Aortic Systolic Blood Pressure Research Articles

Arterial stiffness and blood pressure are similar in naturally menstruating and oral contraceptive pill-using women during the higher hormone phases.

What is the central question of this study? Are there differences in blood pressure, arterial stiffness and indices of pressure waveforms between young oral contraceptive pill-using and naturally menstruating women during lower and higher hormone phases of their cycles? What is the main finding and its importance? Blood pressure, arterial stiffness and indices of pressure waveforms are influenced similarly by exogenous and endogenous hormones. However, lower levels of exogenous hormones moderately increase blood pressure among oral contraceptive pill-using women. Elevations in blood pressure (BP) are understood as having a bidirectional relationship with stiffening of central and peripheral arteries. Arterial stiffness is mitigated by oestrogen, which aides in arterial vasorelaxation. To evaluate whether BP, stiffness, and pressure waveforms were different between young healthy naturally menstruating (non-OCP) and oral contraceptive pill (OCP)-using women, we measured brachial and aortic BPs, carotid-to-femoral pulse wave velocity, carotid β-stiffness, elastic modulus, central augmentation index and augmentation index normalized to a heart rate of 75bpm, and forward and backward pressure waveforms in 22 women (22 (1) years, OCP: n=12). To assess phasic differences, women were studied during the early follicular (≤5days of menstruation onset) and early luteal (4 (2)days post-ovulation) phases of non-OCP and compared to the placebo pill (≤5days of onset) and active pill (≤5days of highest-dose active pill) phases of OCP. During the lower hormone phases, OCP users had significantly higher brachial systolic blood pressure (SBP) (119.3 (8.3) vs. 110.2 (8.3) mmHg, P=0.02) and aortic SBP (104.10 (7.44) vs. 96.80 (6.39) mmHg, P=0.03) as compared to non-OCP users; however, during the higher hormone phases, there were no differences in measures of brachial or aortic BP, arterial stiffness, or indices of BP waveforms between OCP and non-OCP users (P≥0.05). In conclusion, exogenous and endogenous hormones have similar influences on BP and arterial stiffness; however, lower levels of exogenous hormones augment both central and peripheral BPs.

L-Citrulline supplementation attenuates aortic pulse pressure and wave reflection responses to cold stress in older adults

Augmented aortic systolic blood pressure (SBP) and wave reflection via sympathetic-mediated vasoconstriction elevates the risk for adverse cardiovascular events in older adults. L-citrulline (L-CIT) supplementation has shown to reduce aortic SBP and pulse pressure (PP) responses to cold pressor test (CPT) induced sympathoactivation in young men. The aim of this study was to elucidate the efficacy of L-CIT supplementation to attenuate aortic hemodynamic responses to CPT in older adults. Sixteen older adults were randomly assigned to placebo or L-CIT (6g/day) for 14-days in a crossover, double-blind, placebo-controlled design. Brachial SBP and aortic SBP, PP, augmented pressure (AP), augmentation index standardized at 75bpm (AIx@75), and pressure of the forward (Pf) and reflected (Pb) waves were evaluated at rest and during CPT pre- and post-intervention. Although no hemodynamic changes at rest, brachial SBP (Δ-12±18 vs. Δ4±14mmHg; P=0.008) and aortic SBP (Δ-10±14 vs. Δ4±12mmHg; P=0.005), PP (Δ-10±12 vs. Δ4±11mmHg; P=0.002), AP (Δ-4±4 vs. Δ2±7mmHg; P=0.004), AIx@75 (Δ-3.2±7.2 vs. Δ2.2±6.9%; P=0.038), Pf (Δ-6±10 vs. Δ3±9mmHg; P=0.019), and Pb (Δ-4±6 vs. Δ2±6mmHg; P=0.008) responses to the CPT were significantly attenuated following L-CIT supplementation vs. placebo. L-CIT supplementation attenuated aortic pulsatile pressure and pressure wave reflection responses to CPT in older adults, providing possible cardioprotection during cold-induced sympathoactivation in older adults.

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.

Glucose Metabolic Disorders Enhance Vascular Dysfunction Triggered by Particulate Air Pollution: a Panel Study.

Vascular dysfunction is a biological pathway whereby particulate matter (PM) exerts deleterious cardiovascular effects. The effects of ambient PM on vascular function in prediabetic individuals are unclear. A panel study recruited 112 Beijing residents with and without prediabetes. Multiple vascular function indices were measured up to 7 times. The associations between vascular function indices and short-term exposure to ambient PM, including fine particulate matter (PM2.5), ultrafine particles, accumulation mode particles, and black carbon, and the modification of these associations by glucose metabolic status were examined using linear mixed-effects models. Increases in brachial artery pulse pressure, central aortic pulse pressure, and ejection duration, and decreases in subendocardial viability ratio and reactive hyperemia index were significantly associated with at least one PM pollutant in all participants, indicating increased vascular dysfunction. For example, for an interquartile range increment in 5-day moving average ultrafine particles, brachial artery pulse pressure, and central aortic pulse pressure increased 5.4% (0.8%-10.4%) and 6.2% (1.2%-11.5%), respectively. Additionally, PM-associated changes in vascular function differed according to glucose metabolic status. Among participants with high fasting blood glucose levels (≥6.1 mmol/L), PM exposure was significantly associated with increased brachial artery systolic blood pressure, central aortic systolic blood pressure, brachial artery pulse pressure, central aortic pulse pressure, and augmentation pressure normalized to a heart rate of 75 bpm and decreased subendocardial viability ratio and reactive hyperemia index. Weaker or null associations were observed in the low-fasting blood glucose group. Glucose metabolic disorders may exacerbate vascular dysfunction associated with short-term ambient PM exposure.

Color-coded summation images for the evaluation of blood flow in endovascular aortic dissection fenestration

BackgroundTo analyze the benefit of color-coded summation images in the assessment of target lumen perfusion in patients with aortic dissection and malperfusion syndrome before and after fluoroscopy-guided aortic fenestration.MethodsBetween December 2011 and April 2020 25 patients with Stanford type A (n = 13) or type B dissection (n = 12) and malperfusion syndromes were treated with fluoroscopy-guided fenestration of the dissection flap using a re-entry catheter. The procedure was technically successful in 100% of the cases and included additional iliofemoral stent implantation in four patients. Intraprocedural systolic blood pressure measurements for gradient evaluation were performed in 19 cases. Post-processed color-coded DSA images were obtained from all DSA series before and following fenestration. Differences in time to peak (dTTP) values in the compromised aortic lumen and transluminal systolic blood pressure gradients were analyzed retrospectively. Correlation analysis between dTTP and changes in blood pressure gradients was performed.ResultsMean TTP prior to dissection flap fenestration was 6.85 ± 1.35 s. After fenestration, mean TTP decreased significantly to 4.96 ± 0.94 s (p < 0.001). Available systolic blood pressure gradients between the true and the false lumen were reduced by a median of 4.0 mmHg following fenestration (p = 0.031), with significant reductions in Stanford type B dissections (p = 0.013) and minor reductions in type A dissections (p = 0.530). A moderate correlation with no statistical significance was found between dTTP and the difference in systolic blood pressure (r = 0.226; p = 0.351).ConclusionsHemodynamic parameters obtained from color-coded DSA confirmed a significant reduction of TTP values in the aortic target lumen in terms of an improved perfusion in the compromised aortic region. Color-coded DSA might thus be a suitable complementary tool in the assessment of complex vascular patterns prevailing in aortic dissections, especially when blood pressure measurements are not conclusive or feasible.

Aortic haemodynamics: the effects of habitual endurance exercise, age and muscle sympathetic vasomotor outflow in healthy men

PurposeWe determined the effect of habitual endurance exercise and age on aortic pulse wave velocity (aPWV), augmentation pressure (AP) and systolic blood pressure (aSBP), with statistical adjustments of aPWV and AP for heart rate and aortic mean arterial pressure, when appropriate. Furthermore, we assessed whether muscle sympathetic nerve activity (MSNA) correlates with AP in young and middle-aged men.MethodsAortic PWV, AP, aortic blood pressure (applanation tonometry; SphygmoCor) and MSNA (peroneal microneurography) were recorded in 46 normotensive men who were either young or middle-aged and endurance-trained runners or recreationally active nonrunners (10 nonrunners and 13 runners within each age-group). Between-group differences and relationships between variables were assessed via ANOVA/ANCOVA and Pearson product-moment correlation coefficients, respectively.ResultsAdjusted aPWV and adjusted AP were similar between runners and nonrunners in both age groups (all, P > 0.05), but higher with age (all, P < 0.001), with a greater effect size for the age-related difference in AP in runners (Hedges’ g, 3.6 vs 2.6). aSBP was lower in young (P = 0.009; g = 2.6), but not middle-aged (P = 0.341; g = 1.1), runners compared to nonrunners. MSNA burst frequency did not correlate with AP in either age group (young: r = 0.00, P = 0.994; middle-aged: r = − 0.11, P = 0.604).ConclusionThere is an age-dependent effect of habitual exercise on aortic haemodynamics, with lower aSBP in young runners compared to nonrunners only. Statistical adjustment of aPWV and AP markedly influenced the outcomes of this study, highlighting the importance of performing these analyses. Further, peripheral sympathetic vasomotor outflow and AP were not correlated in young or middle-aged normotensive men.

Superiority of 24-Hour Aortic Over 24-Hour Brachial Pressure to Associate With Carotid Arterial Damage on the Basis of Pressure Amplification Variability: the SAFAR Study.

Evidence suggests marginal superiority of static aortic systolic blood pressure (aSBP) compared with brachial SBP (bSBP) regarding the association with organ damage and prognosis of cardiovascular disease (CVD). The noninvasive 24-hour aSBP assessment is feasible and associates better with presence of left ventricular hypertrophy compared with 24-hour bSBP. We aimed at comparing the association of 24-hour aSBP and 24-hour bSBP with indices of arterial damage and examining the role of 24-hour SBP amplification variability (within-subjects' SD) in this association. Consecutive subjects referred for CVD risk assessment underwent 24-hour aortic and brachial ambulatory BP monitoring using a validated oscillometric device (Mobil-O-Graph). Arterial damage was assessed by carotid intima-media thickness (IMT) and detection of carotid and femoral atheromatosis (plaque presence). Cross-sectionally 501 individuals (aged 54±13 years, 57% men, 80% hypertensives) were examined. Multivariable analysis revealed superiority of 24-hour aSBP regarding the association with IMT, carotid hypertrophy and carotid-but not femoral-atheromatosis. In receiver operator characteristics analysis, 24-hour aSBP displayed a higher discriminatory ability-compared to 24-hour bSBP-for the detection of both carotid hypertrophy (area under the curve, 0.662 versus 0.624, P<0.05) and carotid atheromatosis (area under the curve, 0.573 versus 0.547, P<0.05). This effect was more prominent in individuals with above-median 24-hour SD of SBP amplification. Our results suggest that 24-hour aSBP assessment may be of significant value in clinical practice to detect site-specific arterial damage on the basis of pressure amplification variability and should be prospectively examined in clinical trials.

Twenty-four-hour profile of peripheral and central blood pressure in young patients with high-normal blood pressure and hypertension

Aim. To evaluate indicators of daily monitoring of peripheral and central blood pressure in young patients with high-normal blood pressure (HNBP) and essential hypertension (HTN).Material and methods. One hundred twelve patients with HNBP or untreated hypertension aged 25-44 years were included. General clinical investigations were performed. An office blood pressure (BP) were assessed using an automatic BP monitor OMRON M2 Basic. Twenty-four-hour ambulotary BP monitoring (ABPM) on the brachial artery and aorta was carried out for 24 hours using the BpLAB system (OOO Petr Telegin) with an integrated Vasotens system. Depending on BP, patients were divided into groups: with HNBP and hypertension. Statistical processing and comparative analysis of the obtained data were carried out.Results. HNBP group consisted of 47 patients, while the HTN group consisted of 65 patients. The mean age of patients was 34,7±3,2 years. The parameters of daytime and nighttime peripheral BP had significant differences between the HNBP and HTN groups. Aortic BP monitoring revealed following differences: in patients with HTN, central BP values during the day and at night reflected higher values compared to patients from the HNBP group. The number of dippers for peripheral systolic blood pressure (SBP) was more by a quarter (p=0,038) in the HNBP group than in the HTN group. There were no differences in the reduction of diastolic blood pressure (DBP). The reduction in aortic SBP between the groups of HNBP and HTN were comparable. Among hypertensive patients, DBP dippers on the aorta were 20% higher (p=0,04) than in the HNBP group. According to the augmentation and the amplification index reduced to heart rate, there were no significant differences between the groups.Conclusion. Intergroup and intragroup differences were revealed depending on the types of 24-hour profile depending on peripheral and central BP. Reference values and predictive value of central BP require further research.

Twenty-four-hour profile of peripheral and central blood pressure in young patients with high-normal blood pressure and hypertension

Aim. To evaluate indicators of daily monitoring of peripheral and central blood pressure in young patients with high-normal blood pressure (HNBP) and essential hypertension (HTN).Material and methods. One hundred twelve patients with HNBP or untreated hypertension aged 25-44 years were included. General clinical investigations were performed. An office blood pressure (BP) were assessed using an automatic BP monitor OMRON M2 Basic. Twenty-four-hour ambulotary BP monitoring (ABPM) on the brachial artery and aorta was carried out for 24 hours using the BpLAB system (OOO Petr Telegin) with an integrated Vasotens system. Depending on BP, patients were divided into groups: with HNBP and hypertension. Statistical processing and comparative analysis of the obtained data were carried out.Results. HNBP group consisted of 47 patients, while the HTN group consisted of 65 patients. The mean age of patients was 34,7±3,2 years. The parameters of daytime and nighttime peripheral BP had significant differences between the HNBP and HTN groups. Aortic BP monitoring revealed following differences: in patients with HTN, central BP values during the day and at night reflected higher values compared to patients from the HNBP group. The number of dippers for peripheral systolic blood pressure (SBP) was more by a quarter (p=0,038) in the HNBP group than in the HTN group. There were no differences in the reduction of diastolic blood pressure (DBP). The reduction in aortic SBP between the groups of HNBP and HTN were comparable. Among hypertensive patients, DBP dippers on the aorta were 20% higher (p=0,04) than in the HNBP group. According to the augmentation and the amplification index reduced to heart rate, there were no significant differences between the groups.Conclusion. Intergroup and intragroup differences were revealed depending on the types of 24-hour profile depending on peripheral and central BP. Reference values and predictive value of central BP require further research.

Acute Citrulline Blunts Aortic Systolic Pressure during Exercise and Sympathoactivation in Hypertensive Postmenopausal Women.

Hypertensive postmenopausal women (PMW) have exaggerated exercise systolic blood pressure (SBP) due to impaired functional sympatholysis. l-Citrulline (CIT) supplementation attenuates aortic SBP responses to cold pressor test (CPT)-induced vasoconstriction in young men. We hypothesized that acute CIT ingestion would attenuate aortic SBP and leg hemodynamic responses during exercise and CPT (EX + CPT). Fifteen hypertensive PMW (61 ± 7 yr) were randomly assigned to consume either 6 g of CIT or placebo (PL) separated by a minimum 3-d washout phase. Brachial and aortic blood pressure, femoral artery blood flow (FBF), and vascular conductance (FVC) were measured at rest and during 5 min of unilateral plantarflexion exercise with a CPT applied during minutes 4 and 5. No differences between conditions were found in FBF, FVC, and brachial and aortic blood pressure at rest and during exercise alone. Changes in brachial SBP (CIT vs PL, 29 ± 12 vs 40 ± 10 mm Hg) and mean arterial pressure (CIT vs PL, 21 ± 10 vs 33 ± 11 mm Hg), and aortic SBP (CIT vs PL, 27 ± 11 vs 38 ± 9 mm Hg) and mean arterial pressure (CIT vs PL, 23 ± 9 vs 33 ± 11 mm Hg) to EX + CPT were lower in the CIT versus PL condition (P < 0.05). FBF, FVC, and functional sympatholysis (%ΔFVC) were not significantly different between conditions. Acute CIT ingestion attenuated aortic SBP response to exercise and cold-induced sympathetic activation that may prevent left ventricle overload in hypertensive PMW.

The influence of intermittent apnea on aortic hemodynamics in healthy young men

Background: Sleep apnea is known as a high-risk factor for cardiovascular disease (CVD); However, the influence of apnea on aortic blood pressure and augmentation index (AIx), which cardiac load and independent risks for a future CVD event, remains unclear. Therefore, this study aimed to examine the influence of intermittent normoxic apnea on aortic arterial hemodynamics in healthy men. Methods: Sixteen healthy young men (23 ± 1.6 years mean ± SD) underwent the repetitive 20-s apnea with a 40 s interval for 20 min. During the interval, each subject maintained a breath pace at 15 breaths/min. Central hemodynamics were evaluated every 5 min by pulse wave analysis from peripheral (radial) arterial pressure waveforms via general transfer function method and compared among three phases defined as “breath” (for 20 s before apnea), “apnea”, and “rebreathe” (for 20 s after apnea). The baseline values were calculated from the first breathing cycle and compared with each breathing phase every 5 min. Results: Aortic systolic blood pressure and AIx were significantly higher at rebreathe phase than the other phases. Likewise, heart rate and double product (aortic systolic blood pressure × heart rate) were significantly higher in rebreathe phase than the other phases. Conclusions: These results suggest that cardiac load is increased by intermittent normoxic apnea, especially during the rebreathing phase.

Twenty-Four–Hour Central (Aortic) Systolic Blood Pressure: Reference Values and Dipping Patterns in Untreated Individuals

Central (aortic) systolic blood pressure (cSBP) is the pressure seen by the heart, the brain, and the kidneys. If properly measured, cSBP is closer associated with hypertension-mediated organ damage and prognosis, as compared with brachial SBP (bSBP). We investigated 24-hour profiles of bSBP and cSBP, measured simultaneously using Mobilograph devices, in 2423 untreated adults (1275 women; age, 18-94 years), free from overt cardiovascular disease, aiming to develop reference values and to analyze daytime-nighttime variability. Central SBP was assessed, using brachial waveforms, calibrated with mean arterial pressure (MAP)/diastolic BP (cSBPMAP/DBPcal), or bSBP/diastolic blood pressure (cSBPSBP/DBPcal), and a validated transfer function, resulting in 144 509 valid brachial and 130 804 valid central measurements. Averaged 24-hour, daytime, and nighttime brachial BP across all individuals was 124/79, 126/81, and 116/72 mm Hg, respectively. Averaged 24-hour, daytime, and nighttime values for cSBPMAP/DBPcal were 128, 128, and 125 mm Hg and 115, 117, and 107 mm Hg for cSBPSBP/DBPcal, respectively. We pragmatically propose as upper normal limit for 24-hour cSBPMAP/DBPcal 135 mm Hg and for 24-hour cSBPSBP/DBPcal 120 mm Hg. bSBP dipping (nighttime-daytime/daytime SBP) was -10.6 % in young participants and decreased with increasing age. Central SBPSBP/DBPcal dipping was less pronounced (-8.7% in young participants). In contrast, cSBPMAP/DBPcal dipping was completely absent in the youngest age group and less pronounced in all other participants. These data may serve for comparison in various diseases and have potential implications for refining hypertension diagnosis and management. The different dipping behavior of bSBP versus cSBP requires further investigation.

Effect of Aquatic Exercise Training on Aortic Hemodynamics in Middle-Aged and Elderly Adults.

Aquatic exercise is an attractive form of exercise that utilizes the various properties of water to improve physical health, including arterial stiffness. However, it is unclear whether regular head-out aquatic exercise affects aortic hemodynamics, the emerging risk factors for future cardiovascular disease. The purpose of this study was to investigate whether head-out aquatic exercise training improves aortic hemodynamics in middle-aged and elderly people. In addition, to shed light on the underlying mechanisms, we determined the contribution of change in arterial stiffness to the hypothesized changes in aortic hemodynamics. Twenty-three middle-aged and elderly subjects (62 ± 9 years) underwent a weekly aquatic exercise course for 15 weeks. Aortic hemodynamics were evaluated by pulse wave analysis via the general transfer function method. Using a polar coordinate description, companion metrics of aortic pulse pressure (PPC = √{(systolic blood pressure)2 + (diastolic blood pressure)2}) and augmentation index (AIxC = √{(augmentation pressure)2 + (pulse pressure)2}) were calculated as measures of arterial load. Brachial-ankle (baPWV, reflecting stiffness of the abdominal aorta and leg artery) and heart-ankle (haPWV, reflecting stiffness of the whole aortic and leg artery) pulse wave velocities were also measured. The rate of participation in the aquatic training program was 83.5 ± 13.0%. Aortic systolic blood pressure, pulse pressure, PPC, AIxC, baPWV, and haPWV decreased after the training (P < 0.05 for all), whereas augmentation index remained unchanged. Changes in aortic SBP were correlated with changes in haPWV (r = 0.613, P = 0.002) but not baPWV (r = 0.296, P = 0.170). These findings suggest that head-out aquatic exercise training may improve aortic hemodynamics in middle-aged and elderly people, with the particular benefits for reducing aortic SBP which is associated with proximal aortic stiffness.

Aortic systolic blood pressure predicts periprocedural myocardial injury after transcatheter aortic valve implantation

Abstract Background/Introduction Periprocedural myocardial injury (PPMI) is a complication of transcatheter aortic valve implantation (TAVI) associated with worse outcome. Central (aortic) systolic blood pressure (SBP) is an independent predictor of cardiovascular events. Purpose We sought to investigate the effect of TAVI on peripheral and central hemodynamics, as well as the predictive ability of brachial and aortic SBP for PPMI. Methods We enrolled 70 patients (mean age 79.9±8.7 years, 50% males) with severe symptomatic aortic valve stenosis (AVS) undergoing TAVI. Brachial pressures were measured with an oscillometric device and central pressures were assessed by arterial tonometry at baseline and after the procedure at discharge. PPMI was identified based on Valve Academic Research Consortium (VARC-2) criteria. Biomarkers for MI (cardiac troponin and creatinine kinase MB) were analyzed and signs and symptoms according to VARC-2 criteria were collected from clinical records. Stepwise multivariable regression analysis was performed for the prediction of PPMI. Results According to VARC-2 definition, 38 (54%) patients had PPMI. In stepwise multivariable regression analysis, brachial SBP at baseline was not predictive of PPMI (p=0.07) after adjusting for age, sex and history of coronary artery disease. On the contrary, aortic SBP predicted PPMI even after adjustment for the abovementioned confounders (Odds ratio [OR]=1.032, 95% Confidence Interval [CI] 1.004–1.061, p=0.026). Interestingly, both SBP and aortic SBP were higher at discharge in patients with PPMI compared to patients without PPMI after adjustment (p=0.021 and p=0.006, respectively). On the contrary, the periprocedural changes of aortic SBP and SBP were not different between patients with PPMI and without PPMI. Conclusions Aortic SBP, as assessed by tonometry, is an independent predictor stronger than brachial SBP for PPMI in AVS patients treated with TAVI. This finding suggests the possible clinical role of aortic pressures as a risk stratification tool for PPMI prior to TAVI, as well as, warrants further investigation on their role as therapeutic targets to decrease the incidence of PPMI. Funding Acknowledgement Type of funding sources: None.

Aortic hemodynamic parameters as predictors of incident or deteriorating hypertension during carfilzomib therapy in patients with relapsed multiple myeloma

Abstract Background Carfilzomib (CFZ) improves survival in relapsed/refractory multiple myeloma but is associated with cardiovascular adverse events, among which hypertension is commonly reported. Purpose To evaluate aortic hemodynamics as possible predictors for CFZ-associated hypertension. Methods In a prospective study of 48 patients treated with Kd (CFZ 20/56 mg/m2 and dexamethasone) followed until disease progression or cycle 6 for a median of 10 months, patients underwent peripheral hemodynamic assessment, including applanation tonometry, which allows estimation of aortic blood pressure and arterial wave reflections and assessment of pulse wave velocity, which allows estimation of aortic stiffness. Hemodynamic parameters were examined at baseline and at pre-specified time points before and 24 hours after drug infusion. Results Thirteen patients (27.1%) developed hypertension or merited more intensive anti-hypertensive treatment (grade I or II: 6.25%, grade III: 20.8%). Patients with new onset or worsening hypertension had increased aortic [130±12.9 mmHg versus 115±16.7 mmHg, p=0.004] and peripheral systolic blood pressure (SBP) [145±15.7 mmHg versus 130±19.5 mmHg, p=0.001] at baseline. Patients distributed at highest tertile of baseline aortic SBP (log-rank test p=0.0001, Figure) or baseline peripheral SBP (log-rank test p=0.002) had significantly higher risk for CFZ associated hypertension as compared to those distributed at lower tertiles. After adjustment for age, gender and baseline hypertension, increased aortic [HR=8.0, 95% CIs 2.4–26.6, p=0.001] and peripheral SBP [HR=4.85, 95% CIs 1.53–15.4, p=0.007] remained significantly associated with hypertension. After adjustment for both baseline peripheral and aortic SBP in the same multivariable core model, aortic SBP was the only independent predictor of the study outcome (p=0.041). Accordingly, baseline aortic SBP was associated with higher discriminative value as compared to peripheral SBP [AUC: 0.819, 95% CIs 0.722–0.916 versus 0.724, 95% CIs 0.570–0.878, respectively]. Further adjustment for all cardiotoxicity risk factors using forced inclusion in non-parsimonious multivariable Cox regression models, revealed that increased aortic and peripheral SBP remained independent predictors of hypertensive events (p&amp;lt;0.05 for both). Conclusion Baseline aortic hemodynamics are associated with hypertension during CFZ treatment. Aortic SBP at baseline was the strongest predictor of CFZ-associated hypertensive adverse events, suggesting that an initial assessment of aortic blood pressure may facilitate discrimination of patients in need of close monitoring during treatment. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Funding from the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT), under grant agreement No [1285].

Efficacy and safety of bisoprolol compared to other selective beta-1 blockers in the treatment of hypertension: a systematic review and meta-analysis of randomized parallel clinical trials

Abstract Background Bisoprolol, a highly cardioselective beta-1 blocker (s-BB) has theoretical advantage over other cardio selective betablockers by way of better potency and tolerability in treating hypertension (HT). Individual published trials comparing s-BB are typically small. Meta-analysis of such trials clarifies the issue and position of bisoprolol in HT therapy. Purpose This meta-analysis compares bisoprolol with other s-BBs (Atenolol, Betaxolol, Esmolol, Acebutolol, Metoprolol, Nebivolol) for their efficacy and safety in patients with HT. Methods Literature databases PubMed, Embase, Cochrane Library, Clinicaltrials.gov, Surveillance, Epidemiology and End Results Program and 12 PV databases were searched systematically to identify randomized, parallel clinical trials published from inception to October 2019. Studies which compared bisoprolol with other s-BBs in HT patients were evaluated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random effects meta-analyses were conducted to assess mean difference (MD) and 95% confidence interval (95% CI) for blood pressure (BP), heart rate (HR) and lipid profile. Results 13 studies compared bisoprolol with other s-BBs (metoprolol, atenolol) were included in this meta-analysis. Bisoprolol reported significant reduction in aortic systolic BP [MD: −8.00; 95% CI: −11.57, −4.43; P&amp;lt;0.01] and diastolic BP [MD: −2.90; 95% CI: −4.98, −0.82; P&amp;lt;0.01] during 8 weeks (w) treatment compared to other s-BBs. Bisoprolol treatment for 12w showed significant change in ambulatory heart rate (AHR) [MD: −5.22; 95% CI: −8.37, −2.07; P&amp;lt;0.01], daytime AHR [MD: −5.75; 95% CI: −9.16, 2.34; P&amp;lt;0.01] and nighttime AHR [MD: −3.22; 95% CI: −6.18, −0.26; P=0.03] in comparison to other s-BBs. Significant increase in low frequency HR variability [MD: 100.79; 95% CI: 16.66, 184.91; P=0.02] was reported with bisoprolol treated for 8w compared to other s-BBs. Baroreflex sensitivity significantly favored bisoprolol treated for 8w [MD: 1.01; 95% CI: 0.03, 1.98; P=0.04] in comparison to other s-BBs. HDL-C significantly increased with bisoprolol treated for 52w [MD: 6.80; 95% CI: 3.01, 10.60; P&amp;lt;0.01], 104w [MD: 12.00; 95% CI: 5.04, 18.96; P&amp;lt;0.01] and 156w [MD: 8.00; 95% CI: 0.58, 15.42; P=0.03]. There were no significant changes in total cholesterol [MD: −3.06; P=0.38], LDL-C [MD: −3.60; P=0.18] and triglyceride [MD: −21.00; P=0.26] on treatment with bisoprolol. Serious adverse events did not differ significantly on treatment with bisoprolol compared to other s-BBs. Conclusion The results of this meta-analysis reveal that bisoprolol showed a significant reduction of BP, HR, baroreflex sensitivity and improved HDL cholesterol levels compared to other s-BBs. Our results highlight the heterogeneity amongst the s-BBs and highlights the benefit of choosing bisoprolol in comparison to other s-BB in the management of HT. Funding Acknowledgement Type of funding sources: None.

Predictors of CT-derived FFR in patients with suspected CAD beyond severity of coronary stenosis

Abstract Background Functional assessment of coronary stenosis using computational fluid dynamics is increasingly used, however other factors besides coronary stenosis may affect the results. We assessed several predictors for CT-derived fractional flow reserve (CT-FFR) in patients with suspected coronary artery disease (CAD) undergoing coronary computed tomographic angiography (CCTA). Methods 2505 consecutive patients with suspected CAD undergoing CCTA from 2008 to 2016 were screened, 1549 were excluded due to incomplete data (934), image quality (345), software error (147) or other reasons (123). Minimal CT-FFR was measured using an on-site prototype (cFFR Version 3.0, Siemens Healthineers, Forchheim, Germany) in coronaries ≥2mm. Several clinical as well as technical criteria were assessed for predicting the minimal CT-FFR per patient. Results 956 patients (51±12 years, 51.2% men) were included in this analysis. Mean EF was 59.4±7.4%, heart rate 63±9 bpm, systolic (126.5±20mmHg) and diastolic (70±11 mmHg) blood pressure (BP). Regression analysis and ANOVA showed low but significant impact on minimal CT-FFR (mean 0.85±0.10) by EF, aortic valvular dysfunction, heart rate and systolic blood pressure as well as image quality (esp. blooming and image noise). See Tables 1 and 2. Conclusion Coronary stenosis may not be the only relevant predictor for CT-FFR. Several clinical criteria (EF, heart rate, BP, aortic valve dysfunction) as well as image criteria (image quality, artifacts) can affect CT-FFR results. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Cleveland Clinic Foundation Table 1. ANOVA analysisTable 2. Regression analysis

Leukocyte telomerase concentration is inversely associated with central wave reflection in patients with hypertension

Abstract Introduction Telomere length and telomerase are biomarkers of aging and cardiovascular diseases. Arterial stiffness is associated with vascular age and higher risk of cardiovascular diseases. Decreased reparative cell's potential may cause vascular ageing and predispose to the progression of hypertension. Objective To determine association leukocyte telomerase concentration (TC) and relative telomere length (RTL) with arterial stiffness in hypertensive patients. Material and methods The study included 120 people (70 patients with uncomplicated arterial hypertension (AH) and 50 normotensive individuals). Mean age of hypertensives was 54.8±9.3 and of normotensives was 50.2±9.73 years. Dietary habits, smoking, level of physical activity, body mass index, waist circumference, presence of obesity, blood pressure (BP) level, family history of cardiovascular deseases, depressive episodes and psychological stress according the international questionnaires, glucose; cholesterol, angiotensin II, renin and aldosteron in blood were assessed in the participants. Aortic BP, aortic pulse pressure, augmentation index (AIx), AIx adjusted for heart rate 75 beats per minute (Aix@HR75), pulse wave velocity (PWV) were determined by the applanation tonometry. RTL of peripheral blood leukocytes was performed by real-time PCR. The leukocyte TC was measured using the enzyme immunoassay. Results There were no differences between patients with AH and normotensives in both leukocyte TC (4.9 (4.0; 8.0) versus 6.2 (4.1; 9.4), p=0.281) and RTL (0.94 (0.86; 1.0) versus 0.96 (0.83; 1.0), p=0.978). In hypertensive and normotensive groups the mean systolic aortic BP were 130.6±17,7 and 109.9±11.7 mmHg (p&amp;lt;0.001), aortic pulse pressure – 41.5±9,7 and 33.6±10,4 mmHg (p&amp;lt;0.001), Aix@HR75 – 16.0 (7.0; 28.0) and 27.0 (13.0; 35.0)% (p=0.004), PWV –7.9±1.4 and 8.1±1,7 m/s (p=0.409) respectively. In patients with AH the mean leukocyte TC was lower with an increased Aix@75 (&amp;gt;25%) in contrast to the group of patients with normal Aix@75 (4.45 (3.9; 7.8) versus 7.97 (4.6; 10.0) ng/ml; p=0.043). Based on the multivariate logistic regression analysis independent factors influencing on the Aix@75 were leukocyte TC &amp;lt;5 ng/ml with the family history of AH (OR=1.9, 95% CI: 1.1–3.4; p=0.036), the degree of AH combined with decreased salt sensitivity (OR=3.1; 95% CI: 1.3–7.5; p=0.010) and age (OR=1.2; 95% CI: 1.1–1.2; p=0.001). Conclusions Decrease of the leukocyte telomerase concentration associated with the raise of augmentation index in patient with uncomplicated AH. As a parameter of central wave reflection the augmentation index may considered as an early sign of biological and vascular aging in hypertension. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The state program of scientific research “Fundamental and applied sciences for medicine”

Hemodynamic response and pulse wave analysis after upper- and lower-body resistance exercise with and without blood flow restriction

ABSTRACT Resistance exercise (RE) has been shown to elevate hemodynamics and pulse wave reflection. However, the effects of acute RE with blood flow restriction (BFR) on hemodynamics and pulse wave reflection are unclear. The purpose of this study was to evaluate the differences between upper- and lower-body RE with and without BFR on hemodynamics and pulse wave reflection. Twenty-three young resistance-trained individuals volunteered for the study. Hemodynamics and pulse wave reflection were assessed at rest, 10, 25, 40, and 55 min after either upper- or lower-body with or without BFR. The upper-body RE (URE) consisted of the latissimus dorsi pulldown and chest press; the lower-body RE (LRE) consisted of knee extension and knee flexion. The BFR condition consisted of four sets of 30, 15, 15, and 15 repetitions at 30% 1-repetition maximum (1RM) while the without BFR condition consisted of four sets of 8 repetitions at 70% 1RM. Heart rate, rate pressure product, and subendocardial viability ratio significantly (p < 0.05) increased after all exercises. Brachial and aortic systolic blood pressure (BP) significantly (p < 0.05) elevated after LRE while brachial and aortic diastolic BP significantly (p < 0.05) reduced after URE. Augmentation pressure, augmentation index (AIx), AIx normalized at 75 bpm, and wasted left ventricular pressure energy significantly (p < 0.05) increased after URE while transit time of reflected wave significantly (p < 0.05) decreased after LRE. URE places greater stress on pulse wave reflection while LRE results in greater responses in BP. Regardless of URE or LRE, the cardiovascular responses between BFR and without BFR are similar. HIGHLIGHTS High-load resistance exercise and low-load resistance exercise with blood flow restriction may produce similar cardiovascular responses. Upper-body resistance exercise generates greater changes on pulse wave reflections while lower-body resistance exercise induces greater elevations in systolic blood pressure.

Influence of Left Ventricular Function on the "Aortic Regurgitation Index" Proposed for the Hemodynamic Assessment of Postprocedural Aortic Regurgitation.

The aortic regurgitation (AR) index, proposed as an objective indicator of postprocedural AR, decreases in proportion to AR severity, besides reportedly providing additional prognostic information. Meanwhile, left ventricular (LV) function has also been considered an essential prognostic factor. This study aimed to clarify whether LV function affected the AR index using cardiac catheterization data.A retrospective study was performed in patients whose LV function was evaluated using a micromanometer-tipped catheter. Patients with grade 2 or higher AR were excluded to explore non-AR factors affecting the AR index value. The AR index was calculated as a ratio of the gradient between the aortic diastolic blood pressure (DBP) and the LV end-diastolic pressure (EDP) to the aortic systolic blood pressure (SBP): AR Index = [ (DBP - LVEDP) / SBP] × 100.A total of 64 patients [age, 62 (interquartile range: 48-70) years; LV ejection fraction, 19% (16%-26%) ] were examined. AR index values ranged from 18.3 to 68.6. Despite having no AR, two patients displayed an AR index < 25, indicating significant AR. Multiple-regression analysis revealed that LV diastolic stiffness (β = -0.750, P < 0.001), LV max dP/dt (β = -0.296, P = 0.006), and heart rate (β = 0.284, P = 0.011) were independent determinants of the AR index value.Patients with impaired LV diastolic function and preserved systolic function had low AR index values. The additional prognostic information of the AR index may be related to LV diastolic function.