Cellular growth factors in relation to mortality from cardiovascular disease in middle-aged Japanese: the JACC study

Abstract

Objective: Limited evidence has been available on the relationships of cellular growth factors with cardiovascular disease in population-based samples.

Methods: We conducted a nested case-control study under a large prospective cohort study (JACC study) where a total of 39,242 subjects aged 40-79 years provided serum sample. We measured cellular growth factors [insulin-like growth factors I, II and binding protein-3 (IGF-I, IGF-II and IGFBP-3) and transforming growth factor (TGF-β1)] among cases and controls, matched for sex, age, area of residence and year of serum storage.

Results and conclusions: During the follow-up for 9 years, there were 233 deaths from total stroke (49 subarachnoid hemorrhages, 55 intraparenchymal hemorrhages, 71 ischemic strokes), and 97 deaths from coronary heart disease. The multivariable odds ratio (95%CI) of intraparenchymal hemorrhage associated with a 1-SD increment of IGF-I (men:4 8 ng/ml, women: 61 ng/ml) was 0.31 (0.14-0.71). That of ischemic stroke associated with a 1-SD increment of TGF-β1 (men: 8.0 ng/ml, women: 10.9 ng/ml) was 0.58 (0.34-0.98). Serum IGF-II and IGFBP-3 were not associated with mortality from any outcomes. In conclusion, IGF-I was inversely associated with mortality from intraparenchymal hemorrhage while TGF-β1 was so with ischemic stroke, suggesting potential roles of cellular proliferation in the development or prognosis of stroke.