Low glomerular filtration rate and risk of myocardial infarction: A systematic review and meta-analysis
Introduction
Chronic kidney disease (CKD) and its associated complications are of widespread growing concern in the United States. The overall prevalence in the U.S. general population is 14%, and that number continues to rise [1]. In a previous large-scale observational cohort, worsening estimated glomerular filtration (eGFR) was shown to be associated with increased cardiovascular events, cardiovascular deaths, and hospitalizations [2]. Consequently, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative defines CKD as a “non-traditional” risk factor for cardiovascular disease and recommends that patients with CKD be viewed as high risk subjects [3]. Conversely, the American Heart Association recommends calculating eGFR for all routine evaluations of patients with cardiovascular disease or at high risk for cardiovascular disease [4].
Though CKD and cardiovascular disease share common risk factors such as hypertension and diabetes, it has been previously hypothesized that increased systemic inflammation stemming from CKD may independently increase the risk for coronary events [5], [6], [7]. This separate increase in risk may also be explained by oxidative stress linked to retained uremic solutes due to declining renal filtration [8]. Furthermore, studies evaluating cardiovascular disease among hemodialysis patients have shown that end-stage renal disease confers a greater risk for cardiovascular events than the associated standard risk factors alone [9], [10]. Patients with low eGFR without requiring dialysis therefore may be at an increased risk for cardiovascular disease independent of other associated shared conditions.
To this end, previous systematic reviews have indicated that worsening eGFR is associated with increasing risk for cerebrovascular disease and any form of cardiovascular disease with other risk factors being adjusted [11], [12]. Despite this well-acknowledged fear of future cardiovascular disease in patients suffering from CKD, no meta-analysis of observational studies evaluating the association between CKD and myocardial infarction, a key component of cardiovascular burden, has been conducted. Identifying the association between CKD and myocardial infarction and stratifying the risk of myocardial infarction based on eGFR levels are clinically warranted to further ascertain the role of CKD as a risk factor for cardiovascular disease.
The following is a comprehensive review and meta-analysis of observational studies associating low eGFR with follow-up risk for myocardial infarction. Subgroup analyses were completed to identify groups of subjects with CKD at particularly increased risk. Lastly, we reviewed relevant literature and assessed the role of CKD as a risk factor for coronary artery disease.
Section snippets
Methods
The search strategy was conducted following the recommendations detailed by The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) Group [13]. We searched PubMed, EMBASE, and the Cochrane Library from database onset to February 14, 2016 using the following search strategy: “chronic kidney disease” AND “myocardial infarction”. The search strategy was limited to humans only with no language restrictions. Relevant citations in the selected studies were also searched for possible
Results
The initial database search retrieved 4785 records for review. 196 studies were considered for detailed assessment while 4589 abstracts were eliminated for further review for failing to fulfill inclusion criteria. Of the remaining 196 records, 178 studies were excluded after assessment of the full publications. Nineteen studies were selected for inclusion in the meta-analysis. The search of comprehensive reviews retrieved 940 records for review. We selected 19 comprehensive reviews that were
Discussion
Our systematic review including 26 observational studies and almost 2,000,000 subjects suggests that even mild renal dysfunction increases the risk for myocardial infarction and that the risk augments with declining eGFR. All studies reported multivariable-adjusted RR ratios, thus attenuating the concern for confounding. Through our subgroup analyses, we found a higher risk for myocardial infarction for men compared to women for stage II CKD. The less severe degree of CKD may play a more
Conclusions
Our findings overall indicate that patients with known CKD have more than a 50% increase in risk for future myocardial infarction regardless of baseline cardiovascular comorbidities. In the context of the previous literature, CKD has an association with not only myocardial infarction but also overall cardiovascular burden and mortality. It is currently unclear if CKD is equitable to other traditional coronary risk factors such as diabetes or smoking. Our results imply that healthcare providers
Contributions
B.O., M.L., and V.V. conceived the study. M.L. and V.V. designed the selection criteria. V.V. and M.L. completed the study search. M.L. and Y.L.W. completed the data analysis. V.V., M.L., and S.B. drafted the manuscript. All authors commented on the final draft and approved the manuscript.
Disclosures
None.
Acknowledgements
We would like to thank Udayan Bhatt, M.D. at the Ohio State University College of Medicine, Department of Nephrology for his contributions towards the project.
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2022, Nutrition, Metabolism and Cardiovascular DiseasesCitation Excerpt :Kon S et al. [34] reported that eGFR was an independent risk factor of CVD in the Japanese Health Examination and Guidance Project, with a hazard ratio of 2.28 after adjusting for confounding factors. Vishal Vashistha et al. [35] also demonstrated decreased baseline eGFR was strongly associated with future myocardial infarction (eGFR < 60 mL/min/1.73 m2, relative risk of myocardial infarction was 1.52; relative risk for eGFR of 60–90 mL/min/1.73 m2 was 1.21). However, controversial results have emerged, such as the Framingham Heart Study, a 15-year follow-up of 6233 people in the United States, which found that the association between mild renal insufficiency and ASCVD was not independent [36].
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Vashistha and Lee contributed equally to the manuscript.