@article{3077647,
    title = "Reactive vasodilation predicts mortality in primary systemic light-chain amyloidosis",
    author = "Stamatelopoulos, K. and Georgiopoulos, G. and Athanasouli, F. and Nikolaou, P.-E. and Lykka, M. and Roussou, M. and Gavriatopoulou, M. and Laina, A. and Trakada, G. and Charakida, M. and Delialis, D. and Petropoulos, I. and Pamboukas, C. and Manios, E. and Karakitsou, M. and Papamichael, C. and Gatsiou, A. and Lambrinoudaki, I. and Terpos, E. and Stellos, K. and Andreadou, I. and Dimopoulos, M.A. and Kastritis, E.",
    journal = "Circulation Research",
    year = "2019",
    volume = "125",
    number = "8",
    pages = "744-758",
    publisher = "Lippincott Williams and Wilkins",
    issn = "0009-7330, 1524-4571",
    doi = "10.1161/CIRCRESAHA.119.314862",
    keywords = "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",
    abstract = "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."
}