CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers

Søren Zöga Diederichsen*, Mette Hjortdal Grønhøj, Hans Mickley, Oke Gerke, Flemming Hald Steffensen, Jess Lambrechtsen, Niels Peter Rønnow Sand, Lars Melholt Rasmussen, Michael Hecht Olsen, Axel Diederichsen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Objectives This study sought to determine the incidence and progression of coronary artery calcification (CAC) in asymptomatic middle-aged subjects and to evaluate the value of a broad panel of biomarkers in the prediction of CAC growth. Background CAC continues to be a major risk factor, but the value of biochemical markers in predicting CAC incidence and progression remains unresolved. Methods At baseline, 1,227 men and women underwent traditional risk assessment and a computed tomography (CT) scan to determine the CAC score. Biomarkers of calcium-phosphate metabolism (calcium, phosphate, vitamin D3, parathyroid hormone, osteoprotegerin), lipid metabolism (triglyceride, high- and low-density lipoprotein, total cholesterol), inflammation (C-reactive protein, soluble urokinase-type plasminogen activator receptor), kidney function (creatinine, cystatin C, urate), and myocardial necrosis (cardiac troponin I) were analyzed. A second CT scan was scheduled after 5 years. General linear models were performed to examine the association between biomarkers and ΔCAC score, and additionally, sensitivity analyses were performed in terms of binary and ordinal logistic regressions. Results A total of 1,006 participants underwent a CT scan after 5 years. Among the 562 participants with a baseline CAC score of 0, 189 (34%) had incident CAC, whereas 214 (48%) of the 444 participants with baseline CAC score >0 had significant progression (>15% annual increase in CAC score). In the multivariate models (n = 1,006), age, sex, hypertension, diabetes, dyslipidemia, and smoking were associated with ΔCAC, whereas the strongest predictor was baseline CAC score. Low-density lipoprotein and total cholesterol levels were independently associated with CAC incidence (n = 562; incidence rate ratio [IRR]: 1.47; 95% confidence interval [CI]: 1.05 to 2.05; and IRR: 1.34; 95% CI: 1.01 to 1.77, respectively), whereas phosphate level was associated with CAC progression (n = 444; IRR: 3.60; 95% CI: 1.42 to 9.11). Conclusions In this prospective study, a large part of participants had incident CAC or progression of prevalent CAC at 5 years of follow-up. Low-density lipoprotein and total cholesterol were associated with CAC incidence and phosphate with CAC progression, whereas 12 other biomarkers had little value.

Original languageEnglish
JournalJACC: Cardiovascular Imaging
Volume10
Issue number8
Pages (from-to)858-866
ISSN1936-878X
DOIs
Publication statusPublished - 2017

Fingerprint

Growth
Incidence
LDL Cholesterol
Confidence Intervals
Urokinase Plasminogen Activator Receptors
Osteoprotegerin
Cystatin C
Troponin I
Dyslipidemias
Uric Acid
Parathyroid Hormone
Lipid Metabolism
Linear Models
Creatinine
Logistic Models
Smoking
Prospective Studies
Kidney

Keywords

  • biomarkers
  • coronary artery calcification
  • imaging
  • X-ray computed tomography

Cite this

@article{b15ab56332fd472fa65709c077c23529,
title = "CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers",
abstract = "Objectives This study sought to determine the incidence and progression of coronary artery calcification (CAC) in asymptomatic middle-aged subjects and to evaluate the value of a broad panel of biomarkers in the prediction of CAC growth. Background CAC continues to be a major risk factor, but the value of biochemical markers in predicting CAC incidence and progression remains unresolved. Methods At baseline, 1,227 men and women underwent traditional risk assessment and a computed tomography (CT) scan to determine the CAC score. Biomarkers of calcium-phosphate metabolism (calcium, phosphate, vitamin D3, parathyroid hormone, osteoprotegerin), lipid metabolism (triglyceride, high- and low-density lipoprotein, total cholesterol), inflammation (C-reactive protein, soluble urokinase-type plasminogen activator receptor), kidney function (creatinine, cystatin C, urate), and myocardial necrosis (cardiac troponin I) were analyzed. A second CT scan was scheduled after 5 years. General linear models were performed to examine the association between biomarkers and ΔCAC score, and additionally, sensitivity analyses were performed in terms of binary and ordinal logistic regressions. Results A total of 1,006 participants underwent a CT scan after 5 years. Among the 562 participants with a baseline CAC score of 0, 189 (34{\%}) had incident CAC, whereas 214 (48{\%}) of the 444 participants with baseline CAC score >0 had significant progression (>15{\%} annual increase in CAC score). In the multivariate models (n = 1,006), age, sex, hypertension, diabetes, dyslipidemia, and smoking were associated with ΔCAC, whereas the strongest predictor was baseline CAC score. Low-density lipoprotein and total cholesterol levels were independently associated with CAC incidence (n = 562; incidence rate ratio [IRR]: 1.47; 95{\%} confidence interval [CI]: 1.05 to 2.05; and IRR: 1.34; 95{\%} CI: 1.01 to 1.77, respectively), whereas phosphate level was associated with CAC progression (n = 444; IRR: 3.60; 95{\%} CI: 1.42 to 9.11). Conclusions In this prospective study, a large part of participants had incident CAC or progression of prevalent CAC at 5 years of follow-up. Low-density lipoprotein and total cholesterol were associated with CAC incidence and phosphate with CAC progression, whereas 12 other biomarkers had little value.",
keywords = "biomarkers, coronary artery calcification, imaging, X-ray computed tomography",
author = "Diederichsen, {S{\o}ren Z{\"o}ga} and Gr{\o}nh{\o}j, {Mette Hjortdal} and Hans Mickley and Oke Gerke and Steffensen, {Flemming Hald} and Jess Lambrechtsen and {R{\o}nnow Sand}, {Niels Peter} and Rasmussen, {Lars Melholt} and Olsen, {Michael Hecht} and Axel Diederichsen",
year = "2017",
doi = "10.1016/j.jcmg.2017.05.010",
language = "English",
volume = "10",
pages = "858--866",
journal = "J A C C: Cardiovascular Imaging",
issn = "1936-878X",
publisher = "Elsevier",
number = "8",

}

CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers. / Diederichsen, Søren Zöga; Grønhøj, Mette Hjortdal; Mickley, Hans; Gerke, Oke; Steffensen, Flemming Hald; Lambrechtsen, Jess; Rønnow Sand, Niels Peter; Rasmussen, Lars Melholt; Olsen, Michael Hecht; Diederichsen, Axel.

In: JACC: Cardiovascular Imaging, Vol. 10, No. 8, 2017, p. 858-866.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers

AU - Diederichsen, Søren Zöga

AU - Grønhøj, Mette Hjortdal

AU - Mickley, Hans

AU - Gerke, Oke

AU - Steffensen, Flemming Hald

AU - Lambrechtsen, Jess

AU - Rønnow Sand, Niels Peter

AU - Rasmussen, Lars Melholt

AU - Olsen, Michael Hecht

AU - Diederichsen, Axel

PY - 2017

Y1 - 2017

N2 - Objectives This study sought to determine the incidence and progression of coronary artery calcification (CAC) in asymptomatic middle-aged subjects and to evaluate the value of a broad panel of biomarkers in the prediction of CAC growth. Background CAC continues to be a major risk factor, but the value of biochemical markers in predicting CAC incidence and progression remains unresolved. Methods At baseline, 1,227 men and women underwent traditional risk assessment and a computed tomography (CT) scan to determine the CAC score. Biomarkers of calcium-phosphate metabolism (calcium, phosphate, vitamin D3, parathyroid hormone, osteoprotegerin), lipid metabolism (triglyceride, high- and low-density lipoprotein, total cholesterol), inflammation (C-reactive protein, soluble urokinase-type plasminogen activator receptor), kidney function (creatinine, cystatin C, urate), and myocardial necrosis (cardiac troponin I) were analyzed. A second CT scan was scheduled after 5 years. General linear models were performed to examine the association between biomarkers and ΔCAC score, and additionally, sensitivity analyses were performed in terms of binary and ordinal logistic regressions. Results A total of 1,006 participants underwent a CT scan after 5 years. Among the 562 participants with a baseline CAC score of 0, 189 (34%) had incident CAC, whereas 214 (48%) of the 444 participants with baseline CAC score >0 had significant progression (>15% annual increase in CAC score). In the multivariate models (n = 1,006), age, sex, hypertension, diabetes, dyslipidemia, and smoking were associated with ΔCAC, whereas the strongest predictor was baseline CAC score. Low-density lipoprotein and total cholesterol levels were independently associated with CAC incidence (n = 562; incidence rate ratio [IRR]: 1.47; 95% confidence interval [CI]: 1.05 to 2.05; and IRR: 1.34; 95% CI: 1.01 to 1.77, respectively), whereas phosphate level was associated with CAC progression (n = 444; IRR: 3.60; 95% CI: 1.42 to 9.11). Conclusions In this prospective study, a large part of participants had incident CAC or progression of prevalent CAC at 5 years of follow-up. Low-density lipoprotein and total cholesterol were associated with CAC incidence and phosphate with CAC progression, whereas 12 other biomarkers had little value.

AB - Objectives This study sought to determine the incidence and progression of coronary artery calcification (CAC) in asymptomatic middle-aged subjects and to evaluate the value of a broad panel of biomarkers in the prediction of CAC growth. Background CAC continues to be a major risk factor, but the value of biochemical markers in predicting CAC incidence and progression remains unresolved. Methods At baseline, 1,227 men and women underwent traditional risk assessment and a computed tomography (CT) scan to determine the CAC score. Biomarkers of calcium-phosphate metabolism (calcium, phosphate, vitamin D3, parathyroid hormone, osteoprotegerin), lipid metabolism (triglyceride, high- and low-density lipoprotein, total cholesterol), inflammation (C-reactive protein, soluble urokinase-type plasminogen activator receptor), kidney function (creatinine, cystatin C, urate), and myocardial necrosis (cardiac troponin I) were analyzed. A second CT scan was scheduled after 5 years. General linear models were performed to examine the association between biomarkers and ΔCAC score, and additionally, sensitivity analyses were performed in terms of binary and ordinal logistic regressions. Results A total of 1,006 participants underwent a CT scan after 5 years. Among the 562 participants with a baseline CAC score of 0, 189 (34%) had incident CAC, whereas 214 (48%) of the 444 participants with baseline CAC score >0 had significant progression (>15% annual increase in CAC score). In the multivariate models (n = 1,006), age, sex, hypertension, diabetes, dyslipidemia, and smoking were associated with ΔCAC, whereas the strongest predictor was baseline CAC score. Low-density lipoprotein and total cholesterol levels were independently associated with CAC incidence (n = 562; incidence rate ratio [IRR]: 1.47; 95% confidence interval [CI]: 1.05 to 2.05; and IRR: 1.34; 95% CI: 1.01 to 1.77, respectively), whereas phosphate level was associated with CAC progression (n = 444; IRR: 3.60; 95% CI: 1.42 to 9.11). Conclusions In this prospective study, a large part of participants had incident CAC or progression of prevalent CAC at 5 years of follow-up. Low-density lipoprotein and total cholesterol were associated with CAC incidence and phosphate with CAC progression, whereas 12 other biomarkers had little value.

KW - biomarkers

KW - coronary artery calcification

KW - imaging

KW - X-ray computed tomography

U2 - 10.1016/j.jcmg.2017.05.010

DO - 10.1016/j.jcmg.2017.05.010

M3 - Journal article

C2 - 28797406

AN - SCOPUS:85026855879

VL - 10

SP - 858

EP - 866

JO - J A C C: Cardiovascular Imaging

JF - J A C C: Cardiovascular Imaging

SN - 1936-878X

IS - 8

ER -