Supine Diastolic Blood Pressure Research Articles

Prepregnancy physiology and subsequent preterm preeclampsia

BackgroundPreeclampsia is a common pregnancy complication with debated etiology. ObjectiveTo evaluate the contribution of prepregnancy physiology, biochemistry and anthropometrics to the subsequent development of preterm preeclampsia. Study DesignOne-hundred twenty-four participants were recruited through open recruitment and targeted mailings. Participants included 81 nulliparous women and 43 with a history of preterm preeclampsia. We characterized cardiovascular function, metabolic profile, and body composition in 100 non-pregnant women who went on to subsequent pregnancy. Measures included plasma volume, baseline cardiovascular function and cardiovascular response to volume challenge, body composition and circulating biochemical measures. Pregnancy outcome was obtained through chart review. Prepregnancy metrics for women who developed preterm preeclampsia were compared with measurements for those who did not, with adjustment for a history of prior preterm preeclampsia. Logistic regression modeling was used to identify the strongest prepregnancy factors associated with preterm preeclampsia. ResultsPregnancy outcomes included 11 women with preterm preeclampsia, 7 women with term preeclampsia, 20 women with other hypertension affecting their pregnancy, and 62 with uncomplicated pregnancies. We observed no difference in maternal age, study cycle day, lean body mass, uterine hemodynamics, or flow mediated dilation across groups. Women with preterm preeclampsia had greater android fat content 3215+1143 vs. 1918+1510 grams (p=0.002), faster supine pulse, 77+7 vs. 67+10 beats per minute (p=0.001), higher supine diastolic blood pressure 82+6 vs. 68+6 mmHg (p< 0.001), increased cardiac output 5.6+1.1 vs. 4.6+1 L/min (p=0.002), faster aortic-popliteal pulse wave velocity 4.5+0.7 vs. 3.8+0.5 m/sec (p<0.001), and exaggerated cardiac output response to volume challenge 20+9 vs. 9+12 L/min (p=0.002) compared to those with other pregnancy outcomes. Women who developed preterm preeclampsia also had reduced renal vascular resistance index 0.86+0.08 vs. 0.97+0.12 (p=0.005) compared with other pregnancy outcomes when assessed prior to pregnancy. Women with subsequent preterm preeclampsia had higher serum c-reactive protein 10.7+12.5 vs. 4.1+5.8mg/mL (p=0.003) and greater insulin resistance, as assessed by HOMA-IR calculation 2.2+1.1 vs. 1.2+0.9 (p<0.001). ConclusionPrepregnancy physiology is linked to subsequent preterm preeclampsia. The same factors associated with metabolic syndrome are more prominent in patients who develop preterm pre-eclampsia than those who do not, including increased vessel stiffness, low vascular compliance, high cardiac output, reduced renal vascular resistance index, insulin resistance and increased android fat, all consistent with subclinical features of the metabolic syndrome.

Abstract P007: Timing Of Orthostatic Hypotension And Its Relationship With Falls In Older Adults

Background: There is inconsistent evidence on the optimal time after standing to assess orthostatic hypotension (OH). Objectives: To characterize the timing of OH after standing in older adults and the fall risk associated with OH at specific times. Methods: We performed a secondary analysis of the Study to Understand Fall Reduction and Vitamin D in You (STURDY). Blood pressure (BP) was measured in the supine position. Participants stood upright and underwent 6 standing BP measurements: 3 (M1-M3) immediately after standing, and 3 (M4-M6) after 3 minutes of standing. OH was defined as a decrease from supine systolic BP (SBP) of 20 or supine diastolic BP (DBP) of 10 mm Hg. We used generalized estimating equations to characterize changes in SBP, DBP, and OH over time. We used Cox models to examine the relationship between OH at each time point and subsequent falls. Results: There were 425 falls among 491 adults with 6,055 BP measurements and a median follow-up of 275 days. SBP/DBP decreased by a mean 9.5/2.6 mm Hg immediately after standing (M1) vs. 2.2/0.9 about 5 minutes after standing (M6). OH was observed in 32% of assessments at M1, and only 16% at M5 and M6 ( Table ). Only OH at M5 (Hazard Ratio = 1.84 [95% confidence interval = 1.17, 2.91]) and M6 (1.85 [1.03, 2.91]) predicted higher fall risk among individual time points. However, average OH from early (M1-3) and late (M4-6) measurements, respectively, also predicted higher fall risk (M1-3 = 1.65 [1.08, 2.52]; M4-6 = 1.73 [1.03, 2.91]). Conclusions: OH was most prevalent immediately after standing, but most informative for fall risk in late and average measurements. Multiple standing BP measurements may improve the clinical assessment of OH.

Posture-Related Differences in Cardiovascular Function Between Young Men and Women: Study of Noninvasive Hemodynamics in Rural Malawi.

BackgroundCardiovascular risk is higher in men than in women, but little information exists about sex‐related differences in cardiovascular function from low‐income countries. We compared hemodynamics between sexes in rural Malawi in a cohort followed up since their birth.Methods and ResultsSupine, seated, and standing hemodynamics were recorded from 251 women and 168 men (mean age, 21 years; body mass index, 21 kg/m2) using oscillometric brachial waveform analyses (Mobil‐O‐Graph). The results were adjusted for estimated glomerular filtration rate, and plasma potassium, lipids, and glucose. Men had higher brachial and aortic systolic blood pressure and stroke index regardless of posture (P<0.001), and higher upright but similar supine diastolic blood pressure than women. Regardless of posture, heart rate was lower in men (P<0.001), whereas cardiac index did not differ between sexes. Women presented with lower supine and standing systemic vascular resistance index (P<0.001), whereas supine‐to‐standing increase in vascular resistance (P=0.012) and decrease in cardiac index (P=0.010) were higher in women. Supine left cardiac work index was similar in both sexes, whereas standing and seated left cardiac work index was higher in men than in women (P<0.001).ConclusionsIn young Malawian adults, men had higher systolic blood pressure, systemic vascular resistance, and upright cardiac workload, whereas women presented with higher posture‐related changes in systemic vascular resistance and cardiac output. These findings show systematic sex‐related differences in cardiovascular function in a cohort from a low‐income country with high exposure to prenatal and postnatal malnutrition and infectious diseases.

Trajectory Analysis of Orthostatic Hypotension in Parkinson's Disease: Results From Parkinson's Progression Markers Initiative Cohort.

Background: Orthostatic hypotension (OH) in Parkinson’s disease (PD) can lead to falls, impair quality of life, and increase mortality. A trajectory analysis of OH could be useful to predict and prevent the hypotension incidence early.Methods: The longitudinal data of 660 patients with PD with disease duration up to 12 years were extracted from an integrated PD database. We used latent class mixed modeling (LCMM) to identify patient subgroups, demonstrating trajectories of changes in orthostatic blood pressure (BP) over time. The optimal number of subgroups was selected by several criteria including the Bayesian Information Criterion. Baseline information comparison between groups and backward stepwise logistic regression were conducted to define the distinguishing characteristics of these subgroups and to investigate the predictors for BP trajectory.Results: We identified three trajectories for each orthostatic change of systolic blood pressure (ΔSBP), namely, Class 1 (i.e., the increasing class) consisted of 18 participants with low ΔSBP that increased continuously during the follow-up; Class 2 (i.e., the low-stable class) consisted of 610 participants with low ΔSBP that remained low throughout the follow-up; and Class 3 (i.e., the high-stable class) consisted of 32 participants with high ΔSBP at baseline that was relatively stable throughout the follow-up. Several parameters differed among subgroups, but only male sex [odds ratio (OR) = 4.687, 95% confidence interval (CI) = 1.024–21.459], lower supine diastolic blood pressure (DBP) (OR = 0.934, 95% CI = 0.876–0.996), and lower level of total protein at baseline (OR = 0.812, 95% CI = 0.700–0.941) were significant predictors of an increasing ΔSBP trajectory.Conclusion: This study provides new information on the longitudinal development of ΔSBP in patients with PD with distinct trajectories of rapidly increasing, low-stable, and high-stable class. The parameters such as male sex, lower supine DBP, and lower total proteins help to identify the rapidly increasing class.

Decreased Serum NCAM Levels Associated with Cognitive Impairment in Vascular Dementia.

Objective Neural cell adhesion molecule (NCAM), a glycoprotein widely distributed in the brain, has recently been shown to regulate neuroplasticity. However, the role of NCAM in vascular dementia (VaD) is still unclear. The purpose of this study is to determine whether NCAM is involved in the course of VaD. Methods Continuous recruitment of VaD patients and control population to join this study. Doctors or nurses are responsible for collecting their clinical characteristics including age, gender, formal education, heart rate, supine systolic blood pressure, supine diastolic blood pressure, fasting glucose, high-density lipoprotein, and low-density lipoprotein. Each participant received the Montreal Cognitive Assessment (MoCA) scale after being enrolled in the group. At the same time, their peripheral blood was collected, and their serum NCAM levels were measured by enzyme-linked immunosorbent assay (ELISA). Results 98 VaD patients and 83 age- and sex-matched controls were enrolled. There was no significant statistical difference between the VaD group and the control group in terms of the comparison of clinical characteristics (p > 0.05). The MoCA score of VaD patients was significantly lower than that of the controls (27.9 ± 1.4 vs. 23.0 ± 2.1 points, p < 0.001). In addition, the circulating NCAM level of VaD patients was also significantly lower than that of controls (21.7 ± 3.8 vs. 17.6 ± 4.2 ng/mL, p < 0.001). The circulating NCAM level of VaD patients was significantly positively correlated with MoCA score (r = 0.285, p = 0.026). After adjusting for clinical characteristics, circulating NCAM levels are still an independent pathogenic factor of VaD (regression coefficient = 0.223, p = 0.034). Conclusions VaD patients have low circulating NCAM levels, which can be used as a potential predictor of VaD.

Circulating levels of growth hormone in postural orthostatic tachycardia syndrome

Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder with poorly understood etiology and underlying pathophysiology. Since cardiovascular morbidity has been linked to growth hormone (GH), we studied GH levels in patients with POTS. We conducted an age-sex-matched case–control study in patients with POTS (age 31 ± 9 years; n = 42) and healthy controls (32 ± 9 years; n = 46). Plasma GH levels were measured using high-sensitivity chemiluminescence sandwich immunoassay. The burden of orthostatic intolerance symptoms was assessed by the Orthostatic Hypotension Questionnaire (OHQ), consisting of a symptom assessment scale (OHSA) and a daily activity scale (OHDAS). POTS patients had significantly higher composite OHQ score than controls, more symptoms and less activity. Supine heart rate and diastolic blood pressure (BP), but not systolic BP, were significantly higher in POTS. Median plasma GH levels were significantly lower in POTS (0.53 ng/mL) than controls (2.33 ng/mL, p = 0.04). GH levels were inversely related to OHDAS in POTS and supine systolic BP in POTS and controls, but not heart rate neither group. POTS is associated with lower GH levels. Impairment of daily life activities is inversely related with GH in POTS. A higher supine diastolic BP is inversely associated with GH levels in POTS and healthy individuals.

Stretching is Superior to Brisk Walking for Reducing Blood Pressure in People With High-Normal Blood Pressure or Stage I Hypertension.

Aerobic exercise is recommended for reducing blood pressure; however, recent studies indicate that stretching may also be effective. The authors compared 8 weeks of stretching versus walking exercise in men and women with high-normal blood pressure or stage 1 hypertension (ie,130/85-159/99mmHg). Forty men and women (61.6y) were randomized to a stretching or brisk walking exercise program (30min/d, 5d/wk for 8wk). Blood pressure was assessed during sitting and supine positions and for 24 hours using a portable monitor before and after the training programs. The stretching program elicited greater reductions than the walking program (P < .05) for sitting systolic (146 [9] to 140 [12] vs 139 [9] to 142 [12]mmHg), supine diastolic (85 [7] to 78 [8] vs 81 [7] to 82 [7]mmHg), and nighttime diastolic (67 [8] to 65 [10] vs 68 [8] to 73 [12]mmHg) blood pressures. The stretching program elicited greater reductions than the walking program (P < .05) for mean arterial pressure assessed in sitting (108 [7] to 103 [6] vs 105 [6] vs 105 [8]mmHg), supine (102 [9] to 96 [9] vs 99 [6] to 99 [7]mmHg), and at night (86 [9] to 83 [10] vs 88 [9] to 93 [12]mmHg). An 8-week stretching program was superior to brisk walking for reducing blood pressure in individuals with high-normal blood pressure or stage 1 hypertension.

Abstract 15153: Functional Cardiac Adaptation to 60 Days Strict Head-Down-Tilt Bedrest

Background: Reduced physical activity increases the risk for heart failure. Myocardial strain measurements capture subtle abnormalities in myocardial function. We tested the hypothesis that bedrest deconditioning produces cardiac dysfunction in healthy persons. Methods: In the AGBRESA study, which assessed artificial gravity through centrifugation as potential countermeasure for space travel, 24 healthy persons (8 women) were submitted to 60 days strict -6°-head-down-tilt bedrest. 8 subjects each were included in a control group or groups subjected to continuous artificial gravity training on a short-arm centrifuge [30 minutes/day] or intermittent centrifugation [6x5 min/day]. We assessed cardiac morphology, function, strain and hemodynamics by cardiac-MRI (baseline, end of bedrest, recovery) and echocardiography (baseline, end of bedrest). Before and after bedrest, we assessed orthostatic heart rate responses as measure of cardiovascular deconditioning. Results: We conducted a pooled analysis because cardiovascular responses to bedrest did not differ between groups. Supine heart rate (baseline: 64±9.6bpm; bedrest: 72.3±10.5bpm; recovery: 69.6±10.5bpm, p &lt;0.0001) and diastolic blood-pressure (69.6±7.3mmHg; bedrest: 78.5±6.9mmHg; recovery: 70.3±6.3mmHg, p &lt;0.0001) increased with bedrest. With head-up tilt, heart rate increased 22.8±10.5bpm before and 45.9±213bpm at the end of bedrest ( p &lt;0.0001) consistent with cardiovascular deconditioning. Cardiac-output decreased from 6.6±0.9l/min to 6±1l/min at end of bedrest (recovery: 6.8±1.2l/min, p =0.0096). Left ventricular ejection fraction and mass-index did not change. Echocardiographic global longitudinal strain (baseline: -19.90±2.1%; bedrest: -18.1±2.1%, p &lt;0.0001) decreased, whereas global circumferential strain in MRI tended to increase (baseline: -18.6±1.7%; bedrest: -19.1±1.6%, p =0.0843). After four days of recovery MRI measurements had returned to baseline. Conclusion: In healthy persons, cardiovascular deconditioning through 60 days head-down-tilt bedrest does not lead to cardiac atrophy or sustained reductions in cardiac performance. The transient nature of cardiac strain changes suggests functional rather than structural changes in the heart.

Twenty-four-hour urine NE level as a predictor of the therapeutic response to metoprolol in children with recurrent vasovagal syncope.

Vasovagal syncope (VVS) is a heterogeneous disorder that creates challenges for treatment. Metoprolol is an important therapeutic option for children with VVS. The study examined the predictive value of 24-h urine norepinephrine (NE) levels in the assessment of the therapeutic efficacy of metoprolol for recurrent VVS in children. Thirty-eight children with recurrent VVS and 20 healthy children were enrolled in our study. Twenty-four-hour urine NE levels were measured by LC-MS-MS. VVS children were diagnosed by BHUTT and/or SNHUTT, and received metoprolol treatment for 3months. Symptom scoring was utilized to evaluate the therapeutic effect. A ROC curve was used to investigate the predictive value of 24-h urine norepinephrine levels. There exists significant correlation between 24-h urine NE levels and supine systolic and diastolic blood pressures. The 24-h urine NE levels of responders (40.75 ± 12.86μg/24h) were higher than those of nonresponders (21.48 ± 6.49μg/24h), and there was a significant difference between the two groups (P < 0.001). A ROC curve of the predictive value of 24h urine NE levels revealed that the area under the curve was 0.926. A cutoff value for 24-h urine NE level of 34.84μg/24h produced both high sensitivity (70%) and specificity (100%) in predicting the efficacy of metoprolol therapy for VVS. Patients with high 24-h urine NE levels have higher supine systolic and diastolic pressures and more effective responses to metoprolol. A 24-h urine norepinephrine level of > 34.84μg/24h was an indicator of the effectiveness of metoprolol therapy for VVS in children.

Excess early postnatal weight gain and blood pressure in healthy young children

Blood pressure (BP) tracks from childhood to adulthood, and early BP trajectories predict cardiovascular disease risk later in life. Excess postnatal weight gain is associated with vascular changes early in life. However, to what extent it is associated with children's BP is largely unknown. In 853 healthy 5-year-old children of the Wheezing-Illnesses-Study-Leidsche-Rijn (WHISTLER) birth cohort, systolic (SBP) and diastolic BP (DBP) were measured, and z scores of individual weight gain rates adjusted for length gain rates were calculated using at least two weight and length measurements from birth until 3 months of age. Linear regression analyses were conducted to investigate the association between weight gain rates adjusted for length gain rates and BP adjusted for sex and ethnicity. Each standard deviation increase in weight gain rates adjusted for length gain rates was associated with 0.9 mmHg (95% CI 0.3, 1.5) higher sitting SBP after adjustment for confounders. Particularly in children in the lowest birth size decile, high excess weight gain was associated with higher sitting SBP values compared to children with low weight gain rates adjusted for length gain rates. BMI and visceral adipose tissue partly explained the association between excess weight gain and sitting SBP (β 0.5 mmHg, 95% CI -0.3, 1.3). Weight gain rates adjusted for length gain rates were not associated with supine SBP or DBP. Children with excess weight gain, properly adjusted for length gain, in the first three months of life, particularly those with a small birth size, showed higher sitting systolic BP at the age of 5 years.

Prevalence of Orthostatic Hypotension in the Elderly in Anambra State

Background: Orthostatic hypotension is a condition in which blood pressure drops abnormally when a person stands up from a sitting or a lying down position. It is a sustained reduction of systolic blood pressure of at least 20mmHg or diastolic blood pressure of at least 10mmHg within three minutes of standing or a head-up tilt to at least 60 degrees on a tilt table. Orthostatic hypotension has been observed in all age groups, but it occurs more in the elderly, especially in persons who are sick and frail. The burden of Orthostatic hypotension on public health is substantial, with a prevalence of 7% to 55% in the elderly and is higher in those with risk factors. The diagnosis of orthostatic hypotension is therefore important in the treatment of elderly patients. Methods: This cross-sectional study was designed to evaluate the prevalence of orthostatic hypotension in community-dwelling elderly in Anambra State, Nigeria. The study population was a 400 persons aged 60 years and older selected by multistage sampling method. Results: The total prevalence of OH was 14.8% (n=59). The prevalence of OH was related to presence of hypertension, diabetes, raised supine systolic and raised supine diastolic BP (P ≤ 0.05). Diabetics [OR: 4.689 (95% CI: 1.121-19.984)] and those with supine diastolic hypertension [OR: 1.699 (95% CI: 0.401-7.209)] were more likely to have OH. Conclusion: The prevalence of orthostatic hypotension in 60 years and older adults in Anambra State was high and was found to be higher in hypertensives and diabetics.

Prevalence of orthostatic hypotension in patients aged 80 or over and associated risk factors

Objective To investigate the prevalence of orthostatic hypotension in hypertensive patients aged 80 or over and associated risk factors at level A tertiary hospitals. Methods A multi-center cross-sectional study was conducted among very old hypertensive patients(≥80 years) at 28 level A tertiary hospitals by using questionnaire-based surveys. A total of 1298 hypertensive subjects aged between 80 and 101 years were enrolled in this study. Blood pressures was measured in the supine position and the upright position within three minutes of standing, and 316 patients were assigned to the orthostatic hypotension(OH) group and the other 982 patients to the non-orthostatic hypotension(NOH) group. Additional information was acquired through patients' medical records and the questionnaire. Results The prevalence of OH was 24.3%(316 cases) There were no significan different betueen OH patienl with NOHones in gender and age.OH patients had higher supine systolic and diastolic blood pressure(P=0.003 and 0.000, respectively), lower standing systolic and diastolic blood pressure(P=0.000 and 0.000, respectively), and higher rates of past coronary heart disease, stroke and renal abnormalities(P=0.037, 0.001 and 0.014, respectively) than NOH patients. Logistic regression analysis showed that the prevalence of OH in the patients was positively correlated with supine systolic blood pressure(OR=1.196, CI: 1.153-1.242, P=0.000) and supine diastolic blood pressure(OR=1.740, CI: 1.602-1.885, P=0.000) and was negatively correlated with standing systolic blood pressure(OR=0.824, CI: 0.795-0.855, P=0.000) and standing diastolic blood pressure(OR=0.584, CI: 0.539-0.634, P=0.000). Conclusions The prevalence of orthostatic hypotension is high in hypertensive patients aged 80 years or over at level A tertiary hospitals. Poor blood pressure control may increase the risk of orthostatic hypotension. Key words: Elderly, aged over 80 years; Hypertension; Hypotension

Changes of plasma intermedin during head-up tilt test in children with postural tachycardia syndrome and its significance

To explore possible mechanisms of postural tachycardia syndrome (POTS) by comparing plasma intermedin (IMD) during head-up tilt test (HUTT) in children with POTS. The study subjects were divided into two groups: POTS group and control group. The POTS group consisted of twenty-nine children (male 14, female 15) with POTS, the mean age (12.4 ±3.1) years old, admitted into Peking University First Hospital from November 2013 to June 2014. The control group consisted of 32 healthy children (male 17, female 15). Their mean age was (11.6±2.2) years old, who were confirmed as healthy by physical examination and HUTT. Finapres Medical System was used to continuously monitor heart rate and blood pressure during HUTT, and electrocadiogram was performed. Supine systolic and diastolic blood pressure, mean arterial pressure (MAP), ΔMAP (standing mean arterial pressure-supine MAP), supine heart rate and ΔHR (standing HR-supine HR) were compared between POTS group and control group. Sandwich immunoluminescence assay was used to test plasma IMD. The plasma IMD level was compared in supine between POTS and control group. The plasma IMD level in supine was compared with HUTT in POTS group. No significant differences were found in age, height, weight, supine systolic and diastolic blood pressure, MAP, ΔMAP and supine heart rate between POTS group and control group (P>0.05). ΔHR in POTS group was significantly higher than that of control group ((48±10) vs. (22±7) beats /min, t=9.797, P<0.05). The plasma IMD level in POTS group was lower than that of control group in supine position ((497±61)×10(-6) vs. (529±58)×10(-6) mg/L, t=2.117, P<0.05). But, it was higher during HUTT than supine IMD in POTS group ((537±57) ×10(-6) vs. (497±61)×10(-6) mg/L, t=-2.464, P<0.05). The plasma delta IMD level (HUTT vs. supine) was positively correlated with delta HR in POTS group (r=0.435, P<0.05). The excessively high heart rate during HUTT have a positive correlation with plasma IMD, which may play a role in the pathogenesis of POTS in children.

Effects of desvenlafaxine on blood pressure in patients treated for major depressive disorder: a pooled analysis

Objective:To evaluate the effect of the serotonin-norepinephrine re-uptake inhibitor desvenlafaxine on blood pressure and incidence of new onset hypertension in pooled short-term studies and in two longer-term, randomized withdrawal studies.Research design and methods:Data from patients randomly assigned to desvenlafaxine 10 mg to 400 mg/day or placebo in 11 short-term (8–12 weeks), fixed-dose, double-blind, placebo-controlled studies of major depressive disorder (MDD) were pooled for analysis; two desvenlafaxine randomized withdrawal studies (36 and 46 weeks) were analyzed separately.Clinical trial registration:www.clinicaltrials.gov, NCT00072774, NCT00073762, NCT00277823, NCT00300378, NCT00384033, NCT00798707, NCT00863798, NCT01121484, NCT00824291, NCT01432457, NCT00075257, NCT00887224.Main outcome measures:Outcomes included change from baseline in supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP), assessed using a mixed model repeated measures (MMRM) analysis, and incidence of hypertension (defined as three consecutive second SDBP measures ≥90 mm Hg AND increase of ≥10 mm Hg from baseline and/or SSBP ≥140 mm Hg AND increase of ≥10 mm Hg), analyzed using Cochran Mantel Hanzael tests. Potential predictors of change in SSBP and SDBP at LOCF were examined by including predictor variables in a regression model.Results:In the pooled, short-term studies, mean changes from baseline over time in SSBP and SDBP were statistically significant compared with placebo for the desvenlafaxine doses of 10 mg/day or greater for SSBP (p ≤ 0.0004; MMRM) and 25 mg/day or greater for SDBP (p ≤ 0.0449; MMRM). The proportion of patients with new onset hypertension differed significantly from placebo for the 50, 200, and 400 mg/day doses (1.9%, 2.4%, 4.8%, respectively, vs 0.8%; all p ≤ 0.0244). Predictors of change in BP included baseline SDBP, baseline SSBP, dose, body mass index, gender, age, race, and history of hypertension.Limitations:Data were pooled from studies which differed somewhat in study design and patient demographics. None of the studies were originally designed to examine treatment effects on BP. Study entry criteria limit generalization of these results to medically stable patients with a primary diagnosis of MDD.Conclusions:Short-term desvenlafaxine treatment was associated with small but statistically significant increases in SSBP and SDBP.

Wave reflections, arterial stiffness, and orthostatic hypotension.

The effect of wave reflections on blood pressure change associated with posture remains unclear. We therefore applied a wave separation technique to investigate the relations of the backward pressure wave amplitude with orthostatic pressure changes and orthostatic hypotension (OH). We analyzed data from 613 subjects who had participated in our hemodynamic studies. Measurements of brachial systolic (SBP) and diastolic blood pressures (DBP), carotid-femoral pulse wave velocity (cf-PWV), and backward pressure wave amplitude from a decomposed carotid pressure wave (Pb) were obtained at supine position. SBP and DBP were measured again 3 minutes after standing. OH was defined as a fall of ≥20 mm Hg in SBP and/or ≥10 mm Hg in DBP. Subjects with OH (n = 100) were characterized with significantly higher supine SBP and DBP and significantly lower standing SBP and DBP when compared with subjects without OH. Subjects with OH were also characterized with significantly higher cf-PWV and Pb. cf-PWV and Pb separately were significantly associated with the orthostatic SBP change in univariable and multivariable analyses. Also, cf-PWV and Pb separately were significant predictors of OH in univariable and multivariable analyses. cf-PWV predicted OH in the younger but less so in the older subgroup, whereas Pb demonstrated similar prediction in both subgroups. In a final multivariable model, both cf-PWV and Pb were significant independent predictors of OH. Wave reflections are an independent determinant of orthostatic SBP change and OH in both younger and older subjects.

Factors associated with prevention of postural hypotension by leg compression bandaging

Aim. We evaluated the eventual effects of leg compression on seating-induced postural hypotension (PH) in the context of various relevant clinical variables. Methods. Included were 73 hospitalized patients with various acute conditions, aged ≥ 60 years, bedridden for ≥ 8 h, with diagnosed PH [≥ 20 mmHg systolic and/or ≥ 10 mmHg diastolic blood pressure (BP) falls] at the first seating. BP, heart rhythm, dizziness and palpitations were recorded before and during 5 min of sitting. The next day, the patients were reevaluated, this time using compression bandages applied along both legs before seating. Results. Compared with the non-bandaged state, PH was registered in only 53% of bandaged patients (p < 0.001). Moreover, the appearance of PH symptoms decreased (p < 0.001). On the second day (bandaged), supine diastolic BP values were higher in the persisting vs non-persisting PH group (p = 0.027). In the bandaged state, PH symptoms were significantly reduced in the non-persisting PH group (p = 0.003). Even in patients with persistent PH, the magnitude of BP decline and appearance of PH symptoms were decreased while wearing bandages (p = 0.004 and 0.002, respectively). Conclusion. During mobilization of inpatients, leg compression seems to reduce the seating-induced PH and relevant symptoms. Even in patients with persisting PH, bandaging may improve hemodynamics and attenuate associated symptoms.

Benin stroke score in the diagnosis of acute brain infarct: a pilot study in Senegalese Africans.

The Benin stroke score (BSS) is a validated tool in the diagnosis of intracerebral hemorrhage (ICH) but not in the diagnosis of brain infarct. The aim of this report is to specifically validate the BSS in the clinical diagnosis of acute brain infarct. A total of 60 participants with a presumptive diagnosis of acute stroke in a busy tertiary neurologic care centre in Francophone West Africa were evaluated within 48 h of onset of symptoms with the BSS after basic data were obtained, before computed tomography or magnetic resonance imaging scans was used as gold standard. BSS is a three-item tool that scores age, supine diastolic blood pressure, and Glasgow coma scale with a minimum score of 0 and a maximum score of 3.5. A score of 2.5 or less is diagnostic for a brain infarct. The sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratios of BSS in the diagnosis of brain infarct were 83.78%, 69.56%, 81.57%, 72.72%, 2.75, and 0.23, respectively. BSS agreed with neuroimaging in the diagnosis of all stroke subtypes significantly on kappa statistics (k = 0.538, P < 0.001) and interrater and intrarater reliability between two cadres of medical personnel in the use of BSS were significant (r = 0.9. 0.95, 0.95, P < 0.001, <0.001, <0.001), respectively. BSS as a simple clinical tool could be used with appreciable levels of accuracy in the clinical diagnosis of acute brain infarct where neuroimaging may not be available or immediately inaccessible, much the same way it is being used for ICH.

Randomised, Double-Blind, Placebo-Controlled, Dose-Escalating Phase I Study of QGC001, a Centrally Acting Aminopeptidase A Inhibitor Prodrug

Inhibition of brain aminopeptidase A (APA), which converts angiotensin II into angiotensin III, has emerged as a novel antihypertensive treatment, as demonstrated in several experimental animal models. QGC001 (originally named RB150) is a prodrug of the specific and selective APA inhibitor EC33, and as such it is the prototype of a new class of centrally acting antihypertensive agents. Given by the oral route in hypertensive rats, it enters the brain and generates EC33, which blocks the brain renin-angiotensin system activity and normalises blood pressure. The aim of the present study was to evaluate the safety, pharmacokinetics and pharmacodynamic effects of QGC001 in humans. Fifty-six healthy male volunteers were randomly assigned to receive in double-blind and fasted conditions single oral doses of 10, 50, 125, 250, 500, 750, 1,000 and 1,250 mg of QGC001 (n = 6/dose) or placebo (n = 2/dose). We measured plasma and urine concentrations of both QGC001 and EC33 by liquid chromatography-tandem mass spectrometry, plasma renin concentrations (PRC), plasma and free urine aldosterone (PAldo and UAldo), plasma copeptine (PCop), and plasma and urine cortisol (PCort and UCort) concentrations, and supine systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) at various time points. All doses of QGC001 were clinically and biologically well-tolerated. Peak plasma concentrations (Cmax) of QGC001 and EC33 increased linearly with the dose, with a median time to reach Cmax (tmax) of 1.5 h for QGC001 and 3.0 h for EC33. The median plasma elimination half-life of QGC001 was 1.6 h consistently throughout doses. Urinary excretion of QGC001 and EC33 was below 2% of the administered dose. When compared with placebo, QGC001 did not significantly change PRC, PAldo, UAldo, PCop, PCort or UCort. No significant change was observed for supine HR, SBP and DBP in any treatment group. Single oral administration of QGC001 up to 1,250 mg in healthy volunteers was well-tolerated. Following oral administration, QGC001 is absorbed via the gastrointestinal tract and converted partially into its active metabolite EC33 in plasma. As in animal experiments, in normotensive subjects QGC001 had no effect on the systemic renin-angiotensin-aldosterone parameters and on PCop concentrations, a marker of vasopressin release. In normotensive subjects, a single dose of QCG001 had no effect on SBP, DBP or HR. These data support further evaluation of multiple oral doses of QGC001 in human volunteers and its clinical efficacy in hypertensive patients.

Cholecalciferol Treatment to Reduce Blood Pressure in Older Patients With Isolated Systolic Hypertension

Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension. No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension, the most common pattern of hypertension in older people. To test whether high-dose, intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension. Parallel group, double-blind, placebo-controlled randomized trial. Primary care clinics and hospital clinics. Patients 70 years and older with isolated systolic hypertension (supine systolic blood pressure >140 mm Hg and supine diastolic blood pressure <90 mm Hg) and baseline 25-hydroxyvitamin D levels less than 30 ng/mL were randomized into the trial from June 1, 2009, through May 31, 2011. A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year. Difference in office blood pressure, 24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, insulin resistance, and b-type natriuretic peptide level during 12 months. A total of 159 participants were randomized (mean age, 77 years). Mean baseline office systolic blood pressure was 163/78 mm Hg. Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group (+8 ng/mL at 1 year, P < .001). No significant treatment effect was seen for mean (95% CI) office blood pressure (−1 [−6 to 4]/−2 [−4 to 1] mm Hg at 3 months and 1 [−2 to 4]/0 [−2 to 2] mm Hg overall treatment effect). No significant treatment effect was evident for any of the secondary outcomes (24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, glucose level, and walking distance). There was no excess of adverse events in the treatment group, and the total number of falls was nonsignificantly lower in the group receiving vitamin D (36 vs 46, P = .24). Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension. isrctn.org Identifier: ISRCTN92186858.

Prevention of seating-induced postural hypotension and its symptoms by leg compression bandaging during mobilization of inpatients

Purpose: Seating-induced Postural Hypotension (PH) has been reported in older inpatients. However, little is known about its prevention. We aimed to evaluate the eventual effects of leg compression bandages on seating-induced PH in the context of various relevant clinical variables. Methods: Included were 73 hospitalized patients with various acute conditions, aged 60 years and more, bedridden for at least 8 hours, with diagnosed PH (≥20 mm Hg systolic and/or ≥10 mm Hg diastolic blood pressure falls) at the first seating. Blood pressure, heart rhythm, dizziness and palpitations were recorded before and during 5 minutes of sitting. On the next day, the patients were reevaluated, this time using moderate compression bandages applied along both legs before seating. Depending on the persistence of PH at the 2nd day of the study, the patients were divided into two groups: with and without persisting PH. Results: Compared to non-bandaged state, PH was registered only in 53% of bandaged patients (P<0.001). Moreover, appearance of PH symptoms was decreased (43.8% vs. 34.2%, respectively, P<0.001). Demographic characteristics, main reasons for admission, duration of bed rest, prevalence of comorbidities and treatment with relevant medications were comparable between patients with or without persisting PH. However, on the 2nd day mean values of supine diastolic blood pressure were significantly higher in the group with persisting PH (82.1±17.7 vs. 73.6±14.3 mm Hg, P=0.027). In patients with PH disappearing following bandaging, the PH symptoms were significantly reduced at the 2nd day (P=0.003). Even in patients with persistent PH, the magnitude of blood pressure decline and appearance of PH symptoms were decreased while wearing bandages (P=0.004 and 0.002, respectively). Conclusions: During mobilization of inpatients, leg compression bandages seem beneficial for reducing the seating-induced PH and relevant symptoms. Even in patients with persisting PH, bandaging would be advantageous for improving hemodynamics and attenuating the associated symptoms.