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JMIR Res Protoc ; 7(6): e163, 2018 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-29959115


BACKGROUND: Dyslipidemia is a major modifiable risk factor for atherosclerotic cardiovascular disease. Current South African guidelines recommend titrating lipid-lowering therapy (LLT) to low-density lipoprotein cholesterol (LDL-C) targets stratified by cardiovascular risk. The LDL-C goal for very high-risk patients is <1.8 mmol/L. In international studies, approximately 30% of patients do not achieve this goal despite receiving maximally tolerated statin doses. There is, however, a paucity of data on LDL-C goal achievement in very high-risk South African patients receiving maximal statin doses. OBJECTIVE: The goal of the research it to assess LDL-C goal achievement in, and clinical characteristics of, very high cardiovascular risk dyslipidemic patients receiving maximal tolerated statin doses with or without ezetimibe. METHODS: This is an observational, cross-sectional South African registry study that plans to include up to 30 sites and 500 study participants. Adult patients with very high cardiovascular risk status receiving stable, maximally tolerated statin doses (with or without ezetimibe) will be eligible for inclusion. RESULTS: Funding has been awarded and enrollment began on November 15, 2017, and was completed on April 13, 2018, with 507 participants. Database lock was done on June 21, 2018. The statistical analysis has commenced and we expect the final clinical study report to be completed by October 2018. CONCLUSIONS: This study will document the adequacy of LLT in those at highest risk and will thus fill an important data gap in South Africa. This data may be useful in assessing the need for novel LLTs like proprotein convertase subtilisin/kexin 9 inhibitors that substantially lower cholesterol levels in addition to optimal statin therapy. REGISTERED REPORT IDENTIFIER: RR1-10.2196/9248.

PLoS One ; 9(1): e86350, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24466047


BACKGROUND: Addison's disease (AD) has been associated with an increased risk of cardiovascular disease. Glucocorticoid receptor polymorphisms that alter glucocorticoid sensitivity may influence metabolic and cardiovascular risk factors in patients with AD. The 9ß polymorphism of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance and has been reported to increase the risk of myocardial infarction in the elderly. We explored the impact of this polymorphism in patients with AD. MATERIALS AND METHODS: 147 patients with AD and 147 age, gender and ethnicity matched healthy controls were recruited. Blood was taken in a non-fasted state for plasma lipid determination, measurement of cardiovascular risk factors and DNA extraction. RESULTS: Genotype data for the 9ß polymorphism was available for 139 patients and 146 controls. AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense LDL (p = 0.003), increased triglycerides (p = 0.002), reduced HDLC (p<0.001) an elevated highly sensitive C-reactive protein (p = 0.01), compared with controls. The 9ß polymorphism (at least one G allele) was found in 28% of patients and controls respectively. After adjusting for age, gender, ethnicity, BMI and hydrocortisone dose per metre square of body surface area in patients, there were no significant metabolic associations with this polymorphism and hydrocortisone doses were not higher in patients with the polymorphism. CONCLUSIONS: This study did not identify any associations between the 9ß polymorphism and cardiovascular risk factors or hydrocortisone dose and determination of this polymorphism is therefore unlikely to be of clinical benefit in the management of patients with AD.

Doença de Addison/genética , Receptores de Glucocorticoides/genética , Doença de Addison/tratamento farmacológico , Adulto , Anti-Inflamatórios/administração & dosagem , Doenças Cardiovasculares/genética , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Hidrocortisona/administração & dosagem , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco
Cardiovasc J Afr ; 24(6): 238-42, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24217264


AIM: The aim of the CEntralised Pan-South African survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS SA) was to evaluate the current use and efficacy of lipid-lowering drugs (LLDs) in urban patients of different ethnicity with hyperlipidaemia, and to identify possible patient characteristics associated with failure to achieve low-density lipoprotein cholesterol (LDL-C) targets. There is little published data on LDL-C attainment from developing countries. METHOD: The survey was conducted in 69 study centres in South Africa and recruited consecutive patients who had been prescribed LLDs for at least three months with no dose adjustment for six weeks. All patients provided written consent. One visit was scheduled for data collection, including fasting lipid and glucose, and HbA1c levels. RESULTS: Of the 3 001 patients recruited, 2 996 were included in the final analyses; 1 385 subjects were of Caucasian origin (818 male), 510 of African ancestry (168 male), 481 of mixed ancestry (222 male) and 620 of Asian origin (364 male). Only 60.5% of patients on LLDs for at least three months achieved the LDL-C targets recommended by the NCEP ATP III/2004 updated NCEP ATP III guidelines and 52.3% the fourth JETF/South African guidelines. African females were on average younger than females of other ethnic origins, and had the lowest smoking rates but the highest prevalence of obesity, hypertension, the metabolic syndrome and diabetes mellitus (DM), with the worst glycaemic control. Although women were less likely than men to reach goal [OR 0.65 (CI 0.54-0.77), p < 0.001 for NCEP ATP III guidelines and OR 0.76 (CI 0.64-0.91), p < 0.003 for fourth JETF guidelines], women of African ancestry were just as likely not to reach goal as their Caucasian counterparts. CONCLUSION: The results of this survey highlight the sub-optimal lipid control achieved in many South African patients, and profile important gender and ethnic differences. Control of cardiovascular disease risk factors across gender and ethnic groups remains poor.

Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Grupos Étnicos , Hipercolesterolemia/tratamento farmacológico , Grupo com Ancestrais do Continente Africano , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etnologia , LDL-Colesterol/sangue , Comorbidade , Países em Desenvolvimento , Grupo com Ancestrais do Continente Europeu , Feminino , Fidelidade a Diretrizes , Pesquisas sobre Serviços de Saúde , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/etnologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Prevalência , Fatores de Risco , Fatores Sexuais , África do Sul/epidemiologia , Resultado do Tratamento , Saúde da População Urbana
Semin Vasc Med ; 4(1): 43-50, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15199432


Mutations in the low-density lipoprotein (LDL) receptor gene cause familial hypercholesterolemia. In homozygous familial hypercholesterolemia, both genes for the LDL- receptor are mutated and LDL levels are markedly elevated. High-density lipoprotein cholesterol concentration is often reduced and lipoprotein(a) levels are high when corrected for apolipoprotein(a) isoforms. Cutaneous and tendinous xanthomata develop in childhood and are the most common reason for initial presentation. The diagnosis can be confirmed by analysis of LDL-receptor genes or studies of LDL receptor function in cultured cells. Severe aortic and coronary atherosclerosis usually occurs within the first or second decades of life. Left ventricular outflow tract obstruction may be at the level of the aortic valve or the supravalvar aorta. Treatment for the hyperlipidemia is with plasmapheresis, high-dose statins, and ezetimibe. Liver transplantation reverses the metabolic defect but requires chronic immunosupression, and rejection may still occur. Liver transplantation is indicated if cardiac transplantation becomes necessary. Portocaval shunt may still play a role in patients with coronary artery disease who do not have access to plasmapheresis. Gene therapy is currently not practicable but is being actively developed.

Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/terapia , Biomarcadores/sangue , Gerenciamento Clínico , Predisposição Genética para Doença/genética , Homozigoto , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/metabolismo
Semin Vasc Med ; 4(1): 93-5, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15199438


South Africa, especially the Caucasian part of the population, has one of the highest incidences of familial hypercholesterolemia in the world. The founder effect in this region has led to this high incidence and to a limited number of mutations in the low-density lipoprotein-receptor gene. This chapter describes current situation concerning the management of familial hypercholesterolemia in South Africa.

Hiperlipoproteinemia Tipo II/epidemiologia , Humanos , Incidência , África do Sul/epidemiologia