Abstract MP075: Fetuin-A and Risk of Ischemic Stroke Among Women

Introduction: Fetuin-A, a protein secreted primarily by the liver, has been associated with non-alcoholic fatty liver disease and insulin resistance. A recent study found that high fetuin-A levels were associated with increased cardiovascular risk, particularly for ischemic stroke; however, the data have not been replicated. Methods: A nested case-control design was utilized to examine the relationship between fetuin-A and ischemic stroke among female participants of the Nurses’ Health Study who provided blood samples. A total of 462 incident cases of ischemic stroke were identified and confirmed by medical records according to the National Survey of Stroke criteria between 1990-2006 and were matched to 462 controls by age, menopausal status, hormone therapy use, and smoking status. Fetuin-A was measured on blood samples collected and stored between 1989-1990. Conditional logistic regression was used to evaluate the multivariable adjusted association between fetuin-A and ischemic stroke. Results: Fetuin-A levels were higher in those with elevated cholesterol (p=0.02), current hormone use (p=0.002) and hypertension (p=0.05) in univariate analyses. Significant partial spearman correlations, adjusted for matching factors, were found between fetuin-A and triglycerides (r=0.18; p<0.001), C-reactive protein (r=0.12; p=0.002), and BMI (r=0.13; p<0.001). Fetuin-A quartiles were not significantly associated with increased risk of incident ischemic stroke when adjusted for matching factors, or when additionally adjusted for other CVD risk factors (see Table 1). Further adjustment for other biomarkers, modestly strengthened the association, but p for trend remained nonsignificant (p=0.37). Conclusions: In this population of women, fetuin-A was not significantly associated with a greater risk of ischemic stroke. Further research is needed to explore this association. Table 1 Multivariable adjusted relative risk (95% CI) of ischemic stroke by Fetuin-A quartiles Quartiles of Fetuin-A p-value for trend Q1 Q2 Q3 Q4 Range (μ g/mL) <377 377-<449 449-<526 526-1538 Cases/Controls 108/116 136/115 102/113 112/116 Model 1 * 1.00 1.22 (0.86-1.75) 0.92 (0.62-1.35) 1.05 (0.71-1.55) 0.79 Model 2 † 1.00 1.32 (0.88-1.99) 1.00 (0.64-1.56) 1.28 (0.81-2.01) 0.52 Model 3 ‡ 1.00 1.34 (0.88-2.03) 1.06 (0.67-1.69) 1.24 (0.78-1.98) 0.59 Model 4 § 1.00 1.41 (0.82-2.42) 1.00 (0.55-1.84) 1.33 (0.73-2.42) 0.37 * Model 1: Conditional on matching factors (age, menopausal status, hormone use, smoking) † Model 2: Model 1 + aspirin use, alcohol intake, physical activity, healthy diet score, current post-menopausal hormone use ‡ Model 3: Model 2 + aspirin use, alcohol intake, physical activity, healthy diet score, current post-menopausal hormone use, history of diabetes, elevated cholesterol, high blood pressure, and CHD or revascularization. § Model 4: Model 3+ HbA1c, ln(CRP), ln(triglycerides), ln(cholesterol/HDL)