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CMV seropositivity and T‐cell senescence predict increased cardiovascular mortality in octogenarians: results from the Newcastle 85+ study
Summary Although chronic infection with cytomegalovirus (CMV) is known to drive T lymphocytes toward a senescent phenotype, it remains controversial whether and how CMV can cause coronary heart disease (CHD). To explore whether CMV seropositivity or T‐cell populations associated with immunosenescenc...
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| Published in: | Aging cell 2016-04, Vol.15 (2), p.389-392 |
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| creator | Spyridopoulos, Ioakim Martin‐Ruiz, Carmen Hilkens, Catharien Yadegarfar, Mohammad E. Isaacs, John Jagger, Carol Kirkwood, Tom Zglinicki, Thomas |
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Although chronic infection with cytomegalovirus (CMV) is known to drive T lymphocytes toward a senescent phenotype, it remains controversial whether and how CMV can cause coronary heart disease (CHD). To explore whether CMV seropositivity or T‐cell populations associated with immunosenescence were informative for adverse cardiovascular outcome in the very old, we prospectively analyzed peripheral blood samples from 751 octogenarians (38% males) from the Newcastle 85+ study for their power to predict survival during a 65‐month follow‐up (47.3% survival rate). CMV‐seropositive participants showed a higher prevalence of CHD (37.7% vs. 26.7%, P = 0.030) compared to CMV‐seronegative participants together with lower CD4/CD8 ratio (1.7 vs. 4.1, P |
| doi_str_mv | 10.1111/acel.12430 |
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Although chronic infection with cytomegalovirus (CMV) is known to drive T lymphocytes toward a senescent phenotype, it remains controversial whether and how CMV can cause coronary heart disease (CHD). To explore whether CMV seropositivity or T‐cell populations associated with immunosenescence were informative for adverse cardiovascular outcome in the very old, we prospectively analyzed peripheral blood samples from 751 octogenarians (38% males) from the Newcastle 85+ study for their power to predict survival during a 65‐month follow‐up (47.3% survival rate). CMV‐seropositive participants showed a higher prevalence of CHD (37.7% vs. 26.7%, P = 0.030) compared to CMV‐seronegative participants together with lower CD4/CD8 ratio (1.7 vs. 4.1, P < 0.0001) and higher frequencies of senescence‐like CD4 memory cells (41.1% vs. 4.5%, P < 0.001) and senescence‐like CD8 memory cells (TEMRA, 28.1% vs. 6.7%, P < 0.001). CMV seropositivity was also associated with increased six‐year cardiovascular mortality (HR 1.75 [1.09–2.82], P = 0.021) or death from myocardial infarction and stroke (HR 1.89 [107–3.36], P = 0.029). Gender‐adjusted multivariate Cox regression analysis revealed that low percentages of senescence‐like CD4 T cells (HR 0.48 [0.32–0.72], P < 0.001) and near‐senescent (CD27 negative) CD8 T cells (HR 0.60 [0.41–0.88], P = 0.029) reduced the risk of cardiovascular death. For senescence‐like CD4, but not near‐senescent CD8 T cells, these associations remained robust after additional adjustment for CMV status, comorbidities, and inflammation markers. We conclude that CMV seropositivity is linked to a higher incidence of CHD in octogenarians and that senescence in both the CD4 and CD8 T‐cell compartments is a predictor of overall cardiovascular mortality as well as death from myocardial infarction and stroke.</description><identifier>ISSN: 1474-9718</identifier><identifier>EISSN: 1474-9726</identifier><identifier>DOI: 10.1111/acel.12430</identifier><identifier>PMID: 26696322</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Age Factors ; Aged, 80 and over ; aging ; Cardiovascular Diseases - blood ; Cardiovascular Diseases - immunology ; Cardiovascular Diseases - microbiology ; Cardiovascular Diseases - mortality ; CD4 ; CD8 ; Chronic Disease - mortality ; Comparative analysis ; Coronary heart disease ; Cytomegalovirus ; Cytomegalovirus infections ; Cytomegalovirus Infections - blood ; Cytomegalovirus Infections - immunology ; Cytomegalovirus Infections - mortality ; Cytomegalovirus Infections - pathology ; Female ; Humans ; immunosenescence ; Male ; Memory (Computers) ; Mortality ; octogenarians ; Patient outcomes ; Prognosis ; Short Take ; survival ; T cells ; T lymphocytes ; T-Lymphocytes - immunology ; T-Lymphocytes - pathology ; United Kingdom - epidemiology</subject><ispartof>Aging cell, 2016-04, Vol.15 (2), p.389-392</ispartof><rights>2015 The Authors. published by the Anatomical Society and John Wiley & Sons Ltd.</rights><rights>2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.</rights><rights>COPYRIGHT 2015 John Wiley & Sons, Inc.</rights><rights>Copyright © 2016 The Anatomical Society and John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6180-7491017aee7c978ddd17cb63428a0491f929ee92ccbd3f59e6e0e0a15c7878d53</citedby><cites>FETCH-LOGICAL-c6180-7491017aee7c978ddd17cb63428a0491f929ee92ccbd3f59e6e0e0a15c7878d53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783336/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1771316151?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,11541,25731,27901,27902,36989,36990,44566,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26696322$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Spyridopoulos, Ioakim</creatorcontrib><creatorcontrib>Martin‐Ruiz, Carmen</creatorcontrib><creatorcontrib>Hilkens, Catharien</creatorcontrib><creatorcontrib>Yadegarfar, Mohammad E.</creatorcontrib><creatorcontrib>Isaacs, John</creatorcontrib><creatorcontrib>Jagger, Carol</creatorcontrib><creatorcontrib>Kirkwood, Tom</creatorcontrib><creatorcontrib>Zglinicki, Thomas</creatorcontrib><title>CMV seropositivity and T‐cell senescence predict increased cardiovascular mortality in octogenarians: results from the Newcastle 85+ study</title><title>Aging cell</title><addtitle>Aging Cell</addtitle><description>Summary
Although chronic infection with cytomegalovirus (CMV) is known to drive T lymphocytes toward a senescent phenotype, it remains controversial whether and how CMV can cause coronary heart disease (CHD). To explore whether CMV seropositivity or T‐cell populations associated with immunosenescence were informative for adverse cardiovascular outcome in the very old, we prospectively analyzed peripheral blood samples from 751 octogenarians (38% males) from the Newcastle 85+ study for their power to predict survival during a 65‐month follow‐up (47.3% survival rate). CMV‐seropositive participants showed a higher prevalence of CHD (37.7% vs. 26.7%, P = 0.030) compared to CMV‐seronegative participants together with lower CD4/CD8 ratio (1.7 vs. 4.1, P < 0.0001) and higher frequencies of senescence‐like CD4 memory cells (41.1% vs. 4.5%, P < 0.001) and senescence‐like CD8 memory cells (TEMRA, 28.1% vs. 6.7%, P < 0.001). CMV seropositivity was also associated with increased six‐year cardiovascular mortality (HR 1.75 [1.09–2.82], P = 0.021) or death from myocardial infarction and stroke (HR 1.89 [107–3.36], P = 0.029). Gender‐adjusted multivariate Cox regression analysis revealed that low percentages of senescence‐like CD4 T cells (HR 0.48 [0.32–0.72], P < 0.001) and near‐senescent (CD27 negative) CD8 T cells (HR 0.60 [0.41–0.88], P = 0.029) reduced the risk of cardiovascular death. For senescence‐like CD4, but not near‐senescent CD8 T cells, these associations remained robust after additional adjustment for CMV status, comorbidities, and inflammation markers. We conclude that CMV seropositivity is linked to a higher incidence of CHD in octogenarians and that senescence in both the CD4 and CD8 T‐cell compartments is a predictor of overall cardiovascular mortality as well as death from myocardial infarction and stroke.</description><subject>Age Factors</subject><subject>Aged, 80 and over</subject><subject>aging</subject><subject>Cardiovascular Diseases - blood</subject><subject>Cardiovascular Diseases - immunology</subject><subject>Cardiovascular Diseases - microbiology</subject><subject>Cardiovascular Diseases - mortality</subject><subject>CD4</subject><subject>CD8</subject><subject>Chronic Disease - mortality</subject><subject>Comparative analysis</subject><subject>Coronary heart disease</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus infections</subject><subject>Cytomegalovirus Infections - blood</subject><subject>Cytomegalovirus Infections - immunology</subject><subject>Cytomegalovirus Infections - mortality</subject><subject>Cytomegalovirus Infections - pathology</subject><subject>Female</subject><subject>Humans</subject><subject>immunosenescence</subject><subject>Male</subject><subject>Memory (Computers)</subject><subject>Mortality</subject><subject>octogenarians</subject><subject>Patient outcomes</subject><subject>Prognosis</subject><subject>Short Take</subject><subject>survival</subject><subject>T cells</subject><subject>T lymphocytes</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - pathology</subject><subject>United Kingdom - epidemiology</subject><issn>1474-9718</issn><issn>1474-9726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>PIMPY</sourceid><recordid>eNqNks9uEzEQxlcIREvhwgMgS1wQVYL_7K7XHJCiqBSkAJfC1XLs2dTVrp3a3lS58QAceEaepN6mBIoQwj7Y8vzm88ynKYqnBE9JXq-Uhm5KaMnwveKQlLycCE7r-_s7aQ6KRzFeYEy4wOxhcUDrWtSM0sPi2_zDFxQh-LWPNtmNTVuknEFnP75-z7JdjjmIGpwGtA5grE7IOh1ARTBIq2Cs36ioh04F1PuQVDdKWIe8Tn4FTgWrXHyNAsShSxG1wfconQP6CFdaxdQBaqpjFNNgto-LB63qIjy5PY-Kz29PzubvJotPp-_ns8VE16TBE14KkltRAFwL3hhjCNfLmpW0UTjHWkEFgKBaLw1rKwE1YMCKVJo3Ga_YUfFmp7selj2Y3F0KqpPrYHsVttIrK-9GnD2XK7-RJW8YY3UWeHErEPzlADHJ3sbRLuXAD1ES3lSUUcLpf6CckrLMxWf0-R_ohR-Cy06MFGGkJhX5Ra1UB9K61ucS9SgqZxxXXAhWjtT0L1TeBnqrvYPW5vc7CS93CTr4GAO0ezsIluOYyXHM5M2YZfjZ7wbu0Z9zlQGyA67yN9t_SMnZ_GSxE70GlL3e4Q</recordid><startdate>201604</startdate><enddate>201604</enddate><creator>Spyridopoulos, Ioakim</creator><creator>Martin‐Ruiz, Carmen</creator><creator>Hilkens, Catharien</creator><creator>Yadegarfar, Mohammad E.</creator><creator>Isaacs, John</creator><creator>Jagger, Carol</creator><creator>Kirkwood, Tom</creator><creator>Zglinicki, Thomas</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</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>7QP</scope><scope>7TK</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7U9</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>201604</creationdate><title>CMV seropositivity and T‐cell senescence predict increased cardiovascular mortality in octogenarians: results from the Newcastle 85+ study</title><author>Spyridopoulos, Ioakim ; Martin‐Ruiz, Carmen ; Hilkens, Catharien ; Yadegarfar, Mohammad E. ; Isaacs, John ; Jagger, Carol ; Kirkwood, Tom ; Zglinicki, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6180-7491017aee7c978ddd17cb63428a0491f929ee92ccbd3f59e6e0e0a15c7878d53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Age Factors</topic><topic>Aged, 80 and over</topic><topic>aging</topic><topic>Cardiovascular Diseases - blood</topic><topic>Cardiovascular Diseases - immunology</topic><topic>Cardiovascular Diseases - microbiology</topic><topic>Cardiovascular Diseases - mortality</topic><topic>CD4</topic><topic>CD8</topic><topic>Chronic Disease - mortality</topic><topic>Comparative analysis</topic><topic>Coronary heart disease</topic><topic>Cytomegalovirus</topic><topic>Cytomegalovirus infections</topic><topic>Cytomegalovirus Infections - blood</topic><topic>Cytomegalovirus Infections - immunology</topic><topic>Cytomegalovirus Infections - mortality</topic><topic>Cytomegalovirus Infections - pathology</topic><topic>Female</topic><topic>Humans</topic><topic>immunosenescence</topic><topic>Male</topic><topic>Memory (Computers)</topic><topic>Mortality</topic><topic>octogenarians</topic><topic>Patient outcomes</topic><topic>Prognosis</topic><topic>Short Take</topic><topic>survival</topic><topic>T cells</topic><topic>T lymphocytes</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - pathology</topic><topic>United Kingdom - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Spyridopoulos, Ioakim</creatorcontrib><creatorcontrib>Martin‐Ruiz, Carmen</creatorcontrib><creatorcontrib>Hilkens, Catharien</creatorcontrib><creatorcontrib>Yadegarfar, Mohammad E.</creatorcontrib><creatorcontrib>Isaacs, John</creatorcontrib><creatorcontrib>Jagger, Carol</creatorcontrib><creatorcontrib>Kirkwood, Tom</creatorcontrib><creatorcontrib>Zglinicki, Thomas</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Biological Sciences</collection><collection>Biological Science Database</collection><collection>Publicly Available Content 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>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Aging cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Spyridopoulos, Ioakim</au><au>Martin‐Ruiz, Carmen</au><au>Hilkens, Catharien</au><au>Yadegarfar, Mohammad E.</au><au>Isaacs, John</au><au>Jagger, Carol</au><au>Kirkwood, Tom</au><au>Zglinicki, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CMV seropositivity and T‐cell senescence predict increased cardiovascular mortality in octogenarians: results from the Newcastle 85+ study</atitle><jtitle>Aging cell</jtitle><addtitle>Aging Cell</addtitle><date>2016-04</date><risdate>2016</risdate><volume>15</volume><issue>2</issue><spage>389</spage><epage>392</epage><pages>389-392</pages><issn>1474-9718</issn><eissn>1474-9726</eissn><abstract>Summary
Although chronic infection with cytomegalovirus (CMV) is known to drive T lymphocytes toward a senescent phenotype, it remains controversial whether and how CMV can cause coronary heart disease (CHD). To explore whether CMV seropositivity or T‐cell populations associated with immunosenescence were informative for adverse cardiovascular outcome in the very old, we prospectively analyzed peripheral blood samples from 751 octogenarians (38% males) from the Newcastle 85+ study for their power to predict survival during a 65‐month follow‐up (47.3% survival rate). CMV‐seropositive participants showed a higher prevalence of CHD (37.7% vs. 26.7%, P = 0.030) compared to CMV‐seronegative participants together with lower CD4/CD8 ratio (1.7 vs. 4.1, P < 0.0001) and higher frequencies of senescence‐like CD4 memory cells (41.1% vs. 4.5%, P < 0.001) and senescence‐like CD8 memory cells (TEMRA, 28.1% vs. 6.7%, P < 0.001). CMV seropositivity was also associated with increased six‐year cardiovascular mortality (HR 1.75 [1.09–2.82], P = 0.021) or death from myocardial infarction and stroke (HR 1.89 [107–3.36], P = 0.029). Gender‐adjusted multivariate Cox regression analysis revealed that low percentages of senescence‐like CD4 T cells (HR 0.48 [0.32–0.72], P < 0.001) and near‐senescent (CD27 negative) CD8 T cells (HR 0.60 [0.41–0.88], P = 0.029) reduced the risk of cardiovascular death. For senescence‐like CD4, but not near‐senescent CD8 T cells, these associations remained robust after additional adjustment for CMV status, comorbidities, and inflammation markers. We conclude that CMV seropositivity is linked to a higher incidence of CHD in octogenarians and that senescence in both the CD4 and CD8 T‐cell compartments is a predictor of overall cardiovascular mortality as well as death from myocardial infarction and stroke.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>26696322</pmid><doi>10.1111/acel.12430</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Aging cell, 2016-04, Vol.15 (2), p.389-392 |
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| source | Wiley Online Library Open Access; Publicly Available Content Database; PubMed Central |
| subjects | Age Factors Aged, 80 and over aging Cardiovascular Diseases - blood Cardiovascular Diseases - immunology Cardiovascular Diseases - microbiology Cardiovascular Diseases - mortality CD4 CD8 Chronic Disease - mortality Comparative analysis Coronary heart disease Cytomegalovirus Cytomegalovirus infections Cytomegalovirus Infections - blood Cytomegalovirus Infections - immunology Cytomegalovirus Infections - mortality Cytomegalovirus Infections - pathology Female Humans immunosenescence Male Memory (Computers) Mortality octogenarians Patient outcomes Prognosis Short Take survival T cells T lymphocytes T-Lymphocytes - immunology T-Lymphocytes - pathology United Kingdom - epidemiology |
| title | CMV seropositivity and T‐cell senescence predict increased cardiovascular mortality in octogenarians: results from the Newcastle 85+ study |
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