future research on hypertension

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Hypertension: Current trends and future perspectives

Affiliation.

1 Department of Renal Medicine, Royal Infirmary of Edinburgh & University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, UK.
PMID: 33733505
DOI: 10.1111/bcp.14825

Hypertension is a significant and increasing global health issue. It is a leading cause of cardiovascular disease and premature death worldwide due to its effects on end organs, and through its associations with chronic kidney disease, diabetes mellitus and obesity. Despite current management strategies, many patients do not achieve adequate blood pressure (BP) control. Hypertension-related cardiovascular mortality rates are rising in tandem with the increasing global prevalence of chronic kidney disease, diabetes mellitus and obesity. Improving BP control must therefore be urgently prioritised. Strategies include utilising existing antihypertensive agents more effectively, and using treatments developed for co-existing conditions (such as sodium-glucose cotransporter 2 inhibitors for diabetes mellitus) that offer additional BP-lowering and cardiovascular benefits. Additionally, novel therapeutic agents that target alternative prohypertensive pathways and that offer broader cardiovascular protection are under development, including dual angiotensin receptor-neprilysin inhibitors. Nonpharmacological strategies such as immunotherapy are also being explored. Finally, advancing knowledge of the human genome and molecular modification technology may usher in an exciting new era of personalised medicine, with the potential to revolutionise the management of hypertension.

Keywords: diabetes; hypertension; kidney disease; treatments.

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Top Ten Breakthroughs in Clinical Hypertension Research in 2022

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Hypertension is a major global public health concern whose disease burden affects an estimated 1.4 billion people worldwide and is associated with 10.8 million deaths annually. Despite substantial advances in medical care, the prevalence of hypertension has markedly increased, owing to population aging; poor treatment adherence; and increases in risk factors, such as excessive salt intake, and overweight and obesity. Consequently, the disability-adjusted life years have increased by 40%, primarily because of elevated risk of stroke, coronary atherosclerosis, heart failure, and kidney failure. Major outstanding problems associated with the treatment and management of hypertension include determining optimal blood pressure targets, developing innovative antihypertensive medications and devices, and implementing effective and feasible hypertension management strategies. To address these challenges, numerous clinical trials are currently underway. This article highlights the most influential ten clinical studies on hypertension in 2022. The rational use of antihypertensive medications is concluded to be important for effective hypertension management. Important considerations include medication types and dosing times; optimal blood pressure targets; the development of new drugs and therapeutic devices; specific community characteristics, such as village doctor-led care; and healthful diets.

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Nonstandard Abbreviations and Acronyms: ACC, American College of Cardiology; AHA, American Heart Association; BP, Blood pressure; CVDs, Cardiovascular diseases; DBP, Diastolic blood pressure; EBA, Endovascular baroreflex amplification; ESC, European Society of Cardiology; RDN, Renal denervation; SBP, Systolic blood pressure

The Best Time to Take Antihypertensive Medication—TIME Study

The circadian rhythm of blood pressure (BP) shows a dipper pattern, defined by low BP during sleep and peaks after awakening. A non-dipper rhythm, including nocturnal and morning hypertension, is considered an important predictor of adverse cardiovascular outcomes [ 1 , 2 ], and its management has been emphasized in The HOPE Asia network 2022 update consensus statement [ 3 ]. Moreover, taking antihypertensive medication in the evening has been demonstrated to normalize the circadian BP rhythm [ 4 ], thus leading to the hypothesis that evening administration of antihypertensive medication may improve cardiovascular outcomes more effectively than morning administration. This hypothesis has been strongly supported by the MAPEC trial (RR=0.33, 95% CI 0.19–0.55) and the Hygia trial (RR=0.58, 95% CI 0.49–0.68) [ 5 , 6 ]. However, the design of these trials was flawed, primarily because of issues with the randomization process. Furthermore, although significant differences were observed between the treatment and control groups after 1 year, the overall trial duration was 6.3 years, thus leading to ethical concerns. Consequently, the interpretation of the findings from these two studies remains debated in the scientific community [ 7 , 8 ].

The results of the Treatment in Morning versus Evening (TIME) study, a prospective, pragmatic randomized controlled clinical study by Thomas M MacDonald, were presented at the European Society of Cardiology (ESC) Congress 2022. A total of 21,104 adults with hypertension who were taking at least one antihypertensive medication were recruited. The participants were randomly assigned to a morning (06:00–10:00) or an evening (20:00–00:00) medication administration group by a computer algorithm generated through a randomization process, with no restriction, stratification, or minimization randomization methods. Because of the nature of the intervention, neither patients nor investigators were blinded to the group allocation. However, the endpoint assessors were blinded to group allocation to minimize potential bias in the study results.

The primary outcome was a composite of vascular death or hospitalization for non-fatal myocardial infarction or non-fatal stroke. The results indicated no statistically significant differences in cardiovascular outcomes between groups (HR=0.95, 95% CI 0.83–1.10, P=0.53).

The secondary outcomes included the components of the primary outcome, all-cause mortality, and hospitalization or death from congestive heart failure. No statistically significant differences were found in any outcomes.

Moreover, taking medication in the evening was found to be safe, because a lower incidence of falls and comparable incidence of fractures were observed the evening dosing group.

Outcomes were assessed with an unadjusted Cox proportional hazards model, Yates’ chi-square test, or t-test, as appropriate. The median follow-up time was 5.2 (IQR 4.9–5.7) years.

The results were published in The Lancet [ 9 ], which concurrently commented that the TIME study demonstrated that the optimal dosing time of antihypertensive medication should be decided jointly by patients and clinicians, according to each patient’s lifestyle and situation, to achieve the best medication adherence and optimal BP control [ 10 ].

The findings of the TIME study markedly differed from those of the aforementioned MAPEC and Hygia trials; this discrepancy has prompted reevaluation of the optimal antihypertensive medication dosing time. In addition, two similar clinical trials, the BedMed (NCT02990663) and BedMed-Frail (NCT04054648) trials, are currently being conducted to investigate the effects of antihypertensive medication timing on morbidity and mortality in patients with hypertension. The BedMed-Frail trial specifically focuses on the frail population [ 11 ]. The findings of these studies are expected to provide valuable guidance for the development of future hypertension guidelines, which currently lack specific recommendations regarding the optimal timing of antihypertensive medication. However, the TIME study did not investigate the effects of different antihypertensive medications on cardiovascular outcomes associated with morning or evening dosing; such an investigation would enable more precise and detailed intervention guidance regarding the dosing time of hypertension medication. Thus, further investigations in this area are necessary.

Effects of Renal Denervation on Blood Pressure—Spyral HTN-ON MED Pilot Study With Long-Term Follow-up for 3 years

To achieve the target BP, multiple antihypertensive medications are frequently prescribed in numerous patients, thus often resulting in low adherence, drug intolerance, and high healthcare costs. Consequently, novel therapies are needed. With the rapid development of interventional techniques in recent years, transcatheter renal denervation (RDN) has emerged as a potential approach for BP lowering. The unblinded clinical trials SYMPLICITY HTN-1 and HTN-2 have indicated significant decreases in systolic BP (SBP) 6 months after RDN, by 25 mmHg and 33 mmHg, respectively [ 12 , 13 ]. However, the blinded and sham-controlled SYMPLICITY HTN-3 trial has demonstrated no significant differences in SBP and 24-hour ambulatory SBP at 6 months between patients who underwent RDN and sham surgery. The discrepant results observed between the SYMPLICITY HTN trials may be attributable to various factors, including differences in the trial design, patient populations, and execution of the RDN procedure. The rigorous design of the HTN-3 trial effectively eliminated regression to the mean, and the Hawthorne and placebo effects. However, the uncertain adherence to medication between groups and the suboptimal execution of the RDN procedure as a result of operators’ limited experience in the HTN-3 trial might have introduced confounding effects, thereby hindering the ability to distinguish between the experimental and control groups, and leading to an absence of statistically significant results [ 14 ]. Therefore, caution is warranted in interpreting the 6-month follow-up results of the HTN-3 trial. Consequently, studies were subsequently conducted to further elucidate the role of RDN in the management of hypertension [ 15 – 19 ].

The 3-year follow-up results of SPYRAL HTN-ON MED, a randomized, single-blind, sham-controlled clinical study, were presented at the American College of Cardiology (ACC) Conference 2022. The study enrolled 80 patients meeting the inclusion criteria of SBP of 150–180 mmHg, diastolic BP (DBP) of at least 90 mmHg, mean 24-hour SBP of 140–170 mmHg, and taking one to three antihypertensive medications. The patients were randomly assigned to either a radiofrequency RND group (n=38) or a sham group (n=42).

The primary outcome was the difference in 24-hour SBP at 6 months between the RDN group and the sham group. The RDN group, compared with the sham group, demonstrated a reduction of 7 mmHg (95% CI −12.0 to −2.1) in 24-hour SBP and 4.3 mmHg (95% CI −7.8 to −0.8) in 24-hour DBP [ 15 ]. After 3 years of follow-up, the RDN group exhibited reductions of 10.0 mmHg (95% CI −16.6 to −3.3) and 4.3 mmHg (95% CI −10.1 to −1.8) in 24-hour SBP and DBP, respectively compared to the sham group.

The secondary outcome included assessment of changes in 24-hour, morning, daytime, nighttime, and office SBP changes at 24 and 36 months; statistically significant differences were observed in all these measures.

Outcomes were assessed in SAS statistical software with T-tests or analysis of covariance, as appropriate.

The Lancet published results demonstrating that radiofrequency RDN consistently and significantly decreases BP in patients with hypertension without serious adverse events, independently of the antihypertensive medications taken. Moreover, after 3 years of RDN treatment, the observed 10 mmHg decrease in 24-hour SBP was sustained throughout the day and was associated with significantly lower rates of cardiovascular outcomes, thus suggesting that RDN may potentially be a viable alternative for patients with resistant hypertension, or those unwilling or unable to tolerate multiple antihypertensive medications [ 20 , 21 ].

The results of several other RDN clinical trials were reported in 2022. The 6-month follow-up results of the Spyral HTN-ON MED Expansion study, which were presented at American Heart Association (AHA) Scientific Sessions 2022, indicated that the RDN group, compared with the sham group, had a significant reduction of 3.7 mmHg (P=0.001) in nocturnal ambulatory SBP. However, the 24-hour SBP change between groups was 1.9 mmHg (P=0.119), which didn’t meet the primary endpoint. In addition, the 3-year follow-up results of the SYMPLICITY HTN-3 study were reported in The Lancet [ 22 ]. The difference between the RDN and sham groups was 22.1 mmHg (95% Cl −27.2 to −17.0) in SBP and 16.5 mmHg (95% CI −20.5 to −12.5) in 24-hour SBP, The distinct difference, in contrast with the negative results of 6-month follow-up, confirms the effectiveness and long-term durability of RDN. Furthermore, the 3-year follow-up results of the Global SYMPLICITY Registry study were reported in JACC [ 23 ]. After RDN, a sustained average 16.7 mmHg decrease in BP over 3 years and a higher amount of time spent in the therapeutic range of BP were observed compared with the baseline, with lower major cardiovascular outcomes. Because of its demonstrated efficacy and safety, RDN is considered a viable antihypertensive therapy in the 2023 Hypertension Guidelines of China, Europe, and the Netherlands [ 24 , 25 ].

However, several limitations should be considered before RDN becomes a standard treatment option for patients with hypertension. First, no clinically convenient and feasible method to detect renal sympathetic nerve activity is currently available. Therefore, the response to RDN in some patients is unsatisfactory. Second, the population of patients optimally suited for RDN has yet to be determined, because the mechanism and effects of RDN have not been fully elucidated. Third, the lack of standardized operation procedures, coupled with challenges in training operators and managing potential interventional complications, pose obstacles to the development of RDN.

Phase II Trial of the Aldosterone Synthase Inhibitor Baxdrostat on Resistant Hypertension—BrigHTN Study

Approximately 10% of individuals with hypertension are classified as having treatment resistance [ 26 ], such that their condition cannot be effectively controlled, even with the administration of multiple antihypertensive medications [ 27 ]. Aldosterone exacerbates hypertension by promoting sodium reabsorption in distal nephrons by increasing the number and opening frequency of epithelium sodium channels, thereby leading to volume expansion. Additionally, aldosterone damages various target organs, including vessels, kidneys, and the heart, via multiple mechanisms, such as upregulation of connective tissue growth factor and subsequent fibrosis; production of proinflammatory molecules contributing to organ and extracellular matrix remodeling; oxidative stress; and stimulation of cell migration, proliferation, and apoptosis [ 28 ]. Moreover, target organ damage may worsen hypertension. Previous studies have explored the effectiveness of mineralocorticoid receptor antagonists in the treatment of hypertension. However, limitations of these treatments have been identified to include adverse events, such as an augmented aldosterone response, hyperkalemia, and gynecomastia. In addition, mineralocorticoid receptor antagonists are not appropriate for patients with intermediate or advanced chronic kidney disease [ 29 ]. Therefore, researchers have focused on another mechanism: the inhibition of aldosterone synthase. Nevertheless, because of the 93% sequence similarity between the enzymes synthesizing aldosterone and cortisol, the development of highly selective inhibitors of aldosterone synthase has led to a bottleneck. However, in recent preclinical and phase I trials, baxdrostat, an oral small-molecule aldosterone synthase inhibitor, has been found to substantially decrease plasma aldosterone levels without a concomitant decline in cortisol levels; these findings have increased interest in, and focus on, the inhibition of aldosterone synthase [ 30 ].

The phase II results of the BrigHTN study, a multicenter, double-blind, dose-ranging randomized controlled trial, were presented at AHA Scientific Sessions 2022. A total of 275 patients with resistant hypertension, defined by a BP above 130/80 mmHg, who were taking at least three antihypertensive medications including a diuretic, were recruited. Patients were randomly assigned to receive baxdrostat at doses of 0.5 mg, 1 mg, or 2 mg once per day, or a placebo for 12 weeks.

The study’s primary efficacy endpoint was the change in mean seated SBP from baseline to the end of the 12-week treatment period. The results indicated that baxdrostat exhibited dose-dependent antihypertensive effect: the mean seated SBP decreased by 20.3 mmHg, 17.5 mmHg, 12.1 mmHg, and 9.4 mmHg in the baxdrostat group with doses of 2 mg, 1 mg, or 0.5 mg, and placebo, respectively. Moreover, the 2 mg baxdrostat group exhibited a significant antihypertensive effect, with placebo-adjusted SBP and DBP decreases of 11.0 mmHg (95% CI −16.4 to −5.5) and 5.2 mmHg (95% CI −8.7 to −1.6).

The secondary outcomes included the change in the mean seated DBP with respect to baseline. The results indicated a difference in DBP between the baxdrostat 2-mg group and the placebo group of 5.2 mmHg (95% CI −8.7 to −1.6).

Safety endpoints included adverse events, vital signs, and the results of physical examinations. Two patients developed high serum potassium levels exceeding 6.0 mmol/L, which did not recur after withdrawal and re-initiation of the drug.

In conclusion, this study first demonstrated significant antihypertensive effectiveness of baxdrostat in patients with resistant hypertension, without any adverse effects on cortisol levels or adrenocortical function, or causing severe hyperkalemia. The results were published in NEJM [ 31 ]. These results highlight the potential for baxdrostat to serve as a new treatment option for diseases including resistant hypertension and primary aldosteronism.

However, because baxdrostat was not compared with existing antihypertensive medications, and the renal function of all participants was normal, further studies are necessary to evaluate the long-term effectiveness and safety of this drug, and to identify patient populations in which its use would be appropriate.

Phase III Trial of Dual Endothelin Antagonist Aprocitentan on Resistant Hypertension—PRECISION study

Prior studies have shown the antihypertensive effects of endothelin receptor antagonists [ 32 , 33 ]. These agents act by blocking the endothelin pathway, which is active primarily in endothelial cells and vascular smooth muscle cells, and is involved in cell proliferation and vessel vasoconstriction. Endothelin levels are known to be elevated in hypertension; diseases susceptible to resistant hypertension, such as obesity and obstructive sleep apnea; and complications associated with resistant hypertension, such as diabetes and chronic renal disease; moreover, the resulting changes in vascular tone contribute to the pathogenesis of hypertension and related cardiovascular diseases (CVDs) [ 34 – 37 ]. Aprocitentan is an oral antagonist of the dual endothelin A and B receptor. In a phase II clinical trial, aprocitentan monotherapy has been found to have more effective antihypertensive effects at doses of 10–25 mg compared to dose of 50 mg [ 38 ].

The phase III results of the PRECISION study, a multicenter, blinded randomized controlled trial, were presented at AHA Scientific Sessions 2022. A total of 730 patients with resistant hypertension were recruited, all of whom had a seated SBP above 140 mmHg and were taking at least three antihypertensive medications including a diuretic. The study comprised three parts. In part 1, participants were randomly assigned in a 1:1:1 ratio to receive aprocitentan at doses of 12.5 mg or 25 mg, or a placebo treatment in a double-blind period for 4 weeks. Then all participants took aprocitentan 25 mg for 32 weeks in part 2. Finally, in part 3, patients were randomly reassigned to two groups (1:1) to receive aprocitentan 25 mg or a placebo treatment in a double-blind period for 12 weeks.

The primary and key secondary endpoints were SBP changes from baseline to week 4 and from medication withdrawal from baseline (at the beginning of part 3) to week 40. From baseline to week 4, SBP decreased by 3.8 mmHg (97.5% CI −6.8 to −0.8) in the 12.5 mg aprocitentan group and 3.7 mmHg (97.5% CI −6.7 to −0.8) in the 25 mg group, as compared with the placebo group. After 4 weeks of medication withdrawal, SBP increased by 5.8 mmHg (95% CI 3.7 to 7.9) in the placebo treatment group compared with the aprocitentan treatment group.

The study indicated that, despite its concurrent use with other antihypertensive medications, aprocitentan produced statistically and clinically significant decreases in BP among patients with resistant hypertension, and this effect was maintained for at least 1 year. The results were published in The Lancet , which commended the remarkably well-designed medication research protocol in this study. Notably, the study revealed that aprocitentan, because of its new pharmacological mechanism, may have the potential to serve as a novel option for more than 100 million patients with resistant hypertension worldwide. Moreover, the study also highlighted the long-term efficacy of aprocitentan. This durable treatment option may effectively prevent cardiovascular events, thus providing the first breakthrough in antihypertensive medication in 30 years.

Nonetheless, the effect of aprocitentan is modest, and its clinical value must be further evaluated by comparison with other fourth-line antihypertensive medications (such as spironolactone) [ 39 , 40 ].

Best Time for Mild Chronic Hypertension Treatment During Pregnancy—CHAP study

Mild chronic hypertension during pregnancy has a prevalence ranging from 0.9% to 1.5%, and is associated with elevated risk of placental abruption, premature birth, low birth weight, and perinatal death, as well as multiple maternal adverse events, such as heart failure, stroke, and acute kidney injury [ 41 – 43 ]. The treatment threshold for pregnant women with chronic hypertension varies among guidelines. Specifically, the American College of Obstetricians and Gynecologists (ACOG) guidelines recommend treatment when the BP is at or above 160/110 mmHg, whereas the cutoff in the ESC guidelines is 150/95 mmHg. The World Health Organization, in contrast, does not have a specific recommendation [ 41 , 44 , 45 ]. Doubts have been raised regarding potential harm to the fetus from reduced uteroplacental circulation and in utero exposure to antihypertensive medications during BP lowering, whereas the benefits to maternal health are unclear, thus futher investigations into therapies for BP between 140–159/90–109 mmHg are required. A previous study with small sample sizes has demonstrated the lack of utility of antihypertensive treatment for mild chronic hypertension during pregnancy [ 46 ], whereas a secondary analysis has indicated a higher risk of adverse outcomes among patients with mild chronic hypertension during pregnancy than those with normal BP, in a BP-dependent manner [ 47 ]. The 2015 randomized controlled study CHIPS has revealed that, in comparison with loosely controlled BP (DBP ≤100 mmHg), strictly controlled BP (DBP ≤85 mmHg) decreases the risk of severe maternal hypertension with no adverse effects on fetal growth; however, no statistically significant difference was observed in pregnancy outcomes within 28 days after delivery [ 48 ]. On the basis of the results, numerous associations have lowered the treatment threshold in their recommendations, except for ACOG and the Society for Maternal Fetal Medicine (SMFM), owing to doubts regarding the low statistical power of the CHIPS study, given that its sample size was smaller than anticipated, and it lacked long-term follow-up.

The results of an open-label, randomized trial with a larger sample size and improved regional and racial representation with respect to prior studies, the CHAP study, were presented at the ACC Conference 2022. A total of 2480 pregnant women with mild chronic hypertension and a single fetus of gestational age less than 23 weeks were included and randomly allocated to either an active treatment group (BP ≤140/90) or a standard treatment group (BP ≤160/105).

The primary outcome was a composite of severe preeclampsia, medically indicated preterm births before 35 weeks, placental abruption, and fetal/neonatal death. Compared with the standard treatment group, the active treatment group maintained lower BP (129.5/79.1 mmHg vs. 132.6/81.5 mmHg) and had a lower incidence of the primary outcome (HR=0.82, 95% CI 0.74–0.92), particularly regarding decreased incidence of preeclampsia and medically indicated preterm births.

In conclusion, the CHAP study has indicated that active antihypertensive treatment (target BP ≤140/90) for mild chronic hypertension during pregnancy considerably decreases adverse pregnancy outcomes without increasing the risk of small-for-gestational-age infants. The results were published in NEJM [ 49 ].

The CHAP study has demonstrated that early-stage antihypertensive therapies are needed for mild chronic hypertension during pregnancy, thus leading to a decrease in the treatment threshold to 140/90 mmHg for pregnant women with chronic hypertension in the updated guidelines issued by SMFM and the Society of Obstetricians and Gynaecologists of Canada in 2022. The updated guidelines may result in more women receiving antihypertensive therapy during pregnancy, thus potentially improving outcomes for both mothers and infants. Healthcare providers should be aware of these updated guidelines, and should consider them when managing hypertension during pregnancy. However, although no statistical differences in neonatal outcomes were observed between groups, the potential long-term effects of active antihypertensive therapies on offspring exposed in utero remain unclear. Therefore, further follow-up studies are necessary to assess the effects on the health and well-being of the offspring. Such research will be crucial to ensure that interventions aimed at improving maternal and fetal health do not have unintended adverse effects on offspring in the long term, and to inform clinical decision-making in this area.

Comparison Between Chlorthalidone and Hydrochlorothiazide for Hypertension—DCP study

Thiazide diuretics, represented by chlorthalidone and hydrochlorothiazide, are the first-line medication recommended by current hypertension guidelines [ 50 ]. Previous studies have illustrated the superiority of chlorthalidone to hydrochlorothiazide [ 51 , 52 ], as also supported by the 2017 ACC/AHA Guidelines for High Blood Pressure [ 53 ], whereas several observational studies have recently demonstrated no significant difference between chlorthalidone and hydrochlorothiazide [ 54 , 55 ]. However, hydrochlorothiazide is more commonly used by clinicians, owing to concerns regarding the hypokalemic effects of chlorthalidone. Thus, further evidence is urgently needed to elucidate current ambiguities.

At AHA Scientific Sessions 2022, the results of the Diuretic Comparison Project (DCP) study, a pragmatic, open-label trial, were presented. A total of 13,523 patients with hypertension, mainly veterans over the age of 65 years, were randomly allocated to a hydrochlorothiazide group (25 or 50 mg/d) or chlorthalidone group (12.5 or 25 mg/d).

The primary outcome was a composite of non-cancer deaths or nonfatal cardiovascular events, defined as nonfatal stroke, myocardial infarction, emergency revascularization for unstable angina, or acute heart failure. The results indicated that during a mean follow-up period of 2.4 years, the incidence of the primary outcome, as well as its components, was comparable (HR=1.04, 95% CI 0.94–1.16) between the chlorthalidone group (10.4%) and the hydrochlorothiazide group (10.0%). Additionally, a subgroup analysis demonstrated that, among participants with a history of myocardial infarction or stroke, the primary outcome was reduced in the chlorthalidone group (HR=0.73, 95% CI 0.57–0.94), whereas among those without such a history, chlorthalidone tended to increase the primary outcome (HR=1.12, 95% CI 1.00–1.26).

Regarding safety outcomes, the incidence of hypokalemia in the chlorthalidone group (6.0%) was higher than that in the hydrochlorothiazide group (4.4%). These findings confirmed clinicians’ longstanding concerns. Moreover, new allergic or adverse reactions were more common in the chlorthalidone group (1.6%) than the hydrochlorothiazide group (0.3%), whereas no statistical difference was found in hospitalization for any cause. Thus, healthcare providers should consider the safety profiles of different diuretics when choosing treatment plans for their patients, and should take steps to minimize the risks of adverse reactions.

The results were published in NEJM [ 56 ]. The DCP study demonstrated that, compared with the clinically commonly used hydrochlorothiazide, chlorthalidone did not decrease the incidence of major cardiovascular outcomes or non-cancer deaths. This discovery challenges the established belief that chlorthalidone is the preferred treatment option, as supported by various guidelines. Therefore, in selecting the antihypertensive medication, consideration of each patient’s medical history, renal function, complications, and other relevant factors is critical in making the most appropriate decision. However, a notable limitation is that this study focused on only participants 65 years of age or older, and the population was predominantly male. Age and sex are important factors influencing the response to antihypertensive therapy and the risk of adverse outcomes. Therefore, the findings of this study may not be directly applicable to younger adults and women, and caution should be exercised when extrapolating the results to these groups. Further studies in different patient populations are necessary to confirm the applicability of these findings.

Effectiveness of Blood Pressure Interventions Led by Village Doctors in Rural China—the CRHCP Study

Approximately 75% of patients with hypertension live in low- and middle-income countries with scarce resources, thus resulting in a low rate of hypertension control [ 57 ]. In rural China, only 5.5% of patients with hypertension have their BP under control [ 58 ]. Village doctors provide basic medical care in rural China and are likely to play a crucial part in the prevention and control of hypertension, if they are properly trained in areas including standardized BP measurement; health coaching on lifestyle modifications; and protocol-driven antihypertensive treatment involving a treatment algorithm, medication selection, contraindications of medications, and adjustment strategies [ 59 , 60 ].

The China Rural Hypertension Control Project (CRHCP) study was a cluster randomized trial initiated by Yingxian Sun at the First Hospital of China Medical University. A total of 33,995 individuals over 40 years of age living in 326 Chinese villages, who had an untreated BP above 140/90 mmHg or treated BP above 130/80 mmHg, were enrolled and randomized (1:1) to an intervention group or a control group receiving conventional antihypertensive medications. In the intervention group, patients received a comprehensive treatment approach initiated by village doctors, including the initiation of antihypertensive medication according to established guidelines, provision of discounted or free medications, guidance on home BP monitoring, health coaching on lifestyle modifications, and organization of social support groups. Follow-up assessments were conducted every 6 months to monitor BP levels and other associated conditions in participants. Notably, however, the study design had several limitations, including practical limitations regarding the recruitment of all patients in a village and variations in the sizes of the clusters. In addition, because the intervention in this study was conducted primarily through oral coaching and guidance by village doctors, the quality of communication between the doctors and patients, as well as patients’ ability to understand and accept treatment, are crucial factors that might have influenced the effectiveness of the intervention. The uncontrollable communication among village doctors and patients between the intervention and control groups might have diminished the observed intervention effect. The phase I (18 months of follow-up) results were presented at AHA Scientific Sessions 2021 and published in The Lancet . The outcome of phase II (36 months of follow-up) was presented at AHA Scientific Sessions 2022 [ 61 ].

The primary outcome was a composite of myocardial infarction, stroke, heart failure requiring hospitalization, and CVD death. The primary outcome rate was substantially lower (HR=0.64, 95% CI 0.58–0.70) in the intervention group (1.6%) than the control group (2.4%).

The secondary outcomes included the components of the primary outcome and death due to all causes. The intervention group showed statistically significant decreases in all these outcomes, as compared with the control group, thus indicating a broad benefit of the intervention in decreasing the risk of cardiovascular events and death due to all causes.

Moreover, the mean SBP in the intervention and control groups decreased by 30.9 mmHg and 7.8 mmHg, whereas the mean DBP decreased by 14.8 mmHg and 4.9 mmHg, respectively. The differences between groups in SBP and DBP were 23.1 mmHg (95% CI −24.4 to –21.9) and 9.9 mmHg (95% CI −10.6 to −9.3).

The results demonstrated the effectiveness and feasibility of implementing interventions led by village doctors to achieve target BP levels in poorly resourced villages, and may provide guidance for the development of government policies to allow trained village doctor-led interventions for uncomplicated hypertension in low- and middle-income countries, by using a standard protocol under supervision by physicians. This approach has the potential to significantly improve hypertension management and alleviate the burden of healthcare expenses, while increasing access to care for rural populations.

AHA 2022 has noted that this study empowered primary medical staff with enhanced capabilities through Chinese innovation, and the effects of the nearly 1% absolute risk reduction of primary outcome in the intervention group have notable implications for hypertension management in low- and middle-income countries worldwide with a high burden of hypertension.

The Chinese Heart-Healthy Diet on Hypertension—DECIDE-Diet Study

In 2017, an estimated 11 million deaths and 255 million disability-adjusted life years—a time-based measure that combines years of life lost because of premature mortality and time lived in states of less than full health or disability—were attributable to dietary risk factors [ 62 ]. Similarly, CVDs are significantly correlated with diets. Numerous studies have demonstrated that healthful diets [ 63 ], such as the Dietary Approaches to Stop Hypertension (DASH) diet and the Mediterranean diet, markedly decrease BP and CVD risk [ 64 – 67 ]. These diets emphasize the consumption of plant-based foods and olive oil, and limitation of red meat consumption. Despite the demonstrated health benefits of these diets, their implementation is often hindered by a perceived lack of flavor. Moreover, implementing Western-style diets in China, which has a high prevalence of CVDs, is challenging, because of the substantial differences in dietary patterns between Chinese and Western populations. Therefore, developing a healthful and palatable diet is imperative for the prevention and management of hypertension and CVDs in Chinese populations.

Circulation has reported the results of the Chinese Heart-Healthy (CHH) Diet pattern study, developed by Yangfeng Wu at the Peking University Clinical Research Institute [ 68 ]. A total of 265 patients with SBP of 130–159 mmHg participated in the Exercise and Cardiovascular Health-Diet (DECIDE-Diet) study, a single-blind randomized trial. After a 7-day run-in period, participants were randomized to either a normal diet or CHH diet. The CHH diet included four major Chinese cuisines—Shandong, Huaiyang, Cantonese, and Szechuan—tailored to the geographic locations of the participants, and included nonrepetitive dishes in a cycle of at least 2 weeks. In contrast, the normal diet was developed on the basis of commonly consumed local foods. During the 28-day intervention period, the study achieved a high rate of participant compliance: 97% of the participants completed the study and consumed an average of 97% of the meals provided.

The primary outcome was the change in SBP, which decreased by 5.0 mmHg (95% CI –6.5 to –3.5) in the normal diet group and 15.0 mmHg (95% CI –16.5 to –13.5) in the CHH diet group after 28 days. The differences observed for SBP and DBP between groups were 10.0 mmHg (95% CI –12.1 to –7.9) and 3.8 mmHg (95% CI –5.0 to –2.5).

Moreover, both diets were generally well received by participants, and the decrease in SBP by 1 mmHg cost only an additional CNY 0.4 (USD 0.06) per day. The author further estimated that adherence to the CHH diet was associated with a 20% decrease in CVD, a 28% decrease in heart failure, and a 13% decrease in all-cause mortality, thus indicating the efficacy, palatability, and cost-effectiveness of the CHH diet. These findings may provide valuable guidance for the Chinese government and other nations in developing guidelines and policies associated with health management.

However, the study has several limitations including confounding factors, such as the relatively short intervention time; enrollment below anticipated goals; and the controlled design. First, the intervention period was short, lasting only 4 weeks. Consequently, limited evidence suggesting a sustained hypertensive effect in the long term was found. Second, because whole food analysis was not used to measure nutrient composition, the intake of relevant nutrient components could not be ensured in the CHH diet. Third, the intended enrollment goals were not achieved because of the effects of the COVID-19 pandemic. Given the controlled design of this study, the generalizability of its findings to real-world scenarios warrants further validation.

Effectiveness of the Endovascular Baroreflex Amplification Technique on Hypertension—CALM-FIM Study with Long-Term Follow-up for 3 years

Despite the availability of various antihypertensive medications, 86% of patients with hypertension continue to experience uncontrolled hypertension, thus increasing their risk of developing CVDs. Therefore, investigating novel antihypertensive techniques and their potential effects on BP management is critical. Stimulating baroreceptors can lower BP by activating sympathetic and parasympathetic nerves [ 69 ]. Two antihypertensive techniques have been developed: baroreflex activation therapy and endovascular baroreflex amplification (EBA). MobiusHD, an implant for the internal carotid artery, belongs to the EBA category; this modality decreases BP through passive mechanical stimulation of baroreceptors, rather than using electrical stimulation as in baroreflex activation therapy [ 42 , 70 , 71 ].

The Controlling and Lowering Blood Pressure With the MobiusHD–First in Man (CALM-FIM) study was a prospective, open-label trial to assess the effectiveness of implanted MobiusHD in the unilateral internal carotid artery in 47 patients with resistant hypertension.

The primary outcomes were the incidence of adverse events and changes in BP, 24-hour ambulatory BP, and antihypertensive medication use after implantation. The results of the 6-month follow-up, published in The Lancet , indicated that BP was lowered by 30/12 mmHg (95% CI −38 to −21/−17 to −8 mmHg), and ambulatory BP was lowered by 21/12 mmHg (95% CI −19 to −14/−16 to −7 mmHg) [ 72 ]. After 3 years, the BP decrease remained at 30/12 mmHg (95% CI −38 to −21/−17 to −8 mmHg).

Regarding safety outcomes, the occurrence of five serious adverse events, including hypotension (n=2), hypertension (n=1), vascular access complications (n=2), and two transient ischemic attacks, were observed within 30 days post-implantation. By 30 days post-implantation, six serious adverse reactions had occurred, including strokes (n=2), transient neurologic symptoms (n=1), hypertension (n=1), and hypotension (n=2).

The occurrence of these serious adverse events underscores the importance of continued monitoring and evaluation of the safety and effectiveness of this device. Although the adverse events observed in patients who underwent implantation of the MobiusHD device eventually resolved, the high incidence rate of these events has prompted concern regarding the safety of this method. Therefore, future studies should assess the long-term safety and efficacy of the MobiusHD device, to provide a more comprehensive understanding of its benefits and risks and to inform evidence-based clinical practice. The results were published in JACC Cardiovascular Intervention [ 73 ].

Although the CALM-FIM study demonstrated the efficacy of MobiusHD based on EBA, the study had several limitations. First, the study design lacked a control group, thus preventing accurate evaluation of the outcomes and adverse events associated with the treatment. Second, the study’s observational design had the potential for confounding factors such as the Hawthorne effects, placebo effects, and regression to the mean. Furthermore, the study did not use urine or blood tests to assess medication compliance, thus posing challenges in ruling out the influence of medication differences among participants.

Therefore, although the study has provided preliminary evidence of the efficacy of MobiusHD, further trials with a more rigorous design are necessary to evaluate the benefit-risk profile of this technique.

Characteristics of Primary Care Institutions Associated with Hypertension Awareness, Treatment, and Control—China PEACE-Million Persons Project

China’s primary medical and health care system consists of approximately 900,000 institutions and 3 million workers, and provides basic public health services on a nationwide scale. The quality of primary medical care is reflected by the awareness, treatment, and control rate of hypertension [ 74 ]. Over the past few years, China has implemented substantial investments and reforms to its primary care system, aimed at improving the quality of care provided. However, characteristics including financing methods, medical treatment patterns, and medical personnel capacity vary among regions [ 60 ], and the relationships between various characteristics of primary care institutions and the awareness, treatment, and control rates of hypertension remain unclear [ 75 ]. Understanding these relationships will be crucial for improving the quality of primary medical care and hypertension management in China’s primary care system.

Research conducted by Xi Li and Jiapeng Lu from Fuwai Hospital Chinese Academy of Medical Sciences enrolled 433 primary care institutions from the Million Persons Project, which selected sites in all 31 provinces of mainland China through a convenience sampling strategy, to demonstrate the diversity of geographic distribution and demographics, risk factor exposure, and disease patterns. Among these sites, 660,565 patients with hypertension 35–75 years of age who had lived in the selected area for at least 6 of the prior 12 months were included.

Data were collected through standardized face-to-face interviews conducted by trained personnel using electronic questionnaires with real-time logic-checking capabilities. Univariate analyses of each institution-level were conducted with T-test or ANOVA. Moreover, multi-level logistic models with all participant-level variables were established. Institution-level variables with P<0.05 were retained in the final model. All these analyses were performed in SAS statistical software.

The results of standardized rates for hypertension awareness (8.2% to 81.0%), treatment (2.6% to 96.5%), and control (0% to 62.4%) were reported, and 10% of the awareness rate, 21% of the treatment rate, and 12% of the control rate were ascribed to primary care institutions. Characteristics of primary care institutions conducive to hypertension management included bonuses associated with performance (treatment rate OR=1.39, 95% CI 1.07–1.80), referrals through the online system (treatment rate OR=1.41, 95% CI 1.14–1.73; control rate OR=1.17, 95% CI 1.03–1.33), a family doctor service pattern (awareness OR=1.13, 95% CI 1.00–1.28; control rate OR=1.30, 95% CI 1.15–1.46), and a high proportion of practitioners (awareness OR=1.04, 95% CI 1.01–1.08; treatment rate OR=1.08, 95% CI 1.02–1.14). In contrast, characteristics detrimental to hypertension management included governmental allocation of resources, financial problems affecting daily work, and salaries associated with the numbers of outpatients and inpatients. The results have been published in The Lancet Global Health [ 76 ]. Considering the current situation in China, the training of primary care physicians must urgently be enhanced to increase the proportion of licensed practitioners, improve coordination between superior and subordinate hospitals, establish a robust network referral system, and optimize the incentive mechanism of performance bonuses. These strategies may also be relevant and applicable to other countries facing similar challenges.

However, this study had several limitations. The time mismatch between participant data (obtained from 2014 to 2021) and institutional characteristics data (obtained from 2016 to 2017) might have introduced bias in the observed associations, particularly given that some new policies were issued after 2017. Moreover, focusing on institutional characteristics without adjusting for individual health-care seeking behaviors might also have influenced the results of the analysis. Furthermore, the primary care institution characteristics included in the analysis, such as physician access to the clinical practice guidelines, might not have been comprehensive. Together, these limitations might have led to underestimation or overestimation of the effects of specific characteristics on hypertension management in primary healthcare systems, and affected the reliability and generalizability of the findings. Therefore, further studies including qualitative in-depth interviews and randomized controlled trials to assess these features would be essential and informative. In conclusion, this study highlighted the critical roles of primary care institution characteristics in the quality of medical care, and identified potential avenues for improving hypertension management in primary healthcare systems.

Conclusions

Hypertension is the most common chronic non-communicable disease. The ten aforementioned clinical studies have offered valuable insights into the treatment and management of hypertension ( Table 1 ). However, notable challenges in the management of hypertension remain to be addressed and elucidated in further research, to support evidence-based medicine, and achieve well-treated, controlled, and managed hypertension.

Classification of Top Ten Breakthroughs in 2022 Clinical Studies of Hypertension.

Number	Classification	Research	Conclusion	Published/presented
1	Management of hypertension	TIME	No statistically significant difference was found between taking antihypertensive medication in the morning or evening.	Lancet [ ]; ESC 2022
2		CHAP	Active antihypertensive treatment (target BP ≤140/90) for mild chronic hypertension during pregnancy considerably decreased pregnancy-related outcomes without elevating the risk of small-for-gestational-age infants.	NEJM [ ]; ACC 2022
3		CRHCP	The effectiveness of hypertensive interventions led by rural physicians in poorly resourced villages is demonstrated.	Lancet [ ]; AHA 2022
4		China PEACE Project	Evidence for the critical role of primary care institutions’ characteristics in the quality of medical care is provided.	The Lancet Global Health [ ]
5	Treatment of hypertension	Spyral HTN-ON MED Pilot	RDN consistently improved BP without serious adverse events, independently of the antihypertensive medication taken.	Lancet [ ]; ACC 2022
6		BrigHTN	Baxdrostat considerably decreased BP in a dose-dependent manner.	NEJM [ ]; AHA 2022
7		PRECISIN	Aprocitentan had antihypertensive effects at week 4, which were sustained until week 48.	Lancet [ ]; AHA 2022
8		DCP	Compared with hydrochlorothiazide, chlorothiazide did not lessen the occurrence of major cardiovascular outcomes or non-cancer deaths.	NEJM [ ]; AHA 2022
9		DECIDE-Diet	The efficacy, palatability, and cost-effectiveness of the Chinese Heart-Healthy diet are demonstrated.	Circulation [ ]
10		CALM-FIM	The efficacy and safety of MobiusHD are corroborated through endovascular baroreflex amplification.	JACC Cardiovascular [ ]

Conflict of interests

The authors declare no conflicts of interest.

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NIH-supported research helps shape the future of blood pressure measurement

Mature woman at the doctor, controlling blood pressure

Pipeline of smart technologies could expand detection of hypertension, save lives

It’s the drill at the start of virtually every doctor or hospital visit: having your blood pressure measured. A technician straps a cuff to your upper arm and tightly inflates it. The beeps begin as a machine generates numbers. The cuff slowly deflates. The tech announces the all-important readings.

For some, the experience can be unsettling—not simply because of increased pressure on the arm, but because of the nervous anticipation of what the numbers will tell.

Yet for more than a century, this bulky arm-cuff device—formally known as a sphygmomanometer—has been the gold standard for detecting hypertension, a treatable disease that affects half of the adult population in the United States and is the leading risk factor for stroke and heart disease.

But things are changing—and fast.

Researchers supported by the NIH are helping develop new and improved monitoring devices in a stepped-up effort to stem the epidemic rates of uncontrolled hypertension. They include a new wave of electronics—from skin patches to smartwatches—that can easily be used at home. And that’s good news, as recent studies show some of these devices can provide more reliable and informative readings than those taken in clinics and help significantly reduce a person’s chances of stroke and heart disease. “In the U.S., less than half of people with high blood pressure have it under control,” said David Goff, M.D., Ph.D., director of the Division of Cardiovascular Sciences at NHLBI. “Given the poor level of control, it’s time to test creative approaches to preventing the development of hypertension and improving control. Technologies that empower patients to be more involved in monitoring their blood pressure are promising approaches that might benefit from more research and development.” Better blood pressure devices that are less intrusive, faster, easier to use, and affordable could help improve blood pressure control, researchers say. At-home devices can also overcome challenges such as “white coat syndrome,” a condition that affects people who are so anxious about being in a medical setting that their blood pressure registers higher than it would in a normal setting. Finally, some devices may be able to facilitate continuous monitoring of blood pressure, which researchers say is important because blood pressure varies throughout the day and from one day to the next. But while these new devices may be a potential improvement over the standard ones, they come with their own challenges. One is accuracy validation. A recent study showed that most home blood pressure monitors currently on the market have not been validated for accuracy by a testing agency that does not have ties to any manufacturer. Another hurdle is implementation—how to get the new devices into the community in a way that is effective, affordable, and sustainable in routine daily care and practice. But researchers are optimistic these challenges can be met over time as they continue testing the devices and consumers seek to take charge of their health. “You have to know your blood pressure numbers,” said George Mensah, M.D., Director of the Center for Translation Research & Implementation Science at NHLBI. “And we have to take steps to improve those numbers.” This call to action, he said, is important for all men and women but particularly for African American men, who have the highest hypertension-related stroke and heart disease death rates of any racial or ethnic group in the country.

Here’s a glimpse at some of the technologies that are in the works: Finger pressing

This photo shows a smartphone-based device that allows users to monitor their blood pressure by pressing down on the surface of the phone

Ramakrishna Mukkamala, Ph.D., a professor of electrical and computer engineering at Michigan State University, is leading a team of scientists that developed, with partial funding from NHLBI, smartphone-based devices that can monitor blood pressure using the pressure of a person’s index finger. It works like this: A person steadily presses his or her index finger on the phone. Guided by an animated cursor on the phone screen, the user keeps pressing until prompted to lift the finger. Optical and force sensors in the phone then combine to translate the arterial pressure from the fingertip into a blood pressure reading in millimeters of mercury, just like the standard reading from a blood pressure cuff. The reading shows up on your phone, and the whole process takes place in less than half a minute. A normal blood pressure reading is less than 120/80 millimeters of mercury (mm Hg). The top number—known as systolic pressure— measures the pressure in your arteries when your heart beats, while the bottom number— known as diastolic pressure—measures the pressure in your arteries when your heart rests between beats.

In early tests on a few dozen people, the device performed just as accurately as an FDA-approved device called a volume-clamp, which uses a special cuff on a finger, but somewhat less accurately than a conventional arm-cuff device. “We want to develop truly cuff-less devices that are accurate and readily accessible,” Mukkamala said, noting that other cuff-less devices require cuff measurements periodically to give blood pressure in mm Hg. The devices could be on the market in a few years, he said. The sensors can be inserted in an add-on phone case or integrated into the existing architecture of a cell phone, while some phones already have the necessary sensors. The researcher hopes to eventually turn the device into a complete hypertension management system, one that uses an alarm to warn users if they have high blood pressure or sends them a text to remind users when to take their blood pressure medication. The system also shows promise for addressing high rates of hypertension in developing areas of the world, where smartphone use is growing, Mukkamala said. Ultrasound patch In 2017, a research team funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) developed a noninvasive skin patch that can be worn on the neck for continuous measurement of blood pressure. Unlike conventional devices that measure peripheral blood pressure through arteries in the arm, the patch measures central blood pressure—the flow of blood from the heart through the carotid arteries in the neck. Doctors consider measurements taken from this area to be a more accurate predictor of developing heart problems, including heart attacks. This wearable patch can also measure blood pressure at other parts of the body including the arm, wrist, and foot.

The prototype device, which is made of a thin sheet of silicone polymer integrated with an array of tiny electronic parts, measures blood pressure through ultrasound , or high-frequency sound waves. The patch, which is the size of a postage stamp, is soft and can bend and twist in the presence of motion. It sends and picks up reflecting sound waves from the pulsing blood vessels in the neck and translates them into signals that are read by customized software in an external device that is wired to the patch. It is ideal for use in the ICU and operating room, the researchers said.

A tiny skin patch, about the size of a postage stamp, shows promise as a wearable device that can be worn on the neck to measure blood pressure.

In early studies, the skin patch measurements were better than or comparable to those made by other instruments now used in the clinic to measure central blood pressure. Researchers hope to develop the patch into a completely wireless device in the future. “Our patch represents a step toward precision medicine for monitoring blood pressure and managing and preventing acute and chronic cardiovascular diseases,” said Sheng Xu, Ph.D., study leader and an assistant professor of nanoengineering at the University of California San Diego in La Jolla. “The continuous data stream generated is unique for each subject, and that allows physicians and other healthcare providers to design specific regimens for that specific patient.” Smartwatch One of the most sought-after pieces of real estate for blood pressure monitoring is the wrist, which means the ever-popular smartwatch continues to be transformed in even more functional ways.

Man walking down the street with a smartwatch on.

In another project funded by NIBIB, researchers at the Georgia Institute of Technology developed a smartwatch that measures blood pressure by recording chest vibrations produced by the heartbeat. Called a SeismoWatch, it looks like any other smartwatch and contains miniature motion sensors.

To work it, you hold the watch up to your chest, and sensors in the watch detect micro-vibrations of the chest wall associated with the heartbeat. As pressure waves move along the artery walls from the heart to the wrist, an accelerometer and optical sensor on the watch measure the signals to estimate blood pressure. The whole process takes about 10 to 15 seconds.

So far, the researchers have tested the prototype on about 50 people, some in the lab and some at home, with results comparable to some conventional blood pressure devices. Although the prototype is externally wired to a monitor and contains no readable watch face, the researchers say the future version can be engineered to be wireless and have a readout like a regular smartwatch.

“Our hope is that the SeismoWatch will become an affordable, reliable tool for blood pressure measurement in medically underserved minority populations, where rates of hypertension are very high,” said study leader Omer Inan, Ph.D., an associate professor at the university. NHLBI’s Mensah said he would welcome that. “Any of these innovative devices that are affordable, reliable, and easy to use will go a long way in helping us detect high blood pressure and inform our actions to control this silent killer,” he said. While this new crop of measurement devices is being refined, doctors and researchers urge everybody to act now to reduce their risk of hypertension by limiting sodium intake, staying physically active, maintaining a healthy weight, taking medicines as prescribed, stopping smoking, limiting alcohol, and seeing their doctors on a regular basis. People are also encouraged to measure their blood pressure regularly.

More Information

Hypertension

Hypertension, or high blood pressure, is a risk factor for cardiovascular disease and stroke—the two leading causes of death in the United States ( 1–3 ).

Featured Chart

Explore data, definitions, key findings, hypertension in adults age 20 and older.

This line graph shows the percentage of adults age 20 and older with hypertension from 2001 through 2004 to 2017 through March 2020.

The age-adjusted percentage of adults age 20 and older with hypertension did not change significantly from 2001–2004 to 2017–March 2020. See Featured Chart for additional analysis.

SOURCE: National Center for Health Statistics, National Health and Nutrition Examination Survey. See Sources and Definitions, National Health and Nutrition Examination Survey (NHANES) and Health, United States , 2022 Table Htn .

Estimates are based on the U.S. civilian noninstitutionalized population. See Sources and Definitions, Population .
Age-adjusted estimates are presented to eliminate differences that result from changes in the distribution of age in the population over time. See Sources and Definitions, Age adjustment .
For information on the methods used to assess trends, see Sources and Definitions, Statistical testing .
The NHANES program suspended field operations in March 2020 due to the COVID-19 pandemic. As a result, data collection for the 2019–2020 cycle was not completed. Consequently, data collected during 2019–March 2020 were combined with data from the 2017–2018 cycle to create a 2017–March 2020 prepandemic file. This file covers 3.2 years of data collection. For more information, see: “ National Health and Nutrition Examination Survey, 2017–March 2020 Prepandemic File: Sample Design, Estimation, and Analytic Guidelines .”

Hypertension in men age 20 and older

This line graph shows the percentage of men age 20 and older with hypertension from 2001 through 2004 to 2017 through March 2020.

The age-adjusted percentage of men age 20 and older with hypertension did not change significantly from 2001–2004 to 2017–March. See Featured Chart for additional analysis.

Hypertension in women age 20 and older

This line graph shows the percentage of women age 20 and older with hypertension from 2001 through 2004 to 2017 through March 2020.

The age-adjusted percentage of women age 20 and older with hypertension did not change significantly from 2001–2004 to 2017–March 2020 (42.1% in 2017–March 2020). See Featured Chart for additional analysis.

From 2001–2004 to 2017–March 2020, hypertension was stable across all ages and was higher among older adults for both men and women.

Figure 1 is a two-panel chart with line graphs showing the percentage of men (left graph) and women (right graph) age 20 and older with hypertension from 2001 through 2004 to 2017 through March 2020. Age groups shown are 75 and older, 65 through 74, 55 through 64, 45 through 54, 35 through 44, and 20 through 34.

NOTE: “Stable” refers to no statistically significant trend during the period.

From 2001–2004 to 2017–March 2020, the percentage of men and women age 20 and older with hypertension did not change significantly for any age group.
Throughout the period, the percentage of men and women with hypertension generally increased with increasing age.
For men in 2017–March 2020, the percentage of those with hypertension ranged from 28.0% for men ages 20–34 to 83.2% for men age 75 and older.
For women in 2017–March 2020, the percentage of those with hypertension ranged from 13.6% for women ages 20–34 to 84.1% for women age 75 and older.
In 2017–March 2020, men were more likely to have hypertension than women for those younger than age 55. For those age 55 and older, the prevalence of hypertension was similar for men and women.

From 2001–2004 to 2017–March 2020, the age-adjusted percentage of adults age 20 and older with hypertension did not change significantly for Black, Mexican, and White adults. The percentage for Asian adults increased from 2013–2016 to 2017–March 2020 .

Figure 2 is a line graph showing the percentage of adults age 20 and older with hypertension by race and Hispanic origin from 2001 through 2004 to 2017 through March 2020. Categories shown are Black non-Hispanic, White non-Hispanic, Mexican, and Asian non-Hispanic.

1 Data for the Asian population are available only starting in 2013.

From 2001–2004 to 2017–March 2020, the age-adjusted percentage of adults age 20 and older with hypertension did not change significantly for Black, Mexican, and White adults.
For Asian adults, the age-adjusted percentage of hypertension increased from 41.2% in 2013–2016 to 46.2% in 2017–March 2020.
Throughout the period, hypertension was higher in Black adults compared with Mexican, White, and Asian adults.
In 2017–March 2020, the age-adjusted percentage of adults with hypertension was 58.9% for Black adults, 46.2% for Asian adults, 44.5% for White adults, and 42.6% for Mexican adults.
Estimates are Age-adjusted estimates are presented to eliminate differences that result from changes in the distribution of age in the population over time. See Sources and Definitions, Age adjustment .
Race groups (Asian, Black, and White) are non-Hispanic.
Data on race and Hispanic origin are presented in the greatest detail possible considering the quality of the data, the amount of missing data, and the number of observations. Although data for Hispanic people are available starting in 2007–2008, to provide estimates for the entire period starting with 2001–2004, estimates for people of Mexican origin are presented in the figure rather than Hispanic. Data for Asian people are available starting in 2011–2012.

Hypertension in adults age 20 and older, by selected characteristics: United States, selected years 1988–1994 to 2017–March 2020

SOURCE: National Center for Health Statistics, National Health and Nutrition Examination Survey.

NCHS Data Query System
Data.CDC.gov

Cholesterol in adults age 20 and older, by selected characteristics: United States, selected years 1988–1994 to 2017–March 2020

Hypertension: Defined as having measured high blood pressure (systolic pressure of at least 130 mm Hg or diastolic pressure of at least 80 mm Hg), taking high blood pressure medication, or both. Those who report taking high blood pressure medication may not have measured high blood pressure but are still classified as having hypertension. See Sources and Definitions, Hypertension .
Mexican: People of Mexican or Hispanic origin may be of any race. For 1999–2006, the NHANES sample was designed to provide estimates specifically for people of Mexican origin and not for all Hispanic-origin people. Starting with 2007–2008 data, estimates for all Hispanic people are available. To provide the full trend, estimates for people of Mexican origin only are presented in the figure. For data on the Hispanic population, see Health, United States, 2022 Table Htn . Also see Sources and Definitions, Hispanic origin .
Race: Estimates are presented according to the 1997 Office of Management and Budget’s “Revisions to the Standards for the Classification of Federal Data on Race and Ethnicity” and are for people who reported only one racial group. Starting in 2011, NHANES oversampled the Asian non-Hispanic population. In Health, United States , estimates are presented for Asian non-Hispanic, Black non-Hispanic, and White non-Hispanic people, as well as for people of Hispanic and Mexican origin. Insufficient numbers of observations are available during this period to meet statistical reliability or confidentiality requirements for reporting estimates for additional race categories. See Sources and Definitions, Race .
Centers for Disease Control and Prevention. High blood pressure . 2023.
Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: A report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Hypertension 71(6):e13-e115. 2018.
Kochanek KD, Murphy SL, Xu J, Arias E. Deaths: Final data for 2020. NCHS National Vital Statistics Reports; vol 72 no 10. Hyattsville, MD: National Center for Health Statistics. 2023. DOI: https://dx.doi.org/10.15620/cdc:131355 .

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Fluid keeps your brain from crushing itself and shields your spine from shock—what happens when it stops working

by Danielle Wilhour, The Conversation

Cerebrospinal fluid, or CSF , is a clear, colorless liquid that plays a crucial role in maintaining the health and function of your central nervous system. It cushions the brain and spinal cord, provides nutrients and removes waste products.

Despite its importance, problems related to CSF often go unnoticed until something goes wrong.

I am a neurologist and headache specialist . In my work treating patients with CSF pressure disorders, I have seen these conditions present in many different ways. Here's what happens when your cerebrospinal fluid stops working:

What is cerebrospinal fluid?

CBF is made of water, proteins, sugar, ions and neurotransmitters. It is primarily produced by a network of cells called the choroid plexus , which is located in the brain 's ventricles, or cavities.

The choroid plexus produces approximately 500 milliliters of CSF daily , but only about 150 milliliters are present within the central nervous system at any given time due to constant absorption and replenishment in the brain. This fluid circulates through the ventricles of the brain , the central canal of the spinal cord and the subarachnoid space surrounding the brain and spinal cord .

CSF has several critical functions . It protects the brain and spinal cord from injury by absorbing shocks. Suspending the brain in this fluid reduces its effective weight and prevents it from being crushed under its own mass. Additionally, CSF helps maintain a stable chemical environment in the central nervous system, facilitating the removal of metabolic waste and the distribution of nutrients and hormones.

When the production, circulation or absorption of cerebrospinal fluid is disrupted, this can lead to significant health issues. Two notable conditions are CSF leaks and idiopathic intracranial hypertension .

A CSF leak occurs when the fluid escapes through a tear or hole in the dura mater—the tough, outermost layer of the meninges that surrounds the brain and spinal cord.

The dura can be damaged from head injuries or be punctured during surgical procedures involving the sinuses, brain or spine, such as lumbar puncture , epidurals, spinal anesthesia or myelogram. Spontaneous CSF leaks can also occur without any identifiable cause.

CSF leaks were originally thought to be relatively rare, with an estimated annual incidence of 5 per 100,000 people . However, with increased awareness and advances in imaging, health care providers are discovering more and more leaks. They tend to occur more frequently in middle-aged adults and are more common in women than men.

Risk factors for the condition include connective tissue disorders such as Ehlers-Danlos syndrome as well as postural orthostatic tachycardia syndrome.

Unfortunately, it's common for health care providers to misdiagnose a CSF leak as another condition, like migraine, sinus infections or allergies. What can make diagnosing a CSF leak challenging is its broad symptoms. Most people with CSF leak have a positional headache that improves when lying down and worsens when standing. Pain is usually felt in the back of the head and may involve the neck and between the shoulder blades. In addition to headaches, patients may experience ringing in the ears, vision disturbances, memory problems, brain fog, dizziness and nausea.

Imaging may help guide diagnosis , including an MRI of your brain or entire spine, or a myelogram of the space surrounding your spinal cord. Features of a CSF leak that are visible in a scan include your brain sagging down in the base of your skull as well as a fluid collection outside of your dura. However, an estimated 19% of people with a CSF leak can have normal scans , so not seeing signs of a leak on imaging does not entirely rule it out.

Conservative treatment for a CSF leak involves rest, lying flat and increasing your fluid intake to give your spine time to heal the puncture. Increasing your caffeine consumption to an equivalent of three to four cups of coffee per day can also help by increasing CSF production through stimulating the choroid plexus. Caffeine also relieves pain by interacting with adenosine receptors , which are key players in the body's pain perception mechanisms.

If a conservative approach is not successful, an epidural blood patch may be necessary. In this procedure, blood is drawn from your arm and injected into your spine. The injected blood can help form a covering over the hole and promote the healing process. Headache improvement can be fast, but if the patch does not work or the results are short-lived, additional testing may be needed to better locate the site of the leak. In rare cases, surgery may be recommended . Most patients with CSF leak respond to some form of these treatments.

Idiopathic intracranial hypertension

Idiopathic intracranial hypertension is a disorder involving an excess of CSF that elevates pressure inside the skull and compresses the brain. The term "idiopathic" indicates that the cause of the raised pressure is unknown.

Most patients with idiopathic intracranial hypertension have a history of obesity or recent weight gain. Other risk factors include taking certain medications such as tetracycline, excessive vitamin A, tretinoin, steroids and growth hormone. Middle-aged obese women are 20 times more likely to be diagnosed with idiopathic intracranial hypertension than other patient groups. As obesity becomes more prevalent, so too does the incidence of this condition.

Patients with idiopathic intracranial hypertension typically experience headaches and vision changes , tinnitus or eye pain. Papilledema , or swelling of the optic disk, is the hallmark finding on a fundoscopic examination of the back of the eye. Clinicians may also observe paralysis of the patient's eye muscles.

Brain imaging of patients suspected of having idiopathic intracranial hypertension is crucial to excluding other causes of elevated CSF pressure, such as brain tumors or blood clots in the brain. A lumbar puncture or spinal tap to measure the pressure and composition of CSF is also central to diagnosis.

Since high intracranial pressure can damage the optic nerve and lead to permanent vision loss , the primary goal of treatment is to decrease pressure and preserve the optic nerve. Treatment options include weight loss, dietary changes and medications to reduce CSF production. Surgical procedures can also reduce intracranial pressure.

Future directions and unknowns

Cerebrospinal fluid is indispensable for brain health. Despite advancements in understanding diseases related to CSF, several aspects remain unclear.

The exact mechanisms that lead to conditions like CSF leaks and idiopathic intracranial hypertension are not fully understood, though there are many theories . Further research is vital to enhance diagnostic accuracy and effective treatments for CSF disorders.

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Hypertension is high blood pressure. It is generally defined in adults as systolic blood pressure greater than or equal to 140mmHg and/or diastolic blood pressure greater than or equal to 90mmHg. Rarely associated with obvious symptoms, hypertension can result in heart disease, vascular disease, stroke and/or chronic kidney disease

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PMC10627159

Trends in exercise for hypertension: a bibliometric analysis

1 Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, China

2 Key Laboratory of Rehabilitation Medicine in Sichuan Province, Sichuan University, Chengdu, China

3 Department of Nursing, Zhejiang Zhoushan Tourism and Health College, Zhoushan, China

Yongzhen Qiu

4 Department of Nursing, Lishui Central Hospital and Fifth Affiliated Hospital of Wenzhou Medical College, Lishui, China

5 Department of Nursing, Hangzhou Normal University, Hangzhou, China

Jiajia Chen

6 Department of Nursing, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China

Associated Data

To investigate development trends and research hotspots of exercise for hypertension research and provide researchers with fresh perspectives for further studies.

Materials and methods

Articles and reviews regarding exercise and hypertension spanning May 1st 2003 to May 18th 2023 were retrieved from the Web of Science Core Collection (WOSCC) database. VOSviewer and Citespace were mainly used to perform and visualize co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references and keywords in this field.

A total of 1,643 peer-reviewed papers were identified, displaying a consistent increasing trend over time. The most prolific country and institution were Brazil and University of Sao Paulo, respectively. And we identified the most productive author was lrigoyen, Maria Claudia C, while Pescatello Linda S was the most co-cited author. Journal of hypertension was the most prominent journal, and Hypertension was the journal which was the most co-cited. And this field can be divided into 3 research themes: exercise interventions for hypertension, age-specific relevance of exercise for hypertension, and the global burden of hypertension and the role of exercise. According to the result of keywords analysis, epidemiological information, types of exercise, target population, mechanism, and study design are significant research areas. “Resistance training”, “adults”, and “heart rate variability” were identified as the major future research foci.

Conclusions

The findings offer a scientific insight into exercise for hypertension research, presenting researchers with valuable information to understand the current research status, hotspots, and emerging trends for future investigation.

Introduction

Hypertension, commonly known as high blood pressure, is characterized as a persistent elevation in blood pressure with an unclear etiology, thereby amplifying the risk for cerebral, cardiac, and renal events ( 1 ). The precise medical definition of hypertension varies among clinicians due to differential guideline recommendations. Some suggest that hypertension is defined by consistent readings exceeding 130/80 mmHg, whereas others advocate for a threshold of 140/90 mmHg ( 2 ). In the year 2010, hypertension was reported in approximately 31.1% of the global adult population. Projections predicted a rise of 60% by 2025, resulting in a prevalence of 29.2%, or around 1.56 billion individuals ( 3 , 4 ). By 2010, hypertension had emerged as the predominant single risk factor contributing to the global disease burden, accountable for 9.4 million deaths and 7.0% of global disability-adjusted life years, with impacts across all socio-economic strata ( 5 , 6 ). The economic implications of hypertension are also considerable. In 2003, the cumulative direct and indirect expenses associated with the management of hypertension in the US were estimated to be USD 50.3 billion ( 7 ).

The challenge with hypertension lies in its often-asymptomatic nature, making it difficult for individuals to realize their condition. If left uncontrolled over extended periods, hypertension can precipitate severe medical conditions, such as heart failure, myocardial infarction, stroke, vision complications, and kidney disease ( 1 ). Therefore, patient monitoring is a crucial aspect of hypertension management. It's typically controlled by medication and lifestyle changes, with exercise playing a crucial role. Numerous therapeutic exercise regimens have been implemented as interventions in hypertension management ( 8 ). In recent years, a multitude of studies have demonstrated that aerobic and resistance exercise, coupled with flexibility and balance exercises, can augment the quality of life for patients with hypertension ( 9 , 10 ). These improvements manifest in various ways such as enhancing cardiovascular system function, optimizing blood pressure control, and reducing the risk of apoplexy ( 11 , 12 ).

Bibliometric analysis, a robust quantitative research methodology, offers an objective framework to trace the intellectual evolution and structural composition of a specific research domain ( 13 ). It has been widely utilized to probe developmental trends and hotspots within various areas of publication ( 14 – 16 ). To our understanding, despite the steady increase in publications relating to exercise in the hypertension research field, no bibliometric analysis has yet been conducted. Findings derived from such bibliometric studies can enable investigators to pinpoint current research concerns, thereby guiding future research directions ( 17 ). Owing to its considerable advantages, the application of bibliometric methods holds significant value in the domain of exercise for hypertension research.

In this study, our objective is to conduct a thorough bibliometric analysis of research concerning exercise for hypertension. The intention is to offer a comprehensive assessment of the evolution within this field. By meticulously examining past achievements, evaluating the present state, and projecting potential future directions, we aspire to illuminate the landscape of exercise for hypertension research.

Data acquisition

The Web of Science Core Collection (WOSCC) database was searched extensively for publications relating to exercise for hypertension on 19 May 2023, which is frequently used and accepted for scientific or bibliometric studies. A peer-reviewed and supervised search term development process was conducted under the guidance of an expert with ten years of information retrieval experience. The data search strategy was “TI = (exercise* OR kinesitherapy OR train* OR “physical activit*” OR sport* OR fitness OR walk* OR run* OR swim* OR jog* OR cycling OR pilate* OR yoga OR qigong OR “tai chi” OR motion* OR athletic OR liuzijue OR wuqinxi OR dance OR yijinjing OR baduanjin OR taekwondo) AND TI = (hyperten* OR “high blood pressure”) AND Language = “English”. In this study, the publication types were restricted to “article” or “review”, time span = 2003.01.01–2023.05.18 ( Figure 1 ).

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Flowchart of the publications selection.

Data analysis and visualization

The data, which incorporates fully recorded and cited references, was downloaded from WOSCC. In addition to the Online Analysis Platform of Literature Metrology ( https://bibliometric.com/ ), VOSviewer 1.6.17, and CiteSpace 6.1.R3, this information was also imported into several analysis tools. The key metrics adopted in bibliometric studies encompass co-authorship, co-citation, and co-occurrence analysis. Specifically, co-authorship analysis aims to investigate the relationships among authors, nations, or institutions, predicated on the quantity of jointly produced papers. Co-occurrence analysis employs a quantitative methodology to explore the relationship between different elements, based on their concurrent appearances. Co-citation analysis reveals the relational strength of cited elements by considering the number of elements that cite them.

The Online Analysis Platform of Literature Metrology was employed for conducting co-authorship and publication analyses across various countries/regions. VOSviewer serves as a software tool for the creation and visualization of bibliometric networks, which may be formulated leveraging citations, common citations, or co-authorship collaborations ( 18 ). In the map instantiated by VOSviewer, each node symbolizes an element. In the context of this study, VOSviewer facilitated the analysis of clustering patterns among countries, institutions, authors, and journals, taking into account the number of publications, citations, and the linkage potency of each constituent. A wide link width between nodes signifies a robust degree of cooperation, and larger nodes denote a higher number of reflections. Concurrently, CiteSpace served as an invaluable tool for bibliometric analysis ( 19 , 20 ). Utilizing CiteSpace, we assessed keyword/reference clustering and timelines, as well as the centrality of countries, institutions, authors, and keywords. CiteSpace parameters were set as follows: (1) Time slice from 2003 to 2023, with each slice representing one year; (2) Single node type selection at a time; (3) Selection criteria were based on the g-index, with k = 15; (4) Pruning was performed via the pathfinder method. Moreover, Microsoft Excel 2019 was deployed to illustrate the global output and developmental trend of relevant papers. Impact factor (IF) and category quartile data were derived from the Journal Citation Reports (JCR) 2022 ( 21 ). The H-index is a composite index that serves as a significant metric for evaluating the quantity and quality of academic output produced by a scientific researcher, country, journal, or institution.

Research ethics

The data sources utilized in our study were derived from publicly accessible databases. As such, obtaining approval from an ethics committee was deemed unnecessary.

General information

Analysis of publications.

A total of 1,643 publications focused on exercise for hypertension research were identified between Jan 1st, 2003 and May 18th, 2023, including 1,485 articles and 158 reviews. The average annual output was 83. As presented in Figure 2 , the field of exercise for hypertension research exhibited a fluctuating publication output from 2003 to 2016, with an overall upward trend since 2017. The sustained increase in publications after 2017 likely reflects the growing recognition of exercise as a non-pharmacological intervention for hypertension prevention and management. The rising volume of publications on exercise for hypertension indicates that more studies are being conducted in this field, leading to the generation of new knowledge. The increasing interest in this topic might also indicate a recognition of the importance of non-pharmacological interventions for hypertension. Moreover, the 1,643 publications in this research field were cited a total of 32,491 times from 2003 to 2023. The number of citations increased from 5 in 2003 to 4,203 in 2022. The increase in citation rates over time indicates that the findings and insights produced by these studies are significant and relevant to the scientific community.

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The number of publications and total citations.

Analysis of countries/regions

Publications were published in 80 different countries/regions ( Figure 3 ). Table 1 lists the top 10 most productive countries/regions, with Brazil ( n = 420) leading, followed by the USA ( n = 382), and China ( n = 197). The USA had the highest citation count (9,414 times) and H-index = 49. Figure 3A shows a concentration of publications in North America, South America, Europe, and East Asia. Notably, China exhibited a substantial increase in publication output in 2021 ( Figure 3B ); this may be due to increased investment in research and development, an aging population, and high rates of hypertension prevalence ( 22 – 24 ). The cooperation network between countries and regions is depicted in Figures 3C,D , indicating that the USA collaborates with various countries, particularly Brazil and China. Total link strength (TLS) measures global co-authorship and is represented by the width of the lines connecting nodes. The visual co-authorship map reveals that the top three countries in terms of TLS are the USA, Brazil, and England. Beyond the USA, collaboration among other nations is limited. This underscores the need for fostering international partnerships to further advance exercise for hypertension research. Collaboration can pool resources, expertise, and knowledge from various regions to conduct more comprehensive and impactful studies.

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Visual map of countries/region. ( A ) Geographic distribution map based on the total publications of different countries/regions. ( B ) Number of annual publications and growth trends of the top 10 countries/regions. ( C ) Collaboration network analysis of the countries/regions. ( D ) The international network cooperation between the countries/regions.

Top 10 countries in the field of exercise for hypertension.

Rank	Countries	Counts	Citations	TLS	H-index	Centrality
1	Brazil	420	6,359	143	38	0.23
2	USA	382	9,414	222	49	0.47
3	China	197	2,243	74	27	0.06
4	England	92	1,682	121	25	0.35
5	Italy	80	1,299	49	21	0.16
6	South Korea	77	1,112	29	19	0.02
7	Australia	72	1,515	60	22	0.07
8	Canada	70	1,967	40	25	0.13
9	Japan	60	954	22	9	0.07
10	Germany	52	1,288	47	19	0.06

Analysis of institutions

Publications originated from 2197 different institutions ( Figure 4 ). Table 2 lists the top 10 most productive institutions. The University of Sao Paulo published the most papers ( n = 139), followed by Federal University of Sao Paulo ( n = 32) and Universidade Federal do Rio Grande do Sul ( n = 32).

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Collaboration network analysis of institutions.

Top 10 institutions in the field of exercise for hypertension.

Rank	Institution	Country	Counts	Citations	TLS	H-index	Centrality
1	University of Sao Paulo	Brazil	139	3,208	132	34	0.08
2	Federal University of Sao Paulo	Brazil	32	526	46	15	0.17
3	Universidade Federal do Rio Grande do Sul	Brazil	32	662	42	16	0.00
4	The Federal University of Minas Gerais	Brazil	26	432	37	14	0.07
5	University Catholic of Brazil	Brazil	25	596	33	12	0.13
6	Universidade Estadual de Londrina	Brazil	22	258	20	9	0.06
7	University of Illinois	USA	21	877	32	15	0.02
8	University of Copenhagen	Denmark	21	586	19	15	0.06
9	University of Queensland	Australia	21	612	15	14	0.21
10	University of Connecticut	USA	20	689	37	12	0.08

Analysis of journals

Over the past 20 years, 280 academic journals published articles related to exercise for hypertension. The top 10 journals published 23.25% ( n = 382) of these papers, as shown in Table 3 . The average IF of the top 5 journals is 5.914. Hypertension ( n = 48, IF = 9.897), a journal from the USA, had the highest IF among these journals. It focuses on basic science, clinical treatment, and prevention of hypertension and related cardiovascular, metabolic and renal diseases. The articles published in Hypertension are expected to remain significant for years to come. In terms of publications volume, the top three journals were Journal of hypertension (IF = 4.776), Hypertension (IF = 9.897), and Hypertension research (IF = 5.528). The Journal of Hypertension , based in the USA, focuses on research related to the basic science, clinical treatment, and prevention of hypertension, as well as associated cardiovascular, metabolic, and renal diseases. Given the quality and scope of its published papers, they are expected to remain significant for years to come.

Top 10 journals in the field of exercise for hypertension.

Rank	Journals	Counts	Citations	H-index	IF (2022)	JCR quartile
1	Journal of hypertension	59	832	17	4.776	Q1
2	Hypertension	48	1,573	20	9.897	Q1
3	Hypertension research	47	689	12	5.528	Q1
4	Clinical and experimental hypertension	44	296	10	2.088	Q3
5	American journal of hypertension	40	773	14	3.080	Q2
6	Journal of human hypertension	35	441	14	2.877	Q2
7	Frontiers in physiology	32	156	7	4.755	Q2
8	Journal of clinical hypertension	28	329	10	2.885	Q2
9	International journal of environmental research and public health	26	157	6	4.614	Q1
10	Journal of applied physiology	23	290	9	3.880	Q1

Analysis of authors

As many as 8,145 authors contributed to the research on exercise for hypertension. Table 4 presents the top 10 authors in exercise for hypertension research, with Maria Claudia C. Irigoyen ranking first ( n = 18), followed by Linda S. Pescatello ( n = 17), Li-jun Shi ( n = 15). The cooperation map ( Figure 5 ) indicates that the scale of collaboration among authors is relatively light, suggesting a need for increased overall connections between researchers in this field.

Top 10 authors in the field of exercise for hypertension.

Rank	Author	Counts	Citations	TLS	H-index	Country	Institution
1	Maria Claudia C. Irigoyen	18	340	25	11	Brazil	Universidade de Sao Paulo
2	Linda S. Pescatello	17	1,713	51	11	USA	University of Connecticut
3	Li-jun Shi	15	154	32	9	China	Fudan University
4	Claudia L. M. Forjaz	15	324	20	9	Brazil	University of São Paulo
5	Alexandre M. Lehnen	14	131	27	6	Brazil	Fundação Universidade de Cardiologia
6	Guilherme V. Guimarães	14	622	55	11	Brazil	Instituto do Coração do Hospital
7	James Sharman	13	374	19	11	Brazil	University of Tasmania
8	Antonio José Natali Marcos	13	149	49	7	Brazil	Universidade Federal de Viçosa
9	Polito Thales	13	133	40	7	Brazil	Universidade Estadual de Londrina
10	Nicolau Primo NP Gomes	12	142	48	7	Brazil	Universidade Federal de Viçosa

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Collaboration network analysis of authors.

Research hotspots

Analysis of co-cited journals.

The top 10 most-cited journals are displayed in Table 5 . A journal's influence in its respective field is determined by the frequency of co-citations, serving as a measure of its significance. Notably, nine journals in Table 5 have been cited over 1,000 times. The three most frequently co-cited publications were Hypertension (IF = 9.897), Circulation (IF = 39.918), and Annals of Internal Medicine (IF = 51.598).

Top 10 Co-cited journals in the field of exercise for hypertension.

Rank	Journals	Country	Citations	TLS	JCR quartile	IF (2022)
1	Hypertension	USA	4,206	1,75,831	Q1	9.897
2	Circulation	USA	2,859	1,34,912	Q1	39.918
3	Annals of Internal Medicine	USA	2,309	1,07,842	Q1	51.598
4	Medicine and Science in Sports and Exercise	USA	2,010	86,709	Q1	6.29
5	Journal of Applied Physiology	USA	1,536	69,997	Q2	3.880
6	American Journal of Hypertension	USA	1,253	64,058	Q2	3.080
7	Journal of the American College of Cardiology	USA	1,090	48,485	Q2	6.106
8	Lancet	USA	1,046	44,257	Q1	202.731
9	American Journal of Physiology-heart and Circulatory Physiology	USA	1,027	46,038	Q1	5.125
10	Journal of the American Medical Association	USA	973	47,731	Q1	151.335

Analysis of co-cited authors

The network map of co-cited authors is shown in Figure 6 . Linda S. Pescatello ranked first with 482 citations, followed by Cornelissen Véronique A, Mancia Giuseppe, and Chobanian Aram V with 411, 325, and 297 citations, respectively ( Table 6 ). The top 10 co-cited authors collectively exceeded 2,000 citations, highlighting their prominence and influence in the domain of exercise for hypertension research.

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The network visualization map of co-cited authors.

Top 10 Co-cited authors in the field of exercise for hypertension.

Rank	Author	Citations	TLS	Country	Institution
1	Linda S. Pescatello	482	4,602	USA	University of Connecticut
2	Cornelissen, Véronique A	411	3,887	Belgium	Catholic University of Leuven
3	Mancia, Giuseppe	325	2,679	Italy	Centro di Fisiologia Clinica e Ipertensione
4	Chobanian, Aram V	297	2,165	USA	Boston University School of Medicine
5	Fagard, R H	222	2,533	Belgium	University of Leuven
6	Whelton, Paul K	204	1,721	USA	University of Tulane
7	Whelton, Seamus P	142	1,471	USA	University of Tulane
8	Hagberg, J M	138	1,646	USA	University of Maryland
9	Kelley, G A	130	1,854	USA	University of Northern Illinois
10	Williams, Bryan	126	1,009	UK	University of Leicester

Analysis of co-cited references

Reference co-citation analysis determines highly co-cited references that are frequently cited together by other articles, making it a common approach for exploring research foci in a given academic field. The network map of co-cited references is displayed in Figure 7 , and Table 7 lists the top ten articles according to number of citations. We concluded that these ten articles concentrate on 3 research themes: (1) exercise interventions for hypertension prevention and treatment, (2) age-specific relevance of exercise for hypertension, (3) the global burden of hypertension and the role of exercise.

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The network visualization map of co-cited references.

Top 10 references in the field of exercise for hypertension research from 2003 to 2023.

Rank	Co-cited reference	Journal	Years	Co-cited counts	JCR quartile	IF (2022)
1	The seventh report of the Joint National Committee on prevention, detection and treatment of high blood pressure	Hypertension	2003	252	Q1	9.897
2	Exercise and hypertension	Medicine & Science In Sports & Exercise	2004	240	Q1	6.29
3	Exercise training for blood pressure: a systematic review and meta-analysis	Journal of The American Heart Association	2013	169	Q2	6.106
4	Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials	Annals of Internal Medicine	2002	139	Q1	51.598
5	Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors	Hypertension	2005	120	Q1	9.897
6	Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies	Lancet	2002	91	Q1	202.731
7	Global burden of hypertension: analysis of worldwide data	Lancet	2005	88	Q1	202.731
8	The role of exercise training in the treatment of hypertension: an update	Sports Medicine	2000	70	Q1	11.928
9	Exercise for Hypertension: A Prescription Update Integrating Existing Recommendations with Emerging Research	Current Hypertension Reports	2015	65	Q3	3.036
10	Impact of resistance training on blood pressure and other cardiovascular risk factors: a meta-analysis of randomized, controlled trials	Hypertension	2011	61	Q1	9.897

Analysis of keywords co-occurrence

Keywords summarize the core material of a paper in great detail. Table 8 reports the top 20 keywords, while Figures 8A , ,B B illustrate the co-occurrence and cluster analysis of these keywords, respectively. Within the exercise for hypertension research, significant research areas encompass epidemiological information (e.g., risk, mortality, prevalence), types of exercise (e.g., aerobic exercise, resistance exercise), target population (e.g., adults, men), mechanism (e.g., adrenergic blockade, oxidative stress), and study design (e.g., meta-analysis). To display temporal trends, a timeline plot was constructed ( Figure 8C ). In the field of exercise for hypertension, a total of seven clusters have been identified, with “#2 hypertension-induced diastolic heart failure,” “#3 isometric handgrip training,” “#5 hypertensive response,” and “#7 atrial natriuretic peptide” emerging as recent research hotspots.

Top 20 keywords in the field of exercise for hypertension.

Rank	Keywords	Occurrences	Centrality	Rank	Keywords	Occurrences	Centrality
1	Risk	244	0.01	11	Intensity	81	0.09
2	Aerobic exercise	180	0.01	12	Response	80	0.03
3	Adults	167	0.02	13	Prevalence	80	0.03
4	Adrenergic blockade	131	0.01	14	Men	75	0.05
5	Meta-analysis	131	0.01	15	Arterial stiffness	74	0.05
6	Management	126	0.03	16	Postexercise hypotension	69	0.03
7	Oxidative stress	115	0.06	17	Mechanisms	69	0.02
8	Mortality	109	0.04	18	Cardiovascular disease	62	0.01
9	Prevention	106	0.07	19	Resistance exercise	60	0.05
10	Nitric oxide	82	0.05	20	Guideline	57	0.10

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Analysis of keywords. ( A ) Keywords co-occurrence. ( B ) Keyword clustering. ( C ) Timeline of keywords.

Global trends of exercise for hypertension research

Analysis of keywords with the strongest citation bursts.

Since 2003, a total of 30 keywords have experienced significant bursts. The results of burst detection are illustrated in Figure 9 , showing that keywords such as “resistance training”, “adults”, “heart rate variability” gained prominence in recent years. This indicates that research concerning these topics is currently garnering attention and signifies potential developmental trends in the field of exercise for hypertension research.

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Visualization map of top 30 keywords with the strongest citation bursts.

The timeline view of co-cited references serves as a visual diagram reflecting the temporal characteristics of research hotspots in this field. Among the 12 clusters depicted in Figure 10 , the #8 cluster, focusing on aortic endothelium-dependent vasorelaxation, emerged as the earliest research hotspot. Currently, the most prevalent research hotspots are #0 systematic review and #2 essential hypertension.

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Timeline of co-cited reference.

The research on exercise for hypertension has been extensively studied over the last two decades. The subject has been researched in 80 countries, with eight developed and only two developing countries among the top 10 countries studied. Despite ranking second in published papers, the USA has the highest centrality score, indicating its leadership in this research area. This can be attributed to the country's high prevalence of hypertension and substantial investment in exercise treatment for hypertension. Brazil ranks first in the number of articles published on this topic. This may be associated with the high incidence of hypertension in the country and the low cost of exercise treatment ( 25 ). China follows closely in third place, which may also be credited to the high incidence of hypertension and the popularity of traditional Chinese practices such as Baduan Jin and Tai Chi ( 26 , 27 ). The top 10 institutions make up 21.85% of total publication yields, indicating significant academic accomplishments. Brazil's University of Sao Paulo, the country's leading comprehensive university, is the top-ranked institution, closely working with the fifth-ranked University Catholic of Brazil.

A total of 280 diverse academic journals published articles related to exercise for hypertension research, with the top 10 journals accounting for 23.25% of the publications. Among these, the Journal of Hypertension was the most frequently published journal, while it was challenging to publish relevant papers in high impact factor journals. The identification of crucial authors can aid investigators in finding potential collaborators. Irigoyen Maria Claudia C, Linda S. Pescatello, and Shi Li-jun were the most productive and influential authors in this area. Irigoyen Maria Claudia C is a researcher from the Universidade de Sao Paulo whose work focuses on exploring the relationship between physical activity, heart health, and hypertension. Her research supports the use of exercise therapy as a complementary approach to managing hypertension and improving overall cardiovascular health ( 28 , 29 ).

According to the co-cited authors, Linda S. Pescatello from USA is the top-ranked author for co-citations. In her most recent work, she discovered that, in individuals with resistant hypertension, a 12-week aerobic exercise regimen resulted in 24-hour and ambulatory daytime blood pressure, as well as office systolic blood pressure. Her discovery strengthens the evidence base advocating for the integration of moderate-intensity aerobic exercise as a standard adjunctive therapy for this patient demographic ( 30 , 31 ). The highest co-cited reference was published by Linda S. Pescatello in 2003 in the journal Hypertension ( 32 ). This paper reported that a healthy lifestyle can lower blood pressure, with exercise being an important way to promote recovery from hypertension.

Our analysis of co-occurrence keywords revealed five important research areas: epidemiological information, types of exercise, target population, mechanism, and study design. Hypertension epidemiology has been a hot topic due to its increasing global incidence; the latest data reveals that hypertension affects 34% of the world's population ( 32 , 33 ). It is a significant risk factor for cardiovascular disease(CVD), chronic kidney disease, dementia, and other major illnesses. Aerobic and resistance exercises are currently the most popular methods used to intervene in hypertension. Exercise training results in considerable reductions in all hypertension blood pressure measures in individuals with hypertension ( 34 ). While further evidence is necessary to determine whether exercise can replace anti-hypertensive drugs, exercise training, particularly using aerobic modalities, appears to be an effective adjunctive therapy treatment for hypertension ( 35 ). Resistance exercise training has also been shown to reduce blood pressure ( 9 , 36 ). Among the target population, hypertensive patients are prevalent among adults with men older than 50 years at higher risk for hypertension ( 37 , 38 ).

The mechanism of exercise in treating hypertension is a research hotspot, particularly regarding adrenergic blockade and oxidative stress. Adrenergic blockade is one of the most important drug treatments for hypertension and heart disease. It can inhibit the effects of adrenaline on the body via β-blockers or α -blockers, which slow the heart rate, dilate blood vessels, and lower blood pressure ( 39 , 40 ). Combined with exercise, adrenergic blocking drugs can synergistically control hypertension. During aerobic exercise, adrenaline secretion is suppressed, achieving better blood pressure-lowering effects. Additionally, aerobic exercise reduces the level of adrenaline in the blood ( 41 ). Furthermore, numerous studies have shown that exercise can reduce oxidative stress and inflammatory responses, leading to blood pressure reduction, and improvements in vascular function ( 42 , 43 ). The hormone Atrial Natriuretic Peptide (ANP), currently a pivotal area of research, is secreted by the heart, playing a significant role in the regulation of processes such as blood pressure and fluid balance. Studies indicate that ANP levels often decrease in patients with hypertension. This reduction could stem from cardiovascular alterations caused by hypertension, hampering ANP secretion or perhaps due to adaptive bodily mechanisms causing a decrease in ANP levels. Conversely, exercise has demonstrated potential in enhancing ANP levels by stimulating ANP production via increased cardiac output and heightened Sympathetic Nervous System activity. This amelioration leads to a reduction in blood pressure and assists in balancing body fluid ( 44 – 46 ).

Meta-analysis is a systematic and statistical method for integrating existing studies that combines the results of independent studies to evaluate the overall effect of a specific variable or intervention. It is commonly used in exercise for hypertension research due to the large number of studies, variability in findings, ability to assess effect sizes, and development of appropriate guidelines and recommendations. By combining multiple studies, it improves the reliability and accuracy of overall studies, allowing physicians and the public to better understand how to prevent and treat hypertension. Since 2020, 55 meta-analyses on exercise interventions for hypertension have been published. One of the highest IF meta-analyses was published in the British Journal of Sports Medicine (IF = 18.479) ( 47 ). This study revealed that short-duration exercise of any type can reduce the risk of all-cause mortality and serious adverse events in patients with hypertension, type 2 diabetes, or CVD.

Global trends

Research frontier themes are frequently indicated by keywords with citation bursts. A thorough examination of the most recent keyword bursts revealed three new trends in exercise for hypertension research. These are what they are:

I. Resistance training: Resistance training, also referred to as strength or weight training, is a type of exercise that primarily aims to develop and strengthen skeletal muscles. Its positive effect on hypertension has been well-documented in several studies, which have shown a decrease in blood pressure among individuals with hypertension who engage in resistance training. This can be attributed to the improvement of arterial compliance, vascular function, and reduction of arterial stiffness, all of which contribute to better blood flow and lower blood pressure ( 48 , 49 ). Moreover, resistance training promotes muscle growth and overall cardiovascular health, further supporting its effectiveness as an adjunct therapy for hypertension ( 36 ). Combining resistance training with aerobic exercise may provide additional benefits for individuals with hypertension. Nonetheless, more research is required to determine the optimal frequency, intensity, and duration of resistance training for different populations with hypertension ( 9 , 50 , 51 ).
II. Adults: The World Health Organization defines individuals aged 18 years and older as adults, a group that is differentiated from children and adolescents in the fields of medicine and public health due to varying health concerns and risks. Adults are more susceptible to chronic diseases, including hypertension, which poses a significant economic and public health burden. Improving lifestyles, particularly through exercise, among young people is crucial in preventing age-related increases in blood pressure. Management strategies for hypertension in older adults must consider factors such as frailty, complex medical comorbidities, and psycho-social factors on an individual basis. Non-pharmacological lifestyle interventions should be encouraged to reduce the risk of developing hypertension and to serve as adjunctive therapy to lower the need for medications ( 36 , 37 , 49 ).
III. Heart rate variability (HRV): HRV refers to the variation in the time interval between consecutive heartbeats, also known as the change in the speed of the heartbeat. Higher HRV is generally associated with better cardiovascular function and resilience, while lower HRV is linked to a higher risk of anxiety and depression, as well as increased mortality from CVD ( 52 ). Regular exercise, particularly endurance training, has been found to improve HRV levels. In a study involving middle-aged hypertensive women, combined aerobic and resistance training resulted in significant improvements in HRV parameters ( 53 ). As such, exercise programs that incorporate both aerobic and resistance training may be beneficial for the management of hypertension by enhancing cardiac autonomic control ( 54 ).

There are several limitations to note in this study. Firstly, we only utilized WOSCC as our database, which may have led to the omission of relevant papers from other databases. Secondly, there is a possibility that significant non-English papers were overlooked, resulting in research bias and a reduction in credibility. Finally, due to the constant updates of the database, recently published high-quality articles may have been underestimated because of their inadequate citations.

The analysis of literature on exercise for hypertension from 2003 to 2023 shows an increasing interest, with major contributions from the US and University of São Paulo. Publications primarily come from Brazil, USA, and China, underscoring the importance of international collaboration in this domain. Exercise is gaining prominence as an essential non-pharmacological means to prevent and manage hypertension. Notable authors include Maria Claudia C. Irigoyen and Linda S. Pescatello. Increasing author collaborations are observed, though further cooperation is needed. Key themes include hypertension prevention and treatment through exercise, age-specific relevance, and global impact. New trends focus on “hypertension-induced diastolic heart failure” and “isometric handgrip training.” This bibliometric review offers valuable insights on emerging trends and future research direction in exercise for hypertension.

Acknowledgments

The authors also thank Shaojie Wu and Wenyue Sun for their effort in polishing the English content of this manuscript.

Funding Statement

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.

Author contributions

YL: Data curation, Methodology, Writing – original draft, Writing – review & editing. NS: Methodology, Software, Writing – review & editing. MZ: Formal analysis, Methodology, Software, Writing – review & editing. YQ: Data curation, Methodology, Supervision, Writing – review & editing. JW: Data curation, Methodology, Software, Writing – review & editing. JC: Formal analysis, Methodology, Software, Supervision, Writing – review & editing.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at https://www.frontiersin.org/articles/10.3389/fcvm.2023.1260569/full#supplementary-material

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