Prognostic impact of circulating soluble LR11 on long-term clinical outcomes in patients with coronary artery disease
Abstract Background LR11, a member of LDL receptor family, is a novel marker of the proliferation of intimal smooth muscle cells (SMCs). LR11 is released in soluble form (sLR11) by proteolytic shedding and has biological activity toward SMC migration. We previously showed that circulating sLR11 posi...
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| creator | Ogita, Manabu Miyauchi, Katsumi Kasai, Takatoshi Tsuboi, Shuta Wada, Hideki Naito, Ryo Konishi, Hirokazu Dohi, Tomotaka Tamura, Hiroshi Okazaki, Shinya Yanagisawa, Naotake Shimada, Kazunori Suwa, Satoru Jiang, Meizi Bujo, Hideaki Daida, Hiroyuki |
| description | Abstract Background LR11, a member of LDL receptor family, is a novel marker of the proliferation of intimal smooth muscle cells (SMCs). LR11 is released in soluble form (sLR11) by proteolytic shedding and has biological activity toward SMC migration. We previously showed that circulating sLR11 positively correlates with carotid intima-medial thickness (IMT) independently of classical atherosclerotic risk factors and that it significantly associates with the severity of CAD. However, the association between sLR11 and long-term clinical outcomes remain uncertain. Methods and results This study included 438 consecutive patients (mean age, 65.8 ± 9.6 y; male, 82.4%) who underwent coronary intervention between March 2003 and December 2004 at our institution. The patients were assigned to quartiles according to pre-procedural sLR11 values. The primary endpoints were composite cardiovascular disease (CVD) endpoints including cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke. During median follow-up of 2876 days, composite CVD endpoints occurred 97 (22.1%) patients including 41 (9.4%) with cardiovascular disease (CVD)-related death, 36 (8.2%) non-fatal ACS and 20 (4.6%) non-fatal strokes. The hazard ratio (HR) for composite CVD endpoints significantly and dose-dependently increased with sLR11 levels (p for trend = 0.0077). A higher logarithm-transformed sLR11 value was associated with a greater risk of composite CVD endpoints, and the increased number of adverse long-term clinical outcomes persisted even after adjustment for other independent variables (HR 1.87 95%CI 1.02–3.31, p = 0.0435). Conclusions Elevated sLR11 levels were significantly associated with higher long-term adverse cardiac events in patients with CAD. Further extensive studies are expected to elucidate the mechanistic role of sLR11 and its clinical value as a prognostic marker in the development of atherosclerosis. |
| doi_str_mv | 10.1016/j.atherosclerosis.2015.11.004 |
| format | Article |
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LR11 is released in soluble form (sLR11) by proteolytic shedding and has biological activity toward SMC migration. We previously showed that circulating sLR11 positively correlates with carotid intima-medial thickness (IMT) independently of classical atherosclerotic risk factors and that it significantly associates with the severity of CAD. However, the association between sLR11 and long-term clinical outcomes remain uncertain. Methods and results This study included 438 consecutive patients (mean age, 65.8 ± 9.6 y; male, 82.4%) who underwent coronary intervention between March 2003 and December 2004 at our institution. The patients were assigned to quartiles according to pre-procedural sLR11 values. The primary endpoints were composite cardiovascular disease (CVD) endpoints including cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke. During median follow-up of 2876 days, composite CVD endpoints occurred 97 (22.1%) patients including 41 (9.4%) with cardiovascular disease (CVD)-related death, 36 (8.2%) non-fatal ACS and 20 (4.6%) non-fatal strokes. The hazard ratio (HR) for composite CVD endpoints significantly and dose-dependently increased with sLR11 levels (p for trend = 0.0077). A higher logarithm-transformed sLR11 value was associated with a greater risk of composite CVD endpoints, and the increased number of adverse long-term clinical outcomes persisted even after adjustment for other independent variables (HR 1.87 95%CI 1.02–3.31, p = 0.0435). Conclusions Elevated sLR11 levels were significantly associated with higher long-term adverse cardiac events in patients with CAD. Further extensive studies are expected to elucidate the mechanistic role of sLR11 and its clinical value as a prognostic marker in the development of atherosclerosis.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/j.atherosclerosis.2015.11.004</identifier><identifier>PMID: 26687467</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Aged ; Biomarker ; Biomarkers - blood ; Cardiovascular ; Coronary artery disease ; Coronary Artery Disease - blood ; Coronary Artery Disease - epidemiology ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Humans ; Japan - epidemiology ; LDL-Receptor Related Proteins - blood ; Long-term outcomes ; Male ; Membrane Transport Proteins - blood ; Middle Aged ; Morbidity - trends ; Nerve Tissue Proteins ; Prognosis ; Prospective Studies ; Risk Factors ; Smooth muscle cell ; Survival Rate - trends ; Time Factors</subject><ispartof>Atherosclerosis, 2016-01, Vol.244, p.216-221</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2015 Elsevier Ireland Ltd</rights><rights>Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-85a3552720f84b57fc118514d722e5b185d9a5cfba6fc7ee1153fd8e10e79dec3</citedby><cites>FETCH-LOGICAL-c444t-85a3552720f84b57fc118514d722e5b185d9a5cfba6fc7ee1153fd8e10e79dec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0021915015302008$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26687467$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ogita, Manabu</creatorcontrib><creatorcontrib>Miyauchi, Katsumi</creatorcontrib><creatorcontrib>Kasai, Takatoshi</creatorcontrib><creatorcontrib>Tsuboi, Shuta</creatorcontrib><creatorcontrib>Wada, Hideki</creatorcontrib><creatorcontrib>Naito, Ryo</creatorcontrib><creatorcontrib>Konishi, Hirokazu</creatorcontrib><creatorcontrib>Dohi, Tomotaka</creatorcontrib><creatorcontrib>Tamura, Hiroshi</creatorcontrib><creatorcontrib>Okazaki, Shinya</creatorcontrib><creatorcontrib>Yanagisawa, Naotake</creatorcontrib><creatorcontrib>Shimada, Kazunori</creatorcontrib><creatorcontrib>Suwa, Satoru</creatorcontrib><creatorcontrib>Jiang, Meizi</creatorcontrib><creatorcontrib>Bujo, Hideaki</creatorcontrib><creatorcontrib>Daida, Hiroyuki</creatorcontrib><title>Prognostic impact of circulating soluble LR11 on long-term clinical outcomes in patients with coronary artery disease</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><description>Abstract Background LR11, a member of LDL receptor family, is a novel marker of the proliferation of intimal smooth muscle cells (SMCs). LR11 is released in soluble form (sLR11) by proteolytic shedding and has biological activity toward SMC migration. We previously showed that circulating sLR11 positively correlates with carotid intima-medial thickness (IMT) independently of classical atherosclerotic risk factors and that it significantly associates with the severity of CAD. However, the association between sLR11 and long-term clinical outcomes remain uncertain. Methods and results This study included 438 consecutive patients (mean age, 65.8 ± 9.6 y; male, 82.4%) who underwent coronary intervention between March 2003 and December 2004 at our institution. The patients were assigned to quartiles according to pre-procedural sLR11 values. The primary endpoints were composite cardiovascular disease (CVD) endpoints including cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke. During median follow-up of 2876 days, composite CVD endpoints occurred 97 (22.1%) patients including 41 (9.4%) with cardiovascular disease (CVD)-related death, 36 (8.2%) non-fatal ACS and 20 (4.6%) non-fatal strokes. The hazard ratio (HR) for composite CVD endpoints significantly and dose-dependently increased with sLR11 levels (p for trend = 0.0077). A higher logarithm-transformed sLR11 value was associated with a greater risk of composite CVD endpoints, and the increased number of adverse long-term clinical outcomes persisted even after adjustment for other independent variables (HR 1.87 95%CI 1.02–3.31, p = 0.0435). Conclusions Elevated sLR11 levels were significantly associated with higher long-term adverse cardiac events in patients with CAD. Further extensive studies are expected to elucidate the mechanistic role of sLR11 and its clinical value as a prognostic marker in the development of atherosclerosis.</description><subject>Aged</subject><subject>Biomarker</subject><subject>Biomarkers - blood</subject><subject>Cardiovascular</subject><subject>Coronary artery disease</subject><subject>Coronary Artery Disease - blood</subject><subject>Coronary Artery Disease - epidemiology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Japan - epidemiology</subject><subject>LDL-Receptor Related Proteins - blood</subject><subject>Long-term outcomes</subject><subject>Male</subject><subject>Membrane Transport Proteins - blood</subject><subject>Middle Aged</subject><subject>Morbidity - trends</subject><subject>Nerve Tissue Proteins</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Risk Factors</subject><subject>Smooth muscle cell</subject><subject>Survival Rate - trends</subject><subject>Time Factors</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks-P1CAUx4nRuOPqv2C4mHhp5VEonYMmZqOrySQaf5wJpa-zjLSMQNfMfy_N7HrYkxfg8Pm-Bx8eIa-A1cCgfXOoTb7BGJL16-pSzRnIGqBmTDwiG-jUtgLRicdkwxiHaguSXZBnKR1YIRR0T8kFb9tOiVZtyPI1hv0cUnaWuulobKZhpNZFu3iT3bynKfil90h33wBomKkP877KGCdqvZudNZ6GJdswYaJupseSwjkn-sflG2pDDLOJJ2piiZzo4BKahM_Jk9H4hC_u9kvy8-OHH1efqt2X689X73eVFULkqpOmkZIrzsZO9FKNFqCTIAbFOcq-nIetkXbsTTtahQggm3HoEBiq7YC2uSSvz3WPMfxeMGU9uWTRezNjWJIGJRvesLYTBX17Rm2xmiKO-hjdVK6ugenVvD7oB-b1al4D6OK15F_etVr6CYd_6XvVBbg-A1gefOsw6mSLKYuDi2izHoL771bvHlS6_4lfeMJ0CEuci1UNOnHN9Pd1DNYpKHYYZ6xr_gJjQLXB</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Ogita, Manabu</creator><creator>Miyauchi, Katsumi</creator><creator>Kasai, Takatoshi</creator><creator>Tsuboi, Shuta</creator><creator>Wada, Hideki</creator><creator>Naito, Ryo</creator><creator>Konishi, Hirokazu</creator><creator>Dohi, Tomotaka</creator><creator>Tamura, Hiroshi</creator><creator>Okazaki, Shinya</creator><creator>Yanagisawa, Naotake</creator><creator>Shimada, Kazunori</creator><creator>Suwa, Satoru</creator><creator>Jiang, Meizi</creator><creator>Bujo, Hideaki</creator><creator>Daida, Hiroyuki</creator><general>Elsevier Ireland Ltd</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>7X8</scope></search><sort><creationdate>20160101</creationdate><title>Prognostic impact of circulating soluble LR11 on long-term clinical outcomes in patients with coronary artery disease</title><author>Ogita, Manabu ; Miyauchi, Katsumi ; Kasai, Takatoshi ; Tsuboi, Shuta ; Wada, Hideki ; Naito, Ryo ; Konishi, Hirokazu ; Dohi, Tomotaka ; Tamura, Hiroshi ; Okazaki, Shinya ; Yanagisawa, Naotake ; Shimada, Kazunori ; Suwa, Satoru ; Jiang, Meizi ; Bujo, Hideaki ; Daida, Hiroyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-85a3552720f84b57fc118514d722e5b185d9a5cfba6fc7ee1153fd8e10e79dec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aged</topic><topic>Biomarker</topic><topic>Biomarkers - blood</topic><topic>Cardiovascular</topic><topic>Coronary artery disease</topic><topic>Coronary Artery Disease - blood</topic><topic>Coronary Artery Disease - epidemiology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Japan - epidemiology</topic><topic>LDL-Receptor Related Proteins - blood</topic><topic>Long-term outcomes</topic><topic>Male</topic><topic>Membrane Transport Proteins - blood</topic><topic>Middle Aged</topic><topic>Morbidity - trends</topic><topic>Nerve Tissue Proteins</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Risk Factors</topic><topic>Smooth muscle cell</topic><topic>Survival Rate - trends</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ogita, Manabu</creatorcontrib><creatorcontrib>Miyauchi, Katsumi</creatorcontrib><creatorcontrib>Kasai, Takatoshi</creatorcontrib><creatorcontrib>Tsuboi, Shuta</creatorcontrib><creatorcontrib>Wada, Hideki</creatorcontrib><creatorcontrib>Naito, Ryo</creatorcontrib><creatorcontrib>Konishi, Hirokazu</creatorcontrib><creatorcontrib>Dohi, Tomotaka</creatorcontrib><creatorcontrib>Tamura, Hiroshi</creatorcontrib><creatorcontrib>Okazaki, Shinya</creatorcontrib><creatorcontrib>Yanagisawa, Naotake</creatorcontrib><creatorcontrib>Shimada, Kazunori</creatorcontrib><creatorcontrib>Suwa, Satoru</creatorcontrib><creatorcontrib>Jiang, Meizi</creatorcontrib><creatorcontrib>Bujo, Hideaki</creatorcontrib><creatorcontrib>Daida, Hiroyuki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ogita, Manabu</au><au>Miyauchi, Katsumi</au><au>Kasai, Takatoshi</au><au>Tsuboi, Shuta</au><au>Wada, Hideki</au><au>Naito, Ryo</au><au>Konishi, Hirokazu</au><au>Dohi, Tomotaka</au><au>Tamura, Hiroshi</au><au>Okazaki, Shinya</au><au>Yanagisawa, Naotake</au><au>Shimada, Kazunori</au><au>Suwa, Satoru</au><au>Jiang, Meizi</au><au>Bujo, Hideaki</au><au>Daida, Hiroyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic impact of circulating soluble LR11 on long-term clinical outcomes in patients with coronary artery disease</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>244</volume><spage>216</spage><epage>221</epage><pages>216-221</pages><issn>0021-9150</issn><eissn>1879-1484</eissn><abstract>Abstract Background LR11, a member of LDL receptor family, is a novel marker of the proliferation of intimal smooth muscle cells (SMCs). LR11 is released in soluble form (sLR11) by proteolytic shedding and has biological activity toward SMC migration. We previously showed that circulating sLR11 positively correlates with carotid intima-medial thickness (IMT) independently of classical atherosclerotic risk factors and that it significantly associates with the severity of CAD. However, the association between sLR11 and long-term clinical outcomes remain uncertain. Methods and results This study included 438 consecutive patients (mean age, 65.8 ± 9.6 y; male, 82.4%) who underwent coronary intervention between March 2003 and December 2004 at our institution. The patients were assigned to quartiles according to pre-procedural sLR11 values. The primary endpoints were composite cardiovascular disease (CVD) endpoints including cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke. During median follow-up of 2876 days, composite CVD endpoints occurred 97 (22.1%) patients including 41 (9.4%) with cardiovascular disease (CVD)-related death, 36 (8.2%) non-fatal ACS and 20 (4.6%) non-fatal strokes. The hazard ratio (HR) for composite CVD endpoints significantly and dose-dependently increased with sLR11 levels (p for trend = 0.0077). A higher logarithm-transformed sLR11 value was associated with a greater risk of composite CVD endpoints, and the increased number of adverse long-term clinical outcomes persisted even after adjustment for other independent variables (HR 1.87 95%CI 1.02–3.31, p = 0.0435). Conclusions Elevated sLR11 levels were significantly associated with higher long-term adverse cardiac events in patients with CAD. Further extensive studies are expected to elucidate the mechanistic role of sLR11 and its clinical value as a prognostic marker in the development of atherosclerosis.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>26687467</pmid><doi>10.1016/j.atherosclerosis.2015.11.004</doi><tpages>6</tpages></addata></record> |
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| subjects | Aged Biomarker Biomarkers - blood Cardiovascular Coronary artery disease Coronary Artery Disease - blood Coronary Artery Disease - epidemiology Enzyme-Linked Immunosorbent Assay Female Follow-Up Studies Humans Japan - epidemiology LDL-Receptor Related Proteins - blood Long-term outcomes Male Membrane Transport Proteins - blood Middle Aged Morbidity - trends Nerve Tissue Proteins Prognosis Prospective Studies Risk Factors Smooth muscle cell Survival Rate - trends Time Factors |
| title | Prognostic impact of circulating soluble LR11 on long-term clinical outcomes in patients with coronary artery disease |
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