Recently, a report was published describing inverse associations between HTRA1 activity (based on an in vitro assay of HTRA1-protease activity to LTBP1 [latent transforming growth factor beta binding protein 1]) and risks of stroke and coronary artery disease.40 While we replicated the relationship between HTRA1-protease activity and ischemic stroke, the relationship with HTRA1-protease activity and coronary artery disease or acute MI was dependent on the inclusion of R227W (Figure S1A through S1D; Table S12). Here, LTBP1 is linked to ischemic stroke.