Does Oxidative Status Predict Progress in Subclinical Atherosclerosis: An Analysis of the Insulin Resistance Atherosclerosis Study
Creators: name: Williamson, Shayla
Publisher: name: Georgia State University
Year: 2020

description: Purpose: There has been a strong biological plausibility for a causal role of reactive oxygen species in cardiovascular disease pathology. However, randomized clinical trials of antioxidants showed no association between antioxidant intake and reduced risk of CVD mortality nor morbidity. To date, there has been no direct epidemiological evidence linking oxidative status to subclinical atherosclerosis progression. We examined prospective relationships between oxidative status (urinary F2-Isoprostanes) and subclinical atherosclerosis (common/internal carotid intima-media thickness) in the Insulin Resistance Atherosclerosis Study cohort (N=857) to determine if elevated systemic levels of F2-isoprostnaes are directly correlated with progression in subclinical atherosclerosis.
Methods
This study utilized data from the Insulin Resistance Atherosclerosis Study (IRAS), a prospective cohort study that was designed to examine the relationships between insulinemia, glycemia, insulin resistance, and cardiovascular risk in a racially and metabolically diverse population including African Americans, non-Hispanic whites, and Hispanics between 40-69 years of age at baseline 27. Between October 1992 and April 1994, 1625 men and women were recruited to participate in the study and followed up after 5 years27. Four urinary F2-isoprostane isomers were quantified at baseline using liquid chromatography/tandem mass spectrometry and were summarized as a composite F2-isoprostane index, which was used as a marker for oxidative status. Linear and logistic regression were used to assess the relationship between F2-isoprostanes and the outcome of interest, subclinical atherosclerosis, measured by common carotid artery intima-media thickness (CCIMT) as well as internal carotid artery intima-media thickness (ICIMT). CCIMT and ICIMT were assessed at baseline and at the follow-up examinations. In logistic regression models, progression of CCIMT and ICIMT was defined as a >15% change during the follow-up examination and the main exposure was the baseline F2-isoprostane index. The covariates included age, sex, ethnicity and baseline BMI, smoking status, and systolic blood pressure (SBP). In linear regression models, natural log transformed CCIMT/ICIMT at follow-up were dependent variables and the baseline F2-isoporstane index was the main exposure with the baseline natural log transformed CCIMT/ICIMT and the same covariates included as predictors.
Results
After adjustment for age, sex, ethnicity, BMI status, smoking status and systolic blood pressure, logistic regression models showed that F2-isoprostanes had an inverse association with CCIMT progression (OR= 0.76, 95% CI [0.58, 1.01]) and no association with progression of ICIMT (OR = 0.94, 95% CI [0.76, 1.17]). Linear regression also showed a tendency of inverse relationships between F2-isoprostane index and change in CCIMT and ICIMT: beta-coefficients for F2-isoprostane index were -0.014, 95% CI (-0.029,0.0006)] and -0.0021, 95% CI (-0.030,0.026), in the models predicting change in CCIMT and ICIMT, respectively.

Conclusion
The result from this study suggest that elevated levels of F2-isoprostanes do not directly predict subclinical atherosclerosis progression. Future studies are needed to get a better understanding of the different forms of oxidative status markers and their influence on cardiovascular disease risk.