May 20, 2026
Lipoprotein(a) and Adverse Cardiovascular Outcomes in Dialysis Patients: A Systematic Review and Meta-Analysis
- 1Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, Medical School, Athens, Greece
Protocol Citation: Ioannis Bellos 2026. Lipoprotein(a) and Adverse Cardiovascular Outcomes in Dialysis Patients: A Systematic Review and Meta-Analysis. protocols.io https://dx.doi.org/10.17504/protocols.io.dm6gp7491gzp/v1
License: This is an open access protocol distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: Working
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Created: May 20, 2026
Last Modified: May 20, 2026
Protocol Integer ID: 317585
Keywords: adverse cardiovascular outcomes in dialysis patient, adverse cardiovascular outcomes in dialysis population, regarding dialysis modality, dialysis patient, dialysis population, dialysis modality, undergoing maintenance dialysis, risk factor for atherosclerotic cardiovascular disease, adverse cardiovascular outcome, maintenance dialysis, receiving maintenance dialysis, cardiovascular outcomes in patient, atherosclerotic cardiovascular disease, cardiovascular outcome, cardiovascular mortality in the general population, cardiovascular mortality, atherosclerosis, major alterations in lipid metabolism, profound cardiovascular burden, lipid metabolism, chronic inflammation
Abstract
Elevated lipoprotein(a) [Lp(a)] concentrations are an established risk factor for atherosclerotic cardiovascular disease and cardiovascular mortality in the general population. Patients receiving maintenance dialysis represent a particularly high-risk population characterized by profound cardiovascular burden, accelerated atherosclerosis, chronic inflammation, and major alterations in lipid metabolism. Although several observational studies have evaluated the association between Lp(a) and adverse cardiovascular outcomes in dialysis populations, findings have remained inconsistent, with substantial heterogeneity regarding dialysis modality, exposure definition, outcome assessment, and adjustment for confounding variables. Therefore, we designed this systematic review and meta-analysis to comprehensively evaluate the prognostic role of Lp(a) for mortality and cardiovascular outcomes in patients undergoing maintenance dialysis.
Study selection The systematic review will be conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Because only data from previously published studies will be used, ethical approval will not be required.
Eligibility criteria The review population will include adults with kidney failure receiving maintenance hemodialysis or peritoneal dialysis. Studies involving predialysis chronic kidney disease populations or kidney transplant recipients will be excluded. The exposure of interest will be serum lipoprotein(a) [Lp(a)] concentration, evaluated either as a continuous variable or according to prespecified categories or thresholds defined in the original studies. When applicable, comparisons will be performed between the highest and lowest exposure categories. Outcomes of interest will include all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events, including myocardial infarction, stroke, heart failure, coronary or peripheral revascularization, and composite cardiovascular outcomes. Studies evaluating only surrogate biomarkers or nonclinical outcomes will be excluded. Eligible study designs will include prospective and retrospective cohort studies. Case-control studies, cross-sectional studies, case series, case reports, conference abstracts, animal studies, and in vitro studies will be excluded.
Search strategy The following electronic databases will be systematically searched from inception through May 5, 2026: MEDLINE (via PubMed), Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL). In addition, the reference lists of all included studies and relevant reviews will be manually screened to identify potentially eligible articles not captured by the primary search (snowball method). The search strategy will combine controlled vocabulary terms (Medical Subject Headings [MeSH]) and free-text keywords related to Lp(a), dialysis, and cardiovascular outcomes. No language restrictions will be applied.
Study selection Study selection will be performed in 3 sequential stages. First, the titles and abstracts of all retrieved records will be screened for potential eligibility. Second, the full texts of studies considered potentially eligible will be independently assessed. Third, studies that do not report the outcomes of interest or meet predefined exclusion criteria will be excluded, and the reasons for exclusion will be documented. Study selection will be conducted independently by 2 reviewers. Any disagreements will be resolved through discussion among all authors.
Quality assessment Risk of bias will be assessed independently by 2 reviewers using the ROBINS-E (Risk Of Bias In Non-randomized Studies of Exposures) tool, evaluating bias due to confounding, exposure measurement, participant selection, post-exposure interventions, missing data, outcome measurement, and selective reporting. Particular emphasis will be placed on adequacy of adjustment for dialysis-specific confounders, including prior cardiovascular disease, dialysis modality and vintage, inflammation, nutritional status, diabetes, and residual kidney function. Exposure assessment will focus on the timing and methodology of Lp(a) measurement, including assay standardization and baseline ascertainment before outcome occurrence, whereas participant-selection bias will be evaluated according to incident versus prevalent dialysis sampling and exclusions related to biomarker availability. Outcome assessment will consider the objectivity and adjudication of cardiovascular and mortality endpoints, and selective reporting will be evaluated based on the availability of prespecified analytical approaches. Overall risk of bias will be categorized as low, moderate, high, or critical. Any disagreements will be resolved through discussion among all authors.
Statistical analysis When at least 3 studies report sufficiently comparable adjusted effect estimates for the same outcome, quantitative synthesis will be performed using random-effects meta-analysis. The primary effect measure will be the adjusted hazard ratio (HR) with 95% confidence interval (CI) for the association between higher Lp(a) concentration and each outcome. For studies reporting categorical Lp(a), the most fully adjusted HR comparing the highest versus lowest available Lp(a) category will be preferentially extracted. When studies report dichotomous exposure groups, the HR comparing elevated versus lower Lp(a) will be used. Separate meta-analyses will be planned for all-cause mortality, cardiovascular mortality, and composite cardiovascular events or major adverse cardiovascular events (MACE). Random-effects models will be used because clinical and methodological heterogeneity is anticipated across studies. Between-study variance (τ²) will be estimated using the restricted maximum likelihood (REML) method, with Hartung-Knapp adjustment applied for confidence intervals. Statistical heterogeneity will be quantified using the inconsistency index (I²). Studies reporting continuous Lp(a) associations, including per log-unit or per unit increase estimates, will not be pooled with categorical estimates in the primary analysis. These studies will be synthesized separately when at least 3 comparable estimates are available; otherwise, they will be summarized narratively.