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Arquivos Brasileiros de Cardiologia

Print version ISSN 0066-782X

Arq. Bras. Cardiol. vol.102 no.2 São Paulo Feb. 2014

http://dx.doi.org/10.5935/abc.20130242 

Original Articles

Study of Risk Factors Associated with Peripheral Arteriopathy in Japanese-Brazilians from Bauru (SP)

Luciana Garofolo1 

Sandra Roberta G. Ferreira2 

Fausto Miranda Junior3 

1Universidade Federal de São Paulo (Unifesp), São Paulo, SP - Brazil

2Faculdade de Saúde Pública - Universidade de São Paulo (USP), São Paulo, SP - Brazil

3Departamento de Cirurgia - Universidade Federal de São Paulo (Unifesp), São Paulo, SP - Brazil

ABSTRACT

Background:

Cardiovascular diseases are the major cause of morbidity and mortality in developed and emerging countries. Their main etiology, atherosclerosis, is a disseminated disease that affects the coronary, cerebral and peripheral territories. The peripheral arterial disease (PAD), as well as its consequences, indicates the involvement of the coronary territory. Therefore, its better understanding enables proper treatment, delaying local and long-term complications, reducing the cost to the health system.

Objective:

This study estimates the percentage of PAD in Japanese-Brazilians from Bauru (SP), recognized by the high prevalence of metabolic disorders such as hypertension (43%), diabetes mellitus (33%) and hypercholesterolemia (60%), and examines the association with risk biomarkers.

Methods:

This cross-sectional population study evaluated 1,330 Japanese-Brazilians of both genders aged ≥ 30 who underwent a complete physical examination, anthropometric measurements, laboratory tests and ankle-brachial index (ABI). Participants with ABI ≤ 0.90 were diagnosed as having PAD. After applying the exclusion criteria, 1,038 individuals were part of the analysis. We used Poisson regression to analyze associations with PAD.

Results:

The mean age was 56.8 years and the percentage of PAD was 21.1%, equal among the genders. PAD was associated with smoking (PR 2.16 [1.33 to 3.48]) and hypertension (PR 1.56 [1.12-2.22]).

Conclusion:

The percentage of PAD in Japanese-Brazilians was similar to other populations of adverse cardiometabolic profile (US PARTNERS and POPADAD). The independent association of PAD with smoking and hypertension, but not with other classical risk factors, may depend on the very high frequencies of metabolic disorders in this population.

Key words: Risk factors; Peripheral arterial disease; Migration; Atherosclerosis; Diabetes mellitus; Coronary diseases

Introduction

Despite changes in lifestyle and a growing therapeutic arsenal, cardiovascular diseases are still the leading cause of morbidity and mortality in developed and emerging countries. Data from the Ministry of Health showed that they are the leading cause of death in Brazil. In 2006, they accounted for 29.4% of deaths in the country, while neoplasias accounted for 15.1%1.

PAD (peripheral arterial disease) of atherosclerotic etiology is increasingly prevalent in modern society, partly due to increased life expectancy, affecting 202 million people worldwide in 2010. In the last decade, there was an increase of 28.7% in its prevalence in countries of low and middle per capita income, and 13.1% in high-income countries2. The growing interest in the early diagnosis of PAD is occurring not only for its increased prevalence associated with an aging population, but also because it is related to atherosclerotic disease in other territories, such as coronary and cerebral3.

Being a chronic disease, the resources needed for treatment are high. In the U.S. population, the estimated cost per year was US$ 5,955 per patient with PAD4.

Moreover, the progression of PAD is associated with coronary artery disease. We found an increased risk of cardiovascular events of 2.8 times in three years in patients with PAD compared to those without the disease3. A study conducted in patients undergoing coronary angiography found concomitance between PAD and coronary artery disease in 90.7% of patients5.

Immigrants of Japanese descent in the Americas have high rates of diabetes mellitus and other metabolic disorders6. It is believed that exposure to the Western environment should have exacerbated a genetic tendency to accumulate body fat, increasing cardiovascular risk. Genetically homogenous populations with an adverse cardiometabolic profile represent an opportunity to study the PAD, as well as other atherosclerotic manifestations and their relationship with risk factors6 , 7.

In view of this scenario, it can be argued that it is worth studying this population, the traditional and non-traditional risk factors for PAD, which are similar to those of coronary artery disease, enabling a better treatment of the disease, delaying complications and reducing the cost to the health system.

Methods

This cross-sectional study was based on the Japanese-Brazilian population living in Bauru (SP). The data used in this analysis belong to the second phase of the main study conducted in 2000. Individuals of both genders, aged ≥ 30, of Nipponese origin, first and second generations, were invited to participate. Methodological details were previously described7. The study was approved by the institutional ethics committee, and consent was signed by all participants. A total of 1,330 individuals, which corresponded to one third of the local Nipponese population, agreed to participate in the study and were interviewed using standardized questionnaires on clinical status (smoking and history of previous diseases) and nutrition. The participants were invited to undergo clinical examination (including anthropometric measurements, blood pressure and Doppler ankle-brachial index - ABI) and blood collection. Exclusion criteria for this analysis were incomplete questionnaire data and clinical and laboratory evaluation (255 participants), ABI > 1.40 (one participant) and concentration of C-reactive protein (hs-CRP) > 10 mg/L (36 participants). Therefore, 1,038 individuals were studied.

Weight (Filizola® scale) and height were determined with minimal clothing and no shoes for the calculation of body mass index (BMI)8. Waistline circumference8 was measured with a nondistensible measuring tape at the midpoint between the last floating rib and the iliac crest parallel to the ground, and hip measurement was determined by the buttock level, through the pubic symphysis. The waist-hip9 ratio was determined by the ratio between these circumferences. For diagnosing obesity and central obesity, the values recommended by the Japan Society for the Study of Obesity8 were employed, and for the waist-hip ratio, those of the World Health Organization were used9.

Blood pressure was measured in an automatic device (Omron HEM-712C, Omron Health Care, USA) after five minutes in the sitting position. The mean of the two last measurements was considered the final value of systolic and diastolic pressure. Hypertension was diagnosed in those with blood pressure values > 140 × 90 mmHg or those who reported drug treatment10.

After fasting for 12 hours and prior tracking with blood glucose, the participants underwent oral glucose tolerance testing with 75 g. Besides those who reported drug treatment, those who met the American Diabetes Association (ADA) criteria were diagnosed as diabetics11. The participants with fasting glucose < 100 mg/dL and two hours after overload < 140 mg/dL were considered normal. Those with fasting glucose ranging from 100 to 125 mg/dL and two-hour fasting < 140 mg/dL were considered as having impaired fasting glucose (IFG). Impaired glucose tolerance (IGT) was diagnosed when fasting glucose was ≥ 100 mg/dL, but with glucose after overload between 140-199 mg/dL. Diabetes was diagnosed by fasting glucose ≥ 126 mg/dL or overload ≥ 200 mg/dL.

For the diagnosis of dyslipidemia, the criteria of the Executive Summary of the Third Report of the National Cholesterol Education Program - Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adults Treatment Panel III) were employed12. Participants with total cholesterol ≤ 200 mg/dL, LDL-cholesterol ≤ 130 mg/dL, HDL cholesterol ≥ 35 mg/dL for men and ≥ 45 mg/dL for women, and triglycerides ≤ 200 mg/dL were considered normal as to the lipid profile. Those with abnormalities in at least one of these parameters were considered dyslipidemic.

Uric acid concentrations of up to 6 mg/dL for women and of up to 7 mg/dL for men were considered normal13. For homocysteine, the cutoff value was 15 μmol/L14; for hs-CRP, the cutoff value corresponded to the median of the population: 1.1 mg/L.

Plasma glucose and lipoproteins were determined by enzymatic methods. The determination of homocysteine was based on the methodology described by Pfeiffer et al15 CRP concentrations were determined by chemiluminescence.

Diagnosis of PAD

This diagnosis was done using continuous wave 8 MHz Imbracios® Doppler. The ABI value was calculated by the quotient of the pressure auscultated in the ankle arteries by the highest pressure determined in the brachial arteries. As recommended by the Transatlantic Society Consensus16, an index of ≤ 0.9 and > 1.40 was considered abnormal. The PAD was diagnosed in the participant who presented an index of ≤ 0.9 in at least one of the arteries analyzed (posterior tibial artery or the dorsalis pedis artery) in one of the ends.

Statistical Analysis

Data are presented as percentages or means and standard deviations. Participants were stratified according to the presence of PAD or according to the ABI values (≤ 0.70; 0.71 to 0.90; ≥ 0.90)17.

Frequencies were compared by chi-square, and prevalence ratios (PR) are presented by point and interval with 95% confidence. In the comparison of means, Student's t test or Bonferroni's analysis of variance was used.

We used the Poisson regression model to determine the RP of PAD according to the risk factors. The initial model included all the variables associated with PAD with p < 0.15 in the crude analysis. One by one, these variables were removed from the model, considering the statistics of maximum verisimilitude. A similar procedure was adopted to determine the odds ratios in the ordered logistic regression analysis according to the ABI values (≤ 0.70; 0.71 to 0.90; ≥ 0.90).

The analyses used the software Stata 8.0 (Statacorp, 2004. Stata statistical software release 7.0 College Station, TX Stata Corporation). A p value < 0.05 was considered significant.

Results

The average age of the 1,038 participants (46% male) was 56.8 (± 12.9 years). The men had higher values of BMI, waist-hip ratio, blood pressure, fasting glucose, triglycerides, uric acid and homocysteine, whereas the women had higher concentrations of total cholesterol, LDL-cholesterol, HDL-cholesterol and CRP (Table 1).

Table 1 Média (DP) de variáveis demográficas, antropométricas, clínicas e bioquímicas segundo o sexo de uma amostra de 1.038 nipo-brasileiros da cidade de Bauru (SP) 

  Men N = 473 Women N = 565 Total N = 1.038 p
Mean (SD) Mean (SD) Mean (SD)
Age (years) 56.7 (12.9) 56.9 (12.4) 56.8 (12.6) 0.364
Cigarettes per day* 18.1 (7.5) 16.8 (7.7) 17.7 (7.6) 0.138
Body mass index (kg/m2) 25.2 (3.8) 24.5 (3.8) 24.8 (3.8) 0.001
Waist-hip ratio 0.91 (0.06) 0.84 (0.07) 0.88 (0.08) < 0.001
Diastolic blood pressure (mmHg) 81.5 (13.5) 77.5 (13.0) 79.3 (13.4) < 0.001
Systolic blood pressure (mmHg) 135.5 (23.0) 131.7 (25.5) 133.4 (24.5) 0.006
Fasting glucose level (mg/dL)* 127.2 (31.3) 122.3 (36.8) 124.5 (34.4) < 0.001
2-hour glucose (mg/dL)* 168.5 (85.8) 159.9 (68.8) 163.9 (77.2) 0.169
Total cholesterol (mg/dL) 211.9 (41.8) 216.9 (42.9) 214.6 (42.5) 0.030
Triglycerides (mg/dL)* 279.9 (244.0) 198.7 (139.6) 231.6 (197.5) < 0.001
HDL-cholesterol (mg/dL)* 49.7 (12.5) 52.4 (10.3) 51.2 (11.4) < 0.001
LDL-cholesterol (mg/dL) 127.3 (37.8) 132.9 (38.0) 130.4 (38.0) 0.009
Homocysteine (mg/dL)* 13.1 (7.5) 9.9 (4.1) 11.4 (6.1) < 0.001
Hs-CRP (mg/L)* 1.6 (1.7) 1.9 (1.8) 1.8 (1.8) 0.015
Uric acid (mg/dL)* 7.0 (1.8) 5.3 (1.3) 6.1 (1.8) < 0.001

*Values transformed into logarithms for analysis.

The total population presented high levels of abdominal obesity (51.4%), hypertension (45.4%), diabetes mellitus (34.9%), hypercholesterolemia (62.2%), increased LDL-cholesterol (48.4%), increased triglycerides (64.3%). The percentages of risk factors stratified by sex are shown in Table 2. Especially among men, there was a high frequency of smoking (p = 0.01). The hypertension did not differ between the genders. Regarding glucose tolerance disorders, the percentage of DM was significantly higher in men (38.7% versus 31.7%, p = 0.008). They also presented more frequently hypertriglyceridemia, low HDL-cholesterol, hyperuricemia and hyperhomocysteinemia, but high levels of LDL-cholesterol and hs-CRP were more frequent in women.

Table 2 Percentages of the main cardiovascular risk factors in a sample of 1,038 Japanese-Brazilians from Bauru (Sao Paulo) according to gender 

  Men n = 473 Women n = 565 p value
N % N %
Age ≤ 60 years 284 60.0 335 59.3 0.806
  < 60 years 189 40.0 230 40.7  
Smoking No 218 46.2 499 88.8 < 0.001
  Yes (past) 91 19.3 39 6.9  
  Yes (current) 163 34.5 24 4.3  
Central obesity No 350 74.3 153 27.1 < 0.001
  Yes 121 25.7 411 72.9  
Body mass index < 23 kg/m2 131 27.8 213 37.7 0.001
  23.0-24.9 kg/m2 107 22.6 130 23.0  
  ≥ 25 kg/m2 234 49.6 222 39.3  
Hypertension No 250 52.8 317 56.1 0.295
  Yes 223 47.2 248 43.9  
Glucose tolerance Normal 16 3.4 42 7.5 0.008
  IFG 170 35.9 207 36.7  
  IGT 104 22.0 136 24.1  
  DM 183 38.7 179 31.7  
Hypercholesterolemia No 189 40.0 203 35.9 0.182
  Yes 284 60.0 362 64.1  
Low HDL No 395 83.5 514 91.0 < 0.001
Increased LDL Yes 78 16.5 51 9.0 0.002
No 269 56.9 267 47.3
  Yes 204 43.1 298 52.7  
Hypertriglyceridemia No 131 27.7 236 41.8 < 0.001
  Yes 342 72.3 329 58.2  
hs-CPR ≤ 1.1 mg/L 252 53.3 257 45.5 0.012
  1.1-9.9 mg/L 221 46.7 308 54.5  
Homocysteine ≤ 15 mg/dL 286 77.3 414 92.2 < 0.001
  > 15 mg/dL 84 22.7 35 7.8  
Hyperuricemia No 216 45.7 139 24.6 < 0.001
  Yes 257 54.3 426 75.4  

IFG: impaired fasting glucose; IGT: Impaired glucose tolerance; DM: Diabetes mellitus.

The PAD percentage was 21.1% (95% CI 18.4-24.1; n = 219) with no difference between the genders (19.2% versus 22.7%). Stratifying by gender, the results of participants with and without PAD maintained the same pattern, and were, therefore, presented together. The average age of participants with PAD was higher compared to those without the disease (60 versus 56 years, p < 0.001).

About 53% of patients with PAD were hypertensive and their average systolic blood pressure was statistically higher than those without the disease (data not shown). Similarly, the participants presented higher average homocysteine values (12.2 versus 11.1 mg/dL, p = 0.004).

The percentages of PAD were significantly higher in the older age group, in hypertensive patients and in those with hyperhomocysteinemia (Table 3). There were no differences in the distribution of participants with and without PAD in the categories of smoking, adiposity, glucose tolerance and dyslipidemia. The same happened with the categories of hs CRP and uric acid.

Table 3 Number, percentage and prevalence ratios (95% confidence intervals) of categories of demographic and clinical variables of a sample of 1,038 Japanese-Brazilians from Bauru (Sao Paulo) stratified according to the presence of PAD 

  With PAD n = 219 Without PAD n = 819 Total n= 1.038 Chi-square PR CI95%
N % N % N %
Gender Women 128 22.7 437 77.3 565 100 1.80 1  
  Men 91 19.2 382 80.8 473 100   0.85 0.67-1.08
Age ≤ 60 years 110 17.8 509 82.2 619 100 10.2 1  
  > 60 years 109 26.0 310 74.0 419 100   1.46 1.16-1.85
Smoking No 150 20.9 567 79.1 717 100 0.39 1  
  Yes (past) 38 20.3 149 79.7 187 100   0.97 0.71-1.33
  Yes (current) 30 23.1 100 76.9 130 100   1.10 0.78-1.56
Waist-hip ratio No 101 20.1 402 79.9 503 100 0.57 1  
  Yes 117 22.0 415 78.0 532 100   1.10 0.86-1.39
Body mass index < 23 kg/m2 76 22.1 268 77.9 344 100 3.10 1  
  23.0-24.9 kg/m2 57 24.1 180 75.9 237 100   1.09 0.81-1.47
  ≥ 25 kg/m2 85 18.6 371 81.4 456 100   0.84 0.64-1.11
Hypertension No 101 17.8 466 82.2 567 100 8.1 1  
  Yes 118 25.1 353 74.9 471 100   1.41 1.11-1.78
Glucose tolerance Normal 8 13.8 50 86.2 58 100 4.40 1  
  IFG 73 19.4 304 80.6 377 100   1.40 0.71-2.76
  IGT 59 24.6 181 75.4 240 100   1.78 0.90-3.52
  DM 79 21.8 283 78.1 362 100   1.58 0.81-3.10
Hypercholesterolemia No 81 20.7 311 79.3 392 100 0.07 1  
  Yes 138 21.4 508 78.6 646 100   1.03 0.81-1.32
Low HDL No 190 20.9 719 79.1 909 100 0.17 1  
  Yes 29 22.5 100 77.5 129 100   1.08 0.72-1.52
High LDL No 112 20.9 424 79.1 536 100 0.03 1  
  Yes 107 21.3 395 78.7 502 100   1.02 0.81-1.29
Hypertriglyceridemia No 76 20.7 291 79.3 367 100 0.05 1  
  Yes 143 21.3 528 78.7 671 100   1.03 0.80-1.32
hs-CRP ≤ 1.1 mg/L 100 19.6 409 80.4 509 100 1.26 1  
  1.1-9.9 mg/L 119 22.5 410 77.5 529 100   1.15 0.90-1.45
Homocysteine ≤ 15 mg/dL 140 20.0 560 80.0 700 100 5.36 1  
  > 15 mg/dL 35 29.4 84 70.6 119 100   1.47 1.07-2.02

PR: prevalence ratio. CI95%: confidence interval; PAD: peripheral arterial disease; IFG: impaired fasting glucose; IGT: Impaired glucose tolerance; DM: Diabetes mellitus.

The adjusted analysis of the data detected associations of PAD with smoking and hypertension (Table 4).

Table 4 Prevalence ratios (PR) of PAD and their intervals with 95% confidence intervals (CI95%) in a sample of 1,038 Japanese-Brazilians from Bauru (Sao Paulo) according to the presence of selected variables (initial and final model) 

  Initial model Adjusted model
Variable   PR CI95% PR CI95%
Gender Women 1   1  
  Men 0.66 0.42-1.02 0.66 0.44-1.01
Age ≤ 60 years 1   1  
  > 60 years 0.98 0.71-1.36 0.94 0.69-1.23
Smoking No 1   1  
  Yes (past) 1.45 0.91-2.31 1.44 0.92-2.33
  Yes (current) 2.14 1.32-3.50 2.16 1.34-3.48
Hypertension No 1   1  
  Yes 1.61 1.12-2.31 1.56 1.12-2.22
Glucose tolerance Normal 1      
  IFG 0.67 0.38-1.21 0.71 0.40-1.32
  IGT 0.76 0.42-1.38 0.65 0.43-1.44
  DM 0.66 0.37-1.17 0.65 0.39-1.23
Homocysteine ≤ 15mg/dL 1   1  
  > 15mg/dL 1.25 0.88-1.77 1.26 0.89-1.78

PR: prevalence ratio; IC95%: confidence interval; IFG: impaired fasting glucose; IGT: Impaired glucose tolerance; DM: Diabetes mellitus.

When we stratify the ABI into three categories (≤ 0.70, 0.71-0.90 and > 0.90), the behavior of these results was maintained (data not shown). The average age of participants with ABI ≤ 0.70 was statistically higher than in other categories (p <0.001). Regarding the disorders of glucose tolerance, the highest fasting glucose and two-hour glucose averages were observed in patients with ABI ≤ 0.70 (p = 0.002 and p = 0.001, respectively), and 70% of those with ABI ≤ 0.70 had diabetes mellitus. The smokers had the highest proportion of ABI ≤ 0.70 (3.9%). Those who had the lowest ABI values (≤ 0.70) were those who smoked the highest number of cigarettes per day (22.5 cigarettes). As to the WHR, 70% of those with ABI ≤ 0.70 presented increased values of this variable. Average systolic blood pressure and average homocysteine were higher in participants with ABI ≤ 0.70 (p < 0.001 and p = 0.031, respectively) and 85% of these had hypertension (data not shown).

Discussion

In this population-based study, 21.1% of Japanese-Brazilians living in Bauru had PAD. Considering the unfavorable cardiometabolic profile previously described18, this high percentage was expected. Although higher frequencies of cardiovascular risk factors among men were found, the PAD was similar between the genders.

As in our study, other studies in populations at high cardiovascular risk found high PAD values. The US PARTNERS program, designed to study the prevalence of PAD and other cardiovascular diseases, found a prevalence of PAD of 29% in individuals aged > 70 or > 50 with comorbidities (diabetes and smoking)19. The POPADAD program evaluated 8,000 diabetic patients aged ≥ 40 and found PAD prevalence of 20.1%20.

In our community, a multicenter study on the prevalence of PAD conducted in the general population of 72 urban centers (n = 1170) found a prevalence of only 10.5%. It is important to note that the age group was lower (≥ 18 years) and the sample represented best the Brazilian population for neither including individuals genetically homogeneous nor those at high cardiovascular risk21. Publications of our group confirmed that the Japanese-Brazilians from Bauru are at high risk, based on the levels of obesity, diabetes mellitus, hypertension and dislipidemia22.

Classical risk factors were independently associated with PAD, such as smoking (current) and hypertension in the population studied. Smoking has been considered the most important preventable risk factor for PAD23. This risk factor is more strongly associated with PAD than the coronary artery disease24 , 25. The adjusted risk of PAD reported for age and sex is 1.9 for moderate smokers and 3.9 for heavy smokers, in contrast to the risk of coronary heart disease of 1.6 and 1.7, respectively25.

Hypertension was present in more than half the population of Japanese-Brazilians from Bauru affected by PAD and was associated with this complication regardless of other risk factors. Our findings agreed with Lip et al26 who found hypertension in 55% of arteriopathic patients studied in a systematic review. Evaluating in isolation our hypertensive population, we found 25% of arteriopathic patients, which was statistically higher than that of non-hypertensive patients (25% versus 17%, p < 0,05). In the same line, Wiinberg et al27 evaluating a population of 1,044 individuals from 20 centers (591 women, mean age 71 years) also found higher percentage of PAD in hypertensive patients (10.5% versus 6.2%; p <0.05).

The diagnosis of diabetes mellitus itself was not associated with PAD in this study. However, mean fasting glucose level and two-hour post-overload glucose were significantly higher in individuals with ABI ≤ 0.70, and 70% of them were diabetic. For the American Diabetes Association, diabetes and smoking represent the most important risk factors for PAD; if diabetes is present, this risk increases with age, with disease duration and the presence of diabetic neuropathy28. In our study, 32.3% of Japanese-Brazilians from Bauru, affected by diabetes, knew they had the disease (n = 117), and the average time of diagnosis was 11.8 years. It is possible that the duration of the disease in the population studied has not caused a greater impact on this complication, since an average time of 16.2 years of diabetes has been described for the development of PAD29.

An interesting finding was the increased WHR in 70% of Japanese-Brazilians from Bauru with ABI ≤ 0.70, unlike the BMI, which was not associated with PAD. Our findings agreed with those of Planas et al30 who found a positive association between PAD and WHR, but not with BMI in Europeans. These authors considered that the BMI is not a good indicator of atherosclerotic disease, especially in the older population, because the body fat may increase without changing or even reducing body weight due to loss of lean body mass. In our population, participants with ABI ≤ 0.70 in fact were the oldest ones, supposedly with some reduction of lean mass.

Homocysteine concentrations were associated with PAD in the crude analysis and were also higher in patients with ABI ≤ 0.70. Several studies have shown this association, including our group. We had also detected in male Japanese-Brazilians living in Bauru a positive and independent association between these variables14. A meta-analysis concluded that patients with PAD had higher homocysteine levels than controls without the disease, although a causal relationship cannot be ensure yet31.

An association of lipid abnormalities with PAD would be expected. However, a previous publication from our group showed how high is the frequency of dyslipidemia in this population of Japanese-Brazilians from Bauru, which may have made it difficult to reach statistical significance32. The literature is scant as to evidence regarding the relationship of lipid variables with the peripheral territory. Murabito et al33 found a positive relationship of PAD only with low HDL-cholesterol concentrations.

hs-CRP was not associated with PAD in our study. Only patients with ABI ≤ 0.70 presented higher values, but without statistical significance. hs-CRP has been used as a marker of chronic subclinical inflammation, which is present early in the natural history of atherosclerosis and diabetes mellitus, hypertension, dyslipidemia and other diseases. There is much controversy about the relationship between hs-CRP and PAD in the literature. The individuals included in this study are mostly in the advanced stage of evolution of these diseases, therefore its prognostic value may be small. The vast majority of literature studies that evaluate the relationship of hs-CRP with atherosclerotic disease has focused on the coronary arteries. A study conducted at Clínica Mayo in 247 individuals referred for investigation of asymptomatic PAD using ABI also found no association between high levels of hs-CRP and PAD34.

There is evidence that the concentration of CRP has an hereditary component. It was found that certain polymorphisms in the PCR gene were able to influence their blood concentrations35. Genetic epidemiology has assisted in obtaining evidence about the involvement of CRP in atherosclerosis because, since PCR is causally involved in atherosclerosis, individuals carrying alleles that promote high plasma concentrations of CRP would present an increased risk of cardiovascular disease, where this risk is proportional to increased PCR35 , 36. However, studies published35 , 36 are still not able to ensure a causal role of CRP in atherosclerosis.

Our data indicated that, with the severity of PAD, there was an increase in the numbers of major cardiovascular risk factors, and individuals with ABI values ≤ 0.70 had the worst cardiometabolic profile. There is a need for early diagnosis and treatment of PAD, since its presence indicates widespread atherosclerotic process, compromising the survival of the individuals. Belch et al37 considered PAD a distinct atherothrombotic syndrome that is able to predict the occurrence of stroke, AMI and death. In the absence of concomitance with coronary disease, the PAD has been undertreated and poorly controlled38.

The REACH Registry39 a multicenter study of patients with established arterial disease (coronary disease, cerebrovascular or peripheral disease), concluded that the profile of risk factors is similar in the regions analyzed, with a high proportion of hypertensive patients (81.8%), diabetic patients (44.3%) and patients with hypercholesterolemia (72.4%). The treatment of these factors is inadequate and there is disparity between the established guidelines and clinical practice in sick individuals or patients at risk for atherothrombotic disease.

Conclusion

Our study shows a high percentage of subclinical atherosclerotic disease that is similar to other populations of adverse cardiometabolic profile. High frequencies of metabolic disorders in this population may explain the independent relationship of PAD only with smoking and hypertension but not with other classical risk factors. The associations with modifiable risk factors (smoking and hypertension) should serve to motivate and guide interventions and thereby reduce the cost to the health system.

Study Association

This article is part of the thesis of doctoral submitted by Luciana Garofolo, from UNIFESP.

Author contributions

Conception and design of the research, Acquisition of data, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Garofolo L, Ferreira SRG; Analysis and interpretation of the data: Garofolo L, Ferreira SRG, Miranda Junior F; Statistical analysis: Garofolo L; Obtaining funding: Ferreira SRG.

Sources of Funding

This study was funded by FAPESP.

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Received: May 30, 2013; Revised: October 13, 2013; Accepted: October 16, 2013

Mailing address: Luciana Garofolo, Rua Dr. Rafael de Barros, 497, Paraíso. CEP 04003-040, São Paulo, SP - Brazil. E-mail: lgarofolo@ig.com.br, garofolo@unifesp.br

Potential Conflict of Interest

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

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