Fibroblast Growth Factor-23 and Cardiovascular Disease in the General Population

Abstract

Background Fibroblast growth factor-23 (FGF-23) is a phosphate regulatory hormone that directly stimulates left ventricular hypertrophy in experimental models. The role of FGF-23 in cardiovascular disease development in the general population is unclear. We tested associations of FGF-23 with major subclinical and clinical cardiovascular disease outcomes in a large prospective cohort. Methods and Results We evaluated 6,547 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who were initially free of cardiovascular disease. We measured serum FGF-23 using the Kainos immunoassay. The MESA measured left ventricular (LV) mass by magnetic resonance imaging, coronary calcium (CAC) by computed tomography, and carotid intima-medial thickness (IMT) by ultrasound. The MESA adjudicated incident heart failure, coronary heart disease, and stoke by medical record review. After adjustment, the highest FGF-23 quartile was associated with an estimated 2.4 gram greater LV mass (95% CI 0.4, 4.5 greater) and a 26% greater odds of higher CAC scores (95% CI 9% to 46% greater) compared to the lowest quartile. Over 7.5 years follow-up, each 20-pg/mL higher FGF-23 concentration was associated with a 19% greater risk of heart failure (95% CI 3% to 37% greater) and a 14% greater risk of coronary heart disease (95% CI 1% to 28% greater). FGF-23 was not associated with carotid IMT or stroke. Conclusions Higher serum FGF-23 concentrations are associated with subclinical cardiac disease and with new heart failure and coronary disease events, but not with carotid IMT or stroke. FGF-23 may be a novel cardiovascular risk factor in the general population.

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

“…Specific associations have been reported for incident hypertension, LVH, incident HF, higher coronary calcium scores, and incident coronary heart disease 17, 19, 27, 28. In this study we confirmed previous findings reported by Kestenbaum et al linking serum FGF‐23 to incident HF, and further studied the association with subtypes of HFpEF and HFrEF.…”

“…Furthermore, Seliger et al demonstrated that LVH was associated with higher risk of both types of HF, but especially HFrEF in older adults without prior HF or myocardial infarction in the Cardiovascular Health Study 41. Our findings of a strong association between higher FGF‐23 and higher risk of HFpEF cannot be explained fully by previous observations of the association between FGF‐23 and LV mass 18, 19. In sensitivity analyses we found that the association of FGF‐23 and HF remained significant even after adjusting for LV mass, suggesting that other pathological mechanisms could be mediating the association between FGF‐23 and the development of HF as mentioned in previous paragraphs.…”

“…Previous studies examined the association between FGF‐23 with EF as a continuous variable. Kestenbaum et al found no significant relationship between FGF‐23 and EF 19. In previous community‐based studies, FGF‐23 was associated with reduced EF 44, 49.…”

“…The administration of recombinant FGF‐23 promotes cardiomyocyte growth in animal models and higher circulating FGF‐23 concentrations are associated with HF and cardiovascular events in kidney disease and general populations 18. Among 6542 participants in MESA (Multiethnic Study of Atherosclerosis), higher FGF‐23 concentrations were associated with all incident HF events over 7.5 years of follow‐up 19. Such associations could represent HFpEF, given known biological effects of FGF‐23 on ventricular hypertrophy.…”

Association of serum intact fibroblast growth factor 23 with left ventricular mass and different echocardiographic findings in patients on hemodialysis

“…FGF23 is not only involved in the pathogenesis of CVD but also a marker of higher risk of CHF. [10,11,15] It has been shown that FGF23 concentrations are elevated in patients who are on dialysis; [10][11][12] , however whether there is an association between FGF23 levels and LVH and other echocardiographic indexes of LV dysfunction in patients who are on dialysis is still unproven. [13,14,16] Therefore, in this study, we decided to evaluate the role of FGF23 on LVH, left ventricular mass index (LVMI), and other echocardiographic findings in a group of patients on hemodialysis without known CVD.…”