| 1. |
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| 2. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 3. |
- Palmer, M. K., et al.
(författare)
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Comparing a novel equation for calculating low-density lipoprotein cholesterol with the Friedewald equation: A VOYAGER analysis
- 2019
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 64, s. 24-29
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Tidskriftsartikel (refereegranskat)abstract
- Treating elevated low-density lipoprotein cholesterol (LDL-C) to risk-stratified target levels is recommended in several guidelines. Thus, accurate estimation of LDL-C is required. LDL-C is typically calculated using the Friedewald equation: (total cholesterol) - (non-high-density lipoprotein cholesterol [non-HDL-C]) - (triglycerides [TGs]/5). As the equation uses a fixed value equal to 5 as a divisor for TGs, it does not account for inter-individual variability, often resulting in underestimation of risk and potentially undertreatment. It is specifically inapplicable in patients with fasting triglycerides >= 400 mg/dL. A novel method of LDL-C calculation was derived and validated by Martin et al.: (non-HDL-C) - (triglycerides/adjustable factor). This equation uses an adjustable factor, the median TG:very-low-density lipoprotein cholesterol ratio in strata defined by levels of TG and non-HDLC, as divisor for TGs, and the adjustable factor ranging from 3 to 12 has been shown to provide more accurate estimates of LDL-C compared with the Friedewald equation using a direct assay as the gold standard. We used 70,209 baseline and on-treatment lipid values from the VOYAGER meta-analysis database to determine the difference in calculated LDL-C values using the Friedewald and novel equations. In patients with TGs < 400 mg/dL, LDL-C values calculated using the novel equation were plotted against those calculated using the Friedewald equation. The novel equation generally resulted in LDL-C values greater than the Friedewald calculation, with differences increasing with decreasing LDL-C levels; 23% of individuals who reached a LDL-C target of 70 mg/dL with the Friedewald equation did not achieve this target when the novel equation was used to calculate LDL-C; these figures were 8% and 2% for < 100 mg/dL and < 130 mg/dL targets, respectively. In patients with triglycerides >= 400 mg/dL, in whom the Friedewald equation is not valid, lipid values calculated using the novel equation were compared with those obtained by beta-quantification. Values calculated with the novel equation did not appear to be closely related with those calculated by beta-quantification in these patients. In conclusion, the novel equation provides a higher estimation of exact LDL-C values than the Friedewald equation, particularly in patients with low LDL-C levels, which may result in undertreatment of some patients whose LDL-C was calculated using the Friedewald method. However, neither may be suitable for patients with TG >= 400 mg/dL.
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| 4. |
- Akiba, K., et al.
(författare)
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Measurement of thermal properties of the LHCb VELO detector using track-based software alignment
- 2023
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Ingår i: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 18:10
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Tidskriftsartikel (refereegranskat)abstract
- The thermal properties of the LHCb Vertex Locator (VELO) are studied using the real-time detector alignment procedure. The variation of the position and orientation of the detector elements as a function of the operating temperature of the VELO is presented. This study uses a dataset collected by the LHCb experiment during a VELO temperature scan performed at the end of LHC Run 2 (October 2018). Significant shrinkage of the VELO modules is observed at the operating temperature of -30(degrees)C compared to the laboratory measurements on a single module taken at a range of temperatures from +45(degrees)C to -25(degrees)C. The thermal shrinkage expected from the extrapolation of laboratory measurements to lower temperatures, and the results of this alignment study are in good agreement.
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| 5. |
- Karlson, Björn W., 1953, et al.
(författare)
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Achievement of combined goals of low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol with three different statins: Results from VOYAGER
- 2014
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Ingår i: IJC Metabolic and Endocrine. - : Elsevier Ireland Ltd. - 2214-7624. ; 5, s. 61-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: Guidelines suggest that the combination of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) is the most clinically relevant goal for lipid-lowering treatments. Methods: Data from VOYAGER, an individual patient data meta-analysis including 32,258 patients from 37 clinical trials, was used to determine the percentage of patients reaching combined goals of LDL-C and non-HDL-C following treatment with simvastatin, atorvastatin, or rosuvastatin. Paired comparisons were made between each dose of rosuvastatin and the same or higher doses of simvastatin and atorvastatin. Results: Each dose of rosuvastatin brought significantly more patients to the combined goal of LDL-C <. 100. mg/dL and non-HDL-C <. 130. mg/dL than the same or double dose of atorvastatin; atorvastatin 80. mg was significantly superior to rosuvastatin 10. mg (all p. <. 0.001). Each dose of rosuvastatin helped significantly more patients reach the combined goal than any dose of simvastatin (all p. <. 0.001), except for rosuvastatin 10. mg versus simvastatin 80. mg (non-significant). Also, each dose of rosuvastatin helped significantly more patients to reach the combined goal of LDL-C <. 70. mg/dL and non-HDL-C <. 100. mg/dL than the same or double dose of atorvastatin (all p. <. 0.001). Every dose of rosuvastatin was significantly superior to all doses of simvastatin (all p. ≤. 0.020), except for rosuvastatin 10. mg versus simvastatin 40. mg and 80. mg (non-significant). Conclusions: Physicians' choice of statin and dose is important in helping patients achieve the combined LDL-C and non-HDL-C goals recommended in established guidelines.
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| 8. |
- Karlson, Björn W., 1953, et al.
(författare)
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A VOYAGER Meta-Analysis of the Impact of Statin Therapy on Low-Density Lipoprotein Cholesterol and Triglyceride Levels in Patients With Hypertriglyceridemia
- 2016
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 117:9, s. 1444-1448
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Tidskriftsartikel (refereegranskat)abstract
- Elevated triglyceride (TG) levels are associated with increased cardiovascular disease risk. In patients with mild-to-moderate hypertriglyceridemia, defined by the European Atherosclerosis Society Consensus Panel as a TG level of 177 to 885 mg/dl (2.0 to 10.0 mmol/L), low-density lipoprotein cholesterol (LDL-C) reduction remains the primary treatment goal. Using data from the indiVidual patient meta-analysis Of statin therapY in At risk Groups: Effects of Rosuvastatin, atorvastatin and simvastatin (VOYAGER) meta-analysis, we analyzed LDL-C and TG reductions in patients with baseline TG 2177 mg/dl (>= 2.0 mmol/L). Least squares mean percentage change from baseline in LDL-C and TG was compared using 15,800 patient exposures to rosuvastatin 5 to 40 mg, atorvastatin 10 to 80 mg, and simvastatin 10 to 80 mg in patients with baseline TG >= 177 mg/dl (>= 2.0 mmol/L). Comparisons were made using mixed-effects models with data only from studies directly comparing treatments by randomized design. Mean LDL-C reductions ranged from -26.9% to -55.5%. Rosuvastatin 10 to 40 mg resulted in significantly greater LDL-C reductions than equal or double doses of atorvastatin and simvastatin (p <0.05). Mean TG reductions ranged from -15.1% to -31.3%. Rosuvastatin 10 mg resulted in significantly greater TG reductions than atorvastatin 10 mg (p <0.05). Rosuvastatin 20 and 40 mg resulted in TG reductions similar to those with equal doses of atorvastatin. Rosuvastatin 10 to 40 mg resulted in significantly greater TG reductions than equal or double doses of simvastatin (p <0.05). In conclusion, in patients with hypertriglyceridemia, LDL-C reduction was substantial and dependent on the choice and dose of statin. TG reduction was numerically less than for LDL-C, and additional TG-lowering therapy may be considered to further reduce residual cardiovascular risk. (C) 2016 Elsevier Inc. All rights reserved.
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| 9. |
- Karlson, Björn W., 1953, et al.
(författare)
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Achievement of 2011 European low-density lipoprotein cholesterol (LDL-C) goals of either < 70 mg/dl or >= 50% reduction in high-risk patients: Results from VOYAGER
- 2013
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 228:1, s. 265-269
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Tidskriftsartikel (refereegranskat)abstract
- Objective Guidelines published in 2011 by the European Atherosclerosis Society and the European Society of Cardiology recommend a goal of either low-density lipoprotein cholesterol (LDL-C) <70 mg/dl (∼1.8 mmol/l) or ≥50% reduction in LDL-C for patients at very high cardiovascular risk. The aim of this study was to determine the percentage of high-risk patients from the VOYAGER individual patient data meta-analysis treated with rosuvastatin 10–40 mg, atorvastatin 10–80 mg or simvastatin 10–80 mg who achieved this goal. Methods We analysed 25,075 patient exposures from high-risk patients. Paired comparisons were made between each rosuvastatin dose and an equal or higher dose of either atorvastatin or simvastatin, with a series of meta-analyses that included only randomised studies that directly compared rosuvastatin and its comparator treatments. Results As statin dose increased, higher percentages of patients achieved LDL-C <70 mg/dl or ≥50% LDL-C reduction. A greater percentage achieved this goal with rosuvastatin 10–40 mg (43.8–79.0%) than with equal or double milligram doses of atorvastatin (16.1–65.2%) or simvastatin (0–39.7%). Paired comparisons showed statistically significant differences for: rosuvastatin 10 mg vs. atorvastatin 10–20 mg and simvastatin 10–20 mg; rosuvastatin 20 mg vs. atorvastatin 20–40 mg and simvastatin 20–80 mg; and rosuvastatin 40 mg vs. atorvastatin 40–80 mg and simvastatin 40–80 mg (all p < 0.001). Conclusion These data from VOYAGER highlight the importance of an effective statin at an appropriate dose to achieve treatment goals for LDL-C in patients with very high cardiovascular risk.
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| 10. |
- Karlson, Björn W., 1953, et al.
(författare)
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Comparison of the effects of different statins and doses on lipid levels in patients with diabetes: Results from VOYAGER
- 2012
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Ingår i: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 22:9, s. 697-703
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Diabetes mellitus is a well-known risk factor for cardiovascular disease, and brings an increased risk of vascular events and a higher mortality rate. Treatment guidelines recommend statins in patients with diabetes, with low-density lipoprotein cholesterol (LDL-C) targets of 100 mg dl(-1) (similar to 2.5 mmol l(-1)), and 80 (similar to 2.0 mmol l(-1)) or 70 mg dl(-1) (similar to 1.8 mmol l(-1)) in especially high-risk patients. The current study used the VOYAGER (an indiVidual patient data-meta-analysis Of statin therapY in At risk Groups: Effects of Rosuvastatin, atorvastatin, and simvastatin) database to characterise effects of rosuvastatin, atorvastatin and simvastatin in different doses on lipid levels in diabetes patients. Methods and results: The VOYAGER database included individual patient data from 37 studies involving comparisons of rosuvastatin with either atorvastatin or simvastatin. Of the 32 258 patients included, 8859 (27.5%) had diabetes. Rosuvastatin appeared to be the most efficacious of the three statins, both for lowering LDL-C and for reaching a target level of <70 mg dl(-1) for LDL-C. It was also more effective than atorvastatin at raising high-density lipoprotein cholesterol in the diabetes population. These results are consistent with the overall VOYAGER results. Conclusions: This meta-analysis of 8859 patients with diabetes mellitus shows favourable effects on lipids with the three statins studied, in line with results for the overall VOYAGER population. The importance of using an effective statin at an effective dose to reach treatment goals for such high-risk patients is evident. (c) 2012 Elsevier B.V. All rights reserved.
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| 11. |
- Karlson, Björn W., 1953, et al.
(författare)
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Effects of age, gender and statin dose on lipid levels: Results from the VOYAGER meta-analysis database
- 2017
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 265, s. 54-59
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims The effectiveness of statins in the treatment of dyslipidaemia and reduction of cardiovascular risk is well established. However, the association of statin-mediated lipid effects with age and gender is unclear. This study aimed to determine whether age and gender are associated with statin-mediated changes in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and non-HDL-C. Methods Individual patient data (n = 32,258) were obtained from VOYAGER. Least-squares mean percentage change from baseline in LDL-C, non-HDL-C and HDL-C with atorvastatin 10–80 mg, rosuvastatin 5–40 mg or simvastatin 10–80 mg was estimated in women aged <70 years, women aged ≥70 years, men aged <70 years and men aged ≥70 years. Results All statins and doses gave significant dose-dependent reductions in LDL-C and non-HDL-C, and increases in HDL-C, in all four patient groups. A 2.1% greater reduction in LDL-C was observed in women, compared with men (p < 0.0001). Patients aged ≥70 years experienced a 2.7% greater reduction in LDL-C compared with younger patients (p < 0.0001). Similar results were also observed for statin-mediated changes in non-HDL-C. Men experienced a significantly greater increase in HDL-C than women, and patients aged ≥70 years achieved a significantly greater increase than younger patients (both p = 0.001). Conclusions While statins improve the lipid profile in all gender and age groups analysed, the improvements are greater in women than in men and in those aged ≥70 years compared with those aged <70 years. © 2017 Elsevier B.V.
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| 12. |
- Karlson, Björn W., 1953, et al.
(författare)
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Modeling Statin-Induced Reductions of Cardiovascular Events in Primary Prevention: A VOYAGER Meta-Analysis
- 2018
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Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 140:1, s. 30-34
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We used individual patient data from the VOYAGER database to estimate cardiovascular (CV) risk reduction with commonly used high-intensity statins. Methods: In patients with known atherosclerotic CV disease (ASCVD) treated with high-intensity statin therapy (n = 6,735), the predicted risk reduction was estimated using the Cholesterol Treatment Trialists' Collaboration meta-analysis, which determined risk reduction per 38.7 mg/dL statin-mediated reduction in low-density lipoprotein cholesterol. Results: The greatest reductions in risk were seen in major vascular events (estimated rate ratios ranged from 0.55 with rosuvastatin [RSV] 40 mg to 0.60 with atorvastatin [ATV] 40 mg) and coronary heart disease death (estimated rate ratios ranged from 0.58 with RSV 40 mg to 0.64 with ATV 40 mg). Conclusions: Our results show that, in individuals without clinical ASCVD, statin therapy has the potential to reduce the frequency of CV events. (C) 2018 S. Karger AG, Basel
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| 13. |
- Karlson, Björn W., 1953, et al.
(författare)
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To what extent do high-intensity statins reduce low-density lipoprotein cholesterol in each of the four statin benefit groups identified by the 2013 American College of Cardiology/American Heart Association guidelines? A VOYAGER meta-analysis
- 2015
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 241:2, s. 450-454
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Tidskriftsartikel (refereegranskat)abstract
- Background: The 2013 American College of Cardiology and American Heart Association (ACC/AHA) guidelines identify four patient groups who benefit from moderate-or high-intensity statin treatment; those with: 1) atherosclerotic cardiovascular disease (ASCVD); 2) low-density lipoprotein cholesterol (LDL-C) >= 190 mg/dl; 3) diabetes; or 4) a 10-year ASCVD risk >= 7.5%. High-intensity statins, anticipated to reduce LDL-C by >= 50%, were identified as rosuvastatin 20-40 mg and atorvastatin 40-80 mg. Methods and Results: Individual patient data (32,258) from the VOYAGER database of 37 studies were used to calculate least-squares mean (LSM) percentage change in LDL-C during 8496 patient exposures to rosuvastatin 20-40 mg, and atorvastatin 40-80 mg in the four patient benefit groups. LSM percentage reductions in LDL-C with rosuvastatin 20 and 40 mg were greater than with atorvastatin 40 mg, overall and in each statin benefit group, and with rosuvastatin 40 mg were greater than with atorvastatin 80 mg overall and in three of the four benefit groups (all p < 0.05). For example, in the ASCVD group, 40%, 59%, 57% and 71% of patients treated with atorvastatin 40 mg, atorvastatin 80 mg, rosuvastatin 20 mg and rosuvastatin 40 mg, respectively, had a >= 50% reduction in LDL-C. Conclusions: The choice and dose of statin have an impact both on the percentage LDL-C reduction and achievement of >= 50% reduction in LDL-C, overall and within each of the four statin benefit groups outlined by the 2013 ACC/AHA guidelines. This may be of importance for clinicians in their choice of treatment for individual patients. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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| 14. |
- Palmer, M. K., et al.
(författare)
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Achievement of LDL-C goals depends on baseline LDL-C and choice and dose of statin: An analysis from the VOYAGER database
- 2013
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 20:6, s. 1080-1087
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Tidskriftsartikel (refereegranskat)abstract
- Background Reducing low-density lipoprotein cholesterol (LDL-C) levels decreases cardiovascular risk in direct proportion to the decrease in LDL-C. Design The aim of this study was to assess the importance of baseline LDL-C and choice and dose of statin in achievement of LDL-C goals of 100 and 70mg/dl, using a novel statistical model. The analysis included 30,102 patient exposures to rosuvastatin 10-40mg or atorvastatin 10-80mg from 31 direct comparative trials in the VOYAGER database. Methods For each statin dose, percentage goal achievement was plotted for 20 equally large subgroups defined by baseline LDL-C. Logistic regression analysis was then performed for each statin dose to estimate the percentage of patients reaching target. Best-fit logistic regression curves were plotted pair-wise', comparing each rosuvastatin dose with equal or higher doses of atorvastatin. Results LDL-C <100mg/dl was achieved by 53.7-85.5% of patients on rosuvastatin 10-40mg and 43.3-80.0% of those on atorvastatin 10-80mg, whereas LDL-C <70mg/dl was achieved by 4.5-44.0% of rosuvastatin-treated patients and 6.5-41.4% of those on atorvastatin. Similar differences in efficacy favouring rosuvastatin over equal or double doses of atorvastatin were observed across the range of baseline LDL-C levels for both LDL-C goals, being more pronounced at higher baseline values. Conclusions Baseline LDL-C and choice and dose of statin are important for LDL-C goal achievement. The present analysis may allow prediction of individual patient response to different statins at different doses.
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| 15. |
- Johnson, Katherine, et al.
(författare)
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Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression : Diagnostic and mechanistic relevance
- 2022
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Ingår i: JHEP Reports. - : Elsevier. - 2589-5559. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages.Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR.Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2-4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5-8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2-4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p.Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD.Lay summary: MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy.
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| 27. |
- Kastelein, John J. P., et al.
(författare)
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Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment
- 2008
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 117:23, s. 3002-3009
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Tidskriftsartikel (refereegranskat)abstract
- Background - Low-density lipoprotein (LDL)cholesterol is the principal target of lipid-lowering therapy, but recent evidence has suggested more appropriate targets. We compared the relationships of on-treatment levels of LDL cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B, as well as ratios of total/HDL cholesterol, LDL/HDL cholesterol, and apolipoprotein B/A-I, with the occurrence of cardiovascular events in patients receiving statin therapy. Methods and Results - A post hoc analysis was performed that combined data from 2 prospective, randomized clinical trials in which 10 001 ("Treating to New Targets") and 8888 ("Incremental Decrease in End Points through Aggressive Lipid Lowering") patients with established coronary heart disease were assigned to usual-dose or high-dose statin treatment. In models with LDL cholesterol, non-HDL cholesterol and apolipoprotein B were positively associated with cardiovascular outcome, whereas a positive relationship with LDL cholesterol was lost. In a model that contained non-HDL cholesterol and apolipoprotein B, neither was significant owing to collinearity. Total/HDL cholesterol ratio and the apolipoprotein B/A-I ratio in particular were each more closely associated with outcome than any of the individual proatherogenic lipoprotein parameters. Conclusions - In patients receiving statin therapy, on-treatment levels of non-HDL cholesterol and apolipoprotein B were more closely associated with cardiovascular outcome than levels of LDL cholesterol. Inclusion of measurements of the antiatherogenic lipoprotein fraction further strengthened the relationships. These data support the use of non-HDL cholesterol or apolipoprotein B as novel treatment targets for statin therapy. Given the absence of interventions that have been proven to consistently reduce cardiovascular disease risk through raising plasma levels of HDL cholesterol or apolipoprotein A-I, it seems premature to consider the ratio variables as clinically useful.
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