Determinants of Fasting and Post-Methionine Homocysteine Levels in Families Predisposed to Hyperhomocysteinemia and Premature Vascular Disease
Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial t...
Gespeichert in:
| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 1999-05, Vol.19 (5), p.1316-1324 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1324 |
|---|---|
| container_issue | 5 |
| container_start_page | 1316 |
| container_title | Arteriosclerosis, thrombosis, and vascular biology |
| container_volume | 19 |
| creator | de Jong, S.C Stehouwer, C.D.A van den Berg, M Kostense, P.J Alders, D Jakobs, C Pals, G Rauwerda, J.A |
| description | Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial traits. We investigated determinants of fasting, postmethionine and delta (ie, post-methionine minus fasting levels) tHcy levels in 510 subjects of 192 HHC-prone families including 161 patients with clinical vascular disease and 349 without vascular disease. We focused on tHcy levels in relation to levels of vitamin B12, B6 and folate and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Multivariate linear analyses adjusted for the presence of vascular disease showed that fasting tHcy was significantly related to folate and vitamin B12, and the presence of the MTHFR TT genotype and the T allele, and to age, smoking habits, and serum levels of creatinine. Both post-methionine and delta tHcy levels were related to serum folate levels, and the presence of the MTHFR TT genotype and the T allele, and to postmenopausal status, and body mass index. An interaction was found between MTHFR TT genotype and serum folate levels for both fasting and post-methionine tHcy, ie, for a given decrease in serum folate, homocysteine levels increased more in subjects with the TT genotype than in those with the CC genotype. Fasting, post-methionine and delta tHcy were higher in patients with vascular disease than in their healthy siblings, but these levels were less dependent on serum folate levels (P |
| doi_str_mv | 10.1161/01.ATV.19.5.1316 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69748906</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>41900846</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4724-74d4fd8ae99f0b5a24579682bab05edaae842629c0233d787e50483821d4591f3</originalsourceid><addsrcrecordid>eNpdkU1v1DAQhiMEoqVw54QsVHFL8HfiY9XSLtIieii9Wt5kwro48eJJqPZP8JvxKiu14mDZIz3vaDxPUbxntGJMs8-UVRd39xUzlaqYYPpFccoUl6XUQr_Mb1qbUmnJT4o3iA-UUsk5fV2cMCq4qBt1Wvy9ggnS4Ec3TkhiT64dTn78SdzYkduIU_kNpq2Pox-BrOIQ2z1OcCjW8AcCEj_myOCDByS3CTqPu4jQkSmS1X4HafssM3i39E0wuGlOQO4dtnNwiVx5BIfwtnjVu4Dw7nifFT-uv9xdrsr195uvlxfrspV1_l8tO9l3jQNjerpRjktVG93wjdtQBZ1z0EiuuWkpF6KrmxoUlY1oOOukMqwXZ8Wnpe8uxd8z4GQHjy2E4EaIM1ptatkYqjP48T_wIc5pzLNZnrdppKIiQ3SB2hQRE_R2l_zg0t4yag-iLGU2i7LMWGUPonLkw7HvvBmgexZYzGTg_AjkFbnQJze2Hp-4uuFC84zJBXuMIYvEX2F-hGS34MK0tQfjQlNVMmMMVbks8-FS_APIAKxA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>204294503</pqid></control><display><type>article</type><title>Determinants of Fasting and Post-Methionine Homocysteine Levels in Families Predisposed to Hyperhomocysteinemia and Premature Vascular Disease</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>Journals@Ovid Complete</source><creator>de Jong, S.C ; Stehouwer, C.D.A ; van den Berg, M ; Kostense, P.J ; Alders, D ; Jakobs, C ; Pals, G ; Rauwerda, J.A</creator><creatorcontrib>de Jong, S.C ; Stehouwer, C.D.A ; van den Berg, M ; Kostense, P.J ; Alders, D ; Jakobs, C ; Pals, G ; Rauwerda, J.A</creatorcontrib><description>Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial traits. We investigated determinants of fasting, postmethionine and delta (ie, post-methionine minus fasting levels) tHcy levels in 510 subjects of 192 HHC-prone families including 161 patients with clinical vascular disease and 349 without vascular disease. We focused on tHcy levels in relation to levels of vitamin B12, B6 and folate and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Multivariate linear analyses adjusted for the presence of vascular disease showed that fasting tHcy was significantly related to folate and vitamin B12, and the presence of the MTHFR TT genotype and the T allele, and to age, smoking habits, and serum levels of creatinine. Both post-methionine and delta tHcy levels were related to serum folate levels, and the presence of the MTHFR TT genotype and the T allele, and to postmenopausal status, and body mass index. An interaction was found between MTHFR TT genotype and serum folate levels for both fasting and post-methionine tHcy, ie, for a given decrease in serum folate, homocysteine levels increased more in subjects with the TT genotype than in those with the CC genotype. Fasting, post-methionine and delta tHcy were higher in patients with vascular disease than in their healthy siblings, but these levels were less dependent on serum folate levels (P<0.05), whereas the effect of MTHFR genotype was stronger (P = 0.01). This study found evidence that post-methionine and delta tHcy levels are not only influenced by factors affecting homocysteine transsulfuration but also by factors that affect remethylation. The explained variances of fasting, post-methionine and delta tHcy were 49%, 62%, and 78%, respectively. We also found evidence, in patients with premature vascular disease but not in their healthy siblings, for a factor that increases tHcy levels but weakens the normal inverse relation between folate and tHcy and amplifies the effect of the MTHFR genotype. (Arterioscler Thromb Vasc Biol. 1999;19:1316-1324.)</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/01.ATV.19.5.1316</identifier><identifier>PMID: 10323785</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Adult ; Age Factors ; Amino Acid Substitution ; Arteriosclerosis - genetics ; Biological and medical sciences ; Body Mass Index ; Cardiology. Vascular system ; Comorbidity ; Coronary heart disease ; Fasting - blood ; Female ; Folic Acid - blood ; Genetic Predisposition to Disease ; Genotype ; Heart ; Homocysteine - biosynthesis ; Homocysteine - blood ; Humans ; Hyperhomocysteinemia - blood ; Hyperhomocysteinemia - genetics ; Hypertension - epidemiology ; Lipids - blood ; Male ; Medical sciences ; Menopause ; Methionine - pharmacokinetics ; Methylenetetrahydrofolate Reductase (NADPH2) ; Middle Aged ; Oxidoreductases Acting on CH-NH Group Donors - genetics ; Polymorphism, Genetic ; Pyridoxine - blood ; Smoking - epidemiology ; Vitamin B 12 - blood</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 1999-05, Vol.19 (5), p.1316-1324</ispartof><rights>1999 American Heart Association, Inc.</rights><rights>1999 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. May 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4724-74d4fd8ae99f0b5a24579682bab05edaae842629c0233d787e50483821d4591f3</citedby><cites>FETCH-LOGICAL-c4724-74d4fd8ae99f0b5a24579682bab05edaae842629c0233d787e50483821d4591f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1782362$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10323785$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Jong, S.C</creatorcontrib><creatorcontrib>Stehouwer, C.D.A</creatorcontrib><creatorcontrib>van den Berg, M</creatorcontrib><creatorcontrib>Kostense, P.J</creatorcontrib><creatorcontrib>Alders, D</creatorcontrib><creatorcontrib>Jakobs, C</creatorcontrib><creatorcontrib>Pals, G</creatorcontrib><creatorcontrib>Rauwerda, J.A</creatorcontrib><title>Determinants of Fasting and Post-Methionine Homocysteine Levels in Families Predisposed to Hyperhomocysteinemia and Premature Vascular Disease</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial traits. We investigated determinants of fasting, postmethionine and delta (ie, post-methionine minus fasting levels) tHcy levels in 510 subjects of 192 HHC-prone families including 161 patients with clinical vascular disease and 349 without vascular disease. We focused on tHcy levels in relation to levels of vitamin B12, B6 and folate and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Multivariate linear analyses adjusted for the presence of vascular disease showed that fasting tHcy was significantly related to folate and vitamin B12, and the presence of the MTHFR TT genotype and the T allele, and to age, smoking habits, and serum levels of creatinine. Both post-methionine and delta tHcy levels were related to serum folate levels, and the presence of the MTHFR TT genotype and the T allele, and to postmenopausal status, and body mass index. An interaction was found between MTHFR TT genotype and serum folate levels for both fasting and post-methionine tHcy, ie, for a given decrease in serum folate, homocysteine levels increased more in subjects with the TT genotype than in those with the CC genotype. Fasting, post-methionine and delta tHcy were higher in patients with vascular disease than in their healthy siblings, but these levels were less dependent on serum folate levels (P<0.05), whereas the effect of MTHFR genotype was stronger (P = 0.01). This study found evidence that post-methionine and delta tHcy levels are not only influenced by factors affecting homocysteine transsulfuration but also by factors that affect remethylation. The explained variances of fasting, post-methionine and delta tHcy were 49%, 62%, and 78%, respectively. We also found evidence, in patients with premature vascular disease but not in their healthy siblings, for a factor that increases tHcy levels but weakens the normal inverse relation between folate and tHcy and amplifies the effect of the MTHFR genotype. (Arterioscler Thromb Vasc Biol. 1999;19:1316-1324.)</description><subject>Adult</subject><subject>Age Factors</subject><subject>Amino Acid Substitution</subject><subject>Arteriosclerosis - genetics</subject><subject>Biological and medical sciences</subject><subject>Body Mass Index</subject><subject>Cardiology. Vascular system</subject><subject>Comorbidity</subject><subject>Coronary heart disease</subject><subject>Fasting - blood</subject><subject>Female</subject><subject>Folic Acid - blood</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Heart</subject><subject>Homocysteine - biosynthesis</subject><subject>Homocysteine - blood</subject><subject>Humans</subject><subject>Hyperhomocysteinemia - blood</subject><subject>Hyperhomocysteinemia - genetics</subject><subject>Hypertension - epidemiology</subject><subject>Lipids - blood</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Menopause</subject><subject>Methionine - pharmacokinetics</subject><subject>Methylenetetrahydrofolate Reductase (NADPH2)</subject><subject>Middle Aged</subject><subject>Oxidoreductases Acting on CH-NH Group Donors - genetics</subject><subject>Polymorphism, Genetic</subject><subject>Pyridoxine - blood</subject><subject>Smoking - epidemiology</subject><subject>Vitamin B 12 - blood</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1v1DAQhiMEoqVw54QsVHFL8HfiY9XSLtIieii9Wt5kwro48eJJqPZP8JvxKiu14mDZIz3vaDxPUbxntGJMs8-UVRd39xUzlaqYYPpFccoUl6XUQr_Mb1qbUmnJT4o3iA-UUsk5fV2cMCq4qBt1Wvy9ggnS4Ec3TkhiT64dTn78SdzYkduIU_kNpq2Pox-BrOIQ2z1OcCjW8AcCEj_myOCDByS3CTqPu4jQkSmS1X4HafssM3i39E0wuGlOQO4dtnNwiVx5BIfwtnjVu4Dw7nifFT-uv9xdrsr195uvlxfrspV1_l8tO9l3jQNjerpRjktVG93wjdtQBZ1z0EiuuWkpF6KrmxoUlY1oOOukMqwXZ8Wnpe8uxd8z4GQHjy2E4EaIM1ptatkYqjP48T_wIc5pzLNZnrdppKIiQ3SB2hQRE_R2l_zg0t4yag-iLGU2i7LMWGUPonLkw7HvvBmgexZYzGTg_AjkFbnQJze2Hp-4uuFC84zJBXuMIYvEX2F-hGS34MK0tQfjQlNVMmMMVbks8-FS_APIAKxA</recordid><startdate>199905</startdate><enddate>199905</enddate><creator>de Jong, S.C</creator><creator>Stehouwer, C.D.A</creator><creator>van den Berg, M</creator><creator>Kostense, P.J</creator><creator>Alders, D</creator><creator>Jakobs, C</creator><creator>Pals, G</creator><creator>Rauwerda, J.A</creator><general>American Heart Association, Inc</general><general>Lippincott</general><scope>IQODW</scope><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>K9.</scope><scope>7X8</scope></search><sort><creationdate>199905</creationdate><title>Determinants of Fasting and Post-Methionine Homocysteine Levels in Families Predisposed to Hyperhomocysteinemia and Premature Vascular Disease</title><author>de Jong, S.C ; Stehouwer, C.D.A ; van den Berg, M ; Kostense, P.J ; Alders, D ; Jakobs, C ; Pals, G ; Rauwerda, J.A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4724-74d4fd8ae99f0b5a24579682bab05edaae842629c0233d787e50483821d4591f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adult</topic><topic>Age Factors</topic><topic>Amino Acid Substitution</topic><topic>Arteriosclerosis - genetics</topic><topic>Biological and medical sciences</topic><topic>Body Mass Index</topic><topic>Cardiology. Vascular system</topic><topic>Comorbidity</topic><topic>Coronary heart disease</topic><topic>Fasting - blood</topic><topic>Female</topic><topic>Folic Acid - blood</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype</topic><topic>Heart</topic><topic>Homocysteine - biosynthesis</topic><topic>Homocysteine - blood</topic><topic>Humans</topic><topic>Hyperhomocysteinemia - blood</topic><topic>Hyperhomocysteinemia - genetics</topic><topic>Hypertension - epidemiology</topic><topic>Lipids - blood</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Menopause</topic><topic>Methionine - pharmacokinetics</topic><topic>Methylenetetrahydrofolate Reductase (NADPH2)</topic><topic>Middle Aged</topic><topic>Oxidoreductases Acting on CH-NH Group Donors - genetics</topic><topic>Polymorphism, Genetic</topic><topic>Pyridoxine - blood</topic><topic>Smoking - epidemiology</topic><topic>Vitamin B 12 - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Jong, S.C</creatorcontrib><creatorcontrib>Stehouwer, C.D.A</creatorcontrib><creatorcontrib>van den Berg, M</creatorcontrib><creatorcontrib>Kostense, P.J</creatorcontrib><creatorcontrib>Alders, D</creatorcontrib><creatorcontrib>Jakobs, C</creatorcontrib><creatorcontrib>Pals, G</creatorcontrib><creatorcontrib>Rauwerda, J.A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Jong, S.C</au><au>Stehouwer, C.D.A</au><au>van den Berg, M</au><au>Kostense, P.J</au><au>Alders, D</au><au>Jakobs, C</au><au>Pals, G</au><au>Rauwerda, J.A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Determinants of Fasting and Post-Methionine Homocysteine Levels in Families Predisposed to Hyperhomocysteinemia and Premature Vascular Disease</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>1999-05</date><risdate>1999</risdate><volume>19</volume><issue>5</issue><spage>1316</spage><epage>1324</epage><pages>1316-1324</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial traits. We investigated determinants of fasting, postmethionine and delta (ie, post-methionine minus fasting levels) tHcy levels in 510 subjects of 192 HHC-prone families including 161 patients with clinical vascular disease and 349 without vascular disease. We focused on tHcy levels in relation to levels of vitamin B12, B6 and folate and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Multivariate linear analyses adjusted for the presence of vascular disease showed that fasting tHcy was significantly related to folate and vitamin B12, and the presence of the MTHFR TT genotype and the T allele, and to age, smoking habits, and serum levels of creatinine. Both post-methionine and delta tHcy levels were related to serum folate levels, and the presence of the MTHFR TT genotype and the T allele, and to postmenopausal status, and body mass index. An interaction was found between MTHFR TT genotype and serum folate levels for both fasting and post-methionine tHcy, ie, for a given decrease in serum folate, homocysteine levels increased more in subjects with the TT genotype than in those with the CC genotype. Fasting, post-methionine and delta tHcy were higher in patients with vascular disease than in their healthy siblings, but these levels were less dependent on serum folate levels (P<0.05), whereas the effect of MTHFR genotype was stronger (P = 0.01). This study found evidence that post-methionine and delta tHcy levels are not only influenced by factors affecting homocysteine transsulfuration but also by factors that affect remethylation. The explained variances of fasting, post-methionine and delta tHcy were 49%, 62%, and 78%, respectively. We also found evidence, in patients with premature vascular disease but not in their healthy siblings, for a factor that increases tHcy levels but weakens the normal inverse relation between folate and tHcy and amplifies the effect of the MTHFR genotype. (Arterioscler Thromb Vasc Biol. 1999;19:1316-1324.)</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>10323785</pmid><doi>10.1161/01.ATV.19.5.1316</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1079-5642 |
| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 1999-05, Vol.19 (5), p.1316-1324 |
| issn | 1079-5642 1524-4636 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69748906 |
| source | MEDLINE; Alma/SFX Local Collection; Journals@Ovid Complete |
| subjects | Adult Age Factors Amino Acid Substitution Arteriosclerosis - genetics Biological and medical sciences Body Mass Index Cardiology. Vascular system Comorbidity Coronary heart disease Fasting - blood Female Folic Acid - blood Genetic Predisposition to Disease Genotype Heart Homocysteine - biosynthesis Homocysteine - blood Humans Hyperhomocysteinemia - blood Hyperhomocysteinemia - genetics Hypertension - epidemiology Lipids - blood Male Medical sciences Menopause Methionine - pharmacokinetics Methylenetetrahydrofolate Reductase (NADPH2) Middle Aged Oxidoreductases Acting on CH-NH Group Donors - genetics Polymorphism, Genetic Pyridoxine - blood Smoking - epidemiology Vitamin B 12 - blood |
| title | Determinants of Fasting and Post-Methionine Homocysteine Levels in Families Predisposed to Hyperhomocysteinemia and Premature Vascular Disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T20%3A43%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Determinants%20of%20Fasting%20and%20Post-Methionine%20Homocysteine%20Levels%20in%20Families%20Predisposed%20to%20Hyperhomocysteinemia%20and%20Premature%20Vascular%20Disease&rft.jtitle=Arteriosclerosis,%20thrombosis,%20and%20vascular%20biology&rft.au=de%20Jong,%20S.C&rft.date=1999-05&rft.volume=19&rft.issue=5&rft.spage=1316&rft.epage=1324&rft.pages=1316-1324&rft.issn=1079-5642&rft.eissn=1524-4636&rft.coden=ATVBFA&rft_id=info:doi/10.1161/01.ATV.19.5.1316&rft_dat=%3Cproquest_cross%3E41900846%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=204294503&rft_id=info:pmid/10323785&rfr_iscdi=true |