RESUMEN
Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is used for decades, lowering serum LDL-C levels by more than 70% directly after the treatment. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.
Asunto(s)
Eliminación de Componentes Sanguíneos , Consenso , Homocigoto , Humanos , Eliminación de Componentes Sanguíneos/métodos , Niño , Resultado del Tratamiento , Lipoproteína(a)/sangre , LDL-Colesterol/sangre , Adolescente , Trasplante de Hígado , Biomarcadores/sangre , Hiperlipoproteinemia Tipo I/diagnóstico , Hiperlipoproteinemia Tipo I/terapia , Hiperlipoproteinemia Tipo I/sangre , Hiperlipoproteinemia Tipo I/genética , Fenotipo , Hiperlipoproteinemia Tipo II/terapia , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/diagnóstico , Preescolar , Lipoproteínas/sangre , Predisposición Genética a la EnfermedadRESUMEN
Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is well established since three decades, lowering serum LDL-C levels by more than 70% per session. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment targets and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.
RESUMEN
Diabetes mellitus type 1 (T1DM) is an autoimmune disease characterized by a markedly elevated cardiovascular (CV) risk due to premature atherosclerosis. Previous studies have shown that intense glycemic control reduces the incidence of CV disease. Antiplatelet therapy is considered to be a very important therapy for secondary prevention of recurrent atherothrombotic events in patients with DM, while it may be considered for primary prevention in individuals with T1DM with additional CV risk factors. The aim of the present review is to summarize existing literature data regarding the thrombotic risk in T1DM patients and discuss current treatment strategies.
Asunto(s)
Aterosclerosis , Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 1 , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevención SecundariaRESUMEN
AIM: We evaluated the lipid-lowering (LL) effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with heterozygous familial hypercholesterolemia (HeFH) treated with LL-drugs and lipoprotein apheresis (LA). PATIENTS AND METHODS: The PCSK9i treatment (evolocumab 420 mg/4 weeks, alirocumab 150 mg/2 weeks, or alirocumab 75 mg/2 weeks: 9, 6, and 2 patients, respectively) was initiated in patients with HeFH (n = 17; aged 35-69 years, 10 men, previously treated with statins + ezetimibe ± colesevelam and LA sessions for 2-12 years). A lipid profile was obtained before and immediately after the LA session and before, 1 and 2 months after switching to PCSK9i treatment. The duration of PCSK9i therapy ranged from 3 to 18 months. RESULTS: Median total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels before LA were 268, 198, 46, and 126 mg/dL, respectively, and decreased (at the end of the LA session) to 117, 50, 40, and 51 mg/dL, respectively (P < .001 for TC and P = .001 for all other comparisons). The median time-averaged LDL-C levels following LA were 155 (121, 176; median [25th, 75th percentile]) mg/dL. Median TC, LDL-C, and TG levels before PCSK9i therapy were 269, 190, and 127 mg/dL and decreased to 152, 100, and 95 mg/dL, respectively (P = .002, P < .002, and P < .03, respectively). Steady LDL-C levels with PCSK9i treatment were significantly lower compared with time-averaged LDL-C levels following LA (median value: 100 vs 155 mg/dL; P = .008). With PCSK9i, from 13 patients with CHD, 6 (46.1%) patients achieved LDL-C <70 mg/dL, and 2 patients (15.4%) achieved LDL-C <100 mg/dL. Lipoprotein apheresis was discontinued in all patients except for 2 who continued once monthly. CONCLUSIONS: PCSK9i can reduce LDL-C more consistently over time compared with a transient decrease following LA in HeFH patients. PCSK9i therapy may reduce the frequency of LA. Larger trials are required to establish the clinical implications of PCSK9i in patients previously on LA.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticolesterolemiantes/uso terapéutico , Eliminación de Componentes Sanguíneos , LDL-Colesterol/sangre , Hiperlipoproteinemia Tipo II/terapia , Inhibidores de PCSK9 , Inhibidores de Serina Proteinasa/uso terapéutico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticolesterolemiantes/efectos adversos , Biomarcadores/sangre , Eliminación de Componentes Sanguíneos/efectos adversos , Terapia Combinada , Femenino , Predisposición Genética a la Enfermedad , Grecia , Heterocigoto , Humanos , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Masculino , Persona de Mediana Edad , Mutación , Fenotipo , Proproteína Convertasa 9/metabolismo , Receptores de LDL/genética , Inhibidores de Serina Proteinasa/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Homozygous familial hypercholesterolemia (hoFH) may cause life-threatening atherosclerotic cardiovascular disease in childhood. Lipoprotein apheresis (LA) is considered a pivotal treatment option, but data on its efficacy, safety and optimal performance are limited. We therefore established an international registry on the execution and outcomes of LA in HoFH children. Here we report LA policies and short-term outcomes. METHODS: We approached centers worldwide, involved in LA in children with hoFH for participation. We collected information on clinical and treatment characteristics on patients aged 0-19 years between November 2016 and November 2018. RESULTS: We included 50 children, treated at 15 sites. Median (IQR) LDL-C levels at diagnosis, on medication and on LA were 19.2 (16.2-22.1), 14.4 (10.8-16.7) mmol/L and 4.6 mmol/L, respectively. Median (IQR) time between diagnosis and start of LA was 2.8 (1.0-4.7) years. Six (12%) patients developed cardiovascular disease during that period. Most children received LA either weekly (43%) or biweekly (37%). Seven (17%) patients reached mean LDL-C levels <3.5 mmol/L, all of them treated at least weekly. Xanthomas were present in 42 (84%) patients at diagnosis and disappeared completely in 19 (45%) on LA. Side effects of LA were minor. There were significant differences in LA conduction between sites in terms of frequency, responsible medical specialities and vascular access. CONCLUSIONS: LA is a safe treatment and may effectively lower LDL-C in children with HoFH. However, there is room for improvement with respect to time of onset and optimization of LA therapy in terms of frequency and execution.
Asunto(s)
Eliminación de Componentes Sanguíneos , LDL-Colesterol/sangre , Hiperlipoproteinemia Tipo II/terapia , Adolescente , Factores de Edad , Biomarcadores/sangre , Eliminación de Componentes Sanguíneos/efectos adversos , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/prevención & control , Niño , Preescolar , Regulación hacia Abajo , Femenino , Predisposición Genética a la Enfermedad , Factores de Riesgo de Enfermedad Cardiaca , Homocigoto , Humanos , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Lactante , Recién Nacido , Masculino , Fenotipo , Sistema de Registros , Factores de Tiempo , Resultado del Tratamiento , Xantomatosis/sangre , Xantomatosis/prevención & control , Adulto JovenRESUMEN
BACKGROUND: Rs619203 (Cys2229Ser) and rs529038 (Asp2213Asn) polymorphisms in the ROS1 gene have been studied in relation to myocardial infarction (MI) yielding inconsistent results. We investigated the role of ROS1 rs529038 polymorphism in coronary artery disease (CAD) in Greeks using a case-control study. METHODS: Genotyping for rs529038 polymorphism was performed using a multiplex PCR technique in patients with CAD (n=294) and controls (n=311). Logistic regression analysis was used to calculate crude and adjusted odds ratios (ORs). RESULTS: Logistic regression analysis did not show any statistically significant effect of ROS1 polymorphism in the occurrence of CAD (AG vs. AA, OR: 1.08, p=0.635; GG vs. AA, OR: 0.62, p=0.220). Adjustment for confounding factors gave similar results, irrespective of the type of disease (i.e., stable coronary artery disease vs. acute coronary syndrome). CONCLUSIONS: Our findings do not support the hypothesis that ROS1 rs529038 polymorphism is an important contributing factor in the etiology of CAD in the Greek population.
Asunto(s)
Asparagina/genética , Ácido Aspártico/genética , Infarto del Miocardio/genética , Polimorfismo Genético , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Anciano , Estudios de Casos y Controles , Femenino , Grecia , Humanos , Masculino , Persona de Mediana Edad , Proteínas Tirosina Quinasas/química , Proteínas Proto-Oncogénicas/químicaRESUMEN
BACKGROUND: This study assessed the gender-specific influence of the cholesteryl ester transfer protein (TaqIB, I405V) and lipoprotein lipase (S447X) polymorphisms on the response to an oral fat tolerance test in heterozygotes for familial hypercholesterolaemia. METHODS: We selected and genotyped 80 men and postmenopausal women heterozygous for familial hypercholesterolaemia (main group) as well as 11 healthy control subjects. Patients were subgrouped based on their response to oral fat tolerance test. The oral fat tolerance test was defined as pathological when postprandial triglyceride concentration was higher than the highest triglyceride concentration observed in healthy subjects (220 mg/dl) at any time (2, 4, 6 or 8 h). RESULTS: In the pathological subgroup, men had significantly higher incremental area under the curve after oral fat tolerance test than postmenopausal women. Furthermore, multivariate analysis revealed a gender association of TaqIB and I405V influence on postprandial lipaemia in this subgroup. CONCLUSION: In conclusion, it seems that gender and TaqIB polymorphism of the cholesteryl ester transfer protein gene were both associated with the distribution of triglyceride values after oral fat tolerance test, only in subjects with a pathological response to oral fat tolerance test. Specifically, men carrying the B2 allele of the TaqIB polymorphism showed a higher postprandial triglyceride peak and a delayed return to basal values compared with women carrying B2. However, further investigations in larger populations are required to replicate and confirm these findings.
Asunto(s)
Proteínas de Transferencia de Ésteres de Colesterol/genética , Hiperlipoproteinemia Tipo II/genética , Lipoproteína Lipasa/genética , Polimorfismo de Nucleótido Simple/genética , Periodo Posprandial/genética , Caracteres Sexuales , Triglicéridos/sangre , Alelos , Estudios de Casos y Controles , Femenino , Humanos , Hiperlipoproteinemia Tipo II/sangre , Masculino , Análisis Multivariante , Análisis de RegresiónRESUMEN
BACKGROUND: Apolipoprotein (apo) E polymorphism has been associated with coronary heart disease (CHD) and obesity. We aimed to determine whether apoE polymorphism is related to CHD in patients with different body mass index (BMI). PATIENTS AND METHODS: A total of 359 CHD men and 248 healthy controls with BMI <27 kg/m2 were genotyped for the apoE polymorphism. The CHD patients were divided into: normoweight (BMI: 24 +/- 1 kg/m2, n=98), overweight (BMI: 27 +/- 1 kg/m2, n=189) and obese (BMI: 32 +/- 2 kg/m2, n=72) groups. RESULTS: There was a significant difference in apoE genotype frequency between normoweight CHD patients and healthy controls (epsilon2epsilon2 + epsilon2epsilon3: 6% vs. 15%, p=0.029; epsilon3epsilon3: 83% vs. 70%, p=0.045, respectively). The apo epsilon3epsilon4 + epsilon4epsilon4 frequency was higher in obese compared with normoweight CHD patients (p=0.043). The severity of CHD was similar in all patients with CHD. CONCLUSION: Normoweight CHD patients, despite having a lower BMI and more favorable lipid profile, did not display any significant difference in CHD severity. This could be partially attributed to the lower frequency of the epsilon2 cardio-protective allele in normoweight CHD patients compared with normoweight healthy individuals.
Asunto(s)
Apolipoproteínas E/genética , Enfermedad Coronaria/genética , Predisposición Genética a la Enfermedad , Obesidad/genética , Polimorfismo Genético , Adolescente , Adulto , Anciano , Apolipoproteínas E/sangre , Índice de Masa Corporal , Comorbilidad , Enfermedad Coronaria/sangre , Enfermedad Coronaria/epidemiología , Femenino , Genotipo , Grecia/epidemiología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/epidemiología , Oportunidad Relativa , Adulto JovenRESUMEN
Postprandial hypertriglyceridaemia, defined as an increase in plasma triglyceride-containing lipoproteins following a fat meal, is a potential risk predictor of atherosclerotic cardiovascular disease and other chronic diseases. Several non-modifiable factors (genetics, age, sex and menopausal status) and lifestyle factors (diet, physical activity, smoking status, obesity, alcohol and medication use) may influence postprandial hypertriglyceridaemia. This narrative review considers the studies published over the last decade that evaluated postprandial hypertriglyceridaemia. Additionally, the genetic determinants of postprandial plasma triglyceride levels, the types of meals for studying postprandial triglyceride response, and underlying conditions (e.g. familial dyslipidaemias, diabetes mellitus, metabolic syndrome, non-alcoholic fatty liver and chronic kidney disease) that are associated with postprandial hypertriglyceridaemia are reviewed; therapeutic aspects are also considered.
Asunto(s)
Análisis Químico de la Sangre/normas , Enfermedades Cardiovasculares/epidemiología , Hipertrigliceridemia/diagnóstico , Periodo Posprandial , Triglicéridos/sangre , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/genética , Consenso , Predisposición Genética a la Enfermedad , Humanos , Hipertrigliceridemia/sangre , Hipertrigliceridemia/epidemiología , Hipertrigliceridemia/genética , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Regulación hacia ArribaRESUMEN
Residual vascular risk exists despite the aggressive lowering of Low-Density Lipoprotein Cholesterol (LDL-C). A contributor to this residual risk may be elevated fasting, or non-fasting, levels of Triglyceride (TG)-rich lipoproteins. Therefore, there is a need to establish whethe a standardised Oral Fat Tolerance Test (OFTT) can improve atherosclerotic Cardiovascular (CV) Disease (ASCVD) risk prediction in addition to a fasting or non-fasting lipid profile. An expert panel considered the role of postprandial hypertriglyceridaemia (as represented by an OFTT) in predicting ASCVD. The panel updated its 2011 statement by considering new studies and various patient categories. The recommendations are based on expert opinion since no strict endpoint trials have been performed. Individuals with fasting TG concentration <1 mmol/L (89 mg/dL) commonly do not have an abnormal response to an OFTT. In contrast, those with fasting TG concentration ≥2 mmol/L (175 mg/dL) or nonfasting ≥2.3 mmol/L (200 mg/dL) will usually have an abnormal response. We recommend considering postprandial hypertriglyceridaemia testing when fasting TG concentrations and non-fasting TG concentrations are 1-2 mmol/L (89-175 mg/dL) and 1.3-2.3 mmol/L (115-200 mg/dL), respectively as an additional investigation for metabolic risk prediction along with other risk factors (obesity, current tobacco abuse, metabolic syndrome, hypertension, and diabetes mellitus). The panel proposes that an abnormal TG response to an OFTT (consisting of 75 g fat, 25 g carbohydrate and 10 g proteins) is >2.5 mmol/L (220 mg/dL). Postprandial hypertriglyceridaemia is an emerging factor that may contribute to residual CV risk. This possibility requires further research. A standardised OFTT will allow comparisons between investigational studies. We acknowledge that the OFTT will be mainly used for research to further clarify the role of TG in relation to CV risk. For routine practice, there is a considerable support for the use of a single non-fasting sample.
Asunto(s)
Análisis Químico de la Sangre/normas , Enfermedades Cardiovasculares/epidemiología , Hipertrigliceridemia/diagnóstico , Periodo Posprandial , Triglicéridos/sangre , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Consenso , Humanos , Hipertrigliceridemia/sangre , Hipertrigliceridemia/epidemiología , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Regulación hacia ArribaRESUMEN
Hypertriglyceridemia is observed in many metabolic diseases such as the metabolic syndrome, diabetes mellitus, or mixed dyslipidemia frequently leading to premature coronary heart disease (CHD). Additionally, several studies have shown that postprandial hypertriglyceridemia is pronounced in patients with CHD, metabolic syndrome, hypertension, and other pathologic conditions. The triglyceride-rich lipoprotein remnants accumulating in the postprandial state seem to be involved in atherogenesis and in events leading to thrombosis. Since abnormal postprandial lipemia is associated with pathologic conditions, its treatment is of clinical importance.Fibrates are of significant help in managing hypertriglyceridemia. This review summarizes the effect of fibric acid derivatives on postprandial lipemia. Fibrates decrease the production of and enhance the catabolism of triglyceride-rich lipoproteins through the activation of peroxisome proliferator-activated receptor-alpha. Results of clinical studies with fibrates have confirmed their action in decreasing postprandial triglyceride levels by increasing lipoprotein lipase activity, decreasing apolipoprotein CIII production, and by increasing fatty acid oxidation in the liver.It is concluded that fibrates are effective agents in lowering the postprandial increase in remnant lipoprotein particles and retinyl palmitate. Furthermore, fibrates can also affect the postprandial lipid profile by increasing hepatic lipase levels and in some cases, by reducing cholesterol ester transfer protein activity. The main target of fibrate therapy is to improve fasting hypertriglyceridemia, which is an essential component associated with improving postprandial lipemia. Fibrates are well tolerated by patients and adverse effects have been reported rarely after their administration.
Asunto(s)
Ácido Clofíbrico/farmacología , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/farmacología , Animales , Ensayos Clínicos como Asunto , Ácido Clofíbrico/efectos adversos , Ácido Clofíbrico/uso terapéutico , Humanos , Hiperlipidemias/sangre , Hipolipemiantes/efectos adversos , Hipolipemiantes/uso terapéutico , Periodo Posprandial , Triglicéridos/sangreRESUMEN
Plasma concentrations of lipids, lipoproteins, and apolipoproteins (apo) are established risk factors for coronary heart disease (CHD). The knowledge of lipid profile may predict the potential victims of cardiovascular disease before its initiation and progression and offer the opportunity for primary prevention. The most common apo E polymorphism has been found to influence blood lipid concentrations and its correlation with CHD has been extensively investigated in the last decade. At younger ages, death from CHD is influenced by genetic factors, while the genetic effect decreases at older ages where environmental factors may play a more prominent role. If apo E polymorphism is an important genetic factor in the pathogenesis of atherosclerosis, it could affect the age of CHD onset. This review analyses the influence of apo E polymorphism on blood lipids and CHD in respect to age.
Asunto(s)
Envejecimiento/genética , Apolipoproteínas E/genética , Enfermedad Coronaria/genética , Apolipoproteínas E/fisiología , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad Coronaria/fisiopatología , Genotipo , Humanos , Metabolismo de los Lípidos/genética , Metabolismo de los Lípidos/fisiología , Lípidos/sangre , Polimorfismo Genético/genética , Factores de RiesgoRESUMEN
The insulin resistance/metabolic syndrome is characterized by the variable co-existence of hyperinsulinemia, obesity, dyslipidemia (small dense low-density lipoprotein, hypertriglyceridemia, and decreased high-density lipoprotein cholesterol), and hypertension. The pathogenesis of the syndrome has multiple origins. However, obesity and sedentary lifestyle coupled with diet and still largely unknown genetic factors clearly interact to produce the syndrome. This multifactorial and complex trait of metabolic syndrome leads to increased risk of cardiovascular disease. The scope of this review is to examine the differences in prevalence of the metabolic syndrome in various groups (eg, according to age, sex, ethnicity, social status, or presence of obesity) that could help with the better understanding of the pathogenesis of this syndrome. This review also considers the impact of metabolic syndrome on cardiovascular disease.
Asunto(s)
Síndrome Metabólico/epidemiología , Enfermedades Cardiovasculares , Humanos , Grupos de Población , PubMed , Literatura de Revisión como Asunto , Factores de RiesgoRESUMEN
The aim of this study was to evaluate the influence of gender differences on triglyceride (TG) response after a fatty meal in clinically defined heterozygous (h) patients with familial hypercholesterolemia (FH). Nineteen hFH men were age-matched with an equal number of premenopausal women. Plasma TG was measured before and 2, 4, 6, and 8 hr after a standardized fat load. The men with hFH had a greater body mass index (BMI) than hFH women. An abnormal postprandial response was observed in 63% and 16% of hFH men and women, respectively. The mean TG-area under the curve value was higher in hFH men compared to hFH women. Both gender (p = 0.032) and BMI (p = 0.006) equally affected postprandial TG response, but fasting TG levels (p <0.001) were the main determinant. In summary, hFH men have higher BMI, fasting TG level, and postprandial TG level, compared to age-matched premenopausal hFH women, which may partially explain the earlier onset of coronary heart disease in hFH men.
Asunto(s)
Heterocigoto , Hipercolesterolemia/fisiopatología , Hiperlipidemias/diagnóstico , Periodo Posprandial , Triglicéridos/sangre , Adulto , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/genética , Hiperlipidemias/sangre , Hiperlipidemias/genética , Masculino , Persona de Mediana Edad , Caracteres SexualesRESUMEN
Acute coronary syndrome (ACS) is associated with both short- and long-term unfavorable prognosis. Therefore, medical societies developed risk scores for predicting mortality and assessing decision-making regarding early aggressive treatment in patients presenting an ACS. The Thrombolysis In Myocardial Infarction and the Global Registry of Acute Coronary Events risk scores are the most extensively investigated scores for ACS. Clinical judgment is also important. Significant differences in aggressive treatment of ACS still exist with respect to gender, age, and ethnicity. The reasons for these discrepancies need to be further elucidated in future studies. Therefore, generalizability of stratifications and risk scores in certain populations should be performed with caution.
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Síndrome Coronario Agudo , Infarto del Miocardio , Humanos , Pronóstico , Sistema de Registros , Medición de RiesgoRESUMEN
The limited distribution of lipoprotein (a) (Lp(a)) to humans, Old World primates and to the European hedgehog, has raised considerable interest and speculation regarding its possible physiological role. Lp(a) has variable circulating concentrations (<0.1 - >100 mg/ml) which are highly genetically determined in humans. These characteristics gave rise to several theories concerning the origins and evolution of Lp(a). Lp(a) has a protective role after injury since Lp(a) particles bind to macrophages and platelets membrane receptors, leading to fibrin activation and injury healing. On the other hand, Lp(a) seems to be implicated in the formation of atheromatic plaques but also in cerebrovascular events and stenosis of the aortic valve. The main genetic factor determining plasma Lp(a) levels is the Lp(a) gene (LPA). Most Caucasian people have normal plasma Lp(a) concentrations, but there is important distribution variation according to race. Women seem to have increased Lp(a) levels compared with men, while diabetes mellitus type 2 favours lower plasma Lp(a) levels. Nutrition, hormones and several drugs may also influence circulating Lp(a) levels.
Asunto(s)
Lipoproteínas , Animales , Humanos , Lipoproteínas/sangre , Lipoproteínas/genéticaRESUMEN
The metabolic syndrome (MetS) is a cluster of metabolic abnormalities including abdominal obesity, glucose intolerance, hypertension and dyslipidaemia and is associated with an increased risk of vascular events. Since the initial description of the MetS, several expert groups produced different definitions. This variability led to confusion and absence of comparability between studies. Although there is agreement that the MetS is a major public health challenge worldwide and consistent evidence stresses the need for intervention, the definition of the syndrome remains a matter of debate. This review considers the different definitions of the MetS. These include those proposed by the World Health Organisation, the European Group for the Study of Insulin Resistance, the National Cholesterol Education Program Adult Treatment Panel III, the American College of Endocrinology and American Association of Clinical Endocrinologists and the latest International Diabetes Federation definition which includes ethnic-specific waist circumference cut-off points. These definitions share several features but also include important differences; all have limitations. Selected (after a Medline search) studies comparing the different definitions are also considered. There is a need for a standardised definition of the MetS. Furthermore, a definition tailored for children and adolescents is essential. Prospective long-term studies are needed to validate the prognostic power of these definitions. As new information becomes available the definition of the MetS might be further modified.
Asunto(s)
Clasificación Internacional de Enfermedades , Síndrome Metabólico/clasificación , Terminología como Asunto , Adolescente , Factores de Edad , Albuminuria/complicaciones , Albuminuria/epidemiología , Albuminuria/etnología , Niño , Dislipidemias/complicaciones , Dislipidemias/epidemiología , Dislipidemias/etnología , Etnicidad , Europa (Continente)/epidemiología , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Hipertensión/etnología , Resistencia a la Insulina/etnología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Síndrome Metabólico/etnología , Programas Nacionales de Salud , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/etnología , Prevalencia , Sociedades Médicas , Estados Unidos/epidemiología , Organización Mundial de la SaludRESUMEN
BACKGROUND: The metabolic syndrome (MetS) is associated with an increased incidence of coronary heart disease (CHD). Postprandial hypertriglyceridaemia is also associated with CHD. The aim of this study was to evaluate the postprandial lipaemia after an oral fat tolerance test (OFTT) in women with MetS. METHODS: OFTT, was given to 21 menopausal women with MetS (defined by the Adult Treatment Panel III) and to 12 healthy menopausal women. Triglyceride (TG) levels were measured before and 2, 4, 6 and 8h after the OFTT. The postprandial response was quantified by the areas under the curve (AUC) of TG levels. MetS women were subdivided according to body mass index (BMI) < or > or =30kg/m(2), and to fasting TG levels < or > or =150mg/dl. RESULTS: The response to the OFTT was significantly higher in the MetS group compared to healthy [AUC(S.D.), in mg/dl/h; 2014(933) versus 732(197), p<0.001]. The subjects with BMI < or > or =30kg/m(2) had similar fasting TG levels [157(60)mg/dl versus 158(67) mg/dl] and AUC [1975(898) versus 2072(1044), respectively]. The MetS women with TG> or =150mg/dl had higher AUC compared to those with TG<150mg/dl [2502(854) versus 1281(441), p=0.002]. In linear regression analysis, where BMI, high-density lipoprotein cholesterol, fasting TG, HOMA-IR and QUICKI were the independent variables, only fasting TGs significantly predicted the AUC (coefficient B=11.866, p=0.008). CONCLUSIONS: The fasting TG concentration is the main determinant of postprandial lipaemia. The obesity state was not an additional determinant for exaggerated postprandial response in MetS women. The abnormal postprandial lipaemia could be added as an important metabolic disturbance to the MetS.
Asunto(s)
Grasas de la Dieta/farmacocinética , Menopausia , Síndrome Metabólico/sangre , Periodo Posprandial/fisiología , Triglicéridos/metabolismo , Área Bajo la Curva , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Humanos , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
BACKGROUND: Several groups of patients at high risk for cardiovascular disease have been found to show an exaggerated postprandial hypertriglyceridemia. Postprandial lipemia (PPL) therefore has been implicated as a potential additional risk factor that has been evading us. The purpose of this study was to test the effect of high fasting high-density lipoprotein cholesterol (HDL-C) levels on PPL in postmenopausal females. METHODS: Oral fat tolerance test, as quantified by the areas under the curve (AUC) of triglyceride (TG) levels, was given to 3 groups: normal postmenopausal females (control), postmenopausal females with exceptionally high HDL-C and a familial history of longevity (longevity syndrome), and postmenopausal females that were heterozygotes of familial hypercholesterolemia (hFH) with exceptionally high HDL-C. RESULTS: The PPL was not different between the control and longevity syndrome groups but was significantly higher in the hFH group; AUC (SD), in mg/dl/h; 749 (195), 882 (278) and 1244 (497) respectively, p=0.002. In linear regression analysis only fasting TG levels were a significant predictor of the AUC (Coefficient B = 11.779, p < 0.001). CONCLUSIONS: In subjects with longevity syndrome the PPL is similar to controls, which means that high fasting HDL-C has not any beneficial influence on PPL. The fasting TG concentration is the main determinant of PPL. Furthermore, postmenopausal females with hFH have higher TG response postprandially, even in the case of high fasting HDL-C. Whether there is a threshold below or above, where HDL-C becomes a significant independent determinant of PPL is a question to be answered by future research.
Asunto(s)
HDL-Colesterol/sangre , Ayuno , Lípidos/sangre , Posmenopausia , Periodo Posprandial , Anciano , Glucemia/análisis , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana EdadRESUMEN
A 13-year-old Greek boy with severe dyslipidemia, large tuberous xanthomas over the knees and elbows, Achilles' tendon xanthomas, and a bilateral corneal arcus was referred to the Lipid Clinic. He had a supravalvular aortic stenosis, 50% to 60% stenosis of both carotid arteries, and normal coronary arteries. Familial hypercholesterolemia was clinically diagnosed. A V408M null low-density lipoprotein receptor (LDLR) mutation was identified in homozygosity. He responded to lipid-lowering drugs by decreasing total cholesterol by 32%, low-density lipoprotein cholesterol by 33%, and triglyceride levels by 30%. Additional treatment with low-density lipoprotein-apheresis further decreased total cholesterol by 52%, low-density lipoprotein cholesterol by 55%, and triglycerides by 43%. Low-density lipoprotein cholesterol levels between apheresis sessions showed a declining pattern. A significant regression of tuberous xanthomas was noted. A suitable combination of lipid-lowering drugs is effective even in this case of homozygosity for a null LDLR mutation. Furthermore, the coadministration of statins, cholestyramine, and ezetimibe during low-density lipoprotein-apheresis tends to counterbalance the postapheresis relapse in low-density lipoprotein cholesterol levels.