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Association between hyperlipidemia and mortality after incident acute myocardial infarction or acute decompensated heart failure: a propensity score matched cohort study and a meta-analysis

Objective To examine the effect of HLP, defined as having a pre-existing or a new in-hospital diagnosis based on low density lipoprotein cholesterol (LDL-C) level ≥100 mg/dL during index hospitalisation or within the preceding 6 months, on all-cause mortality after hospitalisation for acute myocardial infarction (AMI) or acute decompensated heart failure (ADHF) and to determine whether HLP modifies mortality associations of other competing comorbidities. A systematic review and meta-analysis to place the current findings in the context of published literature. Design Retrospective study, 1:1 propensity-score matching cohorts; a meta-analysis. Setting Large academic centre, 1996–2015. Participants Hospitalised patients with AMI or ADHF. Main outcomes and measures All-cause mortality and meta-analysis of relative risks (RR). Results Unmatched cohorts: 13 680 patients with AMI (age (mean) 68.5 ± (SD) 13.7 years; 7894 (58%) with HLP) and 9717 patients with ADHF (age, 73.1±13.7 years; 3668 (38%) with HLP). In matched cohorts, the mortality was lower in AMI patients (n=4348 pairs) with HLP versus no HLP, 5.9 versus 8.6/100 person-years of follow-up, respectively (HR 0.76, 95% CI 0.72 to 0.80). A similar mortality reduction occurred in matched ADHF patients (n=2879 pairs) with or without HLP (12.4 vs 16.3 deaths/100 person-years; HR 0.80, 95% CI 0.75 to 0.86). HRs showed modest reductions when HLP occurred concurrently with other comorbidities. Meta-analyses of nine observational studies showed that HLP was associated with a lower mortality at ≥2 years after incident AMI or ADHF (AMI: RR 0.72, 95% CI 0.69 to 0.76; heart failure (HF): RR 0.67, 95% CI 0.55 to 0.81). Conclusions Among matched AMI and ADHF cohorts, concurrent HLP, compared with no HLP, was associated with a lower mortality and attenuation of mortality associations with other competing comorbidities. These findings were supported by a systematic review and meta-analysis.


SUPPLEMENT TABLE 2. Characteristics of studies and participants included in meta-analysis
Acute myocardial infarction cohort, after PS-matching N = 8,696

PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) 2015 checklist: recommended items to address in a systematic review protocol* Title:
Association between hyperlipidemia and mortality after incident acute myocardial infarction or acute decompensated heart failure: A propensity score matched cohort study and a meta-analysis Journal:

BMJ Open
Original title of the manuscript: Hyperlipidemia is associated with lower mortality after incident acute myocardial infarction or acute decompensated heart failure: A propensity matched cohort study and a meta-analysis Provide an explicit statement of the question(s) the review will 2 address with reference to participants, interventions, comparators, and outcomes (PICO) METHODS Eligibility criteria 8 Specify the study characteristics (such as PICO, study design, setting, time frame) 7 and report characteristics (such as years considered, language, publication status) to be used as criteria for eligibility for the review Information sources 9 Describe all intended information sources (such as electronic databases, contact with study 6, 7 authors, trial registers or other grey literature sources) with planned dates of coverage Search strategy 10 Present draft of search strategy to be used for at least one electronic database, including 6 planned limits, such that it could be repeated Study records: Data management 11a Describe the mechanism(s) that will be used to manage records and data throughout the review 6, 7 Selection process 11b State the process that will be used for selecting studies (such as two independent reviewers) 7 through each phase of the review (that is, screening, eligibility and inclusion in meta-analysis) Data collection process 11c Describe planned method of extracting data from reports (such as piloting forms, done independently, 6, 7 in duplicate), any processes for obtaining and confirming data from investigators Data items 12 List and define all variables for which data will be sought (such as PICO items, funding sources), 7 any pre-planned data assumptions and simplifications Outcomes and prioritization 13 List and define all outcomes for which data will be sought, including prioritization of main and 7 additional outcomes, with rationale Risk of bias in individual studies 14 Describe anticipated methods for assessing risk of bias of individual studies, including whether 7 this will be done at the outcome or study level, or both; state how this information will be used in data synthesis Data synthesis 15a Describe criteria under which study data will be quantitatively synthesised 6, 7 15b If data are appropriate for quantitative synthesis, describe planned summary measures, 6,7 methods of handling data and methods of combining data from studies, including any planned exploration of consistency (such as I 2 , Kendall's τ) 15c Describe any proposed additional analyses (such as sensitivity or subgroup a 9 nalyses, meta-regression) 15d If quantitative synthesis is not appropriate, describe the type of summary planned 9 Meta-bias(es) 16 Specify any planned assessment of meta-bias(es) (such as publication bias across studies, 6, 7 selective reporting within studies) Confidence in cumulative 17 Describe how the strength of the body of evidence will be assessed (such as GRADE) 9

STROBE Statement
Checklist of items that is included Title: Association between hyperlipidemia and mortality after incident acute myocardial infarction or acute decompensated heart failure: A propensity score matched cohort study and a meta-analysis Journal: Statistical methods 12 (a) Describe all statistical methods, including those used to control for confounding 7,8,9 (b) Describe any methods used to examine subgroups and interactions 8,9 (c) Explain how missing data were addressed 8,9 (d) Cohort study-If applicable, explain how loss to follow-up was addressed Case-control study-If applicable, explain how matching of cases and controls was addressed Cross-sectional study-If applicable, describe analytical methods taking account of sampling strategy 8,9 (e) Describe any sensitivity analyses 8,9

Results
Participants 13* (a) Report numbers of individuals at each stage of study-eg numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed 9 (b) Give reasons for non-participation at each stage (c) Consider use of a flow diagram Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders 9,10 (b) Indicate number of participants with missing data for each variable of interest 9 (c) Cohort study-Summarise follow-up time (eg, average and total amount) 10 Outcome data 15* Cohort study-Report numbers of outcome events or summary measures over time 9,10 Case-control study-Report numbers in each exposure category, or summary measures of exposure 10 Cross-sectional study-Report numbers of outcome events or summary measures 10 Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence interval). Make clear which confounders were adjusted for and why they were included 10, 11,12 (b) Report category boundaries when continuous variables were categorized 9, 10 (c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period Other analyses 17 Report other analyses done-eg analyses of subgroups and interactions, and sensitivity analyses 11, 12 Discussion Key results 18 Summarize key results with reference to study objectives 13 Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and magnitude of any potential bias 16