Clinical Hypertension最新文献

Background: Pulmonary arterial hypertension (PAH) leads to heart failure, with limited treatment options to prevent adverse remodeling and metabolic dysfunctions. Exercise and bioactive compounds like blueberry extract show potential, but their combined effects are unclear. We tested if combining resistance exercise training (RT) and blueberry extract could protect against cardiac and skeletal muscle remodeling and metabolic disruptions in monocrotaline (MCT)-induced PAH.

Methods: Male rats received MCT (60 mg/kg), blueberry extract (100 mg/kg/day), and RT (ladder climbing; 15 climbs at 55-65% max load, 5 times/week). Exercise tolerance, blood lactate levels, and echocardiography were assessed. After euthanasia, heart and biceps brachii were analyzed. RT and blueberry attenuated mortality, weight loss, and exercise intolerance in hypertensive rats.

Results: Both interventions reduced pulmonary artery resistance and partially prevented right ventricular (RV) pressure overload and dysfunction, while their combination fully preserved left ventricular function. Hypertension-induced cardiac myocyte remodeling was mitigated by both interventions, with RT improving contractile function, whereas blueberry had no effect. Both treatments reduced oxidative stress and improved metabolic biomarkers in the RV. Blueberry preserved hypertrophy signaling pathways, while RT increased phospho (p)-Akt expression. Both interventions partially prevented reductions in p-mTOR, p-4E-BP1, and eIF4E, with their combination fully preserving these markers.

Conclusions: RT program and blueberry extract employed, either alone or in combination, demonstrated protective effects against the progression of cardiac and skeletal muscle remodeling and metabolism disruptions in the MCT-induced PAH model.

Background: Indirect estimates of pulse wave velocity (PWV) have been proposed as a feasible alternative for PWV assessment in clinical practice; however, their validity and clinical applicability remain uncertain. This study aimed to evaluate the relationships between indirect measures of arterial stiffness and directly measured PWV to determine their potential utility in clinical settings.

Methods: In this multicentre, international study, data from 4,206 individuals from Brazil, Greece, Korea, and Australia were analysed. The relationships between estimated PWV (ePWV), 24-hour (24h)-pulse pressure (PP), Early Vascular Aging Ambulatory Score (EVAAS), and carotid-femoral (cf-PWV) and/or brachial-ankle (ba-PWV) PWV were assessed through correlation and multivariate linear regression analyses. Subgroup-specific associations were also examined.

Results: The study population had a mean age of 57.6 ± 14.3 years, with 42.5% being male and 82.1% having pre-existing hypertension. After adjusting for multiple factors related to arterial stiffness, ePWV demonstrated a strong association with cf-PWV (β = 0.599, P < 0.001) and ba-PWV (β = 1.342, P < 0.001). 24h-PP and EVAAS showed moderate associations with both cf-PWV and ba-PWV. Subgroup analyses indicated that ePWV correlated more strongly with both cf-PWV and ba-PWV in individuals without traditional cardiovascular risk factors.

Conclusions: ePWV may be used as a surrogate marker for arterial stiffness, particularly in individuals without major cardiometabolic comorbidities. Although 24h-PP and EVAAS are also associated with PWV, their clinical utility varies across subgroups. Future research should explore their role in improving cardiovascular risk prediction and guiding personalized treatment strategies for vascular aging.

Trial registration: PROSPERO Identifier: CRD420250618863.

Background: Isometric resistance exercise has been shown to reduce blood pressure (BP), particularly when involving large muscle groups. Isometric plank exercise (IPE), which elicits extensive muscle activation, may offer similar benefits; however, its acute effects on ambulatory blood pressure monitoring (ABPM) and variability remain unclear. This study aimed to examine the acute effects of IPE on ABPM, blood pressure variability (BPV) and ambulatory arterial stiffness index (AASI) in young adults with prehypertension.

Methods: Twelve young adults (mean age, 26.4 ± 5.4 years) with prehypertension (systolic BP [SBP] 120-139 mmHg or diastolic BP [DBP] 80-89 mmHg) participated in a randomized cross-over trial. Each participant completed 2 sessions in random order: 1) 4 × 2-minute IPE session with 1-minute rest, and 2) a non-exercise control session. Office BP was measured at baseline, 30 minutes, and 90 minutes post-trial. ABPM, BPV and AASI were recorded over the following 24 hours.

Results: A significant interaction effect was observed for systolic office BP (P = 0.009), with post-hoc analysis revealing a significant reduction at 90 minutes post-IPE session (P = 0.048). Twenty-four-hour average systolic and DBP were significantly lower in the IPE session compared to control session (P = 0.004, P = 0.031, respectively). In addition, both daytime SBP (P = 0.020) and nighttime DBP (P = 0.014) significantly decreased after the IPE session. Nighttime systolic BPV was also significantly decreased after the IPE session (P = 0.040). No significant changes were observed in other BPV index and AASI.

Conclusions: IPE significantly reduced 24-hour SBP and DBP and improved nighttime BP variability in young adults with prehypertension. These findings provide preliminary evidence that IPE may serve as a potential nonpharmacologic strategy for early BP management. Large-scale interventional studies are warranted to confirm and extend on these effects.

Resistant hypertension (RH) remains a major clinical challenge, defined as uncontrolled blood pressure (BP) despite the use of 3 antihypertensive agents, including a renin-angiotensin system inhibitor, a calcium channel blocker, and a diuretic, or the need for 4 or more agents. Spironolactone has been considered the most effective fourth-line therapy, supported by the PATHWAY-2 trial, but its real-world use is limited by adverse effects such as gynecomastia, menstrual irregularities, and hyperkalemia. Therefore, there was a clinical need for alternative agents, and thus the use of amiloride, an epithelial sodium channel (ENaC) inhibitor and potassium-sparing diuretic, has been proposed. Data from PATHWAY-2 suggested amiloride's comparable BP-lowering efficacy, though based only on an open-label extension. Recently, the SPironolactone versus Amiloride for REsistant hypertension (SPARE) trial provided the first randomized evidence directly comparing the 2 agents. In 118 patients with RH inadequately controlled on fixed-dose triple therapy, participants were randomized to spironolactone 12-25 mg or amiloride 5-10 mg for 12 weeks. Mean reductions in home systolic blood pressure (SBP) were -14.7 mmHg with spironolactone and -13.6 mmHg with amiloride, meeting the prespecified non-inferiority margin. Safety profiles were favorable, with only one discontinuation due to hyperkalemia in the amiloride group and no reports of gynecomastia. Subgroup analyses suggested greater efficacy of amiloride in patients with higher body mass index and lower aldosterone-renin ratios, highlighting a potentially distinct mechanism of action. Unlike spironolactone, whose efficacy correlated with aldosterone activity, amiloride showed consistent SBP reduction across renin and aldosterone levels. Beyond its renal ENaC inhibition, amiloride may also modulate vascular biology. In addition to its inhibition of renal ENaCs, amiloride may also have an impact on vascular biology. Experimental studies indicate that ENaC is present in endothelial cells, where its activation can lead to reduced nitric oxide release, increased oxidative stress, endothelial stiffness, and vascular fibrosis. Amiloride may consistently lower BP across a wide range of renin-aldosterone activity by improving endothelial function through the inhibition of ENaC, as well as by decreasing intravascular volume. The findings from the SPARE trial suggest that amiloride may be a viable alternative to spironolactone for RH, particularly in patients who are intolerant to mineralocorticoid receptor antagonists. While spironolactone remains the preferred option due to its established role in blocking systemic aldosterone activation and proven cardiovascular benefits, amiloride can provide a practical and well-tolerated alternative.

Earlier Aldosterone synthase inhibitors (ASIs) were non-selective, with a risk of cortisol insufficiency. A new generation of ASIs has emerged with improved selectivity and pharmacological properties, although their efficacy and safety remain debated. This meta-analysis evaluates the efficacy and safety of selective ASIs in adults with uncontrolled primary hypertension. We selected randomized controlled trials (RCTs) from 6 databases/registries, comparing selective ASIs with placebo in adults aged ≥ 18 years with primary uncontrolled hypertension. Quality was assessed using the risk of bias 2 tool. Random-effects models were used to pool mean differences for continuous variables and calculate odds ratios (ORs) for binary outcomes. Certainty of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Five RCTs, involving 2,456 patients, were included. Least-squares mean (LSM) systolic blood pressure (SBP) was significantly lower with ASIs than placebo in both standard-dose (difference in LSM [LSMD], -9.05 mmHg; 95% confidence interval [CI], -10.98 to -7.12; P < 0.001) and high-dose regimens (LSMD, -9.04 mmHg; 95% CI, -10.99 to -7.08; P < 0.001). LSM diastolic blood pressure was also significantly lower with ASIs using standard dose (LSMD, -3.54 mmHg; 95% CI, -4.99 to -2.09; P < 0.001) and high dose (LSMD, -4.17 mmHg; 95% CI, -5.72 to -2.62; P < 0.001) compared with placebo. For safety endpoints, mild hyperkalemia (5.5-6 mmol/L) was more frequent with ASIs at both standard dose (OR, 7.50; 95% CI, 2.46 to 22.85; P < 0.001) and high dose (OR, 11.63; 95% CI, 3.82 to 35.39; P < 0.001). The rate of moderate-to-severe hyperkalemia (greater than 6 mmol/L) was comparable between the ASI and placebo groups for standard doses. In contrast, high doses were associated with an increased rate in the ASI group (OR, 4.43; 95% CI, 1.10 to 17.82; P = 0.036). The certainty of evidence was high for both SBP and mild hyperkalemia, and moderate for moderate to severe hyperkalemia. Selective ASIs appear to be a promising treatment in terms of efficacy and safety for uncontrolled hypertensive patients. Larger RCTs with extended follow-up periods are warranted to establish long-term evidence.

Trial registration: PROSPERO Identifier: CRD420251108664.

Background: Blood pressure variability (BPV) represents an independent predictor of cardiovascular disease, distinct from mean blood pressure (BP). While home BP monitoring is widely recommended, the associations between home BPV and vascular, metabolic, and inflammatory markers remain unclear. We aimed to clarify these associations.

Methods: We analyzed 519 hypertensive patients from a prospective multicenter registry. Home BPV was assessed using standard deviation, coefficient of variation (CV), average real variability, variability independent of the mean, and range. Patients were stratified by the median CV of home systolic BP (SBP). We used Pearson correlation coefficients to evaluate the relationships between home BPV and office BPV, metabolic parameters, and arterial stiffness indices.

Results: Based on stratification by the CV of home SBP, the high-BPV group was characterized by older age, a greater proportion of women, and a lower body mass index compared with the low-BPV group. Correlations between home and office BP were stronger for mean values than for variability indices. Home systolic BPV indices correlated positively with high-sensitivity C-reactive protein (r = 0.11-0.12, P < 0.05) and with arterial stiffness parameters, particularly the second systolic peak (r = 0.23-0.35, P ≤ 0.01), but not with lipid or glucose profiles. Home diastolic BPV indices exhibited weaker and inconsistent associations.

Conclusions: Home systolic BPV showed consistent associations with vascular inflammation and arterial stiffness, but not with metabolic parameters. These findings support home BPV as a distinct cardiovascular risk marker with potential relevance for risk stratification and preventive management.

Trial registration: ClinicalTrials.gov Identifier: NCT06394934.

Atherosclerosis remains a major contributor to cardiovascular morbidity and mortality, characterized by endothelial dysfunction, chronic inflammation, and metabolic dysregulation. Both exercise and metformin have demonstrated cardiovascular benefits through overlapping molecular mechanisms, notably involving AMP-activated protein kinase (AMPK) activation, mitochondrial biogenesis, anti-inflammatory pathways, and autophagy regulation. This review synthesizes current evidence on how these 2 interventions individually and jointly modulate vascular remodeling and atherogenesis. We critically examine their synergistic effects and potential conflicts, particularly regarding AMPK signaling intensity, tissue-specific responsiveness, and the influence of intervention timing, dose, and host metabolic state. We also explore how exercise and metformin interact dynamically across key molecular networks, including the M3-calcium/calmodulin-dependent protein kinase kinase beta-AMPK axis and downstream effectors such as sirtuin 1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha. While emerging data suggest potential benefits from the combined intervention in attenuating vascular aging and plaque formation, evidence remains mixed, and context-dependent responses are increasingly recognized. This review highlights the need for individualized intervention strategies and proposes mechanistic models to guide future research. Overall, a deeper understanding of the dynamic crosstalk between exercise and metformin may enhance the development of personalized therapies for atherosclerotic cardiovascular disease.

Background: Despite its substantial burden, hypertensive heart disease (HHD) remains underrecognized. We aimed to investigate the global burden of HHD projected up to 2050.

Methods: We utilized data from the Global Burden of Disease Study (GBD) 2021 to estimate the global HHD burden. The burden was assessed using prevalence, death, and disability-adjusted life years (DALYs), stratified by region, age, sex, and Socio-demographic Index (SDI), with all estimates accompanied by 95% uncertainty intervals (UIs). We ranked age-standardized DALY rates attributable to six risk factors. Forecasting analysis was conducted using the GBD 2021 forecast framework, supplemented by Das Gupta decomposition analysis.

Results: From 1990 to 2021, the global age-standardized prevalence rate increased from 125.44 per 100,000 population (95% UI, 98.97-157.96) to 148.32 (117.32-186.28). In contrast, age-standardized mortality and DALY rates declined to 16.31 per 100,000 population (95% UI, 13.76-18.01) and 301.58 (255.06-332.06), respectively. HHD burden increased with age and was more pronounced in women, particularly among older populations. High systolic blood pressure ranked first among six identified risk factors. Forecasting up to 2050 projected increases in age-standardized mortality (19.11 [95% UI, 13.24-27.45]) and DALY rates (367.80 [255.27-524.52]), despite declining trends over the past three decades. Population growth was the main driver of the projected increase, as shown by Das Gupta decomposition.

Conclusions: The rising burden of HHD calls for a shift away from traditional, fragmented approaches focused solely on blood pressure control. Integrated clinical and policy responses are urgently needed to address the complex and multifactorial nature of the disease.

Background: An exaggerated blood pressure response (EBPR) to exercise predicts future hypertension and cardiovascular disease. Although aerobic exercise (AE) and inspiratory muscle strength training (IMST) lower resting blood pressure (BP), their capacity to attenuate EBPR has not been compared. This study examined the effects of AE and IMST on EBPR during maximal exercise testing in hypertensive patients.

Methods: Twenty-four participants were randomly assigned to AE (n = 12, 40-70% of heart rate reserve, 30 minutes) or IMST (n = 12, 55-75% of maximal inspiratory pressure, 30 breaths/day), 5 days/week for 8 weeks. Brachial BP and heart rate were measured at rest, during each stage of a graded cycle-ergometer test, and during recovery. EBPR was defined as peak systolic BP (SBP) ≥ 210 mmHg (men) or ≥ 190 mmHg (women). Primary outcomes were changes in SBP across exercise stages and prevalence of EBPR.

Results: Both interventions reduced resting SBP (-8.0 mmHg) and diastolic BP (-4.2 mmHg). The prevalence of EBPR declined from 62.5% to 45.8%, though this did not reach statistical significance (χ² = 1.34, P = 0.25). Subgroup analysis showed greater SBP attenuation at moderate intensity with AE (-9.2 mmHg, P = 0.020) and at higher intensity with IMST (-8.8 mmHg, P = 0.042).

Conclusions: Both AE and IMST attenuated SBP responses during submaximal exercise in hypertensive individuals. These findings highlight a potential for exercise training to mitigate EBPR in hypertension.