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      Value of Estimated Glomerular Filtration Rate and Albuminuria in Predicting Cardiovascular Risk in Patients with Type 2 Diabetes without Cardiovascular Disease

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          Abstract

          Introduction

          Onset of nephropathy in patients with type 2 diabetes (T2DM) increases the cardiovascular disease (CVD) risk. Association of the parameters of diabetic nephropathy such as albuminuria and estimated Glomerular filtration rate (eGFR) with predicted CVD risk has not been studied in Sri Lankan patients with T2DM.

          Methods

          In a cross-sectional study of patients who underwent single visit screening at a diabetes center in Sri Lanka, we obtained demographic and biochemical data. Those with urine albumin excretion over 30 mg/g creatinine were considered as having albuminuria, and eGFR was calculated using modified diet in renal disease (MDRD) formula. Ten-year coronary heart disease risk (CHDR) in all patients was calculated using United Kingdom Prospective Diabetes Study risk engine, and those with CHDR > 10% were considered as having high risk. Spearman correlation was used to study the association between eGFR and CHDR, and logistic regression analysis was carried out to study the association of albuminuria and eGFR with high (>10%) CHDR.

          Results

          Of the patients with diabetes studied (n=2434), 64% (1563) were males. Mean (SD) age and duration of diabetes were 52 (11) and 9 (3) years, respectively. Normoalbuminuria, microalbuminuria, and macroalbuminuria were observed in 16.4%, 14.8%, and 68.7% of patients, respectively. Three hundred ninety-four (16.2%) patients had eGFR < 60 ml/min. Moderate correlation was observed between eGFR and predicted CHDR [r = (-0.4), P<0.01] and between eGFR and fatal CHDR (FCHDR) [r = (-0.5), P<0.01]. Independent t-test showed that patients with eGFR < 60 ml/min were older and had longer diabetes duration and lesser BMI compared to those who had eGFR > 60 ml/min (P < 0.01). On logistic regression, nephropathy according to eGFR became a strong predictor for high CHDR (OR; 3.497, 95% CI 2.08 to 5.87), and nephropathy according to albuminuria and both albuminuria and eGFR was not significant predictor of CHDR.

          Conclusions

          Predicted CHDR shows a moderate and significant association with eGFR in patients with T2DM without symptomatic CVD. eGFR is a stronger predictor than albuminuria in predicting high CHDR in patients with T2DM. Intensification of CVD prevention measures should be done more confidently among patients with T2DM and reduced eGFR than in those with albuminuria alone.

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          Estimated glomerular filtration rate and albuminuria are independent predictors of cardiovascular events and death in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

          Paul Drury, C Pardy, Timothy M E Davis … (2010)
          We investigated effects of renal function and albuminuria on cardiovascular outcomes in 9,795 low-risk patients with diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Baseline and year 2 renal status were examined in relation to clinical and biochemical characteristics. Outcomes included total cardiovascular disease (CVD), cardiac and non-cardiac death over 5 years. Lower estimated GFR (eGFR) vs eGFR ≥90 ml min⁻¹ 1.73 m⁻² was a risk factor for total CVD events: (HR [95% CI] 1.14 [1.01-1.29] for eGFR 60-89 ml min⁻¹ 1.73 m⁻²; 1.59 [1.28-1.98] for eGFR 30-59 ml min⁻¹ 1.73 m⁻²; p < 0.001; adjusted for other characteristics). Albuminuria increased CVD risk, with microalbuminuria and macroalbuminuria increasing total CVD (HR 1.25 [1.01-1.54] and 1.19 [0.76-1.85], respectively; p = 0.001 for trend) when eGFR ≥90 ml min⁻¹ 1.73 m⁻². CVD risk was further modified by renal status changes over the first 2 years. In multivariable analysis, 77% of the effect of eGFR and 81% of the effect of albumin:creatinine ratio were accounted for by other variables, principally low HDL-cholesterol and elevated blood pressure. Reduced eGFR and albuminuria are independent risk factors for cardiovascular events and mortality rates in a low-risk population of mainly European ancestry. While their independent contributions to CVD risk appear small when other risk factors are considered, they remain excellent surrogate markers in clinical practice because they capture risk related to a number of other characteristics. Therefore, both should be considered when assessing prognosis and treatment strategies in patients with diabetes, and both should be included in risk models.
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            Diverging Association of Reduced Glomerular Filtration Rate and Albuminuria With Coronary and Noncoronary Events in Patients With Type 2 Diabetes

            Anna Solini, Giuseppe Penno, Enzo Bonora … (2011)
            OBJECTIVE Although a reduced estimated glomerular filtration rate (eGFR) was shown to be a powerful independent predictor of cardiovascular disease (CVD), other studies suggested that it confers a much lower risk than albuminuria alone, whereas the combination of the two abnormalities is associated with multiplicative risk. This study aimed at assessing the independent association of previous CVD events, either total or by vascular bed, with eGFR and albuminuria and chronic kidney disease (CKD) phenotypes. RESEARCH DESIGN AND METHODS This cross-sectional study evaluated 15,773 patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study in 19 outpatient diabetes clinics in years 2007–2008. Albuminuria was assessed by immunonephelometry or immunoturbidimetry. GFR was estimated by the simplified Modification of Diet in Renal Disease Study and the Chronic Kidney Disease-Epidemiology Collaboration equation. CKD was defined as an eGFR <60 mL/min/1.73 m2 or micro- or macroalbuminuria. Major acute CVD events were adjudicated based on hospital discharge records or specialist visits. RESULTS CVD risk increased linearly with eGFR decline and albuminuria and became significant for values <78 mL/min/1.73 m2 and ≥10.5 mg/24 h, respectively. Beyond traditional CVD risk factors, total CVD showed an independent association with albuminuria alone (odds ratio 1.20 [95% CI 1.08–1.33]), reduced eGFR alone (1.52 [1.34–1.73]), and both abnormalities (1.90 [1.66–2.19]). However, coronary events were associated predominantly with reduced eGFR alone, whereas cerebrovascular and peripheral events showed a stronger correlation with the albuminuric CKD phenotypes. CONCLUSIONS These data, although cross-sectional, show that reduced eGFR, irrespective of albuminuria, is associated with significant CVD, particularly in the coronary district.
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              Diabetes Mellitus, Microalbuminuria, and Subclinical Cardiac Disease: Identification and Monitoring of Individuals at Risk of Heart Failure

              Peter P Swoboda, Adam McDiarmid, Bara Erhayiem … (2017)
              Background Patients with type 2 diabetes mellitus and elevated urinary albumin:creatinine ratio (ACR) have increased risk of heart failure. We hypothesized this was because of cardiac tissue changes rather than silent coronary artery disease. Methods and Results In a case‐controlled observational study 130 subjects including 50 ACR+ve diabetes mellitus patients with persistent microalbuminuria (ACR >2.5 mg/mol in males and >3.5 mg/mol in females, ≥2 measurements, no previous renin–angiotensin–aldosterone therapy, 50 ACR−ve diabetes mellitus patients and 30 controls underwent cardiovascular magnetic resonance for investigation of myocardial fibrosis, ischemia and infarction, and echocardiography. Thirty ACR+ve patients underwent further testing after 1‐year treatment with renin–angiotensin–aldosterone blockade. Cardiac extracellular volume fraction, a measure of diffuse fibrosis, was higher in diabetes mellitus patients than controls (26.1±3.4% and 23.3±3.0% P=0.0002) and in ACR+ve than ACR−ve diabetes mellitus patients (27.2±4.1% versus 25.1±2.9%, P=0.004). ACR+ve patients also had lower E′ measured by echocardiography (8.2±1.9 cm/s versus 8.9±1.9 cm/s, P=0.04) and elevated high‐sensitivity cardiac troponin T 18% versus 4% ≥14 ng/L (P=0.05). Rate of silent myocardial ischemia or infarction were not influenced by ACR status. Renin–angiotensin–aldosterone blockade was associated with increased left ventricular ejection fraction (59.3±7.8 to 61.5±8.7%, P=0.03) and decreased extracellular volume fraction (26.5±3.6 to 25.2±3.1, P=0.01) but no changes in diastolic function or high‐sensitivity cardiac troponin T levels. Conclusions Asymptomatic diabetes mellitus patients with persistent microalbuminuria have markers of diffuse cardiac fibrosis including elevated extracellular volume fraction, high‐sensitivity cardiac troponin T, and diastolic dysfunction, which may in part be reversible by renin–angiotensin–aldosterone blockade. Increased risk in these patients may be mediated by subclinical changes in tissue structure and function. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01970319.
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                Author and article information

                Contributors
                Thilak Weerarathna:
                ORCID: http://orcid.org/0000-0003-0047-6669
                Journal
                Journal ID (nlm-ta): Biomed Res Int
                Journal ID (iso-abbrev): Biomed Res Int
                Journal ID (publisher-id): BMRI
                Title: BioMed Research International
                Publisher: Hindawi
                ISSN (Print): 2314-6133
                ISSN (Electronic): 2314-6141
                Publication date Collection: 2018
                Publication date (Electronic): 26 December 2018
                Volume: 2018
                Electronic Location Identifier: 8178043
                Affiliations
                1Professor in Medicine, Department of Medicine, Faculty of Medicine, University of Ruhuna, PO Box 70, Galle, Sri Lanka
                2Senior Lecturer in Pharmacology, Department of Pharmacology, Faculty of Medicine, University of Ruhuna, PO Box 70, Galle, Sri Lanka
                3Senior Lecturer in Medicine, Department of Medicine, Faculty of Medicine, University of Ruhuna, PO Box 70, Galle, Sri Lanka
                4Medical Student, Faculty of Medicine, University of Colombo, Sri Lanka
                5Lecturer in Pharmacology, Department of Pharmacology, Faculty of Medicine, University of Ruhuna, PO Box 70, Galle, Sri Lanka
                Author notes

                Guest Editor: Roger Ho

                Author information
                http://orcid.org/0000-0003-0047-6669
                http://orcid.org/0000-0003-3601-0609
                http://orcid.org/0000-0003-0342-3984
                Article
                DOI: 10.1155/2018/8178043
                PMC ID: 6343162
                PubMed ID: 30729117
                SO-VID: b946f21a-4a4a-45c1-b2de-0112afd08882
                Copyright © Copyright © 2018 Thilak Weerarathna et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 4 October 2018
                Date accepted : 3 December 2018
                Categories
                Subject: Research Article

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