Mean 24-hour Diastolic Blood Pressure Research Articles

Analysis of the Relationship between Recent Small Subcortical Infarcts and Autonomic Nervous Dysfunction.

Autonomic Nervous System (ANS) dysfunction may be involved in the pathogenesis of Cerebral Small Vessel Disease (CSVD). The study aimed to explore the relationship between Recent Small Subcortical Infarct (RSSI) and Blood Pressure Variability (BPV), and Heart Rate Variability (HRV). A total of 588 patients from the CSVD registration research database of Henan Province were included in this study, and were divided into two groups according to the presence of RSSI. Clinical data, including demographic characteristics, disease history, laboratory indexes, 24-hour ambulatory blood pressure and electrocardiogram indicators, and imaging markers of CSVD, were collected. Univariate and binary logistic regression analyses were used to study the relationship between RSSI and indicators of laboratory, HRV and BPV in the CSVD population. Multivariate analysis showed that higher 24-hour mean Diastolic Blood Pressure (DBP)[Odds Ratios (OR)=1.083,95% Confidence Intervals (CI)=(1.038,1.129), p < 0.001], Standard Deviation (SD) of 24-hour DBP [OR=1.059,95%CI=(1.000,1.121), p = 0.049], nocturnal mean Systolic Blood Pressure (SBP) [OR=1.020,95%CI=(1.004,1.035), p = 0.012], nocturnal mean DBP [OR=1.025,95%CI=(1.009,1.040), p = 0.002] were independent risk factors for RSSI. In contrast, the decrease of the standard deviation of N-N intervals (SDNN) [OR=0.994,95%CI=(0.989,1.000), p = 0.035] was beneficial to the occurrence of RSSI. In addition, neutrophil counts [OR=1.138,95%CI=(1.030,1.258), p = 0.011], total cholesterol (TC) [OR=1.203,95%CI=(1.008,1.437), p = 0.041] and High-Density Lipoprotein (HDL) [OR=0.391, 95%CI=(0.195,0.786), p = 0.008] were also independently associated with the occurrence of RSSI. After adjusting for confounding factors, except for TC, the other factors remained associated with the occurrence of RSSI. Increased 24-hour mean DBP, nocturnal mean SBP and DBP, SD of 24-hour DBP and decreased SDNN were independently correlated with RSSI occurrence, suggesting that sympathetic overactivity plays a role in the pathogenesis of RSSI.

The correlation between ambulatory blood pressure parameters and cardiovascular risk factors in older adults with high-risk hypertension

Objective: To explore the correlation of 24-hour ambulatory blood pressure (BP) monitoring (ABPM) parameters and cardiovascular risk factors in older adults with high-risk hypertension. Material and method: A cross-sectional study was conducted on 96 older adults (≥ 60 years old) with treated high-risk hypertension. Socio-demographic and cardiovascular risk information were gathered. The patients were performed 24-hour ABPM. Results: The mean age was 70.88 ± 7.86 years, and 64.6% were women. The prevalence of cardiovascular risk factors was as follows: dyslipidemia: 80.2%, family history of hypertension: 54.2%, diabetes mellitus: 51%, smoking: 24%, prior stroke: 11.5%. Significant differences in 24-hour, awake, and sleep systolic BP were observed between men and women. There were significant correlations between 24-hour mean systolic BP with age (r = 0.229, p = 0.025), dyslipidemia (r = 0.223, p = 0.029), family history of hypertension (r = 0.214, p = 0.036), BMI (r = 0.212, p = 0.039), waist circumference (r = 0.226, p = 0.027) and creatinine level (r = 0.207, p = 0.043). There were significant correlations between 24-hour mean diastolic BP with BMI (r = 0.289, p = 0.004) and prior stroke (r = -0.224, p = 0.029). There were significant correlations between 24-hour mean BP with BMI (r = 0.268, p = 0.009), waist circumference (r = 0.220, p = 0.032) and prior stroke (r = -0.215, p = 0.036). Conclusion: There were significant correlations between ABPM parameters and cardiovascular risk factors in older adults with high-risk hypertension. Key words: 24-hour ambulatory blood pressure, cardiovascular risk factors, high-risk hypertension, older adults, correlation.

Long-Term Blood Pressure Control After Hypertensive Pregnancy Following Physician-Optimized Self-Management

Pregnancy hypertension results in adverse cardiac remodeling and higher incidence of hypertension and cardiovascular diseases in later life. To evaluate whether an intervention designed to achieve better blood pressure control in the postnatal period is associated with lower blood pressure than usual outpatient care during the first 9 months postpartum. Randomized, open-label, blinded, end point trial set in a single hospital in the UK. Eligible participants were aged 18 years or older, following pregnancy complicated by preeclampsia or gestational hypertension, requiring antihypertensive medication postnatally when discharged. The first enrollment occurred on February 21, 2020, and the last follow-up, November 2, 2021. The follow-up period was approximately 9 months. Participants were randomly assigned 1:1 to self-monitoring along with physician-optimized antihypertensive titration or usual postnatal care. The primary outcome was 24-hour mean diastolic blood pressure at 9 months postpartum, adjusted for baseline postnatal blood pressure. Two hundred twenty participants were randomly assigned to either the intervention group (n = 112) or the control group (n = 108). The mean (SD) age of participants was 32.6 (5.0) years, 40% had gestational hypertension, and 60% had preeclampsia. Two hundred participants (91%) were included in the primary analysis. The 24-hour mean (SD) diastolic blood pressure, measured at 249 (16) days postpartum, was 5.8 mm Hg lower in the intervention group (71.2 [5.6] mm Hg) than in the control group (76.6 [5.7] mm Hg). The between-group difference was -5.80 mm Hg (95% CI, -7.40 to -4.20; P < .001). Similarly, the 24-hour mean (SD) systolic blood pressure was 6.5 mm Hg lower in the intervention group (114.0 [7.7] mm Hg) than in the control group (120.3 [9.1] mm Hg). The between-group difference was -6.51 mm Hg (95% CI, -8.80 to -4.22; P < .001). In this single-center trial, self-monitoring and physician-guided titration of antihypertensive medications was associated with lower blood pressure during the first 9 months postpartum than usual postnatal outpatient care in the UK. ClinicalTrials.gov Identifier: NCT04273854.

Machine Learning-Based prediction of Post-Treatment ambulatory blood pressure in patients with hypertension

Purpose. Pre-treatment prediction of individual blood pressure (BP) response to anti-hypertensive medication is important to determine the specific regimen for promptly and safely achieving a target BP. This study aimed to develop supervised machine learning (ML) models for predicting patient-specific treatment effects using 24-hour ambulatory BP monitoring (ABPM) data. Materials and Methods. A total of 1,129 patients who had both baseline and follow-up ABPM data were randomly assigned into training, validation and test sets in a 3:1:1 ratio. Utilising the features including clinical and laboratory findings, initial ABPM data, and anti-hypertensive medication at baseline and at follow-up, ML models were developed to predict post-treatment individual BP response. Each case was labelled by the mean 24-hour and daytime BPs derived from the follow-up ABPM. Results. At baseline, 616 (55%) patients had been treated using mono or combination therapy with 45 anti-hypertensive drugs and the remaining 513 (45%) patients had been untreated (drug-naïve). By using CatBoost, the difference between predicted vs. measured mean 24-hour systolic BP at follow-up was 8.4 ± 7.0 mm Hg (% difference of 6.6% ± 5.7%). The difference between predicted vs. measured mean 24-hour diastolic BP was 5.3 ± 4.3 mm Hg (% difference of 6.8% ± 5.5%). There were significant correlations between the CatBoost-predicted vs. the ABPM-measured changes in the mean 24-hour Systolic (r = 0.74) and diastolic (r = 0.68) BPs from baseline to follow-up. Even in the patients with renal insufficiency or diabetes, the correlations between CatBoost-predicted vs. ABPM-measured BP changes were significant. Conclusion. ML algorithms accurately predict the post-treatment ambulatory BP levels, which may assist clinicians in personalising anti-hypertensive treatment.

Effects of Decompressive Cervical Surgery on Blood Pressure in Cervical Spondylosis Patients With Hypertension: A Time Series Cohort Study

The blood pressure of cervical spondylosis (CS) patients with hypertension often returns to normal after decompressive cervical surgery (DCS). However, the effect of DCS on the blood pressure of patients with CS has not been rigorously studied. We recruited 50 consecutive CS patients with hypertension from 2014-2017 and investigated the changes in blood pressure after DCS using a time series design. Ambulatory blood pressure monitoring (ABPM) was performed at 3 and 0 days before DCS and at 30 and 90 days after DCS. The primary outcome was mean 24-hour systolic blood pressure (SBP). Secondary outcomes included mean 24-hour diastolic blood pressure (DBP), office blood pressure, and the percentage of patients on antihypertensive medication. Paired t test was used for assessing the changes in blood pressure over time and a McNemar test was used for comparison among different medication groups. The mean 24-hour SBP did not vary significantly among 4 time points (134.5 ± 14.7, 132.8 ± 14.7, 131.5 ± 13.3, and 133.2 ± 14.6, respectively; P = .42). The mean 24-hour DBP showed a similar trend. However, mean office SBP/DBP decreased significantly from 142.5/82.0 mm Hg before surgery to 127.3/76.6 mm Hg after surgery (both P < .01). The corresponding percentage of patients on antihypertensive medication decreased significantly, from 84% to 54% (P < .01). This study confirmed previous findings of reduction in office blood pressure associated with DCS among CS patients with hypertension. However, this was not confirmed by multiple-time series of 24-hour ABPM. 3.

The relationship between mean platelet volume and reverse dipping blood pressure pattern in patients with essential hypertension

ABSTRACT Objective An association between increased mean platelet volume (MPV) and cardiovascular events is well established. Recent studies suggest that a nondipper blood pressure pattern is closely related to increased MPV. Because little information has been revealed about the relationship between reverse dipper hypertension (RDHT) and MPV, we aimed to investigate this relation. Methods A total of 317 patients were retrospectively evaluated by analyzing the records of ambulatory blood pressure monitoring (ABPM). Patients were categorized into three groups according to their ABPM values as RDHT (n = 63), non-dipper hypertension (NDHT) (n = 95), and dipper hypertension (DHT) groups (n = 159). MPV and biochemical analyses were recorded from the hospital database. Results The largest MPV was found in patients with RDHT, followed by patients with NDHT and DHT group (9.1 ± 0.4 fl, 8.8 ± 0.6 fl, and 8.6 ± 0.5 fl, respectively, for all p < .05). MPV was positively correlated with mean 24-hour systolic blood pressure (SBP), mean 24-hour diastolic blood pressure (DBP), mean daytime SBP, mean nighttime SBP and mean nighttime DBP. In multivariate logistic regression analysis, MPV (OR 1.761, 95% CI 1.329 to 2.334, p = .001) and age (OR 1.065, 95% CI 1.019 to 1.113, p = .001) were found to be associated with RDHT. ROC curve analysis of MPV for prediction of RDHT showed that at the cutoff value of >9,1 fl with a sensitivity of 60% and specificity of 69%, respectively (AUC = 0.696 ± 0.035, 95% CI: 0.627–0.764). Our data show that the RDHT pattern is associated with increased MPV values in patients with essential hypertension.

THE RELATIONSHIP BETWEEN CIRCADIAN RHYTHM OF BLOOD PRESSURE AND LEFT ATRIAL PHASIC FUNCTION IN HYPERTENSION

Objective: Objective: We used two dimensional speckle tracking echocardiography (2DSTE)-based strain and strain rate imaging to evaluate left atrial (LA) mechanics and investigated its correlation with circadian rhythm of blood pressure in essential hypertension (HT). Design and method: Design and Methods: We enrolled 249 HT patients. All subjects were evaluated by ambulatory 24-hour blood pressure monitoring and 2D-STE. According to blood pressure (BP) patterns, these patients were divided into three groups. Group I (dipper, n = 91), patients with a 10%-20% reduction in BP at nighttime; Group II (non-dipper, n = 129), patients with a &lt; 10% reduction in BP at nighttime; Group III (reverse dipper, n = 29), patients with higher BP at nighttime compared with daytime. The strain and strain rate images were studied, and the following parameters were measured: LA reservoir strain and strain rate (LAS-S, LASR-S), LA conduit strain and strain rate (LAS-E and LASR-E), LA booster strain and strain rate (LAS-A and LASR-A). LA stiffness index (LASI) was defined as the ratio of E/e‘ to LAS-S. In the present study, we also explored the correlation between LASI and cardiovascular risk factors as well as ambulatory blood pressure indexes. The factors related to LASI were evaluated by multivariate regression analysis to find the independent factors. Results: Results: LASI was significantly higher in Group III than Group I (p &lt; 0.05). LAS-E and LASR-E were significantly lower in Group III than Group I and II (p &lt; 0.05 for both). However, there were no significant differences between the Group I and II (p &gt; 0.05). Otherwise, LAS-S, LASR-S, LAS-A and LASR-A were not significantly different among these three groups. We also found LASI was correlated with ages, diabetes, courses of HT, 24-hour mean systolic blood pressure (24h-mSBP), 24-hour mean diastolic blood pressure (24h-mDBP), daytime mean SBP (d-SBP), nighttime mean SBP (n-SBP) and nighttime mean DBP (n-DBP). Multivariate regression analysis revealed that age, n-SBP and n-DBP were independent factors related to LASI. Conclusions: Conclusions: Left atrial function is associated with circadian rhythm of blood pressure. Nocturnal blood pressure may have more influence on left atrial stiffness and conduit function.

Safety and Efficacy of a New Renal Denervation Catheter in Hypertensive Patients in the Absent of Antihypertensive Medications: A Pilot Study.

Aim The aim of present study was to determine the safety and efficacy of a new renal artery denervation system for treatment of hypertensive patients. Methods Hypertensive patients with mean office systolic blood pressure ≥150mmHg and ≤180mmHg or an average of 24-hour ambulatory systolic blood pressure ≥145mmHg and ≤170mmHg after stopping hypertensive medications for 2 weeks or more were enrolled to undergo renal denervation (RDN) using a new RDN system. Changes in office blood pressure and mean 24-hour ambulatory blood pressure and safety were assessed after 6 months. Results Fifteen patients underwent RDN and followed up for 6 months. At the 6-month follow-up, office systolic blood pressure decreased 11.5±9.9mmHg (P<0.01) and office diastolic blood pressure decreased 6.9±4.8mmHg (P<0.01); mean 24-hour ambulatory systolic blood pressure decreased 7.5±7.7mmHg (P<0.05) and mean 24-hour diastolic blood pressure decreased 3.3±4.7mmHg (P>0.05) compared to baseline values. There were no serious RDN-related adverse events during follow-up. Conclusion Our results demonstrate that the new RDN system is safe and could significantly reduce blood pressure in hypertensive patients in the absence of antihypertensive medications. This trial is registered with ChiCTR1800017815.

Untreated Obstructive Sleep Apnea Is Associated With Myocardial Injury Independent of Blood Pressure Control in Hypertension.

Obstructive sleep apnea (OSA) and hypertension are independent risk factors of cardiovascular morbidities. This study aims to investigate the relationship between OSA, blood pressure (BP) control, and myocardial injury in patients with difficult-to-control hypertension. Patients with hypertension who required three or more medications were prospectively recruited at a tertiary referral center. In-laboratory polysomnography, followed by blood tests for fasting glucose, glycated hemoglobin, lipids, high-sensitivity troponin I (hsTnI), B-type natriuretic peptide (BNP), C-reactive protein, and advanced oxidation protein products were performed. After polysomnography, 24-hour ambulatory BP monitoring was arranged. A total of 98 participants were analyzed, with mean age 51 ± 9 years and body mass index 30 ± 5 kg/m2. Previously undiagnosed severe OSA (apneahypopnea index [AHI] ≥ 30 events/h) was present in 51 patients (52%). hsTnI was negatively correlated with nocturnal dip in systolic BP (r = -.205, P = .048). After controlling for confounders, including BP control, AHI and oxygen desaturation index (ODI) were positively correlated with hsTnI (r = .282, P = .009 and r = .279, P = .010, respectively) and C-reactive protein (r = .302, P = .005 and r = .285, P = .008, respectively), but not with BNP or advanced oxidation protein products. Age, ODI, and loss of nocturnal systolic BP dip were significant determinants of hsTnI level (β = .225, P = .022; β = .293, P = .003; and β = -.215, P = .029; R2 = .151). Age, female sex, 24-hour mean diastolic BP, and metabolic syndrome, but not indices of apnea severity, were predictors of BNP level. Unrecognized severe OSA was common in patients with difficult-to-control hypertension, and OSA severity was associated with myocardial injury, independent of BP control with medications. Registry: ClinicalTrials.gov, Title: A Cross-sectional Study of the Occurrence and Effect of Obstructive Sleep Apnea in Subjects With Resistant Hypertension, Identifier: NCT00843583, URL: https://clinicaltrials.gov/ct2/show/NCT00843583.

Prevalence, risk factors, and prognostic significance of masked hypertension in diabetic patients.

The aims of present study were to evaluate the prevalence, risk factors, and prognostic significance of masked hypertension in diabetic patients. Using a cross-sectional design, 266 patients with documented type 2 diabetes mellitus and clinic blood pressure (BP) <140/90 mm Hg without antihypertension treatment were enrolled; 24-hour ambulatory BP monitoring was applied to evaluate mean 24-hour systolic/diastolic BP. Demographics, medical histories, and medications usage were obtained using questionnaire. Fasting venous blood was drawn for biochemical analysis. Approximately 26.5% of participants were diagnosed as masked hypertension with mean 24-hour systolic BP >130 mm Hg and/or mean 24-hour diastolic BP >80 mm Hg. Compared with those without masked hypertension, other than significantly higher mean 24-hour systolic/diastolic BP, patients with masked hypertension were more elderly, had higher serum glycated hemoglobin (HbA1c) and C-reactive protein (CRP) levels and higher prevalence of coronary heart disease (CHD). Multivariate regression analysis showed that aging, increased HbA1c and CRP levels, and prevalent CHD were independently associated with masked hypertension. Logistic regression analysis revealed that after adjusted for traditional risk factors including age, male sex, smoking status, low-density lipoprotein-cholesterol, CRP, clinic systolic BP, and HbA1c, masked hypertension remained independently associated with prevalent cardiovascular disease (CVD), with odds ratio of 1.31 and 95% confidence interval of 1.11 to 1.85. In summary, in diabetic patients, concurrent masked hypertension increases the odds of having CVD. Future randomized controlled trials are warranted to investigate whether screening and managing masked hypertension could reduce cardiovascular events in diabetic patients.

Long-term follow-up of cardiovascular risk factors after exercise training in obese children

We previously demonstrated beneficial effects of physical activity on cardiovascular disease (CVD) risk factors, body mass index (BMI) and fat mass in pre-pubescent obese children. The aim of this study was to determine whether these changes were maintained 2 years later. Two years after the Randomised Controlled Trial, we performed a follow-up study with 20 of 38 subjects (11.4 ± 1.8 years). Outcomes included blood pressure (BP) by ambulatory monitoring; arterial function and structure using high-resolution ultrasound, BMI, body composition by dual-energy x-ray absorptiometry (DXA), physical activity using accelerometer, and biological markers. During the 2-year follow-up period, mean 24-hour diastolic BP z-score significantly decreased (1.4 ± 1.2 vs. 0.3 ± 1.4, p = 0.04), while systolic BP z-score was slightly reduced (2.4 ± 1.5 vs. 1.4 ± 1.7, p = 0.067). Blood pressure changes were greater in children who diminished their BMI z-score compared with the ones who did not. Systolic hypertension rates dropped from 50 to 28% and diastolic hypertension from 42 to 6%. In addition, arterial intima-media thickness (0.51 ± 0.03 vs. 0.51 ± 0.06, p = 0.79), BMI z-score (2.9 ± 0.8 vs. 2.9 ± 1.1 kg.cm(-2), p = 0.27), body fat (41.9 ± 6.9 vs. 42.8 ± 6.7%; p = 0.39) and physical activity count (703 ± 209 vs. 574 ± 244 cpm, p = 0.30) were stable. To our knowledge, this is the first study reporting that beneficial effects on adiposity and CVD risk factors of a physical activity centred intervention are sustained 2 years after the cessation of training in obese children. Subjects stabilized BMI z-score and maintained physical activity with further improvement of BP and stabilization of arterial wall remodelling. We conclude that it is important to encourage physical activity in this population. Effects of Aerobic Exercise Training on Arterial Function and Insulin Resistance Syndrome in Obese Children: A Randomised Controlled Trial: NCT00801645.

Hypertension and Cerebral Vascular Reactivity in Childhood: Challenge and Opportunity

HomeStrokeVol. 42, No. 7Hypertension and Cerebral Vascular Reactivity in Childhood: Challenge and Opportunity Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBHypertension and Cerebral Vascular Reactivity in Childhood: Challenge and Opportunity Rebecca Ichord, MD Rebecca IchordRebecca Ichord From the Department Neurology & Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA. Search for more papers by this author Originally published26 May 2011https://doi.org/10.1161/STROKEAHA.111.617803Stroke. 2011;42:1805–1806Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 See related article, pages 1834–1838The study of childhood origins of adult cardiovascular disease has grown dramatically in the past decade. Childhood-onset obesity, hypertension, and hyperlipidemia confer increased risk of cardiovascular morbidity and mortality in adulthood.1 The mechanisms for these relationships are incompletely understood. Even less is known about the extent to which end-organ injury referable to these risk factors actually begins during childhood. The study by Wong et al2 provides new insights concerning the early-life effects of hypertension on cerebrovascular physiology. The rapid increase in prevalence of cardiovascular risk factors such as obesity and hypertension among US children underscores the public health implications of their observations.Wong et al evaluated cerebrovascular reactivity to hypercapnia among children with essential hypertension compared with normotensive control subjects. They tested the hypothesis that hypertension is associated with impaired hypercapnic reactivity measured by increased cerebral blood flow velocity on transcranial Doppler. Hypertension was carefully measured and quantified using well-defined and standardized 24-hour ambulatory blood pressure monitoring methods. Cerebrovascular reactivity measures were likewise well-defined and carried out in a standardized manner. These transcranial Doppler data on cerebrovascular reactivity are interesting and novel in their own right, because there are few published studies reporting transcranial Doppler data, much less hypercapnic reactivity, in awake, neurologically well children. They found hypercapnic reactivity is decreased in hypertensive children compared with normotensive control subjects with a negative linear correlation between reactivity and both mean 24-hour diastolic blood pressure and diastolic load. The relatively small sample size precluded additional analyses of potential modifying factors such as sex, race, age, and the effect of treatment with antihypertensive drugs.Having confirmed that hypertension is associated with decreased cerebrovascular reactivity, as is seen in adults, a number of compelling questions beg to be further evaluated. The authors have raised the question, for example, as to whether impaired cerebrovascular reactivity with hypertension is associated with impaired neurocognitive function in children as is seen in adults. A few tantalizing clues already exist in a small number of published studies that support an association between hypertension and diminished neurocognitive function and academic attainment in children.3,4Much more study is needed, however, to reproduce these observations in larger populations to determine the longitudinal trends through different stages of childhood and beyond to adult life and, importantly, to establish what the causal relationships and mechanisms may be. For example, there are no published studies evaluating neuroimaging correlates of neurocognitive impairments in hypertensive children. The existence of potentially quantifiable and anatomically specific structural neuroimaging markers of cerebral injury from childhood hypertension may provide additional insights concerning mechanism as well as objective end points for interventions. Juonala et al5 reported age-dependent associations between cardiovascular risk factors and the findings of early atherosclerosis on vessel imaging in children and adolescents. It would be of great interest to evaluate the relative contribution of childhood hypertension compared with other cardiovascular risk factors such as obesity and hyperlipidemia on vessel wall markers of early atherosclerosis and to understand how this is related, if at all, to the development of disturbed cerebrovascular reactivity.Ultimately, a clearer understanding of the mechanisms and epidemiology of childhood precursors of cerebrovascular disease will be essential for designing interventions and subjecting these to clinical trial. The magnitude of the public health implications of these problems can hardly be overstated. Studies such as that of Dr Wong and colleagues are groundbreaking by demonstrating that understanding and effectively preventing chronic adult-onset cardiovascular and cerebrovascular disease may best begin in childhood. Moreover, the dividends of treating childhood precursors of adult disease may become evident in childhood by halting or reversing clinically significant end-organ injury even early in life.DisclosuresNone.FootnotesThe opinions in this editorial are not necessarily those of the editors or of the American Heart Association.Correspondence to Rebecca Ichord, MD, CTRB 10th Floor, Department of Neurology, Children's Hospital of Philadelphia, 3501 Civic Center Boulevard, Philadelphia, PA 19104. E-mail [email protected]chop.edu

Genetic Architecture of Ambulatory Blood Pressure in the General Population

Genetic determinants of blood pressure are poorly defined. We undertook a large-scale, gene-centric analysis to identify loci and pathways associated with ambulatory systolic and diastolic blood pressure. We measured 24-hour ambulatory blood pressure in 2020 individuals from 520 white European nuclear families (the Genetic Regulation of Arterial Pressure of Humans in the Community Study) and genotyped their DNA using the Illumina HumanCVD BeadChip array, which contains ≈50 000 single nucleotide polymorphisms in &gt;2000 cardiovascular candidate loci. We found a strong association between rs13306560 polymorphism in the promoter region of MTHFR and CLCN6 and mean 24-hour diastolic blood pressure; each minor allele copy of rs13306560 was associated with 2.6 mm Hg lower mean 24-hour diastolic blood pressure ( P =1.2×10 −8 ). rs13306560 was also associated with clinic diastolic blood pressure in a combined analysis of 8129 subjects from the Genetic Regulation of Arterial Pressure of Humans in the Community Study, the CoLaus Study, and the Silesian Cardiovascular Study ( P =5.4×10 −6 ). Additional analysis of associations between variants in gene ontology-defined pathways and mean 24-hour blood pressure in the Genetic Regulation of Arterial Pressure of Humans in the Community Study showed that cell survival control signaling cascades could play a role in blood pressure regulation. There was also a significant overrepresentation of rare variants (minor allele frequency: &lt;0.05) among polymorphisms showing at least nominal association with mean 24-hour blood pressure indicating that a considerable proportion of its heritability may be explained by uncommon alleles. Through a large-scale gene-centric analysis of ambulatory blood pressure, we identified an association of a novel variant at the MTHFR/CLNC6 locus with diastolic blood pressure and provided new insights into the genetic architecture of blood pressure.

Effect of Combining Extended‐Release Carvedilol and Lisinopril in Hypertension: Results of the COSMOS Study

Hypertension treatment commonly requires multiple agents to achieve target blood pressure (BP). β-blockers and angiotensin-converting enzyme inhibitors (ACEIs) are commonly co-prescribed in clinical practice although few data are available that test their additivity on BP lowering. The efficacy and safety of once-daily extended-release carvedilol (carvedilol CR) combined with the ACEI lisinopril in a double-blind, randomized, factorial design study were studied. Patients (N=656) with stage 1 or 2 hypertension were randomized evenly to 1 of 15 groups for 6 weeks: carvedilol CR monotherapy 20 mg, 40 mg, or 80 mg/d; lisinopril monotherapy 10 mg, 20 mg, or 40 mg/d; or 1 of 9 combinations of carvedilol CR plus lisinopril initiated simultaneously. Primary efficacy measures (assessed by ambulatory BP monitoring [ABPM]) were change from baseline in 24-hour mean diastolic BP (DBP) and in trough (20-24 hours) DBP. Continuous efficacy variables were assessed using analysis of covariance. Whether any combination dose was superior to its monotherapy components was assessed using the Hung AVE procedure. Despite the presence of additional BP lowering observed with most of the combinations compared with their monotherapy components, the Hung AVE test was not significant for either primary efficacy measures. Post hoc analyses of the high-dose combination groups (carvedilol CR/lisinopril regimens of 80/10 mg, 80/20 mg, 80/40 mg, 20/40 mg, and 40/40 mg) showed a significant treatment difference compared with both carvedilol CR 80 mg and lisinopril 40 mg for 24-hour mean DBP but not for trough DBP. With the exception of dizziness, individual adverse events did not increase with ascending doses or combinations. The superiority of initiating combination treatment with carvedilol CR and lisinopril compared with the monotherapy components was not demonstrated with the ABPM measurements. Nonetheless, the post hoc assessment combining all high-dose groups did produce significant 24-hour mean BP reduction when compared with the high-dose monotherapy groups. The tolerability profile of initiating combination therapy was generally comparable to the initiation of treatment with monotherapy.

Effects of the renin inhibitor MK-8141 (ACT-077825) in patients with hypertension

The renin inhibitor MK-8141 (ACT-077825) demonstrates substantial immunoreactive active renin (ir-AR) increase (sevenfold) without a persistent plasma renin activity (PRA) decrease. The present study assessed the antihypertensive efficacy of MK-8141 in hypertensive patients. In this double-blind, placebo- and active comparator-controlled study, 195 patients with hypertension (trough sitting diastolic blood pressure ≥92 to <105 mm Hg, trough sitting systolic blood pressure <170 mm Hg, and 24-hour mean diastolic blood pressure [DBP] ≥80 mm Hg) were randomized to one of four treatments (stratified by race, black versus others): MK-8141 250 mg, MK-8141 500 mg, enalapril 20 mg, or placebo. Blood pressure was measured at trough and as 24-hour ambulatory blood pressure monitoring. The primary end point was change from baseline in 24-hour mean ambulatory DBP measured after 4 weeks. At week 4, the change from baseline in 24-hour mean (95% CI) ambulatory DBP compared with placebo was −1.6 mm Hg (−4.2, 1.1), −1.1 mm Hg (−3.9, 1.6), and −4.9 (−7.5, −2.2) for MK-8141 250 mg, MK-8141 500 mg, and enalapril 20 mg, respectively. Only mean ambulatory DBP-lowering with enalapril 20 mg was statistically significant. Enalapril, but not MK-8141, also significantly lowered 24-hour mean ambulatory systolic blood pressure (SBP) compared with placebo (−6.7 mm Hg [−10.5, −2.8]). Neither enalapril nor MK-8141 significantly lowered trough DBP and SBP compared with placebo. MK-8141 was generally well tolerated. In patients with hypertension, MK-8141 (ACT-077825) did not produce significant blood pressure–lowering efficacy despite a demonstrated effect of the drug on ir-AR, in the absence of durable PRA suppression.

Beneficial Effect of Efonidipine, an L- and T-Type Dual Calcium Channel Blocker, on Heart Rate and Blood Pressure in Patients With Mild-to-Moderate Essential Hypertension

Background and ObjectivesEfonidipine hydrochloride, an L- and T-type dual calcium channel blocker, is suggested to have a heart rate (HR)-slowing action in addition to a blood pressure (BP)-lowering effect. The aim of this study was to determine the effect of efonidipine on HR and BP in patients with mild-to-moderate hypertension.Subjects and MethodsIn a multi-center, prospective, open-labeled, single-armed study, we enrolled 53 patients who had mild-to-moderate hypertension {sitting diastolic BP (SiDBP) 90-110 mmHg}. After a 2-week washout, eligible patients were treated with efonidipine (40 mg once daily for 12 weeks). The primary end point was the change in HR from baseline to week 12. The secondary end-point included the change in trough sitting BP and 24-hour mean BP between baseline and week 12. Laboratory and clinical adverse events were monitored at each study visit (4, 8, and 12 weeks).ResultsFifty-two patients were included in the intention-to-treat analysis. After 12 weeks of treatment with efonidipine, the resting HR decreased significantly from baseline to week 12 {from 81.5±5.3 to 71.8±9.9 beats/minute (difference, -9.9±9.0 beats/minute), p<0.0001}. The trough BP {sitting systolic blood pressure (SiSBP) and SiDBP} and 24-hour mean BP also decreased significantly (SiSBP: from 144.6±8.2 to 132.9±13.5 mmHg, p<0.0001; SiDBP: from 96.9±5.4 to 88.3±8.6 mmHg, p<0.0001, 24-hour mean systolic BP: from 140.4±13.5 to 133.8±11.6 mmHg, p<0.0001; 24-hour mean diastolic BP: from 91.7±8.7 to 87.5±9.5 mmHg, p<0.0001).ConclusionEfonidipine was effective in controlling both HR and BP in patients with mild-to-moderate hypertension.

Effect of Exercise Training on 24‐Hour Ambulatory Blood Pressure Monitoring in Heart Failure Patients

The aim of this study was to evaluate the 24-hour ambulatory blood pressure monitoring (ABPM) response to exercise training (ET) in heart failure (HF) patients. Twelve HF patients and 15 sedentary healthy controls underwent ET for 2 months (3 times per week from 80%-90% of the ventilatory threshold). ABPM was performed before and 2 days after the last exercise season. Despite the fact that ET in HF patients was associated with significant improvements in peak oxygen consumption (pVO2), there were no significant changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR). On the other hand, controls decreased 24-hour mean SBP (117+/-8-115+/-9 mm Hg, P=.019) and 24-hour mean DBP (73+/-6-71+/-5 mm Hg, P=.016), mainly at nighttime SBP (107+/-8-103+/-9, P=.0004) and DBP (63+/-5-59+/-5 mm Hg, P<.0001). No changes in HR were found in controls. Values of 24-hour blood pressure did not change with ET in HF patients.

Effect of Sitagliptin, a Dipeptidyl Peptidase‐4 Inhibitor, on Blood Pressure in Nondiabetic Patients With Mild to Moderate Hypertension

The effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on ambulatory blood pressure was assessed in nondiabetic patients with mild to moderate hypertension in a randomized, double-blind, placebo-controlled, 3-period crossover study. Nineteen patients on stable treatment with antihypertensive agent(s) received sitagliptin 100 mg b.i.d., 50 mg b.i.d., or placebo for 5 days, with at least a 7-day washout interval between periods. Twenty-four-hour ambulatory blood pressure, including systolic blood pressure, diastolic blood pressure, and mean arterial pressure, were monitored on days 1 and 5. Relative to placebo on day 1, the mean difference in 24-hour systolic blood pressure was -0.9 mm Hg (90% confidence interval: -2.9 to 1.1; P = .46) with sitagliptin 50 mg b.i.d. and -2.8 mm Hg (90% confidence interval: -4.9 to -0.8; P < .05) with 100 mg b.i.d. On day 5, the mean difference in 24-hour systolic blood pressure was -2.0 mm Hg (90% confidence interval: -3.5 to -0.4; P < .05) with 50 mg b.i.d. and -2.2 mm Hg (90% confidence interval: -3.7 to -0.6; P < .05) with 100 mg b.i.d. relative to placebo. For 24-hour diastolic blood pressure, there were no between-group differences in mean 24-hour diastolic blood pressure on day 1. On day 5, sitagliptin 50 mg and 100 mg b.i.d significantly (P < .05) lowered mean 24-hour diastolic blood pressure by -1.8 mm Hg (90% confidence interval: -2.8 to -0.8) and -1.6 mm Hg (90% confidence interval: -2.6 to -0.7), respectively, relative to placebo. Sitagliptin produced small but statistically significant reductions of 2 mm Hg to 3 mm Hg in 24-hour ambulatory blood pressure measurements acutely (day 1) and at steady state (day 5), and was generally well tolerated in nondiabetic patients with mild to moderate hypertension.

757 Ambulatory blood pressure monitoring and 2D-echo in predicting non arrhythmic cardiac events after ICD implantation for MADIT II criteria. A new prognostic index

Aim:We compared ambulatory blood pressure monitoring (ABPM) and 2D echo to predict cardiac death and heart failure (combined end-point) after implantation of internal cardiac defibrillator (ICD) in 135 consecutive patients, all fulfilling MADIT II criteria; 115 men and 20 females, mean age 66±7, 86 with dual chamber ICD, 20 with cardiac resinchronization therapy (CRT), 29 patients received single chamber ICD. Methods: ABPM was performed 2 weeks after ICD implantation on outpatients basis with Spacelabs 90207. Mostpatients were on medical therapy with betablockers (75%), ace-inhibitors (90%) and diuretics (90%) at the time of ABPM evaluation. ABPM variables considered were: mean 24hour Systolic Blood Pressure (m24hSBP), mean 24hour Diastolic Blood Pressure (m24hDBP), mean 24h Heart Rate (m24hHR), Pulse pressure (PP). 2D-echo was performed before ICD implantation. LVEF was calculated by Simpson rule. Age, Blood Creatinine (BC) and CRT were also considered in statistical analysis. Results: At 1 year follow-up there were 25 cardiac events (18%), 4 cardiac deaths (cardiogenic shock) and 21 hospitalizations for pulmonary oedema or congestive heart failure. Age (p= 0.007), m24hDBP (p=0.02) and BC (p=0.02) were significantly associated with events, but not LVEF (p = 0.6), m24hSBP (p=0.09), m24hHR (p=0.08), PP (p= 0.27) and CRT (p=0.96). Only age (Odds ratio 3.8, p=0.01) and m24hDBP (Odds Ratio 2.3 p=0.04) remained significantly associated with clinical events in multivariate analysis. A prognostic index (PI) was built from these variables (m24hDBP and age) according to the formula: 120− age + m24hDBP. PI was significantly lower in patients with clinical events (107± 9 vs 121± 14, p 108 remained event-free in contrast with 55% of patients with PI ≤108 (p <0.001 by Log-rank test). Multivariate Cox regression analysis (including as covariates PI, age, LVEF, m24hDBP) confirmed that only PI was significantly associated with events (Hazard Ratio 11.4 with 95% confidence interval 2.4-55 with p =0.003). Conclusion:The PI built bym24hDBP and age could be a simple method to stratify the hemodynamic risk in patients with uniformally depressed LVEF (≤ 30% by MADIT II criteria) and ICD. .

Ambulatory Blood Pressure and Endothelial Dysfunction in Patients with Autosomal Dominant Polycystic Kidney Disease

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED), which is an early manifestation of vascular injury, has been shown in patients with ADPKD. However, the association between ambulatory blood pressure and ED has not been investigated in these patients. Forty-one patients with ADPKD having well-preserved renal function were included in the study. Ambulatory blood pressure monitoring was performed in all patients. Patients were divided into dipper and non-dipper groups. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation was expressed as the percentage change in the brachial artery diameter from baseline to reactive hyperemia. The mean 24-hour systolic blood pressure was similar in both groups (125.5 ± 10.7 mmHg in dippers and 121.2 ± 14.3 in non-dippers, p > 0.05). There was also no significant difference between the mean 24-hour diastolic blood pressures in both groups (82.3 ± 9.6 mmHg in dippers and 77.1 ± 8.6 mmHg in non-dippers, p > 0.05). The nocturnal fall rate in systolic blood pressure was 11.1 ± 1.2% in dippers and 0.98 ± 0.9% in non-dippers (p = 0.001). The nocturnal fall rate in diastolic blood pressure was 14.0 ± 0.9% in dippers and 3.8 ± 0.8% in non-dippers (p = 0.001). Endothelial-dependent dilatation was significantly higher in dippers compared to non-dippers (6.22 ± 4.14% versus 3.57 ± 2.52%, p = 0.025). Non-dipper patients with ADPKD show significant ED, which has an important impact on cardiovascular morbidity and mortality.