Relation between platelet coagulant and vascular function, sex-specific analysis in adult survivors of childhood cancer compared to a population-based sample

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Abstract

Female sex is a risk factor for long-term adverse outcome in cancer survivors, however very little is known for the underlying pathophysiological mechanisms rendering the increased risk. This study investigated sex-specifically the relation between thrombin generation (TG) with and without presence of platelets and vascular function in 200 adult survivors of a childhood cancer compared to 335 population-based control individuals. TG lag time, peak height and endogenous thrombin potential (ETP) measured in presence and absence of platelets were correlated to reflection index (RI) and stiffness index (SI). A sex-specific correlation analysis showed a negative relation in female survivors for platelet-dependent peak height and/or ETP and RI only. An age adjusted linear regression model confirmed the negative association between RI and platelet-dependent ETP (beta estimate: −6.85, 95% confidence interval: −12.19,−1.51) in females. Adjustment for cardiovascular risk factors resulted in loss of the association, whereby arterial hypertension and obesity showed the largest effects on the observed association. No other relevant associations were found in male and female cancer survivors and all population-based controls. This study demonstrates a link between platelet coagulant and vascular function of resistance vessels, found in female cancer survivors, potentially mediated by the presence of arterial hypertension and obesity.

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Most cited references 23

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Why women live longer than men: sex differences in longevity.

Steven Austad (2006)

Historically, women have lived longer than men in almost every country in the world. A similar pattern of sex differences in longevity is also found in many other species; however, it is not clear if there are more species in which females live longer or vice versa. For virtually all the primary causes of death and at virtually all ages, mortality rates are higher for men. Women do not live longer than men because they age more slowly, but because they are more robust at every age. Paradoxically, although women have lower mortality rates they have higher overall rates of physical illness than do men. Several hypotheses have been proposed for sex differences in longevity, including more active female immune functioning, the protective effect of estrogen, compensatory effects of the second X chromosome, reduction in the activity of growth hormone and the insulin-like growth factor 1 signaling cascade, and the influence of oxidative stress on aging and disease. At present, none of these hypotheses are strongly supported, although weak support is available for the oxidative stress hypothesis. With the advent of more rapid genome sequencing, molecular tools will become available for more species, thus further detailing the causes for the differences in longevity between the sexes.

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Differences between Men and Women in Mortality and the Health Dimensions of the Morbidity Process

Eileen M. Crimmins, Hyunju Shim, Yuan S Zhang … (2019)

Do men have worse health than women? This question is addressed by examining sex differences in mortality and the health dimensions of the morbidity process that characterize health change with age. We also discuss health differences across historical time and between countries. Results from national-level surveys and data systems are used to identify male/female differences in mortality rates, prevalence of diseases, physical functioning, and indicators of physiological status. Male/female differences in health outcomes depend on epidemiological and social circumstances and behaviors, and many are not consistent across historical time and between countries. In all countries, male life expectancy is now lower than female life expectancy, but this was not true in the past. In most countries, women have more problems performing instrumental activities of daily living, and men do better in measured performance of functioning. Men tend to have more cardiovascular diseases; women, more inflammatory-related diseases. Sex differences in major cardiovascular risk factors vary between countries—men tend to have more hypertension; women, more raised lipids. Indicators of physiological dysregulation indicate greater inflammatory activity for women and generally higher cardiovascular risk for men, although women have higher or similar cardiovascular risk in some markers depending on the historical time and country. In some aspects of health, men do worse; in others, women do worse. The lack of consistency across historical times and between countries in sex differences in health points to the complexity and the substantial challenges in extrapolating future trends in sex differences.

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Noninvasive vascular function measurement in the community: cross-sectional relations and comparison of methods.

Ascan Warnholtz, Philipp Wild, Renate B. Schnabel … (2011)

Several methods of noninvasive vascular function testing have been suggested for cardiovascular risk screening in the community. A direct comparison of the different methods and their relation to classical cardiovascular risk factors in a large cohort is missing. In 5000 individuals (mean age, 55.5 ± 10.9 years; age range, 35 to 74 years; women, 49.2%) of the population-based Gutenberg Heart Study, we performed simultaneous measurement of flow-mediated dilation (FMD) and peripheral arterial volume pulse determined by infrared photo (reflection index) and pneumatic plethysmography (PAT) and explored their associations. All function measures were recorded at baseline and after reactive hyperemia induced by 5-minute brachial artery occlusion. Correlations between different measures of vascular function were statistically significant but moderate. The strongest association for hyperemic response variables was observed for PAT ratio and FMD (Spearman r = 0.17; age- and sex-adjusted partial correlation, 0.068). Classical risk factors explained between 15.8% (baseline reflection index) and 58.4% (brachial artery diameter) of the baseline values but only accounted for 3.2% (reflection index), 15.4% (FMD), and 13.9% (PAT ratio) of the variability of reflective hyperemic response. Regression models varied in their relations to classical risk factors for the individual vascular function measures. Consistently associated with different vascular function methods were age, sex, body mass index, and indicators of hypertension. Peripheral tonometry also showed a relation to fasting glucose concentrations. Noninvasive measures of conduit artery and peripheral arterial function are modestly correlated, differ in their relation to classical cardiovascular risk factors, and may thus reflect different pathologies.

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Author and article information

Contributors

Marina Panova-Noeva: Marina.Panova-Noeva@unimedizin-mainz.de

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 27 December 2019

Publication date PMC-release: 27 December 2019

Publication date Collection: 2019

Volume: 9

Electronic Location Identifier: 20090

Affiliations

[1 ]GRID grid.410607.4, Center for Thrombosis and Hemostasis (CTH), , University Medical Center of the Johannes Gutenberg-University Mainz, ; Mainz, Germany

[2 ]GRID grid.410607.4, Preventive Cardiology and Preventive Medicine, Center for Cardiology, , University Medical Center of the Johannes Gutenberg-University Mainz, ; Mainz, Germany

[3 ]GRID grid.410607.4, Department of Pediatric Hematology/Oncology/Hemostaseology, Center for Pediatric and Adolescent Medicine, , University Medical Center of the Johannes Gutenberg-University Mainz, ; Mainz, Germany

[4 ]ISNI 0000 0004 0480 1382, GRID grid.412966.e, Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), , Maastricht University Medical Center, ; Maastricht, The Netherlands

[5 ]GRID grid.410607.4, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), , University Medical Center of the Johannes Gutenberg-University Mainz, ; Mainz, Germany

[6 ]GRID grid.410607.4, Institute for Clinical Chemistry and Laboratory Medicine, , University Medical Center of the Johannes Gutenberg-University Mainz, ; Mainz, Germany

[7 ]DZHK (German Center for Cardiovascular Research), Partner Site RhineMain, Mainz, Germany

Author information

Markus Nagler http://orcid.org/0000-0003-4942-9353

Philipp S. Wild http://orcid.org/0000-0003-4413-9752

Article

Publisher ID: 56626

DOI: 10.1038/s41598-019-56626-1

PMC ID: 6934665

PubMed ID: 31882836

SO-VID: 58a58991-0a7c-4928-93db-61dcc5af61a1

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 5 July 2019

Date accepted : 11 December 2019

Funding

Funded by: The CVSS study is funded by the Deutsche Forschungsgemeinschaft (DFG) (SP 1381/2-1 & 2, FA 1038/2-1 & 2, WI 3881/2-1 & 2). The Gutenberg Health Study is funded through the government of Rhineland-Palatinate ("Stiftung Rheinland-Pfalz für Innovation", contract AZ 961-386261/733), the research programs "Wissen schafft Zukunft" and "Center for Translational Vascular Biology (CTVB)" of the Johannes Gutenberg-University of Mainz, and its contract with Boehringer Ingelheim and PHILIPS Medical Systems, including an unrestricted grant for the Gutenberg Health Study.

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Keywords: hypertension,epidemiology

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ScienceOpen disciplines: Uncategorized

Keywords: hypertension, epidemiology

Relation between platelet coagulant and vascular function, sex-specific analysis in adult survivors of childhood cancer compared to a population-based sample

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Most cited references 23

Why women live longer than men: sex differences in longevity.

Differences between Men and Women in Mortality and the Health Dimensions of the Morbidity Process

Noninvasive vascular function measurement in the community: cross-sectional relations and comparison of methods.

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