Revista Española de Cardiología (English Edition) Revista Española de Cardiología (English Edition)
Rev Esp Cardiol. 2007;60:251-8 - Vol. 60 Num.03 DOI: 10.1016/S1885-5857(07)60149-2

Factors Predictive of Cardiovascular Disease in Patients With Type-2 Diabetes and Hypercholesterolemia. ESODIAH Study

Xavier Pintó a, Emili Corbella a, Rosaura Figueras a, Josefina Biarnés b, Wifredo Ricart b, Clotilde Morales c, Liliana Falkon d, Luis Masana e

a Unidad de Lípidos, Servicio de Medicina Interna, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, España,
b Servicio de Endocrinología, Hospital de Girona Dr, Josep Trueta, Girona, España,
c Unidad de Lípidos, Servicio de Medicina Interna, Hospital General de Manresa, Manresa, Barcelona, España,
d Departamento Médico, Lácer, S,A, Barcelona, España,
e Unidad de Lípidos, Servicio de Medicina Interna, Hospital Sant Joan, Reus, Tarragona, España,


Diabetes mellitus. Cardiovascular disease. Hypercholesterolemia. Cardiovascular risk factors. Follow-up studies.


Introduction and objectives. We investigated the pattern of cardiovascular disease and the factors that predict such disease in outpatients with type-2 diabetes and hypercholesterolemia. Methods. This prospective open observational study included outpatients of both sexes (mean age 62 [8] years) with type-2 diabetes and hypercholesterolemia. Clinical manifestations of cardiovascular disease (e.g., angina, myocardial infarction, stroke and peripheral arterial disease), glucose and HbA1c levels, and cardiovascular risk factors were recorded every 4 months throughout the 2-year follow-up period. Overall, 838 patients completed follow-up. Results. During follow-up, 81 patients (9.6%) presented with a cardiovascular event, nine of which were fatal. Cardiovascular events were more frequent in patients with a history of an ischemic condition than in those without: 58 of 258 (22.5%) and 23 of 579 (4%), respectively (P<.01). Previous angina or myocardial infarction was the strongest predictor of cardiovascular risk (relative risk [RR]=4.08, 95% confidence interval [CI] 2.39-6.95), followed by previous stroke (RR=2.96, 95% CI 1.26-6.93), high low-density lipoprotein (LDL)-cholesterol level ≥135 mg/dL (RR=2.79, 95% CI 1.56-5.01), peripheral arterial disease (RR=2.44, 95% CI 1.27-4.68), a high HbA1c level (RR=2.08, 95% CI 1.22-3.57), and obesity (RR=1.69, 95% CI 1.0-2.86). Conclusions. The incidence of cardiovascular disease in this southern European population of patients with type-2 diabetes and hypercholesterolemia was high. A history of an ischemic condition and a high LDL-cholesterol level during follow-up were the strongest predictors of cardiovascular disease.



Diabetes mellitus affects approximately 100 million individuals worldwide and it is predicted that there will be an increase of 30% by 2025, due in particular to an increase in the prevalence of obesity and the progressive ageing of the population.1 Cardiovascular disease is the main cause of morbidity and mortality in patients with type-2 diabetes.2 In those patients, the risk of death due to ischemic heart disease or stroke is 2 to 3 times greater,3 and that, along with the high incidence of other macrovascular complications such as ischemia of the lower limbs or amputations implies a significant health burden and an enormous cost to the health care system. Identification of predictors of increased cardiovascular risk in diabetic patients is of particular interest in order to establish more effective preventive strategies.

While it is accepted that diabetic microangiopathy is mainly associated with hyperglycemia, the role of factors associated with the disease is less well understood.4-6 Thus, the cardiovascular risk attributable to hyperglycemia has yet to be determined and it is also unknown to what extent it is independent of other atherogenic factors.7-9 Hypercholesterolemia plays a major role in the cardiovascular risk associated with these patients10; however, there are other anomalies of lipid metabolism that are more characteristic of diabetes, such as hypertriglyceridemia, high-density lipoprotein cholesterol (HDL-C) deficiency, and alterations in the composition of low-density lipoprotein (LDL) particles, which are smaller, have a higher density, and are more atherogenic.11,12 It is also not known with any certainty which of these lipid abnormalities best predicts cardiovascular risk in diabetes. The principal aim of this project, which forms part of the ESODIAH study (observational study in diabetic patients with hypercholesterolemia), was to assess predictors of cardiovascular disease in a sample of Spanish diabetic patients with hypercholesterolemia over a 2-year follow-up period. The secondary aims were to describe the incidence of cardiovascular disease in that group and the prevalence of cardiovascular risk factors, along with the level of management of those factors.


The ESODIAH study was proposed as a prospective, open, observational, naturalistic study. Between February 1999 and December 2002, 930 patients with type-2 diabetes and hypercholesterolemia were included in the study and followed for 2 years in 26 different hospital lipid and cardiovascular risk units (n=520, 55.9%) and primary care clinics (n=410, 44.1%) throughout Spain, with the exception of the Autonomous Regions of the Balearic Islands, Canary Islands, and Castile-La Mancha.

Inclusion criteria were as follows: type-2 diabetes diagnosed at least 6 months previously according to the criteria of the American Diabetes Association13 and recorded concentrations in the last 2 years of LDL-C >135 mg/dL or total cholesterol >220 mg/dL when triglyceride concentrations were greater than 400 mg/dL. These lipid concentrations must have been confirmed 3 months after having received dietary advice. The exclusion criteria were as follows: type-1 diabetes, pregnancy, body mass index (BMI) ≥ 40, excretion of albumin in the urine >300 mg per 24 hours, serum creatinine >1.7 mg/dL, renal disease, severe hepatic disease, or other severe chronic diseases.

The patients who met the criteria for inclusion were invited to participate in the ESODIAH study and signed an informed consent form. In all patients, clinical assessment and laboratory analyses were performed at the baseline visit (visit 1) and subsequently every 4 months over a period of 2 years (visits 2 to 7); 838 patients completed the follow-up period (Table 1). Ischemic manifestations of cardiovascular disease such as angina, symptomatic or silent (electrocardiographic findings) myocardial infarction, transient ischemic attack, stroke, and peripheral artery disease, which included intermittent claudication and revascularization or amputation procedures, were assessed. Recording of these manifestations included medical visits and review of patient charts. For recording of physical activity, patients were considered sedentary if they walked for less than 20 minutes per day, moderately active if they walked for 20 to 60 minutes per day, and active if they walked for more than 60 minutes per day or undertook other sporting activities. The other variables collected in the study were as follows: a) history of diabetes, hypercholesterolemia, or heart disease in first-degree relatives; b) date of appearance of diabetes and diagnosis of hypercholesterolemia; c) retinopathy; d) diabetic nephropathy; e) anthropometric variables (weight, height, waist circumference, and hip circumference), electrocardiogram, and resting systolic and diastolic blood pressure; and f) drug treatment at the beginning of the study. In terms of drug treatment at the beginning of the study, 54.9% of patients received hypolipidemic treatment and statins were the most commonly used drugs (47%). Antihypertensive treatment was used in 49.1% of patients, with angiotensin converting enzyme inhibitors the most frequently prescribed (27.8%). Oral antidiabetic treatment was used by 71.9% of patients. The study was approved by the ethics committee of Bellvitge University Hospital and conducted in accordance with the Declaration of Helsinki.

Laboratory analyses included glucose, glycosylated hemoglobin (HbA1C), creatinine, transaminases, creatinine kinase, total cholesterol, HDL-C, LDL cholesterol (LDL-C), triglycerides, complete blood count, albumin excretion in urine, and urine culture and/or sedimentation. Excretion of albumin in urine was measured in 24-hour urine samples, or when such samples were unavailable, recent urine. Samples with positive findings in urine culture or abnormal urine sedimentation were excluded.

Statistical Analysis

An independent company was used to manage the data, which was subject to quality control checks.

Comparisons between patients with and without history of cardiovascular disease were made using the χ 2 test for qualitative variables and analysis of variance for quantitative variables. Bivariate Kaplan-Meier survival analysis was used to select variables for inclusion in a Cox regression model. A P value less than .05 was considered significant. Statistical analyses were performed using the statistical package SPSS 10.0 (1999 SPSS Inc, Chicago, Illinois, USA).


Table 1 shows the baseline patient characteristics of the study group. Of all the patients included in the study, 320 (38.8%) had a family history of cardiovascular disease, 494 (58.9%) were hypertensive, 114 (13.8%) had a history of angina, 112 (13.5%) of acute myocardial infarction, 43 (5.2%) of stroke, 65 (7.9%) of peripheral artery disease, and 141 (16.8%) of retinopathy.

During the 2 years of follow-up, 81 patients presented an episode of cardiovascular disease, most as angina (n=33, 41%) or peripheral artery disease (n=21, 26%), and to a lesser extent, as myocardial infarction (n=14, 17%) or stroke (n=13, 16%). Nine of the 81 ischemic episodes were fatal, 8 due to ischemic heart disease and 1 due to stroke. Three patients who did not present an ischemic event died as a result of noncardiovascular disease.

Table 2 shows the baseline characteristics that were significantly different between patients who presented clinical signs of cardiovascular disease during follow-up and those who did not. The former included a higher proportion of individuals aged more than 65 years, with poor management of blood sugar, and the majority of the individuals were sedentary. Likewise, patients who developed ischemic episodes more often had a history of cardiovascular disease and had a higher prevalence of retinopathy and abnormal albuminuria. No significant differences were observed between the groups in terms of sex, obesity (BMI ≥ 30), family history of cardiovascular disease, smoking, systolic and diastolic blood pressure, hypertension, number of years with diabetes (>6 years), cholesterol, LDL-C, HDL-C, ratio of total cholesterol to HDL-C ( ≥ 5), non-HDL cholesterol, or triglycerides.

Episodes of cardiovascular disease were more frequent in patients with a history of ischemia than in those without (58 out of 258 [22.5%] vs 23 out of 579 [4%]; P<.01).

Table 3 shows the mean values for the main cardiovascular risk factors over the course of the follow-up period in patients with and without cardiovascular disease. LDL-C, total cholesterol, ratio of total cholesterol to HDL-C, non-HDL cholesterol, and HbA1C were higher in patients with signs of cardiovascular disease, while HDL-C was lower in that group. A higher proportion of patients with cardiovascular disease had a BMI ≥ 30 and albuminuria ≥ 30 mg/24 h.

Table 4 shows the significant results obtained in the bivariate Kaplan-Meier analysis of time free of signs of cardiovascular disease. A history of cardiovascular disease or microangiopathy (retinopathy or abnormally high albuminuria) was associated with a shorter period free of disease. Poor control of blood sugar levels, obesity, sedentary lifestyle, hypercholesterolemia, hypertriglyceridemia, increased ratio of total cholesterol to HDL-C, and elevated non-HDL cholesterol during follow-up were also associated with reduced survival free of cardiovascular disease. No significant differences were observed in terms of sex, smoking, years with diabetes, hypertension, total cholesterol, low HDL-C (less then 40 mg/dL in men or less than 50 mg/dL in women), or systolic or diastolic blood pressure.

Cox regression analysis was performed with inclusion of those variables that had previously shown significant differences in the Kaplan-Meier analysis. That analysis revealed that history of ischemic heart disease (angina or infarction) was strongly associated with the risk of presenting an episode of cardiovascular disease and to a greater degree than other variables (relative risk [RR]=4.08; 95% confidence interval [CI], 2.39-6.95) (Table 5). History of stroke (RR=2.96; 95% CI, 1.26-6.93) and excess LDL-C (RR=2.79; 95% CI, 1.56-5.01) were also strongly associated with the risk of presenting ischemic episodes, as was also true, to a lesser extent, of peripheral artery disease (RR=2.44; 95% CI, 1.27-4.68), poor control of blood sugar levels (RR=2.08; 95% CI, 1.22-3.57), and obesity (RR=1.69; 95% CI, 1.002-2.86).


This prospective study performed in a group of Spanish diabetic patients with hypercholesterolemia shows that cardiovascular risk, that is, the risk of coronary heart disease, stroke, or peripheral artery disease, is strongly and independently associated with a history of ischemic disease, elevated LDL-C, poor management of hyperglycemia, and obesity.

The high incidence of ischemic signs of cardiovascular disease in this population from the south of Europe, close to 20% over a period of 2 years, is notable as a result of being within the upper limits of that described in populations from the north of Europe.14 In addition, this high incidence, which was observed in patients with or without prior history of ischemic episodes, occurred in a health care setting selected on the basis of ability to participate in epidemiologic studies, and therefore, with a quality of care that may have been slightly above average. In the group of patients without prior history of ischemia, 4% presented cardiovascular disease during the 2-year follow-up period. That rate corresponds to a 20% risk of coronary disease over 10 years, according to National Cholesterol Education Program (NCEP) criteria.15 This finding may be explained by the advanced age of the population, which was selected according to presence of hypercholesterolemia, the relatively long period of time with diabetes, the high prevalence of atherogenic factors, and poor management of those factors. More than three quarters of the patients had increased systolic blood pressure, 76% had LDL-C concentrations greater than 135 mg/dL, a third were obese, and 41% had HbA1C values clearly above the therapeutic range. These data show that, as in other geographic regions,16 the control of atherogenic factors in diabetic patients is not strictly achieved and highlight the need for improved strategies to achieve the therapeutic targets recommended by the relevant scientific societies and expert panels.17-19

Prior history of ischemic heart disease was the strongest predictor of cardiovascular disease and was associated with a 4 times greater risk of presenting new ischemic episodes. Cerebrovascular disease and peripheral artery disease were also associated with increased cardiovascular risk, although to a lesser degree.

In agreement with our results, other studies undertaken in diabetic patients with a history of ischemia also showed increased morbidity and mortality.20 This highlights the need for strict control of atherogenic factors in these patients.

A consensus is yet to be achieved on whether diabetic patients present an increased risk compared with ischemic patients who are not diabetic. Taking into account the data from various observational and follow-up studies performed in a Finnish population,21 the guidelines of the NCEP indicate that the cardiovascular risk in patients with type-2 diabetes is equivalent to that of patients with ischemic heart disease,15 and our results concur with that definition. However, in another study performed in a Scottish population, the patients with infarction presented a greater risk than diabetic patients,22 a finding that was attributed to a longer period with diabetes than that observed in the patients from the Finnish study. Resolving this apparent discrepancy is not easy and requires other prospective studies to be undertaken in patients recently diagnosed with type-2 diabetes and myocardial infarction, with adjustment for age and atherogenic factors.

Prior history of microangiopathy, including diabetic retinopathy or pathologic albuminuria, was more common in patients who presented an episode of cardiovascular disease during follow-up. However, microangiopathy was not found to be an independent predictor in the multivariate analysis, in which the remaining cardiovascular risk factors were included. This lack of predictive power has been observed in other studies23 and may be attributable to the strong association between other atherogenic factors, particularly hyperglycemia, and microangiopathy, a finding that would indicate that it is more a consequence than a cause of arterial disease.

There is increasing evidence, based on pathophysiology and epidemiology as well as clinical trials, indicating that hyperglycemia plays an important role in the origin of cardiovascular disease in diabetic patients.10,24,25 In addition, in these recent studies it has been demonstrated that HbA1C is an independent predictor of cardiovascular risk, even within concentration ranges that could be considered normal or slightly elevated.26 In this study, high concentrations of HbA1C, both at baseline and during follow-up, were more common in patients who presented an episode of cardiovascular disease, and values greater than or equal to 7.5% were associated with a 2-fold greater risk of presenting such events. On the other hand, it has been observed that management of hyperglycemia, expressed by a reduction in HbA1C levels, reduces cardiovascular risk.7,27 In the United Kingdom Prospective Diabetes Study, it was demonstrated that for each 1% reduction in HbA1C the incidence of myocardial infarction or stroke in patients with type-2 diabetes was reduced by 14% and 12%, respectively.23

The patients in this study who presented excess LDL-C (>=135 mg/dL) during follow-up had a 3-fold higher risk of presenting an ischemic episode than those with lower concentrations. LDL-C was the lipid variable that showed the greatest predictive power for cardiovascular disease. Triglycerides, HDL-C, the ratio of total cholesterol to HDL-C, and non-HDL cholesterol were not independently associated with cardiovascular risk when LDL-C was included in the statistical model. The predictive power for cardiovascular disease of the triglycerides is disputed, probably as a result of the high within-individual variability and the strong inverse correlation with HDL-C concentration.28 There is greater consensus on the role of HDL-C and the ratios that relate cholesterol associated with these lipoproteins to total cholesterol29 as predictors of cardiovascular disease. Two recent studies highlighted the role of the ratio of total cholesterol to HDL-C and of non-HDL cholesterol in the prediction of cardiovascular disease in the diabetic population,30,31 particularly in patients with hypertriglyceridemia. The third report of the NCEP recognized the significance of non-HDL-C in diabetes and considered it to be a secondary therapeutic target15; nevertheless, LDL-C is defined as the main therapeutic target in the management of diabetic dyslipidemia. Increasing amounts of data have demonstrated the benefit of reducing LDL-C through the use of statins in the diabetic population,29,32,33 even in those individuals with cholesterol levels that are slightly elevated or fall within the reference values. These findings have led to treatment with statins being recommended in all diabetic patients with increased cardiovascular risk, even in the absence of elevated concentrations of cholesterol.18 In contrast, although hypertriglyceridemia and low HDL-C are more common than excess LDL-C in the diabetic population,34 less data is available on their predictive power in relation to cardiovascular disease35,36 or on the benefit of their treatment.37

Obesity is a risk factor for the presentation of diabetes and increases the severity of the disease in individuals who are already diabetic, while weight loss improves the management of hyperglycemia.38-40 The data from this study confirm the importance of obesity as a risk factor for cardiovascular disease in patients with type-2 diabetes, since its predictive power is independent of other atherogenic factors.


The diabetic population studied presented a high level of short-term cardiovascular morbidity and mortality. The main predictors of presenting the disease were history of ischemia, particularly in the coronary arteries, and excess LDL-C. The high prevalence and inadequate control of hypercholesterolemia and atherogenic factors highlight the need to improve measures to prevent cardiovascular disease in this population.


Juan Parra, Pedro Sáenz de Aranzubia, Xavier Pintó, Alicia Val, Ana Espinola, Rosaura Figueras, Emili Corbella, Josefa Panisello, Andreu Nubiola, Clotilde Morales, Joan Tobías, Josep Cañellas, Gabriel Martín Pueyo, Jesús Castillo, Pere Farrás, Antonio Morales, Isabel Roig, Ramon Barberà, Miguel González, Rosa Rosell, Montse García, Enric Ballestar, Eduarda Pizarro, Montse Fortuny, Carmen Carrazoni, Adoración Cama, Jordi Argimon, Juan Antonio Garrido, Gonzalo Pía, Wifred Ricart, Josefina Biarnés, Alfonso Cantero, Francisco Luque, Luis M. de la Rimada, Rocío Aguado, Ferrán Rius, Maravall Royo, Ángel Julián Brea, Daniel Mosquera, Pilar Sierra Polo, Abel Gutiérrez, Francisco Adán, José Ignacio Vidal Pardo, Manuel Botana, Rosa Argüeso, José María de Matías, Antonio Ruiz, Fco. Javier Gordillo, Juan Carlos Hermosa, Rodrigo Alonso, Javier Aranda, Juan Carlos Rodríguez, Jacinto Fernández, Antonio Hernández, Javier Tebar, María Jesús Díaz, Juan Pedro Benítez, Tomás García Santos, Tomás Hernández Corral, José Luis Iraola, Antonio Rodrigo, José María Cobo, L. Fernando Sánchez, Lluis Masana, Núria Plana, Diego Godoy, Alfonso González-Cruz, Concepción Terroba, Adalberto Serrano, Javier Antón, Lourdes Uribe-Etxebarría, Enrique de los Arcos, Manuel Serrano, Pilar Buil, Teresa Abad, Luis Zarate, Ana Loriz, José Ramón Villar, Virginia Muñoz Leire, and María Concepción Hermosa.


HDL-C: high-density lipoprotein cholesterol

LDL-C: low-density lipoprotein cholesterol

CI: confidence interval

RR: relative risk

*Members of the ESODIAH study group are listed at the end of the article.

This study was partially funded by grants from Laboratorios Lácer, the Foundation for Research and Prevention of Cardiovascular Diseases (Fundación para la Investigación y Prevención de las Enfermedades Cardiovasculares, FIPEC), and the Genetic Hyperlipidemias Network of the Carlos III Health Institute (GO3/181).

Correspondence: Dr. X. Pintó.
Unidad de Lípidos. Servicio de Medicina Interna.
Hospital Universitari de Bellvitge. IDIBELL.
Feixa Llarga, s/n. 08907 L'Hospitalet de Llobregat. Barcelona. España.

Received March 21, 2006.
Accepted for publication November 2, 2006.


1. King H, Aubert RE, Herman WH. Global burden of diabetes 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;21:141-31.
2. Bosch X, Alfonso F, Bermejo J. Diabetes y enfermedad cardiovascular. Una mirada hacia la nueva epidemia del siglo XXI. Rev Esp Cardiol. 2002;55:525-7.
3. Almdal T, Scharling H, Jensen JS, Vestergaard H. The independent effect of type 2 diabetes mellitus on ischaemic heart disease, stroke, and death. A population-based study of 13000 men and women with 20 years of follow-up. Arch Int Med. 2004;164:1422-6.
4. Pi-Sunyer FX. Type 2 diabetes outcomes. Obesity Res. 2002;10:22S-6S.
5. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16;434-44.
6. Boccara F, Cohen A. Interplay of diabetes and coronary heart disease on cardiovascular mortality. Heart. 2004;90:1371-3.
7. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348:383-93.
8. Genuth S, Eastman R, Kahn R, Klein R, Lachin J, Lebovitz H, et al. American Diabetes Association. Implications of the United kingdom prospective diabetes study. Diabetes Care. 2003;26 Suppl 1:28-32.
9. Huang ES, Meigs JB, Singer DE. The effect of interventions to prevent cardiovascular disease in patients with type 2 diabetes mellitus. Am J Med. 201;1111:633-42
10. Selvin E, Marinopoulos S, Berkenblit G, Rami T, Brancati FL, Powe NR, et al. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med. 2004;141:421-31.
11. Austin MA, King M-C, Vranizian KM, Krauss RM. Atherogenic lipoprotein phenotype: a proposed genetic marker for coronary heart disease risk. Circulation. 1990;82:495-506.
12. Sniderman AD, Scantlebury T, Cianflone K. Hypertriglyceridemic hyperapob: the unappreciated atherogenic dyslipoproteinemia in type 2 diabetes mellitus. Ann Intern Med. 2001;135:44759.
13. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2002;25 Suppl 1:5-20.
14. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-53.
15. Expert Panel on Detectio.n, Evaluatio.n, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the 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). JAMA. 2001;285:2486-97.
16. Meigs JB, Stafford RS. Cardiovascular disease prevention practices by US physicians for patients with diabetes. J Gen Intern Med. 2000;15:220-8.
17. Rubies-Prat J, Reverter JL, Senti M, Pedro-Botet J, Salinas I, Lucas A, et al. Calculated low-density lipoprotein cholesterol should not be used for management of lipoprotein abnormalities in patients with diabetes mellitus. Diabetes Care. 1993;16:1081-6.
18. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2004;27 Suppl 1:15-35.
19. Jones DW, Hall JE. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and evidence from new hypertension trials. Hypertension. 2004;43:1-3.
20. Murcia AM, Hennekens CH, Lamas GA, Jiménez-Navarro M, Ruleau JL, Flaker GC, et al. Impact of diabetes on mortality in patients with myocardial infarction and left ventricular dysfunction. Arch Int Med. 2004;164:2273-9.
21. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229-34.
22. Evans JM, Wang J, Morris AD. Comparison of cardiovascular risk between patients with type 2 diabetes and those who had had a myocardial infarction: cross-sectional and cohort studies. BMJ. 2002;324:939-42.
23. Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ. 1998;316:823-8.
24. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405-12.
25. Cefalu WT. Glycemic control and cardiovascular disease: should we reassess clinical goals? N Engl J Med. 2005;353:2707-9.
26. Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N. Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk. Ann Intern Med. 2004;141:413-20.
27. Dormandy JA, Charbonel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279-89.
28. Hsia SH. Non-HDL cholesterol: into the spotlight. Diabetes Care. 2003;26:240-2.
29. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383-9.
30. Lu W, Resnick HE, Jablonski KA, Jones KL, Jain AK, Howard WJ, et al. Non-HDL cholesterol as a predictor of cardiovascular disease in type 2 diabetes: the strong heart study. Diabetes Care. 2003;26:16-23.
31. Jiang R, Schulze MB, Li T, Rifai N, Stampfer MJ, Rimm EB, et al. Non-HDL cholesterol and apolipoprotein B predict cardiovascular disease events among men with type 2 diabetes. Diabetes Care. 2004;27:1991-7.
32. Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005-16.
33. Colhoun HM, Thomason MJ, Mackness MI, Maton SM, Betteridge DJ. Collaborative AtoRvastatin Diabetes Study(CARDS). Design of the Collaborative AtoRvastatin Diabetes Study (CARDS) in patients with type 2 diabetes. Diabet Med. 2002;19:201-11.
34. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA. 2002;287:2570-81.
35. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999;341:810-30.
36. Effect of fenofibrate on progression of coronary artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Stud.y, a randomised study. Lancet. 2001;357:905-10.
37. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, et al. FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849-61.
38. Wannamethee SG, Shaper AG. Weight change and duration of overweight and obesity in the incidence of type 2 diabetes. Diabetes Care. 1999;22:1266-72.
39. Maggio CA, Pi-Sunyer FX. The prevention and treatment of obesity. Application to type 2 diabetes. Diabetes Care. 1997;20:1744-66.
40. Kelley DE, Wing R, Buonocore C, Sturis J, Polonsky K, Fitzsimmons M. Relative effects of calorie restriction and weight loss in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1993;77:1287-93.

1885-5857/© 2007 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved

To improve our services and products, we use cookies (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.
Cookies policy
To improve our services and products, we use cookies (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.