RESUMEN
BACKGROUND: Cardiovascular disease (CVD) begins early in life and is associated with both the number of risk factors present and length of exposure to these risk factors including hyperlipidemia. OBJECTIVES: The clinical benefit of intensive lipid therapy over 25 years was investigated in the Familial Atherosclerosis Treatment Study-Observational Study. METHODS: Of 175 coronary artery disease subjects with mean low-density lipoprotein cholesterol (LDL-C) of 191 mg/dL and mean age of 50 years, who completed the randomized and placebo-controlled Familial Atherosclerosis Treatment Study, 100 chose receiving lipid management by their physicians (usual care [UC]) and 75 elected to receive an intensive treatment [IT] for lipid management with lovastatin (40 mg/d), niacin (2.5 g/d), and colestipol (20 g/d) from 1989 to 2004, followed by double therapy with simvastatin (40-80 mg/d) and niacin from 2005 to 2006 and by triple therapy of ezetimibe 10 mg and simvastatin 40 to 80 mg/d plus niacin during 2007 to 2012. Deaths from CVD, non-CVD, and any cause were compared between UC and IT using Cox proportional hazards model. RESULTS: UC and IT groups were similar in risk factors with the exception that IT had more severe coronary artery disease. Mean LDL-C levels were 167 mg/dL from 1988 to 2004, 97 from 2005 to 2006, and 96 from 2007 to 2012 in surviving subjects receiving UC. IT lowered LDL-C to 119, 97, and 83 mg/dL in the 3 periods, respectively. Compared with UC, IT significantly reduced total mortality (11.1 vs 26.3 per 1000 person years [PY], hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.26-0.77, P = .003) and CVD mortality (10.6 vs 27.7 per 1000 PY, HR = 0.34, 95% CI: 0.15-0.80, P = .009). The non-CVD mortality was also reduced but was not of statistical significance (6.8 vs 12.7 per 1000 PY, HR = 0.55, 95% CI: 0.27-1.14, P = .11). CONCLUSIONS: Long-term intensive lipid therapy significantly reduced total and cardiovascular mortality in Familial Atherosclerosis Treatment Study-Observational Study. These results support the importance of lifetime risk management to improve long-term outcome.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Adulto , Aterosclerosis/mortalidad , Azetidinas/uso terapéutico , LDL-Colesterol/sangre , Ensayos Clínicos como Asunto , Colestipol/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Lovastatina/uso terapéutico , Masculino , Persona de Mediana Edad , Niacina/uso terapéutico , Modelos de Riesgos Proporcionales , Simvastatina/uso terapéutico , Triglicéridos/sangreRESUMEN
BACKGROUND: Studies have documented the short-term vascular benefits of combination lipid therapy. OBJECTIVE: Our objective was to evaluate the long-term effects of combination lipid therapy on carotid intima-media thickness (CIMT) in patients with coronary artery disease. METHODS: We performed a case-control study in patients who had finished the Familial Atherosclerosis Treatment Study (FATS) and returned to usual care with statin therapy alone or had elected to participate in the 20-year FATS-Observational Study (FATS-OS) and received combination therapy with lovastatin (40 mg/day), niacin (2-3 g/day), and colestipol (20 gm/day) for 11 years, then continued with simvastatin (10-80 mg/day) or lovastatin (40-80 mg/day) plus niacin (2-4 g/day). After 17.8 ± 0.8 years with combination therapy and 19.0 ± 0.8 years with usual care, cholesterol levels and CIMT were collected in 43 FATS-OS patients and 26 usual care patients. RESULTS: Combination therapy group had a greater decrease in total cholesterol (-42 ± 14% vs -31 ± 17%, P = .008) and low-density lipoprotein cholesterol (LDL-C) (-57 ± 13% vs -38 ± 25%, P < .001) and greater increase in high-density lipoprotein cholesterol (HDL-C) (38 ± 43% vs 15 ± 23%, P = .02) as compared with usual care. CIMT (0.902 ± 0.164 vs 1.056 ± 0.169 mm, P < .001) on intensive therapy was significantly less compared with usual care. Multivariate regression analysis (coefficient, 95% CI) showed that combination therapy (-0.13; -0.21 to -0.04, P = .003) and on-therapy LDL-C (0.15; 0.02 to 0.28, P = .03) were significant independent predictors of CIMT. CONCLUSIONS: Prolonged combination lipid therapy is associated with greater improvements in LDL-C and HDL-C levels and less atherosclerotic burden as compared with statin therapy alone.
Asunto(s)
Aterosclerosis/diagnóstico por imagen , Aterosclerosis/tratamiento farmacológico , Grosor Intima-Media Carotídeo , Hipolipemiantes/farmacología , Adulto , Aterosclerosis/sangre , Aterosclerosis/complicaciones , Estudios de Casos y Controles , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Quimioterapia Combinada , Femenino , Humanos , Hipolipemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Two large studies in populations selected for cardiovascular disease (CVD) demonstrated that raising high-density lipoprotein (HDL) cholesterol with niacin added to statin therapy did not decrease CVD. We examine the association of lipoprotein subfractions with niacin and changes in coronary stenosis and CVD event risk. One hundred and seven patients from 2 previous studies using niacin in combination with either statin or bile acid-binding resin were selected to evaluate changes in lipoproteins separated by density-gradient ultracentrifugation to progression of coronary artery disease as assessed by quantitative coronary angiography. Improvement in coronary stenosis was significantly associated with the decrease of cholesterol in the dense low-density lipoprotein (LDL) particles and across most of the intermediate density lipoprotein (IDL) and very low density lipoprotein particle density range, but, not with any of the HDL fraction or of the more buoyant LDL fractions. Event-free survival was significantly associated with the decrease of cholesterol in the dense LDL and IDL; there was no association with changes in cholesterol in the HDL and buoyant LDL fractions. Niacin combination therapy raises HDL cholesterol and decreases dense LDL and IDL cholesterol levels. Changes in LDL and IDL are related to improvement in CVD. Lipoprotein subfraction analysis should be performed in larger studies utilizing niacin in combination with statins.
Asunto(s)
Ácidos y Sales Biliares/antagonistas & inhibidores , Enfermedades Cardiovasculares/prevención & control , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Lipoproteínas/sangre , Niacina/administración & dosificación , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/tratamiento farmacológico , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estenosis Coronaria/sangre , Combinación de Medicamentos , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Compare gradient gel electrophoresis (GGE), vertical auto profile ultracentrifugation (VAP-II), nuclear magnetic resonance spectroscopy (NMR), and ion mobility for their ability to relate low- (LDL), intermediate- (IDL), very-low-density (VLDL) and high-density lipoprotein (HDL) subfraction concentrations to atherosclerotic progression. METHODS AND RESULTS: Regression analyses of 136 patients who received baseline and follow-up coronary angiographies and subfraction measurements by all four methods in the HDL Atherosclerosis Treatment Study. Prior analyses have shown that the intervention primarily affected disease progression in proximal arteries with <30% stenoses at baseline. Three-year increases in percent stenoses were consistently associated with higher on-study plasma concentrations of small, dense LDL as measured by GGE (LDLIIIb, P=10(-6); LDLIVa, P=0.006; LDLIVb, P=0.02), VAP-II (LDL4, P=0.002), NMR (small LDL, P=0.001), and ion mobility (LDL IIb, P=0.04; LDLIIIa, P=0.002; LDLIIIb, P=0.0007; LDLIVa, P=0.05). Adjustment for triglycerides, HDL-cholesterol, and LDL-cholesterol failed to eliminate the statistical significance for on-study GGE estimated LDLIIIb (P=10(-5)) and LDLIVa (P=0.04); NMR-estimated small LDL (P=0.03); or ion mobility estimated large VLDL (P=0.02), LDLIIIa (P=0.04) or LDLIIIb (P=0.02). All methods show that the effects were significantly greater for the on-study than the baseline small, dense LDL concentrations, thus establishing that the values concurrent to the progression of disease were responsible. The rate of disease progression was also related to individual VLDL, IDL, and HDL subclasses to differing extents among the various analytic methods. CONCLUSION: Four methodologies confirm the association of small, dense LDL with greater coronary atherosclerosis progression, and GGE, NMR, and ion mobility confirm that the associations were independent of standard lipid measurements. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov/ct2/show/NCT00000553.
Asunto(s)
Electroforesis de las Proteínas Sanguíneas , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Lipoproteínas/sangre , Resonancia Magnética Nuclear Biomolecular , Espectrometría de Masa por Ionización de Electrospray , Ultracentrifugación , HDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Progresión de la Enfermedad , Femenino , Humanos , Lipoproteínas/clasificación , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVE: Test whether angiographically-documented changes in percent stenosis and clinical endpoints (coronary-related deaths, myocardial infarctions, stroke, revascularization for worsening ischemia) in the HDL-Atherosclerosis Treatment Study (HATS) were attributable to specific LDL-subclasses. METHODS: Gradient gel electrophoresis of on-study LDL-subclass cholesterol concentrations were measured in 32 placebo, 33 simvastatin-niacin, 38 antioxidant, and 39 simvastatin-niacin & antioxidant treated participants. The prespecified primary end point was the mean change per patient from the initial arteriogram to the final arteriogram in the percent stenosis caused by the most severe lesion in each of the nine proximal coronary segments. RESULTS: The change in the percent stenosis of the most severe proximal lesions increased in association with higher concentrations of the small LDL subfractions LDL-IIIb (24.2-24.6 nm) and LDL-IVa (23.3-24.1 nm) before (both Pâ=â0.002) and after (Pâ=â0.01 and Pâ=â0.03 respectively) adjustment for treatment group and on-study HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations. The associations appeared specific to lesions with <30% baseline stenosis. When adjusted for age, sex, baseline BMI and cigarette use, the odds for primary clinical endpoints (death from coronary causes, nonfatal myocardial infarction, stroke, or revascularization for worsening ischemia) were significantly greater in subjects with higher on-study LDL-IIIb levels both before (Pâ=â0.01) and after (Pâ=â0.03) adjustment for treatment group and the standard lipid values. CONCLUSIONS: Plasma LDL-IIIb cholesterol concentrations were related to changes in coronary artery stenosis and cardiovascular events in patients with coronary artery disease and low HDL-cholesterol. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000553.
Asunto(s)
Aterosclerosis/sangre , Aterosclerosis/patología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad Coronaria/sangre , Enfermedad Coronaria/etiología , Progresión de la Enfermedad , Anciano , Aterosclerosis/complicaciones , Aterosclerosis/tratamiento farmacológico , Estenosis Coronaria/sangre , Estenosis Coronaria/tratamiento farmacológico , Determinación de Punto Final , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Análisis de RegresiónRESUMEN
Although the effect of niacin on the glucose levels in subjects with diabetes mellitus has been investigated, niacin's effects on the glucose levels and atherosclerosis in subjects with normal glucose levels have not been well established. We examined the effect of niacin on the glucose levels, coronary stenosis progression using quantitative coronary angiography, and clinical events in 407 subjects who had a baseline glucose level <100 mg/dl and were enrolled in the Familial Atherosclerosis Treatment Study (FATS), HDL-Atherosclerosis Treatment Study (HATS), Armed Forces Regression Study (AFREGS), or Carotid Plaque Composition by MRI during lipid-lowering (CPC) study testing active niacin therapy. Although the fasting glucose levels increased significantly within 3 years in both subjects treated with niacin (from 85.6 ± 9.5 to 95.5 ± 19.7 mg/dl, p <0.001) and without niacin (from 85.2 ± 9.6 to 90 ± 17.9 mg/dl, p = 0.009), those treated with niacin had a significantly larger increase in glucose levels than those not taking niacin (9.88 vs 4.05 mg/dl, p = 0.002). Overall, 29% of subjects developed impaired fasting glucose within 3 years. Incident impaired fasting glucose was significantly more likely to be observed in subjects treated with niacin than in those who were not. However, the frequency of new-onset diabetes mellitus did not differ significantly between the 2 groups (5.6% vs 4.8%, p = 0.5). Niacin-treated subjects compared to untreated subjects had significantly less change in mean coronary stenosis (0.1 ± 0.3% vs 2 ± 12%, p <0.0001) and less major cardiovascular events (8% vs 21%, p = 0.001). In conclusion, the use of niacin for 3 years in subjects with normal baseline glucose levels was associated with an increase in blood glucose levels and the risk of developing impaired fasting glucose, but not diabetes mellitus, and was associated with a significantly reduced incidence of coronary stenosis progression and major cardiovascular events.
Asunto(s)
Glucemia/metabolismo , Estenosis Carotídea/tratamiento farmacológico , Estenosis Coronaria/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Lípidos/sangre , Imagen por Resonancia Magnética/métodos , Placa Aterosclerótica/tratamiento farmacológico , Estenosis Carotídea/sangre , Estenosis Carotídea/complicaciones , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Angiografía Coronaria , Estenosis Coronaria/diagnóstico , Estenosis Coronaria/etiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Niacina/uso terapéutico , Placa Aterosclerótica/sangre , Placa Aterosclerótica/complicaciones , Resultado del TratamientoRESUMEN
We examined the association between rate of cholesterol esterification in plasma depleted of apolipoprotein B-containing lipoproteins (FER(HDL)), atherogenic index of plasma (AIP) [(log (TG/HDL-C)], concentrations, and size of lipoproteins and changes in coronary artery stenosis in participants in the HDL-Atherosclerosis Treatment Study. A total of 160 patients was treated with simvastatin (S), niacin (N), antioxidants (A) and placebo (P) in four regimens. FER(HDL) was measured using a radioassay; the size and concentration of lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy. The S+N and S+N+A therapy decreased AIP and FER(HDL), reduced total VLDL (mostly the large and medium size particles), decreased total LDL particles (mostly the small size), and increased total HDL particles (mostly the large size). FER(HDL) and AIP correlated negatively with particle sizes of HDL and LDL, positively with VLDL particle size, and closely with each other (r = 0.729). Changes in the proportions of small and large lipoprotein particles, which were reflected by FER(HDL) and AIP, corresponded with findings on coronary angiography. Logistic regression analysis of the changes in the coronary stenosis showed that probability of progression was best explained by FER(HDL) (P = 0.005). FER(HDL) and AIP reflect the actual composition of the lipoprotein spectrum and thus predict both the cardiovascular risk and effectiveness of therapy. AIP is already available for use in clinical practice as it can be readily calculated from the routine lipid profile.
Asunto(s)
Aterosclerosis/sangre , Aterosclerosis/diagnóstico por imagen , Colesterol/metabolismo , Angiografía Coronaria , Lipoproteínas/química , Tamaño de la Partícula , Antioxidantes/uso terapéutico , Apolipoproteínas B/metabolismo , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Colesterol/sangre , Estenosis Coronaria/complicaciones , Estenosis Coronaria/tratamiento farmacológico , Combinación de Medicamentos , Esterificación , Humanos , Lipoproteínas/sangre , Niacina/uso terapéutico , Simvastatina/uso terapéuticoRESUMEN
We examined the impact of metabolic syndrome (MS) on coronary stenosis progression and major cardiovascular (CV) events and investigated the mitigating effects of low-density lipoprotein (LDL) cholesterol lowering and LDL cholesterol lowering plus high-density lipoprotein (HDL) cholesterol increasing. This analysis combined individual patient data from 445 subjects who participated in 3 double-blinded, randomized, placebo-controlled trials (FATS, HATS, and AFREGS) comparing intensive lipid therapy to placebos on coronary stenosis progression by quantitative coronary angiography and on major CV events. The primary end points were change in mean proximal coronary diameter stenosis (Delta%S(prox)) over 3 years and the frequency of the predefined composite of coronary artery disease death, nonfatal myocardial infarction, stroke, and revascularization due to worsening ischemia. Patients with MS had 50% more rapid coronary stenosis progression and 64% increased CV event frequency compared to those without. More rapid coronary stenosis progression was significantly and independently associated with a 3.5-fold increased event risk (p <0.001). Combination lipid therapy significantly decreased stenosis progression by 83% (Delta%S(prox) 0.5 vs 2.9, p <0.001) in patients with MS and induced a small net regression in those without (Delta%S(prox) -0.3 vs 2.0, p <0.001). Combination therapy decreased the event rate by 54% (13% vs 28%, p = 0.03) in those with MS and by 82% (3% vs 17%, p = 0.002) without. On average, each 10% decrease in LDL cholesterol or 10% increase in HDL cholesterol was significantly associated with a 0.3 Delta%S(prox) decrease. Each 10% decrease in LDL cholesterol or 10% increase in HDL cholesterol was associated with 11% (p = 0.02) or 22% (p <0.001) event risk decrease. In conclusion, patients with MS have significantly more rapid coronary stenosis progression and a higher frequency of CV events. Greater stenosis progression rate is associated with a higher event rate. LDL cholesterol-lowering and HDL cholesterol-increasing therapies independently and significantly decrease coronary stenosis progression and decrease CV events.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Aterosclerosis/tratamiento farmacológico , HDL-Colesterol/sangre , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/tratamiento farmacológico , Síndrome Metabólico/complicaciones , Adulto , Anciano , Aterosclerosis/genética , Biomarcadores/sangre , Índice de Masa Corporal , LDL-Colesterol/sangre , Angiografía Coronaria , Estenosis Coronaria/sangre , Estenosis Coronaria/complicaciones , Estenosis Coronaria/diagnóstico , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Persona de Mediana Edad , Personal Militar , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Factores de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The current guidelines for the treatment of high risk lipid disorders do not specify a therapeutic target level of high-density lipoprotein (HDL) cholesterol for cardiovascular disease prevention in high-risk populations. However, as described in this report, there is a substantial body of evidence from basic science and epidemiologic studies and from clinical trials providing the strong, consistent message that raising HDL cholesterol by therapeutic means will effectively reduce cardiovascular risk independently of reductions in low-density lipoprotein (LDL) cholesterol. Therapeutic HDL cholesterol raising, most effectively achieved by nicotinic acid (niacin), appears to be at least as effective as comparable percentages of LDL cholesterol lowering for the reduction of atherosclerosis progression or clinical cardiovascular events, over a broad range of risk levels. The widespread adoption of this strategy awaits the results of large, ongoing controlled clinical trials of HDL cholesterol raising.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Dislipidemias/tratamiento farmacológico , Niacina/uso terapéutico , Enfermedades Cardiovasculares/etiología , HDL-Colesterol/efectos de los fármacos , LDL-Colesterol/efectos de los fármacos , Ácido Clofíbrico/uso terapéutico , Quimioterapia Combinada , Dislipidemias/complicaciones , Humanos , Hiperlipidemias/tratamiento farmacológico , Niacina/farmacología , Factores de Riesgo , Conducta de Reducción del RiesgoAsunto(s)
Anticolesterolemiantes/uso terapéutico , Azetidinas/uso terapéutico , LDL-Colesterol/sangre , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Simvastatina/uso terapéutico , HDL-Colesterol , Quimioterapia Combinada , Ezetimiba , Humanos , Hiperlipoproteinemia Tipo II/patología , Resultado del Tratamiento , Triglicéridos/sangre , Túnica Íntima/patología , Túnica Media/patologíaRESUMEN
OBJECTIVES: This study evaluated the safety and lipid-altering efficacy of ezetimibe/simvastatin (E/S) coadministered with extended-release niacin (N) in patients with type IIa or IIb hyperlipidemia. BACKGROUND: Current guidelines recommend consideration of combination drug therapy to achieve optimal low-density lipoprotein cholesterol (LDL-C) lowering and broader lipid-altering effects when treating hypercholesterolemic patients at high risk for atherosclerotic cardiovascular events. METHODS: In this 24-week multicenter, randomized, double-blind study, 1,220 type IIa or IIb hyperlipidemic patients were randomized to treatment with E/S (10/20 mg/day) + N (titrated to 2 g/day), or N (titrated to 2 g/day), or E/S (10/20 mg/day). Changes from baseline in LDL-C (primary) and other secondary variables were assessed in the completers and modified intent-to-treat populations. RESULTS: Coadministered E/S with N resulted in significantly greater reductions in LDL-C, non-high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipid/lipoprotein ratios, compared with either agent alone (p < 0.001). The combination increased levels of apolipoprotein A-I and high-density lipoprotein cholesterol significantly more than E/S (p < 0.001), and reduced high-sensitivity C-reactive protein levels significantly more than N (p = 0.005). A significantly greater percentage of patients discontinued the study in the N (25.0%) and N + E/S (23.3%) groups, compared with E/S (9.6%, p < 0.001) because of clinical adverse experiences (primarily flushing). Incidences of other clinical and laboratory adverse experiences (liver-, muscle-, and gastrointestinal-related) were similar for all groups. CONCLUSIONS: Combination treatment with E/S plus N showed superior lipid-altering efficacy compared with N or E/S in type IIa or IIb hyperlipidemia patients and was generally well tolerated aside from N-associated flushing. This combination offers an effective, broad, lipid-altering therapy with improvements in lipid effects beyond LDL-C in these patients. (To Evaluate Ezetimibe/Simvastatin and Niacin [Extended Release Tablet] in Patients With High Cholesterol.
Asunto(s)
Azetidinas/uso terapéutico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Lípidos/sangre , Niacina/uso terapéutico , Simvastatina/uso terapéutico , Adolescente , Adulto , Anticolesterolemiantes/uso terapéutico , Apolipoproteínas/efectos de los fármacos , Azetidinas/administración & dosificación , Azetidinas/efectos adversos , HDL-Colesterol/efectos de los fármacos , LDL-Colesterol/efectos de los fármacos , Preparaciones de Acción Retardada , Quimioterapia Combinada , Ezetimiba , Femenino , Humanos , Hipolipemiantes/administración & dosificación , Hipolipemiantes/efectos adversos , Masculino , Persona de Mediana Edad , Niacina/administración & dosificación , Niacina/efectos adversos , Simvastatina/administración & dosificación , Simvastatina/efectos adversosAsunto(s)
Anticolesterolemiantes/administración & dosificación , Apolipoproteína A-I/administración & dosificación , Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Fosfatidilcolinas/administración & dosificación , Animales , Arterias Carótidas/efectos de los fármacos , Estenosis Carotídea/diagnóstico , Estenosis Carotídea/tratamiento farmacológico , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Imagen por Resonancia Magnética , Masculino , Conejos , Resultado del Tratamiento , Ultrasonografía , Ultrasonografía IntervencionalAsunto(s)
Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/orina , Ultrasonografía Intervencional , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/patología , Biomarcadores , Ensayos Clínicos como Asunto/métodos , Estudios de Cohortes , Angiografía Coronaria/estadística & datos numéricos , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/fisiopatología , Progresión de la Enfermedad , Endotelio Vascular/fisiopatología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Infarto del Miocardio/etiología , Infarto del Miocardio/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Ultrasonografía Intervencional/estadística & datos numéricosRESUMEN
Are progressive changes in intravascular ultrasound (IVUS)-derived indexes of plaque size sufficiently predictive of in-trial or future cardiovascular event risk that IVUS can serve as an efficient surrogate for clinical events in coronary disease trials? This question remains unanswered by clinical trials reported to date. Indeed, the answer may well be "yes." Nevertheless, there are enough concerns about the physical limitations, the fundamental assumptions, and the interpretation of the IVUS measurements that the answer cannot be taken for granted. Here, we review the evidence to date, discuss some of the concerns, and compare IVUS results with those of quantitative arteriography.
Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Ultrasonografía Intervencional , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/fisiopatología , Progresión de la Enfermedad , Medicina Basada en la Evidencia/métodos , Humanos , Proyectos de Investigación , Sensibilidad y EspecificidadAsunto(s)
Enfermedades Cardiovasculares/prevención & control , Testimonio de Experto , Rubor/inducido químicamente , Hipolipemiantes/uso terapéutico , Niacina/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Hipolipemiantes/efectos adversos , Niacina/efectos adversosRESUMEN
BACKGROUND: Metabolic syndrome, insulin resistance and diabetes are associated with an increased risk of cardiovascular disease. Niacin is known to increase insulin resistance, and have adverse effects on blood glucose levels, but to have beneficial effects on plasma lipids and lipoproteins. We therefore aimed to determine whether intensive lipid therapy with a niacin-containing regimen would have a beneficial effect on cardiovascular disease, despite an expected increase in plasma glucose and insulin resistance in subjects with the metabolic syndrome, insulin resistance or abnormal fasting plasma glucose levels. METHODS: The effect of three years' treatment with niacin plus simvastatin (N+S) on both angiographic and clinical outcomes were analyzed in the 160 subjects with coronary artery disease (CAD) and low levels of high density lipoproteins (HDL) from the HDL-Atherosclerosis Treatment Study (HATS). A subgroup analysis was performed on the basis of: (1) the presence or absence of the metabolic syndrome, (2) higher or lower insulin resistance, and (3) the presence or absence of impaired fasting glucose or diabetes (dysglycemia). Individuals classified as having the MS, increased insulin resistance or dysglycemia would be expected to have increased cardiovascular risk. RESULTS: N+S reduced the change in mean proximal percent stenosis (Δ%S) compared to placebo (PL) in subjects with the metabolic syndrome (Δ%Sprox 0.3 vs 3.0, p=0.003) and in the more insulin resistant group of subjects (Δ%Sprox 0.5 vs 2.7, p=0.001), while subjects with dysglycemia (impaired fasting glucose or diabetes) showed a lesser benefit (Δ%Sprox 1 vs 3.2, p=0.13). These changes occurred despite increased in-treatment fasting glucose levels (3%), fasting insulin (19%) and decreased insulin sensitivity (-10%). Overall primary clinical events were reduced by 60% with N+S compared to PL (p=0.02). A similar reduction of the rate of primary events was seen in patients with metabolic syndrome, insulin resistance, and to a lesser extent in patients with dysglycemia in the N+S group compared to PL. CONCLUSIONS: These data indicate that, in CAD patients with low HDL, treating the atherogenic dyslipidemia with a combination of N+S leads to substantial benefits in terms of stenosis progression and clinical events, independently of whether the patient has the metabolic syndrome or is insulin resistant. Over a 3 year period, the beneficial effect of niacin in combination with simvastatin appears to offset the modest adverse effect of niacin on glucose metabolism and insulin resistance in at higher risk patients, as long as careful attention is paid to glycemic control.
RESUMEN
The current guidelines for treatment of high-risk of lipid disorders do not specify a therapeutic target level of high-density lipoprotein cholesterol (HDL-C) for prevention of vascular disease in high-risk populations. However, there is a substantial body of evidence from basic science and epidemiologic studies and from clinical trials, providing the strong, consistent message that raising HDL-C by therapeutic means will effectively and independently reduce cardiovascular risk. This review summarizes epidemiologic evidence and the results of a meta-analysis of 23 published, prospective, randomized, placebo-controlled clinical trials. It focuses on the effects of lipid therapies on coronary stenosis progression, as measured by quantitative arteriography and/or, on clinical cardiovascular endpoints. Among the seven drug/treatment classes into which individual study results were categorized and averaged, reduction in stenosis progression and reduction in clinical events are both very highly correlated with the composite lipid variable (%ΔHDL-C - %Δ low-density lipoprotein cholesterol [LDL-C]; where %Δ is percent change relative to the placebo group response). This holds true for all lipid drug classes or combinations of lipid drug therapy, with the exception of the unexpectedly anomalous effects of the torcetrapib-atorvastatin combination. There is a strong and consistent body of evidence that therapeutic HDL-C-raising is at least as effective as comparable percentages of LDL-C-lowering for reduction of atherosclerosis progression or clinical cardiovascular events over a broad range of risk levels. Adoption of this strategy into guidelines probably awaits results of at least one large controlled HDL-C-raising clinical trial, of which two are ongoing and one other is planned.
RESUMEN
PURPOSE OF REVIEW: Our analysis presents an alternative hypothesis to the prevailing view that low-density lipoprotein-C is the only important target of lipid therapy. RECENT FINDINGS: Two recently published studies showed surprising results. In the Armed Forces Regression Study, low-density lipoprotein-C was lowered only 22% with cholystyramine, niacin and gemfibrozil. Coronary stenosis regressed, however, and the primary clinical event rate was reduced by 54%. Conversely, in the FIELD trial, the primary event rate reduction was only 11% (P = NS). These differences appeared to be explained largely by the difference in high-density lipoprotein response to these regimens (38 vs. 3%). This meta-analysis of 23 trials strongly supports the notion that the sum of percent reduction in low-density lipoprotein-C plus percent increase in high-density lipoprotein-C predicts benefits much more effectively than either lipoprotein component. SUMMARY: Epidemiology suggests that the cardiovascular event rate is reduced by nearly 1% for each 1% reduction in low-density lipoprotein-C and by at least 1% for each 1% increase in high-density lipoprotein. These effects are statistically independent; thus, for moderate lipid changes, they are additive. If this simple algorithm is proven accurate, a 30% high-density lipoprotein-C increase and a 40% low-density lipoprotein-C reduction would result in a nearly 70% CHD risk reduction - and a revolution in cardiovascular prevention.
Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Enfermedades Cardiovasculares/metabolismo , Quimioterapia Combinada , Humanos , Hipolipemiantes/uso terapéutico , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
PURPOSE: Cardiovascular magnetic resonance (CMR) can characterize carotid atherosclerosis. The purpose of this study is to evaluate reader agreement of carotid atherosclerotic lesion types by CMR. METHODS: Carotid arteries of 34 patients (29 men, 5 women; mean age, 53 years) were imaged on a 1.5-T scanner. Images with 4 contrast weightings (T1, T2, proton density, and 3-dimensional time-of-flight) were acquired on each axial slice of the carotid arteries. Modified AHA criteria were used for lesion type assessment on the 4 selected axial slices (1 from the common carotid artery, 1 from the carotid bifurcation, and 2 from the internal carotid artery). The modified AHA criteria are as follows: type I-II, near-normal wall thickness without calcification; type III, diffuse wall thickening or small eccentric plaque without calcification; type IV-V, plaque with a lipid rich necrotic core surrounded by fibrous tissue with possible calcification; type VI, complex plaque with a possible surface defect, hemorrhage, or thrombus; type VII, calcified plaque; and type VIII, fibrotic plaque without a lipid core and with possible small calcifications. RESULTS: Of the 272 possible axial slices (34 patients x 2 arteries per patient x 4 slices per artery), 256 slices were available for lesion type assessment. The majority (94%) of the lesions were of type I-II and III. kappa was 0.80 and 0.60 for intra-reader and inter-reader agreement of lesion types, respectively. Inter-reader disagreement for type I-II and type III occurred in 82% of lesions. Weighted kappa was 0.92 and 0.83 for intra-reader and inter-reader agreement of lesion types, respectively. CONCLUSION: The difference between type I-II and III lesions lies in the definition of the vessel wall. The moderate inter-reader agreement suggests further efforts such as establishment of normal carotid artery wall thickness by a quantitative measure are needed for carotid atherosclerotic lesion characterization.