Blood pressure and heart rate variability are linked with hyperphosphatemia in chronic kidney disease patients

Abstract

Hyperphosphatemia is a common complication of chronic kidney disease (CKD) and is associated with cardiovascular disease (CVD), which has contributed to an increase in mortality of CKD patients. The onset of CVD often varies by time-of-day. Acute myocardial infarction or ventricular arrhythmia occurs most frequently during early morning. Blood pressure (BP) and heart rate circadian rhythms account for the diurnal variations in CVD. Preservation of normal circadian time structure from the cardiomyocyte level to the whole organ system is essential for cardiovascular health and CVD prevention. Independent risk factors, such as reduced heart rate variability (HRV) and increased BP variability (BPV), are particularly prevalent in patients with CKD. Analysis of HRV is an important clinical tool for characterizing cardiac autonomic status, and reduced HRV has prognostic significance for various types of CVD. Circadian BP rhythms are classified as extreme dipper, dipper, non-dipper or riser. It has been reported that nocturnal riser BP pattern contributes to cardiovascular threats. Previous studies have indicated that the circadian rhythm of serum phosphate in CKD patients is consistent with the general population, with the highest diurnal value observed in the early morning hours, followed by a progressive decrease to the lowest value of the day, which occurs around 11:00 am. Rhythm abnormalities have become the main therapeutic target for treating CVD in CKD patients. It has been reported that high levels of serum phosphate are associated with reduced HRV and increased BPV in CKD patients. However, the mechanisms related to interactions between hyperphosphatemia, HRV and BPV have not been fully elucidated. This review focuses on the evidence and discusses the potential mechanisms related to the effects of hyperphosphatemia on HRV and BPV.

Phosphate, the forgotten mineral in hypertension

“…A similar association has been demonstrated in the general population without CKD [19**]. Elevated levels of serum Pi was associated with a blunted decline in nocturnal BP in hypertensive patients without CKD in one study [20]. A large prospective observational study in more than 9,000 hypertensive patients in the Glasgow Blood Pressure Clinic cohort showed that elevated baseline serum Pi is associated with poor BP control over 5 years of follow-up [19**].…”

Hyperphosphatemia and Cardiovascular Disease

“…• Activation of NF-κB-AKT/ERK pathway (Li et al, 2017;Shuvy et al, 2019;Zhou et al, 2020) • Increased expression of pit-1 (Husseini et al, 2013) Atherosclerosis • Reduction of eNOS and promotes ROS in endothelial (Stevens et al, 2017;Roumeliotis et al, 2020) • Increase of FGF-23 and α-klotho deficiency (Hu and Moe, 2012;Mencke et al, 2015;Richter et al, 2016;Verkaik et al, 2018) • Endothelial cell apoptosis (Roumeliotis et al, 2020) • FGF-23 related dyslipidemia (Ellam and Chico, 2012) • Reduction of calcitriol promoting ox-LDL uptake in macrophages (Oh et al, 2009) LVH and VF • α-klotho independent binding of FGF-23 with FGFR4 (Faul et al, 2011;Grabner et al, 2015;Leifheit-Nestler et al, 2016) • Ca 2+ dependent cardiomyocyte hypertrophy (Ca 2+ -CAMK II-IP3 pathway) (Mhatre et al, 2018) • FGF-23 induced ROS and RAAS (Böckmann et al, 2019;Dong et al, 2019) pressure in hypertensive patients without CKD (Wang et al, 2018). A large prospective observational study in more than 9,000 hypertensive patients showed that elevated baseline serum phosphate is associated with poor blood pressure control over 5 years of follow-up (Patel et al, 2015).…”

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

“…On the other hand, hyperphosphatemia is associated with myocardial hypertrophy in rats [ 296 ] and humans with CKD [ 297 , 298 , 299 ]. High serum P i is also associated with increased cardiovascular morbidity and mortality in these patients [ 299 , 300 ]. Finally, hyperphosphatemia can often cause vascular calcification in CKD, and the extent and histoanatomic type of calcification predict subsequent mortality [ 301 , 302 ].…”