The Progression of Hypertensive Heart Disease

Drazner, Mark H.

doi:10.1161/circulationaha.108.845792

Cited by 669 publications

(544 citation statements)

References 114 publications

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“…Remarkably, the inhibitory effects of local LepA on LVH and aortic and mitral valve leaflet thickening occurred despite continuous systemic AngII administration and subsequent hypertension. These results underscore the significance of AVC activation as an underappreciated force driving LV remodeling and aortic valve disease 49, 50…”

Section: Discussionmentioning

confidence: 70%

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

Ben‐Zvi

Savion

Kolodgie

et al. 2016

JAHA

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BackgroundAscending thoracic aortic aneurysm (ATAA) is driven by angiotensin II (AngII) and contributes to the development of left ventricular (LV) remodeling through aortoventricular coupling. We previously showed that locally available leptin augments AngII‐induced abdominal aortic aneurysms in apolipoprotein E–deficient mice. We hypothesized that locally synthesized leptin mediates AngII‐induced ATAA.Methods and ResultsFollowing demonstration of leptin synthesis in samples of human ATAA associated with different etiologies, we modeled in situ leptin expression in apolipoprotein E–deficient mice by applying exogenous leptin on the surface of the ascending aorta. This treatment resulted in local aortic stiffening and dilation, LV hypertrophy, and thickening of aortic/mitral valve leaflets. Similar results were obtained in an AngII‐infusion ATAA mouse model. To test the dependence of AngII‐induced aortic and LV remodeling on leptin activity, a leptin antagonist was applied to the ascending aorta in AngII‐infused mice. Locally applied single low‐dose leptin antagonist moderated AngII‐induced ascending aortic dilation and protected mice from ATAA rupture. Furthermore, LV hypertrophy was attenuated and thickening of aortic valve leaflets was moderated. Last, analysis of human aortic valve stenosis leaflets revealed de novo leptin synthesis, whereas exogenous leptin stimulated proliferation and promoted mineralization of human valve interstitial cells in culture.ConclusionsAngII‐induced ATAA is mediated by locally synthesized leptin. Aortoventricular hemodynamic coupling drives LV hypertrophy and promotes early aortic valve lesions, possibly mediated by valvular in situ leptin synthesis. Clinical implementation of local leptin antagonist therapy may attenuate AngII‐induced ATAA and moderate related LV hypertrophy and pre–aortic valve stenosis lesions.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00449306.

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Section: Discussionmentioning

confidence: 70%

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

Ben‐Zvi

Savion

Kolodgie

et al. 2016

JAHA

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“…Stage B HF is defined as the presence of structural heart disease in the absence of symptoms of HF and represents the tip of the iceberg compared with the morbidity, mortality, and cost associated with stage C disease 15, 16. Currently, routine cardiac imaging to screen for LVH is not recommended, attributed, in part, to the observation that the progression of LVH to symptomatic HF is heterogeneous 17. Malignant LVH defines a subgroup of LVH patients, representing 7% of MESA participants, by definition free of known CVD, and independent of the presence of hypertension, who may potentially benefit from increased surveillance.…”

Section: Discussionmentioning

confidence: 99%

“Malignant” Left Ventricular Hypertrophy Identifies Subjects at High Risk for Progression to Asymptomatic Left Ventricular Dysfunction, Heart Failure, and Death: MESA (Multi‐Ethnic Study of Atherosclerosis)

Peters

Seliger

Christenson

et al. 2018

JAHA

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BackgroundAs heart failure (HF)‐associated morbidity and mortality continue to escalate, enhanced focus on prevention is increasingly important. “Malignant” left ventricular (LV) hypertrophy (LVH): LVH combined with an elevated cardiac biomarker reflecting either injury (high‐sensitivity cardiac troponin T), or strain (amino‐terminal pro‐B‐type natriuretic peptide) has predicted accelerated progression to HF. We sought to determine whether malignant LVH identified community‐dwelling adults initially free of cardiovascular disease at high risk of asymptomatic decline in LV ejection fraction or a clinical cardiovascular event.Methods and ResultsA total of 4985 of 6814 individuals without prevalent cardiovascular disease underwent baseline cardiac magnetic resonance for LVH in combination with measurement of plasma high‐sensitivity cardiac troponin T and amino‐terminal pro‐B‐type natriuretic peptide as part of MESA (Multi‐Ethnic Study of Atherosclerosis) and were subsequently divided into 4 groups: (1) No LVH, no elevated biomarkers (n=2206; 44.3%); (2) No LVH, ≥1 elevated biomarkers (n=2275; 45.7%); (3) LVH, no elevated biomarkers (n=153; 3.0%); and (4) LVH, ≥1 elevated biomarkers (malignant LVH; n=351; 7.0%). Cardiac magnetic resonance was repeated 10 years later (n=2831) for assessment of LV ejection fraction <50%. Median follow‐up was 12.2 years. Malignant LVH was associated with 7.0‐, 3.5‐, and 2.6‐fold adjusted increases in incidence of HF, cardiovascular death, and asymptomatic LV dysfunction, respectively, versus group 1. New‐onset HF was predominately HF with reduced ejection fraction (9.5‐fold increase).ConclusionsMalignant LVH is predictive of progression to asymptomatic LV dysfunction, HF (particularly HF with reduced ejection fraction), and cardiovascular death. Consequently, malignant LVH represents a high‐risk phenotype among individuals without known cardiovascular disease, which should be targeted for increased surveillance and more‐aggressive therapies.

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“…Cardiac hypertrophy, which may eventually trigger the transition to heart failure, occurs in many forms of clinical conditions, including hypertension and valvular heart disease 1, 2. Although it is widely accepted that inflammation including various cytokines and receptors are involved in the pathological process of pressure overload‐induced cardiac hypertrophy and cardiac dysfunction 3, 4, 5, the molecular mechanisms underlying the progression of cardiac hypertrophy and succedent heart failure have not yet been completely defined.…”

Section: Introductionmentioning

confidence: 99%

Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure

Zhang

Liu

Jiang

et al. 2015

J Cellular Molecular Medi

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Inflammation plays a key role in pressure overload‐induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High‐mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload‐induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild‐type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin‐embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC‐induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up‐regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload‐induced cardiac hypertrophy and cardiac dysfunction.

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The Progression of Hypertensive Heart Disease

Cited by 669 publications

References 114 publications

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

“Malignant” Left Ventricular Hypertrophy Identifies Subjects at High Risk for Progression to Asymptomatic Left Ventricular Dysfunction, Heart Failure, and Death: MESA (Multi‐Ethnic Study of Atherosclerosis)

Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure

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