESULTS: RLP-cholesterol and RLP-TG levels were not significantly influenced by the APOAV variants either in whole population or in males and females, if analyzed separately. CONCLUSIONS: We conclude that variations T-1131/C, Ser19/Trp and Val153/Met in the APOAV gene have no effect on plasma levels of remnant particles.

APOAV (T-1131>C) variant has no effect on mother's height in a large population study.

The important role of APOAV gene T-1131>C variant in determination of plasma triglyceride levels has been proved on many population studies. Recently, associations between C-1131 allele and higher mother's height as well as with longer fetal birth length were suggested. In 1,305 females, aged between 28 and 67 years and having at least one child, we have analyzed a putative association between T-1131>C APOAV variant (analyzed by PCR and restriction analysis) and body height. Mother's body height did not differ between T/T homozygotes (N = 1093, 162.5 +/- 6.5 cm) and C allele carriers (N = 212, 162.1 +/- 6.4 cm). Thus we have failed to confirm, that mothers with APOAV C-1131 allele are higher than T/T-1131 homozygotes.

Polymorphisms in CYP-7A1, not APOE, influence the change in plasma lipids in response to population dietary change in an 8 year follow-up; results from the Czech MONICA study.

OBJECTIVES: To evaluate the influence of variation in the genes for apolipoprotein E (APOE; epsilon2, epsilon3, epsilon4) and cholesterol-7alpha hydroxylase (CYP-7A1; -204A-->C) on plasma lipid level changes. DESIGN AND METHODS: 131 males for whom dietary composition markedly changed and total cholesterol decreased (from 6.21 +/- 1.31 mmol/L in 1988 - 5.43 +/- 1.06 mmol/L in 1996) over an 8 yr follow-up study. Polymorphisms were investigated using PCR. RESULTS: APOE genotype influenced plasma total and LDL cholesterol, with carriers of the epsilon4 having the highest and epsilon2 carriers the lowest levels, this reached borderline significance for cholesterol in 1988 (p = 0.06) and strongly affected the 1996 levels of LDL cholesterol (p = 0.008). However, APOE did not influence the change in these measures over time. In contrast, the CYP-7A1 -204A-->C polymorphism did not affect lipid measures per se but was strongly associated with a decrease in plasma total cholesterol [AA -0.38 (+/- 0.20) mmol/L, AC -0.65 +/- (0.08), CC -1.33 (+/- 0.3) mmol/L, p = 0.01] over the 8 yr time period. CONCLUSIONS: Variation in the CYP-7A1 gene may play an important role in an individual's sensitivity to dietary composition.

Apolipoprotein AV gene polymorphisms (T-1131/C and Ser19/Trp) influence plasma triglyceride levels and risk of myocardial infarction.

BACKGROUND: The importance of an apolipoprotein AV (apoAV) gene for plasma triglyceride (TG) level determination has been shown on transgenic and knockout mice. The influence of apoAV polymorphisms (T-1131/C and Ser19/Trp) on plasma TG levels was evaluated in a representative sample of 1191 men and 1368 women, in 435 patients with myocardial infarction (MI) and in 83 individuals with extreme TG levels (20.4+/-12.8 mmol/L). METHODS: ApoAV variants were analyzed using polymerase chain reaction and restriction analysis. RESULTS: T-1131/C variation in the apoAV gene affects plasma TG levels, showing a higher level in C-1131 carriers than in T/T-1131 homozygotes. This association has been observed both in men (P<0.05) and in women (P<0.01). TG levels were also influenced by the Ser19/Trp apoAV genotypes. In both males and females, the Trp19 carriers have higher plasma TGs (P<0.01) than do Ser19 homozygotes. In hypertriglyceridemic patients, the frequency of carriers of the T/C-1131 and C/C-1131 genotypes (32.5% versus 15.4%, P<0.0001) and Ser/Trp19 and Trp/Trp19 genotypes (30.1% versus 14.1%, P<0.0001) was much higher than in the population sample. In a group of MI patients (n=435), the frequency of the disadvantageous homozygous genotypes, with their effect of increasing the TG concentration (C/C-1131 and/or Trp/Trp19), was significantly higher than in the population sample (7.4% versus 2.0%, P<0.00001). CONCLUSION: Variation(s) in the apoAV gene play an important role in the genetic determination of plasma TG levels and influence the risk of MI.

Is the CD14 receptor gene a marker for smoking dependence?

BACKGROUND: The CD14 receptor is a myeloid cell-specific receptor, which plays a role in host defense and cell stimulation. CD14 positive cells have been detected in lung, and also in brain, and the CD14 receptor is thought to play a role in asthma and allergy reactions. C-159-->T polymorphism in the promoter of the CD14 gene has been associated with myocardial infarction, but not in all studies. Our goal was to establish whether this polymorphism is associated with some of the risk factors of MI. MATERIAL/METHODS: With PCR and subsequent restriction analysis we evaluated C-159-->T polymorphism in the CD14 gene in 135 representative selected male Caucasians. RESULTS: We detected a significantly higher frequency of T/T homozygotes (p<0.025) in subjects who had never smoked (15 of 60, 25.0%) as compared to smokers and past smokers (6 of 75, 8.0%). CONCLUSIONS: The C-159-->T polymorphism in the CD14 gene could be a genetic marker associated with smoking dependence, but confirmation in a large population study is necessary.

Polymorphisms in the lipopolysaccharide-binding protein and bactericidal/permeability-increasing protein in patients with myocardial infarction.

Gram-negative bacterial infection, namely Chlamydia pneumoniae has been recently discussed as a risk factor for myocardial infarction. The lipopolysaccharide-binding protein (LBP) and the bactericidal/permeability-increasing protein (BPI) play a role in the processes leading to recognition and neutralisation of the Chlamydia pneumoniae and their endotoxins lipopolysaccharides (LPS). LPS interact with plasma LBP, and LBP-LPS complex activates monocytes/macrophages, which can influence the atherosclerotic process. BPI is cytotoxic for Gram-negative bacteria and BPI-LPS complexes do not activate monocytes. We have analysed the polymorphisms in the LBP gene (Gly98-->Cys; Pro436-->Leu) and BPI gene (Lys216-->Glu; PstI polymorphism in intron-5; G545-->C) in 313 patients after myocardial infarction (MI) and in 302 control individuals. Genotype frequencies in the LBP gene and BPI gene did not differ between MI patients and control individuals. Our findings suggest that LBP and BPI polymorphisms do not influence the risk of MI.