Fibroblast Growth Factor-23 and Cardiovascular Disease in the General Population: The Multi-Ethnic Study of Atherosclerosis

Study Questions:

Is fibroblast growth factor-23 (FGF-23) associated with major subclinical and clinical cardiovascular disease outcomes?

Methods:

Data from Multi-Ethnic Study of Atherosclerosis (MESA) were used for the present analysis. Only participants who were free of cardiovascular disease at baseline were included. Two participants with severe chronic kidney disease and three participants with FGF-23 values extremely out of range were excluded. FGF-23, a phosphate regulatory hormone that directly stimulates left ventricular (LV) hypertrophy in experimental models, was measured at baseline. LV mass was measured by magnetic resonance imaging, coronary artery calcium (CAC) by computed tomography, and carotid intima-medial thickness (IMT) by ultrasound. The MESA adjudicated incident heart failure, coronary heart disease, and stroke by medical record review.

Results:

A total of 6,547 participants were included in this study. The median and mean (standard deviation) serum FGF-23 concentration was 37.7 and 40.0 (15.2) pg/ml, respectively. Mean serum FGF-23 concentrations were quantitatively similar, although statistically different by race/ethnicity: 41.7 pg/ml in Caucasians, 39.3 pg/ml in African Americans, 39.8 pg/ml in Chinese-Americans, and 38.1 pg/ml in Hispanics. Mean FGF-23 concentrations were on average 1.0 pg/ml higher in men compared to women (p = 0.01). After adjustment, the highest FGF-23 quartile was associated with an estimated 2.4 gram greater LV mass (95% confidence interval [CI], 0.4%-4.5% greater) and a 26% greater odds of higher CAC scores (95% CI, 9%-46% greater) compared to the lowest quartile. Over 7.5 years of follow-up, each 20 pg/ml higher FGF-23 concentration was associated with a 19% greater risk of heart failure (95% CI, 3%-37% greater) and a 14% greater risk of coronary heart disease (95% CI, 1%-28% greater). FGF-23 was not associated with carotid IMT or stroke.

Conclusions:

The investigators concluded that 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.

Perspective:

These data from a large multi-ethnic population suggest that FGF-23 may be a novel factor, which can be used to identify patients at increased risk for heart failure and coronary events.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure

Keywords: Stroke, Atherosclerosis, European Continental Ancestry Group, Coronary Disease, Fibroblast Growth Factors, Hispanic Americans, Medical Records, Heart Diseases, Tomography, Heart Failure, Cardiovascular Diseases, Hypertrophy, United States


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