Luciana Moreira Lima

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.

ApoB/ApoA-I ratio in young patients with ischemic cerebral stroke or peripheral arterial disease.

Although smoking and hypertension are classic risk factors for atherothrombotic diseases, the relationship of dyslipidemia and vascular diseases, other than myocardial infarction, is less clearly established, especially in young subjects. In the current study, a detailed analysis of the lipid and apolipoprotein profiles was conducted in young patients of ischemic cerebral stroke (IS) and peripheral arterial disease (PAD). Plasma levels of C-reactive protein (hs-CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides (TG), and apolipoproteins A-I (ApoA-I) and apolipoproteins B (ApoB), which include the ApoB/ApoA-I ratio, were analyzed in a group of 81 patients who presented with IS (n = 46) or PAD (n = 35) as well as in 167 control subjects. Significant differences were observed for hs-CRP, TC, HDLc, LDLc, TG, ApoA-I, and ApoB levels, as well as for the ApoB/ApoA-I ratio, between the control and the IS or PAD groups. However, after adjustment for sex, age, smoking, hypertension, hs-CRP, and dyslipidemia (LDLc, TC, HDLc, TG, ApoA, ApoB, and ApoB/ApoA-I ratio), hs-CRP, ApoB, and the ApoB/ApoA-I ratio were independently associated with increased risks of IS or PAD. Increased ApoB/ApoA-I ratio and hs-CRP levels are independently associated with occurrence of IS and PAD in young patients and are significant markers of alterations on lipid and apolipoproteic profiles and inflammatory responses, respectively, in these patients.

Índice apo B/apo A-I e predição de risco cardiovascular

Apolipoproteins are proteins associated with lipids in lipoprotein particles. They play important roles in lipoprotein metabolism, such as transport of these hydrophobic molecules in plasma aqueous medium, binding to specific receptors in cell surface to correctly direct lipids to target organs and body tissues, and activation or inhibition of enzymes involved in lipid metabolism

Atheromatosis Extent in Coronary Artery Disease is not Correlated with Apolipoprotein-E Polymorphism and its Plasma Levels, but Associated with Cognitive Decline

BACKGROUND Apolipoprotein-E (apoE) ε4 allele is a known risk factor for Alzheimers disease (AD). Polymorphism of apoE is also one of the most important genetic markers for coronary artery disease (CAD). The allelic variation in the apoE gene has a significant effect on inter-individual variation of lipids and lipoprotein plasma levels as well. This study investigated whether apoE polymorphism affects the plasma levels of apoE and the possible association to CAD extent and cognitive functions. METHODS Plasma apoE levels and apoE genotypes were evaluated of subjects with normal coronary arteries, and individuals with angiographycally confirmed mild/moderate or severe atheromatosis. The cognitive performance of the volunteers was also measured by mini-mental state examination (MMSE). RESULTS Out of the 6 expected genotypes, only 5 were detected in participants: E3/3 (56.0%), E3/4 (23.6%), E4/4 (8.2%), E2/4 (3.3%), E2/3 (8.9%). The ε3 allele (72%) was the most frequent, followed by ε4 (22%) and ε2 (6%). No difference was found in plasma levels of either apoE or in apoE genotype frequencies among the groups, however MMSE scores of CAD patients irrespective of their atheromatosis extent were significantly lower than that seen in the normal population. CONCLUSIONS Although neither apoE plasma levels, nor apoE polymorphism in patients presenting with mild/moderate or severe atheromatosis showed to be associated with CAD severity, the presence of atheromatosis in the heart vessels positively correlated with cognitive dysfunction.

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.

Proteína C-reativa ultra-sensível em pacientes com diagnóstico de doença arterial coronariana estabelecido por angiografia

C-reactive protein (CPR) is an acute phase protein, synthesized by the liver in response to cytokines, and reflects active inflammation. Inflammation has a potential role in atherosclerosis triggering and progression. Plasma markers of chronic inflammation have been consistently associated to the risk of coronary artery disease (CAD), being high-sensitivity C-reactive protein the marker most studied. The aim of the present study was to determine the high-sensitivity C-reactive protein plasma levels in a group of subjects undergoing coronary angiography, trying to establish a possible correlation between this parameter and the severity of the CAD. High-sensitivity C-reactive protein plasma levels had been determined in blood of 17 subjects with no atheromatosis (controls), 12 subjects presenting mild/moderate atheromatosis and 28 subjects presenting severe atheromatosis, using Biotechnical Reactive C-Protein Turbidimetric Kit with specific high-sensitivity methodology for Cardiology, with linearity to 0.1 up 15mg/l. Significant differences between the means of the three groups were not observed, however the mean values of mild/moderate atheromatosis and severe atheromatosis had remained above the reference values used in Cardiology (0.1-2.5mg/dl). The mean values of the three groups presented an increasing rise from the control group to the severe atherosclerosis, suggesting inflammatory progression due to atherosclerotic injury.

Homocysteine and methylenetetrahydrofolate reductase in subjects undergoing coronary angiography

OBJECTIVE To determine plasma homocysteine levels and the incidence of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in a group of subjects who underwent coronary angiography, in an attempt to establish a correlation between these parameters and the severity of coronary artery disease (CAD), as well as investigate the correlation between hyperhomocysteinemia and the presence of polymorphism. METHODS Twenty subjects with no coronary atheromatosis (controls), fourteen subjects with mild/moderate atheromatosis, and twenty-nine subjects with severe atheromatosis were evaluated. RESULTS Significant differences were observed in mean homocysteine levels between the control and the severe atheromatosis groups (p < 0.001). No significant differences were observed among the other groups. The severe atheromatosis group showed rates of 62.0% and 6.9% for the C677T MTHFR gene polymorphism, in heterozygous and homozygous subjects, respectively. However, there was no correlation between the presence of mutation and hyperhomocysteinemia. A positive correlation of 41.91% (p < 0.001) was found between hyperhomocysteinemia and CAD. CONCLUSION The most important finding of this study was the association between hyperhomocysteinemia and coronary stenosis > 70%; yet, whether elevated plasma homocysteine worsens atherosclerosis or is a consequence remains to be established.

PAI-1 4G/5G polymorphism and plasma levels association in patients with coronary artery disease

BACKGROUND Type-1 plasminogen activator inhibitor (PAI-1) 4G/5G polymorphism may influence the PAI-1 expression. High plasma levels of PAI-1 are associated with coronary artery disease (CAD). OBJECTIVE This study investigated the influence of PAI-1 4G/5G polymorphism on plasma PAI-1 levels and its association with CAD assessed by coronary angiography. METHODS Blood sample of 35 individuals with angiographically normal coronary arteries, 31 individuals presenting mild/moderate atheromatosis, 57 individuals presenting severe atheromatosis and 38 healthy individuals (controls) were evaluated. In patients and controls, the PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. Plasma PAI-1 levels were quantified by ELISA assay (American Diagnostica). RESULTS No difference was found between groups regarding age, gender and body mass index. Plasma PAI-1 levels and 4G/4G genotype frequency were significantly higher in the severe atheromatosis group compared to the other groups (p<0.001). Furthermore, patients with 4G/4G genotype (r=0.28, p<0.001) had significantly higher plasma PAI-1 levels than those with 5G/5G genotype (r=0.02, p=0.4511). In addition, in a multiple logistic regression model, adjusted for all the other variables, PAI-1 was observed to be independently associated with CAD > 70% (p<0.001). CONCLUSION The most important finding of this study was the association between 4G/4G genotype, high plasma PAI-1 levels and coronary stenosis higher than 70% in Brazilian individuals. Whether high plasma PAI-1 levels are a decisive factor for atherosclerosis worsening or it is a consequence remains to be established.

Lipoproteína (a) em pacientes portadores de doença arterial obstrutiva periférica e/ou diabetes mellitus tipo 2

BACKGROUND: Peripheral arterial obstructive disease (PAOD) constitutes an excellent marker for systemic atherosclerosis and type 2 diabetes mellitus (DM2) is among the greatest risk factors for this disease. It is believed that lipoprotein (a) [Lp(a)] is linked to increased risk of atherosclerosis, although the mechanisms responsible for that are not widely known. Elevated levels of Lp(a) seem to be associated with a higher risk of coronary artery disease (CAD), as well as PAOD and cerebrovascular disease. OBJECTIVES: To assess the plasma levels of Lp(a) and other lipid parameters in patients with PAOD and/or DM2. Material and methods: Plasma levels of Lp(a), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG) and apolipoproteins A-I and B were measured in blood samples of 12 subjects carrying neither PAOD nor DM2 (control group), 17 patients with PAOD, 18 with DM2 and 19 with both PAOD and DM2. The subjects selected for this study showed homogeneity and no statistical difference for gender, age, and socioeconomic status. RESULTS: The Lp(a) showed a tendency to elevation both in groups PAOD only and PAOD + DM2 simultaneously. Significant differences were observed among the groups as to HDL-c and apolipoprotein A-I levels, with positive correlation between these two parameters. TC/HDL-c ratio showed significant difference among the groups. Positive correlation was found between Lp(a) and LDL-c, and negative one, between the ankle-arm index and LP(a). CONCLUSION: As to the lipid parameters studied, significant statistical differences were found between HDL-c and apolipoprotein A-I plasma levels only. For Lp(a) parameter, higher plasma levels were observed in PAOD and PAOD + DM2, which have also shown concomitant and significant HDL-c reduction.

Improved cognitive, affective and anxiety measures in patients with chronic systemic disorders following structured physical activity

Mental illnesses are frequent co-morbid conditions in chronic systemic diseases. High incidences of depression, anxiety and cognitive impairment complicate cardiovascular and metabolic disorders such as hypertension and diabetes mellitus. Lifestyle changes including regular exercise have been advocated to reduce blood pressure and improve glycaemic control. The purpose of this project was to evaluate the effect of physical training on the most prevalent corollary psychiatric problems in patients with chronic organic ailments. This longitudinal study assessed the mental health of hypertensive (age: 57 ± 8 years) and/or diabetic (age: 53 ± 8 years) patients using mini-mental state examination, Beck’s depression inventory, Beck’s anxiety inventory and self-reporting questionnaire-20 before and after a 3-month supervised resistance and aerobic exercise programme comprising structured physical activity three times a week. Clinically relevant improvement was observed in the Beck’s depression inventory and Beck’s anxiety inventory scores following the 12-week training (61%, p = 0.001, and 53%, p = 0.02, respectively). Even though statistically not significant (p = 0.398), the cognitive performance of this relatively young patient population also benefited from the programme. These results demonstrate positive effects of active lifestyle on non-psychotic mental disorders in patients with chronic systemic diseases, recommending exercise as an alternative treatment option.