Blood Pressure In Healthy Subjects Research Articles

Hemodynamic effects of intraoperative 30% versus 80% oxygen concentrations: an exploratory analysis.

Supplemental oxygen leads to an increase in peripheral vascular resistance which finally increases systemic blood pressure in healthy subjects and patients with coronary artery disease, heart failure, undergoing heart surgery, and with sepsis. However, it is unknown whether this effect can also be observed in anesthetized patients having surgery. Thus, we evaluated in this exploratory analysis of a randomized controlled trial the effect of 80% versus 30% oxygen on intraoperative blood pressure and heart rate. We present data from a previous study including 258 patients, who were randomized to a perioperative inspiratory FiO2 of 0.8 (128 patients) versus 0.3 (130 patients) for major abdominal surgery. Continuous arterial blood pressure values were recorded every three seconds and were exported from the electronic anesthesia record system. We calculated time-weighted average (TWA) and Average Real Variability (ARV) of mean arterial blood pressure and of heart rate. There was no significant difference in TWA of mean arterial pressure between the 80% (80 mmHg [76, 85]) and 30% (81 mmHg [77, 86]) oxygen group (effect estimate -0.16 mmHg, CI -1.83 to 1.51; p = 0.85). There was also no significant difference in TWA of heart rate between the 80 and 30% oxygen group (median TWA of heart rate in the 80% oxygen group: 65 beats.min-1 [58, 72], and in the 30% oxygen group: 64 beats.min-1 [58; 70]; effect estimate: 0.12 beats.min-1, CI -2.55 to 2.8, p = 0.94). Also for ARV values, no significant differences between groups could be detected. In contrast to previous results, we did not observe a significant increase in blood pressure or a significant decrease in heart rate in patients, who received 80% oxygen as compared to patients, who received 30% oxygen during surgery and for the first two postoperative hours. Thus, hemodynamic effects of supplemental oxygen might play a negligible role in anesthetized patients. https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1.

PS-C08-6: COMPARING BLOOD PRESSURE MEASUREMENTS BETWEEN A NOVEL CUFF-LESS EARPHONE-TYPE DEVICE BASED ON GREEN REFLECTED PHOTOPLETHYSMOGRAPHY AND A STANDARD CUFF-BASED SPHYGMOMANOMETER

Objective: Blood pressure (BP) measurement with conventional sphygmomanometers often causes discomfort and pain to the users due to arterial occlusion pressure caused by the inflatable cuff, making it difficult to perform continuous or frequent measurements for rigid blood pressure control. Developing unconstrained wearable electronics that can measure BP continuously would be useful in the healthcare field. We have developed a novel earphone-type device for cuff-less BP monitoring based on photoplethysmography with green light. In the present study, we compared the measured BP values between this novel cuff-less BP monitoring device and a conventional cuff-based sphygmomanometer. Design and Methods: From August 2020 to October 2021, 20 healthy subjects and 40 hypertensive patients (outpatients attending Yokohama City University Hospital and Yokohama Minami Kyosai Hospital, Yokohama, Japan) were recruited. Each participant's BP was measured using the novel cuff-less BP monitoring device as well as a standard cuff-based sphygmomanometer under four different conditions: static, BP rising and falling, and reproducible after the one-month interval. The results of measurements under the four conditions were integrated and analyzed. The BP measurements were determined to be comparable between the standard cuff-based sphygmomanometer and the novel cuff-less earphone-type device, if the mean absolute difference (MAD) of the measurements was within 7 mmHg. We also performed Bland-Altman agreement analyses. Results: The participants’ characteristics were as follows. Male to female ratio was approximately 50% in both groups. Age was 27.5 [interquartile (IQR) 24.5–33.0] years old for the healthy subjects and 65.0 [IQR 49.5–74.0] years old for the patients with hypertension (HTN). BMI was 21.2 [IQR 20.1–22.5] kg/m 2 and 23.8 [IQR 21.8–24.9] kg/ m 2, respectively. MAD between the novel cuff-less device and the reference using the standard cuff-based sphygmomanometer among the healthy subjects was 5.8 mmHg for systolic BP (SBP) and 5.3 mmHg for diastolic BP (DBP). MAD in the patients with HTN was 7.8 mmHg for SBP and 4.4 mmHg for DBP. In Bland-Altman agreement analyses, mean difference in the healthy subjects was 2.7 (95% confidence interval [CI] −13.4, 16.8) mmHg for SBP and 2.4 (95% CI −10.7, 15.5) mmHg for DBP. Mean difference in the patients with HTN was 0.9 (95% CI −20.0, 21.9) mmHg for SBP and 0.7 (95% CI −10.9, 12.3) mmHg for DBP. Conclusions: Our newly developed cuff-less earphone-type device based on green reflected photoplethysmography able to predict BP in healthy subjects, but it was difficult to predict SBP in the patients with HTN.

REL-1017 (Esmethadone) Increases Circulating BDNF Levels in Healthy Subjects of a Phase 1 Clinical Study.

Brain-derived neurotrophic factor (BDNF), a neurotrophin widely expressed in the central nervous system, exhibits important effects on neural plasticity. BDNF has been implicated in the mechanism of action of ketamine, a N-methyl-d-aspartic acid receptor (NMDAR) antagonist with rapid anti-depressant effects in humans. REL-1017 (esmethadone), the d-optical isomer of the racemic mixture d-l-methadone, is devoid of clinically relevant opioid activity at doses expected to exert therapeutic NMDAR antagonistic activity in humans. The present study was conducted to ascertain the effects of oral administration of 25 mg of REL-1017 for 10 days on plasma BDNF in healthy subjects confined to an inpatient unit for a phase 1 clinical trial. We observed an increase in post-treatment BDNF plasma levels compared to pre-treatment levels. Post-treatment, Day 10 BDNF plasma levels ranged from 2 to 17 times pre-treatment levels in the 25 mg REL-1017 treatment group, whereas in the placebo group, BDNF plasma levels remained unchanged (p = 0.028). Diastolic blood pressure decreased significantly in subjects treated with REL-1017, while no effect could be observed in the placebo group. In conclusion, the administration of 25 mg REL-1017 significantly increased BDNF plasma levels and significantly decreased diastolic blood pressure in healthy subjects confined to an inpatient unit for a phase 1 clinical trial.

Comparison of peak expiratory flow rate and blood pressure in healthy subjects performing yoga and healthy subjects performing aerobics

Background: Exercise is any bodily activity that enhances or maintains physical fitness and thereby overall health. Non-pharmacological mode of treatment of respiratory ailments and hypertension is gaining popularity, of which yoga and aerobic exercise are well sought -after. Both of these help in improving cardiorespiratory functions. Aim and Objective: The aim of this study was to analyze the effects of yoga and aerobic exercise on peak expiratory flow rate (PEFR) and blood pressure (BP). Materials and Methods: A total of 86 healthy subjects aged between 30 and 40 years doing respective exercise regularly for ≥6 months, 5 days/week; without any comorbid respiratory or cardiovascular ailments such as ischemic heart disease/diabetes mellitus/asthma/chronic obstructive pulmonary disease were enrolled in this cross-sectional study. Demographic details such as age, gender, and history of respiratory or cardiac symptoms were taken by detailed medical history and physical examination. PEFR and BP of subjects of both the groups were measured and evaluated. PEFR was measured using Wrights handheld peak flow meter. BP was measured using sphygmomanometer. Results: Statistically significant (P < 0.05) difference was seen in PEFR of subjects doing yoga versus aerobics. About 43.75% of males doing yoga had PEFR between 351 and 400 L/min, while same for aerobics was 25%. About 50% of females doing yoga had PEFR between 301 and 350 L/min, while same for aerobics was 35.7%. Conclusion: PEFR was found statistically higher in subjects doing yoga than aerobics. No significant correlation could be found between BP and yoga/aerobics as various factors, especially genetics, affect it which is a limitation of this study.

Negative priming is diminished under high blood pressure in healthy subjects.

The ability to ignore distracting objects is a core mechanism in selective attention and has been analyzed particularly with respect to its clinical implications (e.g., depression, schizophrenia, or unhealthy life-style). Here, we investigated the correlation between an established experimental task to measure distractor-processing and participants' blood pressure. We used the negative priming (NP) task in which participants show worse performance to target stimuli that were distractors in the previous trial. Notably, our participants were all healthy, young subjects but nevertheless we observed a correlation between blood pressure levels and NP effects, the higher the blood pressure the less NP was shown by participants. Our results suggest that processes modulated by higher blood pressure diminish the ability to successful ignore distracting objects not only at hypertension levels.

Validity of transit time-based blood pressure measurements in patients with and without heart failure or pulmonary arterial hypertension across different breathing maneuvers.

Pulse transit time (PTT) derived by ECG and plethysmographic signal can be a promising alternative to invasive or oscillometry-based blood pressure (BP) monitoring in sleep laboratories because it does not cause arousals from sleep. Therefore, this study assessed the validity of PTT for BP monitoring under sleep laboratory-like conditions. Ten volunteers (55.8 ± 19.6years), 12 patients with heart failure with reduced ejection fraction (HFrEF; 67.3 ± 8.6years), and 14 patients with Nizza class I pulmonary arterial hypertension (PAH; 59.5 ± 13.4years) performed different breathing patterns to simulate nocturnal sleep-disordered breathing (SDB). BP was measured at least every 15min over 1h using oscillometry (Task Force Monitor™) and PTT (SOMNOscreen™) devices in free breathing conditions and during SDB simulation (alternating phases of hyperventilation and apneas). One hundred forty-two points of measurements were collected. No difference was found in both mean systolic BP (SBP) and diastolic BP (DBP) between oscillometric PTT-based BP measurements in the whole population and throughout the whole recording (SBP 111.3 ± 15.1mmHg versus 110.0 ± 14.7mmHg, p = 0.051; DBP 69.9 ± 12.2 versus 69.9 ± 14.2mmHg, p = 0.701). Likewise, no significant difference in SBP and DBP was found between the two methods in the subgroups of healthy subjects, HFrEF patients and PAH patients, both in free breathing conditions (p > 0.05) and during SDB simulation (p > 0.05). When monitoring BP in healthy subjects, and in patients with HFrEF or PAH, PTT provides a BP estimation comparable with oscillometric measurement, though slightly inaccurate, both in the condition of regular and unstable breathing.

Dietary Nitrate from Beetroot Juice for Hypertension: A Systematic Review.

According to current therapeutic approaches, a nitrate-dietary supplementation with beetroot juice (BRJ) is postulated as a nutritional strategy that might help to control arterial blood pressure in healthy subjects, pre-hypertensive population, and even patients diagnosed and treated with drugs. In this sense, a systematic review of random clinical trials (RCTs) published from 2008 to 2018 from PubMed/MEDLINE, ScienceDirect, and manual searches was conducted to identify studies examining the relationship between BRJ and blood pressure. The specific inclusion criteria were: (1) RCTs; (2) trials that assessed only the BRJ intake with control group; and (3) trials that reported the effects of this intervention on blood pressure. The search identified 11 studies that met the inclusion criteria. This review was able to demonstrate that BRJ supplementation is a cost-effective strategy that might reduce blood pressure in different populations, probably through the nitrate/nitrite/nitric oxide (NO3−/NO2−/NO) pathway and secondary metabolites found in Beta vulgaris. This easily found and cheap dietary intervention could significantly decrease the risk of suffering cardiovascular events and, in doing so, would help to diminish the mortality rate associated to this pathology. Hence, BRJ supplementation should be promoted as a key component of a healthy lifestyle to control blood pressure in healthy and hypertensive individuals. However, several factors related to BRJ intake (e.g., gender, secondary metabolites present in B. vulgaris, etc.) should be studied more deeply.

Experimental Weight Gain Increases Ambulatory Blood Pressure in Healthy Subjects: Implications of Visceral Fat Accumulation

ObjectiveTo examine whether experimentally induced weight gain raises ambulatory blood pressure (BP) in healthy subjects and identify any relationship between changes in BP and changes in regional fat distribution. Patients and MethodsTwenty-six normal weight subjects were randomized to 8 weeks of weight gain through overfeeding (n=16; age, 30.4±6.6 years) or to weight maintenance (controls; n=10; age, 27.1±7.7 years) between July 2004 and August 2010. Measures of body composition via dual energy X-ray absorptiometry and computed tomography, circulating biomarkers, and 24-hour ambulatory BP were obtained at baseline and after the 8-week experimental phase. ResultsOverfeeding resulted in 3.7 kg (95% CI, 2.9-4.5) increase in body weight in weight gainers, with increments in total (46.2 cm2; 95% CI, 27.6-64.9), visceral (13.8 cm2; 95% CI, 5.8-21.9), and subcutaneous fat (32.4 cm2; 95% CI, 13.5-51.3). No changes occurred in the maintenance group. Increases in 24-hour systolic BP (4 mm Hg; 95% CI, 1.6-6.3), mean BP (1.7 mm Hg; 95% CI, 0.3-3.3), and pulse pressure (2.8 mm Hg; 95% CI, 1.1-4.4) were evident after weight gain in the experimental group, whereas BP remained unchanged in controls. Changes in mean BP correlated only with changes in visceral fat (ρ=0.45; P=.02), but not with changes in other body composition measures. ConclusionModest weight gain causes elevation in 24-hour BP in healthy subjects. The association between increased BP and abdominal visceral fat accumulation suggests that visceral deposition of adipose tissue may contribute specifically to the enhanced risk of hypertension associated with weight gain.

Effect of sodium nitrite on renal function and sodium and water excretion and brachial and central blood pressure in healthy subjects: a dose-response study

Sodium nitrite (NaNO2) is converted to nitric oxide (NO) in vivo and has vasodilatory and natriuretic effects. Our aim was to examine the effects of NaNO2 on hemodynamics, sodium excretion, and glomerular filtration rate (GFR). In a single-blinded, placebo-controlled, crossover study, we infused placebo (0.9% NaCl) or 0.58, 1.74, or 3.48 μmol NaNO2·kg-1·h-1 for 2 h in 12 healthy subjects, after 4 days of a standard diet. Subjects were supine and water loaded. We measured brachial and central blood pressure (BP), plasma concentrations of renin, angiotensin II, aldosterone, arginine vasopressin (P-AVP), and plasma nitrite (P-[Formula: see text]), GFR by Cr-EDTA clearance, fractional excretion of sodium (FENa) free water clearance (CH2O), and urinary excretion rate of guanosine 3',5'-cyclic monophosphate (U-cGMP). The highest dose reduced brachial systolic BP (5.6 mmHg, P = 0.003), central systolic BP (5.6 mmHg, P = 0.035), and CH2O (maximum change from 3.79 to 1.27 ml/min, P = 0.031) and increased P-[Formula: see text] (from 0.065 to 0.766 μmol/l, P < 0.001), while reducing U-cGMP (from 444 to 247 pmol/min, P = 0.004). GFR, FENa, P-AVP, and the components in the renin-angiotensin-aldosterone system did not change significantly. In conclusion, intravenous NaNO2 induced a dose-dependent reduction of brachial and central BP. The hemodynamic effect was not mediated by the renin-angiotensin-aldosterone system. NaNO2 infusion resulted in a vasopressin-independent decrease in CH2O and urine output but no change in urinary sodium excretion or GFR. The lack of increase in cGMP accompanying the increase in [Formula: see text] suggests a direct effect of nitrite or nitrate on the renal tubules and vascular bed with little or no systemic conversion to NO.

Phase 1, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Trial to Evaluate the Effects of Erenumab (AMG 334) and Concomitant Sumatriptan on Blood Pressure in Healthy Subjects (P2.161)

Phase 1, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Trial to Evaluate the Effects of Erenumab (AMG 334) and Concomitant Sumatriptan on Blood Pressure in Healthy Subjects (P2.161)

Amiloride-sensitive cation channel 2 genotype affects the response to a carbon dioxide panic challenge.

Until recently, genetic research into panic disorder (PD) has had only limited success. Inspired by rodent research, demonstrating that the acid-sensing ion channel 1a (ASIC1a) is critically involved in the behavioral fear response to carbon dioxide (CO2) exposure, variants in the human homologue gene amiloride-sensitive cation channel 2 (ACCN2) were shown to be associated with PD. However, the relationship between changes in brain pH and ACCN2, as done in rodents by CO2 exposure, has not been investigated yet in humans. Here, we examined this link between the ACCN2 gene and the response to CO2 exposure in two studies: in healthy volunteers as well as PD patients and using both behavioral and physiological outcome measures. More specifically, 107 healthy volunteers and 183 PD patients underwent a 35% CO2 inhalation. Negative affect was assessed using visual analogue scales and the panic symptom list (PSL), and, in healthy volunteers, cardiovascular measurements. The single nucleotide polymorphism rs10875995 was significantly associated with a higher emotional response in PD patients and with an increase in systolic as well as diastolic blood pressure in healthy subjects. In all measurements, subjects homozygous for the T-allele showed a heightened reactivity to CO2. Furthermore, a trend towards an rs685012 genotype effect on the emotional response was found in PD patients. We provide the first evidence that genetic variants in the ACCN2 are associated with differential sensitivity to CO2 in PD patients as well as healthy volunteers, further supporting ACCN2 as a promising candidate for future research to improve current treatment options.

Lower diastolic blood pressure in healthy subjects with vitamin K deficiency: a preliminary cross-sectional study

Introduction. There is a growing body of evidence for the role of vitamin K in cardiovascular health. As a cofactor of carboxylation of the matrix Gla protein it prevents arterial calcification. However, the data on the relationship between vitamin K status and the blood pressure are scarce, and particularly so in persons without the burden of cardiovascular risk factors. Material and Methods. We performed a pilot cross‑sectional study, in which we hypothesized that vitamin K deficiency is associated with a higher blood pressure in young, healthy people. The concentration of protein induced by vitamin K absence‑II (PIVKA‑II) larger than 2 ng/mL was chosen as a proxy for vitamin K deficiency; it was assessed in serum using ELISA. Blood pressure was measured using a validated, automated oscillometric monitor in triplicate.Results. Twenty‑three healthy subjects were enrolled (16 female; mean age 21.3 ± 1.6 years; body mass index 20.6 ± 2.4 kg/m2). The diastolic blood pressure (DBP) was lower in vitamin K‑deficient subjects (58 ± 9 vs. 67 ± 5 mmHg, p = 0.01). The mean arterial blood pressure also differed (75 ± 9 vs. 83 ± 6, p = 0.02). PIVKA‑II levels correlated with DBP only (Pearson’s R = -0.41, p &lt; 0.05; Spearman’s ρ ns.). Stepwise regression identified PIVKA‑II concentrations as the only independent parameter associated with DBP (adjusted R2 = 13.1%; PIVKA‑II: β = -0.41; 95%CI -1.87-(-0.00098), t = -2.08, p &lt; 0.05).Conclusions. The relationship between vitamin K deficiency and low DBP in young adults should be investigated further.

Lower diastolic blood pressure in healthy subjects with vitamin K deficiency: a preliminary cross-sectional study

Introduction. There is a growing body of evidence for the role of vitamin K in cardiovascular health. As a cofactor of carboxylation of the matrix Gla protein it prevents arterial calcification. However, the data on the relationship between vitamin K status and the blood pressure are scarce, and particularly so in persons without the burden of cardiovascular risk factors. Material and Methods. We performed a pilot cross-sectional study, in which we hypothesized that vitamin K deficiency is associated with a higher blood pressure in young, healthy people. The concentration of protein induced by vitamin K absence-II (PIVKA-II) larger than 2 ng/mL was chosen as a proxy for vitamin K deficiency; it was assessed in serum using ELISA. Blood pressure was measured using a validated, automated oscillometric monitor in triplicate.Results. Twenty-three healthy subjects were enrolled (16 female; mean age 21.3 ± 1.6 years; body mass index 20.6 ± 2.4 kg/m2). The diastolic blood pressure (DBP) was lower in vitamin K-deficient subjects (58 ± 9 vs. 67 ± 5 mmHg, p = 0.01). The mean arterial blood pressure also differed (75 ± 9 vs. 83 ± 6, p = 0.02). PIVKA-II levels correlated with DBP only (Pearson’s R = -0.41, p &lt; 0.05; Spearman’s ? ns.). Stepwise regression identified PIVKA-II concentrations as the only independent parameter associated with DBP (adjusted R2 = 13.1%; PIVKA-II: ß = -0.41; 95%CI -1.87-(-0.00098), t = -2.08, p &lt; 0.05).Conclusions. The relationship between vitamin K deficiency and low DBP in young adults should be investigated further.

The effect of hyperoxia on central blood pressure in healthy subjects

IntroductionHyperoxia increases total peripheral resistance by acting locally but also inhibits the activity of carotid body chemoreceptors. We studied the effect of hyperoxia on central pressure in normotensive subjects.Material and methodsMedical air followed by 100% oxygen was provided to 19 subjects (12/7 female/male, age 28.2 ±1.1 years) for 15 min through a non-rebreather mask. Central blood pressure was then measured using applanation tonometry.ResultsAfter the first 2 min of hyperoxia, heart rate decreased significantly (65 ±2.6 beats/min vs. 61 ±2.1 beats/min, p = 0.0002). Peripheral and central blood pressure remained unchanged, while hemoglobin oxygen saturation and subendocardial viability ratio index increased (97 ±0.4% vs. 99 ±0.2%, p = 0.03; 168 ±8.4% vs. 180 ±8.2%, p = 0.009). After 15 min of 100% oxygen ventilation, heart rate and peripheral and central blood pressures remained unchanged from the first 2 min. The augmentation index, augmentation pressure and ejection duration increased as compared to baseline values and those obtained at 2 min (–5.1 ±2.9% vs. –1.2 ±2.6%, p = 0.005 and –4.6 ±2.7% vs. –1.2 ±2.6%, p = 0.0015; –1.3 ±0.7 mm Hg vs. –0.2 ±1.2 mm Hg, p = 0.003 and –1.1 ±0.7 mm Hg vs. –0.2 ±1.2 mm Hg, p = 0.012; 323 ±3.6 ms vs. 330 ±3.5 ms, p = 0.0002 and 326 ±3.5 ms vs. 330 ±3.5 ms, p = 0.021, respectively).ConclusionsThe present study shows that hyperoxia does not affect central blood pressure in young healthy subjects and may improve myocardial blood supply estimated indirectly from applanation tonometry.

Effect of Cuff Placement on Blood Pressure Measurement in Conscious Healthy Dogs

Blood pressure determination is a very helpful aid in the diagnosis and monitoring of several diseases in small animal medicine. Non-invasive methods for blood pressure measurement are currently the most rapid and practical alternative in the clinical setting, however only few studies have dealt with selecting the best cuff position for its determination. The aim of the study was to determine the best site for cuff placement (limbs and tail) during noninvasive blood pressure in healthy subjects. Arterial blood pressure was measured by use of an oscilometric system in 22 clinically healthy dogs. Five consecutive measurements were obtained from five different sites: left and right median arteries, left and right tibial cranial arteries and coccygeal artery then were compared. Significant differences were found in systolic blood pressure measured from the right hind limb. Heart rate, age, and weight were not found to have a significant influence on arterial blood pressure. We suspect that the long duration of the procedure was the culprit, leading to stress, which as a result, led to higher blood pressure on the mentioned limb. Based on our results, we concluded that all limbs as well as the tail are suitable sites for routine blood pressure determination, as long as the procedure is completed within a rational time period.

Ascending Aorta Elastography After Kawasaki Disease Compared to Systemic Hypertension

Kawasaki disease (KD) is a systemic vasculitis, classically affecting large- and medium-size arteries. The coronary arteries draw most of the clinical attention, whereas few studies have taken interest in the ascending aorta. Using a proprietary imaging-based mechanical biomarker (ImBioMark), we sought to determine aortic stiffness in KD compared to systemic hypertension (HTN) and healthy children. We evaluated parasternal long-axis views focused on the ascending aorta in 20 controls, 12 KD, and 8 HTN as a comparative clinical model of vascular stiffness. We calculated systolic and diastolic aortic wall strain with ImBioMark. Strain was tested for normality against height, systolic, and diastolic blood pressure in normal subjects. Strain from KD and HTN was normalized (Z score) accordingly. Z score comparisons were performed using nonparametric statistics. Age was similar between KD and HTN (9.1 ± 5.3 and 9.9 ± 5.3 years old; p = NS). Systolic and diastolic strain values were normally distributed against height, systolic blood pressure, and diastolic blood pressure in healthy subjects. HTN subjects had abnormal systolic and diastolic strain values (p < 0.0001). Whereas KD subjects had normal diastolic strain, systolic strain was significantly lower (p < 0.001), and systolic strain was intermediate between controls and HTN. There were no significant differences in aortic strain among KD, however, according to the presence of coronary artery aneurysms. Despite normal blood pressure, the ascending aorta in KD exhibits reduced strain during systole. This may reflect in situ rigidity of the aorta. The normal diastolic strain in KD may, in contrast, reflect normal peripheral vascular resistance.

Plasma C-terminal proEndothelin-1 (CTproET-1) is affected by age, renal function, left atrial size and diastolic blood pressure in healthy subjects

Endothelin-1 (ET-1) is a short chained peptide primarily of endothelial origin. Concentrations of this peptide are increased in subjects with hypertension, primary pulmonary hypertension and myocardial infarction, however its short half-life makes quantification difficult. The C-terminal of proET-1 (CTproET-1) is stoichiometrically secreted with its bioactive peptide and would be a valid method of measuring the active peptide as it has a stable half-life and is less resistant to proteolytic cleavage. The objective of this study was to understand the factors (clinical, echocardiographic and biochemical) that specifically influence plasma CTproET-1 in healthy subjects. 518 healthy volunteers were recruited from a screening study. Plasma CTproET-1 concentrations were quantified using a novel immunoluminometric sandwich assay. In multivariate analyses, age (P<0.001), diastolic BP (P=0.007), LA size (P=0.001) and eGFR (P<0.001) were independently predictive of plasma CTproET-1 levels in the healthy subjects. Therefore the interpretation of plasma CTproET-1 levels in such individuals should take into account these variables to avoid potential confounding.

Pharmacokinetics, Tolerability, and Safety of the Single Oral Administration of AGSAV301 vs Exforge: A Randomized Crossover Study of Healthy Male Volunteers

Valsartan, an angiotensin receptor blocker, is often used with calcium channel blockers (CCBs) such as amlodipine to control hypertension. Recently, the fixed-dose combination (FDC) of amlodipine 10mg/valsartan 160mg (Exforge) was approved. Amlodipine is a racemic mixture of CCB; S-amlodipine has higher activity than R-form. Therefore, AGSAV301, the FDC of S-amlodipine 5mg/valsartan 160mg was recently developed. The objective of this study was to compare the pharmacokinetic (PK) characteristics of S-amlodipine and valsartan when administered as one tablet each of Exforge and AGSAV301 to healthy male subjects. This was a single-dose, randomized, open-label, two-way, two-period crossover study. Each subject received a single dose of AGSAV301 and Exforge, separated by a 3-week washout period. Plasma samples for the PK analysis of valsartan and S-amlodipine were collected at predose (0) and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, and 168h after administration. Tolerability was also evaluated. A total of 29 subjects were enrolled; 24 completed this study. The S-amlodipine maximum plasma concentration (C max) geometric mean ratio (GMR) between AGSAV301 and Exforge was 0.951 (90% CI 0.983-1.014), and area under the concentration-time curve from time 0 to last measured time point (AUClast) was 0.917 (90% CI 0.861-0.976). The GMR of valsartan C max was 0.994 (90% CI 0.918-1.076), and the AUClast was 0.927 (90% CI 0.821-1.047). All adverse events (AEs) were resolved without sequelae; no serious AEs were reported. Two drugs showed similar tendencies to lower blood pressure in healthy subjects. The PK profiles of AGSAV301 and Exforge were bioequivalent. Both drugs were also well tolerated, with comparable AE profiles and similar blood pressure-lowering tendencies in healthy volunteers, suggesting equivalent therapeutic indications.

Serum 25-hydroxyvitamin D is associated with both arterial and ventricular stiffness in healthy subjects

BackgroundVitamin D regulates the renin–angiotensin system, suppresses proliferation of vascular smooth muscle and improves endothelial cell dependent vasodilatation. These mechanisms may play a role on pathogenesis of arterial and left ventricular stiffness. ObjectivesWe aimed to investigate the association between serum 25-hydroxyvitamin D with arterial and left ventricular stiffness in healthy subjects. MethodsWe studied 125 healthy subjects without known cardiovascular risk factors or overt heart disease (mean age: 60.2±11.9 years). Serum 25-hydroxyvitamin D was measured using a direct competitive chemiluminescent immunoassay. The subjects were divided into two groups according to the serum vitamin D level; vitamin D sufficient (≥20ng/ml, n=56) and vitamin D deficient (<20ng/ml, n=69). Indexes of LV stiffness such as E/A and E/E′ were measured. Pulse wave velocity (PWV), which reflects arterial stiffness, was calculated using the single-point method via the Mobil-O-Graph® ARC solver algorithm. ResultsSystolic blood pressure, level of serum calcium, PWV and E/E′ values were higher and E/A values were lower in vitamin D deficient group compared with vitamin D sufficient group. Multiple linear regression analysis showed that vitamin D level was independently associated with E/E′ (β=−0.364, p<0.001), serum calcium (r=−0.136, p=0.014), PWV (β=−0.203, p=0.003), E/A (β=0.209, p=0.001) and systolic blood pressure (β=−0.293, p<0.001). Conclusion25-Hydroxyvitamin D levels are associated with increased ventricular and arterial stiffness as well as systolic blood pressure in healthy subjects.

Autonomic effects of suggestive placebo interventions to increase or decrease blood pressure: A randomized controlled trial in healthy subjects

ObjectivePlacebo effects on pain and other subjective parameters are well-established, but the evidence for placebo effects on autonomic functions is scarce. Our randomized-controlled trial aimed to investigate autonomic responses after a suggestive placebo intervention intended to increase or decrease blood pressure (BP). Methods92 healthy subjects inhaled a placebo spray with the prior suggestion that it contained an effective drug to either increase or decrease BP, or the information that a placebo was administered (controls). BP, heart rate, stroke volume, peripheral resistance, heart rate variability and skin conductance level were monitored 30min before and after placebo administration. The expected and the subjectively perceived drug effect were measured by means of visual analog scales. ResultsWe found no statistically significant differences between the groups with respect to BP, heart rate, stroke volume, total peripheral resistance and heart rate variability responses to the verbal suggestions. Skin conductance response was more pronounced in the BP decrease group compared with controls (p=0.04), but this finding might be due to chance, given the multiple tests. Within the total study sample, BP, total peripheral resistance, low frequency power of heart rate variability and skin conductance were significantly higher after the placebo spray independent of the associated suggestions. Subjects in the BP increase and BP decrease condition had higher ratings of the expected and the subjectively perceived drug effect compared with controls (all p<0.05). ConclusionWe found no evidence that specific verbal suggestions during placebo interventions affect BP in healthy subjects.