Pre-Dialysis Systolic Blood Pressure-Variability Is Independently Associated with All-Cause Mortality in Incident Haemodialysis Patients

<div><p>Systolic blood pressure variability is an independent risk factor for mortality and cardiovascular events. Standard measures of blood pressure predict outcome poorly in haemodialysis patients. We investigated whether systolic blood pressure variability was associated with mortality in incident haemodialysis patients. We performed a longitudinal observational study of patients commencing haemodialysis between 2005 and 2011 in East Anglia, UK, excluding patients with cardiovascular events within 6 months of starting haemodialysis. The main exposure was variability independent of the mean (VIM) of systolic blood pressure from short-gap, pre-dialysis blood pressure readings between 3 and 6 months after commencing haemodialysis, and the outcome was all-cause mortality. Of 203 patients, 37 (18.2%) patients died during a mean follow-up of 2.0 (SD 1.3) years. The age and sex-adjusted hazard ratio (HR) for mortality was 1.09 (95% confidence interval (CI) 1.02–1.17) for a one-unit increase of VIM. This was not altered by adjustment for diabetes, prior cardiovascular disease and mean systolic blood pressure (HR 1.09, 95% CI 1.02–1.16). Patients with VIM of systolic blood pressure above the median were 2.4 (95% CI 1.17–4.74) times more likely to die during follow-up than those below the median. Results were similar for all measures of blood pressure variability and further adjustment for type of dialysis access, use of antihypertensives and absolute or variability of fluid intake did not alter these findings. Diastolic blood pressure variability showed no association with all cause mortality. Our study shows that variability of systolic blood pressure is a strong and independent predictor of all-cause mortality in incident haemodialysis patients. Further research is needed to understand the mechanism as this may form a therapeutic target or focus for management.</p></div

Figure 1

<p>Mortality for patients with high versus low variability of systolic blood pressure.</p

Hazard ratios for one unit increase in measures of systolic BP variability and other covariates from fully adjusted model.

<p>SD – standard deviation; COV – coefficient of variation; VIM – Variation independent of the mean; SBP – Systolic blood pressure.</p

Schematic of forearm blood flow protocol.

<p>ACh: Acetylcholine; SNP: Sodium Nitroprusside; L-NMMA: N^G-monomethyl-L-arginine; H: Haemodynamic measurements.</p

Baseline Demographics of CVD Patients and HV arms.

<p>Data are presented as mean (standard deviation - SD) or numbers (%). ACE-I: Angiotensin Converting Enzyme Inhibitor; ARB: Angiotensin Receptor Blocker; CVD: cardiovascular disease; EtOH: Alcohol; HV: healthy volunteer.</p

Post-hoc correlation between serum lycopene concentrations and EDV.

<p>Relationship between absolute change in serum lycopene concentrations and absolute change in endothelial dependent vasodilatation (EDV; forearm blood flow response to 15 µg/min acetylcholine measured as %change from preceding saline baseline) for all trial subjects. Absolute change in serum lycopene calculated as final visit serum lycopene minus baseline serum lycopene. Absolute change in EDV calculated as final visit EDV minus baseline EDV. r: correlation coefficient calculated using Pearson correlation analysis.</p

Post-hoc comparisons of baseline values between CVD Patients and HV arms.

<p>Data are presented as mean values (standard deviation - SD). *<i>P</i>-value is for comparison between cardiovascular disease (CVD) patients arm and healthy volunteer (HV) arm at baseline using unpaired, 2-tailed Student <i>t</i>-tests. AIx – augmentation index; DBP – diastolic blood pressure; HDL – high-density lipoprotein; hsCRP – high sensitivity C-reactive protein; LDL – low-density lipoprotein; ox-LDL – oxidised low-density lipoprotein, PWV – pulse wave velocity; SBP – systolic blood pressure.</p

Flow diagram of subjects through the study.

<p>The safety population consisted of anyone who received at least 1*Reasons for failure to enrol included not meeting inclusion criteria, an inability to attend laboratory for assessments within the appropriate timeframe, patient withdrawal, inability to lie flat for a period of time for the studies, or an inability to cannulate the brachial artery. **Quality control evaluation done by two independent parties. Reasons for non-evaluable data and consequent exclusion from final forearm blood flow (FBF) analysis (before unblinding and statistical analysis) included incomplete data sets, non-evaluable sets, and FBF procedure variation.</p

Vascular and Laboratory Assessments in CVD Patients Arm.

<p>Data are presented as mean values (standard error - SE). *<i>P</i>-value is for overall comparison in delta (day 56 - day 1) values across placebo and lycopene treated groups. AIx – augmentation index; CVD: cardiovascular disease; DBP – diastolic blood pressure; HDL – high-density lipoprotein; hsCRP – high sensitivity C-reactive protein; IL – interleukin; LDL – low-density lipoprotein; MMP-9– matrix metalloproteinase; ox-LDL – oxidised low-density lipoprotein, PWV – pulse wave velocity; SBP – systolic blood pressure; TNF – tumour necrosis factor.</p

National figures for number of general practices, total prescribing and total hospital admissions.

<p>ASTRO-PU - age, sex and temporary resident adjusted prescribing unit</p