Planned intervention: On Wednesday April 3rd 05:30 UTC Zenodo will be unavailable for up to 2-10 minutes to perform a storage cluster upgrade.
Published January 20, 2020 | Version v1
Journal article Open

Risk for Cardiovascular Events Responds Nonlinearly to Carotid Intima-Media Thickness in the KORA F4 Study

  • 1. Helmholtz Zentrum München, Institute of Radiation Medicine, 85764, Oberschleißheim, Germany
  • 2. Helmholtz Zentrum München, Institute of Epidemiology, 85764, Oberschleißheim, Germany
  • 3. Helmholtz Zentrum München, Institute of Epidemiology, 85764, Oberschleißheim, Germany; Chair of Epidemiology, Ludwig-Maximilians-University München, UNIKA-T Augsburg, Augsburg, Germany
  • 4. Diabetes Centre, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany; Clinical Cooperation Group Diabetes, Ludwig-Maximilians-Universität München and Helmholtz Zentrum München, Munich, Germany
  • 5. Helmholtz Zentrum München, Institute of Epidemiology, 85764, Oberschleißheim, Germany; Chair of Epidemiology, Ludwig-Maximilians-University München, Munich, Germany

Description

Background and aims: Risk assessment studies on the impact of carotid intima-media thickness (CIMT) on cardiovascular events (CVEs) often apply a linear relationship in Cox models of proportional hazards. However, CVEs are mostly induced through rupture of plaques driven by nonlinear mechanical properties of the arterial wall. Hence, the risk response might be nonlinear as well and should be detectable in CVE incidence data when associated with CIMT as surrogate variable for atherosclerotic wall degeneration.

Methods: To test this hypothesis, we investigate the KORA F4 study comprising 2580 participants with CIMT measurements and 153 first CVEs (86 strokes and 67 myocardial infarctions). CIMT is only a moderate predictor of CVE risk due to confounding by attained age. Biological evidence suggests that age-related CIMT growth is not entirely connected with atherosclerosis. To explore the complex relations between age, CIMT and CVE risk, we apply linear and nonlinear models of both CIMT and dnCIMT, defined as deviation from a sex and age-adjusted normal value.

Results: Based on goodness-of-fit and biological plausibility, threshold and logistic step models clearly reveal nonlinear risk response relations for vascular covariables CIMT and dnCIMT. The effect is more pronounced for models involving dnCIMT as novel risk factor, which is not correlated with age.

Conclusions: Compared to the standard approach of risk assessment with linear models involving CIMT, the application of excess dnCIMT with nonlinear risk responses leads to a more precise identification of asymptomatic high risk patients, especially at younger age.

Notes

This project has received funding from the EURATOM research and training programme 2014-2018 under grant agreement No 755523 (MEDIRAD). The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Centre for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Measurement of CIMT was partly funded by grants of the Karl-Wilder-Foundation (JS) and the Deutsche Diabetes-Gesellschaft (CT).

Files

Cardiovascular_Risk_nonlinear_with_CIMT.pdf

Files (1.1 MB)

Name Size Download all
md5:838f9b09f04054976e44efab62833c4e
1.1 MB Preview Download

Additional details

Funding

MEDIRAD – Implications of Medical Low Dose Radiation Exposure 755523
European Commission