von Willebrand Factor Independently Predicts Long-term Survival in Patients With Pulmonary Arterial Hypertension

Kawut, Steven M.; Horn, Evelyn M.; Berekashvili, Ketevan; Widlitz, Allison; Rosenzweig, Erika B.; Barst, Robyn J.

doi:10.1378/chest.128.4.2355

Cited by 75 publications

(63 citation statements)

References 48 publications

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“…Optimal plasma biomarkers would be causal (or at least closely linked) to the extent of pulmonary vascular disease or degree of right heart dysfunction [10]. Circulating von Willebrand factor (vWF) and other substances are released by the vascular endothelium and are increased in PAH [60][61][62]. Higher vWF levels at baseline and despite therapy are independently associated with an increased risk of death in PAH [60].…”

Section: Plasma Biomarkersmentioning

confidence: 99%

“…Circulating von Willebrand factor (vWF) and other substances are released by the vascular endothelium and are increased in PAH [60][61][62]. Higher vWF levels at baseline and despite therapy are independently associated with an increased risk of death in PAH [60]. Similarly, a variety of biomarkers tied to cardiac function have been investigated in PAH [38,50,63,64].…”

Section: Plasma Biomarkersmentioning

confidence: 99%

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Surrogate End Points in Pulmonary Arterial Hypertension: Assessing the Response to Therapy

Snow¹,

Kawut²

2007

Clinics in Chest Medicine

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Pulmonary arterial hypertension (PAH) is a rare disease which is characterized by increased pulmonary vascular resistance and right heart failure. Recent discoveries in disease pathophysiology have been translated into effective therapies tested in clinical trials. The studies which have led to the regulatory board approval of therapies for PAH have focused on surrogate and intermediate end points, thought to reflect quantity and quality of life, respectively. However, validation of many of these surrogates is incomplete. It is also unknown which indicators of function or long-term survival should be used to formulate decisions regarding addition, discontinuation, or combination of therapies. Identification of suitable end points would therefore not only help investigators design appropriate clinical trials, but also assist clinicians in caring for patients with PAH. Hemodynamic, cardiac imaging, plasma biomarkers, and exercise testing hold some promise as potential surrogate end points for PAH. Functional status and quality of life assessments may also have important roles. Future studies should validate the most promising surrogate markers, so that patients, clinicians, subjects, and investigators may benefit from the advantages they confer on clinical care and on clinical trials.The past several years have yielded an explosion of randomized clinical trials (RCTs) of several new medical therapies for pulmonary arterial hypertension (PAH). The hopes for these and all treatments for potentially fatal diseases are 1) to improve how a patient feels or functions and/ or 2) to prolong survival. While simply stated, the assessment of progress towards these goals may be quite complex [1][2][3][4][5][6].New PAH therapies have gained regulatory board approval based on studies with intermediate and surrogate end points as primary outcomes, believed to reflect the impact of these drugs on quality of life (QOL) and survival, respectively. While hemodynamic, plasma, cardiac imaging, exercise, functional, and QOL parameters are promising candidates, the reliability and validity of these measures are not clearly established. In addition, there are no RCTs addressing the use of such end points in guiding management decisions in PAH, such as changing, intensifying, escalating, or combining therapies. Despite this lack of evidence, clinicians who

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Section: Plasma Biomarkersmentioning

confidence: 99%

Section: Plasma Biomarkersmentioning

confidence: 99%

Surrogate End Points in Pulmonary Arterial Hypertension: Assessing the Response to Therapy

Snow¹,

Kawut²

2007

Clinics in Chest Medicine

Self Cite

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show abstract

“…Since vWF is stored in Weibel Palade bodies within the EC, the loss of vWF is indicative of an extensive endothelial damage and/or loss. Therefore, it is not surprising that increased plasma levels of vWF and Ang2, and circulating endothelial cells in PAH are considered markers of poor prognosis (Kawut 2005, Kümpers 2010, Smadja 2010. It is worth noting here that both vWF and Ang2 are stored in Weibel Palade bodies and during stress/activation, these bodies deliver their cargo at the endothelial cell surface.…”

Section: Enhanced Expression Of Caveolin-1 In Smcmentioning

confidence: 93%

Pulmonary Hypertension: Endothelial Cell Function

Mathew¹

2011

Pulmonary Hypertension - From Bench Research to Clinical Challenges

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“…Athletic conditioning induces angiogenesis that enhances tissue perfusion and oxygenation, mitigates flow resistance, reduces blood pressure, and enhances ejection fraction, which slows heart rate via the Starling mechanism [24, 270,[302][303][304][305][306][307][308][309][310][311][312][313][314][315][316][317]. Allostatic load accelerates capillary senescence [318][319][320] that increases vascular resistance, impairs tissue and organ perfusion, inhibits glucose uptake, and causes diabetes and essential hypertension [142,192,231,232,267,273,276,277,279,[321][322][323][324][325][326][327].…”

Section: The Capillary Gate Mechanismmentioning

confidence: 99%

Stress repair mechanism activity explains inflammation and apoptosis

Coleman¹

2012

ABB

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von Willebrand Factor Independently Predicts Long-term Survival in Patients With Pulmonary Arterial Hypertension

Cited by 75 publications

References 48 publications

Surrogate End Points in Pulmonary Arterial Hypertension: Assessing the Response to Therapy

Surrogate End Points in Pulmonary Arterial Hypertension: Assessing the Response to Therapy

Pulmonary Hypertension: Endothelial Cell Function

Stress repair mechanism activity explains inflammation and apoptosis

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