Journal: Circulation research
Rationale: Use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. Objective: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in COVID-19 patients with hypertension. Methods and Results: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [IQR 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [IQR 57-69]; 53.5% men), who were admitted to nine hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. Unadjusted mortality rate was lower in the ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%; P = 0.01). In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted HR, 0.42; 95% CI, 0.19-0.92; P =0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted HR, 0.37; 95% CI, 0.15-0.89; P = 0.03). Further subgroup propensity score-matched analysis indicated that, compared to use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted HR, 0.30; 95%CI, 0.12-0.70; P = 0.01) in COVID-19 patients with hypertension. Conclusions: Among hospitalized COVID-19 patients with hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.
Infection with the novel coronavirus, SARS-CoV-2, produces a clinical syndrome known as COVID-19. When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm and elevations of cardiac injury biomarkers. Here we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.
Evidence suggests the gut microbiome is involved in the development of cardiovascular disease (CVD), with the host-microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for CVD from large-scale studies in humans. In particular, there was no strong evidence for association between CVD and aberrant blood lipid levels Objective: To identify intestinal bacteria taxa, whose proportions correlate with body mass index (BMI) and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, gender and host genetics.
Conventional three-dimensional (3D) printing techniques cannot produce structures of the size at which individual cells interact.
Until now, no cohort studies have evaluated the relationship between high-risk human papillomavirus (HPV) infection and new-onset cardiovascular diseases (CVD).
Rationale: Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is caused by mutations in cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) genes. Sinoatrial node dysfunction associated with CPVT may increase the risk for ventricular arrhythmia. Objective: To test the hypothesis that CPVT is suppressed by supraventricular overdrive stimulation. Methods and Results: Using CPVT mouse models (Casq2-/- and RyR2(R4496C)+/- mice), the effect of increasing sinus heart rate was tested by pretreatment with atropine and by atrial overdrive pacing. Increasing intrinsic sinus rate with atropine before catecholamine challenge suppressed ventricular tachycardia (VT) in 86% of Casq2-/- mice (6/7) and significantly reduced the ventricular arrhythmia (VA) score (atropine: 0.6±0.2 vs. vehicle: 1.7±0.3, p<0.05). Atrial overdrive pacing completely prevented VA in 16/19 (84%) Casq2-/- and in 7/8 (88%) RyR2(R4496C)+/- mice and significantly reduced ventricular premature beats in both CPVT models (p<0.05). Rapid pacing also prevented spontaneous calcium waves and triggered beats in isolated CPVT myocytes. In humans, heart-rate dependence of CPVT was evaluated by screening a CPVT patient registry for antiarrhythmic drug-naïve individuals that reached >85% of their maximum predicted heart rate during exercise testing. All 18 CPVT patients who fulfilled the inclusion criteria exhibited VA before reaching 87% of maximum heart rate. In six CPVT patients (33%), VA were paradoxically suppressed as sinus heart rates increased further with continued exercise. Conclusions: Accelerated supraventricular rates suppress VAs in two CPVT mouse models and in a subset of CPVT patients. Hypothetically, atrial overdrive pacing may be a therapy for preventing exercise-induced VT in treatment-refractory CPVT patients.
Rationale: Increased arginine-vasopressin (AVP) secretion is a key physiological response to hyperosmotic stress and may be part of the mechanism by which high-salt diets induce or exacerbate hypertension. Objective: Employing deoxycorticosterone acetate (DOCA)-salt hypertension model rats, we sought to test the hypothesis that changes in GABAA receptor-mediated inhibition in AVP-secreting magnocellular neurons contribute to the generation of Na(+)-dependent hypertension. Methods and Results: In-vitro gramicidin-perforated recordings in the paraventricular (PVN) and supraoptic nuclei (SON) revealed that the GABAergic inhibition in AVP-secreting neurons was converted into excitation in this model, due to the depolarization of GABA equilibrium potential (EGABA). Meanwhile, invivo extracellular recordings in the SON showed that the GABAergic baroreflexive inhibition of magnocellular neurons was transformed to excitation, so that baroreceptor activation may increase AVP release. The depolarizing EGABA shift in AVP-secreting neurons occurred progressively over weeks of DOCA-salt treatment along with gradual increases in plasma AVP and blood pressure. Further, the shift was associated with changes in chloride transporter expression and partially reversed by bumetanide (Na(+)-K(+)-2Cl- co-transporter inhibitor). Intracerebroventricular bumetanide administration during DOCA-salt treatment hindered the development of hypertension and rise in plasma AVP level. Muscimol (GABAA agonist) microinjection into the SON in hypertensive rats increased blood pressure, which was prevented by prior intravenous V1a AVP antagonist injection. Conclusions: We conclude that the inhibitory-to-excitatory switch of GABAA receptor-mediated transmission in AVP neurons contributes to the generation of Na(+)-dependent hypertension by increasing AVP release. We speculate that normalizing the EGABA may have some utility in treating Na(+)-dependent hypertension.
Rationale: Vascular smooth muscle cell (VSMC) differentiation from neural crest cells (NCCs) is critical for cardiovascular development, but the mechanisms remain largely unknown. Objective: TGF-β function in VSMC differentiation from NCCs is controversial. We therefore determined the role and the mechanism of a TGF-β downstream signaling intermediate Smad2 in NCC differentiation to VSMCs. Methods and Results: By using Cre/loxP system, we generated NCC tissue-specific Smad2 knockout mouse model and found that Smad2 deletion resulted in defective NCC differentiation to VSMCs in aortic arch arteries during embryonic development and caused vessel wall abnormality in adult carotid arteries where the VSMCs are derived from NCCs. The abnormalities included missing one layer of VSMCs in the media of the arteries with distorted and thinner elastic lamina, leading to a thinner vessel wall as compared to the wild type vessel. Mechanistically, Smad2 interacted with MRTFB to regulate VSMC marker gene expression. Smad2 was required for TGF-β-induced MRTFB nuclear translocation whereas MRTFB enhanced Smad2 binding to VSMC marker promoter. Moreover, we found that Smad2, but not Smad3, was a progenitor-specific transcription factor mediating TGF-β-induced VSMC differentiation from NCCs. Smad2 appeared to be also involved in determining the physiological differences between NCC- and mesoderm-derived VSMCs. Conclusions: Smad2 is an important factor in regulating progenitor-specific VSMC development and physiological differences between NCC- and mesoderm-derived VSMCs.
Epidemiologic evidence indicates that exposures to fine particulate matter air pollution (PM2.5) contribute to global burden of disease, primarily as a result of increased risk of cardiovascular morbidity and mortality. However, mechanisms by which PM2.5 exposure induces cardiovascular injury remain unclear. PM2.5-induced endothelial dysfunction and systemic inflammation have been implicated, but direct evidence is lacking.
Physiological studies have long documented the key role played by the autonomic nervous system in modulating cardiovascular functions and in controlling blood pressure values, both at rest and in response to environmental stimuli. Experimental and clinical investigations have tested the hypothesis that the origin, progression, and outcome of human hypertension are related to dysfunctional autonomic cardiovascular control and especially to abnormal activation of the sympathetic division. Here, we review the recent literature on the adrenergic and vagal abnormalities that have been reported in essential hypertension, with emphasis on their role as promoters and as amplifiers of the high blood pressure state. We also discuss the possible mechanisms underlying these abnormalities and their importance in the development and progression of the structural and functional cardiovascular damage that characterizes hypertension. Finally, we examine the modifications of sympathetic and vagal cardiovascular influences induced by current nonpharmacological and pharmacological interventions aimed at correcting elevations in blood pressure and restoring the normotensive state.