ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients
Aims/hypothesis A high serum angiopoietin-like 2 (ANGPTL2) concentration is an independent risk factor for developing diabetes and is associated with insulin resistance and atherosclerosis. In this work, we have examined the impact of serum ANGPTL2 on improving cardiovascular (CV) risk stratificatio...
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| Veröffentlicht in: | Diabetologia 2016-11, Vol.59 (11), p.2321-2330 |
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| creator | Gellen, Barnabas Thorin-Trescases, Nathalie Sosner, Philippe Gand, Elise Saulnier, Pierre-Jean Ragot, Stéphanie Fraty, Mathilde Laugier, Stéphanie Ducrocq, Grégory Montaigne, David Llaty, Pierre Rigalleau, Vincent Zaoui, Philippe Halimi, Jean-Michel Roussel, Ronan Thorin, Eric Hadjadj, Samy |
| description | Aims/hypothesis
A high serum angiopoietin-like 2 (ANGPTL2) concentration is an independent risk factor for developing diabetes and is associated with insulin resistance and atherosclerosis. In this work, we have examined the impact of serum ANGPTL2 on improving cardiovascular (CV) risk stratification in patients with type 2 diabetes.
Methods
A prospective, monocentric cohort of consecutive type 2 diabetes patients (the SURDIAGENE cohort; total of 1353 type 2 diabetes patients; 58% men, mean ± SD age 64 ± 11 years) was followed for a median of 6.0 years for death as primary endpoint and major adverse CV events (MACE; i.e. CV death, myocardial infarction or stroke) as a secondary endpoint. Patients with end-stage renal disease, defined as a requirement for dialysis or a history of kidney transplantation, were excluded. Patients were grouped into quartiles according to ANGPTL2 concentrations at inclusion: 19.5 (Q4) ng/ml.
Results
During follow up, 367 patients (representing 4.5% of the total person-years) died and 290 patients (representing 3.7% of the total person-years) presented with MACE. Both the survival and MACE-free survival rates were significantly different between ANGPTL2 quartiles (logrank 82.12,
p
|
| doi_str_mv | 10.1007/s00125-016-4066-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1827929976</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4197510501</sourcerecordid><originalsourceid>FETCH-LOGICAL-c518t-3675b02c6525b41b90afdcb4644c71a25b5b6e047d5ca91cb4ab4198141adc2e3</originalsourceid><addsrcrecordid>eNqNkV9LHDEUxUOx1NX2A_hSAr70ZWxuJn8mjyJWhcX2YQXfwp0kW6O7M2syo_Tbm2G3IgWhTxfu-Z1zuRxCjoCdAGP6e2YMuKwYqEowpSr5gcxA1Lxigjd7ZDbJFTTqdp8c5HzPGKulUJ_IPtfCQFPXM-JPry9-Leacxkwx595FHIKnz3G4o9jR2LkUMJdNivmB9kvqMPnYP2F24woTDU-hG4q189QHLKbYUR-xDUN0dINDnOTP5OMSVzl82c1DcvPjfHF2Wc1_Xlydnc4rJ6EZqlpp2TLulOSyFdAahkvvWqGEcBqwLGWrAhPaS4cGioIFMw0IQO94qA_Jt23uJvWPY8iDXcfswmqFXejHbKHh2nBjtPofVHLQkomCHv-D3vdj6sojEyVAm6Y2hYIt5VKfcwpLu0lxjemPBWantuy2LVvaslNbVhbP113y2K6Df3X8racAfAvkInW_Q3pz-t3UF5utnh0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1824179839</pqid></control><display><type>article</type><title>ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Gellen, Barnabas ; Thorin-Trescases, Nathalie ; Sosner, Philippe ; Gand, Elise ; Saulnier, Pierre-Jean ; Ragot, Stéphanie ; Fraty, Mathilde ; Laugier, Stéphanie ; Ducrocq, Grégory ; Montaigne, David ; Llaty, Pierre ; Rigalleau, Vincent ; Zaoui, Philippe ; Halimi, Jean-Michel ; Roussel, Ronan ; Thorin, Eric ; Hadjadj, Samy</creator><creatorcontrib>Gellen, Barnabas ; Thorin-Trescases, Nathalie ; Sosner, Philippe ; Gand, Elise ; Saulnier, Pierre-Jean ; Ragot, Stéphanie ; Fraty, Mathilde ; Laugier, Stéphanie ; Ducrocq, Grégory ; Montaigne, David ; Llaty, Pierre ; Rigalleau, Vincent ; Zaoui, Philippe ; Halimi, Jean-Michel ; Roussel, Ronan ; Thorin, Eric ; Hadjadj, Samy</creatorcontrib><description>Aims/hypothesis
A high serum angiopoietin-like 2 (ANGPTL2) concentration is an independent risk factor for developing diabetes and is associated with insulin resistance and atherosclerosis. In this work, we have examined the impact of serum ANGPTL2 on improving cardiovascular (CV) risk stratification in patients with type 2 diabetes.
Methods
A prospective, monocentric cohort of consecutive type 2 diabetes patients (the SURDIAGENE cohort; total of 1353 type 2 diabetes patients; 58% men, mean ± SD age 64 ± 11 years) was followed for a median of 6.0 years for death as primary endpoint and major adverse CV events (MACE; i.e. CV death, myocardial infarction or stroke) as a secondary endpoint. Patients with end-stage renal disease, defined as a requirement for dialysis or a history of kidney transplantation, were excluded. Patients were grouped into quartiles according to ANGPTL2 concentrations at inclusion: <11.2 (Q1), 11.2–14.7 (Q2), 14.8–19.5 (Q3) or >19.5 (Q4) ng/ml.
Results
During follow up, 367 patients (representing 4.5% of the total person-years) died and 290 patients (representing 3.7% of the total person-years) presented with MACE. Both the survival and MACE-free survival rates were significantly different between ANGPTL2 quartiles (logrank 82.12,
p
< 0.0001 for death; and logrank 65.14,
p
< 0.0001 for MACE). Patients with ANGPTL2 concentrations higher than 19.5 ng/ml (Q4) had a significantly higher risk of death and MACE than those with ANGPTL2 levels of 19.5 ng/ml or less (Q1–3) (HR for death 2.44 [95% CI 1.98, 3.00],
p
< 0.0001; HR for MACE 2.43 [95% CI 1.92, 3.06],
p
< 0.0001) after adjustment for sex, age and established CV risk factors. Using ANGPTL2 concentrations, prediction of the risk of mortality, as assessed by integrated discrimination improvement (IDI), was significantly improved (IDI 0.006 ± 0.002,
p
= 0.0002).
Conclusions/interpretation
In patients with type 2 diabetes, serum ANGPTL2 concentrations were independently associated with death and MACE. Therefore, ANGPTL2 is a promising candidate biomarker for improving risk stratification in type 2 diabetes patients, and may prove to be a valuable therapeutic target.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-016-4066-5</identifier><identifier>PMID: 27491833</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Aged ; Angiopoietin-like Proteins ; Angiopoietins - blood ; Atherosclerosis ; Biomarkers ; Biomarkers - blood ; Cardiovascular disease ; Cardiovascular Diseases - blood ; Cardiovascular Diseases - epidemiology ; Cardiovascular Diseases - mortality ; Diabetes ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - epidemiology ; Diabetes Mellitus, Type 2 - mortality ; Female ; Heart failure ; Human Physiology ; Humans ; Inflammation ; Insulin resistance ; Internal Medicine ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Middle Aged ; Mortality ; Myocardial Infarction - blood ; Myocardial Infarction - epidemiology ; Myocardial Infarction - mortality ; Prospective Studies ; Risk Factors ; Stroke - blood ; Stroke - epidemiology ; Stroke - mortality</subject><ispartof>Diabetologia, 2016-11, Vol.59 (11), p.2321-2330</ispartof><rights>Springer-Verlag Berlin Heidelberg 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-3675b02c6525b41b90afdcb4644c71a25b5b6e047d5ca91cb4ab4198141adc2e3</citedby><cites>FETCH-LOGICAL-c518t-3675b02c6525b41b90afdcb4644c71a25b5b6e047d5ca91cb4ab4198141adc2e3</cites><orcidid>0000-0002-1128-2985</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-016-4066-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-016-4066-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27491833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gellen, Barnabas</creatorcontrib><creatorcontrib>Thorin-Trescases, Nathalie</creatorcontrib><creatorcontrib>Sosner, Philippe</creatorcontrib><creatorcontrib>Gand, Elise</creatorcontrib><creatorcontrib>Saulnier, Pierre-Jean</creatorcontrib><creatorcontrib>Ragot, Stéphanie</creatorcontrib><creatorcontrib>Fraty, Mathilde</creatorcontrib><creatorcontrib>Laugier, Stéphanie</creatorcontrib><creatorcontrib>Ducrocq, Grégory</creatorcontrib><creatorcontrib>Montaigne, David</creatorcontrib><creatorcontrib>Llaty, Pierre</creatorcontrib><creatorcontrib>Rigalleau, Vincent</creatorcontrib><creatorcontrib>Zaoui, Philippe</creatorcontrib><creatorcontrib>Halimi, Jean-Michel</creatorcontrib><creatorcontrib>Roussel, Ronan</creatorcontrib><creatorcontrib>Thorin, Eric</creatorcontrib><creatorcontrib>Hadjadj, Samy</creatorcontrib><title>ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
A high serum angiopoietin-like 2 (ANGPTL2) concentration is an independent risk factor for developing diabetes and is associated with insulin resistance and atherosclerosis. In this work, we have examined the impact of serum ANGPTL2 on improving cardiovascular (CV) risk stratification in patients with type 2 diabetes.
Methods
A prospective, monocentric cohort of consecutive type 2 diabetes patients (the SURDIAGENE cohort; total of 1353 type 2 diabetes patients; 58% men, mean ± SD age 64 ± 11 years) was followed for a median of 6.0 years for death as primary endpoint and major adverse CV events (MACE; i.e. CV death, myocardial infarction or stroke) as a secondary endpoint. Patients with end-stage renal disease, defined as a requirement for dialysis or a history of kidney transplantation, were excluded. Patients were grouped into quartiles according to ANGPTL2 concentrations at inclusion: <11.2 (Q1), 11.2–14.7 (Q2), 14.8–19.5 (Q3) or >19.5 (Q4) ng/ml.
Results
During follow up, 367 patients (representing 4.5% of the total person-years) died and 290 patients (representing 3.7% of the total person-years) presented with MACE. Both the survival and MACE-free survival rates were significantly different between ANGPTL2 quartiles (logrank 82.12,
p
< 0.0001 for death; and logrank 65.14,
p
< 0.0001 for MACE). Patients with ANGPTL2 concentrations higher than 19.5 ng/ml (Q4) had a significantly higher risk of death and MACE than those with ANGPTL2 levels of 19.5 ng/ml or less (Q1–3) (HR for death 2.44 [95% CI 1.98, 3.00],
p
< 0.0001; HR for MACE 2.43 [95% CI 1.92, 3.06],
p
< 0.0001) after adjustment for sex, age and established CV risk factors. Using ANGPTL2 concentrations, prediction of the risk of mortality, as assessed by integrated discrimination improvement (IDI), was significantly improved (IDI 0.006 ± 0.002,
p
= 0.0002).
Conclusions/interpretation
In patients with type 2 diabetes, serum ANGPTL2 concentrations were independently associated with death and MACE. Therefore, ANGPTL2 is a promising candidate biomarker for improving risk stratification in type 2 diabetes patients, and may prove to be a valuable therapeutic target.</description><subject>Aged</subject><subject>Angiopoietin-like Proteins</subject><subject>Angiopoietins - blood</subject><subject>Atherosclerosis</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular Diseases - blood</subject><subject>Cardiovascular Diseases - epidemiology</subject><subject>Cardiovascular Diseases - mortality</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - epidemiology</subject><subject>Diabetes Mellitus, Type 2 - mortality</subject><subject>Female</subject><subject>Heart failure</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Insulin resistance</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Myocardial Infarction - blood</subject><subject>Myocardial Infarction - epidemiology</subject><subject>Myocardial Infarction - mortality</subject><subject>Prospective Studies</subject><subject>Risk Factors</subject><subject>Stroke - blood</subject><subject>Stroke - epidemiology</subject><subject>Stroke - mortality</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkV9LHDEUxUOx1NX2A_hSAr70ZWxuJn8mjyJWhcX2YQXfwp0kW6O7M2syo_Tbm2G3IgWhTxfu-Z1zuRxCjoCdAGP6e2YMuKwYqEowpSr5gcxA1Lxigjd7ZDbJFTTqdp8c5HzPGKulUJ_IPtfCQFPXM-JPry9-Leacxkwx595FHIKnz3G4o9jR2LkUMJdNivmB9kvqMPnYP2F24woTDU-hG4q189QHLKbYUR-xDUN0dINDnOTP5OMSVzl82c1DcvPjfHF2Wc1_Xlydnc4rJ6EZqlpp2TLulOSyFdAahkvvWqGEcBqwLGWrAhPaS4cGioIFMw0IQO94qA_Jt23uJvWPY8iDXcfswmqFXejHbKHh2nBjtPofVHLQkomCHv-D3vdj6sojEyVAm6Y2hYIt5VKfcwpLu0lxjemPBWantuy2LVvaslNbVhbP113y2K6Df3X8racAfAvkInW_Q3pz-t3UF5utnh0</recordid><startdate>20161101</startdate><enddate>20161101</enddate><creator>Gellen, Barnabas</creator><creator>Thorin-Trescases, Nathalie</creator><creator>Sosner, Philippe</creator><creator>Gand, Elise</creator><creator>Saulnier, Pierre-Jean</creator><creator>Ragot, Stéphanie</creator><creator>Fraty, Mathilde</creator><creator>Laugier, Stéphanie</creator><creator>Ducrocq, Grégory</creator><creator>Montaigne, David</creator><creator>Llaty, Pierre</creator><creator>Rigalleau, Vincent</creator><creator>Zaoui, Philippe</creator><creator>Halimi, Jean-Michel</creator><creator>Roussel, Ronan</creator><creator>Thorin, Eric</creator><creator>Hadjadj, Samy</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</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>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</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>7X8</scope><orcidid>https://orcid.org/0000-0002-1128-2985</orcidid></search><sort><creationdate>20161101</creationdate><title>ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients</title><author>Gellen, Barnabas ; Thorin-Trescases, Nathalie ; Sosner, Philippe ; Gand, Elise ; Saulnier, Pierre-Jean ; Ragot, Stéphanie ; Fraty, Mathilde ; Laugier, Stéphanie ; Ducrocq, Grégory ; Montaigne, David ; Llaty, Pierre ; Rigalleau, Vincent ; Zaoui, Philippe ; Halimi, Jean-Michel ; Roussel, Ronan ; Thorin, Eric ; Hadjadj, Samy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c518t-3675b02c6525b41b90afdcb4644c71a25b5b6e047d5ca91cb4ab4198141adc2e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aged</topic><topic>Angiopoietin-like Proteins</topic><topic>Angiopoietins - blood</topic><topic>Atherosclerosis</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular Diseases - blood</topic><topic>Cardiovascular Diseases - epidemiology</topic><topic>Cardiovascular Diseases - mortality</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - epidemiology</topic><topic>Diabetes Mellitus, Type 2 - mortality</topic><topic>Female</topic><topic>Heart failure</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Insulin resistance</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Myocardial Infarction - blood</topic><topic>Myocardial Infarction - epidemiology</topic><topic>Myocardial Infarction - mortality</topic><topic>Prospective Studies</topic><topic>Risk Factors</topic><topic>Stroke - blood</topic><topic>Stroke - epidemiology</topic><topic>Stroke - mortality</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gellen, Barnabas</creatorcontrib><creatorcontrib>Thorin-Trescases, Nathalie</creatorcontrib><creatorcontrib>Sosner, Philippe</creatorcontrib><creatorcontrib>Gand, Elise</creatorcontrib><creatorcontrib>Saulnier, Pierre-Jean</creatorcontrib><creatorcontrib>Ragot, Stéphanie</creatorcontrib><creatorcontrib>Fraty, Mathilde</creatorcontrib><creatorcontrib>Laugier, Stéphanie</creatorcontrib><creatorcontrib>Ducrocq, Grégory</creatorcontrib><creatorcontrib>Montaigne, David</creatorcontrib><creatorcontrib>Llaty, Pierre</creatorcontrib><creatorcontrib>Rigalleau, Vincent</creatorcontrib><creatorcontrib>Zaoui, Philippe</creatorcontrib><creatorcontrib>Halimi, Jean-Michel</creatorcontrib><creatorcontrib>Roussel, Ronan</creatorcontrib><creatorcontrib>Thorin, Eric</creatorcontrib><creatorcontrib>Hadjadj, Samy</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>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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>MEDLINE - Academic</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gellen, Barnabas</au><au>Thorin-Trescases, Nathalie</au><au>Sosner, Philippe</au><au>Gand, Elise</au><au>Saulnier, Pierre-Jean</au><au>Ragot, Stéphanie</au><au>Fraty, Mathilde</au><au>Laugier, Stéphanie</au><au>Ducrocq, Grégory</au><au>Montaigne, David</au><au>Llaty, Pierre</au><au>Rigalleau, Vincent</au><au>Zaoui, Philippe</au><au>Halimi, Jean-Michel</au><au>Roussel, Ronan</au><au>Thorin, Eric</au><au>Hadjadj, Samy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2016-11-01</date><risdate>2016</risdate><volume>59</volume><issue>11</issue><spage>2321</spage><epage>2330</epage><pages>2321-2330</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
A high serum angiopoietin-like 2 (ANGPTL2) concentration is an independent risk factor for developing diabetes and is associated with insulin resistance and atherosclerosis. In this work, we have examined the impact of serum ANGPTL2 on improving cardiovascular (CV) risk stratification in patients with type 2 diabetes.
Methods
A prospective, monocentric cohort of consecutive type 2 diabetes patients (the SURDIAGENE cohort; total of 1353 type 2 diabetes patients; 58% men, mean ± SD age 64 ± 11 years) was followed for a median of 6.0 years for death as primary endpoint and major adverse CV events (MACE; i.e. CV death, myocardial infarction or stroke) as a secondary endpoint. Patients with end-stage renal disease, defined as a requirement for dialysis or a history of kidney transplantation, were excluded. Patients were grouped into quartiles according to ANGPTL2 concentrations at inclusion: <11.2 (Q1), 11.2–14.7 (Q2), 14.8–19.5 (Q3) or >19.5 (Q4) ng/ml.
Results
During follow up, 367 patients (representing 4.5% of the total person-years) died and 290 patients (representing 3.7% of the total person-years) presented with MACE. Both the survival and MACE-free survival rates were significantly different between ANGPTL2 quartiles (logrank 82.12,
p
< 0.0001 for death; and logrank 65.14,
p
< 0.0001 for MACE). Patients with ANGPTL2 concentrations higher than 19.5 ng/ml (Q4) had a significantly higher risk of death and MACE than those with ANGPTL2 levels of 19.5 ng/ml or less (Q1–3) (HR for death 2.44 [95% CI 1.98, 3.00],
p
< 0.0001; HR for MACE 2.43 [95% CI 1.92, 3.06],
p
< 0.0001) after adjustment for sex, age and established CV risk factors. Using ANGPTL2 concentrations, prediction of the risk of mortality, as assessed by integrated discrimination improvement (IDI), was significantly improved (IDI 0.006 ± 0.002,
p
= 0.0002).
Conclusions/interpretation
In patients with type 2 diabetes, serum ANGPTL2 concentrations were independently associated with death and MACE. Therefore, ANGPTL2 is a promising candidate biomarker for improving risk stratification in type 2 diabetes patients, and may prove to be a valuable therapeutic target.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>27491833</pmid><doi>10.1007/s00125-016-4066-5</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-1128-2985</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Angiopoietin-like Proteins Angiopoietins - blood Atherosclerosis Biomarkers Biomarkers - blood Cardiovascular disease Cardiovascular Diseases - blood Cardiovascular Diseases - epidemiology Cardiovascular Diseases - mortality Diabetes Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - epidemiology Diabetes Mellitus, Type 2 - mortality Female Heart failure Human Physiology Humans Inflammation Insulin resistance Internal Medicine Male Medicine Medicine & Public Health Metabolic Diseases Middle Aged Mortality Myocardial Infarction - blood Myocardial Infarction - epidemiology Myocardial Infarction - mortality Prospective Studies Risk Factors Stroke - blood Stroke - epidemiology Stroke - mortality |
| title | ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients |
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