Vitamin C: Effects of exercise and requirements with training

Ascorbic acid or vitamin C is involved in a number of biochemical pathways that are important to exercise metabolism and the health of exercising individuals. This review reports the results of studies investigating the requirement for vitamin C with exercise on the basis of dietary vitamin C intakes, the response to supplementation and alterations in plasma, serum, and leukocyte ascorbic acid concentration following both acute exercise and regular training. The possible physiological significance of changes in ascorbic acid with exercise is also addressed. Exercise generally causes a transient increase in circulating ascorbic acid in the hours following exercise, but a decline below pre-exercise levels occurs in the days after prolonged exercise. These changes could be associated with increased exercise-induced oxidative stress. On the basis of alterations in the concentration of ascorbic acid within the blood, it remains unclear if regular exercise increases the metabolism of vitamin C. However, the similar dietary intakes and responses to supplementation between athletes and nonathletes suggest that regular exercise does not increase the requirement for vitamin C in athletes. Two novel hypotheses are put forward to explain recent findings of attenuated levels of cortisol postexercise following supplementation with high doses of vitamin C.

The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells

Lipid homeostasis is controlled by the peroxisome proliferator-activated receptors (PPARalpha, -beta/delta, and -gamma) that function as fatty acid-dependent DNA-binding proteins that regulate lipid metabolism. In vitro and in vivo genetic and pharmacological studies have demonstrated PPARalpha regulates lipid catabolism. In contrast, PPARgamma regulates the conflicting process of lipid storage. However, relatively little is known about PPARbeta/delta in the context of target tissues, target genes, lipid homeostasis, and functional overlap with PPARalpha and -gamma. PPARbeta/delta, a very low-density lipoprotein sensor, is abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for approximately 40% of total body weight. Skeletal muscle is a metabolically active tissue, and a primary site of glucose metabolism, fatty acid oxidation, and cholesterol efflux. Consequently, it has a significant role in insulin sensitivity, the blood-lipid profile, and lipid homeostasis. Surprisingly, the role of PPARbeta/delta in skeletal muscle has not been investigated. We utilize selective PPARalpha, -beta/delta, -gamma, and liver X receptor agonists in skeletal muscle cells to understand the functional role of PPARbeta/delta, and the complementary and/or contrasting roles of PPARs in this major mass peripheral tissue. Activation of PPARbeta/delta by GW501516 in skeletal muscle cells induces the expression of genes involved in preferential lipid utilization, beta-oxidation, cholesterol efflux, and energy uncoupling. Furthermore, we show that treatment of muscle cells with GW501516 increases apolipoprotein-A1 specific efflux of intracellular cholesterol, thus identifying this tissue as an important target of PPARbeta/delta agonists. Interestingly, fenofibrate induces genes involved in fructose uptake, and glycogen formation. In contrast, rosiglitazone-mediated activation of PPARgamma induces gene expression associated with glucose uptake, fatty acid synthesis, and lipid storage. Furthermore, we show that the PPAR-dependent reporter in the muscle carnitine palmitoyltransferase-1 promoter is directly regulated by PPARbeta/delta, and not PPARalpha in skeletal muscle cells in a PPARgamma coactivator-1-dependent manner. This study demonstrates that PPARs have distinct roles in skeletal muscle cells with respect to the regulation of lipid, carbohydrate, and energy homeostasis. Moreover, we surmise that PPARgamma/delta agonists would increase fatty acid catabolism, cholesterol efflux, and energy expenditure in muscle, and speculate selective activators of PPARbeta/delta may have therapeutic utility in the treatment of hyperlipidemia, atherosclerosis, and obesity.

Blood lipid associations in 18 year-old men

The association of cigarette smoking, physical activity at work, and social class with total cholesterol and with high and low density lipoprotein cholesterol were examined in a random sample of 238 males, of 18 years of age, of Rosario, Argerntina. The mean (mg/dl) total serum cholesterol of the whole sample was 174.7, the high density lipoprotein cholesterol 52.8, and the low density lipoprotein cholesterol 121.5. Black tobacco consumers, evenly distributed by social class, had higher levels of total and low density lipoprotein cholesterol. Total cholesterol was higher in the high social class, differently from what smokers' distribution by social class, would lead one to expect. While a highly negative association was found between social class and physical activity at work, there were no significant diferences in lipoprotein levels between manual and non-manual workers. It is possible that the nutritional differences by social class still prevail over the smoking habit in their influence on the lipoprotein levels in these subjects.

Estudo de dislipidemias familiares monogénicas raras

A dislipidemia é um distúrbio do perfil lipídico, seja por elevação ou diminuição de partículas lipídicas. O objetivo deste trabalho é fazer uma revisão dos casos com dislipidemia rara em estudo no Instituto Nacional de Saúde Doutor Ricardo Jorge, apresentando os dados clínicos e moleculares mais relevantes. O perfil lipídico foi determinado para cada caso índex e familiares e o estudo molecular dos genes envolvidos foi realizado por amplificação por PCR e sequenciação de Sanger. Foram estudados, ou está em curso o estudo, de 14 casos índex com os seguintes diagnósticos clínicos: Deficiência familiar em lipoproteína lípase (3), Lipodistrofia familiar parcial de Dunningan Tipo 2 (1), Deficiência em lípase ácida lisossomal (3), Abeta/hipobetalipoproteinemia (2), Deficiência em HDL (1), Hipertrigliceridemia autossómica recessiva (3), Sitosterolemia (1). O fenótipo clínico de cada caso índex é variável dependendo de cada condição. Foi encontrada a causa genética da doença em 8/14 doentes, estando os restantes ainda em estudo. Doentes com as várias dislipidemias raras apresentadas têm um risco acrescido de ter outras doenças graves como pancreatite, doença cardiovascular ou complicações neurológicas e devem, por esta razão, ser identificados o mais precocemente possível, de forma a minimizar ou prevenir os efeitos nefastos destas condições.

Food frequency consumption and lipoproteins serum levels in the population of an urban area, Brazil

OBJECTIVE: To identify the association between food group consumption frequency and serum lipoprotein levels among adults. METHODS: The observations were made during a cross-sectional survey of a representative sample of men and women over 20 years old living in Cotia county, S. Paulo, Brazil. Data on food frequency consumption, serum lipids, and other covariates were available for 1,045 adults. Multivariate analyses adjusted by age, gender, body mass index, waist-to-hip ratio, educational level, family income, physical activity, smoking, and alcohol consumption were performed. RESULTS: Consumption of processed meat, chicken, red meat, eggs and dairy foods were each positively and significantly correlated with LDL-C, whereas the intake of vegetables and fruits showed an inverse correlation. Daily consumption of processed meat, chicken, red meat, eggs, and dairy foods were associated with 16.6 mg/dl, 14.5 mg/dl, 11.1 mg/dl, 5.8 mg/dl, and 4.6 mg/dl increase in blood LDL-C, respectively. Increases of daily consumption of fruit and vegetables were associated with 5.2 mg/dl and 5.5 mg/dl decreases in LDL-C, respectively. Alcohol beverage consumption showed a significant positive correlation with HDL-C. CONCLUSIONS: Dietary habits in the study population seem to contribute substantially to the variation in blood LDL and HDL concentrations. Substantially CHD risk reduction could be achieved with dietary changes.

Relationship of PON1 192 and 55 gene polymorphisms to calcific valvular aortic stenosis

Introduction and Objectives - Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation. Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical and pathophysiological risk factors of CAD and calcific aortic valve stenosis (CAVS), we postulated a link between PON1 alleles and CAVS progression. Methods - We investigated the association between PON1 55 and 192 single nucleotide polymorphisms (SNPs), their enzyme activity, and CAVS progression assessed by aortic valve area and transvalvular peak velocity in 67 consecutive patients with moderate CAVS and 251 healthy controls. Results - PON1 paraoxonase activity was higher in CAVS patients (P<0.001). The PON1 genotype Q192R SNP (P=0.03) and variant allele (R192) (P=0.01) frequencies differed between CAVS patients and controls. Significant association existed between PON1 enzyme activity, phenotypic effects of PON1 192 genotype polymorphisms, and CAVS progression, but not between PON1 55 and high-density lipoprotein (P=0.44) or low-density lipoprotein cholesterol (P=0.12), between 192 genotype and high-density lipoprotein (P=0.24) or low-density lipoprotein cholesterol (P=0.52). Conclusion - The PON1 genotype Q192R SNP has an important effect on CAVS disease progression. This study helps outline a genotype-phenotype relationship for PON1 in this unique population.

Endothelial lipase correlated positively with EPA/AA ratio in RBCs membrane

The fatty acid profile of erythrocyte membranes has been considered a good biomarker for several pathologic situations. Dietary intake, digestion, absorption, metabolism, storage and exchange amongst compartments, greatly influence the fatty acids composition of different cells and tissues. Lipoprotein and hepatic lipases were also involved in fatty acid availability. In the present work we examined the correlations between fatty acid in Red Blood Cells (RBCs) membranes, the fatty acid desaturase and elongase activities, glycaemia, blood lipids, lipoproteins and apoproteins, and the endothelial lipase (EL) mass in plasma. Twenty one individuals were considered in the present study, with age >18 y. RBCs membranes were obtained and analysed for fatty acid composition by gas chromatography. The amount of fatty acids (as percentage) were analysed, and the ratios between fatty acid 16:1/16:0; 18:1/18:0; 18:0/16:0; 22:6 n-3/20:5 n-3 and 20:4 n-6/18:2 n-6 were calculated. Bivariate analysis (rs) and partial correlations were determined. SCD16 estimation activity correlated positively with BMI (rs=0.466, p=0.043) and triacylglycerols (TAG) (rs=0.483, p=0.026), and negatively with the ratio ApoA1/ApoB (rs=-0.566, p=0.007). Endothelial lipase (EL) correlated positively with the EPA/AA ratio in RBCs membranes (rs=0.524, p=0.045). After multi-adjustment for BMI, age, hs-CRP and dietary n3/n6 ratio, the correlations remained significant between EL and EPA/AA ratio. At the best of our knowledge this is the first report that correlated EL with the fatty acid profile of RBCs plasma membranes. The association found here can suggest that the enzyme may be involved in the bioavailability and distribution of n-3/n-6 fatty acids, suggesting a major role for EL in the pathophysiological mechanisms involving biomembranes’ fatty acids, such as in inflammatory response and eicosanoids metabolites pathways.

Impact of academic exposure on health status of university students

OBJECTIVE: To assess the impact of academic life on health status of university students. METHODS: Longitudinal study including 154 undergraduate students from the Universidade de Aveiro, Portugal, with at least two years of follow-up observations. Sociodemographic and behavioral characteristics were collected using questionnaires. Students' weight, height, blood pressure, serum glucose, serum lipids and serum homocysteine levels were measured. Regression analysis was performed using linear mixed-effect models, allowing for random effects at the participant level. RESULTS: A higher rate of dyslipidemia (44.0% vs. 28.6%), overweight (16.3% vs. 12.5%) and smoking (19.3% vs. 0.0%) was found among students exposed to the academic life when compared to freshmen. Physical inactivity was about 80%. Total cholesterol, high density lipoprotein-cholesterol (HDL-C), triglycerides, systolic blood pressure, and physical activity levels were significantly associated with gender (p<0.001). Academic exposure was associated with increased low density lipoprotein-cholesterol (LDL-C) levels (about 1.12 times), and marginally with total cholesterol levels (p=0.041). CONCLUSIONS: High education level does not seem to have a protective effect favoring a healthier lifestyle and being enrolled in health-related areas does not seem either to positively affect students' behaviors. Increased risk factors for non-transmissible diseases in university students raise concerns about their well-being. These results should support the implementation of health promotion and prevention programs at universities.

Metabolic syndrome in fixed-shift workers

OBJECTIVE To analyze if metabolic syndrome and its altered components are associated with demographic, socioeconomic and behavioral factors in fixed-shift workers.METHODS A cross-sectional study was conducted on a sample of 902 shift workers of both sexes in a poultry processing plant in Southern Brazil in 2010. The diagnosis of metabolic syndrome was determined according to the recommendations from Harmonizing the Metabolic Syndrome. Its frequency was evaluated according to the demographic (sex, skin color, age and marital status), socioeconomic (educational level, income and work shift), and behavioral characteristics (smoking, alcohol intake, leisure time physical activity, number of meals and sleep duration) of the sample. The multivariate analysis followed a theoretical framework for identifying metabolic syndrome in fixed-shift workers.RESULTS The prevalence of metabolic syndrome in the sample was 9.3% (95%CI 7.4;11.2). The most frequently altered component was waist circumference (PR 48.4%; 95%CI 45.5;51.2), followed by high-density lipoprotein. Work shift was not associated with metabolic syndrome and its altered components. After adjustment, the prevalence of metabolic syndrome was positively associated with women (PR 2.16; 95%CI 1.28;3.64), workers aged over 40 years (PR 3.90; 95%CI 1.78;8.93) and those who reported sleeping five hours or less per day (PR 1.70; 95%CI 1.09;2.24). On the other hand, metabolic syndrome was inversely associated with educational level and having more than three meals per day (PR 0.43; 95%CI 0.26;0.73).CONCLUSIONS Being female, older and deprived of sleep are probable risk factors for metabolic syndrome, whereas higher educational level and higher number of meals per day are protective factors for metabolic syndrome in fixed-shift workers.

Assessment of oltipraz in schistosomiasis mansoni clinical trial

Seventy three children (6-15 years) and 75 adults (18-47 years) with active schistosomiasis mansoni were treated with oltipraz. All cases had at least 100 eggs per gram of feces as determined by the Kato-Katz technique. Children and adults were divided in two groups receiving respectively 25 or 30 mg/kg, as a single oral dose. Clinical examination, laboratories tests (haemogram, urinalysis, hepatic and kidney functions tests, glycemia, cholesterol, triglicerides, lipoprotein — HLD and LDL) and ECG were performed before, 3 or 7 days and 1 month after treatment. Parasitological control with 3 daily coprological examinations, was done on the 1st, 3rd j 6th month after drug administration. Giddiness, somnolence, headache, nausea, vomiting and abdominal distress were the most frequent side effects. Pain in the finger tips that need further investigations also occurred. No significant alteration in complementary tests were observed, whereas eosinophilia 1 month after treatment was detected, probably indicating worm death. The cure rate in children was 81.8% and 74.2% with 25 and 30 mg/kg respectively, and in adults 75.0% and 81.2% of the patients. No statistical significant difference was observed between cure rate and side effects at different dosages employed, neither between adults nor children. In all groups the percentage of egg reduction in feces in the non cured patients was higher than 96.0%. Further investigation with this new compound is necessary to accomplish the real value of oltipraz in the schistosomiasis chemotherapy.

Hemolymphatic components in vectors of Trypanosoma cruzi: study in several species of the subfamily Triatominae (Hemiptera: Reduviidae)

The members of the subfamily Triatominae (Hemiptera : Reduviidae) comprise a great number of species of medical importance in the transmission of the T. cruzi (American trypanosomiasis). The aim of this study was to contribute to the knowledge about the chemical composition in proteins, lipids, lipoproteins, and carbohydrates of vectors of Chagas' disease corresponding to twelve members of the subfamily Triatominae. This study was carried out in ninphs of the fifth instar and adult males of the species: T. delpontei, T. dimidiata, T. guasayana, T. infestans, T. mazzotti, T. pallidipennis, T. patagonica, T. platensis, T. rubrovaria, T. sordida of the Triatoma genus, and D. maximus and P. megistus of the Dipatalogaster and Panstrongylus genera respectively. The results show on one hand, qualitative differences in the protein composition, and on the other hand, similarity in the lipoprotein profiles. Lipids, proteins, and carbohydrates did not show significant differences between species or/and stages.

Vitamin D Intake and Cardiometabolic: Risk Factors in Adolescents

Background: A growing body of research suggests that vitamin D might play an important role in overall health. No data exist on vitamin D intake for the Azorean adolescent population. The purpose of this study was to assess vitamin D intake and investigate a possible association between vitamin D intake and cardiometabolic risk factors in Azorean adolescents. Methods: A cross-sectional school-based study was conducted on 496 adolescents (288 girls) aged 15–18 years from the Azorean Islands, Portugal. Anthropometric measurements (waist circumference and height), blood pressure (systolic), and plasma biomarkers [fasting glucose, insulin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs)] were measured to assess metabolic risk. Homeostasis model assessment (HOMA), TC-to-HDL-C ratio, and waist-to-height ratio were calculated. For each of these variables, a Z-score was computed by age and sex. A metabolic risk score was constructed by summing the Zscores of all individual risk factors. High risk was considered when the individual had ‡ 1 standard deviation(SD) of this score. Vitamin D intake was assessed with a semiquantitative food frequency questionnaire. Participants were classified into quartiles of vitamin D intake. Logistic regression was used to determine odds ratios for high cardiometabolic risk scores after adjusting for total energy intake, pubertal stage, fat mass percentage, and cardiorespiratory fitness. Results: Mean (SD) vitamin D intake was 5.8 (6.5) mg/day, and 9.1% of Azorean adolescents achieved the estimated average requirement of vitamin D (10 mg/day or 400 IU). Logistic regression showed that the odds ratio for a high cardiometabolic risk score was 3.35 [95% confidence interval (CI) 1.28–8.75] for adolescents in the lowest vitamin D intake quartile in comparison with those in the highest vitamin D intake quartile, even after adjustment for confounders. Conclusion: A lower level of vitamin D intake was associated with worse metabolic profile among Azorean adolescents.

Intake of milk, but not total dairy, yogurt, or cheese, is negatively associated with the clustering of cardiometabolic risk factors in adolescents

Epidemiologic studies have reported an inverse association between dairy product consumption and cardiometabolic risk factors in adults, but this relation is relatively unexplored in adolescents. We hypothesized that a higher dairy product intake is associated with lower cardiometabolic risk factor clustering in adolescents. To test this hypothesis, a cross-sectional study was conducted with 494 adolescents aged 15 to 18 years from the Azorean Archipelago, Portugal. We measured fasting glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, body fat, and cardiorespiratory fitness. We also calculated homeostatic model assessment and total cholesterol/high-density lipoprotein cholesterol ratio. For each one of these variables, a z score was computed using age and sex. A cardiometabolic risk score (CMRS) was constructed by summing up the z scores of all individual risk factors. High risk was considered to exist when an individual had at least 1 SD from this score. Diet was evaluated using a food frequency questionnaire, and the intake of total dairy (included milk, yogurt, and cheese), milk, yogurt, and cheese was categorized as low (equal to or below the median of the total sample) or “appropriate” (above the median of the total sample).The association between dairy product intake and CMRS was evaluated using separate logistic regression, and the results were adjusted for confounders. Adolescents with high milk intake had lower CMRS, compared with those with low intake (10.6% vs 18.1%, P = .018). Adolescents with appropriate milk intake were less likely to have high CMRS than those with low milk intake (odds ratio, 0.531; 95% confidence interval, 0.302-0.931). No association was found between CMRS and total dairy, yogurt, and cheese intake. Only milk intake seems to be inversely related to CMRS in adolescents.

Influence of Apolipoprotein E Plasma Levels and Tobacco Smoking on the Induction of Neutralising Antibodies to Interferon-Beta

Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the development of NAbs. Thirty-one female MS patients treated with subcutaneously administered IFN-beta were included. Demographic and clinical characteristics were compared between NAbs response groups using t tests for continuous and logistic regression analysis and Fisher's exact tests for categorical data, respectively. Multivariate logistic regression was used to evaluate the effect of potential confounders. Patients who developed NAbs had lower apoE levels before treatment, 67 (47-74) mg/L median (interquartile range), and at the moment of NAb analysis, 53 (50-84) mg/L, in comparison to those who remained NAb-negative, 83 (68-107) mg/L, P = 0.03, and 76 (66-87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a one-standard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04-0.77), P = 0.04. When adjusting for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3-87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta.

Marcadores inflamatórios de instabilidade da placa aterosclerótica coronária : caraterização e potencial utilização clínica

RESUMO:Introdução: Reviu-se o conhecimento epidemiológico, fisiopatológico e clínico atual sobre a doença coronária, da sua génese até ao evento agudo, o Enfarte Agudo do Miocárdio (EAM). Valorizou-se, em especial, a teoria inflamatória da aterosclerose, que foi objeto de grandes desenvolvimentos na última década. Marcadores de instabilidade da placa aterosclerótica coronária: Aprofundou-se o conhecimento da placa aterosclerótica coronária instável. Descreveram-se detalhadamente os biomarcadores clínicos e laboratoriais associados à instabilidade da placa, com particular ênfase nos mecanismos inflamatórios. Objetivos:Estão divididos em dois pontos fundamentais:(1) Estudar em doentes com EAM a relação existente entre as moléculas inflamatórias: Interleucina-6 (IL-6), Fator de Necrose Tumoral-α (TNF-α) e Metaloproteinase de Matriz-3 (MMP3), não usados em contexto clínico, com um marcador inflamatório já em uso clínico: a Proteína C-Reativa ultrassensível (hs-CRP). Avaliar a relação de todas as moléculas inflamatórias com um biomarcador de lesão miocárdica: a Troponina Cardíaca I (cTnI). (2) Avaliar, no mesmo contexto de EAM, a Resposta de Fase Aguda (RFA) . Pretende-se demonstrar o impacto deste fenómeno, com repercussão clínica generalizada, no perfil lipídico e nos biomarcadores inflamatórios dos doentes. Métodos:(1) Estudo observacional prospetivo de doentes admitidos consecutivamente por EAM (grupo EAM) numa única unidade coronária, após exclusão de trauma ou infeção. Doseamento no sangue periférico, na admissão, de IL-6, TNF-α, MMP3, hs-CRP e cTnI. Este último biomarcador foi valorizado também nos valores séricos obtidos 6-9 horas depois. Procedeu-se a correlação linear (coeficiente de Pearson, de Rho-Spearman e determinação do R2) entre os 3 marcadores estudados com os valores de hs-CRP e de cTnI (valores da admissão e 6 a 9 horas após). Efetuou-se o cálculo dos coeficientes de regressão linear múltipla entre cTnI da admissão e cTnI 6-9h após, com o conjunto dos fatores inflamatórios estudados. (2) Estudo caso-controlo entre o grupo EAM e uma população aleatória de doentes seguidos em consulta de cardiologia, após exclusão de eventos cardiovasculares de qualquer território (grupo controlo) e também sem infeção ou trauma. Foram doseados os mesmos marcadores inflamatórios no grupo controlo e no grupo EAM. Nos dois grupos dosearam-se, ainda, as lipoproteínas: Colesterol total (CT), Colesterol HDL (HDLc), com as suas subfrações 2 e 3 (HDL 2 e HDL3), Colesterol LDL oxidado (LDLox),Triglicéridos (TG), Lipoproteína (a) [Lp(a)], Apolipoproteína A1 (ApoA1), Apolipoproteína B (ApoB) e Apolipoproteína E (ApoE). Definiram-se, em cada grupo, os dados demográficos, fatores de risco clássicos, terapêutica cardiovascular e o uso de anti-inflamatórios. Procedeu-se a análise multivariada em relação aos dados demográficos, fatores de risco e à terapêutica basal. Compararam-se as distribuições destas mesmas caraterísticas entre os dois grupos, assim como os valores séricos respetivos para as lipoproteínas estudadas. Procedeu-se à correlação entre as moléculas inflamatórias e as lipoproteínas, para todos os doentes estudados. Encontraram-se os coeficientes de regressão linear múltipla entre cada marcador inflamatório e o conjunto das moléculas lipídicas, por grupo. Finalmente, efetuou-se a comparação estatística entre os marcadores inflamatórios do grupo controlo e os marcadores inflamatórios do grupo EAM. Resultados: (1) Correlações encontradas, respetivamente, Pearson, Rho-Spearman e regressão-R2: IL-6/hs-CRP 0,549, p<0,001; 0,429, p=0,001; 0,302, p<0,001; MMP 3/hsCRP 0,325, p=0,014; 0,171, p=0,202; 0,106, p=0,014; TNF-α/hs-CRP 0,261, p=0,050; 0,315, p=0,017; 0,068, p=0.050; IL-6/cTnI admissão 0,486, p<0,001; 0,483, p<0,001; 0,236, p<0,001; MMP3/cTnI admissão 0,218, p=0,103; 0,146, p=0,278; 0,048, p=0,103; TNF-α/cTnI admissão 0,444, p=0,001; 0,380, p=0,004; 0,197, p=0,001; IL-6/cTnI 6-9h 0,676, p<0,001; 0,623, p<0,001; 0,456, p<0,01; MMP3/cTnI 6-9h 0,524, p=0,001; 0,149, p=0,270; 0,275, p<0,001; TNF-α/cTnI 6-9h 0,428, p=0,001, 0,452, p<0,001, 0,183, p<0,001. A regressão linear múltipla cTnI admissão/marcadores inflamatórios produziu: (R=0,638, R2=0,407) p<0,001 e cTnI 6-9h/marcadores inflamatórios (R=0,780, R2=0,609) p<0,001. (2) Significância da análise multivariada para idade (p=0,029), IMC>30 (p=0.070), AAS (p=0,040) e grupo (p=0,002). Diferenças importantes entre as distribuições dos dados basais entre os dois grupos (grupo controlo vs EAM): idade (47,95±11,55 vs 68,53±2,70 anos) p<0.001; sexo feminino (18,18 vs 22,80%) p=0,076; diabetes mellitus (9,09% vs 36,84%) p=0,012; AAS (18,18 vs 66,66%) p<0,001; clopidogrel (4,54% vs 66,66%) p=0,033; estatinas (31,81% vs 66,14%) p=0,078; beta-bloqueadores (18,18% vs 56,14%) p=0,011; anti-inflamatórios (4,54% vs 33,33%) p=0,009. Resultados da comparação entre os dois grupos quanto ao padrão lipídico (média±dp ou mediana/intervalo interquartil, grupo controlo vs EAM): CT (208,45±35,03 vs 171,05±41,63 mg/dl) p<0,001; HDLc (51,50/18,25 vs 42,00/16,00 mg/dl) p=0,007; HDL2 (8,50/3,25 vs 10,00/6,00 mg/dl) p=0,292; HDL3 (41,75±9,82 vs 31,75±9,41 mg/dl) p<0,001; LDLox (70,00/22,0 vs 43,50/21,00 U/L) p<0,001; TG (120,00/112,50 vs 107,00/86,00 mg/dl) p=0,527; Lp(a) (0,51/0,73 vs 0,51/0,50 g/L) p=0,854; ApoA1 (1,38±0,63 vs 1,19±0,21 g/L) p=0,002; ApoB (0,96±0,19 vs 0,78±0,28 g/L) p=0,004; ApoE (38,50/10,00 vs 38,00/17,00 mg/L) p=0,574. Nas correlações lineares entre as variáveis inflamatórias e as variáveis lipídicas para todos os doentes, encontrámos uma relação negativa entre IL-6 e CT, HDLc, HDL3, LDLox, ApoA1 e ApoB. A regressão múltipla marcadores inflamatórios/perfil lipídico (grupo controlo) foi: hs-CRP (R=0,883, R2=0,780) p=0,022; IL-6 (R=0,911, R2=0,830) p=0,007; MMP3 (R=0,498, R2=0,248) p=0,943; TNF-α (R=0,680, R2=0,462) p=0,524. A regressão múltipla marcadores inflamatórios/perfil lipídico (grupo EAM) foi: hs-CRP (R=0,647, R2=0,418) p=0,004; IL-6 (R=0,544, R2=0,300), p=0,073; MMP3 (R=0,539, R2=0,290) p=0,089; TNF-α (R=0,595; R2=0,354) p=0,022. Da comparação entre os marcadores inflamatórios dos dois grupos resultou (mediana/intervalo interquartil, grupo controlo vs EAM): hs-CRP (0,19/0,27 vs 0,42/2,53 mg/dl) p=0,001, IL-6 (4,90/5,48 vs 13,07/26,41 pg/ml) p<0,001, MMP3 (19,70/13,70 vs 10,10/10,40 ng/ml) p<0,001;TNF-α (8,67/6,71 vs 8,26/7,80 pg/dl) p=0,805. Conclusões: (1) Nos doentes com EAM, existe correlação entre as moléculas inflamatórias IL-6, MMP3 e TNF-α, quer com o marcador inflamatório hs-CRP, quer com o marcador de lesão miocárdica cTnI. Esta correlação reforça-se para os valores de cTnI 6-9 horas após admissão, especialmente na correlação múltipla com o grupo dos quatro marcadores inflamatórios. (2) IL-6 está inversamente ligada às lipoproteínas de colesterol; hs-CRP e IL-6 têm excelentes correlações com o perfil lipídico valorizado no seu conjunto. No grupo EAM encontram-se níveis séricos mais reduzidos para as lipoproteínas de colesterol. Para TNF-α não foram encontradas diferenças significativas entre os grupos, as quais foram observadas para a IL-6 e hs-CRP (mais elevadas no grupo EAM). Os valores de MMP3 no grupo controlo estão mais elevados. ABSTRACT: 0,524, p=0,001; 0,149, p=0,270; 0,275, p<0,001; TNF-α/cTnI 6-9h 0,428, p=0,001, 0,452, p<0,001, 0,183, p<0,001. A regressão linear múltipla cTnI admissão/marcadores inflamatórios produziu: (R=0,638, R2=0,407) p<0,001 e cTnI 6-9h/marcadores inflamatórios (R=0,780, R2=0,609) p<0,001. (2) Significância da análise multivariada para idade (p=0,029), IMC>30 (p=0.070), AAS (p=0,040) e grupo (p=0,002). Diferenças importantes entre as distribuições dos dados basais entre os dois grupos (grupo controlo vs EAM): idade (47,95±11,55 vs 68,53±2,70 anos) p<0.001; sexo feminino (18,18 vs 22,80%) p=0,076; diabetes mellitus (9,09% vs 36,84%) p=0,012; AAS (18,18 vs 66,66%) p<0,001; clopidogrel (4,54% vs 66,66%) p=0,033; estatinas (31,81% vs 66,14%) p=0,078; beta-bloqueadores (18,18% vs 56,14%) p=0,011; anti-inflamatórios (4,54% vs 33,33%) p=0,009. Resultados da comparação entre os dois grupos quanto ao padrão lipídico (média±dp ou mediana/intervalo interquartil, grupo controlo vs EAM): CT (208,45±35,03 vs 171,05±41,63 mg/dl) p<0,001; HDLc (51,50/18,25 vs 42,00/16,00 mg/dl) p=0,007; HDL2 (8,50/3,25 vs 10,00/6,00 mg/dl) p=0,292; HDL3 (41,75±9,82 vs 31,75±9,41 mg/dl) p<0,001; LDLox (70,00/22,0 vs 43,50/21,00 U/L) p<0,001; TG (120,00/112,50 vs 107,00/86,00 mg/dl) p=0,527; Lp(a) (0,51/0,73 vs 0,51/0,50 g/L) p=0,854; ApoA1 (1,38±0,63 vs 1,19±0,21 g/L) p=0,002; ApoB (0,96±0,19 vs 0,78±0,28 g/L) p=0,004; ApoE (38,50/10,00 vs 38,00/17,00 mg/L) p=0,574. Nas correlações lineares entre as variáveis inflamatórias e as variáveis lipídicas para todos os doentes, encontrámos uma relação negativa entre IL-6 e CT, HDLc, HDL3, LDLox, ApoA1 e ApoB. A regressão múltipla marcadores inflamatórios/perfil lipídico (grupo controlo) foi: hs-CRP (R=0,883, R2=0,780) p=0,022; IL-6 (R=0,911, R2=0,830) p=0,007; MMP3 (R=0,498, R2=0,248) p=0,943; TNF-α (R=0,680, R2=0,462) p=0,524. A regressão múltipla marcadores inflamatórios/perfil lipídico (grupo EAM) foi: hs-CRP (R=0,647, R2=0,418) p=0,004; IL-6 (R=0,544, R2=0,300), p=0,073; MMP3 (R=0,539, R2=0,290) p=0,089; TNF-α (R=0,595; R2=0,354) p=0,022. Da comparação entre os marcadores inflamatórios dos dois grupos resultou (mediana/intervalo interquartil, grupo controlo vs EAM): hs-CRP (0,19/0,27 vs 0,42/2,53 mg/dl) p=0,001, IL-6 (4,90/5,48 vs 13,07/26,41 pg/ml) p<0,001, MMP3 (19,70/13,70 vs 10,10/10,40 ng/ml) p<0,001;TNF-α (8,67/6,71 vs 8,26/7,80 pg/dl) p=0,805. Conclusões: (1) Nos doentes com EAM, existe correlação entre as moléculas inflamatórias IL-6, MMP3 e TNF-α, quer com o marcador inflamatório hs-CRP, quer com o marcador de lesão miocárdica cTnI. Esta correlação reforça-se para os valores de cTnI 6-9 horas após admissão, especialmente na correlação múltipla com o grupo dos quatro marcadores inflamatórios. (2) IL-6 está inversamente ligada às lipoproteínas de colesterol; hs-CRP e IL-6 têm excelentes correlações com o perfil lipídico valorizado no seu conjunto. No grupo EAM encontram-se níveis séricos mais reduzidos para as lipoproteínas de colesterol. Para TNF-α não foram encontradas diferenças significativas entre os grupos, as quais foram observadas para a IL-6 e hs-CRP (mais elevadas no grupo EAM). Os valores de MMP3 no grupo controlo estão mais elevados. ------------- ABSTRACT: Introduction: We reviewed the epidemiology, pathophysiology and current clinical knowledge about coronary heart disease, from its genesis to the acute myocardial infarction (AMI). The inflammatory theory for atherosclerosis, which has undergone considerable development in the last decade, was especially detailed. Markers of coronary atherosclerotic vulnerable plaque: The clinical and laboratory biomarkers associated with the unstable coronary atherosclerotic plaque vulnerable plaque are detailed. An emphasis was placed on the inflammatory mechanisms. Objectives: They are divided into two fundamental points: (1) To study in AMI patients, the relationship between the inflammatory molecules: Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Matrix metalloproteinase-3 (MMP3), unused in the clinical setting, with an inflammatory marker in clinical use: ultrasensitive C-reactive protein (hs-CRP), as well as a biomarker of myocardial injury: cardiac troponin I (cTnI). (2) To study, in the context of AMI, the Acute Phase Response (APR). We intend to demonstrate the impact of that clinical relevant phenomenon in the lipid profile and inflammatory biomarkers of our patients. Methods: (1) Prospective observational study of patients consecutively admitted for AMI (AMI group) in a single coronary care unit, after exclusion of trauma or infection. A peripheral assay at admission for IL-6, TNF-α, MMP3, hs-CRP and cTnI was performed. The latter was also valued in assays obtained 6-9 hours after admission. Linear correlation (Pearson's correlation coefficient, Spearman Rho's correlation coefficient and R2 regression) was performed between the three markers studied and the values of hs-CRP and cTnI (on admission and 6-9 hours after admission). Multiple linear regression was also obtained between cTnI on admission and 6-9h after, with all the inflammatory markers studied. (2) Case-control study between the AMI group and a random population of patients from an outpatient cardiology setting (control group). Cardiovascular events of any kind and infection or trauma were excluded in this group. The same inflammatory molecules were assayed in control and AMI groups. The following lipoproteins were also assayed: total cholesterol (TC), HDL cholesterol (HDLc) and subfractions 2 and 3 (HDL2 and HDL 3), oxidized LDL cholesterol (oxLDL), Triglycerides (TG), Lipoprotein (a) [Lp(a)], Apolipoprotein A1 (apoA1), Apolipoprotein B (ApoB) and Apolipoprotein E (ApoE). Demographics, classical risk factors, cardiovascular therapy and the use of anti-inflammatory drugs were appreciated in each group. The authors conducted a multivariate analysis with respect to demographics, risk factors and baseline therapy. The distribution of the same baseline characteristics was compared between the two groups, as well as the lipoprotein serum values. A correlation was performed between each inflammatory molecule and each of the lipoproteins, for all the patients studied. Multiple linear regression was determined between each inflammatory marker and all the lipid molecules per group. Finally, the statistical comparison between the inflammatory markers in the two groups was performed. Results: (1) The correlation coefficients recorded, respectively, Pearson, Spearman's Rho and regression-R2, were: IL-6/hs-CRP 0.549, p <0.001; 0.429, p=0.001; 0.302, p <0.001; MMP 3/hsCRP 0.325, p=0.014; 0.171, p=0.202; 0.106, p=0.014; TNF-α/hs-CRP 0.261, p=0.050; 0.315, p=0.017; 0.068, p=0.050; IL-6/admission cTnI 0.486, p<0.001; 0.483, p<0.001; 0.236, p<0.001; MMP3/admission cTnI 0.218, p=0.103; 0.146, p=0.278; 0.048, p=0.103; TNF-α/admission cTnI 0.444, p=0.001; 0.380, p=0.004; 0.197, p=0.001; IL-6/6-9 h cTnI 0.676, p<0.001; 0.149, p<0.001; 0.456, p <0.01; MMP3/6-9h cTnI 0.428, p=0.001; 0.149, p<0.001; 0.183, p=0.001; TNF-α/6-9 h cTnI 0.676, p<0,001; 0.452, p<0.001; 0.183, p<0,001. The multiple linear regression admission cTnI/inflammatory markers produced: (R=0.638, R2=0.407) p<0.001 and 6-9 h cTnI/inflammatory markers (R=0.780, R2=0.609) p<0.001. (2) Significances of the multivariate analysis were found for age (p=0.029), IMC>30 (p=0.070), Aspirin (p=0.040) and group (p=0.002). Important differences between the baseline data of the two groups (control group vs AMI): age (47.95 ± 11.55 vs 68.53±12.70 years) p<0.001; gender (18.18 vs 22.80%) p=0.076; diabetes mellitus (9.09% vs 36. 84%) p=0.012; Aspirin (18.18 vs. 66.66%) p<0.001; Clopidogrel (4, 54% vs 66.66%) p=0.033; Statins, 31.81% vs 66.14%, p=0.078, beta-blockers 18.18% vs 56.14%, p=0.011; anti-inflammatory drugs (4.54% vs 33.33%) p=0.009. Significant differences in the lipid pattern of the two groups (mean±SD or median/interquartile range, control group vs AMI): TC (208.45±35.03 vs 171.05±41.63 mg/dl) p<0.001; HDLc (51.50/18.25 vs 42.00/16.00 mg/dl) p=0.007; HDL2 (8.50/3.25 vs 10.00/6.00 mg/dl) p=0.292; HDL3 (41.75±9.82 vs 31.75±9.82 mg/dl) p<0.01; oxLDL (70.00/22.0 vs 43.50/21.00 U/L) p <0.001; TG (120.00/112.50 vs 107.00/86.00 mg/dl) p=0.527; Lp(a) (0.51/0.73 vs 0,51/0.50 g/L) p=0.854; apoA1 (1.38±0.63 vs 1.19±0.21 g/L) p=0.002; ApoB (0.96± 0.39 vs 0.78±0.28 g/L) p=0.004; ApoE (38.50/10,00 vs 38.00 /17,00 mg/L) p=0.574. In the linear correlations between inflammatory variables and lipid variables for all patients, we found a negative relationship between IL-6 and TC, HDLc, HDL3, ApoA1 and ApoB. The multiple linear regression inflammatory markers/lipid profile (control group) was: hs-CRP (R= 0.883, R2=0.780) p=0.022; IL6 (R=0.911, R2=0.830) p=0.007; MMP3 (R=0.498, R2=0.248) p=0.943; TNF-α (R=0.680, R2=0.462) p=0.524. For the linear regression inflammatory markers/lipid profile (AMI group) we found: hs-CRP (R=0.647, R2=0.418) p=0.004; IL-6 (R=0.544, R2=0.300) p=0.073; MMP3 (R=0.539, R2 =0.290) p=0.089; TNF-α (R=0.595, R2=0.354) p=0.022. The comparison between inflammatory markers in both groups (median/interquartile range, control group vs AMI) resulted as: hs-CRP (0.19/0.27 vs 0.42/2.53 mg/dl) p=0.001; IL-6 (4.90/5.48 vs 13.07/26.41 pg/ml) p<0.001; MMP3 (19.70/13.70 vs 10.10/10.40 ng/ml) p<0.001; TNF-α (8.67/6.71 vs 8.26/7.80 pg/dl) p=0.805. Conclusions: (1) In AMI patients there is a correlation between the inflammatory molecules IL-6, TNF-α and MMP3 with both the inflammatory marker hs-CRP and the ischemic marker cTnI. This correlation is strengthened for the cTnI at 6-9h post admission, particularly in the multiple linear regression to the four inflammatory markers studied. (2) IL-6 correlates negatively with the cholesterol lipoproteins. Hs-CRP and IL-6 are strongly correlated to the whole lipoprotein profile. AMI patients display reduced serum lipid levels. For the marker TNF-α no significant differences were found between groups, which were observed for IL-6 and hs-CRP (higher in the AMI group). MMP3 values are higher in the control group.