Baseline C-Reactive Protein Levels and Life Prognosis in Parkinson Disease

Abstract

Background: C-reactive protein (CRP) is a biomarker of inflammation, and high levels of CRP correlate with vascular death. Chronic inflammation is considered to be involved in neurodegeneration, although there is no evidence linking it with the process of neurodegenerative diseases.

Objective: To determine the role of baseline CRP levels in the prognosis of patients with Parkinson disease (PD).

Methods: A cohort of 313 patients with a mean age of 69.1 and mean PD duration of 7.9 years was retrospectively followed for a mean observation time of 1,753 days. CRP was measured when patients were not diagnosed with any infections, and levels were repetitively measured to investigate a tendency of "regression to mean." The primary outcome measure was a survival time from study enrollment to death.

Results: During the observation period 56 patients died. Baseline CRP was log-linearly associated with a risk of death in PD. Mean survival time was 3,149 (95% confidence interval; 3,009-3,289) days in patients with CRP ≤ 0.8mg/L (lower two thirds) and 2,620 (2,343-2,897) days in those with CRP > 0.8 mg/L (top third, p < 0.001, log-rank test). The adjusted hazard ratio (HR) per two-fold higher CRP concentration for all deaths was 1.29 (1.10-1.52), and after excluding PD-unrelated deaths, such as cancer or stroke, HR was 1.23 (1.01-1.49) (adjusted for age, sex, PD duration, modified Hohen-Yahr stages, MMSE scores, and serum albumin).

Conclusions: Baseline CRP concentrations were associated with the risk of death and predicted life prognosis of patients with PD. The associations were independent from PD duration, PD severity, cognitive function, ages, and nutritional conditions, suggesting the possibility that subclinical chronic inflammation is associated with a neurodegenerative process in PD.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Serial changes in CRP levels in patients with low, mid, and high baseline CRP concentrations.

CRP was measured at study enrollment and during the follow-up period (21–180 days, 181–360 days, 361–720 days, and 721–1080 days after study enrollment). Patients were assigned to three groups: those with low-level ( 0.8 mg/L) CRP at enrollment. Data represent median, and top and bottom error bars represent 75 and 25 percentile values, respectively.

Fig 2. Survival curves of PD patients according to baseline clinical features.

Cumulative survival rates according to CRP levels (A), PD disease duration (B), modified H-Y stages (C), MMSE score (D), age (E), sex (F), NSAID use (G), and serum albumin (H). There was a statistically significant difference in the survival rate between patients with CRP > 0.8 mg/L and ≤ 0.8 mg/L (p = 0.00004) (A), patients with PD disease duration ≤ 8 years and > 8 years (p = 0.00004) (B), those with modified H-Y 1–3 and modified H-Y 4–5 (p = 0.00001) (C), and those with albumin > 4.0mg/dL and albumin ≤ 4.0mg/dL (p = 0.004). However, the survival rate was not influenced by MMSE score, (p = 0.499) (D), age (p = 0.117) (E), sex (p = 0.186) (F), or NSAID use (p = 0.846). Statistical significance was tested using the Log-rank test.

Fig 3. Relative risk of death by CRP concentration.

Relative risk of death was estimated as hazard ratios (HRs) using Cox proportional hazard models. Unadjusted HRs of all deaths correlated with log CRP concentrations (A). To exclude possible confounders, HRs of all deaths were adjusted for age, sex, PD disease duration, MMSE (≤24 vs. >24), mH-Y (1–3 vs. 4–5), and serum albumin levels, and the analysis showed a log-linear association with CRP concentrations (B). Similarly unadjusted and adjusted HRs of death, excluding PD-unrelated deaths, correlated with CRP concentrations (C, D). Unadjusted and age- and sex-adjusted HRs of deaths from pneumonia correlated with CRP concentrations (E, F). Unadjusted and age- and sex-adjusted HRs of sudden deaths correlated with CRP concentrations, although there was no significance (G, H). Unadjusted and age- and sex-adjusted HRs of deaths from cancer correlated with CRP concentration, although there was no significance (I, J).

Fig 4. Survival curves of PD patients according to CRP levels.

The cumulative survival rate was compared in patients with CRP ≤ 0.8 mg/L and those with CRP > 0.8 mg/L and was stratified by age (A), sex (B), PD duration (C), modified H-Y stage (D), MMSE (E), and serum albumin (F). The cumulative survival rate was significantly higher in patients with CRP ≤ 0.8 mg/L than those with CRP > 0.8 mg/L. Statistical significance was calculated in pooled models.