Showing papers in "Hypertension in 2023"
TL;DR: In this paper , a study revealed that COVID-19 survivors exhibit sympathetic overactivation, vascular dysfunction, cardiac morpho-functional changes, impaired exercise capacity, and increased oxidative stress.
Abstract: Background: COVID-19 has become a dramatic health problem during this century. In addition to high mortality rate, COVID-19 survivors are at increased risk for cardiovascular diseases 1-year after infection. Explanations for these manifestations are still unclear but can involve a constellation of biological alterations. We hypothesized that COVID-19 survivors compared with controls exhibit sympathetic overdrive, vascular dysfunction, cardiac morpho-functional changes, impaired exercise capacity, and increased oxidative stress. Methods: Nineteen severe COVID-19 survivors and 19 well-matched controls completed the study. Muscle sympathetic nerve activity (microneurography), brachial artery flow-mediated dilation and blood flow (Doppler-Ultrasound), carotid-femoral pulse wave velocity (Complior), cardiac morpho-functional parameters (echocardiography), peak oxygen uptake (cardiopulmonary exercise testing), and oxidative stress were measured ~3 months after hospital discharge. Complementary experiments were conducted on human umbilical vein endothelial cells cultured with plasma samples from subjects. Results: Muscle sympathetic nerve activity and carotid-femoral pulse wave velocity were greater and brachial artery flow-mediated dilation, brachial artery blood flow, E/e′ ratio, and peak oxygen uptake were lower in COVID-19 survivors than in controls. COVID-19 survivors had lower circulating antioxidant markers compared with controls, but there were no differences in plasma-treated human umbilical vein endothelial cells nitric oxide production and reactive oxygen species bioactivity. Diminished peak oxygen uptake was associated with sympathetic overdrive, vascular dysfunction, and reduced diastolic function in COVID-19 survivors. Conclusions: Our study revealed that COVID-19 survivors have sympathetic overactivation, vascular dysfunction, cardiac morpho-functional changes, and reduced exercise capacity. These findings indicate the need for further investigation to determine whether these manifestations are persistent longer-term and their impact on the cardiovascular health of COVID-19 survivors.
9 citations
TL;DR: A review of the evidence available in experimental models and humans to examine the progress made and identify remaining gaps in knowledge is provided in this paper , where the authors provide a critical evaluation.
Abstract: Hypertension affects a significant proportion of the adult and aging population and represents an important risk factor for vascular cognitive impairment and late-life dementia. Chronic high blood pressure continuously challenges the structural and functional integrity of the cerebral vasculature, leading to microvascular rarefaction and dysfunction, and neurovascular uncoupling that typically impairs cerebral blood supply. Hypertension disrupts blood-brain barrier integrity, promotes neuroinflammation, and may contribute to amyloid deposition and Alzheimer pathology. The mechanisms underlying these harmful effects are still a focus of investigation, but studies in animal models have provided significant molecular and cellular mechanistic insights. Remaining questions relate to whether adequate treatment of hypertension may prevent deterioration of cognitive function, the threshold for blood pressure treatment, and the most effective antihypertensive drugs. Recent advances in neurovascular biology, advanced brain imaging, and detection of subtle behavioral phenotypes have begun to provide insights into these critical issues. Importantly, a parallel analysis of these parameters in animal models and humans is feasible, making it possible to foster translational advancements. In this review, we provide a critical evaluation of the evidence available in experimental models and humans to examine the progress made and identify remaining gaps in knowledge.
7 citations
TL;DR: Aurora Project as discussed by the authors evaluated the accuracy of wearable cuffless BP devices based on pulse wave analysis (applied to a photoplethysmography or tonometry waveform) with or without use of pulse arrival time, and the overall results from 1125 participants were clear-cut negative.
Abstract: Conventional blood pressure (BP) measurement devices based on an inflatable cuff only provide a narrow view of the continuous BP profile. Cuffless BP measuring technologies could permit numerous BP readings throughout daily life and thereby considerably improve the assessment and management of hypertension. Several wearable cuffless BP devices based on pulse wave analysis (applied to a photoplethysmography or tonometry waveform) with or without use of pulse arrival time are now available on the market. The key question is: Can these devices provide accurate measurement of BP? Microsoft Research recently published a complex article describing perhaps the most important and highest resource project to date (Aurora Project) on assessing the accuracy of several pulse wave analysis and pulse wave analysis-pulse arrival time devices. The overall results from 1125 participants were clear-cut negative. The present article motivates and describes emerging cuffless BP devices and then summarizes the Aurora Project. The study methodology and findings are next discussed in the context of regulatory-cleared devices, physiology, and related studies, and the study strengths and limitations are pinpointed thereafter. Finally, the implications of the Aurora Project are briefly stated and recommendations for future work are offered to finally realize the considerable potential of cuffless BP measurement in health care.
5 citations
TL;DR: In this article , the authors evaluate recent epidemiological data and highlight current knowledge from studies investigating sex-specific mechanisms of salt-sensitive blood pressure (SSBP), concluding that women of all ethnicities are more salt sensitive than men, at all ages both premenopausal and postmenopausal.
Abstract: Several clinical and large population studies indicate that women are more salt-sensitive than men, yet the precise mechanisms by which the sexually dimorphic onset manifests remains incompletely understood. Here, we evaluate recent epidemiological data and highlight current knowledge from studies investigating sex-specific mechanisms of salt-sensitive blood pressure (SSBP). Emerging evidence indicates that women of all ethnicities are more salt-sensitive than men, at all ages both premenopausal and postmenopausal. However, menopause exacerbates severity and prevalence of SSBP, suggesting that female sex chromosomes predispose to and female sex hormones mitigate SSBP. Results from both human and rodent studies support the contribution of enhanced and inappropriate activation of the aldosterone-ECMR (endothelial cell mineralocorticoid receptor) axis promoting vascular dysfunction in females. Increases in adrenal response to angiotensin II, in association with higher ECMR expression and activation of endothelial ENaC (epithelial sodium channel) in females compared to males, are emerging as central players in the development of endothelial dysfunction and SSBP in females. Female sex increases the prevalence and susceptibility of SSBP and sex hormones and sex chromosome complement may exert antagonistic effects in the development of the female heightened SSBP.
5 citations
TL;DR: The exact molecular mechanisms underlying hypertension are unclear, but recent discoveries indicate an important role for reduced nitric oxide generation, oxidative stress, endothelin-1, prostaglandins, endothelial dysfunction, increased sympathetic outflow, and microvascular rarefaction as mentioned in this paper .
Abstract: Contemporary anticancer drugs have significantly improved cancer survival at the expense of cardiovascular toxicities, including heart disease, thromboembolic disease, and hypertension. One of the most common side effects of these drugs is hypertension, especially in patients treated with vascular endothelial growth factor inhibitors, as well as tyrosine kinase inhibitors and proteasome inhibitors. Adjunctive therapy, including corticosteroids, calcineurin inhibitors, and nonsteroidal anti-inflammatories, as well as anti-androgen hormone therapy for prostate cancer, may further increase blood pressure in these patients. Cancer therapy-induced hypertension is often dose limiting, increases cardiovascular mortality in cancer survivors, and is usually reversible after interruption or discontinuation of treatment. The exact molecular mechanisms underlying hypertension are unclear, but recent discoveries indicate an important role for reduced nitric oxide generation, oxidative stress, endothelin-1, prostaglandins, endothelial dysfunction, increased sympathetic outflow, and microvascular rarefaction. In addition, genetic polymorphisms in vascular endothelial growth factor receptors are implicated in vascular endothelial growth factor inhibitor-induced hypertension. Diagnosis, management, and follow-up of cancer therapy-induced hypertension follow national hypertension guidelines because evidence-based clinical trials specifically addressing patients who develop hypertension as a result of cancer therapy are currently lacking. Rigorous baseline assessment of patients before therapy is started requires particular emphasis on assessing and treating cardiovascular risk factors. Hypertension management follows guidelines for the general population, although special attention should be given to rebound hypotension after termination of cancer therapy. Management of these complex patients requires collaborative care involving oncologists, cardiologists, hypertension specialists, primary care professionals, and pharmacists to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.
5 citations
TL;DR: In this article , the authors estimated circulating proportions of 12 leukocyte subsets from the lymphoid and myeloid lineages by deconvolving cell-type-specific DNA methylation data from 4124 women.
Abstract: Background: The development and consequences of hypertension involve multiple biological systems that may include changes in immune profiles. Whether hypertension is related to peripheral immune cell composition has not been examined in large human cohorts. Methods: We estimated circulating proportions of 12 leukocyte subsets from the lymphoid and myeloid lineages by deconvolving cell-type-specific DNA methylation data from 4124 women. Hypertension status at baseline was defined by current use of antihypertensive medication and blood pressure measurements while new incident cases were identified during follow-up via annual health questionnaires. Results: Among hypertension-free women at baseline, higher B cell and lower naïve CD4+ helper T cell proportions were associated with subsequent increased hazard of hypertension incidence (B cells; adjusted HR: 1.17 [95% CI: 1.02–1.35]; P =0.03; naïve CD4+ T cell, adjusted HR: 0.88 [95% CI: 0.78–0.99]; P =0.04). Blood pressure measurements at baseline were similarly positively associated with B cells and inversely associated with naïve CD4+ helper T cells. Compared to normotensive women, women with hypertension had higher circulating proportions of neutrophils (adjusted odds ratio: 1.18 [95% CI: 1.07–1.31]; P =0.001) and lower proportions of CD4+ helper T cells (adjusted odds ratio: 0.90 [95% CI: 0.81–1.00] P =0.05), natural killers (adjusted odds ratio: 0.82 [95% CI: 0.74–0.91]; P <0.001), and B cells (adjusted odds ratio: 0.84 [95% CI: 0.74–0.96]; P =0.01). Conclusions: These observations suggest that shifts in lymphocyte subsets occur before hypertension development, followed by later changes to neutrophils and additional lymphocytes.
5 citations
TL;DR: In this article , the authors conducted a 2-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, or cognition on hypertension (FinnGen study, 70 651 cases/223 663 controls; UK Biobank, 77 723 cases/330 366 controls) and blood pressure (International Consortium of Blood Pressure, 757 601 participants).
Abstract: Education, intelligence, and cognition are associated with hypertension, but which one plays the most prominent role in the pathogenesis of hypertension and which modifiable risk factors mediate the causal effects remains unknown.Using summary statistics of genome-wide association studies of predominantly European ancestry, we conducted 2-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, or cognition on hypertension (FinnGen study, 70 651 cases/223 663 controls; UK Biobank, 77 723 cases/330 366 controls) and blood pressure (International Consortium of Blood Pressure, 757 601 participants), and used 2-step Mendelian randomization to evaluate 25 potential mediators of the association and calculate the mediated proportions.Meta-analysis of inverse variance weighted Mendelian randomization results from FinnGen and UK Biobank showed that genetically predicted 1-SD (4.2 years) higher education was associated with 44% (95% CI: 0.40-0.79) decreased hypertension risk and 1.682 mm Hg lower systolic and 0.898 mm Hg lower diastolic blood pressure, independently of intelligence and cognition. While the causal effects of intelligence and cognition on hypertension were not independent of education; 6 out of 25 cardiometabolic risk factors were identified as mediators of the association between education and hypertension, ranked by mediated proportions, including body mass index (mediated proportion: 30.1%), waist-to-hip ratio (22.8%), body fat percentage (14.1%), major depression (7.0%), high-density lipoprotein cholesterol (4.7%), and triglycerides (3.4%). These results were robust to sensitivity analyses.Our findings illustrated the causal, independent impact of education on hypertension and blood pressure and outlined cardiometabolic mediators as priority targets for prevention of hypertension attributable to low education.
5 citations
TL;DR: In this article , the relationship between protein levels of sFLT1 and PlGF in maternal serum measured at ≈36 weeks and placental tissue lysates obtained after term delivery in 82 women with preeclampsia, 50 women with FGR, and 132 controls was determined.
Abstract: Preeclampsia and fetal growth restriction (FGR) are both associated with an increased ratio of sFLT1 (soluble fms-like tyrosine kinase-1) to PlGF (placenta growth factor) in maternal serum. In preeclampsia, it is assumed that increased placental release of sFLT1 results in PlGF being bound and inactivated. However, direct evidence for this model is incomplete, and it is unclear whether the same applies in FGR.We conducted a prospective cohort study where we followed 4212 women having first pregnancies from their dating ultrasound, obtained blood samples serially through the pregnancy, and performed systematic sampling of the placenta after delivery. The aim of the present study was to determine the relationship between protein levels of sFLT1 and PlGF in maternal serum measured at ≈36 weeks and placental tissue lysates obtained after term delivery in 82 women with preeclampsia, 50 women with FGR, and 132 controls.The sFLT1:PlGF ratio was increased in both preeclampsia and FGR in both the placenta and maternal serum. However, in preeclampsia, the maternal serum ratio of sFLT1:PlGF was strongly associated with placental sFLT1 level (r=0.45; P<0.0001) but not placental PlGF level (r=-0.17; P=0.16). In contrast, in FGR, the maternal serum ratio of sFLT1:PlGF was strongly associated with placental PlGF level (r=-0.35; P=0.02) but not sFLT1 level (r=0.04; P=0.81).We conclude that the elevated sFLT1:PlGF ratio is primarily driven by increased placental sFLT1 in preeclampsia, whereas in FGR, it is primarily driven by decreased placental PlGF.
4 citations
TL;DR: In this article , a meta-analysis of the microneurographic studies evaluating the BP and muscle sympathetic nerve activity (MSNA) responses to RDN in drug-resistant or uncontrolled hypertension (RHT) patients was performed.
Abstract: Whether and to what extent the reported blood pressure (BP) lowering effects of renal denervation (RDN) are associated with a central sympathoinhibition is controversial. We examined this issue by performing a meta-analysis of the microneurographic studies evaluating the BP and muscle sympathetic nerve activity (MSNA) responses to RDN in drug-resistant or uncontrolled hypertension (RHT).This analysis comprised 11 studies including a total of >400 RHT patients undergoing RDN and were followed up for 6 months. Evaluation was extended to the relationships of MSNA with clinic heart rate and BP changes associated with RDN.MSNA showed a significant reduction after RDN (-4.78 bursts/100 heart beats; P<0.04), which was also accompanied by a significant systolic (-11.45 mm Hg; P<0.002) and diastolic (-5.24 mm Hg; P=0.0001) BP decrease. No significant quantitative relationship was found between MSNA and systolic (r=-0.96, P=0.19) or diastolic BP (r=-0.97, P=0.23) responses to RDN. This was also the case for clinic heart rate (r=0.53, P=0.78, respectively), whose post RDN values were not significant different from the pre-RDN ones. More than 10 renal nerves ablations were found to be needed for obtaining a significant sympathoinhibition.This meta-analysis, the first ever done on the MSNA responses to RDN, shows that in a consistent number of RHT patients RDN is associated with a significant, although modest, central sympathoinhibition, which appears to be unrelated to the BP lowering effects of the procedure. Thus factors other than the central sympathetic outflow inhibition may concur at the BP lowering effects of RDN.
4 citations
TL;DR: In this article , the proportion of ambulatory visits where older adults with hypertension were appropriately intensified on antihypertensives from 2008 to 2018 was determined, based on data from National Ambulatory Medical Care Survey.
Abstract: Hypertension control has worsened nationally, and treatment intensification is important for control. National trends for appropriate blood pressure intensification for older adults are unknown. We determine the proportion of ambulatory visits where older adults with hypertension were appropriately intensified on antihypertensives from 2008 to 2018.Data from National Ambulatory Medical Care Survey were used. National Ambulatory Medical Care Survey is a nationally representative sample of ambulatory visits. Adults 60 years or older were included. Appropriate antihypertensive intensification was defined as addition of an antihypertensive for a blood pressure reading above target. We examined appropriate intensification by blood pressure targets set by the American College of Cardiology-American Heart Association, the European Society of Cardiology, and the American College of Physicians-American Academy of Family Physicians guidelines for older adults. Further, we defined an additional all-inclusive criterion meeting all 3 guidelines.From 2008 to 2018, appropriate intensification by American College of Cardiology/American Heart Association occurred at 11.1% (95% CI, 9.8%-12.5%) of visits, decreasing from 13.6% (95% CI, 15.6%-28.7%) of visits in 2008 to 2009 to 10.4% (95% CI, 10.9%-26.4%) in 2015 to 2018. Appropriate intensification by European Society of Cardiology occurred at 14.2% (12.1%-16.6%) of visits over 2008 to 2018, decreasing from 16.9% (95% CI, 13.5%-21.0%) in 2008 to 2009 to 12.5% (95% CI, 7.4%-20.3%) from 2015 to 2018. Appropriate intensification by American Academy of Family Physicians/American College of Physicians occurred at 18.9% (16.2%-22.0%) of visits over 2008 to 2018, decreasing from 24.7% (95% CI, 20.2%-29.0%) in 2008 to 2009 to 14.9% (95% CI, 9.0%-23.7%) from 2015 to 2018. By all-inclusive criteria, intensification trended toward worsening with time: odds ratio: 0.93 ([95% CI, 0.87-1.00]; P=0.07).Appropriate treatment intensification for older adults with hypertension in the United States was suboptimal over the past decade.
4 citations
TL;DR: In this article , the authors summarize the evidence for the impact of hypertensive disorders of pregnancy on dementia and consider unique associations between HDP and dementia subtypes, concluding that maternal history of HDP is an important risk factor for later development of vascular and all-cause dementia.
Abstract: Prior meta-analyses report a 2- to 4-fold increased risk of later cardiovascular disease among women with a history of hypertensive disorders of pregnancy (HDP). Given HDP's vascular underpinnings, it is hypothesized to also be a risk factor for later dementia. We aim to summarize the evidence for the impact of HDP on dementia and consider unique associations between HDP and dementia subtypes.Observational studies on the relationship between HDP and dementia were identified from online electronic databases to July 1, 2021 (PROSPERO identifier: CRD42020185630). We included observational studies published in English. Exposure among women was any HDP and HDP subtypes: gestational hypertension, preeclampsia/eclampsia, or other/unspecified HDP. Outcome was any dementia and dementia subtypes: Alzheimer's disease, vascular dementia, or other/unspecified dementias.For our primary analyses, we included 5 cohort studies with a total of 183 874 women with and 2 309 705 women without HDP. Pooled analysis found a 38% higher risk of all-cause dementia among women with, versus without, any type of HDP (adjusted hazard ratio, 1.38 [95% CI, 1.18-1.61]; P<0.01). When examining association by HDP and dementia subtypes, we found that women with, versus without, any type of HDP had over a 3-fold higher risk of vascular dementia (adjusted hazard ratio, 3.14 [95% CI, 2.32-4.24]; P<0.01).Our findings indicate that maternal history of HDP is an important risk factor for later development of vascular and all-cause dementia. Further research among more racially/ethnically diverse populations quantifying HDP's effect on all-cause dementia, and specifically vascular dementia, is warranted.
TL;DR: In this paper , a population-based cohort study with within-sibship comparison of frozen embryo transfer (frozen-ET) with natural conception and fresh embryo transfer was conducted, and the risk of hypertensive disorders was higher after frozen-ET compared to natural conception.
Abstract: Background: Frozen embryo transfer (frozen-ET) is increasingly common because of improved cryopreservation methods and elective freezing of all embryos. Frozen-ET is associated with higher risk of hypertensive disorders in pregnancy than both natural conception and fresh embryo transfer (fresh-ET), but whether this is attributable to parental factors or treatment is unknown. Methods: Using the Medical Birth Registries of Denmark (1994–2014), Norway, and Sweden (1988–2015), linked to data from national quality registries and databases on assisted reproduction, we designed a population-based cohort study with within-sibship comparison. We included 4 426 691 naturally conceived, 78 300 fresh-ET, and 18 037 frozen-ET singleton pregnancies, of which 33 209 sibships were conceived using different conception methods. Adjusted odds ratios (aOR) of hypertensive disorders in pregnancy for fresh-ET and frozen-ET versus natural conception with 95% CI were estimated using multilevel logistic regression, where random effects provided conventional population-level estimates and fixed effects gave within-sibship estimates. Main models included adjustment for birth year, maternal age, parity, and country. Results: Risk of hypertensive disorders in pregnancy was higher after frozen-ET compared to natural conception, both at population-level (7.4% versus 4.3%, aOR, 1.74 [95% CI, 1.61–1.89]) and within sibships (aOR, 2.02 [95% CI, 1.72–2.39]). For fresh-ET, risk was similar to natural conception, both at population-level (aOR, 1.02 [95% CI, 0.98–1.07]) and within sibships (aOR, 0.99 [95% CI, 0.89–1.09]). Conclusions: Frozen-ET was associated with substantially higher risk of hypertensive disorders in pregnancy, even after accounting for shared parental factors within sibships.
TL;DR: In this paper , the authors measured upper-arm cuff and invasive aortic BP during coronary angiography in 1615 subjects from the Invasive Blood Pressure Consortium Database and determined the sex differences between cuff systolic BP (SBP) measurements and the difference between the 2 measurements.
Abstract: Background: Accurate blood pressure (BP) measurement is critical for optimal cardiovascular risk management. Age-related trajectories for cuff-measured BP accelerate faster in women compared with men, but whether cuff BP represents the intraarterial (invasive) aortic BP is unknown. This study aimed to determine the sex differences between cuff BP, invasive aortic BP, and the difference between the 2 measurements. Methods: Upper-arm cuff BP and invasive aortic BP were measured during coronary angiography in 1615 subjects from the Invasive Blood Pressure Consortium Database. This analysis comprised 22 different cuff BP devices from 28 studies. Results: Subjects were 64±11 years (range 40–89) and 32% women. For the same cuff systolic BP (SBP), invasive aortic SBP was 4.4 mm Hg higher in women compared with men. Cuff and invasive aortic SBP were higher in women compared with men, but the sex difference was more pronounced from invasive aortic SBP, was the lowest in younger ages, and the highest in older ages. Cuff diastolic blood pressure overestimated invasive diastolic blood pressure in both sexes. For cuff and invasive diastolic blood pressure separately, there were sex*age interactions in which diastolic blood pressure was higher in younger men and lower in older men, compared with women. Cuff pulse pressure underestimated invasive aortic pulse pressure in excess of 10 mm Hg for both sexes in older age. Conclusions: For the same cuff SBP, invasive aortic SBP was higher in women compared with men. How this translates to cardiovascular risk prediction needs to be determined, but women may be at higher BP-related risk than estimated by cuff measurements.
TL;DR: Preeclampsia is a maternal syndrome characterized by the new onset of hypertension and proteinuria after 20 weeks of gestation associated with multisystemic complications, including brain alterations as discussed by the authors .
Abstract: Preeclampsia is a maternal syndrome characterized by the new onset of hypertension and proteinuria after 20 weeks of gestation associated with multisystemic complications, including brain alterations. Indeed, brain complications associated with preeclampsia are the leading direct causes of fetal and maternal morbidity and mortality, especially in low- and middle-income countries. In addition to the well-recognized long-term adverse cardiovascular effects of preeclampsia, women who have had preeclampsia have higher risk of stroke, dementia, intracerebral white matter lesions, epilepsy, and perhaps also cognitive decline postpartum. Furthermore, increasing evidence has also associated preeclampsia with similar cognitive and cerebral disorders in the offspring. However, the mechanistic links between these associations remain unresolved. This article summarizes the current knowledge about the cerebrovascular complications elicited by preeclampsia and the potential pathophysiological mechanisms involved, emphasizing the impaired brain vascular function in the mother and their offspring.
TL;DR: In this paper , the authors used the mean difference in 24-hour potassium excretion between the two groups was used to estimate the quantity of potassium-enriched salt consumed in the intervention group.
Abstract: Background: The SSaSS (Salt Substitute and Stroke Study) recently reported definitive effects of a potassium-enriched salt on cardiovascular outcomes and death. Quantifying the amount of potassium-enriched salt used by trial participants is important for understanding the magnitude of the effect of potassium-enriched salt on risk reduction and how population-wide scale-up might be achieved. Methods: Baseline and annual 24-hour urine samples were collected from subgroups of participants in SSaSS throughout the 5-year follow-up. The mean difference in 24-hour potassium excretion between the 2 groups was used to estimate the quantity of potassium-enriched salt consumed in the intervention group. The corresponding projected difference in sodium intake between groups was calculated and compared with the observed difference. Results: The potassium-enriched salt group, compared to the regular salt group, had a mean increase in 24-hour urinary potassium excretion of 0.80 g/d (95% CI, 0.71–0.90), which equates to consumption of 8.8 g/d (95% CI, 7.8–9.9) of potassium-enriched salt. Based on 8.8 g/d potassium-enriched salt consumption, the projected difference in 24-hour urinary sodium excretion was −0.79 g/d. This compares to an observed difference of −0.35 g/d (95% CI, −0.55 to −0.15) and suggests that 72% of baseline regular salt intake was replaced by potassium-enriched salt. Conclusions: The smaller than anticipated between-group difference in sodium excretion likely results from the joint use of regular salt and potassium-enriched salt in the intervention group. Our findings suggest that even an incomplete replacement of regular salt with potassium-enriched salt can deliver significant health gains. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02092090.
TL;DR: In this article , a review of the pathways potentially involved in the nondipping BP profile in different conditions is presented, including perturbations of the circadian rhythm, the autonomic nervous system, and water and sodium regulation.
Abstract: The nondipping blood pressure (BP) pattern corresponds to a disruption in the circadian BP rhythm with an insufficient decrease in BP levels during nighttime sleep as observed using 24-hour ambulatory BP monitoring. Patients with nondipping BP pattern have poorer renal and cardiovascular outcomes, independent of their average 24-hour BP levels. The pathophysiology of nondipping BP is complex and involves numerous mechanisms: perturbations of (1) the circadian rhythm, (2) the autonomic nervous system, and (3) water and sodium regulation. This review provides an outline of the pathways potentially involved in the nondipping BP profile in different conditions. A recent hypothesis is also discussed involving the role of gut microbiota in the dipping/nondipping patterns, via the fecal diet-derived short chain fatty acids.
TL;DR: In this paper , a de novo assembly of the genome of the spontaneously hypertensive rat, the most widely used model of human cardiovascular disease, was presented. But the assembly was not evaluated with the rat reference gene set, using NCBI automated protocols.
Abstract: We report the creation and evaluation of a de novo assembly of the genome of the spontaneously hypertensive rat, the most widely used model of human cardiovascular disease.The genome is assembled from long read sequencing (PacBio HiFi and continuous long read data [CLR]) and scaffolded with long-range structural information obtained from Bionano optical maps and proximity ligation sequencing proximity analysis of the genome. The genome assembly was polished with Illumina short reads. Completeness of the assembly was investigated using Benchmarking Universal Single Copy Orthologs analysis. The genome assembly was also evaluated with the rat reference gene set, using NCBI automated protocols. We also generated orthogonal single molecule transcript sequence reads (Iso-Seq) from 8 tissues and used them to validate the coding assembly, to annotate the assembly with RNA transcripts representing unique full length transcript isoforms for each gene and to determine whether divergences between RefSeq sequences and the assembly were attributable to assembly errors or polymorphisms.The assembly analysis indicates that this assembly is comparable in contiguity and completeness to the current rat reference assembly, while the use of HiFi sequencing yields an assembly that is more correct at the single base level. Synteny analysis was performed to uncover the extent of synteny and the presence and distribution of chromosomal rearrangements between the reference and this assembly.The resulting genome assembly is reference quality and captures significant structural variation.
TL;DR: In this paper , the authors tested the hypothesis that women who develop gestational hypertension (GH) display abnormal sympathetic action potential (AP) discharge patterns during late pregnancy (32-36 weeks), both at supine rest and during postural stress.
Abstract: Background: We tested the hypothesis that women who develop gestational hypertension (GH) display abnormal sympathetic action potential (AP) discharge patterns during late pregnancy (32–36 weeks), both at supine rest and during postural stress. Methods: Thirteen nonpregnant, female controls (nonpregnant controls [CTRL]) and 32 pregnant women participated; 14 had low-risk (no personal history of GH) normal pregnancies (LR-NP), 10 had high-risk (personal history of GH) normal pregnancies (HR-NP), and 8 developed GH. We measured heart rate, blood pressure, and muscle sympathetic nerve activity (microneurography) at supine rest and 60° head-up tilt. Sympathetic AP patterns were studied using wavelet-based methodology. Results: At rest, muscle sympathetic nerve activity burst frequency was elevated in LR-NP, HR-NP, and GH versus CTRL (all P ≤0.01); however, the AP content per integrated burst was augmented only in GH (20±5 spikes/burst), compared with CTRL (8±3 spikes/burst), LR-NP (9±2 spikes/burst) and HR-NP (11±4 spikes/burst; all P <0.0001). Thus, total AP firing frequency was greater in GH versus each of CTRL, LR-NP, and HR-NP (all P <0.0001). In pregnancy, AP frequency is related directly to systolic (R 2 =46%) and diastolic (R 2 =20%) blood pressure (both P ≤0.01). Unlike CTRL (both P <0.01), women who developed GH were unable to increase within-burst AP firing ( P =0.71) or recruit latent subpopulations of larger-sized APs ( P =0.72) in response to head-up tilt, perhaps related to a ceiling-effect; however, total AP firing frequency in the upright posture was elevated in the GH cohort versus CTRL, LR-NP, and HR-NP (all P <0.05). Conclusions: Women who develop GH display aberrant sympathetic AP firing patterns in both the supine and upright postures.
TL;DR: In this article , the authors investigated mechanisms driving MR gene transcriptional regulation in aging human smooth muscle cells (SMC) by quantifying MR expression in aortic tissue and human aorta.
Abstract: Background: Vascular MR (mineralocorticoid receptor) expression increases with age driving aging-associated vascular stiffness and hypertension. MR has two isoforms (1α and 1β) with distinct 5′-untranslated and promoter sequences (P1 and P2), but the gene regulatory mechanisms remain unknown. We investigated mechanisms driving MR gene transcriptional regulation in aging human smooth muscle cells (SMC). Methods: MR was quantified in aortic tissue and primary human aortic SMC (HASMC) comparing adult and aged donors and adult HASMC treated with H 2 O 2 , to induce aging. Predicted transcription factor (TF) binding sites in the MR gene were validated using chromatin immunoprecipitations and reporter assays. The impact of TF inhibitors on MR isoforms and fibrosis target gene expression was examined. Results: Expression of both MR mRNA isoforms increased with donor age or H 2 O 2 treatment in HASMCs. HIF1α (hypoxia-inducible factor) and the inflammatory TF NFκB (nuclear factor kappa B) both increased with age in HASMCs and are predicted to bind MR promoters. H 2 O 2 induced HIF1α and NFκB expression and DNA binding of HIF1α to the MR P1 promoter and of NFκB to both MR promoters in HASMCs. HIF1α inhibition decreased MR-1α isoform expression while NFκB inhibition decreased both MR isoforms. HIF1α, NFκB, and MR inhibition decreased the expression of a SMC-MR target gene implicated in vascular fibrosis. In human aortic tissues, expression of HIF1α and NFκB each positively correlated with donor age and MR expression ( P <0.0001). Conclusions: These data implicate the inflammatory TF, NFκB, and oxidative stress-induced TF, HIF1α, in regulating SMC MR transcription in aging HASMCs, which drives aging-related vascular stiffness and cardiovascular disease.
TL;DR: In this article , resolvins have beneficial effects in cardiovascular pathologies, but little is known about their effect on cardiovascular damage in hypertension, and they have been shown to protect cardiovascular function and structure when administered before and after the development of hypertension by modifying vascular factors, fibrosis and inflammation.
Abstract: Background: Resolution of inflammation is orchestrated by specialized proresolving lipid mediators (SPMs), and this would be impaired in some cardiovascular diseases. Among SPMs, resolvins (Rv) have beneficial effects in cardiovascular pathologies, but little is known about their effect on cardiovascular damage in hypertension. Methods: Aorta, small mesenteric arteries, heart, and peritoneal macrophages were taken from C57BL/6J mice, infused or not with angiotensin II (AngII; 1.44 mg/kg/day, 14 days) in presence or absence of resolvin D2 (RvD2) (100 ng/mice, every second day) starting 1 day before or 7 days after AngII infusion. Results: Enzymes and receptors involved in SPMs biosynthesis and signaling were increased in aorta or heart from AngII-infused mice. We also observed a differential regulation of SPMs in heart from these mice. Preventive treatment with RvD2 partially avoided AngII-induced hypertension and protected the heart and large and small vessels against functional and structural alterations induced by AngII. RvD2 increased the availability of vasoprotective factors, modified SPMs profile, decreased cardiovascular fibrosis, and increased the infiltration of pro-resolving macrophages. When administered in hypertensive animals with established cardiovascular damage, RvD2 partially improved cardiovascular function and structure, decreased fibrosis, reduced the infiltration of neutrophils, and shifted macrophage phenotype toward a pro-resolving phenotype. Conclusions: There is a disbalance between proinflammatory and resolution mediators in hypertension. RvD2 protects cardiovascular function and structure when administered before and after the development of hypertension by modulating vascular factors, fibrosis and inflammation. Activating resolution mechanisms by treatment with RvD2 may represent a novel therapeutic strategy for the treatment of hypertensive cardiovascular disease.
TL;DR: In this article , a review summarizes the results of the National Heart, Lung, and Blood Institute workshop convened on October 27 to 29, 2021 to assess knowledge gaps and research opportunities in the study of circadian rhythm of blood pressure and chronotherapy for hypertension.
Abstract: Healthy individuals exhibit blood pressure variation over a 24-hour period with higher blood pressure during wakefulness and lower blood pressure during sleep. Loss or disruption of the blood pressure circadian rhythm has been linked to adverse health outcomes, for example, cardiovascular disease, dementia, and chronic kidney disease. However, the current diagnostic and therapeutic approaches lack sufficient attention to the circadian rhythmicity of blood pressure. Sleep patterns, hormone release, eating habits, digestion, body temperature, renal and cardiovascular function, and other important host functions as well as gut microbiota exhibit circadian rhythms, and influence circadian rhythms of blood pressure. Potential benefits of nonpharmacologic interventions such as meal timing, and pharmacologic chronotherapeutic interventions, such as the bedtime administration of antihypertensive medications, have recently been suggested in some studies. However, the mechanisms underlying circadian rhythm-mediated blood pressure regulation and the efficacy of chronotherapy in hypertension remain unclear. This review summarizes the results of the National Heart, Lung, and Blood Institute workshop convened on October 27 to 29, 2021 to assess knowledge gaps and research opportunities in the study of circadian rhythm of blood pressure and chronotherapy for hypertension.
TL;DR: In this article , the association of home and ambulatory BP with cardiovascular prognosis in 1336 practice outpatients with hypertension who underwent both home and ambulance BP measurements in the J-HOP study (Japan Morning Surge-Home Blood Pressure).
Abstract: Background: Although international guidelines for hypertension management recommend home and ambulatory blood pressure (BP) monitoring, few studies have assessed which is more useful in predicting cardiovascular incidence in hypertensive outpatients. Methods: We analyzed the association of home and ambulatory BP with cardiovascular prognosis in 1336 practice outpatients with hypertension who underwent both home and ambulatory BP measurements in the J-HOP study (Japan Morning Surge-Home Blood Pressure). Results: During the median 6.9 years of follow-up, 111 cardiovascular events occurred. Both home and ambulatory systolic BP (SBP) were associated with cardiovascular risk independent of office SBP (hazard ratio [95% CI] per 20 mm Hg of average morning and evening home SBP, 1.46 [1.11–1.93]; 24-hour ambulatory SBP, 1.41 [1.02–1.94]). Moreover, average morning and evening home SBP was also associated with cardiovascular risk even adjusted by 24-hour ambulatory SBP (hazard ratio [95%CI] per 20 mm Hg, 1.38 [1.01–1.87]), but 24-hour ambulatory SBP was not associated with cardiovascular risk adjusted by average morning and evening home SBP. Regarding this relationship, the model-fit was significantly improved by using the analysis of likelihood ratio, but that was not significant in the analysis using C statistics. Additionally, even in patients with well-controlled 24-hour ambulatory BP, uncontrolled morning home BP was associated with cardiovascular risks (hazard ratio [95% CI], 2.15 [1.02–4.50]). In patients with well-controlled average morning and evening home BP, uncontrolled ambulatory BP was not associated with cardiovascular risks. Conclusions: This study demonstrated the prognostic values of home and ambulatory BP in practice hypertensive outpatients. Our findings indicated the modest superiority of home BP compared to ambulatory BP to predict cardiovascular prognosis.
TL;DR: The SPRINT MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension) trial as mentioned in this paper found that participants in the intensive group had a lower incidence rate of probable dementia or mild cognitive impairment than those in the standard group, regardless of DBP quartiles.
Abstract: Background: The potential benefits or harms of intensive systolic blood pressure (BP) control on cognitive function and cerebral blood flow in individuals with low diastolic blood pressure (DBP) remain unclear. Methods: We conducted a post hoc analysis of the SPRINT MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension) that randomly assigned hypertensive participants to an intensive (<120 mm Hg; n=4278) or standard (<140 mm Hg; n=4385) systolic blood pressure target. We evaluated the effects of BP intervention on cognitive outcomes and cerebral blood flow across baseline DBP quartiles. Results: Participants in the intensive group had a lower incidence rate of probable dementia or mild cognitive impairment than those in the standard group, regardless of DBP quartiles. The hazard ratio of intensive versus standard target for probable dementia or mild cognitive impairment was 0.91 (95% CI, 0.73–1.12) in the lowest DBP quartile and 0.70 (95% CI, 0.48–1.02) in the highest DBP quartile, respectively, with an interaction P value of 0.24. Similar results were found for probable dementia (interaction P =0.06) and mild cognitive impairment (interaction P =0.80). The effect of intensive treatment on cerebral blood flow was not modified by baseline DBP either (interaction P =0.25). Even among participants within the lowest DBP quartile, intensive versus standard BP treatment resulted in an increasing trend of annualized change in cerebral blood flow (+0.26 [95% CI, −0.72 to 1.24] mL/[100 g·min]). Conclusions: Intensive BP control did not appear to have a detrimental effect on cognitive outcomes and cerebral perfusion in patients with low baseline DBP. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01206062
TL;DR: In 2019, the World Health Organization (WHO) set sodium benchmarks for packaged foods to guide countries in setting feasible and effective sodium reformulation programs as mentioned in this paper , and the potential impact of Australia's 2020 reformulation targets on the dietary and health impact of full compliance with the WHO's sodium benchmarks in Australia was modeled.
Abstract: In 2021, the World Health Organization (WHO) set sodium benchmarks for packaged foods to guide countries in setting feasible and effective sodium reformulation programs. We modeled the dietary and health impact of full compliance with the WHO's sodium benchmarks in Australia and compared it to the potential impact of Australia's 2020 sodium reformulation targets.We used nationally representative data on food and sodium intake, sodium levels in packaged foods, and food sales volume to estimate sodium intake pre- and post-implementation of the WHO and Australia's sodium benchmarks for 24 age-sex groups. Using comparative risk assessment models, we then estimated the potential deaths, incidence, and disability-adjusted life years averted from cardiovascular disease, chronic kidney disease, and stomach cancer based on the reductions in sodium intake.Compliance with the WHO's sodium benchmarks for packaged foods in Australia could lower mean adult sodium intake by 404 mg/day, corresponding to a 12% reduction. This could prevent about 1770 deaths/year (95% uncertainty interval 1168-2587), corresponding to 3% of all cardiovascular disease, chronic kidney disease, and stomach cancer deaths in Australia, and prevent some 6900 (4603-9513) new cases, and 25 700 (17 655-35 796) disability-adjusted life years/year. Compared with Australian targets, the WHO benchmarks will avert around 3 and a half times more deaths each year (1770 versus 510).Substantially greater health impact could be achieved if the Australian government strengthened its current sodium reformulation program by adopting WHO's more stringent and comprehensive sodium benchmarks.
TL;DR: In this article , the authors used a standard protocol for automated blood pressure measurement combined with impedance cardiography assessment of cardiac output (CO) and total vascular resistance (TPR) in first-trimester normotensive pregnant women.
Abstract: Background: As by definition, mean arterial pressure equals the product of cardiac output (CO) and total vascular resistance (TPR), we hypothesized that, irrespective of thresholds to define hypertension, a CO-TPR imbalance might exist in first-trimester normotensive pregnancies with altered risks for adverse gestational outcomes. Methods: A standard protocol was used for automated blood pressure measurement combined with impedance cardiography assessment of CO and TPR (NICCOMO). First-trimester normotensive pregnant women were categorized into 3 groups relative to the reference 75th percentile (P75) of CO and TPR: (1) normal CO and TPR, (2) high CO, and (3) high TPR. These subgroups were compared at blood pressure thresholds 140/90, 130/85, and 130/80 mmHg. The gestational outcome was categorized after birth according to International Society for Studies of Hypertension in Pregnancy criteria. Results: Compared with pregnancies with normal CO and TPR (≤P75), women with high TPR at blood pressure <140/90 mmHg are at risk for developing gestational hypertension (odds ratio, 3.795 [1.321–10.904]; P <0.010), late-onset preeclampsia (odds ratio, 3.137 [1.060–9.287]; P <0.050), and neonates small for gestational age (odds ratio, 1.780 [1.056–2.998]; P <0.050). Conclusions: Cardiovascular imbalance can present in normotensive women in the first trimester and is associated with increased risks for adverse gestational outcomes. This study illustrates the relevance of CO and TPR assessments as an adjunct to blood pressure measurement and invites for further exploring their value in screening algorithms for gestational hypertensive disorders and/or small for gestational age.
TL;DR: In this article , the authors showed that smooth muscle AT1A receptors exclusively contribute to both medial thickening and adventitial fibrosis regardless of the presence of hypertension in healthy mice.
Abstract: Ang II (angiotensin II) type 1 (AT1) receptors play a critical role in cardiovascular diseases such as hypertension. Rodents have 2 types of AT1 receptor (AT1A and AT1B) of which knock-in Tagln-mediated smooth muscle AT1A silencing attenuated Ang II-induced hypertension. Although vascular remodeling, a significant contributor to organ damage, occurs concurrently with hypertension in Ang II-infused mice, the contribution of smooth muscle AT1A in this process remains unexplored. Accordingly, it is hypothesized that smooth muscle AT1A receptors exclusively contribute to both medial thickening and adventitial fibrosis regardless of the presence of hypertension.About 1 µg/kg per minute Ang II was infused for 2 weeks in 2 distinct AT1A receptor silenced mice, knock-in Tagln-mediated constitutive smooth muscle AT1A receptor silenced mice, and Myh11-mediated inducible smooth muscle AT1A together with global AT1B silenced mice for evaluation of hypertensive cardiovascular remodeling.Medial thickness, adventitial collagen deposition, and immune cell infiltration in aorta were increased in control mice but not in both smooth muscle AT1A receptor silenced mice. Coronary arterial perivascular fibrosis in response to Ang II infusion was also attenuated in both AT1A receptor silenced mice. Ang II-induced cardiac hypertrophy was attenuated in constitutive smooth muscle AT1A receptor silenced mice. However, Ang II-induced cardiac hypertrophy and hypertension were not altered in inducible smooth muscle AT1A receptor silenced mice.Smooth muscle AT1A receptors mediate Ang II-induced vascular remodeling including medial hypertrophy and inflammatory perivascular fibrosis regardless of the presence of hypertension. Our data suggest an independent etiology of blood pressure elevation and hypertensive vascular remodeling in response to Ang II.
TL;DR: In this article , the authors determined the contribution of social determinants of health (SDOH) to the higher proportion of Black adults with uncontrolled blood pressure (BP) compared with white adults.
Abstract: Determining the contribution of social determinants of health (SDOH) to the higher proportion of Black adults with uncontrolled blood pressure (BP) could inform interventions to improve BP control and reduce cardiovascular disease.We analyzed data from 7306 White and 7497 Black US adults taking antihypertensive medication from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study (2003-2007). SDOH were defined using the Healthy People 2030 domains of education, economic stability, social context, neighborhood environment, and health care access. Uncontrolled BP was defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg.Among participants taking antihypertensive medication, 25.4% of White and 33.7% of Black participants had uncontrolled BP. The SDOH included in the current analysis mediated the Black-White difference in uncontrolled BP by 33.0% (95% CI, 22.1%-46.8%). SDOH that contributed to excess uncontrolled BP among Black compared with White adults included low annual household income (percent-mediated 15.8% [95% CI, 10.8%-22.8%]), low education (10.5% [5.6%-15.4%]), living in a health professional shortage area (10.4% [6.5%-14.7%]), disadvantaged neighborhood (11.0% [4.4%-18.0%]), and high-poverty zip code (9.7% [3.8%-15.5%]). Together, the neighborhood-domain accounted for 14.1% (95% CI, 5.9%-22.9%), the health care domain accounted for 12.7% (95% CI, 8.4%-17.3%), and the social-context-domain accounted for 3.8% (95% CI, 1.2%-6.6%) of the excess likelihood of uncontrolled BP among Black compared with White adults, respectively.SDOH including low education, low income, living in a health professional shortage area, disadvantaged neighborhood, and high-poverty zip code contributed to the excess likelihood of uncontrolled BP among Black compared with White adults.
TL;DR: In this paper , the authors investigated whether the average systolic blood pressure (SBP) <130 mm Hg may cause harm in patients with left ventricular hypertrophy (LVH) detected by ECG or echocardiography.
Abstract: Approximately 40% of people with hypertension have left ventricular hypertrophy (LVH) detected by ECG or echocardiography. Because patients with LVH have poor myocardial microcirculation, they may be too sensitive to lowering systolic blood pressure (SBP) too much due to a lack of myocardial perfusion pressure. We aimed to investigate whether the average achieved SBP <130 mm Hg may cause harm in patients with LVH in the Valsartan Antihypertensive Long-Term Use Evaluation trial (VALUE).Of the 15 245 VALUE participants, we identified 13 803 patients without cardiovascular events during the first 6 months after randomization. Of these, 2458 patients had electrocardiographic LVH (ECG-LVH). Cox analyses adjusted for age, gender, and baseline variables compared cardiac and all-cause mortality and other prespecified end points for patients who achieved average SBP 130 to 139 mm Hg (No-LVH group n=4863; ECG-LVH group n=929) and <130 mm Hg (No-LVH group n=2107; ECG-LVH group n=305). Reference groups were patients who achieved average SBP ≥140 mm Hg following the first excluded 6 months (No-LVH group n=4375; ECG-LVH group n=1224).The No-LVH group achieving average SBP <130 mm Hg had a significantly lower incidence of several cardiovascular end points. The ECG-LVH group achieving average SBP <130 mm Hg had higher cardiac mortality (hazard ratio, 1.98 [95% CIs, 1.06-3.70]; P=0.032) and all-cause mortality (hazard ratio, 1.74 [95% CIs, 1.17-2.60]; P=0.007), and SBP <130 mm Hg was not associated with a reduction in any end point.Our findings may be seen as a signal that caution is warranted when treating middle-aged and older patients with electrocardiographic or echocardiographic LVH to SBP <130 mm Hg.
TL;DR: In this article , a review summarizes the existing evidence on women and female-specific risk factors and clinical management of hypertension, to identify critical knowledge gaps relevant to research, clinical practice, and women's heart health awareness.
Abstract: Hypertension is the leading risk factor for cardiovascular disease and premature death among women globally. However, there is a fundamental lack of knowledge regarding the sex-specific pathophysiology of the condition. In addition, risk factors for hypertension and cardiovascular disease unique to women or female sex are insufficiently acknowledged in clinical guidelines. This review summarizes the existing evidence on women and female-specific risk factors and clinical management of hypertension, to identify critical knowledge gaps relevant to research, clinical practice, and women's heart health awareness. Female-specific risk factors relate not only to reproduction, such as the association of gynecological conditions, adverse pregnancy outcomes or menopause with hypertension, but also to the specific roles of women in society and science, such as gender differences in received medical care and the underrepresentation of women in both the science workforce and as participants in research, which contribute to the limited evidence-based, gender- or sex-specific recommendations. A key point is that the development of hypertension starts in young, premenopausal women, often in association with disorders of reproductive organs, and therefore needs to be managed early in life to prevent future cardiovascular disease. Considering the lower blood pressure levels at which cardiovascular disease occurs, thresholds for diagnosis and treatment of hypertension may need to be lower for women.
TL;DR: In this article , the role of integrin CD11b/CD18 in the pathogenesis of hypertension and vascular dysfunction is investigated in mice, and the authors found that targeting integrin may represent a novel therapeutic option for hypertension.
Abstract: Leukocyte adhesion to endothelium is an early inflammatory response and is mainly controlled by the β2-integrins. However, the role of integrin CD11b/CD18 in the pathogenesis of hypertension and vascular dysfunction is unclear.Hypertension was established by angiotensin II (490 ng/kg·per min) or deoxycorticosterone acetate salt. Hypertensive responses were studied in CD11b-deficient (CD11b-/-) mice, bone marrow transplanted and wild-type (WT) mice that were administered anti-CD11b neutralizing antibody or agonist leukadherin-1. Blood pressure was monitored with tail-cuff method and radiotelemetry. Blood and vascular inflammatory cells were assessed by flow cytometry. Aortic remodeling and function were examined using histology and aortic ring analysis. Cell adhesion and migration were evaluated in vitro. The relationship between circulating CD11b+ immune cells and hypertension was analyzed in patients with hypertension.We found that CD11b and CD18 expression as well as the CD45+CD11b+CD18+ myeloid cells were highly increased in the aorta of angiotensin II-infused mice. Ablation or pharmacological inhibition of CD11b in mice significantly alleviated hypertension, aortic remodeling, superoxide generation, vascular dysfunction, and the infiltration of CD11b+ macrophages through reducing macrophage adhesion and migration. These effects were confirmed in WT mice reconstituted with CD11b-deficient bone marrow cells. Conversely, angiotensin II-induced hypertensive response was exacerbated by CD11b agonist leukadherin-1. Notably, circulating CD45+CD11b+CD18+ myeloid cells and the ligand levels in hypertensive patients were significantly higher than in normotensive controls.We demonstrated a critical significance of CD11b+ myeloid cells in hypertension and vascular dysfunction. Targeting CD11b may represent a novel therapeutic option for hypertension.