Performance of cardiovascular risk scores in mortality prediction ten years after Acute Coronary Syndromes

Rev Assoc Med Bras ramb Revista da Associação Médica Brasileira Rev. Assoc. Med. Bras. 0104-4230 1806-9282 Associação Médica Brasileira RESUMO OBJETIVO Avaliar a performance do escore de risco de Framingham (ERF) e do escore proposto pela American College of Cardiology/American Heart Association (ER ACC/AHA) em predizer a mortalidade em pacientes dez anos após síndrome coronariana aguda (SCA). MÉTODOS Trata-se de um estudo de coorte retrospectivo que incluiu pacientes com idade ≥18 anos, com SCA, que estiveram internados na Unidade de Terapia Intensiva Coronariana (UTI) do Hospital das Clínicas de Botucatu, no período de janeiro de 2005 a dezembro de 2006. RESULTADOS Foram avaliados 447 pacientes. Destes, 118 foram excluídos, pois a mortalidade em dez anos não foi obtida. Logo, 329 pacientes com idade de 62,9±13,0 anos foram estudados. Dentre eles, 58,4% eram homens e 44,4% morreram no período de dez anos após a internação. A mediana do ERF foi de 16 (14-18)%, e do ER ACC/AHA foi 18,5 (9,1-31,6)%. Os pacientes que evoluíram a óbito apresentaram maiores valores dos escores. No entanto, quando classificamos os pacientes em alto risco cardiovascular, apenas o ER ACC/AHA foi associado com a mortalidade (p<0,001). Na análise de regressão logística, ambos os escores foram associados com a mortalidade em dez anos (p<0,001). CONCLUSÕES Tanto o ERF quanto o ER ACC/AHA foram associados com a mortalidade. No entanto, para os pacientes classificados como alto risco, apenas o ER ACC/AHA foi associado com a mortalidade em dez anos. INTRODUCTION The ischemic heart diseases are the most common causes of death worldwide.1 Among them are the acute coronary syndromes (ACS), which can be divided into myocardial infarction with ST-segment elevation and non-ST-segment elevation ACS. Despite the reduction tendency of mortality rates, ischemic heart diseases account for more than 1.8 million deaths every year, approximately 20% of all deaths in Europe.1-4 Thus, the identification of patients at risk of developing of coronary artery disease is crucial. The goal of the strategy of screening asymptomatic individuals is to have a more aggressive treatment and, consequently, a reduction of ischemic events and cardiovascular mortality. Among these scores are the Framingham risk score (FRS) and the score proposed by the American College of Cardiology and the American Heart Association (ACC/AHA RS).5-7 Over the last two decades, risk scores have gone through significant changes in order to concentrate on the overall absolute risk as an important key for the assessment of individual risk. In addition, more recent studies seek to improve the performance of the scores already used with the introduction of serum markers of inflammation, heart failure, and myocardial injury. Until the present time, however, risk scores have been developed and validated almost exclusively in developed countries. In addition, the scores have been built, in their majority, in populations with apparently no cardiovascular disease, so their conclusions relate to primary prevention and do not apply to patients with diagnosed coronary disease. For patients post ACS, some instruments of risk stratification have been developed, such as the Grace, Pursuit, and Timi scores.8-10 However, these scores assess intra-hospital mortality or, at most, the mortality after six months of an acute coronary event. Thus, instruments that assess the long-term mortality, such as the Framingham RS and the ACC/AHA RS, have still not been validated for patients with a prior coronary event. In view of these aspects, the objective of this study was to evaluate the performance of the Framingham RS and the ACC/AHA RS in predicting mortality in patients ten years after an ACS. METHODS The present study was approved by the Ethics Committee of our institution, under the protocol (61090116.1.0000.5411). The Informed Consent Form (ICF) was waived in cases which death was identified in the medical or administrative records of the hospital. The present work is an observational retrospective cohort study that included patients aged ≥18 years, with ACS, who were admitted to the Coronary Intensive Care Unit (ICU) of the Hospital das Clínicas de Botucatu - UNESP, in the period from January 2005 to December 2006, and who had the exams for the calculation of cardiovascular risk scores. We excluded patients whose final outcome after ten years was not obtained or those who refused to participate in the study. For the calculation of the sample size, we used the Fisher and Belle formula, with the following variables: mortality ten years after AMI of 30% to 40%, confidence interval of 95%, and a sampling error of 5%. The result was a minimum of 323 patients. The clinical and demographic data and laboratory examinations were collected upon admission to the Coronary Care Unit. The systolic blood pressure, blood glucose, lipid profile used were those of the first measurement taken at the time of admission. The FRS and the ACC/AHA RS were calculated and the overall mortality after ten years of ACS was recorded.5-7 In relation to acute coronary syndromes, they were classified as AMI with ST-segment elevation and non-ST-segment elevation ACS (AMI with no ST elevation and unstable angina). The diagnosis of the ACS was performed according to the guidelines by the American Heart Association.11 Systemic arterial hypertension (SAH) and the presence of diabetes mellitus (DM) were defined according to previous studies13. Smoking was regarded as the current use of tobacco. Laboratory evaluation For the measurement of sodium, potassium, urea, creatinine, CT, HDL, creatine phosphokinase (CPK) and creatine phosphokinase-MB (CKMB), we used the dry chemical method (Ortho-Clinical Diagnostics Vitros 950®, Johnson & Johnson). CPK and CKMB were dosed every six hours after admission and the highest value was recorded. Framingham risk score (FRS) We calculated the Framingham risk score. Patients were considered at high cardiovascular risk when they presented a risk of death greater than 20%. For the calculation of risk, patients younger than 20 years old or older than 80 were classified into the youngest and oldest categories of age, respectively.5 Risk score proposed by the American College of Cardiology and the American Heart Association (ACC/AHA) We calculated the risk score proposed by the ACC/AHA. Patients were considered at high risk for atherosclerotic cardiovascular disease when they had a percentage greater than or equal to 7.5%. For the calculation of risk, patients younger than 40 years old or older than 80 were classified into the youngest and oldest categories of age, respectively.7 STATISTICAL ANALYSIS The data were presented as mean and standard deviation or median and percentiles of 25% and 75%. The categorical variables were analyzed using the c2 test or Fisher’s exact test. Continuous variables were analyzed by Student’s t-test when they presented normal distribution and by the Mann-Whitney test for non-normal distribution. For the evaluation of score performance in relation to mortality, we used the ROC curve. We also used uni- and multivariate logistic regression analyses, adjusted for the variables, which were different in the univariate analysis, except for variables that were already included in the scores and those with multicollinearity. The level of significance was 5%. RESULTS We evaluated 447 patients with ACS admitted to the coronary ICU. Of these, 118 were excluded since their mortality ten years after admission to the ICU was not obtained. Thus, 329 patients with an average age of 62.9±13.0 years were studied. Out of that total, 58.4% were men, and 44.4% died within ten years after hospitalization. Of these, 63% presented non-ST-segment elevation ACS, while 37% had AMI with ST-segment elevation. After comparing these two groups of ACS, mortality was similar (p=0.97). The median of the FRS was 16 (14-18%), with 17% of the patients classified at high cardiovascular risk. In relation to the ACC/AHA RS, the median was 18.5 (9.1-31.6%), with 79% of the patients classified at high cardiovascular risk, according to this score. The demographic, clinical, and laboratory data of the patients evaluated and their relationship with ten-year mortality are presented in Table 1. The patients who died were older and had higher values of creatinine, urea, and potassium, and lower values of total cholesterol upon admission to the coronary ICU. TABLE 1 DEMOGRAPHIC AND CLINICAL DATA AND LABORATORY CHARACTERISTICS OF 329 PATIENTS WITH ACUTE CORONARY SYNDROME. Variables Death within 10 years P-value No (n=183) Yes (n=146) Age, years 57.9±11.4 69.2±12.1 <0.001 Male, No. (%) 108 (59.0) 84 (57.5) 0.87 SAH, No. (%) 138 (75.4) 116 (79.5) 0.46 DM, No. (%) 64 (35.0) 56 (38.4) 0.60 Smoking, No. (%) 73 (39.9) 63 (43.2) 0.63 SBP, mmHg 130 (120-150) 130 (115-150) 0.99 TC, mg/dL 181 (154-218) 169 (143-208) 0.04 HDL, mg/dL 36 (30-46) 36 (30-47) 0.96 CPK, U/L 207 (93-1075) 222 (87-984) 0.72 CKMB, U/L 23 (11-135) 36 (14-115) 0.14 Creatinine, mg/dL 0.9 (0.8-1.11) 1.2 (0.9-1.5) <0.001 Ureia, mg/dL 34.0 (26.5-41.8) 43.0 (34.0-55.0) <0.001 Sodium, mmol/L 138 (137-141) 139 (136-141) 0.93 Potassium, mmol/L 4.1 (3.8-4.5) 4.3 (3.9-4.7) 0.02 SAH: systemic arterial hypertension; DM: diabetes mellitus; SBP: systolic blood pressure; TC: total cholesterol; HDL: HDL-cholesterol; CPK: creatine phosphokinase; CKMB: creatine phosphokinase-MB. Data in percentages and median (25% and 75% percentiles). Furthermore, we found that the patients who progressed to death had higher scores, both on the FRS and the ACC/AHA RS. However, when we classified only patients with high cardiovascular risk, only the ACC/AHA RS was associated with mortality (Table 2). The area under the curve (AUC) of the association between the FRS and ten-year mortality in patients who had ACS was 0.6307, with 95% CI 0.5708-0.6905 and p <0.001. The cut-off point of the score that is associated with the highest mortality is over 14.3%. With the cut-off point of 14.3%, sensitivity was 74.66%, specificity 42.62%, positive predictive 50.93%, and negative predictive value 67.83% (Figure 1). TABLE 2 CARDIOVASCULAR RISK SCORES OF 329 PATIENTS WITH ACUTE CORONARY SYNDROME. Variables Death within 10 years P-value No (n=183) Yes (146) FRS, % 15 (13-17) 17 (14-18) <0.001 FRS > 20% 26 (14.2) 30 (20.5) 0.17 ACC/AHA RS, % 14.1 (6.2-26.1) 23.7 (15.0-40.1) <0.001 ACC/AHA RS ≥ 7,5% 125 (68.3) 136 (93.2) <0.001 FRS: Framingham risk score; AHA RS: risk score proposed by the ACC/AHA. Data in percentages and median (25% and 75% percentiles). FIGURE 1 A. ROC CURVE OF THE ASSOCIATION BETWEEN THE FRAMINGHAM RISK SCORE AND TEN-YEAR MORTALITY AFTER ACUTE CORONARY SYNDROME. B. ROC CURVE OF THE ASSOCIATION BETWEEN THE RISK SCORE PROPOSED BY THE ACC/AHA AND TEN-YEAR MORTALITY AFTER ACUTE CORONARY SYNDROME The area under the curve (AUC) of the association between the ACC/AHA RS and ten-year mortality in patients who had ACS was 0.7015, with 95% CI 0.6455-0.7576 and p <0.001. The cut-off point of the score that is associated with the highest mortality is over 23.56%. With the cut-off point of 23.56%, sensitivity was 50.00%, specificity 71.04%, positive predictive 57.94%, and negative predictive value 64.04% (Figure 1). There was an association between the FRS and the overall mortality after ten years in the univariate logistic regression (OR: 1.115; IC95%: 1.052-1.181; p<0.001) and in the multivariate analysis adjusted for creatinine and potassium (OR: 1.127; IC95%: 1.056-1.204, p<0.001). There was also an association between the ACC/AHA RS and the overall mortality after ten years in the univariate logistic regression (OR: 1.047; IC95%: 1.030-1.064; p<0.001) and in the multivariate analysis adjusted for creatinine and potassium (OR: 1.043; IC95%: 1.025-1.060, p<0.001). DISCUSSION The objective of this study was to evaluate the performance of two known risk scores for cardiovascular events in predicting mortality during the period of ten years in post-ACS patients. Our results show that both the FRS and the ACC/AHA RS were associated with mortality after ten years, with better performance by the ACC/AHA RS. In addition, for patients classified at high risk, only the ACC/AHA RS was associated with mortality after ten years. The first aspect to be considered refers to the fact that, even though hospital mortality is relatively low in ACS, the same concept does not apply for longer periods of observation. Thus, in a period between one and ten years, patients with ACS present a mortality rate of around 10% and 45%, respectively.1 In our study, the mortality after ten years of follow-up was 44%. Our data are in line with those found in the literature, but they also show that, despite the advances introduced in the treatment of these patients, the long-term prognosis remains poor. It is also important to note that there was no difference in mortality after ten years among the patients who had ACS with and without ST-segment elevation, and the same is true n in relation to the CPK and CKMB markers of myocardial injury. This fact is in agreement with studies that show that, in the long term, there is no difference in mortality between patients who had ACS with or without ST-segment elevation.1-3 Another relevant aspect to be observed is that considering that approximately half of the patients with ACS will die in a period of ten years, the risk stratification of these patients becomes a priority. In this sense, the identification of patients at higher risk of unfavorable outcomes after the acute episode would allow for an individualized and more aggressive approach in these cases, improving the prognosis. Taking into account the factors associated with ten-year outcomes, in our study, in addition to advanced age, higher values of the markers of renal function and potassium were also associated with greater mortality. This result is important because creatinine and potassium are not considered in most risk scores for coronary patients.16-18 In addition, there is an association between the decrease in renal function, associated or not to hyperkalemia, with increased risk of cardiovascular events.19 The Framingham and ACC/AHA scores are well-established and used for risk stratification of asymptomatic individuals.21-25 It is important to emphasize that our study was the first to assess and compare these scores in a population that has already presented coronary events. Furthermore, the use of these scores, even in a population that is mostly treated from a perspective of controlling risk factors and comorbidities, allows for the identification of patients who would benefit from more aggressive treatment. Another interesting point is that these scores are quick to be calculated and use laboratory examinations that are cheap and already part of the routine evaluation of patients with ACS. In our study, both the FRS and the ACC/AHA RS were associated with mortality in ten years. Additionally, the ACC/AHA RS had a better performance, despite discreet. Another important finding was that for patients classified at high risk, only the ACC/AHA RS was associated with mortality after ten years. Our results as a whole suggest that, specifically for patients with ACS, the ACC/AHA RS may be a better tool than the FRS for risk stratification in this scenario. Finally, our study must be interpreted considering some limitations. This is a retrospective study, which included patients from a single center. Furthermore, the number of patients without information related to mortality after ten years was high. However, despite these restrictions, we believe that our data provide important information about the use of scores for risk stratification, in the long term, for patients with ACS. CONCLUSION Our data indicate that both the FRS and the ACC/AHA RS were associated with mortality after ten years, with better performance by the ACC/AHA RS. In addition, for patients classified at high risk, only the ACC/AHA RS was associated with mortality after ten years. REFERENCES 1 1. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-77. Ibanez B James S Agewall S Antunes MJ Bucciarelli-Ducci C Bueno H et al 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC) Eur Heart J 2018 39 2 119 177 2 2. Sugiyama T, Hasegawa K, Kobayashi Y, Takahashi O, Fukui T, Tsugawa Y. Differential time trends of outcomes and costs of care for acute myocardial infarction hospitalizations by ST elevation and type of intervention in the United States, 2001-2011. J Am Heart Assoc. 2015;4(3):e001445. Sugiyama T Hasegawa K Kobayashi Y Takahashi O Fukui T Tsugawa Y Differential time trends of outcomes and costs of care for acute myocardial infarction hospitalizations by ST elevation and type of intervention in the United States, 2001-2011 J Am Heart Assoc 2015 4 3 e001445 3 3. Townsend N, Wilson L, Bhatnagar P, Wickramasinghe K, Rayner M, Nichols M. Cardiovascular disease in Europe: epidemiological update 2016. Eur Heart J. 2016;37(42):3232-45. Townsend N Wilson L Bhatnagar P Wickramasinghe K Rayner M Nichols M Cardiovascular disease in Europe: epidemiological update 2016 Eur Heart J 2016 37 42 3232 3245 4 4. Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267-315. Roffi M Patrono C Collet JP Mueller C Valgimigli M Andreotti F et al 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC) Eur Heart J 2016 37 3 267 315 5 5. Dawber TR, Meadors GF, Moore Jr FE. Epidemiological approaches to heart disease: the Framingham Study. Am J Public Health Nations Health. 1951;41(3):279-81. Dawber TR Meadors GF Moore FE Jr Epidemiological approaches to heart disease: the Framingham Study Am J Public Health Nations Health 1951 41 3 279 281 6 6. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-421. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report Circulation 2002 106 25 3143 3421 7 7. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1-45. Stone NJ Robinson JG Lichtenstein AH Bairey Merz CN Blum CB Eckel RH et al 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Circulation 2014 129 25 Suppl 2 S1 45 8 8. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, et al. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003;163(19):2345-53. Granger CB Goldberg RJ Dabbous O Pieper KS Eagle KA Cannon CP et al Predictors of hospital mortality in the global registry of acute coronary events Arch Intern Med 2003 163 19 2345 2353 9 9. Boersma E, Pieper KS, Steyerberg EW, Wilcox RG, Chang WC, Lee KL, et al. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators. Circulation. 2000;101(22):2557-67. Boersma E Pieper KS Steyerberg EW Wilcox RG Chang WC Lee KL et al Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators Circulation 2000 101 22 2557 2567 10 10. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA. 2000;284(7):835-42. Antman EM Cohen M Bernink PJ McCabe CH Horacek T Papuchis G et al The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making JAMA 2000 284 7 835 842 11 11. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004;44(3):E1-E211. Antman EM Anbe DT Armstrong PW Bates ER Green LA Hand M et al ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction) J Am Coll Cardiol 2004 44 3 E1 E211 12 12. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction-2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation. 2002;106(14):1893-900. Braunwald E Antman EM Beasley JW Califf RM Cheitlin MD Hochman JS et al ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction-2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina) Circulation 2002 106 14 1893 1900 13 13. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206-52. Chobanian AV Bakris GL Black HR Cushman WC Green LA Izzo JL Jr et al Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Hypertension 2003 42 6 1206 1252 14 14. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005;28:S4-36. American Diabetes Association Standards of medical care in diabetes Diabetes Care 2005 28 S4 36 15 15. Plakht Y, Shiyovich A, Gilutz H. Predictors of long-term (10-year) mortality postmyocardial infarction: age-related differences. Soroka Acute Myocardial Infarction (SAMI) Project. J Cardiol. 2015;65(3):216-23. Plakht Y Shiyovich A Gilutz H Predictors of long-term (10-year) mortality postmyocardial infarction: age-related differences. Soroka Acute Myocardial Infarction (SAMI) Project J Cardiol 2015 65 3 216 223 16 16. Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol. 1998;9(12 Suppl):S16-23. Foley RN Parfrey PS Sarnak MJ Epidemiology of cardiovascular disease in chronic renal disease J Am Soc Nephrol 1998 9 12 Suppl S16 S23 17 17. Parfrey PS. Cardiac disease in dialysis patients: diagnosis, burden of disease, prognosis, risk factors and management. Nephrol Dial Transplant. 2000;15(Suppl 5):58-68. Parfrey PS Cardiac disease in dialysis patients: diagnosis, burden of disease, prognosis, risk factors and management Nephrol Dial Transplant 2000 15 Suppl 5 58 68 18 18. Levey AS, Beto JA, Coronado BE, Eknoyan G, Foley RN, Kasiske BL, et al. Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis. 1998;32(5):853-906. Levey AS Beto JA Coronado BE Eknoyan G Foley RN Kasiske BL et al Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease Am J Kidney Dis 1998 32 5 853 906 19 19. Beattie JN, Soman SS, Sandberg KR, Yee J, Borzak S, Garg M, et al. Determinants of mortality after myocardial infarction in patients with advanced renal dysfunction. Am J Kidney Dis. 2001;37(6):1191-200. Beattie JN Soman SS Sandberg KR Yee J Borzak S Garg M et al Determinants of mortality after myocardial infarction in patients with advanced renal dysfunction Am J Kidney Dis 2001 37 6 1191 1200 20 20. Dries DL, Exner DV, Domanski MJ, Greenberg B, Stevenson LW. The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol. 2000;35(3):681-9. Dries DL Exner DV Domanski MJ Greenberg B Stevenson LW The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction J Am Coll Cardiol 2000 35 3 681 689 21 21. Magnoni M, Berteotti M, Norata GD, Limite LR, Peretto G, Cristell N, et al. Applicability of the 2013 ACC/AHA Risk Assessment and Cholesterol Treatment Guidelines in the real world: results from a multiethnic case-control study. Ann Med. 2016;48(4):282-92. Magnoni M Berteotti M Norata GD Limite LR Peretto G Cristell N et al Applicability of the 2013 ACC/AHA Risk Assessment and Cholesterol Treatment Guidelines in the real world: results from a multiethnic case-control study Ann Med 2016 48 4 282 292 22 22. Ridker PM, Cook NR. Statins: new American guidelines for prevention of cardiovascular disease. Lancet. 2013;382(9907):1762-5. Ridker PM Cook NR Statins: new American guidelines for prevention of cardiovascular disease Lancet 2013 382 9907 1762 1765 23 23. Karmali KN, Goff DC Jr, Ning H, Lloyd-Jones DM. A systematic examination of the 2013 ACC/AHA pooled cohort risk assessment tool for atherosclerotic cardiovascular disease. J Am Coll Cardiol. 2014;64(10):959-68. Karmali KN Goff DC Jr Ning H Lloyd-Jones DM A systematic examination of the 2013 ACC/AHA pooled cohort risk assessment tool for atherosclerotic cardiovascular disease J Am Coll Cardiol 2014 64 10 959 968 24 24. Liu J, Hong Y,D’Agostino RB Sr, Wu Z, Wang W, Sun J, et al. Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-Provincial Cohort Study. JAMA. 2004;291(21):2591-9. Liu J Hong Y D’Agostino RB Sr Wu Z Wang W Sun J et al Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-Provincial Cohort Study JAMA 2004 291 21 2591 2599 25 25. Brindle P, Emberson J, Lampe F, Walker M, Whincup P, Fahey T, et al. Predictive accuracy of the Framingham coronary risk score in British men: prospective cohort study. BMJ. 2003;327(7426):1267. Brindle P Emberson J Lampe F Walker M Whincup P Fahey T et al Predictive accuracy of the Framingham coronary risk score in British men: prospective cohort study BMJ 2003 327 7426 1267