RESUMO
Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial (hypopnea) or complete interruption (apnea) in breathing during sleep due to airway collapse in the pharyngeal region. OSA and its cardiovascular consequences have been widely explored in observational and prospective studies. Most evidence verifies the positive relationship between OSA and hypertension, coronary artery disease, atrial fibrillation, stroke and heart failure. However, more studies are needed to better assess the impact of OSA, and possible benefit of treatment with continuous positive airway pressure (CPAP) on dyslipidemia, type 2 diabetes, insulin resistance and cardiovascular mortality. The leading pathophysiological mechanisms involved in the changes triggered by OSA, include intermittent hypoxemia and re-oxygenation, arousals and changes in intrathoracic pressure. Hypertension is strongly related with activation of the sympathetic nervous system, stimulation of the renin-angiotensin-aldosterone system and impairment of endothelial function. The high prevalence of OSA in the general population, hypertensive patients and especially obese individuals and patients resistant to antihypertensive therapy, highlights the need for effective screening, diagnosis and treatment of OSA to decrease cardiovascular risk.
Assuntos
Hipertensão/etiologia , Apneia Obstrutiva do Sono/complicações , Humanos , Hipertensão/epidemiologia , Respiração com Pressão Positiva , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapiaRESUMO
Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial (hypopnea) or complete interruption (apnea) in breathing during sleep due to airway collapse in the pharyngeal region. OSA and its cardiovascular consequences have been widely explored in observational and prospective studies. Most evidence verifies the positive relationship between OSA and hypertension, coronary artery disease, atrial fibrillation, stroke and heart failure. However, more studies are needed to better assess the impact of OSA, and possible benefit of treatment with continuous positive airway pressure (CPAP) on dyslipidemia, type 2 diabetes, insulin resistance and cardiovascular mortality. The leading pathophysiological mechanisms involved in the changes triggered by OSA, include intermittent hypoxemia and re-oxygenation, arousals and changes in intrathoracic pressure. Hypertension is strongly related with activation of the sympathetic nervous system, stimulation of the reninangiotensinaldosterone system and impairment of endothelial function. The high prevalence of OSA in the general population, hypertensive patients and especially obese individuals and patients resistant to antihypertensive therapy, highlights the need for effective screening, diagnosis and treatment of OSA to decrease cardiovascular risk.
Assuntos
Apneia Obstrutiva do Sono , Doença da Artéria Coronariana , Doença das Coronárias , HipertensãoAssuntos
Aterosclerose/terapia , Colesterol/sangue , Dislipidemias/terapia , Adolescente , Adulto , Idoso , Aterosclerose/prevenção & controle , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Criança , Ésteres do Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/prevenção & controle , Ácidos Graxos/metabolismo , Feminino , Ácidos Fíbricos/metabolismo , Humanos , Hipercolesterolemia/sangue , Hipertrigliceridemia/sangue , Expectativa de Vida , Lipoproteínas/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Triglicerídeos/sangueAssuntos
Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aterosclerose/terapia , Colesterol/sangue , Dislipidemias/terapia , Aterosclerose/prevenção & controle , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Ésteres do Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/prevenção & controle , Ácidos Graxos/metabolismo , Ácidos Fíbricos/metabolismo , Hipercolesterolemia/sangue , Hipertrigliceridemia/sangue , Expectativa de Vida , Lipoproteínas/metabolismo , Fatores de Risco , Triglicerídeos/sangueAssuntos
Doenças Cardiovasculares/prevenção & controle , Promoção da Saúde , Aspirina/uso terapêutico , Brasil , Medicina Baseada em Evidências , Feminino , Humanos , Hipertensão/prevenção & controle , Metanálise como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: Using candidate gene approach, we have investigated the effect of single nucleotide polymorphism (SNP) in genes related to lipid metabolism and atherosclerosis on dyslipidemia and atorvastatin response. METHODS: The study included 157 patients treated with atorvastatin and 145 controls. Genomic DNA was isolated and genotyped using SNPlex technology. RESULTS: Allele and genotype disease association test revealed that APOB rs693 (OR: 2.2 [1.5-3.2], p=0.0001) and CD36 rs1984112 (OR: 3.7 [1.9-7.0], p=0.0002) SNPs were independent risk factors for hypercholesterolemia. Only APOB rs693 T variant allele was associated with increased LDL cholesterol levels (>160mg/dL). After atorvastatin treatment (10mg/day/4weeks), LIPC -514T allele was positively associated with LDL cholesterol reduction. CONCLUSION: The current study reinforces the current knowledge that carrying APOB rs693 is an independent risk factor for dyslipidemia and higher LDL levels. Furthermore, we found that a variant of CD36 was associated with dyslipidemia as a risk (rs1984112) factor. Finally, atorvastatin response could be predicted by LIPC -514C>T SNP and physical activity. In conclusion, our data evidences the contribution of genetic markers and their interaction with environmental factor in the variability of statin response.
Assuntos
Aterosclerose/complicações , Dislipidemias/tratamento farmacológico , Dislipidemias/genética , Ácidos Heptanoicos/farmacologia , Metabolismo dos Lipídeos/genética , Polimorfismo de Nucleotídeo Único , Pirróis/farmacologia , Atorvastatina , Dislipidemias/complicações , Dislipidemias/metabolismo , Feminino , Genótipo , Ácidos Heptanoicos/farmacocinética , Ácidos Heptanoicos/uso terapêutico , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Pirróis/farmacocinética , Pirróis/uso terapêutico , Resultado do TratamentoRESUMO
The aim of the present study was to determine if there is an association between the single nucleotide polymorphisms (SNPs) of the lipoprotein lipase (LPL) and apolipoprotein E (apo E) genes and the serum lipid profile in pregnancy and puerperium. Non-diabetic women of European descent in the third semester of pregnancy (N = 120) were selected. Those with diseases or other condition that could modify their lipid profile were excluded from the study (N = 32). Serum lipids were measured by routine laboratory procedures and genomic DNA was extracted by a salting out method. LPL (PvuII and HindIII) and apo E (HhaI) SNPs were detected by the polymerase chain reaction and restriction fragment length polymorphism. Categorical and continuous variables were compared by the chi-square test and Student t-test or ANOVA, respectively. Women carrying the LPL P1P1 genotype had higher serum LDL cholesterol (N = 21; 155 +/- 45 mg/dL) than women carrying the P1P2/P2P2 genotypes (N = 67; 133 +/- 45 mg/dL; P = 0.032). During the puerperium period, serum levels of triglycerides and VLDL cholesterol were significantly reduced in women carrying the P1P1 (73%, P = 0.006) and P1P2 (51%, P = 0.002) genotypes but not in women carrying the P2P2 genotype (23%, P > 0.05). On the other hand, serum concentrations of lipids did not differ between the LPL HindIII and apo E genotypes during pregnancy and after delivery. We conclude that LPL PvuII SNP is associated with variations in serum lipids during pregnancy and the puerperal period in non-diabetic women.
Assuntos
Apolipoproteínas E/genética , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Lipídeos/sangue , Lipase Lipoproteica/genética , Período Pós-Parto/sangue , Gravidez/sangue , Adolescente , Adulto , Análise de Variância , DNA/análise , Feminino , Frequência do Gene , Genótipo , Humanos , Lipídeos/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único/genética , Valores de Referência , População BrancaRESUMO
The aim of the present study was to determine if there is an association between the single nucleotide polymorphisms (SNPs) of the lipoprotein lipase (LPL) and apolipoprotein E (apo E) genes and the serum lipid profile in pregnancy and puerperium. Non-diabetic women of European descent in the third semester of pregnancy (N = 120) were selected. Those with diseases or other condition that could modify their lipid profile were excluded from the study (N = 32). Serum lipids were measured by routine laboratory procedures and genomic DNA was extracted by a salting out method. LPL (PvuII and HindIII) and apo E (HhaI) SNPs were detected by the polymerase chain reaction and restriction fragment length polymorphism. Categorical and continuous variables were compared by the chi-square test and Student t-test or ANOVA, respectively. Women carrying the LPL P1P1 genotype had higher serum LDL cholesterol (N = 21; 155 ± 45 mg/dL) than women carrying the P1P2/P2P2 genotypes (N = 67; 133 ± 45 mg/dL; P = 0.032). During the puerperium period, serum levels of triglycerides and VLDL cholesterol were significantly reduced in women carrying the P1P1 (73 percent, P = 0.006) and P1P2 (51 percent, P = 0.002) genotypes but not in women carrying the P2P2 genotype (23 percent, P > 0.05). On the other hand, serum concentrations of lipids did not differ between the LPL HindIII and apo E genotypes during pregnancy and after delivery. We conclude that LPL PvuII SNP is associated with variations in serum lipids during pregnancy and the puerperal period in non-diabetic women.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Apolipoproteínas E/genética , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Lipídeos/sangue , Lipase Lipoproteica/genética , Período Pós-Parto/sangue , Gravidez/sangue , Análise de Variância , DNA , População Branca , Frequência do Gene , Genótipo , Lipídeos/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único/genética , Valores de ReferênciaRESUMO
BACKGROUND: Oxidative stress plays an important role in the pathophysiology of diabetes mellitus. The aim of this study was to evaluate the formation of cholesterol oxides (ChOx) as biomarkers of oxidative stress in subjects with impaired glucose tolerance (IGT) and diabetes. METHODS: Blood plasma levels of cholesterol oxidation products were determined in the following groups: type 1 diabetes mellitus (DM1), type 2 diabetes (DM2), impaired glucose tolerance (IGT), children without diabetes (C1) and adults without diabetes (C2). The serum levels of cholest-5-ene-3alpha,7alpha-diol (7alpha-hydroxycholesterol, 7alpha-OH), cholest-5-ene-3beta,7beta-diol (7beta-hydroxycholesterol, 7beta-OH), 3beta-hydroxycholest-5-7-one (7-ketocholesterol, 7-K), 5alpha-cholestane-3beta,5,6beta-triol (cholestanetriol), 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol (cholesterol-5alpha,6alpha-epoxide,), 5,6beta-epoxy-5beta-cholestan-3beta-ol (cholesterol-5beta,6beta-epoxide) and cholest-5-eno-3beta,25-diol (25-hydroxycholesterol, 25-OH) (trivial name and abbreviations indicated in parentheses) were quantified by gas chromatography using flame ionization detection. RESULTS: The levels of total ChOx were elevated in the DM1 and DM2 groups compared to age-matched subjects without diabetes (p < 0.05). The concentrations of 7beta-hydroxycholesterol, cholesterol-alpha-epoxide and cholesterol-beta-epoxide were higher in the blood plasma of subjects in the DM2 group than in the blood plasma of subjects in the C2 and IGT groups (p < 0.05). Treatment of type 2 diabetic patients with oral hypoglycemic drugs associated with insulin resulted in lower concentrations of nitrotyrosine in the blood plasma without significant changes in the concentrations of glucose and glycated hemoglobin. Moreover, combination with statins in both treatments decreased the concentrations of ChOx. CONCLUSIONS: ChOx are suitable biomarkers of oxidative stress and may be useful in clinical studies to follow drug effects on lipid oxidative modifications in diabetic patients.
Assuntos
Colesterol/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Estresse Oxidativo/fisiologia , Adolescente , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Biomarcadores , Criança , Colestanóis/sangue , Colesterol/análogos & derivados , Colesterol/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Intolerância à Glucose/sangue , Humanos , Hidroxicolesteróis/sangue , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Cetocolesteróis/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Background Rosiglitazone is a thiazolidinedione that reduces insulin resistance and might preserve insulin secretion.
The aim of this study was to assess prospectively the drugs ability to prevent type 2 diabetes in individuals at high risk
of developing the condition.
Methods 5269 adults aged 30 years or more with impaired fasting glucose or impaired glucose tolerance, or both, and
no previous cardiovascular disease were recruited from 191 sites in 21 countries and randomly assigned to receive
rosiglitazone (8 mg daily; n=2365) or placebo (2634) and followed for a median of 3 years. The primary outcome was
a composite of incident diabetes or death. Analyses were done by intention to treat. This trial is registered at
Findings At the end of study, 59 individuals had dropped out from the rosiglitazone group and 46 from the placebo
group. 306 (11·6%) individuals given rosiglitazone and 686 (26·0%) given placebo developed the composite primary
outcome (hazard ratio 0·40, 95% CI 0·350·46; p<0·0001); 1330 (50·5%) individuals in the rosiglitazone group and
798 (30·3%) in the placebo group became normoglycaemic (1·71, 1·571·87; p<0·0001). Cardiovascular event rates
were much the same in both groups, although 14 (0·5%) participants in the rosiglitazone group and two (0·1%) in the
Interpretation Rosiglitazone at 8 mg daily for 3 years substantially reduces incident type 2 diabetes and increases the
likelihood of regression to normoglycaemia in adults with impaired fasting glucose or impaired glucose tolerance, or