Biomarkers of inflammation may be of use for identification of more severe peripheral arterial occlusive disease / Biomarcadores inflamatórios circulantes podem ser úteis para identificar doença arterial obstrutiva periférica mais grave

Background: Atherosclerosis is a multifactorial disease with an inflammatory pathophysiological basis. Cytokines released during the atherosclerotic process induce production of C-reactive protein (CRP) in the liver, which is an important marker of inflammation. Objective: We tested whether inflammatory biomarkers were associated with deterioration of peripheral arterial occlusive disease (PAOD) in a population at high cardiovascular risk. Methods: 1,330 subjects ≥30 years of age underwent clinical and laboratory examinations as part of a population-based study of the prevalence of diabetes. PAOD was defined as an ankle-brachial index (ABI) ≤0.90. After application of exclusion criteria, the sample comprised 1,038 subjects. Traditional risk factors, CRP and interleukin 6 (IL-6) were also compared across three ABI categories (≤0.70; 0.71-0.90; ≥0.90). Mean values for these variables were compared by presence/absence of DAOP (Student's t test) and by ABI categories (ANOVA). Poisson regression and logistic regression models were used to test for associations between risk factors and DAOP and between risk factors and the ABI categories. Pearson's linear correlation coefficients were calculated for the relationship between CRP and IL-6 levels. Results: Mean age was 56.8±12.9 years, 54% of the sample were women and the prevalence of DAOP was 21.0% (95%CI 18.4-24.1). Individuals with ABI ≤0.70 had higher concentrations of CRP-us (2.1 vs. 1.8) and of IL-6 (1.25 vs. 1.17). Concentrations of CRP and IL-6 were only correlated in patients with DAOP, (p=0.004). Conclusions: The finding that CRP and IL-6 levels were only elevated among people with advanced DAOP may suggest that these biomarkers have a role to play as indicators of more severe disease. Prospective studies are needed to test this hypothesis...

Contexto: Aterosclerose é doença multifatorial, cuja base fisiopatológica é um processo inflamatório. Estudos são controversos quanto ao papel dos biomarcadores como fatores de risco. A liberação de citoquinas durante aterogênese promove síntese hepática de proteína C-reativa (PCR), importante marcador inflamatório. Objetivo: Avaliamos se biomarcadores inflamatórios estavam associados à deterioração da doença arterial obstrutiva periférica (DAOP), em população de risco cardiovascular. Métodos: Estudo populacional sobre prevalência de diabetes, em que 1.330 indivíduos com ≥30 anos foram submetidos a exames clínico-laboratoriais. Diagnóstico de DAOP foi feito pelo índice tornozelo-braço (ITB) ≤0,90. Após exclusões, 1.038 indivíduos foram analisados. Fatores de risco tradicionais, PCR e interleucina 6 (IL-6) foram comparados também segundo três categorias de ITB (≤0,70; 0,71-0,90; ≥0,90). Valores médios das variáveis foram comparados segundo presença de DAOP (teste t Student) e categorias do ITB (ANOVA). Utilizou-se modelo de Poisson e regressão logística para avaliar associações da DAOP e categorias do ITB com fatores de risco. Estimou-se coeficiente de correlação linear de Pearson para relação entre os valores de PCR e IL-6. Resultados: A idade média foi 56,8±12,9 anos, 54% mulheres e prevalência de DAOP 21,0% (IC95% 18,4-24,1). Indivíduos com ITB ≤0,70 apresentaram maiores valores de PCR-us (2,1 vs. 1,8) e IL-6 (1,25 vs. 1,17. Apenas em portadores de DAOP, valores de PCR e IL-6 mostraram-se correlacionados (p=0,004). Conclusão: O achado de concentrações mais elevadas de PCR e IL-6 apenas em indivíduos com DAOP avançada pode sugerir um...

Association between peripheral arterial disease and C-reactive protein in the Japanese-Brazilian population.

OBJECTIVE: To evaluate the relationship between peripheral arterial disease and elevated levels of C-reactive protein in the Japanese-Brazilian population of high cardiovascular risk. METHODS: We conducted a cross-sectional study derived from a population-based study on the prevalence of diabetes and associated diseases in the Japanese-Brazilian population. One thousand, three hundred and thirty individuals aged e" 30 underwent clinical and laboratory examination, including measurement of ultrasensitive C-reactive protein. The diagnosis of peripheral arterial disease was performed by calculating the ankle-brachial index. We considered with peripheral arterial disease patients who had ankle-brachial index d" 0.9. After applying the exclusion criteria, 1,038 subjects completed the study. RESULTS: The mean age of the population was 56.8 years; 46% were male. The prevalence of peripheral arterial disease was 21%, with no difference between genders. Data analysis showed no association between peripheral arterial disease and ultrasensitive C-reactive protein. Patients with ankle-brachial index d" 0.70 showed higher values of ultrasensitive C-reactive protein and worse cardiometabolic profile. We found a positive independent association of peripheral arterial disease with hypertension and smoking. CONCLUSION: The association between low levels of ankle-brachial index and elevated levels of ultrasensitive C-reactive protein may suggest a relationship of gravity, aiding in the mapping of high-risk patients.

Association between peripheral arterial disease and creactive protein in the japanese-brazilian population / Avaliação da associação entre doença arterial obstrutiva periférica e níveis aumentados de proteína C-reativa em população nipo-brasileira

OBJECTIVE: To evaluate the relationship between peripheral arterial disease and elevated levels of C-reactive protein in the Japanese-Brazilian population of high cardiovascular risk. METHODS: We conducted a cross-sectional study derived from a population-based study on the prevalence of diabetes and associated diseases in the Japanese-Brazilian population. One thousand, three hundred and thirty individuals aged e" 30 underwent clinical and laboratory examination, including measurement of ultrasensitive C-reactive protein. The diagnosis of peripheral arterial disease was performed by calculating the ankle-brachial index. We considered with peripheral arterial disease patients who had ankle-brachial index d" 0.9. After applying the exclusion criteria, 1,038 subjects completed the study. RESULTS: The mean age of the population was 56.8 years; 46% were male. The prevalence of peripheral arterial disease was 21%, with no difference between genders. Data analysis showed no association between peripheral arterial disease and ultrasensitive C-reactive protein. Patients with ankle-brachial index d" 0.70 showed higher values of ultrasensitive C-reactive protein and worse cardiometabolic profile. We found a positive independent association of peripheral arterial disease with hypertension and smoking. CONCLUSION: The association between low levels of ankle-brachial index and elevated levels of ultrasensitive C-reactive protein may suggest a relationship of gravity, aiding in the mapping of high-risk patients. .

OBJETIVO: avaliar a relação entre a doença arterial obstrutiva periférica e níveis elevados de proteína C-reativa em população nipo-brasileira de alto risco cardiovascular. MÉTODOS: estudo transversal derivado de estudo de base populacional sobre a prevalência de diabetes e doenças associadas em população nipo-brasileira. Mil trezentos e trinta indivíduos com idade >30 foram submetidos a exame clínico e laboratorial, incluindo a dosagem da proteína C-reativa ultrassensível. O diagnóstico da doença arterial obstrutiva periférica foi realizado através do cálculo do índice tornozelo-braço. Foram considerados portadores de doença arterial obstrutiva periférica os pacientes que apresentaram índice tornozelo-braço <0,9. Após aplicação dos critérios de exclusão, 1038 indivíduos completaram o estudo. RESULTADOS: a média de idade da população foi 56,8 anos, 46% pertencentes ao sexo masculino. A prevalência da doença arterial obstrutiva periférica foi 21%, sem diferença entre os sexos. A análise dos dados não mostrou associação entre doença arterial obstrutiva periférica e proteína C-reativa ultrassensível. Os pacientes com índice tornozelo-braço <0,70 apresentaram valores mais elevados de proteína C-reativa ultrassensível e o pior perfil cardiometabólico. Encontramos associação positiva e independente da doença arterial obstrutiva periférica com hipertensão arterial e tabagismo. . CONCLUSÃO: a associação encontrada entre valores baixos de índice tornozelo-braço e níveis elevados de proteína C-reativa ultrassensível pode sugerir uma relação de gravidade auxiliando mapeamento dos pacientes ...

Study of risk factors associated with peripheral arteriopathy in Japanese-Brazilians from Bauru (SP).

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.

Estudo dos Fatores de Risco Associados a Arteriopatia Periferica em Nipo-brasileiros de Bauru (SP) / Study of Risk Factors Associated with Peripheral Arteriopathy in Japanese-Brazilians from Bauru (SP)

Fundamento: As patologias cardiovasculares são a maior causa de morbimortalidade nos países desenvolvidos e emergentes. Sua principal etiologia, a aterosclerose, é doença disseminada acometendo os territórios coronariano, cerebral e periférico. A doença arterial obstrutiva periférica (DAOP), além de suas consequências per se, sinaliza o acometimento do território coronariano. Portanto, seu melhor conhecimento permite tratamento adequado, retardando complicações locais e à distância, diminuindo o custo para o sistema de saúde. Objetivo: Este estudo estima a porcentagem de DAOP em nipo-brasileiros de Bauru (SP), reconhecidos pela alta prevalência de distúrbios metabólicos, como hipertensão arterial (43%), diabetes melito (33%) e hipercolesterolemia (60 %), e analisa a associação com biomarcadores de risco. Métodos: Este estudo transversal populacional avaliou 1.330 nipo-brasileiros de ambos os sexos com idade ≥ 30 anos que foram submetidos a exame físico completo, medidas antropométricas, exames laboratoriais e índice tornozelo-braço (ITB). Participantes com ITB ≤ 0,90 foram diagnosticados como portadores de DAOP. Após aplicação dos critérios de exclusão, 1.038 indivíduos integraram a análise. Empregou-se regressão de Poisson para análise das associações com DAOP. Resultados: A idade média foi 56,8 anos e a porcentagem de DAOP foi 21,1%, igual entre os sexos. DAOP associou-se com tabagismo (RP 2,16 [1,33-3,48]) e hipertensão arterial (RP 1,56 [1,12-2,22]). Conclusão: A porcentagem de DAOP nos nipo-brasileiros foi semelhante à de outras populações de perfil cardiometabólico desfavorável (US PARTNERS e POPADAD). A associação independente de DAOP com tabagismo e hipertensão, ...

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. .

[Analysis of factors associated with extremity ulceration in diabetic subjects with peripheral neuropathy]. / Análise de fatores associados à ulceração de extremidades em indivíduos diabéticos com neuropatia periférica.

Peripheral neuropathy is the main risk factor for foot ulceration in diabetic subjects. This study examined the association of peripheral arterial disease (PAD) with foot ulceration in a sample of diabetic subjects with peripheral neuropathy, and also if inflammatory markers would be associated with this event. We evaluated 32 type 2 diabetic individuals with abnormal 10-g monofilament exam, who were stratified in 2 groups according to history or presence of lower extremities ulcer. The group "with ulcer" (n = 18) included the ones that had active or cicatrized ulcer, or some lower-extremity amputation due to ulcer complications. In addition to the neurological examination and monofilament test, they were submitted to biothesiometry, lower extremity vascular assessment with Doppler, and laboratory determinations. No difference between the groups was found concerning sex distribution, mean age, and duration of diabetes diagnosis. The group with ulcer showed higher mean values of height (1.70 +/- 0.06 vs. 1.63 +/- 0.11 m, p = 0.044), vibration perception threshold measured in medial malleolli (40.9 +/- 13.0 vs. 30.6 +/-12.3 V, p = 0.040) than the group without ulcer. The groups did not differ regarding the mean values of the inflammatory markers. Response to patellae reflex was worse in the group with ulcer (p = 0.047), in which a higher proportion of individuals with abnormal toe-brachial index (p = 0.030) was observed as compared to those without ulcer. We concluded that PAD is associated with the presence of ulcer in neuropathic subjects. The assessment of digital arteries flow in lower limbs (in great toe) contributed to detect such association. Association of diabetic foot ulcers and inflammatory markers was not observed, but cannot be excluded due to limitations of sample size. Prospective studies should examine the sensitivity of the toe-brachial index to identify PAD in diabetic individual at risk of ulceration.

Análise de fatores associados à ulceração de extremidades em indivíduos diabéticos com neuropatia periférica / Analysis of factors associated with extremity ulceration in diabetic subjects with peripheral neuropathy

A neuropatia periférica é o principal fator de risco para ulceração em pé de indivíduos diabéticos. Este estudo testou a associação de doença arterial periférica (DAP) à ulceração do pé em amostra de pacientes com neuropatia sensório-motora simétrica distal e se marcadores inflamatórios subclínicos também se associariam a esse evento. Foram avaliados 32 indivíduos diabéticos tipo 2 com exame do monofilamento de 10 g alterado, estratificados em 2 grupos segundo a história ou presença de úlcera nas extremidades inferiores. O grupo "com úlcera" (n = 18) incluiu aqueles que apresentavam úlcera ativa ou cicatrizada, ou que tiveram alguma amputação em membro inferior decorrente de complicações da úlcera. Além do exame neurológico e monofilamento, foram submetidos a bioestesiometria, avaliação vascular com Doppler e exames laboratoriais. Os grupos foram semelhantes quanto à distribuição dos sexos, média de idade e tempo de diabetes. O grupo com úlcera apresentou valores médios de altura (1,70 ± 0,06 vs. 1,63 ± 0,11 m; p = 0,044) e limiar de percepção vibratória no maléolo medial (40,9 ± 13,0 vs. 30,6 ± 12,3 V; p = 0,040) mais elevados que o sem a úlcera. Os grupos não diferiram entre si quanto à média dos marcadores inflamatórios. A resposta do reflexo patelar foi também pior no grupo com úlcera (p = 0,047), no qual se observou maior proporção de indivíduos com o índice hálux-braquial alterado (p = 0,030) quando comparado ao sem úlcera. Conclui-se que a DAP está associada à presença de úlcera (atual ou pregressa) em membros inferiores de indivíduos diabéticos neuropatas. A pesquisa de alteração de fluxo de artérias digitais de membro inferior (no hálux) contribuiu para detectar tal associação. Associação de neuropatia ulcerada a marcadores inflamatórios não foi observada, não sendo possível excluí-la devido às limitações do tamanho da amostra. Estudos prospectivos deverão examinar a sensibilidade do índice hálux-braquial...

Peripheral neuropathy is the main risk factor for foot ulceration in diabetic subjects. This study examined the association of peripheral arterial disease (PAD) with foot ulceration in a sample of diabetic subjects with peripheral neuropathy, and also if inflammatory markers would be associated with this event. We evaluated 32 type 2 diabetic individuals with abnormal 10-g monofilament exam, who were stratified in 2 groups according to history or presence of lower extremities ulcer. The group "with ulcer" (n = 18) included the ones that had active or cicatrized ulcer, or some lower-extremity amputation due to ulcer complications. In addition to the neurological examination and monofilament test, they were submitted to biothesiometry, lower extremity vascular assessment with Doppler, and laboratory determinations. No difference between the groups was found concerning sex distribution, mean age, and duration of diabetes diagnosis. The group with ulcer showed higher mean values of height (1.70 ± 0.06 vs. 1.63 ± 0.11 m, p = 0.044), vibration perception threshold measured in medial malleolli (40.9 ± 13.0 vs. 30.6 ± 12.3 V, p = 0.040) than the group without ulcer. The groups did not differ regarding the mean values of the inflammatory markers. Response to patellae reflex was worse in the group with ulcer (p = 0.047), in which a higher proportion of individuals with abnormal toe-brachial index (p = 0.030) was observed as compared to those without ulcer. We concluded that PAD is associated with the presence of ulcer in neuropathic subjects. The assessment of digital arteries flow in lower limbs (in great toe) contributed to detect such association. Association of diabetic foot ulcers and inflammatory markers was not observed, but cannot be excluded due to limitations of sample size. Prospective studies should examine the sensitivity of the toe-brachial index to identify PAD in diabetic individual at risk of ulceration.