The hallmark of pro- and anti-inflammatory cytokine ratios in women with polycystic ovary syndrome.

Polycystic Ovary Syndrome (PCOS) is a heterogeneous endocrinopathy considered to be the most common metabolic disorder in women of reproductive age. Women with PCOS present with an increased risk of noncommunicable diseases (NCDs), especially low-grade chronic inflammation mediated by proinflammatory cytokines, and insulin resistance. This study aimed to investigate cytokine levels and their ratios in PCOS women compared to a healthy control group. This study evaluated 97 women with PCOS and 99 healthy women as controls. The PCOS diagnosis was performed according to ESHRE/ASRM. Plasma cytokines were evaluated by flow cytometry. We observed lower TNF levels, and decreased TNF/IL-6, TNF/IL-2, and TNF/IL-4 ratios in PCOS patients compared to the control group (p < 0.05). These results indicate an imbalance between pro- and anti-inflammatory cytokines, with prominent counter-regulatory cytokine production. These changes may be important in explaining the phenotypes present in PCOS and to direct better interventions for patients with this syndrome.

Peripheral blood-derived cytokine gene polymorphisms and metabolic profile in women with polycystic ovary syndrome.

BACKGROUND: The imbalance between proinflammatory and anti-inflammatory pathways plays a role in polycystic ovary syndrome (PCOS) etiology. We aimed to investigate the relationship between polymorphisms of genes encoding inflammation-associated cytokines and the metabolic profile of Brazilian women with PCOS. DESIGN: Case-control study. METHODS: The study included 196 women - 97 with PCOS (diagnosed based on Rotterdam criteria, 2003) and 99 age-matched, healthy women (controls). It was investigated polymorphisms in cytokines genes from peripheral blood-derived DNA by using PCR. RESULTS: The frequencies of alleles, genotypes, and phenotypes were similar between women with PCOS and controls. The GG genotype of the -179C/G polymorphism (IL6) was associated with higher glucose levels, while the GA and AA genotypes of the -1082A/G polymorphism (IL10), CT and TT genotypes of the -819A/T polymorphism (IL10), CA and AA genotypes of the -522A/G (IL10) polymorphism, and TA genotype of the +874T/A polymorphism (IFN-γ) were associated with lower total cholesterol and triglycerides levels. The GA genotype of the -1082A/G polymorphism (IL10) and the CC genotype of the 10T/C polymorphism (TGF-ß1) were associated with lower and higher Ferriman indices, respectively, in women with PCOS. The AA genotype of the -1082A/G polymorphism (IL10) was associated with lower glucose levels, while the TC genotype of the 10T/C polymorphism (TGF-ß1) was associated with a lower lipid accumulation product index and higher high-density lipoprotein cholesterol levels in the PCOS group. CONCLUSIONS: The genetic polymorphisms of cytokines are not associated with PCOS development, but may contribute to common metabolic disorders associated with PCOS.

-1131T>C and SW19 polymorphisms in APOA5 gene and lipid levels in type 2 diabetic patients.

Type 2 diabetes mellitus is a metabolic, vascular, and neuropathic disease with a high risk of atherosclerotic events due to dyslipidemic states. Polymorphisms in Apolipoprotein A5 gene (APOA5) have been associated with increased triglyceride levels in many different populations. This study aimed to identify the frequencies of the APOA5 -1131T>C and SW19 polymorphisms and evaluate their effects on lipid levels in patients with type 2 diabetes. Genotyping of APOA5 -1131T>C and SW19 polymorphisms was performed by PCR-RFLP in 146 diabetic patients and in controls (n = 173), from 30 to 80 years of age. Diabetic patients were divided into two groups: patients not treated with lipid lowering drugs (group G1; n = 62) and those treated with lipid lowering drugs (group G2, n = 84). Lipids and lipoproteins were determined enzymatically. Among participants not treated with lipid-lowering drugs (diabetics G1 and controls; n = 235), the -1131C was associated with lower LDLc levels (p = 0.015). In the diabetic patients, the 19W allele was associated with higher triglyceride levels (p = 0.004). In G1 diabetic patients, the combined analysis of APOA5 -1131T>C and SW19 polymorphisms showed that [TC or CC] + SS carriers presented lower total cholesterol levels than did other genotype combinations (p = 0.049). It could therefore be concluded that APOA5 -1131T>C and SW19 polymorphisms influence lipid levels in type 2 diabetic patients.

Plasma total homocysteine levels and methylenetetrahydrofolate reductase gene polymorphism in patients with type 2 diabetes mellitus.

BACKGROUND: Thrombotic episodes account for approximately 80% of deaths in type 2 diabetic patients. Hyperhomocysteinaemia is a well recognized independent risk factor for atherosclerosis and thromboembolism. Increased homocysteine levels may occur due to a number of factors including inherited gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) C677T. Here, we evaluate plas- ma total homocysteine (tHcy) levels and frequency of the MTHFR C677T gene polymorphism in asymptomatic healthy volunteers and type 2 diabetic patients with hypertension but without nephropathy. We have also investigated the relationship between tHcy levels and the presence of MTHFR C677T gene polymorphism. METHODS: Plasma tHcy levels and MTHFR C677T genotype were investigated in a total of 53 subjects. These included asymptomatic healthy volunteers (n = 16), patients with type 2 diabetes (n = 7), subjects with hypertension (n = 12) and patients with both type 2 diabetes and hypertension (n = 18). Renal function, serum lipids and other metabolites were also assessed. RESULTS: There was no significant difference in tHcy levels between the groups studied. The frequency of MTHFR C677T gene polymorphism observed was similar to that obtained for the general Brazilian population. In patients with type 2 diabetes and hypertension but without impaired renal function, we observed no meaningful correlation between increased tHcy levels and the presence of MTHFR C677T gene polymorphism. CONCLUSIONS: Type 2 diabetics who are homozygous or heterozygous for the MTHFR C677T gene polymorphism showed normal tHcy levels. Our results further suggest that diabetes without an associated adverse risk profile is not an independent correlate of increased tHcy levels.

High-sensitivity C-reactive protein in subjects with type 2 diabetes mellitus and/or high blood pressure.

Type 2 diabetes mellitus (DM2) and high blood pressure (HBP) may contribute to the development of cardiovascular disease, and inflammation may be an important factor in these diseases. In the present study, plasma levels of high-sensitivity C-reactive protein (hs-CRP) were measured in subjects with DM2 and/or HBP and compared to those of normal subjects. Eighty-nine subjects were analyzed for hs-CRP, including 13 normotensive patients with DM2, 17 patients with HBP, 34 hypertensive patients with DM2 (DM2+HBP) and 25 normal subjects. The plasma hs-CRP levels were significantly lower in the controls than in the HBP+DM2 group (p < 0.05). DM2 associated with HBP was also correlated with increased plasma hs-CRP levels (n = 89, r = 0.25, p = 0.0162). Only hypertensive patients with DM2 had higher levels of hs-CRP, a circulating inflammatory marker, than normal subjects. This finding suggests that patients with two associated diseases have a more active inflammatory state.

Apo B/Apo A-I ratio in central and peripheral arterial diseases.

BACKGROUND: The apo B/apo A-I ratio represents the balance between atherogenic particles, rich in apo B, and the antiatherogenic ones, apo A-I rich. This study investigated the association between atherosclerotic diseases in different anatomical sites and apo B/apo A-I ratio. METHODS: Lipids, lipoproteins, and apolipoproteins A-I and B were assessed in 30 subjects with coronary artery disease (CAD), 26 with ischemic stroke (IS), 30 with peripheral arterial obstructive disease (PAOD), and 38 healthy subjects (controls). RESULTS: HDLc and Apo A-I were significantly lower in PAOD and CAD groups, respectively, than in other groups. Significantly higher levels of triglycerides were observed for CAD and PAOD groups than for controls. Apo B was significantly higher in IS group than in control and PAOD groups. The apo B/apo A-I ratio showed significantly higher in CAD and IS groups when compared to control and PAOD groups (p < 0.001). CONCLUSION: The apo B/apo A-I ratio was important for identifying an increased trend for coronary and cerebral atherosclerosis. In spite of the increased trend for apo B/apo A-I ratio in IS and CAD groups, the studied variables cannot be considered in an isolated way, given as those parameters were analyzed together by a binary logistic regression, no association has been demonstrated.

Apolipoprotein polymorphism is associated with pro-thrombotic profile in non-demented dyslipidemic subjects.

Apolipoprotein gene polymorphism has an important role in lipid metabolism and in the development of cerebro- and cardio-vascular disease (CCVD), including dementia. Dyslipidemia and hemostatic abnormalities are key risk factors associated with athero-sclerotic events preceding CCVD. The aim of this study was to evaluate the possible relationships of various apolipoprotein-species with hemostatic parameters and cognitive function. Lipid profile, gene polymorphism, coagulation markers, and mini-mental state examination (MMSE) scores were assessed in 109 dys-lipidemic subjects and in 107 healthy control volunteers. Thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels were significantly higher in apolipoprotein-E2 (apoE2) patients when compared to other apoE forms. The apoA5 -1131T>C polymorphism was associated with elevated D-dimer concentration in dyslipidemic TT homozygous individuals. MMSE did not correlate with lipid or coagulation profile. These data suggest that apoE and apoA5 variants have an effect on hemostatic parameters, but they neither influence nor predict cognitive performance in non-demented individuals.

Hyper-coagulable profile with elevated pro-thrombotic biomarkers and increased cerebro- and cardio-vascular disease risk exist among healthy dyslipidemic women.

Dyslipidemia is one of the pathognomonic elements of athero-genesis, as well as cerebro- and cardio-vascular disease (CCVD). Hemostatic factors are also involved in athero-sclerosis and ischemic changes, however their relationship with disrupted lipid homeostasis is not well characterized. The aim of this study was to determine the coagulation state of dyslipidemic patients and to evaluate their association with CCVD risk factors. Biochemical and hematological parameters, as well as neuro-psychiatric profile of 109 dyslipidemic subjects and 107 normo-lipidic healthy volunteers were assessed. Serum bio-marker levels and cognitive performance generally did not differ in the groups, but prothrombin fragment 1+2 (F1+2) and D-dimer concentrations were markedly higher among women. Hyper-coagulability was not associated with dyslipidemia, but was correlated with the female gender, which might pose an increased thromboembolic risk in asymptomatic women.

Thrombin-activatable fibrinolysis inhibitor (TAFI) levels and its polymorphism rs3742264 are associated with dyslipidemia in a cohort of Brazilian subjects.

BACKGROUND: Dyslipidemia, a metabolic alteration that affects lipoprotein levels, is considered a major risk factor for atherosclerosis and its complications. Dyslipidemia also affects the hemostatic system, especially impairing fibrinolysis, and increased levels of thrombin-activatable fibrinolysis inhibitor (TAFI) have been associated with cardiovascular events. OBJECTIVES AND METHODS: This study evaluated the association of acquired risk factors (hypertension, body mass index - BMI, smoking, sedentary lifestyle, use or not of oral contraceptives and hormone replacement therapy, and post-menopause status), the polymorphisms Thr325Ile (rs1926447), Ala147Thr (rs3742264) and +1542C/G (rs940) in the TAFI gene, and TAFI plasma levels in 109 dyslipidemic and 105 normolipemic individuals. Biochemical analyses and TAFI levels were evaluated by colorimetric/turbidimetric assays and ELISA, respectively. Genotypic and allelic frequencies were determined by polymerase chain reaction (PCR). RESULTS: Hypertension, increased BMI, and menopause were more common in dyslipidemic individuals, who had higher TAFI levels. The alleles 325Ile, Ala147, and C showed association with lower TAFI levels. The rs3742264 polymorphism was associated with dyslipidemia in males. CONCLUSIONS: The results suggest that TAFI levels are independently associated to dyslipidemia and that the polymorphism rs3742264 may be related to cardiovascular risk in male subjects.

Genetic polymorphisms as a risk factor for dyslipidemia in children.

Dyslipidemia is an important etiological factor for development of cardiovascular disease, which is the leading cause of deaths in adults. Given the growing global epidemic of dyslipidemia, lipoprotein metabolism disorders have become an important health problem not only in adulthood, but have also emerged as an increasingly risk factor in childhood. Although several genome-wide association studies in multiple large population-based cohorts of adults and meta-analyses have identified susceptibility genes or loci, especially in lipid-related traits, it is of great importance to evaluate genetic predisposition at an early age. Recent findings suggest that the identification of polymorphisms in the metabolism of lipids in childhood may help fight subclinical atherosclerosis and its progression to cardiovascular complications in adulthood. Therefore, the aim of this study was to review genetic polymorphisms as risk factors associated with dyslipidemia in children and adolescents.

The linkage between inflammation and Type 2 diabetes mellitus.

The Type 2 diabetes mellitus (DM2) is considered nowadays as one of the most important chronic disturbances because of the significant number of people with diabetes and its severe complications, responsible for elevated indexes of morbidity and mortality. DM2 is characterized by several degrees of insulin resistance and relative deficiency in its secretion. Genetic and environmental factors have been described as of major importance in the DM2 development as obesity, which is directly correlated with development of resistance in peripheral tissues and inflammatory state in metabolic activated adipose tissue. Inflammatory responses may have a dual role in DM2, since it may have either a causal relationship leading to resistance to insulin or may be intensified by the hyperglycemic state, resulting in DM2 complications. In this review, we discuss the association of polymorphisms in genes encoding inflammatory cytokines and the increased level of these pro-inflammatory markers, associated to chronic pathologic conditions in DM2.

The polymorphism -1131T>C in apolipoprotein A5 gene is associated with dyslipidemia in Brazilian subjects.

BACKGROUND: Polymorphisms in apolipoprotein A5 gene (APOA5) have been associated with higher triglyceride levels in many populations. The aim of the study was to determine the allelic and genotypic distribution of the APOA5 -1131T>C polymorphism and to identify the association of the genetic variant and the risk for dyslipidemia. METHODS: We genotyped 109 dyslipidemic subjects and 107 controls. The total cholesterol, triglycerides and HDL-c were determined enzymatically. Comparison of means among groups was calculated by ANOVA. Significant differences among groups were evaluated by Student-Newman-Keuls test. RESULTS: The minor allele C was more frequent in dyslipidemic subjects than controls (p=0.019) and confers an increased individual risk for dyslipidemia (OR=1.726, CI 95%=1.095-2.721). The genotype analysis by gender showed that this allele was more frequent in dyslipidemic males (p=0.037; OR=2.050, CI 95%=1.042-4.023). When participants were analyzed according to genotypes TT and TC/CC, C-carriers presented higher cholesterol and triglycerides levels than TT homozygous (p=0.046 and 0.049, respectively). CONCLUSIONS: The allele C confers higher total cholesterol and triglycerides levels in dyslipidemic adults. The APOA5 -1131T>C polymorphism is associated with dyslipidemia in male subjects.

Elevated plasma factor VIII and von Willebrand factor in women with type 2 diabetes: inflammatory reaction, endothelial perturbation or else?

The association between type 2 diabetes and cardiovascular disease is long recognized. Although perturbations of haemostatic markers have been shown to be associated with macrovascular disease in patients with type 2 diabetes, it is unclear whether these are primarily due to endothelial dysfunction or a result of inflammation. The present study was undertaken to elucidate whether elevated levels of factor VIII (FVIII) and von Willebrand factor (vWF) in women with type 2 diabetes represent endothelial dysfunction, inflammation or an alternate mechanism. Sixty-four women with type 2 diabetes were evaluated using ultrasonography Doppler for carotid intima-media thickness (IMT) and were classified as group A--having no (<1  mm), group B - mild (≥1  mm and no plaque) and group C--moderate (≥1 mm and presence of plaque and stenosis) macrovascular disease. Several haemostatic markers including, FVIII, vWF and fibrinogen were assessed. In addition, thrombomodulin, a marker for endothelial damage, and high-sensitivity C-reactive protein (hsCRP), an inflammatory marker, were also measured. A significant association of elevated FVIII was found in group B and C patients (i.e. patients with IMT ≥1 mm and with plaque). Elevated fibrinogen and vWF levels were also found but confined to group C patients. No significant difference among subgroups was found for any other variable evaluated (hsCRP, thrombomodulin and FVII). In conclusion, plasma FVIII levels are elevated in women with type 2 diabetes and macrovascular disease. It also appears that this is not mediated by inflammation or endothelial injury and is likely to be due to an alternate mechanism.

Comparative study of apolipoprotein-E polymorphism and plasma lipid levels in dyslipidemic and asymptomatic subjects, and their implication in cardio/cerebro-vascular disorders.

Polymorphisms in the apolipoprotein-E (apoE) gene may modulate lipoprotein metabolism at different steps and influence total and low density lipoprotein (LDL) cholesterol (LDLc) levels, as well as other lipid features. Population studies have documented significant differences in the frequency of apoE alleles which are related to the prevalence of various cardio-vascular and neuro-psychiatric diseases. In this study, the apoE genotypes and allele frequencies were analyzed in 216 individuals (109 dyslipidemic and 107 normo-lipidic subjects), and the relative contribution of apoE polymorphism on plasma lipid and lipoprotein levels, as well as risk factors was evaluated. In normo-lipidic volunteers, the frequencies of epsilon2, epsilon3 and epsilon4 alleles were 0.042, 0.832 and 0.126, while in dyslipidemic subjects 0.046, 0.835 and 0.119, respectively. No significant difference was observed among epsilon2, epsilon3 or epsilon4 and plasma lipid-lipoprotein levels in the dyslipidemic group. In normo-lipidemics, however, total cholesterol, LDLc and non-HDLc plasma levels were significantly lower in epsilon2 subjects when compared to epsilon3 and epsilon4 individuals. The allelic frequencies of apoE epsilon2, epsilon3 and epsilon4 were similar in dyslipidemic and normo-lipemic subjects, suggesting that apoE polymorphisms have no effect on plasma lipid-lipoprotein levels in dyslipidemic subjects. In contrast, in normo-lipemic subjects the epsilon2 allele showed to be associated with lower total cholesterol and LDLc levels, the mark of a better lipid profile. Depending on other co-existing factors, the epsilon2 allele, therefore, may play either a protective or pathogenic role. This elementary knowledge is a fundamental prerequisite for a possible diagnostic application of these lipoproteins as biomarkers to predict adverse cardio-vascular and/or neuro-psychiatric maladies.

Kinetic peculiarities of human tissue kallikrein: 1--substrate activation in the catalyzed hydrolysis of H-D-valyl-L-leucyl-L-arginine 4-nitroanilide and H-D-valyl-L-leucyl-L-lysine 4-nitroanilide; 2--substrate inhibition in the catalyzed hydrolysis of N alpha-p-tosyl-L-arginine methyl ester.

Hydrolysis of D-valyl-L-leucyl-L-lysine 4-nitroanilide (1), D-valyl-L-leucyl-L-arginine 4-nitroanilide (2), and N alpha-p-tosyl-L-arginine methyl ester (3) by human tissue kallikrein was studied throughout a wide range of substrate concentrations. At low substrate concentrations, the hydrolysis followed Michaelis-Menten kinetics but, at higher substrate concentrations, a deviation from Michaelis-Menten behavior was observed. With the nitroanilides, a significant increase in hydrolysis rates was observed, while with the ester, a significant decrease in hydrolysis rates was observed. The results for substrates (1) and (3) can be accounted for by a model based on the hypothesis that a second substrate molecule binds to the ES complex to produce a more active or an inactive SES complex. The deviation observed for substrate (2) can be explained as a bimolecular reaction between the enzyme-substrate complex and a free substrate molecule.

Frequência do polimorfismo da glicoproteína IIIa de plaquetas (PlA2) em mulheres com diabetes mellitus tipo 2 / Platelet glycoprotein IIIa polymorphism (PlA2) frequency in Type 2 diabetic women

O polimorfismo da glicoproteína IIIa de plaquetas está associado a um aumento no risco de doenças arteriais coronarianas. Mulheres com diabetes mellitus tipo 2 apresentam um aumento de cinco vezes no risco para doenças arteriais coronarianas quando comparadas com mulheres não-diabéticas. O objetivo do presente estudo foi verificar a frequência do polimorfismo da glicoproteína IIIa (PlA2) em mulheres com diabetes mellitus tipo 2 e comparar com a frequência descrita na literatura. A análise do polimorfismo PlA2 foi realizada para 62 mulheres com diabetes mellitus tipo 2 através da reação em cadeia da polimerase seguida de análise do polimorfismo de tamanho de fragmento de restrição (PCR-RFLP). As frequências observadas foram 81 por cento para PlA1A1, 18 por cento para PlA1A2 e 1 por cento para PlA2A2. Não houve diferença significativa entre as frequências observadas e as frequências descritas na literatura. Nossos resultados sugerem que a frequência do polimorfismo PlA2 em mulheres com diabetes mellitus tipo 2 é a mesma observada na população em geral.

The platelet glycoprotein IIIa polymorphism is associated to an increased risk of coronary heart disease. Type 2 diabetic women present a fivefold higher risk of coronary heart disease compared to non-diabetic women. The aim of this study was to verify the frequency of the glycoprotein IIIa polymorphism (PlA2) in type 2 diabetic women and compare this result with the frequency reported for the general population. The PlA polymorphisms of 62 type 2 diabetic women were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The resulting frequencies were 81 percent for PlA1A1, 18 percent for PlA1A2 and 1 percent for PlA2A2. There was no significant difference between observed frequencies and the frequencies described in the literature. Our results suggest that the frequency of the glycoprotein IIIa polymorphism, PlA2, in type 2 diabetic women is similar to that observed in general population

Apo B/Apo A-I ratio in central and peripheral arterial diseases

BACKGROUND: The apo B/apo A-I ratio represents the balance between atherogenic particles, rich in apo B, and the antiatherogenic ones, apo A-I rich. This study investigated the association between atherosclerotic diseases in different anatomical sites and apo B/apo A-I ratio. METHODS: Lipids, lipoproteins, and apolipoproteins A-I and B were assessed in 30 subjects with coronary artery disease (CAD), 26 with ischemic stroke (IS), 30 with peripheral arterial obstructive disease (PAOD), and 38 healthy subjects (controls). RESULTS: HDLc and Apo A-I were significantly lower in PAOD and CAD groups, respectively, than in other groups. Significantly higher levels of triglycerides were observed for CAD and PAOD groups than for controls. Apo B was significantly higher in IS group than in control and PAOD groups. The apo B/apo A-I ratio showed significantly higher in CAD and IS groups when compared to control and PAOD groups (p < 0.001). CONCLUSION: The apo B/apo A-I ratio was important for identifying an increased trend for coronary and cerebral atherosclerosis. In spite of the increased trend for apo B/apo A-I ratio in IS and CAD groups, the studied variables cannot be considered in an isolated way, given as those parameters were analyzed together by a binary logistic regression, no association has been demonstrated.

INTRODUÇÃO: O índice apo B/apo A-I representa o balanço entre partículas de colesterol potencialmente aterogênicas ricas em apo B e partículas anti-aterogênicas ricas em apo A-I. O objetivo deste estudo foi investigar a associação entre doenças ateroscleróticas em diferentes sítios anatômicos e o índice apo B/apo A-I. MÉTODOS: Lípides, lipoproteínas e apolipoproteínas A-I e B foram quantificados em 30 indivíduos apresentando doença arterial coronariana (DAC), 26 com acidente vascular cerebral (AVC), 34 apresentando doença arterial obstrutiva periférica (DAOP) e 38 indivíduos hígidos (grupo controle). RESULTADOS: HDLc e apo A-I apresentaram-se significativamente mais baixos nos grupos DAOP e DAC, respectivamente, quando comparados com os demais grupos. Níveis de triglicérides foram significativamente mais elevados nos grupos DAC e PAOD quando comparados com o grupo controle. Apo B foi significativamente mais elevada no grupo AVC quando comparado com os grupos controle e DAOP. O índice apo B/apo A-I se mostrou significativamente elevado nos grupos DAC e AVC quando comparados com os demais (p < 0,001). CONCLUSÃO: O índice apo B/apo A-I foi importante para identificar uma tendência aumentada para aterosclerose coronariana e cerebral. No entanto, os parâmetros avaliados não podem ser considerados de forma isolada, considerando que nenhuma associação foi demonstrada quando os dados foram analisados pelo modelo de regressão logística binária.

High-sensitivity C-reactive protein in subjects with type 2 diabetes mellitus and/or high blood pressure

Type 2 diabetes mellitus (DM2) and high blood pressure (HBP) may contribute to the development of cardiovascular disease, and inflammation may be an important factor in these diseases. In the present study, plasma levels of high-sensitivity C-reactive protein (hs-CRP) were measured in subjects with DM2 and/or HBP and compared to those of normal subjects. Eighty-nine subjects were analyzed for hs-CRP, including 13 normotensive patients with DM2, 17 patients with HBP, 34 hypertensive patients with DM2 (DM2+HBP) and 25 normal subjects. The plasma hs-CRP levels were significantly lower in the controls than in the HBP+DM2 group (p < 0.05). DM2 associated with HBP was also correlated with increased plasma hs-CRP levels (n = 89, r = 0.25, p = 0.0162). Only hypertensive patients with DM2 had higher levels of hs-CRP, a circulating inflammatory marker, than normal subjects. This finding suggests that patients with two associated diseases have a more active inflammatory state.

Diabetes mellitus tipo 2 (DM2) e hipertensão arterial sistêmica (HAS) podem contribuir para o desenvolvimento de doenças cardiovasculares, e os processos inflamatórios relacionados a estas doenças podem ser considerados importantes fatores para o prognóstico das mesmas. O objetivo deste estudo foi determinar os níveis plasmáticos de proteína C-reativa ultra-sensível (us-PCR) em pacientes adultos com diabetes mellitus e/ou hipertensão arterial, comparando-os com indivíduos hígidos. Foram avaliadas 89 indivíduos, incluindo 13 pacientes normotensos com diabetes mellitus tipo 2 (DM2), 17 pacientes hipertensos (HAS), 34 pacientes hipertensos com diabetes mellitus tipo 2 (DM2+HAS) e 25 indivíduos hígidos. Os níveis plasmáticos de us-PCR foram significativamente mais altos no grupo DM2+HAS quando comparado com o grupo controle (p < 0,05), entretanto o mesmo não aconteceu com os grupos DM2 ou HAS. O grupo DM2+HAS também foi associado com o aumento dos níveis plasmáticos de us-PCR (r = 0,25; p < 0,05) e apresentou a maior freqüência de us-PCR > 3,0 mg/L (59 por cento). Esses dados indicam que a presença combinada de diabetes mellitus tipo 2 e hipertensão arterial promoveu uma maior expressão do estado inflamatório, refletido pelos níveis plasmáticos de us-PCR nos indivíduos avaliados.

Lipoproteína(a) e inibição da fibrinólise na doença arterial coronariana / Lipoprotein(a) and fibrinolysis inhibition in coronary artery disease

O envolvimento da lipoproteína(a) nas doenças ateroscleróticas tem sido alvo de muitos estudos que têm demonstrado que esta lipoproteína é um fator de risco independente para a doença arterial coronariana (DAC). Devido à semelhança estrutural com o plasminogênio, a Lp(a) pode competir com os sítios de ligação deste, diminuindo a geração de plasmina e inibindo a fibrinólise. O trombo formado numa placa aterosclerótica rompida dispara a maioria dos eventos cardiovasculares isquêmicos. Como o trombo é dissolvido através do sistema fibrinolítico, surgiu a hipótese de que uma diminuição da atividade fibrinolítica poderia ser um fator de risco para eventos isquêmicos. Entretanto, alguns estudos demonstraram ausência de associação entre Lp(a) e DAC, enquanto alguns atribuem o real valor preditivo à uma sub-população de Lp(a) com alta afinidade por fibrina. Essa hipótese sugere que alguns fenótipos de Lp(a) não estão associados à aterotrombose. Sendo assim, as pesquisas envolvendo Lp(a) e DAC apresentam resultados controversos, altamente dependentes da população estudada. Na população brasileira, a qual apresenta uma heterogeneidade de etnias, são raros os estudos deste tipo. Diante das notáveis controvérsias, espera-se que a presente revisão possa contribuir para suscitar ânimos no sentido da realização de estudos adicionais envolvendo a dosagem da Lp(a) em pacientes com DAC na nossa população. O conhecimento acumulado ao longo do tempo sobre a associação entre Lp(a) e DAC foi obtido através de estudos conduzidos fora do nosso meio. Assim, estudos fundamentados dentro da nossa realidade poderão trazer respostas mais fidedignas e adequadas para a nossa população.

The role of lipoprotein(a) [Lp(a)] in atherogenesis has been the target of many studies that have demonstrated that this lipoprotein is an independent risk factor for coronary artery disease (CAD). Due to the structural likeness with plasminogen, Lp(a) can compete with binding sites, reducing the plasmin generation and inhibiting fibrinolysis. Thrombus formed due to ruptured atherosclerotic plaque trigger most ischemic cardiovascular events. As the thrombus are dissolved by the fibrinolytic system, the hypothesis that a decrease in fibrinolytic activity might be a risk factor for ischemic events has been suggested. However, some studies have not demonstrated any correlation between Lp(a) and CAD while others attribute the real predictive value to a subpopulation of Lp(a) with high affinity for fibrin. This hypothesis suggests that some Lp(a) phenotypes are not associated with atherothrombosis. Furthermore, research on Lp(a) and CAD is controversial and highly dependent on the studied population. In the Brazilian population, which presents heterogeneity of the ethnic groups, studies of this type are rare. Based on the controversies, it is expected that a contribution of the present review will motivate investigators to develop studies involving the measurement of Lp(a) in patients with CAD in the Brazilian population. The accumulated knowledge on the association between Lp(a) and CAD was obtained through foreign studies. Thus, such studies must be performed in our setting in order to bring a better understanding for a more adequate management of CAD.

D-Dimer plasma levels in patients with coronary artery disease

We have previously reported that prothrombin fragment 1+2 levels were not associated to the presence or severity of coronary artery disease (CAD) and do not provide further information on subjects with CAD diagnosed by angiography. Thus, in the present study another marker of hypercoagulability was evaluated in the same subjects. This study aimed at determining D-Dimer plasma levels in a group of subjects undergoing coronary angiography to establish a likely relation between this parameter and the severity of CAD. D-Dimer plasma levels were determined in 17 subjects with no coronary atheromatosis (controls), 12 subjects with mild/moderate atheromatosis and 28 subjects with severe atheromatosis. No significant differences were observed among the three groups. Data analysis enables an inference on a tendency towards an increase in fibrinolytic activity in patients with atheromatosis, reflected by the increase in D-Dimer concentrations in the severe atheromatosis group in subjects with CAD diagnosed by coronary angiography.

Em estudo prévio, os níveis plasmáticos do fragmento 1+2 da protrombina não foram associados com a presença ou com a gravidade da doença arterial coronariana (DAC), não trazendo benefício adicional pelo menos em indivíduos com diagnóstico de DAC estabelecido por angiografia. Desta forma, neste estudo outro marcador de hipercoagulabilidade foi avaliado nos mesmos pacientes. O presente estudo teve como objetivo determinar os níveis plasmáticos do dímero D de um grupo de indivíduos submetidos à angiografia coronariana, buscando estabelecer a possível correlação entre este parâmetro e a gravidade da DAC. Os níveis plasmáticos do dímero D foram determinados em amostras de sangue de 17 indivíduos com ausência de ateromatose nas coronárias (controles), 12 indivíduos apresentando ateromatose leve/moderada e 28 indivíduos apresentando ateromatose grave. Não foram encontradas diferenças estatisticamente significativas entre as médias dos três grupos para o parâmetro avaliado. Uma análise dos dados permite inferir sobre uma tendência ao aumento da atividade fibrinolítica nos pacientes com ateromatose, refletida pela elevação da concentração de dímero D no grupo ateromatose grave em indivíduos com diagnóstico de DAC estabelecido por angiografia coronariana.