Relative Efficacy of Sacubitril-Valsartan,Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis

Cardiovascular Drugs and Therapy - Sacubitril/valsartan, vericiguat, and the sodium-glucose co-transporter-2 inhibitors (SGLT2i) dapagliflozin and empagliflozin proved effective in phase 3 trials...     

Determinants of Intima-Media Thickness in the Young: The ALSPAC Study

ObjectivesThis study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years.BackgroundGreater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood.MethodsAssociations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences.ResultsFat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p < 0.001), whereas fat mass was negatively associated with cIMT (difference: ?0.0032; 95% CI: 0.004 to ?0.001; p = 0.001). Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor?associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor.ConclusionsSubtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures may be more appropriate for the identification of arterial disease before adulthood.     

Can premenstrual syndrome affect arterial stiffness or blood pressure?

ObjectiveWe tested the hypotheses that monthly fluctuations in markers of arterial stiffness and blood pressure hemodynamics differ between women with and without premenstrual syndrome. We also assessed hypertension prevalence and arterial stiffening in postmenopausal women with or without history of premenstrual symptoms.MethodsTwenty one pre-menopausal women with premenstrual syndrome and 15 women without were prospectively examined in three distinct phases of their menstrual cycle (menses, late follicular and luteal phase). Pulse-wave velocity and analysis were used to assess arterial stiffness and wave reflection indices, respectively. Endothelial function was evaluated by flow-mediated vasodilation. In a cross-sectional substudy, 156 postmenopausal women were assessed for possible associations between retrospectively reported PMS symptoms and hypertension.ResultsIn women with premenstrual syndrome, arterial stiffness significantly increased during the luteal and menses phase (late follicular: 6.48 ± 1.07, luteal: 7.1 ± 1.26, menstruation: 7.12 ± 1.19 m/s, p = 0.003), while blood pressure peaked at the menses phase. Significant interactions between PMS and changes in arterial stiffness and blood pressure but not endothelial function, were observed. Changes in PWV were significantly associated with concomitant changes in blood pressure, C-reactive protein and the severity of PMS symptoms. The prevalence of hypertension (20.9% vs. 40.9%, p = 0.041) and pulse-wave velocity values (8.64 ± 1.52 vs. 9.37 ± 1.1, p = 0.046) were higher in postmenopausal women with 7 or more reported PMS symptoms. Arterial stiffness differences remained significant after adjustment for confounding factors.ConclusionThese results imply that PMS may affect arterial stiffness and BP monthly variability. Whether PMS is associated with new onset hypertension later in life needs further evaluation.     

PDE5 inhibition against acute renal ischemia reperfusion injury in rats: does vardenafil offer protection?

Purpose

To evaluate the effect of vardenafil on renal function after renal ischemia–reperfusion (IR) injury (IRI) in a rat model.

Materials and methods

Seventy-one Wistar rats were divided into 7 groups including (1) a vehicle-treated group, (2) a vehicle pretreated-IR group, (3–6) vardenafil pretreated-IR groups in doses of 0.02, 0.2, 2 and 20 μg/kg, respectively, (7) a group of IR followed by treatment with 2 μg/kg of vardenafil. Vardenafil or vehicle solution was administered one hour before unilateral nephrectomy and the induction of 45 min of ischemia on the contralateral kidney by clamping of renal pedicle. Four hours of reperfusion were allowed after renal ischemia. Studied parameters were serum creatinine, fractional excretion of sodium (FENa), and histological evaluation of renal specimens. In addition, renal tissue cGMP levels, ERK1/2 phosphorylation as well as renal function by renal scintigraphy were also evaluated.

Results

Administration of vardenafil before the induction of ischemia resulted in a significant reduction in creatinine and FENa levels as well as in less histological lesions observed in treated kidneys in comparison with the vehicle-treated group. The underlying mechanism of cytoprotection was cGMP depended and involved the phosphorylation of ERK proteins. Renal scintigraphy confirmed that PDE5 inhibition attenuates renal IRI.

Conclusions

Vardenafil attenuates renal IRI. Based on similar results from relevant studies on other PDE-5 inhibitors in renal and cardiac IRI, it can be assumed that all PDE-5 inhibitors share a common mechanism of cytoprotection.     

Propranolol Versus Metoprolol for Treatment of Electrical Storm in Patients With Implantable Cardioverter-Defibrillator

Background

Electrical storm (ES), characterized by unrelenting recurrences of ventricular arrhythmias, is observed in approximately 30% of patients with implantable cardioverter-defibrillators (ICDs) and is associated with high mortality rates.