Traditional risk factors are not major contributors to the variance in carotid intima-media thickness

Abstract

Background and purpose: Carotid intima-media thickness (cIMT) was a widely accepted ultrasound marker of subclinical atherosclerosis in the past. Although traditional risk factors may explain ≈50% of the variance in plaque burden, they may not explain such a high proportion of the variance in IMT, especially when measured in plaque-freel ocations. We aimed this study to identify individuals with cIMT unexplained by traditional risk factors for future environmental and genetic research.

Methods: As part of the Northern Manhattan Study, 1790 stroke-free individuals (mean age, 69±9 years; 60% women; 61% Hispanic; 19% black; 18% white) were assessed for cIMT using B-mode carotid ultrasound. Multiple linear regression models were evaluated: (1) incorporating prespecified traditional risk factors; and (2) including less traditional factors, such as inflammation biomarkers, adiponectin, homocysteine, and kidney function. Standardized cIMT residual scores were constructed to select individuals with unexplained cIMT.

Results: Mean total cIMT was 0.92±0.09 mm. The traditional model explained 11% of the variance in cIMT. Age (7%), male sex (3%), glucose (<1%), pack-years of smoking (<1%), and low-density lipoprotein cholesterol (<1%) were significant contributing factors. The model, including inflammatory biomarkers, explained 16% of the variance in cIMT. Adiponectin was the only additional significant contributor to the variance in cIMT. We identified 358 individuals (20%) with cIMT unexplained by the investigated risk factors.

Conclusions: Vascular risk factors explain only a small proportion of variance in cIMT. Identification of novel genetic and environmental factors underlying unexplained subclinical atherosclerosis is of utmost importance for future effective prevention of vascular disease.

Keywords: carotid intima-media thickness; carotid ultrasound; risk factors.

Figure 1. Predicted cIMT Distribution versus Masured cIMT Distribution

The three groups of individuals are distributed according to their residual scores computed using the approach from Spence and colleagues [6,12,25]. The solid gray circles represent individuals whose cIMT is explained by the final regression model (Intermediate cIMT), while the black squares (the bottom 10% of regression residuals) and black triangles (the top 10% of regression residuals) represents individuals in whom cIMT is unexplained by the factors included in the final model (Unexplained cIMT).