Impacto de la Proteína-C reactiva en el riesgo cardiovascular de adolescentes

Vários estudos sugerem que a proteína-C reativa (PCR) se correlaciona com doença arterial coronariana em adultos. Entretanto, essa associação ainda é pouco explorada em adolescentes. Avaliar a associação entre a PCR e os fatores de risco cardiovascular em adolescentes obesos. Oitenta e quatro adolescentes (12,6 ± 1,3 anos), ambos os sexos, foram distribuídos nos grupos Eutrófico (n = 28), Sobrepeso (n = 28) e Obeso (n = 28), segundo o índice de massa corpórea (IMC). A concentração de PCR (ELISA ultrassensível), o perfil lipídico e o conteúdo de anticorpos anti-LDLox (ELISA) foram determinados após jejum de 12h. Os grupos foram semelhantes quanto a idade (p = 0,13) e sexo (p = 0,83). Colesterol total, HDL-C, CT/HDL-C e LDL-C/HDL-C apresentaram diferenças significativas entre os grupos Eutrófico e Obeso. Não houve variação significativa no conteúdo de anticorpos anti-LDLox. Os valores de PCR foram diferentes entre os três grupos (p < 0,01). PCR apresentou associação significativa com IMC (β = 2,533), CB (β = 2,645) e CC (β = 2,945), CT (β = 0,006), LDL-C (β = 0,006) e anticorpos anti-LDLox (β = 0,383) e negativa entre HDL-C (β = -0,017). Os resultados indicam que a PCR se associa significativamente com marcadores de risco cardiovascular em adolescentesBACKGROUND: Several studies suggest that C-reactive protein (CRP) is associated with coronary artery disease in adults. However, this association has not been thoroughly explored in cases of adolescents. OBJECTIVE: To evaluate the association between CRP and cardiovascular risk factors in obese adolescents. METHODS: Eighty-four adolescents (12.6 ± 1.3 years) of both genders were divided into the following groups: Normal weight (n = 28), Overweight (n = 28), and Obese (n = 28), according to body mass index (BMI). CRP levels (ultrasensitive ELISA), the lipid profile, and anti-oxLDL antibody levels (ELISA) were determined after a 12-hour fast. RESULTS: The groups were similar in age (p = 0.13) and gender (p = 0.83). Total cholesterol, HDL-C, TC/HDL-C, and LDL-C/HDL-C showed significant differences between Normal weight and Obese groups. There was no significant variation in anti-oxLDL levels. CRP values were different among the three groups (p < 0.01). CRP levels showed a significant association with BMI (β = 2.533), AC (β = 2.645), WC (β = 2.945), TC (β = 0.006), LDL-C (β = 0.006), and anti-oxLDL antibodies (β = 0.383), and a negative association with HDL-C (β = -0.017). CONCLUSION: The results indicate that CRP is significantly associated with markers of cardiovascular risk in adolescentsFUNDAMENTO: Diversos estudios sugieren que la proteína-C reactiva (PCR) se correlaciona con la enfermedad arterial coronaria en adultos. Sin embargo, esta asociación es todavía poco explorada en adolescentes. OBJETIVO: Evaluar la asociación entre la PCR y los factores de riesgo cardiovascular en adolescentes obesos. MÉTODOS: Ochenta y cuatro adolescentes (12,6 ± 1,3 años), de ambos sexos, se distribuyeron en los grupos Eutrófico (n=28), Sobrepeso (n=28) y Obeso (n=28), según el IMC. La concentración de PCR (ELISA ultrasensible), el perfil lipídico y el contenido de anticuerpos anti-LDLox (ELISA) fueron determinados tras ayuno de 12h. RESULTADOS: Los grupos se hallaron semejantes en cuanto a la edad (p=0,13) y sexo (p=0,83). Colesterol total, HDL-C, CT/HDL-C y LDL-C/HDL-C expresaron diferencias significativas entre los grupos Eutrófico y Obeso. No hubo variación significativa en el contenido de anticuerpos anti-LDLox. Los valores de PCR fueron diferentes entre los tres grupos (p<0,01). La PCR expresó asociación significativa con IMC (β=2,533), CB (β=2,645) y CC (β=2,945), CT (β=0,006), LDL-C (β=0,006) y anticuerpos anti-LDLox (β=0,383) y negativa entre HDL-C (β= -0,017). CONCLUSIÓN: Los resultados indican que la PCR se asocia significativamente con marcadores de riesgo cardiovascular en adolescentesFAPESP n. 04/14517-

Auto-anticorpos anti-LDLox e sua correlação com o perfil lipídico e o estado nutricional de adolescentes

OBJETIVO: Avaliar se o conteúdo de auto-anticorpos anti-LDL oxidada (anti-LDLox) no plasma de adolescentes correlaciona-se com suas medidas antropométricas e com o perfil lipídico. MÉTODOS: O estudo incluiu 150 adolescentes com idade entre 10 e 15 anos, recrutados do ambulatório de obesidade da Universidade Federal de São Paulo (SP) e de escolas públicas de Piracicaba (SP). Foram avaliadas medidas antropométricas, como índice de massa corporal, circunferência de cintura e do braço, classificando os adolescentes em eutrófico, sobrepeso e obeso. Para as análises bioquímicas, foi realizado o perfil lipídico através de métodos enzimáticos colorimétricos, e para detecção do conteúdo de auto-anticorpos anti-LDLox, utilizou-se o método de ELISA. RESULTADOS: Segundo análises das variáveis antropométricas, o grupo obeso apresentou perfil alterado em relação aos grupos eutrófico e sobrepeso (p < 0,01), indicando risco cardiovascular. Quando o perfil lipídico foi avaliado, observaram-se diferenças estatisticamente significativas para as concentrações de colesterol total (p = 0,011), HDL-colesterol (p = 0,001) e LDL-colesterol (p < 0,042) nos grupos eutrófico e obeso. Para as análises de auto-anticorpos anti-LDLox plasmática, os grupos sobrepeso (p = 0,012) e obeso (p < 0,001) apresentaram valores superiores ao grupo eutrófico. Também houve correlações entre os auto-anticorpos anti-LDLox e variáveis antropométricas. CONCLUSÃO: A presença de auto-anticorpos anti-LDLox em adolescentes e as alterações metabólicas no perfil lipídico variaram de modo proporcional com parâmetros antropométricos, o que torna o conteúdo de anti-LDLox um potencial indicador bioquímico de risco para síndrome metabólicaFAPESP n. 04/14517-6, 06/51119-4, e 02/9521-9. CNPq n. 132059/2007-0 e 110960/2005-

Association of Lp-PLA activity and fat-soluble antioxidants with cardiometabolic markers in adolescents

Introdução: A obesidade se caracteriza como um processo oxidativo e inflamatório, que predispõe adolescentes, de modo precoce, a eventos até recentemente pouco frequentes nessa faixa etária. Assim, a ação da enzima Fosfolipase A associada às lipoproteínas (Lp-PLA ), que reduz fosfolipídios oxidados e gera lisofosfolipídios, bem como a disponibilidade de antioxidantes plasmáticos, representam um importante tema de pesquisa no contexto cardiovascular. Objetivo: Verificar se a atividade da LP-PLA 2 2 e a concentração de antioxidantes lipossolúveis se associam com os principais marcadores de risco cardiovascular em adolescentes. Métodos: Duzentos e quarenta e dois adolescentes (10 a 19 anos), de ambos os sexos foram distribuídos, segundo o índice de massa corporal (IMC), em três grupos: Eutróficos (n=77), Sobrepeso (n=82) e Obesos (n=83). A amostra foi caracterizada através de parâmetros sócio-econômicos, estado de saúde, uso de medicamentos, antedecentes familiares de doenças crônicas e prática de atividade física. Foram avaliados ainda os dados antropométricos (peso, altura e composição corporal - bioimpedância), e o consumo alimentar por meio de três recordatórios 24 h. A partir de uma amostra de sangue coletada após jejum (12h), realizaram-se as análises da atividade da Lp-PLA , LDL(-) e seus auto-anticorpos, perfil lipídico (colesterol total, LDL-C, HDL-C e triglicerídeos), tamanho da HDL, proteína transportadora de éster de colesterol (CETP), ácidos graxos não esterificados (NEFAs), adipocitocinas, assim como antioxidantes (retinol, licopeno, -tocoferol e -caroteno) no plasma. Resultados: Artigo 1: Lp-PLA maybe an important cardiovascular biomarker in obese adolescents. Verificou-se que o perfil lipídico, insulina, HOMA-IR (resistência à insulina) e LDL(-) evidenciaram um maior risco cardiovascular nos adolescentes obesos. A atividade da enzima Lp-PLA 2 mostrou uma variação proporcional ao IMC, circunferência da cintura e porcentagem de gordura. Essa tendência foi, ainda, reforçada pelas associações positivas entre a enzima e HOMA-IR, glicose, insulina e as variáveis lipídicas. Adicionalmente, associação negativa foi encontrada para ApoAI. As associações mais relevantes foram observadas para ApoB e Apo B / Apo AI (=0,293; P<0,001, =0,343; P<0,001, respectivamente). O melhor modelo preditor para a atividade da enzima incluiu Apo B/Apo AI (= 0,327; P<0,001), tamanho da HDL (=-0,326; P<0,001), circunferência da cintura (=0,171; P=0,006) e glicose (= 0,119; P=0,038). A análise de Odds Ratio mostrou que a mudança de uma unidade na razão entre Apo B/Apo AI esteve associada a 73.5 maior risco para elevada atividade de Lp-PLA 2 . Conclusão: A enzima Lp-PLA , em adolescentes, varia em função do estado nutricional e está relacionada a vários marcadores de risco cardiovascular, especialmente a Apo B/Apo AI. Assim, a atividade da enzima pode representar um importante biomarcador de risco cardiovascular na adolescência. Artigo 2: Antioxidant, and inflammatory aspects of phospholipase A 2 associated to lipoprotein (Lp-PLA ): A review. Esta revisão descreve os principais aspectos relacionados à enzima Lp-PLA 2 e seu impacto no perfil inflamatório e oxidativo da doença aterosclerótica. Artigo 3: Plasma antioxidants, but not the dietary ones, are associated with cardiometabolic risk in adolescents. Neste artigo, observou-se que 2 os antioxidantes -caroteno, licopeno, retinol e -tocoferol variam em função do IMC. Verificou-se que -caroteno e -tocoferol apresentaram valores reduzidos para o grupo obeso em comparação ao eutrófico e ao sobrepeso. Para o -caroteno, verificou-se que essa diferença pôde ser observada inclusive quando comparados sobrepesos e eutróficos. Quando esses antioxidantes foram ajustados pelo colesterol total ou pelo LDL-C essas diferenças se mantiveram. Correlações importantes foram obtidas entre os antioxidantes ajustados por colesterol ou por LDL-C e as variáveis de risco cardiometabólico (perfil lipídico (colesterol total e frações, CETP), resistência à insulina (HOMA-IR, insulina, glicose) e LDL(-)). A obesidade representou um importante fator para a existência dessas correlações, pois após o ajuste por IMC foram reduzidas. Apesar desses resultados, os antioxidantes availados pelo recordatório de 24h não apresentaram nenhuma correlação com os fatores de risco cardiometabólico. Conclusão: Antioxidantes plasmáticos estão relacionados ao risco cardiometabólico em adolescentes, sendo que o IMC desempenha um papel importante para a existência dessas correlações. Tais biomarcadores representam uma melhor maneira de estimar a influência de um padrão dietético sobre o risco cardiometabólico em adolescentes do que a avaliação do inquérito alimentarIntroduction: Obesity is characterized as an oxidative and inflammatory process, which precociously predisposes adolescents to events until recently uncommon in this age group. Thus, the action of Lipoprotein-associated phospholipase A (LpPLA ), which reduces oxidized phospholipids and generates lysophospholipids, as well as the availability of plasma antioxidants, represent important subjects of cardiovascular research. Objetive: To evaluate if the activity of Lp-PLA 2 and the concentration of fat-soluble antioxidants are associated with the most important cardiovascular risk markers in adolescents. Methods: 242 adolescents (10 to 19 years old), from both sexes, were distributed according to Body mass index (BMI) in three groups: Health Weigth (HW, n=77), Overweigth (OV, n=82) and Obeses (OB, n=83). The sample was characterized by socioeconomic parameters, health condition, use of medications, family history of chronic diseases and physical activity. It were evaluated also the anthropometric data (weigth, heigth, body composition - bioimpedance) and the food intake through three 24h-recall. From a blood sample collected after fasting (12h), were analized the Lp-PLA activity, the levels of LDL(-) and it antibodies, the lipid profile (total cholesterol, LDL-C, HDL-C and triglycerides), HDL-size, Non-Esterified Fatty Acids (NEFAs), Cholesteryl Ester Transfer Protein (CETP), adipocytokines, as well as plasma antioxidants (retinol, licopene, -tocopherol e -carotene). Results: Article 1: Lp-PLA as an important biomarker of cardiovascular risk in obese adolescents. It was observed that the lipid profile, the insulin, the HOMA-IR (insulin resistance) and the LDL(-) represented a higher cardiovascular risk in obese adolescents. The activity of Lp-PLA 2 has shown a variation proportional to BMI, waist circumference and fat mass percentage. This tendency was reinforced by positive associations of the enzyme with HOMA-IR, glucose, insulin and lipid variables. Additionaly, a negative association was observed for Apo AI. The most relevant associations were observed for ApoB and Apo B / Apo AI (=0,293; P<0,001, =0,343; P<0,001, respectively). The best predictor model for the enzyme activity included Apo B/Apo AI (= 0,327; P<0,001), HDLsize (=-0,326; P<0,001), waist circumference (=0,171; P=0,006) and glucose (= 0,119; P=0,038). The Odds Ratio analysis showed that the change of one unit in the ratio of Apo B/Apo AI was related to a 73.5 times higher risk of elevated Lp-PLA activity. Conclusion: The enzyme Lp-PLA , in adolescents, varies in function of the nutritional status and it is related to several cardiovascular risk markers, especially to Apo B/Apo AI. Thus, this enzyme activity may represent an important biomarker of cardiovascular risk in adolescence. Article 2: Antioxidant and inflammatory aspects of phospholipase A 2 2 associated to lipoprotein (Lp-PLA ): a review. This review describes the main aspects related to the enzime Lp-PLA 2 and its impact to inflammatory and oxidative profiles of atherosclerotic disease. Article 3: Plasma antioxidants, but not the dietary ones, are associated with cardiometabolic risk in 2 adolescents. It was observed that the antioxidants -carotene, licopene, retinol and -tocopherol vary in function of BMI. It was verified that -carotene and - tocopherol presented reduced values for the OB group in comparison with the HW and OV groups. For -carotene, it was observed that this difference was also verified when OB and OV were compared. These differences remained alike when the antioxidants were adjusted by total cholesterol or by LDL-C. Important correlations were obtained between the antioxidants adjusted by total cholesterol or by LDL-C, and cardiometabolic risk variables (lipid profile (total cholesterol and fractions, CETP), insulin resistance (HOMA-IR, insulin, glucose) and LDL(-)). The obesity represented an important factor to the occurrence of these correlations, since they were reduced after BMI adjustment. Despite these results, the antioxidants evaluated by 24h-diet recall did not show any correlations with cardiometabolic risk. Conclusion: Plasma antioxidants are related to cardiometabolic risk in adolescents, where the BMI represents an important factor. These biomarkers are better than the food intake to estimate the influence of a dietary pattern on the cardiometabolic risk in adolescent

Impact of menopause and diabetes on atherogenic lipid profile: is it worth to analyse lipoprotein subfractions to assess cardiovascular risk in women?

Abstract Cardiovascular disease is the leading cause of death in women at advanced age, who are affected a decade later compared to men. Cardiovascular risk factors in women are not properly investigated nor treated and events are frequently lethal. Both menopause and type 2 diabetes substantially increase cardiovascular risk in the female sex, promoting modifications on lipid metabolism and circulating lipoproteins. Lipoprotein subfractions suffer a shift after menopause towards a more atherogenic lipid profile, consisted of hypertriglyceridemia, lower levels of both total high density lipoprotein (HDL) and its subfraction HDL2, but also higher levels of HDL3 and small low-density lipoprotein particles. This review discusses the impact of diabetes and menopause to the lipid profile, challenges in lipoprotein subfractions determination and their potential contribution to the cardiovascular risk assessment in women. It is still unclear whether lipoprotein subfraction changes are a major driver of cardiometabolic risk and which modifications are predominant. Prospective trials with larger samples, methodological standardizations and pharmacological approaches are needed to clarify the role of lipoprotein subfractions determination on cardiovascular risk prediction and intervention planning in postmenopausal women, with or without DM

Reassessing lipid metabolism and its potentialities in the prediction of cardiovascular risk

There are numerous particles, enzymes, and mechanisms in the lipid metabolism that are involved in the genesis of cardiovascular disease (CVD). Given its prevalence in populations and its impact on mortality, it is relevant to review the lipid metabolism as it may potentially provide subsidies to better prediction. This article reviews the importance of traditional cardiovascular risk factors and comments on the potential of novel lipid biomarkers involved in the physiopathology of CVD. The Framingham cohorts proved the role of traditional risk factors (physical inactivity, smoking, blood pressure, total cholesterol, LDL-C, HDL-C, plasma glucose) in the prediction of cardiovascular events. However, a significant number of individuals that suffer from a cardiovascular event has few or none of these factors. Such finding indicates the need for new biomarkers able to identify plaques that are more susceptible to rupture. Some of bloodstream biomarkers related to lipid metabolism are modified LDL particles, apolipoprotein AI (apo AI), apolipoprotein B, lipoprotein (a) [Lp (a)], cholesteryl ester transfer protein (CETP), subtypes of LDL and HDL particles, and lipoprotein-associated phospholipase A2 (Lp-PLA2). These factors participate in the atherosclerotic process, and are abnormal in individuals at high risk, or in those who suffered from a cardiovascular event. Lp (a) determination is already employed in clinical practice and should be included as a reference parameter for CVD monitoring. Furthermore, there are expectations for wider use of apo B, non-HDL cholesterol and total cholesterol / HDL-C determination to improve cardiovascular risk assessment

Reassessing lipid metabolism and its potentialities in the prediction of cardiovascular risk

There are numerous particles, enzymes, and mechanisms in the lipid metabolism that are involved in the genesis of cardiovascular disease (CVD). Given its prevalence in populations and its impact on mortality, it is relevant to review the lipid metabolism as it may potentially provide subsidies to better prediction. This article reviews the importance of traditional cardiovascular risk factors and comments on the potential of novel lipid biomarkers involved in the physiopathology of CVD. The Framingham cohorts proved the role of traditional risk factors (physical inactivity, smoking, blood pressure, total cholesterol, LDL-C, HDL-C, plasma glucose) in the prediction of cardiovascular events. However, a significant number of individuals that suffer from a cardiovascular event has few or none of these factors. Such finding indicates the need for new biomarkers able to identify plaques that are more susceptible to rupture. Some of bloodstream biomarkers related to lipid metabolism are modified LDL particles, apolipoprotein AI (apo AI), apolipoprotein B, lipoprotein (a) [Lp (a)], cholesteryl ester transfer protein (CETP), subtypes of LDL and HDL particles, and lipoprotein-associated phospholipase A2 (Lp-PLA2). These factors participate in the atherosclerotic process, and are abnormal in individuals at high risk, or in those who suffered from a cardiovascular event. Lp (a) determination is already employed in clinical practice and should be included as a reference parameter for CVD monitoring. Furthermore, there are expectations for wider use of apo B, non-HDL cholesterol and total cholesterol / HDL-C determination to improve cardiovascular risk assessment

Impacto da proteína-C reativa no risco cardiovascular de adolescentes Impacto de la Proteína-C reactiva en el riesgo cardiovascular de adolescentes Impact of C-reactive protein on cardiovascular risk in adolescents

FUNDAMENTO: Vários estudos sugerem que a proteína-C reativa (PCR) se correlaciona com doença arterial coronariana em adultos. Entretanto, essa associação ainda é pouco explorada em adolescentes. OBJETIVO: Avaliar a associação entre a PCR e os fatores de risco cardiovascular em adolescentes obesos. MÉTODOS: Oitenta e quatro adolescentes (12,6 ± 1,3 anos), ambos os sexos, foram distribuídos nos grupos Eutrófico (n = 28), Sobrepeso (n = 28) e Obeso (n = 28), segundo o índice de massa corpórea (IMC). A concentração de PCR (ELISA ultrassensível), o perfil lipídico e o conteúdo de anticorpos anti-LDLox (ELISA) foram determinados após jejum de 12h. RESULTADOS: Os grupos foram semelhantes quanto a idade (p = 0,13) e sexo (p = 0,83). Colesterol total, HDL-C, CT/HDL-C e LDL-C/HDL-C apresentaram diferenças significativas entre os grupos Eutrófico e Obeso. Não houve variação significativa no conteúdo de anticorpos anti-LDLox. Os valores de PCR foram diferentes entre os três grupos (p < 0,01). PCR apresentou associação significativa com IMC (&#946; = 2,533), CB (&#946; = 2,645) e CC (&#946; = 2,945), CT (&#946; = 0,006), LDL-C (&#946; = 0,006) e anticorpos anti-LDLox (&#946; = 0,383) e negativa entre HDL-C (&#946; = -0,017). CONCLUSÃO: Os resultados indicam que a PCR se associa significativamente com marcadores de risco cardiovascular em adolescentes.<br>FUNDAMENTO: Diversos estudios sugieren que la proteína-C reactiva (PCR) se correlaciona con la enfermedad arterial coronaria en adultos. Sin embargo, esta asociación es todavía poco explorada en adolescentes. OBJETIVO: Evaluar la asociación entre la PCR y los factores de riesgo cardiovascular en adolescentes obesos. MÉTODOS: Ochenta y cuatro adolescentes (12,6 ± 1,3 años), de ambos sexos, se distribuyeron en los grupos Eutrófico (n=28), Sobrepeso (n=28) y Obeso (n=28), según el IMC. La concentración de PCR (ELISA ultrasensible), el perfil lipídico y el contenido de anticuerpos anti-LDLox (ELISA) fueron determinados tras ayuno de 12h. RESULTADOS: Los grupos se hallaron semejantes en cuanto a la edad (p=0,13) y sexo (p=0,83). Colesterol total, HDL-C, CT/HDL-C y LDL-C/HDL-C expresaron diferencias significativas entre los grupos Eutrófico y Obeso. No hubo variación significativa en el contenido de anticuerpos anti-LDLox. Los valores de PCR fueron diferentes entre los tres grupos (p<0,01). La PCR expresó asociación significativa con IMC (&#946;=2,533), CB (&#946;=2,645) y CC (&#946;=2,945), CT (&#946;=0,006), LDL-C (&#946;=0,006) y anticuerpos anti-LDLox (&#946;=0,383) y negativa entre HDL-C (&#946;= -0,017). CONCLUSIÓN: Los resultados indican que la PCR se asocia significativamente con marcadores de riesgo cardiovascular en adolescentes.<br>BACKGROUND: Several studies suggest that C-reactive protein (CRP) is associated with coronary artery disease in adults. However, this association has not been thoroughly explored in cases of adolescents. OBJECTIVE: To evaluate the association between CRP and cardiovascular risk factors in obese adolescents. METHODS: Eighty-four adolescents (12.6 ± 1.3 years) of both genders were divided into the following groups: Normal weight (n = 28), Overweight (n = 28), and Obese (n = 28), according to body mass index (BMI). CRP levels (ultrasensitive ELISA), the lipid profile, and anti-oxLDL antibody levels (ELISA) were determined after a 12-hour fast. RESULTS: The groups were similar in age (p = 0.13) and gender (p = 0.83). Total cholesterol, HDL-C, TC/HDL-C, and LDL-C/HDL-C showed significant differences between Normal weight and Obese groups. There was no significant variation in anti-oxLDL levels. CRP values were different among the three groups (p < 0.01). CRP levels showed a significant association with BMI (&#946; = 2.533), AC (&#946; = 2.645), WC (&#946; = 2.945), TC (&#946; = 0.006), LDL-C (&#946; = 0.006), and anti-oxLDL antibodies (&#946; = 0.383), and a negative association with HDL-C (&#946; = -0.017). CONCLUSION: The results indicate that CRP is significantly associated with markers of cardiovascular risk in adolescents