Thoracic aortic aneurysm frequency and dissection are associated with fibrillin-1 fragment concentrations in circulation

Lynn Marshall, Eric J. Carlson, Jean O'Malley, Caryn K. Snyder, Noe L. Charbonneau, Susan Hayflick, Joseph S. Coselli, Scott A. Lemaire, Lynn Sakai

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Rationale: Mutations in fibrillin-1 are associated with thoracic aortic aneurysm (TAA) in Marfan syndrome. Genome-wide association studies also implicate fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is characteristic of TAA. Objective: Immunoassays were generated to test whether circulating fragments of fibrillin-1, or other microfibril fragments, are associated with TAA and dissection. Methods and Results: Plasma samples were obtained from 1265 patients with aortic aneurysm or dissection and from 125 control subjects. Concentrations of fibrillin-1, fibrillin-2, and fibulin-4 were measured with novel immunoassays. One hundred and seventy-four patients (13%) had aneurysms with only abdominal aortic involvement (abdominal aortic aneurysm), and 1091 (86%) had TAA. Of those with TAA, 300 patients (27%) had chronic dissection and 109 (10%) had acute or subacute dissection. Associations of fragment concentrations with TAA (versus abdominal aortic aneurysm) or with dissection (versus no dissection) were estimated with odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, sex, and smoking. Compared with controls, significantly higher percentages of aneurysm patients had detectable levels of fibrillin fragments. TAA was significantly more common (than abdominal aortic aneurysm) in the highest compared with lowest quartile of fibrillin-1 concentration (OR=2.9; 95% CI, 1.6-5.0). Relative to TAA without dissection, acute or subacute dissection (OR=2.9; 95% CI, 1.6-5.3), but not chronic dissection, was more frequent in the highest compared with lowest quartile of fibrillin-1 concentration. Neither TAA nor dissection was associated with fibrillin-2 or fibulin-4. Conclusions: Circulating fibrillin-1 fragments represent a new potential biomarker for TAA and acute aortic dissection. (Circ Res. 2013;113:1159-1168.).

Original languageEnglish (US)
Pages (from-to)1159-1168
Number of pages10
JournalCirculation Research
Volume113
Issue number10
DOIs
StatePublished - Oct 25 2013

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Thoracic Aortic Aneurysm
Dissection
Abdominal Aortic Aneurysm
Odds Ratio
Confidence Intervals
Immunoassay
Aneurysm
Fibrillin-1
Microfibrils
Marfan Syndrome
Aortic Aneurysm
Genome-Wide Association Study
Biomarkers
Smoking

Keywords

  • Aneurysm
  • Dissection
  • Fibrillin
  • Marfan Syndrome
  • Microfibrils

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Thoracic aortic aneurysm frequency and dissection are associated with fibrillin-1 fragment concentrations in circulation. / Marshall, Lynn; Carlson, Eric J.; O'Malley, Jean; Snyder, Caryn K.; Charbonneau, Noe L.; Hayflick, Susan; Coselli, Joseph S.; Lemaire, Scott A.; Sakai, Lynn.

In: Circulation Research, Vol. 113, No. 10, 25.10.2013, p. 1159-1168.

Research output: Contribution to journalArticle

Marshall, Lynn ; Carlson, Eric J. ; O'Malley, Jean ; Snyder, Caryn K. ; Charbonneau, Noe L. ; Hayflick, Susan ; Coselli, Joseph S. ; Lemaire, Scott A. ; Sakai, Lynn. / Thoracic aortic aneurysm frequency and dissection are associated with fibrillin-1 fragment concentrations in circulation. In: Circulation Research. 2013 ; Vol. 113, No. 10. pp. 1159-1168.
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abstract = "Rationale: Mutations in fibrillin-1 are associated with thoracic aortic aneurysm (TAA) in Marfan syndrome. Genome-wide association studies also implicate fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is characteristic of TAA. Objective: Immunoassays were generated to test whether circulating fragments of fibrillin-1, or other microfibril fragments, are associated with TAA and dissection. Methods and Results: Plasma samples were obtained from 1265 patients with aortic aneurysm or dissection and from 125 control subjects. Concentrations of fibrillin-1, fibrillin-2, and fibulin-4 were measured with novel immunoassays. One hundred and seventy-four patients (13{\%}) had aneurysms with only abdominal aortic involvement (abdominal aortic aneurysm), and 1091 (86{\%}) had TAA. Of those with TAA, 300 patients (27{\%}) had chronic dissection and 109 (10{\%}) had acute or subacute dissection. Associations of fragment concentrations with TAA (versus abdominal aortic aneurysm) or with dissection (versus no dissection) were estimated with odds ratios (OR) and 95{\%} confidence intervals (CI) adjusted for age, sex, and smoking. Compared with controls, significantly higher percentages of aneurysm patients had detectable levels of fibrillin fragments. TAA was significantly more common (than abdominal aortic aneurysm) in the highest compared with lowest quartile of fibrillin-1 concentration (OR=2.9; 95{\%} CI, 1.6-5.0). Relative to TAA without dissection, acute or subacute dissection (OR=2.9; 95{\%} CI, 1.6-5.3), but not chronic dissection, was more frequent in the highest compared with lowest quartile of fibrillin-1 concentration. Neither TAA nor dissection was associated with fibrillin-2 or fibulin-4. Conclusions: Circulating fibrillin-1 fragments represent a new potential biomarker for TAA and acute aortic dissection. (Circ Res. 2013;113:1159-1168.).",
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AU - Marshall, Lynn

AU - Carlson, Eric J.

AU - O'Malley, Jean

AU - Snyder, Caryn K.

AU - Charbonneau, Noe L.

AU - Hayflick, Susan

AU - Coselli, Joseph S.

AU - Lemaire, Scott A.

AU - Sakai, Lynn

PY - 2013/10/25

Y1 - 2013/10/25

N2 - Rationale: Mutations in fibrillin-1 are associated with thoracic aortic aneurysm (TAA) in Marfan syndrome. Genome-wide association studies also implicate fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is characteristic of TAA. Objective: Immunoassays were generated to test whether circulating fragments of fibrillin-1, or other microfibril fragments, are associated with TAA and dissection. Methods and Results: Plasma samples were obtained from 1265 patients with aortic aneurysm or dissection and from 125 control subjects. Concentrations of fibrillin-1, fibrillin-2, and fibulin-4 were measured with novel immunoassays. One hundred and seventy-four patients (13%) had aneurysms with only abdominal aortic involvement (abdominal aortic aneurysm), and 1091 (86%) had TAA. Of those with TAA, 300 patients (27%) had chronic dissection and 109 (10%) had acute or subacute dissection. Associations of fragment concentrations with TAA (versus abdominal aortic aneurysm) or with dissection (versus no dissection) were estimated with odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, sex, and smoking. Compared with controls, significantly higher percentages of aneurysm patients had detectable levels of fibrillin fragments. TAA was significantly more common (than abdominal aortic aneurysm) in the highest compared with lowest quartile of fibrillin-1 concentration (OR=2.9; 95% CI, 1.6-5.0). Relative to TAA without dissection, acute or subacute dissection (OR=2.9; 95% CI, 1.6-5.3), but not chronic dissection, was more frequent in the highest compared with lowest quartile of fibrillin-1 concentration. Neither TAA nor dissection was associated with fibrillin-2 or fibulin-4. Conclusions: Circulating fibrillin-1 fragments represent a new potential biomarker for TAA and acute aortic dissection. (Circ Res. 2013;113:1159-1168.).

AB - Rationale: Mutations in fibrillin-1 are associated with thoracic aortic aneurysm (TAA) in Marfan syndrome. Genome-wide association studies also implicate fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is characteristic of TAA. Objective: Immunoassays were generated to test whether circulating fragments of fibrillin-1, or other microfibril fragments, are associated with TAA and dissection. Methods and Results: Plasma samples were obtained from 1265 patients with aortic aneurysm or dissection and from 125 control subjects. Concentrations of fibrillin-1, fibrillin-2, and fibulin-4 were measured with novel immunoassays. One hundred and seventy-four patients (13%) had aneurysms with only abdominal aortic involvement (abdominal aortic aneurysm), and 1091 (86%) had TAA. Of those with TAA, 300 patients (27%) had chronic dissection and 109 (10%) had acute or subacute dissection. Associations of fragment concentrations with TAA (versus abdominal aortic aneurysm) or with dissection (versus no dissection) were estimated with odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, sex, and smoking. Compared with controls, significantly higher percentages of aneurysm patients had detectable levels of fibrillin fragments. TAA was significantly more common (than abdominal aortic aneurysm) in the highest compared with lowest quartile of fibrillin-1 concentration (OR=2.9; 95% CI, 1.6-5.0). Relative to TAA without dissection, acute or subacute dissection (OR=2.9; 95% CI, 1.6-5.3), but not chronic dissection, was more frequent in the highest compared with lowest quartile of fibrillin-1 concentration. Neither TAA nor dissection was associated with fibrillin-2 or fibulin-4. Conclusions: Circulating fibrillin-1 fragments represent a new potential biomarker for TAA and acute aortic dissection. (Circ Res. 2013;113:1159-1168.).

KW - Aneurysm

KW - Dissection

KW - Fibrillin

KW - Marfan Syndrome

KW - Microfibrils

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