A functional haplotype in the 5' flanking region of the factor VII gene is associated with an increased risk of coronary heart disease

Summary.  Aims : The aim of this study was to investigate associations between coronary heart disease risk and polymorphisms in the coagulation factor (F)VII gene in participants of a large prospective study. Methods : One thousand nine hundred and fifty-seven men were genotyped for four FVII polymorphisms, −670A→C, −402G→A, a 10 base pair insertion at −323 (0 > 10) in the promoter, and R353Q in the structural gene. Associations among genotypes and estimated haplotypes, plasma FVII levels, and coronary heart disease risk were evaluated, and the function of the promoter polymorphisms was assessed in reporter gene assays. Results : The −670A→C and −402G→A polymorphisms were in complete allelic association. The haplotype containing −670C and −402A (frequency =0.23) was associated with significantly increased plasma FVII coagulant activity and increased risk of an initial coronary event, particularly acute myocardial infarction, which remained after correction for conventional risk factors. In contrast, the −323 insertion and Q353 alleles (frequency =0.11 and 0.10, respectively) were associated with decreased plasma FVII levels, but hazard ratios for coronary events in carriers of these alleles were not significantly different from unity. In transiently transfected hepatoma cells, increased basal expression of the reporter gene was directed by a promoter fragment with rare haplotype −670C/−630G/−402A rather than by a promoter fragment with common haplotype −670A/−630A/−402G; −402A was not responsible for this effect. Conclusions : The promoter haplotype, −670C/−630G/402A, was associated with significantly increased plasma FVII coagulant activity, risk of an initial coronary event, particularly acute myocardial infarction, and reporter gene expression.     

Polymorphisms and haplotypes of the estrogen receptor-beta gene (ESR2) and cardiovascular disease in men and women

BACKGROUND: Cohort studies suggest an association between variation in the estrogen receptor-alpha gene (ESR1) and cardiovascular disease (CVD), but data are lacking for the effect of variation in the estrogen receptor-beta gene (ESR2). METHODS: Three polymorphisms of the ESR2 gene, and their associated haplotypes, were evaluated in 296 white women from the Women's Health Study and 566 white men from the Physicians' Health Study who developed CVD [myocardial infarction (MI) or ischemic stroke], each matched 1:1 to a member of the cohort study who remained free from CVD. Blood samples and cardiovascular risk information were collected at baseline. RESULTS: Women, but not men, who developed CVD or MI, but not ischemic stroke, were more likely to have the rs1271572 polymorphism variant T allele (P = 0.05 and 0.02) and less likely to have the rs1256049 polymorphism variant A allele (P = 0.003 and 0.004). No associations were observed for rs4986938. In conditional logistic multivariate regression, the rs1271572 variant was associated with increased odds of CVD [odds ratio (OR) = 1.49, 95% CI: 1.10-2.01] and MI (OR = 1.46, 95% CI: 0.96-2.23), whereas the rs1256049 variant was associated with decreased odds of CVD (OR = 0.37, 95% CI: 0.17-0.79) and MI (OR = 0.25, 95% CI: 0.09-0.73) in women. A common haplotype that included the rs1271572 variant was associated with a 7-fold increased risk of MI in women. CONCLUSIONS: Two tightly linked polymorphisms of ESR2 were associated with risk of CVD, particularly MI, in women but not men. Additional studies of ESR2 genetic variation and risk of CVD are warranted.     

Haplotype and genotype effects of the F7 gene on circulating factor VII,coagulation activation markers and incident coronary heart disease in UK men

Background: Evidence for the associations of single nucleotide polymorphisms (SNPs) in the F7 gene and factor (F)VII levels and with risk of coronary heart disease (CHD) is inconsistent. We examined whether F7 tagging SNPs (tSNPs) and haplotypes were associated with FVII levels, coagulation activation markers (CAMs) and CHD risk in two cohorts of UK men. Methods: Genotypes for eight SNPs and baseline levels of FVIIc, FVIIag and CAMs (including FVIIa) were determined in 2773 healthy men from the Second Northwick Park Heart Study (NPHS‐II). A second cohort, Whitehall II study (WH‐II, n = 4055), was used for replication analysis of FVIIc levels and CHD risk. Results: In NPHS‐II the minor alleles of three SNPs (rs555212, rs762635 and rs510317; haplotype H2) were associated with higher levels of FVIIag, FVIIc and FVIIa, whereas the minor allele for two SNPs (I/D323 and rs6046; haplotype H5) was associated with lower levels. Adjusted for classic risk factors, H2 carriers had a CHD hazard ratio of 1.34 [95% confidence interval (CI): 1.12–1.59; independent of FVIIc], whereas H5 carriers had a CHD risk of 1.29 (95% CI: 1.01–1.56; not independent of FVIIc) and significantly lower CAMs. Effects of haplotypes on FVIIc levels were replicated in WH‐II, as was the association of H5 with higher CHD risk [pooled‐estimate odds ratio (OR) 1.16 (1.00–1.36), P = 0.05], but surprisingly, H2 exhibited a reduced risk for CHD. Conclusion: tSNPs in the F7 gene strongly influence FVII levels. The haplotype associated with low FVIIc level, with particularly reduced functional activity, was consistently associated with increased risk for CHD, whereas the haplotype associated with high FVIIc level was not.     

Gender-modulated impact of apolipoprotein A5 gene (APOA5) -1131T>C and c.56C>G polymorphisms on lipids, dyslipidemia and metabolic syndrome in Turkish adults

BACKGROUND: Apolipoprotein A5 (APOA5) gene polymorphisms are usually associated with plasma triglyceride levels. We evaluated the relationship of the APOA5 -1131T>C and c.56C>G polymorphisms [single nucleotide polymorphism (SNP)] with serum lipids, dyslipidemia [low high-density lipoprotein (HDL)/high triglyceride] and the risk for metabolic syndrome (MS) in the Turkish Adult Risk Factor study. METHODS: We genotyped SNPs using the Taqman allelic discrimination assays in 1564 Turkish adults (51.4% female, mean age 54.1+/-11.6 years). MS and dyslipidemia were defined using the criteria of the National Cholesterol Education Program. RESULTS: For both SNPs, rare allele carriers had significantly higher fasting triglyceride levels in both genders, except the c.56G allele in men. The -1131C allele was associated with lower HDL cholesterol (HDL-C) levels in women. In relation to dyslipidemia, the c.56C>G and haplotype 1 had significant gender-genotype interactions (p<0.05). Otherwise, both SNPs were significantly associated with dyslipidemia after adjustment for risk factors in women. After similar adjustment, non-carriers of the haplotype 1 (odds ratio=4.1, p=0.003) increased the MS risk in women. However, no significant associations emerged between SNPs and HDL-C, dyslipidemia or MS in a similar analysis in men. CONCLUSIONS: Excess risk for low HDL-C, dyslipidemia and MS is associated with the rare alleles of the APOA5 SNPs and non-carriers of common haplotype in women.     

Polymorphisms of prostaglandin-endoperoxide synthase 2 gene, and prostaglandin-E receptor 2 gene, C-reactive protein concentrations and risk of atherothrombosis: a nested case–control approach

OBJECTIVE: Recent data have shown an association between polymorphisms of prostaglandin-endoperoxide synthase-2 gene (PTGS2; alias COX-2), and prostaglandin-E receptor-2 gene (PTGER2) and risk of atherothrombotic disorders. METHODS: We evaluated two PTGS2 (rs20417, rs689470), and three PTGER2 (rs708494/uS5, rs708495/uS7, and chr14: 50 764 013/uS10) gene polymorphisms among 600 Caucasian male participants of the Physicians' Health Study with incident myocardial infarction (MI) or ischemic stroke and 600 age- and smoking-matched controls who remained free of all reported cardiovascular disease. RESULTS: Genotype distributions were in Hardy-Weinberg equilibrium in the control groups. Genotype and allele distribution were similar between cases and controls. The polymorphisms tested were in linkage disequilibrium. Results from the adjusted haplotype-based conditional logistic regression analysis showed a modest association of the PTGER2 2-1-1 haplotype with reduced risk of MI (odds ratio = 0.50, 95% CI; CI = 0.26-0.97, P = 0.04), and the 2-2-1 haplotype with reduced risk of ischemic stroke (odds ratio = 0.68, 95% CI = 0.47-0.99, P = 0.048). In contrast to prior data, we found no evidence for an association of the PTGS2 polymorphisms/haplotypes tested with risk of incident MI nor with ischemic stroke. However, we found suggestive evidence for an association of specific PTGER2 haplotypes with reduced risk of these outcomes. CONCLUSION: Although these prospective data implicate the potential involvement of prostaglandin-E receptor-2 gene variation in atherothrombosis, external validation of our findings is needed.     

Cholesterol concentrations in patients with Anorexia Nervosa and in healthy controls

Argentinean women have one of the highest international mortality rates for cardiovascular disease and they are particularly vulnerable to eating pathologies. Cardiovascular risk is exacerbated in women with Anorexia Nervosa (AN), since high cholesterol concentrations have been widely reported. OBJECTIVES: To compare blood cholesterol concentrations in AN patients with controls, and to correlate cholesterol with the body mass index (BMI), patient age, vomiting and tobacco. DESIGN AND METHOD: Cholesterol measurements documented at diagnosis from the clinical notes of patients were recorded from the Association Against Bulimia and Anorexia (ALUBA). Comparison was carried out with data of the general Argentinean public. RESULTS: Total cholesterol, LDL and HDL concentrations were higher in patients compared with controls. Total cholesterol in patients decreased during treatment and it was correlated with the patient age, but with no other variable. CONCLUSION: The abnormal lipid profile places patients at risk for cardiovascular disease. Older and untreated patients may be at particular higher risk of suffering from the consequences of elevated cholesterol concentrations.     

Lipids, waist circumference and body mass index in haemodialysis patients

In the general population, dyslipidaemia and abdominal obesity are risk factors for cardiovascular disease, but less is known about their roles in patients on maintenance haemodialysis (HD). This study investigated the association between blood lipids and abdominal obesity, as determined by waist circumference (WAC), and body mass index (BMI) in 72 HD patients (32 women). Blood lipid levels were measured using routine laboratory methods. Abdominal obesity, based on the WAC measurement, was found in 62.5% of HD patients (75.0% of women; 52.5% of men). Triglyceride levels were higher in abdominally obese compared with abdominally non-obese men. According to BMI measurements, 34.7% of HD patients were overweight/obese and 9.7% were underweight. In men, WAC and BMI were positively correlated with triglyceride levels. In women, WAC was negatively correlated with high-density lipoprotein (HDL) cholesterol and apolipoprotein A levels. The results indicated that there was a negative association of abdominal obesity and BMI with HDL cholesterol in HD patients.     

Factor VII coagulant activity, factor VII −670A/C and −402G/A polymorphisms, and risk of venous thromboembolism

BACKGROUND: Most epidemiological studies have found no association between levels of factor (F) VII:C and venous thromboembolism (VTE). Our Longitudinal Investigation of Thromboembolism Etiology (LITE) had, in contrast, reported an independent, increased risk of VTE after 7.8 years of follow-up for those with high baseline levels of FVII:C. OBJECTIVE: To confirm whether FVII:C is associated with VTE after 12.6 years of follow-up and to examine whether two FVII gene polymorphisms (-670A/C and -402G/A) are related to VTE occurrence. METHODS: In 19 091 LITE participants with no prior history of VTE or cancer, we measured FVII:C at baseline and identified 404 new VTEs. We also performed a nested case-control study to relate the polymorphisms to VTE (n = 490 without exclusion for cancer or prior VTE). RESULTS: FVII:C was not independently associated with VTE occurrence after extended follow-up. Multivariable-adjusted rate ratios for VTE were 1.00, 1.00, 0.94, 1.00, and 1.38 (P-trend = 0.48) for the <25th, 25th-49th, 50th-74th, 75th-94th, and >or=95th percentiles of FVII:C, respectively. The -670C and -402A alleles were in high linkage disequilibrium, and both were associated with greater FVII:C levels. However, neither polymorphism was associated with VTE occurrence. CONCLUSION: After extended follow-up, LITE offers little evidence that a greater FVII level is a risk factor for VTE.     

Impaired fasting glucose and impaired glucose tolerance in women with prior gestational diabetes are associated with a different cardiovascular profile

OBJECTIVE: The purpose of this study was to investigate the association of cardiovascular risk factors to impaired glucose tolerance (IGT) and to impaired fasting glucose (IFG) in women with prior gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We studied 838 women with prior GDM. Postpartum glucose tolerance status was classified as normal, IFG, IGT, IFG plus IGT, and diabetes according to the World Health Organization criteria. Postpartum BMI, waist circumference, blood pressure, triglyceride, cholesterol, and HDL cholesterol were assessed. RESULTS: BMI and blood pressure were significantly higher in women with IFG than in women with normal glucose status. BMI and waist circumference were significantly higher in women with IFG plus IGT than in women with normal glucose status. No differences were observed between women with IGT and normal glucose status. The prevalence of hypertension and obesity was significantly increased in IFG compared with normal glucose status. The prevalence of obesity and abnormal lipids was significantly increased in IFG plus IGT compared with normal glucose status. IGT showed no increased prevalence of cardiovascular risk factors. CONCLUSIONS: Traditional cardiovascular risk factors have a stronger association with isolated IFG than with isolated IGT in women with prior GDM.     

The −589C>T polymorphism in the interleukin‐4 gene (IL‐4) is associated with a reduced risk of myocardial infarction in young individuals

Summary. Background: Inflammatory reactions contribute to the development of arterial disease. We investigated the role of interleukin‐4 (IL‐4) in the development of myocardial infarction (MI) by genotyping patients with MI and control subjects for the ?589C>T (rs2243250) single nucleotide polymorphism (SNP), which tags a functional haplotype of IL‐4. Methods and results: Study of Myocardial Infarctions Leiden (SMILE) included 560 men with a first MI and 646 control subjects. The Valencia study included 305 patients with MI at ≤52 years (men and women) and 310 control subjects. In SMILE no clear overall association with the ?589C>T genotype was found [odds ratio (OR) 0.84; 95% CI 0.37–1.95 for ?589TT and 0.82; 95% CI 0.62–1.07 for ?589CT compared with ?589CC]. In patients younger than 50 years, carriership of one or two ?589T alleles was associated with a reduced risk of MI (OR 0.57: 95% CI 0.34–0.95). This result was replicated in the Valencia study, where carriers of one or two ?589T alleles had a reduced risk of MI (OR 0.67: 95% CI 0.47–0.95), with a strong protective effect of the ?598T allele in homozygous ?589T (OR 0.33: 95% CI 0.10–1.05). In the control subjects of the Valencia study, the ?589T allele was associated with reduced levels of F1+2. Conclusion: Our data indicate that the IL‐4 haplotype tagged by the ?589T allele reduces the risk of MI in young individuals.     

Family history of myocardial infarction is an independent risk factor for venous thromboembolism: the Tromsø study

Summary. Background: Recent studies indicate that arterial cardiovascular diseases and venous thromboembolism (VTE) share common risk factors. A family history of myocardial infarction (MI) is a strong and independent risk factor for future MI. Objectives: The purpose of the present study was to determine the impact of cardiovascular risk factors, including family history of MI, on the incidence of VTE in a prospective, population‐based study. Patients and methods: Traditional cardiovascular risk factors and family history of MI were registered in 21 330 subjects, aged 25–96 years, enrolled in the Tromsø study in 1994–95. First‐lifetime VTE events during follow‐up were registered up to 1 September 2007. Results: There were 327 VTE events (1.40 per 1000 person‐years), 138 (42%) unprovoked, during a mean of 10.9 years of follow‐up. In age‐ and gender‐adjusted analysis, age [hazard ratio (HR) per decade, 1.97; 95% confidence interval (CI), 1.82–2.12], gender (men vs. women; HR, 1.25; 95% CI, 1.01–1.55), body mass index (BMI; HR per 3 kg m^?2, 1.21; 95% CI, 1.13–1.31), and family history of MI (HR, 1.31; 95% CI, 1.04–1.65) were significantly associated with VTE. Family history of MI remained a significant risk factor for total VTE (HR, 1.27; 95% CI, 1.01–1.60) and unprovoked VTE (HR, 1.46; 95% CI, 1.03–2.07) in multivariable analysis. Blood pressure, total cholesterol, HDL‐cholesterol, triglycerides, and smoking were not independently associated with total VTE. Conclusions: Family history of MI is a risk factor for both MI and VTE, and provides further evidence of a link between venous and arterial thrombosis.     

Lipoprotein and apoprotein levels in postmenopausal women during treatment with norethisterone

Lipoprotein and apolipoprotein levels were monitored in 21 postmenopausal women during 6 months' treatment with norethisterone. There was no significant change in low density lipoprotein (LDL) cholesterol but apoprotein B levels rose significantly (p less than 0.001) thus increasing the apoprotein:cholesterol ratio in LDL. High density lipoprotein (HDL) cholesterol levels decreased significantly (p less than 0.001) in the first two months and did not change significantly thereafter. The HDL2 subfraction was reduced to a greater extent than the HDL3 subfraction. Apoprotein AI and AII levels were both reduced as was the apoprotein AI:AII ratio. The ratios of apoproteins AI and AII to HDL cholesterol were increased. We conclude that norethisterone has an adverse effect on the important risk factors for cardiovascular disease.     

A common substitution (Asn291Ser) in lipoprotein lipase is associated with increased risk of ischemic heart disease.

Lipoprotein lipase degrades triglycerides in plasma and as a byproduct produces HDL particles. Genetic variation in lipoprotein lipase may therefore affect cardiovascular risk. We tested 9,214 men and women from a general population sample and 948 patients with ischemic heart disease for the Asn291Ser substitution in lipoprotein lipase. The allele frequency in the general population was 0.024 and 0.026 for women and men, respectively. In comparison with noncarriers, female heterozygous probands had increased plasma triglycerides (delta = 0.23 mmol/liter), while HDL cholesterol was reduced in both female and male carriers (delta = 0.18 mmol/liter and delta = 0.11 mmol/liter, respectively). A similar phenotype was found in six homozygous carriers. On multiple logistic regression analysis, plasma triglycerides and HDL cholesterol were independent predictors of ischemic heart disease in both genders. On univariate analysis, odds ratios for ischemic heart disease in probands were 1.89 in women (95% CI: 1.19-3.01) and 0.90 in men (95% CI: 0.62-1.31), and on multivariate analysis were 1.98 in women (95% CI: 1.11-3.53) and 1.02 in men (95% CI: 0.65-1.60). This study demonstrates that a single common mutation in the lipoprotein lipase gene is associated with elevated plasma triglycerides and reduced HDL cholesterol levels, whereby carriers, in particular women, seem to be predisposed to ischemic heart disease. It cannot be excluded, however, that male carriers of this substitution may represent a subset of low-HDL individuals without raised triglycerides not predisposed to ischemic heart disease.     

Effects of regular walking on cardiovascular risk factors and body composition in normoglycemic women and women with type 2 diabetes

OBJECTIVE: To examine the impact of a 12-week walking program on body composition and risk factors for cardiovascular disease in women with type 2 diabetes and in normoglycemic women with first-degree diabetic relatives. RESEARCH DESIGN AND METHODS: There were 11 postmenopausal women with type 2 diabetes and 20 normoglycemic women of similar age and BMI who were asked to walk 1 h per day on 5 days each week for 12 weeks. Fitness (estimated VO2max) was assessed with a 1.6-km walking test; body composition was measured by dual-energy X-ray absorptiometry; and sex hormone, metabolic, and lipid concentrations were measured in serum. RESULTS: After 12 weeks, estimated VO2max improved in both groups (P < 0.005). In the diabetic women, BMI and fat content of the upper body and android waist region decreased (P < 0.05). Concentrations of fasting blood glucose (P < 0.05) HbAlc (P < 0.05), total cholesterol (P < 0.005), and LDL cholesterol (P < 0.05) decreased, while HDL cholesterol and sex hormones were unchanged. In contrast, normoglycemic women failed to lose body fat after 12 weeks of exercise in a walking program. However, their HbAlc, total cholesterol, LDL cholesterol, sex hormone-binding globulin, and total testosterone concentrations decreased (P < 0.05). On pooling the data and including diabetes as a categorical grouping variable, stepwise multiple regression analysis indicated that the change in centralized body fat, but not the change in VO2max, was related to change in fasting blood glucose. CONCLUSIONS: Twelve weeks of walking increased the fitness of diabetic and normoglycemic women. Improvement of fasting blood glucose was related to the loss of centralized body fat rather than to improved fitness.     

Ethnic trends in lipid tests in general practice

BACKGROUND: South Asian migrants have a higher cardiovascular mortality than the indigenous population. Contributory factors may include a lower rate of cardiovascular risk assessment uptake and compliance. AIM: To compare rates of lipid testing, follow-up and patterns of dyslipidaemia in South Asian and non-South-Asian populations in Manchester. DESIGN: Retrospective cross-sectional survey. METHODS: Lipid requests from 14 general practices were analysed, using name recognition software to assign ethnicity. RESULTS: Compared with non-South-Asians, the age-standardized rate of lipid testing in South Asians was similar in men at 12.1% (95%CI 11.6-12.6) vs. 11.2% (9.5-13.0), but higher in women at 18.6% (15.9-21.2) vs. 13.2% (12.6-13.7). Trends of cholesterol with repeat testing were similar in the two populations. However, South Asian women had lower mean levels of total cholesterol (5.50 vs. 5.68 mmol/l, p = 0.021), lower levels of HDL (1.20 vs. 1.46 mmol/l, p < 0.001), an excess of hypertriglyceridaemia (1.62 vs. 1.45 mmol/l, p = 0.035) and a greater proportion with cholesterol > 5.2 mmol/l combined with low HDL (43.1% vs. 20.2%, p = 0.002). South Asian men had lower levels of total cholesterol (5.17 vs. 5.37 mmol/l, p = 0.048) and lower levels of HDL (1.07 vs. 1.64 mmol/l, p < 0.001). There was no difference in the proportion of South Asians men and women with cholesterol < 5.2 mmol/l combined with low HDL. DISCUSSION: The rate of lipid testing and change in cholesterol levels with repeated testing did not differ between South Asian and non-South-Asian groups. The pattern of dyslipidaemia seen in this South Asian population, especially women, was different from that of the non-South-Asian population, with possible implications for cardiovascular risk assessment.     

Obese women and the relation between cardiovascular risk profile and hormone therapy, glucose tolerance, and psychosocial conditions

OBJECTIVE: To evaluate the relation between cardiovascular disease (CVD) risk factors and hormone therapy, serum hormone levels, glucose tolerance, and psychosocial and psychological conditions in subjectively healthy obese female subjects. RESEARCH DESIGN AND METHODS: The study included 606 women, aged 50-64 years, with BMI 30-40 kg/m(2) and no history of cardiovascular or other severe diseases. One group with a CVD risk profile (n = 473) (i.e., cholesterol >7.0 mmol/l, HDL cholesterol <1.2 mmol/l, triglycerides >2.0 mmol/l, systolic or diastolic blood pressure >140/90 mmHg, or waist-to-hip ratio >0.85) was compared with women without such risk (n = 133). Steroid hormones, leptin, insulin, and oral glucose tolerance tests (OGTTs) were analyzed. A subgroup of women with baseline impaired glucose tolerance (IGT) completed a 2.5-year follow-up OGTT. RESULTS: Fewer obese postmenopausal women with CVD risk had ever used hormone therapy (odds ratio 0.24 [95% CI 0.07-0.75]), after multivariate adjustments. Furthermore, women with CVD risk had a higher testosterone index (1.07 [1.01-1.13]) and more had insulin resistance (1.04 [1.00-1.08]) and IGT (2.92 [1.50-5.69]), while OGTT was similar at follow-up. No differences were observed regarding family history or lifestyle, except that fewer women with CVD risk consumed fruits, boiled vegetables, or whole-grain cereals. More women with CVD risk lived alone (3.26 [1.28-8.31]) and had more mental problems (1.16 [1.05-1.28]). CONCLUSIONS: Previously healthy obese women with a CVD risk profile seemed to have a high risk of diabetes, as well as psychosocial or psychological problems. Hormone therapy was associated with reduced CVD risk. Obesity's growing burden on society makes it more important to further target individuals that are at greatest risk of future health hazards.     

The impact of estrogen replacement therapy and raloxifene on osteoporosis, cardiovascular disease, and gynecologic cancers

OBJECTIVE: To compare the clinical utility of estrogen replacement therapy (ERT) and raloxifene in osteoporosis and cardiovascular disease in postmenopausal women and to evaluate the contrasting adverse effects of these therapies. DATA SOURCES: A MEDLINE search was performed for January 1980 through September 1998 using the key terms raloxifene, estrogen, CVD, lipoproteins, and osteoporosis. STUDY SELECTION AND DATA EXTRACTION: All clinical studies assessing ERT and raloxifene in cardiovascular disease or osteoporosis were evaluated. DATA SYNTHESIS: ERT remains the standard for prevention and treatment of osteoporosis in women. Its use increases total bone mineral density (BMD) up to 12.1% and reduces hip fracture risk by 66-73%. It reduces low-density lipoprotein (LDL) cholesterol by 15-19% and increases high-density lipoprotein (HDL) cholesterol by 6-18%. Raloxifene, an alternative to ERT in the prevention of osteoporosis, increases total BMD by 2.2%. It reduces LDL by 6.2-14.1% and increases HDL by 1.5-5.7%. Preliminary data suggest that raloxifene has contrasting effects on gynecologic cancers compared with the increased risk posed by ERT. CONCLUSIONS: Clinical trials have illustrated greater effects on BMD with ERT than with raloxifene. Studies of significant duration assessing raloxifene and its fracture risk effects are lacking. ERT appears to have greater beneficial cardiovascular risk factor effects than raloxifene. Prospective, primary prevention studies evaluating overall cardiovascular risk reduction do not exist for either intervention. Raloxifene, while more costly, is an alternative that may have a lower associated risk of breast cancer compared with ERT.     

Lipids increase after solitary pancreas transplantation.

OBJECTIVE: The aims of this study were to determine 1) changes in lipids after solitary pancreas transplantation (SPTX) in patients with type 1 diabetes and 2) factors that influence those changes. RESEARCH DESIGN AND METHODS: Lipids were evaluated prospectively in 24 patients who underwent SPTX. Three were excluded because of early graft failure. The remaining patients (n = 21; 13 men, 8 women) were studied for changes in lipids over time (pre-SPTX, 0-2, 3-6, 7-12, and > 12 months). Glycohemoglobin, serum creatinine, BMI, and medications were also analyzed for their effects on lipid changes. RESULTS: Cholesterol, HDL, and LDL decreased in the immediate postoperative period (0-2 months), whereas triglycerides (TGs) increased (P < 0.05). At 3-6 months, cholesterol, HDL, and TG were higher than before the SPTX, whereas LDL returned to pre-SPTX levels. After 12 months, HDL and TG remained higher than their pre-SPTX levels (P < 0.05). During the study, systolic and diastolic blood pressure increased, renal function decreased, glyco-hemoglobin improved, and weight was unchanged. Changes in cholesterol/HDL ratio, HDL, and TG correlated with changes in prednisone dose (P < 0.05), and changes in TG correlated with changes in creatinine (P < 0.05). The same pattern of lipids occurred in patients prescribed or not prescribed hypolipidemic agents. CONCLUSIONS: Lipids do not improve within the 1st year after SPTX, despite improved glycemic control and blood pressure control, and renal function is worse. These results are in contrast to those reported for combined kidney-pancreas transplantation, where lipids, blood pressure, and renal function improved immediately after transplant. Further studies are needed to determine whether lipids continue to change with time after SPTX. The impact of these changes after SPTX on overall cardiovascular risk is unknown.     

HDL phosphatidyl choline and risk-factors of coronary heart disease

As part of our epidemiological study of employees in Westphalia, the concentration of HDL phosphatidyl choline was measured in 1546 men and 778 women. The results were analysed in relation to the corresponding HDL cholesterol values, as well as the various risk factors for coronary heart disease. HDL phosphatidyl choline values were found to be age independent, higher in women than in men (p les than 0.001), and lognormally distributed in both sexes (men: mean 1.162 mmol/l, median 1.13 mmol/l, minimum 0.60 mmol/l, maximum 2.46 mmol/l; women: mean 1.370 mmol/l, median 1.34 mmol/l, minimum 0.55 mmol/l, maximum 2.46 mmol/l). A positive correlation (p less than 0.001) was found in both sexes between HDL phosphatidyl choline and HDL cholesterol (men: r = 0.588; women r = 0.605). A negative correlation was found in both sexes between HDL phosphatidyl choline values and body weight (men: r = -0.102 (p less than 0.001) women: r = -0.129 (p less than 0.001); and in men, but not in women, there was a negative correlation between HDL phosphatidyl choline values and triglycerides (men: r = -0.190 (p less than 0.001) women: r = -0.042). A negative correlation between HDL phosphatidyl choline and cigarette smoking was found only in female smokers (r = -0.121 (p less than 0.05). The correlation coefficients between HDL cholesterol and triglycerides as well as HDL cholesterol and relative body weight in both sexes were clearly higher than the corresponding correlation coefficient of HDL phosphatidyl choline. In men as well as in women the HDL phosphatidyl choline/HDL cholesterol ratio decreased with increasing HDL cholesterol values or decreasing triglyceride values in blood serum.     

beta-adrenergic receptor gene polymorphisms and beta-blocker treatment outcomes in hypertension

Numerous studies have demonstrated that beta(1)- and beta(2)-adrenergic receptor gene (ADRB1 and ADRB2) variants influence cardiovascular risk and beta-blocker responses in hypertension and heart failure. We evaluated the relationship between ADRB1 and ADRB2 haplotypes, cardiovascular risk (death, nonfatal myocardial infarction (MI), and nonfatal stroke), and atenolol-based vs. verapamil sustained-release (SR)-based antihypertensive therapy in 5,895 coronary artery disease (CAD) patients. After an average of 2.8 years, death rates were higher in patients carrying the ADRB1 Ser49-Arg389 haplotype (hazard ratio (HR) 3.66, 95% confidence interval (95% CI) 1.68-7.99). This mortality risk was significant in patients randomly assigned to verapamil SR (HR 8.58, 95% CI 2.06-35.8) but not atenolol (HR 2.31, 95% CI 0.82-6.55), suggesting a protective role for the beta-blocker. ADRB2 haplotype associations were divergent within the treatment groups but did not remain significant after adjustment for multiple comparisons. ADRB1 haplotype variation is associated with mortality risk, and beta-blockers may be preferred in subgroups of patients defined by ADRB1 or ADRB2 polymorphisms.