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Advances in Nutrition (Bethesda, Md.) Sep 2020The Dietary Approaches to Stop Hypertension (DASH) diet is recognized as an effective dietary intervention to reduce blood pressure (BP). However, among randomized... (Meta-Analysis)
Meta-Analysis
Dietary Approaches to Stop Hypertension (DASH) Diet and Blood Pressure Reduction in Adults with and without Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
The Dietary Approaches to Stop Hypertension (DASH) diet is recognized as an effective dietary intervention to reduce blood pressure (BP). However, among randomized controlled trials (RCTs) investigating the DASH diet-mediated BP reduction, there are significant methodological and clinical differences. The purpose of this study was to comprehensively assess the DASH diet effect on BP in adults with and without hypertension, accounting for underlying methodological and clinical confounders. We systematically searched Medline and the Cochrane Collaboration Library databases and identified 30 RCTs (n = 5545 participants) that investigated the BP effects of the DASH diet compared with a control diet in hypertensive and nonhypertensive adults. Both random-effects and fixed-effect models were used to calculate the mean attained systolic BP (SBP) and diastolic BP (DBP) differences during follow-up. Subgroup and meta-regression analyses were also conducted. Compared with a control diet, the DASH diet reduced both SBP and DBP (difference in means: -3.2 mm Hg; 95% CI: -4.2, -2.3 mm Hg; P < 0.001, and -2.5 mm Hg; 95% CI: -3.5, -1.5 mm Hg; P < 0.001, respectively). Hypertension status did not modify the effect on BP reduction. The DASH diet compared with a control diet reduced SBP levels to a higher extent in trials with sodium intake >2400 mg/d than in trials with sodium intake ≤2400 mg/d, whereas both SBP and DBP were reduced more in trials with mean age <50 y than in trials of older participants. The quality of evidence was rated as moderate for both outcomes according to the Grading of Recommendations, Assessment, Development, and Evaluation approach. The adoption of the DASH diet was accompanied by significant BP reduction in adults with and without hypertension, although higher daily sodium intake and younger age enhanced the BP-lowering effect of the intervention. This meta-analysis was registered at www.crd.york.ac.uk/prospero as CRD42019128120.
Topics: Adult; Blood Pressure; Diet, Sodium-Restricted; Dietary Approaches To Stop Hypertension; Humans; Hypertension; Randomized Controlled Trials as Topic
PubMed: 32330233
DOI: 10.1093/advances/nmaa041 -
BMJ (Clinical Research Ed.) Aug 2016To systematically review studies quantifying the associations of long term (clinic), mid-term (home), and short term (ambulatory) variability in blood pressure,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review studies quantifying the associations of long term (clinic), mid-term (home), and short term (ambulatory) variability in blood pressure, independent of mean blood pressure, with cardiovascular disease events and mortality.
DATA SOURCES
Medline, Embase, Cinahl, and Web of Science, searched to 15 February 2016 for full text articles in English.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Prospective cohort studies or clinical trials in adults, except those in patients receiving haemodialysis, where the condition may directly impact blood pressure variability. Standardised hazard ratios were extracted and, if there was little risk of confounding, combined using random effects meta-analysis in main analyses. Outcomes included all cause and cardiovascular disease mortality and cardiovascular disease events. Measures of variability included standard deviation, coefficient of variation, variation independent of mean, and average real variability, but not night dipping or day-night variation.
RESULTS
41 papers representing 19 observational cohort studies and 17 clinical trial cohorts, comprising 46 separate analyses were identified. Long term variability in blood pressure was studied in 24 papers, mid-term in four, and short-term in 15 (two studied both long term and short term variability). Results from 23 analyses were excluded from main analyses owing to high risks of confounding. Increased long term variability in systolic blood pressure was associated with risk of all cause mortality (hazard ratio 1.15, 95% confidence interval 1.09 to 1.22), cardiovascular disease mortality (1.18, 1.09 to 1.28), cardiovascular disease events (1.18, 1.07 to 1.30), coronary heart disease (1.10, 1.04 to 1.16), and stroke (1.15, 1.04 to 1.27). Increased mid-term and short term variability in daytime systolic blood pressure were also associated with all cause mortality (1.15, 1.06 to 1.26 and 1.10, 1.04 to 1.16, respectively).
CONCLUSIONS
Long term variability in blood pressure is associated with cardiovascular and mortality outcomes, over and above the effect of mean blood pressure. Associations are similar in magnitude to those of cholesterol measures with cardiovascular disease. Limited data for mid-term and short term variability showed similar associations. Future work should focus on the clinical implications of assessment of variability in blood pressure and avoid the common confounding pitfalls observed to date.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42014015695.
Topics: Blood Pressure; Blood Pressure Determination; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Cause of Death; Humans
PubMed: 27511067
DOI: 10.1136/bmj.i4098 -
Journal of the American Heart... Dec 2020Background Although exercise training reduces office blood pressure (BP), scarcer evidence is available on whether these benefits also apply to ambulatory blood pressure... (Meta-Analysis)
Meta-Analysis
Background Although exercise training reduces office blood pressure (BP), scarcer evidence is available on whether these benefits also apply to ambulatory blood pressure (ABP), which is a stronger predictor of cardiovascular disease and mortality. The present study aims to assess the effects of exercise training on ABP in patients with hypertension based on evidence from randomized controlled trials. Methods and Results A systematic search of randomized controlled trials on the aforementioned topic was conducted in PubMed and Scopus (since inception to April 1, 2020). The mean difference between interventions (along with 95% CI) for systolic BP and diastolic BP was assessed using a random-effects model. Sub-analyses were performed attending to (1) whether participants were taking antihypertensive drugs and (2) exercise modalities. Fifteen studies (including 910 participants with hypertension) met the inclusion criteria. Interventions lasted 8 to 24 weeks (3-5 sessions/week). Exercise significantly reduced 24-hour (systolic BP, -5.4 mm Hg; [95% CI, -9.2 to -1.6]; diastolic BP, -3.0 mm Hg [-5.4 to -0.6]), daytime (systolic BP, -4.5 mm Hg [-6.6 to -2.3]; diastolic BP, -3.2 mm Hg [-4.8 to -1.5]), and nighttime ABP (systolic BP, -4.7 mm Hg [-8.4 to -1.0]; diastolic BP, -3.1 mm Hg [-5.3 to -0.9]). In separate analyses, exercise benefits on all ABP measures were significant for patients taking medication (all <0.05) but not for untreated patients (although differences between medicated and non-medicated patients were not significant), and only aerobic exercise provided significant benefits (<0.05). Conclusions Aerobic exercise is an effective coadjuvant treatment for reducing ABP in medicated patients with hypertension.
Topics: Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Exercise; Female; Heart Disease Risk Factors; Humans; Hypertension; Male; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 33280503
DOI: 10.1161/JAHA.120.018487 -
Current Hypertension Reports Apr 2023Hypertension is the primary risk factor for cardiovascular disease and adequate blood pressure control is often elusive. The objective of this work was to conduct a... (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
Hypertension is the primary risk factor for cardiovascular disease and adequate blood pressure control is often elusive. The objective of this work was to conduct a meta-analysis of trial data of isometric resistance training (IRT) studies in people with hypertension, to establish if IRT produced an anti-hypertensive effect. A database search (PubMed, CINAHL, Cochrane Central Register of Controlled Trials, and MEDLINE) identified randomised controlled and crossover trials of IRT versus a sedentary or sham control group in adults with hypertension.
RECENT FINDINGS
We included 12 studies (14 intervention groups) in the meta-analyses, with an aggregate of 415 participants. IRT reduced systolic blood pressure (SBP), mean difference (MD) - 7.47 mmHg (95%CI - 10.10, - 4.84), P < 0.01; diastolic blood pressure (DBP) MD - 3.17 mmHg (95%CI - 5.29, - 1.04), P < 0.01; and mean arterial blood pressure (MAP) MD - 7.19 mmHg (95%CI - 9.06, - 5.32), P < 0.0001. Office pulse pressure and resting heart rate was not significantly reduced, neither were 24-h or day-time ambulatory blood pressures (SBP, DBP). Night-time blood pressures, however, were significantly reduced with SBP MD - 4.28 mmHg (95%CI - 7.88, - 0.67), P = 0.02, and DBP MD - 2.22 mmHg (95%CI - 3.55, - 0.88), P < 0.01. IRT does lower SBP, DBP and MAP office and night-time ambulatory SBP and DBP, but not 24-h mean ambulatory blood pressures in people with hypertension.
Topics: Adult; Humans; Hypertension; Resistance Training; Blood Pressure; Cardiovascular Diseases; Hypotension
PubMed: 36853479
DOI: 10.1007/s11906-023-01232-w -
Atherosclerosis Feb 2017Epidemiological evidence suggests an association between consumption of tomato products or lycopene and lower risk for cardiovascular diseases (CVD). Our aim was to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Epidemiological evidence suggests an association between consumption of tomato products or lycopene and lower risk for cardiovascular diseases (CVD). Our aim was to evaluate the state of the evidence from intervention trials on the effect of consuming tomato products and lycopene on markers of cardiovascular (CV) function. We undertook a systematic review and meta-analysis on the effect of supplementing tomato and lycopene on CV risk factors.
METHODS
Three databases including Medline, Web of science, and Scopus were searched from inception to August 2016. Inclusion criteria were: intervention trials reporting effects of tomato products and lycopene supplementation on CV risk factors among adult subjects >18 years of age. The outcomes of interest included blood lipids (total-, HDL-, LDL-cholesterol, triglycerides, oxidised-LDL), endothelial function (flow-mediated dilation (FMD), pulse wave velocity (PWV)) and blood pressure (BP) inflammatory factors (CRP, IL-6) and adhesion molecules (ICAM-1). Random-effects models were used to determine the pooled effect sizes.
RESULTS
Out of 1189 publications identified, 21 fulfilled inclusion criteria and were meta-analysed. Overall, interventions supplementing tomato were associated with significant reductions in LDL-cholesterol (-0.22 mmol/L; p = 0.006), IL-6 (standardised mean difference -0.25; p = 0.03), and improvements in FMD (2.53%; p = 0.01); while lycopene supplementation reduced systolic-BP (-5.66 mmHg; p = 0.002). No other outcome was significantly affected by these interventions.
CONCLUSIONS
The available evidence on the effects of tomato products and lycopene supplementation on CV risk factors supports the view that increasing the intake of these has positive effects on blood lipids, blood pressure and endothelial function. These results support the development of promising individualised nutritional strategies involving tomatoes to tackle CVD.
Topics: Adult; Biomarkers; Blood Pressure; Cardiovascular Diseases; Carotenoids; Chi-Square Distribution; Diet, Healthy; Dietary Supplements; Endothelium, Vascular; Female; Health Status; Humans; Inflammation Mediators; Lipids; Lycopene; Solanum lycopersicum; Male; Middle Aged; Odds Ratio; Prognosis; Protective Factors; Risk Assessment; Risk Factors; Young Adult
PubMed: 28129549
DOI: 10.1016/j.atherosclerosis.2017.01.009 -
The Cochrane Database of Systematic... Feb 2021Increased physical activity has been recommended as an important lifestyle modification for the prevention and control of hypertension. Walking is a low-cost form of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increased physical activity has been recommended as an important lifestyle modification for the prevention and control of hypertension. Walking is a low-cost form of physical activity and one which most people can do. Studies testing the effect of walking on blood pressure have revealed inconsistent findings.
OBJECTIVES
To determine the effect of walking as a physical activity intervention on blood pressure and heart rate.
SEARCH METHODS
We searched the following databases up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 2), Ovid MEDLINE, Ovid Embase, CINAHL, PsycINFO, SPORTDiscus, PEDro, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the following Chinese databases up to May 2020: Index to Taiwan Periodical Literature System; National Digital Library of Theses and Dissertation in Taiwan; China National Knowledge Infrastructure (CNKI) Journals, Theses & Dissertations; and Wanfang Medical Online. We contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
SELECTION CRITERIA
Randomised controlled trials of participants, aged 16 years and over, which evaluated the effects of a walking intervention compared to non-intervention control on blood pressure and heart rate were included.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Where data were not available in the published reports, we contacted authors. Pooled results for blood pressure and heart rate were presented as mean differences (MDs) between groups with 95% confidence intervals (CIs). We undertook subgroup analyses for age and sex. We undertook sensitivity analyses to assess the effect of sample size on our findings.
MAIN RESULTS
A total of 73 trials met our inclusion criteria. These 73 trials included 5763 participants and were undertaken in 22 countries. Participants were aged from 16 to 84 years and there were approximately 1.5 times as many females as males. The characteristics of walking interventions in the included studies were as follows: the majority of walking interventions was at home/community (n = 50) but supervised (n = 36 out of 47 reported the information of supervision); the average intervention length was 15 weeks, average walking time per week was 153 minutes and the majority of walking intensity was moderate. Many studies were at risk of selection bias and performance bias. Primary outcome We found moderate-certainty evidence suggesting that walking reduces systolic blood pressure (SBP) (MD -4.11 mmHg, 95% CI -5.22 to -3.01; 73 studies, n = 5060). We found moderate-certainty evidence suggesting that walking reduces SBP in participants aged 40 years and under (MD -4.41 mmHg, 95% CI -6.17 to -2.65; 14 studies, n = 491), and low-certainty evidence that walking reduces SBP in participants aged 41 to 60 years (MD -3.79 mmHg, 95% CI -5.64 to -1.94, P < 0.001; 35 studies, n = 1959), and those aged 60 years of over (MD -4.30 mmHg, 95% CI -6.17 to -2.44, 24 studies, n = 2610). We also found low certainty-evidence suggesting that walking reduces SBP in both females (MD -5.65 mmHg, 95% CI -7.89 to -3.41; 22 studies, n = 1149) and males (MD -4.64 mmHg, 95% CI -8.69 to -0.59; 6 studies, n = 203). Secondary outcomes We found low-certainty evidence suggesting that walking reduces diastolic blood pressure (DBP) (MD -1.79 mmHg, 95% CI -2.51 to -1.07; 69 studies, n = 4711) and heart rate (MD -2.76 beats per minute (bpm), 95% CI -4.57 to -0.95; 26 studies, n = 1747). We found moderate-certainty evidence suggesting that walking reduces DBP for participants aged 40 years and under (MD -3.01 mmHg, 95% CI -4.44 to -1.58; 14 studies, n = 491) and low-certainty evidence suggesting that walking reduces DBP for participants aged 41 to 60 years (MD -1.74 mmHg, 95% CI -2.95 to -0.52; 32 studies, n = 1730) and those aged 60 years and over (MD -1.33 mmHg, 95% CI -2.40 to -0.26; 23 studies, n = 2490). We found moderate-certainty evidence that suggests walking reduces DBP for males (MD -2.54 mmHg, 95% CI -4.84 to -0.24; 6 studies, n = 203) and low-certainty evidence that walking reduces DBP for females (MD -2.69 mmHg, 95% CI -4.16 to -1.23; 20 studies, n = 1000). Only 21 included studies reported adverse events. Of these 21 studies, 16 reported no adverse events, the remaining five studies reported eight adverse events, with knee injury being reported five times.
AUTHORS' CONCLUSIONS
Moderate-certainty evidence suggests that walking probably reduces SBP. Moderate- or low-certainty evidence suggests that walking may reduce SBP for all ages and both sexes. Low-certainty evidence suggests that walking may reduce DBP and heart rate. Moderate- and low-certainty evidence suggests walking may reduce DBP and heart rate for all ages and both sexes.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Bias; Blood Pressure; Diastole; Female; Heart Rate; Humans; Hypertension; Knee Injuries; Male; Middle Aged; Randomized Controlled Trials as Topic; Systole; Time Factors; Walking; Young Adult
PubMed: 33630309
DOI: 10.1002/14651858.CD008823.pub2 -
Advances in Nutrition (Bethesda, Md.) Jan 2016Hypertension is a major risk factor for developing cardiovascular disease, stroke, and kidney disease. To lower blood pressure (BP), several lifestyle changes are... (Meta-Analysis)
Meta-Analysis Review
Hypertension is a major risk factor for developing cardiovascular disease, stroke, and kidney disease. To lower blood pressure (BP), several lifestyle changes are recommended such as weight loss, exercise, and following a healthy diet. Investigating the effect of single nutrients may have positive results, but food is consumed as part of a whole diet, resulting in nutrient interactions. The aim of this systematic review and meta-analysis was to assess the effect of dietary patterns on BP in adults. Studies that were published between January 1999 and June 2014 were retrieved using Scopus, Web of Science, and the MEDLINE database. Seventeen randomized controlled trials were included in the meta-analysis. The results suggest that healthy dietary patterns such as the Dietary Approaches to Stop Hypertension diet, Nordic diet, and Mediterranean diet significantly lowered systolic BP and diastolic BP by 4.26 mm Hg and 2.38 mm Hg, respectively. These diets are rich in fruit, vegetables, whole grains, legumes, seeds, nuts, fish, and dairy and low in meat, sweets, and alcohol. Lifestyle factors such as exercise and weight loss in combination with dietary changes may also reduce BP. Further research is needed to establish the effect of dietary patterns on BP in different cultures other than those identified in this review. The review was registered on PROSPERO (International prospective register of systematic reviews) as CRD42015016272.
Topics: Adult; Blood Pressure; Diet; Feeding Behavior; Health Behavior; Humans; Hypertension; Life Style
PubMed: 26773016
DOI: 10.3945/an.115.009753 -
Nutrients Jul 2023The aim of this study was to assess the effect of the level of adherence to the DASH diet on hypertension risk by conducting a systematic review and meta-analysis. A... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to assess the effect of the level of adherence to the DASH diet on hypertension risk by conducting a systematic review and meta-analysis. A systematic literature search was performed. Two independent investigators performed the study selection, data abstraction, and assessment of the included studies. The meta-analysis was performed separately with the adjusted hazard (HR) or incident rate ratios (IRR) and the odds ratios (OR) of the highest compared to the lowest DASH diet adherence scores using a random effects model. A total of 12 studies were included in the qualitative and quantitative synthesis. When cohort studies reporting HR were pooled together, high adherence to the DASH diet was associated with a lower risk of hypertension (HR: 0.81, 95% CI 0.73-0.90, = 69%, PI 0.61-1.08) compared to the low adherence. When cross-sectional studies reporting OR were combined, high adherence to the DASH diet was also related to a lower risk of hypertension (OR: 0.80, 95% CI 0.70-0.91, = 81%, PI 0.46-1.39). The findings suggest that high adherence to the DASH diet has a positive effect on reducing hypertension risk compared to low adherence. These data strengthen and are in line with all hypertension guidelines, indicating that lifestyle changes should start early even in populations with normal blood pressure.
Topics: Humans; Dietary Approaches To Stop Hypertension; Cross-Sectional Studies; Hypertension; Blood Pressure; Cohort Studies; Diet
PubMed: 37513679
DOI: 10.3390/nu15143261 -
Journal of Medical Internet Research May 2021Adherence rates of preventative medication for cardiovascular disease (CVD) have been reported as 57%, and approximately 9% of all CVD events in Europe are attributable... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Adherence rates of preventative medication for cardiovascular disease (CVD) have been reported as 57%, and approximately 9% of all CVD events in Europe are attributable to poor medication adherence. Mobile health technologies, particularly mobile apps, have the potential to improve medication adherence and clinical outcomes.
OBJECTIVE
The objective of this study is to assess the effects of mobile health care apps on medication adherence and health-related outcomes in patients with CVD. This study also evaluates apps' functionality and usability and the involvement of health care professionals in their use.
METHODS
Electronic databases (MEDLINE [Ovid], PubMed Central, Cochrane Library, CINAHL Plus, PsycINFO [Ovid], Embase [Ovid], and Google Scholar) were searched for randomized controlled trials (RCTs) to investigate app-based interventions aimed at improving medication adherence in patients with CVD. RCTs published in English from inception to January 2020 were reviewed. The Cochrane risk of bias tool was used to assess the included studies. Meta-analysis was performed for clinical outcomes and medication adherence, with meta-regression analysis used to evaluate the impact of app intervention duration on medication adherence.
RESULTS
This study included 16 RCTs published within the last 6 years. In total, 12 RCTs reported medication adherence as the primary outcome, which is the most commonly self-reported adherence. The duration of the interventions ranged from 1 to 12 months, and sample sizes ranged from 24 to 412. Medication adherence rates showed statistically significant improvements in 9 RCTs when compared with the control, and meta-analysis of the 6 RCTs reporting continuous data showed a significant overall effect in favor of the app intervention (mean difference 0.90, 95% CI 0.03-1.78) with a high statistical heterogeneity (I=93.32%). Moreover, 9 RCTs assessed clinical outcomes and reported an improvement in systolic blood pressure, diastolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol levels in the intervention arm. Meta-analysis of these clinical outcomes from 6 RCTs favored app interventions, but none were significant. In the 7 trials evaluating app usability, all were found to be acceptable. There was a great variation in the app characteristics. A total of 10 RCTs involved health care professionals, mainly physicians and nurses, in the app-based interventions. The apps had mixed functionality: 2 used education, 7 delivered reminders, and 7 provided reminders in combination with educational support.
CONCLUSIONS
Apps tended to increase medication adherence, but interventions varied widely in design, content, and delivery. Apps have an acceptable degree of usability; yet the app characteristics conferring usability and effectiveness are ill-defined. Future large-scale studies should focus on identifying the essential active components of successful apps.
TRIAL REGISTRATION
PROSPERO International Prospective Register of Systematic Reviews CRD42019121385; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=121385.
Topics: Blood Pressure; Cardiovascular Diseases; Humans; Medication Adherence; Mobile Applications; Telemedicine
PubMed: 34032583
DOI: 10.2196/24190 -
Scientific Reports Jan 2023Cardiovascular diseases are the leading cause of death in the world and arterial hypertension (AH) accounts for 13.8% of deaths caused by cardiovascular diseases.... (Meta-Analysis)
Meta-Analysis
Cardiovascular diseases are the leading cause of death in the world and arterial hypertension (AH) accounts for 13.8% of deaths caused by cardiovascular diseases. Strength training interventions could be an important alternative tool for blood pressure control, however, consistent evidence and the most effective training protocol for this purpose are yet to be established. The current study used the Cochrane methodology to systematically review randomized controlled trials (RCTs) that investigated the effect of strength training on blood pressure in hypertensive patients. A systematic search was conducted in the PubMed, EMBASE, Scopus, Cochrane Library, and World Health Organization databases. This review included controlled trials that evaluated the effect of strength training for 8 weeks or more in adults with arterial hypertension, published up to December 2020. Data are described and reported as the weighted mean difference of systolic and diastolic pressure and a 95% confidence interval. Protocol registration: PROSPERO registration number CRD42020151269. A total of 14 studies were identified, including a combined total of 253 participants with hypertension. The meta-analysis showed that mean values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly after strength training interventions. The strongest effect of strength training on decreasing blood pressure was observed in protocols with a moderate to vigorous load intensity (> 60% of one-repetition maximum-1RM), a frequency of at least 2 times per week, and a minimum duration of 8 weeks. We concluded that strength training interventions can be used as a non-drug treatment for arterial hypertension, as they promote significant decreases in blood pressure.
Topics: Adult; Humans; Cardiovascular Diseases; Resistance Training; Randomized Controlled Trials as Topic; Hypertension; Blood Pressure
PubMed: 36604479
DOI: 10.1038/s41598-022-26583-3