Collagen turnover markers in relation to future cardiovascular and noncardiovascular disease

The multi-ethnic study of atherosclerosis

Daniel A. Duprez, Myron D. Gross, Otto A. Sanchez, Jorge Kizer, Joachim H. Ix, Joao Lima, Russell P. Tracy, David R. Jacobs

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND: Sustained remodeling of extracellular matrix can compromise organs and tissues. Procollagen type III N-terminal propeptide (PIIINP) and collagen type I carboxy-terminal telopeptide (ICTP) reflect collagen synthesis and degradation. We studied their predictive value for future death and disease. METHODS: A total of 3068 men and women in the Multi- Ethnic Study of Atherosclerosis who were free of cardiovascular disease (CVD) and in generally good health had a baseline blood sample taken for ICTP and PIIINP. Median follow-up was 13.0 years. Among 4 primary outcomes, CVD events (n = 697) were adjudicated, death (n = 571) was by death certificate, and chronic inflammatory-related severe hospitalization and death (ChrIRD, n = 726) and total cancer (n=327) were classified using International Classification of Diseases codes. We used Poisson regression to study baseline ICTP and PIIINP relative to these outcomes. RESULTS: Mean (SD) PIIINP was 5.47 (1.95) μg/L and ICTP was 3.37 (1.70) μg/L. PIIINP and ICTP were highly correlated with each other and with estimated glomerular filtration rate (EGFR). Adjustment for age and EGFR attenuated relative risks, remaining 20%-30% per SD of both PIIINP and ICTP in prediction for total death and ChrIRD, and of PIIINP for cancer, with little additional attenuation by adjusting for risk factors and inflammatory biomarkers. CVD outcome was generally unrelated to PIIINP but became marginally inversely related to ICTP in the most adjusted model. CONCLUSIONS: The collagen biomarkers PIIINP and ICTP, in part through pathophysiologically parallel associations with renal function, predicted ChrIRD and total death. Moreover, PIIINP predicted future cancer. These collagen markers may help differentiate healthy from unhealthy aging.

Original languageEnglish (US)
Pages (from-to)1237-1247
Number of pages11
JournalClinical Chemistry
Volume63
Issue number7
DOIs
StatePublished - Jul 1 2017

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Collagen Type III
Atherosclerosis
Cardiovascular Diseases
Collagen
Biomarkers
Glomerular Filtration Rate
Neoplasms
Death Certificates
International Classification of Diseases
Collagen Type I
Extracellular Matrix
Hospitalization
Blood
Aging of materials
Health
Tissue
Kidney
Degradation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Collagen turnover markers in relation to future cardiovascular and noncardiovascular disease : The multi-ethnic study of atherosclerosis. / Duprez, Daniel A.; Gross, Myron D.; Sanchez, Otto A.; Kizer, Jorge; Ix, Joachim H.; Lima, Joao; Tracy, Russell P.; Jacobs, David R.

In: Clinical Chemistry, Vol. 63, No. 7, 01.07.2017, p. 1237-1247.

Research output: Contribution to journalArticle

Duprez, Daniel A. ; Gross, Myron D. ; Sanchez, Otto A. ; Kizer, Jorge ; Ix, Joachim H. ; Lima, Joao ; Tracy, Russell P. ; Jacobs, David R. / Collagen turnover markers in relation to future cardiovascular and noncardiovascular disease : The multi-ethnic study of atherosclerosis. In: Clinical Chemistry. 2017 ; Vol. 63, No. 7. pp. 1237-1247.
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abstract = "BACKGROUND: Sustained remodeling of extracellular matrix can compromise organs and tissues. Procollagen type III N-terminal propeptide (PIIINP) and collagen type I carboxy-terminal telopeptide (ICTP) reflect collagen synthesis and degradation. We studied their predictive value for future death and disease. METHODS: A total of 3068 men and women in the Multi- Ethnic Study of Atherosclerosis who were free of cardiovascular disease (CVD) and in generally good health had a baseline blood sample taken for ICTP and PIIINP. Median follow-up was 13.0 years. Among 4 primary outcomes, CVD events (n = 697) were adjudicated, death (n = 571) was by death certificate, and chronic inflammatory-related severe hospitalization and death (ChrIRD, n = 726) and total cancer (n=327) were classified using International Classification of Diseases codes. We used Poisson regression to study baseline ICTP and PIIINP relative to these outcomes. RESULTS: Mean (SD) PIIINP was 5.47 (1.95) μg/L and ICTP was 3.37 (1.70) μg/L. PIIINP and ICTP were highly correlated with each other and with estimated glomerular filtration rate (EGFR). Adjustment for age and EGFR attenuated relative risks, remaining 20{\%}-30{\%} per SD of both PIIINP and ICTP in prediction for total death and ChrIRD, and of PIIINP for cancer, with little additional attenuation by adjusting for risk factors and inflammatory biomarkers. CVD outcome was generally unrelated to PIIINP but became marginally inversely related to ICTP in the most adjusted model. CONCLUSIONS: The collagen biomarkers PIIINP and ICTP, in part through pathophysiologically parallel associations with renal function, predicted ChrIRD and total death. Moreover, PIIINP predicted future cancer. These collagen markers may help differentiate healthy from unhealthy aging.",
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T1 - Collagen turnover markers in relation to future cardiovascular and noncardiovascular disease

T2 - The multi-ethnic study of atherosclerosis

AU - Duprez, Daniel A.

AU - Gross, Myron D.

AU - Sanchez, Otto A.

AU - Kizer, Jorge

AU - Ix, Joachim H.

AU - Lima, Joao

AU - Tracy, Russell P.

AU - Jacobs, David R.

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AB - BACKGROUND: Sustained remodeling of extracellular matrix can compromise organs and tissues. Procollagen type III N-terminal propeptide (PIIINP) and collagen type I carboxy-terminal telopeptide (ICTP) reflect collagen synthesis and degradation. We studied their predictive value for future death and disease. METHODS: A total of 3068 men and women in the Multi- Ethnic Study of Atherosclerosis who were free of cardiovascular disease (CVD) and in generally good health had a baseline blood sample taken for ICTP and PIIINP. Median follow-up was 13.0 years. Among 4 primary outcomes, CVD events (n = 697) were adjudicated, death (n = 571) was by death certificate, and chronic inflammatory-related severe hospitalization and death (ChrIRD, n = 726) and total cancer (n=327) were classified using International Classification of Diseases codes. We used Poisson regression to study baseline ICTP and PIIINP relative to these outcomes. RESULTS: Mean (SD) PIIINP was 5.47 (1.95) μg/L and ICTP was 3.37 (1.70) μg/L. PIIINP and ICTP were highly correlated with each other and with estimated glomerular filtration rate (EGFR). Adjustment for age and EGFR attenuated relative risks, remaining 20%-30% per SD of both PIIINP and ICTP in prediction for total death and ChrIRD, and of PIIINP for cancer, with little additional attenuation by adjusting for risk factors and inflammatory biomarkers. CVD outcome was generally unrelated to PIIINP but became marginally inversely related to ICTP in the most adjusted model. CONCLUSIONS: The collagen biomarkers PIIINP and ICTP, in part through pathophysiologically parallel associations with renal function, predicted ChrIRD and total death. Moreover, PIIINP predicted future cancer. These collagen markers may help differentiate healthy from unhealthy aging.

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