Prognostic utility of rhythmic components in 24-hour ambulatory blood pressure monitoring for the risk stratification of chronic kidney disease patients with cardiovascular co-morbidity

Background: Chronic kidney disease (CKD) represents a significant global burden. Hypertension is a modifiable risk factor for rapid progression of CKD. Methods:We extend the risk stratification by introducing the non-parametric determination of rhythmic components in 24-hour profiles of ambulatory blood pressure monitoring (ABPM) in the African American Study for Kidney Disease and Hypertension (AASK) cohort and the Chronic Renal Insufficiency Cohort (CRIC) using Cox proportional hazards models. Results: We find that rhythmic profiling of BP through JTK_Cycle analysis identifies subgroups of CRIC participants at advanced risk of cardiovascular death. CRIC participants with a history of cardiovascular disease (CVD) and absent cyclic components in their BP profile had at any time a 3.4-times higher risk of cardiovascular death than CVD patients with cyclic components present in their BP profile (HR: 3.38, 95% CI: 1.45-7.88, p=0.005). This substantially increased risk was independent of whether ABPM followed a dipping or non-dipping pattern whereby non-dipping or reverse dipping were not significantly associated with cardiovascular death in patients with prior CVD (p>0.1). In the AASK cohort, unadjusted models demonstrate a higher risk in reaching end stage renal disease among participants without rhythmic ABPM components (HR:1.80, 95% CI: 1.10-2.96); however, full adjustment abolished this association. Conclusions: This study proposes rhythmic blood pressure components as a novel biomarker to unmask excess risk among CKD patients with prior cardiovascular disease.

[1]  J. Lane,et al.  Circadian Rest–Activity Rhythms, Delirium Risk, and Progression to Dementia , 2023, Annals of neurology.

[2]  K. Kario,et al.  Blood pressure variability: methodological aspects, clinical relevance and practical indications for management - a European Society of Hypertension position paper , 2023, Journal of hypertension.

[3]  S. Redline,et al.  Toward Precision Medicine: Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension - 2021 NHLBI Workshop Report. , 2022, Hypertension.

[4]  F. Naef,et al.  Sex-dimorphic and age-dependent organization of 24 hour gene expression rhythms in human , 2022, bioRxiv.

[5]  G. Stergiou,et al.  Blood pressure and its variability: classic and novel measurement techniques , 2022, Nature Reviews Cardiology.

[6]  R. Mohandas,et al.  Circadian rhythms and renal pathophysiology , 2022, The Journal of clinical investigation.

[7]  Mohammad Sohel Rahman,et al.  Time-specific associations of wearable sensor-based cardiovascular and behavioral readouts with disease phenotypes in the outpatient setting of the Chronic Renal Insufficiency Cohort , 2022, medRxiv.

[8]  Y. Sheline,et al.  Phenome-Wide Association Study of Actigraphy in the UK Biobank , 2021, medRxiv.

[9]  T. Grosser,et al.  Nitecap: An Exploratory Circadian Analysis Web Application , 2021, Journal of biological rhythms.

[10]  P. Zee,et al.  Circadian disruption and human health. , 2021, The Journal of clinical investigation.

[11]  N. Powe,et al.  New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. , 2021, The New England journal of medicine.

[12]  R. Linhardt,et al.  Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates , 2021, bioRxiv.

[13]  G. Pucci,et al.  Matrix Metalloproteinases and Hypertension-Mediated Organ Damage: Current Insights , 2020, Integrated blood pressure control.

[14]  Mahboob Rahman,et al.  Prognostic Significance of Ambulatory BP Monitoring in CKD: A Report from the Chronic Renal Insufficiency Cohort (CRIC) Study. , 2020, Journal of the American Society of Nephrology : JASN.

[15]  Sungha Park,et al.  Ambulatory blood pressure variability and risk of cardiovascular events, all-cause mortality, and progression of kidney disease. , 2020, Journal of hypertension.

[16]  Randal S. Olson,et al.  A Pilot Characterization of the Human Chronobiome , 2017, Scientific Reports.

[17]  Anna C. Porter,et al.  Risks of Adverse Events in Advanced CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study. , 2017, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[18]  M. Smolensky,et al.  Circadian mechanisms of 24-hour blood pressure regulation and patterning. , 2017, Sleep medicine reviews.

[19]  M. Young Temporal partitioning of cardiac metabolism by the cardiomyocyte circadian clock , 2016, Experimental physiology.

[20]  Shu Liu,et al.  Smooth-muscle BMAL1 participates in blood pressure circadian rhythm regulation. , 2015, The Journal of clinical investigation.

[21]  M. Joffe,et al.  Estimating GFR among participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. , 2012, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[22]  R. D. Rudic,et al.  Matrix Metalloproteinase 2 and 9 Dysfunction Underlie Vascular Stiffness in Circadian Clock Mutant Mice , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[23]  Karl Kornacker,et al.  JTK_CYCLE: An Efficient Nonparametric Algorithm for Detecting Rhythmic Components in Genome-Scale Data Sets , 2010, Journal of biological rhythms.

[24]  G. FitzGerald,et al.  Circadian Clocks and Vascular Function , 2010, Circulation research.

[25]  J. Staessen,et al.  Night–day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension , 2009, Journal of Human Hypertension.

[26]  A. B. Reddy,et al.  A clockwork web: circadian timing in brain and periphery, in health and disease , 2003, Nature Reviews Neuroscience.

[27]  A. Go,et al.  The Chronic Renal Insufficiency Cohort (CRIC) Study: Design and Methods. , 2003, Journal of the American Society of Nephrology : JASN.

[28]  Keith C. Norris,et al.  The rationale and design of the AASK cohort study. , 2003, Journal of the American Society of Nephrology : JASN.

[29]  C. Dollery,et al.  Circadian rhythm of baroreflex reactivity and adrenergic vascular response. , 1980, Cardiovascular research.

[30]  T. Deegan,et al.  Circadian variations of plasma catecholamine, cortisol and immunoreactive insulin concentrations in supine subjects. , 1974, Clinica chimica acta; international journal of clinical chemistry.

[31]  R. Mehrotra,et al.  Cardiovascular disease in chronic kidney disease , 2012 .

[32]  B. Bagni,et al.  Circadian rhythms of atrial natriuretic peptide, renin, aldosterone, cortisol, blood pressure and heart rate in normal and hypertensive subjects. , 1990, Journal of hypertension.