Higher Blood Pressure Variability Research Articles

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; ••: ••-••.

Postpartum Blood Pressure Variability and Heart Rate Variability in Preeclampsia.

Preeclampsia is associated with autonomic dysregulation during pregnancy; however, less is known about autonomic function in the first week postpartum after preeclampsia. We retrospectively analyzed data from a prospective cohort of women with and without preeclampsia. Continuous blood pressure and heart rate were measured with finger plethysmography within 7 days postpartum. Frequency-domain blood pressure and heart rate variability (HRV) were calculated using spectral analysis. Time-domain HRV was calculated as the root mean square of successive RR interval differences. We compared results between those with and without preeclampsia, as well as between those with new-onset preeclampsia, chronic hypertension with superimposed preeclampsia, and normotensive participants. A total of 70 postpartum women were enrolled: 20 normotensive, 29 new-onset preeclampsia, and 21 superimposed preeclampsia. Both low- and high-frequency blood pressure variabilities were higher in those with preeclampsia compared with controls (P=0.04 and P=0.02, respectively). This difference was driven by those with new-onset preeclampsia. The preeclampsia group had lower high-frequency HRV (P<0.005), a higher low-/high-frequency ratio of HRV (P<0.005), and lower time-domain HRV (P=0.01); this difference was seen in those with and without chronic hypertension. Postpartum patients with preeclampsia with and without chronic hypertension had lower HRV compared with normotensive postpartum controls. Higher blood pressure variability was observed only in those with nonsuperimposed preeclampsia, suggesting that the autonomic profile of preeclampsia may differ in patients with chronic hypertension.

Blood pressure variability in elderly and senior hypertensive patients

Background. In recent years the deterioration of the demographic situation has been noted in most countries of the world that is due to the steady increase in population of arterial hypertension and the aging of the population. According to the statistical forecast of the UN by 2025, the number of people over 60 will exceed 1 billion which is 15% of the entire global population. In Ukraine, according to epidemiological studies, the prevalence of hypertension among circulatory system diseases in adults (18 years and older) is 46.8% and almost half of patients with circulatory system diseases have elevated blood pressure. In patients aged 65 years and older, the prevalence of hypertension varies in the range of 53-72%. It has long been proven that the risk of cardiovascular and cerebrovascular complications in hypertensive patients depends not only on the absolute blood pressure level but also on fluctuations in blood pressure over different periods that is blood pressure variability. Blood pressure is not a static parameter but rather undergoes continuous fluctuations over time due to the interaction between environmental factors and behaviour on the one hand and the internal regulatory mechanisms of the cardiovascular system on the other hand. Elevated blood pressure may indicate cardiovascular dysregulation and itself may be a cardiovascular risk factor associated with increased all-cause mortality and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease and incidence of dementia. Aim. The study aimed to improve the system of prevention and diagnosis of elderly and senior hypertensive patients at the ambulatory-polyclinic stage due to the study of the contribution of blood pressure variability. Materials and methods. The group of examinees was formed taking into account 27 elderly and senile hypertensive patients including those combined with coronary artery disease. For this purpose, ambulatory blood pressure monitoring was used. Results. Systolic blood pressure variability (SD) in hypertensive patients was higher than in the control group (p&lt;0.001). So, during the study, SD was 17.9±7.1 mm Hg. while in the control group 12.1±2.6 mm Hg. The frequency of high blood pressure variability detection in elderly and senile hypertensive patients was 51.9% (n=14). High blood pressure variability compared to low blood pressure variability and control was associated with a more pronounced systolic blood pressure variability (during the active monitoring period), and it was equalled 23.7±5.2 mm Hg compared to 14.8±6.5 mm Hg (p&lt;0.001) and 12.1±2.6 mm Hg. (p&lt;0.001). In elderly and senile hypertensive patients with high and low blood pressure variability, the non-dipper group prevailed over the dipper group in the structure of daily blood pressure rhythm (71.4% vs. 28.6% and 84.6% vs. 15.4% respectively). According to the ambulatory blood pressure monitoring data high blood pressure variability group compared to low blood pressure variability and controls was characterised by higher average values of the number of blood pressure indicators. In the group of high blood pressure variability patients, the average daily systolic blood pressure exceeded the control value by 10% (р&lt;0.05). The daily index of systolic blood pressure in the group of high blood pressure variability patients was 111% higher than in patients with low blood pressure variability (p&lt;0.05). The daily index of diastolic blood pressure in the group of high blood pressure variability patients was 140% higher than in patients with low blood pressure variability (p&lt;0.05). The daily index of average blood pressure in the group of high blood pressure variability patients was 191% higher than in patients with low blood pressure variability (p&lt;0.01). Conclusions. 1. High blood pressure variability has occurred in 16 out of 27 (51.9%) hypertensive elderly and senile patients. 2. The non-dipper group has predominated in the structure of blood pressure diurnal rhythm in elderly and senile hypertensive patients with high and low blood pressure variability patients. _________________________________________________________________________________________ Keywords: arterial hypertension; essential hypertension; blood pressure variability; high blood pressure variability; low blood pressure variability; elderly and senile hypertensive patients

Abstract P345: Long-Term Blood Pressure Variability and Physical Performance Measures in Community-Dwelling Older Adults

High degrees of long-term, visit-to-visit blood pressure variability (BPV) independently predict increased risks of cardiovascular disease, cognitive decline, and frailty in older adults. Measures of physical performance such as gait speed and grip strength can predict loss of independence and mortality in older adults, but are not routinely measured in practice. Shared pathways of underlying physiologic deterioration may exist between high BPV and progressive loss of gait speed and grip strength. We examined the association between long term, visit-to-visit BPV and change in gait speed and grip strength in participants of the ASPirin in Reducing Events in the Elderly (ASPREE) study, a randomized primary prevention trial of low-dose aspirin conducted in 19,114 community-dwelling adults in Australia and the U.S. who were without independence-limiting physical disability at enrollment, and its extended long-term observational follow-up (ASPREE-XT). Long-term BPV was estimated in each participant using the standard deviation (SD) of the means of three within-visit systolic BPs obtained using a validated automated oscillometric BP monitor from the baseline and first two annual ASPREE visits. During ASPREE and continued into ASPREE-XT, participants underwent annual/biennial measures of grip strength using a Jamar hand grip dynamometer, and completed a timed 3 meter walk at normal pace. Linear mixed models were used to examine changes in gait speed and grip strength trajectories over a median of 5.2 years of follow-up after the second annual ASPREE visit (end of BPV estimation window). After covariate adjustment, the highest SD tertile of BPV, compared to the lowest SD tertile, was associated with greater declines in gait speed over time, and reduced grip strength cross-sectionally (see accompanying Table). Our findings suggest that long-term BPV is an important predictor of progressive loss of physical performance, particularly gait speed, in older adults. Since BP is routinely measured in practice, characterization of the visit-to-visit BPV may help identify older adults at risk of future declines in physical function and loss of independence.

Abstract P329: Mycophenolate Mofetil Enhances Short-Term Blood Pressure Variability During Recovery in Salt-Sensitive Hypertensive African Americans

Elevated blood pressure variability (BPV) is an independent risk factor for cardiovascular disease (CVD), kidney disease, dementia, and stroke. High BPV is thought to be caused by arterial stiffness, vascular remodeling, inflammatory cascades, and neurohormonal mechanisms. This study aims to investigate the potential impact of mycophenolate mofetil (MMF) on short-term BPV in the context of salt-sensitive hypertension among African Americans (AA). MMF’s anti-inflammatory properties hold promise as a potential intervention for hypertension management by modulating short-term BPV. AA participants,18-50 years, normotensive, not pregnant, and not on prescription medications were recruited. In this crossover study, 51 participants received either MMF or a placebo daily. Physiological parameters were monitored every 15 minutes during a 3-hour psychosocial stressor assessment with rest, stress, and recovery periods. BPV was assessed using coefficient of variation (CV), standard deviation (SD), and average real variability (ARV). The treatment group showed a significant decrease in SBP CV (p &lt; 0.05) during stress. During recovery, SBP SD (p, 0.05) and SBP ARV (p &lt; 0.05) significantly increased in individuals receiving MMF treatment. Age-stratified analysis maintained significant effects of MMF on BPV during stress. Gender did not significantly alter the observed effects of MMF on BPV. Our study highlights the effectiveness of MMF in reducing BPV during acute stress, potentially lowering adverse cardiovascular events. MMF-treated groups showed increased BPV during recovery, indicating a quicker BP recovery to baseline. While a decrease in BPV during the stress period was observed, it was supported only by CV. The significant increase in BPV in the treatment group during recovery indicates MMF's ability to expedite the inflammatory stress response. The observed decrease in BPV during stress suggests a swifter return to baseline BP, potentially offering benefits for non-stress baseline physiology. Further research is warranted to clarify the mechanisms and clinical significance of these findings, impacting hypertension assessment and management. MMF treatment induces distinct changes in BPV during recovery, suggesting that MMF may positively influence BP regulation through a variety of inflammatory pathways. The alterations in SBP BPV underscore MMF's therapeutic potential for managing BPV and reducing cardiovascular risk in salt-sensitive, hypertensive AAs.

Abstract P344: APOe Genotype Modifies the Association Between Long-Term Blood Pressure Variability and Cognitive Decline/Dementia in Older Adults

We previously reported an increased risk of cognitive decline and dementia with high visit-to-visit long-term blood pressure variability (BPV) in the ASPREE randomized trial of low-dose aspirin, conducted in 19,114 community-dwelling older adults in Australia and the USA who were initially free of significant cognitive impairment and diagnosed dementia at enrollment. Upon completion of the randomized trial phase, ASPREE participants were invited into the ASPREE-eXTension (ASPREE-XT) observational study. In this analysis, we re-examined the risks of cognitive decline and dementia using extended follow-up from ASPREE-XT, and including recently available APOe genotype as an additional covariate. Long-term BPV was estimated in each participant using standard deviation (SD) of the means of three within-visit systolic BPs obtained with a validated automated oscillometric BP monitor from the baseline and first two annual ASPREE visits. During ASPREE and continued into ASPREE-XT, participants underwent annual/biennial standardized cognitive testing (4-test battery). Incident cognitive decline was defined as &gt;1.5 SD decline from baseline score on any cognitive test; incident dementia was a pre-specified secondary endpoint of ASPREE/ASPREE-XT and adjudicated by expert panel using DSM-IV criteria and clinical records. Participants reaching cognitive decline or dementia endpoints during the BPV estimation period were excluded from the analysis. Multivariable Cox proportional hazards regression showed the highest SD tertile of BPV, compared to the lowest SD tertile, remained associated with highest risk of cognitive decline (HR=1.16, 95% CI=1.04-1.30) and dementia (HR=1.27 (95% CI=1.02-1.59) in men, and cognitive decline (HR=1.12, 95% CI=1.01-1.24) in women (see accompanying Table), over a median follow-up of 5.8 years (for cognitive decline) and 6.5 years (for dementia). When APOe genotype was included as an additional covariate in an available subset of the cohort (81%), the presence of APOe4 allele partially attenuated the associations in both sexes, although cognitive decline remained significant in men. Our findings suggest the relationship between high long-term BPV and cognitive decline and dementia is stronger in men than women, but also modified by underlying APOe genotype.

Association between blood pressure variability and clinical outcomes after successful thrombectomy in acute basilar artery occlusion stroke patients: A multicenter cohort study

BackgroundLimited data are available on the appropriate choice of blood pressure management strategy for patients with acute basilar artery occlusion (BAO) treated with mechanical thrombectomy (MT). We evaluated the impact of blood pressure variability on clinical outcomes after MT in patients with acute BAO. MethodsThis multicenter cohort study included 108 patients with acute BAO who underwent successful emergency thrombectomy at two comprehensive stroke centers from 2016 to 2021. Blood pressure was measured hourly during the first 24 h after successful reperfusion. Blood pressure variability was calculated as mean arterial pressure (MAP) assessed by the standard deviation (SD). Multivariate logistic models were used to investigate the association between BPV, the primary outcome (futile recanalization, 90‐day modified Rankin Scale score 3–6), and the secondary outcome (30-day mortality). Subgroup analysis was performed as a sensitivity test. ResultsFutile recanalization occurred in 60 (56 %) patients, while 26 (24 %) patients died within 30 days. In the fully adjusted model, MAP SD was associated with a higher risk of futile recanalization (OR adj=1.36, per 1 mmHg increase, 95 % CI: 1.09–1.69, P=0.006) and 30-day mortality (OR adj=1.56, per 1 mmHg increase, 95 % CI: 1.20–2.04, P=0.001). A significant interaction between MAP SD and the lack of hypertension history on futile recanalization (P<0.05) was observed. ConclusionsAmong recanalized acute BAO ischemic patients, higher blood pressure variability during the first 24 h after MT was associated with worse outcomes. This association was stronger in patients without a history of hypertension.

Short-Term Blood Pressure Variability among Young Adults at High or Low Risk for Depression.

Background: Depression has been shown to have adverse effects on blood pressure (BP) and is associated with high blood pressure variability (BPV). In turn, high short-term BPV has been related to eventual cardiovascular risk. But it is not clear how early in adulthood the detrimental effects of depression on BPV may be discerned, if being at high risk for depression also compromises BPV, and whether the clinical features of depression moderate its adverse effects. We investigated these three issues among young adults using an office-like setting. Methods: In total, 218 subjects with a history of childhood-onset major depressive episodes (probands), 206 never-depressed full biological siblings of the probands (high-risk siblings), and 166 emotionally healthy unrelated controls received a psychiatric evaluation and three standardized-sitting BP measurements 5 min apart. Short-term BPV was defined as the maximum difference between measures (range) for each case. The statistical methods included analyses of variance/covariance, chi-square tests, and multiple regression. Results: Systolic and diastolic BP decreased over consecutive measurements (p < 0.001). After controlling for age, the probands, siblings, and controls did not differ significantly in terms of BPV. However, the number of lifetime depressive episodes did predict the diastolic BP range (p = 0.005): probands with the highest number of depressive episodes had the largest short-term diastolic BPV. Conclusions: On a group level, the adverse effects on BPV of having experienced or being at high risk for depression are not yet evident during young adulthood. However, the number of major depressive episodes, which is an index of lifetime depression burden, predicts higher BPV. Thus, BPV monitoring for young adults with clinical depression histories could be part of an early intervention program to reduce the risk of eventual cardiovascular disease.

Blood pressure variability assessed by office, home, and ambulatory measurements before and during antihypertensive drug treatment: a sub-analysis of the REVERENT randomized trial.

Blood pressure (BP) variability (BPV) can be assessed using office (OBP), home (HBP), or ambulatory BP (ABP) measurements. This analysis investigated the association and agreement between OBP, HBP, and ABP measurements for BPV assessment at baseline and 10 weeks after initiating antihypertensive drug therapy. Untreated hypertensive patients with elevated BPV were randomized to receive an angiotensin-converting enzyme inhibitor (ramipril) or a calcium channel blocker (nifedipine GITS) in a 10-week, open-label, blinded-end point study. BPV was assessed using standard deviation (SD) and coefficient of variation (CV) (reading-to-reading analyses). Data from 146 participants from three research centers (Athens/Greece; Milan/Italy; Shanghai/China) were analyzed [mean age 53 ± 10 (SD) years, male individuals 60%, baseline systolic OBP, HBP, and 24 h ABP 144 ± 9, 138 ± 10, and 143 ± 10 mmHg, respectively]. Post-treatment minus pre-treatment systolic CV difference was: OBP: 0.3%, P = 0.28; HBP: -0.2%, P = 0.20; 24 h ABP: 1.1%, P < 0.001. Home and ambulatory (not office) BPV indices presented weak-to-moderate correlation, both before and during treatment (range of coefficients 0.04-0.33). The correlation coefficient between systolic HBP and awake ABP CV was 0.21 and 0.28 before and during treatment, respectively ( P < 0.05/< 0.001, respectively). Home and ambulatory (not office) BPV indices presented slight-to-fair agreement (range 64-73%) in detecting participants with high systolic BPV (top quartile of respective distributions) both before and during treatment (kappa range 0.04-0.27). These data showed a weak-to-moderate association between out-of-office (but not office) BPV indices both before and during BP-lowering treatment, with reasonable agreement in detecting individuals with high BPV. Out-of-office BP measurements provide more similar and consistent BPV information than office measurements.

Respiratory modulation of sympathetic transduction to blood pressure in health and type 2 diabetes.

Type 2 diabetes (T2D) is often accompanied by hypertension, exaggerated blood pressure (BP) responses to sympatho-excitatory stressors, and raised cardiovascular disease risk. Appropriate respiratory-sympathetic coupling and sympathetic transduction to BP are important for short- and longer-term BP control. We tested the hypotheses that respiratory modulation of muscle sympathetic nerve activity (MSNA) and its transduction to BP would be impaired in T2D and associated with higher BP and respiratory-coupled BP variability. Resting MSNA, respiration and beat-to-beat BP were recorded in 20 T2D (49.1 ± 7.4 years; mean ± SD) and 13 healthy control (46.3 ± 9.4 years) participants. MSNA and the transduction of sympathetic bursts (signal-averaging) to mean arterial pressure (MAP) were compared at low and high lung volume phases. The peak MAP response following a sympathetic burst was lower during the high lung volume than low lung volume phase in controls (P = 0.005), whereas it was unchanged with phase in T2D participants (P = 0.522). Respiratory modulation of MSNA was impaired in T2D participants, who had an attenuated reduction in burst incidence from low to the high lung volume phase, versus controls (27.8 ± 38.4% vs. 49.4 ± 24.6%, respectively; P = 0.043). The T2D participants were grouped into unimpaired respiratory modulators (burst incidence modulation median or above) or impaired respiratory modulators (below median). Impaired modulators had higher systolic BP (133 ± 14 vs. 121 ± 11mmHg, P = 0.046), greater Traube-Hering wave amplitudes (6.3 ± 2.4 vs. 4.6 ± 1.1mmHg; P = 0.028) and higher BP variability (MAP average real variability, 2.0 ± 0.7 vs. 1.4 ± 0.3, P = 0.033). Respiratory modulation of MSNA and sympathetic transduction to BP are altered in T2D patients and may contribute to their increased hypertension and cardiovascular risk. KEY POINTS: Respiratory-sympathetic coupling and sympathetic transduction to blood pressure (BP) contribute to short- and longer-term BP control. Our understanding of these processes in health and type 2 diabetes (T2D), a condition with high prevalence of hypertension and cardiovascular risk, is incomplete. We found that respiration and sympathetic transduction to BP are coupled in healthy individuals. The mean arterial pressure response to a sympathetic burst was reduced during the high lung volume compared to the low lung volume phase. This coupling was absent in T2D. Respiratory modulation of muscle sympathetic nerve activity (MSNA) is impaired in T2D, with a blunted reduction of MSNA observed during the high lung volume phase. T2D patients with impaired respiratory MSNA modulation had augmented systolic BP, respiratory-related BP excursions (Traube-Hering waves) and BP variability. Abnormal respiratory modulation of MSNA and sympathetic transduction to BP in T2D may contribute to altered blood pressure control and cardiovascular risk in this population.

Associations of ultra long-term visit-to-visit blood pressure variability, since childhood with vascular aging in midlife: a 30-year prospective cohort study.

Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. In this study, we aimed to investigate the associations of ultra long-term blood pressure (BP) variability from childhood to midlife with vascular aging in midlife. Using data from the longitudinal cohort of Hanzhong Adolescent Hypertension Study, 2065 participants aged 6-18 years were enrolled and followed up with seven visits over 30 years. Ultra long-term BP variability (BPV) was defined as the standard deviation (SD) and average real variability (ARV) of BP over 30 years (seven visits). Vascular aging included arterial stiffness, carotid hypertrophy, and carotid plaque. After adjusting for demographic variables, clinical characteristics and mean BP over 30 years, higher SD SBP , ARV SBP , SD DBP and ARV DBP since childhood were significantly associated with arterial stiffness in midlife. Additionally, higher SD DBP and ARV DBP were significantly associated with carotid hypertrophy and the presence of carotid plaque in midlife. When we used cumulative exposure to BP from childhood to midlife instead of mean BP as adjustment factors, results were similar. Furthermore, we found a significant association between long-term BPV from childhood to adolescence and the presence of carotid plaque, whereas long-term BPV from youth to adulthood is associated with arterial stiffness. Higher BPV from childhood to adulthood was associated with vascular aging in midlife independently of mean BP or cumulative BP exposure. Therefore, long-term BPV from an early age may serve as a predictor of cardiovascular diseases (CVDs) in later life.

624 A Retrospective Review of Blood Pressure Variability (BPV) and Abdominal Aortic Aneurysm (AAA)

Abstract Background Abdominal aortic aneurysms (AAA) rupture risk increases with expansion. Understanding of factors influencing AAA growth are crucial to reduce the risk of rupture. Blood pressure (BP) is considered a contributor to AAA formation, but the association with AAA growth remains unclear. Blood pressure variability (BPV) has emerged as an important cardiovascular risk factor, yet its relationship with AAA growth has not been investigated. Method A retrospective review of 90 patients participating in a multi-centre AAA growth study (NCT05376514) was conducted. Mean growth (mm/yr) was calculated from first and most recent duplex ultrasound scans. Outpatient BP readings between scans were used to calculate BPV defined as the standard deviation (SD) of systolic and diastolic values. Patients were stratified into high and low BPV groups and again into tertiles. Mann-whitney U and unpaired T-tests were used for group comparisons, Kruskall-Wallis to assess for a dose-response relationship between tertiles of BPV. Multiple regression analysis examined variable impact on growth. Results High diastolic BPV was associated with a faster growth rate (2.05 mm/yr [IQR= 1.00 – 3.00]) vs low diastolic BPV (1.44 mm/ yr ([IQR= 0.475-2.00]p=0.036) with a significant dose-response relationship between the lowest and highest BPV tertiles (p= 0.019). DBPV was a significant predictor of AAA growth in the multiple regression model for tertile classification (p=0.016). There was no association between systolic BPV and faster AAA growth rates. Conclusions There was a significant association between higher diastolic blood pressure variability and AAA growth. DBPV may be an important risk stratification tool.

Blood Pressure Variability and Plasma Biomarkers of Neuronal Injury and Alzheimer's Disease: A Clinic-Based Study of Patients with Diseases Along the Heart-Brain Axis.

Higher blood pressure variability (BPV) predisposes to cognitive decline. To investigate underlying mechanisms, we measured 24-h ambulatory BPV, nocturnal dipping and orthostatic hypotension in 518 participants with vascular cognitive impairment, carotid occlusive disease, heart failure, or reference participants. We determined cross-sectional associations between BPV indices and plasma biomarkers of neuronal injury (neurofilament light chain) and Alzheimer's disease (phosphorylated-tau-181 and Aβ42/Aβ40). None of the BPV indices were significantly associated with any of the biomarkers. Hence, in patients with diseases along the heart-brain axis, we found no evidence for an association between BPV and selected markers of neuronal injury or Alzheimer's disease.

#2227 Exploring the interplay between gut microbiome, fecal metabolomics and ambulatory blood pressure in white-coat hypertensive patients

Abstract Background and Aims Recent evidence showed the relationship between gut microbiota with hypertension. Few studies also demonstrated that ambulatory blood pressure monitoring variables such as dipping status and linear variability are associated with fecal microbiota and metabolomics. However, the relationship between gut microbiota and metabolomic composition of white-coat hypertensive patients has not been studied yet. In addition, although the link between gut microbiota, blood pressure variability and high salt intake has been shown, none of the studies addressed these changes simultaneously in the same study population. Here, we aimed to investigate the interplay between the gut microbiome, fecal metabolites and 24-hour urine sodium levels between hypertensive, white-coat hypertensive (WCH) and healthy participants diagnosed with ambulatory blood pressure monitoring. Method The study included 18 newly diagnosed hypertensive, 8 WCH, and 21 healthy participants from our tertiary center. Ambulatory blood pressure (BP) monitoring was performed in all participants and nighttime dipping, morning BP surge (MBPS), pre-wake MBPS and linear BP variability were calculated. 16S rRNA sequencing was performed using Illumina MiSeq sequencer. DeSeq2 and linear discriminant analysis effect size (LEfSe) were performed with R. Fecal metabolite levels were analyzed by GC-MS. A partial least squares-discriminant analysis (PLS-DA) model was constructed for the feature selector and classifier. The variable importance in the projection (VIP) coefficient was calculated based on the PLS-DA model. Results ANOVA and post-hoc Tukey test showed WHC and hypertensive groups had higher blood pressure variability and morning-thorough MBPS than normotensive patients (p = 0.02 and 0.04, respectively), whereas 24-h urine Na levels were statistically similar between WCH and hypertensive groups (p = 0.11). There were no significant differences in α- and β-diversity metrics of gut microbiome between study groups. Select taxa were specific to WHC patients, notably Rikenellaceae family and Mitsuokella were higher in WHC against normotensive patients, whereas Ruminococcus callidus, Roseburia, Clostridium, Lactobacillus ruminis, Sutterall, Lachospiraceae and Muribaculaceae were decreased in WHC against normotensive patients in DeSeq2 analysis. Dialister was increased, whereas Bacteroides genus and Bacteroides fragilis were decreased in WHC against hypertensive patients. LEfSe analysis showed positive enrichment in Proteobacteria phylum and negative enrichment in Mitsuokella genus in WHC against hypertensive group. Enterococcus, Lachnobacterium, Odoribacter and Pseudomonas genera had positive; whereas Lactobacillus and Clostridium had negative correlations with 24-h urine Na levels. Positive correlations were shown between linear BP variability and Bacteroides and Paraprevotella genera. Several genera and species were enriched in Q3-4 against Q1-2 quartiles of pre-wake and sleep-thorough MBPS in LEfSe analyzes (Fig. 1). Normotensive and essential hypertensive groups could also be differentiated based on fecal metabolomic composition. Specifically, metabolites with the highest VIP values discriminating WCH from normotensive and hypertensive groups were methyl-palmitoleate, oxalic acid and phenyl β-D-glucopyranoside, respectively (Fig. 2). Conclusion In conclusion, we performed the first study focusing on the fecal microbiome and metabolomic characteristics of white-coat hypertensive patients. Urine Na levels and ambulatory blood pressure variables of the WCH group are different than those of the normotensive and similar to the hypertensive group. Comparative and correlation analyses revealed novel relationships between ambulatory blood pressure variables and gut microbiome of both WCH and hypertensive patients. Fecal metabolomic differences between study groups imply possible mechanisms underlying the effects of gut microbiome on blood pressure. Gut microbiota and metabolites may become valuable targets for interventions of both white-coat and essential hypertension in the near future.

BLOOD PRESSURE VARIABILITY AS PREDICTOR OF CANCER THERAPY-RELATED CARDIOVASCULAR TOXICITY IN PATIENTS WITH MULTIPLE MYELOMA

Objective: Blood pressure variability (BPV) is an independent predictor of cardiovascular (CV) events and overall mortality. The potential role of BPV in defining CV risk of patients undergoing anticancer therapy with a potential cancer therapy-related cardiovascular toxicity (CTR-CVT) is currently unknown. The aims of this study were: (i) to assess the predictive value of BPV indexes for CTR-CVT development and defining the corresponding cut-off values; (ii) to identify subgroups of subjects based on BPV, through clustering analysis. Design and method: Patients with Multiple Myeloma, who were eligible to anticancer therapy with Carfilzomib, were consecutively enrolled and underwent a baseline evaluation, including office blood pressure (BP) measurement, 24h-Ambulatory Blood pressure Monitoring (ABPM), PWV, and Echocardiography. Short-term BPV was assessed through standard deviation (SD), weighted standard deviation (wSD), coefficient of variation (CoV), average real variability (ARV), and variability independent of the mean (VIM), evaluated on ABPM measurements. Results: The study population included 124 patients (50% female). During follow-up, CTR-CVT occurred in 70 subjects (56.5% of the total population), including both BP and CV events. Night-time BPV was associated to CTR-CVT, independently by BP, age, smoking, and comorbidities as diabetes and renal dysfunction (night-time systolic CoV: adjusted OR 1.11 [1.01-1.22]; night-time systolic VIM adjusted OR 1.17 [1.03-1.35]; night-time diastolic VIM adjusted OR 1.18 [1.01-1.40]). Cut-off for these BPV parameters were identified as predictor of CTR-CVT occurrence: 10.5 for night-time systolic CoV (sensibility 73%, specificity 47%); 7.8 and 6.4 for systolic and diastolic night-time VIM (sensibility 85% for both; specificity 35% and 39%, respectively). Clustering analysis identified a subgroup of subjects characterized by the highest BPV, who had a greater prevalence of events during follow-up, but no differences in other conventional CV risk factors, as BP, dyslipidaemia, diabetes, renal function, and smoking habit, as well as left ventricular mass and global longitudinal strain. Conclusions: Short-term BPV is an independent predictor of CTR-CVT in patients with Multiple Myeloma undergoing therapy with Carfilzomib. The inclusion of these indexes improves CV risk prediction in these subjects and higher BPV is a distinctive feature predicting adverse events, on top of conventional CV risk factors.

Combined effect of time in target range and variability of systolic blood pressure on cardiovascular outcomes and mortality in patients with hypertension: A prospective cohort study.

Time in target range (TTR) and blood pressure variability (BPV) of systolic blood pressure (SBP) are independent risk factors for major adverse cardiovascular events (MACE) and all-cause mortality in hypertensive patients. However, the association of the combination of low TTR and high BPV of SBP with the risk of MACE and all-cause mortality is unclear. This study sought to investigate the combined effect of the TTR and BPV on the risk of MACE and all-cause mortality in patients with hypertension. A total of 11 496 hypertensive patients from the Kailuan cohort study were included in our study. All participants were divided into four groups according to their TTR and BPV levels. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CI) for incident MACE and all-cause mortality. During a median follow-up of 5.64 years, 839 MACEs (included 99 cases of myocardial infarction, 591 cases of stroke, and 191 cases of heart failure) and 621 deaths occurred. Compared with the high-TTR and low-BPV group, the HRs (95% CI) of MACE and all-cause mortality were 1.309 (1.025-1.671) and 1.842 (1.373-2.473) for the high-TTR and high-BPV group, 1.692 (1.347-2.125) and 1.731 (1.298-2.309) for the low-TTR & low-BPV group, 2.132 (1.728-2.629) and 2.247 (1.722-2.932) for the low-TTR & high-BPV group. Our study suggests that the combination of low TTR and high BPV of SBP was associated with a higher risk of MACE and all-cause mortality in patients with hypertension.

Impact of sleep quality and physical activity on blood pressure variability.

Increased blood pressure variability (BPV) is linked to cardiovascular disease and mortality, yet few modifiable BPV risk factors are known. We aimed to assess the relationship between sleep quality and activity level on longitudinal BPV in a cohort of community-dwelling adults (age ≥18) from 17 countries. Using Withings home measurement devices, we examined sleep quality and physical activity over one year, operationalized as mean daily step count and number of sleep interruptions, both transformed into tertiles. The primary study outcome was high BPV, defined as the top tertile of systolic blood pressure standard deviation. Our cohort comprised 29,375 individuals (mean age = 58.6 years) with 127.8±90.1 mean days of measurements. After adjusting for age, gender, country, body mass index, measurement days, mean blood pressure, and total time in bed, the odds ratio of having high BPV for those in the top tertile of sleep interruptions (poor sleep) was 1.37 (95% CI, 1.28-1.47) and 1.44 (95% CI, 1.35-1.54) for those in the lowest tertile of step count (physically inactive). Combining these exposures revealed a significant excess relative risk of 0.20 (95% CI, 0.04-0.35, p = 0.012), confirming their super-additive effect. Comparing individuals with the worst exposure status (lowest step count and highest sleep interruptions, n = 2,690) to those with the most optimal status (highest step count and lowest sleep interruptions, n = 3,531) yielded an odds ratio of 2.01 (95% CI, 1.80-2.25) for high BPV. Our findings demonstrate that poor sleep quality and physical inactivity are associated with increased BPV both independently and super-additively.

Mediating Effect of Heart Rate Variability on the Relationship Between Anxiety Symptoms and Blood Pressure in Patients with Primary Hypertension.

Patients with hypertension (HTN) are at increased risk of developing cardiovascular disease, which can be reduced with blood pressure (BP) control. Anxiety can contribute to high BP and low heart rate variability (HRV). Although relationships between social support, self-rated health-status (SRHS), anxiety and measures of HRV and BP have been suggested, they have not been clearly established. This cross-sectional correlational study aimed to 1) examine relationships between social support, SRHS, and anxiety; and 2) examine if HRV mediated relationships between anxiety symptoms and BP. Patients with primary HTN were recruited from a cardiovascular outpatient clinic using convenience sampling (N = 300). Data included scale scores for SRHS, social support, and anxiety (Hospital Anxiety and Depression Scale). A handheld limb-lead electrocardiogram monitor measured HRV, using the ratio of low-frequency bands to high-frequency bands; an automatic sphygmomanometer measured systolic and diastolic blood pressure (SBP and DBP, respectively). Path analysis of structural equation models examined relationships between variables; the bootstrap method examined the mediating effects of HRV. Analysis showed scores for SRHS and social support had a direct effect on anxiety scores. Scores for anxiety directly affected HRV and BP. HRV also had a direct effect on BP. Bootstrapping indicated HRV mediated the relationship between anxiety symptoms and BP. The final model indicated SRHS, social support, and anxiety symptoms together explained 80% of SBP and 33% of DBP. These findings suggest HRV could be used to measure the effectiveness of strategies aimed at reducing anxiety and improving control of BP.

Blood Pressure Variability and Plasma Alzheimer's Disease Biomarkers in the SPRINT Trial.

Recent observational studies suggest higher blood pressure (BP) variability (BPV) is associated with Alzheimer's disease (AD) biomarkers amyloid-beta (Aβ) and tau. Less is known about relationships in interventional cohorts with strictly controlled mean BP levels. Investigate the longitudinal relationship between BPV and change in plasma AD biomarkers under standard versus intensive BP treatment. In this post hoc analysis of the SPRINT trial, 457 participants (n = 206 in standard group, n = 251 in intensive group) underwent repeated BP measurement between baseline and 12-months follow-up, and venipuncture at baseline and median (IQR) 3.5 (3.0-4.0) years later to determine plasma AD biomarkers total tau and Aβ1-42:Aβ1-40 ratio. BPV was calculated as tertiles of variability independent of mean. Linear mixed models investigated the effect of BPV×time on AD biomarker levels. Higher BPV was associated with increased levels of total tau in the standard group (β [95% CI] 1st versus 3rd tertiles of BPV: 0.21 [0.02, 0.41], p = 0.035), but not in the intensive group (β [95% CI] 1st versus 3rd tertiles of BPV: -0.02 [-0.19, 0.16], p = 0.843). BPV was not associated with Aβ 1-42:Aβ 1-40 ratio in either group. Mean BP was not associated with biomarkers. Higher BPV was associated with increased plasma total tau under standard BP treatment. Findings add new evidence to prior observational work linking BPV to AD pathophysiology and suggest that, despite strict control of mean BP, BPV remains a risk for pathophysiological change underlying risk for AD.

Nocturnal blood pressure dipping, blood pressure variability, and cognitive function in early and middle-aged adults.

Higher nighttime blood pressure (BP), less BP dipping, and higher BP variability have been linked with worse cognitive function in the elderly. The goal of this study is to explore whether this relationship already exists in early and middle adulthood. We further examined whether ethnic differences between African Americans and European Americans in BP parameters can explain ethnic differences in cognitive function. 24-h ambulatory BP monitoring and cognitive function were obtained from 390 participants (average age: 37.2 years with a range of 25-50; 54.9% African Americans; 63.6% females). We observed that higher nighttime BP, decreased dipping, and higher variability were significantly associated with lower scores on the Picture Sequence Memory Test. Significant negative associations between variability and overall composite scores were also observed. No significant associations between average 24-h or daytime BP and cognitive function were observed. Ethnic differences in nighttime diastolic pressures and dipping can explain 6.81% to 10.8% of the ethnicity difference in the score of the Picture Sequence Memory Test (ps<.05). This study suggests that the associations of nighttime BP, dipping, and variability with cognitive function already exist in young and middle-aged adults. Ethnic differences in nighttime BP and dipping can at least partially explain ethnic differences in cognitive function. The stronger association of these parameters with cognitive function than daytime or average BP in this age range raises the importance of using ambulatory BP monitoring for more precise detection of abnormal BP patterns in young adulthood.