-
1.
Assessment of Omecamtiv Mecarbil for the Treatment of Patients With Severe Heart Failure: A Post Hoc Analysis of Data From the GALACTIC-HF Randomized Clinical Trial.
Felker, GM, Solomon, SD, Claggett, B, Diaz, R, McMurray, JJV, Metra, M, Anand, I, Crespo-Leiro, MG, Dahlström, U, Goncalvesova, E, et al
JAMA cardiology. 2022;(1):26-34
-
-
Free full text
-
Abstract
IMPORTANCE Heart failure with reduced ejection fraction is a progressive clinical syndrome, and many patients' condition worsen over time despite treatment. Patients with more severe disease are often intolerant of available medical therapies. OBJECTIVE To evaluate the efficacy and safety of omecamtiv mecarbil for the treatment of patients with severe heart failure (HF) enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS The GALACTIC-HF study was a global double-blind, placebo-controlled phase 3 randomized clinical trial that was conducted at multiple centers between January 2017 and August 2020. A total of 8232 patients with symptomatic HF (defined as New York Heart Association symptom class II-IV) and left ventricular ejection fraction of 35% or less were randomized to receive omecamtiv mecarbil or placebo and followed up for a median of 21.8 months (range, 15.4-28.6 months). The current post hoc analysis evaluated the efficacy and safety of omecamtiv mecarbil therapy among patients classified as having severe HF compared with patients without severe HF. Severe HF was defined as the presence of all of the following criteria: New York Heart Association symptom class III to IV, left ventricular ejection fraction of 30% or less, and hospitalization for HF within the previous 6 months. INTERVENTIONS Participants were randomized at a 1:1 ratio to receive either omecamtiv mecarbil or placebo. MAIN OUTCOMES AND MEASURES The primary end point was time to first HF event or cardiovascular (CV) death. Secondary end points included time to CV death and safety and tolerability. RESULTS Among 8232 patients enrolled in the GALACTIC-HF clinical trial, 2258 patients (27.4%; mean [SD] age, 64.5 [11.6] years; 1781 men [78.9%]) met the specified criteria for severe HF. Of those, 1106 patients were randomized to the omecamtiv mecarbil group and 1152 to the placebo group. Patients with severe HF who received omecamtiv mecarbil experienced a significant treatment benefit for the primary end point (hazard ratio [HR], 0.80; 95% CI, 0.71-0.90), whereas patients without severe HF had no significant treatment benefit (HR, 0.99; 95% CI, 0.91-1.08; P = .005 for interaction). For CV death, the results were similar (HR for patients with vs without severe HF: 0.88 [95% CI, 0.75-1.03] vs 1.10 [95% CI, 0.97-1.25]; P = .03 for interaction). Omecamtiv mecarbil therapy was well tolerated in patients with severe HF, with no significant changes in blood pressure, kidney function, or potassium level compared with placebo. CONCLUSIONS AND RELEVANCE In this post hoc analysis of data from the GALACTIC-HF clinical trial, omecamtiv mecarbil therapy may have provided a clinically meaningful reduction in the composite end point of time to first HF event or CV death among patients with severe HF. These data support a potential role of omecamtiv mecarbil therapy among patients for whom current treatment options are limited. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02929329.
-
2.
Microcirculation and Macrocirculation in Hypertension: A Dangerous Cross-Link?
Laurent, S, Agabiti-Rosei, C, Bruno, RM, Rizzoni, D
Hypertension (Dallas, Tex. : 1979). 2022;(3):479-490
Abstract
Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.
-
3.
Female Sex and Angiotensin-Converting Enzyme (ACE) Insertion/Deletion Polymorphism Amplify the Effects of Adiposity on Blood Pressure.
Chiriacò, M, Tricò, D, Leonetti, S, Petrie, JR, Balkau, B, Højlund, K, Pataky, Z, Nilsson, PM, Natali, A, ,
Hypertension (Dallas, Tex. : 1979). 2022;(1):36-46
Abstract
The pathophysiological link between adiposity and blood pressure is not completely understood, and evidence suggests an influence of sex and genetic determinants. We aimed to identify the relationship between adiposity and blood pressure, independent of a robust set of lifestyle and metabolic factors, and to examine the modulating role of sex and Angiotensin-Converting Enzyme (ACE) insertion/deletion (I/D) polymorphisms. In the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) study cohort, 1211 normotensive individuals, aged 30 to 60 years and followed-up after 3.3 years, were characterized for lifestyle and metabolic factors, body composition, and ACE genotype. Body mass index (BMI) and waist circumference (WC) were independently associated with mean arterial pressure, with a stronger relationship in women than men (BMI: r=0.40 versus 0.30; WC: r=0.40 versus 0.30, both P<0.01) and in individuals with the ID and II ACE genotypes in both sexes (P<0.01). The associations of BMI and WC with mean arterial pressure were independent of age, sex, lifestyle, and metabolic variables (standardized regression coefficient=0.17 and 0.18 for BMI and WC, respectively) and showed a significant interaction with the ACE genotype only in women (P=0.03). A 5 cm larger WC at baseline increased the risk of developing hypertension at follow-up only in women (odds ratio, 1.56 [95% CI, 1.15-2.10], P=0.004) and in II genotype carriers (odds ratio, 1.87 [95% CI, 1.09-3.20], P=0.023). The hypertensive effect of adiposity is more pronounced in women and in people carrying the II variant of the ACE genotype, a marker of salt sensitivity.
-
4.
Low-dose fentanyl does not alter muscle sympathetic nerve activity, blood pressure, or tolerance during progressive central hypovolemia.
Huang, M, Watso, JC, Belval, LN, Cimino, FA, Fischer, M, Jarrard, CP, Hendrix, JM, Laborde, CH, Crandall, CG
American journal of physiology. Regulatory, integrative and comparative physiology. 2022;(1):R55-R63
Abstract
Hemorrhage is a leading cause of battlefield and civilian trauma deaths. Several pain medications, including fentanyl, are recommended for use in the prehospital (i.e., field setting) for a hemorrhaging solider. However, it is unknown whether fentanyl impairs arterial blood pressure (BP) regulation, which would compromise hemorrhagic tolerance. Thus, the purpose of this study was to test the hypothesis that an analgesic dose of fentanyl impairs hemorrhagic tolerance in conscious humans. Twenty-eight volunteers (13 females) participated in this double-blinded, randomized, placebo-controlled trial. We conducted a presyncopal limited progressive lower body negative pressure test (LBNP; a validated model to simulate hemorrhage) following intravenous administration of fentanyl (75 µg) or placebo (saline). We quantified tolerance as a cumulative stress index (mmHg·min), which was compared between trials using a paired, two-tailed t test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat BP (photoplethysmography) during the LBNP test using a mixed effects model [time (LBNP stage) × trial]. LBNP tolerance was not different between trials (fentanyl: 647 ± 386 vs. placebo: 676 ± 295 mmHg·min, P = 0.61, Cohen's d = 0.08). Increases in MSNA burst frequency (time: P < 0.01, trial: P = 0.29, interaction: P = 0.94) and reductions in mean BP (time: P < 0.01, trial: P = 0.50, interaction: P = 0.16) during LBNP were not different between trials. These data, the first to be obtained in conscious humans, demonstrate that administration of an analgesic dose of fentanyl does not alter MSNA or BP during profound central hypovolemia, nor does it impair tolerance to this simulated hemorrhagic insult.
-
5.
A Comparative Study of Health Efficacy Indicators in Subjects with T2DM Applying Power Cycling to 12 Weeks of Low-Volume High-Intensity Interval Training and Moderate-Intensity Continuous Training.
Li, J, Cheng, W, Ma, H
Journal of diabetes research. 2022;:9273830
Abstract
This study is aimed at comparing the effects of different exercise intensities, namely, high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), on body composition, heart and lung fitness, and blood glucose, and blood pressure indices in patients with type 2 diabetes mellitus (T2DM), using power cycling. A total of 96 T2DM volunteers who met the inclusion criteria were recruited from a hospital in Yangpu, Shanghai. Based on the blood index data of their medical examination results which comprised blood pressure, fasting blood glucose, hemoglobin A1c (HbA1c), and insulin, 37 volunteers were included in the study. Exercise prescription was determined based on T2DM exercise guidelines combined with medical diagnosis and exercise test results, and the patients were randomly assigned to three groups: HIIT group, MICT group, and control (CON) group. HIIT involved one-minute power cycling (80%-95% maximal oxygen uptake (VO2max)), one-minute passive or active rest (25%-30% VO2max), and two-minute rounds of eight groups. MICT required the use of a power bike for 30 minutes of continuous training (50%-70% VO2max) five times a week. The CON group was introduced to relevant medicine, exercise, and nutrition knowledge. The exercise interventions were completed under the supervision of an exercise instructor and hospital doctors. The same indicators were measured after 12 weeks of intervention, and the results of the two tests within and between groups were analyzed for comparison. The weight index of the MICT intervention showed statistically significant within-group differences (difference = 3.52, 95% CI = 2.11-4.92, p = 0.001 < 0.01); group differences for the MICT and CON groups were also statistically significant (difference = 3.52 ± 2.09, Cd1 = -0.39 ± 1.25, p = 0.004 < 0.01). Body mass index (BMI) analysis revealed that the overall means of BMI indicators were not statistically different between groups (F = 0.369, p = 0.694 > 0.05) and the before and after values of the MICT and CON (difference = -1.30 ± 0.79, Cd1 = -0.18 ± 0.45, p = 0.001 < 0.01). No statistically significant difference was observed in the overall mean VO2max index between the groups after the 12-week intervention (F = 2.51, p = 0.100 > 0.05). A statistically significant difference was found in the overall means of the data between the two groups (difference = 0.32, 95% CI = 0.23-0.40, p = 0.001 < 0.01). Analysis of fasting blood glucose (FBG) indicators revealed statistically significant differences between the MICT and control groups (p = 0.028 < 0.05). Analysis of HbA1c and fasting insulin (FI) indicators revealed no statistically significant difference in the overall HbA1c index after the 12-week exercise intervention (F = 0.523, p = 0.598 > 0.05), and the overall difference before and after the experiment between the groups was statistically significant (F = 6.13, p = 0.006 < 0.01). No statistically significant difference was found in the FI index overall after the 12-week exercise intervention (F = 2.50, p = 0.1 > 0.05). Analysis of systolic blood pressure (SBP) revealed statistically significant difference before and after the HIIT and CON interventions (Hd7 = -1.10 ± 1.79, Cd7 = 1.2 ± 1.31, p = 0.018 < 0.05) and statistically significant difference before and after the MICT and CON interventions (Md7 = -0.99 ± 0.91, Cd7 = 1.40 ± 1.78, p = 0.02 < 0.05). The diastolic blood pressure (DBP) revealed no statistically significant within-group differences before and after. Exercise interventions applying both low-volume HIIT and MICT, with both intensity exercises designed for power cycling, improved health-related indicators in the participants; low-volume HIIT had more time advantage. The current experiment compared HIIT with MICT in a safe manner: 50% of the exercise time produced similar benefits and advantages in the two indicators of VO2max and FI. However, MICT was superior to HIIT in the two indicators of body weight (weight) and BMI. The effect of power cycling on FI has the advantages of both aerobic and resistance exercise, which may optimize the type, intensity, and time of exercise prescription according to the individual or the type of exercise program. Our results provide a reference for the personalization of exercise prescription for patients with T2DM.
-
6.
Potential influencing factors of aortic diameter at specific segments in population with cardiovascular risk.
Chen, T, Yang, X, Fang, X, Tang, L, Zhang, Y, Weng, Y, Zhang, H, Wu, J, Mao, P, Xu, B, et al
BMC cardiovascular disorders. 2022;(1):32
Abstract
BACKGROUND Aortic diameter is a critical parameter for the diagnosis of aortic dilated diseases. Aortic dilation has some common risk factors with cardiovascular diseases. This study aimed to investigate potential influence of traditional cardiovascular risk factors and the measures of subclinical atherosclerosis on aortic diameter of specific segments among adults. METHODS Four hundred and eight patients with cardiovascular risk factors were prospectively recruited in the observational study. Comprehensive transthoracic M-mode, 2-dimensional Doppler echocardiographic studies were performed using commercial and clinical diagnostic ultrasonography techniques. The aortic dimensions were assessed at different levels: (1) the annulus, (2) the mid-point of the sinuses of Valsalva, (3) the sinotubular junction, (4) the ascending aorta at the level of its largest diameter, (5) the transverse arch (including proximal arch, mid arch, distal arch), (6) the descending aorta posterior to the left atrium, and (7) the abdominal aorta just distal to the origin of the renal arteries. Multivariable linear regression analysis was used for evaluating aortic diameter-related risk factors, including common cardiovascular risk factors, co-morbidities, subclinical atherosclerosis, lipid profile, and hematological parameters. RESULTS Significant univariate relations were found between aortic diameter of different levels and most traditional cardiovascular risk factors. Carotid intima-media thickness was significantly correlated with diameter of descending and abdominal aorta. Multivariate linear regression showed potential effects of age, sex, body surface area and some other cardiovascular risk factors on aortic diameter enlargement. Among them, high-density lipoprotein cholesterol had a significantly positive effect on the diameter of ascending and abdominal aorta. Diastolic blood pressure was observed for the positive associations with diameters of five thoracic aortic segments, while systolic blood pressure was only independently related to mid arch diameter. CONCLUSION Aortic segmental diameters were associated with diastolic blood pressure, high-density lipoprotein cholesterol, atherosclerosis diseases and other traditional cardiovascular risk factors, and some determinants still need to be clarified for a better understanding of aortic dilation diseases.
-
7.
The effect of grape (Vitis vinifera) seed extract supplementation on flow-mediated dilation, blood pressure, and heart rate: A systematic review and meta-analysis of controlled trials with duration- and dose-response analysis.
Foshati, S, Nouripour, F, Sadeghi, E, Amani, R
Pharmacological research. 2022;:105905
Abstract
The objective of this systematic review and meta-analysis of controlled trials was to assess the long-term effect of grape seed extract (GSE) supplementation on flow-mediated dilation (FMD), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) in adults. Web of Science, Scopus, Medline, Cochrane Library, and Google Scholar were searched up to May 24, 2021. Nineteen trials were included in this study. Weighted mean difference (WMD) and 95% confidence interval (CI) were calculated using a random-effects model. GSE supplementation significantly reduced DBP (WMD: -2.20 mmHg, 95% CI: -3.79 to -0.60, I2 = 88.8%) and HR (WMD: -1.25 bpm, 95% CI: -2.32 to -0.19, I2 = 59.5%) but had no significant effects on FMD (WMD: 1.02%, 95% CI: -0.62 to 2.66, I2 = 92.0%) and SBP (WMD: -3.55 mmHg, 95% CI: -7.59 to 0.49, I2 = 97.4%). Subgroup analysis revealed that the dose and duration of GSE administration and the characteristics of study participants could be sources of between-study heterogeneity. Significant non-linear relationships were found between DBP and the duration of GSE supplementation (P = 0.044) and its dose (P = 0.007). In conclusion, GSE may be beneficial for individuals with or at risk of cardiovascular disease because it may have hypotensive and HR-lowering properties.
-
8.
Hypertensive Retinopathy and the Risk of Stroke Among Hypertensive Adults in China.
Chen, X, Liu, L, Liu, M, Huang, X, Meng, Y, She, H, Zhao, L, Zhang, J, Zhang, Y, Gu, X, et al
Investigative ophthalmology & visual science. 2021;(9):28
-
-
Free full text
-
Abstract
PURPOSE This study aimed to investigate the association between hypertensive retinopathy and the risk of first stroke, examine possible effect modifiers in hypertensive patients, and test the appropriateness of the Keith-Wagener-Barker (KWB) classification for predicting stroke risk. METHODS In total, 9793 hypertensive participants (3727 males and 6066 females) without stroke history from the China Stroke Primary Prevention Trial were included in this study. The primary outcome was first stroke. RESULTS Over a median follow-up of 4.4 years, 592 participants experienced their first stroke (509 ischemic, 77 hemorrhagic, and six unclassifiable strokes). In total, 5590 participants were diagnosed with grade 1 retinopathy (57.08%), 1466 with grade 2 retinopathy (14.97%), 231 with grade 3 retinopathy (2.36%), and three with grade 4 retinopathy (0.03%). Grades 1 and 2 were merged and classified as mild retinopathy, and grades 3 and 4 were merged and classified as severe retinopathy. There was a significant positive association between hypertensive retinopathy and the risk of first stroke and first ischemic stroke, and no effect modifiers were found. The hazard ratios (HRs) for first stroke were as follows: mild versus no retinopathy, 1.26 (95% confidence interval [CI], 1.01-1.58, P = 0.040), and severe versus no retinopathy, 2.40 (95% CI, 1.49-3.84, P < 0.001). The HRs for ischemic stroke were as follows: severe versus no retinopathy, 2.35 (95% CI, 1.41-3.90, P = 0.001), and nonsignificantly increased HRs for mild versus no retinopathy, 1.26 (95% CI, 0.99-1.60, P = 0.057). CONCLUSIONS There was a significant positive association between hypertensive retinopathy and the risk of first stroke in patients with hypertension, indicating that hypertensive retinopathy may be a predictor of the risk of stroke. A simplified two-grade classification system based on the KWB classification is recommended for predicting stroke risk.
-
9.
Shock index predicts up to 90-day mortality risk after intracerebral haemorrhage.
Pana, TA, Quinn, TJ, Perdomo-Lampignano, JA, Szlachetka, WA, Knoery, C, Mamas, MA, Myint, PK, ,
Clinical neurology and neurosurgery. 2021;:106994
Abstract
BACKGROUND Shock index (SI - heart rate/systolic blood pressure) has been studied as a measure of haemodynamic status. We aimed to determine whether SI measures within 72 h of admission were associated with adverse outcomes in intracerebral haemorrhage (ICH). METHODS Patients were drawn from the Virtual International Stroke Trials Archive-Intracerebral Haemorrhage (VISTA-ICH). Multivariable Cox regressions modelled the relationship between SI (on admission, 24, 48, 72 h) and mortality (at 3-, 7-, and 90-days), 90-day incident pneumonia and cardiovascular events (MACE). Ordinal logistic regressions modelled the relationship between SI and 90-day modified Rankin Scale (mRS). RESULTS 979 patients were included. Baseline SI was not associated with mortality. 24 h SI > 0.7 was associated with 7-day mortality (hazard ratio (95% confidence interval) = 3.14 (1.37-7.19)). 48 h and 72 h SI > 0.7 were associated with 7-day (4.23 (2.07-8.66) and 3.24 (1.41-7.42) respectively) and 90-day mortality (2.97 (1.82-4.85) and 2.05 (1.26-3.61) respectively). SI < 0.5 at baseline, 48 h and 72 h was associated with decreased pneumonia risk. 24 h and 48 h SI > 0.7was associated with increased MACE risk. 48 h and 72 h SI > 0.7 was associated with increased odds of higher 90-day mRS. CONCLUSION Higher-than-normal SI subsequent to initial encounter was associated with higher post-ICH mortality at 3, 7, and 90 days. Lower-than-normal SI was associated with a decreased risk of incident pneumonia.
-
10.
Insights into Salt Handling and Blood Pressure.
Ellison, DH, Welling, P
The New England journal of medicine. 2021;(21):1981-1993