| Autor: |
Watthanasuntorn, Kanramon, Shrestha, Bishesh, Bethuel, Nancy, Thongprayoon, Charat, Leungsuwan, Kanjit, Victory, Jennifer, Jenkins, Paul, Hyink, Deborah, Katz, Daniel H, Klotman, Paul, Kandala, Jagdesh, Hutter, Randolph |
| Zdroj: |
Circulation (Ovid); November 2019, Vol. 140 Issue: Supplement 1 pA14785-A14785, 1p |
| Abstrakt: |
Introduction:Smooth muscle cell (SMC) function determines the clinical course of vascular disease via fibrous cap stability. Podocan is a potent suppressor of SMC function by inhibiting SMC Wnt-pathway and is circulating in peripheral blood as is Dickkopf-1 (DKK-1), another Wnt-inhibitor.Hypothesis:Podocan is a novel biomarker predicting MACE in patients with CAD independent of Framingham Cardiovascular Risk Factors in synergy with Dickkopf-1 (DKK-1).Methods:A cohort of 308 patients with angiographic evidence of CAD was enrolled and followed prospectively for MACE (MI, CVA or death). Blood samples were collected on the date of cardiac catheterization to determine Podocan (detection threshold 0.01 ng/ml) and DKK1 levels (median 361.5 pg/ml). Variables were converted to the binary form of present versus absent for Podocan and above versus below median for DKK-1 for all time to event analyses (Fig 1). These two binary variables were used to create an additional three-level variable: 1) Podocan detected and DKK-1 >median (high-high:?HH?); 2) Podocan detected and DKK1<=median or Podocan not detected and DKK1>median (either-or:?EO?) and 3) Podocan not detected and DKK1 <=median (low-low:?LL?).Results:Podocan was not correlated with any clinical variable. Having a detectable Podocan level was significantly positively related to time to MACE at the univariate level (HR=2.60, p=0.014). Levels of DKK1 above median were also positively related to time to MACE at the univariate level (HR=2.44, p=0.028). Podocan-DKK1 composite was strongly related to time to MACE. Specifically, the hazard ratio (HR) for HH versus LL was 5.95 (p=0.018), and the HR for HH versus EO was 2.29, (p=0.036).Conclusions:Podocan is predictive of MACE in CAD patients independent of Framingham cardiovascular risk factors and is a novel biomarker to guide secondary prevention of CAD. Its risk spread for MACE is further enhanced by DKK1. Future multicenter trial is warranted to confirm this finding. |
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