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Abstract: PO1839

Plasma Proteins Associated with eGFR and Incident Cardiovascular Events in the Cardiovascular Health Study Cohort

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Limonte, Christine P., University of Washington, Seattle, Washington, United States
  • Garimella, Pranav S., University of California San Diego, La Jolla, California, United States
  • Gerszten, Robert, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Jalal, Diana I., The University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Odden, Michelle, Stanford University, Stanford, California, United States
  • Shlipak, Michael, University of California San Francisco, San Francisco, California, United States
  • Bansal, Nisha, University of Washington, Seattle, Washington, United States
  • Austin, Thomas R., University of Washington, Seattle, Washington, United States
  • de Boer, Ian H., University of Washington, Seattle, Washington, United States
Background

Proteomics may help identify mechanisms through which low estimated glomerular filtration rate (eGFR) increases risks of heart failure (HF), myocardial infarction (MI), and cardiovascular (CV) death.

Methods

We utilized an aptamer-based assay to measure 1300 proteins among 3185 older adults in the Cardiovascular Health Study. Proteins associated with eGFR were identified using linear regression models. A Bonferroni-corrected p-value less than 7.6x10-8 was used to account for multiple testing. Proteins significantly associated with eGFR were tested for associations with incident HF, MI, and CV death using Cox-proportional hazard regression adjusting for demographic and clinical variables. We evaluated whether proteins mediated associations between eGFR and incident CV events.

Results

The mean baseline eGFR was 70 ml/min/1.73m2 and over a follow-up median of 13 years, there were 1033 incident HF, 555 incident MI, and 963 CV death events. 797 proteins were significantly associated with eGFR. Of these, 52, 0, and 22 proteins were associated with incident HF, MI, and CV death, respectively. All proteins associated with HF and CV death significantly mediated the effects between eGFR and incident CHF and CV death, respectively. The 10 proteins most strongly associated with both HF and CV are shown in the Table.

Conclusion

eGFR is associated with a large number of plasma proteins. A subset of these proteins are also associated with incident HF and CV death and may reflect mechanisms through which reduced eGFR increases the risk of these outcomes.

ProteinBeta (95% CI) corresponding to log2-1SD higher protein concentration for every 10 ml/min/1.73m2 lower eGFR HF CV Death
HR (95% CI) Proportion Mediated α HR (95% CI) Proportion Mediated α
N-terminal pro-BNP0.13
(0.11, 0.15)		1.61
(1.49, 1.74)		0.561.51
(1.40-1.63)		0.54
Growth/differentiation factor 150.29
(27.2, 30.8)		1.35
(1.24, 1.46		0.791.34
(1.23-1.46)		0.78
Tumor necrosis factor receptor superfamily member 1A0.43
(0.42, 0.45)		1.36
(1.23, 1.51)		1.00β 1.26
(1.13-1.40)		0.89
Macrophage metalloelastase0.19
(0.17, 0.21)		1.27
(1.18, 1.37)		0.391.33
(1.23-1.44)		0.48
Angiopoietin-20.18
(0.16, 0.20)		1.24
(1.15-1.33)		0.341.29
(1.20-1.39)		0.42
Tumor necrosis factor receptor superfamily member 11B0.09
(0.08, 0.12)		1.23
(1.14-1.32)		0.181.25
(1.18-1.35)		0.20
Endostatin0.37
(0.35, 0.39)		1.26
(1.16-1.38)		0.831.26
(1.13-1.42)		0.81
Insulin-like growth factor-binding protein 70.12
(0.10, 0.14)		1.23
(1.16-1.31		0.221.18
(1.10-1.26)		0.18
Alpha-1-antitrypsin0.06
(0.04, 0.08)		1.18
(1.11-1.27)		0.121.17
(1.09-1.25)		0.11
Periostin0.09
(0.07, 0.12)		1.15
(1.08-1.24)		0.131.16
(1.09-1.24)		0.14

α Proportion by which protein mediates association between eGFR and CV event; all p-values <1x10-15 βProportion set to 1.0 (original value >1.0)

Funding

  • Other NIH Support