Association of Heart-Type Fatty Acid-Binding Protein with Cardiovascular Risk Factors and All-Cause Mortality in the General Population: The Takahata Study

<div><p>Background</p><p>Despite many recent advances in medicine, preventing the development of cardiovascular diseases remains a challenge. Heart-type fatty acid-binding protein (H-FABP) is a marker of ongoing myocardial damage and has been reported to be a useful indicator for future cardiovascular events. However, it remains to be determined whether H-FABP can predict all-cause and cardiovascular deaths in the general population.</p><p>Methods and Results</p><p>This longitudinal cohort study included 3,503 subjects who participated in a community-based health checkup with a 7-year follow-up. Serum H-FABP was measured in registered subjects. The results demonstrated that higher H-FABP levels were associated with increasing numbers of cardiovascular risk factors, including hypertension, diabetes mellitus, obesity, and metabolic syndrome. There were 158 deaths during the follow-up period, including 50 cardiovascular deaths. Deceased subjects had higher H-FABP levels compared to surviving subjects. Multivariate Cox proportional hazard regression analysis revealed that H-FABP is an independent predictor of all-cause and cardiovascular deaths after adjustments for confounding factors. Subjects were divided into four quartiles according to H-FABP level, and Kaplan-Meier analysis demonstrated that the highest H-FABP quartile was associated with the greatest risks for all-cause and cardiovascular deaths. Net reclassification index and integrated discrimination index were significantly increased by addition of H-FABP to cardiovascular risk factors.</p><p>Conclusions</p><p>H-FABP level was increased in association with greater numbers of cardiovascular risk factors and was an independent risk factor for all-cause and cardiovascular deaths. H-FABP could be a useful indicator for the early identification of high-risk subjects in the general population.</p></div

Clinical characteristics among subjects with 1^st to 4^th quartile.

<p>Data are expressed as mean ± standard deviation or number (%).</p><p>CVD, cardiovascular disease; CKD, chronic kidney disease; Mets, metabolic syndrome; LVH, left ventricular hypertrophy; AF, atrial fibrillation; BP, blood pressure; HbA1c, glycosylated hemoglobin A1c, FBG, fasting blood glucose; eGFR, estimated glomerular filtration rate; BNP, brain natriuretic peptide; H-FABP, heart type fatty acid binding protein. *p<0.05 vs. 1^st quartile, ^†p<0.05 vs. 2^nd quartile, ^‡p<0.05 vs. 3^rd quartile by analysis of variance (ANOVA) with Scheffe post hoc test. ^§p<0.05 by chi-square test.</p

Clinical characteristics of subjects with and without all-cause deaths.

<p>Data are expressed as mean ± standard deviation or number (%).</p><p>CVD, cardiovascular disease; CKD, chronic kidney disease; MetS, metabolic syndrome; LVH, left ventricular hypertrophy; AF, atrial fibrillation; BP, blood pressure; HbA1c, glycosylated hemoglobin A1c, FBG, fasting blood glucose; eGFR, estimated glomerular filtration rate; BNP, brain natriuretic peptide; H-FABP, heart type fatty acid binding protein.</p

Statics for model fit and improvement with the addition of H-FABP on the prediction of all-cause mortality.

<p>AUC, area under the curve; 95%CI, 95% confidence interval; NRI, net reclassification index; IDI, integrated discrimination index; HT, hypertension; DM, diabetes mellitus; Mets, metabolic syndrome; BNP, brain natriuretic peptide; H-FABP, heart type fatty acid binding protein.</p

Univariate Cox proportional hazard analysis for all-cause mortality.

<p>CVD, cardiovascular disease; CKD, chronic kidney disease; MetS, metabolic syndrome; LVH, left ventricular hypertrophy; AF, atrial fibrillation; BP, blood pressure; HbA1c, glycosylated hemoglobin A1c; FBG, fasting blood glucose; eGFR, estimated glomerular filtration rate; BNP, brain natriuretic peptide; H-FABP, heart type fatty acid binding protein.</p

Associations between H-FABP levels and cardiovascular risk factors in the general population.

<p>H-FABP levels were higher in subjects with hypertension (<b>A</b>), diabetes mellitus (<b>B</b>), obesity (<b>C</b>), and metabolic syndrome (<b>D</b>). (<b>E</b>) Higher H-FABP levels were associated with greater numbers of cardiovascular risk factors (Kruskal-Wallis test, P<0.0001). HT, hypertension; DM, diabetes mellitus; MetS, metabolic syndrome.</p

Associations between H-FABP levels and all-cause deaths, cardiovascular deaths, and non-cardiovascular deaths.

<p>Associations between H-FABP levels and all-cause deaths, cardiovascular deaths, and non-cardiovascular deaths.</p