Rigor Reviewed

Rigor-Reviewed Manuscript

Serum Fetuin-A Levels in Patients with Cardiovascular Disease: A Meta-Analysis

Name: Αlpha¹ Rigor Record — Serum Fetuin-A Levels in Patients with Cardiovascular Disease: A Meta-Analysis
Item: Serum Fetuin-A Levels in Patients with Cardiovascular Disease: A Meta-Analysis
Rating: 59
Author: Αlpha¹

Sun ZL, Xie QY, Guo GL, Ma K, Huang YY.

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Αlpha¹ Rigor Review — 1.5★ (Critical), 0 critical, 8 high issues for “Serum Fetuin-A Levels in Patients with Cardiovascular Disease: A Meta-Analysis”

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · August 5, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

1.5 / 5

Critical — a demonstrable failure

Meta-Analysis / Systematic Review

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×3−1.5★
ClaimsOverstated claim−0.5★
ReportingData & code availability not met−0.5★
CopyeditManuscript needs significant editing−0.5★
ReportingScientific premise partially met−0.25★
ReportingReporting transparency partially met−0.25★

Model-reported confidence: moderateReviewer agreement: lowEngine: 7.15.0Source: full text

Not verified in this report

References were not verified against Crossref/OpenAlex.
No data or code availability links were detected to verify.

Problems surfaced6 types

Data and code not shared
Conclusions overstated beyond the evidence
Internal contradictions in the reported numbers
Reporting/transparency gaps
Scientific premise thinly justified
Other integrity concern

This Αlpha¹ Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This meta-analysis has a clear premise and adequate study design, but lacks a data availability statement, does not reference a reporting guideline, and has an internal contradiction in the number of included studies (10 vs. 13). The conclusion overstates the evidence by claiming clinical value for reflecting progression, while the analysis only supports an association with disease presence.

Three independent rigor evaluations were synthesized; all agreed on ethical approvals (N/A) and data code availability (fail), with some divergence on other dimensions. Only the statistical analysis was partially verified (6 tests recomputed consistently, none inconsistent). A copyedit pass identified 15 issues, including a major consistency error. The claim audit flagged one overstated claim.

6 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).

Recomputed 6 tests: 6 consistent, 0 inconsistent; 6 via agent-written checks.

3 integrity concerns flagged (0 high).

Reporting

Eight Dimensions4 pass · 2 warn · 1 fail

The paper cites prior research establishing the biological role of fetuin-A in calcification and insulin resistance, but does not systematically acknowledge strengths and weaknesses of individual studies. The rationale linking fetuin-A to CVD is presented but is somewhat muddled by contradictory evidence, and limitations of prior research are not specifically addressed beyond noting contradictory findings.

Sub-criteria

prior work citedADEQUATE

premise rationaleINADEQUATE

limitations addressedNOT REPORTED

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper establishes a clear scientific premise by reviewing prior research on fetuin-A and cardiovascular disease, but does not explicitly address limitations of prior work.

Evidence

direct quote[Introduction, paragraph 3]

“FA, also known as alpha-2-Schmid Heremans glycoprotein (AHSG), is a phosphorylated glycoprotein and a member of the fetuin group of serum binding proteins, which are all comprised of three O-linked and two N-linked oligosaccharide chains [–].”

direct quote[Introduction, paragraph 4]

“For these reasons, we hypothesized that decreased serum FA concentrations may directly limit cardiac functions by effectively promoting cardiac fibrosis and calcification and thus influence CVD progression [].”

absence[Introduction, entire]

Limitations of prior research are not specifically addressed.

WARNReviewer 2· 85% conf

The premise is established with prior research, but the rationale is somewhat unclear and limitations of prior work are not explicitly addressed.

Evidence

paraphrase[Introduction, paragraphs 2-3]

“The introduction discusses FA's role as an inhibitor of calcification, its relation to insulin resistance, and cites several studies showing both elevated and decreased serum FA levels in CVD.”

direct quote[Introduction, paragraph 3]

“Prospective research has recognized that low serum FA levels are a valid predictor of CVD [, ]. In contrast, controversial opinions have supported the idea that reduced plasma concentrations of FA may increase CVD risk by inducing adipocyte-linked inflammatory cytokines [, ].”

absence[Introduction]

Limitations of prior research are not explicitly addressed.

WARNReviewer 3· 75% conf

The scientific premise is established but relies on incomplete citations and does not explicitly address how limitations of prior research are mitigated.

Evidence

direct quote[Introduction, paragraph 3]

“Prospective research has recognized that low serum FA levels are a valid predictor of CVD [, ].”

paraphrase[Introduction, paragraph 3]

“we hypothesized that decreased serum FA concentrations may directly limit cardiac functions by effectively promoting cardiac fibrosis and calcification and thus influence CVD progression.”

absence[Not found]

No description of how limitations of prior research are addressed.

The meta-analysis uses a random-effects model, assesses heterogeneity, and conducts subgroup and sensitivity analyses. The Newcastle-Ottawa Scale is used for quality assessment. No power analysis for the meta-analysis is reported.

Sub-criteria

controlsADEQUATE

power analysisNOT REPORTED

blinding levelsN/A

outlier handlingADEQUATE

randomization unitN/A

inclusion exclusionADEQUATE

randomization methodN/A

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

The study design is appropriate for a meta-analysis, with clear inclusion/exclusion criteria, risk-of-bias assessment, and sensitivity analysis, but no power analysis for search completeness is reported.

Evidence

direct quote[Materials and Methods, section 2.2]

“We searched throughout for human-associated case-control studies assessing the association of FA serum levels with CVDs and reporting the adjusted standardized mean differences (SMDs) and 95% confidence intervals (CI).”

direct quote[Materials and Methods, section 2.4]

“the two authors used a set of predefined criteria based on the Newcastle-Ottawa scale (NOS) criteria to assess the studies independently [].”

direct quote[Materials and Methods, section 2.5]

“One-way sensitivity analysis was performed by deleting single studies included in our meta-analysis one by one to evaluate whether the results could have been significantly affected.”

WARNReviewer 2· 90% conf

The meta-analysis methodology is described in moderate detail, but lacks some key elements like a pre-registered protocol and assessment of risk of bias in included studies.

Evidence

paraphrase[Methods, Section 2.1]

“The authors list the databases searched and provide general keywords, but the full Boolean search strings are not reproduced.”

direct quote[Methods, Section 2.2]

paraphrase[Methods, Section 2.4]

“The authors used the Newcastle-Ottawa Scale to assess study quality but do not report a detailed risk-of-bias assessment for each study.”

PASSReviewer 3· 85% conf

The meta-analysis uses a comprehensive search strategy, explicit inclusion/exclusion criteria, and quality assessment of included studies.

Evidence

paraphrase[Methods, section 2.1]

“We comprehensively searched PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases up to May 30st, 2014.”

direct quote[Methods, section 2.2]

“We only extracted data from studies that supplied the sample number and sufficient information about serum levels of FA, and we excluded articles with incomplete, unavailable, or inappropriate clinicopathologic data or those regarding CVDs not confirmed by histopathologic examinations.”

paraphrase[Methods, section 2.4]

“the two authors used a set of predefined criteria based on the Newcastle-Ottawa scale (NOS) criteria to assess the studies independently.”

Table 1 provides information on sex, age, ethnicity, and disease type for each study. Health status is indicated by the case-control design. These variables are summarized adequately for a meta-analysis.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 80% conf

Biological variables are partially reported; age, sex, and ethnicity are provided in the table, but weight and health status beyond disease are not reported.

Evidence

paraphrase[Table 1]

“Gender (M/F) | Case | Control | 68/27 | 28/7”

paraphrase[Table 1]

“Age (years) | Case | Control | 67.1 ± 6.5 | 65.0 ± 9.5”

absence[Table 1]

Health status is only defined by disease type; weight and other health metrics are not reported.

WARNReviewer 2· 80% conf

Some biological variables are reported at the study level, but individual patient-level data are not available for assessment.

Evidence

paraphrase[Table 1]

“Gender (M/F) | Age (years) Case | Age (years) Control”

paraphrase[Table 1]

“Ethnicity: Caucasians / Asians”

paraphrase[Table 1]

“Table 1 lists the disease for each study (e.g., CAD, MI), but does not report health status beyond the presence of CVD.”

PASSReviewer 3· 90% conf

Biological variables (sex, age, ethnicity, disease type) are reported across included studies in Table 1.

Evidence

paraphrase[Table 1]

“Gender (M/F) columns in Table 1.”

paraphrase[Table 1]

“Age (years) columns in Table 1.”

paraphrase[Table 1]

“Ethnicity and Disease columns in Table 1.”

The paper only reuses published data, so no IRB or IACUC statement is required.

Sub-criteria

iacuc statementN/A

informed consentN/A

irb ethics statementN/A

regulatory complianceN/A

Per reviewer (3) — the votes behind the verdict

N/AReviewer 1· 95% conf

This is a meta-analysis of published studies; no new human or animal data were collected, so ethics approval is not applicable.

Evidence

direct quote[Abstract]

“Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included.”

N/AReviewer 2· 95% conf

This is a meta-analysis of published studies, which does not generate new subject-level data, so ethical approvals for the included studies are not reported and are not required for this paper.

Evidence

direct quote[Abstract]

“Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included.”

paraphrase[Methods]

“The paper describes a literature search and data extraction from published studies, not new subject enrollment.”

N/AReviewer 3· 95% conf

No ethics statement is required as this is a meta-analysis of published studies.

Evidence

absence[Not found]

No ethics statement is present, which is appropriate for a meta-analysis.

The paper identifies STATA version 12.0 as the analysis software. No antibodies, cell lines, reagents, or organisms are used, so those sub-criteria are not applicable.

Sub-criteria

mycoplasma testingN/A

reagents identifiedN/A

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The statistical software STATA is identified with version and manufacturer, which is the only applicable resource.

Evidence

direct quote[Materials and Methods, section 2.5]

“two investigators input all information in the STATA software version 12.0 (Stata Corp, College Station, TX, USA) separately and arrived at an agreement.”

N/AReviewer 2· 90% conf

This meta-analysis does not use any biological or chemical resources directly; it only analyzes published summary data.

Evidence

direct quote[Abstract]

“Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included.”

PASSReviewer 3· 95% conf

Statistical software is identified; other key resources are not applicable for this meta-analysis.

Evidence

direct quote[Methods, section 2.5]

“two investigators input all information in the STATA software version 12.0 (Stata Corp, College Station, TX, USA) separately and arrived at an agreement.”

The meta-analysis uses Z tests, Cochran's Q, I², and Egger's test. SMDs with 95% CIs are reported. P-values are reported as exact (0.007, 0.026, 0.138). STATA is identified. No arithmetic inconsistencies were found.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical tests are named, effect sizes and confidence intervals are reported, exact p-values are provided, and the software is identified. Assumptions are tested via heterogeneity assessment.

Evidence

direct quote[Materials and Methods, section 2.5]

“To calculate the effect size for each study, the summary SMDs with 95% CI were used for control versus case category of FA serum levels with the Z test.”

direct quote[Results, section 3.2]

“SMD = 1.36, 95%CI: 0.37–2.36, P = 0.007”

direct quote[Results, section 3.2]

“SMD = 1.36, 95% CI: 0.37–2.36”

WARNReviewer 2· 85% conf

Statistical methods are generally described, but there are some reporting gaps regarding exact p-values and presentation of individual study data.

Evidence

direct quote[Methods, Section 2.5]

“The random-effects model was applied when heterogeneity existed among studies, and the fixed-effects model was applied when there was no statistical heterogeneity.”

paraphrase[Results, Section 3.2]

“P = 0.007”

direct quote[Results, Section 3.2]

“SMD = 1.36, 95%CI: 0.37–2.36”

PASSReviewer 3· 80% conf

Statistical tests are named, effect sizes with CIs are reported, and software is identified; some p-values are given as thresholds rather than exact values.

Evidence

paraphrase[Methods, section 2.5]

“we utilized a random-effects model (DerSimonian and Laird method) or a fixed-effects model (Mantel-Haenszel method) of individual study results.”

direct quote[Results, section 3.2]

“SMD = 1.36, 95%CI: 0.37–2.36, P = 0.007”

direct quote[Results, section 3.3]

“Egger's test showed publication bias (both P < 0.001)”

The paper does not include a data availability statement, nor does it deposit the extracted data or analysis code in a public repository. This is a significant reporting gap.

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositNOT REPORTED

data availability statementNOT REPORTED

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 95% conf

No data availability statement, no repository deposit, no code sharing. The paper provides no access to the underlying data or analysis code.

Evidence

absence[Entire manuscript]

No data availability statement is present.

absence[Entire manuscript]

No repository deposit is mentioned.

FAILReviewer 2· 95% conf

No data availability statement is provided, and no data or code are deposited in any repository.

Evidence

absence[Entire paper]

No data availability statement is present in the paper.

absence[Entire paper]

No data repository or code sharing is mentioned.

FAILReviewer 3· 95% conf

No data availability statement is provided, and no data or code repositories are mentioned.

Evidence

absence[Not found]

No data availability statement.

The methods are described in enough detail to be reproducible. No trial registration is applicable. The paper does not mention following a reporting guideline like PRISMA. The conclusion states a correlation but the abstract and conclusion imply a causal relationship, which is an overstatement given the cross-sectional nature of the included studies. Limitations are discussed.

Sub-criteria

funding coiADEQUATE

trial registrationN/A

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalINADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Methods are detailed, limitations are discussed, and conclusions are proportional. However, no reporting guideline (e.g., PRISMA) is referenced, and funding sources are not reported.

Evidence

paraphrase[Materials and Methods, section 2.1]

“To identify all pertinent papers that assessed the correlations between serum FA expression levels and CVDs, we comprehensively searched PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases up to May 30st, 2014.”

paraphrase[Discussion, paragraph 5]

“Our study had several limitations. Firstly, we included four studies that have a limited number of patients which might have impaired the statistical power of analysis...”

direct quote[Conflict of Interests section]

“The authors declare that there is no conflict of interests regarding the publication of this paper.”

WARNReviewer 2· 85% conf

The paper reports methods and results in a reasonable manner but is missing a reference to a reporting guideline and has some overstatement in the conclusion.

Evidence

paraphrase[Methods, Sections 2.1-2.5]

“The methods section includes search strategy, selection criteria, data extraction, quality assessment, and statistical analysis.”

absence[Methods]

No reporting guideline is referenced.

direct quote[Abstract, Conclusion]

“The data indicated that decreased serum FA level is correlated with the development of CVDs. FA might be clinically valuable for reflecting the progression of CVDs.”

WARNReviewer 3· 75% conf

Methods are detailed, limitations are discussed, and conflicts of interest are declared, but no reporting guideline is referenced and funding sources are not stated.

Evidence

paraphrase[Methods, sections 2.1–2.5]

“We comprehensively searched... databases... Data extraction... according to the selection criteria.”

paraphrase[Discussion, paragraph 4]

“Our study had several limitations. Firstly, we included four studies that have a limited number of patients...”

direct quote[Acknowledgments]

“The authors declare that there is no conflict of interests regarding the publication of this paper.”

15 copyedit issues flagged (1 major): mostly grammar, typo, consistency.

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

In post-publication context, the paper's robustness is compromised by the lack of data availability (preventing independent verification of the meta-analysis) and an internal contradiction in the number of included studies (10 vs. 13). An informed reader should weigh these gaps heavily; a correction or erratum is warranted to address the contradiction and to release the extracted data.

1.
HIGHrigor
Resolve the internal contradiction between the abstract (10 studies) and the results section / Figure 1 legend (13 studies) by correcting the number throughout the manuscript.
This inconsistency undermines the reliability of the reported results and is a clear error that must be corrected in an erratum.
2.
HIGHdata code
Deposit the extracted study-level data (effect sizes, sample sizes, study characteristics) in a public repository (e.g., Figshare, Zenodo) and include a data availability statement in the paper.
Without the underlying data, the meta-analysis cannot be independently verified; this is a critical transparency gap for a data-driven study.
3.
HIGHreporting
Temper the claim that FA is 'clinically valuable for reflecting the progression of CVDs' to reflect only an association with the presence of CVD, not progression, as the cross-sectional studies cannot support a progression claim.
This overstated conclusion misrepresents the evidence and is a common reviewer objection; it should be corrected in the abstract and conclusion.
4.
HIGHreporting
Reference the PRISMA reporting guideline for meta-analyses and state adherence in the Methods section.
Reporting guidelines improve transparency and reproducibility; their absence is a notable gap for a meta-analysis.
5.
HIGHstatistics
Report exact p-values for all significance tests, including the Egger's test (currently given as P<0.001).
Threshold p-values leave ambiguity about the exact strength of evidence; exact values are preferred for transparency.
6.
HIGHreporting
Provide the full Boolean search strings for each database in a supplementary file.
Full search strings are essential for reproducibility of the literature search; currently only general keywords are given.
7.
HIGHreporting
Acknowledge funding sources or explicitly state that no funding was received, in a separate Funding statement.
Funding information is required for transparency about potential conflicts of interest; currently only a conflict of interest statement is present.
8.
HIGHcopyedit
Correct the copyedit issues: fix 'myocardiac infarction' to 'myocardial infarction', fix 'Plasmaa2-HSG' spacing, fix 'S-T STEMI' to 'ST-segment elevation myocardial infarction (STEMI)', fix 'May 30st' to 'May 30', and fill all empty brackets with proper citation numbers.
These errors undermine the professionalism of the paper and should be corrected in a revision.
9.
MEDIUMreporting
Clarify in Table 1 that duplicate rows for studies (Zhao and Bilgir) represent different disease subgroups within the same study.
This clarification prevents confusion about the number of independent studies and ensures accurate counting.
10.
MEDIUMstatistics
Report the I² statistic for the overall meta-analysis to quantify heterogeneity.
I² is a standard measure of heterogeneity and should be reported alongside the Q-test p-value.
11.
MEDIUMreporting
Provide a more detailed risk-of-bias assessment for each included study, including specific domains beyond the summary NOS score.
A domain-level assessment enhances transparency about study quality; currently only a total score is given.
12.
LOWreporting
Clarify the direction of the SMD interpretation (e.g., state that SMD was computed as control minus case) in the text.
Clarity about the direction of effect prevents misinterpretation of the results.
13.
LOWcopyedit
Use consistent abbreviation 'CVD' instead of 'CVDs' throughout the manuscript.
Consistency in terminology improves readability and professionalism.
14.
LOWcopyedit
Format the author list with commas or semicolons to separate author names.
Proper formatting of the author list is a basic requirement for submission.

Full text (23,559 chars)Analyzed: Aug 5, 2026

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