Cardiovascular risk and validation of cardiovascular risk prediction functions in a cohort of patients with type 2 diabetes followed for 10 years in Badajoz (SPAIN). AN observational study.

AIMS: To analyse whether diabetes behaves as an equivalent of coronary risk and assess the performance of the original and REGICOR Framingham functions in a cohort of patients with type 2 diabetes observed for 10 years in primary care practices in Badajoz, Spain. METHODS: Observational, longitudinal study. A total of 643 patients (mean age 64.0 years, 55.7% women), without evidence of cardiovascular disease were studied. We assessed the incidence of cardiovascular events and the patients' 10-year coronary risk predicted-values at the time of their recruitment. RESULT: The actual incidence rate of coronary events was 14.5% (15.1% in women and 13.7% in men, p = 0.616). Patients who suffered coronary events were older (66.3 vs 63.6 years, p < 0.05), had higher total cholesterol (236.3 vs 219.5 mg/dl, p < 0.01), fasting plasma glucose levels (177.6 vs 159.8 mg/dl, p < 0.01), glycated haemoglobin (7.3 vs 6.7%, p < 0.05) and also higher prevalence of high blood pressure, dyslipidemia and chronic renal disease. The original Framingham equation overpredicted risk by 88%, whereas the REGICOR Framingham function underpredicted risk by 24%. CONCLUSIONS: Diabetes in our cohort does not behave as a coronary heart disease equivalent and both the original and REGICOR Framingham coronary risk functions have little utility in a diabetic population.

[Active Smoking and Coronary Risk in a Population of a Spanish Health-Care Centre: An Observational Cohort Study]. / Tabaquismo y riesgo coronario en la población de un centro de salud. Estudio de cohortes retrospectivo.

OBJECTIVE: Smoking is a major risk factor for multiple chronic diseases, such as cardiovascular diseases and cancer, and an established risk factor for premature death .The objective was to analyze the association between smoking and total coronary risk (incidence of lethal and non-lethal coronary events) in a cohort of 35-74 years old patients followed for 10 years. METHODS: Longitudinal, observational study of a retrospective cohort followed for ten years in primary care practices in Badajoz (Spain). 1011 patients (mean 55.7 year-old; 56.0% women) without evidence of cardiovascular disease was studied. Multivariate analysis was performed using a binary logistic regression model, introducing as the dependent variable the presence of total coronary events during the follow-up period. RESULTS: 29.1% of the patients were smokers. Smokers were younger (52.1 vs 57.2 years, p smaller than 0.001), with less prevalence of arterial hypertension (46.9% vs 61.5%, p smaller than 0.01), obesity (25.5% vs 31.8%, p=0,055) and lower HDL-cholesterol (45.7 vs 54.0 mg/dl, p smaller than 0.001). During the follow-up, they presented a higher mortality (11.2% vs 6.7%, p smaller than 0.05) and higher incidence of total coronary events (14.3% vs 9.2%, p smaller than 0.05). The final model of the logistic regression multivariate analysis revealed that only smoking and age are predictor variables of total coronary events, the greater odds ratio (OR) corresponding to smoking [OR: 2.33; 95% confidence interval (CI):1.31-4.16; p smaller than 0.01]. CONCLUSIONS: In patients aged 35-74 years followed during 10 years, smoking doubles the risk of total coronary events.

OBJETIVO: El tabaquismo es un importante factor de riesgo para múltiples enfermedades crónicas, tales como enfermedades cardiovasculares y cáncer, y también de muerte prematura. El objetivo fue valorar la relación entre tabaquismo y riesgo coronario total en una cohorte de pacientes de 35 a 74 años de edad. METODOS: Estudio observacional de una cohorte retrospectiva de 1.011 personas (edad media 55,7 años, 56,0% mujeres) sin antecedentes de enfermedades cardiovasculares, seguidas durante 10 años en un centro de salud de Badajoz (Extremadura, España). Se realizó un análisis multivariante mediante regresión logística binaria, incluyéndose como variable dependiente la incidencia de eventos coronarios durante el periodo de seguimiento. RESULTADOS: El 29,1% de la población era fumadora, con menor edad (52,1 vs 57,2 años, p menor que 0,001), menores cifras de colesterol-HDL (45,7 vs 54,0 mg/dl, p menor que 0,001), menor prevalencia de hipertensión arterial (46,9% vs 61,5%, p menor que 0,01) y obesidad (25,5% vs 31,8%, p=0,055) que los pacientes no fumadores. Sin embargo, durante el seguimiento presentaron mayores tasas de mortalidad (11,2% vs 6,7%, p menor que 0,05) e incidencia de eventos coronarios totales (14,3% vs 9,2%, p menor que 0,05). En el análisis multivariante solamente la edad y el tabaquismo se comportaron como variables predictoras de eventos coronarios totales, correspondiendo al tabaquismo las mayores odds ratio (OR: 2,33; IC95%:1,31-4,16; p menor que 0,01). CONCLUSIONES: En personas de 35 a 74 años seguidos durante 10 años el consumo de tabaco duplica el riesgo de eventos coronarios.

Original and REGICOR Framingham functions in a nondiabetic population of a Spanish health care center: a validation study.

PURPOSE: Risk functions can help general practitioners identify patients at high cardiovascular risk, but overprediction inevitably leads to a disproportionate number of patients being targeted for treatment. To assess predicted cardiovascular risk, we analyzed the 10-year performance of the original and REGICOR Framingham coronary risk functions in nondiabetic patients. METHODS: Ours was a longitudinal, observational study of a retrospective cohort of patients observed for 10 years in primary care practices in Badajoz, Spain. Our cohort comprised 447 nondiabetic patients aged 35 to 74 years who had no evidence of cardiovascular disease and were not on lipid-lowering or antihypertensive therapy. We assessed the patients' 10-year coronary risk measurement from the time of their recruitment. We also estimated the percentage of patients who were candidates for antihypertensive and lipid-lowering therapy. RESULTS: The actual incidence rate of coronary events was 6.7%. The original Framingham equation overpredicted risk by 73%, whereas the REGICOR Framingham function underpredicted risk by 64%. The Brier scores were 0.06364 and 0.06093 (P = .365) for the original Framingham and REGICOR Framingham functions, respectively, and the remaining discrimination and calibration parameters were also highly similar for both functions. The original Framingham function classified 14.8% of the population as high risk and the REGICOR Framingham function classified 6.9%. The proportions of patients who, according to the original Framingham and REGICOR functions, would be candidates for lipid-lowering therapy were 14.3% and 6.7%, and for antihypertensive therapy they were 12.5% and 7.8%, respectively. CONCLUSION: The original Framingham equation overestimated coronary risk whereas the REGICOR Framingham function underestimated it. The original Framingham function selected a greater percentage of candidates for antihypertensive and lipid-lowering therapy.

Cardiovascular events in patients with obesity: an observational study.

BACKGROUND: Overweight and obesity are positively correlated with increased risk of morbidity and mortality. AIM: To evaluate whether obesity may be considered an independent cardiovascular risk factor in patients of ages from 35 to 74 years followed-up for 10 years. DESIGN OF STUDY: Observational, longitudinal retrospective study. SETTING: Primary care practices in Badajoz (Spain). METHOD: A cohort of 899 patients (mean 55.7 years; 58.2% female) without evidence of cardiovascular disease was studied. RESULTS: A total of 33.5% of the population were obese (body mass index > or =30 kg/m2). Patients meeting the obesity criteria were more commonly female (36.6%) and were older, had higher mean values of blood pressure and triglycerides, higher percentages of diabetes, and higher coronary risk using either the original Framingham or the Framingham function calibrated for the Spanish population (Framingham-REGICOR). During the follow-up period, the rates of cardiovascular events and death in patients with obesity tended to be higher: 16.3% versus 11.7%, P = 0.056 and 4.7% versus 2.2%, P<0.05, respectively. In the final model of the logistic regression multivariate analysis, the significant predictors of cardiovascular events in patients with obesity were age, sex (male), diastolic blood pressure, diabetes, and smoking. The highest odds ratio corresponded to smoking (odds ratio 2.03; 95% confidence interval = 1.22 to 3.38). CONCLUSION: Obesity may not be considered an independent cardiovascular risk factor in patients aged from 35 to 74 years followed-up for 10 years.

Hidden chronic renal insufficiency and cardiovascular events in patients with hypertension in a primary care center.

OBJECTIVES: The aims of this study were to evaluate whether hidden chronic renal insufficiency (CRI) may be considered an independent cardiovascular risk factor in patients with hypertension and to calculate cardiovascular risk in this population. METHODS: A total of 756 hypertensive patients of ages from 35 to 74 years (mean 57.0 years; 58.2% women) and without evidence of cardiovascular disease were studied and followed during 10 years. Their glomerular filtration rate (GFR) was estimated using the simplified MDRD (result of the Modification of Diet in Renal Disease study) and Cockcroft-Gault formulas. Hidden CRI was identified by a GFR <60 mL/min/1.73 m(2) with normal serum creatinine concentration (<1.4 mg/dL men; <1.3 mg/dL women). RESULTS: Of the patients with hidden CRI using the MDRD equation, 22% presented cardiovascular events (RR, 1.60; 95% confidence interval (CI), 1.06-2.43; p < 0.05). While the estimated coronary risk using the original Framingham function was similar in patients with and without hidden CRI (18.2%), using the REGICOR function it was higher in those with CRI (7.7 vs. 7.2%, p < 0.05). Logistic regression analysis showed that smoking, male sex, age, and diastolic blood pressure were predictors of cardiovascular events. The presence of hidden CRI was not a statistically significant predictor using either the MDRD (OR, 1.37; 95% CI, 0.72-2.61; p = 0.340) or the Cockcroft-Gault (OR, 1.05; 95% CI, 0.50-2.23; p = 0.893) formulas. CONCLUSIONS: The hypertensive population of 35-74 years in age with hidden CRI showed a higher incidence of cardiovascular events, but hidden CRI may not be considered an independent cardiovascular risk factor.

[Cardiovascular events in patients with hidden renal failure detected by equations of glomerular filtration]. / Episodios cardiovasculares en pacientes con insuficiencia renal oculta detectada mediante fórmulas de filtrado glomerular.

OBJECTIVE: The objective of this work was to value the relationship between cardiovascular disease and presence of hidden renal failure in patients between 35 and 74 years followed up for 10 years. DESIGN: Observational, longitudinal, retrospective study of a cohort of patients. SETTING: Primary care health centre. PARTICIPANTS: We studied 875 patients (average age, 55.6 years, with 57.4% women) without evidence of cardiovascular disease, cared for in an urban primary health centre. MEASUREMENTS AND MAIN RESULTS: Glomerular filtration was estimated using Cockcroft-Gault and simplified MDRD equations. Hidden renal failure was considered if the glomerular filtration was <60 mL/min with a normal serum creatinine concentration. Using the Cockcroft-Gault equation 11.2% of study population had hidden renal failure and 12% when using MDRD, and 16.3% of patients with hidden renal failure using Cockcroft-Gault equation had coronary events. The relative risk in this group was 1.8 (95% confidence interval [CI], 1.1-2.9; P< .05). The percentage of coronary events was 16.2% when glomerular filtration was estimated by MDRD (relative risk, 1.9; 95% CI, 1.2-3.1; P< .05). Binary logistic regression analysis showed that age, male sex, smoking, diabetes, and diastolic pressure were the predicting variables of cardiovascular events, the highest odds ratio corresponding to the smoking population. The presence of hidden renal failure was not statistically significant using either Cockcroft (odds ratio, 1.21; 95% CI, 0.64-2.28; P=.566) or MDRD (odds ratio, 1.64; 95% CI, 0.77-3.48; P=.200) CONCLUSIONS: The prevalence of occult renal dysfunction in the 35-74 years population is high, but it does not behave as an independent cardiovascular risk factor.

[Cardiovascular risk in patients with renal failure]. / Riesgo cardiovascular en pacientes con insuficiencia renal.

BACKGROUND AND OBJECTIVE: Patients with renal failure (RF) have an increased risk of cardiovascular events. The aims of the present study were: a) to evaluate if RF is an independent cardiovascular risk factor, and b) to analyze the predictive capacity of the original Framingham and REGICOR functions charts in patients with RF. PATIENTS AND METHOD: A total of 912 patients between 35-74 years old (average: 55.7 years; 56.4% female) with no evidence of cardiovascular disease, were included in the present study. The RF was defined in patients with a glomerular filtration < 60 ml/min (estimated with the equation of Cockroft-Gaukt). RESULTS: 13.5% of the patients presented RF criteria. The final rate of cardiovascular events was higher in the population with RF (21.1% vs 12.0%; p < 0.01; relative risk = 1.76; 95% confidence interval [CI], 1.19-2.59). Statistically significant differences were not found between men and women. The multiple logistic regression analysis showed that cigarette smoking (odds ratio [OR] = 2.17; 95% CI, 1.38-3.35), diabetes (OR = 2.08; 95% CI, 1.37-3.15), RF (OR = 1.83; 95% CI, 1.10-3.06), antihypertensive treatment (OR = 2.03; IC del 95%, 1.32-3.11), and hypertension (OR = 2.06; 95% CI, 1.06-4.05) were important factors for the prediction of coronary and cardiovascular events. The original Framingham function predicted suitably the coronary risk in the population with RF (18.3% versus 17.9%; p = 0.869) whereas REGICOR underestimated it (7.5% versus 17.9%; p < 0.05). The area under the receiver operator characteristic (ROC) curve obtained with the original Framingham function was similar to that of REGICOR function: 0.61 (95% CI, 0.47-0.75) and 0.62 (95% CI, 0.48-0.76), respectively. CONCLUSIONS: The RF behaves like an important cardiovascular risk factor. The area under ROC curve obtained with the original Framingham function was similar to that of REGICOR function.

[Predictive capacity, comparison and clinic consequences of the Framingham-Wilson and REGICOR tables in persons for whom care has been provided at a health care center, Badajoz, Spain]. / Capacidad predictiva, comparación y consecuencias clínicas de las tablas de Framingham-Wilson y regicor en personas atendidas en un centro de salud de Badajoz.

BACKGROUND: Framingham's original equation modified by Wilson and the REGICOR calibration are widely recommended in coronary risk stratification. This study is aimed at: (1) Analyzing the ten-year predictiveness of the Framingham-Wilson and REGICOR tables among a population for which care has been provided at an urban health care center (2) Evaluating the concordance use of hypolipemiant and antihypertensive drugs resulting from these tables. METHODS: Observational, longitudinal, retrospective study of a cohort of patients for whom care was provided at a primary care center. A total of 1011 patients ages 35-74 (mean age 55.7, 56.0% females) without any evidence of cardiovascular disease. Those patients having a > or =20% risk in Wilson and > or =10% in REGICOR were considered high-risk. RESULTS: The actual coronary risk of the population was 10.7%, whilst the mean coronary risk estimated with the functions was 17.0% in Wilson and 6.6% in REGICOR. A total 29.6% was classified high-risk in Wilson as compared to the 18.2% in RECIGOR (p < 0.05). The percentage of high-risk males was significantly higher in Wilson than in REGICOR (49.0% vs. 29.4%, p < 0.01). The Kappa index was 0.70 (95 CI: 0.67, 0.73). A total of 39.5% of the patients (as per Wilson) and 31.4% (as per REGICOR) were candidates for taking hypolipemiant drugs (p < 0.001). The validity criteria of both of these functions are quite discreet: sensitivity, specificity and odds ratio diagnosed at 50.9%, 73.1% and 2.11 in Wilson and 28.7%, 83.1% and 1.98 in REGICOR, respectively. CONCLUSIONS: The Wilson and REGICOR tables show an acceptable degree of concordance, but their validity parameters are discreet. The Framingham-Wilson function screens a higher percentage of patients as being candidates for hypolipemiant drugs.

[Prevalence of hidden renal failure calculated through formulas on the degree of renal function in hypertense patients over 60 referred to out-patients for blood pressure monitoring]. / Prevalencia de insuficiencia renal oculta estimada mediante fórmulas de cálculo del grado de función renal en hipertensos mayores de 60 años, remitidos para medición ambulatoria de la presión arterial.

OBJECTIVES: To validate the Cockroft-Gault and the abbreviated Modification of Diet in Renal Disease (MDRD) formulas in a hypertense population aged over 60 and with blood pressure monitored in out-patients. To evaluate the prevalence of various stages of hidden chronic kidney disease in this population. DESIGN: Descriptive study of validation of diagnostic tests. SETTING: Urban primary care centre. PARTICIPANTS: A total of 113 patients over 60 (53.8% female) with hypertension and no history of chronic kidney disease, on whom blood pressure could be monitored in a 24-hour session. MAIN MEASUREMENTS: Calculation of the glomerular filtration rate. Validity parameters of diagnostic tests. RESULTS: Renal clearance estimated in the Cockroft-Gault and MDRD equations was similar (77.9 mL/min and 76.9 mL/min, respectively). There was 37.3% prevalence of chronic kidney disease, using the Cockroft-Gault equation; and 27.0%, using the MDRD. The degree of agreement between the two equations was excellent in classifying patients with stage-2 chronic kidney disease (kappa index =0.9) and it was acceptable for stage-3 (kappa index =0.5). In both equations, validity indexes were acceptable for the presence of microalbuminuria as a manifestation of renal damage. CONCLUSIONS: There is a high prevalence of hidden chronic kidney disease in the hypertense population over 60 years old. Glomerular filtration should be determined systematically in these patients, even when their plasma creatinine figures are normal.

[Incidence of cardiovascular disease and validity of equations of coronary risk in diabetic patients with metabolic syndrome]. / Incidencia de enfermedad cardiovascular y validez de las tablas de riesgo coronario en pacientes diabéticos con síndrome metabólico.

BACKGROUND AND OBJECTIVE: We aimed to analyze the contribution of the metabolic syndrome (MetS) and the glycemic control on the incidence of cardiovascular disease in type 2 diabetic patients. Our goal was also to validate to 10 years the coronary risk functions charts that use the original Framingham equation (Framingham-Wilson) and the calibrated one for the Spanish population (Framingham-REGICOR) in diabetic patients with MetS. PATIENTS AND METHOD: We included a total of 206 diabetic patients from a primary care center (63.6% with MetS), with no history of cardiovascular disease, in whom the coronary risk could be calculated prior to 1 January 1995. All were followed up during 10 years. RESULTS: The incidence of stroke, coronary and global events was similar in diabetic patients with and without MetS (15.3% vs 14.7%, 9.2% vs 9.3% and 20.6% vs 21.3%, respectively). The presence of glycosylated hemoglobin > or = 7% increased the risk of global cardiovascular events (relative risk [RR], 2.13; 95% confidence interval [CI], 1.10-4.09) and stroke (RR, 3.4; 95% CI, 1.17-9.84). The considered coronary risk in Framingham-Wilson and REGICOR equations was higher in the patients with MetS (29.6% and 12.4% vs 23.4% and 9.4%, respectively; p < 0,01), but the validity criteria of these equations in the diabetic population are very discreet. CONCLUSIONS: A value of glycosylated hemoglobin > or = 7% increases the risk of cardiovascular events in diabetic patients whereas the incidence of this events was similar in patients with and without MetS. The utility of the Framingham-Wilson and REGICOR equations is reduced in the diabetic population.

[Comparison of the REGICOR and SCORE function charts for classifying cardiovascular risk and for selecting patients for hypolipidemic or antihypertensive treatment]. / Comparación de las tablas REGICOR y SCORE para la clasificación del riesgo cardiovascular y la identificación de pacientes candidatos a tratamiento hipolipemiante o antihipertensivo.

INTRODUCTION AND OBJECTIVES: In Spain, use of the Framingham-REGICOR (Registre Gironí del Cor) and SCORE (Systematic Coronary Risk Evaluation) risk charts is recommended for stratifying cardiovascular disease risk. The aims of the present study were to evaluate the degree of agreement between these charts when used to evaluate cardiovascular disease risk in nondiabetic individuals aged 40-65 years and to estimate the percentage of patients recommended for hypolipidemic or antihypertensive treatment. METHODS: The study included 608 nondiabetic patients aged between 40-65 years (mean 52.8 years, 56.7% female) with no evidence of cardiovascular disease who were attending a primary healthcare center between 1990-1994. REGICOR and SCORE equations were used to calculate 10-year cardiovascular disease risks. Patients were classified as high-risk if their risk was > or =10% with REGICOR or > or =5% with SCORE. RESULTS: Some 7.9% of the population was classified as high-risk with REGICOR and 9.2%, with SCORE (P=.41). Only 2.6% and 2.9% (P=.81) of women were classified as high-risk, compared with 14.8% and 17.5% of men, with REGICOR and SCORE, respectively (P=.40). The kappa coefficient was 0.45. According to European professional society guidelines, 23.8% of patients classified by SCORE and 23.0% classified by REGICOR (P=.73) would be recommended hypolipidemic treatment, while 31.2% and 31.7% (P=.85), respectively, would be recommended antihypertensive treatment. CONCLUSIONS: There was moderately good agreement between REGICOR and SCORE charts when used to evaluate nondiabetic individuals aged 40-65 years. They identified similar percentages of patients who would be recommended for hypolipidemic or antihypertensive treatment.

[Comparison of the SCORE function chart and the Framingham-REGICOR equation to estimate the cardiovascular risk in an urban population after 10 years of follow-up]. / Comparación entre la tabla del SCORE y la función Framingham-REGICOR en la estimación del riesgo cardiovascular en una población urbana seguida durante 10 años.

BACKGROUND AND OBJECTIVE: Framingham-REGICOR and SCORE (Systematic Coronary Risk Evaluation) are 2 functions charts recommended to estimate the cardiovascular risk stratification in Spain. The aim of the present study was to validate to 10 years the SCORE and REGICOR functions charts in 40 to 65 years old population. PATIENTS AND METHOD: 608 patients (56.7% female) with non evidence of cardiovascular disease were included in the present study. Patients were classified as high risk by REGICOR (> or = 10%) and by SCORE (> or = 5%) functions. RESULTS: The 90.6% of the population (551 subjects) did not experienced any cardiovascular events during the 10 years follow-up. The REGICOR function chart underestimated the coronary risk (4.9% vs 7.9%; p < 0.001), whereas the SCORE overestimated the cardiovascular risk of death (2.1% vs 1.5%; p < 0.001). In the SCORE function, the average risk of patients with events was 6.1%, whereas the average risk of patients without events was 2.0% (p < 0.001) and 7.1% vs 4.8% (p < 0.001) in the REGICOR equation. The SCORE function obtained better validity criteria than REGICOR with a sensibility of 66.7% (95% confidence interval [CI], 66.2-67.2), especificity of 91.7%, (95% CI, 91.2-92.2) positive likelihood ratio of 8 (95% CI, 7.5-8.5), and eficacy of 91.1% (95% CI, 90.6-91.6). These results were observed in both sexes: women -sensibility: 33.3% (95% CI, 32.4-34.2); especificity: 97.4% (95% CI, 96.5-98.3)- and men -sensibility: 83.3% (95% CI, 82.7-83.9); especificity: 84.0% (95% CI, 83.4-84.6). CONCLUSIONS: The SCORE equation obtains better validity criteria than the REGICOR equation both in the total population and in males and females separately. These results make the SCORE function a powerful tool to estimate the cardiovascular risk.

[Validation of 3 equations of coronary risk in diabetic population of a primary care center]. / Validación de tres ecuaciones de riesgo coronario en población diabética de un centro de salud.

BACKGROUND AND OBJECTIVE: We intended to validate to 10 years 3 equations of coronary risk that use the function of original Framingham (Framingham-Anderson and Framingham-Wilson) and calibrated for Spanish population (Framingham-REGICOR) in diabetic patients type 2. PATIENTS AND METHOD: We included a total of 190 diabetic patients from a primary care center, without coronary heart disease, in whom the coronary risk could be calculated before 1 January 1995. All were followed during 10 years. RESULTS: The highest score of cardiovascular risk was obtained in the Framingham-Wilson function chart (25.4%) and the lowest in the Framingham-REGICOR (10.8%). The real incidence of coronary events was 14.7% (p < 0.001). Statistically significant differences between patients with or without coronary events were only observed in the Framingham-REGICOR equation (13.3% vs 10.3%; p = 0.046). Framingham-Anderson and Framingham-Wilson functions charts more than doubled the risk of coronary disease in men (p < 0.001). The agreement degree between the 3 functions was acceptable except for the calculation of coronary risk in men between Framingham-REGICOR and Framingham-Wilson equations (kappa index = 0.3). Framingham-Anderson and Framingham-Wilson functions charts showed similar profiles for the patients with high coronary risk. Sensitivity was superior in Framingham-Anderson and Framingham-Wilson functions (67.8%) and specificity was optimal in Framingham-REGICOR equation (51.2%). The positives predictive values were low and the negatives predictive values were high. CONCLUSIONS: The equations of Framingham-Wilson and Framingham-Anderson overestimate the coronary risk in diabetics, whereas the Framingham-REGICOR functions underestimates it. The utility of these 3 methods is reduced in the diabetic population.