RESUMO
OBJECTIVE: To compare the effects of combination niacin extended-release + simvastatin (NER/S) versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME, a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia. PATIENTS AND METHODS: Patients (n = 137) with dyslipidemia (not previously receiving statin therapy or having discontinued any lipid-altering treatment 4-5 weeks prior to the study) received NER/S (1000/40 mg/day for four weeks, then 2000/40 mg/day for eight weeks) or atorvastatin 40 mg/day for 12 weeks. Median percent changes in apolipoprotein (apo) A-1, apo B, and the apo B:A-I ratio, and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher's exact test. RESULTS: NER/S treatment produced significantly greater percent changes in apo A-I and apo B:A-I, and, at the final visit, apo B < 80 mg/dL was attained by 59% versus 33% of patients, compared with atorvastatin treatment (P = 0.003). NER/S treatment resulted in greater percent reductions in calculated particle numbers for low-density lipoprotein (LDL, 52% versus 43%; P = 0.022), small LDL (55% versus 45%; P = 0.011), very low-density lipoprotein (VLDL) and total chylomicrons (63% versus 39%; P < 0.001), and greater increases in particle size for LDL (2.7% versus 1.0%; P = 0.007) and VLDL (9.3% versus 0.1%; P < 0.001), compared with atorvastatin. CONCLUSION: NER/S treatment significantly improved apo A-I levels and the apo B:A-I ratio, significantly lowered the number of atherogenic LDL particles and VLDL and chylomicron particles, and increased the mean size of LDL and VLDL particles, compared with atorvastatin.
Assuntos
Aterosclerose/prevenção & controle , Dislipidemias/tratamento farmacológico , Ácidos Heptanoicos/uso terapêutico , Hipolipemiantes/uso terapêutico , Niacina/uso terapêutico , Pirróis/uso terapêutico , Sinvastatina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Atorvastatina , Preparações de Ação Retardada , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/complicações , Feminino , Ácidos Heptanoicos/farmacologia , Ácidos Heptanoicos/normas , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Lipoproteínas/sangue , Lipoproteínas/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Niacina/farmacologia , Niacina/normas , Pirróis/farmacologia , Pirróis/normas , Sinvastatina/farmacologia , Sinvastatina/normas , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Aggressive treatment of low-density lipoprotein cholesterol (LDL-C) fails to prevent most cardiovascular (CV) events. Concurrent treatment of LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) should be considered in patients with dyslipidemia. OBJECTIVE: The efficacy and safety of a proprietary niacin extended-release and simvastatin (NER/S) combination were compared to atorvastatin monotherapy in a multicenter, Prospective, Randomized (3:2), Open-label, Blinded Endpoint (PROBE) study. METHODS: Following ≥4 weeks without lipid-modifying therapies, 193 patients with dyslipidemia were treated with NER/S (n = 114; 1000/40 mg/day, weeks 1 to 4; 2000/40 mg/day weeks 5 to 12) or atorvastatin (n = 79; 40 mg/day, weeks 1 to 12). RESULTS: Compared to atorvastatin, NER/S had a larger beneficial effect on HDL-C (primary end point: 30.1 ± 2.3% and 9.4 ± 2.6%, respectively; P <.001), TG (P = .02), and lipoprotein(a) (Lp[a]; P <.001), and similar effects on LDL-C and non-HDL-C. Two-thirds of patients treated with NER/S concurrently attained LDL-C (CV risk-adjusted goals), HDL-C (≥40 mg/dL), and TG (<150 mg/dL) targets, compared to one-third of patients treated with atorvastatin (P <.001). Flushing was the most common treatment-emergent adverse event (TEAE) (67.5% NER/S and 10.1% atorvastatin; P <.001). Seventy-five percent of flushing episodes were mild to moderate. More patients treated with NER/S discontinued due to TEAEs (21.1% and 3.8%; P <.001); the most common TEAE was flushing. CONCLUSION: Compared to atorvastatin, NER/S provided superior improvements in HDL-C, TG, and Lp(a) and comparable improvements in non-HDL-C and LDL-C. Treatment with NER/S should be considered for patients with dyslipidemia requiring comprehensive lipid control.
Assuntos
Anticolesterolemiantes/uso terapêutico , Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Colesterol/metabolismo , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/patologia , Países Desenvolvidos/estatística & dados numéricos , Humanos , Inflamação/epidemiologiaRESUMO
Atherosclerosis develops over the course of 50 years, beginning in the early teenage years. The causes of this process appear to be lipid retention, oxidation, and modification, which provoke chronic inflammation at susceptible sites in the walls of all major conduit arteries. Initial fatty streaks evolve into fibrous plaques, some of which develop into forms that are vulnerable to rupture, causing thrombosis or stenosis. Erosion of the surfaces of some plaques and rupture of a plaque's calcific nodule into the artery lumen also may trigger thrombosis. The process of plaque development is the same regardless of race/ethnicity, sex, or geographic location, apparently worldwide. However, the rate of development is faster in patients with risk factors such as hypertension, tobacco smoking, diabetes mellitus, obesity, and genetic predisposition. Clinical trial data demonstrate that treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) favorably alters plaque size, cellular composition, chemical composition, and biological activities centered on inflammation and cholesterol metabolism, as well as the risk of clinical events due to atherosclerosis. Even with advanced atherosclerosis, statins begin to improve clinical risk within 4 months. During long-term follow-up in clinical trials for up to 11 years with or without further treatment, clinical benefit remains significant, indicating the durability of treatment-induced changes in the development of plaque. Thus, atherosclerosis, a disease heretofore viewed as inevitably progressive, can be treated to significantly alter arterial lesions and reduce their clinical consequences.
Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Adolescente , Arteriopatias Oclusivas/epidemiologia , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Aterosclerose/patologia , Colesterol/metabolismo , Diabetes Mellitus/epidemiologia , Humanos , Hipertensão/epidemiologia , Obesidade/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Tabagismo/epidemiologia , Trombose Venosa/epidemiologiaRESUMO
This article provides a checklist designed to aid the busy clinician in organizing and implementing an effective course of atherosclerosis evaluation and treatment, and a compendium highlighting a selection of useful guidelines for the general practitioner.
Assuntos
Aterosclerose , Inquéritos e Questionários , Aterosclerose/diagnóstico , Aterosclerose/tratamento farmacológico , Aterosclerose/fisiopatologia , LDL-Colesterol/sangue , Hemoglobinas Glicadas/metabolismo , Humanos , Hipertensão/epidemiologia , Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Fatores de Risco , Fumar/epidemiologiaRESUMO
BACKGROUND: Cardiovascular (CV) event risk is significantly lower in patients with combined low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) at desired levels versus those without lower levels. However, this has not been investigated relative to specific patterns of baseline lipid abnormalities. OBJECTIVE: To evaluate the association between desired combined lipid value achievement and risk of CV events in patients with different baseline lipid profiles. METHODS: A retrospective managed care database analysis among treatment-naïve adults with elevated CV event risk, ≥12 months follow-up, and full lipid panel from January 1, 2001 to December 31, 2001 plus ≥1 panel before a CV event or study end. Patients were stratified into three baseline cohorts: isolated high LDL-C (Cohort 1), high LDL-C + low HDL-C or high TG (Cohort 2), and high LDL-C, low HDL-C, and high TG (Cohort 3). CV event risk stratified by combined desired lipid value achievement was assessed in each cohort. RESULTS: Achievement of combined desired lipid values/median days to achievement was 29% in 385 days (Cohort 1), 11% in 413 days (Cohort 2), and 7% in 505 days (Cohort 3). Achievement of combined desired lipid values was associated with an adjusted 25%-46% lower CV event risk in Cohort 1 (hazards ratio, 0.75; 95% confidence interval 0.65-0.87), Cohort 2 (hazards ratio, 0.54; 95% confidence interval 0.43-0.67), and Cohort 3 (hazard ratio, 0.54; 95% confidence interval 0.37-0.78). CONCLUSION: Patients with combined desired lipid values had lower risk of CV events versus those without such values. The risk reduction was greatest among patients with multiple lipid abnormalities, suggesting a potential benefit of interventions targeting low HDL-C and/or high TG in addition to high LDL-C.
RESUMO
OBJECTIVE: To evaluate attainment of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein cholesterol (LDL-C) goal of less than 100 mg/dL with statin treatments in managed care patients at high risk for coronary heart disease. PATIENTS AND METHODS: In a randomized, open-label, multicenter trial (SOLAR [Satisfying Optimal LDL-C ATP III goals with Rosuvastatin]) performed at 145 US clinical centers from June 5, 2002 to July 12, 2004, high-risk men and women in a managed care population received typical starting doses of rosuvastatin (10 mg/d), atorvastatin (10 mg/d), or simvastatin (20 mg/d) for 6 weeks. Those who did not meet the LDL-C target of less than 100 mg/dL at 6 weeks had their dose titrated (doubled), and all patients were followed up for another 6 weeks. RESULTS: A total of 1632 patients were randomized to 1 of the 3 treatment regimens. After 6 weeks, 65% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 41% with atorvastatin and 39% with simvastatin (P<.001 vs rosuvastatin for both). After 12 weeks, 76% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 58% with atorvastatin and 53% with simvastatin (P<.001 vs rosuvastatin for both). Reductions in the LDL-C level, total cholesterol level, non-high-density lipoprotein cholesterol (non-HDL-C) level, and non-HDL-C/HDL-C ratio were significantly greater with rosuvastatin at both 6 and 12 weeks compared with the other statins. Adverse events were similar in type and frequency in all treatment groups, and only 3% of all patients discontinued treatment because of adverse events. No myopathy was observed, no clinically important impact on renal function was attributed to study medications, and clinically important increases in serum transaminases were rare. CONCLUSION: In a managed care population, 10 mg of rosuvastatin treatment resulted in more patients reaching the NCEP ATP III LDL-C goal compared with 10 mg of atorvastatin and 20 mg of simvastatin, potentially reducing the need for titration visits.
Assuntos
LDL-Colesterol/sangue , Doença das Coronárias/sangue , Fluorbenzenos/administração & dosagem , Ácidos Heptanoicos/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipertrigliceridemia/sangue , Hipertrigliceridemia/tratamento farmacológico , Pirimidinas/administração & dosagem , Pirróis/administração & dosagem , Sinvastatina/administração & dosagem , Sulfonamidas/administração & dosagem , Idoso , Atorvastatina , Creatinina/sangue , Feminino , Humanos , Masculino , Programas de Assistência Gerenciada , Pessoa de Meia-Idade , Rosuvastatina CálcicaRESUMO
INTRODUCTION: A previous study demonstrated the efficacy of a phospholipid (PL) complexed with a protein (apoAI Milano) in causing 4.6% regression of atheroma volume as assessed by intravascular ultrasonography (IVUS) in a group of 47 patients with carotid atherosclerosis. The results of this study raised the question of whether the phospholipid alone could produce a similar effect. METHODS: To answer this question a trial of 39 subjects at five sites was designed. Patients with > 15% stenosis of at least one carotid artery as determined by US underwent intravenous PL (200 mg/kg) or placebo infusions weekly for 8 weeks. The wall/outer wall ratio, percent lipid-rich/necrotic core, and percent calcification were measured as a proportion of the vessel wall by magnetic resonance imaging (MRI) at 0, 4, 8, and 14 weeks. RESULTS: The substudy of seven of these patients evaluated at our site allowed comparison of the dimensions of five unoperated-unoperated carotid pairs and two operated-unoperated pairs. In patient 1, MRI measurements on unoperated left and unoperated right carotids tracked almost identically over the 14-week study. Both carotids showed similar increases in the volumes of the total wall (+61% vs. 56%), the normal wall (+51% vs. 49%), and plaque (+99% vs. 85%). Both carotids showed similar decreases in lumen volume (-11% vs. -17%). The other four unoperated-unoperated carotid pairs showed dimensional changes over 14 weeks similar to those of patient 1. In patient 2, who underwent left endarterectomy, the operated carotid had a total artery volume of 2300 mm(3), about twofold greater than the unoperated carotid (1100 mm(3)). Operated and unoperated carotid measurements tracked in parallel. The unoperated carotid had volume increases of 25% (+200 mm(3)) in total wall, +19% (+100 mm(3)) in normal wall, and 43% (+75 mm(3)) in plaque. The operated carotid lumen showed no significant changes. Patient 7, who also underwent left endarterectomy, exhibited carotid changes similar to those of patient 2. CONCLUSIONS: Individual unoperated carotid pairs have volumes that track almost identically. In unilateral operated carotid pairs, the operated artery has 1.5- to 2.0-fold greater volume than unoperated carotids. In each of our two unilaterally operated patients, the operated carotid had decreased plaque volume (-3%, -58%), whereas the unoperated carotid had increased plaque volume (+43%, +7%). Among the five unoperated patients, one pair had 85%/99% increase in plaque volume; one pair had -15%/-10% decrease; and the other three pairs had intermediate changes. This study provides additional support to the view that unoperated human carotid arteries are bilaterally symmetrical.
Assuntos
Artérias Carótidas/patologia , Estenose das Carótidas/tratamento farmacológico , Estenose das Carótidas/patologia , Imageamento por Ressonância Magnética/métodos , Fosfatidilcolinas/uso terapêutico , Idoso , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , UltrassonografiaRESUMO
The relationship between dyslipidemia and hearing is unclear. This study was conducted to investigate whether elevated serum lipid levels impact auditory function in humans and in guinea pigs. In the human study, a cross-sectional study of 40 volunteers with dyslipidemia was conducted. Pure tone thresholds, distortion product otoacoustic emissions, and lipid profiles were analyzed. When controlled for patient age and sex, we found that elevated triglycerides were associated with reduced hearing. In the guinea pig study, a prospective study of animals fed a high-fat diet for 14 weeks was conducted. Although the high-fat diet led to a dramatic elevation in the average weight and total cholesterol in all animals (from 61 to 589 mg/dl), there were no meaningful changes in distortion product otoacoustic emission magnitudes. These results suggest that whereas chronic dyslipidemia associated with elevated triglycerides may reduce auditory function, short-term dietary changes may not.
Assuntos
Dislipidemias/complicações , Perda Auditiva/etiologia , Emissões Otoacústicas Espontâneas/fisiologia , Adulto , Idoso , Animais , Audiometria de Tons Puros , Limiar Auditivo/fisiologia , Colesterol/sangue , Estudos Transversais , Gorduras na Dieta/administração & dosagem , Feminino , Cobaias , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Triglicerídeos/sangueRESUMO
Bile acid sequestrants (BAS) continue to command a position in the treatment of dyslipidemias 25 years after their introduction. Partial diversion of the enterohepatic circulation using BAS depletes the endogenous bile acid pool by approximately 40%, thus stimulating an increase in bile acid synthesis from cholesterol, which lowers low-density lipoprotein cholesterol (LDL-C) by 15 to 26%. Three BAS are currently used for treating hypercholesterolemia in the United States: the conventional sequestrants, cholestyramine and colestipol, and the specifically engineered BAS, colesevelam hydrochloride (HCl). Compared with conventional BAS, colesevelam HCl has enhanced specificity, greater affinity, and higher capacity for binding bile acids, due to its polymer structure engineered for bile acid sequestration. BAS are not absorbed by the intestine and thus have no systemic drug-drug interactions, but may interfere with the absorption of some drugs. Although BAS monotherapy effectively lowers LDL-C, combination therapy, especially with BAS and statins, is becoming increasingly common due to complementary mechanisms of action. Low-dose statin plus BAS combinations lead to greater or similar LDL-C reductions compared with high-dose statin monotherapy and may have a better safety profile. Combinations of BAS with nonstatin lipid-lowering agents, including niacin, fibrates, and cholesterol absorption inhibitors, may be useful in those patients who require intensive lipid-lowering, but are statin intolerant. BAS treatment can significantly reduce coronary artery disease (CAD) progression and the risk of CAD-associated outcomes. It is also becoming clear that BAS and other therapies that manipulate the bile acid synthetic pathway may have clinically useful therapeutic effects on other metabolic disorders including type 2 diabetes.
Assuntos
Ácidos e Sais Biliares/uso terapêutico , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Alilamina/análogos & derivados , Alilamina/uso terapêutico , Colesterol/análogos & derivados , Colesterol/uso terapêutico , Cloridrato de Colesevelam , Colestipol/uso terapêutico , Dislipidemias/sangue , Humanos , Resultado do TratamentoRESUMO
PURPOSE: To provide sample size calculation for the quantitative assessment of carotid atherosclerotic plaque using non-invasive magnetic resonance imaging in multi-center clinical trials. METHODS. As part of a broader double-blind randomized trial of an experimental pharmaceutical agent, 20 asymptomatic placebo-control subjects were recruited from 5 clinical sites for a multi-center study. Subjects had 4 scans in 13 weeks on GE 1.5 T scanners, using TOF, T1-/PD-/T2- and contrast-enhanced Tl-weighted images. Measurement variability was assessed by comparing quantitative data from the index carotid artery over the four time points. The wall/outer wall (W/OW) ratio was calculated as wall volume divided by outer wall volume. The percent lipid-rich/necrotic core (%LR/NC) and calcification (%Ca) were measured as a proportion of the vessel wall. For %LR/NC and %Ca, only those subjects that exhibited LR/NC or Ca components were used in the analysis. RESULTS: Measurement error was 5.8% for wall volume, 3.2% for W/OW ratio, 11.1% for %LR/NC volume and 18.6% for %Ca volume. Power analysis based on these values shows that a study with 14 participants in each group could detect a 5% change in W/OW ratio, 10% change in wall volume, and 20% change in %LR/NC volume (power = 80%, p < .05). The calculated measurement errors presume any true biological changes were negligible over the 3 months that subjects received placebo. CONCLUSION: In vivo MRI is capable of quantifying plaque volume and plaque composition, such as %lipid-rich/necrotic core and %calcification, in the clinical setting of a multi-center trial with low inter-scan variability. This study provides the basis for sample size calculation of future MRI trials.
Assuntos
Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/patologia , Artéria Carótida Primitiva/patologia , Imageamento por Ressonância Magnética , Tamanho da Amostra , Idoso , Anatomia Transversal , Doenças das Artérias Carótidas/diagnóstico , Artéria Carótida Primitiva/anatomia & histologia , Fatores de Confusão Epidemiológicos , Método Duplo-Cego , Feminino , Humanos , Aumento da Imagem , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
Abstract Raloxifene and low-dose simvastatin can each reduce low-density lipoprotein (LDL) cholesterol without affecting high-density lipoprotein (HDL) cholesterol and triglycerides. The objective of this double-blind, 12-week study is to determine whether raloxifene and simvastatin coadministration gives added benefit beyond either monotherapy in affecting fasting lipoproteins and apolipoproteins. Ninety-five postmenopausal women with moderately elevated LDL cholesterol (mean, 146 mg/dL) were randomized to placebo, raloxifene 60 mg/d, simvastatin 10 mg/d, or raloxifene 60 mg/d coadministered with simvastatin 10 mg/d. Raloxifene, simvastatin, and coadministration therapy reduced mean LDL cholesterol by 10.5%, 23.3%, and 31.0% from baseline, respectively ( P < .003 vs baseline; P < .02 vs placebo), and mean apolipoprotein B by 10.4%, 24.2%, and 30.0% from baseline, respectively ( P < .003 vs baseline; P < .02 vs placebo). Each active treatment decreased non-HDL cholesterol compared with placebo ( P < .01). Coadministration treatment was more effective than either monotherapy in reducing LDL cholesterol ( P < .05). Coadministration treatment reduced mean apolipoprotein B ( P < .001) and non-HDL cholesterol ( P < .001) when compared with raloxifene, but was not significantly different when compared with simvastatin. Coadministration therapy increased HDL cholesterol and apolipoprotein A1 levels compared with placebo ( P < .02). No significant effect on triglycerides, very low density lipoprotein cholesterol, and lipoprotein (a) occurred with any active treatment. Raloxifene, simvastatin, and the coadministration therapy were generally well tolerated with clinical adverse effects similar to placebo. No woman had clinically significant elevated liver function tests requiring drug discontinuation. Further data on safety and lipid-lowering effects are needed before raloxifene and statin coadministration may be considered as therapeutic interventions for treating postmenopausal women to achieve National Cholesterol Education Program-Adult Treatment Panel III treatment guidelines.
Assuntos
Hipercolesterolemia/tratamento farmacológico , Lipídeos/sangue , Pós-Menopausa , Cloridrato de Raloxifeno/administração & dosagem , Sinvastatina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Hipercolesterolemia/sangue , Lipoproteínas/sangue , Pessoa de Meia-Idade , Placebos , Cloridrato de Raloxifeno/uso terapêutico , Sinvastatina/uso terapêuticoRESUMO
PURPOSE: To test the image quality (ImQ) and interscan coverage of MRI for measuring carotid atherosclerosis across multiple centers. MATERIALS AND METHODS: Thirty-nine subjects from five clinical sites (site 1: n=11; site 2: n=16; site 3: n=2; site 4: n=3; site 5: n=7) were imaged on GE 1.5T scanners using a standardized carotid imaging protocol with five weightings (T1, proton density (PD), T2, time-of-flight (TOF), and contrast-enhanced (CE) T1). MR technologists from the five sites received comprehensive protocol training. A maximum coverage of 24 mm (12 slices) was designed for each of four scans (baseline and at four, eight, and 13 weeks). The adequacy of coverage was calculated as the percentage of arteries with at least six slices matched across all four scans. ImQ was evaluated using an established five-point scale for each image. ImQ>or= 3 was considered acceptable for image analysis. RESULTS: Across five sites, the mean ImQ was 3.4-4.2 for T1W, 3.6-4.4 for CE-T1W, 3.4-4.2 for PDW, 3.3-4.2 for T2W, and 3.4-4.0 for TOF. The mean ImQ per site was 3.5-4.2. All sites generated at least six-slice coverage (mean=8.0-9.1) for all index carotid arteries. CONCLUSION: The ImQ and coverage values were comparable among clinical sites using a standardized carotid imaging protocol. With comprehensive protocol training, carotid MRI is technically feasible for use in multicenter studies.
Assuntos
Doenças das Artérias Carótidas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Meios de Contraste , Estudos de Viabilidade , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) can accurately and reproducibly measure the volume of atherosclerotic plaque in human carotid arteries. Atherosclerotic plaques may either progress or regress over time, depending on individual risk factors and treatment regimens. This study was designed to determine if regression or progression of human carotid atherosclerosis in patients receiving statin therapy over 24 months can be detected by high-resolution MRI. METHODS: In 11 subjects who had undergone unilateral carotid endarterectomy and were on statin therapy, volumes for total carotid artery, concentric wall (normal wall), eccentric wall (plaque), and lumen were quantified at 0, 16 and 24 months using a 1.5-T human imager equipped with 6-cm phased array coils. RESULTS: The interobserver mean coefficient of variation (CV) was lowest for the lumen volume (3.1%) and highest for the plaque volume (9.8%). The interscan mean CV was lowest for the total artery volume (3.2%) and highest for the plaque volume (9.9%). As much as 26% regression and 35% progression were observed in individual subject's carotid artery eccentric wall (plaque) volumes over time. Mean eccentric wall volume increased 5% by 16 months and 8% by 24 months. Mean total wall volume increased slightly at both 16 and 24 months (+1.2% and +1.8%). CONCLUSIONS: High-resolution MRI provides a noninvasive reproducible method of tracking changes in carotid atherosclerosis. This pilot study detected changes in individual subjects at both 16 and 24 months. MRI tracking of changes in atherosclerotic plaques should prove useful in assessing vascular disease risk and monitoring the efficacy of interventions designed to induce regression or retard progression.
Assuntos
Arteriosclerose/diagnóstico , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Anticolesterolemiantes/uso terapêutico , Arteriosclerose/sangue , Arteriosclerose/tratamento farmacológico , Atorvastatina , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/tratamento farmacológico , Progressão da Doença , Feminino , Seguimentos , Ácidos Heptanoicos/uso terapêutico , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Projetos Piloto , Pravastatina/uso terapêutico , Pirróis/uso terapêutico , Reprodutibilidade dos Testes , Sinvastatina/uso terapêuticoRESUMO
This study assessed whether the co-administration of ezetimibe and simvastatin would be more effective than simvastatin monotherapy in allowing high-risk patients to achieve a low-density lipoprotein (LDL) cholesterol goal of <100 mg/dl. Men and women with LDL cholesterol >/=130 mg/dl and meeting National Cholesterol Education Program Adult Treatment Panel III criteria for coronary heart disease (CHD) or CHD risk equivalent were randomized to 1 of 4 daily treatments for 23 weeks: simvastatin 20 mg (n = 253), ezetimibe 10 mg plus simvastatin 10 mg (n = 251), ezetimibe 10 mg plus simvastatin 20 mg (n = 109), and ezetimibe 10 mg plus simvastatin 40 mg (n = 97). In all groups, patients not at goal had their simvastatin doses doubled at weeks 6, 12, and/or 18, up to a maximum of 80 mg. The primary efficacy objective was LDL cholesterol goal attainment (<100 mg/dl) after 5 weeks of treatment. Ezetimibe plus any dose of simvastatin produced greater reductions in LDL cholesterol and allowed more patients to achieve goal after 5 weeks (p <0.001) and at the end of the study (p <0.001) than simvastatin 20 mg alone. At 5 weeks, 75%, 83%, and 87% of patients receiving ezetimibe plus simvastatin 10, 20, and 40 mg had LDL cholesterol <100 mg/dl compared with 46% of patients receiving simvastatin 20 mg. In patients who started on ezetimibe plus simvastatin 10, 20 and 40 mg, 33%, 22%, and 12%, respectively, required simvastatin titration during the study compared with 68% of patients who started on simvastatin 20 mg. The corresponding median simvastatin doses used were 10, 20, 40, and 40 mg, respectively. Ezetimibe plus simvastatin was well tolerated, with an overall safety profile similar to that of simvastatin monotherapy. Thus, through the dual inhibition of cholesterol absorption and synthesis, ezetimibe plus simvastatin allowed more patients to reach LDL cholesterol <100 mg/dl at a lower simvastatin dose and with fewer dose titrations than simvastatin monotherapy.
Assuntos
Anticolesterolemiantes/administração & dosagem , Azetidinas/administração & dosagem , LDL-Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Sinvastatina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/efeitos adversos , Azetidinas/efeitos adversos , Doença das Coronárias/prevenção & controle , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Ezetimiba , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Fatores de Risco , Sinvastatina/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Combination therapy to improve the total lipid profile may achieve greater coronary risk reductions than lowering low-density lipoprotein cholesterol (LDL-C) alone. A new extended-release niacin (niacin ER)/lovastatin tablet substantially lowers LDL-C, triglyceride, and lipoprotein(a) levels and raises high-density lipoprotein cholesterol (HDL-C) level. We evaluated these serum lipid responses to niacin ER/lovastatin at all clinically reasonable doses. METHODS: Men (n = 85) and women (n = 79) with type IIa or IIb primary hyperlipidemia after diet were randomized among 5 parallel treatment arms. Each arm had 5 sequential 4-week treatment periods: niacin ER (starting at 500 mg/d, increasing in 500-mg increments to 2500 mg/d); lovastatin (starting at 10 mg, increasing to 20 mg, then 40 mg/d); and 3 combinations arms, each with a constant lovastatin dose and escalating niacin ER doses. RESULTS: For primary comparisons, mean LDL-C level reductions from baseline were greater with niacin ER/lovastatin (1500/20 mg) than with lovastatin (20 mg) (35% vs 22%, P<.001) and with niacin ER/lovastatin (2000/40 mg) than with lovastatin (40 mg) (46% vs 24%, P<.001). Each 500-mg increase in niacin ER, on average, decreased LDL-C levels an additional 4% and increased HDL-C levels 8%. The maximum recommended dose (2000/40 mg/d) increased HDL-C levels 29% and decreased LDL-C levels 46%, triglyceride levels 38%, and lipoprotein(a) levels 14%. All lipid responses were dose dependent and generally additive. Graphs of the dose-response relationships as 3-dimensional surfaces documented the strength and consistency of these responses. CONCLUSIONS: Niacin ER/lovastatin combination therapy substantially improves 4 major lipoprotein levels associated with atherosclerotic disease. Dose-response surfaces provide a practical guide for dose selection.
Assuntos
Hipercolesterolemia/tratamento farmacológico , Lovastatina/administração & dosagem , Niacina/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Hipercolesterolemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Probabilidade , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.
Assuntos
Arteriosclerose/patologia , Doença das Coronárias/etiologia , Doença Aguda , Arteriosclerose/classificação , Arteriosclerose/complicações , Consenso , Morte Súbita Cardíaca/etiologia , Progressão da Doença , Humanos , Modelos Cardiovasculares , Medição de Risco , Síndrome , Terminologia como AssuntoRESUMO
Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.
Assuntos
Doença da Artéria Coronariana/epidemiologia , Morte Súbita Cardíaca/epidemiologia , Infarto do Miocárdio/epidemiologia , Medição de Risco/organização & administração , Animais , Biomarcadores , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Programas de Rastreamento , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Miocárdio/patologia , Índice de Gravidade de Doença , Suínos , Trombofilia/sangue , Trombofilia/complicações , Trombofilia/genéticaRESUMO
BACKGROUND AND PURPOSE: Atherosclerosis is a principal cause of stroke and myocardial infarction. The carotid arteries provide a site at which progression of atherosclerosis can be monitored reproducibly and noninvasively. This study was conducted to determine the similarity of atherosclerotic plaques in the left and right carotid arteries. This question was explored with the use of perfusion-fixed cadaveric carotid arteries and 2 noninvasive clinical imaging techniques, MRI and electron-beam CT. METHODS: Fifty pairs of carotid arteries from cadaveric donors (aged 48 to 98 years) were imaged with MRI and electron-beam CT. Thirty-eight of the pairs met the criteria for rigorous analysis. Carotid artery wall volumes were measured from the MRI images, and calcification scores were computed from the electron-beam CT images. RESULTS: Total wall volumes of the left (972.5+/-241.6 mm3) and right (1016.3+/-275.0 mm3) carotid arteries were moderately correlated (concordance correlation coefficient [r(c)]=0.71). Calcification scores were highly correlated, with r(c)=0.95 for the Agatston scores and r(c)=0.94 for the calcium volume scores. CONCLUSIONS: Total wall volume and plaque calcification in the left and right human carotid arteries are substantially similar. These results suggest that atherosclerosis of the human carotid arteries is generally a bilaterally symmetrical disease. This evidence of symmetry suggests that diagnostic information about atherosclerotic plaque in one carotid artery can be used to infer information about the composition and volume of atherosclerotic plaque in the contralateral artery.