Greater Systolic Blood Pressure Research Articles

Impaired bone matrix glycoprotein pattern is associated with increased cardio-metabolic risk profile in patients with type 2 diabetes mellitus

Osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC) are matrix glycoproteins which mediate bone mineralization; moreover, their effects on glucose/insulin homeostasis have recently been demonstrated. Higher circulating OPN and OPG levels have been associated with the presence of insulin resistance, atherosclerosis and coronary heart disease. No data are available on contextual changes of these markers in type 2 diabetes mellitus (T2DM). Therefore, aims of this study were to evaluate serum OPN, OPG and OC levels in T2DM patients and their clinical correlates. We recruited 83 consecutive T2DM patients referring to our diabetes outpatient clinics at Sapienza, University of Rome, and 71 non-diabetic sex and age-comparable subjects as a control group. Study population underwent metabolic characterization and carotid ultrasound for intima-media thickness measurement. Plasma OPN, OPG and OC were measured by MILLIPLEX Multiplex Assays Luminex. T2DM patients had significantly higher circulating OPN and OPG levels than controls (14.3 ± 13.6 vs 10.6 ± 13.7ng/ml p < 0.001, 0.70 ± 0.60 vs 0.54 ± 4.1ng/ml, p = 0.02) while OC levels were similar in the two cohorts (6.35 ± 5.8 vs 7.80 ± 7.0ng/ml, p = n.s). OPN and OPG positively correlated with greater systolic blood pressure (SBP) values, HOMA-IR and HOMA-β, and with the presence of dyslipidemia and carotid atherosclerosis. The association between greater OPN and OPG levels and SBP was independent from possible confounders (both p = 0.01). Circulating OPN and OPG levels are increased in T2DM patients and identify a particularly unfavourable metabolic profile, mostly expressed by higher SBP. Bone peptides may represent novel markers of vascular stress and accelerated atherosclerosis in diabetes, constituting a possible tool for cardiovascular risk stratification in diabetes.

Pharmacological Treatment of Arterial Hypertension in Children and Adolescents: A Network Meta-Analysis.

Pharmacological treatment is indicated in children and adolescents with hypertension unresponsive to lifestyle modifications, but there is not enough evidence to recommend 1 class of antihypertensive drugs over others. We performed a network meta-analysis to compare the results of available randomized clinical trials on pharmacological treatment of pediatric hypertension. From a total of 554 potentially relevant studies, 13 randomized placebo-controlled clinical trials enrolling ≥50 patients and a follow-up ≥4 weeks were included. The reduction of systolic blood pressure (SBP) and diastolic BP (DBP) after treatment were the coprimary end points. A total of 2378 pediatric patients, with a median age of 12 years, were included in the analysis. After a median follow-up of 35 days, lisinopril and enalapril were found to be superior to placebo in reducing SBP and DBP, whereas only for DBP, losartan was found to be superior to placebo and lisinopril and enalapril were found to be superior to eplerenone. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were associated with a greater SBP and DBP reduction compared with placebo, likewise the mineralocorticoid receptor antagonist was inferior to angiotensin-converting enzyme inhibitors in DBP reduction. The analysis was adjusted for study-level mean age, percentage of women, mean baseline blood pressure, and mean weight, only the latter significantly affected DBP reduction. According to the present analysis, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers could represent the best choice as antihypertensive treatment for pediatric hypertension. However, because of the paucity of available data for the other classes of antihypertensive drugs, definitive conclusions are not allowed and further randomized controlled trials are warranted.

Efficacy and Safety of Ertugliflozin across Racial Groups in Patients with Type 2 Diabetes Mellitus (T2DM)

Ertugliflozin (ERTU) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor for the treatment of T2DM. Pharmacokinetic analysis indicates ERTU plasma exposure is not affected by race. The efficacy and safety of ERTU by race was assessed in pooled analyses from 3 randomized, double-blind, placebo (PBO)-controlled, Phase 3 trials. Patients received ERTU 5 mg, 15 mg or PBO for 26 weeks. Least-squares (LS) means for change from baseline to Week 26 were calculated for hemoglobin A1C (A1C), body weight (BW) and systolic blood pressure (SBP). General and prespecified adverse events (AEs) were evaluated. The analysis included 1544 patients (white 73%; black 7%; asian 15%; other 5%). Baseline demographics and characteristics were generally similar across treatment groups and racial groups, except lower mean BW and BMI in Asians. No notable differences in A1C, BW and SBP reductions were observed across racial groups (Table 1), except for a greater SBP reduction observed in Blacks. Across racial groups there were no notable differences in general AEs with ERTU vs. PBO. An increase in genital mycotic infections was seen with ERTU vs. PBO across all racial groups. Precision of between-treatment effects was limited in Blacks, Asians and Others due to small group size. ERTU efficacy and safety was generally similar across racial groups although a greater reduction in SBP was observed in Blacks.Table 1. Least-squares Mean Change (Placebo-corrected) in A1C, Body Weight and SBP from Baseline to Week 26 by Racial Group (Excluding Rescue Approach)RaceErtugliflozin Dose (N)*δA1C (%) LS mean (95% CI)δBody Weight (kg) LS mean (95% CI)δSBP (mmHg) LS mean (95% CI)Overall5 mg (519)-0.8 (-0.9, -0.7)-1.8 (-2.2, -1.4)-3.4 (-4.8, -2.0)15 mg (510)-0.9 (-1.0, -0.8)-1.8 (-2.2, -1.4)-3.5 (-4.9, -2.0)White5 mg (382)-0.8 (-1.0, -0.7)-1.9 (-2.3, -1.4)-3.3 (-4.9, -1.6)15 mg (374)-1.0 (-1.1, -0.8)-1.7 (-2.2, -1.2)-3.5 (-5.1, -1.8)Black5 mg (34)-0.7 (-1.2, -0.2)-1.1 (-2.8, 0.6)-9.5 (-16.0, -2.9)15 mg (37)-0.8 (-1.3, -0.3)-2.2 (-3.9, -0.6)-8.1 (-14.6, -1.7)Asian5 mg ( 77)-0.8 (-1.1, -0.5)-1.9 (-2.6, -1.1)-1.8 (-5.3, 1.8)15 mg (77)-1.0 (-1.3, -0.8)-2.1 (-2.8, -1.4)-1.9 (-5.4, 1.7)Other5 mg (26)-0.3 (-0.9, 0.3)-1.7 (-3.2, -0.2)-3.5 (-11.3, 4.4)15 mg (22)-0.9 (-1.5, -0.3)-1.5 (-3.0, 0.1)-4.4 (-12.8, 3.9)CI, confidence interval; LS, Least Squares *N is the number of randomized patients who took at least one dose of study medication. The LS Means for Change from Baseline to Week 26 were estimated from a constrained longitudinal data analysis model. Disclosure J. Liu: None. L. Tarasenko: Employee; Self; Pfizer Inc.. Stock/Shareholder; Self; Pfizer Inc.. A. Pong: None. S. Huyck: Employee; Self; Merck &amp; Co., Inc.. L. Wu: None. J.P. Mancuso: Employee; Self; Pfizer Inc.. Stock/Shareholder; Self; Pfizer Inc.. Employee; Spouse/Partner; Pfizer Inc.. Stock/Shareholder; Spouse/Partner; Pfizer Inc. S. Terra: Employee; Self; Pfizer Inc. B. Lauring: Employee; Self; Merck &amp; Co., Inc..

The Association of Posttraumatic Stress Disorder With Clinic and Ambulatory Blood Pressure in Healthy Adults.

Posttraumatic stress disorder (PTSD) is associated with incident cardiovascular risk. We tested the association of PTSD with clinic and ambulatory blood pressure (ABP) in a sample of healthy participants and tested ABP reactivity to anxiety as a mechanism by which PTSD may influence blood pressure (BP). Participants were originally enrolled during workplace BP screenings at three sites; approximately 6 years (standard deviation = 1.0) later, they completed nine clinic BP assessments within three visits, 1 week apart. Before the third visit, participants were screened for PTSD (≥33 on the PTSD Checklist-Civilian) and depression (Beck Depression Inventory) and then completed 24-hour ABP monitoring with electronic diary assessment of anxiety (0-100) at each awake reading. Of 440 participants, 92 (21%) screened positive for PTSD. In regression models adjusted for depression and demographic and clinical variables, PTSD was associated with greater mean systolic BP (3.8 mm Hg clinic [95% confidence interval {CI}] = 1.1-6.5, p = .006), 3.0 mm Hg awake ABP [95% CI = 0.1-5.9, p = .04], and a nonsignificant 2.1 mm Hg ABP during sleep [95% CI = -1.0 to 5.1, p = .18]). PTSD was associated with greater 24-hour median anxiety (p < .001), and changes in anxiety were positively associated with concurrent systolic ABP (p < .001). ABP reactivity to anxiety was greater in participants with PTSD, which partially explained the association of PTSD with ABP. PTSD is associated with greater systolic BP, partly because of greater anxiety, and systolic BP reactivity to anxiety throughout the day. Daily anxiety and related BP reactivity may be targets for interventions to reduce the cardiovascular risk associated with PTSD.

Abstract 065: Induction of Human Endothelin-1 Overexpression for 3 Months Causes Blood Pressure Rise and Renal Injury

Introduction: Endothelium-derived endothelin (ET)-1 has been implicated in hypertension and renal disease but the mechanisms are complex and remain unclear. We have shown that tamoxifen-inducible endothelium-restricted human ET-1 overexpressing (ieET-1) mice exhibited BP rise after 3 weeks of induction in an ET type A receptor (ET A R)-dependent manner, in absence of renal injury. It is unknown whether long-term exposure to ET-1 overexpression results in sustained BP elevation and renal injury. Methods: Adult male ieET-1 and control tamoxifen-inducible endothelium-restricted Cre recombinase (ieCre) mice were treated with tamoxifen (1 mg/kg/day, SC) for 5 days and 2.5 months later were treated or not with an ET A R blocker, atrasentan (10 mg/kg/day, PO) for 2 weeks. Blood pressure (BP) by telemetry, renal artery flow (RAF) by ultrasonography, immune cell infiltration by flow cytometry, kidney injury molecule (KIM)-1 expression by immunofluorescence, 24h urinary albumin by ELISA and creatinine by alkaline picrate method were determined at the end of the study. Results: Induction of ET-1 overexpression for 3 months resulted in greater systolic BP (135±4 vs 114±2 mmHg, P &lt;0.001) and reduced RAF (1.7±0.2 vs 3±0.3 mL/min, P &lt;0.05). ieET-1 mice presented increased myeloid (21255±5294 vs 5146±1987 CD11b + cells/kidney, P &lt;0.001) and myeloid-derived suppressor cells (5332±1463 vs 1126±507 CD11b + Gr-1 + cells/kidney, P &lt;0.01) renal infiltration associated with greater frequency of CD11b + (23.2±1.8 vs 7.5±1.6 % of CD45 + cells, P &lt;0.001) and non-immune renal cells (CD45 - , 5.7±0.8 vs 3.2±0.6 % of CD45 - cells, P &lt;0.001) expressing a pro-inflammatory maker, CD36. Early renal injury was demonstrated in ieET-1 by increased KIM-1 expression in proximal tubules (4.0±0.7 vs 1.0±0.2 % of renal cortex, P &lt;0.05) and unchanged albumin/creatinine ratio (327±74 vs 173±36 μg/mg, P=0.215). Atrasentan reversed or reduced all of the above except the decreased RAF ( P &lt;0.05). Conclusions: Long-term exposure to endothelial ET-1 overexpression caused sustained BP elevation and renal injury via ET A R.

Abstract WP359: Higher Risk of Intracerebral Hemorrhage Recurrence Among African American and Latino/Hispanic Individuals

Introduction: Intracerebral hemorrhage (ICH) is more prevalent among African American (AA) and Latino/Hispanic (LH) individuals. While ICH survivors are at high risk for rebleeding, it is unclear whether recurrence risk differs based on race / ethnicity. Hypothesis: We sought to clarify: 1) whether ICH recurrence risk is higher for AA and LH patients; 2) whether this disparity is explained by the most potent ICH risk factors, i.e. hypertension severity and the APOE gene variant ε4. Methods: We conducted a single-center longitudinal study enrolling 738 ICH survivors presenting to a single center from January 2006 to December 2014. Participants had APOE genotype determined at enrollment, and were followed via phone calls and review of medical records. We captured hypertension severity as absolute blood pressure (BP) measures, as well as BP variability (average percent variation during follow-up). We created univariable and multivariable (Cox regression) models to identify risk factors for ICH recurrence. Results: Systolic BP (SBP) was associated with increased ICH recurrence risk ( Hazard Ratio [HR]=1.30, 95% Confidence Interval [CI] 1.02 -1.66, p=0.036), as was SBP variation (HR=1.75 per variation quartile, 95% CI 1.09-2.81, p=0.021). APOE ε4 was also associated with ICH recurrence (HR=1.66, 95% CI 1.10-2.50, p=0.016). After adjusting for BP and APOE ε4, both LH ( HR=1.68, 95% CI 1.01-2.78, p = 0.045 ) and AA ( HR= 2.12, 95% CI 1.14-3.95, p = 0.019 ) patients when at higher risk for ICH recurrence. Both AA and LH patients had a significantly higher systolic BP (SBP) during follow-up (Figure, A); AA individuals also had greater SBP variation during follow up (Figure, B ). Conclusions: AA and LH patients are at higher risk for ICH recurrence, and hypertension severity / APOE ε4 did not fully account for this disparity. Additional studies will be required to further elucidate biological determinants for this health

Prevalence and Determinants of Hypertension among Iranian Adults, Birjand, Iran.

Background:Hypertension (HTN) is a major cause of noncommunicable diseases. In this study, we report the prevalence rate of HTN in Birjand population.Methods:This cross-sectional study was conducted on 1286 individuals in Birjand in 2014. Individuals with systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg were considered as hypertensive. Data were analyzed using Chi-square test, independent t-test, and one-way ANOVA. P < 0.05 was considered as statistically significant.Results:Among the 1286 participants, 659 were women (51.2%). Prevalence of HTN was 20.1% (10.3% systolic HTN and 6.9% diastolic HTN). Prevalence self-reported HTN was 12.3%. SBP and DBP means were higher in men (P < 0.001). Mean scores of SBP and DBP increased by aging and body mass index (P < 0.001). Diabetic individuals had higher SBP scores (P < 0.001). Dyslipidemic patients had greater SBP and DBP (P < 0.001).Conclusions:Prevalence of HTN in our study is high. About one-fifth of the participants had HTN. In addition, BP is higher in men, elderly, and diabetic individual. Therefore, it is necessary to control BP regularly in different groups in society.

Abstract 030: Low-dose Aspirin During Pregnancy Does Not Prevent Augmentation of Arterial Contractions to Thromboxane A 2 in a Rat Model of Pregnancy-Induced Hypertension

Background: Daily intake of low dose aspirin after 12 weeks of gestation is currently recommended as a preventative intervention in pregnancies at high risk of developing preeclampsia. We previously showed that treating pregnant rats with a synthetic ligand of Toll-like receptor 9 (TLR9; ODN2395) activated the innate immune system causing preeclampsia-like characteristics such as maternal hypertension, vascular oxidative stress, and augmented vascular responses to thromboxane A 2 (TxA 2 ). Hypothesis: Low-dose aspirin treatment would ameliorate ODN2395-induced augmented responses to TxA 2 in maternal arteries. Methods: Pregnant rats were treated with ODN2395 (300 μg) or vehicle on gestational day (GD) 14, 16, 18. Daily low-dose aspirin treatment (1.5 mg/kgBW) started on GD10 and continued throughout gestation. Systolic blood pressure was measured using the tail-cuff method on GD19. On GD21, uterine (UTA) and mesenteric resistance artery (MES) responses to a TxA 2 mimetic (U46619, 10 -9 -10 -6 M) was measured with a wire myograph. Results: Uterine arteries from the ODN2395+Aspirin-treated group had greater contractile responses to U46619 compared to all other groups [Emax, %KCl: Control (n=6): 109.2±8.8; ODN2395 (n=5): 124.4±20.2; Aspirin (n=5): 76.08±11.2; ODN2395+Aspirin (n=5): 134.7±4.5, p&lt;0.05]. Aspirin alone reduced MES responses to U46619 compared to control and MES from ODN2395 and ODN2395+Aspirin groups had greater contractile responses to U46619 compared to Aspirin alone [Emax, %KCl: Control (n=8): 109.8±5.2; ODN2395 (n=6): 111.1±4.3; Aspirin (n=7): 89.4±3.6; ODN2395+Aspirin (n=8): 121.7±6.3, p&lt;0.05]. Rats treated with ODN2395 and ODN+Aspirin had greater systolic blood pressure compared to control rats [control (n=8): 97.3±3.2 mmHg, ODN2395 (n=6): 121.3±4.3 mmHg, Aspirin (n=8): 100.3±2.9 mmHg, ODN2395+Aspirin (n=7): 127.5 ±6.7 mmHg, p&lt;0.05]. Conclusion: Exposure to a TLR9 agonist during pregnancy resulted in augmented contractile responses to a TxA 2 mimetic in maternal arteries when rats were in a regime of low-dose aspirin. This was shown in arteries from both reproductive and non-reproductive vascular beds.

Impact of Intraoperative Blood Pressure Control and Temporary Parent Artery Blocking on Prognosis in Cerebral Aneurysms Surgery.

Objective In cerebral aneurysm clipping and embolization, blood pressure control and temporary parent artery blocking are common methods to prevent aneurysm rupture. Their influence on the prognosis is uncertain. In this study, we try to find out the association between methods above and prognostic indicators.Methods We held a retrospective analysis on patients' medical records of cerebral aneurysms surgical clipping and endovascular coiling , and recorded gender, age, diagnosis, Hunt-Hess grade, Glasgow coma scale score, treatment methods, a history of hypertension, preoperative systolic blood pressure, with or without controlled hypotension, systolic blood pressure difference before and after controlled hypotension, with or without temporary artery blocking, with or without hypertension after treated aneurysm, prognostic indicators including mortality after 1 month, intensive care unit (ICU) stay time of survivors, discharged Glasgow outcome scale (GOS) score. Prognostic indicators were regarded as dependent variable, all the factors were regarded as independent variable, and the strength analysis of influence factors on prognostic indicators was made by binary logistic regression.Results Total cases were 165, including 68 males and 97 females, with an average age of 56 (12-85) years. The mortality after 1 month was 10.9% (18 cases). The ICU stay time of survivors was 7.35 (0-67) days. GOS score at discharge was 1-3 in 40 (24.2%) patients and 4-5 in 125 (75.8%) patients. Systolic blood pressure difference before and after controlled hypotension was an independent factor influencing mortality (t=2.273, P=0.024), and the greater the difference was, the higher the mortality would be. Timely hypertension after aneurysm treated was an independent factor affecting ICU stay time of survivors and patients with hypertension had shorter ICU stay time (χ2=10.017, P=0.001). Blood pressure control (χ2=0.088, P=0.767) and temporary blocking (χ2=1.307, P=0.253) did not show significant influence on GOS score at discharge.Conclusions Timely controlled hypertension after aneurysm clipping and embolization can significantly shorten the stay time in ICU. The degree of controlled hypotension associates with postoperative mortality, the greater systolic blood pressure difference before and after antihypertensive treatment is, the higher the mortality will be.

Predictors of Development of Echocardiographic Left Ventricular Diastolic Dysfunction in the Subjects Aged 40 to 59 Years (from the Oulu Project Elucidating Risk of Atherosclerosis Study)

Factors in the middle age that are associated with the risk for development of diastolic dysfunction in long term are not fully established. The Oulu Project Elucidating Risk of Atherosclerosis OPERA study randomly selected middle-aged subjects with hypertension and age- and gender-matched control subjects (n= 1,045, age 51 ± 6years, men 49.8%). After >20years of follow-up, majority of the subjects still alive were available for reexaminations (n= 600). After excluding the subjects with mitral regurgitation, left ventricular ejection fraction <50%, and those from whom echocardiographic septal E/E' could not be reliably measured, the present analysis included 460 subjects. E/E' was divided into 3subgroups (subgroup 1: E/E' ≤8, subgroup 2: 8 < E/E' < 15, subgroup 3: E/E' ≥15), subgroup 3 suggesting a significant diastolic dysfunction. Several baseline variables were associated with diastolic dysfunction: greater age (p= 0.001), female gender (p= 0.001), shorter height (p <0.001), larger body mass index (p= 0.008), greater systolic blood pressure (p= 0.001), greater pulse pressure (p <0.001), lower baroreflex sensitivity (p=0.007), lower estimated glomerular filtration rate (p= 0.02), greater atrial natriuretic peptide (p= 0.001), greater fasting plasma glucose (p= 0.001), more common occurrence of diabetes (p= 0.011), and more common usage of antihypertensive medication (p=0.001). After adjustments in the multivariate model, only systolic blood pressure(p=0.001), shorter height (p= 0.002), and estimated glomerular filtration rate (p=0.006) retained a significant association with the risk of developing diastolic dysfunction. In conclusion, greater systolic blood pressure, short height, and lower estimated glomerular filtration rate of the middle-aged subjects were the main determinants of development of diastolic dysfunction during a 20-year follow-up.

Differences in risk factors for the onset of albuminuria and decrease in glomerular filtration rate in people with Type 2 diabetes mellitus: implications for the pathogenesis of diabetic kidney disease.

AimsTo determine differences in predictors of albuminuria and decreased estimated GFR in Japanese people with Type 2 diabetes mellitus without chronic kidney disease.MethodsThis single‐centre observational cohort study involved 1802 Japanese people with Type 2 diabetes with normoalbuminuria and estimated GFR ≥ 60 ml/min/1.73 m2 (740 women; mean ± sd age 58 ± 12 years). Two separate outcomes were evaluated: onset of albuminuria ( ≥ 30 mg/g creatinine, albuminuria cohort; n = 1655) and decrease in estimated GFR ( < 60 ml/min/1.73 m2; estimated GFR cohort; n = 1777). A Cox proportional hazards model was used to identify significant predictors for each outcome.ResultsDuring a median follow‐up period of 6.9 years for the albuminuria cohort and 8.0 years for the estimated GFR cohort, 181 and 316 individuals reached the respective outcome. The 5‐year cumulative incidence of albuminuria was 8.3%, and that of decreased estimated GFR was 10.4%. In the multivariate Cox model, greater urinary albumin‐to‐creatinine ratio, presence of diabetic retinopathy and higher HbA1c levels were associated with both outcomes. Unique risk factors for onset of albuminuria were male gender and higher uric acid levels; those for decreased estimated GFR were older age, greater systolic blood pressure, and lower baseline estimated GFR and HDL cholesterol levels.ConclusionsIdentification of both common and distinct predictive factors for onset of albuminuria and decreased estimated GFR support the hypothesis that both common and distinct pathophysiological mechanisms are involved in the development of these two manifestations of chronic kidney disease in diabetes.

Abstract 506: Blood Pressure-lowering Effects Of Anti-hypertensive Drugs And Combinations: Meta-regression Of Published Clinical Trials. The Atom Study

Background and aim: The use of antihypertensive drugs should be based on the knowledge of their blood pressure (BP)-lowering effect . Most of the clinical trials only assess such effects by comparing 2 different drugs or treatment strategies. However, the relative effect of major antihypertensive drug classes or the most used compounds inside each class is less known. The aim of the study was to assess the BP-lowering effect of most commonly used drugs or drug combinations, by reviewing data from clinical trials based on drug efficacy. Patients and methods: Clinical trials with at least 50 patients recruited, in which BP reduction was the primary outcome, were obtained from a systematic review of Medline and Cochrane Central Register of Controlled Trials. Studies without clearly established data of doses or baseline or final BP values were excluded. Data were analyzed by Bayesian meta-regression, adjusted by baseline BP, age, gender, ethnicity, and number of patients included. Only those drugs with a minimum number of studies, which allowed the Bayesian meta-regression, were included. Results: 253 studies including 937 treatment arms were reviewed. Total number of patients included was 138,971. Systolic BP reduction with monotherapy did not, generally, overcome 20 mmHg, with bisoprolol (mean -15,6 mmHg, 95% CI: -27,4; -1,7) and olmesartan (-15,3 mmHg, 95% CI -18.2; -11,7) resulting the most efficacious drugs. Diastolic BP was reduced by 10 mmHg; being olmesartan the drug promoting a more pronounced reduction (-11.5 mmHg, 95% CI: -13.5; - 9.4). In studies using antihypertensive combinations, the greatest systolic BP reduction was obtained with olmesartan/amlodipine (-31.6 mmHg, CI: -54.6; -22.6) and valsartan/hydrochlorothiazide (-31.4 mmHg, CI: -39.0; -23.0). Conclusions: This systematic review reflects the expected BP reductions with the use of the most common antihypertensive compounds or combinations. The results may allow the clinician to choose the most appropriate treatment taking into account patients’ BP and the required reduction to reach the goal.

Visit-to-Visit Variability in Blood Pressure and Kidney and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Nephropathy: A Post Hoc Analysis From the RENAAL Study and the Irbesartan Diabetic Nephropathy Trial

Increased systolic blood pressure variability between outpatient visits is associated with increased incidence of cardiovascular end points. However, few studies have examined the association of visit-to-visit variability in systolic blood pressure with clinically relevant kidney disease outcomes. We analyzed the association of systolic blood pressure visit-to-visit variability with renal and cardiovascular morbidity and mortality among individuals with diabetes and nephropathy. Observational analysis of IDNT (Irbesartan Diabetic Nephropathy Trial) and the RENAAL (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study. 2,739 participants with type 2 diabetes and nephropathy with at least 1 year of blood pressure measurements available. Systolic blood pressure visit-to-visit variability was calculated from the SD of the systolic blood pressure from 4 visits occurring 3-12 months postrandomization. The kidney disease outcome was defined as time to confirmed doubling of serum creatinine level, end-stage renal disease, or death; the cardiovascular outcome was defined as time to cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, or revascularization. Mean visit-to-visit variability in systolic blood pressure from 3 to 12 months postrandomization was 12.0±6.8(SD)mmHg. Following this ascertainment period, there were 954 kidney disease and 542 cardiovascular events. Greater systolic blood pressure visit-to-visit variability was associated independently with increased risk of the composite kidney disease end point (HR per 1-SD increment, 1.08 [95%CI, 1.01-1.16]; P=0.02) and end-stage renal disease, but not with the cardiovascular outcome. Observational study with the potential for confounding. In diabetic individuals with nephropathy, systolic blood pressure visit-to-visit variability is associated independently with hard kidney disease outcomes.

Social stressors and cardiovascular response: Influence of ambivalent relationships and behavioral ambivalence

ObjectiveThe protective influence of social relationships on health is well documented; however, not all relationships are positive and negative aspects of relationships may be detrimental. Relatively less is known about the relationships characterized by both positivity and negativity (i.e., ambivalence). The goal of this study was to examine the relative influence of ambivalence in relationship quality and social behavior on cardiovascular response. Methods104 healthy young adults were randomly assigned to bring in either a supportive or ambivalent same-sex friend to the experiment. Participants were also randomly assigned to receive positive, negative, ambivalent or ambiguous feedback from their friend after giving a series of speeches. Cardiovascular response was obtained before, during, and after the social stressor (speech task). ResultsResults indicate a significant effect of relationship type before, during, and after the stressor task. Adjusting for baseline, heart rate reactivity and anxiety was significantly higher among those assigned to ambivalent friends relative to those assigned to supportive friends during the stressor task (ps<.05). There was also a significant effect of behavioral feedback during the speech task, such that those receiving ambivalent messages had the greatest systolic blood pressure (SBP) and diastolic blood pressure (DBP) reactivity (p<.05); however, there was no interaction between relationship and feedback conditions. Those in the ambivalent friend condition also exhibited significantly higher SBP, DBP, and anxiety during the baseline and recovery periods (ps<.05). ConclusionsThese findings suggest that both relationship quality and the actions of relationships may have a significant influence on health-relevant physiology.

Chronic pain and cardiovascular stress responses in a general population: the Tromsø Study.

We tested whether cardiovascular stress responsiveness is elevated in individuals experiencing chronic pain in a large general population sample. Blood pressure (BP) and heart rate (HR) were assessed at rest, during the cold pressor test, and during subsequent recovery in 554 individuals reporting daily chronic pain and 3,082 individuals free of chronic pain. After correcting for potential confounds, differences as a function of chronic pain status were noted for only 5 of 23 cardiovascular outcomes despite very high statistical power. Compared to the pain-free group, the chronic pain group displayed higher baseline HR/mean arterial pressure (MAP) ratio (p=.03), greater systolic BP (SBP) reactivity during the cold pressor test (p=.04), and higher HR/MAP ratio (p=.047) and significantly less SBP (p=.017) and MAP (p=.041) return to baseline during recovery. Findings suggest that changes in cardiovascular stress responsiveness associated with chronic pain are of limited clinical significance and unlikely to contribute to increased cardiovascular risk in the chronic pain population.

Validation of Oscillometric Pulse Wave Analysis Measurements in Children

Pulse wave analysis (PWA) has emerged as a noninvasive, valid, reliable, and widely used technique to investigate central blood pressures and systemic arterial wave reflection (augmentation index). The gold-standard technique is tonometry, but this technique can be challenging, especially when used on children. The purpose of this study was to validate oscillometric PWA for use in children. Fifty-seven healthy children were recruited for participation. Central blood pressures and peripheral augmentation index (pAIx) were measured objectively using oscillometric (Pulsecor R7) and tonometric (SphygmaCor) devices. All measurements were made during the same visit under standardized conditions between the hours of 8 am and 10 am in the fasted state. Tonometric measurements were unsuccessful on 1 child. Comparisons were made on 56 children (mean age = 9.8±1.0 y; 57% male). A very strong relationship was found between devices for central systolic (r = 0.94; P < 0.001), diastolic (r = 0.99; P < 0.001) and mean (r = 0.96; P < 0.001) blood pressures. However, Bland-Altman analysis indicated a bias toward greater systolic blood pressures with the oscillometric monitor (mean difference = 4.5mm Hg; 95% confidence interval (CI) = -5.16 to -3.89). A good relationship was found for pAIx (r = 0.71; P < 0.001); the mean difference between devices was -1.70% (95% CI = -4.47% to 1.08%), which is not significantly different from zero. Findings from this study suggest that oscillometric PWA provides valid measures of central blood pressure and arterial wave reflection in children aged 8-10 years.

Parasympathetic Cardiac Activity is Associated with Cardiorespiratory Fitness in Overweight and Obese Adolescents

The aim of this study was to investigate the association between cardiac parasympathetic activity and cardiorespiratory fitness, insulin, and hemodynamic profile in overweight and obese adolescent girls and boys (aged 12-16 years). Data were taken from the Multidisciplinary Obesity Treatment Program. Only post-intervention measurements are presented herein. Body composition, cardiorespiratory fitness, blood pressure, and metabolic profile (insulin and glucose profile) of adolescents were assessed. Cardiac parasympathetic activity was determined by resting heart rate variability, which was analyzed using a heart rate monitor. Greater parasympathetic cardiac activity was associated with higher levels of cardiorespiratory fitness in both girls and boys (0.375 ≤ r ≤ 0.900), while the sympathetic-vagal balance was negatively related to maximal oxygen uptake (VO2max) in girls (r = 0.478). An association between lower parasympathetic activity and insulin resistance was noted in girls (mean of R-R intervals [RRmean] and homeostasis model assessment insulin-resistance index [HOMA-IR]: r = -0.678), while greater systolic blood pressure (SBP) and lower parasympathetic activity were associated in both sexes (RRmean and SBP: r = -0.526; high frequency [HF (nu)] and SBP: r = -0.754). In conclusion, autonomic nervous system activity was associated with cardiorespiratory fitness, insulin resistance, and SBP in overweight and obese adolescents. The identification of these potential relationships assists with the establishment of future long-term exercise interventions that evaluate the improvements in parasympathetic nervous system activity, in addition to metabolic profile and cardiorespiratory fitness in overweight and obese adolescents.

Effect of telmisartan vs. ramipril on ‘dipping’ status and blood pressure variability: pooled analysis of the PRISMA studies

A retrospective pooled analysis of the 'Prospective, Randomized Investigation of the Safety and Efficacy of MICARDIS vs. Ramipril Using ABPM' studies conducted in Europe and South Africa (PRISMA I) and in the United States of America and Canada (PRISMA II) was carried out to investigate the effects of telmisartan and ramipril on dipper status (extreme dippers, dippers, non-dippers, risers/reverse dippers), and blood pressure (BP) variability in 1279 patients (with normal sleeping patterns and valid 24-h ambulatory BP monitoring recordings at baseline and end point). After 14 weeks' treatment, telmisartan had a greater systolic BP (SBP) reduction and higher smoothness index in all four dipper groups compared with ramipril. In addition, the tendency toward dipping was significantly higher in patients treated with) telmisartan than ramipril (P=0.032; odds ratio for telmisartan vs. ramipril: 1.27 (95% confidence interval: 1.102-1.58)). In patients with an early morning SBP surge 35 mm Hg, telmisartan treatment was associated with significantly greater reductions from baseline in the night-time low mean, early morning mean and early morning SBP surge compared with ramipril (P=0.026, P<0.0001 and P=0.0006, respectively). In this retrospective analysis, telmisartan was shown to normalize the circadian BP pattern to a dipper profile in a larger proportion of patients than ramipril, and reduce early-morning SBP surge in high-risk patients, indicative of a cardioprotective effect. These findings need to be confirmed in long-term prospective trials and observational studies.

Early combination therapy with telmisartan plus amlodipine for rapid achievement of blood pressure goals

Rapid and sustained blood pressure (BP) goal attainment is important to reduce cardiovascular risk. Initial use of combination therapy may improve BP goal attainment. The Boehringer Ingelheim trial database was searched for randomised, double-blind studies comparing telmisartan/amlodipine combination therapy with monotherapy. Eight studies were identified. Eight separate analyses were used to compare combination therapy with respective monotherapies at the earliest available time points (weeks 1, 2 and/or 4). In patients initiated on combination therapy, greater systolic BP (SBP)/diastolic BP (DBP) reductions were seen with combination therapy (p < 0.0001); BP (< 140/90 mmHg), SBP (< 140 mmHg) and DBP (< 90 mmHg) goal attainment rates were significantly higher with combination therapy at all time points. In patients uncontrolled by monotherapy, greater SBP/DBP reductions were seen with combination therapy (p < 0.05 in all but one measure), and all goal attainment rates were significantly higher with combination therapy, except in one measure. Many people can achieve their BP targets when taking a combination of telmisartan and amlodipine after failing to do so with monotherapy. Furthermore, BP targets can be achieved more rapidly using a combination of telmisartan and amlodipine as initial therapy than with either monotherapy.

Acute and chronic flow-mediated dilation and blood pressure responses to daily intake of boysenberry juice: a preliminary study

There is an increasing interest in dietary polyphenols for risk reduction in cardiovascular diseases. The aim of this study was to evaluate acute and chronic flow-mediated dilation (FMD) and blood pressure responses to daily intake of boysenberry juice. FMD of the brachial artery was measured in six subjects in the initial, intermediate and follow-up stages of a 4-week open-label intervention study. The intake of boysenberry juice (180 ml/d) increased FMD with progression of intervention stage, and FMD differed in the follow-up stage compared with pre-intake baseline (p = 0.0163 < 0.0167 = 0.1/6) using Bonferroni correction. Changes in systolic blood pressure (SBP) correlated negatively with SBP before intake only in the follow-up stage (r = −0.961 and p = 0.0007 at 3.5 h), indicating a greater SBP reduction in subjects with higher SBP. These results suggest that daily intake of boysenberry juice is beneficial for reducing cardiovascular risk.