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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.

The Reasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black and White Americans aged ≥45 years from 2003 to 2007. In this case-cohort study, after 5.5 years of follow-up, circulating baseline HGF was measured in 557 participants with incident ischemic stroke and in a cohort random sample of 964 participants. Hazard ratios (HRs) per SD log-transformed 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.

Median HGF was 295 (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).

In the REGARDS study, higher HGF was associated with increased risk of incident ischemic stroke in Black and White adults, with a doubling in risk of HGF in the top quintile compared with the lowest quintile after adjusting for other stroke risk factors.

• Hepatocyte growth factor (HGF) is produced in response to blood vessel damage. • We studied whether higher baseline HGF is associated with incident stroke in a large cohort study. • Higher HGF was strongly associated with stroke independent of other stroke risk factors. • Participants in the highest quintile HGF had double risk of stroke compared with the lowest.