TY - JOUR
T1 - Assessment of plasma ceramides as predictor for subclinical atherosclerosis
AU - Mishra, Pashupati P.
AU - Mishra, Binisha H.
AU - Lyytikäinen, Leo Pekka
AU - Hilvo, Mika
AU - Juonala, Markus
AU - Kähönen, Mika
AU - Hutri-Kähönen, Nina
AU - Fotiadis, Dimitrios I.
AU - Raitakari, Olli T.
AU - Laaksonen, Reijo
AU - Lehtimäki, Terho
N1 - Funding Information:
The Young Finns Study has been financially supported by the Academy of Finland: grants 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research ; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association ; This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreements No 848146 (To Aition) and No 755320 (TAXINOMISIS); This project has received funding from the European Research Council ( ERC ) advanced grants under grant agreement No 742927 (MULTIEPIGEN project); Tampere University Hospital Supporting Foundation and Finnish Society of Clinical Chemistry. Binisha H. Mishra was supported by: Laboratoriolääketieteen Edistämissäätiö Sr; Ida Montinin Säätiö; Kalle Kaiharin säätiö, the Finnish Cultural Foundation (grant 50191928) and Faculty of Medicine and Health Technology, Tampere University.
PY - 2021/11
Y1 - 2021/11
N2 - Background and aims: Ceramides have been identified as novel biomarkers for cardiovascular disease (CVD) related events and mortality but their role in etiology of subclinical atherosclerosis is unknown. We aimed to assess association between plasma ceramides and carotid intima-media thickness (CIMT) and evaluate predictive value of the ceramides for high CIMT over traditional CVD risk factors. Methods: Association between plasma ceramides and CIMT in the Young Finns Study participants was analyzed with CIMT as outcome and ceramides along with traditional risk factors as predictors with regression model. Predictive value of the ceramides and related coronary event risk test (CERT) score for high CIMT as surrogate marker of subclinical atherosclerosis was assessed by comparing logistic regression-based prediction models including, i) traditional risk factors and ceramides, ii) traditional risk factors and CERT score, iii) age, sex and ceramides or alternatively CERT score with a reference model including only traditional risk factors. The prediction models were fitted to training data (70% data) and tested on test data (30% data). The predictive models were assessed with area under the receiver operating curve (AUC). The variance of AUC was estimated by repeating the model fitting and testing for 1000 bootstraps of the original data. Results: Predictive models with plasma ceramides or alternatively with CERT score in addition to age and sex variables were able to predict high CIMT with AUC 0.726 and 0.720 respectively. However, the ceramides and CERT score did not have statistically significant added predictive value for high CIMT over traditional risk factors. Conclusions: The new systemic biomarkers, high-risk plasma ceramides and CERT score, showed promising predictive performance for high CIMT with only age and sex as additional variables. This may help in predicting subclinical atherosclerosis for primary prevention.
AB - Background and aims: Ceramides have been identified as novel biomarkers for cardiovascular disease (CVD) related events and mortality but their role in etiology of subclinical atherosclerosis is unknown. We aimed to assess association between plasma ceramides and carotid intima-media thickness (CIMT) and evaluate predictive value of the ceramides for high CIMT over traditional CVD risk factors. Methods: Association between plasma ceramides and CIMT in the Young Finns Study participants was analyzed with CIMT as outcome and ceramides along with traditional risk factors as predictors with regression model. Predictive value of the ceramides and related coronary event risk test (CERT) score for high CIMT as surrogate marker of subclinical atherosclerosis was assessed by comparing logistic regression-based prediction models including, i) traditional risk factors and ceramides, ii) traditional risk factors and CERT score, iii) age, sex and ceramides or alternatively CERT score with a reference model including only traditional risk factors. The prediction models were fitted to training data (70% data) and tested on test data (30% data). The predictive models were assessed with area under the receiver operating curve (AUC). The variance of AUC was estimated by repeating the model fitting and testing for 1000 bootstraps of the original data. Results: Predictive models with plasma ceramides or alternatively with CERT score in addition to age and sex variables were able to predict high CIMT with AUC 0.726 and 0.720 respectively. However, the ceramides and CERT score did not have statistically significant added predictive value for high CIMT over traditional risk factors. Conclusions: The new systemic biomarkers, high-risk plasma ceramides and CERT score, showed promising predictive performance for high CIMT with only age and sex as additional variables. This may help in predicting subclinical atherosclerosis for primary prevention.
KW - Cardiovascular diseases
KW - Carotid intima media thickness
KW - Lipidomics
KW - Plasma ceramides
KW - Prediction models
KW - Subclinical atherosclerosis
U2 - 10.1016/j.athplu.2021.09.005
DO - 10.1016/j.athplu.2021.09.005
M3 - Article
AN - SCOPUS:85119261075
SN - 2667-0909
VL - 45
SP - 25
EP - 31
JO - Atherosclerosis Plus
JF - Atherosclerosis Plus
ER -