CD4+ T-Cell Legumain Deficiency Attenuates Hypertensive Damage via Preservation of TRAF6.

BACKGROUND: T cells are central to the immune responses contributing to hypertension. LGMN (legumain) is highly expressed in T cells; however, its role in the pathogenesis of hypertension remains unclear. METHODS: Peripheral blood samples were collected from patients with hypertension, and cluster of differentiation (CD)4+ T cells were sorted for gene expression and Western blotting analysis. TLGMNKO (T cell-specific LGMN-knockout) mice (Lgmnf/f/CD4Cre), regulatory T cell (Treg)-specific LGMN-knockout mice (Lgmnf/f/Foxp3YFP Cre), and RR-11a (LGMN inhibitor)-treated C57BL/6 mice were infused with Ang II (angiotensin II) or deoxycorticosterone acetate/salt to establish hypertensive animal models. Flow cytometry, 4-dimensional label-free proteomics, coimmunoprecipitation, Treg suppression, and in vivo Treg depletion or adoptive transfer were used to delineate the functional importance of T-cell LGMN in hypertension development. RESULTS: LGMN mRNA expression was increased in CD4+ T cells isolated from hypertensive patients and mice, was positively correlated with both systolic and diastolic blood pressure, and was negatively correlated with serum IL (interleukin)-10 levels. TLGMNKO mice exhibited reduced Ang II-induced or deoxycorticosterone acetate/salt-induced hypertension and target organ damage relative to wild-type (WT) mice. Genetic and pharmacological inhibition of LGMN blocked Ang II-induced or deoxycorticosterone acetate/salt-induced immunoinhibitory Treg reduction in the kidneys and blood. Anti-CD25 antibody depletion of Tregs abolished the protective effects against Ang II-induced hypertension in TLGMNKO mice, and LGMN deletion in Tregs prevented Ang II-induced hypertension in mice. Mechanistically, endogenous LGMN impaired Treg differentiation and function by directly interacting with and facilitating the degradation of TRAF6 (tumor necrosis factor receptor-associated factor 6) via chaperone-mediated autophagy, thereby inhibiting NF-κB (nuclear factor kappa B) activation. Adoptive transfer of LGMN-deficient Tregs reversed Ang II-induced hypertension, whereas depletion of TRAF6 in LGMN-deficient Tregs blocked the protective effects. CONCLUSIONS: LGMN deficiency in T cells prevents hypertension and its complications by promoting Treg differentiation and function. Specifically targeting LGMN in Tregs may be an innovative approach for hypertension treatment.

Effects of Sedentary Behavior Reduction on Blood Pressure in Desk Workers: Results From the RESET-BP Randomized Clinical Trial.

BACKGROUND: Sedentary behavior (SB) is observationally associated with cardiovascular disease risk. However, randomized clinical trials testing causation are limited. We hypothesized that reducing SB would decrease blood pressure (BP) and pulse wave velocity (PWV) in sedentary adults. METHODS: This parallel-arm, 3-month randomized clinical trial recruited desk workers, age 18 to 65 years, with systolic BP 120 to 159 or diastolic BP (DBP) 80 to 99 mm Hg, off antihypertensive medications, and reporting <150 min/wk of moderate to vigorous intensity physical activity. Participants were randomized to a SB reduction intervention or a no-contact control group. The intervention sought to replace 2 to 4 h/d of SB with standing and stepping through coaching, a wrist-worn activity prompter, and a sit-stand desk. SB and physical activity were measured with a thigh-worn accelerometer and quantified during all waking hours and separately during work and nonwork times. Clinic-based resting systolic BP (primary outcome) and DBP, 24-hour ambulatory BP, and PWV were assessed by blinded technicians at baseline and 3 months. RESULTS: Participants (n=271) had a mean age of 45 years and systolic BP/DBP 129/83 mm Hg. Compared with controls, intervention participants reduced SB (-1.15±0.17 h/d), increased standing (0.94±0.14 h/d), and increased stepping (5.4±2.4 min/d; all P<0.05). SB and activity changes mainly occurred during work time and were below the goal. The intervention did not reduce BP or PWV in the intervention group compared with controls. Between-group differences in resting systolic BP and DBP changes were -0.22±0.90 (P=0.808) and 0.13±0.61 mm Hg (P=0.827), respectively. The findings were similarly null for ambulatory BP and PWV. Decreases in work-time SB were associated with favorable reductions in resting DBP (r=0.15, P=0.017). Contrary to our hypotheses, reductions in work-time SB (r=-0.19, P=0.006) and increases in work-time standing (r=0.17, P=0.011) were associated with unfavorable increases in carotid-femoral PWV. As expected, increases in nonwork-time standing were favorably associated with carotid-femoral PWV (r=-0.14, P=0.038). CONCLUSIONS: A 3-month intervention that decreased SB and increased standing by ≈1 hour during the work day was not effective for reducing BP. Future directions include examining effects of interventions reducing SB through activity other than work-time standing and clarifying association between standing and PWV in opposite directions for work and nonwork time. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03307343.

Glycemia Reduction in Type 2 Diabetes - Microvascular and Cardiovascular Outcomes.

BACKGROUND: Data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to microvascular and cardiovascular disease outcomes in persons with type 2 diabetes. METHODS: We assessed the comparative effectiveness of four commonly used glucose-lowering medications, added to metformin, in achieving and maintaining a glycated hemoglobin level of less than 7.0% in participants with type 2 diabetes. The randomly assigned therapies were insulin glargine U-100 (hereafter, glargine), glimepiride, liraglutide, and sitagliptin. Prespecified secondary outcomes with respect to microvascular and cardiovascular disease included hypertension and dyslipidemia, confirmed moderately or severely increased albuminuria or an estimated glomerular filtration rate of less than 60 ml per minute per 1.73 m2 of body-surface area, diabetic peripheral neuropathy assessed with the Michigan Neuropathy Screening Instrument, cardiovascular events (major adverse cardiovascular events [MACE], hospitalization for heart failure, or an aggregate outcome of any cardiovascular event), and death. Hazard ratios are presented with 95% confidence limits that are not adjusted for multiple comparisons. RESULTS: During a mean 5.0 years of follow-up in 5047 participants, there were no material differences among the interventions with respect to the development of hypertension or dyslipidemia or with respect to microvascular outcomes; the mean overall rate (i.e., events per 100 participant-years) of moderately increased albuminuria levels was 2.6, of severely increased albuminuria levels 1.1, of renal impairment 2.9, and of diabetic peripheral neuropathy 16.7. The treatment groups did not differ with respect to MACE (overall rate, 1.0), hospitalization for heart failure (0.4), death from cardiovascular causes (0.3), or all deaths (0.6). There were small differences with respect to rates of any cardiovascular disease, with 1.9, 1.9, 1.4, and 2.0 in the glargine, glimepiride, liraglutide, and sitagliptin groups, respectively. When one treatment was compared with the combined results of the other three treatments, the hazard ratios for any cardiovascular disease were 1.1 (95% confidence interval [CI], 0.9 to 1.3) in the glargine group, 1.1 (95% CI, 0.9 to 1.4) in the glimepiride group, 0.7 (95% CI, 0.6 to 0.9) in the liraglutide group, and 1.2 (95% CI, 1.0 to 1.5) in the sitagliptin group. CONCLUSIONS: In participants with type 2 diabetes, the incidences of microvascular complications and death were not materially different among the four treatment groups. The findings indicated possible differences among the groups in the incidence of any cardiovascular disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).

Inhibition of a novel Dickkopf-1-LDL receptor-related proteins 5 and 6 axis prevents diabetic cardiomyopathy in mice.

BACKGROUND AND AIMS: Anti-hypertensive agents are one of the most frequently used drugs worldwide. However, no blood pressure-lowering strategy is superior to placebo with respect to survival in diabetic hypertensive patients. Previous findings show that Wnt co-receptors LDL receptor-related proteins 5 and 6 (LRP5/6) can directly bind to several G protein-coupled receptors (GPCRs). Because angiotensin II type 1 receptor (AT1R) is the most important GPCR in regulating hypertension, this study examines the possible mechanistic association between LRP5/6 and their binding protein Dickkopf-1 (DKK1) and activation of the AT1R and further hypothesizes that the LRP5/6-GPCR interaction may affect hypertension and potentiate cardiac impairment in the setting of diabetes. METHODS: The roles of serum DKK1 and DKK1-LRP5/6 signalling in diabetic injuries were investigated in human and diabetic mice. RESULTS: Blood pressure up-regulation positively correlated with serum DKK1 elevations in humans. Notably, LRP5/6 physically and functionally interacted with AT1R. The loss of membrane LRP5/6 caused by injection of a recombinant DKK1 protein or conditional LRP5/6 deletions resulted in AT1R activation and hypertension, as well as ß-arrestin1 activation and cardiac impairment, possibly because of multiple GPCR alterations. Importantly, unlike commonly used anti-hypertensive agents, administration of the anti-DKK1 neutralizing antibody effectively prevented diabetic cardiac impairment in mice. CONCLUSIONS: These findings establish a novel DKK1-LRP5/6-GPCR pathway in inducing diabetic injuries and may resolve the long-standing conundrum as to why elevated blood DKK1 has deleterious effects. Thus, monitoring and therapeutic elimination of blood DKK1 may be a promising strategy to attenuate diabetic injuries.

Hypothetical 22-Year Intervention With the Dietary Approaches to Stop Hypertension and Risk of Heart Failure in a General Population.

We used design principles of target trial methodology to emulate the effect of sustained adherence to the Dietary Approaches to Stop Hypertension (DASH) diet on the 22-year risk of heart failure. Women and men aged 45-83 years without previous heart failure, who answered questionnaires in 1997 from the Swedish Mammography Cohort and the Cohort of Swedish Men, were eligible. Follow-up questionnaires were sent in 2008-2009. Incidence of heart failure was ascertained using the Swedish Patient Register, updated until December 31, 2019. The parametric g-formula was used to estimate the 22-year risk of heart failure under sustained adherence to a population-adapted DASH diet compared with no intervention. Intakes before 1997 for before-baseline adjustment was available only for women. In total, 31,238 women and 34,939 men were eligible. The 22-year risk of heart failure was 14.5% with long-term adherence to the DASH diet compared with 15.2% with no intervention (risk difference = -0.7%, 95% confidence interval: 1.6, 0.0%) in women and correspondingly in men 15.3% vs. 16.2% (risk difference = -0.9%, 95% confidence interval: -1.6, -0.2%). Our hypothetical intervention suggests that sustained adherence to the population-adapted DASH diet may reduce risk of heart failure in middle-aged and elderly Swedish women and men.

The Melatonin Derivative ITH13001 Prevents Hypertension and Cardiovascular Alterations in Angiotensin II-Infused Mice.

Inflammatory mechanisms and oxidative stress seem to contribute to the pathogenesis of hypertension. ITH13001 is a melatonin-phenyl-acrylate hybrid that moderately induces the antioxidant transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) and has a potent oxidant scavenging effect compared with other derivatives of its family. Here we investigated the effect of ITH13001 on hypertension and the associated cardiovascular alterations. Angiotensin II (AngII)-infused mice were treated with ITH13001 (1 mg/kg per day, i.p.) for 2 weeks. The ITH13001 treatment prevented: 1) the development of hypertension, cardiac hypertrophy, and increased collagen and B-type natriuretic peptide (Bnp) expression in the heart; 2) the reduction of elasticity, incremental distensibility, fenestrae area, intraluminal diameter, and endothelial cell number in mesenteric resistance arteries (MRA); 3) the endothelial dysfunction in aorta and MRA; 4) the plasma and cardiovascular oxidative stress and the reduced aortic nitric oxide (NO) bioavailability; 5) the increased cardiac levels of the cytokines interleukin (IL)-1ß, IL-6, and C-C motif chemokine ligand 2 (Ccl2), the T cell marker cluster of differentiation 3 (Cd3), the inflammasome NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3), the proinflammatory enzymes inducible nitric oxide synthase (iNOS) and COX-2, the toll-like receptor 4 (TLR4) adapter protein myeloid differentiation primary response 88 (MyD88), and the nuclear factor kappa B (NF-κB) subunit p65; 6) the greater aortic expression of the cytokines tumor necrosis factor alpha (Tnf-α), Ccl2 and IL-6, Cd3, iNOS, MyD88, and NLRP3. Although ITH13001 increased nuclear Nrf2 levels and heme oxygenase 1 (HO-1) expression in vascular smooth muscle cells, both cardiac and vascular Nrf2, Ho-1, and NADPH quinone dehydrogenase 1 (Nqo1) levels remained unmodified irrespective of AngII infusion. Summarizing, ITH13001 improved hypertension-associated cardiovascular alterations independently of Nrf2 pathway activation, likely due to its direct antioxidant and anti-inflammatory properties. Therefore, ITH13001 could be a useful therapeutic strategy in patients with resistant hypertension. SIGNIFICANCE STATEMENT: Despite the existing therapeutic arsenal, only half of the patients treated for hypertension have adequately controlled blood pressure; therefore, the search for new compounds to control this pathology and the associated damage to end-target organs (cerebral, cardiac, vascular, renal) is of particular interest. The present study demonstrates that a new melatonin derivative, ITH13001, prevents hypertension development and the associated cardiovascular alterations due to its antioxidant and anti-inflammatory properties, making this compound a potential candidate for treatment of resistant hypertensive patients.

Protective hemodynamics: a novel strategy to manage blood pressure.

PURPOSE OF REVIEW: This editorial aims to highlight the evolving concept of protective hemodynamics in the management of critically ill patients. RECENT FINDINGS: Recent literature underscores the limitations of rigid blood pressure targets, particularly in the context of critical care and perioperative management. High blood pressure targets, especially when coupled with high-dose vasopressors, can lead to poor outcomes. 'Protective hemodynamics' aims to maintain cardiovascular stability while reducing risks associated with interventions. SUMMARY: The implications of adopting protective hemodynamics are profound for both clinical practice and research. Clinically, this approach can reduce iatrogenic harm and improve long-term outcomes for critically ill patients. For research, it opens new avenues for investigating individualized hemodynamic management strategies that prioritize overall patient stability and long-term health over rigid target attainment.

HEARTS in the Americas: Targeting Health System Change to Improve Population Hypertension Control.

PURPOSE OF REVIEW: HEARTS in the Americas is the regional adaptation of Global Hearts, the World Health Organization initiative for cardiovascular disease (CVD) prevention and control. Its overarching goal is to drive health services to change managerial and clinical practice in primary care settings to improve hypertension control and CVD risk management. This review describes the HEARTS in the Americas initiative. First, the regional epidemiological situation of CVD mortality and population hypertension control trends are summarized; then the rationale for its main intervention components: the primary care-oriented management system and the HEARTS Clinical Pathway are described. Finally, the key factors for accelerating the expansion of HEARTS are examined: medicines, team-based care, and a system for monitoring and evaluation. RECENT FINDINGS: Thus far, 33 countries in Latin America and the Caribbean have committed to integrating this program across their primary healthcare network by 2025. The increase in hypertension coverage and control in primary health care settings compared with the traditional model is promising and confirms that the interventions under the HEARTS umbrella are feasible and acceptable to communities, patients, providers, decision-makers, and funders. This review highlights some cases of successful implementation. Scaling up effective treatment for hypertension and optimization of CVD risk management is a pragmatic way to accelerate the reduction of CVD mortality while strengthening primary healthcare systems to respond effectively, with quality, and equitably, to the challenge of non-communicable diseases, not only in low-middle income countries but in all communities globally.

Diet to Stop Hypertension: Should Fats be Included?

PURPOSE OF REVIEW: International guidelines emphasize advice to incorporate dietary measures for the prevention and in the management of hypertension. Current data show that modest reductions in weight can have an impact on blood pressure. Reducing salt and marine oils have also shown consistent benefit in reducing blood pressure. Whether other dietary constituents, in particular the amount and type of fat that play important roles in cardiovascular prevention, influence blood pressure sufficiently to be included in the management of hypertension is less certain. In this review, we provide a summary of the most recent findings, with a focus on dietary patterns, fats and other nutrients and their impact on blood pressure and hypertension. RECENT FINDINGS: Since reducing salt consumption is an established recommendation only corollary dietary advice is subject to the current review. Population studies that have included reliable evaluation of fat intake have indicated almost consistently blood pressure lowering with consumption of marine oils and fats. Results with vegetable oils are inconclusive. However dietary patterns that included total fat reduction and changes in the nature of vegetable fats/oils have suggested beneficial effects on blood pressure. Plant-based foods, dairy foods and yoghurt particularly, may also lower blood pressure irrespective of fat content. Total fat consumption is not directly associated with blood pressure except when it is part of a weight loss diet. Consumption of marine oils has mostly shown moderate blood pressure lowering and possibly greatest effect with docosahexaenoic acid-rich oil.

Angiotensin-(1-7) Treatment Early in Life Prevents Cardiac Hypertrophy in Adult Hypertensive Rats.

ABSTRACT: Angiotensin (Ang)-(1-7) is a cardioprotective peptide of the renin-angiotensin system. Prepuberty has been considered as a later susceptible window of development, and stressful factors in this life phase can induce chronic diseases in adulthood. We aimed to investigate whether the treatment with Ang-(1-7) during the prepuberty could attenuate the development of hypertension and cardiac injury in adult spontaneously hypertensive rats (SHRs). SHRs were treated with Ang-(1-7) (24 µg/kg/h) from age 4 to 7 weeks. Systolic blood pressure was measured by tail-cuff plethysmography up to 17th week. Thereafter, echocardiography was performed, and the rats were euthanized for the collection of tissues and blood. Ang-(1-7) did not change the systolic blood pressure but reduced the septal and posterior wall thickness, and cardiomyocyte hypertrophy and fibrosis in SHR. In addition, Ang-(1-7) reduced the gene expression of atrial natriuretic peptide and brain natriuretic peptide, increased the metalloproteinase 9 expression, and reduced the extracellular signal-regulated kinases 1/2 phosphorylation. Ang-(1-7) also prevented the reduction of Mas receptor but did not change the protein expression of angiotensin-converting enzyme, angiotensin-converting enzyme 2, AT1, and AT2. The treatment with Ang-(1-7) decreased the malondialdehyde (MDA) levels and increased superoxide dismutase-1 and catalase activities and protein expression of catalase. Our findings demonstrate that the treatment of SHR with Ang-(1-7) for 3 weeks early in life promotes beneficial effects in the heart later in life, even without altering blood pressure, through mechanisms involving the reduction of oxidative stress and ERK1/2 phosphorylation. In addition, this study supports the prepuberty as an important programming window.

Effects of the Chinese Heart-Healthy Diet (Sichuan Cuisine Version) on the 10-year CVD risk and vascular age: a randomised controlled feeding trial.

Sichuan cuisine was previously fitted into the Chinese Heart-Healthy Diet (CHH) trial to verify the antihypertensive effect. Whether the modified Sichuan diet lessens cardiovascular disease (CVD) is not fully explored. We aimed to estimate the effects of the Sichuan version of CHH diet (CHH diet-SC) on the 10-year risk of CVD and vascular age. A single-blinded randomised controlled feeding trial was conducted. General CVD prediction model was used in manners of intention-to-treat and per-protocol set. After a 7-d run-in period, fifty-three participants with pre- and grade I hypertension from local communities were randomised and provided with either CHH diet-SC (n 27) or a control diet (n 26) for 4 weeks. Mean absolute and relative estimated CVD risks were reduced by 4·5 % and 27·9 % in the CHH diet-SC group, and the between-group relative risk reduction was 19·5 % (P < 0·001) using linear mixed-effects models. The sensitivity analysis with datasets and models showed consistent results, and pre-specified factors were not associated with the intervention effects. The vascular age of CHH-SC group was theoretically 4·4 years younger than that of the control group after intervention. Compared with a typical diet, adopting the CHH diet-SC over 1 month significantly reduced 10-year CVD risks and vascular ages among local adults with mild hypertension.

The blood pressure control effect of the sodium-restricted dietary approaches to stop hypertension diet: a systematic review.

The Dietary Approaches to Stop Hypertension (DASH) diet is highly effective in controlling blood pressure (BP). Although Na restriction is not a primary focus within the DASH diet, it is recommended that it be added to control BP. Therefore, we aimed to systematically review the characteristics and BP-lowering effects of Na-restricted DASH diet interventions. We searched thirteen databases, namely, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, KoreaMed, KISS, KMbase, RISS, CINAHL, Scopus, ClinicalTrials.gov, Grey Literature Report, OpenGrey and PQDT Global, for articles published through May 2023. The randomised controlled trials assessing the BP-lowering effect of the Na-restricted DASH diet in adults aged 18 years and older were included. The study protocol was registered in the PROSPERO registry (CRD42023409996). The risk of bias in the included studies was also assessed. Nine articles were included in this review. Interventions were categorised into three types: feeding, provision and education, and the study results were compared by intervention type. BP was significantly reduced in two of the three feeding studies, one of the three provisional studies and none of the educational studies. In eight studies, effect sizes varied among both systolic BP (-7·7 to -2·4) and diastolic BP (-8·3 to 0·1). Six studies showed an overall high risk of bias. In conclusion, Na-restricted DASH may have beneficial effects on BP control. Additionally, compared with control interventions, feeding interventions appeared to have a greater BP-lowering effect. Further high-quality studies are needed to improve the quality of the evidence.

The potential impact fraction of population weight reduction scenarios on non-communicable diseases in Belgium: application of the g-computation approach.

BACKGROUND: Overweight is a major risk factor for non-communicable diseases (NCDs) in Europe, affecting almost 60% of all adults. Tackling obesity is therefore a key long-term health challenge and is vital to reduce premature mortality from NCDs. Methodological challenges remain however, to provide actionable evidence on the potential health benefits of population weight reduction interventions. This study aims to use a g-computation approach to assess the impact of hypothetical weight reduction scenarios on NCDs in Belgium in a multi-exposure context. METHODS: Belgian health interview survey data (2008/2013/2018, n = 27 536) were linked to environmental data at the residential address. A g-computation approach was used to evaluate the potential impact fraction (PIF) of population weight reduction scenarios on four NCDs: diabetes, hypertension, cardiovascular disease (CVD), and musculoskeletal (MSK) disease. Four scenarios were considered: 1) a distribution shift where, for each individual with overweight, a counterfactual weight was drawn from the distribution of individuals with a "normal" BMI 2) a one-unit reduction of the BMI of individuals with overweight, 3) a modification of the BMI of individuals with overweight based on a weight loss of 10%, 4) a reduction of the waist circumference (WC) to half of the height among all people with a WC:height ratio greater than 0.5. Regression models were adjusted for socio-demographic, lifestyle, and environmental factors. RESULTS: The first scenario resulted in preventing a proportion of cases ranging from 32.3% for diabetes to 6% for MSK diseases. The second scenario prevented a proportion of cases ranging from 4.5% for diabetes to 0.8% for MSK diseases. The third scenario prevented a proportion of cases, ranging from 13.6% for diabetes to 2.4% for MSK diseases and the fourth scenario prevented a proportion of cases ranging from 36.4% for diabetes to 7.1% for MSK diseases. CONCLUSION: Implementing weight reduction scenarios among individuals with excess weight could lead to a substantial and statistically significant decrease in the prevalence of diabetes, hypertension, cardiovascular disease (CVD), and musculoskeletal (MSK) diseases in Belgium. The g-computation approach to assess PIF of interventions represents a straightforward approach for drawing causal inferences from observational data while providing useful information for policy makers.

Low-Chloride Diet Prevents the Development of Arterial Hypertension and Protects Kidney Function in Angiotensin II-Infused Mice.

INTRODUCTION: A comprehensive pathophysiological mechanism to explain the relationship between high-salt intake and hypertension remains undefined. Evidence suggests that chloride, as the accompanying anion of sodium in dietary salt, is necessary to develop hypertension. We evaluated whether reducing dietary Cl- while keeping a standard Na+ intake modified blood pressure, cardiac hypertrophy, renal function, and vascular contractility after angiotensin II (AngII) infusion. METHODS: C56BL/6J mice fed with standard Cl- diet or a low-Cl- diet (equimolar substitution of Cl- by a mixture of Na+ salts, both diets with standard Na+ content) received AngII (infusion of 1.5 mg/kg/day) or vehicle for 14 days. We measured systolic blood pressure (SBP), glomerular filtration rate (GFR), natriuretic response to acute saline load, and contractility of aortic rings from mice infused with vehicle and AngII, in standard and low-Cl- diet. RESULTS: The mice fed the standard diet presented increased SBP and cardiac hypertrophy after AngII infusion. In contrast, low-Cl- diet prevented the increase of SBP and cardiac hypertrophy. AngII-infused mice fed a standard diet presented hampered natriuretic response to saline load, meanwhile the low-Cl- diet preserved natriuretic response in AngII-infused mice, without change in GFR. Aortic rings from mice fed with standard diet or low-Cl- diet and infused with AngII presented a similar contractile response. CONCLUSION: We conclude that the reduction in dietary Cl- as the accompanying anion of sodium in salt is protective from AngII pro-hypertensive actions due to a beneficial effect on kidney function and preserved natriuresis.

Association between socio-demographic factors, lifestyle, eating habits and hypertension risk among middle-aged and older rural Chinese adults.

BACKGROUND AND AIMS: Hypertension is a global health issue with increasing prevalence. This study aimed to understand the epidemiological characteristics and influencing factors of hypertension in rural Chinese populations and help develop effective prevention and control strategies. METHODS AND RESULTS: This cross-sectional study used database from the Early Diagnosis and Early Treatment Project of Esophageal Cancer conducted in a rural population from September 2012 to December 2017. A total of 10,111 subjects aged 35-75 years residing in Huai'an District, Huai'an City, Jiangsu Province for at least three years were included. Unconditional univariate and multivariate logistic regression models were performed to evaluate the association between socio-demographic information, lifestyle habits, dietary characteristics and the risk of hypertension. The prevalence of hypertension was 34.32 % in this rural population. Men and older individuals are more likely to have hypertension when compared with women and young individuals, respectively. Factors associated with an increased risk of hypertension included: fast eating speed, a high-salt diet (both currently and ten years ago), a high-spicy diet ten years ago, high BMI, poor educational attainment, preference for fatty meats, hot diet, green tea drinking, intake of pickled potherb mustard and corn flour, family smoking and alcohol consumption. Light smoking in males, consumption of fruits, adzuki bean, and pork liver were associated with reduced risk of hypertension. CONCLUSIONS: The study identified some factors, including eat habits and lifestyle, associated with hypertension risk, and highlighted the need for targeted policies and interventions in rural China to address potential risk factors for hypertension.

Effect of ketogenic diet on blood pressure: A GRADE-Assessed systematic review and meta-analysis of randomized controlled trials.

AIMS: Cardiovascular diseases (CVDs) are major causes of mortality around the world. High blood pressure (BP) or hypertension is one of the most significant predisposing factors to CVDs. Ketogenic diets (KDs) have been the center of attention for their possible health benefits. The aim of this analysis is to study the impact of KDs on BP through the existing literature. DATA SYNTHESIS: We investigated the impact of KDs on systolic and diastolic blood pressures (SBP and DBP) conducted in the format of randomized controlled trials (RCTs). Four online databases (PubMed/Medline, SCOPUS, Cochrane Library, and Google Scholar) were searched from inception up to November 2022. Subgroup analyses were carried out to find the sources of heterogeneities. Twenty-three RCTs with 1664 participants were identified. KDs did not exert any significant impacts on SBP (WMD: -0.87 mmHg, 95% CI: -2.05, 0.31) nor DBP (WMD: -0.11 mmHg, 95% CI -1.14, 0.93). Subgroup analyses did not reveal any further information. Also, non-linear dose-response analysis could not detect any associations between the percentage of calorie intake from fat in the KD format and BP levels. CONCLUSION: KDs do not seem to be effective in improving BP. Nonetheless, further investigations are recommended to examine the proportion of fat intake needed to induce favorable clinical impacts.

Interplay of the Mediterranean diet and genetic hypertension risk on blood pressure in European adolescents: Findings from the HELENA study.

Early-life onset of high blood pressure is associated with the development of cardiovascular diseases in adulthood. In adolescents, limited evidence exists regarding the association between adherence to the Mediterranean Diet (MedDiet) and normal blood pressure (BP) levels, as well as its potential to modulate genetic predisposition to HTN. This study investigated the interaction between a MedDiet score and a recently developed HTN-genetic risk score (HTN-GRS) on blood pressure levels in a European adolescent cohort. The MedDiet score was derived from two non-consecutive 24-h dietary recalls and ranged from 0 (indicating low adherence) to 9 (indicating high adherence). Multiple linear regression models, adjusted for covariates, were employed to examine the relationship between the MedDiet score and BP z-scores and to assess the interaction effects between the MedDiet score and HTN-GRS on BP z-scores. MedDiet score showed a negative association with z-systolic BP (SBP) (ß = -0.40, p < 0.001) and z-diastolic BP (DBP) (ß = -0.29, p = 0.001). Additionally, a significant interaction effect was identified between the MedDiet score and HTN-GRS on z-SBP (ß = 0.02, p < 0.001) and z-DBP (ß = 0.02, p < 0.001). The modulatory effect of the MedDiet was more pronounced in females than in males, and HTN-GRS exhibited a stronger influence on DBP than on SBP.   Conclusion: The study suggests that higher adherence to the MedDiet is associated with reduced BP levels in adolescents and provides evidence of a genetic-diet interaction influencing BP in adolescents. What is Known: • Adherence to the Mediterranean diet may reduce BP levels. What is New: • It is the first study to assess the connection between adherence to a Mediterranean diet, a hypertension genetic risk score, and how they interact in influencing blood pressure. • It is conducted within a multicenter cohort of European adolescents.

Effect of soy isoflavone supplementation on blood pressure: a meta-analysis of randomized controlled trials.

BACKGROUND: Previous experimental studies have suggested that the consumption of soy isoflavones may have a potential impact on lowering blood pressure. Nevertheless, epidemiological studies have presented conflicting outcomes concerning the correlation between soy isoflavone consumption and blood pressure levels. Consequently, a comprehensive meta-analysis of all eligible randomized controlled trials (RCTs) was conducted to explore the influence of soy isoflavones on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults. METHODS: A thorough search of PubMed, Embase, and the Cochrane Library for relevant literature up to April 30, 2023 was conducted. RCTs involving adults that compared soy isoflavone supplementation with a placebo (the same matrix devoid of soy isoflavone) were included. The combined effect size was presented as the weighted mean difference (WMD) along with 95% confidence interval (CI), employing a fixed-effects model. RESULTS: Our meta-analysis included a total of 24 studies involving 1945 participants. The results revealed a significant reduction in both SBP and DBP with soy isoflavone supplementation. Subgroup analyses suggested more pronounced reductions in SBP and DBP for interventions lasting ≥6 months, in individuals receiving mixed-type soy isoflavone, and among patients with metabolic syndrome or prehypertension. However, we did not detect significant nonlinear associations between supplementation dosage and intervention duration concerning both SBP and DBP. The overall quality of evidence was deemed moderate. CONCLUSIONS: The current meta-analysis revealed that supplementation with soy isoflavones alone effectively reduces blood pressure. Additional high-quality studies are required to investigate the efficacy of blood pressure reduction through supplementation with an optimal quantity and proportion of soy isoflavone.

The dietary approaches to stop hypertension (DASH) dietary pattern in childhood in relation to cardiometabolic risk in adolescence and early adulthood in the ALSPAC birth cohort.

OBJECTIVE: To investigate the relationship between the dietary approaches to stop hypertension (DASH)-style dietary patterns in childhood and cardiometabolic risk (CMR) in adolescence/early adulthood. DESIGN: Data were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort. Diet diary data collected at 7, 10 and 13 years were used to calculate DASH-style diet scores (DDS). Multivariable linear regression models were used to investigate the associations between the DDS at 7, 10 and 13 years and CMR scores, calculated at 17 and 24 years. SETTING: The ALSPAC cohort included children born in south-west England in 1991-1992. PARTICIPANTS: Children with complete dietary, covariate and cardiometabolic data at 17 (n 1,526) and 24 years (n 1,524). RESULTS: A higher DDS at 7 and 10 years was negatively associated with CMR scores at 17 years (ß = -0·64 (95 % CI -1·27, -0·006), Ptrend=0·027 for fifth v. first DDS quintile at 7 years; ß = -0·73 (95 % CI -1·35, -0·12) and Ptrend=0·037 for fifth v. first DDS quintile at 10 years) and at 24 years (ß = -0·92 (95 % CI -1·49, -0·34) Ptrend = 0·001 for fifth v. first DDS quintile at 7 years; ß = -0·60 (95 % CI -1·20, -0·05) Ptrend = 0·092 for fifth v. first DDS quintile at 10 years). No associations were found between the DDS at 13 years and CMR score at 17 and 24 years. CONCLUSION: Greater adherence with a DASH-style diet during childhood was associated with better cardiometabolic health in adolescence/adulthood in the ALSPAC cohort. The components of the DASH diet could be recommended to improve children's cardiometabolic health.

Association between joint physical activity and healthy dietary patterns and hypertension in US adults: cross-sectional NHANES study.

BACKGROUND: Lack of physical activity (PA), poor dietary habits, or other unhealthy lifestyle behaviors are potential modifiable risk factors for hypertension. It has been sufficiently demonstrated in previous studies that physical activity or healthy dietary patterns can reduce the risk of hypertension. However, no research focused on the joint effects of PA and healthy dietary patterns on hypertension in a representative sample of adults. METHODS: We used data collected from the 2007-2018 National Health and Nutrition Examination Survey. Healthy dietary patterns were assessed with the Healthy Eating Index 2015 (HEI-2015), and PA was measured using the metabolic equivalent minutes per week reported in questionnaires. We created four lifestyle categories based on the HEI-2015 and PA: (1) unhealthy diet and physically inactive (less than recommended PA), (2) healthy diet but physically inactive, (3) unhealthy diet but physically active (recommended PA), (4) healthy diet and physically active. Logistic regression was used to evaluate the association between joint PA and HEI-2015 and hypertension. RESULTS: A total of 24,453 participants were enrolled in the study. Compared with unhealthy diet and physically inactive individuals, only healthy diet and physically active participants (adjusted odds ratio [AOR]: 0.77, 95% CI 0.65-0.9) were negatively associated with hypertension, while healthy diet but physically inactive participants (AOR: 0.89, 95% CI 0.76-1.03) and unhealthy diet but physically active participants (AOR: 0.9, 95% CI 0.76-1.06) were not associated with hypertension. CONCLUSION: In a representative sample of US adults, our findings suggest that individuals with recommended PA and healthy dietary patterns have a lower risk of hypertension than those with an unhealthy diet or less than recommended PA. Healthy eating habits and regular PA are potential preventive precautions against hypertension.