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Prediction of future development of cardiovascular disease with an equation to estimate apolipoprotein B: A community-based cohort study.
Hwang, YC, Park, CY, Ahn, HY, Cho, NH
Medicine. 2016;(24):e3644
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Abstract
Apolipoprotein B (apoB) has additional benefits over conventional lipid measurements in predicting future cardiovascular disease (CVD). We aimed to validate the clinical relevance of our equation to estimate apoB in a large-scale, prospective, community-based cohort study (Ansung-Ansan cohort study).A total of 9001 Korean subjects were assessed. We excluded subjects with history of CVD (n = 228), taking lipid-lowering medications (n = 51), and those whose outcome data were not available (n = 33). Finally, a total of 8713 subjects (4126 men and 4587 women) with a mean age of 52.2 years were enrolled and followed up biannually for a mean 8.1 years.At baseline, 24.9% of subjects were current smokers, 12.5% had diabetes, and 22.2% had hypertension. Incident case of CVD occurred in 600 of the study subjects (493 ischemic heart disease and 424 stroke). Independent variables included in the models were age, sex, waist circumference, current smoking, and presence of diabetes and hypertension. Both non-HDL cholesterol (HR per 1-SD [95% CI]; 1.13 [1.05-1.23], P = 0.002) and estimated apoB (HR per 1-SD [95% CI]; 1.14 [1.05-1.24], P = 0.001) were independently associated with the development of CVD; however, the LDL cholesterol level was not predictive of future CVD (HR per 1-SD [95% CI]; 1.07 [0.99-1.16], P = 0.08).Both non-HDL cholesterol and estimated apoB level were independently associated with the development of CVD. Because LDL cholesterol has limited value to predict incident CVD, we recommend calculating non-HDL cholesterol or apoB with our equation to predict risk of incident CVD in the general Korean population.
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Alteration of relation of atherogenic lipoprotein cholesterol to apolipoprotein B by intensive statin therapy in patients with acute coronary syndrome (from the Limiting UNdertreatment of lipids in ACS With Rosuvastatin [LUNAR] Trial).
Ballantyne, CM, Pitt, B, Loscalzo, J, Cain, VA, Raichlen, JS
The American journal of cardiology. 2013;(4):506-9
Abstract
The low-density lipoprotein (LDL) cholesterol goal of <70 mg/dl, recommended for patients with acute coronary syndrome, typically requires intensive therapy with high-dose statins. The secondary goals of non-high-density lipoprotein (non-HDL) cholesterol <100 mg/dl and apolipoprotein B (ApoB) <80 mg/dl have been recommended to reduce excess cardiovascular risk not captured by LDL cholesterol. The present post hoc analysis from the Limiting UNdertreatment of lipids in Acute coronary syndrome with Rosuvastatin (LUNAR) study examined the relation of ApoB with LDL cholesterol and non-HDL cholesterol at baseline and during treatment with intensive statin therapy. The LUNAR participants had acute coronary syndrome and received rosuvastatin 40 mg/day or 20 mg/day or atorvastatin 80 mg/day for 12 weeks. Linear regression analyses were used to compare ApoB, direct LDL cholesterol, and non-HDL cholesterol at baseline and during therapy. Of the 682 patients included in the analysis, 220 had triglycerides ≥200 mg/dl. Linear regression analysis showed that correlation of ApoB and non-HDL cholesterol was stronger than that of ApoB and LDL cholesterol and stronger with statin therapy than at baseline (R(2) = 0.93 for ApoB vs non-HDL cholesterol with statins). The target of ApoB of 80 mg/dl correlated with LDL cholesterol of 90 mg/dl and non-HDL cholesterol of 110 mg/dl at baseline and with LDL cholesterol of 74 mg/dl and non-HDL cholesterol of 92 mg/dl with statin therapy. For high-triglyceride patients, the corresponding on-treatment targets were LDL cholesterol of 68 mg/dl and non-HDL cholesterol of 92 mg/dl. In conclusion, non-HDL cholesterol is an adequate surrogate of ApoB during statin therapy, independent of triglyceride status. However, to match LDL cholesterol and ApoB treatment goals in the very-high-risk category, the current non-HDL cholesterol goal should be lowered by 8 to 10 mg/dl.
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Achievement of specified low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol apolipoprotein B, and high-sensitivity C-reactive protein levels with ezetimibe/simvastatin or atorvastatin in metabolic syndrome patients with and without atherosclerotic vascular disease (from the VYMET study).
Robinson, JG, Ballantyne, CM, Hsueh, W, Rosen, J, Lin, J, Shah, A, Lowe, RS, Hanson, ME, Tershakovec, AM
Journal of clinical lipidology. 2011;(6):474-82
Abstract
BACKGROUND Metabolic syndrome (MetS) and atherosclerotic vascular disease (AVD) are associated with increased coronary heart disease risk. OBJECTIVE To assess percent change from baseline in lipids and high-sensitivity C-reactive protein (hs-CRP) levels and the proportion of subjects reaching specified low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B (Apo B) single, dual, and triple targets and hs-CRP <2 mg/L among subjects with and without AVD treated with ezetimibe/simvastatin or atorvastatin for 6 weeks. METHODS Adults (N = 1143) with MetS and hypercholesterolemia were randomized to starting and next higher doses of ezetimibe/simvastatin (10/20 or 10/40 mg) or atorvastatin (10, 20, or 40 mg). RESULTS Ezetimibe/simvastatin produced significantly greater reductions in evaluated lipids than atorvastatin for most prespecified dose comparisons. More subjects without AVD achieved LDL-C levels <100 mg/dL, non-HDL-C levels <130 mg/dL, and dual LDL-C/non-HDL targets (83%-92% vs 62%-76%) and Apo B <90 mg/dL or triple targets (65%-75% vs 41%-49%) with 40 mg of atorvastatin or 10/20-40 mg of ezetimibe/simvastatin compared with 10 or 20 mg of atorvastatin, respectively. More subjects with AVD achieved LDL-C<70 mg/dL and non-HDL-C<100 mg/dL single and dual targets (65%-80%) and Apo B <80 mg/dL (53%-63%) with 10/20-40 mg of ezetimibe/simvastatin than with 40 mg of atorvastatin (40%-49%). More subjects achieved triple lipid targets with 10/20-40 mg of ezetimibe/simvastatin versus 10-40 mg of atorvastatin (50%-63% vs 24%-40%). Achievement of hs-CRP <2 mg/L was similar across all doses regardless of AVD status. CONCLUSIONS More intensive therapy was required for >80% of subjects to achieve LDL-C <100 mg/dL and non-HDL-C <130 mg/dL and for the majority of subjects to achieve lower levels of LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and/or Apo B <90 mg/dL. The effect of ezetimibe on cardiovascular risk reduction has yet to be established. (Clintrials.gov no: NCT00409773).
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Effect of a traditional Mediterranean diet on apolipoproteins B, A-I, and their ratio: a randomized, controlled trial.
Solá, R, Fitó, M, Estruch, R, Salas-Salvadó, J, Corella, D, de La Torre, R, Muñoz, MA, López-Sabater, Mdel C, Martínez-González, MA, Arós, F, et al
Atherosclerosis. 2011;(1):174-80
Abstract
OBJECTIVES Apolipoprotein (Apo)B, ApoA-I, and their ratio could predict coronary heart disease (CHD) risk more accurately than conventional lipid measurements. Our aim was to assess the effect of a traditional Mediterranean diet (TMD) on apolipoproteins. METHODS High-cardiovascular risk subjects (n=551, 308 women and 243 men), aged 55-80 years, were recruited into a large, multicenter, randomized, controlled, parallel-group, clinical trial (The PREDIMED Study) aimed at testing the efficacy of TMD on primary cardiovascular disease prevention. Participants assigned to a low-fat diet (control) (n=177), or TMDs (TMD+virgin olive oil (VOO), n=181 or TMD+nuts, n=193) received nutritional education and either free VOO (ad libitum) or nuts (dose: 30 g/day). A 3-month evaluation was performed. RESULTS Both TMDs promoted beneficial changes on classical cardiovascular risk factors. ApoA-I increased, and ApoB and ApoB/ApoA-I ratio decreased after TMD+VOO, the changes promoting a lower cardiometabolic risk. Changes in TMD+VOO versus low-fat diet were -2.9 mg/dL (95% CI, -5.6 to -0.08), 3.3mg/dL (95% CI, 0.84 to 5.8), and -0.03 mg/dL (-0.05 to -0.01) for ApoB, ApoA-I, and ApoB/ApoA-I ratio, respectively. CONCLUSIONS Individuals at high-cardiovascular risk who improved their diet toward a TMD pattern rich in virgin olive oil, reduced their Apo B and ApoB/ApoA-I ratio and improved ApoA-I concentrations.
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Concordance between plasma apolipoprotein B levels and cholesterol indices among patients receiving statins and nonstatin treatment: Post-hoc analyses from the U.K. InPractice study.
Idris, I, Tate, H, Ahmad, A, McCormack, T
Journal of clinical lipidology. 2011;(4):316-23
Abstract
BACKGROUND Apolipoprotein B (ApoB) is a superior predictor of low-density-lipoprotein (LDL) particle number and cardiovascular disease (CVD) risk compared with LDL-cholesterol (LDL-C) levels. Current evidence has shown a degree of discordance between LDL-C with ApoB levels among patients not receiving lipid-lowering therapy. The extent of this discordance among patients receiving LDL-lowering therapies however is less clear. METHODS We performed a post hoc analysis of the InPractice data looking at the concordance between LDL-C, non-high density lipoprotein-cholesterol (nonHDL-C) and total cholesterol with ApoB values. The study involved 786 high-risk CVD patients from 34 primary care centers initially treated with simvastatin (S) 40 mg at baseline subsequently randomized to adding ezetimibe 10 mg to S 40 mg (E/S40) or changed to atorvastatin (A) 40 mg or to rosuvastatin (R) 5-10 mg for 6 weeks. RESULTS At 6 weeks after treatment, the association between LDL-C and ApoB values for the different treatment regimes were similar; Pearson's correlation coefficients between LDL-C and ApoB were 0.84 (E/S40), 0.82 (A), and 0.83 (R). Overall, ApoB appeared to have a slightly greater correlation with nonHDL-C than with LDL-C across all treatment groups, for baseline and posttreatment values. The analysis of quintile frequencies showed a similar pattern; the proportion of patients who had values that fell in the same quintile post treatment for ApoB and LDL-C levels were 52.2% (E/S40), 44.5% (A), and 49.4% (R). Concordance between ApoB and nonHDL-C was 60.6% (E/S40), 62.4% (A), and 61.8% (R). Kappa analysis confirmed fair agreement between LDL-C and ApoB levels for all treatment groups; 0.59 (E/S40), 0.54 (A), and 0.56(R). CONCLUSION We showed that the association between ApoB and LDL-C is similar across different lipid-lowering treatment regimes, which suggests that the use of different lipid-lowering agent confers similar ability to predict ApoB levels. When determining CVD risk at an individual patient level, limitation exists when using LDL-C or nonHDL-C per se as risk markers. In the absence of ApoB measurement, we believe that information from both LDL-C and nonHDL-C should be used together to improve the estimation of residual CVD risk among patients who are already receiving lipid lowering therapy.
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Switching from statin monotherapy to ezetimibe/simvastatin or rosuvastatin modifies the relationships between apolipoprotein B, LDL cholesterol, and non-HDL cholesterol in patients at high risk of coronary disease.
Vaverkova, H, Farnier, M, Averna, M, Missault, L, Viigimaa, M, Dong, Q, Shah, A, Johnson-Levonas, AO, Brudi, P
Clinical biochemistry. 2011;(8-9):627-34
Abstract
OBJECTIVE To evaluate relationships between apolipoprotein B (Apo B), LDL cholesterol (LDL-C), and non-HDL-C in high-risk patients treated with lipid-lowering therapy. DESIGN AND METHODS This post-hoc analysis calculated LDL-C and non-HDL-C levels corresponding to an Apo B of 0.9 g/L following treatment with 1) statin monotherapy (baseline) and 2) ezetimibe/simvastatin 10/20mg or rosuvastatin 10mg (study end). The percentages of patients reaching LDL-C, non-HDL-C, and Apo B targets were calculated at study end. RESULTS After switching to ezetimibe/simvastatin or rosuvastatin, the LDL-C and non-HDL-C corresponding to Apo B=0.9 g/L were closer to the more aggressive LDL-C and non-HDL-C goals (1.81 and 2.59 mmol/L, respectively). Only slightly >50% of the patients who reached minimum recommended LDL-C or non-HDL-C at study end also had an Apo B level <0.9 g/L with both treatments. CONCLUSION The use of Apo B for monitoring the efficacy of lipid-altering therapy would likely lead to more stringent criteria for lipid lowering.
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Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus: Relevance for non-HDL cholesterol and apolipoprotein B guideline targets.
Kappelle, PJ, Dallinga-Thie, GM, Dullaart, RP, ,
Biochimica et biophysica acta. 2010;(1):89-94
Abstract
The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein (apo) B. Changes in LDL size and RLP-C were determined in fasting plasma from type 2 diabetic patients after 30 weeks administration of atorvastatin (10 mg daily, n=65; 80 mg daily, n=62) or placebo (n=58). LDL subfraction cholesterol was measured in 74 participants. Atorvastatin lowered LDL cholesterol, non-HDL cholesterol, triglycerides, apo B and RLP-C (P<0.001 for all at each dose) and LDL mean peak particle diameter remained unchanged. Atorvastatin treatment decreased cholesterol concentrations in all LDL subfractions (P<0.001 for each dose). RLP-C at follow-up was lower in those patients achieving the non-HDL cholesterol or the apo B guideline targets (P<0.01), but the LDL cholesterol cut-off value failed to discriminate. In conclusion, atorvastatin lowers fasting RLP-C and LDL subfraction cholesterol in diabetes. The proposed guideline cut-off levels for non-HDL cholesterol and apo B may be superior to the LDL cholesterol target in discriminating between higher and lower RLP-C levels.
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Targets of statin therapy: LDL cholesterol, non-HDL cholesterol, and apolipoprotein B in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS).
Charlton-Menys, V, Betteridge, DJ, Colhoun, H, Fuller, J, France, M, Hitman, GA, Livingstone, SJ, Neil, HA, Newman, CB, Szarek, M, et al
Clinical chemistry. 2009;(3):473-80
Abstract
BACKGROUND LDL can vary considerably in its cholesterol content; thus, lowering LDL cholesterol (LDLC) as a goal of statin treatment implies the existence of considerable variation in the extent to which statin treatment removes circulating LDL particles. This consideration is particularly applicable in diabetes mellitus, in which LDL is frequently depleted of cholesterol. METHODS Type 2 diabetes patients randomly allocated to 10 mg/day atorvastatin (n = 1154) or to placebo (n = 1196) for 1 year were studied to compare spontaneous and statin-induced apolipoprotein B (apo B) concentrations (a measure of LDL particle concentration) at LDLC and non-HDL cholesterol (non-HDLC) concentrations proposed as statin targets in type 2 diabetes. RESULTS Patients treated with atorvastatin produced lower serum apo B concentrations at any given LDLC concentration than patients on placebo. An LDLC concentration of 1.8 mmol/L (70 mg/dL) during atorvastatin treatment was equivalent to a non-HDLC concentration of 2.59 mmol/L (100 mg/dL) or an apo B concentration of 0.8 g/L. At the more conservative LDLC targets of 2.59 mmol/L (100 mg/dL) and 3.37 mmol/L (130 mg/dL) for non-HDLC, however, the apo B concentration exceeded the 0.9-g/L value anticipated in the recent Consensus Statement from the American Diabetes Association and the American College of Cardiology. CONCLUSIONS The apo B concentration provides a more consistent goal for statin treatment than the LDLC or non-HDLC concentration.
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Achieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target levels in high-risk patients: Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY (MERCURY) II.
Ballantyne, CM, Bertolami, M, Hernandez Garcia, HR, Nul, D, Stein, EA, Theroux, P, Weiss, R, Cain, VA, Raichlen, JS
American heart journal. 2006;(5):975.e1-9
Abstract
BACKGROUND National Cholesterol Education Program Adult Treatment Panel III guidelines for patients at a high risk of coronary heart disease set a low-density lipoprotein cholesterol (LDL-C) target of < 100 mg/dL. This target can be difficult to attain with diet and current therapy. METHODS In a 16-week multinational trial, 1993 high-risk patients were randomized to rosuvastatin 20 mg, atorvastatin 10 mg, atorvastatin 20 mg, simvastatin 20 mg, or simvastatin 40 mg for 8 weeks. Patients either remained on starting treatment or switched to lower or milligram-equivalent doses of rosuvastatin for 8 more weeks. RESULTS At 16 weeks, more patients achieved their LDL-C target by switching to rosuvastatin 10 mg than staying on atorvastatin 10 mg (66% vs 42%, P < .001) or simvastatin 20 mg (73% vs 32%, P < .001). Changing to rosuvastatin 20 mg brought more patients to their LDL-C target than staying on atorvastatin 20 mg (79% vs 64%, P < .001) or simvastatin 40 mg (84% vs 56%, P < .001). More very high risk patients achieved an LDL-C target of < 70 mg/dL when changed to rosuvastatin from atorvastatin or simvastatin (within-arm comparisons P < .01). More hypertriglyceridemic patients (triglycerides > or = 200 mg/dL) met LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B targets by changing to rosuvastatin. Switching to rosuvastatin produced greater reductions in LDL-C, total cholesterol, non-HDL-C, apolipoprotein B, and lipid ratios. All treatments were well tolerated, with no differences among treatment groups in skeletal muscle, hepatic, or renal toxicity. CONCLUSION Rosuvastatin 10 or 20 mg is an effective and safe therapeutic option for high-risk patients to achieve their lipid and apolipoprotein targets.
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Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel.
Barter, PJ, Ballantyne, CM, Carmena, R, Castro Cabezas, M, Chapman, MJ, Couture, P, de Graaf, J, Durrington, PN, Faergeman, O, Frohlich, J, et al
Journal of internal medicine. 2006;(3):247-58
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Abstract
There is abundant evidence that the risk of atherosclerotic vascular disease is directly related to plasma cholesterol levels. Accordingly, all of the national and transnational screening and therapeutic guidelines are based on total or LDL cholesterol. This presumes that cholesterol is the most important lipoprotein-related proatherogenic risk variable. On the contrary, risk appears to be more directly related to the number of circulating atherogenic particles that contact and enter the arterial wall than to the measured concentration of cholesterol in these lipoprotein fractions. Each of the atherogenic lipoprotein particles contains a single molecule of apolipoprotein (apo) B and therefore the concentration of apo B provides a direct measure of the number of circulating atherogenic lipoproteins. Evidence from fundamental, epidemiological and clinical trial studies indicates that apo B is superior to any of the cholesterol indices to recognize those at increased risk of vascular disease and to judge the adequacy of lipid-lowering therapy. On the basis of this evidence, we believe that apo B should be included in all guidelines as an indicator of cardiovascular risk. In addition, the present target adopted by the Canadian guideline groups of an apo B <90 mg dL(-1) in high-risk patients should be reassessed in the light of the new clinical trial results and a new ultra-low target of <80 mg dL(-1) be considered. The evidence also indicates that the apo B/apo A-I ratio is superior to any of the conventional cholesterol ratios in patients without symptomatic vascular disease or diabetes to evaluate the lipoprotein-related risk of vascular disease.