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Symptomatic Peripheral Arterial Disease in Women : Nontraditional Biomarkers of Elevated Risk
Most investigations of novel biomarkers for prediction of cardiovascular disease pertain to coronary artery disease. Few large-scale prospective studies have critically assessed plasma-based factors as predictors of peripheral arterial disease (PAD), and comparative data between individual biomarker...
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| Published in: | Circulation (New York, N.Y.) N.Y.), 2008-02, Vol.117 (6), p.823-831 |
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| container_end_page | 831 |
| container_issue | 6 |
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| container_title | Circulation (New York, N.Y.) |
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| creator | PRADHAN, Aruna D SHRIVASTAVA, Sanjay COOK, Nancy R RIFAI, Nader CREAGER, Mark A RIDKER, Paul M |
| description | Most investigations of novel biomarkers for prediction of cardiovascular disease pertain to coronary artery disease. Few large-scale prospective studies have critically assessed plasma-based factors as predictors of peripheral arterial disease (PAD), and comparative data between individual biomarkers and lipid levels are sparse, especially among women.
We evaluated the relationship between baseline levels of several novel biomarkers and confirmed incident symptomatic PAD (n=100) in a prospective cohort study (median follow-up, 12.3 years) involving 27,935 US female health professionals > or = 45 years of age without diagnosed vascular disease at baseline. Biomarkers assessed were high-sensitivity C-reactive protein, fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1), homocysteine, lipoprotein(a), hemoglobin A1c, creatinine, and conventional lipid levels. In univariate analyses, levels of high-sensitivity C-reactive protein, fibrinogen, sICAM-1, homocysteine, lipoprotein(a), creatinine clearance, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and the ratio of total cholesterol to HDL-C (TC:HDL-C) were significantly related to PAD (all P |
| doi_str_mv | 10.1161/CIRCULATIONAHA.107.719369 |
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We evaluated the relationship between baseline levels of several novel biomarkers and confirmed incident symptomatic PAD (n=100) in a prospective cohort study (median follow-up, 12.3 years) involving 27,935 US female health professionals > or = 45 years of age without diagnosed vascular disease at baseline. Biomarkers assessed were high-sensitivity C-reactive protein, fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1), homocysteine, lipoprotein(a), hemoglobin A1c, creatinine, and conventional lipid levels. In univariate analyses, levels of high-sensitivity C-reactive protein, fibrinogen, sICAM-1, homocysteine, lipoprotein(a), creatinine clearance, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and the ratio of total cholesterol to HDL-C (TC:HDL-C) were significantly related to PAD (all P<0.05). However, after multivariable adjustment, risk associations were significant only for high-sensitivity C-reactive protein (adjusted hazard ratio [HR] extreme tertiles, 2.1; 95% confidence interval, 1.2 to 3.7), sICAM-1 (adjusted HR, 4.0; 95% confidence interval, 1.9 to 8.6), HDL-C (adjusted HR, 0.4; 95% confidence interval, 0.3 to 0.8), and TC:HDL-C (adjusted HR, 2.2; 95% confidence interval, 1.2 to 3.9). In a model simultaneously controlling for traditional risk factors plus these significant biomarkers, sICAM-1 remained independently predictive of PAD (adjusted HR in each tertile, 1.0 [reference], 2.3, and 3.5).
Among a broad range of biomarkers of cardiovascular risk, only 4 factors, sICAM-1, high-sensitivity C-reactive protein, HDL-C, and TC:HDL-C, were significantly associated with incident symptomatic PAD in women. Findings pertaining to novel biomarkers provide clinical confirmation of a prominent role of endothelial activation and leukocyte recruitment in lower-extremity arterial disease.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.107.719369</identifier><identifier>PMID: 18227386</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Biological and medical sciences ; Biomarkers - blood ; Blood and lymphatic vessels ; C-Reactive Protein - analysis ; Cardiology. Vascular system ; Cholesterol, HDL - blood ; Coronary heart disease ; Creatinine - metabolism ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Female ; Fibrinogen - analysis ; Heart ; Humans ; Intercellular Adhesion Molecule-1 - blood ; Lipoprotein(a) - blood ; Medical sciences ; Middle Aged ; Multivariate Analysis ; Peripheral Vascular Diseases - blood ; Prospective Studies ; Risk Assessment - methods</subject><ispartof>Circulation (New York, N.Y.), 2008-02, Vol.117 (6), p.823-831</ispartof><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c330t-858efd662d4305b884c2900a61006f342382a5954f5af0ea3e48bdedc5e838df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20086633$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18227386$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PRADHAN, Aruna D</creatorcontrib><creatorcontrib>SHRIVASTAVA, Sanjay</creatorcontrib><creatorcontrib>COOK, Nancy R</creatorcontrib><creatorcontrib>RIFAI, Nader</creatorcontrib><creatorcontrib>CREAGER, Mark A</creatorcontrib><creatorcontrib>RIDKER, Paul M</creatorcontrib><title>Symptomatic Peripheral Arterial Disease in Women : Nontraditional Biomarkers of Elevated Risk</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Most investigations of novel biomarkers for prediction of cardiovascular disease pertain to coronary artery disease. Few large-scale prospective studies have critically assessed plasma-based factors as predictors of peripheral arterial disease (PAD), and comparative data between individual biomarkers and lipid levels are sparse, especially among women.
We evaluated the relationship between baseline levels of several novel biomarkers and confirmed incident symptomatic PAD (n=100) in a prospective cohort study (median follow-up, 12.3 years) involving 27,935 US female health professionals > or = 45 years of age without diagnosed vascular disease at baseline. Biomarkers assessed were high-sensitivity C-reactive protein, fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1), homocysteine, lipoprotein(a), hemoglobin A1c, creatinine, and conventional lipid levels. In univariate analyses, levels of high-sensitivity C-reactive protein, fibrinogen, sICAM-1, homocysteine, lipoprotein(a), creatinine clearance, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and the ratio of total cholesterol to HDL-C (TC:HDL-C) were significantly related to PAD (all P<0.05). However, after multivariable adjustment, risk associations were significant only for high-sensitivity C-reactive protein (adjusted hazard ratio [HR] extreme tertiles, 2.1; 95% confidence interval, 1.2 to 3.7), sICAM-1 (adjusted HR, 4.0; 95% confidence interval, 1.9 to 8.6), HDL-C (adjusted HR, 0.4; 95% confidence interval, 0.3 to 0.8), and TC:HDL-C (adjusted HR, 2.2; 95% confidence interval, 1.2 to 3.9). In a model simultaneously controlling for traditional risk factors plus these significant biomarkers, sICAM-1 remained independently predictive of PAD (adjusted HR in each tertile, 1.0 [reference], 2.3, and 3.5).
Among a broad range of biomarkers of cardiovascular risk, only 4 factors, sICAM-1, high-sensitivity C-reactive protein, HDL-C, and TC:HDL-C, were significantly associated with incident symptomatic PAD in women. Findings pertaining to novel biomarkers provide clinical confirmation of a prominent role of endothelial activation and leukocyte recruitment in lower-extremity arterial disease.</description><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Blood and lymphatic vessels</subject><subject>C-Reactive Protein - analysis</subject><subject>Cardiology. Vascular system</subject><subject>Cholesterol, HDL - blood</subject><subject>Coronary heart disease</subject><subject>Creatinine - metabolism</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Female</subject><subject>Fibrinogen - analysis</subject><subject>Heart</subject><subject>Humans</subject><subject>Intercellular Adhesion Molecule-1 - blood</subject><subject>Lipoprotein(a) - blood</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Peripheral Vascular Diseases - blood</subject><subject>Prospective Studies</subject><subject>Risk Assessment - methods</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNpVkEtLAzEUhYMoWqt_QeJCd1PzmGQy7sZatVBaqRVXMqQzNxg7j5pMBf-9kRbF1X3wnXsPB6FzSgaUSno1HM-Hz5NsMZ5Ns4dsQEkySGjKZbqHelSwOIoFT_dRjxCSRgln7Agde_8eRskTcYiOqGIs4Ur20OvTV73u2lp3tsCP4Oz6DZyucOa6MITm1nrQHrBt8EtbQ4Ov8bRtOqdL29m2CcSNDXK3Audxa_Cogk_dQYnn1q9O0IHRlYfTXe2j57vRYvgQTWb342E2iQrOSRcpocCUUrIy5kQslYoLlhKiJQ2ODY8ZV0yLVMRGaENAc4jVsoSyEKC4Kg3vo8vt3bVrPzbgu7y2voCq0g20G58nhCWpUCyA6RYsXOu9A5OvnQ3uv3JK8p9s8__ZhnWSb7MN2rPdk82yhvJPuQszABc7QPtCV8bpprD-l2OEKCk5599A1YQQ</recordid><startdate>20080212</startdate><enddate>20080212</enddate><creator>PRADHAN, Aruna D</creator><creator>SHRIVASTAVA, Sanjay</creator><creator>COOK, Nancy R</creator><creator>RIFAI, Nader</creator><creator>CREAGER, Mark A</creator><creator>RIDKER, Paul M</creator><general>Lippincott Williams & Wilkins</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>7X8</scope></search><sort><creationdate>20080212</creationdate><title>Symptomatic Peripheral Arterial Disease in Women : Nontraditional Biomarkers of Elevated Risk</title><author>PRADHAN, Aruna D ; SHRIVASTAVA, Sanjay ; COOK, Nancy R ; RIFAI, Nader ; CREAGER, Mark A ; RIDKER, Paul M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c330t-858efd662d4305b884c2900a61006f342382a5954f5af0ea3e48bdedc5e838df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Blood and lymphatic vessels</topic><topic>C-Reactive Protein - analysis</topic><topic>Cardiology. Vascular system</topic><topic>Cholesterol, HDL - blood</topic><topic>Coronary heart disease</topic><topic>Creatinine - metabolism</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Female</topic><topic>Fibrinogen - analysis</topic><topic>Heart</topic><topic>Humans</topic><topic>Intercellular Adhesion Molecule-1 - blood</topic><topic>Lipoprotein(a) - blood</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Peripheral Vascular Diseases - blood</topic><topic>Prospective Studies</topic><topic>Risk Assessment - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PRADHAN, Aruna D</creatorcontrib><creatorcontrib>SHRIVASTAVA, Sanjay</creatorcontrib><creatorcontrib>COOK, Nancy R</creatorcontrib><creatorcontrib>RIFAI, Nader</creatorcontrib><creatorcontrib>CREAGER, Mark A</creatorcontrib><creatorcontrib>RIDKER, Paul M</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>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PRADHAN, Aruna D</au><au>SHRIVASTAVA, Sanjay</au><au>COOK, Nancy R</au><au>RIFAI, Nader</au><au>CREAGER, Mark A</au><au>RIDKER, Paul M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Symptomatic Peripheral Arterial Disease in Women : Nontraditional Biomarkers of Elevated Risk</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2008-02-12</date><risdate>2008</risdate><volume>117</volume><issue>6</issue><spage>823</spage><epage>831</epage><pages>823-831</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Most investigations of novel biomarkers for prediction of cardiovascular disease pertain to coronary artery disease. Few large-scale prospective studies have critically assessed plasma-based factors as predictors of peripheral arterial disease (PAD), and comparative data between individual biomarkers and lipid levels are sparse, especially among women.
We evaluated the relationship between baseline levels of several novel biomarkers and confirmed incident symptomatic PAD (n=100) in a prospective cohort study (median follow-up, 12.3 years) involving 27,935 US female health professionals > or = 45 years of age without diagnosed vascular disease at baseline. Biomarkers assessed were high-sensitivity C-reactive protein, fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1), homocysteine, lipoprotein(a), hemoglobin A1c, creatinine, and conventional lipid levels. In univariate analyses, levels of high-sensitivity C-reactive protein, fibrinogen, sICAM-1, homocysteine, lipoprotein(a), creatinine clearance, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and the ratio of total cholesterol to HDL-C (TC:HDL-C) were significantly related to PAD (all P<0.05). However, after multivariable adjustment, risk associations were significant only for high-sensitivity C-reactive protein (adjusted hazard ratio [HR] extreme tertiles, 2.1; 95% confidence interval, 1.2 to 3.7), sICAM-1 (adjusted HR, 4.0; 95% confidence interval, 1.9 to 8.6), HDL-C (adjusted HR, 0.4; 95% confidence interval, 0.3 to 0.8), and TC:HDL-C (adjusted HR, 2.2; 95% confidence interval, 1.2 to 3.9). In a model simultaneously controlling for traditional risk factors plus these significant biomarkers, sICAM-1 remained independently predictive of PAD (adjusted HR in each tertile, 1.0 [reference], 2.3, and 3.5).
Among a broad range of biomarkers of cardiovascular risk, only 4 factors, sICAM-1, high-sensitivity C-reactive protein, HDL-C, and TC:HDL-C, were significantly associated with incident symptomatic PAD in women. Findings pertaining to novel biomarkers provide clinical confirmation of a prominent role of endothelial activation and leukocyte recruitment in lower-extremity arterial disease.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>18227386</pmid><doi>10.1161/CIRCULATIONAHA.107.719369</doi><tpages>9</tpages></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 2008-02, Vol.117 (6), p.823-831 |
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| subjects | Biological and medical sciences Biomarkers - blood Blood and lymphatic vessels C-Reactive Protein - analysis Cardiology. Vascular system Cholesterol, HDL - blood Coronary heart disease Creatinine - metabolism Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Female Fibrinogen - analysis Heart Humans Intercellular Adhesion Molecule-1 - blood Lipoprotein(a) - blood Medical sciences Middle Aged Multivariate Analysis Peripheral Vascular Diseases - blood Prospective Studies Risk Assessment - methods |
| title | Symptomatic Peripheral Arterial Disease in Women : Nontraditional Biomarkers of Elevated Risk |
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