This review examines determinants across structural, institutional, interpersonal, and individual domains that contribute to hypertensive disorders of pregnancy (HDPs) in American Indian and Alaska Native (AI/AN) populations and their long-term cardiovascular consequences. It suggests paths forward for equitable research and clinical practice. AI/AN women have the highest HDP prevalence among all racial and ethnic groups at 9.1
To evaluate the crosstalk between the liver, heart, and kidneys in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), highlighting the distinct regulatory roles of non-traditional hepatokines, and to assess shared therapeutic targets and molecular mechanisms driving cardiorenal complications in MASLD patients. Emerging evidence highlights that hepatic lipid accumulation drives cardiac damage, which manifests as adverse remodeling, diastolic dysfunction, and coronary microvascular dysfunction. These abnormalities are mediated primarily by systemic lipotoxicity, inflammation of epicardial adipose tissue, and a pro-thrombotic environment. Mechanistically, altered hepatokine signaling mediates systemic cross-talk. Specifically, the downregulation of cardioprotective and renoprotective brain-derived neurotrophic factor (BDNF) and the dual metabolic roles of nerve growth factor (NGF), fibroblast growth factor (FGF) 19, and FGF21 accelerate the progression of both heart failure and chronic kidney disease (CKD). Concurrently, metabolic therapies such as glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and peroxisome proliferator-activated receptor (PPAR) agonists demonstrate significant efficacy in ameliorating steatosis, inflammation, and overall metabolic outcomes. MASLD acts as a systemic driver of multi-organ dysfunction within the cardio-renal-hepatic axis. Profiling specific hepatokine signatures offers a promising frontier for identifying novel therapeutic targets and biomarkers of disease acceleration. Furthermore, while current metabolic therapies show remarkable potential, rigorous clinical testing remains critical to definitively determine whether their cardiovascular and renal benefits stem from direct tissue-specific protective mechanisms or secondary metabolic improvements.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic cardiometabolic disease. This review summarizes recent advances in epidemiology, pathophysiology, biomarkers, and treatment relevant to cardiovascular risk assessment and management. Fibrosis stage is the strongest independent predictor of cardiovascular outcomes in MASLD, conferring up to a 2.5-fold increase in events beyond traditional risk factors. Noninvasive tools, including Fibrosis-4 (FIB-4) and liver stiffness measurement, also predict cardiovascular mortality. Semaglutide and resmetirom offer dual hepatic and cardiometabolic benefits. MASLD affects 38
To review contemporary evidence regarding optimal aspirin dosing for prevention of preeclampsia, focusing on dose–response relationships, timing of initiation, and phenotype-specific prophylaxis. Recent trials and meta-analyses have produced conflicting findings regarding whether higher-dose aspirin (100–162 mg daily) provides greater protection against preeclampsia than conventional 75–81 mg regimens. Benefit appears greatest in placental-risk phenotypes and select high-risk populations, including patients with obesity, multifetal gestation, chronic hypertension, diabetes, and multiple concurrent risk factors. Pharmacokinetic studies indicate altered aspirin metabolism and reduced platelet inhibition during pregnancy, supporting biologic plausibility for higher-dose strategies. However, pragmatic real-world studies remain mixed, and definitive recommendations are lacking. Aspirin efficacy is phenotype-dependent, and optimal dosing likely varies according to placental biology, pharmacokinetics, and baseline risk. Emerging evidence supports individualized prophylaxis emphasizing early initiation and consideration of higher-dose aspirin in select high-risk populations.
Tissue perfusion is tightly regulated by central neural circuits that integrate autonomic and sensory inputs to match blood flow to tissue metabolic demand. This review synthesizes current knowledge on the central mechanisms governing tissue perfusion in both physiological and pathological states, with emphasis on the organization of brain networks involved in cardiovascular control. Recent advances reveal that tissue perfusion is modulated not only by classical reflex pathways, but also by humoral, metabolic, immune, and neuromodulatory systems. Key brain regions, particularly within the brainstem, coordinate sympathetic and parasympathetic outflows through complex and state-dependent interactions that dynamically regulate vasomotion and cardiac function. Emerging evidence also demonstrates that maladaptive remodeling of these central networks contributes to vascular dysfunction in disorders such as hypertension and heart failure, promoting tissue hypoxia and end-organ damage. Central neural mechanisms play a pivotal role in the regulation of tissue perfusion under both healthy and diseased conditions. A comprehensive understanding of the neural circuits and signaling pathways involved in perfusion control may support the development of targeted therapeutic strategies aimed at restoring vascular homeostasis and improving outcomes in cardiocirculatory and neurovascular diseases.
The purpose of this review is to describe the intersection between pediatric hypertension and advancing stages of cardiovascular, kidney metabolic syndrome in children and adolescents. Cardiovascular-kidney-metabolic syndrome is highly prevalent in the pediatric population. The onset of CKM in childhood is influenced by the presence of antenatal risk factors such as maternal hypertensive disorders of pregnancy. Advancing stages of CKM in children and adolescents are strongly influenced by food insecurity and social determinants of health that impact the risk for childhood obesity. Activation of the renin-angiotensin-aldosterone system is a key mediator in the relationship between antenatal risk, early life course exposure and hypertension in children and adolescents. Effective strategies for slowing the rate of advancement of CKM staging in children and adolescents require attention to early course factors that influence the development of hypertension and obesity. Likewise, management strategies and therapeutic interventions that address these factors are critical to mitigating CKM stage advancement. Although hypertension is a component of the CKM framework, the presence of hypertension in children and adolescents drives higher CKM staging. Together, hypertension and higher CKM staging are associated with increased atherosclerotic cardiovascular disease risk. Social factors, including access to healthy foods and attention to early life course nutrition are critical strategies to improving CKM and hypertension related outcomes in children and adolescents.
To evaluate the emerging role of aldosterone synthase inhibitors (ASIs) in combination with sodium–glucose cotransporter 2 (SGLT2) inhibitors for the management of uncontrolled hypertension in patients with chronic kidney disease (CKD), and to assess their potential cardiorenal benefits. SGLT2 inhibitors confer modest blood pressure reduction alongside cardiorenal protection across diverse CKD populations. ASIs such as baxdrostat and lorundrostat demonstrate clinically meaningful reductions in systolic blood pressure, with early evidence suggesting favorable effects on albuminuria. Recent trials in CKD populations demonstrate improved blood pressure control and reductions in proteinuria, while combination therapy suggests mitigation of hyperkalemia risk through SGLT2 inhibitor–induced kaliuresis. Ongoing large-scale trials are evaluating long-term renal and cardiovascular outcomes of this combination strategy. The combination of ASIs and SGLT2 inhibitors represents a mechanistically complementary approach to targeting RAAS dysregulation, volume status, and metabolic pathways. This strategy has the potential to redefine treatment paradigms for CKD-associated uncontrolled hypertension, pending evaluation of long-term outcome benefits.
Resistant hypertension (RH) affects more than a tenth of adults and yet remains relatively underrecognized and undertreated. The electronic health record (EHR) now stands as a critical tool for overcoming barriers to the diagnosis and treatment of RH, specifically with respect to aiding in detection, excluding alternate diagnoses, and guiding clinical decision making. We review how the EHR has clarified the population level prevalence of RH and its impact on both quality of life and longevity. We examine how the EHR can be leveraged to identify relevant specific causes of elevated blood pressure such as medication non-adherence, clinical inertia, White Coat Effect, and hyperaldosteronism, among others. Additionally, we highlight the promises and potential pitfalls that warrant consideration when implementing novel EHR interventions to address clinical challenges such as RH. In particular, we discuss the importance of balancing augmented data availability with the need for streamlined data flow to clinicians, so that enhanced workflows can both maximize efficiency and improve quality of care. As the EHR continues to transform the practice of care delivery, RH represents a uniquely well-suited area for improving clinical identification and management in ways that could not be otherwise readily achieved in practice.
This review evaluates the antihypertensive potential of next-generation incretin-based therapies, including GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists. It examines their effects on blood pressure reduction, underlying mechanisms, clinical benefits, and implications for future guidelines. Recent large-scale trials demonstrate that incretin-based therapies such as semaglutide and tirzepatide significantly reduce body weight, blood pressure, and cardiovascular outcomes. Mediation analyses indicate that weight loss explains a substantial proportion of blood pressure reduction, while direct effects on vascular function, renal sodium handling, and neurohumoral pathways also contribute. These effects are consistent across diverse populations, including individuals without overt hypertension. Incretin-based therapies represent a promising approach in hypertension management, combining metabolic and cardiovascular benefits. Despite the lack of trials with blood pressure as a primary endpoint, current evidence supports their use in selected high-risk populations and suggests an emerging role in future guideline recommendations.
To review clinical trial and meta-analysis data on the effects of blood pressure (BP) pharmacologic treatment for hypertension on orthostatic hypotension (OH) to identify BP goals for patients with these concomitant conditions. Hypertension and OH are commonly found together. The autonomic reflex that prevents hypotension upon standing also prevents hypertension when supine. OH, a fixed difference in systolic BP (≥ 20 mmHg) or diastolic BP (≥ 10 mmHg) between supine (or seated) and standing positions, can thus be associated with adverse outcomes related to low BP (e.g., syncopal events and falls) or high BP (e.g., coronary heart disease and stroke). While all OH stems from some degree of autonomic dysfunction, the type and extent of deficit has implications on the severity and reproducibility of the OH. Treatment strategies, moreover, differ based on predominant risks as well as OH etiology, specifically: neurologic, acute, pharmacologic, or hypertensive (cardiovascular). Hypertensive (cardiovascular) OH has been viewed traditionally through the lens of hypotensive event prevention, but emerging evidence suggests that more intensive therapy may reduce OH and prevent CVD disease with minimal effects on hypotensive events. Careful medication selection, however, is essential to reduce supine or seated hypertension, improve orthostatic BP regulation, and prevent hypotensive complications of treatment in these complex patients. Mounting evidence does not consider OH a deterrent for hypertension management; however, careful phenotyping of OH etiology and patient risks are essential for more precise patient care.
Examine current evidence on the impact of environmental exposures including noise, light at night, air pollution, temperature, metals, greenspace, and neighborhood on sleep and hypertension. Light exposure during sleep, air pollution (especially ozone), higher temperature, and neighborhood disadvantage were consistently associated with poor sleep; associations for noise (children), metals (adults), greenspace, and walkability were mixed. For hypertension, air pollution, increased ambient heat, and neighborhood disadvantage showed consistent associations whereas findings for noise, light, and greenspace had mixed findings. Neighborhood reinvestment, social cohesion, and safer environment was associated with healthier sleep and normal blood pressure. Minoritized and low-socioeconomic status populations face greater environmental exposures and had higher risk of poor sleep and hypertension. Pregnancy represents a window of vulnerability to the effects of air pollution, heat, humidity, and metals on hypertension. Future research should employ personal sensors for better exposure assessments and longitudinal designs to determine causal pathways.
Historically, blood pressure (BP) guidelines emphasized the implementation of aerobic exercise. However, more recent guidelines started highlighting the benefits of resistance exercise. The primary aim of this brief review is to determine if resistance training offers comparable benefits to aerobic exercise on BP in individuals with hypertension. Aerobic exercise training consistently produces the greatest effect, lowering systolic/diastolic BP by 7/5 mmHg in individuals with hypertension. Dynamic resistance training elicits more modest reductions ( 2/2 mmHg), whereas isometric resistance training, though evaluated in fewer and smaller studies, has shown clinically meaningful reductions of 5/5 mmHg. However, the impacts of resistance exercise training on ambulatory BP remain non-significant and marginal. Strategies to reduce BP should prioritize aerobic exercise rather than resistance training, especially when the primary goal is BP management.
Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, and hypertension is a modifiable risk factor with the strongest association for developing heart disease. This review evaluates the attributable risk of hypertension for CVD at the population level and examines how this risk varies by demographic, geographic, and socioeconomic factors. Understanding the extent to which hypertension contributes to CVD can help inform targeted prevention and intervention treatment strategies. Recent studies have examined the attributable risk of hypertension for CVD across different populations. Hypertension had the highest population attributable risk (PAR) and population attributable fraction (PAF) values for overall CVD, stroke, heart failure, and coronary heart disease, especially among Black adults, younger individuals, and residents of low- and middle-income countries. Although hypertension prevalence has increased over time, some high-income countries have observed a decline in its attributable risk for CVD. This decline is likely due to improved blood pressure management and public health interventions. In the US, recent data shows blood pressure control among adults remains low. Population-level interventions such as sodium restrictions in the food supply, standardized treatment protocols to improve blood pressure control, and improved healthcare access have been shown to mitigate the burden of hypertension. Despite advancements in awareness and treatment, hypertension continues to be a major driver of the global CVD burden. The meaningful attributable risk for CVD highlights the need for improved public health protocols. Interventions that combine clinical management with population-level prevention strategies offer the greatest potential for reducing disparities and improving cardiovascular outcomes.
Hypertension remains a leading cause of cardiovascular morbidity and mortality in the United States. The 2025 American Heart Association (AHA)/American College of Cardiology (ACC) Guideline for the Management of High Blood Pressure in Adults provides the first major update since 2017. It reveals new evidence in the diagnosis, risk assessment, and treatment of hypertension. This review summarizes key updates, contrasts them with prior recommendations, and discusses implications for clinical practice. The 2025 AHA/ACC Hypertension Guideline introduces several major updates that reshape risk assessment, diagnosis, and treatment strategy. Adoption of the PREVENT risk calculator replaces the pooled cohort equations, improving cardiovascular risk estimation by incorporating renal function, statin use, and social drivers of health. Screening for primary aldosteronism is expanded to all patients with stage 2 or resistant hypertension, addressing underdiagnosis of this secondary cause. Renal denervation is introduced as an adjunctive option for select patients with resistant hypertension. The guideline also provides expanded recommendations for special populations, including those with chronic kidney disease, diabetes, pregnancy, and neurologic disorders. Enhanced emphasis on home blood pressure monitoring, lifestyle modification, and team-based care highlights the growing importance of patient engagement and coordinated care. The 2025 AHA/ACC Hypertension Guideline marks a pivotal shift toward risk-based, patient-centered hypertension management. It reinforces the need for tailored strategies that bridge clinical practice and population health. Effective implementation will depend on interdisciplinary collaboration and equitable access to preventative and therapeutic resources.
This narrative review aims to summarize what is currently understood about Neurofibromatosis Type 1 (NF-1) and renovascular hypertension (RVH) in children, including clinical presentation and diagnosis, epidemiology, genetics, and management considerations including advances in treatment modalities. Most of what is currently understood about NF-1 and arterial dysplasia leading to RVH relies on the inclusion of patients with NF-1 in single-institution reports. The management of pediatric RVH often requires multi-modal therapies inclusive of anti-hypertensive medications and revascularization for refractory cases, through catheter-based (i.e., endovascular) and open surgical means. There is a need to develop genotype-targeted guidelines for the diagnosis and management of pediatric aorto-renal dysplasia resulting in RVH in patients with NF-1. While our understanding of pediatric RVH and NF-1 has evolved over the past decade, critical research questions have emerged that encompass epidemiology, etiology and genetics. These research questions require immediate attention to establish and optimize standardized diagnostic and treatment guidelines.
This review examines the protective angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas receptor axis of the renin–angiotensin system. We sought to integrate evidence from preclinical and early human studies on how activation of this pathway influences vascular, cardiac, renal, hepatic and metabolic health, and to identify methodological lessons for developing future therapies. Animal models show that augmenting this axis improves endothelial function, limits cardiac remodelling, enhances insulin sensitivity, reduces renal injury and mitigates hepatic steatosis associate with MASH/NAFLD. Early-phase trials of recombinant angiotensin-converting enzyme 2 and angiotensin-(1–7) analogues demonstrate favourable safety profiles and clear pharmacodynamic target engagement but inconsistent immediate clinical effects. Emerging work highlights the value of biomarker ratios, gene and lifestyle based modulation and patient stratification strategies. Activation of the angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas receptor axis offers a promising route to address cardiometabolic disease. Filling gaps in long-term outcomes, receptor-specific mechanisms and precision patient selection could transform this counter-regulatory pathway into a cornerstone of next-generation therapies.
Hypertension affects over 120 million Americans, yet immigrant and refugee populations face disproportionate barriers to effective hypertension care. With nearly 48 million immigrants and growing refugee populations in the US, understanding these disparities has become a crucial public health issue. This review synthesizes current evidence on hypertension disparities among immigrant and refugee populations, examining barriers across the hypertension care cascade from screening through control, and discusses promising interventions. Hypertension prevalence varies across immigrant populations. These populations face multiple barriers throughout care: limited screening access, delayed treatment initiation, and poor long-term control. The intersectionality of structural barriers, cultural factors, economic limitations, and healthcare system limitations creates a cumulative cycle of disadvantages. The political threats and “othering” process, discrimination and cultural marginalization, further worsen these challenges, affecting trust, care-seeking behavior, and treatment adherence. Evidence-based interventions show that culturally responsive, community-centered approaches can meaningfully reduce disparities. Community health worker programs achieved remarkable improvements in blood pressure control among immigrant populations. Technology-enhanced interventions, partnerships with faith-based organizations, culturally adapted educational resources, and Clinician cultural humility training often show promising results. However, addressing these disparities requires approaches at the individual, community, healthcare system, and policy levels to be implemented simultaneously. There need to be a sustained commitment to health equity, recognizing that the health of immigrants affects community well-being and the stability of the national and global healthcare system.
To summarize important novel but controversial discoveries in pediatric hypertension and prevention. This review also aims to provide some answers to previously unexpected findings in randomized clinical trials that failed to lower blood pressure in youth. Emerging longitudinal investigations have elucidated the temporal progression of cardiac structural changes, revealing that arterial stiffness precedes the development of hypertension and cardiac remodeling. These temporal insights have important implications for physical activity interventions, as traditional recommendations emphasizing moderate-to-vigorous physical activity to lower blood pressure have demonstrated limited efficacy in randomized controlled trials. Recent evidence suggests that light physical activity provides superior blood pressure-lowering capacity compared to moderate-to-vigorous physical activity due to the confounding effect of muscle mass. Moreover, sedentary behavior may be a causal risk factor for progressive cardiovascular deterioration. Elevated blood pressure and hypertension during childhood and adolescence represent a critical risk factor for premature cardiovascular morbidity and mortality in adulthood. While the association between pediatric hypertension and adverse cardiovascular events is well-established, the temporal sequencing of pathophysiological mechanisms leading from blood pressure elevation to end-organ damage remains unclear. This comprehensive review synthesizes emerging evidence regarding the temporal relationships between pediatric hypertension and cardiac consequences, highlighting temporal trends that could inform evidence-based physical activity interventions for optimizing cardiovascular health trajectories from childhood through young adulthood.
Hypertension is a major driver of cardiovascular morbidity and mortality in women, with risk trajectories that evolve across the female life course. From reproductive years through menopause, sex-specific biological, hormonal, and social factors contribute to unique patterns of blood pressure risk and cardiovascular vulnerability. To provide a life-course review of hypertension in adult women and highlight stage-specific risk factors, clinical considerations, and opportunities for prevention and management. Women experience distinct exposures that influence hypertension risk, including hypertensive disorders of pregnancy, adverse pregnancy outcomes, psychosocial stressors, cardiometabolic changes, and the transition through menopause. This review integrates key recommendations from the 2025 American College of Cardiology/American Heart Association High Blood Pressure Guideline and emphasizes practical, stage-specific approaches to screening, risk stratification, and treatment tailored to women. A life-stage–specific, sex-informed approach to hypertension is essential to improve early identification, optimize treatment, and reduce long-term cardiovascular risk in women. Addressing persistent evidence gaps and prioritizing implementation of sex-specific care strategies will be critical to advancing equitable cardiovascular outcomes.
