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Arquivos Brasileiros de Cardiologia

Print version ISSN 0066-782X

Arq. Bras. Cardiol. vol.91 no.6 São Paulo Dec. 2008

http://dx.doi.org/10.1590/S0066-782X2008001800008 

ORIGINAL ARTICLE

 

Prevalence and risk factors associated with peripheral arterial disease in the hearts of Brazil project

 

 

Marcia MakdisseI, II; Alexandre da Costa PereiraIII; David de Pádua BrasilIV; Jairo Lins BorgesV; George Luiz Lins Machado-CoelhoVI; José Eduardo KriegerIII; Raimundo Marques Nascimento NetoVI; Antonio Carlos Palandri ChagasIII; on behalf of the investigators of the Hearts of Brazil Study and Peripheral Arterial Disease Committee of the Brazilian Society of Cardiology/Funcor

IHospital Israelita Albert Einstein, São Paulo, SP - Brazil
IIUniversidade Federal de São Paulo (Unifesp), São Paulo, SP - Brazil
IIIInstituto do Coração da Faculdade de Medicina da Universidade de São Paulo (Incor USP), São Paulo, SP - Brazil
IVFaculdade de Ciências Médicas de Minas Gerais, Belo Horizonte, MG - Brazil
VInstituto Dante Pazzanese de Cardiologia, São Paulo, SP - Brazil
VIDepartamento de Ciências Médicas da Universidade Federal de Ouro Preto, Ouro Preto, MG - Brazil

Mailing Address

 

 


SUMMARY

BACKGROUND: Peripheral arterial disease (PAD) is associated with increased cardiovascular risk. In Brazil, data on PAD prevalence and risk factors are scarce.
OBJECTIVE: To assess prevalence and risk factors related to PAD in Brazilian urban centers with more than 100,000 inhabitants.
METHODS: National, multicenter, cross-sectional study of 1,170 individuals (>18 years), from 72 major Brazilian urban centers participating in the "Hearts of Brazil Project". PAD diagnosis was based on ankle-brachial index (ABI) < 0.90. The statistical analysis used the corrected Chi-square (Pearson) test for complex samples and confidence intervals. P< 0.05 was considered statitically significant.
RESULTS: PAD prevalence was 10.5%. Intermittent claudication (IC) was present in only 9% of PAD patients. A significant association was found between PAD and the following factors: diabetes, total and abdominal obesity, stroke and ischemic heart disease (IHD). There was a trend of higher PAD prevalence among individuals with hypertension, heart failure, chronic renal failure on dialysis, as well as those who had smoked over 20 pack-years. For females, presence of IHD was associated with a 4.9-fold greater risk of PAD. Among males, a 6.6-fold increased risk of PAD was found for diabetic in comparison to non-diabetic individuals.
CONCLUSION: PAD prevalence was markedly high, considering the low mean age of the studied population (44±14.7 yrs). IC was detected in a minority of PAD subjects, indicating a considerable number of asymptomatic individuals. Diabetes, obesity, stroke and IHD were the stronger predictors of PAD. The authors concluded that ABI measurement should be considered in the evaluation of moderate to high cardiovascular risk patients.

Key words: Arterial occlusive diseases; prevalence; risk factors; Brazil; intermittent claudication.


 

 

Introduction

It is estimated that 27 million individuals have peripheral arterial disease (PAD) in Europe and North America1. This number might be underestimated, as most of the patients is asymptomatic or does not present the classic symptom of the disease, intermittent claudication2.

The PAD, both symptomatic and asymptomatic, is associated to obstructive arterial disease in other vascular beds (coronary, cerebral, carotid) and, consequently, to a higher risk of cardiovascular events (death, acute myocardial infarction, cerebral vascular accident), of around 4 to 6% a year, in individuals with the disease3-5.

The assessment of the asymptomatic PAD through the ankle-brachial index (ABI) has become an important tool in the stratification of cardiovascular risk, especially in patients with intermediate risk6-7.

In Brazil, study data related to the prevalence of DAP and its risk factors are scarce and restricted to specific populations, with almost all of them carried out in the Southeast region of the country. Among them, two population-based studies are noteworthy: The Bambui Project, which evaluated 1,485 elderly individuals (> 65 years) that lived in Bambui (state of Minas Gerais), and showed a prevalence of 2.5% of intermittent claudication8 and the Epidoso Study, which evaluated 176 elderly individuals (> 75 years), living in the city of Sao Paulo, through the ABI and found a prevalence of 36.4% of PAD9. A more recent study, also carried out in the state of Minas Gerais, found 37.5% of PAD in patients with pre-dialytic chronic kidney disease10.

Considering that, the primary objective of the present study was to evaluate, through the ABI, the prevalence of symptomatic and asymptomatic PAD in a proportional population sample from 72 Brazilian urban centers with more than 100,000 inhabitants. The secondary objective was to correlate the diagnosis of PAD to several sociodemographic variables, presence of cardiovascular risk factors and the presence of comorbidities.

 

Methods

Study Design

Transversal, multicenter observational cohort study.

Population

The universe of the study consisted in the set of inhabitants of Brazilian urban centers with more than 100,000 inhabitants in 2004, aged > 18 years.

Sample Plan

This is a stratified sample with a bietapic sampling, calculated as 2,500 interviews, distributed in the regions proportionally to the number of inhabitants, per sex and age range, based on data from IBGE (Instituto Brasileiro de Geografia e Estatística - The Brazilian Institute of Geography and Statistics). A total of 72 cities were chosen in the five regions. The minimum sample size was set at 15, for smaller towns, up to 400, for the city of Sao Paulo. In the selected cities, the "households" constituted the second-stage units, with one interview per household.

The choice of the individual occurred in three stages. In the cities, the census sectors were selected. In the sectors, one street was elected and following randomization rules (random start and fixed interval of 10 households), the household was chosen. The respondent was selected based on pre-defined criteria (birth date closest to the date of the interview), respecting the stratification per sex and age. When the respondent was not present at the first contact, he/she could be sampled at two subsequent visits at another date, by the same interviewer. The interviewees were invited to attend a medical consultation on an appropriate day. The planning previewed 7 to 8 interviews per census sector, characterizing a third stage in the sample plan.

Observed sample

Of a total of 2,520 home interviews, 1,134 individuals attended the medical consultation. The distribution of these individuals did not follow the distribution of the household sample and some urban centers did not have volunteers for the second phase. Consequently, a supplementary sampling was carried out, with 498 telephone interviews in Sao Paulo, Rio de Janeiro, Belo Horizonte and Florianopolis. In those cities, 141 individuals attended the medical consultation and underwent a medical assessment. Two cities - Manaus and Vitoria – were disregarded from the analysis of risk factors, as they had only one individual in this sample. The sample, with ABI measurement and risk factor information, consisted of 1,170 individuals. The Project was approved by the Ethics Committee in Research of the Institute of Arterial Hypertension of Minas Gerais and, as suggested by The National Committee of Ethics in Research (Comissao Nacional de Etica em Pesquisa - CONEP), was submitted and approved by the National Council of City Secretaries of Health (Conselho Nacional dos Secretarios Municipais de Saude - CONASEMS), which facilitated the contact between the field researchers and the City Secretaries of Health. All the participants signed the Free and Informed Consent Form.

Data collection

The data collection occurred in two stages. The first, started in July 2004, was carried out by professionals from the Vox Populi Survey Institute, which applied structured questionnaires during the household interview. At the second stage, a standard medical consultation was carried out, with medical questionnaires, clinical examination, blood pressure measurements, anthropometric measurements, ABI and biological material collection.

PAD Assessment

The presence of PAD was assessed through the measurement of ABI, which was measured at rest in the supine position, with a portable vascular Doppler equipment (MEDPEJ DV-2001, 10 MHZ) and sphygmomanometer. The cuff size was selected based on the right brachial circumference (BC, measured at midpoint between the acromion and the olecranon: BC < 25 cm (small size), BC = 25-32 cm (middle size), BC= 32-42 cm (large size) and BC > 42 cm (thigh). To standardize the ABI measurement technique, at least one researcher from each center (doctor and/or nurse) was trained in ABI workshops, coordinated by the main author. The systolic pressure was measured twice in each artery, in the arms (brachial artery) and ankles (pedal artery and posterior tibial artery).

The pressure recorded for each artery was the mean of two measurements, as long as the difference between them was < 6 mmHg; otherwise, another pair of measurements was carried out. To calculate the ABI, we used the highest systolic pressure of the ankle (mean pedal or mean posterior tibial pressure), divided by the highest arm pressure (right brachial or mean left pressure), with a value of ABI being calculated for each lower limb11.

ABI values < 0.90 in one or both lower limbs were considered diagnostic of PAD. The absence of PAD was defined as levels of ABI from 0.91 to 1.40, in the absence of arterial revascularization of the lower limbs. ABI values > 1.40 were excluded from the analysis, as they do not define the diagnosis of PAD.

Intermittent claudication assessment

The presence of intermittent claudication was defined by the criteria of the Edinburgh Claudication Questionnaire, validated for Brazilian Portuguese12.

Definition of ankle pulse abnormalities

The palpation of the ankle pulses was carried out bilaterally in the pedal and posterior tibial arteries and classified as present or absent.

Laboratory assessment

At the second stage, after fasting, capillary examinations were carried out by the use of the point-of-care technology (Roche Diagnostics, Accu-Check) for the assessment of capillary glycemia, total cholesterol and triglycerides.

Statistical analysis

The prevalence estimates were calculated based on a complex sampling model. Each individual was assigned a weight, according to his/her sex, city and region. The association between PAD and each variable was determined by Pearson's Chi-square test (X2), corrected by the complex sampling plan. P values < 0.05 were considered indicative of significant association between PAD and the variable. The comparison of the means of the continuous variables was carried out through confidence intervals (CI), based on the complex sampling plan. In the absence of overlapping between the CI, it was considered that there was a significant difference.

A multivariable logistic regression model was constructed according to the methodology of Hosmer and Lemeshow13. Initially, univariable analyses were performed to obtain crude Odds Ratios (OR). Then, the multivariable analysis was started, including the listed variables (sex, smoking status, hypertension, diabetes, age, obesity, cholesterol and triglycerides) as possible predictors of PAD and the socioeconomic variables that could have an impact on the health-related phenomena, such as family income and schooling.

The variables sex, smoking status, hypertension, diabetes, age and obesity were categorized as 0 (absent) or 1 (present) and the variables cholesterol and triglycerides were included as continuous variables. Individuals were considered hypertensive when they were known to be hypertensive, used antihypertensive medication, or whose blood pressure on the day of the medical consultation showed to be > 140x90 mmHg; individuals were considered diabetics when they were known to have diabetes, used antidiabetic drugs medication or had capillary glycemia > 126 mg/dL on the day of the medical consultation; individuals were considered to be hypercholesterolemic when they were known to have hypercholesterolemia, used lipid lowering medication or had total cholesterol > 200 mg/dL on the day of the medical consultation.

At this phase, variables included in the model presented a p < 0.25. Due to the multicolinearity between income and schooling, only the variable schooling, categorized as 0 (illiterate), 1 (complete or incomplete Elementary School) or 2 (High School or College/University) was maintained.

The data were analyzed with the software packages Stata (Release 9) and SPSS 13.0 for Windows (Statistical Package for Social Sciences), Complex Samples module.

At the third phase, the possible interactions with a biological meaning and/or evidence of importance at the analyses of the crossed tables were included, considering p (entry) < 0.25. In the final model, the variables that presented significance at 5% remained or those which, even though were not significant, were confounders. The modeling process was concluded and the colinearity and confounding were tested between the risk factors at each step. The adjusted statistical model was represented by the equation:

where βi (i = 0,1,...,8) are the coefficients of the terms of the model, x1 = Diabetes, x2 = Sex, x3 = Ischemic heart disease (IHD), x4 = Hypertension, x5 = College/University education.

The OR of the variables not present in the interactions were obtained by the exponentiation of the β coefficients. When there is an interaction between a factor and another variable, the OR estimate for the factor depends on the value of the variable that is interacting with it. In this situation, due to the impossibility of estimating the OR by simple exponentiation of the β coefficient, we used the differences between logits, defined as a function of model. As the statistical packages did not have a routine to calculate OR and CI for interactions, they were calculated manually by the team based on the methodology of Archer and Lemeshow14. The final model contains the interactions Diabetes X Sex, IHD X Sex and Hypertension X College/University education. The model adjustment was verified by the test of Hosmer and Lemeshow, with the software Stata, using an adequate procedure (Archer, K.J. & Lemeshow S., 2006) developed for the aforementioned test in complex samples. With this procedure, we obtained the value: F-adjusted = 0.266 and p = 0.98.

 

Results

Of a total of 1,170 individuals, 11 were excluded due to ABI > 1.40 (0.85%), resulting in a final sample of 1,159. There was a predominance of young adults (53.6% aged up to 45 years, 30.8% between 45 and 59 years and 15.6% > 60 years) and the mean age was 43.82 ± 14.68 years (95%CI: 43.02 – 44.64), women (53.3%) and Caucasian ethnicity (Caucasian: 56.9%, Afro-descendants: 9.2%, Brazilian mulattoes: 31,8%, Brazilian natives: 0.9% and others:1.3%). Most of them had finished Elementary School (Illiterate: 2.4%, did not finish Elementary School: 9.6%, finished Elementary School: 45.0%, finished High School: 32,9% and finished College/University: 10.0%) and family income of up to 5 minimum wages (MW) (< 1 MW: 8.9%, from 1 to 5 MW: 54.3%, from 5 to 10 MW: 22.6% and > 10 MW: 14.2%). Figure 1 shows the distribution of the participants regarding the Brazilian regions.

 

 

The prevalence of PAD was 10.5% (n=134), distributed as follows in the Brazilian regions: North/Midwest=17.8% (n=22/119), South=12.0% (24/199), Southeast=11.7% (76/592), Northeast=4.6% (12/173). There was no significant difference regarding prevalence of PAD among the regions (p=0.35).

Univariate analysis

The comparisons between the groups with and without PAD regarding the sociodemographic characteristics, life habits, coexisting clinical conditions, medication use, presence of symptoms, pulse evaluation and laboratory assessment are shown in Tables 1, 2, 3 and 4, respectively.

 

 

 

 

 

 

 

 

Multivariable logistic regression

In order to analyze the interaction IHD x Sex, the OR of the IHD were estimated for each sex (Table 5). The OR value for IHD present for the male sex was 1.21 (0.44; 3.31), which was non-significant, whereas for the female sex it was 4.92 (2.52; 9.59), highly significant, clearly showing the interaction. The analysis of the interaction Diabetes versus Sex shows that the effect of Diabetes in the male sex was highly significant OR = 6.65 (2.6; 17.01). For the female sex, this risk was not significant, with an OR = 1.19 (0.55; 2.57) (Chart 1).

 

 

 

 

The discriminatory performance of the model was validated using the C-index, which corresponds to the area under the ROC (Receiver Operation Curve). An area of 0.621 95%CI (0.568; 0.675) was obtained.

 

Discussion

The "Hearts of Brazil" Project is an epidemiological study on the prevalence of cardiovascular risk factors in a random population sample from 72 Brazilian urban centers. A population sample aged > 18 years, which resided in urban centers with more than 100,000 inhabitants, was analyzed. This project was a pioneer one in Brazil, by objectively evaluating the prevalence of PAD, both symptomatic and asymptomatic, through the measurement of ABI and the Edinburgh Claudication Questionnaire12.

The prevalence of PAD was 10.5%, which means approximately 6 million individuals, considering that there are 57 million inhabitants in Brazil with the characteristics of the population evaluated in this study (IBGE).

The mean age was older in those individuals with PAD in comparison with individuals that did not present the disease (49.02 years x 44.23 years, p=0.049). There was an association trend between PAD and age range (p=0.08), with an increasing prevalence of the disease as the age range increased. The small number of individuals older than 60 years, as the study was not specifically designed to evaluate the prevalence of PAD, but to evaluate the several risk factors and to be representative of the Brazilian population and the broad age ranges of the study (43.82 ± 14.68) might have reduced the power of the sample to detect such association with a p value < 0.05. However, the p value obtained indicated a consistent trend that the association between PAD and age range really existed. Studies that specifically evaluated the elderly (> 65 years), reported a prevalence between 7% and 36%9,15-18 whereas, in younger populations, as the one in the present study, the prevalence ranged from 3% to 16% 19-24. In populations with high cardiovascular risk, it ranged from 29% to 40.5%25,26.

In the present study there was a higher prevalence of PAD among the women, similar to other published studies9,20,21,27, although a higher frequency is often reported among men16,17,22,23. In the GetABI study, the prevalence was higher among men at the younger age ranges (65-74 years), whereas it was higher among women at the older age ranges (> 75 years)16.

We observed a trend of higher prevalence of PAD among those that did not practice physical activity (p=0.08). The sedentary lifestyle can be seen as a risk factor for the development of PAD as well as the result of the functional impairment of the lower limbs, caused by the disease28. The prevalence of PAD was 2-fold higher among individuals that smoked > 20 years/pack when compared to those who smoked fewer cigarettes. Similar data were reported by the GetABI study (34.5% and 19.5% among those who smoked > 20 years/pack and < 20 years/pack respectively) 16. There was no association between alcohol consumption and PAD. The Rotterdam study showed an inverse association between alcohol consumption and PAD only in non-smoking individuals29.

The individuals with PAD presented a 3-fold increase in the prevalence of stroke and a 2-fold increase in the prevalence of IHD, manifesting as angina pectoris and/or myocardial infarction, in comparison to the group without PAD. The coexistence of PAD and atherosclerotic lesions in other vascular beds has been reported, especially among the elderly. In one of these studies, in the presence of DAP, the prevalence of IHD was 68% and of stroke, 42%30.

There was a trend of higher prevalence of arterial hypertension, dialytic CKF and heart failure in the group with PAD. Several studies have reported these associations. In the SHEP (Systolic Hypertension in the Elderly Program) study, the prevalence of PAD among hypertensive individuals was 27%31. Among those with advanced CKF, the prevalence of the disease varied from 17 to 48%32 and in the Cardiovascular Health Study, the presence of PAD was an independent predictor of HF (RR = 1.61)33.

Regarding dyslipidemia, there was no association between PAD and reported dyslipidemia and no significant difference was observed concerning the mean levels of cholesterol and triglycerides between the groups. The use of lipid lowering drugs was similar in the groups with and without PAD and must not have contributed to the lack of association between the variables. In the GetABI study, the power of the association between lipidic parameters and PAD was considered limited, when compared to the other cardiovascular risk factors34. It is noteworthy the fact that although 24.6% of the individuals with PAD reported dyslipidemia, only 4.5% used lipid lowering drugs.

The prevalence of diabetes among individuals with PAD was 2.7-fold higher, when compared to individuals without PAD. The glycemia levels were slightly more elevated in the group with PAD; however, this difference did not have statistical significance. Diabetes is an important risk factor for the development of PAD. Studies that used the ABI to assess PAD among diabetic individuals demonstrated a prevalence of the disease between 20 and 29%26,35.

Obesity was evaluated in this study based on the measurements of body mass index (BMI), abdominal circumference (AC) and waist/hip ratio (WHR). The BMI > 30 as well as the increased WHR were associated with PAD, with the association between WHR and PAD more expressive among women. There was no association between AC measurement and PAD. Some studies have shown an association between PAD and abdominal obesity, but not with BMI, while others have shown an association between PAD and total and abdominal obesity only among women36,37.

The prevalence of intermittent claudication was 7%. In the literature, the prevalence varies from 0.4% to 14%, depending on the age, sex, risk profile and the diagnostic method that was used2. Among those with PAD, the prevalence of claudication was only 9% and its presence was not associated with PAD. In a study that evaluated different ethnic groups, the prevalence of claudication was 7.5%38. As most of the individuals with PAD is asymptomatic or presents unspecific symptoms, the claudication questionnaires, useful to identify symptomatic patients, are inefficient to asses PAD, which reinforces the role of the ABI measurement in the assessment of populations that are at-risk for the occurrence of the disease.

It is worth mentioning the association between the presence of pain or discomfort in the leg(s) during walking and PAD, even when the criteria for claudication have not been met, as such complaint was reported by more than half of the individuals with PAD, which suggests that its presence must be taken into account during the clinical assessment of these patients. Such finding had been previously described by our group in elderly individuals participating in the Epidoso study9.

The absence of ankle pulses to palpation, especially of the posterior tibial pulses, was associated with PAD. The abnormalities in the posterior tibial pulses are more sensitive and specific for the presence of PAD than the abnormalities of the pedal pulses, as approximately 10% of the healthy population does not have these palpable pulses39.

When we analyze the interaction between gender and the coexisting clinical conditions, we observed that the women with IHD included in the "Hearts of Brazil" Project presented an approximate 5-fold higher risk of having PAD than those without IHD, whereas diabetic men had a 6.6-fold higher risk of presenting PAD in comparison to nondiabetic ones. A possible explanation, in the case of the women, would be the trend to develop cardiovascular disease at an older age, due to the hormonal protection factor. The post-menopausal period could increase the chance of manifestations of vascular involvement in more than one territory. On the other hand, male sex and diabetes are two factors that have been associated with PAD at younger age ranges16.

Clinical implications

The data from the "Hearts of Brazil" Project raise a warning for the Brazilian medical community on the need to assess PAD in clinical practice. This warning is based not only on the elevated prevalence of PAD found in the study, but mainly in the expressive number of asymptomatic individuals (91%), who, if diagnosed early, could benefit from preventive measures to reduce the risk of acute myocardial infarction, stroke and cardiovascular death. The simple implementation of the ABI measurement as part of the assessment of patients with moderate and high cardiovascular risk would implicate in a significant impact on the early detection of asymptomatic individuals with PAD.

Limitations

This study was not designed with the objective of estimating the prevalence of PAD at city level, as in some of them the sample consisted of only 15 individuals, but at regional level. Its main limitation is not having enough sample power to be representative of he Brazilian population as a whole. Its power is enough to represent the Brazilian population of urban centers with more than 100,000 inhabitants, estimated as 57 million. A secondary limitation was that the complex study sample design excluded towns such as Marilia, Petropolis and Santa Maria from the analysis of the variable mean duration time of the physical activities, based on the insufficient number of valid individuals in the sample.

Acknowledgements

To the Board of the Brazilian Society of Cardiology (SBC) – 2004/2005 term, especially SBC President, Dr. Antônio Felipe Simão.

To the doctors, SBC members, nurses, medical and nursing students, nursing technicians, laboratory technicians who voluntarily participated in the 2nd phase of the study.

To the Sponsors, Instructors, Investigators and Field Coordinators of the "Hearts of Brazil Project" listed in the Appendix available at:

http://www.arquivosonline.com.br/2008/.

To the statisticians Elsa Cristina de Mundstock, M.Sc., Jandyra Maria Guimarães Fachel, Ph.D., and Vinicius Nunes Machado, B.Sc. in Statistics .

 

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Mailing Address:
Marcia Makdisse
Rua Dr. Franco da Rocha 205 / 51, Perdizes
05015-040 - São Paulo, SP - Brazil
E-mail: mmakdisse@einstein.br, mmakdisse@yahoo.com, mmakdisse@cardiol.br

Manuscript received on 06/30/08; revised manuscript received on 08/06/08; accepted on 08/15/08.

 

 

Appendix: sponsors, instructors, investigators and field coordinators of the "Hearts of Brazil Project".

This study was carried out with data obtained at the "Hearts of Brazil Project" and the Peripheral Artery Disease Risk Factor had the institutional financial support of Libbs Pharmaceuticals. The "Hearts of Brazil Project" also had the institutional support of the following enterprises: AstraZeneca, Biosintética, Biolab, Novartis, Sanofi-Aventis, Omron, Roche Diagnósticos, Centrais Elétricas Furnas, Ministry of Health and Conselho Nacional de Secretários Municipais de Saúde (Conasems).

Instructors:

1) Dra. Elizabete Viana de Freitas (President of the Department of Cardiogeriatrics/SBC);

2) Dr. Alexandre da Costa Pereira (Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo- InCor-USP);

3) Dr. Alexandra Alberta dos Santos (Unifesp);

4) Dr. Anderson Rodrigues de Oliveira (Universidade Federal de São Paulo – Unifesp);

5) Dr. Antonio Carlos Palandri Chagas (President of SBC);

6) Dr. Álvaro Avezum Junior (Previous President - SBC/FUNCOR);

7) Dra. Maria Elizabeth Navegantes Caetano Costa (President of the Department of. Cardiopathy and Pregnancy / SBC);

8) Dr. David de Pádua Brasil (Faculdade de Ciências Médicas de MG);

9) Dr. Eduardo Papa (Unifesp);

10) Dr. Fábio Rocha Farias (Unifesp);

11) Dr. Fábio Zanerato (Unifesp);

12) Dr. Andrei Carvalho Sposito (President of the Department of Atherosclerosis/SBC);

13) Dr. George Luiz Lins Machado Coelho (Universidade Federal de Ouro Preto);

14) Dr. Jairo Lins Borges (Instituto de Cardiologia Dante Pazzanese);

15) Dr. José Carlos Simões (Unifesp);

16) Dr. José Eduardo Krieger (InCor-USP);

17) Dr. Jorge Ilha Guimarães (Future President of SBC);

18) Dr. Lucélia Magalhães (Universidade Federal da Bahia);

19) Dr. Manes Erlichman (Unifesp);

20) Dr. Marcia Makdisse (Hospital Israelita Albert Einstein/Unifesp);

21) Dr. Ari Timerman ( President of SOCESP).

Investigators and field coordinators:

1) Alagoas - Maceió: Investigator: Dr. Marco Antônio Mota Gomes, Field Coordinator: Marilúcia Mota de Moraes;

2) Amazonas - Manaus: Investigator: Dra. Maria Christina Cavalcanti Ballut, Field Coordinator: Anderson da Silva Terrazas;

3) Bahia - Feira de Santana: Investigator: Dra. Idália Vieira Azevedo Silva, Field Coordinator: Leonor da Silva Bastos;

Salvador - Investigator: Dr. Mário de Seixas Rocha, Field Coordinator: Maria Tereza Esteves Brito Costa;

4) Ceará - Fortaleza: Investigator: Dr. José Maria Bonfim de Morais, Field Coordinator: Sandra Solange Leite Campos;

5) Distrito Federal - Brasília e Taguatinga: Investigator: Dr. Geniberto Paiva Campos, Field Coordinators: Romero Bezerra Barbosa e Rosa Nancy Urribari Runzer Sallenave;

6) Espírito Santo - Vila Velha: Investigator: Dr. Antônio Carlos Avanza Júnior, Field Coordinator: Fernanda Almeida Tarden;

Vitória: Investigator: Dr. Antônio Carlos Avanza Júnior, Field Coordinator: Fernanda Motta Del Caro;

7) Goiás - Anápolis: Investigator: Dr. Ricardo Nogueira de Paiva, Field Coordinator: Rosana Mendes Bezerra;

Goiânia: Investigator: Dr. Weimar Kunz Sebba Barroso de Souza, Field Coordinator: Priscila Valverde de Oliveira Vitorino;

Uruaçu: Investigator: Dr. Oswaldo Barroso de Souza Filho;

8) Maranhão - São Luis: Investigator: Dr. José Benedito Buhatem, Field Coordinator: Rachel Jorge Dino Cosseti;

9) Mato Grosso - Cuiabá: Investigator: Dra. Marta de Medeiros Neder, Field Coordinator: Luzia Helena Franco Carvalho Moya;

10) Mato Grosso Do Sul - Campo Grande: Investigator: Dr. Ricardo Ayache, Field Coordinator: Rose Mary Uehara;

11) Minas Gerais - Alfenas: Investigator: Dr. Giovanni Guarda Garcia, Field Coordinator: Lucas Bellusci Paolucci Amorim;

Barbacena: Investigator: Dr. José Gabriel Guimarães, Field Coordinator: Edivaldo José de Souza;

Belo Horizonte: Investigator: Dr. Raimundo M. do Nascimento Neto, Field Coordinators: Bernardo Luiz Fornaciari Ramos, Eduardo Viana Lobato, Guilherme Cardoso Parreiras e Tiago Damázio Godoy de Abreu;

Divinópolis: Investigator: Dr. Otaviano José Greco Rodrigues, Field Coordinator: Maria Inês Ribeiro Leão;

Governador Valadares: Investigator: Dr. Guilherme Gustavo do Valle, Field Coordinator: Eliene Nascimento Boneares;

Ipatinga: Investigator: Dr. Hamilton José Gonçalves, Field Coordinator: Gilda Grécia Gonçalves;

Juiz de Fora: Investigator: Dr. Wilson Coelho Pereira Filho, Field Coordinator: Marcos Cardoso Benhami; Montes Claros: Investigator: Dr. Evânio Rodrigues Cordeiro, Field Coordinator: Daniela Oliveira Lima;

Poços de Caldas: Investigator: Dr. José Tasca;

Pouso Alegre: Investigator: Dra. Nadja Sotero Natividade Mendes, Field Coordinator: Cristiane Maciel Zambolim;

Uberaba: Investigator: Dr. Luiz Antônio P. R. de Resende, Field Coordinator: Rodrigo Gimenez Pissutti Modolo;

Uberlândia: Investigator: Dr. Elmiro Santos Resende, Field Coordinator: Eduardo Moreira dos Santos;

Varginha: Investigator: Dr. Armando Martins Pinto, Field Coordinator: Fernanda Curry Carneiro Pinto;

12) Pará - Belém: Investigator: Dra. Sonia Conde Cristino, Field Coordinator: Rosa Helena Ribeiro Castro;

13) Paraíba - Campina Grande: Investigator: Dr. Miguel Pereira Ribeiro, Field Coordinator: Ademilda M. G. S. Garcia de Campo;

João Pessoa: Investigator: Dr. João Cavalcanti A. Filho, Field Coordinator: Jusara Gabriel Ramos da Costa;

14) Paraná - Cascavel: Investigator: Dr. Walter de Assumpção, Field Coordinator: Mauricio Figueiredo Lima e Marchese;

Curitiba: Investigator: Dr. Dalton Bertolim Precoma, Field Coordinator: Thaís Harén Rufino;

Foz do Iguaçú: Investigator: Dr. Odilon Sehn, Field Coordinator: Vera Lúcia Gomes; Londrina: Investigator: Dr. Wellington Antônio Moreira da Silva, Field Coordinator: Paulo Müller Ramos,

Maringá: Investigator: Dr. Mário Lins Peixoto, Field Coordinator: Lídia Cristina Troca;

15) Pernambuco: Recife: Investigador (a): Dra. Silvana Maria Daconti; Field Coordinator: Carlos Eduardo Lucena Montenegro;

16) Piauí: Teresina: Investigator: Dr. José Carlos Formiga L. de Sousa, Field Coordinator: Lucíola Galvão Gondim Corrêa Feitosa;

17) Rio de Janeiro - Campos dos Goytacazes: Investigator: Dr. Jamil da Silva Soares, Field Coordinator: Leandro Cordeiro Soares;

Niterói: Investigator: Dr. Antônio Alves Couto, Field Coordinator: Annelise Cisari Constanza;

Nova Iguaçu: Investigator: Dra. Sônia Regina Reis Zimbaro, Field Coordinator: Maria da Guia de Souza;

Petrópolis: Investigator: Nome: Dr. José Osman Gomes Aguiar, Field Coordinator: Miguel Osman Dias Aguiar;

Rio de Janeiro: Investigator: Dr. Rafael Arow Abitbol, Field Coordinators: Danielle Reis de Almeida e Mônica Carla dos Santos Sobreira;

São Gonçalo: Investigator: Dr. Adalberto Oliveira, Field Coordinator: Cláudia Márcia Cabral Feijó Oliveira;

Volta Redonda: Investigator: Dr. Jair Nogueira Filho, Field Coordinator: Tatiana Cunha de Paiva;

18) Rio Grande do Norte - Natal: Investigator: Dra. Maria Fátima de Azevedo, Field Coordinator: Fábio Gerson Sá Gabriel da Silva;

19) Rio Grande do Sul - Canoas: Investigator: Dr. Ilmar Kohler, Field Coordinator: Sandra Maria Borges;

Caxias do Sul: Investigator: Dr. Fábio Allgayer, Field Coordinator: Marciane Andréia Maschio;

Novo Hamburgo: Investigator: Dr. Leandro E. Roese, Field Coordinator: Cláudia Zuquetto;

Pelotas: Investigator: Dr. André Avelino Steffens, Field Coordinator: Katiuscia Milano Rosales;

Porto Alegre: Investigator: Dra. Leila Beltrami Moreira, Field Coordinator: Ricardo Flores da Costa;

Santa Maria: Investigator: Dr. Alexandre Antonio Naujorks, Field Coordinator: Simone Kroll Rabelo;

20) Santa Catarina - Blumenau: Investigator: Dr. Siegmar Starke, Field Coordinator: Daniela Moser Carlini;

Florianópolis: Investigator: Dr. Miguel de Patta, Field Coordinator: Dulcinéia Ghizoni Schneider;

Joinville: Investigator: Dr. Carlos Roberto Campos, Field Coordinator: Niucéia Lari Schor Krelling;

21) São Paulo - Araras: Investigator: Dr. Agnaldo Píspico, Field Coordinator: Alexandre Franco Garcia;

Bauru: Investigator: Dr. André Saab, Field Coordinator: Fabiana Cristina do Nascimento;

Campinas: Investigator: Dr. José Francisco Kerr Saraiva, Field Coordinator: Larissa Lopes de Assis Balsani;

Franca: Investigator: Dr. Ulisses Máquez Gianecchini, Field Coordinator: Cyntia Kallás Bachur;

Jundiaí: Investigator: Wagner Tadeu Ligabó; Field Coordinator: Lourenço Texeira Ligabó; Marília: Investigator: Dr. Ricardo José Tofano, Field Coordinator: Sueli Hissami Higute Ajeka;

Mogi das Cruzes: Investigator: Dr. Marcos Sleiman Molina,

Piracicaba: Investigator: Dra. Celise Alessandra Sobral Denardi, Field Coordinator: Maria Ângela Adâmoli M. Rossetto;

Presidente Prudente: Investigator: Dr. Luiz Carlos Pontes, Field Coordinator: Silvana Maria Furlanetto Tiezzi Pontes;

Ribeirão Preto: Investigator: Dr. Décio de Lima Pinho, Field Coordinator: Eugênia Veludo Veiga;

Santo André / São Bernardo / São Caetano: Investigator: Dra. Carla Janice Lantieri Merten, Field Coordinator: Marisa Beraldo;

Santos: Investigator: Dr. Hermes Tóros Xavier; Field Coordinator: Lucas Pedroso Fernandes Ferreira Leal;

São José do Rio Preto: Investigator: Dr. José Carlos Aidar Ayoub, Field Coordinator: Camila Vigano Zanoti;

São José dos Campos: Investigator: Dr. Carlos Costa Magalhães, Field Coordinator: Maria Cecília M. Pires Hirga;

São Paulo: Investigator: Dr. Carlos Alberto Machado, Field Coordinators: Eliete Morishige Yokoya, Maria Cecília Guimarães M. Arruda;

Sorocaba: Investigator: Dr. João Nóbrega de Almeida Filho, Field Coordinator: Cláudia Cristina Pereira Rabello;

22) Sergipe - Aracaju: Investigator: Dra. Geodete Batista Costa, Field Coordinator: Thiago Augusto Silva Nascimento.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Sources of Funding

This study was carried out with data obtained at the "Hearts of Brazil Project" and the Peripheral Artery Disease Risk Factor had the institutional financial support of Libbs Pharmaceuticals. The "Hearts of Brazil Project" also had the institutional support of the following enterprises: AstraZeneca, Biosintética, Biolab, Novartis, Sanofi-Aventis, Omron, Roche Diagnósticos, Centrais Elétricas Furnas, Ministry of Health and Conselho Nacional de Secretários Municipais de Saúde (Conasems).

Study Association

This study is not associated with any graduation program.