scholarly journals Shared Genetics Between Age at Menopause, Early Menopause, POI and Other Traits

2021 ◽  
Vol 12 ◽  
Author(s):  
Yvonne V. Louwers ◽  
Jenny A. Visser
Keyword(s):  
Cardiovascular Disease ◽  
Age At Menarche ◽  
Early Age ◽  
Nucleotide Polymorphisms ◽  
Age At Menopause ◽  
Estrogen Exposure ◽  
Increased Risk ◽  
Cardiovascular Disease In Women ◽  
Reproductive Ageing ◽  
Artery Disease

Reproductive ageing leading to menopause is characterized by depletion of follicles and its regulating mechanisms are only partly understood. Early age at menopause and premature ovarian insufficiency (POI) are associated with several other traits such as cardiovascular disease, dyslipidemia, osteoporosis and diabetes. In large cohorts of Northern European women hundreds of Single Nucleotide Polymorphisms (SNPs) have been identified to be associated with age at menopause. These SNPs are located in genes enriched for immune and mitochondrial function as well as DNA repair and maintenance processes. Genetic predisposition to earlier menopause might also increase the risk of other associated traits. Increased risk for cardiovascular disease in women has been associated with age at menopause lowering SNPs. Pleiotropy between early age at menopause and increased mortality from coronary artery disease has been observed, implicating that genetic variants affecting age at menopause also affect the risk for coronary deaths. This review will discuss the shared genetics of age at menopause with other traits. Mendelian Randomization studies implicate causal genetic association between age at menopause and age at menarche, breast cancer, ovarian cancer, BMD and type 2 diabetes. Although the shared biological pathways remain to be determined, mechanisms that regulate duration of estrogen exposure remain an important focus.

scholarly journals Impact of established cardiovascular disease on 10-year death after coronary revascularization for complex coronary artery disease

2021 ◽  
Author(s):  
Rutao Wang ◽  
Scot Garg ◽  
Chao Gao ◽  
Hideyuki Kawashima ◽  
Masafumi Ono ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Revascularization ◽  
Long Term Outcomes ◽  
Vital Status ◽  
Increased Risk ◽  
Artery Disease ◽  
The Impact

Abstract Aims To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD). Methods The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD. Results Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08–1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83–1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11–4.23, p < 0.001) compared to those without CVD. Conclusions The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

scholarly journals Risk factors mediating the effect of body-mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis

2020 ◽  
Author(s):  
Dipender Gill ◽  
Verena Zuber ◽  
Jesse Dawson ◽  
Jonathan Pearson-Stuttard ◽  
Alice R Carter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Body Mass Index ◽  
Body Mass ◽  
European Ancestry ◽  
Standard Deviation Increase ◽  
Waist To Hip Ratio ◽  
Increased Risk ◽  
Artery Disease

Background: Higher body-mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits and smoking is not fully understood. Methods: Using consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, MR mediation analysis was performed to investigate the degree to which genetically predicted systolic blood pressure (SBP), diabetes, lipid traits and smoking mediated an effect of genetically predicted BMI and WHR on risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke. Results: The 49% (95% confidence interval [CI] 39%-60%) increased risk of CAD conferred per 1-standard deviation increase in genetically predicted BMI attenuated to 34% (95% CI 24%-45%) after adjusting for genetically predicted SBP, to 27% (95% CI 17%-37%) after adjusting for genetically predicted diabetes, to 47% (95% CI 36%-59%) after adjusting for genetically predicted lipids, and to 46% (95% CI 34%-58%) after adjusting for genetically predicted smoking. Adjusting for all the mediators together, the increased risk attenuated to 14% (95% CI 4%-26%). A similar pattern of attenuation was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcomes. Conclusions: Measures to reduce obesity will lower risk of cardiovascular disease primarily by impacting on downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongside control and management of its mediators is likely to be most effective for minimizing the burden of obesity.

scholarly journals Inflammation, depression and cardiovascular disease in women: the role of the immune system across critical reproductive events

2019 ◽  
Vol 13 ◽  
pp. 175394471985195 ◽  
Author(s):  
Gabriella F. Mattina ◽  
Ryan J. Van Lieshout ◽  
Meir Steiner
Keyword(s):  
Cardiovascular Disease ◽  
Sex Differences ◽  
Immune System ◽  
Perinatal Period ◽  
Kynurenine Pathway ◽  
Adverse Outcomes ◽  
Health History ◽  
Increased Risk ◽  
Mental Health History ◽  
Cardiovascular Disease In Women

Women are at increased risk for developing depression and cardiovascular disease (CVD) across the lifespan and their comorbidity is associated with adverse outcomes that contribute significantly to rates of morbidity and mortality in women worldwide. Immune-system activity has been implicated in the etiology of both depression and CVD, but it is unclear how inflammation contributes to sex differences in this comorbidity. This narrative review provides an updated synthesis of research examining the association of inflammation with depression and CVD, and their comorbidity in women. Recent research provides evidence of pro-inflammatory states and sex differences associated with alterations in the hypothalamic–pituitary–adrenal axis, the renin–angiotensin–aldosterone system and the serotonin/kynurenine pathway, that likely contribute to the development of depression and CVD. Changes to inflammatory cytokines in relation to reproductive periods of hormonal fluctuation (i.e. the menstrual cycle, perinatal period and menopause) are highlighted and provide a greater understanding of the unique vulnerability women experience in developing both depressed mood and adverse cardiovascular events. Inflammatory biomarkers hold substantial promise when combined with a patient’s reproductive and mental health history to aid in the prediction, identification and treatment of the women most at risk for CVD and depression. However, more research is needed to improve our understanding of the mechanisms underlying inflammation in relation to their comorbidity, and how these findings can be translated to improve women’s health.

SECULAR TREND AND INTRAPOPULATIONAL VARIATION IN AGE AT MENOPAUSE IN SPANISH WOMEN

2000 ◽  
Vol 32 (3) ◽  
pp. 383-393 ◽  
Author(s):  
C. VAREA ◽  
C. BERNIS ◽  
P. MONTERO ◽  
S. ARIAS ◽  
A. BARROSO ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Secular Trend ◽  
Fetal Loss ◽  
Ageing Process ◽  
Age At Menarche ◽  
Individual Level ◽  
Age At Menopause ◽  
Reproductive Ageing ◽  
Spanish Women ◽  
The Individual

Menopause is associated with the general ageing process and marks the end of follicular depletion, a process that begins in the intrauterine stage and lasts throughout the lifetime of women until their reproductive senescence. Controversy persists about whether the age at menopause is sensitive to the ecological determinants prevailing during the lifecycle or whether it has a predominantly genetic component that would allow groups of women to be characterized with respect to particular menstrual characteristics manifested throughout their fertile life. By contrast, there is a definite secular trend in age at menarche in populations that have registered improvements in their environment: sexual maturation is closely associated with the general processes of growth and development. These aspects were analysed in a sample of Spanish women, mothers and daughters, born between 1883 and 1941. The results show (a) indications – although not conclusive – of a secular trend in the age at menopause, (b) a possible association between the age at menopause of mothers and their daughters, and (c) an association at the individual level between age at menarche, particular characteristics of ovarian function (fetal loss) and age at menopause. The reproductive ageing process therefore seems to result from the expression of the influence of ecological conditions in which the lifecycle of the women develops and of a degree of heritability that affects not only the age at menopause but also a range of characteristics of ovarian function.

scholarly journals Association between AST to ALT ratio and peripheral artery disease in Chinese adults with hypertension：a cross-sectional study

2020 ◽  
Author(s):  
Hui Liu ◽  
Xiaoyuan Zha ◽  
Congcong Ding ◽  
Lihua Hu ◽  
Minghui Li ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Peripheral Artery Disease ◽  
Reference Group ◽  
Final Analysis ◽  
Multivariate Logistic Regression Model ◽  
Peripheral Artery ◽  
Chinese Adults ◽  
Cross Sectional ◽  
Increased Risk ◽  
Artery Disease

Abstract Background: Previous studies had shown that aspartate aminotransferase to alanine aminotransferase (AST/ALT ratio) plays a role in cardiovascular disease. Peripheral artery disease (PAD) is an important risk factor for cardiovascular disease. However, there are a little research on the association between the AST/ALT ratio and Peripheral artery disease (PAD). Methods: A total of 10, 900 hypertensive patients from the Chinese Hypertension Registry Study were included in the final analysis. The association between AST / ALT and peripheral arterial disease (PAD), which was defined as ABI ≤ 0.9 in either leg, was estimated by a multivariate logistic regression model.Results: Overall, the prevalence of PAD was 3.21%. After adjusting for potential confounders, AST / ALT ratio was independently and positively associated with the risk of PAD (OR: 1.31, 95% CI: 1.13 to 1.59), and a statistically significant increased risk of PAD for the third tertile (T3) of AST / ALT ratio compared to the first tertile (T1) (OR:1.49, 95% CI: 1.09 to 2.04, P-trend= 0.005) was found. Moreover, when the T1-T2 group was combined into one group and used it as a reference group, the risk of PAD increased with the increase of AST/ALT and the risk ratio was 1.52 (95% CI :1.20 to 1.95). Conclusion: A higher AST/ALT ratio (≥1.65) was associated with PAD risk in Chinese adults with hypertension. The presented results suggested that AST / ALT may help us highlight patients who are at high risk of vascular endpoints.Trial registration: CHICTR, CHiCTR1800017274. Registered 20 July 2018.

scholarly journals Age at menarche, age at menopause, reproductive years and risk of fatal stroke occurrence among Chinese women: the Guangzhou Biobank Cohort Study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhi-bing Hu ◽  
Ze-xiong Lu ◽  
Feng Zhu
Keyword(s):  
Cohort Study ◽  
Postmenopausal Women ◽  
Proportional Hazards ◽  
Chinese Women ◽  
Cox Proportional Hazards ◽  
Age At Menarche ◽  
Age At Menopause ◽  
Fatal Stroke ◽  
Increased Risk ◽  
Menarche Age

Abstract Background The relationship between women’s reproductive characteristics and stroke events is unclear. We aimed to investigate age at menarche, age at menopause and number of reproductive years in relation to fatal stroke occurrence in the Guangzhou Biobank Cohort Study. Methods In total, 16,504 postmenopausal women without stroke, heart disease or a cancer history at baseline were included and followed up for a median of 12.0 years. After review of available records, 222 stroke deaths were recorded. Cox proportional hazards regression was used to assess the associations between the risk of fatal stroke occurrence and age at menarche, age at menopause and number of reproductive years. Results In the whole cohort, compared with those aged 15 years at menarche, an increased risk of fatal stroke among women at menarche showed respectively in those aged 12 years (aHR (adjusted hazard ratio) = 1.86, 95% confidence interval (CI) 0.96–3.60), aged 13 years (aHR = 1.69, 95% CI 0.98–2.92), aged 17 years (aHR = 1.83, 95% CI 1.10–3.05) and aged ≥ 18 years (aHR = 1.66, 95% CI 1.03–2.70), wherein the associations revealed an atypically U-shaped; similar U-shaped association to the cohort of postmenopausal women born before 1940 released a range of incremental risks of fatal stroke in women at menarche aged ≤ 12 years (aHR = 3.68, 95% CI 1.68–8.05), aged 13 years (aHR = 2.11, 95% CI 1.02–4.34), aged 14 years (aHR = 2.07, 95% CI 1.04), aged 17 years (aHR = 2.30, 95% CI 1.20–4.39) and aged 18 years (aHR = 2.50, 95% CI 1.37–4.57), respectively. Compared with menopausal women aged 51–52 years, those aged < 43 years at menopause had an increased risk for fatal stroke among postmenopausal women born in and after 1940 (aHR = 1.64, 95% CI 0.97–2.78) and postmenopausal women born before 1940 (aHR = 1.97, 95% CI 1.05–3.69). Additionally, compared with those with 32–34 reproductive years, women with ≤ 28 reproductive years had an increased risk for fatal stroke in the whole cohort (aHR = 1.91, 95% CI 1.28–2.86) and the cohort of postmenopausal women born before 1940 (aHR = 1.79, 95% CI 1.15–2.80). Conclusions Younger and older age at menarche, younger age at menopause and fewer reproductive ages were related to an increased risk of fatal stroke in postmenopausal women.

scholarly journals Cohort profile: role of lipoproteins in cardiovascular disease—the LipidCardio study

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e030097 ◽  
Author(s):  
Maximilian König ◽  
Samita Joshi ◽  
David M Leistner ◽  
Ulf Landmesser ◽  
David Sinning ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Family History ◽  
Obstructive Coronary Artery Disease ◽  
Strong Association ◽  
Exclusion Criterion ◽  
Nucleotide Polymorphisms ◽  
Coronary Syndrome ◽  
Reasonable Evidence ◽  
Artery Disease

PurposeThe LipidCardio Study was established for in-depth analyses of cardiovascular risk factors, providing well-defined cardiovascular and metabolic phenotypes. In particular, the role of lipoproteins in the pathobiological process and treatment of cardiovascular disease (CVD) will be a main focus.Participants1005 individuals aged 21 years and older undergoing cardiac catheterisation during 17 months at a tertiary academic cardiology centre were enrolled (troponin-positive acute coronary syndrome was exclusion criterion). The baseline data not only contain detailed phenotyping, broad biochemical parameters, genetic data, but also standardised personal and family history, a screening test for cognitive impairment, pulse wave analysis and measurements of hand grip strength, among others. Blood samples were stored in a biobank for future analyses.Findings to dateThe mean age of the participants at enrolment was 70.9±11.1 years (70% male). Coronary angiography provided evidence of obstructive coronary artery disease (CAD) in 69.9% of participants. Those with evidence of CAD were significantly more likely to be male, inactive, diabetic and with a family history of CVD than participants without CAD.About 20% of patients had lipoprotein(a) (Lp(a)) concentrations above 106.9 nmol/L (fifth quintile). These patients had significantly increased odds of obstructive CAD compared with participants in quintiles 1–4 (crude OR 1.70, 95% CI 1.17 to 2.48, p=0.005). There was reasonable evidence that with increasing severity of CAD the odds of having elevated Lp(a) increased. We were able to replicate the established strong association between specified single nucleotide polymorphisms (SNPs) in theLPAgene (rs10455872, rs3798220 and rs186696265) and theAPOEgene (rs7412), and the concentration of Lp(a), validating our phenotype database and biobank.Future plansMortality information will be obtained in 2 year intervals. Follow-up phone interviews will be conducted at 3 and 6 years after enrolment. We seek to cooperate with other researchers, for example, by sharing data and biobank samples.

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