High-dose testosterone is associated with atherosclerosis in postmenopausal women

OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless.     

Psychological factors and subclinical atherosclerosis in postmenopausal Chinese women in Hong Kong

Background

Substantial evidence shows that psychological factors are associated with cardiovascular diseases. However, data on the association between psychological factors and subclinical atherosclerosis is lacking in postmenopausal Chinese women.

Objectives

To examine the associations of perceived stress and trait anxiety with subclinical atherosclerosis in postmenopausal Chinese women in Hong Kong. Their relationships with biological and behavioral risk factors were also examined.

Methods

Between 2002 and 2004, we recruited 518 postmenopausal women aged 50–64 years. Perceived stress and trait anxiety were evaluated by the perceived stress scale and the state-trait anxiety inventory, respectively. Subclinical atherosclerosis was determined by measuring carotid intima-media thickness (IMT) and plaque using B-mode ultrasonography.

Results

Perceived stress and trait anxiety showed no significant association with IMT or plaque. Multivariate analyses showed high perceived stress scores were associated with an increased risk of elevated total cholesterol (OR = 2.10; 95% CI = 1.17–3.77) and elevated low-density lipoprotein cholesterol (LDL-C) (OR = 2.39; 95% CI = 1.36–4.21). High trait anxiety scores were associated with a 2.7-fold risk of elevated LDL-C (OR = 2.74; 95% CI = 1.56–4.80). Women with high perceived stress or trait anxiety scores were more likely to be physically inactive.

Conclusions

Perceived stress and trait anxiety were associated with atherogenic lipid levels, but not subclinical atherosclerosis. Maintaining high physical activity may help alleviate psychological stress and anxiety.     

CYP4A11基因多态性与心肌梗死相关

目的 研究在不同性别中CYP4A11基因多态性与心肌梗死的关系.方法 166例心肌梗死患者和158例对照组,选择CYPA11基因的3个SNPs(rs9332978、rs3890011和rs1126742),应用TaqMan SNP基因分型法进行基因分型,并应用病例对照的研究方法进行相关性分析.结果 rs3890011的基因分型在心肌梗死组和对照组之间的分布存在明显差异(P＜0.05),心肌梗死组携带GG基因型(GG vs CC+ GC)高于对照组(P＜0.05),在排除吸烟、高血压、糖尿病等混杂因素后,仍存在显著性差异(95％ CI:1.138～2.432,P＜0.01).结论 CYP4A11基因的rs3890011多态性与心肌梗死相关,rs3890011的GG基因型可作为心肌梗死易感基因标记.     

Association of general and abdominal obesities and metabolic syndrome with subclinical atherosclerosis in asymptomatic Chinese postmenopausal women

OBJECTIVE: This study aimed to investigate the relationships between obesity, especially abdominal obesity, andmetabolic syndrome (MS) with carotid intima-media thickness (IMT) and plaque, markers of subclinical atherosclerosis, in asymptomatic Chinese postmenopausal women in Hong Kong. DESIGN: A total of 518 postmenopausal women aged 50 to 64 years were recruited through random telephone dialing. Body mass index (BMI), waist circumference, waist-to-hip ratio, sociodemographic characteristics, blood pressures, medical, biochemical and lifestyle factors were obtained. MS was defined on the basis of the National Cholesterol and Education Program, Adult Treatment Panel III criteria. Subclinical atherosclerosis was determined by measuring IMT and plaque using high-resolution B-mode ultrasonography. RESULTS: Women with a BMI of 25 kg/mor greater, a waist circumference of 80 cm or greater, a waist-to-hip ratio of 0.85 or greater, or MS were observed to have higher IMT values and prevalence of plaque. Multivariate analyses revealed that waist circumference was significantly associated with IMT independent of age, hormone therapy, lifestyle and sociodemographic factors, and BMI (P < 0.05), whereas a waist-to-hip ratio of 0.85 or greater was significantly associated with plaque (odds ratio = 1.7; 95% CI: 1.0-2.8) after controlling for age, hormone therapy, lifestyle and sociodemographic factors, BMI, and the traditional cardiovascular risk factors. MS was also associated with IMT after adjustment for age, hormone therapy, lifestyle and sociodemographic factors, and BMI (P < 0.05), whereas its association with plaque was also significant (odds ratio = 1.7; 95% CI: 1.0-2.6) after controlling for age. CONCLUSIONS: Abdominal obesity and MS are independent of general obesity markers of subclinical atherosclerosis in Chinese postmenopausal women.     

Apolipoprotein E polymorphism is not associated with spinal bone mineral density in peri- and postmenopausal Greek women

OBJECTIVES: A number of studies have shown a positive relation between ApoE gene and osteoporosis or fracture risk but this finding has not been uniform in all populations studied. The aim of the present study was to determine the possible effect of ApoE gene polymorphism on spinal bone mineral density and metabolic bone markers in Greek women. METHODS: One hundred and forty-seven healthy peri- and postmenopausal women (mean age 54.3 +/- 7.8 years) participated in the study. In all participants, ApoE gene genotype was determined and spinal bone mineral density (BMD) as well as biochemical bone markers were measured. The ApoE genotypes distribution was 0.7% (n = 1) for E2/2, 5.4% (n = 8) for E2/3, 2% (n = 3) for E2/4, 73.5% (n = 108) for E3/3, 16.3% (n = 24) for E3/4 and 2% (n = 3) for E4/4. Participants were divided in two groups according to the presence of the E4 haplotype: E4 carriers (n = 30) and E4 non-carriers (n = 117). RESULTS: Spinal BMD was similar in the two groups, after adjusting for age, weight, height and years since menopause (mean +/- S.D., 0.835 +/- 0.16 g/cm2 in E4 non-carriers versus 0.831 +/- 0.16 g/cm2 in E4 carriers, P = 0.99). Serum osteocalcin levels did not differ significantly in the two groups (median (interquartile range, IQR), 0.55 (0.58) nmol/l in E4 non-carriers versus 0.51 (0.43) nmol/l in E4 carriers), whereas urinary hydroxyproline/creatinine ratio was significantly higher in the E4 non-carriers group (median (IQR), 5.18 (6.04) micromol/mmol in E4 non-carriers versus 1.73 (3.45) micromol/mmol in E4 carriers, P < 0.01). Urinary pyridinoline/creatinine and deoxypyridinoline/creatinine ratios, measured in a subgroup of 51 women, were similar between ApoE carriers and non-carriers, respectively (median (IQR), 25.1 (9.3) nmol/mmol in E4 non-carriers versus 21.8 (7) nmol/mmol in E4 carriers and 6.7 (3.1) nmol/mmol in E4 non-carriers versus 7 (2.2) nmol/mmol in E4 carriers). CONCLUSION: In conclusion, in a Greek female postmenopausal population, ApoE gene does not seem to play an important role in determining BMD and neither does it affect the majority of metabolic bone markers.     

The ACE-DD genotype is associated with endothelial dysfunction in postmenopausal women

OBJECTIVE: To evaluate the effects of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), the angiotensinogen M235T and the angiotensin II type 1 receptor A1166C polymorphisms, and hormone therapy used on endothelial function in postmenopausal women without manifestation of coronary artery disease. DESIGN: Sixty-four postmenopausal women (42 hormone therapy users and 22 hormone therapy nonusers) without clinical manifestation of coronary artery disease were evaluated using external vascular ultrasonography to measure endothelium-dependent (hyperemic response, flow-mediated dilatation) and -independent (nitroglycerin) dilatation. Genotypes were determined by polymerase chain reaction amplification. RESULTS: Women with the ACE-DD genotype displayed a lower flow-mediated dilatation compared to those with the ACE-II genotype (8.4% +/- 3.9% vs 12.6% +/- 5.4%, P = 0.04). Endothelial function was not associated with the angiotensinogen M235T and anglotensin II type 1 receptor A1166C polymorphisms. ACE polymorphism seems to modulate endothelial function among postmenopausal women without hormone therapy (8.2% +/- 5.1% vs 18.4% +/- 5.9% for the DD and the II genotype, respectively, P = 0.02). However, in hormone therapy users, flow-mediated dilatation was similar according to the ACE genotypes. CONCLUSIONS: Our findings suggest that ACE-I/D polymorphism is related to endothelial dysfunction in postmenopausal women. Furthermore, a potential interaction between estrogen users and ACE polymorphism on endothelial function may be present.     

Thyroid stimulating hormone is associated with metabolic syndrome in euthyroid postmenopausal women

Objectives

The aim of this study was to investigate the relationship between thyroid stimulating hormone (TSH) and metabolic syndrome (MetS) in euthyroid postmenopausal women.

Methods

We conducted a cross-sectional study of 2205 Korean postmenopausal women. Subjects who were not euthyroid were excluded. Fasting TSH, free thyroxine (FT4), insulin, glucose, and the level of insulin resistance, estimated by the homeostasis model assessment for insulin resistance (HOMA-IR) were measured. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria.

Results

TSH levels were associated with total cholesterol, LDL-cholesterol, triglycerides and diastolic blood pressure. Using a multiple linear regression analysis, LDL-cholesterol, and triglycerides levels were identified as independently associated with TSH. Multivariate logistic regression analysis determined that TSH levels strongly contributed to MetS. Compared with the lower most quartile (TSH, 0.3–1.44 mIU/L), the adjusted odds ratio for MetS was 1.95 in the upper most quartile (TSH, 2.48–4.00 mIU/L). The prevalence of MetS increased as the TSH quartile showed a gradual increase.

Conclusion

We found a close relationship between TSH and MetS in euthyroid postmenopausal women. Therefore, more attention should be focused on postmenopausal women with high normal TSH levels for the management of cardiovascular disease.     

Anger is associated with subclinical atherosclerosis in low SES but not in higher SES men and women. The Cardiovascular Risk in Young Finns Study

We investigated the associations of anger and cynicism with carotid artery intima-media thickness (IMT) and whether these associations were moderated by childhood or adulthood socioeconomic status (SES). The participants were 647 men and 893 women derived from the population-based Cardiovascular Risk in Young Finns Study. Childhood SES was measured in 1980 when the participants were aged 3–18. In 2001, adulthood SES, anger, cynicism, and IMT were measured. There were no associations between anger or cynicism and IMT in the entire population, but anger was associated with thicker IMT in participants who had experienced low SES in childhood. This association persisted after adjustment for a host of cardiovascular risk factors. It is concluded that the ill health-effects of psychological factors such as anger may be more pronounced in individuals who have been exposed to adverse socioeconomic circumstances early in life.     

Hepatic lipase promoter C-480T polymorphism is associated with serum lipids levels, but not subclinical atherosclerosis: The Cardiovascular Risk in Young Finns Study

The common C‐480T polymorphism (rs1800588) of the hepatic lipase gene (LIPC) has been associated with high‐density lipoprotein (HDL) cholesterol, atherosclerosis, and coronary artery disease. In this study, we examined whether the polymorphism is associated with serum lipid and lipoprotein concentrations, as well as with subclinical atherosclerosis in Young Finns. The participants comprised 2041 men and women (aged 24–39 years) enrolled in the Cardiovascular Risk in Young Finns Study with complete data concerning the rs1800588 polymorphism and serum lipids concentration. All participants underwent an ultrasound examination for brachial artery flow‐mediated vasodilatation (FMD) and carotid artery intima‐media thickness (IMT) measurement. The marker of arterial elasticity, carotid artery compliance (CAC), was also calculated by means of ultrasound and concomitant brachial blood pressure measurements. In all subjects, serum total cholesterol (p < 0.001), HDL cholesterol (p = 0.006), apolipoprotein AI (apoAI, p < 0.001), and triglyceride (p = 0.009) concentrations increased according to rs1800588 genotype in the order CC, CT, and TT. The same order applied only to apoAI after adjustment for age, body mass index, systolic and diastolic blood pressure, smoking, alcohol consumption, physical activity, diabetes, hypertension, contraceptive hormone use in women, and concentrations of glucose, insulin and C‐reactive protein in men and women separately (p = 0.007 and p = 0.003, respectively). The polymorphism was also associated with HDL cholesterol, total cholesterol, and triglyceride levels in women (adjusted p = 0.004, p = 0.007 and 0.02, respectively), but not in men (p was not significant for all). No significant association between the rs1800588 and brachial FMD, carotid IMT, or CAC was found among the entire study population or among women or men separately, with or without adjustment for the above‐mentioned factors. The rs1800588 is associated with serum lipid and apolipoprotein concentrations, especially in women, but does not seem to be a determinant of brachial artery FMD, carotid IMT, or CAC in young healthy adults.     

Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women

High bone resorption by the osteoclast results in osteoporosis, a disease affecting 40% of women after the menopause. Calcitonin, used to treat osteoporosis, inhibits bone resorption via receptors located on the osteoclasts. Two alleles of the calcitonin receptor gene ( CTR ) exist: a base mutation T-->C in the third intracellular C-terminal domain changes a proline (CCG) at position 447 to a leucine (CTG). We therefore studied the distribution of these alleles in a cohort of 215 post-menopausal Caucasian women suffering or not from osteoporotic fractures. The region of interest within the point mutation was amplified by PCR and screened for single strand conformation polymorphism. This work was followed by DNA sequencing of the fragments amplified. We found that bone mineral density (BMD) at the femoral neck was significantly higher in heterozygous subjects with the Rr genotype compared with the homozygous leucine (RR) and homozygous proline (rr) genotypes. Also, a decreased fracture risk was observed in heterozygote subjects. In conclusion, our results suggest that polymorphism of CTR could be associated with osteoporotic fractures and BMD in a population of post-menopausal women. CTR heterozygotes could produce both alleles of the receptor. The heterozygous advantage effect of Rr subjects could explain their protection against osteoporosis: higher bone density and decreased fracture risk. Establishing the genotype of the CTR gene in post-menopausal women could be of value in evaluating their risk of developing fractures.      

Combined oestrogen-progestin replacement therapy prevents atherosclerosis in postmenopausal women

The incidence of atherosclerotic plaques in the aorta and in the carotid and iliac arteries was investigated using high resolution B-mode ultrasonography in 40 postmenopausal women using sequentially combined oestradiol valerate 2 mg—levonorgestrel 0.25 mg replacement therapy. In addition, serum lipid, lipoprotein and apolipoprotein levels were measured. Similar studies were performed for 40 postmenopausal women using oestradiol valerate alone and for 40 women who had never used hormone replacement therapy (HRT). Ultrasonograhpically observed atherosclerotic plaques were less common (P = 0.011) in oestradiol valerate—levonorgestrel users than in women without HRT. More than three atherosclerotic plaques were observed in 62% of the women without HRT but only in 30% of the women using combined therapy (P = 0.003). The total number of plaques did not differ between the two hormone using groups. The mean serum triglyceride, total cholesterol and apolipoprotein B levels were lowest in oestradiol valerate — levonorgestrel users when compared with those of women with oestradiol valerate monotherapy and those of women without HRT. Combined oestradiol valerate — levonorgestrel replacement therapy, like oestradiol valerate monotherapy, prevents the progression of atherosclerosis in postmenopausal women. The lipid patterns were not adversely affected by the addition of the androgenic levonorgestrel.     

Role of genetic variant A-204C of cholesterol 7alpha-hydroxylase (CYP7A1) in susceptibility to gallbladder cancer

Gallbladder carcinoma (GBC) usually arises in the background of gallstone disease. Cholesterol 7alpha-hydroxylase (CYP7A1) is a rate-limiting enzyme for cholesterol catabolism and bile acid synthesis. A-204C genetic polymorphism in CYP7A1 may influence gene expression and thus affect the risk of gallstone disease and GBC. We aimed to study the association of A-204C variation of CYP7A1 gene promoter polymorphism in GBC patients, gallstone patients and healthy subjects. The study included 141 histopathologically proven GBC patients, ultrasonographically proven 185 symptomatic gallstone patients and 200 gallstone-free healthy subjects. Genotyping was done by PCR-RFLP method. CYP7A1 A-204C genotypes in control population were in Hardy-Weinberg equilibrium. The CC genotype conferred marginally significant risk for gallstone disease (p=0.051; OR=1.54; 95% CI=0.9-3.4). In GBC patients, the CYP7A1 A-204C polymorphism conferred high risk for GBC at genotype (p=0.005; OR=2.78; 95% CI: 1.3-5.6) as well as allele levels (p=0.008; OR=1.58 and 95% CI: 1.1-2.2). After stratification of GBC patients on the basis of presence or absence of gallstones, CC genotype imparted higher risk for GBC without stones (p=0.002; OR=4.44: 95% CI=1.7-11.3). The association of the polymorphism with GBC was more pronounced in female GBC patients, and also in cancer patients who developed GBC at advanced age. The CC genotype of CYP7A1 is an independent genetic risk factor for GBC but plays a modest role in susceptibility to gallstone disease. The GBC pathogenesis by CYP7A1 polymorphism appears to be independent of gallstone pathway and probably involves genotoxicity due to lipid peroxidation mechanisms.     

Cardiovascular risk factors are associated with subclinical atherosclerosis in high functioning older adults

Background

The prevalence of subclinical atherosclerosis and its relationship with cardiovascular risk factors (CVRFs) is not well known in high functioning older adults. These data can help to decide if the implementation of preventive measures is necessary in this population.

Objective

To determine the prevalence and progression of subclinical atherosclerosis in high functioning older adults, the relationship between subclinical atherosclerosis and CVRFs, and the influence of the CVRFs on subclinical atherosclerosis progression.

Methods

Longitudinal cohort study. 246 high functioning older adults without clinical atherosclerotic disease. All subjects underwent carotid Doppler ultrasound at entry and 176 at 24 months.

Results

Plaque was observed in 146 (59.3%) subjects at baseline. CVRFs showed a linear relationship to the presence of plaque: plaque was observed in 32% of subjects with no CVRFs, 54.2% with 1 factor, 61.6% with 2 factors, and 69.3% with 3 or more (p = .001). Only hypertension was independently associated with the presence of plaque (OR 2.0; 95% CI 1.2–3.6; p = .013), adjusted for CVRFs. At 24 months, new plaque was observed in 20 (11.4%) subjects and carotid intima-media thickness had increased 0.02 mm per year. Subjects with plaque at baseline had a higher risk of greater total carotid plaque diameter at 2 years (OR 58.0; 95% CI, 19.7–170.5; p < .001), adjusted for all other CVRFs.

Conclusions

Subclinical atherosclerosis is common in high functioning older adults and is associated with the classic CVRFs. Controlling these factors could be helpful in reducing atherosclerosis in older patients.