Romain Capoulade1, Nancy Côté1, Patrick Mathieu1, Kwan L Chan2, Marie-Annick Clavel1, Jean G Dumesnil1, Koon K Teo3, James W Tam4, Dominique Fournier1, Jean-Pierre Després1, Philippe Pibarot5. 1. Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada. 2. University of Ottawa Heart Institute, Ottawa, Ontario, Canada. 3. McMaster University, Hamilton, Ontario, Canada. 4. St Boniface General Hospital, Winnipeg, Manitoba, Canada. 5. Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada. Electronic address: philippe.pibarot@med.ulaval.ca.
Abstract
BACKGROUND: Matrix γ-carboxyglutamate protein is an inhibitor of cardiovascular calcification. The objective of this substudy of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial was to examine the relationship between total (ie, carboxylated [active] form + uncarboxylated [inactive] form) circulating desphosphorylated matrix γ-carboxyglutamate protein (dpMGP) level and the progression rate of aortic stenosis (AS). METHODS: Among the patients included in the ASTRONOMER trial, 215 patients had measures of baseline circulating total dpMGP level and an echocardiographic follow-up (mean follow-up: 3.5 ± 1.3 years). Progression of AS was assessed according to the measurement of the annualized increase in peak aortic jet velocity. RESULTS: In the whole cohort, baseline dpMGP level was associated with faster progression rate of peak aortic jet velocity (r = 0.16; P = 0.02) in individual analysis but not in multivariable analysis (P = 0.40). However, there was a significant interaction (P = 0.03) between dpMGP level and age, with respect to the effect on AS progression. After dichotomization according to median value of age (ie, 57 years old), total dpMGP level was associated with faster AS progression rate (r = 0.24; P = 0.008) in the younger patients, and this association remained significant in multivariable analysis (P = 0.04), but not in the older ones. The independent correlates of dpMGP level were fasting glucose (P = 0.009) and oxidized low-density lipoprotein (P = 0.01). CONCLUSIONS: This is the first prospective study to demonstrate a relationship between increased circulating levels of total dpMGP and faster progression rate of AS in younger individuals. Future studies are needed to determine if dpMGP is simply a marker or a contributing factor to ectopic mineralization of aortic valve.
RCT Entities:
BACKGROUND: Matrix γ-carboxyglutamate protein is an inhibitor of cardiovascular calcification. The objective of this substudy of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial was to examine the relationship between total (ie, carboxylated [active] form + uncarboxylated [inactive] form) circulating desphosphorylated matrix γ-carboxyglutamate protein (dpMGP) level and the progression rate of aortic stenosis (AS). METHODS: Among the patients included in the ASTRONOMER trial, 215 patients had measures of baseline circulating total dpMGP level and an echocardiographic follow-up (mean follow-up: 3.5 ± 1.3 years). Progression of AS was assessed according to the measurement of the annualized increase in peak aortic jet velocity. RESULTS: In the whole cohort, baseline dpMGP level was associated with faster progression rate of peak aortic jet velocity (r = 0.16; P = 0.02) in individual analysis but not in multivariable analysis (P = 0.40). However, there was a significant interaction (P = 0.03) between dpMGP level and age, with respect to the effect on AS progression. After dichotomization according to median value of age (ie, 57 years old), total dpMGP level was associated with faster AS progression rate (r = 0.24; P = 0.008) in the younger patients, and this association remained significant in multivariable analysis (P = 0.04), but not in the older ones. The independent correlates of dpMGP level were fasting glucose (P = 0.009) and oxidized low-density lipoprotein (P = 0.01). CONCLUSIONS: This is the first prospective study to demonstrate a relationship between increased circulating levels of total dpMGP and faster progression rate of AS in younger individuals. Future studies are needed to determine if dpMGP is simply a marker or a contributing factor to ectopic mineralization of aortic valve.
Authors: Neil Venardos; Daine Bennett; Michael J Weyant; Thomas Brett Reece; Xianzhong Meng; David A Fullerton Journal: J Surg Res Date: 2015-04-25 Impact factor: 2.192