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Association between sleep-disordered breathing and arterial stiffness in heart failure patients with reduced or preserved ejection fraction.

ABSTRACT:

Aims

Sleep-disordered breathing (SDB) is associated with arterial stiffness, which may be one of the factors that lead to heart failure (HF). We examined the relationship between pulse wave velocity (PWV) and SDB in patients who have HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF).

Methods and results

We measured the apnoea-hypopnoea index (AHI) by polysomnography, echocardiographic parameters, and PWV in 221 HF patients. Age, blood pressure, and PWV were higher in HFpEF (ejection fraction > 50%, n = 70) patients than in HFrEF (ejection fraction < 50%, n = 151) patients. All HF patients were divided into three groups according to AHI: none-to-mild SDB group (AHI < 15 times/h, n = 77), moderate SDB group (15 < AHI < 30 times/h, n = 59), and severe SDB group (AHI > 30 times/h, n = 85). Although blood pressure and echocardiographic parameters did not differ among the three groups, PWV was significantly higher in the severe SDB group than in the none-to-mild and moderate SDB groups (P = 0.002). When the HFrEF and HFpEF patients were analysed separately, PWV was significantly higher in the severe SDB group than in the none-to-mild and moderate SDB groups in patients with HFpEF (P = 0.002), but not in those with HFrEF (P = 0.068). In the multiple regression analysis to determine PWV, the presence of severe SDB was found to be an independent predictor of high PWV in HFpEF (β = 0.234, P = 0.005), but not in HFrEF patients.

Conclusions

Severe SDB is associated with elevated arterial stiffness and may be related to the pathophysiology of HF, especially in HFpEF patients.

SUBMITTER: Suzuki S

PROVIDER: S-EPMC5933962 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objective: Sleep-disordered breathing (SDB) is a widespread disease that is often associated with heart failure (HF) with preserved ejection fraction (HFpEF). HFpEF is more frequent in women than in men, but detailed pathomechanisms remain unclear. We investigated HFpEF in women and men in a high-risk cohort with SDB monitoring. Methods and Results: Three hundred twenty-seven patients (84.4% men) undergoing elective coronary artery bypass grafting were prospectively subjected to SDB monitoring, and an apnea-hypopnea index (AHI) ≥15/h defined SDB. HF was classified according to current guidelines. HFpEF was significantly more frequent in SDB patients compared to those without SDB (28 vs. 17%, P = 0.016). This distribution was driven by an increased frequency of HFpEF in female SDB patients (48% vs. only 25% in male, P = 0.022). In accordance, female patients with SDB exhibited significantly more impaired diastolic left ventricular filling compared to men (echocardiographic E/e'). In contrast to men, in women, minimum oxygen saturation (O2min, measured by polygraphy, R 2 = 0.470, P < 0.001) and time of oxygen saturation <90% (R 2 = 0.165, P = 0.044) were significantly correlated with E/e'. Moreover, the correlation between O2min and E/e' was significantly different in women compared to men (P < 0.001). Intriguingly, this association remained independent of clinical covariates in women [age, body mass index, systolic contractile dysfunction, diabetes mellitus, and glomerular filtration rate (GFR), R 2 = 0.534, P = 0.042, multivariate regression analysis]. Since angiotensin II signaling has been mechanistically linked to HF, we measured protein expression of its cleavage enzyme ACE2 in human right atrial appendage biopsies (Western blot). Intriguingly, we found a significantly decreased ACE2 expression preferentially in women with SDB (2.66 ± 0.42 vs. 4.01 ± 2.47 in men with SDB, P = 0.005). In accordance, left ventricular mass index was significantly increased in women with SDB compared to women without SDB. Conclusion: In patients with SDB, HFpEF and diastolic dysfunction were more frequent in women compared to men. In contrast to men, the severity of SDB was associated with the degree of diastolic dysfunction in women. These insights might help to find sex-specific therapies for patients with sleep-disordered breathing and heart failure. Clinical Trial Registration: Unique identifier: NCT02877745, URL: http://www.clinicaltrials.gov.

Project description:BackgroundMicrovascular dysfunction plays an important role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link between systemic microvasculature and congestion, a central feature of the syndrome, has yet been investigated.ObjectivesThis study aimed to investigate capillary-interstitium fluid exchange in HFpEF, including lymphatic drainage and the potential osmotic forces exerted by any hypertonic tissue Na+ excess.MethodsPatients with HFpEF and healthy control subjects of similar age and sex distributions (n = 16 per group) underwent: 1) a skin biopsy for vascular immunohistochemistry, gene expression, and chemical (water, Na+, and K+) analyses; and 2) venous occlusion plethysmography to assess peripheral microvascular filtration coefficient (measuring capillary fluid extravasation) and isovolumetric pressure (above which lymphatic drainage cannot compensate for fluid extravasation).ResultsSkin biopsies in patients with HFpEF showed rarefaction of small blood and lymphatic vessels (p = 0.003 and p = 0.012, respectively); residual skin lymphatics showed a larger diameter (p = 0.007) and lower expression of lymphatic differentiation and function markers (LYVE-1 [lymphatic vessel endothelial hyaluronan receptor 1]: p < 0.05; PROX-1 [prospero homeobox protein 1]: p < 0.001) compared with control subjects. In patients with HFpEF, microvascular filtration coefficient was lower (calf: 3.30 [interquartile range (IQR): 2.33 to 3.88] l × 100 ml of tissue-1 × min-1 × mm Hg-1 vs. 4.66 [IQR: 3.70 to 6.15] μl × 100 ml of tissue-1 × min-1 × mm Hg-1; p < 0.01; forearm: 5.16 [IQR: 3.86 to 5.43] l × 100 ml of tissue-1 × min-1 × mm Hg-1 vs. 5.66 [IQR: 4.69 to 8.38] μl × 100 ml of tissue-1 × min-1 × mm Hg-1; p > 0.05), in keeping with blood vascular rarefaction and the lack of any observed hypertonic skin Na+ excess, but the lymphatic drainage was impaired (isovolumetric pressure in patients with HFpEF vs. control subjects: calf 16 ± 4 mm Hg vs. 22 ± 4 mm Hg; p < 0.005; forearm 17 ± 4 mm Hg vs. 25 ± 5 mm Hg; p < 0.001).ConclusionsPeripheral lymphatic vessels in patients with HFpEF exhibit structural and molecular alterations and cannot effectively compensate for fluid extravasation and interstitial accumulation by commensurate drainage. Reduced lymphatic reserve may represent a novel therapeutic target.