Growth Differentiation Factor 15, Ischemia Modified Albumin and Pregnancy-Associated Plasma Protein A in Patients with Coronary Artery Disease

Purpose: To investigate the levels of pregnancy-associated plasma protein A (PAPP-A) or insulin-like growth factor -1 (IGF-1) in patients with acute coronary syndrome. Methods: Serum PAPP-A and IGF-1 was measured with biotin–tyramide-amplified enzyme immunoassay and Enzyme Linked Immuoserbent Assay, respectively, in patients with ST elevation acute myocardial infarction (STEMI, n=12), unstable angina (UAP, n=15), and stable angina (n=15). PAPP-A and IGF-1 was also measured in 16 healthy subjects (control group). Results: The serum levels of PAPP-A in the STEMI (16.9±10.3 mIU/L) and UAP group (15.2±10.5 mIU/L) were higher than in the stable angina (8.5±3.1 mIU/L) or control group (8.4±2.0 mIU/L, P < 0.01). The serum levels of IGF-1 in the STEMI (132.3±40.9 µg/L) and UAP group (127.3±36.0 µg/L) were also higher than in the stable angina (44.9±18.5 µg/L) or control group (67.7±24.5µg/L, P < 0.01). There were no differences in serum levels of PAPP-A or IGF-1 among the single, double and three vessel lesion groups. The serum levels of PAPP-A (19.9±10.1 mIU/L) and IGF-1 (153.2±52.4 µg/L) after PCI were higher than those before PCI (15.1±10.0 mIU/L and 91.4±51.0 µg/L, respectively, P < 0.01). A positive correlation was found between PAPP-A and IGF-1 levels in the STEMI and UAP group before PCI (r=0.48?P < 0.01). Conclusion: PAPP-A and IGF-1 are elevated in patients with acute coronary syndrome. They may be used as biomarkers for vulnerable plaques in patients with coronary artery disease. Whether post-PCI elevation of IGF-1 can be used to predict restenosis of coronary arteries remains to be seen.

Download Full-text

Activated macrophages and coronary artery disease: The role of neopterin and growth differentiation factor 15

Journal of Clinical & Experimental Cardiology ◽

10.4172/2155-9880.c1.056 ◽

2016 ◽

Vol 07 (11) ◽

Author(s):

Pablo Avanzas

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Activated Macrophages ◽

Growth Differentiation Factor 15 ◽

Differentiation Factor ◽

Artery Disease

Download Full-text

Determinants of growth differentiation factor 15 in patients with stable and acute coronary artery disease. A prospective observational study

Cardiovascular Diabetology ◽

10.1186/s12933-016-0375-8 ◽

2016 ◽

Vol 15 (1) ◽

Cited By ~ 14

Author(s):

Serdar Farhan ◽

Matthias K. Freynhofer ◽

Ivan Brozovic ◽

Veronika Bruno ◽

Birgit Vogel ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Observational Study ◽

Prospective Observational Study ◽

Growth Differentiation Factor 15 ◽

Differentiation Factor ◽

Artery Disease ◽

Acute Coronary Artery Disease

Download Full-text

Abstract 13448: Impact of Diabetes on Growth Differentiation Factor 15 and Mortality in Patients With Stable Coronary Artery Disease: The ANOX Study

Circulation ◽

10.1161/circ.142.suppl_3.13448 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Hiromichi Wada ◽

Takashi Unoki ◽

masahiro suzuki ◽

Morihiro Matsuda ◽

Yoichi Ajiro ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

General Population ◽

Growth Differentiation Factor 15 ◽

Diabetic Status ◽

Differentiation Factor ◽

Risk Of Mortality ◽

Artery Disease ◽

Stable Cad ◽

The Impact

Background: Diabetes mellitus (DM) is still significantly associated with the risk of mortality in the general population. Higher circulating growth differentiation factor 15 (GDF-15) levels are associated with the risk of mortality in the general population, in patients with DM, and in those with coronary artery disease (CAD). However, whether GDF-15 levels differ according to the diabetic status and whether DM modifies the relationship between GDF-15 and mortality in patients with stable CAD are unclear. Methods: Using data from a multicenter, prospective cohort of 1460 patients with stable CAD, we assessed the association between diabetic status and GDF-15 and the impact of DM on the association between GDF-15 levels and the risk of all-cause death. GDF-15 was measured in 797 DM and 663 non-DM patients enrolled in the ANOX Study. Results: The mean age (standard deviation [SD]) of the patients was 71.7 (9.4) years; 74.4% were men. Patients with DM exhibited significantly higher levels of GDF-15 compared to those without DM (median [interquartile range], 1472 [1049-2258] vs. 1274 [868-1874] pg/mL, respectively; P <0.001). Stepwise multiple linear regression analysis revealed that the log-transformed (Ln-) GDF-15 level was independently associated with higher age, DM, current smoking, lower estimated glomerular filtration rate, anemia, no use of aspirin, Ln-N-terminal pro-natriuretic peptide, and Ln-high-sensitivity C-reactive protein ( P <0.005 for all). In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders (hazard ratio per 1-SD increase [HR], 1.51; 95% confidence interval [CI], 1.33-1.71). This association was still significant in patients with DM (HR, 1.52; 95% CI, 1.30-1.79) and in those without DM (HR, 1.57; 95% CI, 1.25-1.96). However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in the entire cohort and in patients with DM, but not in those without DM. Conclusions: Higher levels of GDF-15 were independently associated with DM in patients with stable CAD. The prognostic value of GDF-15 on mortality was pronounced in patients with DM.

Download Full-text

Abstract 5016: Growth-Differentiation Factor-15 is an Independent Predictor of Cardiovascular Events and Mortality in Patients with Stable Coronary Artery Disease

Circulation ◽

10.1161/circ.118.suppl_18.s_1132 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Tibor Kempf ◽

Jan-Malte Sinning ◽

Anja Quint ◽

Christoph Bickel ◽

Christoph Sinning ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Independent Predictor ◽

Troponin T ◽

Receiver Operating Curve ◽

Growth Differentiation Factor 15 ◽

Differentiation Factor ◽

All Cause Mortality ◽

Artery Disease ◽

Stable Cad

Circulating levels of the TGF β-related cytokine, growth-differentiation factor-15 (GDF-15), provide independent prognostic information in patients with unstable coronary artery disease (CAD). To explore the prognostic utility of GDF-15 in patients with stable CAD, we analyzed the relation of GDF-15 to mortality and cardiovascular (CV) events in the AtheroGene registry which enrolled consecutive patients with stable angina and at least one stenosis >30% in a larger coronary artery. Patients were followed for a median of 3.6 years. Serum samples for measurement of GDF-15 along with other biomarkers were available from 1352 patients. Two pre-specified cutoff points (1200 and 1800 ng/L) were used to identify different risk groups. 55.9%, 26.4%, and 17.7% of the patients presented with GDF-15 values <1200 ng/L, between 1200 and 1800 ng/L, and >1800 ng/L, respectively. Increasing levels of GDF-15 were related to age (P<0.001), hypertension (P=0.01), diabetes mellitus (P<0.001), low HDL cholesterol (P<0.001), and the extent of CAD (P=0.001). Moreover, significant relations to hsCRP, troponin T, NT-proBNP, and reduced renal function (GFR) were observed (all P<0.001). Increasing levels of GDF-15 were associated with an increased risk of all-cause mortality (P<0.001, log-rank test), CV mortality (P<0.001), and CV events (P<0.001). Receiver operating curve analyses confirmed GDF-15 as a strong marker of 2-year adverse outcomes (area under the curve for all-cause mortality, 0.79; CV mortality, 0.81; CV events, 0.70). By multiple Cox regression analysis, GDF-15 emerged as an independent predictor of all-cause mortality (HR 2.1 per one standard deviation of lnGDF-15 [95% CI 1.6 –2.8], P<0.001), CV mortality (HR 2.2 [95% CI 1.5–3.3], P<0.001), and CV events (HR 1.7 [95% CI 1.3–2.4], P=0.001) after adjustment for baseline characteristics, clinical variables, LDL/HDL ratio, hsCRP, troponin T, NT-proBNP, and GFR. Patients with a GDF-15 level above 1800 ng/L had a highly elevated risk of CV mortality even in the fully adjusted model (HR 5.2 [95% CI 1.6 –16.1], P=0.005). These data identify GDF-15 as a powerful and independent biomarker of mortality and CV events in patients with stable CAD.

Download Full-text