Association of Circulating Osteoprotegerin Level with Blood Pressure Variability in Patients with Chronic Kidney Disease

Circulating osteoprotegerin (OPG) is a biomarker for cardiovascular complications that are closely related to chronic kidney disease (CKD). To investigate the association between circulating OPG level with long-term visit-to-visit blood pressure variability (BPV) in patients with pre-dialysis CKD, a total of 1855 subjects with CKD from stage 1 to pre-dialysis stage 5 from a prospective cohort were analyzed. Long-term visit-to-visit BPV was determined by average real variability (ARV), standard deviation (SD), and coefficient of variation (CoV) of systolic and diastolic blood pressure (SBP and DBP). ARV of SBP (Adjusted β coefficient 0.143, 95% confidence interval 0.021 to 0.264) was significantly associated with serum OPG level. Although SD and CoV of SBP were not significantly associated with serum OPG level in multivariate linear regression analyses, restricted cubic spline visualized the linear correlation of serum OPG level with all of ARV, SD, and CoV. The association between serum OPG level and DBP variability was not significant. Subgroup analyses revealed that the association of serum OPG with BPV is more prominent in the subjects with Charlson comorbidity index ≤3 and in the subjects without history of diabetes mellitus. In conclusion, circulating OPG level is potentially associated with long-term visit-to-visit BPV in patients with pre-dialysis CKD.

Blood Pressure Variability in Fabry Disease Patients

<b><i>Introduction:</i></b> Fabry disease is a rare metabolic, multisystemic, and X-linked lysosomal storage disorder. The involvement of the autonomic nervous system is well defined; however, data on the variability of the blood pressure (BP) and heart rate in Fabry disease are largely missing. In this study, we aimed to examine the circadian variations of BP and heart rate variability in Fabry disease patients. <b><i>Methods:</i></b> We recruited 31 consecutive adult (age &#x3e;18 years) Fabry disease patients (16 males and 15 females) who were regularly followed up in our outpatient clinic between July 2019 and March 2020. We performed ambulatory blood pressure monitoring and echocardiography in all patients. We used standard deviation (SD), coefficient of variation (CV), and average real variability as the measures of variability. We constructed 2 control groups for propensity score matching using age, sex, and eGFR parameters in the first group and adding antihypertensive drug use to the above parameters in the second group. <b><i>Results:</i></b> All BP measurements were significantly lower in the FD group compared to that of the control groups, except the nighttime systolic BP. Regarding nondipping and reverse dipping statuses, FD patients and controls were similar. We found that none of the BP variability measures were higher in FD patients. Regarding heart rate variability data, both the nighttime SD and CV were significantly lower in FD patients compared to those of the controls. <b><i>Conclusion:</i></b> A decrease in heart rate variability, rather than an increase in BP variability, might be an early marker of autonomic involvement in FD.

Effect of Heart Rate Variabilities on Outcome After Acute Intracerebral Hemorrhage: A Post Hoc Analysis of ATACH‐2

Background To explore how the clinical impact of heart rate (HR) and heart rate variabilities (HRV) during the initial 24 hours after acute intracerebral hemorrhage (ICH) contribute to worse clinical outcomes. Methods and Results In the ATACH‐2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial, the HR was recorded for every 15 minutes from baseline to 1 hour and hourly during the initial 24 hours post‐randomization. We calculated the following: mean, standard deviation, coefficient of variation, successive variation, and average real variability (ARV). Outcomes were hematoma expansion at 24 hours and unfavorable functional outcome, defined as modified Rankin Scale score 4 to 6 at 90 days. Of the 1000 subjects in ATACH‐2, 994 with available HR data were included in the analyses. Overall, 262 experienced hematoma expansion, and 362 had unfavorable outcomes. Increased mean HR was linearly associated with unfavorable outcome (per 10 bpm increase adjusted odds ratio [aOR], 1.31, 95% CI, 1.14–1.50) but not with hematoma expansion, while HR‐ARV was associated with hematoma expansion (aOR, 1.06, 95% CI, 1.01–1.12) and unfavorable outcome (aOR, 1.07, 95% CI, 1.01–1.3). Every 10‐bpm increase in mean HR increased the probability of unfavorable outcome by 4.3%, while every 1 increase in HR‐ARV increased the probability of hematoma expansion by 1.1% and unfavorable outcome by 1.3%. Conclusions Increased mean HR and HR‐ARV within the initial 24 hours were independently associated with unfavorable outcome in acute ICH. Moreover, HR‐ARV was associated with hematoma expansion at 24 hours. This may have future therapeutic implications to accommodate HR and HRV in acute ICH. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01176565.

An Analysis of Frequency of Continuous Blood Pressure Variation and Haemodynamic Responses during Haemodialysis

<b><i>Background:</i></b> Higher beat-to-beat blood pressure (BP) variation during haemodialysis (HD) has been shown to be associated with elevated cardiac damage markers and white matter ischaemic changes in the brain suggesting relevance to end-organ perfusion. We aimed to characterize individual patterns of BP variation and associated haemodynamic responses to HD. <b><i>Methods:</i></b> Fifty participants underwent continuous non-invasive haemodynamic monitoring during HD and BP variation were assessed using extrema point (EP) frequency analysis. Participants were divided into those with a greater proportion of low frequency (LF, <i>n</i> = 21) and high frequency (HF, <i>n</i> = 22) of BP variation. Clinical and haemodynamic data were compared between groups. <b><i>Results:</i></b> Median EP frequencies for mean arterial pressure (MAP) of mid-week HD sessions were 0.54 Hz (interquartile range 0.18) and correlated with dialysis vintage (<i>r</i> = 0.32, <i>p</i> = 0.039), NT pro-BNP levels (<i>r</i> = 0.32, <i>p</i> = 0.038), and average real variability (ARV) of systolic BP (<i>r</i> = 0.33, <i>p</i> = 0.029), ARV of diastolic BP (<i>r</i> = 0.46, <i>p</i> = 0.002), and ARV of MAP (<i>r</i> = 0.57, <i>p</i> &#x3c; 0.001). In the LF group, MAP positively correlated with cardiac power index (CPI) in each hour of dialysis, but not with total peripheral resistance index (TPRI). In contrast, in the HF group, MAP correlated with TPRI in each hour of dialysis but only with CPI in the first hour. <b><i>Conclusions:</i></b> EP frequency analysis of continuous BP monitoring during dialysis allows assessment of BP variation and categorization of individuals into low- or high-frequency groups, which were characterized by different haemodynamic responses to dialysis. This may assist in improved individualization of dialysis therapy.

Blood pressure variability and night-time dipping assessed by 24-hour ambulatory monitoring: Cross-sectional association with cardiac structure in adolescents

Greater blood pressure (BP) is associated with greater left ventricular mass indexed to height2.7 (LVMi2.7) in adolescents. This study examined whether greater BP variability and reduced night-time dipping are associated with cardiac remodeling in a general population of adolescents. A cross-sectional analysis was undertaken in 587 UK adolescents (mean age 17.7 years; 43.1% male). BP was measured in a research clinic and using 24-hour ambulatory monitoring. We examined associations (for both systolic and diastolic BP) of: 1) clinic and 24-hour mean BP; 2) measures of 24-hour BP variability: standard deviation weighted for day/night (SDdn), variability independent of the mean (VIM) and average real variability (ARV); and 3) night-time dipping with cardiac structures. Cardiac structures were assessed by echocardiography: 1) LVMi2.7; 2) relative wall thickness (RWT); 3) left atrial diameter indexed to height (LADi) and 4) left ventricular internal diameter in diastole (LVIDD). Higher systolic BP was associated with greater LVMi2.7. Systolic and diastolic BP were associated with greater RWT. Associations were inconsistent for LADi and LVIDD. There was evidence for associations between both greater SDdn and ARV and higher RWT (per 1 SD higher diastolic ARV, mean difference in RWT was 0.13 SDs, 95% CI 0.045 to 0.21); these associations with RWT remained after adjustment for mean BP. There was no consistent evidence of associations between night-time dipping and cardiac structure. Measurement of BP variability, even in adolescents with blood pressure in the physiologic range, might benefit risk of cardiovascular remodeling assessment.

School-based surveillance on visit-to-visit blood pressure variability and high blood pressure in children and adolescents

Background The predictive importance of visit-to-visit blood pressure variability (VVV) for high blood pressure (HBP) in a pediatric population has been largely unsettled. We aimed to evaluate it based on Health Promotion Program for Children and Adolescents (HPPCA), a school-based surveillance conducted from 2012 to 2018 in Suzhou, China. Methods A total of 330,618 participants had BP measurement in 2018 and ≥ 3 BP records during 2012–2017, were recruited from HPPCA. Absolute BP values (in mmHg) were converted into age-, sex- and height- normalized z-scores. VVV was expressed as standard deviation (SD), coefficient of variation (CV) or average real variability (ARV) of BP z-scores during 2012–2017. Logistic regression models were used to assess the associations between VVV and HBP in 2018. Results In 2018, 42,554 (12.87%) subjects were defined as HBP. VVV, except for SBP-CV and DBP-CV, was significantly higher in the HBP group than normotensives group. After adjusting for covariates including mean BP values from 2012 to 2017, SBP-SD, SBP-ARV, DBP-SD and DBP-ARV, increased the risk of HBP by 5.70 [95% confidence interval (95% CI) 5.54–5.87], 4.10 (95% CI 4.01–4.20), 4.70 (95% CI 4.50–4.90) and 3.39 (95% CI 3.28–3.50) times, respectively. Notably, SBP-SD significantly improved risk discrimination of HBP based on other risk variables (c-statistics, net reclassification index and integrated discrimination improvement significantly increased). Conclusions Higher SD or ARV of BP, was independently related with higher probability of HBP in Chinese pediatric population. SBP-SD could be potentially helpful for detecting HBP. Future researches investigating the predictive value of VVV are warrant.

Visit-to-visit variability of serum uric acid measurements and the risk of all-cause mortality in the general population

Background Evidence on longitudinal variability of serum uric acid (SUA) and risk of all-cause mortality in the general population is limited, as many prior studies focused on a single measurement of SUA. Methods A total of 53,956 participants in the Kailuan study who underwent three health examinations during 2006 to 2010 were enrolled. Variability of SUA was measured using the coefficient of variation (primary index), standard deviation, average real variability, and variability independent of the mean. Cox proportional hazard regressions were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the association of variability of SUA with subsequent risk of all-cause mortality, considering its magnitude and the direction and across different baseline SUA categories. Results Over a median follow-up of 7.04 years, 2728 participants died. The highest variability of SUA was associated with an increased risk of all-cause mortality, the HR was 1.33 (95% CI, 1.20–1.49) compared with the lowest variability. In this group, both a large fall (HR, 1.28; 95% CI, 1.14–1.44) and rise (HR, 1.18; 95% 1.05–1.32) in SUA were related to risk of all-cause mortality. These associations were similar across different baseline SUA categories. Consistent results were observed in alternative measures of SUA variability. Moreover, individuals with higher variability in SUA were more related to common risk factors than those with stable SUA. Conclusions Higher variability in SUA was independently associated with the risk of all-cause mortality irrespective of baseline SUA and direction of variability in the general population.

Fasting Glucose Variation Predicts Microvascular Risk in ACCORD and VADT

Aims The association of glycemic variability with microvascular disease complications in type 2 diabetes (T2D) has been understudied and remains unclear. We investigated this relationship using both Action to Control Cardiovascular Risk in Diabetes (ACCORD) and the Veteran Affairs Diabetes Trial (VADT). Methods In ACCORD, fasting plasma glucose (FPG) was measured 1-3 times/year for up to 84 months in 10,251 individuals. In the VADT, FPG was measured every 3 months for up to 87 months in 1,791 individuals. Variability measures included coefficient of variation (CV) and average real variability (ARV) for fasting glucose. The primary composite outcome was time to either severe nephropathy or retinopathy event and secondary outcomes included each outcome individually. To assess the association, we considered variability measures as time-dependent covariates in Cox proportional hazard models. We conducted a meta-analysis across the two trials to estimate the risk of fasting glucose variability as well as to assess the heterogenous effects of FPG variability across treatment arms. Results In both ACCORD and the VADT, CV and ARV of FPG were associated with development of future microvascular outcomes even after adjusting for other risk factors, including measures of average glycemic control (i.e., cumulative average of HbA1c). Meta-analyses of these two trials confirmed these findings and indicated FPG variation may be more harmful in those with less intensive glucose control. Conclusions This post-hoc analysis indicates that variability of FPG plays a role in, and/or is an independent and readily available marker of, development of microvascular complications in T2D.

Long term habitual vigorous physical activity is associated with lower visit-to-visit systolic blood pressure variability

Objective Our work aimed to investigate the association between vigorous physical activity and visit-to-visit systolic blood pressure variability (BPV). Methods We conducted a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a well-characterized cohort of participants randomized to intensive (&lt;120 mmHg) or standard (&lt;140 mmHg) SBP targets. We assessed whether patients with hypertension who habitually engage in vigorous physical activity would have lower visit-to-visit systolic BPV compared with those who do not engage in vigorous physical activity. Visit-to-visit systolic BPV was calculated by standard deviation (SD), average real variability (ARV), and standard deviation independent of the mean (SDIM) using measurements taken during the 1-, 2-, 3-, 6-, 9- and 12-month study visits. A medical history questionnaire assessed vigorous physical activity, which was divided into three categories according to the frequency of vigorous physical activity. Results A total of 7571 participants were eligible for analysis (34.8% female, mean age 67.9±9.3 years). During a follow-up of 1-year, vigorous physical activity could significantly reduce SD, ARV, and SDIM across increasing frequency of vigorous physical activity. There were negative linear trends between frequency of vigorous physical activity and visit-to-visit systolic BPV. Conclusions Long-term engagement in vigorous physical activity was associated with lower visit-to-visit systolic BPV.

Cross-sectional association of blood pressure variability and night-time dipping with cardiac structure in adolescents

Greater blood pressure variability (BP) and reduced night-time BP dipping are associated with cardiovascular disease independently of mean BP in adults. This study examines whether these associations are apparent in adolescents. A cross-sectional analysis was undertaken in 587 UK adolescents. We examined associations between measures of blood pressure dipping and variability (including standard deviation weighted for day/night (SDdn), average real variability (ARV) and variability independent of the mean (VIM)) with cardiac structure measures assessed by echocardiography: (1) left ventricular mass indexed to height2.7 (LVMi2.7), (2) relative wall thickness (RWT), (3) left atrial diameter indexed to height (LADi), and (4) left ventricular internal diameter in diastole (LVIDD)). Greater BP variability was associated with cardiac structures including higher RWT, which persisted after adjustment for mean BP. There was no evidence for an association between night-time dipping and cardiac structures. Measurement of BP variability might benefit cardiovascular risk assessment in adolescents.