AMBULATORY BLOOD PRESSURE VARIABILITY IN YOUNG ADULTS WITH LONG-COVID SYNDROME.

OBJECTIVE: The aim: To perform an overall assessment of BP and BP variability using ambulatory measurements in young adults with long COVID syndrome. PATIENTS AND METHODS: Materials and methods: We enrolled young patients with diagnosed long-COVID syndrome (n = 58, mean age 23.07 ± 1.54 years), compared with an age-matched healthy subjects who had not suffered from COVID-19 (n = 57, mean age 22.9 ± 1.83 years). Patients with long-COVID syndrome had recovered from mild/moderate illness and none had required hospitalization. Ambulatory 24 hours blood pressure (AMBP) parameters (mean BP, daytime BP, nighttime BP, pulse pressure, nocturnal systolic BP dipping, dipper status) were measured in all participants. The variability of systolic BP (SBP) and diastolic BP (DBP) values was assessed by the following common metrics, including the average real variability (ARV), the coefficient of variation (CV), the standard deviation (SD), and the weighed SD of SBP and DBP. RESULTS: Results: The average values of 24-hour ambulatory blood pressure, mean BP, daytime and nighttime systolic BP, diastolic BP and pulse pressure were found to be significantly different among patients with long COVID syndrome and control group. Group analyses showed that this difference was in SBP mean values (127.1 ± 6.65 mmHg and 115.93 ± 6.24 mmHg respectively) and DBP mean values (73.31 ± 5.30 mmHg and 68.79 ± 5.5 mmHg respectively) mainly at night. PP values at daytime were almost similar among groups, but PP values at nighttime were higher in patients with long-COVID syndrome (53.8 (52.44- 55.14) mmHg and 47.14 (46.45 - 47.88) mmHg respectively). Nocturnal SBP dipping was better in control group than in patients with long-COVID syndrome ( 5.3 ± 5.68 and 3.1 ± 3.79 mmHg respectively). Only 13 (22.4%) patients with long-COVID syndrome had normal dip-per status while more than half - 38 (66.7%) in healthy subjects. The values of ARV of SBP and DBP over 24-hour, awake, and asleep time frames were found to be greater in patients with long COVID syndrome than healthy controls (p < 0.05). CONCLUSION: Conclusions: Patients with long- COVID syndrome have higher BP mean values of 24-hour ABPM particularly at nightime, significant blood pressure BP variability, which increases the risk of cardiovascular events in future. Nevertheless, the further prospective investigations is warranted to investigate the potential mechanisms and causality associations.

Cardiac surgical outcome prediction by blood pressure variability indices Poincaré plot and coefficient of variation: a retrospective study.

BACKGROUND: Recent literature suggests a significant association between blood pressure variability (BPV) and postoperative outcomes after cardiac surgery. However, its outcome prediction ability remains unclear. Current prediction models use static preoperative patient factors. We explored the ability of Poincaré plots and coefficient of variation (CV) by measuring intraoperative BPV in predicting adverse outcomes. METHODS: In this retrospective, observational, cohort study, 3687 adult patients (> 18 years) undergoing cardiac surgery requiring cardio-pulmonary bypass from 2008 to 2014 were included. Blood pressure variability was computed by Poincare plots and CV. Standard descriptors (SD) SD1, SD2 were measured with Poincare plots by ellipse fitting technique. The outcomes analyzed were the 30-day mortality and postoperative renal failure. Logistic regression models adjusted for preoperative and surgical factors were constructed to evaluate the association between BPV parameters and outcomes. C-statistics were used to analyse the predictive ability. RESULTS: Analysis found that, 99 (2.7%) patients died within 30 days and 105 (2.8%) patients suffered from in-hospital renal failure. Logistic regression models including BPV parameters (standard descriptors from Poincare plots and CV) performed poorly in predicting postoperative 30-day mortality and renal failure [Concordance(C)-Statistic around 0.5]. They did not add any significant value to the standard STS risk score [C-statistic: STS alone 0.7, STS + BPV parmeters 0.7]. CONCLUSIONS: In conclusion, BP variability computed from Poincare plots and CV were not predictive of mortality and renal failure in cardiac surgical patients. Patient comorbid conditions and other preoperative factors are still the gold standard for outcome prediction. Future directions include analysis of dynamic parameters such as complexity of physiological signals in identifying high risk patients and tailoring management accordingly.

Preoperative Blood Pressure Complexity Indices as a Marker for Frailty in Patients Undergoing Cardiac Surgery.

OBJECTIVE: Frailty, a state of decreased physiological reserve, increases the risk of adverse outcomes. There is no standard tool for frailty during perioperative period. Autonomic dysfunction, an underlying process in frailty, could result in hemodynamic fluctuations. Complexity, the physiological adaptability of a system can quantify these fluctuations. The authors hypothesized that complexity could be a marker for frailty and explored their relationship in cardiac surgical patients. DESIGN: Prospective, observational study. SETTING: Single-center teaching hospital. PARTICIPANTS: Three hundred and sixty-four adult patients undergoing cardiac surgery. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Preoperative beat-to-beat systolic arterial pressure (SAP) and mean arterial pressure (MAP) time series were obtained. Complexity indices were calculated using multiscale entropy (MSE) analysis. Frailty was assessed from: age >70 years, body mass index <18.5, hematocrit <35%, albumin <3.4 g/dL, and creatinine >2.0 mg/dL. The association between complexity indices and frailty was explored by logistic regression and predictive ability by C-statistics. In total, 190 (52%) patients had frailty. The complexity index (MSEΣ) median (quartile 1, quartile 3) of SAP and MAP time series decreased significantly in frail patients (SAP: 8.32 [7.27, 9.24] v 9.13 [8.00, 9.72], p < 0.001 and MAP: 8.56 [7.56; 9.27] v 9.18 [8.26; 9.83], p < 0.001). MSE Σ demonstrated a fair predictive ability of frailty (C-statistic: SAP 0.62 and MAP 0.64). CONCLUSION: Preoperative BP complexity indices correlate and predict frailty. Impaired autonomic control is the underlying mechanism to explain this finding. A simple automated measure of preoperative BP complexity in the surgeon's office has the potential to reliably assess frailty.

Negative association between plasma aldosterone concentration/plasma renin activity and morning blood pressure surge in never-treated hypertensive patients.

Morning blood pressure (BP) surge (MS) has been known to be a predictor of cardiovascular events. Currently, few studies have evaluated the underlying mechanism underlying MS, which may include neurohormonal factors and the renin-angiotensin-aldosterone system (RAAS). This study aimed to examine plasma aldosterone concentration (PAC) and plasma renin activity (PRA) and BP parameters with or without MS in never-treated subjects with essential hypertension. This cross-sectional study included a total of 261 patients (mean age: 48.8 years; 60.5% male) with never-treated essential hypertension who were registered in a working group at The Catholic University of Korea. The patients were divided into the MS group, which was defined as having the highest quartile of morning BP increase from sleep (>31 mmHg; n = 66) and the non-MS group (≤31 mmHg; n = 195). We collected 24-h ambulatory BP, pulse wave velocity, ankle brachial index, PAC and PRA from all patients. The measured PAC and PRA were lower in the MS group than in the non-MS group (PAC: 9.0 ± 5.4 ng/dl versus 12.2 ± 8.7 ng/dl, p < 0.001; PRA: 1.7 ± 1.3 ng/ml/h versus 2.6 ± 3.6 ng/ml/h, p = 0.002). The MS group had greater variations in daytime, nighttime and 24-h systolic blood pressure (SBPs) than the non-MS group (24-h SBP: 15.6 ± 4.4 mm Hg for the non-MS group and 18.9 ± 4.9 mmHg for the MS group; p < 0.001 for each). It is generally accepted that the sympathetic nervous system plays a major role in the regulation of BP variability. Therefore, further studies on sympathetic nervous system activation in hypertensives with extreme MS are needed. MS in enrolled patients who were at relatively low risk in this study may be less affected by the RAAS.

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.

Association between Short-Term Blood Pressure Variability and Intracranial Atherosclerotic Plaque Vulnerability: A High-Resolution Magnetic Resonance Imaging Study.

AIM: short-term blood pressure variability (BPV) as a risk factor of atherosclerosis and cardiovascular events has been investigated. However, its association with atherosclerotic plaque vulnerability remains unknown. The objective of this study was to determine the association between short-term BPV and intracranial atherosclerotic plaque vulnerability. METHODS: this is a cross-sectional analysis of 267 ischemic stroke patients with symptomatic intracranial atherosclerosis (mean age, 65±12 years old; 60.3% male), which were prospectively recruited in a comprehensive stroke center. Systolic and diastolic BP SD, CV, and BP variability ratio (BPVR) from 24 hours, daytime, and nighttime were calculated from 24-h ambulatory blood pressure monitoring, intracranial atherosclerotic plaque burden and vulnerability were evaluated by high-resolution magnetic resonance vessel wall imaging. Logistic regression analysis was used to locate the correlation between short-term BPV and plaque vulnerability. RESULTS: a total of 36.3% subjects presented with intraplaque hemorrhage (IPH) in this study. Multivariate logistic regression suggested that nighttime diastolic BP CV and 24-h BPVR were associated with intracranial IPH independently after adjusted for cardiovascular risk factors, odds ratio (OR) and 95% confidence interval (CI) for per SD BPV changes were 1.418 (1.051, 1.914) and 0.731 (0.548, 0.976), respectively, and this association also independent of atherosclerosis burden and 24-h mean systolic BP level. Further subgroup analysis by age and hypertension history demonstrated that the statistical correlation could only establish in the elder, and subjects with hypertension. CONCLUSION: nighttime diastolic BP CV and 24-h BPVR were associated with intracranial IPH independently, especially in the elderly and subjects with hypertension.

Intradialytic BP variability is associated with cardiovascular mortality and hospitalization in HD patients.

INTRODUCTION: Studies showed that pre-dialysis BP variability (BPV) was an independent risk factor of cardiovascular disease (CVD) among HD patients, but which is limited on how intradialytic BPV affects prognosis. METHODS: In this study, we designed a retrospective cohort study to examine the association between intradialytic BPV and CVD outcomes in HD patients. A total of 202 patients who underwent HD in our center were included, and all intradialytic BP measurements of November 2017 were obtained from the database. Patients were divided into four groups according to variability independent of the mean (VIM) interquartile. RESULTS: The mean age was 62.1 ± 14.3 years, 60.9% were male, and median VIM was 14.75 (12.60-18.59). Multiple-regression analyses showed patients age, dialysis vintage, serum albumin, and the percentage of intradialytic weight gain as significant predictors of VIM (all p values were <0.05). Kaplan-Meier survival curves showed that CVD mortality was greater in patients with higher VIM (p = 0.05), whereas all-cause mortality had no significant difference between the four groups overall (p = 0.149). Furthermore, multivariate regression analyses demonstrated that VIM (HR = 1.091, p < 0.004) and age (HR = 1.059, p = 0.003) were significant independent predictors for CVD death. Logistic-regression models revealed that higher VIM groups were more likely to have CVD-related hospitalization (OR = 1.085, p = 0.030), whereas the association between VIM and all-cause hospitalization was not statistically significant (OR = 1.015, p = 0.669). CONCLUSIONS: This retrospective study suggested that higher intradialytic BPV was associated with increasing age, longer dialysis vintage, lower albumin, and greater ultrafiltration; intradialytic BPV could be an effective predictor for CVD mortality and hospitalization in the HD population.

Feeding during Dialysis Increases Intradialytic Blood Pressure Variability and Reduces Dialysis Adequacy.

Whether hemodialysis patients should be allowed or even encouraged to eat during dialysis remains a controversial topic. This cross-over study aimed to evaluate the impact of feeding during dialysis on intradialytic blood pressure (BP) profile and dialysis adequacy in 26 patients receiving thrice-weekly, in-center hemodialysis. Over three consecutive mid-week dialysis sessions, intradialytic BP was monitored using the Mobil-O-Graph device (IEM, Stolberg, Germany). Blood samples were also obtained for the determination of the urea reduction ratio (URR). At baseline, patients underwent dialysis without the provision of a meal. In phases A and B, a meal with either high-protein (1.5 gr/kg of body weight) or low-protein (0.7 gr/kg of body weight) content was administered 1 h after the initiation of dialysis. The sequence of meals (high-protein and low-protein or vice versa) was randomized. Average intradialytic systolic BP (SBP) was similar on all three occasions. However, compared with baseline, the standard deviation (SD) (11.7 ± 4.1 vs. 15.6 ± 7.6 mmHg, p < 0.01), coefficient of variation (CV) (9.5 ± 3.7% vs. 12.4 ± 6.0%, p < 0.01) and average real variability (ARV) (9.4 ± 3.9 vs. 12.1 ± 5.2 mmHg, p < 0.01) of intradialytic SBP were higher in phase A. Similarly, compared with the baseline evaluation, all three indices of intradialytic SBP variability were higher in phase B (SD: 11.7 ± 4.1 vs. 14.1 ± 4.5 mmHg, p < 0.05; CV: 9.5 ± 3.7% vs. 11.1 ± 3.8%, p < 0.05; ARV: 9.4 ± 3.9 vs. 10.9 ± 3.9 mmHg, p < 0.05). Compared with dialysis without a meal, the consumption of a high-protein or low-protein meal resulted in a lower URR (73.4 ± 4.3% vs. 65.7 ± 10.7%, p < 0.001 in phase A and 73.4 ± 4.3% vs. 67.6 ± 4.3%, p < 0.001 in phase B, respectively). In conclusion, in the present study, feeding during dialysis was associated with higher intradialytic SBP variability and reduced adequacy of the delivered dialysis.

Variability independent of mean blood pressure as a real-world measure of cardiovascular risk.

Background: Individual-level blood pressure (BP) variability, independent of mean BP levels, has been associated with increased risk for cardiovascular events in cohort studies and clinical trials using standardized BP measurements. The extent to which BP variability relates to cardiovascular risk in the real-world clinical practice setting is unclear. We sought to determine if BP variability in clinical practice is associated with adverse cardiovascular outcomes using clinically generated data from the electronic health record (EHR). Methods: We identified 42,482 patients followed continuously at a single academic medical center in Southern California between 2013 and 2019 and calculated their systolic and diastolic BP variability independent of the mean (VIM) over the first 3 years of the study period. We then performed multivariable Cox proportional hazards regression to examine the association between VIM and both composite and individual outcomes of interest (incident myocardial infarction, heart failure, stroke, and death). Findings: Both systolic (HR, 95% CI 1.22, 1.17-1.28) and diastolic VIM (1.24, 1.19-1.30) were positively associated with the composite outcome, as well as all individual outcome measures. These findings were robust to stratification by age, sex and clinical comorbidities. In sensitivity analyses using a time-shifted follow-up period, VIM remained significantly associated with the composite outcome for both systolic (1.15, 1.11-1.20) and diastolic (1.18, 1.13-1.22) values. Interpretation: VIM derived from clinically generated data remains associated with adverse cardiovascular outcomes and represents a risk marker beyond mean BP, including in important demographic and clinical subgroups. The demonstrated prognostic ability of VIM derived from non-standardized BP readings indicates the utility of this measure for risk stratification in a real-world practice setting, although residual confounding from unmeasured variables cannot be excluded. Funding: This study was funded in part by National Institutes of Health grants R01-HL134168, R01-HL131532, R01-HL143227, R01-HL142983, U54-AG065141; R01-HL153382, K23-HL136853, K23-HL153888, and K99-HL157421; China Scholarship Council grant 201806260086; Academy of Finland (Grant no: 321351); Emil Aaltonen Foundation; Finnish Foundation for Cardiovascular Research.

Once versus twice daily antihypertensive medications for the control of nocturnal blood pressure: a comparative study.

BACKGROUND: Blood pressure (BP) shows short-term variability within the 24 h, which can only be assessed with 24-h ambulatory blood pressure monitoring (ABPM). It is of utmost importance to control BP throughout the night to reduce incidence of hypertension complications. The purpose of this study is to evaluate the effect of timing and frequency of antihypertensive medications on the average nighttime and 24-h blood pressure control. RESULTS: The study enrolled 199 hypertensive patients with controlled office blood pressure; 135 (67.8%) patients were on once daily antihypertensive medication (group 1) while 64 (32.2%) patients were on twice daily doses (group 2). The mean office SBP was 128.7 ± 7.8 mmHg in group 1 vs 129.6 ± 6.6 mmHg in group 2, (p = 0.421). ABPM readings for both groups were as follows: mean daytime SBP was 125.4 ± 11.6 mmHg vs 130.1 ± 12.9, p = 0.011; mean nighttime SBP was 117.0 ± 12.4 mmHg vs 123.1 ± 13.9 mmHg, p = 0.002, and mean 24-h SBP was 122.7 ± 10.6 mmHg vs 127.5 ± 12.0, p = 0.005. The prevalence of non-dipping was 68.9% in group 1 vs 70.3% in group 2 patients, p = 0.8 (the mean dipping ratio was 0.93 ± 0.08 in group 1 vs 0.95 ± 0.07 in group 2, p = 0.198). The prevalence of masked hypertension was higher in group 2 (28.1% vs 43.8%, p = 0.029). CONCLUSION: Taking an extra antihypertensive pill at night did not show a decrease in the nighttime or the average 24H blood pressure in hypertensive patients with controlled office BP. On the contrary, patients who used twice daily antihypertensive medications seem to have higher nighttime and 24-h SBP, although the dipping ratio was comparable in both groups.

Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study.

PURPOSE: Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. METHODS: This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. FINDINGS: Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition, escalating the dose of either nifedipine GITS or valsartan revealed a similar occurrence of adverse effects with low-dose monotherapy or the low-dose combination. IMPLICATIONS: Compared with up-titration of the angiotensin receptor blocker valsartan, up-titration of the calcium channel blocker nifedipine GITS provided no additional increased safety concerns and revealed better mean reductions in BP without affecting short-term BP variability. ClinicalTrials.gov identifier: NCT01071122.

Sleep duration and insomnia in the elderly: associations with blood pressure variability and carotid artery remodeling.

BACKGROUND: Recent studies have shown that short and long sleep durations and insomnia are associated with increased home-measured blood pressure (BP) variability, which in turn has a relationship with arterial stiffness. However, the determinants for visit-to-visit systolic blood pressure (SBP) variability have rarely been investigated in relation to sleep duration, insomnia, and carotid arterial stiffness. METHOD: The subjects were 201 elderly individuals (79.9±6.4 years old) with one or more cardiovascular risks. Based on 12 visits, visit-to-visit BP variability (expressed as a coefficient of variation [CV]) and δ (maximum - minimum) BP were measured. Self-reported sleep duration and insomnia questionnaires were used to classify the patients according to sleep duration period and insomnia status. RESULTS: After multivariable adjustment, long sleep duration (≥ 9 hours per night) had significant positive associations with SBP δ (P < 0.05), while persistent insomnia had significant positive associations with SBP CV (P < 0.05) and δ (P < 0.01). Additionally, significant interactions were found in terms of long sleep duration by carotid artery stiffness parameter ß (P < 0.05), persistent insomnia by intima-media thickness (P < 0.01), and persistent insomnia by stiffness parameter ß (P < 0.05) for SBP δ. CONCLUSION: In elderly patients at high risk for cardiovascular disease, long sleep duration as well as persistent insomnia were significantly associated with higher visit-to-visit BP variability. Long sleep duration and persistent insomnia each had synergetic interactions with carotid artery stiffness and with visit-to-visit BP variability.