ORIGINAL ARTICLE JIACM 2010; 11(4): 277-81 Impact of Renal Dysfunction on the Outcome of Acute Myocardial Infarction Shagun Sachdeva*, NP Singh**, Renuka Saha*** Abstract The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infarction. End-stage renal disease is associated with one of the highest risks, but the influence of milder degrees of renal impairment is less well defined. This study attempts to assess the prevalence of renal dysfunction in patients of acute myocardial infarction (AMI) and to study its short-term prognostic significance. Out of a total of 150 cases studied, 20% below 45 and 33% above the age of 45 had renal dysfunction. 49% of the AMI patients who did not have renal dysfunction and 77% of AMI patients who had renal dysfunction developed an adverse outcome (recurrent acute coronary syndromes, revascularisation (PTCA/CABG), left ventricular failure, and death) after AMI. Patients with renal dysfunction had a significantly increased risk (almost 4 times) of developing an adverse outcome after AMI. Further studies are recommended in view of the short duration of study and the small sample size. Key words: Renal dysfunction, acute myocardial infarction, acute renal failure. Introduction The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infarction 1-5. Patients with end-stage renal disease, as defined by a glomerular filtration rate (GFR) of less than 15.0 ml per minute per 1.73 m 2 are known to have decreased survival after myocardial infarction, especially if they are receiving renal-replacement therapy. But limited information exists on the risks and survival associated with lesser degrees of renal dysfunction in patients who have had an acute myocardial infarction (AMI). Also, the majority of what is known relates to the serum creatinine level, which is an insensitive indicator of renal function. Furthermore, many of these studies have concentrated on fatal outcomes 6-8. Keeping this in mind, this study is planned to assess the prevalence of renal dysfunction in patients of acute myocardial infarction and to study it s impact on the outcomes after acute myocardial infarction. Material and methods This study was conducted on one hundred fifty (150) consecutive patients (who fulfilled the inclusion and exclusion criteria) admitted to the internal medicine ward of Lok Nayak Hospital, New Delhi. Eligible patients included men and women, 18 of age or older, who had had an acute myocardial infarction, who were treated according to the standard protocol of treatment of AMI, and who were willing to participate in the study. All serious and unconscious patients and those who were not able to respond and who were treated out of the standard protocol for the treatment of AMI were not included. Patients of end-stage renal disease (GFR of < 15 ml/min/1.73 m 2 of body surface area for more than 3 months) were also excluded. After the selection of the patients, informed consent was obtained from each of them, and were evaluated with a detailed history and examination. The investigations carried-out were: cardiac enzymes-troponins, CPK, serum creatinine, blood urea, serum uric acid, urinary protein levels, and blood sugar. Creatinine clearance was derieved from Cockroft Gault equation. (Creatinine clearance = [(140-age) *body mass] / (plasma creatinine * 0.72) * GF- GF (gender correction factor). Females - 0.85, males - 1.0. Adverse outcome in this study refers to recurrent acute coronary syndromes, revascularisation (PTCA/CABG), left ventricular failure, and death. The data was recorded in a questionnaire with information about all the parameters as discrete and continuous data. Once the data was collected, the patients were divided into two groups, with renal dysfunction and without renal dysfunction. The data under both these categories was compared using appropriate statistical methods. The diagnosis of renal * Research Associate, ** Professor, *** Statistician, Department of Medicine, Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi - 110 002.
dysfunction was based on history, physical examination, estimation of serum creatinine, and glomerular filtration rate calculated by the Cockroft Gault equation, supplemented with urinary protein and glucose estimation 15. The diagnosis of AMI was based on the WHO criteria 16. The study was approved the by institutional ethics commitee. Observations and results A total of 150 cases were studied out of which, 76% were males and 24 % were females. 15% of these cases were below 45 of age. Age-wise distribution of renal dysfunction among AMI patients 20% of the cases below the age of 45 and 33% of the cases above the age of 45 had renal dysfunction. In total, 31% of all cases of AMI studied had renal dysfunction (Fig. 1). 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Age<45 AMI without renal dysfunction AMI with renal dysfunction Age>45 Fig. 1: Prevalence of renal dysfunction in AMI. Age-wise distribution of adverse outcome after AMI. 58% of all AMI patients studied developed an adverse outcome after AMI. Out of which, 73% of cases were below the age of 45, and 55% who were above the age of 45, developed an adverse outcome after AMI (Fig. 2). Impact of renal dysfunction on the outcome after AMI Renal dysfunction was found in 31% of all cases of AMI. 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% The risk of an adverse outcome after an AMI was found to be significantly higher in patients with renal dysfunction than in patients without renal dysfunction (77% vs 49%, odds ratio 3.54 with confidence interval 1.23-10.43) (Fig. 3). In this study no significant association was found between the other variables considered and the outcome after AMI. Therefore, a multivariate analysis was not required for their adjustment in order to find an association between renal dysfunction and outcomes after AMI. Discussion Adverse outcome absent after AMI Adverse outcome present after AMI Age<45 Age>45 Fig. 2: Prevalence of adverse outcome after AMI. Acute renal failure (ARF) has traditionally been defined as the abrupt loss of kidney function that results in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. The loss of kidney function is most easily detected by measurement of the serum creatinine which is used to estimate the glomerular filtration rate (GFR) 14. Chronic kidney disease (CKD) has a more rigid definition: The National Kidney Foundation (kidney disease outcomes and quality initiative guidelines, 2002) define CKD as kidney damage for > 3 months with or without decrease in the GFR as manifested by either pathologic abnormality or markers of kidney damage including 278 Journal, Indian Academy of Clinical Medicine Vol. 11, No. 4 October-December, 2010
Fig. 3: AMI with renal dysfunction Adverse outcome No adverse outcome AMI without renal dysfunction Adverse outcome No adverse outcome abnormality in composition of blood and urine, or abnormality in imaging techniques and GFR < 60 ml/min/ 1.73 m 2 for > 3 months with or without kidney damage. The Joint National Committee (JNC) for Detection and Treatment of Hypertension recognises renal dysfunction as an independent cardiovascular risk factor. Renal disease was a common and significant independent risk factor for adverse events in patients who had a myocardial infarction complicated by heart failure, left ventricular systolic dysfunction, or both 1-9. The loss of kidney function is most easily detected by measurement of the serum creatinine which is used to estimate the glomerular filtration rate (GFR). Some prior studies have used the serum creatinine level 11 rather than the estimated GFR to detect renal dysfunction. The accuracy of the serum creatinine level as a marker of renal function is limited, owing to nonlinear associations with GFR that vary according to age, sex, race, and lean body mass. Three problems are associated with the use of the serum creatinine to quantitatively define ARF. Firstly, serum creatinine does not accurately reflect the GFR in a patient who is not in a steady state. In the early stages of severe acute renal failure, the serum creatinine may be low even though the actual (not estimated) GFR is markedly reduced since there may not have been sufficient time for the creatinine to accumulate. Secondly, creatinine is removed by dialysis. As a result, it is usually not possible to assess kidney function by measuring the serum creatinine once dialysis is initiated. One exception is when the serum creatinine continues to fall on days when haemodialysis is not performed, indicating recovery of renal function. And lastly, numerous epidemiologic studies and clinical trials have used different cut-off values for serum creatinine to quantitatively define ARF 14. The lack of consensus in the quantitative definition of ARF, in particular, has hindered clinical research since it confounds comparisons between studies. Some definitions employed in clinical studies have been extremely complex with graded increments in serum creatinine for different baseline serum creatinine values 12. As an example, in a classic study of the epidemiology of hospital-acquired acute renal failure, ARF was defined as a 0.5 mg/dl increase in serum creatinine if the baseline serum creatinine was 1.9 mg/dl, an 1.0 mg/dl increase in serum creatinine if the baseline serum creatinine was 2.0 to 4.9 mg/dl, and a 1.5 mg/dl increase in serum creatinine if the baseline serum creatinine was 5.0 mg/ dl 14. Consequently, the National Kidney Foundation uses GFR rather than the serum creatinine level to define renal dysfunction 6-8,13,15. Data on the effect of mild renal insufficiency in patients with coronary artery disease/ami are limited 10,11. But from whatever studies that were done, it was found that a low estimated GFR was independently associated with an increased risk of death and complications from cardiovascular causes, reinforcing the concept that renal disease is a risk factor for cardiovascular events. Several studies have suggested that cut-off values for an estimated GFR of less than 60.0 ml per minute per 1.73 m 2 are predictive of adverse cardiovascular outcomes. Findings suggest that patients with renal impairment Journal, Indian Academy of Clinical Medicine Vol. 11, No. 4 October-December, 2010 279
already have an increased risk of cardiovascular events and that this risk increases with worsening renal function 1,4,6. Our study is in agreement with the latter. Mechanisms by which renal dysfunction increases cardiovascular risk are under investigation. The progressive increase in cardiovascular risk with worsening estimated GFR is partly explained by factors associated with renal decline, including anaemia, oxidative stress, derangements in calcium-phosphate homoeostasis, inflammation, and conditions promoting coagulation, all of which are associated with accelerated atherosclerosis and endothelial dysfunction. Another possible explanation could be that a decrease in renal function may be associated with other non-traditional risk factors. Such factors include, for example, changes in coagulation, lipids, endothelial dysfunction, homocysteine and/or the presence of anaemia, oxidative stress, proteinuria, and inflammation. On the other hand, renal dysfunction may be the result of both duration and severity of other causes of cardiovascular disease, such as hypertension. Thus, reduced kidney function may reflect residual confounding from CVD risk factors 1, 2, 6. Our study demonstrates that a significant proportion of patients who present with AMI have abnormal renal function. 31% of all cases of AMI studied were found to have renal dysfunction. Explanations for the higher frequency of renal dysfunction in our cohort than in previous cohorts include possible selection bias for patients with nearly normal renal function in other studies and an increasing incidence of chronic kidney disease. This possibility is partly accounted for by increasing rates of hypertension and diabetes mellitus. 49% of the AMI patients who did not have renal dysfunction and 77% of AMI patients who had renal dysfunction developed an adverse outcome after AMI. Thus, among patients who have had a myocardial infarction, any degree of renal impairment should be considered a potent, independent, and easily identifiable risk factor for cardiovascular complications 1. This study extends previous observations regarding the association of renal dysfunction and adverse clinical outcomes among patients with coronary artery disease. In the presence of STEMI, elevated creatinine and/or reduced creatinine clearance on presentation are associated with increased mortality, independent of other conventional risk factors. Retrospective analyses have demonstrated that renal dysfunction is associated with an increased risk of CHF and mortality after acute MI 7,13. Because creatinine levels were measured at presentation, these creatinine levels likely reflect renal status near the time of onset of the event and less likely reflect changes in renal haemodynamics due to impaired systemic perfusion. Limitations of the study The sample size was small. This resulted in certain known statistically significant relationships to come out to be statistically insignificant. Also, since the serum creatinine levels were measured at presentation and since the patients were followed-up for only one month, it is not possible for us to comment on the acuteness or the chronicity of the renal dysfunction. Conclusion In conclusion, the present study showed that renal dysfunction is strongly associated with an increased risk of adverse outcome after AMI in men and women from the general population. The underlying mechanism behind this relationship is unclear but seems to be independent from common risk factors such as hypertension, diabetes, smoking, BMI, alcohol intake, physical activity, and dyslipidaemia. Thus, estimation of GFR in addition to the consideration of present conventional risk factors may be a valuable tool for individual cardiovascular risk assessment. Further studies are needed to investigate the pathophysiological mechanisms underlying this association. References 1. Anavekar NS, McMurray JV, Velazquez SC. Relation between Renal Dysfunction and Cardiovascular Outcomes after Myocardial Infarction. NEJM 2004; 351: 1285-95. 2. Al Suwaidi J, Reddan DN, Williams K et al. Prognostic implications of abnormalities in renal function in patients with acute coronary syndromes. Circulation 2002; 106: 974-80. 3. Wright RS, Reeder GS, Herzog CA et al. Acute myocardial infarction and renal dysfunction: a high-risk combination. Division of Cardiology, Mayo Alliance for Clinical Trials, Mayo Clinic. Ann Intern Med 2002; 137: 563-70. 280 Journal, Indian Academy of Clinical Medicine Vol. 11, No. 4 October-December, 2010
4. Shlipak MG, Heidenreich PA, Noguchi H et al. Association of renal insufficiency with treatment and outcomes after myocardial infarction in elderly patients. General Internal Medicine Section, Veterans Affairs Medical Center (111A1) and University of California, San Francisco, USA. shlip@itsa.ucsf.edu 5. Thomas H, Hostetter MD. Chronic Kidney Disease Predicts Cardiovascular Disease. NEJM 2004; 351: 1344-6. 6. Gibson CM, Pinto DS, Murphy SA et al. Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality. J Am Coll Cardiol 2003; 42: 1535-43. 7. Tokmakova M, Skali H, Solomon SD et al. Moderate renal dysfunction augments cardiovascular risk after myocardial infarction. Presented at the European Society of Cardiology Congress, Vienna, August 30 September 3, 2003. 8. Sorensen CR, Brendorp B, Rask-Madsen C et al. The prognostic importance of creatinine clearance after acute myocardial infarction. Eur Heart J 2002; 23: 948-52. 9. Wheeler DC. Cardiovascular disease in patients with chronic renal failure. Lancet 1996; 348:1673-4. [PMID: 8973424]. 10. Mann JF, Gerstein HC, Pogue J et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomised trial. Ann Intern Med 2001; 134: 629-36. 11. Herzog CA, Ma JZ, Collins AJ. Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med 1998; 339: 799-805. 12. Walsh CR, O Donnell CJ, Camargo CA Jr et al. Elevated serum creatinine is associated with 1-year mortality after acute myocardial infarction. Am Heart J 2002; 144: 1003-11. 13. Freeman RV, Mehta RH, Al Badr W et al. Influence of concurrent renal dysfunction on outcomes of patients with acute coronary syndromes and implications of the use of glycoprotein IIb/IIIa inhibitors. J Am Coll Cardiol 2003; 41: 718-24. 14. Mehta RL, Chertow GM. Acute renal failure definitions and classification: time for change? J Am Soc Nephrol 2003; 14: 2178. 15. Stevens LA, Levey AS. Measurement of kidney function. In: Medical Clinics of North America, Singh AK, (Ed), W.B. Saunders, Philadelphia 2005; p. 457. 16. ISFC/WHO Task Force on Standardisation of Clinical Nomenclature and Criteria for Diagnosis of Ischaemic Heart Disease;Nomenclature and Criteria for Diagnosis of Ischaemic. Heart Disease Circulation 1979; 59 (3): 607-09. Journal, Indian Academy of Clinical Medicine Vol. 11, No. 4 October-December, 2010 281