RESUMEN
Hypertension and hyperlipidemia, two powerful risk factors of cardiovascular disease (CVD), often coexist. Therefore, treatment should consider the beneficial properties of drugs used to treat either condition. Statins, the mainstay of lipid-lowering therapy, result in a significant clinical benefit both in primary and secondary CVD prevention. In addition to their hypolipidemic capacity, other properties may contribute to statin-induced benefits. Clinical and experimental evidence indicates that statins may modulate blood pressure (BP). The mechanisms by which statins reduce BP seem to be largely independent of their lipid effects. Although small, reductions in BP are possibly clinically relevant. Large landmark studies confirm that statins can reduce CVD risk in hypertensive patients. These findings suggest that statins could be prescribed as an adjunct in treating hypertension with dyslipidemia or even in patients with "normal" cholesterol levels. Whether the effect of statins on BP is accompanied by an additional decrease in clinical outcomes needs to be investigated in long-term, large-scale trials.
Asunto(s)
Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Animales , Endotelina-1/efectos de los fármacos , Endotelina-1/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Humanos , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Hiperlipidemias/fisiopatología , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Hipertensión/metabolismo , Hipertensión/fisiopatología , Péptidos y Proteínas de Señalización Intracelular/efectos de los fármacos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Óxido Nítrico/biosíntesis , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Quinasas Asociadas a rhoRESUMEN
The metabolic syndrome is a clustering of risk factors including central obesity, insulin resistance, dyslipidaemia and hypertension. This syndrome is associated with increased risk of cardiovascular disease and is a common early abnormality in the development of type 2 diabetes. The pathogenesis of the syndrome has multiple origins. Obesity and sedentary lifestyle coupled with genetic factors interact to produce the syndrome. Here, we consider two components of the metabolic syndrome, dyslipidaemia and hypercoagulability.
Asunto(s)
Enfermedades Cardiovasculares/etiología , Dislipidemias/complicaciones , Síndrome Metabólico/complicaciones , Trombofilia/complicaciones , Tejido Adiposo/metabolismo , Adiposidad , Animales , Aspirina/uso terapéutico , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/metabolismo , HDL-Colesterol/sangre , Ácido Clofíbrico/uso terapéutico , Dislipidemias/sangre , Dislipidemias/tratamiento farmacológico , Dislipidemias/metabolismo , Factor VII/metabolismo , Fibrinolíticos/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipolipemiantes/uso terapéutico , Mediadores de Inflamación/metabolismo , Resistencia a la Insulina , Estilo de Vida , Lipoproteínas LDL/sangre , Síndrome Metabólico/sangre , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/metabolismo , Obesidad/sangre , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Inhibidor 1 de Activador Plasminogénico/sangre , Inhibidor 1 de Activador Plasminogénico/metabolismo , Trombofilia/sangre , Trombofilia/tratamiento farmacológico , Trombofilia/metabolismo , Triglicéridos/sangre , Factor de von Willebrand/metabolismoRESUMEN
Several studies have shown that angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are useful in the treatment of hypertension, cardiovascular disease, chronic heart failure, and some types of nephropathy. In this context, dual renin-angiotensin system blockade with both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may be more effective than treatment with each agent alone. Many clinical trials have demonstrated the beneficial effect of this combined treatment on proteinuria, hypertension, heart failure, and cardiovascular events. Moreover, these studies demonstrated that dual renin-angiotensin system blockade is generally safe and well tolerated. Long-term studies are under way to confirm these effects and also investigate the effectiveness of dual renin-angiotensin system blockade on cerebrovascular disease and prevention of type 2 diabetes mellitus. These studies are expected to define the optimal use of combination treatment in everyday clinical practice. This review considers the most important clinical trials that evaluated the effect of dual renin-angiotensin system blockade on blood pressure, heart failure, and renal function.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Ensayos Clínicos como Asunto , Quimioterapia Combinada , Humanos , Hipertensión/tratamiento farmacológico , Insuficiencia Renal/prevención & control , Sistema Renina-Angiotensina/efectos de los fármacos , Accidente Cerebrovascular/prevención & controlRESUMEN
Migraine is a common and disabling neurological disorder. Studies have shown that patients with migraine (especially those with typical aura with migraine) have an unfavorable cardiovascular risk profile and an increased risk of early-onset (<45 years) ischemic stroke. Statins are effective hypolipidemic drugs that reduce cardiovascular-related morbidity and death in patients with or without established atherosclerotic vascular disease. We report a patient whose frequent attacks of typical aura with migraine completely resolved after the initiation of treatment with a statin. In this context, we comment on the possible effects of statins on the pathophysiology of migraine. We suggest that statins may be useful drugs in the treatment of migraine because they could reduce the increased cardiovascular risk in these patients and also attenuate migraine attacks. Only a randomized prospective study in this population could provide a definite answer to these speculations.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Trastornos Migrañosos/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/complicaciones , Migraña con Aura/complicaciones , Migraña con Aura/tratamiento farmacológico , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & controlRESUMEN
BACKGROUND: We have previously shown that apolipoprotein E (apo E-) polymorphism may affect serum creatinine concentration and predicted glomerular filtration rate in healthy individuals. On the other hand, there are limited data regarding the possible influence of apo E- polymorphism on serum uric acid (SUA) levels. METHODS: Two hundred ninety (148 male, 142 female) apparently healthy white individuals were studied. apo E- genotypes, serum lipid parameters including apolipoproteins, insulin resistance using the homeostasis model assessment (HOMA) as a marker, serum and urine creatinine levels, and serum and urine uric acid concentration were determined in all participants. RESULTS: The apo E-2 allele was associated with lower serum levels of total cholesterol, higher levels of triglycerides and apo E-, and increased serum creatinine concentration compared with the apo E-3 and apo E-4 alleles in our population. Furthermore, the apo E-2 allele was associated with higher SUA levels (321.3+/-101.1 micrmol/L [5.4+/-1.7 mg/dL]) compared with the apo E-3 allele (261.8+/-89.2 micromol/L [4.4+/-1.5 mg/dL]; p= .012) and the apo E-4 allele (243.9+/-65.4 micromol/L [4.1+/-1.1 mg/dL]; p= .010), whereas the apo E-2 allele was associated with a nonsignificantdecrease in the fractional renal excretion of uric acid (FEUA) compared with the apo E-3 and apo E-4 alleles (7.9+/-2.2% vs 8.7+/-4.2% vs 8.9+/-5.1%, respectively; p = .53). These observations remained statistically significant when the effect of apo E- polymorphism on SUA levels was adjusted for gender, age, systolic and diastolic blood pressure, body mass index, serum creatinine, and triglyceride and apo E- levels, as well as for HOMA index and FEUA. CONCLUSIONS: Our data provide evidence, for the first time, that the apo E-2 allele is independently associated with increased SUA levels in healthy individuals.
Asunto(s)
Apolipoproteínas E/genética , Ácido Úrico/sangre , Anciano , Alelos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Valores de ReferenciaAsunto(s)
Anticolesterolemiantes/uso terapéutico , Enfermedad Coronaria/sangre , Lipoproteínas LDL/sangre , Ensayos Clínicos Controlados Aleatorios como Asunto , Atorvastatina , Azetidinas/uso terapéutico , Enfermedad Coronaria/prevención & control , Quimioterapia Combinada , Ezetimiba , Ácidos Heptanoicos/uso terapéutico , Humanos , Lipoproteínas LDL/efectos de los fármacos , Pirroles/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Resultado del TratamientoAsunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Benzopiranos/uso terapéutico , Etanolaminas/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Humanos , Persona de Mediana Edad , Nebivolol , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
BACKGROUND AND AIM: HDL-cholesterol (HDL-C) is inversely related to the risk of ischemic heart disease. Many genes are reported to affect HDL-C serum levels in both hyperlipidemic and normolipidemic populations, though the data are controversial. We examined the effect of common gene polymorphisms known to interfere with HDL-C metabolism (apolipoprotein E, cholesterol ester transfer protein and apolipoprotein A-IV gene polymorphisms) on HDL-C plasma levels in normolipidemic subjects. METHODS AND RESULTS: The study population consisted of 200 normolipidemic individuals visiting our clinic for a routine check-up. None of the above gene polymorphisms affected HDL-C levels in our population. However, participants carrying the allele E4 of the apolipoprotein (apo) E gene, the allele B1 of the TaqIB polymorphisms in the cholesterol ester transfer protein (CETP) gene and the allele T of the apoA-IV gene (A to T polymorphism at site 347) (n = 28) had statistically significantly lower HDL-C levels compared to those not carrying the above allele combination (0.99+/-0.33 vs 1.28+/-0.35 mmol/L, p = 0.04). CONCLUSION: In this study, we describe a subgroup of normolipidemic individuals with low HDL-C levels due to genetic variability, and we discuss the underlying possible mechanisms involved.
Asunto(s)
Apolipoproteínas A/genética , Apolipoproteínas E/genética , Proteínas Portadoras/genética , HDL-Colesterol/sangre , HDL-Colesterol/genética , Glicoproteínas/genética , Polimorfismo Genético , Adulto , Alelos , Proteínas de Transferencia de Ésteres de Colesterol , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Genotipo , Humanos , Masculino , Isquemia Miocárdica/genéticaAsunto(s)
Diabetes Mellitus/etiología , Diabetes Mellitus/prevención & control , Trasplante de Riñón/efectos adversos , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Rechazo de Injerto/prevención & control , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéuticoRESUMEN
BACKGROUND: Statin therapy has been shown to significantly decrease vascular events and overall mortality in primary and secondary prevention trials. This review considers the pharmacology, nonlipid-lowering effects and clinical trial evidence of fluvastatin based on a survey of PubMed entries. FINDINGS: Recent clinical data show that treatment with fluvastatin is associated with a variety of benefits in different high-risk populations along with a good safety profile. Fluvastatin exerts non-lipid lowering-associated pleiotropic effects in both clinical and experimental studies. Furthermore, an extended-release formulation of fluvastatin with a favourable pharmacokinetic profile is available. CONCLUSION: Treatment with fluvastatin offers a convenient, safe and evidence-based approach to managing dyslipidaemias and preventing vascular events.
Asunto(s)
Ácidos Grasos Monoinsaturados/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hipercolesterolemia/tratamiento farmacológico , Indoles/farmacología , Lípidos/sangre , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/prevención & control , Ácidos Grasos Monoinsaturados/efectos adversos , Ácidos Grasos Monoinsaturados/uso terapéutico , Fluvastatina , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/complicaciones , Indoles/efectos adversos , Indoles/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoAsunto(s)
Angina Inestable/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Anciano , Angina Inestable/diagnóstico , Angina Inestable/mortalidad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Resultado del Tratamiento , Reino UnidoRESUMEN
OBJECTIVE: The more atherogenic lipid profile seen in peritoneal dialysis (PD) patients cannot fully explain the increased incidence of atherosclerosis in this population. Oxidative modification of low-density lipoproteins (LDL) is considered to play a central role in the atherogenic process, whereas high-density lipoprotein (HDL) protects LDL from oxidation. On the other hand, it has been suggested that the LDL and HDL of PD patients are more resistant to oxidation than those of control subjects, while PD-HDL equally protects LDL from oxidation compared to control-HDL. Two HDL-associated enzymes have been shown to protect both LDL and HDL from oxidation: paraoxonase (PON1) and HDL-associated platelet-activating factor acetylhydrolase (HDL-PAF-AH). Furthermore, low PON1 activity and high total plasma PAF-AH concentration, which represents mainly the LDL-associated enzyme, have been shown to be independent risk factors for coronary artery events in the general population. However, there are limited data regarding possible alterations of these enzymes in PD patients. The aim of our study was to examine the possible alterations of PON1 and PAF-AH activities in patients undergoing PD. DESIGN: A cross-sectional study. SETTING: A university medical center. PARTICIPANTS: 56 PD patients of Caucasian origin and 86 matched controls were studied. MEASUREMENTS: In all subjects, serum PON1 activity toward paraoxon (paraoxonase) and phenylacetate (arylesterase), as well as total serum and HDL-PAF-AH activities were measured; PON1 genetic polymorphisms known to influence PON1 activity (Q192R and M55L) were determined. RESULTS: The PD patients exhibited significantly increased serum PON1 (paraoxonase) and PON1 (arylesterase) activities compared to controls, regardless of the PON1 polymorphisms or the levels of HDL cholesterol. Additionally, PD patients had significantly elevated activities of total serum PAF-AH and HDL-PAF-AH, independently of the levels of LDL or HDL cholesterol. The ratio of HDL-PAF-AH/ total PAF-AH, which has recently been suggested to be a potential marker of atherogenicity, was decreased in these patients compared to controls. Moreover, no difference in the prevalence of PON1 polymorphisms between PD patients and controls was found. CONCLUSION: The elevated activities of PON1 and HDL-PAF-AH could explain the increased resistance of PD-HDL to oxidation; the higher activity of total PAF-AH and the decreased HDL-PAF-AH/ total PAF-AH ratio could contribute to the increased incidence of atherosclerosis in these patients.
Asunto(s)
1-Alquil-2-acetilglicerofosfocolina Esterasa/metabolismo , Arteriosclerosis/metabolismo , Arildialquilfosfatasa/metabolismo , Fallo Renal Crónico/enzimología , Diálisis Peritoneal Ambulatoria Continua , Arildialquilfosfatasa/genética , Estudios de Casos y Controles , Enfermedad Coronaria/metabolismo , Estudios Transversales , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana EdadRESUMEN
Apolipoprotein (apo) E gene polymorphism and its effect on serum lipid parameters were examined in a Greek population originating from northwestern Greece (n = 555). The allele frequencies were epsilon2: 6.3%, epsilon3: 80.7%, and epsilon4: 13.0%. The epsilon4 allele frequency was higher in our population than was previously reported in individuals from other parts of Greece. ApoE polymorphism was associated with significant differences in serum lipid, and lipoprotein levels. Particularly, individuals with the epsilon2 allele had higher serum triglyceride and apoE levels and lower levels of total cholesterol, low-density lipoprotein cholesterol, and apoB, compared to those with the alleles epsilon3 and epsilon4. However, the impact of the epsilon4 allele on lipid parameters seen in other populations was not observed in our population. Furthermore, the combination of apoE polymorphism and serum apoE concentration explained a larger percentage of serum lipid variability than the polymorphism alone. In conclusion, the results of our study suggest that ethnic differences, as well as alterations of serum apoE levels, significantly modify the relationship between apoE gene polymorphism and serum lipid variability.
Asunto(s)
Apolipoproteínas E/genética , Frecuencia de los Genes , Hiperlipoproteinemias/genética , Polimorfismo Genético , Estudios Seroepidemiológicos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Grecia/epidemiología , Humanos , Hiperlipoproteinemias/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Apolipoprotein E (ApoE) polymorphism has been shown to influence serum lipid parameters and ApoE levels in both healthy subjects and hemodialysis (HD) patients. Conversely, ApoE concentration significantly affects serum lipid levels in the general population, independently of ApoE polymorphism, by modulating lipoprotein production, lipolytic conversion, and receptor-mediated clearance. Therefore, studying the effect of ApoE polymorphism on serum lipid levels without taking into account ApoE levels could lead to confounding results. However, such a combined study has not been performed in HD patients to date. METHODS: Three hundred one patients without diabetes on long-term maintenance HD therapy and 200 matched healthy subjects were studied. Determination of levels of fasting serum ApoE and other lipid parameters, as well as common ApoE genotypes, was performed in all subjects. RESULTS: HD patients had a significantly lower prevalence of the epsilon4 allele and greater levels of ApoE compared with the control population. ApoE2 allele carriers had significantly lower levels of ApoB and serum total, low-density lipoprotein, and non-high-density lipoprotein cholesterol, as well as increased ApoE levels. When ApoE levels were included in analysis, ApoE levels themselves were proven to be important determinants of serum lipid levels, whereas the effect of ApoE polymorphism became more pronounced. The combination of these 2 factors explains a much greater percentage of the variation in the studied parameters than each factor alone. CONCLUSION: For the first time, our study provides data to support that ApoE concentration in combination with the ApoE polymorphism significantly influences serum lipid parameters in HD patients.
Asunto(s)
Apolipoproteínas E/sangre , Apolipoproteínas E/genética , Fallo Renal Crónico/sangre , Lípidos/sangre , Polimorfismo Genético , Diálisis Renal , Anciano , Alelos , Apolipoproteína E2 , Apolipoproteína E4 , Apolipoproteínas B/sangre , Glucemia/análisis , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Fallo Renal Crónico/genética , Lipoproteínas/sangre , Masculino , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
BACKGROUND: There are conflicting results regarding the effect of apolipoprotein (ApoE) polymorphisms on the progression of a variety of renal diseases. However, there are no data on the possible effect of the ApoE alleles on serum creatinine levels and predicted glomerular filtration rate (GFR) in healthy subjects. METHODS: 290 apparently healthy individuals were studied. ApoE genotyping was performed by the polymerase chain reaction; the Modification of Diet in Renal Disease equation (MDRD) predicted the GFR. RESULTS: ApoE2 was associated with lower levels of total cholesterol, low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol, as well as with higher levels of triglycerides in our population. Furthermore, the ApoE2 allele was associated with increased serum creatinine levels compared with both the E3 and E4 alleles (1.04+/-0.13 vs 0.92+/-0.13 vs 0.88+/- 0.11 mg/dl, respectively, P = 0.0077), while the MDRD-predicted GFR was decreased in ApoE2 carriers compared with both E3 and E4 carriers (80.3+/-10.2 vs 88.1+/-9.6 vs 89.3+/-9.7 ml/min/1.73 m(2), respectively, P = 0.031). These observations remained significant statistically even if the effect of ApoE polymorphisms on age- and body-mass index-adjusted serum creatinine and MDRD-predicted GFR was separately analysed in both men and women. Although, ApoE4 carriers tended to exhibit lower levels of serum creatinine and higher values of predicted GFR compared with the E3 carries, these differences did not reach statistical significance. CONCLUSIONS: ApoE2 allele seems to be associated with increased serum creatinine levels and decreased MDRD-predicted GFR in healthy subjects.