Systolic Blood Pressure Variability Research Articles

Abstract 4123826: Very Short-Term Blood Pressure Variability Determined by Pulse Transit Time Predicts Major Adverse Cardiac and Cerebrovascular Event in Patients with Heart Failure

Introduction: It has been reported that day-to-day blood pressure (BP) variability (BPV) is associated with major adverse cardiac and cerebrovascular events (MACCE) in patients with heart failure (HF). However, the clinical significance of beat-to-beat BPV is unclear. Methods and Results: We recruited data on patients with HF who underwent nighttime pulse transit time (PTT)-based continuous beat-to-beat BP measurement (n = 379, median age 71, male sex 53.6%). Standard deviation (SD) of PTT-based BP was considered as BPV. The primary outcome was MACCE defined as coronary artery disease, stroke, or death due to HF, acute coronary syndrome or ventricular fibrillation. Median values (25th and 75th percentiles) of SD of PTT-based systolic, diastolic, and mean BP were 4.2 (3.5, 5.3), 3.3 (2.7, 4.1), and 3.4 (2.8, 4.1) mmHg, respectively. During the follow-up period of median 1,083 days after BPV evaluation, 43 patients experienced MACCE. When patients were divided into three tertiles based on the systolic, diastolic, and mean BPV, MACCE occurred more frequently in those with higher tertiles of BPV ( Figure ). In the Cox proportional hazard analysis, systolic, diastolic, and mean BPV as continuous variables were associated with MACCE (hazard ratio, 1.191, 1.228, and 1.243, respectively). Conclusion: Beat-to-beat BPV was associated with MACCE in patients with HF.

Relationship between blood pressure variability and blood pressure phenotypes: a home blood pressure monitoring study

Objective: Home blood pressure (BP) variability (BPV) and BP phenotypes such as white-coat hypertension (WCH), white-coat uncontrolled hypertension (WUCH), masked hypertension (MH) and masked uncontrolled hypertension (MUCH) are predictors of adverse cardiovascular events. This study compared home BPV across BP phenotypes built from abnormal office BP (OBP) and home BP monitoring (HBPM) thresholds defined by three distinct societies [European Society of Hypertension (ESH): OBP ≥ 140/90 mmHg and HBPM ≥ 135/85 mmHg; American College of Cardiology/American Heart Association (ACC/AHA): OBP and HBPM ≥ 130/80 mmHg and Brazilian Society of Cardiology (BSC): OBP ≥ 140/90 mmHg and HBPM ≥ 130/80 mmHg]. Methods: This cross-sectional study evaluated 51 194 treated (37% men, age = 61 ± 15 years) and 56 100 untreated (41% men, age = 54 ± 16 years) individuals from 1045 Brazilian centers who underwent OBP and HBPM measurements. Systolic and diastolic home BPV were estimated as the: standard deviation, coefficient of variation, and the variability independent of the mean of HBPM. Results: Results of adjusted analysis showed that home BPV parameters were significantly greater in individuals with WCH/WUCH according to the BSC criteria, in those with MH/MUCH defined by the ACC/AHA criteria, and tended to be greater in individuals with either MH/MUCH or WCH/WUCH defined by the ESH criteria. Furthermore, restricted cubic spline analysis showed a U-shaped association between BPV and the difference between OBP and HBPM in treated and untreated individuals. Conclusion: Home BPV was greater in WCH/WUCH and/or MH/MUCH depending on the criteria used to define abnormal OBP and HBPM thresholds. These findings underscore the need to standardize abnormal BP criteria in clinical practice.

Patient-specific multifactorial mortality risk assessment using classification and regression tree analysis in the context of ambulatory blood pressure monitoring.

Ambulatory blood pressure monitoring is essential for understanding blood pressure patterns beyond clinical visits, aiding in risk assessment, treatment evaluation, and managing hypertension. This retrospective cohort study aimed to identify risk factors for all-cause mortality and major cardiovascular events in patients who underwent ambulatory blood pressure monitoring. Eligible participants aged 18 or older, with an estimated glomerular filtration rate (eGFR) > 60ml/min/1.73m2, who underwent ambulatory blood pressure monitoring for various reasons, were included in the study. Data were gathered through telephone interviews, electronic health records, and the national health record system. Descriptive analysis and classification and regression tree modeling were used to uncover significant risk factors related to all-cause mortality and cardiovascular events, and to assess the model's performance compared to traditional Cox survival analysis. The study included 1291 patients, primarily male (51.8%) with a mean age of 61.1 ± 15.2years. During a mean follow-up of 46.9months, 76 (5.9%) patients died of any cause, and 195 (15.1%) had a cardiovascular event. The highest survival rates were observed in patients with a diastolic blood pressure (BP) dipping percentage between -2% and 29%, nighttime systolic BP variability below 32mmHg, and age below 72. Conversely, smokers with a diastolic BP dipping percentage below -10% showed the lowest survival rates. The best cardiovascular outcomes were observed in patients with diastolic BP dipping above -11%, nighttime mean systolic BP < 144mmHg, no statin use, normotensive status, and daytime mean heart rate ≥ 60bpm. Conversely, the worst outcomes were seen in patients with diastolic BP dipping below -11% and a morning surge ≥ 14mmHg. In all-cause mortality and cardiovascular event analysis, the combined model demonstrated excellent calibration and predictive power, like the classification and regression tree model and traditional analysis. These findings highlight the potential of a combined model for assessing mortality and cardiovascular event risk in patients who have undergone ambulatory blood pressure monitoring.

Blood pressure variability associated with falls in nursing home residents.

High variations in serially measured blood pressures (BPs) portend a variety of adverse clinical events including dementia, cardiovascular sequelae and frailty. In this study, systolic blood pressure variability (BPV) was examined for its association with fall frequency and time to next fall among older adults living in nursing homes. BP values and falls over time were extracted from medical records of nursing home residents aged ≥65 years over a 10-month period. BPV was measured as the standard deviation of 17 to 20 systolic values, and its correlation with falls and time to next fall were evaluated according to quartile values. One hundred patient charts were analyzed with nearly 2000 BP data points. All older adults had at least one fall incident. Higher BPV was related to more falls, shorter time between the first and second fall and fewer average days between falls. Subgroups of high BP and different diagnoses affected this association between BPV and falls. People who fall often show a high variability in BP; as the number of falls increases, the BPV also increases. This study suggests that BPV may be marker for patients who might benefit from more aggressive application of fall reduction strategies. Geriatr Gerontol Int 2024; ••: ••-••.

Abnormal Autonomic Nervous Regulation in Patients with Globus Pharyngeus.

Globus pharyngeus could be described as a benign sensation of lump or foreign object in the throat. The etiology of the globus as a solitary syndrome is still unknown, but it is proposed that stress could have an important role in symptom emergence. To evaluate the autonomic nervous regulation in patients with globus compared to healthy controls in reaction to stress. Patients included in the study were diagnosed based on ROME IV criteria for Disorders of Gut Brain Interaction. Besides globus, the patients did not suffer any other substantial medical condition. As a control group, measurement of healthy volunteers was performed. Both groups underwent the same stress protocol assessment in the same laboratory settings. The protocol consist of two types of stressors: cold pressor test and mental arithmetic test to test different types of autonomic reactivity. Baroreflex sensitivity was significantly decreased in patients compared to controls in all phases of the protocol. Low-frequency band of systolic blood pressure variability was significantly increasedduring both stress phases in patients compared to controls. High-frequency band of heart rate variability was significantly decreased in patients compared to controls during the both of the stress phases. The results of this study shows discrete abnormalities in complex autonomic reflex control which are predominantly manifested in response to stressful stimuli indicating altered neurocardiac regulation as a reaction to stress associated with globus pharynegus. This fact could have an important role in the personalized management of globus patients such as biofeedback.

Cardiorespiratory and circadian clock markers in intensive care unit patients.

Biological synchronized rhythmicity is a critical physiological process. The lack of synchronized rhythms, mainly those showing a circadian basis, like sleep, the heart rate (HR) and arterial blood pressure (BP), often leads to several organic challenges, usually associated with adverse outcomes. The aim of the study was to investigate whether the intensive care unit (ICU) environment favors clock genes and cardiorespiratory changes. A total of 22 critically ill patients (16 males; 72.73%) with a mean age of 60.82 ±20.07 years and well-established cardiovascular conditions were selected from ICU. Blood samples were obtained, and total RNA was isolated and reverse-transcribed into complementary DNA (cDNA). A quantitative polymerase chain reaction (qPCR) was performed to assess the target gene expression levels. The urinary concentration levels of melatonin (MEL) were assessed. The heart rate, BP (systolic - SBP, diastolic - DBP and mean - MBP) and the oxygen saturation (SpO2) levels were assessed as continuous variables. The urinary MEL and Brain and muscle Arnt-like protein-1 (BMAL1) levels were shown to have a non-linear relationship with HR (coefficient (coef): 2.318, p = 0.032; coef: 2.722, p = 0.006, respectively) and SBP (coef: 1.000, p = 0.008; coef: 2.000, p = 0.037, respectively), with an explanatory power of up to 50.3% and 39.7% of the HR and SBP variability, respectively. Melatonin, but not BMAL1, was also shown to have a non-linear relationship with MBP (coef: 1.000, p = 0.007), with an explanatory power of up to 31.3% regarding the MBP variability. The HR and SBP oscillatory dynamics was shown to be related to changes in the genetic expression of BMAL1 and the urinary MEL concentrations. To a lower degree, MEL also impacted the variation of MBP. Our results suggest that not only are circadian functional matrices crucial for the dynamics of vital parameters in critically ill patients, but also that routinely assessed cardiovascular parameters like HR and BP may constitute important markers for the circadian timing system function. These parameters are easy to assess and have a relevant prognostic value regarding recovery outcomes, as well as the morbidity and mortality rates in ICU.

Acute effects of bolus water intake on post-exercise orthostatic hypotension and cardiovascular hemodynamics.

Water intake is known to be effective in preventing orthostatic hypotension (OH). However, it is unknown whether water intake would be effective in acutely preventing exercise-induced OH. Fourteen adults (men/women: 7/7, age: 20 ± 8years) were recruited. Each subject underwent two protocols with and without 500ml water intake using a randomized crossover design (Water vs. Control). Participants underwent 30min of cycle ergometry at the 60-70% predicted VO2 max. OH and hemodynamics were assessed before and after exercise, and immediately (Water 1) and 20min (Water 2) after the water intake. OH was evaluated with a 1-min standing test as the criteria for systolic blood pressure (SBP) < 90mmHg. A cross-spectral analysis for RR and SBP variability was used to evaluate the cardiac autonomic activity and baroreflex sensitivity. In both protocols, the incidence of OH increased after the exercise. The incidence of OH was lower in Water than in Control at Water 1 (OR: 0.093, 95% CI: 0.015-0.591). Heart rate was lower and SBP was higher in Water than in Control at Water 1 and 2 (P < 0.05). High-frequency power of RR variability and transfer function gains in Water were normalized and higher than in Control at Water 1 and 2 (P < 0.05). The ratio of low- to high-frequency power of RR variability in Water was normalized and lower in Water than in Control at Water 1 (P < 0.05). Our findings indicate that water intake may prevent acute exercise-induced OH, accompanied by normalized cardiac autonomic activity and baroreflex sensitivity.

Beat-to-beat analysis of hemodynamic response to mental and psychological stress in sickle cell anemia

Abstract Vaso-occlusive crises are a hallmark symptom of sickle cell disease. Physical stressors can trigger decreased microvascular blood flow and increase the risk for vaso-occlusive crises. However, the effect of mental and psychological stressors on vascular physiology in sickle cell disease is not well-established. We hereby examined fluctuations in continuous blood pressure to evaluate hemodynamic changes in sickle cell disease patients during mental and psychological stress. Thirteen sickle cell disease subjects from the Children’s Hospital Los Angeles and 11 healthy volunteers were recruited. Continuous blood pressure was recorded during two mental tasks and one psychological stress task. Systolic beat-to-beat blood pressure variability measurements were calculated for each subject. Three very short-term blood pressure variability metrics served as outcome measures: standard deviation, coefficient of variation, and average real variability. Peripheral augmentation index was calculated from arterial waveforms. Linear mixed effects models evaluated associations between patient factors and outcome measures. Sickle cell disease patients exhibit increased systolic blood pressure variability in response to psychological stress. All subjects exhibited a decrease in systolic blood pressure variability in response to mental stress tasks. During mental stress, both groups displayed increased augmentation index, reflective of stress-induced vasoconstriction, while psychological stress in sickle cell disease patients led to both decreased mean arterial pressure and increased augementation index, suggestive of uncompensated vasoconstriction. These findings emphasize the impact of mental and psychological stressors on vascular function in sickle cell disease and the potential for monitoring physiological signals to predict vaso-occlusive crisis events.

Design and implementation of digital home blood pressure monitoring based on Bluetooth and WeChat App in the FAIR-Pilot study

Abstract Background Home blood pressure monitoring (HBPM) could be an alternative way to office blood pressure and ambulatory blood pressure monitoring for hypertensive patient management. However, the measurement protocol of HBPM still requires standardization, which may be improved by digital technology. Purpose To investigate the use of digital HBPM management in hypertensive patients and its application in clinical practice. Methods Fractional Flow Reserve to Determine the Appropriateness of Percutaneous Renal Artery Intervention in Atherosclerosis Renal Hypertension Patients (FAIR)-pilot study is a multicenter pilot randomized controlled trial exploring the application of fractional flow reserve (FFR) to guide the renal artery stenting in patients with renovascular hypertension. After randomization and FFR measurement, participants were divided into stenting with FFR≥ 0.8 (Stent group), no stent implantation with FFR≥ 0.8 (No stent group), and stenting with FFR＜ 0.8 (Controlled group). Participants of the FAIR-pilot study enrolled from February 1st, 2023 to February 25th, 2024 were included. A validated Bluetooth blood pressure monitor was given to every participant at the time of enrollment. Participants were taught to undertake standardized HBP and were advised to take morning and night HBPs every day. HBPM data were automatically uploaded to a WeChat App developed by FAIR investigators and could be reviewed by both participants and investigators. Twice-daily blood pressure reports were automatically generated and sent to investigators for participant compliance monitoring and reminding (Figure 1). HBPM data and blood pressure variability were analyzed. Results A total of 93 participants with 58 males (62.4%) and a mean age of 59.97 ± 16.18 years, including 26,802 HBP readings were analyzed. The average numbers of daily HBP measurement were similar between three groups and were all less than twice a day. Systolic HBP decreased from 143.11 ± 14.91 to 133.01 ± 13.01mmHg after the procedure in the Controlled group, which was more than the other two groups (140.51 ± 13.38 to 138.53 ± 17.30 mmHg and 136.20 ± 15.67 to 130.84 ± 11.04 mmHg). During the follow-up after the procedure, the HBP variability (BPV) of overall participants was 13.78 ± 4.87 and 5.46 ± 3.14 for systolic and diastolic BP, respectively. The systolic BPV of No stent group was higher than the other two groups (No stent vs. Stent vs. Controlled: 33.00 ± 9.49 vs. 8.34 ± 2.86 vs. 9.12 ± 2.71, P=0.125), however without statistical significance. Similar was found for morning and night systolic BPVs. (Table 1). Conclusion Digital HBPM management via novel information technology is feasible in the hypertension field and could be a helpful tool in clinical practice.

Comparative insights into type non-A non-B vs type B acute aortic syndromes and their blood pressure management: a monocentric, retrospective, 11-year study

Abstract Background Acute aortic syndromes (AAS) are classified either as type A, if the ascending aorta is involved, or as type B, if only the descending aorta is; AAS affecting the aortic arch, alone or in combination with the descending aorta, have recently been classified as type non-A-non-B (NANB). Few and discordant data are available about the differences between type B and type NANB AAS, especially in terms of presentation, management and prognosis. Little evidence also exists about the effects of blood pressure (BP) management, peaks and variability on in-hospital outcomes in such context. In particular, the largest international AAS registry suggests a comparable course and prognosis, while a recent meta-analysis indicates a poorer clinical outcome with higher rate of complications, need of invasive treatment and mortality in the case of type NANB AAS. Methods We conducted a monocentric, observational, analytical, retrospective registry study including all patients ≥ 18 years old admitted to our tertiary referral hospital with a diagnosis of type B or type NANB AAS from January 2011 to December 2021. Epidemiological, clinical, operative and outcome data were analyzed by comparing type B and type NANB AAS patients. We also focused on systolic and diastolic BP, in terms of both peak values as well as BP variability (BPV); BPV was defined as the difference between the peak and the through value on a certain day. Blood pressure variables were analyzed in relationship with mortality and the failure of an initial conservative management. Results 274 type B and 44 type NANB AAS patients were enrolled. The only significant differences between the two groups were a higher rate of pre-operative complications in type NANB patients (p=0.002) resulting in a higher rate of invasive management (p=0.005), particularly as failure of an initial conservative strategy (p=0.018). However, comparable rates of post-operative complications and in-hospital mortality (overall 7%) were observed. In the overall population, lower limb ischemia, ST segment depression, and post-operative visceral ischemia were associated with higher in-hospital mortality. Peri-aortic effusion was independently associated with failure of conservative management, whereas diagnosis of intramural hematoma (as opposed to other subtypes of AAS) appeared to be protective. Among all BP variables (including anti-hypertensive treatment intensity and daily systolic or diastolic BP peaks and variability), only peak systolic BP on day 5 was found to be non-independently associated with a higher risk of in-hospital mortality and failure of an initially conservative strategy. Conclusions In our study type NANB AAS were more often complicated and treated invasively than type B AAS, while having the same rates of post-operative complications and overall mortality. BP peaks had only a minor effect on outcomes, while BPV and BP management intensity did not have any significant impact.OutcomesBlood Pressure

Continuous Blood Pressure Indices During the First 72 Hours and Functional Outcome in Patients with Spontaneous Intracerebral Hemorrhage.

Management of intracerebral hemorrhage (ICH) is challenged by limited therapeutic options and a complex relationship between blood pressure (BP) dynamics, especially BP variability (BPV) and ICH outcome. In an exploratory analysis of prospectively collected data on consecutive patients with nontraumatic ICH between 2015 and 2020, continuous BP accessed via an arterial line extracted from the Intellispace Critical Care and Anesthesia information system (Philips Healthcare) was analyzed over the first 72 h post admission. Arterial lines were used as part of standard clinical practice in the intensive care, ensuring high fidelity and real-time data essential for acute care settings. BPV was assessed through successive variation (SV), standard deviation (SD), and coefficient of variation using all available BP measurements. Multivariate regression models were applied to evaluate the association between BPV indices and functional outcome at 3 months. Among 261 patients (mean age 69.6 ± 15.2 years, 47.9% female, median National Institutes of Health Stroke Scale [NIHSS] score 6 [interquartile range 2-12]) analyzed, lower systolic BP upon admission (< 140 mm Hg) and lower systolic BPV were significantly associated with favorable outcome, whereas higher diastolic BPV correlated with improved outcomes. In the multivariate analysis, diastolic BPV (SD, SV) within the first 72 h post admission emerged as an independent predictor of good functional outcome (modified Rankin Scale score < 3; odds ratio 1.123, 95% confidence interval CI 1.008-1.184, p = 0.035), whereas systolic BPV (SD) showed a negative association. Patients with better outcomes also exhibited distinct clinical characteristics, including younger age, lower median NIHSS scores, and less prevalence of anticoagulation therapy upon admission. This study shows the prognostic value of BPV in the acute phase of ICH. Lower systolic BPV (SD) and higher diastolic BPV (SD, SV) were associated with better functional outcomes, challenging traditional BP management strategies. These findings might help to tailor a personalized BP management in ICH.

20-HETE, Blood Pressure, and Vascular Stiffness in Young Adults.

Cytochrome-P450 eicosanoids from arachidonic acid, including vasodilator epoxyeicosatrienoic acids (EETs) and the vasoconstrictor 20-HETE, are important in regulating blood pressure, vascular tone, and cardiac and renal function. This study examined plasma 20-HETE and EETs in relation to blood pressure and vascular stiffness in a cohort of 1054 community-dwelling young adults from the Raine Study at 27 years. Plasma 20-HETE, EETs, and their hydroxylated products were measured by liquid chromatography-tandem mass spectrometry. Pulse wave velocity and aortic distensibility were measured to assess vascular stiffness. Sex differences were assessed using univariate analysis. Multiple regression models assessed the relationship between 20-HETE and systolic blood pressure (SBP) and measures of vascular stiffness. The regression model for SBP showed a positive relationship with plasma 20-HETE (β, 0.092; P<0.0001), after adjusting for sex (P<0.0001), body mass index (P<0.0001), (ln)triglycerides (P<0.0001), and (ln)HOMA-IR (P=0.015), and accounted for 29% of the variance in SBP. 20-HETE was positively related to pulse wave velocity (β, 0.059; P=0.021); after adjusting for sex (P<0.0001), SBP (P<0.0001), (ln)triglycerides (P=0.014), (ln)HOMA-IR (P=0.0001), (ln)high-sensitivity C-reactive protein (P=0.005), and age (P=0.002), the model accounted for 34% of the variance in pulse wave velocity. 20-HETE was inversely associated with aortic distensibility (β, -0.051; P=0.029), independent of sex (P<0.0001), SBP (P<0.0001), and (ln)HOMA-IR (P<0.0001); the model accounted for 25% of the variance in aortic distensibility. Plasma EETs were not significant predictors of SBP or vascular stiffness. In young adults, 20-HETE may play a fundamental role in regulating blood pressure and vascular stiffness independent of numerous cardiometabolic risk factors and cytochrome 450-derived EETs. URL: https://www.anzctr.org.au; Unique identifier: CTRN12617001599369.

Short-Term and Mid-Term Blood Pressure Variability and Long-Term Mortality

Until recently, a focus has been made on exploring the influence of average blood pressure on risk of mortality. We go beyond average blood pressure to also investigate mortality risk with respect to variation in blood pressure over two timescales – short-term variation among multiple measures at one visit, and medium-term variation between the measures at two visits several months apart. We present an application of Bayesian hierarchical modeling to the problem of estimating the effect of blood pressure (BP) variability on all-cause and cardiovascular (CV) mortality. We use data from the Third National Health and Nutrition Examination Survey linked with up to 27 years of mortality follow-up. We find that medium-term systolic BP variability had a very significant predictive value for CV and all-cause mortality, around one-third as large as the well-established impact of mean systolic BP. Medium-term diastolic variability had an additional, though smaller, predictive effect. Short-term variability, on the other hand, had little or no measurable predictive value. The medium-term variability effect persisted when controlling for Framingham risk score.

Cardiovascular handgrip responses during treadmill exercise: randomized pilot trial.

The isometric exercise performed using the handgrip (HG) acutely promotes elevation of systolic blood pressure (SBP) and diastolic blood pressure (DBP), and in a non-consensual manner among articles elevation or maintenance of heart rate (HR). Currently, although there is a vast literature on the hemodynamic effects of interval training and isometric exercise with HG alone, there is still no consistent evidence of such adjustments occurring in the association between the two. Therefore, the objective of this study was to describe the acute hemodynamic responses found only during interval training and when combined with isometric contraction with HG. This is a pilot study of a crossover clinical trial. Seven male volunteers, aged 24±3.9 years, underwent three protocols on an ergometric treadmill, with a 3-minute warm-up at 30% of heart rate reserve (HRR), four sprints 2 minutes at 50% HRR and active intervals at the same speed as the warm-up. Randomization was carried out in a simple random manner. The protocols were classified according to the use of HG during sprints, as follows: PI = without HG; PII = HG 30% of handgrip strength (HGS) and PIII = 60% of HGS). Variations (Δ) in HR, double product (DP), SBP and DBP were evaluated. The presence of HG did not change HR behavior, but it increased DP (PI: 10,472±2,539 vs. PII: 12,217±1,933 vs. PIII: 13,369±3,089) through SBP, which in PI had a plateau behavior of 15±22.2 mmHg, while PII varied with an average of 41±12.2 mmHg and PIII 47±11.1 mmHg, in the 4th sprint. DBP fell in PI with 12±13.2 mmHg, while PII and PIII showed an drop of 0±19.6 and 6±13.0 mmHg in the last sprint, respectively. The use of HG during interval training directly modulates hemodynamic variables, promoting an increase in SBP elevation, attenuation of the drop in DBP and an increase in DP, without an increase in HR. RBR-78fhyrf. Available in https://ensaiosclinicos.gov.br/rg/RBR-78fhyrf.

Speeding up interval estimation for R2-based mediation effect of high-dimensional mediators via cross-fitting.

Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed iterative Sure Independence Screening (iSIS) in two subsamples to exclude the non-mediators, followed by ordinary least squares regressions for the variance estimation. We then constructed confidence intervals based on the newly derived closed-form asymptotic distribution of the R2 measure. Extensive simulation studies demonstrated that this proposed procedure is much more computationally efficient than the resampling-based method, with comparable coverage probability. Furthermore, when applied to the Framingham Heart Study, the proposed method replicated the established finding of gene expression mediating age-related variation in systolic blood pressure and identified the role of gene expression profiles in the relationship between sex and high-density lipoprotein cholesterol level. The proposed estimation procedure is implemented in R package CFR2M.

Systolic blood pressure variability in late-life predicts cognitive trajectory and risk of Alzheimer's disease.

The relationship of systolic blood pressure variability (SBPV) with Alzheimer's disease (AD) remains controversial. We aimed to explore the roles of SBPV in predicting AD incidence and to test the pathways that mediated the relationship of SBPV with cognitive functions. Longitudinal data across 96 months (T0 to T4) were derived from the Alzheimer's disease Neuroimaging Initiative cohort. SBPV for each participant was calculated based on the four measurements of SBP across 24 months (T0 to T3). At T3, logistic regression models were used to test the SBPV difference between 86 new-onset AD and 743 controls. Linear regression models were used to test the associations of SBPV with cognition and AD imaging endophenotypes for 743 non-demented participants (median age = 77.0, female = 42%). Causal mediation analyses were conducted to explore the effects of imaging endophenotypes in mediating the relationships of SBPV with cognitive function. Finally, Cox proportional hazard model was utilized to explore the association of SBPV with incident risk of AD (T3 to T4, mean follow-up = 3.5 years). Participants with new-onset AD at T3 had significantly higher SBPV compared to their controls (p = 0.018). Higher SBPV was associated with lower scores of cognitive function (p = 0.005 for general cognition, p = 0.029 for memory, and p = 0.016 for executive function), higher cerebral burden of amyloid deposition by AV45 PET (p = 0.044), lower brain metabolism by FDG PET (p = 0.052), and higher burden of white matter hyperintensities (WMH) (p = 0.012). Amyloid pathology, brain metabolism, and WMH partially (ranging from 17.44% to 36.10%) mediated the associations of SBPV with cognition. Higher SBPV was significantly associated with elevated risk of developing AD (hazard ratio = 1.29, 95% confidence interval = 1.07 to 1.57, p = 0.008). These findings supported that maintaining stable SBP in late life helped lower the risk of AD, partially by modulating amyloid pathology, cerebral metabolism, and cerebrovascular health.

Association of systolic blood pressure variability with cognitive decline in type 2 diabetes: A post hoc analysis of a randomized clinical trial.

We aimed to explore the association between visit-to-visit systolic blood pressure variability (BPV) and cognitive function in individuals with type 2 diabetes. We performed a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORD-MIND) substudy. A total of 2867 diabetes patients with ≥3 BP measurements between the 4- and 20-month visits were included. Visit-to-visit systolic BPV was calculated. Cognitive decline was defined as a Mini-Mental State Exam (MMSE), Digit Symbol Substitution Test (DSST), or Rey Auditory Verbal Learning Test (RAVLT) score greater than 1 standard deviation (SD) below the baseline mean, or a Stroop test score more than 1 SD above the baseline mean. The associations of systolic BPV with risks of cognitive decline were examined using Cox proportional hazards models, and with changes in brain magnetic resonance imaging parameters were evaluated using mixed models. The risk of cognitive decline defined by the DSST score (but not by other scores) increased significantly with systolic BPV quartiles (p for trend = 0.008), and there was a 55% increased risk for BPV quartile 4 versus quartile 1 (hazard ratio = 1.55, 95% confidence interval 1.10-2.19). Furthermore, a positive correlation was observed between systolic BPV and change in white matter lesion volume (β = 0.07, 95% CI 0.01-0.13). A greater visit-to-visit systolic BPV was significantly associated with an increased risk of cognitive decline measured by DSST and an increase in white matter lesion volume in patients with type 2 diabetes.

Home Blood Pressure Variability Risk Prediction Score for Cardiovascular Disease Using Data From the J-HOP Study.

Home blood pressure (BP) is more closely associated with cardiovascular event risk than office BP, but cardiovascular risk prediction based on home BP variability is lacking. This study developed a simple cardiovascular event prediction score, including home BP variability data, from the J-HOP study (Japan Morning Surge-Home Blood Pressure). The J-HOP study extended follow-up from December 2017 to May 2018 generated the study data set (4231 patients). Cardiovascular events included fatal/nonfatal stroke (n=94), coronary heart disease (n=124), heart failure (n=42), and aortic dissection (n=8). Cox proportional hazards models were used to predict overall cardiovascular risk. Potential covariates included age, sex, body mass index, smoking, history of diabetes, statin use, history of cardiovascular disease, total cholesterol:high-density lipoprotein cholesterol ratio, office systolic BP (SBP), mean of morning-evening average (MEave), home SBP, and average real variability of MEave home SBP. A risk score and models were constructed, and model performance was assessed. Model performance was best when average real variability of MEave SBP was included (C statistic, 0.760). The risk score assigns points for age (5-year bands), sex, cardiovascular disease history, high-density lipoprotein cholesterol, mean MEave home SBP, and average real variability of MEave home SBP. Estimated 10-year cardiovascular risk ranged from ≤0.6% (score ≤0) to >32% (score ≥26). Calibration 2 statistics values for the model (2.66) and risk score (5.29) indicated excellent goodness of fit. This simple cardiovascular disease prediction algorithm, including day-by-day home BP variability, could be used as part of a home BP-centered approach to hypertension management in clinical practice.

The Effect of Fludrocortisone on Ambulatory Blood Pressure Markers of Falls Risk Amongst Older People with Falls

Abstract Background Fludrocortisone is frequently used to raise blood pressure in older patients with falls due to hypotension, yet evidence to support its use is limited. The aim of this study was to assess changes in Ambulatory Blood Pressure Monitors (ABPM) markers of future falls risk seen after commencing/increasing Fludrocortisone in older people with falls due to orthostatic hypotension (OH) or vasovagal syncope. Methods A cohort of older patients (≥65 years) attending a tertiary-referral falls &amp; syncope unit and prescribed Fludrocortisone were included. ABPM at index visit and follow-up (after commencing/increasing Fludrocortisone) were analysed, with specific focus on markers of future falls risk: overall Systolic Blood Pressure (sBP), minimum sBP, sBP variability &amp; ‘dips’ in systolic sBP &amp;lt;100 mm Hg. These variables were compared pre and post Fludrocortisone using paired t-tests. Results Twenty-three patients (median age 74 years (SD 6.05), 3/4 with OH) were followed for median 4.5 (SD 6.53) months. Two-thirds were commenced on Fludrocortisone, with the dose increased in the rest. Patients commencing Fludrocortisone had a significant increase in overall sBP from 110.13mmHg (95% CI 104.26 – 116.00) to 127.93mmHg (95% CI 120.00 – 135.87) (p&amp;lt;0.001) at follow-up, and a significant increase in minimum sBP from 82.2mmHg (95% CI 76.25 – 88.15) to 99.87mmHg (95% CI 91.47 – 108.26) (p=0.001). There was also a significant reduction in the number of SBP ‘dips’ after commencing Fludrocortisone (9.6 pre to 2.67 post, (95% CI 0.08 – 5.25), p=0.004)), and after commencing/increasing Fludrocortisone dose (8.09 pre to 2.74 post (95% CI 0.62 – 4.85) (p=0.012)). Conclusion This study provides clinical data on the effectiveness of Fludrocortisone in older patients with falls due to hypotension, demonstrating significantly improved markers of future falls risk. Overall sBP increased significantly by 16% and minimum sBP increased by over 20% after starting Fludrocortisone. The number of SBP ‘dips’ also significantly reduced, by over 70% in those who commenced Fludrocortisone.

Mathematical Modelling Approach for Administration of Palatable Diet to Quantify Blood Glucose Level – A Reference to Systolic Blood Pressure

The study concerns the Mathematical analysis of some variations that arise in systolic blood pressure (SBP) for different human age groups due to endocrine disorders (diabetes). An attempt has been made to improve the blood glucose levels (both pre-prandial and post prandial) associated with SBP by the suitable administration of palatable diet. Red portions (Protein and Fat) and Black Portions (Carbohydrates containing sugar and starch) have been considered with the assumption of “weight” of an individual as constant. A Mathematical model has been developed by using coupled nonlinear ordinary differential equations to study the behaviour of blood glucose levels. These equations involve the terms as, the change in glucose and the change in insulin with respect to time, the food intake sensitivity constants and the step function which can provide the quantification of normal blood glucose levels. The effectiveness in the variation of systolic blood pressure is analysed for various age groups. The response of men and women aged 25 years and above and the case of juvenile is studied using multiple linear regression model. The assumption that the weight of an individual as constant is confirmed by ANOVA for the determination of blood-Glucose levels. The palatable diet composed of Protein (P), Fat (F) and Carbohydrate (C) as PFC model is simulated with Joselin’s Principle.