Non-alcoholic fatty liver disease (NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma (HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism (SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis (NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention on the risk of disease-related outcomes. Well-structured future studies would demonstrate if this vision can become a reality.
BackgroundHeart failure with reduced ejection fraction (HFrEF) is a clinical condition frequently diagnosed in clinical practice. In patients affected by HFrEF, sleep apnea (SA) can be detected among the most frequent comorbidities. Sacubitril–valsartan (sac/val) association has been proven to be effective in reducing disease progression and all-cause mortality in HFrEF patients. Sac/val treatment can potentially attenuate SA development via several pathophysiologic mechanisms, including improvement of global hemodynamics, reduction of extracellular fluid overload, and decrease of sympathetic neural activity.MethodsWe recruited 132 patients affected by HFrEF and SA, already under treatment with continuous positive airway pressure (CPAP), which was discontinued 24 h before the scheduled study timepoints. Physical examination, echocardiography, nocturnal cardio-respiratory monitoring, and laboratory tests were performed in each patient at baseline and after a 6-month treatment with sac/val.ResultsAfter 6 months, sac/val induced statistically significant changes in clinical, hemodynamic, biohumoral (NT-proBNP, serum electrolytes, creatinine, and uric acid), and echocardiographic parameters. In particular, cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS) improved. Moreover, polysomnography, carried out during a temporary CPAP interruption, revealed a significant reduction in global apnea-hypopnea index (AHI) value (p < 0.0001), central AHI (p < 0.0001), obstructive AHI (p < 0.0001), oxygen desaturation index (ODI) (p < 0.0001), and percentage time of saturation below 90% (TC90) (p < 0.0001). The changes of CI, estimated glomerular filtration rate (eGFR), NT-proBNP, and tricuspid annular plane excursion (TAPSE) contributed to 23.6, 7.6, 7.3, and 4.8% of AHI variability, respectively, and the whole model accounted for a 43.3% of AHI variation.ConclusionsOur results suggest that treatment with sac/val is able to significantly improve the cardiorespiratory performance of patients with HFrEF and SA, integrating the positive impact of CPAP. Thus, both CPAP and sac/val therapy may synergistically contribute to lower the risks of both cardiac and pulmonary complications in HFrEF patients with SA.
Background: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular morbidity and mortality, and it has a detrimental effect on renal function. Obesity is the major risk factor for OSAS, and represents a risk factor for chronic kidney disease. Continuous positive airway pressure (CPAP) is the suggested therapy for moderate-to-severe OSAS. We designed this study to evaluate the effect of CPAP on estimated glomerular filtration rate (e-GFR) in a cohort of obese patients with moderate-to-severe OSAS and normal renal function.Methods: We enrolled 198 obese subjects, divided into two groups (OSAS+ and OSAS–), on the basis of cardiorespiratory monitoring; mild OSAS patients (n = 33) were excluded from the study, thus the analyses were conducted on 165 patients. Comparisons between groups were made by Student t-test or χ2 test as appropriate. Linear regression analyses were used to assess the relationship between baseline e-GFR and different covariates and, in the OSAS+ group, between Δe-GFR and different covariates. A multivariate regression analysis was performed to determinate the independent predictor of the Δe-GFR.Results: OSAS+ subjects showed significantly increased values of systolic blood pressure, HOMA, pulse wave velocity, high-sensitivity C reactive protein and uric acid compared with OSAS– group. OSAS+ group showed significantly lower values of e-GFR and increased values of microalbuminuria. At linear regression analysis e-GFR resulted significantly and inversely related to AHI in the whole study population and in the two groups. After 6 months of CPAP therapy, OSAS+ subjects showed an improvement in respiratory parameters, as well as a significant increase in e-GFR values (104.2 + 19.0 vs. 84.0 + 13.1 ml/min/1.73 m2, P < 0.0001). At multiple regression analysis, Δ apnea/hypopnea index (AHIa) resulted the main independent predictor of Δe-GFR explaining 22% of its variation.Conclusions: Obese OSAS patients show significantly lower values of e-GFR, even if in the normal range, compared with obese non-OSAS subjects. After 6 months of CPAP, e-GFR significantly improved (+20 ml/min/1.73 m2) and ΔAHIa resulted the most important independent predictor of Δe-GFR.
Background Heart failure with reduced ejection fraction (HFrEF) is a clinical condition frequently diagnosed in clinical practice. In patients affected by HFrEF, sleep apnea (SA) can be detected among the most frequent comorbidities. Sacubitril–valsartan (sac/val) association has been proven to be effective in reducing disease progression and all-cause mortality in HFrEF patients. Sac/val treatment can potentially attenuate SA development via several pathophysiologic mechanisms, including improvement of global hemodynamics, reduction of extracellular fluid overload, and decrease of sympathetic neural activity. Purpose The aim of this work is to evaluate the effects of a 6-month therapy with sac/val on hemodynamic and metabolic parameters, as well as on the occurrence of apnea/hypopnea and oxygen saturation in patients with HFrEF and SA, already treated with CPAP. Methods We recruited 132 patients affected by HFrEF and SA, already under treatment with continuous positive airway pressure (CPAP), which was discontinued 24 hours before the scheduled study timepoints. Physical examination, echocardiography, nocturnal cardio-respiratory monitoring, and laboratory tests were performed in each patient at baseline and after a 6-month treatment with sac/val. Results After 6 months, sac/val induced statistically significant changes in clinical, hemodynamic, biohumoral (NT-proBNP, serum electrolytes, creatinine and uric acid), and echocardiographic parameters. In particular, cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS) improved. Moreover, polysomnography, carried out during a temporary CPAP interruption, revealed a significant reduction in global apnea-hypopnea index (AHI) value (p<0.0001), central AHI (p<0.0001), obstructive AHI (p<0.0001), oxygen desaturation index (ODI) (p<0.0001), and percentage time of saturation below 90% (TC90) (p<0.0001). The changes of CI, estimated glomerular filtration rate (eGFR), NT-proBNP and tricuspid annular plane excursion (TAPSE) contributed to 23.6%, 7.6%, 7.3% and 4.8% of AHI variability, respectively, and the whole model accounted for a 43.3% of AHI variation. Conclusions Our results suggest that treatment with sac/val is able to significantly improve the cardiorespiratory performance of patients with HFrEF and SA, integrating the positive impact of CPAP. Thus, both CPAP and sac/val therapy may synergistically contribute to lower the risks of both cardiac and pulmonary complications in HFrEF patients with SA. Funding Acknowledgement Type of funding sources: None.
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