Nocturnal Blood Pressure is Associated with Sympathetic Nervous Activity and Vascular Endothelial Function in Patients with Chronic Kidney Disease
Authors: Jeong Jinhee , Fonkoue Ida T. , Quyyumi Arshed A. , DaCosta Dana , Park Jeanie 
Published: April 2020

Background

Hypertension (HTN) is an important risk factor for adverse cardiovascular (CV) and renal outcomes in patients with chronic kidney disease (CKD). Disrupted diurnal blood pressure (BP) patterns such as elevated nocturnal BP and nocturnal nondipping are frequently observed in CKD and are better predictors of target organ damage, CV mortality and CKD progression than standard office BP. The sympathetic nervous system (SNS) is thought to contribute to diurnal hemodynamic changes and the vascular endothelium plays a fundamental role in BP regulation; however, the mechanistic roles of the SNS and endothelial function on abnormal 24‐hour BP patterns have not been established in patients with CKD. Therefore, we hypothesized that SNS overactivity and endothelial dysfunction in CKD are linked to elevated nocturnal BP and nocturnal nondipping.

Method

30 CKD participants with hypertension (55±8 yr, BMI:32±5 kg/m2) and 14 controls (CON, 52±8 yr, BMI:29±4 kg/m2) were recruited for this study. Resting office BP via an automated sphygmomanometer, 24‐hour BP via an ambulatory BP device, resting muscle sympathetic nerve activity (MSNA) via microneurography and resting vascular endothelial function via flow‐mediated dilation (FMD) were collected. The CKD group was further divided into dippers (nighttime BP average >10% lower than the daytime BP average, n= 8) and nondippers (n=22) for subgroup ANOVA analysis.

Results

Nighttime diastolic BP (p=0.024) and mean arterial BP (p=0.038) were higher and the magnitude of dipping in nighttime diastolic BP was lower (p=0.051) in CKD compared to CON despite comparable daytime BP between groups. MSNA was higher in CKD‐nondippers compared to CKD‐dippers (p=0.026) and CON (49±9 vs 41±6 and 32±20 bursts/min respectively, p=0.002). Likewise, FMD was lower in CKD‐nondippers compared to CKD‐dippers (p=0.016) and CON (2.1±2.5 vs 4.7±1.8 and 5.7±4.2 % respectively, p=0.003). In CKD patients, nighttime average, minimum systolic BP and the magnitude of dipping, but not office resting BP, were correlated with MSNA (r=0.488, p=0.01; r=0.656, p<0.001 and r=−0.374, p=0.055 respectively) and FMD (r=−0.502, p=0.005; r=−0.548, p=0.002; r=0.332, p=0.073 respectively).

Conclusion

Our novel findings demonstrate that unfavorable nocturnal BP profiles are associated with elevated SNS activity and impaired vascular endothelial function in patients with CKD. Specifically, individuals with higher nighttime BP and the nondipping pattern have higher MSNA and lower FMD. These support our hypothesis that SNA and vascular endothelial function are involved in the regulation of nighttime BP as well as the magnitude of BP lowering at nighttime in CKD patients. Further studies are warranted to determine the causal relationship of elevated nocturnal BP with SNS overactivity and endothelial dysfunction and whether therapeutic strategies targeting the SNS and endothelial function could modify nocturnal HTN and long‐term CV risk in patients with CKD.

Support or Funding Information

This work was supported by NIH K23‐098744, R01‐HL‐135183.