Increased risk of atherosclerosis in women after the menopause.

Bonithon‐Kopp, Claire; Scarabin, Pierre‐Yves; Taquet, AN; Touboul, Pierre‐Jean; Damé, B.; Guize, L

doi:10.1136/bmj.298.6683.1311-b

Cited by 10 publications

(8 citation statements)

References 4 publications

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“…Often, these age‐related changes differ among the sexes. For example, total cholesterol levels tend to peak around age 50 in men (Kronmal et al, ; Jousilahti et al, ) and at menopause in women (Hjortland et al, ; Bonithon‐Kopp et al, ; Matthews et al, ). Why lipid levels change over time is likely due to a number of factors, but whether or not the genetic effects of variants important in lipid metabolism vary with age has yet to be thoroughly explored.…”

Section: Introductionmentioning

confidence: 99%

Post-Genome-Wide Association Study Challenges for Lipid Traits: Describing Age as a Modifier of Gene-Lipid Associations in the Population Architecture Using Genomics and Epidemiology (PAGE) Study

Dumitrescu

Carty

Franceschini

et al. 2013

Annals of Human Genetics

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Summary Numerous common genetic variants that influence plasma high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) distributions have been identified via genome-wide association studies (GWAS). However, whether or not these associations are age dependent has largely been overlooked. We conducted an association study and meta-analysis in more than 22,000 European Americans between 49 previously identified GWAS variants and the three lipid traits, stratified by age (males: <50 or ≥50 years of age; females: pre- or post-menopausal). For each variant, a test of heterogeneity was performed between the two age strata and significant Phet values were used as evidence of age-specific genetic effects. We identified seven associations in females and eight in males that displayed suggestive heterogeneity by age (Phet<0.05). The association between rs174547 (FADS1) and LDL-C in males displayed the most evidence for heterogeneity between age groups (Phet=1.74E-03, I2=89.8), with a significant association in older males (P=1.39E-06) but not younger males (P=0.99). However, none of the suggestive modifying effects survived adjustment for multiple testing, highlighting the challenges of identifying modifiers of modest SNP-trait associations despite large sample sizes.

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Section: Introductionmentioning

confidence: 99%

Post-Genome-Wide Association Study Challenges for Lipid Traits: Describing Age as a Modifier of Gene-Lipid Associations in the Population Architecture Using Genomics and Epidemiology (PAGE) Study

Dumitrescu

Carty

Franceschini

et al. 2013

Annals of Human Genetics

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“…There is a very substantial increase in the risk of both CHD 4 and atherosclerosis 5 among women after surgical menopause. For natural menopause, mortality data from the United Kingdom 6 and the United States 7 do not show an abrupt change in mortality rates near the age of menopause.…”

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confidence: 99%

Serum estrone concentrations and coronary artery disease in postmenopausal women.

Cauley

Gutai

Glynn

et al. 1994

Arterioscler Thromb

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Little is known about the relation between serum sex hormones and either coronary heart disease or the development of atherosclerosis in women. We measured serum estrone concentrations in 87 postmenopausal women (age, 50 to 81 years) who were admitted for diagnostic cardiac catheterization. None of the women were on estrogen replacement therapy. Cases (n=62) were defined as those women who had si coronary artery with £50% occlusion. All control subjects (n=25) had 0% to 24% occlusion of all coronary arteries. Estrone concentrations, as measured by a combination of extraction, column chromatography, and radioimmunoassay, showed little difference between cases and control subjects. A difference of 6 pg/mL in the estrone level was not associated with a significantly increased risk of coronary artery disease (odds ratio [OR], 1.85; 95% confidence intervals [CI], 0.60, 5.2). Examination of mean estrone levels on the basis of the number of occluded vessels was also not significant. The primary predictors of coronary artery disease in this population were a history of diabetes (OR, 8.8; CI, 1.5, 51.4) and age (5-year increments; OR, 2.1; CI, 1.2, 3.8). There was also some suggestion that women who reported higher lifetime physical activity levels were at a reduced risk for developing coronary artery disease (OR, 0.18; CI, 0.05, 0.65). These preliminary results do not support the hypothesis that serum estrogens are related to coronary artery disease in older women, but these findings need to be replicated in larger populations of older women. (ArterioscUr Thromb. 1994 There are approximately 250 000 deaths in women due to heart disease each year in the United States. The observations of a predominance of CHD among men, the diminishing differences in CHD rates in males versus females with increasing age, comparison of the risk of CHD across menopause, data on the use of oral contraceptives and noncontraceptive estrogens, and the risk of CHD strongly suggest that hormonal factors, specifically sex hormones, may play a major role in the development of CHD. The relation of serum sex hormones to both fatal and nonfatal CHD 2 and to the extent of atherosclerosis 3 has been examined in men. In contrast, little is known about the relation of serum sex hormones to CHD or to the development of atherosclerosis in women.There is a very substantial increase in the risk of both CHD 4 and atherosclerosis 5 among women after surgical menopause. For natural menopause, mortality data from the United Kingdom 6 and the United States 7 do not show an abrupt change in mortality rates near the age of menopause. However, data from the Framingham Study suggest that female CHD morbidity rates accelerate more quickly than do those of males after age 45. There has also been considerable research on the relation of exogenous estrogens to CHD in women. On the basis of a critical review and meta-analysis of all epidemiological data, Bush 9 has estimated that long-term use of postmenopausal estrogen decreases the risk of cardiovascular diseas...

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“…There is a very substantial increase in the risk both of coronary heart disease [24] and atheroscle rosis [25] among women after surgical meno pause. Human epidemiological studies [26] indicate that estrogen replacement therapy re duces the risk of coronary heart disease.…”

Section: Discussionmentioning

confidence: 99%

Effects of Sex Hormones on Cyclic Nucleotide Metabolism in Cultured Bovine Aortic Endothelial Cells

Ahmad

1995

Cell Physiol Biochem

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The effects of testosterone and estradiol on the regulation of the cyclic nucleotide metabolism in primary cultured endothelial cells from bovine aortae were examined. Testosterone added 24 h after plating increased the adenosine 3’,5’-cyclic monophosphate (cAMP) concentration from 20.3 to 40.6 pmol/mg protein, whereas the guanosine 3’,5’-cyclic monophosphate (cGMP) level decreased from 1.9 to 0.8 pmol/mg protein over a 5-day period. Estradiol increased cAMP from 20.3 to 30.3 pmol/mg protein and increased cGMP from 1.9 to 3.5 pmol/mg protein. The action of testosterone was potentiated by the addition of 10 mM theophylline. The basal level of the adenylate cyclase activity in control cells and the elevated level in treated cells were stimulated by sodium fluoride. In the presence of isobutylmethylxanthine, prostacyclin produced the most significant stimulation followed by isoproterenol and prostaglandin E₁. In contrast, phenylephrine failed to stimulate the adenylate cyclase activity significantly. Testosterone added to subconfluent cultures at a low concentration (1 × 10^–9M) failed to stimulate adenylate cyclase, but did inhibit low-K_m phosphodiesterase (p < 0.05). A high concentration (1 × 10^–7M) of testosterone stimulated the adenylate cyclase activity, markedly decreased the activities of high- and low-K_m phosphodiesterase, and caused a reduction in matrix fibronectin, rearrangement of actin, and a change in cell surface topography. This study showed that testosterone induced a major change in endothelial cell cyclic nucleotide metabolism by modulating the activities of adenylate cyclase and cAMP phosphodiesterase, whereas estradiol induced a major change in cGMP metabolism.

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Increased risk of atherosclerosis in women after the menopause.

Cited by 10 publications

References 4 publications

Post-Genome-Wide Association Study Challenges for Lipid Traits: Describing Age as a Modifier of Gene-Lipid Associations in the Population Architecture Using Genomics and Epidemiology (PAGE) Study

Post-Genome-Wide Association Study Challenges for Lipid Traits: Describing Age as a Modifier of Gene-Lipid Associations in the Population Architecture Using Genomics and Epidemiology (PAGE) Study

Serum estrone concentrations and coronary artery disease in postmenopausal women.

Effects of Sex Hormones on Cyclic Nucleotide Metabolism in Cultured Bovine Aortic Endothelial Cells

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