scholarly journals Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women

Circulation ◽  
2020 ◽  
Author(s):  
Michael C. Honigberg ◽  
S. Maryam Zekavat ◽  
Abhishek Niroula ◽  
Gabriel K. Griffin ◽  
Alexander G. Bick ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Postmenopausal Women ◽  
Premature Menopause ◽  
Cox Models ◽  
Clonal Hematopoiesis ◽  
Age Related ◽  
Artery Disease ◽  
The Uk

Background: Premature menopause is an independent risk factor for cardiovascular disease in women, but mechanisms underlying this association remain unclear. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of hematopoietic cells with leukemogenic mutations without detectable malignancy, is associated with accelerated atherosclerosis. Whether premature menopause is associated with CHIP is unknown. Methods: We included postmenopausal women from the UK Biobank (N=11,495) aged 40-70 years with whole exome sequences and from the Women's Health Initiative (WHI, N=8,111) aged 50-79 years with whole genome sequences. Premature menopause was defined as natural or surgical menopause occurring before age 40 years. Co-primary outcomes were the presence of (1) any CHIP and (2) CHIP with variant allele frequency (VAF) >0.1. Logistic regression tested the association of premature menopause with CHIP, adjusted for age, race, the first 10 principal components of ancestry, smoking, diabetes mellitus, and hormone therapy use. Secondary analyses considered natural vs. surgical premature menopause and gene-specific CHIP subtypes. Multivariable-adjusted Cox models tested the association between CHIP and incident coronary artery disease (CAD). Results: The sample included 19,606 women, including 418 (2.1%) with natural premature menopause and 887 (4.5%) with surgical premature menopause. Across cohorts, CHIP prevalence in postmenopausal women with vs. without a history of premature menopause was 8.8% vs. 5.5% (P<0.001), respectively. After multivariable adjustment, premature menopause was independently associated with CHIP (all CHIP: OR 1.36, 95% 1.10-1.68, P=0.004; CHIP with VAF >0.1: OR 1.40, 95% CI 1.10-1.79, P=0.007). Associations were larger for natural premature menopause (all CHIP: OR 1.73, 95% CI 1.23-2.44, P=0.001; CHIP with VAF >0.1: OR 1.91, 95% CI 1.30-2.80, P<0.001) but smaller and non-significant for surgical premature menopause. In gene-specific analyses, only DNMT3A CHIP was significantly associated with premature menopause. Among postmenopausal middle-aged women, CHIP was independently associated with incident coronary artery disease (HR associated with all CHIP: 1.36, 95% CI 1.07-1.73, P=0.012; HR associated with CHIP with VAF >0.1: 1.48, 95% CI 1.13-1.94, P=0.005). Conclusions: Premature menopause, especially natural premature menopause, is independently associated with CHIP among postmenopausal women. Natural premature menopause may serve as a risk signal for predilection to develop CHIP and CHIP-associated cardiovascular disease.

Abstract 15887: Clonal Hematopoiesis Links Premature Menopause to Cardiovascular Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Michael C Honigberg ◽  
Seyedeh Zekavat ◽  
Abhishek Niroula ◽  
Gabirel K Griffin ◽  
Alexander G Bick ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Strong Association ◽  
Premature Menopause ◽  
Uk Biobank ◽  
Clonal Hematopoiesis ◽  
Age Related ◽  
Cardiovascular Disease In Women ◽  
History Of ◽  
Artery Disease ◽  
The Uk

Introduction: Premature menopause is an independent risk factor for cardiovascular disease in women, but mechanisms underlying this association remain unclear. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of hematopoietic cells with leukemogenic mutations, is associated with accelerated atherosclerosis. Whether premature menopause is associated with CHIP is unknown. Methods: We included postmenopausal women from the UK Biobank (N=11,509) aged 40-70 years with whole exome sequences and from the Women’s Health Initiative (WHI, N=8,111) aged 50-79 years with whole genome sequences. Premature menopause was defined as natural or surgical menopause occurring before age 40 years. Co-primary outcomes were the presence of (1) any CHIP and (2) CHIP with variant allele fraction (VAF) >0.1. Logistic regression tested the association of premature menopause with CHIP, adjusted for age, race, the first 10 principal components, smoking, diabetes mellitus, and hormone therapy use. Results: Across cohorts, prevalence of CHIP in women with vs. without a history of premature menopause was 8.8% vs. 5.5% (P<0.001), respectively. After multivariable adjustment, premature menopause was independently associated with CHIP, driven by associations with natural premature menopause (OR for all CHIP: 1.73, 95% CI 1.23-2.44; OR for CHIP with VAF >0.1: 1.91, 95% CI 1.30-2.80; Figure ). In gene-specific analyses, DNMT3A CHIP had a strong association with natural premature menopause but no association with surgical premature menopause. Among postmenopausal middle-aged women in the UK Biobank and WHI, CHIP was independently associated with incident coronary artery disease (meta-analyzed HR 1.52, 95% CI 1.17-1.99). Conclusions: Premature menopause, especially natural premature menopause, is independently associated with CHIP. CHIP may contribute to the excess cardiovascular risk associated with premature menopause.

Short-term Anti-Ischemic Effect of 17β-Estradiol in Postmenopausal Women With Coronary Artery Disease

Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 2837-2841 ◽  
Author(s):  
Giuseppe M.C. Rosano ◽  
Adriano Mendes Caixeta ◽  
Sergio Chierchia ◽  
Siguemituzo Arie ◽  
Miguel Lopez-Hidalgo ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Postmenopausal Women ◽  
Short Term ◽  
17Β Estradiol ◽  
Artery Disease

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

Inflammatory response of coronary artery disease postmenopausal women is associated with the IVS1-397T > C estrogen receptor α polymorphism

2009 ◽  
Vol 130 (3) ◽  
pp. 355-364 ◽  
Author(s):  
Jolanta Myśliwska ◽  
Aleksandra Rutkowska ◽  
Łukasz Hak ◽  
Janusz Siebert ◽  
Krzysztof Szyndler ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Estrogen Receptor ◽  
Coronary Artery ◽  
Inflammatory Response ◽  
Postmenopausal Women ◽  
Estrogen Receptor Α ◽  
Artery Disease

scholarly journals Plasma alkylresorcinols, biomarkers of whole-grain intake, are not associated with progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease

2015 ◽  
Vol 19 (2) ◽  
pp. 326-331 ◽  
Author(s):  
Nicola M McKeown ◽  
Adela Hruby ◽  
Rikard Landberg ◽  
David M Herrington ◽  
Alice H Lichtenstein
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Postmenopausal Women ◽  
Vessel Diameter ◽  
Whole Grains ◽  
Plasma Samples ◽  
Whole Grain ◽  
Coronary Artery Atherosclerosis ◽  
Artery Disease ◽  
Change In Mean

AbstractObjectiveThe objective of the present study was to examine the relationship between plasma alkyresorcinol (AR) concentrations, which are biomarkers of whole-grain intake, and atherosclerotic progression over 3 years in postmenopausal women with coronary artery disease.DesignPlasma AR concentrations were measured by a validated GC–MS method in fasting plasma samples. Atherosclerosis progression was assessed using change in mean minimal coronary artery diameter (MCAD) and percentage diameter stenosis (%ST), based on mean proximal vessel diameter across up to ten coronary segments. Dietary intake was estimated using a 126-item interviewer-administered FFQ.SettingA prospective study of postmenopausal women participating in the Estrogen Replacement and Atherosclerosis trial.SubjectsFor the analysis of plasma AR concentrations and atherosclerotic progression, plasma samples and follow-up data on angiography were available for 182 women.ResultsMean whole-grain intake was 9·6 (se 0·6) servings per week. After multivariate adjustment, no significant associations were observed between plasma AR concentrations and change in mean MCAD or progression of %ST. Plasma AR concentrations were significantly correlated with dietary whole grains (r=0·35, P<0·001), cereal fibre (r=0·33, P<0·001), bran (r=0·15, P=0·05), total fibre (r=0·22, P=0·003) and legume fibre (r=0·15, P=0·04), but not refined grains, fruit fibre or vegetable fibre.ConclusionsPlasma AR concentrations were not significantly associated with coronary artery progression over a 3-year period in postmenopausal women with coronary artery disease. A moderate association was observed between plasma AR concentrations and dietary whole grains and cereal fibre, suggesting it may be a useful biomarker in observational studies.

CYP3A4 *1B Gene Polymorphism in Coronary Artery Disease Patients with Obesity Undergoing Statin Treatment

2021 ◽  
Vol 18 ◽  
Author(s):  
Elifcan Gezer ◽  
Mehtap Cevik ◽  
Cansu Selcan Akdeniz ◽  
Ismail Polat Canbolat ◽  
Selen Yurdakul ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Statin Therapy ◽  
Plasma Lipid ◽  
Blood Cholesterol ◽  
Study Group ◽  
Genotype Distribution ◽  
Obese Patients ◽  
Artery Disease

Objective: Coronary artery disease (CAD) is the one of the leading cause of morbidity and mortality worldwide and statins are frequently prescribed in the treatment of CAD to help lower blood cholesterol levels. Since the main enzyme involved in the metabolism of statins is CYP3A4, we aimed to investigate the effect of CYP3A4 * 1B genotypes on plasma lipid profile in Turkish cardiovascular disease subject with and without obesity taking statin. Materials and Methods: The study group consisted of 85 cardiovascular disease patients who were prescribed statins and had routine biochemical analysis data. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) assay were performed for genotyping of CYP3A4 *1B (rs2740574) polymorphism. Results: Genotype distribution of CYP3A4 *1B polymorphism was found for homozygous wild (AA) and homozygous polymorphic (GG) genotypes as 94.1% and 5.9% respectively. We did not detect patients with heterozygous genotype in our study group. We found that the mean LDL-c, TG and TC levels were higher in patients with CYP3A4 *1B GG compared to AA genotype. The frequency of CYP3A4 *1B GG genotype frequency (9.5%) was detected higher in the obese patients compared to the non-obese patients (7.7%) (χ2=0.037, p=0.85). Conclusions: Our results demonstrate that CYP3A4 *1B homozygous polymorphic genotype distribution tend to be higher in obese patients compared to non- obese patients with cardiovascular disease which may point *1B allele to have a slight effect on serum lipids during statin therapy. Additional studies with higher samples are needed for evaluating the role of CYP3A4 *1B on lipids in patients under statin therapy.

scholarly journals Epicardial Adipose Tissue as a Source of Nuclear Factor-κB and c-Jun N-Terminal Kinase Mediated Inflammation in Patients with Coronary Artery Disease

2009 ◽  
Vol 94 (1) ◽  
pp. 261-267 ◽  
Author(s):  
A. R. Baker ◽  
A. L. Harte ◽  
N. Howell ◽  
D. C. Pritlove ◽  
A. M. Ranasinghe ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Inflammatory Profile ◽  
Artery Disease ◽  
And Control

Abstract Context: Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated. Objectives: The objectives of the study were to: 1) examine key mediators of the nuclear factor-κB (NFκB) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects. Design: Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies. Results: Western blotting showed epicardial AT had significantly higher NFκB, inhibitory-κB kinase (IKK)-γ, IKKβ, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-α. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 ± 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 ± 0.57 EU/ml; P&lt;0.05]. Conclusion: Epicardial AT from patients with CAD shows increased NFκB, IKKβ, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NFκB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue.

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