RESUMO
In 2016, meetings of groups of physicians and paediatricians with a special interest in lipid disorders and familial hypercholesterolaemia were held to discuss several domains of management of familial hypercholesterolaemia in adults and children in Hong Kong. After reviewing the evidence and guidelines for the diagnosis, screening, and management of familial hypercholesterolaemia, consensus was reached on the following aspects: clinical features, diagnostic criteria, screening in adults, screening in children, management in relation to target plasma low-density lipoprotein cholesterol levels, detection of atherosclerosis, lifestyle and behaviour modification, and pharmacotherapy.
Assuntos
Anticolesterolemiantes/uso terapêutico , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Adulto , Doenças Cardiovasculares/prevenção & controle , Criança , Consenso , Gerenciamento Clínico , Humanos , Guias de Prática Clínica como AssuntoRESUMO
WHAT IS KNOWN AND OBJECTIVE: The oral plasma clearance of midazolam and the ratio of 6ß-hydroxycortisol (6ß-OHF) to cortisol (F) in urine are two potential markers for evaluating CYP3A activity in vivo. We assessed the influence of two common CYP3A polymorphisms on the pharmacokinetics of oral midazolam and urinary ratio of 6ß-OHF/F in healthy Chinese. METHODS: Single oral 15 mg doses of midazolam were given to 20 healthy male Chinese subjects who were genotyped for the CYP3A5*3 and CYP3A4*1G polymorphisms. The plasma concentrations of midazolam were determined by LC/MS/MS. Morning urine samples were collected after overnight fasting, and urine F and 6ß-OHF concentrations were measured using UPLC. RESULTS AND DISCUSSION: There were no significant correlations between the pharmacokinetic parameters of midazolam and urinary ratios of 6ß-OHF/F. The CYP3A polymorphisms examined had no significant associations with the urinary ratios of 6ß-OHF/F or the pharmacokinetics of midazolam. However, diplotype analysis suggested that CYP3A5 expressers with the CYP3A4*1/*1G genotype (n = 3) had significantly lower midazolam AUC0-∞ values (210·0 ± 33·5 vs. 313·9 ± 204·6 hâng/mL, P = 0·044) and higher CL/F values (1·16 ± 0·16 vs. 0·88 ± 0·48 L/h/kg, P = 0·005) compared to subjects with the CYP3A4*1/*1 genotype (n = 4), which is consistent with some previous studies with tacrolimus. WHAT IS NEW AND CONCLUSION: There were no significant associations between midazolam pharmacokinetic parameters and urinary ratios of 6ß-OHF/F and the two CYP3A polymorphisms were not associated with the urinary ratios of 6ß-OHF/F or midazolam pharmacokinetic parameters. The possible association of CYP3A5*3 and CYP3A4*1G polymorphisms on CYP3A activity and their potential interaction require confirmation in a larger study.
Assuntos
Biomarcadores/urina , Citocromo P-450 CYP3A/genética , Hidrocortisona/análogos & derivados , Hidrocortisona/urina , Midazolam/farmacocinética , Polimorfismo Genético/genética , Adulto , Povo Asiático/genética , Biomarcadores/sangue , Estudos Cross-Over , Genótipo , Humanos , Masculino , Midazolam/administração & dosagem , Midazolam/sangue , Tacrolimo/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: It is unclear if higher-dose oseltamivir provides benefit beyond the standard dose in influenza patients who require hospitalization. METHODS: A prospective intervention study was performed in 2 acute care general hospitals in Hong Kong over 4 seasonal peaks (2010-2012). Adults (≥18 years) with laboratory-confirmed influenza (85 A/H3N2, 34 A/H1N1pdm09, 36 B) infections who presented within 96 hours were recruited. Study regimen of either 150 mg or 75 mg oseltamivir twice daily for 5 days was allocated by site, which was switched after 2 seasons. Subjects with preexisting renal impairment (creatinine clearance, 40-60 mL/minute) received 75 mg oseltamivir twice daily. Viral clearance by day 5 and clinical responses were compared between groups. Plasma steady-state trough oseltamivir carboxylate (OC) concentration was measured by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Altogether, 41 and 114 patients received 150 mg and 75 mg twice-daily oseltamivir, respectively; their enrollment characteristics (mean age, 61 ± 18 vs 66 ± 16 years) and illness severity were comparable. Trough OC levels were higher in the 150-mg group (501.0 ± 237.0 vs 342.6 ± 192.7 ng/mL). There were no significant differences in day 5 viral RNA (44.7% vs 40.2%) or culture negativity (100.0% vs 98.1%), RNA decline rate, and durations of fever, oxygen supplementation, and hospitalization. Results were similar when analyzed by study arm (all cases and among those without renal impairment). Subanalysis of influenza B patients showed faster RNA decline rate (analysis of variance, F = 4.14; P = .05) and clearance (day 5, 80.0% vs 57.1%) with higher-dose treatment. No oseltamivir resistance was found. Treatments were generally well tolerated. CONCLUSIONS: We found no additional benefit of higher-dose oseltamivir treatment in adults hospitalized with influenza A, but an improved virologic response in influenza B. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, NCT01052961.
Assuntos
Antivirais/administração & dosagem , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Oseltamivir/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antivirais/sangue , Antivirais/farmacocinética , Feminino , Hong Kong/epidemiologia , Hospitalização , Humanos , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Oseltamivir/sangue , Oseltamivir/farmacocinética , Estudos Prospectivos , Resultado do Tratamento , Carga ViralRESUMO
WHAT IS KNOWN AND OBJECTIVE: Niacin commonly causes cutaneous flushing, which is partially alleviated by laropiprant, a selective antagonist of prostaglandin D2 at the DP1 receptor. Here we report an unusually high incidence of exanthematous eruption associated with the use of the extended-release (ER) niacin/laropiprant combination treatment in Hong Kong Chinese patients. CASE DESCRIPTION: Among 201 patients treated with ER niacin/laropiprant 1000/20 mg over 7 days to assess flushing symptoms and 166 of the patients who continued the treatment for 12 weeks (doubling the dose after 4 weeks), 28 patients (14%) developed a highly pruritic cutaneous eruption at a mean of 5 days after starting the treatment or 4 days after increasing the dose. This resolved over several days after drug withdrawal with symptomatic treatment. Compared with the subjects who completed 12-weeks treatment uneventfully, those who developed cutaneous eruption were older, had significantly lower body weight, were taking background lipid-lowering treatment more frequently and had greater flushing responses in the first few days of treatment. WHAT IS NEW AND CONCLUSION: The relationship of the exanthematous eruption with lower body weight and the increase in dosage suggests a pharmacokinetic effect that may be related to increased exposure to niacin or its metabolites and provoked by inhibition of the DP1 receptor with laropiprant, as we have not seen this rash with niacin used alone. This may suggest that the southern Chinese population may have some genetic predisposition; as such, a high frequency of exanthematous reactions has not been reported in other populations.
Assuntos
Toxidermias/epidemiologia , Indóis/efeitos adversos , Niacina/efeitos adversos , Vitaminas/efeitos adversos , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Biópsia , Peso Corporal/fisiologia , Combinação de Medicamentos , Toxidermias/patologia , Exantema/patologia , Feminino , Antagonistas dos Receptores Histamínicos/uso terapêutico , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prurido/induzido quimicamente , Prurido/patologia , Pele/patologiaRESUMO
A sensitive and specific liquid chromatography tandem mass spectrometric method was developed and validated for the simultaneous determination of rosuvastatin (ROS) and N-desmethyl rosuvastatin (NOR-ROS) in human plasma using deuterium-labeled internal standards. The plasma samples were prepared using liquid-liquid extraction with diethyl ether. Chromatographic separation was accomplished on an Xterra MS C18 column. The mobile phase consisted of a gradient mixture of 15 µmol/L ammonium acetate in water and in methanol, maintained at a flow rate of 0.4 mL/min. Mass spectrometric detection was carried out in negative electrospray ionization mode and monitored by quantification and qualification transitions for each analyte. Using 300 µL plasma samples, the lower limits of quantification of ROS and NOR-ROS were 0.05 and 0.02 µg/L respectively. The linearity of ROS and NOR-ROS ranged from 0.05 to 42 and 0.02 to 14 µg/L respectively. The relative standard deviations of ROS and NOR-ROS were <13 and 9%, respectively, while the deviations from expected values were within -4.7-9.8 and -5.2-4.6%, respectively. The present method offered high sensitivity and was successfully applied to a 24 h pharmacokinetic study of ROS and NOR-ROS in healthy subjects receiving a single dose of 10 mg ROS.
Assuntos
Cromatografia Líquida/métodos , Fluorbenzenos/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/sangue , Pirimidinas/sangue , Espectrometria de Massas por Ionização por Electrospray/métodos , Sulfonamidas/sangue , Humanos , Limite de Detecção , Rosuvastatina Cálcica , Espectrometria de Massas em Tandem/métodosRESUMO
BACKGROUND: Allopurinol has been reported as a common cause of severe cutaneous adverse reactions (SCARs). Recent studies in various populations suggest that HLA-B*58:01 is a strong genetic marker for allopurinol-induced SCAR, especially in populations with a high frequency of HLA-B*58:01. OBJECTIVES: To confirm the association link between HLA-B*58:01 and hypersensitivity reactions attributed to allopurinol use in Han Chinese patients in Hong Kong. METHODS: We performed a case-control study to investigate whether the HLA-B*58:01 allele predisposes to allopurinol-induced SCAR in Han Chinese patients in Hong Kong. The HLA-B*58:01 genotyping was performed in 20 patients with allopurinol-induced SCAR or erythema multiforme major (EMM; n = 1) and in 30 patients tolerant to allopurinol. RESULTS: All of the 19 patients with allopurinol-induced SCAR examined but not the patient with EMM carried HLA-B*58:01 whereas only four (13%) of the control patients had this allele. The positive rate of the HLA-B*58:01 was significantly higher in the cases than in the allopurinol-tolerant control group [odds ratio (OR) 123·5, 95% confidence interval (CI) 12·8-1195·1; P < 1 × 10(-4) ] and was even higher after removal of the patient with EMM (OR 229·7, 95% CI 11·7-4520·4). The sensitivity and specificity of the HLA-B*58:01 allele for prediction of allopurinol-induced SCAR were 100% and 86·7%, respectively. CONCLUSIONS: This study confirmed the strong association between the HLA-B*58:01 and allopurinol-induced SCAR in Hong Kong Han Chinese patients. A screening test for the HLA-B*58:01 allele should effectively reduce the risk for allopurinol-induced SCAR in Chinese populations.
Assuntos
Alopurinol/efeitos adversos , Toxidermias/genética , Antígenos HLA-B/genética , Uricosúricos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/etnologia , Estudos de Casos e Controles , Toxidermias/etnologia , Feminino , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Genótipo , Hong Kong/etnologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To ascertain the effect of rosuvastatin on carotid atherosclerosis and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: Fifty RA patients were randomized in a double-blind placebo-controlled trial to receive 10 mg rosuvastatin (n = 24) or placebo (n = 26). Patients were followed prospectively every 3 months for 12 months. Intima-media thickness (IMT), augmentation index (AIx), and subendocardial viability ratio (SEVR) were measured at baseline, 6 and 12 months. RESULTS: Rosuvastatin resulted in statistically significant reductions of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and urate levels vs. placebo. However, rosuvastatin had no significant effect on changes in inflammatory markers, including C-reactive protein (CRP) levels [from 2.9 (1.4-11.0) to 3.1 (0.9-13.3) mg/L in the rosuvastatin group compared with from 5.8 (2.6-14.2) to 4.4 (1.2-12.3) mg/L in the placebo group]. Nonetheless, a significant improvement in the Disease Activity Score (DAS) and a reduction in fibrinogen level was observed at 6 and 12 months compared with baseline in the rosuvastatin group. The treatment group exhibited a significant increase in SEVR (from 157 ± 28% to 163 ± 33% in the rosuvastatin group compared with from 143 ± 18% to 143 ± 26% in the placebo group, p = 0.023), but no significant effect was observed in the changes in IMT and AIx. CONCLUSION: Our data suggest that rosuvastatin has a modest anti-inflammatory effect in RA patients with low disease activity in terms of reduction in DAS and fibrinogen level. Rosuvastastin may also improve subendocardial perfusion and lower the urate level.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Fluorbenzenos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Rigidez Vascular/efeitos dos fármacos , Apolipoproteínas B/sangue , Artrite Reumatoide/fisiopatologia , Aterosclerose/fisiopatologia , Espessura Intima-Media Carotídea , Estenose das Carótidas/diagnóstico por imagem , Colesterol/sangue , Progressão da Doença , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Fatores de Risco , Rosuvastatina Cálcica , Índice de Gravidade de Doença , Resultado do Tratamento , Rigidez Vascular/fisiologiaRESUMO
WHAT IS KNOWN AND OBJECTIVE: Diltiazem shows a pharmacokinetic interaction with statins that are CYP3A substrates but this may not result in myopathy unless additional genetic or clinical factors are present. Subsequent changes in treatment or underlying disease may result in a delayed onset of this adverse affect. Our objective is to report on two cases of statin-induced myopathy associated with concomitant use of diltiazem and other contributing factors, and to briefly review the related literature. COMMENT: A 63-year-old Chinese woman with hypertension and familial hypercholesterolaemia (FH) taking diltiazem 90 mg twice daily had elevation of creatine kinase (CK) to 4016 U/L and alanine aminotransferase (ALT) to 165 IU/L 4 weeks after increasing the dose of simvastatin from 40 to 80 mg daily. Another 80-year-old Chinese woman with FH, mild vascular dementia and hypertension was hospitalized with bilateral lower limb weakness associated with raised CK (8869 IU/L), lactate dehydrogenase (1384 IU/L) and ALT (288 IU/L) after taking diltiazem 60 mg twice daily with simvastatin 40 mg for 11 months. Statin-associated myopathy was suspected and simvastatin was stopped in both cases, and symptoms resolved and all laboratory parameters returned to normal in 2 weeks. The myopathy in both cases is likely to have resulted from an interaction of higher doses of simvastatin with diltiazem through inhibition of CYP3A enzymes and drug transporters. The strength of simvastatin-diltiazem interactions in the two cases estimated by the Drug Interaction Probability Scale (DIPS) indicated a possible association. WHAT IS NEW AND CONCLUSION: The two cases reported here and the brief literature review emphasize the potential interaction between two drugs frequently coadministered, simvastatin and diltiazem and we suggest that diltiazem should not be used with higher doses of those statins metabolized by CYP3A such as simvastatin or atorvastatin and even with lower doses caution should be exercised in patients who may have cause for impaired metabolism.
Assuntos
Anti-Hipertensivos/uso terapêutico , Diltiazem/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Musculares/etiologia , Sinvastatina/efeitos adversos , Idoso de 80 Anos ou mais , Biotransformação/genética , Citocromo P-450 CYP3A/genética , Interações Medicamentosas , Feminino , Hong Kong , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Pessoa de Meia-Idade , Doenças Musculares/induzido quimicamente , Polimorfismo Genético , Sinvastatina/farmacocinética , Resultado do TratamentoRESUMO
OBJECTIVE: To examine the distribution of traditional and novel risk factors of cardiovascular disease (CVD) in patients with PsA compared with healthy controls. METHODS: We compared risk factors for CVD between 102 consecutive PsA patients and 82 controls, adjusting for BMI. We also assessed the role of inflammation on the CVD risk factor by using a BMI and high-sensitivity CRP (hsCRP)-adjusted model. RESULTS: The BMI of PsA patients were significantly higher than healthy controls. After adjusting for the BMI, PsA patients still have a higher prevalence of diabetes mellitus (DM) [odds ratio (OR) 9.27, 95% CI 2.09, 41.09) and hypertension (OR 3.37, 95% CI 1.68, 6.72), but a lower prevalence of low high density lipoprotein (HDL) cholesterol (OR 0.16, 95% CI 0.07, 0.41). PsA patients have significantly increased systolic and diastolic blood pressures, insulin resistance and inflammatory markers (hsCRP and white cell count) compared to controls. PsA patients have higher HDL cholesterol and apolipoprotein (Apo) A1 levels; and lower total cholesterol (TC) and low density lipoprotein cholesterol levels; and a lower TC/HDL ratio. However, the Apo B level (P < 0.05), and the Apo B/Apo A1 ratio (P = 0.07) were higher in PsA patients. Further adjustment for hsCRP level rendered the differences in the prevalence of hypertension and DM; the TC, and sugar levels; and white cell count non-significant between the two groups; while the differences in other parameters remained significant. CONCLUSION: These data support the hypothesis that PsA may be associated with obesity, hypertension, dyslipidaemia and insulin resistance because of the shared inflammatory pathway.
Assuntos
Artrite Psoriásica/complicações , Doenças Cardiovasculares/complicações , Adulto , Apolipoproteínas A/análise , Apolipoproteínas B/análise , Artrite Psoriásica/sangue , Artrite Psoriásica/imunologia , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/imunologia , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Diabetes Mellitus/sangue , Diabetes Mellitus/imunologia , Dislipidemias/sangue , Dislipidemias/complicações , Dislipidemias/imunologia , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/imunologia , Inflamação , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/imunologia , Prevalência , Medição de Risco/métodosAssuntos
Proteínas Facilitadoras de Transporte de Glucose/genética , Gota/genética , Hiperuricemia/genética , Polimorfismo de Nucleotídeo Único , Ácido Úrico/sangue , Povo Asiático , China/etnologia , Feminino , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Gota/etnologia , Humanos , Hiperuricemia/etnologia , Masculino , Fatores SexuaisRESUMO
The relationship between the apolipoprotein E (APOE) exon 4 polymorphism and white matter changes (WMC) in elderly subjects or patients with Alzheimer's disease is controversial. To investigate this polymorphism in relation to WMC in patients with lacunar infarcts, we prospectively observed 67 patients with acute lacunar infarct and 134 age- and sex-matched controls. Genotypes were determined using a nested polymerase chain reaction. WMC were measured quantitatively and were divided into two groups, severe and mild, with the mean volume of WMC as the cut point. Twenty-two patients (33%) had severe WMC. There was a significant difference in the distribution of APOE epsilon2, epsilon3, and epsilon4 alleles between severe and mild WMC groups (P = 0.002). The frequency of epsilon4 alleles was higher in patients with severe WMC than in those with mild WMC (25% vs. 7%, P = 0.003). These results suggest that APOE epsilon4 may exacerbate WMC in patients with lacunar infarcts. Further studies are required to confirm this finding.
Assuntos
Alelos , Apolipoproteínas E/genética , Infarto Encefálico/diagnóstico , Infarto Encefálico/genética , Encéfalo/patologia , Imageamento por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína E2 , Apolipoproteína E3 , Apolipoproteína E4 , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
PURPOSE: To identify the relationship between smoking and the metabolic profile and existing vascular disease in Chinese type 2 diabetic patients. METHODS: 1710 diabetic patients were screened for complications, and biochemical and anthropometric vascular risk factors. As most smokers were male, differences were only compared between male current (n = 196) and never smoking patients (n = 300). RESULTS: The smokers had higher glycosylated haemoglobin levels (8.2 +/- 2.0 vs. 7.6 +/- 1.8%, p < 0.001) than never smokers, despite a greater proportion receiving hypoglycaemic agents (87.5 vs. 79.6%, p = 0.003). Male smokers compared to never smokers had lower HDL-cholesterol levels (1.12 +/- 0.31 vs. 1.20 +/- 0.30 mmol/L, p = 0.006), and elevated albumin-to-creatinine ratio (3.57 [2.68-4.75] vs. 2.47 [1.99-3.05] mg/mmol, p = 0.040). However, diastolic blood pressure was lower in the smoking group (78 +/- 12 vs. 82 +/- 12 mmHg, p = 0.001) even though they received less blood pressure-lowering treatments (23.8 vs. 33.2%, p = 0.034). The prevalence of peripheral vascular disease was increased in the diabetic patients who smoked compared to nonsmokers (7.1 vs. 2.8%, p = 0.039). CONCLUSIONS: Smoking was associated with a more adverse metabolic profile and peripheral vascular disease. As mainland China undergoes rapid modernisation and urbanisation, the observed effects of smoking means tobacco control becomes increasingly important to prevent or minimise potential health impacts and chronic disease.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Fumar/efeitos adversos , Adulto , Idoso , Povo Asiático , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Socio-economic status, comorbidities and adherence to statin therapy might affect the cost-effectiveness of statin therapy in hyperlipidemia. OBJECTIVE: To examine the effects size of demographic factors, clinical factors and adherence to statin therapy on the direct medical costs for Chinese patients at high risk of coronary heart disease (CHD). METHODS: This was a prospective, observational cohort study conducted in the outpatient departments of a public teaching hospital in Hong Kong. Patients at high risk of CHD who had been on statin monotherapy for < 12 months were recruited. Baseline demographic and clinical data were obtained. Statin adherence was monitored prospectively over 6 months using the Medication Event Monitoring System. Total direct medical costs per member per month (cPMPM), including cost for clinic visits, statin medication, laboratory tests on lipids and management of CHD events if any, were calculated from the perspective of a public healthcare organization. RESULTS: 83 patients completed the study. Median cPMPM in 80 patients (96% of 83 patients) without a new CHD event (USD 42) and for 3 (4%) patients who experienced CHD events (USD 444) were significantly different (p = 0.003). History of congestive heart failure (beta = 1,957, 95% CI = 1,006 - 2,909), male gender (beta = 584, 95% CI = 215 - 952), coronary atherosclerosis (beta = 1,436, 95% CI = 538 - 2,334) and diabetes mellitus (beta = 604, 95% CI = 136 - 1,07 1) were positive predictors for cPMPM. CONCLUSION: In this pilot study male gender, diabetes mellitus, congestive heart failure and coronary atherosclerosis appear to be significantly associated with higher costs for Chinese patients at high risk of CHD.
Assuntos
Doença das Coronárias/prevenção & controle , Custos de Cuidados de Saúde , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Estudos de Coortes , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/economia , Doença das Coronárias/economia , Doença das Coronárias/etiologia , Análise Custo-Benefício , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/economia , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/economia , Hong Kong , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/economia , Hiperlipidemias/complicações , Hiperlipidemias/economia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Projetos Piloto , Estudos Prospectivos , Fatores de Risco , Distribuição por Sexo , Fatores SexuaisRESUMO
Overswinging or CHAT (brief for Circadian Hyper-Amplitude-Tension), that is an excessive circadian variation in blood pressure (BP), has been associated with a large increase in cardiovascular disease risk, present even in the absence of an elevated BP itself. This usually asymptomatic condition is usually overlooked by current practice based on spot-checks, because to be diagnosed, measurements need to be taken around-the-clock, preferably for 7 days at the outset. Once diagnosed, however, a usual circadian BP pattern can be restored by means of certain non-pharmacologic or pharmacologic interventions timed appropriately. Thereby, it is possible to reduce the risk of cardiovascular morbidity and mortality, cerebral ischemic events and nephropathy in particular. For the preparation of guidelines regarding the diagnosis of BP disorders and for the institution of primary as well as secondary preventive measures, it is important to know what the incidence of CHAT is on a global basis. We found 191 cases of CHAT among 1602 mostly 7-day/24-h BP profiles, obtained from several centers in different countries participating in an ongoing project on the BIOsphere and the COSmos (BIOCOS). CHAT incidence is about the same between men and women, but it is diagnosed more often among patients with borderline hypertension or with glucose intolerance. It is also more common among MESOR-hypertensive than among MESOR-normotensive individuals. Priority should be given to the development of an unobtrusive and affordable device to automatically monitor BP and to analyze the data as-one-goes, so that cardiovascular disease risk can be prevented.
Assuntos
Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Hipertensão/diagnóstico , Adulto , Feminino , Intolerância à Glucose/complicações , Frequência Cardíaca/fisiologia , Humanos , Hipertensão/epidemiologia , Japão/epidemiologia , Masculino , Medição de Risco , População Rural , Acidente Vascular Cerebral/epidemiologia , População UrbanaRESUMO
BACKGROUND: Lp(a) lipoprotein level is an independent risk factor for premature coronary artery disease and cerebrovascular accident. Concentrations of this lipoprotein tend to increase after menopause. OBJECTIVE: To determine whether oral estrogen was effective in lowering concentrations of Lp(a) lipoprotein in postmenopausal women. METHODS: A double-blind, placebo-controlled, cross-over study was conducted during a 12-month period in 100 postmenopausal women who had undergone hysterectomy. They were randomized into two groups: group 1 received oral estradiol, 2 mg/d, for the first 6 months and placebo for the second, and group 2 received these treatments in the reverse order. After completion of the crossover study, the effect of prolonged administration of oral estradiol was examined by placing all patients on active treatment and repeating the lipoprotein measurements approximately 12 months later. RESULTS: No significant differences were noted between the two groups at the commencement of the study (median concentration of Lp[a] lipoprotein, 10.78 mg/dL [range, 2.2 to 108.5 mg/dL] in group 1 and 12.74 mg/dL [range, 0.8 to 98.1 mg/dL] in group 2). Crossover analysis showed a 9.62% reduction in values of Lp(a) lipoprotein with estradiol treatment compared with placebo during 12 months of treatment (P < .001). With prolonged treatment, the median concentration of Lp(a) lipoprotein for those in group 1 decreased from 8.12 mg/dL (range, 1.05 to 57.4 mg/dL) to 5.77 mg/dL (range, 0.84 to 75.39 mg/dL) (P < .001). In group 2, the median concentration decreased from 8.19 mg/dL (range, 2.52 to 99.82 mg/dL) to 7.07 mg/dL (range, 0.70 to 48.79 mg/dL), but this difference was not significant (P = .63). CONCLUSIONS: The results of this study confirm the beneficial effect of oral estradiol on the basic lipoprotein pattern and demonstrate that this treatment is effective in reducing concentrations of Lp(a) lipoprotein in postmenopausal women.
Assuntos
Estradiol/farmacologia , Estriol/farmacologia , Terapia de Reposição de Estrogênios , Lipoproteína(a)/sangue , Lipoproteína(a)/efeitos dos fármacos , Pós-Menopausa/sangue , Pós-Menopausa/efeitos dos fármacos , Administração Oral , Adulto , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To compare the metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients. RESEARCH DESIGN AND METHODS: After a 2-wk run-in period on dietary treatment alone, 12 Chinese normotensive patients with uncomplicated NIDDM were randomized to receive either metformin, or glibenclamide for 4 wk before being crossed-over to the alternative treatment for an additional 4 wk. Metabolic and hemodynamic index, including cardiac output estimation by impedance cardiography, were measured at baseline and at the end of each treatment period. RESULTS: Body mass index was reduced more with metformin than with glibenclamide, although glycemic control was similar with both drugs. Plasma total cholesterol concentration fell more with metformin (mean difference -0.65 mM, 95% confidence interval -0.96 to -0.32) than glibenclamide (mean difference -0.20 mM, 95% confidence interval -0.54-0.12) (P < 0.05). Compared with baseline values, erect diastolic blood pressure was reduced more by metformin (12.9% [95% confidence interval -21.5 to -4.4%]) than glibenclamide (-6.8% [95% confidence interval -14.9 to 1.2%]) (P < 0.001). The relative changes in the systemic vascular resistance index also differed between the two treatments (glibenclamide, 6.2 [-4.3 to 16.6%]; metformin, -1.2 [95% confidence interval -8.8-6.4%]) (P < 0.05)]. CONCLUSIONS: In normotensive NIDDM patients, treatment with metformin was associated with greater reductions in body weight, plasma total cholesterol concentration, and erect diastolic blood pressure, whereas the systemic vascular resistance index increased after treatment with glibenclamide. These findings merit long-term investigation.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Glibureto/farmacologia , Glibureto/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Metformina/farmacologia , Metformina/uso terapêutico , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Frutosamina , Hemoglobinas Glicadas/análise , Frequência Cardíaca/efeitos dos fármacos , Hexosaminas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Postura , Triglicerídeos/sangue , Resistência Vascular/efeitos dos fármacosRESUMO
OBJECTIVE: To compare the effects of nifedipine and enalapril on carbohydrate and lipoprotein metabolism in Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension. RESEARCH DESIGN AND METHODS: A 12-week, double-blind, randomized study of plasma lipid levels and glycemic control in patients treated with nifedipine (n = 52) or enalapril (n = 50) was conducted. None of the patients were treated with insulin. Diet and dosages of oral hypoglycemic agents remained unchanged during the 12-week treatment period. RESULTS: Mean arterial pressure was reduced more by nifedipine than by enalapril (23.1 vs. 11.1 mmHg, P < 0.001). Similar reductions in body mass index and plasma triglycerides and increases in apolipoprotein A-I were seen with both treatments, but HbA1 was reduced more during treatment with enalapril than with nifedipine (0.49 vs. 0.20%, P = 0.035) and serum apolipoprotein B (apoB) also declined more with enalapril than with nifedipine (8.2 vs. 2.3 mg/dl, P = 0.009). CONCLUSIONS: Twelve weeks of treatment with enalapril in hypertensive NIDDM patients was associated with greater improvement in glycemic control and greater reduction in serum apoB concentration, although the reduction in blood pressure was less than with nifedipine. These changes in cardiovascular risk profile warrant investigation for a longer term.