Τίτλος:
Reactive vasodilation predicts mortality in primary systemic light-chain amyloidosis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
RATIONALE: Cardiac involvement and hypotension dominate the prognosis of light-chain amyloidosis (AL). Evidence suggests that there is also peripheral vascular involvement in AL but its prognostic significance is unknown. OBJECTIVE: To evaluate vascular dysfunction in patients with AL as a potential future area of intervention, we assessed the prognostic utility of flow-mediated dilatation (FMD), a marker of vascular reactivity, which is augmented under conditions of hypotension and autonomic dysfunction. METHODS AND RESULTS: We prospectively evaluated 115 newly diagnosed untreated AL patients in whom FMD was measured. FMD in AL patients was significantly higher than age-, sex-and risk factors-matched controls (4.0% versus 2.32%; P=0.006) and comparable with control groups at lower cardiovascular risk (P>0.1). Amyloidosis patients presented increased plasma and exhaled markers of the NO pathway while their FMD significantly correlated with augmented sustained vasodilatation after sympathetic stimulation. Increased FMD (=4.5%) was associated with early mortality (hazard ratio, 4.36; 95% CI, 1.41-13.5; P=0.010) and worse survival (hazard ratio, 2.11; 95% CI, 1.17-3.82; P=0.013), even after adjustment for Mayo stage, nerve involvement and low systolic blood pressure. This finding was confirmed in a temporal validation AL cohort (n=55; hazard ratio, 4.2; 95% CI, 1.45-12.3; P=0.008). FMD provided significant reclassification value over the best prognostic model (continuous Net Reclassification Index, 0.61; P=0.001). Finally, better hematologic response was associated with lower posttreatment FMD. CONCLUSIONS: FMD is relatively increased in AL and independently associated with inferior survival with substantial reclassification value. Reactive vasodilation merits further investigation as a novel risk biomarker in AL. VISUAL OVERVIEW: An online visual overview is available for this article. © 2019 American Heart Association, Inc.
Συγγραφείς:
Stamatelopoulos, K.
Georgiopoulos, G.
Athanasouli, F.
Nikolaou, P.-E.
Lykka, M.
Roussou, M.
Gavriatopoulou, M.
Laina, A.
Trakada, G.
Charakida, M.
Delialis, D.
Petropoulos, I.
Pamboukas, C.
Manios, E.
Karakitsou, M.
Papamichael, C.
Gatsiou, A.
Lambrinoudaki, I.
Terpos, E.
Stellos, K.
Andreadou, I.
Dimopoulos, M.A.
Kastritis, E.
Περιοδικό:
Circulation Research
Εκδότης:
Lippincott Williams and Wilkins
Λέξεις-κλειδιά:
corticosteroid; lenalidomide; nitric oxide; proteasome inhibitor, adrenergic stimulation; adult; age; all cause mortality; amyloidosis; Article; autonomic dysfunction; blood flow; blood vessel reactivity; cardiovascular risk; cohort analysis; controlled study; correlation analysis; echography; female; gender; hazard ratio; human; hypotension; major clinical study; male; middle aged; mortality; priority journal; prognosis; risk factor; survival rate; systemic light chain amyloidosis; systemic light chain amyloidosis; systolic blood pressure; vascular disease; vasodilatation; aged; AL amyloidosis; blood pressure; diagnostic imaging; laser Doppler flowmetry; mortality; pathophysiology, Aged; Blood Pressure; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Laser-Doppler Flowmetry; Male; Middle Aged; Regional Blood Flow; Survival Rate; Vasodilation
DOI:
10.1161/CIRCRESAHA.119.314862
