Serum Fetuin-A Levels in Patients with Cardiovascular Disease: A Meta-Analysis
Sun ZL, Xie QY, Guo GL, Ma K, Huang YY.
- DOI
- 10.1155/2014/691540
- Record issued
- 2026-08-05
- Engine
- 7.15.0
- Exported
- 2026-09-19
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/ff109a1a-a66a-4737-89e6-6bfd8e2bf5fa is authoritative.
How this rating was calculated
- 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★
- References were not verified against Crossref/OpenAlex.
- No data or code availability links were detected to verify.
- 01Data and code not shared
No data availability statement, no repository deposit, no code sharing. The paper provides no access to the underlying data or analysis code.
- 02Internal contradictions in the reported numbers
The abstract states 10 case-control studies were included, but the results section (3.1) states 'Thirteen case-control studies were included in this meta-analysis.' This is a clear internal contradiction.
Abstract: 'Ten case-control studies... were included.' Results: 'Thirteen case-control studies were included in this meta-analysis.'
Abstractreviewer’s wording - 03Internal contradictions in the reported numbers
The number of included studies is stated as 10 in the results text but as 13 in the Figure 1 legend.
Our present meta-analysis included a total of 10 case-control papers... Figure 1: Thirteen case-control studies were included in this meta-analysis.
Figure 1reviewer’s wording - 04Conclusion reaches beyond the evidence
FA might be clinically valuable for reflecting the progression of CVDs.
“FA might be clinically valuable for reflecting the progression of CVDs.”
Discussion
This Kaimen Rigor review uses Kaimen 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.
Numerical inconsistencies
1 finding · worst mediumValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
- Internal contradictions in the reported numbersAssessed
Recomputed 3 tests: 3 consistent, 0 inconsistent; 3 via agent-written checks.
- CONSISTENTreported p = .007 · recomputed p = .007Reviewers 1, 3Two-tailed p-value for overall SMD from 95% CIHow we recomputed it: pCI(1.36, 0.37, 2.36, 0)
- CONSISTENTreported p = .026 · recomputed p = .027Reviewers 1, 3Two-tailed p-value for Caucasian subgroup SMD from 95% CIHow we recomputed it: pCI(1.73, 0.20, 3.26, 0)
- CONSISTENTreported p = .138 · recomputed p = .135Reviewers 1, 3Two-tailed p-value for Asian subgroup SMD from 95% CIHow we recomputed it: pCI(1.04, -0.33, 2.40, 0)
- mediuminternal contradictionThe abstract states 10 case-control studies were included, but the results section (3.1) states 'Thirteen case-control studies were included in this meta-analysis.' This is a clear internal contradiction.
Abstract: 'Ten case-control studies... were included.' Results: 'Thirteen case-control studies were included in this meta-analysis.'
Abstractreviewer’s wording - mediuminternal contradictionThe number of included studies is stated as 10 in the results text but as 13 in the Figure 1 legend.
Our present meta-analysis included a total of 10 case-control papers... Figure 1: Thirteen case-control studies were included in this meta-analysis.
Figure 1reviewer’s wording
Overstated conclusions
2 findings · worst mediumConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
- Conclusions overstated beyond the evidenceAssessed
- Conclusions only partially backed by the presented evidenceAssessed
6 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).
- overstatedReviewers 1, 2, 3FA might be clinically valuable for reflecting the progression of CVDs.The meta-analysis only demonstrates an association between FA levels and the presence of CVD, not progression. The claim goes beyond the evidence.Evidence: Cross-sectional case-control data cannot assess progression.
“FA might be clinically valuable for reflecting the progression of CVDs.”
Discussion - partialReviewer 1Serum FA levels were possibly related to the presence and severity of CVDs.The evidence supports an association with presence, but severity was not directly analyzed; the claim is partially supported.Evidence: No analysis of severity is reported; only presence vs. controls.
“serum FA levels were possibly related to the presence and severity of CVDs.”
Discussion - partialReviewers 1, 2, 3Decreased serum FA level is correlated with the development of CVDs.The meta-analysis shows an association, but the direction of effect is ambiguous (some studies show higher FA in cases) and publication bias is present.Evidence: Overall SMD = 1.36, 95%CI: 0.37–2.36, P = 0.007, but Egger's test indicates publication bias (P < 0.001).
“The data indicated that decreased serum FA level is correlated with the development of CVDs.”
Discussion - partialReviewers 1, 2, 3Low serum FA levels are related to CVDs in Caucasians but not in Asians.Subgroup analyses show a significant association in Caucasians and non-significant in Asians, but the analysis is limited by small sample sizes and potential confounding.Evidence: Subgroup analysis: SMD = 1.73, 95%CI: 0.20–3.26, P = 0.026 for Caucasians; SMD = 1.04, 95%CI: −0.33–2.40, P = 0.138 for Asians.
“Ethnicity-subgroup analysis implied that low serum FA levels are related to CVDs in Caucasians (SMD = 1.73, 95%CI: 0.20–3.26, P = 0.026), but not in Asians (SMD = 1.04, 95%CI: −0.33–2.40, P = 0.138).”
Results - supportedReviewer 2There is a significant association between lower serum levels of FA and CVDs.The meta-analysis provides a pooled SMD of 1.36 (95% CI: 0.37–2.36, P = 0.007), which supports this claim.Evidence: Pooled SMD = 1.36, 95% CI: 0.37–2.36, P = 0.007
“The results showed significant differences in serum levels of FA between the CVDs patients and the healthy controls (SMD = 1.36, 95%CI: 0.37–2.36, P = 0.007).”
Abstract - supportedReviewer 3Significant differences in serum FA levels between CVD patients and healthy controls (SMD = 1.36, 95%CI: 0.37–2.36, P = 0.007).The meta-analysis provides the reported effect size and confidence interval, and the p-value is consistent with the CI.Evidence: Results section 3.2: SMD = 1.36, 95%CI: 0.37–2.36, P = 0.007.
“SMD = 1.36, 95%CI: 0.37–2.36, P = 0.007”
Results
Data authenticity concerns
1 finding · worst lowAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
- Other integrity concernAssessed
3 integrity concerns flagged (0 high).
- lowotherThe paper reports Egger's test P < 0.001 indicating significant publication bias, yet the conclusions do not adequately temper the findings in light of this bias.
Egger's test showed publication bias (both P < 0.001).
Discussionreviewer’s wording
Reporting gaps
3 findings · worst highRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Data and code not sharedAssessed
- Reporting/transparency gapsAssessed
- Scientific premise thinly justifiedAssessed
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.
“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 [–].”
“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 [].”
“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 [, ].”
“Prospective research has recognized that low serum FA levels are a valid predictor of CVD [, ].”
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.
“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).”
“the two authors used a set of predefined criteria based on the Newcastle-Ottawa scale (NOS) criteria to assess the studies independently [].”
“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.”
“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).”
“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.”
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.
The paper only reuses published data, so no IRB or IACUC statement is required.
“Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included.”
“Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included.”
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.
“two investigators input all information in the STATA software version 12.0 (Stata Corp, College Station, TX, USA) separately and arrived at an agreement.”
“Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included.”
“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.
“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.”
“SMD = 1.36, 95%CI: 0.37–2.36, P = 0.007”
“SMD = 1.36, 95% CI: 0.37–2.36”
“The random-effects model was applied when heterogeneity existed among studies, and the fixed-effects model was applied when there was no statistical heterogeneity.”
“SMD = 1.36, 95%CI: 0.37–2.36”
“SMD = 1.36, 95%CI: 0.37–2.36, P = 0.007”
“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.
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.
“The authors declare that there is no conflict of interests regarding the publication of this paper.”
“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.”
“The authors declare that there is no conflict of interests regarding the publication of this paper.”
Broken references and links
None found · partly checkedReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.
Copyediting
1 finding · worst lowWording, consistency and formatting errors that need correcting before submission.
- Wording or formatting errors that need correctingAssessed
15 copyedit issues flagged (1 major): mostly grammar, typo, consistency.
- MAJORconsistencyResults vs Figure 1 legend“Our present meta-analysis included a total of 10 case-control papers... Figure 1: Thirteen case-control studies were included in this meta-analysis.”→ Ensure the number of included studies is consistent throughout the manuscript.Text says 10 studies, figure legend says 13.
- MINORtypoKeywords, line 1“myocardiac infarction”→ myocardial infarctionMisspelling of 'myocardial'.
- MINORtypoTable 1, footnote (10)“Plasmaa2-HSG”→ Plasma a2-HSGMissing space between 'Plasma' and 'a2-HSG'.
- MINORgrammarDiscussion, paragraph 2“S-T STEMI”→ ST-segment elevation myocardial infarction (STEMI)Inconsistent abbreviation; 'S-T' is non-standard.
- MINORconsistencyEntire manuscript“CVDs”→ CVDBoth 'CVDs' and 'CVD' are used; consistency is preferred.
- MINORgrammarIntroduction, paragraph 1“CVD's estimated mortality rate”→ CVD estimated mortality ratePossessive form is unnecessary.
- MINORgrammarAbstract, Methods“Method . Potential relevant studies were identified covering the following databases”→ Methods: Potential relevant studies were identified from the following databasesFragment sentence and missing preposition.
- MINORtypoMethods, Section 2.1“May 30st”→ May 30Incorrect ordinal suffix.
- MINORgrammarAbstract, Results“The results showed significant differences in serum levels of FA between the CVDs patients and the healthy controls”→ The results showed significant differences in serum levels of FA between CVD patients and healthy controlsUnnecessary article 'the' before CVDs.
- MINORconsistencyResults, Section 3.1“Thirteen case-control studies were included in this meta-analysis.”→ Ten case-control studies were included in this meta-analysis.Abstract says 10 studies; text here says 13, which is inconsistent.
- MINORclarityIntroduction, paragraph 3“Because of the existence of contradictory theories on this subject, we conducted the following meta-analysis on downregulated serum FA levels and its contributory effects on CVD.”→ Given the contradictory evidence, we conducted a meta-analysis to evaluate the association between serum FA levels and CVD.Awkward phrasing and unclear rationale.
- MINORtypoTitle/Author list“Sun Ze-Lin Xie Qi-Ying Guo Gong-Liang Ma Ke Huang Yuan-Yuan”→ Separate author names with commas or semicolons, e.g., 'Sun Ze-Lin, Xie Qi-Ying, Guo Gong-Liang, Ma Ke, Huang Yuan-Yuan'Author list is not properly formatted.
- MINORclarityAbstract“Fetuin-A (FA) suppresses arterial calcification, promotes insulin resistance, and appears to be elevated in patients with cardiovascular diseases (CVD), but the data is still inconsistent.”→ Consider rephrasing for clarity: 'Fetuin-A (FA) suppresses arterial calcification and promotes insulin resistance; its serum levels appear elevated in patients with cardiovascular disease (CVD), but evidence remains inconsistent.'Run-on sentence with multiple clauses.
- MINORpunctuationThroughout“[]”→ Replace empty brackets with proper citation numbers or superscripts.Multiple instances of empty brackets indicating missing references.
- MINORgrammarIntroduction, paragraph 2“the fetuin-A (FA) protein has recently been the target of an increasing number of investigated cardiovascular disease”→ Change to 'the fetuin-A (FA) protein has recently been the target of an increasing number of investigations in cardiovascular disease'Missing preposition and awkward phrasing.
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.HIGHrigorResolve 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 codeDeposit 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.HIGHreportingTemper 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.HIGHreportingReference 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.HIGHstatisticsReport 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.HIGHreportingProvide 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.HIGHreportingAcknowledge 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.HIGHcopyeditCorrect 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.MEDIUMreportingClarify 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.MEDIUMstatisticsReport 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.MEDIUMreportingProvide 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.LOWreportingClarify 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.LOWcopyeditUse consistent abbreviation 'CVD' instead of 'CVDs' throughout the manuscript.Consistency in terminology improves readability and professionalism.
- 14.LOWcopyeditFormat the author list with commas or semicolons to separate author names.Proper formatting of the author list is a basic requirement for submission.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.