SUN-075 Higher Fibrinogen and Clot Density in Patients with Acromegaly: The Role of Adverse Body Composition to the Increased Thrombotic Potential

SUN-075 Higher Fibrinogen and Clot Density in Patients with Acromegaly: The Role of Adverse Body Composition to the Increased Thrombotic Potential

Introduction: Patients with acromegaly have increased mortality rates compared with the general population, particularly due to cardiovascular and cerebrovascular disease. We hypothesized that one mechanism through which GH/IGF-1 excess increases vascular disease is via effects on hemostasis/fibrino...

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Veröffentlicht in:Journal of the Endocrine Society 2019-04, Vol.3 (Supplement_1)
Hauptverfasser: Kyriakakis, Nikolaos, Lynch, Julie, Seejore, Khyatisha, Phoenix, Fladia, Oxley, Natalie, Orme, Stephen, Ajjan, Ramzi, Murray, Robert
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Cardiovascular Endocrinology
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container_issue Supplement_1
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container_title Journal of the Endocrine Society
container_volume 3
creator Kyriakakis, Nikolaos
Lynch, Julie
Seejore, Khyatisha
Phoenix, Fladia
Oxley, Natalie
Orme, Stephen
Ajjan, Ramzi
Murray, Robert
description Introduction: Patients with acromegaly have increased mortality rates compared with the general population, particularly due to cardiovascular and cerebrovascular disease. We hypothesized that one mechanism through which GH/IGF-1 excess increases vascular disease is via effects on hemostasis/fibrinolysis and subsequent clot formation. Patients and Methods: We conducted a case-control study in 40 patients with acromegaly and 40 age and sex-matched healthy controls. We measured parameters of metabolic profile, fibrinogen using the Clauss method and performed clot structure analysis using a validated turbidimetric assay. Results: Forty patients with acromegaly (21 males, mean age 53±13 years) were recruited. 30% had active disease (GH>1mcg/L and IGF-1 above the reference range), 27.5% had dichotomous GH/IGF-1 results and 42.5% were in remission. Compared with controls, patients had a less favorable metabolic profile with higher BMI (30±5.5 vs. 26.7±4.1 kg/m 2 , p=0.003), waist/hip ratio (0.91±0.08 vs. 0.87±0.08, p=0.045), total fat mass (29.8±10 vs. 23.4±10 kg, p=0.003) and triglycerides (1.5±0.9 vs. 1.1±0.5 mmol/L, p=0.02). Significantly higher fibrinogen levels were found in the patient group (3.59±1.56 vs. 2.58±0.37 mg/ml, p
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We hypothesized that one mechanism through which GH/IGF-1 excess increases vascular disease is via effects on hemostasis/fibrinolysis and subsequent clot formation. Patients and Methods: We conducted a case-control study in 40 patients with acromegaly and 40 age and sex-matched healthy controls. We measured parameters of metabolic profile, fibrinogen using the Clauss method and performed clot structure analysis using a validated turbidimetric assay. Results: Forty patients with acromegaly (21 males, mean age 53±13 years) were recruited. 30% had active disease (GH&gt;1mcg/L and IGF-1 above the reference range), 27.5% had dichotomous GH/IGF-1 results and 42.5% were in remission. Compared with controls, patients had a less favorable metabolic profile with higher BMI (30±5.5 vs. 26.7±4.1 kg/m 2 , p=0.003), waist/hip ratio (0.91±0.08 vs. 0.87±0.08, p=0.045), total fat mass (29.8±10 vs. 23.4±10 kg, p=0.003) and triglycerides (1.5±0.9 vs. 1.1±0.5 mmol/L, p=0.02). Significantly higher fibrinogen levels were found in the patient group (3.59±1.56 vs. 2.58±0.37 mg/ml, p&lt;0.001). Patients had raised clot maximum absorbance (a measure of clot density), compared with controls (0.38±0.13 vs. 0.32±0.08 arbitrary units, p=0.02). Regarding fibrinolysis, no statistical difference in clot lysis times was found between the two groups, however patients with acromegaly had numerically more prolonged lysis times compared with controls at all lysis stages (times from maximum clot optic density to 25%, 50% and 75% lysis were respectively: 15.5±16.6 vs. 10.4±5.4 min, p=0.067; 29±22.2 vs. 23.2±11.8 min, p=0.15; and 40.8±22.5 vs. 35.3±12.5 min, p=0.18). In the patient group smoking was associated with higher fibrinogen levels (coefficient 0.8, p=0.03), higher clot density (coefficient 0.07, p=0.035) and reduced lag time for clot formation (coefficient -39.3, p=0.02). Diagnosis of diabetes, higher BMI and total fat mass were associated with more prolonged lysis time (coefficients 13, p=0.04; 1.7, p=0.007; and 0.9, p=0.009 respectively). Total fat mass was also positively associated with higher clot density (coefficient 0.005, p=0.01). Additionally, a positive correlation was found between fibrinogen and clot density (coefficient 0.05, p&lt;0.001). Conclusions: Patients with acromegaly demonstrate abnormalities in clot structure properties, particularly in clot formation, with higher fibrinogen and clot density, suggesting increased thrombotic potential with more compact clots. The adverse metabolic profile of these patients is a contributing factor to these clotting abnormalities. Prospective studies are required to assess whether hemostatic abnormalities in acromegaly are reversible after successful treatment.</description><identifier>ISSN: 2472-1972</identifier><identifier>EISSN: 2472-1972</identifier><identifier>DOI: 10.1210/js.2019-SUN-075</identifier><language>eng</language><publisher>Washington, DC: Endocrine Society</publisher><subject>Cardiovascular Endocrinology</subject><ispartof>Journal of the Endocrine Society, 2019-04, Vol.3 (Supplement_1)</ispartof><rights>Copyright © 2019 Endocrine Society 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553314/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553314/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,53790,53792</link.rule.ids></links><search><creatorcontrib>Kyriakakis, Nikolaos</creatorcontrib><creatorcontrib>Lynch, Julie</creatorcontrib><creatorcontrib>Seejore, Khyatisha</creatorcontrib><creatorcontrib>Phoenix, Fladia</creatorcontrib><creatorcontrib>Oxley, Natalie</creatorcontrib><creatorcontrib>Orme, Stephen</creatorcontrib><creatorcontrib>Ajjan, Ramzi</creatorcontrib><creatorcontrib>Murray, Robert</creatorcontrib><title>SUN-075 Higher Fibrinogen and Clot Density in Patients with Acromegaly: The Role of Adverse Body Composition to the Increased Thrombotic Potential</title><title>Journal of the Endocrine Society</title><description>Introduction: Patients with acromegaly have increased mortality rates compared with the general population, particularly due to cardiovascular and cerebrovascular disease. We hypothesized that one mechanism through which GH/IGF-1 excess increases vascular disease is via effects on hemostasis/fibrinolysis and subsequent clot formation. Patients and Methods: We conducted a case-control study in 40 patients with acromegaly and 40 age and sex-matched healthy controls. We measured parameters of metabolic profile, fibrinogen using the Clauss method and performed clot structure analysis using a validated turbidimetric assay. Results: Forty patients with acromegaly (21 males, mean age 53±13 years) were recruited. 30% had active disease (GH&gt;1mcg/L and IGF-1 above the reference range), 27.5% had dichotomous GH/IGF-1 results and 42.5% were in remission. Compared with controls, patients had a less favorable metabolic profile with higher BMI (30±5.5 vs. 26.7±4.1 kg/m 2 , p=0.003), waist/hip ratio (0.91±0.08 vs. 0.87±0.08, p=0.045), total fat mass (29.8±10 vs. 23.4±10 kg, p=0.003) and triglycerides (1.5±0.9 vs. 1.1±0.5 mmol/L, p=0.02). Significantly higher fibrinogen levels were found in the patient group (3.59±1.56 vs. 2.58±0.37 mg/ml, p&lt;0.001). Patients had raised clot maximum absorbance (a measure of clot density), compared with controls (0.38±0.13 vs. 0.32±0.08 arbitrary units, p=0.02). Regarding fibrinolysis, no statistical difference in clot lysis times was found between the two groups, however patients with acromegaly had numerically more prolonged lysis times compared with controls at all lysis stages (times from maximum clot optic density to 25%, 50% and 75% lysis were respectively: 15.5±16.6 vs. 10.4±5.4 min, p=0.067; 29±22.2 vs. 23.2±11.8 min, p=0.15; and 40.8±22.5 vs. 35.3±12.5 min, p=0.18). In the patient group smoking was associated with higher fibrinogen levels (coefficient 0.8, p=0.03), higher clot density (coefficient 0.07, p=0.035) and reduced lag time for clot formation (coefficient -39.3, p=0.02). Diagnosis of diabetes, higher BMI and total fat mass were associated with more prolonged lysis time (coefficients 13, p=0.04; 1.7, p=0.007; and 0.9, p=0.009 respectively). Total fat mass was also positively associated with higher clot density (coefficient 0.005, p=0.01). Additionally, a positive correlation was found between fibrinogen and clot density (coefficient 0.05, p&lt;0.001). Conclusions: Patients with acromegaly demonstrate abnormalities in clot structure properties, particularly in clot formation, with higher fibrinogen and clot density, suggesting increased thrombotic potential with more compact clots. The adverse metabolic profile of these patients is a contributing factor to these clotting abnormalities. Prospective studies are required to assess whether hemostatic abnormalities in acromegaly are reversible after successful treatment.</description><subject>Cardiovascular Endocrinology</subject><issn>2472-1972</issn><issn>2472-1972</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpVkctKBDEQRRtRUNS12_qB1jz74UIYxyeIio91SKerZzL0JEMSlfkNv9gMiuiqCureU3BvURxRckwZJSeLeMwIbcvn1_uS1HKr2GOiZiVta7b9Z98tDmNcEJKlXLRC7BWfPw64sbM5BriyXbDOz9CBdj1MR5_gAl20aQ3WwaNOFl2K8GHTHCYm-CXO9Lg-hZc5wpMfEfwAk_4dQ0Q49_0apn658tlvvYPkIWXdrTMBdcQ-uzKh88kaePQpk60eD4qdQY8RD3_mfvF6dfkyvSnvHq5vp5O70lBeyXKojW46I0XbiaqWsmsqY5APaPpGoOTYtR1S1tYNqwSRSFujGZENYVXFSSP4fnH2zV29dUvsTf4e9KhWwS51WCuvrfp_cXauZv5dVVJyTjeAk29AjiHGgMOvlxK1qUUtotrUonLIKofMvwCeK4Mz</recordid><startdate>20190430</startdate><enddate>20190430</enddate><creator>Kyriakakis, Nikolaos</creator><creator>Lynch, Julie</creator><creator>Seejore, Khyatisha</creator><creator>Phoenix, Fladia</creator><creator>Oxley, Natalie</creator><creator>Orme, Stephen</creator><creator>Ajjan, Ramzi</creator><creator>Murray, Robert</creator><general>Endocrine Society</general><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20190430</creationdate><title>SUN-075 Higher Fibrinogen and Clot Density in Patients with Acromegaly: The Role of Adverse Body Composition to the Increased Thrombotic Potential</title><author>Kyriakakis, Nikolaos ; Lynch, Julie ; Seejore, Khyatisha ; Phoenix, Fladia ; Oxley, Natalie ; Orme, Stephen ; Ajjan, Ramzi ; Murray, Robert</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1365-f7ca8bc549b46755b86cce3fecd84e53eb9be1297826405e19ca2058026630843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Cardiovascular Endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kyriakakis, Nikolaos</creatorcontrib><creatorcontrib>Lynch, Julie</creatorcontrib><creatorcontrib>Seejore, Khyatisha</creatorcontrib><creatorcontrib>Phoenix, Fladia</creatorcontrib><creatorcontrib>Oxley, Natalie</creatorcontrib><creatorcontrib>Orme, Stephen</creatorcontrib><creatorcontrib>Ajjan, Ramzi</creatorcontrib><creatorcontrib>Murray, Robert</creatorcontrib><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the Endocrine Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kyriakakis, Nikolaos</au><au>Lynch, Julie</au><au>Seejore, Khyatisha</au><au>Phoenix, Fladia</au><au>Oxley, Natalie</au><au>Orme, Stephen</au><au>Ajjan, Ramzi</au><au>Murray, Robert</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SUN-075 Higher Fibrinogen and Clot Density in Patients with Acromegaly: The Role of Adverse Body Composition to the Increased Thrombotic Potential</atitle><jtitle>Journal of the Endocrine Society</jtitle><date>2019-04-30</date><risdate>2019</risdate><volume>3</volume><issue>Supplement_1</issue><issn>2472-1972</issn><eissn>2472-1972</eissn><abstract>Introduction: Patients with acromegaly have increased mortality rates compared with the general population, particularly due to cardiovascular and cerebrovascular disease. We hypothesized that one mechanism through which GH/IGF-1 excess increases vascular disease is via effects on hemostasis/fibrinolysis and subsequent clot formation. Patients and Methods: We conducted a case-control study in 40 patients with acromegaly and 40 age and sex-matched healthy controls. We measured parameters of metabolic profile, fibrinogen using the Clauss method and performed clot structure analysis using a validated turbidimetric assay. Results: Forty patients with acromegaly (21 males, mean age 53±13 years) were recruited. 30% had active disease (GH&gt;1mcg/L and IGF-1 above the reference range), 27.5% had dichotomous GH/IGF-1 results and 42.5% were in remission. Compared with controls, patients had a less favorable metabolic profile with higher BMI (30±5.5 vs. 26.7±4.1 kg/m 2 , p=0.003), waist/hip ratio (0.91±0.08 vs. 0.87±0.08, p=0.045), total fat mass (29.8±10 vs. 23.4±10 kg, p=0.003) and triglycerides (1.5±0.9 vs. 1.1±0.5 mmol/L, p=0.02). Significantly higher fibrinogen levels were found in the patient group (3.59±1.56 vs. 2.58±0.37 mg/ml, p&lt;0.001). Patients had raised clot maximum absorbance (a measure of clot density), compared with controls (0.38±0.13 vs. 0.32±0.08 arbitrary units, p=0.02). Regarding fibrinolysis, no statistical difference in clot lysis times was found between the two groups, however patients with acromegaly had numerically more prolonged lysis times compared with controls at all lysis stages (times from maximum clot optic density to 25%, 50% and 75% lysis were respectively: 15.5±16.6 vs. 10.4±5.4 min, p=0.067; 29±22.2 vs. 23.2±11.8 min, p=0.15; and 40.8±22.5 vs. 35.3±12.5 min, p=0.18). In the patient group smoking was associated with higher fibrinogen levels (coefficient 0.8, p=0.03), higher clot density (coefficient 0.07, p=0.035) and reduced lag time for clot formation (coefficient -39.3, p=0.02). Diagnosis of diabetes, higher BMI and total fat mass were associated with more prolonged lysis time (coefficients 13, p=0.04; 1.7, p=0.007; and 0.9, p=0.009 respectively). Total fat mass was also positively associated with higher clot density (coefficient 0.005, p=0.01). Additionally, a positive correlation was found between fibrinogen and clot density (coefficient 0.05, p&lt;0.001). Conclusions: Patients with acromegaly demonstrate abnormalities in clot structure properties, particularly in clot formation, with higher fibrinogen and clot density, suggesting increased thrombotic potential with more compact clots. The adverse metabolic profile of these patients is a contributing factor to these clotting abnormalities. Prospective studies are required to assess whether hemostatic abnormalities in acromegaly are reversible after successful treatment.</abstract><cop>Washington, DC</cop><pub>Endocrine Society</pub><doi>10.1210/js.2019-SUN-075</doi><oa>free_for_read</oa></addata></record>
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title SUN-075 Higher Fibrinogen and Clot Density in Patients with Acromegaly: The Role of Adverse Body Composition to the Increased Thrombotic Potential
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