Hepatocyte growth factor and risk of incident stroke in Black and White Americans in REGARDS

Introduction Hepatocyte growth factor (HGF) is a cytokine produced in response to endothelial damage. Higher levels correlate with cardiovascular risk factors including hypertension and diabetes. We hypothesized that HGF is associated with stroke. Methods The Reasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black and White Americans aged ≥45 from 2003-2007. In this case-cohort study, after 5.5 years follow-up, circulating baseline HGF was measured in 557 participants with incident ischemic stroke and a cohort random sample of 964 participants. Hazard ratios per standard deviation (SD) log HGF and by HGF quintile were calculated using Cox proportional hazards models adjusting for stroke risk factors and other correlates of HGF. Differences by race and sex were tested using interaction terms. Results Median HGF was 295 pg/ml (IQR 209, 402 pg/ml). HGF was higher with older age, male sex, prevalent cardiovascular disease, smoking, and warfarin use, but did not differ by race. the adjusted HR of incident ischemic stroke per SD higher baseline HGF (145 pg/ml) was 1.30 (CI 1.00, 1.70), with no difference by sex or race. HGF in the highest (>434 pg/mL) vs. lowest quintile (<135 pg/mL) was associated with an adjusted HR of incident stroke of 2.12 (CI 1.31-3.41). Conclusion In REGARDS, higher HGF was associated with increased risk of incident ischemic stroke in Black and White adults, with a doubling in risk for HGF in the top quintile compared to the lowest quintile after adjusting for other stroke risk factors.