Serum insulin-like growth factor-1 and its binding protein-7: potential novel biomarkers for heart failure with preserved ejection fraction.

BACKGROUND: Insulin-like growth factor binding protein-7 (IGFBP-7) modulates the biological activities of insulin-like growth factor-1 (IGF-1). Previous studies demonstrated the prognostic value of IGFBP-7 and IGF-1 among patients with systolic heart failure (HF). This study aimed to evaluate the IGF1/IGFBP-7 axis in HF patients with preserved ejection fraction (HFpEF). METHODS: Serum IGF-1 and IGFBP-7 levels were measured in 300 eligible consecutive patients who underwent comprehensive cardiac assessment. Patients were categorized into 3 groups including controls with normal diastolic function (n = 55), asymptomatic left ventricular diastolic dysfunction (LVDD, n = 168) and HFpEF (n = 77). RESULTS: IGFBP-7 serum levels showed a significant graded increase from controls to LVDD to HFpEF (median 50.30 [43.1-55.3] vs. 54.40 [48.15-63.40] vs. 61.9 [51.6-69.7], respectively, P < 0.001), whereas IGF-1 levels showed a graded decline from controls to LVDD to HFpEF (120.0 [100.8-144.0] vs. 112.3 [88.8-137.1] vs. 99.5 [72.2-124.4], p < 0.001). The IGFBP-7/IGF-1 ratio increased from controls to LVDD to HFpEF (0.43 [0.33-0.56] vs. 0.48 [0.38-0.66] vs. 0.68 [0.55-0.88], p < 0.001). Patents with IGFB-7/IGF1 ratios above the median demonstrated significantly higher left atrial volume index, E/E' ratio, and NT-proBNP levels (all P ≤ 0.02). CONCLUSION: In conclusion, this hypothesis-generating pilot study suggests the IGFBP-7/IGF-1 axis correlates with diastolic function and may serve as a novel biomarker in patients with HFpEF. A rise in IGFBP-7 or the IGFBP-7/IGF-1 ratio may reflect worsening diastolic function, adverse cardiac remodeling, and metabolic derangement.

Metabolic syndrome with or without diabetes contributes to left ventricular diastolic dysfunction.

OBJECTIVE: Left ventricular diastolic dysfunction (LVDD) is considered a precursor of diabetic cardiomyopathy, while the metabolic syndrome (MetS) is associated with an increased risk of cardiovascular morbidity and mortality. This study aimed to evaluate the association between LVDD, MetS and glucose metabolism disturbances classified by oral glucose tolerance testing (oGTT). METHODS AND RESULTS: The presence of LVDD was evaluated in 166 subjects with normal ejection fraction, 43 (26%) of whom had type 2 diabetes at inclusion. In subjects without diabetes, an oGTT was performed. The MetS was diagnosed as indentified by the NCEPIII-criteria, while LVDD was verified and graded according to the current guidelines. MetS was diagnosed in 97 (59%) patients, 44% of whom had known diabetes. The prevalence of LVDD was 68% in subjects with MetS vs. 19% in patients without MetS, respectively (P < 0.001). A severe form of LVDD was observed in 34% and 15% of patients with and without MetS, respectively (P = 0.001), whereupon the prevalence of mild and severe diastolic dysfunction increased with the number of MetS criteria (P= 0.001). In the MetS group, early diastolic tissue relaxation velocity (E') was significantly reduced (6.9 +/- 1.8 cm/s vs. 7.7 +/- 2.1 cm/s; P= 0.009) and the E/E' ratio was significantly higher (10.5 +/- 3.9 vs. 9.1 +/- 3.0 cm/s, P = 0.015) as compared to the group without MetS (n = 69). CONCLUSION: MetS was associated with a higher prevalence and severity of LVDD, whereupon coexisting diabetes aggravates these inding.Patients displaying MetS with concomitant LVDD might represent a target population in which appropriate medical care for early heart failure prevention should be initiated.

Insulin resistance and glycemic abnormalities are associated with deterioration of left ventricular diastolic function: a cross-sectional study.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is considered a precursor of diabetic cardiomyopathy, while insulin resistance (IR) is a precursor of type 2 diabetes mellitus (T2DM) and independently predicts heart failure (HF). We assessed whether IR and abnormalities of the glucose metabolism are related to LVDD. METHODS: We included 208 patients with normal ejection fraction, 57 (27%) of whom had T2DM before inclusion. In subjects without T2DM, an oral glucose tolerance test (oGTT) was performed. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The lower limit of the top quartile of the HOMA-IR distribution (3.217) was chosen as threshold for IR. LVDD was verified according to current guidelines. RESULTS: IR was diagnosed in 38 (18%) patients without a history of diabetes. The prevalence of LVDD was 92% in subjects with IR vs. 72% in patients without IR (n = 113), respectively (p = 0.013). In the IR group, the early diastolic mitral inflow velocity (E) in relation to the early diastolic tissue Doppler velocity (averaged from the septal and lateral mitral annulus, E'av) ratio (E/E'av) was significantly higher compared to those without IR (9.8 [8.3-11.5] vs. 8.1 [6.6-11.0], p = 0.011). This finding remains significant when patients with IR and concomitant T2DM based on oGTT results were excluded (E/E'av ratio 9.8 [8.2-11.1)] in IR vs. 7.9 [6.5-10.5] in those without both IR and T2DM, p = 0.014). There were significant differences among patients with and without LVDD regarding the HOMA-IR (1.71 [1.04-3.88] vs. 1.09 [0.43-2.2], p = 0.003). The HOMA-IR was independently associated with LVDD on multivariate logistic regression analysis, a 1-unit increase in HOMA-IR value was associated with an odds ratio for prevalent LVDD of 2.1 (95% CI 1.3-3.1, p = 0.001). Furthermore, the E/E'av ratio increases along the glucose metabolism status from normal glucose metabolism (7.6 [6.2-10.1]) to impaired glucose tolerance (8.8 [7.4-11.0]) and T2DM (10.5 [8.1-13.2]), respectively (p < 0.001). CONCLUSIONS: Insulin resistance is independently associated with LVDD in subjects without overt T2DM. Patients with IR and glucose metabolism disorders might represent a target population to prevent the development of HF. Screening programs for glucose metabolism disturbances should address the assessment of diastolic function and probably IR.