American journal of physiology. Heart and circulatory physiology最新文献

{"title":"Splicing Factor Kinase SRPK1 inhibition in Monocyte: A Novel Therapeutic Approach for Peripheral Arterial Disease.","authors":"Tohru Fukai, Masuko Ushio-Fukai","doi":"10.1152/ajpheart.00156.2025","DOIUrl":"https://doi.org/10.1152/ajpheart.00156.2025","url":null,"abstract":"","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ventriculo-arterial coupling in pulmonary regurgitation following transannular patch repair of pulmonary stenosis.","authors":"Rahi S Alipour Symakani, Wouter J van Genuchten, Lotte M Zandbergen, Alexander Hirsch, Piotr Alfred Wielopolski, Thierry Bové, Yannick J H J Taverne, Willem A Helbing, Beatrijs Bartelds, Daphne Merkus","doi":"10.1152/ajpheart.00614.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00614.2024","url":null,"abstract":"<p><p>Pulmonary regurgitation is a common consequence following the repair of tetralogy of Fallot and can lead to heart failure. Early detection of right ventricular dysfunction remains challenging, and current clinical markers have limited predictive value to identify which patients are at risk for heart failure and require interventions. This study aimed to investigate the potential of ventriculo-arterial coupling as a marker of early right ventricular dysfunction in a porcine model of chronic pulmonary regurgitation following transannular patch repair of neonatal pulmonary stenosis. Neonatal swine were subjected to pulmonary artery banding for 1 month to induce RV pressure overload, followed by transannular patch repair (rTAP, n=10) to create chronic pulmonary regurgitation, and were compared to Sham animals (n=6). Longitudinal hemodynamic assessments, including pressure-volume analysis and cardiac magnetic resonance imaging, were performed. VAC was defined as the ratio of end-systolic elastance to effective arterial elastance. Over the follow-up period of 4 months, VAC was preserved in the rTAP group. Effective arterial elastance was significantly lower in rTAP animals (P=0.001), while end-systolic elastance remained unchanged. Lower end-diastolic pulmonary artery pressures and increased early systolic ejection were observed in rTAP, correlating with higher VAC. Ventriculo-arterial coupling remains preserved in chronic pulmonary regurgitation due to decreased afterload, making it unsuitable as an early marker for right ventricular dysfunction. Low afterload, a consequence of diastolic emptying of the pulmonary artery into the right ventricle, may pseudo-normalize systolic function. Alternative markers e.g. focusing on diastolic function and atrio-ventricular interactions should be investigated.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac remodeling in heart disease and the importance of thyroid hormones.","authors":"Anthony Martin Gerdes","doi":"10.1152/ajpheart.00748.2024","DOIUrl":"https://doi.org/10.1152/ajpheart.00748.2024","url":null,"abstract":"<p><p>Cardiac remodeling is the process of adaptive or maladaptive growth of the heart in response to altered loading conditions or growth stimuli. A landmark review by Linzbach in 1960 and reports by Grant (1965) and Grossman (1975) brought attention to anatomical remodeling of the heart in cardiac hypertrophy and heart failure (HF). This was largely the age of cardiac physiology with many focusing on <i>in vivo</i> and <i>in vitro</i> studies in animal models of heart disease. The <i>neurohormonal hypothesis</i> became a major driving force with realization that plasma norepinephrine levels increase with progression to HF. This led drug companies to develop compounds aimed at these targets. Prior to the discovery of angiotensin converting enzyme (ACE) inhibitors, available drugs offered symptomatic relief but had little effect on mortality. Cardiac remodeling became a hot area of HF research in the late 1980s and early 1990s. This field took off when investigators observed that reductions in mortality by neurohormonal inhibition in HF were intimately linked to beneficial changes in cardiac anatomy. More recent work, highlights the critical role of thyroid hormones (THs) in maintaining myocyte shape and internal myocyte structures involved in calcium handling. This overview focuses on the role of myocyte remodeling related to chamber remodeling and wall stress. Another goal was to provide technical advice and information for researchers to improve critical analysis of data in this area of research. A comprehensive understanding of the molecular basis of myocyte remodeling is evolving and would require a separate communication to address.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational arsenite exposure alters maternal postpartum heart size and induces Ca²⁺-handling dysregulation in cardiomyocytes.","authors":"Nicole Taube, Morgan Steiner, Obialunanma V Ebenebe-Kasonde, Raihan Kabir, Haley Garbus-Grant, Sarah-Marie Alam El Din, Emily Illingworth, Nadan Wang, Brian L Lin, Mark J Kohr","doi":"10.1152/ajpheart.00266.2024","DOIUrl":"10.1152/ajpheart.00266.2024","url":null,"abstract":"<p><p>Cardiovascular disease is the leading cause of mortality in the United States. Studies suggest a role for environmental exposures in the etiology of cardiovascular disease, including exposure to arsenic through drinking water. Arsenic exposure during pregnancy has been shown to have effects on offspring, but few studies have examined impacts on maternal cardiovascular health. Although our prior work documented the detrimental effect of arsenic on the maternal heart during pregnancy, our current study examines the effect of gestational arsenic exposure on the maternal heart postpartum. Timed-pregnant wild-type (C57BL/6J) mice were exposed to 0, 100, or 1,000 µg/L sodium arsenite (NaAsO₂) via drinking water from <i>embryonic day 2.5</i> until parturition. Postpartum heart structure and function was assessed via transthoracic echocardiography and gravimetric measurement. Hypertrophic markers were probed via qRT-PCR and Western blot. Isolated cardiomyocyte Ca²⁺-handling and contraction were also assessed, along with the expression of with Ca²⁺-handling and contractile proteins. Interestingly, we found that exposure to either 100 or 1,000 µg/L sodium arsenite increased postpartum heart size at <i>postpartum day 12</i> vs. nonexposed postpartum controls. At the cellular level, we found altered cardiomyocyte Ca²⁺-handling and contraction, along with expression changes of key contractile proteins, including α-actin and cardiac myosin binding protein C (cMyBP-c). Together, these findings suggest that gestational arsenic exposure impacts the postpartum maternal heart, possibly inducing long-term cardiovascular changes. Furthermore, these findings highlight the importance of reducing arsenic exposure during pregnancy, and the need for more research on the impact of arsenic on maternal heart health and adverse pregnancy events.<b>NEW & NOTEWORTHY</b> Gestational exposure to sodium arsenite at environmentally relevant doses (100 and 1,000 µg/L) increases postpartum heart size, and induces dysregulated Ca²⁺ homeostasis and impaired shortening in isolated cardiomyocytes. This is the first study to demonstrate that gestational arsenic exposure impacts postpartum heart structure and function beyond the exposure period.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H460-H471"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"K⁺ currents in ventricular cardiomyocytes of p.N98S-calmodulin mutant mice.","authors":"Shuai Guo, Andy Hudmon, Firoj K Sahoo, Madeline R Motes, Wen-Chin Tsai, Peng-Sheng Chen, Michael Rubart","doi":"10.1152/ajpheart.00470.2024","DOIUrl":"10.1152/ajpheart.00470.2024","url":null,"abstract":"<p><p>Missense mutations in calmodulin (CaM)-encoding genes are associated with life-threatening ventricular arrhythmia syndromes. Here, we investigated the role of cardiac K⁺ channel dysregulation in arrhythmogenic long QT syndrome (LQTS) using a knock-in mouse model heterozygous for a recurrent mutation (p.N98S) in the <i>Calm1</i> gene (<i>Calm1</i>^N98S/+). Single-cell patch-clamp technique and whole heart optical voltage mapping were used to assess action potentials and whole cell currents. Ventricular action potential duration (APD) at baseline was similar between genotypes. The β-adrenergic agonist isoproterenol prolonged APD in myocytes and isolated perfused hearts from <i>Calm1</i>^N98S/+, but not wild-type (<i>Calm1</i>^+/+), mice. Current density-voltage relationships for the small-conductance calcium-activated K⁺ (SK) current and the inward rectifier K⁺ current did not significantly differ between <i>Calm1</i>^+/+ and <i>Calm1</i>^N98S/+ ventricular cardiomyocytes ± isoproterenol. Peak densities of other voltage-gated K⁺ currents were significantly larger in <i>Calm1</i>^N98S/+ versus <i>Calm1</i>^+/+ cells at voltages ≥40 mV, both without and with isoproterenol. Isoproterenol reduced outward K_ATP currents more in <i>Calm1</i>^N98S/+ versus <i>Calm1</i>^+/+ myocytes. Dialysis of <i>Calm1</i>^+/+ cardiomyocytes with exogenous wild-type or N98S-CaM protein (5 µmol/L) via the pipette, respectively, increased and eliminated SK currents. The specific SK channel inhibitor apamin did not significantly alter the APD of <i>Calm1</i>^+/+ or <i>Calm1</i>^N98S/+ hearts ± isoproterenol. Thus, dysregulation of SK or voltage-gated K⁺ channels does not contribute to the β-adrenergic-induced LQTS of <i>Calm1</i>^N98S/+ mice, possibly because cardiomyocyte content of endogenous N98S-CaM and/or its affinity for CaM-binding domains may be too low to modulate channel properties. The larger K_ATP current inhibition by isoproterenol may delay <i>Calm1</i>^N98S/+ myocyte repolarization at low intracellular [ATP].<b>NEW & NOTEWORTHY</b> Despite in vitro and in silico evidence implicating cardiac K⁺ channel dysregulation in LQTS associated with missense mutations in genes-encoding calmodulin, their effects on native cardiac K⁺ currents are unknown. Using a knock-in mouse model harboring the p.N98S mutation in the <i>Calm1</i> gene, we found no evidence for dysregulation of major cardiac K⁺ channels. Although these data do not support mechanistic findings from heterologous systems, our finding impacts efforts to improve therapies for calmodulinopathies.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H658-H675"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma levels of sTREM2 in chronic heart failure: predictors and prognostic relevance.","authors":"Jan Traub, Niklas Beyersdorf, Roxanne Sell, Stefan Frantz, Stefan Störk, Guido Stoll, Anna Frey","doi":"10.1152/ajpheart.00728.2024","DOIUrl":"10.1152/ajpheart.00728.2024","url":null,"abstract":"<p><p>Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein expressed on myeloid cells, including macrophages and microglia, and is involved in modulating inflammation and lipid metabolism. Elevated plasma levels of soluble TREM2 (sTREM2) have been associated with heart failure (HF) and neurodegenerative diseases, such as Alzheimer's disease (AD). This post hoc analysis explored the association of plasma sTREM2 with cognition and mortality in the Cognition.Matters-HF cohort of 148 patients with chronic HF. Plasma sTREM2 levels were measured using a bead-based immunoassay, and the cohort was split into high and low sTREM2 groups based on a median concentration of 16.6 ng/mL. Higher sTREM2 levels were associated with worse cognitive performance, particularly in working memory (<i>T</i> = -2.67, <i>P</i> = 0.009) and visual/verbal memory (<i>T</i> = -2.16, <i>P</i> = 0.032), but not with cardiac function. In univariate Cox regression, a higher plasma sTREM2 concentration was linked to increased mortality (HR = 1.28, 95% CI 1.05-1.57, <i>P</i> = 0.015), although this association did not remain significant after adjusting for age and heart failure severity (adjusted HR = 0.95, 95% CI 0.70-1.28, <i>P</i> = 0.720). These findings suggest that plasma sTREM2 reflects cognitive impairment more than cardiac dysfunction in HF, highlighting its potential as a biomarker for neuroinflammation in patients with HF.<b>NEW & NOTEWORTHY</b> This study establishes a significant association between elevated plasma sTREM2 levels and cognitive impairment in chronic patients with heart failure (HF), particularly in working memory and attention. Although higher sTREM2 levels correlated with worse survival in unadjusted analyses, they did not emerge as independent predictors of mortality once adjustments had been made for age and heart failure severity. These findings suggest that plasma sTREM2 may serve as a valuable biomarker for detecting HF-related mild cognitive impairment.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H594-H602"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of kinin B1 receptor alleviates SARS-CoV-2-induced long-lasting cardiovascular complications.","authors":"Drew Theobald, Lisandra E de Castro Braz, Shaw M Akula, Jeffrey B Eells, Srinivas Sriramula","doi":"10.1152/ajpheart.00861.2024","DOIUrl":"10.1152/ajpheart.00861.2024","url":null,"abstract":"<p><p>Long COVID has been associated with significant cardiovascular complications, including fibrosis, functional impairment, and chronic inflammatory and immune responses. However, the underlying mechanisms driving these cardiac pathologies following COVID-19 infection remain understudied. Previously, we characterized a mouse model of long COVID and observed enhanced expression of kinin B1 receptor (B1R) in the infected animals. Here, we investigated the role of B1R in mediating long-COVID-induced cardiac pathologies. K18-hACE2 transgenic mice were infected intranasally with SARS-CoV-2 and evaluated at 28 days postinfection (dpi) to model long COVID and the effects of pharmacological blockade of B1R were evaluated. Persistent upregulation of B1R expression was accompanied by apoptosis, disrupted cardiomyocyte architecture, fibrosis, impaired gap junction integrity, and sustained inflammation and immune cell infiltration. B1R blockade restored gap junction integrity, reduced fibrosis and apoptosis, and mitigated inflammation and immune activation. Together, these data indicate that B1R plays a critical role in long-COVID-induced cardiac remodeling and damage, highlighting its potential as a target for treating long-lasting cardiovascular complications following SARS-CoV-2 infection.<b>NEW & NOTEWORTHY</b> We are the first to report that elevated B1R expression may drive the long-lasting cardiovascular effects associated with recovery from COVID-19 infection. We have also collected novel evidence showing that blockade of B1R can reduce the cardiac complications associated with long COVID and may serve as a novel therapeutic target to mitigate SARS-CoV-2-induced long-term cardiac damage in affected individuals.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H711-H718"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and functional remodeling for elite cyclists during exercise; pressure-volume loops and hemodynamic forces analysis.","authors":"Alessio Pellegrino, Loira Toncelli, Simone Vanni, Alessandra Modesti, Gianni Pedrizzetti, Pietro Amedeo Modesti","doi":"10.1152/ajpheart.00882.2024","DOIUrl":"10.1152/ajpheart.00882.2024","url":null,"abstract":"<p><p>The study was designed to investigate the pattern of intraventricular hemodynamic forces (HDFs) and myocardial performance during exercise in elite cyclists (ECs). Transthoracic stress echocardiography was performed on 19 ECs and 13 age-matched sedentary controls (SCs) at three incremental exercise intensities based on heart rate reserve (HRR). Left ventricular (LV) HDFs were computed from echocardiography long-axis datasets using a novel technique based on endocardial boundary tracking, both in apex-base and latero-septal directions. Pressure volume (PV) loops were noninvasively investigated using the single-beat approach. Differences between groups were investigated using mixed model analysis. At PV loops, EC showed a steeper increase in stroke work compared with SC, without acute changes in ventricular capacity (EDVI₂₀). Contractility, measured as ventricular elastance (E_es), increased during exercise with no difference between groups (<i>P</i> = 0.625). At rest, EC had significantly lower heart rates and generated lower HDF than SC. However, during exercise, the pressure gradient developed by EC in systole, and therefore systolic HDF, was significantly higher than that developed by SC (<i>P</i> < 0.009), also showing a greater elastic rebound in late systole compared with SC (<i>P</i> < 0.032). Importantly, during early diastolic filling, EC showed lower HDF deceleration than SC (<i>P</i> < 0.043), indicating a facilitated relaxation of the left ventricle. Analysis of the HDF pattern during exercise shows the functional changes that occur in EC, characterized by increased HDF generation in systole, and facilitated relaxation in early diastole. This is the first time LV structural and functional remodeling is reported for elite cyclists during exercise.<b>NEW & NOTEWORTHY</b> Analysis of the hemodynamic forces shows that the functional changes that occur in elite cyclists during exercise are characterized by increased hemodynamic forces generation in systole, and facilitated relaxation in early diastole.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H393-H400"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term hemodynamic responses and reverse remodeling after pharmacotherapy in HFpEF versus HFrEF: a systematic review and meta-analysis.","authors":"Arno A van de Bovenkamp, Soufiane Nassiri, Adrianus J Bakermans, George L Burchell, Frances S de Man, Ramon B van Loon, M Louis Handoko","doi":"10.1152/ajpheart.00544.2024","DOIUrl":"10.1152/ajpheart.00544.2024","url":null,"abstract":"<p><p>The acute response to therapeutic afterload reduction differs between heart failure with preserved (HFpEF) versus reduced ejection fraction (HFrEF), with larger left ventricular (LV) stroke work augmentation in HFrEF compared with HFpEF. This may (partially) explain the neutral effect of HFrEF-medication in HFpEF. It is unclear whether such differences in hemodynamic response persist and/or differentially trigger reverse remodeling in the case of long-term afterload reduction. A systematic search was performed, identifying 21 clinical trials investigating renin-angiotensin-aldosterone system (RAAS) inhibitors, β-blockers, and sodium-glucose cotransport 2 inhibitors that report data on afterload reduction, stroke volume, and reverse remodeling in HFpEF and/or HFrEF. In both HFpEF and HFrEF, meta-analyses revealed limited long-term change in systolic/diastolic blood pressure (-5.6/-3.2 and -4.6/-1.4 mmHg, respectively) and LV afterload reduction (arterial elastance: -0.039 and -0.055 mmHg/mL, respectively). Long-term treatment did not result in an increase in stroke volume, with the exception of β-blockers in HFrEF. Indexed LV mass decreased slightly in both HFpEF and HFrEF (-2.8 and -2.3 g/m², respectively). In HFrEF, treatment reduced LV end-diastolic and end-systolic volume (-8 and -6 mL, respectively), whereas in HFpEF there was no relevant change. Contrary to acute heart failure studies, long-term afterload reduction had little effect on blood pressure and stroke volume augmentation in both HFpEF and HFrEF. However, reverse remodeling was clearly present in HFrEF but was essentially absent in HFpEF.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H419-H432"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allostatic load and cardiometabolic health in a young adult South African population: the African-PREDICT study.","authors":"A Wentzel, W Smith, E Jansen van Vuren, R Kruger, Y Breet, E Wonkam-Tingang, N A Hanchard, S T Chung","doi":"10.1152/ajpheart.00845.2024","DOIUrl":"10.1152/ajpheart.00845.2024","url":null,"abstract":"<p><p>Sustained stress, assessed as a high allostatic load score (ALS), is an independent cardiovascular disease (CVD) risk factor in older adults but its associations in young people are undefined. Since neurological maturation impacts stress adaptation and CVD risk, we assessed the relationship of ALS with CVD profile by using a tiered approach stratified by age [emerging adults (EA) aged 20-24 yr vs. young adults (YA) aged 25-30 yr] and ALS (high vs. low). In 1,054 healthy participants of the African Prospective Study on Early Detection and Identification of Cardiovascular Disease and Hypertension (African-PREDICT), we determined: <i>1</i>) ALS in EA versus YA; <i>2</i>) the relationship between ALS and cardiovascular (CV) health, and <i>3</i>) the odds of high ALS > 4 to identify masked hypertension (HT) and prediabetes as cardiometabolic outcomes. A nine-component, four-domain ALS was compiled: neuroendocrine [dehydroepiandrosterone (DHEA), cortisol], inflammatory [interleukin-6 (IL-6), C-reactive protein (CRP)], cardiovascular [systolic blood pressure (SBP) and diastolic blood pressure (DBP)], and metabolic [total cholesterol, high density lipoprotein cholesterol (HDL-cholesterol), body mass index (BMI)]. Retinal vessel caliber, pulse wave velocity (PWV), and cardiac structure and function were assessed. Median ALS was 3 (range: 1-9). A high-ALS > 4 was more common in YA versus EA (47 vs. 35%, <i>P</i> = 0.032). Higher ALS associated with narrower retinal arteries (<i>P</i> < 0.01), greater PWV (<i>P ≤</i> 0.01), lower diastolic function (<i>P</i> < 0.01), and left ventricular (LV) function (<i>P</i> < 0.01). High-ALS increased the odds of having masked hypertension, prediabetes, narrower retinal arteries, higher LV mass, poorer diastolic and ventricular functions (all <i>P</i> ≤ 0.01), in EA and YA independent of traditional CVD risk factors. The composite ALS identified early-stress dysregulation in cardiometabolic health and higher odds for masked hypertension and prediabetes in young adults. Cumulative stress may be a modifiable, independent cardiometabolic risk factor in younger populations that needs further investigation.<b>NEW & NOTEWORTHY</b> This is the first study to assess the effect of stress, as a composite allostatic load score, on micro-, macrovascular, and central cardiac features in healthy emerging and young adults, independent of traditional cardiovascular risk markers. It exemplifies independent stress-induced changes throughout the cardiovascular tree, which may increase the risk of cardiometabolic complications, masked hypertension, and prediabetes. Sustained stress may be a key etiological factor in cardiometabolic disease development in a young population.</p>","PeriodicalId":7692,"journal":{"name":"American journal of physiology. Heart and circulatory physiology","volume":" ","pages":"H581-H593"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}