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      Albuminuria, Reduced Kidney Function, and the Risk of ST‐ and non–ST‐segment–elevation myocardial infarction

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          Abstract

          Background

          Chronic kidney disease is a recognized independent risk factor for cardiovascular disease, but whether the risks of ST‐segment–elevation myocardial infarction ( STEMI) and non–ST‐segment–elevation myocardial infarction ( NSTEMI) differ in the chronic kidney disease population is unknown.

          Methods and Results

          Using administrative data from Ontario, Canada, we examined patients ≥66 years of age with an outpatient estimated glomerular filtration rate ( eGFR) and albuminuria measure for incident myocardial infarction from 2002 to 2015. Adjusted Fine and Gray subdistribution hazard models accounting for the competing risk of death were used. In 248 438 patients with 1.2 million person‐years of follow‐up, STEMI, NSTEMI, and death occurred in 1436 (0.58%), 4431 (1.78%), and 30 015 (12.08%) patients, respectively. The highest level of albumin‐to‐creatinine ratio (>30 mg/mmol) was associated with a 2‐fold higher adjusted risk of both STEMI and NSTEMI among patients with eGFR≥60 mL/(min·1.73 m 2) compared to albumin‐to‐creatinine ratio <3 mg/mmol. The lowest level of eGFR (<30 mL/[min·1.73 m 2]) was not associated with higher STEMI risk but with a 4‐fold higher risk of NSTEMI compared to those with eGFR≥60 mL/(min·1.73 m 2). The lowest eGFR (<30 mL/[min·1.73 m 2]) and highest albumin‐to‐creatinine ratio (>30 mg/mmol) were associated with a greater than 4‐fold higher risk of both STEMI and NSTEMI (subdistribution hazard models [95% confidence interval] 4.53 [3.30‐6.21] and 4.42 [3.67‐5.32], respectively) compared to albumin‐to‐creatinine ratio <3 mg/mmol and eGFR≥60 mL/(min·1.73 m 2).

          Conclusions

          Elevations in albuminuria are associated with a higher risk of both NSTEMI and STEMI, regardless of kidney function, whereas reduced kidney function alone is associated with a higher NSTEMI risk.

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          Most cited references26

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          Chronic kidney disease and mortality risk: a systematic review.

          Current guidelines identify people with chronic kidney disease (CKD) as being at high risk for cardiovascular and all-cause mortality. Because as many as 19 million Americans may have CKD, a comprehensive summary of this risk would be potentially useful for planning public health policy. A systematic review of the association between non-dialysis-dependent CKD and the risk for all-cause and cardiovascular mortality was conducted. Patient- and study-related characteristics that influenced the magnitude of these associations also were investigated. MEDLINE and EMBASE databases were searched, and reference lists through December 2004 were consulted. Authors of 10 primary studies provided additional data. Cohort studies or cohort analyses of randomized, controlled trials that compared mortality between those with and without chronically reduced kidney function were included. Studies were excluded from review when participants were followed for < 1 yr or had ESRD. Two reviewers independently extracted data on study setting, quality, participant and renal function characteristics, and outcomes. Thirty-nine studies that followed a total of 1,371,990 participants were reviewed. The unadjusted relative risk for mortality in participants with reduced kidney function compared with those without ranged from 0.94 to 5.0 and was significantly more than 1.0 in 93% of cohorts. Among the 16 studies that provided suitable data, the absolute risk for death increased exponentially with decreasing renal function. Fourteen cohorts described the risk for mortality from reduced kidney function, after adjustment for other established risk factors. Although adjusted relative hazards were consistently lower than unadjusted relative risks (median reduction 17%), they remained significantly more than 1.0 in 71% of cohorts. This review supports current guidelines that identify individuals with CKD as being at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority.
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            Relation between kidney function, proteinuria, and adverse outcomes.

            The current staging system for chronic kidney disease is based primarily on estimated glomerular filtration rate (eGFR) with lower eGFR associated with higher risk of adverse outcomes. Although proteinuria is also associated with adverse outcomes, it is not used to refine risk estimates of adverse events in this current system. To determine the association between reduced GFR, proteinuria, and adverse clinical outcomes. Community-based cohort study with participants identified from a province-wide laboratory registry that includes eGFR and proteinuria measurements from Alberta, Canada, between 2002 and 2007. There were 920 985 adults who had at least 1 outpatient serum creatinine measurement and who did not require renal replacement treatment at baseline. Proteinuria was assessed by urine dipstick or albumin-creatinine ratio (ACR). All-cause mortality, myocardial infarction, and progression to kidney failure. The majority of individuals (89.1%) had an eGFR of 60 mL/min/1.73 m(2) or greater. Over median follow-up of 35 months (range, 0-59 months), 27 959 participants (3.0%) died. The fully adjusted rate of all-cause mortality was higher in study participants with lower eGFRs or heavier proteinuria. Adjusted mortality rates were more than 2-fold higher among individuals with heavy proteinuria measured by urine dipstick and eGFR of 60 mL/min/1.73 m(2) or greater, as compared with those with eGFR of 45 to 59.9 mL/min/1.73 m(2) and normal protein excretion (rate, 7.2 [95% CI, 6.6-7.8] vs 2.9 [95% CI, 2.7-3.0] per 1000 person-years, respectively; rate ratio, 2.5 [95% CI, 2.3-2.7]). Similar results were observed when proteinuria was measured by ACR (15.9 [95% CI, 14.0-18.1] and 7.0 [95% CI, 6.4-7.6] per 1000 person-years for heavy and absent proteinuria, respectively; rate ratio, 2.3 [95% CI, 2.0-2.6]) and for the outcomes of hospitalization with acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level. The risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria.
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              Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial.

              The cardiovascular risk associated with early renal insufficiency is unknown. Clinicians are often reluctant to use angiotensin-converting enzyme inhibitors in patients with renal insufficiency. To determine whether mild renal insufficiency increases cardiovascular risk and whether ramipril decreases that risk. Post hoc analysis. The Heart Outcomes and Prevention Evaluation (HOPE) study, a randomized, double-blind, multinational trial involving 267 study centers. 980 patients with mild renal insufficiency (serum creatinine concentration >/= 124 micromol/L [>/=1.4 mg/dL]) and 8307 patients with normal renal function (serum creatinine concentration 0.2 for the difference). In patients who had preexisting vascular disease or diabetes combined with an additional cardiovascular risk factor, mild renal insufficiency significantly increased the risk for subsequent cardiovascular events. Ramipril reduced cardiovascular risk without increasing adverse effects.
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                Author and article information

                Contributors
                msood@toh.ca
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                11 October 2018
                16 October 2018
                : 7
                : 20 ( doiID: 10.1002/jah3.2018.7.issue-20 )
                : e009995
                Affiliations
                [ 1 ] Department of Medicine University of Ottawa Ontario Canada
                [ 2 ] Institute for Clinical Evaluative Sciences Toronto Ontario Canada
                [ 3 ] Schulich Heart Center Sunnybrook Health Services Center Toronto Ontario Canada
                [ 4 ] Institute for Health Policy, Management and Evaluation (IHPME) University of Toronto Ontario Canada
                [ 5 ] Department of Medicine McMaster University Hamilton Ontario Canada
                [ 6 ] Department of Medicine University of Alberta Edmonton Alberta Canada
                [ 7 ] Department of Medicine Queen's University Kingston Ontario Canada
                [ 8 ] Clinical Epidemiology Program Ottawa Hospital Research Institute Ottawa Ontario Canada
                Author notes
                [*] [* ] Correspondence to: Manish M. Sood, MD, MSc, Ottawa Hospital Research Institute, Civic Campus, 2‐014 Administrative Services Building, 1053 Carling Avenue, Box 693, Ottawa, Ontario K1Y 4E9, Canada. E‐mail: msood@ 123456toh.ca
                Article
                JAH33555
                10.1161/JAHA.118.009995
                6474966
                30371280
                145d4462-aaee-4d54-867a-be7334a9b7b2
                © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 04 June 2018
                : 21 August 2018
                Page count
                Figures: 3, Tables: 3, Pages: 10, Words: 6878
                Funding
                Funded by: Institute for Clinical Evaluative Sciences (ICES) Western and Ottawa Site
                Funded by: Ontario Ministry of Health and Long‐Term Care
                Funded by: Academic Medical Organization of Southwestern Ontario
                Funded by: Schulich School of Medicine and Dentistry
                Funded by: Western University
                Funded by: Lawson Health Research Institute
                Funded by: Canadian Institutes of Health Research
                Categories
                Original Research
                Original Research
                Epidemiology
                Custom metadata
                2.0
                jah33555
                16 October 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.0.1 mode:remove_FC converted:16.10.2018

                Cardiovascular Medicine
                chronic kidney disease,competing risks,epidemiology,myocardial infarction,non–st‐segment–elevation acute coronary syndrome,st‐segment–elevation myocardial infarction,risk factors

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