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True Effects or Bias? MMP-2 and MMP-9 Serum Concentrations after Acute Stroke
Stefan H Kreisel1, Mark Stroick, Martin Griebe
1Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany.
Background:
Average serum matrix metalloproteinase (MMP) concentrations in patients with acute stroke have shown to be varying across studies. Possibly, next to true effects, other factors may influence MMP levels. The aim of this study was to investigate the dynamics of these enzymes in repeated measurements in the acute post-stroke period, in respect to different stroke etiologies, and highlight potential sources for variability.
Methods:
Serum in 233 patients with acute ischemic or hemorrhagic stroke (stroke cohort; SC) was ascertained within 24 h after onset and then 1, 3 and 7 days thereafter. One hundred five controls (control cohort; Co) were recruited. Multi-variable adjustment was carried out using salient extraneous covariates including stroke etiology, clinical severity and lesion size next to a set of routine laboratory parameters.
Results:
Unadjusted SC MMP-2 concentrations are significantly lower (SC 165.4, 95% CI 158.5-172.4; Co 203.7 ng/ml, 95% CI 190.7-216.5; p < 0.001) and MMP-9 concentrations significantly higher than in controls (SC 608.5 ng/ml, 95% CI 555.3-661.8; Co 475.6 ng/ml, 95% CI 413.6-537.6; p < 0.001). Adjustment mitigates associations between MMP concentrations and stroke etiology, clinical severity, lesion size or differences in temporal profile shown present without adjustment. Salient covariates absorb much of the effect: age, leukocyte count and albumin concentrations are associated significantly with MMP-2 concentrations; only leukocyte count is significantly associated with MMP-9.
Conclusions:
Concentrations of MMP-2 and MMP-9 in serum in humans measured after acute stroke are potentially influenced by extraneous covariates rather than being directly associated with characteristics of the underlying stroke.
Insights
Serum matrix metalloproteinase (MMP) levels in acute stroke patients vary due to factors beyond stroke characteristics. Routine lab parameters like leukocyte count significantly influence MMP-2 and MMP-9 concentrations.
Area of Science:
- Biochemistry
- Neurology
- Clinical Chemistry
Background:
- Serum matrix metalloproteinase (MMP) levels show variability in acute stroke patients across studies.
- Potential influencing factors beyond true biological effects require investigation.
- Understanding these dynamics is crucial for accurate stroke assessment.
Purpose of the Study:
- To investigate the temporal dynamics of matrix metalloproteinases (MMPs) in acute stroke.
- To analyze MMP variations concerning stroke etiology and clinical parameters.
- To identify sources of variability in serum MMP measurements post-stroke.
Main Methods:
- Serum samples from 233 acute stroke patients and 105 controls were analyzed.
- Repeated measurements of MMP-2 and MMP-9 were taken within 24 hours, and at 1, 3, and 7 days post-stroke.
- Multivariable analysis adjusted for stroke etiology, clinical severity, lesion size, and routine laboratory parameters.
Main Results:
- Unadjusted MMP-2 levels were lower and MMP-9 levels higher in stroke patients compared to controls.
- Statistical adjustment for covariates significantly reduced associations between MMPs and stroke characteristics.
- Leukocyte count, age, and albumin concentrations were significantly associated with MMP-2; leukocyte count with MMP-9.
Conclusions:
- Serum MMP-2 and MMP-9 concentrations in acute stroke are significantly influenced by extraneous covariates.
- Factors such as age and leukocyte count, rather than stroke specifics, may drive observed MMP levels.
- These findings highlight the importance of considering confounding variables in MMP-related stroke research.
