BackgroundChildhood hypertension is strongly associated with the development of cardiovascular diseases in adulthood. Understanding the epidemiological patterns of disease burden is crucial for developing effective prevention strategies.MethodsThis cross-sectional study utilized data from the Global Burden of Disease Study (GBD) 2021, including 204 countries and territories. The analysis estimated deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) attributable to high systolic blood pressure (sBP) among individuals under the age of 20 within the GBD comparative risk assessment (CRA) framework, covering the period from 1990 to 2021. Trends and regional disparities in disease burden were examined, emphasizing correlations between DALY rates and socio-demographic indices (SDI).ResultsIn 2021, the global DALY rate was 2.39 (95% uncertainty interval [UI], 1.75 to 2.88) per 100,000 population, representing a 20.11% decrease (95% UI, −35.02 to 10.21) compared to 1990. The YLL rate showed a decrease of 21.06% (95% UI, −36.21 to 9.95), contributing to the decline in the DALY rate, whereas the YLD rate showed an increase of 22.33% (95% UI, 4.16 to 40.74). The DALY rates were negatively correlated with Socio-demographic Index. Among the 21 GBD regions in 2021, Middle East and North Africa (MENA) showed the highest disease burden across all metrics. Western Sub-Saharan Africa (SSA) demonstrated a pronounced gender disparity. High-income North America experienced the largest increase in disease burden.ConclusionsGlobal DALYs and deaths attributable to high sBP among children and adolescents suggested a declining trend from 1990 to 2021, although the 95% UIs were compatible with no clear change. DALYs showed a negative correlation with SDI, with highest burden in MENA and notable gender disparities in Western SSA. High-income North America showed the largest increase since 1990.

BackgroundWhile the transgenerational impact of famine on adult health is well-documented, its impact on blood pressure (BP) trajectories from childhood to adolescence remains poorly understood. We aimed to capture multi-generational BP trajectories and identify the primary drivers of adolescent BP elevation.MethodsUtilizing data from the China Health and Nutrition Survey, we analyzed BP trajectories in the F1 (n = 5,357) and F2 (n = 2,349) generations. The F1 generation was categorized into 2 groups: famine exposed and non-exposed groups, while the F2 generation was divided into 4 groups: no parental exposure, father-only-exposed, mother-only-exposed, and both-parents-exposed. Linear mixed-effects models and causal mediation analyses were conducted to ascertain BP trajectories and the mediation of parental body mass index (BMI).ResultsIn the F1 generation, BP of famine-exposed individuals surpassed that of controls after age 40. In the F2 generation, BP trajectory divergence occurred at approximately age 14. By age 18, all exposed groups had significantly higher BP than controls, independent of parental hypertension (P < 0.01). Notably, the mother-only-exposed group exhibited the highest velocity of BP elevation; however, after excluding offspring with hypertensive parents, the father-only-exposed group exhibited the fastest velocity of BP increase. Mediation analysis revealed that over 85% of this effect was direct, with parental BMI accounting for only 14.51% and 10.08% of the effect for systolic and diastolic BP, respectively.ConclusionsIndividuals with direct famine exposure possess higher rate of BP elevation. Furthermore, parental famine exposure programs an accelerated BP velocity in offspring that manifests during early adolescence. These findings suggest that the famine exposure creates a subclinical vascular risk that requires early monitoring, independent of adiposity and hypertension.

BackgroundPatients with repaired coarctation of the aorta (CoAo) remain at risk for left ventricular hypertrophy (LVH) even in the absence of hypertension. Alterations in wave reflection and the timing of reflected pressure waves may contribute to ventricular remodeling beyond pressure load alone.MethodsWe performed a cross-sectional analysis of patients with repaired CoAo. Office and ambulatory blood pressure (ABPM), non-invasive central hemodynamics, and echocardiographic indices of left ventricular structure were assessed. Linear and multivariable regression models evaluated associations with posterior wall thickness in diastole (PWTd) and interventricular septal thickness in diastole. Computational simulations were conducted to examine the impact of heart rate on ventricular remodeling.ResultsFifty-seven patients (median post-repair follow-up 11 years) were included. LVH prevalence was 15.2% (95% confidence interval [CI], 4.8, 25.6). Although 42% met criteria for hypertension based on ABPM, no patients exhibited elevated central blood pressure and LVH. Heart rate–adjusted augmentation index (AIX@75) was inversely associated with PWTd and remained independently associated after multivariable adjustment (R2 = 0.40, P < 0.01). Replacing AIX@75 by heart rate improved model performance (R2 = 0.44), with lower heart rate independently associated with greater PWTd. Simulation modeling showed that a 10% increase in heart rate reduced mean PWTd and decreased posterior wall hypertrophy prevalence from 30.9% to 2.4% (odds ratio, 0.10; 95% CI, 0.01, 0.44).ConclusionsVentricular remodeling occurs despite normal central blood pressure in CoAo. A lower heart rate associates with increased ventricular mass. Heart rate–mediated modulation of wave reflection timing represents a potential mechanistic and therapeutic target.

Renal denervation (RDN) has re-emerged as a therapeutic option for hypertension following contemporary sham-controlled randomized trials demonstrating modest but consistent blood pressure (BP) reductions. Despite these advances, substantial heterogeneity in treatment response persists, sustaining debate regarding the clinical value and appropriate role of RDN. Increasing evidence suggests that patient-related factors, rather than device technology alone, may critically determine therapeutic success. This narrative review synthesizes evidence from randomized clinical trials, meta-analyses, and key observational studies published between 2009 and 2024. Relevant literature was identified through searches of PubMed, Embase, and major cardiovascular society publications. We evaluated the influence of hypertension phenotype, baseline BP, medication adherence, sympathetic nervous system activity, renal artery anatomy, and comorbid conditions on BP response to RDN. Accumulating data indicate that response to RDN is highly variable and strongly influenced by patient-specific characteristics. Sustained hypertension confirmed by ambulatory BP monitoring, higher baseline BP, features suggestive of sympathetic overactivity, favorable renal artery anatomy, and challenges with long-term medication adherence are consistently associated with greater BP reduction. In contrast, pseudoresistance, white-coat hypertension, advanced arterial stiffness, and unfavorable anatomy are linked to attenuated or inconsistent responses. Reassessment of sham-controlled trials highlights that observed BP reductions, although modest, are clinically meaningful when appropriately contextualized. The efficacy of RDN is highly context-dependent and should not be viewed as universal or ineffective. By shifting from a device-centered paradigm to mechanism-based patient phenotyping, RDN may be more accurately positioned as a targeted, adjunctive therapy within personalized hypertension management. A structured framework for patient selection may help reconcile prior controversies, optimize clinical implementation, and inform the design of future trials.

Hypertension remains a leading contributor to global cardiovascular (CV) morbidity and mortality, yet blood pressure (BP) control rates remain suboptimal worldwide. Therapeutic inertia, delayed treatment intensification, dose-dependent adverse effects, and limited healthcare access continue to hinder effective management. Low-dose combination therapy has emerged as a strategy to enhance efficacy while improving tolerability by targeting complementary pathophysiological pathways at reduced drug doses. This review describes the evolution of low- and ultra-low-dose combination therapy from its pharmacologic rationale and early proof-of-concept studies to contemporary randomized and pragmatic trials. Meta-analytic and clinical evidence have demonstrated that combining antihypertensive agents at fractional doses produces additive BP reductions with fewer dose-related adverse effects. Subsequent trials evaluating quarter-dose and one-third-dose multidrug regimens confirmed substantial BP lowering with favorable safety profiles. Pragmatic studies further supported the feasibility of simplified, protocol-based single-pill strategies in real-world and resource-limited settings. More recent phase III trials have shown that single-pill low- and ultra-low-dose triple combinations achieve BP reductions comparable to or greater than those of standard-dose monotherapy, without compromising safety. Current evidences support low- and ultra–low-dose single-pill combination therapy as a practical and scalable first-line approach to improving global hypertension control. However, the current evidence base is dominated by trials evaluating short-term BP lowering rather than long-term CV outcomes. Although the magnitude and consistency of BP reduction provide a strong rationale for this strategy, evidence for reductions in CV events and mortality is warranted.

The recently released 2026 Korean Society of Hypertension (KSH) guidelines incorporate contemporary advances in the diagnosis and management of hypertension. This highlight summarizes the most important updates, focusing on the underlying evidence and key changes, particularly the newly introduced and revised recommendations. The major additions include the incorporation of isolated diastolic hypertension into blood pressure (BP) classification, the first integration of cuffless BP devices into clinical practice, and the incorporation of a new therapy with a BP-lowering effect (angiotensin receptor–neprilysin inhibitors, sodium–glucose cotransporter 2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and aldosterone synthase inhibitors). A dose-based classification of single-pill combination therapies has been introduced to enhance treatment adherence. In addition, obesity, hypertension in young adults, hypertensive emergencies, and patient-centered care have been incorporated and emphasized. Major updates include expanded screening for primary aldosteronism, adoption of more intensive BP targets, and risk-based initiation of pharmacological therapy in individuals with prehypertension. Lifestyle recommendations have been broadened to include e-smoking cessation and mind-body practices. Furthermore, the definition and management of uncontrolled (or resistant) hypertension have been updated, and BP targets in older adults are now individualized according to frailty status and overall cardiovascular risk; intensive BP lowering to 130/80 mmHg is recommended in selected high-risk older individuals. Finally, BP management during pregnancy has also been refined to emphasize active BP control at < 140/90 mmHg and the use of out-of-office BP measurements for more accurate diagnosis. Overall, the new KSH guidelines provide a more evidence-based framework for hypertension management, with the goal of improving BP control and reducing cardiovascular morbidity and mortality.

BackgroundThe optimal treatment for individuals with high-normal blood pressure (BP, systolic BP 130–139 mmHg and diastolic BP < 90 mmHg) is debated. This study evaluates whether pharmacologically reducing systolic BP to below 130 mmHg could prevent major adverse cardiovascular events (MACE) in high-normal BP cases with no comorbidities and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥ 7.5%.MethodsIn this randomized, controlled, parallel, unicentric trial, participants were assigned to either an intervention group (pharmacotherapy plus diet control) or a control group (diet control only). The study aimed for 1,600 participants but was terminated after the first phase due to limited resources and recruitment challenges. Fixed-dose combinations of valsartan and amlodipine were administered as BP-lowering agents. Follow-up visits every 3 months adjusted pharmacotherapy to maintain systolic BP < 130 mmHg in the intervention group and < 140 mmHg in the control group. MACE was the primary endpoint, with its components (cardiovascular death, myocardial infarction, stroke, and heart failure) as secondary endpoints. Multivariable Cox regression analysis was utilized to compare the group endpoints.ResultsOf 14,562 screened individuals, 231 in the intervention and 235 in the control group were included in the final intention-to-treat analysis. At baseline, the control group had a slightly higher mean age than the intervention group (67.7 vs. 66.1 years; P = 0.013). Females comprised a minority in both groups (19.5% in intervention vs. 16.2% in control; P = 0.397). The mean 10-year ASCVD risk was slightly higher in the control group (17.4% vs. 15.9%; P = 0.013). The MACE occurred in 9 participants (1.57 per 100 person-year) in the intensive treatment group vs. 24 (4.16 per 100 person-year) in the control group (adjusted hazard ratio [aHR], 0.26; 95% confidence interval [CI], 0.11–0.62; P = 0.003). The incidence of serious adverse events (hypotension, syncope, injurious falls, electrolyte imbalances, or acute kidney injury) was similar between the groups (aHR, 1.47; 95% CI, 0.82–2.62; P = 0.195).ConclusionsPRINT-TAHA9 findings suggest that pharmacological BP reduction may benefit healthy asymptomatic individuals with high-normal BP and ASCVD risk ≥ 7.5%.Trial RegistrationIranian Registry of Clinical Trials Identifier: IRCT20191002044961N1

[This retracts the article 3 in vol. 22, PMID: 26973794.].

BackgroundHypertension is a leading risk factor for cardiovascular disease and mortality. It is often treated as a uniform entity despite evidence highlighting distinct outcomes associated with isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and combined systolic-diastolic hypertension (SDH). ISH predominates in older adults and is linked to adverse outcomes through arterial stiffness and increased pulse pressure, whereas IDH is more common in younger populations, with unclear long-term mortality implications. In this study we aim to explore differences in mortality between ISH, IDH and SDH in the general population and in patients with coronary artery disease (CAD).MethodsWe conducted a longitudinal analysis using National Health and Nutrition Examination Survey data (1999–2020), examining 47,582 adults aged 20 to 84. Participants were categorized by hypertension subtypes: ISH, IDH, SDH, or normotensive. Mortality data (1999–2018) were obtained via the National Death Index. Primary outcomes included demographic and clinical differences across groups; secondary outcomes assessed all-cause mortality using weighted logistic regression and Kaplan-Meier survival analysis. Analyses were stratified by CAD status and adjusted for key sociodemographics and comorbidities.ResultsISH patients were older (mean age 65.9) with higher Medicare coverage and lower education levels; IDH patients were younger, predominantly male, and more likely to be uninsured. Age-adjusted mortality was highest in ISH (adjusted odds ratio [aOR], 1.32, 95% confidence interval [CI], 1.24–1.41), followed by SDH (aOR, 1.60, 95% CI, 1.39–1.84). IDH showed no significant mortality risk at blood pressure (BP) ≥ 130/80 but demonstrated increased risk at diastolic BP ≥ 90 mmHg (aOR, 1.45, 95% CI, 1.12–1.89). ISH remained a significant mortality predictor after adjusting for age. IDH showed a shift from apparent protection in unadjusted models to risk after adjustment, suggesting heterogeneity based on age and severity.ConclusionsThis study sheds focus on systolic and diastolic components of hypertension. ISH is associated with increased mortality, independent of age, and should prompt prioritizing systolic control. IDH—more prevalent in younger adults—warrants age-specific management strategies. Findings support differential treatment thresholds for hypertension subtypes and underscore the need for longitudinal studies to better define IDH’s long-term risk.