Increased Dephospho-uncarboxylated Matrix Gla-Protein Is Associated With Lower Axial Skeletal Muscle Mass in Patients With Hypertension.

BACKGROUND: Matrix Gla-protein (MGP) is a well-established inhibitor of vascular calcification that is activated by vitamin K-dependent carboxylation. In the setting of vitamin K2 deficiency, dephospho-uncarboxylated MGP (dpucMGP) levels increase, and have been associated with large artery stiffening. Vitamin K2 is also a mitochondrial electron carrier in muscle, but the relationship of vitamin K2 deficiency and dpucMGP with muscle mass is not well understood. We therefore aimed to examine the association of vitamin K2 deficiency and dpucMGP with skeletal muscle mass in patients with hypertension. METHODS: We studied 155 hypertensive adults without heart failure. Axial skeletal muscle mass was measured using magnetic resonance imaging from axial steady-state free precession images. DpucMGP was measured with ELISA. Carotid-femoral pulse wave velocity (CF-PWV) was measured from high-fidelity arterial tonometry recordings. RESULTS: We found an inverse relationship between dpucMGP levels and axial muscle mass, with progressively rising dpucMGP levels correlating with decreasing axial muscle mass. In an unadjusted linear regression model, correlates of dpucMGP included axial skeletal muscle area factor (ß = -0.32; P < 0.0001) and CF-PWV (ß = 0.31; P = 0.0008). In adjusted analyses, independent correlates of dpucMGP included axial skeletal muscle area factor (ß = -0.30; P = 0.0003) and CF-PWV (ß = 0.20; P = 0.019). CONCLUSIONS: In hypertensive adults, dpucMGP is independently associated with lower axial muscle mass, in addition to increased large artery stiffness. Further studies are required to investigate the role of vitamin K supplementation in this population.

Body Composition, Natriuretic Peptides, and Adverse Outcomes in Heart Failure With Preserved and Reduced Ejection Fraction.

OBJECTIVES: The purpose of this study was to determine the relationship between body composition, N-terminal B-type natriuretic peptide (NT-proBNP) levels, and heart failure (HF) phenotypes and outcomes. BACKGROUND: Abnormalities in body composition can influence metabolic dysfunction and HF severity; however, data assessing fat distribution and skeletal muscle (SM) size in HF with reduced (HFrEF) and preserved EF (HFpEF) are limited. Further, whether NPs relate more closely to axial muscle mass than measures of adiposity is not well studied. METHODS: We studied 572 adults without HF (n = 367), with HFrEF (n = 113), or with HFpEF (n = 92). Cardiac magnetic resonance was used to assess subcutaneous and visceral abdominal fat, paracardial fat, and axial SM size. We measured NT-proBNP in 334 participants. We used Cox regression to analyze the relationship between body composition and mortality. RESULTS: Compared with controls, pericardial and subcutaneous fat thickness were significantly increased in HFpEF, whereas patients with HFrEF had reduced axial SM size after adjusting for age, sex, race, and body height (p < 0.05 for comparisons). Lower axial SM size, but not fat, was significantly predictive of death in unadjusted (standardized hazard ratio: 0.63; p < 0.0001) and multivariable-adjusted analyses (standardized hazard ratio = 0.72; p = 0.0007). NT-proBNP levels more closely related to lower axial SM rather than fat distribution or body mass index (BMI) in network analysis, and when simultaneously assessed, only SM (p = 0.0002) but not BMI (p = 0.18) was associated with NT-proBNP. However, both NT-proBNP and axial SM mass were independently predictive of death (p < 0.05). CONCLUSIONS: HFpEF and HFrEF have distinct abnormalities in body composition. Reduced axial SM, but not fat, independently predicts mortality. Greater axial SM more closely associates with lower NT-proBNP rather than adiposity. Lower NT-proBNP levels in HFpEF compared with HFrEF relate more closely to muscle mass rather than obesity.

Axial Muscle Size as a Strong Predictor of Death in Subjects With and Without Heart Failure.

Background The impact of skeletal muscle size, quantified using simple noninvasive images routinely obtained during cardiac magnetic resonance imaging studies on mortality in the heart failure ( HF ) population is currently unknown. Methods and Results We prospectively enrolled 567 subjects without HF (n=364), with HF with reduced ejection fraction (n=111), or with HF with preserved ejection fraction (n=92), who underwent a cardiac magnetic resonance imaging. Skeletal muscle cross-sectional area was assessed with manual tracing of major thoracic muscle groups on axial chest magnetic resonance images. Factor analysis was used to identify a latent factor underlying the shared variability in thoracic muscle cross-sectional area. Cox regression was used to assess the relationship between these measurements and all-cause mortality (median follow up, 36.4 months). A higher overall thoracic muscle area factor assessed with principal component analysis was independently associated with lower mortality (standardized hazard ratio, 0.51; P<0.0001). The thoracic muscle area factor was predictive of death in subjects with HF with preserved ejection fraction, HF with reduced ejection fraction, and those without HF . Among all muscle groups, the pectoralis major cross-sectional area was the most representative of overall muscle area and was also the most robust predictor of death. A higher pectoralis major cross-sectional area predicted a lower mortality (standardized hazard ratio, 0.49; P<0.0001), which persisted after adjustment for various confounders (standardized hazard ratio, 0.55; P=0.0017). Conclusions Axial muscle size, and in particular smaller size of the pectoralis major, is independently associated with higher risk of mortality in patients with and without HF . Further work should clarify the role of muscle wasting as a therapeutic target in patients with HF .