Impact of Male Origin Microchimerism on Cardiovascular Disease in Women: A Prospective Cohort Study

Author(s):  
Sara Hallum ◽  
Thomas Alexander Gerds ◽  
Thomas Steen Gyldenstierne Sehested ◽  
Marianne Antonius Jakobsen ◽  
Anne Tjønneland ◽  
...  

Abstract Increasing parity is associated with an increased risk of ischemic heart disease (IHD) and stroke in women. This is likely attributed to biological responses of pregnancy. Male cells of presumed fetal origin are commonly present in women years after pregnancy—a phenomenon termed male origin microchimerism. Here, we investigated whether male origin microchimerism was associated with risk of IHD and ischemic stroke in women. We evaluated the association between male origin microchimerism and ischemic events in a cohort of 766 Danish women enrolled in the Diet, Cancer and Health cohort during 1993–1997 when aged 50–64 years. Of these, 545 (71.2%) tested positive for male origin microchimerism by targeting the Y-chromosome (DYS14) in women’s blood. Multiple Cox regression models were used to report hazard ratios with 95% confidence intervals. We found male origin microchimerism was associated with a significantly reduced rate of IHD (HR=0.44, 95% CI: 0.23, 0.83), but not ischemic stroke (HR=0.80, 95% CI: 0.46, 1.41). Our findings show that microchimerism-positivity is associated with a lower rate of later IHD development in women. Although the underlying mechanisms are presently unknown, male origin microchimerism may be relevant in women’s cardiovascular health. More studies are needed to confirm these findings.

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Oluwaseun Fashanu ◽  
Anas Bizanti ◽  
Ahmad Al-Abdouh ◽  
Di Zhao ◽  
Matthew J Budoff ◽  
...  

Introduction: Stroke is a leading cause of morbidity and mortality in the United States. Identification of individuals at risk for stroke is important for implementation of preventive therapies. Prevalent valvular calcification (VC) has been shown to be associated with stroke but less is known about associations of VC progression with stroke. Methods: Progression (interval increase >0 Agatston units/year) of aortic valvular calcification (AVC) and mitral annular calcification (MAC) was assessed by two cardiac CTs over a median of 2.4 years. We determined the risk of adjudicated total and ischemic stroke using Cox regression adjusted for cardiovascular disease (CVD) risk factors. Results: We studied 5,606 multiethnic participants (39.6% White, 26.9% Black, 21.4% Hispanic, 12.2% Chinese) free of baseline CVD enrolled in MESA. Baseline mean ± SD age was 62 ± 10 years; 53% were women; 12% had prevalent AVC and 9% prevalent MAC at the baseline visit; 83% had no progression of VC, 14%, progression at one site (AVC or MAC), and 3% progression at both sites (AVC and MAC) at follow-up. Over a median of 12 years, 214 total and 170 ischemic strokes occurred. The number of sites with VC progression (range 0-2) was not associated with total and ischemic stroke (all p>0.05). We found MAC progression to be associated with increased risk of total stroke [adjusted hazard ratios (95% CI) 1.59 (1.11 - 2.27)] and ischemic stroke [1.64 (1.10 - 2.43)] in the whole cohort (model 3) and after further adjustment for baseline coronary artery calcification (model 4) ( Table ). Results remained significant for total stroke risk after excluding participants with interim atrial fibrillation or coronary heart disease [1.60 (1.01 - 2.54)]. In women, AVC progression was associated with ischemic stroke [1.87 (1.04 - 3.36)] (p-for-interaction=0.03). Conclusion: Progression of MAC over 2.4 years is associated with increased risk of total and ischemic stroke, and in women, AVC progression with higher ischemic stroke risk.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 78-78 ◽  
Author(s):  
Lara Sigurdardottir ◽  
Unnur Anna Valdimarsdottir ◽  
Lorelei Mucci ◽  
Katja Fall ◽  
Jennifer R. Rider ◽  
...  

78 Background: While a large number of studies have reported a positive association between sleep disruption and breast cancer, little is known about its potential role in prostate cancer. Methods: Within the prospective AGES-Reykjavik cohort study, we followed 2102 men from 2002-2006 until the end of 2009. The men answered questions on sleep disturbances, which were combined in various ways to reflect onset and/or maintenance insomnia. Information on the occurrence of prostate cancer was obtained through record-linkages across the Icelandic Cancer and Causes of Death Registers. We used Cox regression models with 95% confidence intervals [CIs] to estimate age- and multivariable adjusted hazard ratios [HR] of prostate cancer by symptoms of insomnia. Results: During follow-up, 135 men (6,4%) were diagnosed with prostate cancer. Compared to men without insomnia, men with severe onset and maintenance insomnia and very severe insomnia were at increased risk of total prostate cancer with HR 1.9 (CI 1.2, 3.0) and 2.2 (CI 1.3, 3.8), respectively. For advanced prostate cancer, the corresponding HRs were 2.3 (CI 0.9-6.2) and 3.7 (CI 1.4-9.9), respectively. Conclusions: These data suggest that insomnia may confer an increased risk of prostate cancer. Reduced melatonin levels represent a plausible biological explanation, although additional studies using biomarkers and longer follow-up times are needed to further clarify the underlying mechanisms.


2021 ◽  
Vol 23 (3) ◽  
pp. 312-326
Author(s):  
Sherif Hafez ◽  
Zeina Eid ◽  
Sara Alabasi ◽  
Yasenya Darwiche ◽  
Sara Channaoui ◽  
...  

Ischemic stroke is a leading cause of death and disability. Tissue plasminogen activator is the only U.S. Food and Drug Administration approved thrombolytic therapy for ischemic stroke patients till date. However, its use is limited due to increased risk of bleeding and narrow therapeutic window. Most of the preclinically tested pharmacological agents failed to be translated to the clinic. This drives the need for alternative therapeutic approaches that not only provide enhanced neuroprotection, but also reduce the risk of stroke. Physical exercise is a sort of preconditioning that provides the body with brief ischemic episodes that can protect the body from subsequent severe ischemic attacks like stroke. Physical exercise is known to improve cardiovascular health. However, its role in providing neuroprotection in stroke is not clear. Clinical observational studies showed a correlation between regular physical exercise and reduced risk and severity of ischemic stroke and better outcomes after stroke. However, the underlying mechanisms through which prestroke exercise can reduce the stroke injury and improve the outcomes are not completely understood. The purpose of this review is to: demonstrate the impact of exercise on stroke outcomes and show the potential role of exercise in stroke prevention and recovery; uncover the underlying mechanisms through which exercise reduces the neurovascular injury and improves stroke outcomes aiming to develop novel therapeutic approaches.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Svendsen ◽  
H.W Krogh ◽  
J Igland ◽  
G.S Tell ◽  
L.J Mundal ◽  
...  

Abstract Background and aim We have previously reported that individuals with familial hypercholesterolemia (FH) have a two-fold increased risk of acute myocardial infarction (AMI) compared with the general population. The consequences of having an AMI on re-hospitalization and mortality are however less known. The aim of the present study was to compare the risk of re-hospitalization with AMI and CHD and risk of mortality after incident (first) AMI-hospitalization between persons with and without FH (controls). Methods The original study population comprised 5691 persons diagnosed with FH during 1992–2014 and 119511 age and sex matched controls randomly selected from the general Norwegian population. We identified 221 individuals with FH and 1947 controls with an incident AMI registered in the Norwegian Patient Registry (NPR) or the Cardiovascular Disease in Norway Project during 2001–2017. Persons with incident AMI were followed until December 31st 2017 for re-hospitalization with AMI or coronary heart disease (CHD) registered in the NPR, and for mortality through linkage to the Norwegian Cause of Death Registry. Risk of re-hospitalization was compared with sub-hazard ratios (SHR) from competing risk regression with death as competing event, and mortality was compared using hazard ratios (HR) from Cox regression. All models were adjusted for age. Results Risk of re-hospitalization was 2-fold increased both for AMI [SHR=2.53 (95% CI: 1.88–3.41)] and CHD [SHR=1.82 (95% CI: 1.44–2.28)]. However, persons with FH did not have increased 28-day mortality following an incident AMI (HR=1.05 (95% CI: 0.62–1.78), but the longer-term (>28 days) mortality after first AMI was increased in FH [HR=1.45 (95% CI: 1.07–1.95]. Conclusion This study yields the important finding that persons with FH have increased risk of re-hospitalization of both AMI and CHD after incident AMI. These findings call for more intensive follow-up of individuals with FH after an AMI. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): University of Oslo and Oslo University Hospital


2018 ◽  
Vol 26 (2) ◽  
pp. 187-195 ◽  
Author(s):  
Morten Fenger-Grøn ◽  
Mogens Vestergaard ◽  
Henrik S Pedersen ◽  
Lars Frost ◽  
Erik T Parner ◽  
...  

Background Depression is associated with an increased risk of a series of cardiovascular diseases and with increased symptom burden in patients with atrial fibrillation. The aim of this study was to determine the association between depression as well as antidepressant treatment and the risk of incident atrial fibrillation. Design A nationwide register-based study comparing the atrial fibrillation risk in all Danes initiating antidepressant treatment from 2000 to 2013 ( N = 785,254) with that in a 1:5-matched sample from the general population. Methods Cox regression was used to estimate adjusted hazard ratios (aHRs) and associated 95% confidence intervals (95% CIs), both after initiation of treatment and in the month before when patients were assumed to have medically untreated depression. Results Antidepressant treatment was associated with a three-fold higher risk of atrial fibrillation during the first month (aHR = 3.18 (95% CI: 2.98–3.39)). This association gradually attenuated over the following year (aHR = 1.37 (95% CI: 1.31–1.44) 2–6 months after antidepressant therapy initiation, and aHR = 1.11 (95% CI: 1.06–1.16) 6–12 months after). However, the associated atrial fibrillation risk was even higher in the month before starting antidepressant treatment (aHR = 7.65 (95% CI: 7.05–8.30) from 30 to 15 days before, and aHR = 4.29 (95% CI: 3.94–4.67) the last 15 days before). Overall, 0.4% of patients were diagnosed with atrial fibrillation from 30 days before to 30 days after antidepressant treatment. Conclusions Antidepressant users had a substantially increased atrial fibrillation risk, particularly before treatment initiation. Whether this mirrors a causal relation between depression and atrial fibrillation may have large consequences for public health and should be discussed.


2021 ◽  
Vol 108 (Supplement_8) ◽  
Author(s):  
Bengt Novik ◽  
Gabriel Sandblom ◽  
Christoph Ansorge ◽  
Anders Thorell

Abstract Aim The HerniaSurge guidelines concerning mesh and fixation options in laparoscopic totally extraperitoneal (TEP) and transabdominal preperitoneal (TAPP) groin hernia repair are based on studies focusing on either mesh or fixation. We hypothesized that the value of such recommendations is limited by lacking knowledge on how mesh and fixation interact. The present registry-based nationwide cohort study compared different mesh/fixation combinations regarding relative risks for reoperation after TEP and TAPP. Material and Methods All TEP and TAPP with standard polypropylene (StdPPM) or lightweight (LWM) flat meshes, combined with either tacks, fibrin glue, or no fixation, registered in the Swedish Hernia Registry 2005-2017 were included. Endpoint was reoperation due to recurrence as of December 31, 2018. Multivariable Cox regression rendered relative risk differences between the exposures, expressed as hazard ratios (HR) with 95% confidence intervals (CI). Results Of 25 190 repairs, 924 (3.7%) were later reoperated for recurrence. The lowest, mutually equivalent, reoperation risks were associated with StdPPM without fixation (HR 1), StdPPM with metal tacks (HR 0.8, CI 0.4-1.4), StdPPM with fibrin glue (HR 1.1, CI 0.7-1.6), and LWM with fibrin glue (HR 1.2, CI 0.97-1.6). LWM correlated otherwise with increased risk, whether without fixation (HR 2.0, CI 1.6-2.6), or affixed with metal (HR 1.7, CI 1.1-2.7), or absorbable tacks (HR 2.4, CI 1.8-3.1). Conclusions With StdPPM, fixation seems not to improve outcomes, despite being costlier. Thus, for this mesh category, we recommend non-fixation. With LWM, we recommend fibrin glue fixation, which was the only LWM alternative on par with non-affixed StdPPM.


Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Julio Fernandez-Mendoza ◽  
Fan He ◽  
Alexandros N Vgontzas ◽  
Duanping Liao ◽  
Edward O Bixler

Introduction: It remains unknown whether individuals with chronic insomnia are at increased risk of mortality, particularly cardiovascular or cerebrovascular (CVD/CBV) mortality. Given the higher prevalence of insomnia in women than in men, it is unknown whether its prognosis in terms of mortality is also different across sexes. Hypothesis: The risk of CVD/CBV mortality associated with chronic insomnia is significantly higher than in non-complaining individuals and this risk is modified by sex. Methods: We addressed this question in the Penn State Adult Cohort, a random, general population sample of 1,741 men and women (48.7 ± 13.5 years) who were studied in the sleep laboratory and followed-up for their cause of death up to 15 years. Sleep difficulty was assessed based on three levels of severity: chronic insomnia (i.e., a complaint of chronic sleep difficulties lasting at least 1 year), poor sleep (i.e., moderate-to-severe sleep difficulties at any given time) and none (i.e., absence of either of the two categories). Cox regression models controlled for potential confounders, including age, race, body mass index, years of education, smoking, sleep disordered breathing, alcohol use, mental health problems, hypertension, diabetes, heart disease, stroke and other physical health problems. Results: Poor sleep and chronic insomnia were significantly more prevalent in females (26.7% and 10.7%, respectively) than males (17.6% and 4.1%, respectively). A significant interaction (p = 0.04) showed that the risk of CVD/CBV mortality associated with chronic insomnia was modified by male sex, while poor sleep was not significantly associated with increased risk of CVD/CBV mortality in either males or females. Chronic insomnia was associated with a 2.9-fold (95%CI=1.53-5.61) increased risk of CVD/CBV mortality in males even after adjusting for all confounders, while this risk was not significantly elevated in females (HR=1.13, 95%CI=0.56-2.31). Conclusions: Chronic insomnia is associated with increased risk of CVD/CBV mortality in males, while it has a better prognosis in females despite its higher prevalence. These data suggest potential sex-related vulnerabilities in the underlying mechanisms linking chronic insomnia with CVD/CBV morbidity and mortality.


2019 ◽  
Vol 35 (3) ◽  
pp. 295-303
Author(s):  
Sanne A. E. Peters ◽  
◽  
Ling Yang ◽  
Yu Guo ◽  
Yiping Chen ◽  
...  

AbstractPregnancy and pregnancy loss may be associated with increased risk of diabetes in later life. However, the evidence is inconsistent and sparse, especially among East Asians where reproductive patterns differ importantly from those in the West. We examined the associations of pregnancy and pregnancy loss (miscarriage, induced abortion, and still birth) with the risk of incident diabetes in later life among Chinese women. In 2004–2008, the nationwide China Kadoorie Biobank recruited 302 669 women aged 30–79 years from 10 (5 urban, 5 rural) diverse localities. During 9.2 years of follow-up, 7780 incident cases of diabetes were recorded among 273,383 women without prior diabetes and cardiovascular disease at baseline. Cox regression yielded multiple-adjusted hazard ratios (HRs) for the risk of diabetes associated with pregnancy and pregnancy loss. Overall, 99% of women had been pregnant, of whom 10%, 53%, and 6% reported having a history of miscarriage, induced abortion, and stillbirth, respectively. Among ever pregnant women, each additional pregnancy was associated with an adjusted HR of 1.04 (95% CI 1.03; 1.06) for diabetes. Compared with those without pregnancy loss, women with a history of pregnancy loss had an adjusted HR of 1.07 (1.02; 1.13) and the HRs increased with increasing number of pregnancy losses, irrespective of the number of livebirths; the adjusted HR was 1.03 (1.00; 1.05) for each additional pregnancy loss. The strength of the relationships differed marginally by type of pregnancy loss. Among Chinese women, a higher number of pregnancies and pregnancy losses were associated with a greater risk of diabetes.


Cephalalgia ◽  
2013 ◽  
Vol 34 (5) ◽  
pp. 327-335 ◽  
Author(s):  
Knut Hagen ◽  
Eystein Stordal ◽  
Mattias Linde ◽  
Timothy J Steiner ◽  
John-Anker Zwart ◽  
...  

Background Headache has not been established as a risk factor for dementia. The aim of this study was to determine whether any headache was associated with subsequent development of vascular dementia (VaD), Alzheimer’s disease (AD) or other types of dementia. Methods This prospective population-based cohort study used baseline data from the Nord-Trøndelag Health Study (HUNT 2) performed during 1995–1997 and, from the same Norwegian county, a register of cases diagnosed with dementia during 1997–2010. Participants aged ≥20 years who responded to headache questions in HUNT 2 were categorized (headache free; with any headache; with migraine; with nonmigrainous headache). Hazard ratios (HRs) for later inclusion in the dementia register were estimated using Cox regression analysis. Results Of 51,383 participants providing headache data in HUNT 2, 378 appeared in the dementia register during the follow-up period. Compared to those who were headache free, participants with any headache had increased risk of VaD ( n = 63) (multivariate-adjusted HR = 2.3, 95% CI 1.4–3.8, p = 0.002) and of mixed dementia (VaD and AD ( n = 52)) (adjusted HR = 2.0, 95% CI 1.1–3.5, p = 0.018). There was no association between any headache and later development of AD ( n = 180). Conclusion In this prospective population-based cohort study, any headache was a risk factor for development of VaD.


2016 ◽  
Vol 47 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Wesley T. O'Neal ◽  
Hooman Kamel ◽  
Dawn Kleindorfer ◽  
Suzanne E. Judd ◽  
George Howard ◽  
...  

Background: It is currently unknown if premature atrial contractions (PACs) detected on the routine screening electrocardiogram are associated with an increased risk of ischemic stroke. Methods: We examined the association between PACs and ischemic stroke in 22,975 (mean age 64 ± 9.2; 56% women; 40% black) participants from the Reasons for Geographic and Racial Differences in Stroke study. Participants who were free of stroke at baseline were included. PACs were detected from centrally read electrocardiograms at baseline. Cox regression was used to examine the association between PACs and ischemic stroke events through March 31, 2014. Results: PACs were present in 1,687 (7.3%) participants at baseline. In a Cox regression model adjusted for stroke risk factors and potential confounders, PACs were associated with an increased risk of ischemic stroke (hazards ratio (HR) 1.34, 95% CI 1.04-1.74). The relationship was limited to non-lacunar infarcts (HR 1.42, 95% CI 1.08-1.87), and not lacunar strokes (HR 1.01, 95% CI 0.51-2.03). An interaction by sex was detected, with the association between PACs and ischemic stroke being stronger among women (HR 1.82, 95% CI 1.29-2.56) than men (HR 1.03, 95% CI 0.69-1.52; p-interaction = 0.0095). Conclusion: PACs detected on the routine electrocardiogram are associated with an increased risk for non-lacunar ischemic strokes, especially in women.


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