Secreted Frizzled Related Protein 3 in Chronic Heart Failure: Analysis from the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA).
BACKGROUND
We have previously demonstrated an association between increased sFRP3 expression and adverse outcome in a population of HF irrespective of cause and left ventricular ejection fraction. In this study we evaluated the prognostic value of sFRP3 in older patients with chronic systolic HF of ischemic origin.


METHODS
We evaluated sFRP3, by tertiles, as a risk factor for the primary endpoint (cardiovascular [CV] mortality, nonfatal myocardial infarction, nonfatal stroke), all-cause mortality, CV mortality, death from worsening HF (WHF), any coronary event, including sudden death, as well as hospitalizations for CV causes and WHF in 1444 patients from the CORONA population, randomly assigned to 10 mg rosuvastatin or placebo.


RESULTS
Kaplan-Meier curves for the primary endpoint, as well as all-cause- and CV mortality revealed a markedly better survival for patients with sFRP3 levels in the middle tertile of compared to the 1st and 3rd tertile. In multivariable Cox-regression, after full adjustment including high-sensitive CRP and NT-proBNP, a lower event rate for the primary end point, all cause and CV mortality was observed for patients with tertile 2 sFRP3 levels (HR 0.57 [0.44-0.74], 0.55 [0.44-0.74] and 0.52 [0.39-0.69]; p<0.001), as well as for the number of coronary events (HR 0.62 [0.47-0.82], p = 0.001) and sudden death (HR 0.55 [0.37-0.82], p = 0.002). Applying sFRP3 values to the fully adjusted regression model resulted in highly significant continuous net reclassification improvements for the primary endpoint, all cause and CV mortality, coronary events and sudden death (range 0.24-0.31; p≤0.002 for all).


CONCLUSIONS
Intermediate serum sFRP3 levels are associated with better survival and fewer CV events than low or high sFRP3 levels, independently of conventional risk factors, in older patients with chronic systolic HF of ischemic origin. Our study suggests that balanced Wnt activity might confer protective effects in a clinical HF setting.


BACKGROUND
http://www.clinicaltrials.gov NCT00206310.
Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; K. G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Oslo, Norway.
Erik Tandberg
ET
Askevold
Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; K. G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Oslo, Norway.
Lars
L
Gullestad
Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Ståle
S
Nymo
Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; K. G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Oslo, Norway.
John
J
Kjekshus
Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; K. G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Oslo, Norway; K. G. Jebsen Inflammatory Research Center, Oslo, Norway.
Arne
A
Yndestad
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
Roberto
R
Latini
Department of Cardiology, Hull York Medical School, University of Hull, Castle Hill Hospital, Kingston-upon-Hull, United Kingdom.
John G F
JG
Cleland
British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
John J V
JJ
McMurray
Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; K. G. Jebsen Inflammatory Research Center, Oslo, Norway; K. G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway.
Pål
P
Aukrust
Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; K. G. Jebsen Inflammatory Research Center, Oslo, Norway; K. G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway.
Thor
T
Ueland
D000368:Aged; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011506:Proteins / Q000032:analysis*; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*; D016896:Treatment Outcome; D000094742:Secreted Frizzled-Related Proteins
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011506:Proteins; D000068718:Rosuvastatin Calcium; D000094742:Secreted Frizzled-Related Proteins