Thyroid Function and Cardiovascular Disease: The Mediating Role of Coagulation Factors
Abstract Context Mechanisms linking high and high-normal thyroid function to increased cardiovascular risk remain unclear. Hypothetically, coagulation can play a role. Objective To investigate (i) the association of thyroid function with coagulation factors and (ii) whether coagulation factors media...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2019-08, Vol.104 (8), p.3203-3212 |
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| container_title | The journal of clinical endocrinology and metabolism |
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| creator | Bano, Arjola Chaker, Layal de Maat, Moniek P M Atiq, Ferdows Kavousi, Maryam Franco, Oscar H Mattace-Raso, Francesco U S Leebeek, Frank W G Peeters, Robin P |
| description | Abstract
Context
Mechanisms linking high and high-normal thyroid function to increased cardiovascular risk remain unclear. Hypothetically, coagulation can play a role.
Objective
To investigate (i) the association of thyroid function with coagulation factors and (ii) whether coagulation factors mediate the association of thyroid function with cardiovascular disease (CVD).
Design and Setting
Rotterdam Study, a population-based prospective study.
Participants and Main Outcome Measures
In 5918 participants (mean age, 69.1 years), we measured TSH, free T4 (FT4), and coagulation factors [von Willebrand factor antigen (VWF:Ag), ADAMTS13 activity, fibrinogen]. Participants were followed up for the occurrence of cardiovascular events and deaths. Associations of thyroid function with coagulation factors (standardized z scores) and CVD were assessed through linear regression and Cox proportional hazards models, adjusted for potential confounders. We performed causal mediation analyses to evaluate whether the effect of thyroid function on CVD is mediated by coagulation.
Results
Higher FT4 levels were associated with higher VWF:Ag (β = 0.34; 95% CI = 0.22, 0.47), lower ADAMTS13 activity (β = −0.22; 95%CI = −0.35, −0.09), and higher fibrinogen (β = 0.26; 95% CI = 0.13, 0.39); 857 incident cardiovascular events and 690 cardiovascular deaths occurred. FT4 levels were positively associated with cardiovascular events and deaths. The effect of FT4 on incident cardiovascular events was minimally mediated by fibrinogen (1.6%) but not by VWF:Ag and ADAMTS13. VWF:Ag and fibrinogen together mediated 10.0% of the effect of FT4 on cardiovascular deaths.
Conclusions
Higher FT4 levels were associated with higher VWF:Ag, lower ADAMTS13 activity, and higher fibrinogen levels, indicating a procoagulant state. VWF:Ag and fibrinogen explained up to 10% of the link between FT4 and CVD.
This study investigated whether coagulation factors mediate the role of thyroid function on cardiovascular disease. VWF:Ag and fibrinogen partly explained the link of FT4 with cardiovascular disease. |
| doi_str_mv | 10.1210/jc.2019-00072 |
| format | Article |
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Context
Mechanisms linking high and high-normal thyroid function to increased cardiovascular risk remain unclear. Hypothetically, coagulation can play a role.
Objective
To investigate (i) the association of thyroid function with coagulation factors and (ii) whether coagulation factors mediate the association of thyroid function with cardiovascular disease (CVD).
Design and Setting
Rotterdam Study, a population-based prospective study.
Participants and Main Outcome Measures
In 5918 participants (mean age, 69.1 years), we measured TSH, free T4 (FT4), and coagulation factors [von Willebrand factor antigen (VWF:Ag), ADAMTS13 activity, fibrinogen]. Participants were followed up for the occurrence of cardiovascular events and deaths. Associations of thyroid function with coagulation factors (standardized z scores) and CVD were assessed through linear regression and Cox proportional hazards models, adjusted for potential confounders. We performed causal mediation analyses to evaluate whether the effect of thyroid function on CVD is mediated by coagulation.
Results
Higher FT4 levels were associated with higher VWF:Ag (β = 0.34; 95% CI = 0.22, 0.47), lower ADAMTS13 activity (β = −0.22; 95%CI = −0.35, −0.09), and higher fibrinogen (β = 0.26; 95% CI = 0.13, 0.39); 857 incident cardiovascular events and 690 cardiovascular deaths occurred. FT4 levels were positively associated with cardiovascular events and deaths. The effect of FT4 on incident cardiovascular events was minimally mediated by fibrinogen (1.6%) but not by VWF:Ag and ADAMTS13. VWF:Ag and fibrinogen together mediated 10.0% of the effect of FT4 on cardiovascular deaths.
Conclusions
Higher FT4 levels were associated with higher VWF:Ag, lower ADAMTS13 activity, and higher fibrinogen levels, indicating a procoagulant state. VWF:Ag and fibrinogen explained up to 10% of the link between FT4 and CVD.
This study investigated whether coagulation factors mediate the role of thyroid function on cardiovascular disease. VWF:Ag and fibrinogen partly explained the link of FT4 with cardiovascular disease.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2019-00072</identifier><identifier>PMID: 30938758</identifier><language>eng</language><publisher>Washington, DC: Endocrine Society</publisher><subject>ADAMTS13 Protein - blood ; Aged ; Aged, 80 and over ; Analysis ; Blood Coagulation - physiology ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - blood ; Cardiovascular Diseases - etiology ; Cardiovascular Diseases - physiopathology ; Coagulation factors ; Female ; Fibrin ; Fibrinogen ; Fibrinogen - analysis ; Health risk assessment ; Humans ; Male ; Mediation ; Middle Aged ; Pharmaceutical industry ; Population studies ; Proportional Hazards Models ; Prospective Studies ; Regression analysis ; Thyroid ; Thyroid gland ; Thyroid Gland - physiopathology ; Thyroid-stimulating hormone ; Thyroxine ; Thyroxine - blood ; Von Willebrand factor ; von Willebrand Factor - analysis</subject><ispartof>The journal of clinical endocrinology and metabolism, 2019-08, Vol.104 (8), p.3203-3212</ispartof><rights>Copyright © 2019 Endocrine Society 2019</rights><rights>Copyright © Oxford University Press 2015</rights><rights>Copyright © 2019 Endocrine Society.</rights><rights>COPYRIGHT 2019 Oxford University Press</rights><rights>Copyright © 2019 Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5022-138b5d4d5696f052fcff21546ecfaa1d9cbc7beaf9e3d7d01951712688d28d0e3</citedby><cites>FETCH-LOGICAL-c5022-138b5d4d5696f052fcff21546ecfaa1d9cbc7beaf9e3d7d01951712688d28d0e3</cites><orcidid>0000-0003-0956-7145</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2364266372?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,776,780,21367,27901,27902,33721,33722,43781</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30938758$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bano, Arjola</creatorcontrib><creatorcontrib>Chaker, Layal</creatorcontrib><creatorcontrib>de Maat, Moniek P M</creatorcontrib><creatorcontrib>Atiq, Ferdows</creatorcontrib><creatorcontrib>Kavousi, Maryam</creatorcontrib><creatorcontrib>Franco, Oscar H</creatorcontrib><creatorcontrib>Mattace-Raso, Francesco U S</creatorcontrib><creatorcontrib>Leebeek, Frank W G</creatorcontrib><creatorcontrib>Peeters, Robin P</creatorcontrib><title>Thyroid Function and Cardiovascular Disease: The Mediating Role of Coagulation Factors</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Abstract
Context
Mechanisms linking high and high-normal thyroid function to increased cardiovascular risk remain unclear. Hypothetically, coagulation can play a role.
Objective
To investigate (i) the association of thyroid function with coagulation factors and (ii) whether coagulation factors mediate the association of thyroid function with cardiovascular disease (CVD).
Design and Setting
Rotterdam Study, a population-based prospective study.
Participants and Main Outcome Measures
In 5918 participants (mean age, 69.1 years), we measured TSH, free T4 (FT4), and coagulation factors [von Willebrand factor antigen (VWF:Ag), ADAMTS13 activity, fibrinogen]. Participants were followed up for the occurrence of cardiovascular events and deaths. Associations of thyroid function with coagulation factors (standardized z scores) and CVD were assessed through linear regression and Cox proportional hazards models, adjusted for potential confounders. We performed causal mediation analyses to evaluate whether the effect of thyroid function on CVD is mediated by coagulation.
Results
Higher FT4 levels were associated with higher VWF:Ag (β = 0.34; 95% CI = 0.22, 0.47), lower ADAMTS13 activity (β = −0.22; 95%CI = −0.35, −0.09), and higher fibrinogen (β = 0.26; 95% CI = 0.13, 0.39); 857 incident cardiovascular events and 690 cardiovascular deaths occurred. FT4 levels were positively associated with cardiovascular events and deaths. The effect of FT4 on incident cardiovascular events was minimally mediated by fibrinogen (1.6%) but not by VWF:Ag and ADAMTS13. VWF:Ag and fibrinogen together mediated 10.0% of the effect of FT4 on cardiovascular deaths.
Conclusions
Higher FT4 levels were associated with higher VWF:Ag, lower ADAMTS13 activity, and higher fibrinogen levels, indicating a procoagulant state. VWF:Ag and fibrinogen explained up to 10% of the link between FT4 and CVD.
This study investigated whether coagulation factors mediate the role of thyroid function on cardiovascular disease. VWF:Ag and fibrinogen partly explained the link of FT4 with cardiovascular disease.</description><subject>ADAMTS13 Protein - blood</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Blood Coagulation - physiology</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - blood</subject><subject>Cardiovascular Diseases - etiology</subject><subject>Cardiovascular Diseases - physiopathology</subject><subject>Coagulation factors</subject><subject>Female</subject><subject>Fibrin</subject><subject>Fibrinogen</subject><subject>Fibrinogen - analysis</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Male</subject><subject>Mediation</subject><subject>Middle Aged</subject><subject>Pharmaceutical industry</subject><subject>Population studies</subject><subject>Proportional Hazards Models</subject><subject>Prospective Studies</subject><subject>Regression analysis</subject><subject>Thyroid</subject><subject>Thyroid gland</subject><subject>Thyroid Gland - physiopathology</subject><subject>Thyroid-stimulating hormone</subject><subject>Thyroxine</subject><subject>Thyroxine - blood</subject><subject>Von Willebrand factor</subject><subject>von Willebrand Factor - analysis</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kc1vEzEQxS0EoqFw5IpW4sJlgz_W6zW3KhCo1AoJBcTNcuxx4uCsU3uXqv89TpMWURXNwdLo996M5yH0muApoQS_35gpxUTWGGNBn6AJkQ2vBZHiKZpgTEktBf15gl7kvMGYNA1nz9EJw5J1gncT9GOxvknR22o-9mbwsa90b6uZTtbH3zqbMehUffQZdIYP1WIN1SVYrwffr6pvMUAVXTWLelW4W_VcmyGm_BI9czpkeHV8T9H3-afF7Et98fXz-ezsojYcU1oT1i25bSxvZeswp844RwlvWjBOa2KlWRqxBO0kMCts-ScngtC26yztLAZ2it4dfHcpXo2QB7X12UAIuoc4ZkVpOYGUjIqCvn2AbuKY-rKdoqxtaNsyQf9SKx1A-d7FIWmzN1VnZSxvBWeyUNNHqFIWtt7EHpwv_X8E9UFgUsw5gVO75Lc63SiC1T5HtTFqn6O6zbHwb47Ljsst2Hv6LrgCkANwHcMAKf8K4zUktQYdhvVD0_rO9HisOO7-N_-I_gGtRLHg</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Bano, Arjola</creator><creator>Chaker, Layal</creator><creator>de Maat, Moniek P M</creator><creator>Atiq, Ferdows</creator><creator>Kavousi, Maryam</creator><creator>Franco, Oscar H</creator><creator>Mattace-Raso, Francesco U S</creator><creator>Leebeek, Frank W G</creator><creator>Peeters, Robin P</creator><general>Endocrine Society</general><general>Copyright Oxford University Press</general><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0956-7145</orcidid></search><sort><creationdate>20190801</creationdate><title>Thyroid Function and Cardiovascular Disease: The Mediating Role of Coagulation Factors</title><author>Bano, Arjola ; Chaker, Layal ; de Maat, Moniek P M ; Atiq, Ferdows ; Kavousi, Maryam ; Franco, Oscar H ; Mattace-Raso, Francesco U S ; Leebeek, Frank W G ; Peeters, Robin P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5022-138b5d4d5696f052fcff21546ecfaa1d9cbc7beaf9e3d7d01951712688d28d0e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>ADAMTS13 Protein - blood</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Blood Coagulation - physiology</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular Diseases - blood</topic><topic>Cardiovascular Diseases - etiology</topic><topic>Cardiovascular Diseases - physiopathology</topic><topic>Coagulation factors</topic><topic>Female</topic><topic>Fibrin</topic><topic>Fibrinogen</topic><topic>Fibrinogen - analysis</topic><topic>Health risk assessment</topic><topic>Humans</topic><topic>Male</topic><topic>Mediation</topic><topic>Middle Aged</topic><topic>Pharmaceutical industry</topic><topic>Population studies</topic><topic>Proportional Hazards Models</topic><topic>Prospective Studies</topic><topic>Regression analysis</topic><topic>Thyroid</topic><topic>Thyroid gland</topic><topic>Thyroid Gland - physiopathology</topic><topic>Thyroid-stimulating hormone</topic><topic>Thyroxine</topic><topic>Thyroxine - blood</topic><topic>Von Willebrand factor</topic><topic>von Willebrand Factor - analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bano, Arjola</creatorcontrib><creatorcontrib>Chaker, Layal</creatorcontrib><creatorcontrib>de Maat, Moniek P M</creatorcontrib><creatorcontrib>Atiq, Ferdows</creatorcontrib><creatorcontrib>Kavousi, Maryam</creatorcontrib><creatorcontrib>Franco, Oscar H</creatorcontrib><creatorcontrib>Mattace-Raso, Francesco U S</creatorcontrib><creatorcontrib>Leebeek, Frank W G</creatorcontrib><creatorcontrib>Peeters, Robin P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bano, Arjola</au><au>Chaker, Layal</au><au>de Maat, Moniek P M</au><au>Atiq, Ferdows</au><au>Kavousi, Maryam</au><au>Franco, Oscar H</au><au>Mattace-Raso, Francesco U S</au><au>Leebeek, Frank W G</au><au>Peeters, Robin P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thyroid Function and Cardiovascular Disease: The Mediating Role of Coagulation Factors</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2019-08-01</date><risdate>2019</risdate><volume>104</volume><issue>8</issue><spage>3203</spage><epage>3212</epage><pages>3203-3212</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract>Abstract
Context
Mechanisms linking high and high-normal thyroid function to increased cardiovascular risk remain unclear. Hypothetically, coagulation can play a role.
Objective
To investigate (i) the association of thyroid function with coagulation factors and (ii) whether coagulation factors mediate the association of thyroid function with cardiovascular disease (CVD).
Design and Setting
Rotterdam Study, a population-based prospective study.
Participants and Main Outcome Measures
In 5918 participants (mean age, 69.1 years), we measured TSH, free T4 (FT4), and coagulation factors [von Willebrand factor antigen (VWF:Ag), ADAMTS13 activity, fibrinogen]. Participants were followed up for the occurrence of cardiovascular events and deaths. Associations of thyroid function with coagulation factors (standardized z scores) and CVD were assessed through linear regression and Cox proportional hazards models, adjusted for potential confounders. We performed causal mediation analyses to evaluate whether the effect of thyroid function on CVD is mediated by coagulation.
Results
Higher FT4 levels were associated with higher VWF:Ag (β = 0.34; 95% CI = 0.22, 0.47), lower ADAMTS13 activity (β = −0.22; 95%CI = −0.35, −0.09), and higher fibrinogen (β = 0.26; 95% CI = 0.13, 0.39); 857 incident cardiovascular events and 690 cardiovascular deaths occurred. FT4 levels were positively associated with cardiovascular events and deaths. The effect of FT4 on incident cardiovascular events was minimally mediated by fibrinogen (1.6%) but not by VWF:Ag and ADAMTS13. VWF:Ag and fibrinogen together mediated 10.0% of the effect of FT4 on cardiovascular deaths.
Conclusions
Higher FT4 levels were associated with higher VWF:Ag, lower ADAMTS13 activity, and higher fibrinogen levels, indicating a procoagulant state. VWF:Ag and fibrinogen explained up to 10% of the link between FT4 and CVD.
This study investigated whether coagulation factors mediate the role of thyroid function on cardiovascular disease. VWF:Ag and fibrinogen partly explained the link of FT4 with cardiovascular disease.</abstract><cop>Washington, DC</cop><pub>Endocrine Society</pub><pmid>30938758</pmid><doi>10.1210/jc.2019-00072</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-0956-7145</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2019-08, Vol.104 (8), p.3203-3212 |
| issn | 0021-972X 1945-7197 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2202199327 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; ProQuest Central |
| subjects | ADAMTS13 Protein - blood Aged Aged, 80 and over Analysis Blood Coagulation - physiology Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - blood Cardiovascular Diseases - etiology Cardiovascular Diseases - physiopathology Coagulation factors Female Fibrin Fibrinogen Fibrinogen - analysis Health risk assessment Humans Male Mediation Middle Aged Pharmaceutical industry Population studies Proportional Hazards Models Prospective Studies Regression analysis Thyroid Thyroid gland Thyroid Gland - physiopathology Thyroid-stimulating hormone Thyroxine Thyroxine - blood Von Willebrand factor von Willebrand Factor - analysis |
| title | Thyroid Function and Cardiovascular Disease: The Mediating Role of Coagulation Factors |
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