Dataset Information

Zinc deficiency and risk of intracerebral hemorrhage: a retrospective cohort study.

ABSTRACT:

Background

Intracerebral hemorrhage (ICH) accounts for 10-20% of all strokes but contributes disproportionately to stroke-related mortality and disability. Zinc, an essential trace element crucial for vascular integrity and antioxidant defense, may influence cerebrovascular health through mechanisms affecting endothelial function and blood-brain barrier stability. However, no large-scale longitudinal study has examined the association between zinc deficiency and ICH risk.

Methods

We conducted a retrospective cohort study using the TriNetX Research Network database, including adults who underwent serum zinc testing between 2010 and 2023. Patients were categorized into zinc deficiency (serum zinc <70 μg/dL) and control groups (70-120 μg/dL). After applying exclusion criteria and 1:1 propensity score matching based on demographics, comorbidities, medications, and laboratory values, we analyzed the association between zinc deficiency and 12-month outcomes, including ICH, mortality, pneumonia, poor blood pressure control, and major adverse cardiac events (MACEs), using Cox proportional hazards regression.

Results

The final matched cohort included 147,302 patients (73,651 per group). Zinc-deficient patients demonstrated a significantly elevated risk of ICH [hazard ratio (HR): 1.75, 95% confidence interval (CI): 1.35-2.25, p < 0.001], all-cause mortality (HR: 1.90, 95% CI: 1.77-2.03, p < 0.001), pneumonia (HR: 1.50, 95% CI: 1.40-1.60, p < 0.001), poor blood pressure control (HR: 1.26, 95% CI: 1.20-1.32, p < 0.001), and MACEs (HR: 1.12, 95% CI: 1.07-1.18, p < 0.001). A clear dose-response relationship was observed, with severe zinc deficiency (<50 μg/dL) conferring a greater ICH risk (HR: 2.44, 95% CI: 1.50-3.95, p < 0.001). The ICH association remained consistent across patient subgroups, with no significant effect modification. Multivariate analysis confirmed zinc deficiency as an independent ICH predictor (adjusted HR: 1.87, 95% CI: 1.53-2.29, p < 0.001).

Conclusion

Zinc deficiency is a novel, independent, and potentially modifiable risk factor for ICH. The dose-dependent relationship and consistency across patient populations supports biological plausibility. These findings suggest that routine zinc assessment and targeted supplementation in deficient patients may offer new opportunities for ICH prevention, warranting prospective intervention trials to establish causality and optimal therapeutic strategies.

SUBMITTER: Chen IW

PROVIDER: S-EPMC12554597 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature

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Publications

Zinc deficiency and risk of intracerebral hemorrhage: a retrospective cohort study.

Chen I-Wen IW Weng Hsiu-Lan HL Ho Chun-Ning CN Liao Shu-Wei SW Lai Yi-Chen YC Wu Jheng-Yan JY Hung Kuo-Chuan KC

Frontiers in nutrition 20251013

<h4>Background</h4>Intracerebral hemorrhage (ICH) accounts for 10-20% of all strokes but contributes disproportionately to stroke-related mortality and disability. Zinc, an essential trace element crucial for vascular integrity and antioxidant defense, may influence cerebrovascular health through mechanisms affecting endothelial function and blood-brain barrier stability. However, no large-scale longitudinal study has examined the association between zinc deficiency and ICH risk.<h4>Methods</h4> ...[more]

PMID: 41158645

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Project description:Introduction: MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development.<br><br>Methods: A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n=29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n=35) consisted of a random sample of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. miRNA profiling was performed using formalin-fixed, paraffin-embedded tumors. Biomarkers related to metastatic potential were identified independent of clinical stage, and a cutoff point was selected based on the optimal sensitivity and specificity (ROC curve). Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential. <br><br>Results: miRNA expression profiling identified several miRNAs that were either specific and shared across all clinical stages (p?0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family), cell proliferation and invasion (hsa-miR-16 and has-miR-205) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were up-regulated in metastatic cases of CSI and II. Furthermore, the combination of the 3 miRNAs identified for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs. <br><br>Conclusions: Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis. These miRNAs therefore represent new risk biomarkers of breast cancer metastasis and may be useful for future targeted therapies.

Dataset Information

Zinc deficiency and risk of intracerebral hemorrhage: a retrospective cohort study.

Background

Methods

Results

Conclusion

Publications

Zinc deficiency and risk of intracerebral hemorrhage: a retrospective cohort study.

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