Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure
Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and...
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| Veröffentlicht in: | Heart and vessels 2021-07, Vol.36 (7), p.965-977 |
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| creator | Hiraiwa, Hiroaki Okumura, Takahiro Kondo, Toru Kato, Toshiaki Kazama, Shingo Kimura, Yuki Ishihara, Toshikazu Iwata, Etsuo Shimojo, Masafumi Kondo, Sayano Aoki, Soichiro Kanzaki, Yasunori Tanimura, Daisuke Sano, Hiroaki Awaji, Yoshifumi Yamada, Sumio Murohara, Toyoaki |
| description | Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and phenylalanine) are increased. To date, we have reported the prognostic value of the BCAA/AAA ratio (Fischer’s ratio) in patients with HF. However, the leucine/phenylalanine ratio, which is a simpler index than the Fischer’s ratio, has not been examined. Therefore, the prognostic value of the leucine/phenylalanine ratio in patients with HF was investigated. Overall 157 consecutive patients hospitalized for worsening HF (81 men, median age 78 years) were enrolled in the study. Plasma amino acid levels were measured when the patients were stabilized at discharge. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. A total of 46 cardiac events occurred during the median follow-up period of 238 (interquartile range 93–365) days. The median leucine/phenylalanine ratio was significantly lower in patients with cardiac events than in those without cardiac events (1.4 vs. 1.8,
P
|
| doi_str_mv | 10.1007/s00380-020-01765-z |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2480298214</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2536820464</sourcerecordid><originalsourceid>FETCH-LOGICAL-c399t-e42c73e7502a8fe1afc1aa1d294a32b3a4402716120103501c3fa2c2783451063</originalsourceid><addsrcrecordid>eNp9kEFP3DAQhS3Uqrtd-gc4IEu9cAnMjJ3EOSIEtNJK7aE9cLIGrwNeZZPFTpDg12NYoBKHHizb8vfePD8hDhCOEaA-SQDKQAGUF9ZVWTzuiTlWWBZU1uqTmEODUBhF9Ux8TWkNgGWDzRcxU0obBFPNxdXvONz0QxqDk_fcTV4Orez85ELvT7a3vn_ouOM-32TkMQySk-Re8ib0-ezCSm7j0IbuRXfrOY6y5dBN0e-Lzy13yX973Rfi78X5n7MfxfLX5c-z02XhVNOMhdfkauXrEohN65Fbh8y4okazomvFWgPV-VcECKoEdKplclQbpUuESi3E0c43B7mbfBrtJiTnu5zaD1OypA1QYwh1Rr9_QNfDFPuczlKpKkOgq2eKdpSLQ0rRt3Ybw4bjg0Wwz8XbXfE2F29firePWXT4aj1db_zqXfLWdAbUDkj5qb_x8d_s_9g-AVrqjQc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2536820464</pqid></control><display><type>article</type><title>Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure</title><source>SpringerLink Journals - AutoHoldings</source><creator>Hiraiwa, Hiroaki ; Okumura, Takahiro ; Kondo, Toru ; Kato, Toshiaki ; Kazama, Shingo ; Kimura, Yuki ; Ishihara, Toshikazu ; Iwata, Etsuo ; Shimojo, Masafumi ; Kondo, Sayano ; Aoki, Soichiro ; Kanzaki, Yasunori ; Tanimura, Daisuke ; Sano, Hiroaki ; Awaji, Yoshifumi ; Yamada, Sumio ; Murohara, Toyoaki</creator><creatorcontrib>Hiraiwa, Hiroaki ; Okumura, Takahiro ; Kondo, Toru ; Kato, Toshiaki ; Kazama, Shingo ; Kimura, Yuki ; Ishihara, Toshikazu ; Iwata, Etsuo ; Shimojo, Masafumi ; Kondo, Sayano ; Aoki, Soichiro ; Kanzaki, Yasunori ; Tanimura, Daisuke ; Sano, Hiroaki ; Awaji, Yoshifumi ; Yamada, Sumio ; Murohara, Toyoaki</creatorcontrib><description>Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and phenylalanine) are increased. To date, we have reported the prognostic value of the BCAA/AAA ratio (Fischer’s ratio) in patients with HF. However, the leucine/phenylalanine ratio, which is a simpler index than the Fischer’s ratio, has not been examined. Therefore, the prognostic value of the leucine/phenylalanine ratio in patients with HF was investigated. Overall 157 consecutive patients hospitalized for worsening HF (81 men, median age 78 years) were enrolled in the study. Plasma amino acid levels were measured when the patients were stabilized at discharge. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. A total of 46 cardiac events occurred during the median follow-up period of 238 (interquartile range 93–365) days. The median leucine/phenylalanine ratio was significantly lower in patients with cardiac events than in those without cardiac events (1.4 vs. 1.8,
P
< 0.001). The best cutoff value of the leucine/phenylalanine ratio was determined as 1.7 in the receiver operating characteristic (ROC) curve for cardiac events. Following a Kaplan–Meier survival analysis, the low group (leucine/phenylalanine ratio < 1.7,
n
= 72) had more cardiac events than the high group (leucine/phenylalanine ratio ≥ 1.7,
n
= 85) (log-rank,
P
< 0.001). Multivariate Cox proportional hazards regression analysis showed that the leucine/phenylalanine ratio was an independent predictor of cardiac events. Furthermore, on comparing the prognostic values for cardiac events based on ROC curves of leucine levels, BCAA levels, Fischer’s ratio, and leucine/phenylalanine ratio, the leucine/phenylalanine ratio was the most accurate in predicting future cardiac events (area under the curve 0.763,; sensitivity 0.783,; specificity 0.676,;
P
< 0.001). The leucine/phenylalanine ratio could be a useful predictor of future cardiac events in patients with HF, reflecting an imbalance in amino acid metabolism.</description><identifier>ISSN: 0910-8327</identifier><identifier>EISSN: 1615-2573</identifier><identifier>DOI: 10.1007/s00380-020-01765-z</identifier><identifier>PMID: 33481086</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Amino acids ; Biomedical Engineering and Bioengineering ; Cardiac Surgery ; Cardiology ; Chain branching ; Congestive heart failure ; Heart failure ; Isoleucine ; Leucine ; Medicine ; Medicine & Public Health ; Metabolism ; Muscles ; Original Article ; Phenylalanine ; Protein biosynthesis ; Protein synthesis ; Regression analysis ; Skeletal muscle ; Survival analysis ; Tyrosine ; Valine ; Vascular Surgery</subject><ispartof>Heart and vessels, 2021-07, Vol.36 (7), p.965-977</ispartof><rights>Springer Japan KK, part of Springer Nature 2021</rights><rights>Springer Japan KK, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-e42c73e7502a8fe1afc1aa1d294a32b3a4402716120103501c3fa2c2783451063</citedby><cites>FETCH-LOGICAL-c399t-e42c73e7502a8fe1afc1aa1d294a32b3a4402716120103501c3fa2c2783451063</cites><orcidid>0000-0001-5076-2052 ; 0000-0002-1606-7037</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/s00380-020-01765-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00380-020-01765-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33481086$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hiraiwa, Hiroaki</creatorcontrib><creatorcontrib>Okumura, Takahiro</creatorcontrib><creatorcontrib>Kondo, Toru</creatorcontrib><creatorcontrib>Kato, Toshiaki</creatorcontrib><creatorcontrib>Kazama, Shingo</creatorcontrib><creatorcontrib>Kimura, Yuki</creatorcontrib><creatorcontrib>Ishihara, Toshikazu</creatorcontrib><creatorcontrib>Iwata, Etsuo</creatorcontrib><creatorcontrib>Shimojo, Masafumi</creatorcontrib><creatorcontrib>Kondo, Sayano</creatorcontrib><creatorcontrib>Aoki, Soichiro</creatorcontrib><creatorcontrib>Kanzaki, Yasunori</creatorcontrib><creatorcontrib>Tanimura, Daisuke</creatorcontrib><creatorcontrib>Sano, Hiroaki</creatorcontrib><creatorcontrib>Awaji, Yoshifumi</creatorcontrib><creatorcontrib>Yamada, Sumio</creatorcontrib><creatorcontrib>Murohara, Toyoaki</creatorcontrib><title>Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure</title><title>Heart and vessels</title><addtitle>Heart Vessels</addtitle><addtitle>Heart Vessels</addtitle><description>Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and phenylalanine) are increased. To date, we have reported the prognostic value of the BCAA/AAA ratio (Fischer’s ratio) in patients with HF. However, the leucine/phenylalanine ratio, which is a simpler index than the Fischer’s ratio, has not been examined. Therefore, the prognostic value of the leucine/phenylalanine ratio in patients with HF was investigated. Overall 157 consecutive patients hospitalized for worsening HF (81 men, median age 78 years) were enrolled in the study. Plasma amino acid levels were measured when the patients were stabilized at discharge. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. A total of 46 cardiac events occurred during the median follow-up period of 238 (interquartile range 93–365) days. The median leucine/phenylalanine ratio was significantly lower in patients with cardiac events than in those without cardiac events (1.4 vs. 1.8,
P
< 0.001). The best cutoff value of the leucine/phenylalanine ratio was determined as 1.7 in the receiver operating characteristic (ROC) curve for cardiac events. Following a Kaplan–Meier survival analysis, the low group (leucine/phenylalanine ratio < 1.7,
n
= 72) had more cardiac events than the high group (leucine/phenylalanine ratio ≥ 1.7,
n
= 85) (log-rank,
P
< 0.001). Multivariate Cox proportional hazards regression analysis showed that the leucine/phenylalanine ratio was an independent predictor of cardiac events. Furthermore, on comparing the prognostic values for cardiac events based on ROC curves of leucine levels, BCAA levels, Fischer’s ratio, and leucine/phenylalanine ratio, the leucine/phenylalanine ratio was the most accurate in predicting future cardiac events (area under the curve 0.763,; sensitivity 0.783,; specificity 0.676,;
P
< 0.001). The leucine/phenylalanine ratio could be a useful predictor of future cardiac events in patients with HF, reflecting an imbalance in amino acid metabolism.</description><subject>Amino acids</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Cardiac Surgery</subject><subject>Cardiology</subject><subject>Chain branching</subject><subject>Congestive heart failure</subject><subject>Heart failure</subject><subject>Isoleucine</subject><subject>Leucine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolism</subject><subject>Muscles</subject><subject>Original Article</subject><subject>Phenylalanine</subject><subject>Protein biosynthesis</subject><subject>Protein synthesis</subject><subject>Regression analysis</subject><subject>Skeletal muscle</subject><subject>Survival analysis</subject><subject>Tyrosine</subject><subject>Valine</subject><subject>Vascular Surgery</subject><issn>0910-8327</issn><issn>1615-2573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kEFP3DAQhS3Uqrtd-gc4IEu9cAnMjJ3EOSIEtNJK7aE9cLIGrwNeZZPFTpDg12NYoBKHHizb8vfePD8hDhCOEaA-SQDKQAGUF9ZVWTzuiTlWWBZU1uqTmEODUBhF9Ux8TWkNgGWDzRcxU0obBFPNxdXvONz0QxqDk_fcTV4Orez85ELvT7a3vn_ouOM-32TkMQySk-Re8ib0-ezCSm7j0IbuRXfrOY6y5dBN0e-Lzy13yX973Rfi78X5n7MfxfLX5c-z02XhVNOMhdfkauXrEohN65Fbh8y4okazomvFWgPV-VcECKoEdKplclQbpUuESi3E0c43B7mbfBrtJiTnu5zaD1OypA1QYwh1Rr9_QNfDFPuczlKpKkOgq2eKdpSLQ0rRt3Ybw4bjg0Wwz8XbXfE2F29firePWXT4aj1db_zqXfLWdAbUDkj5qb_x8d_s_9g-AVrqjQc</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Hiraiwa, Hiroaki</creator><creator>Okumura, Takahiro</creator><creator>Kondo, Toru</creator><creator>Kato, Toshiaki</creator><creator>Kazama, Shingo</creator><creator>Kimura, Yuki</creator><creator>Ishihara, Toshikazu</creator><creator>Iwata, Etsuo</creator><creator>Shimojo, Masafumi</creator><creator>Kondo, Sayano</creator><creator>Aoki, Soichiro</creator><creator>Kanzaki, Yasunori</creator><creator>Tanimura, Daisuke</creator><creator>Sano, Hiroaki</creator><creator>Awaji, Yoshifumi</creator><creator>Yamada, Sumio</creator><creator>Murohara, Toyoaki</creator><general>Springer Japan</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5076-2052</orcidid><orcidid>https://orcid.org/0000-0002-1606-7037</orcidid></search><sort><creationdate>20210701</creationdate><title>Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure</title><author>Hiraiwa, Hiroaki ; Okumura, Takahiro ; Kondo, Toru ; Kato, Toshiaki ; Kazama, Shingo ; Kimura, Yuki ; Ishihara, Toshikazu ; Iwata, Etsuo ; Shimojo, Masafumi ; Kondo, Sayano ; Aoki, Soichiro ; Kanzaki, Yasunori ; Tanimura, Daisuke ; Sano, Hiroaki ; Awaji, Yoshifumi ; Yamada, Sumio ; Murohara, Toyoaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-e42c73e7502a8fe1afc1aa1d294a32b3a4402716120103501c3fa2c2783451063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Amino acids</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Cardiac Surgery</topic><topic>Cardiology</topic><topic>Chain branching</topic><topic>Congestive heart failure</topic><topic>Heart failure</topic><topic>Isoleucine</topic><topic>Leucine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolism</topic><topic>Muscles</topic><topic>Original Article</topic><topic>Phenylalanine</topic><topic>Protein biosynthesis</topic><topic>Protein synthesis</topic><topic>Regression analysis</topic><topic>Skeletal muscle</topic><topic>Survival analysis</topic><topic>Tyrosine</topic><topic>Valine</topic><topic>Vascular Surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hiraiwa, Hiroaki</creatorcontrib><creatorcontrib>Okumura, Takahiro</creatorcontrib><creatorcontrib>Kondo, Toru</creatorcontrib><creatorcontrib>Kato, Toshiaki</creatorcontrib><creatorcontrib>Kazama, Shingo</creatorcontrib><creatorcontrib>Kimura, Yuki</creatorcontrib><creatorcontrib>Ishihara, Toshikazu</creatorcontrib><creatorcontrib>Iwata, Etsuo</creatorcontrib><creatorcontrib>Shimojo, Masafumi</creatorcontrib><creatorcontrib>Kondo, Sayano</creatorcontrib><creatorcontrib>Aoki, Soichiro</creatorcontrib><creatorcontrib>Kanzaki, Yasunori</creatorcontrib><creatorcontrib>Tanimura, Daisuke</creatorcontrib><creatorcontrib>Sano, Hiroaki</creatorcontrib><creatorcontrib>Awaji, Yoshifumi</creatorcontrib><creatorcontrib>Yamada, Sumio</creatorcontrib><creatorcontrib>Murohara, Toyoaki</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Heart and vessels</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hiraiwa, Hiroaki</au><au>Okumura, Takahiro</au><au>Kondo, Toru</au><au>Kato, Toshiaki</au><au>Kazama, Shingo</au><au>Kimura, Yuki</au><au>Ishihara, Toshikazu</au><au>Iwata, Etsuo</au><au>Shimojo, Masafumi</au><au>Kondo, Sayano</au><au>Aoki, Soichiro</au><au>Kanzaki, Yasunori</au><au>Tanimura, Daisuke</au><au>Sano, Hiroaki</au><au>Awaji, Yoshifumi</au><au>Yamada, Sumio</au><au>Murohara, Toyoaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure</atitle><jtitle>Heart and vessels</jtitle><stitle>Heart Vessels</stitle><addtitle>Heart Vessels</addtitle><date>2021-07-01</date><risdate>2021</risdate><volume>36</volume><issue>7</issue><spage>965</spage><epage>977</epage><pages>965-977</pages><issn>0910-8327</issn><eissn>1615-2573</eissn><abstract>Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and phenylalanine) are increased. To date, we have reported the prognostic value of the BCAA/AAA ratio (Fischer’s ratio) in patients with HF. However, the leucine/phenylalanine ratio, which is a simpler index than the Fischer’s ratio, has not been examined. Therefore, the prognostic value of the leucine/phenylalanine ratio in patients with HF was investigated. Overall 157 consecutive patients hospitalized for worsening HF (81 men, median age 78 years) were enrolled in the study. Plasma amino acid levels were measured when the patients were stabilized at discharge. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. A total of 46 cardiac events occurred during the median follow-up period of 238 (interquartile range 93–365) days. The median leucine/phenylalanine ratio was significantly lower in patients with cardiac events than in those without cardiac events (1.4 vs. 1.8,
P
< 0.001). The best cutoff value of the leucine/phenylalanine ratio was determined as 1.7 in the receiver operating characteristic (ROC) curve for cardiac events. Following a Kaplan–Meier survival analysis, the low group (leucine/phenylalanine ratio < 1.7,
n
= 72) had more cardiac events than the high group (leucine/phenylalanine ratio ≥ 1.7,
n
= 85) (log-rank,
P
< 0.001). Multivariate Cox proportional hazards regression analysis showed that the leucine/phenylalanine ratio was an independent predictor of cardiac events. Furthermore, on comparing the prognostic values for cardiac events based on ROC curves of leucine levels, BCAA levels, Fischer’s ratio, and leucine/phenylalanine ratio, the leucine/phenylalanine ratio was the most accurate in predicting future cardiac events (area under the curve 0.763,; sensitivity 0.783,; specificity 0.676,;
P
< 0.001). The leucine/phenylalanine ratio could be a useful predictor of future cardiac events in patients with HF, reflecting an imbalance in amino acid metabolism.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>33481086</pmid><doi>10.1007/s00380-020-01765-z</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-5076-2052</orcidid><orcidid>https://orcid.org/0000-0002-1606-7037</orcidid></addata></record> |
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| subjects | Amino acids Biomedical Engineering and Bioengineering Cardiac Surgery Cardiology Chain branching Congestive heart failure Heart failure Isoleucine Leucine Medicine Medicine & Public Health Metabolism Muscles Original Article Phenylalanine Protein biosynthesis Protein synthesis Regression analysis Skeletal muscle Survival analysis Tyrosine Valine Vascular Surgery |
| title | Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure |
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