6 results on '"Nordestgaard, Børge G"'
Search Results
2. Low LDL Cholesterol by PCSK9 Variation Reduces Cardiovascular Mortality.
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Benn, Marianne, Tybjærg-Hansen, Anne, and Nordestgaard, Børge G
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CAUSES of death , *RESEARCH , *GENETIC mutation , *GENETICS , *RESEARCH methodology , *CARDIOVASCULAR diseases , *LOW density lipoproteins , *GENETIC polymorphisms , *EVALUATION research , *MEDICAL cooperation , *RISK assessment , *COMPARATIVE studies ,CARDIOVASCULAR disease related mortality - Abstract
Background: Reduced low-density lipoprotein (LDL) cholesterol due to inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) reduces cardiovascular events and may therefore also reduce cardiovascular and all-cause mortality.Objectives: This study tested the hypothesis that genetically low LDL cholesterol due to PCSK9 variation is causally associated with low cardiovascular and all-cause mortality in the general population.Methods: A total of 109,566 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were genotyped for PCSK9 R46L (rs11591147), R237W (rs148195424), I474V (rs562556), and E670G (rs505151). During a median follow-up of 10 years (range 0 to 42 years) and 1,247,225 person-years, there were 3,828 cardiovascular deaths and 16,373 deaths from any cause. Results were validated using data on 431,043 individuals from the UK Biobank.Results: An increasing number of weighted PCSK9 alleles were associated with stepwise lower LDL cholesterol of up to 0.61 mmol/l (24 mg/dl; 18.2%; p for trend <0.001) and with lower cardiovascular mortality (p = 0.001), but not with lower all-cause mortality (p = 0.11). In causal, genetic analyses, a 0.5-mmol/l (19.4-mg/dl) lower LDL cholesterol was associated with risk ratios for cardiovascular and all-cause mortality of 0.79 (95% confidence interval [CI]: 0.63 to 0.99; p = 0.04) and 1.02 (95% CI: 0.94 to 1.12; p = 0.63) in the Copenhagen studies, 0.79 (95% CI: 0.58 to 1.08; p = 0.14) and 0.98 (95% CI: 0.87 to 1.10; p = 0.75) in the UK Biobank, and of 0.79 (95% CI: 0.65 to 0.95; p = 0.01) and 1.01 (95% CI: 0.94 to 1.08; p = 0.85), respectively, in studies combined.Conclusions: Genetically low LDL cholesterol due to PCSK9 variation was causally associated with low risk of cardiovascular mortality, but not with low all-cause mortality in the general population. [ABSTRACT FROM AUTHOR]- Published
- 2019
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3. Primary Prevention With Statins: ACC/AHA Risk-Based Approach Versus Trial-Based Approaches to Guide Statin Therapy.
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Mortensen, Martin B., Afzal, Shoaib, Nordestgaard, Børge G., and Falk, Erling
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STATINS (Cardiovascular agents) , *CARDIOVASCULAR diseases , *CLINICAL trials , *COMPARATIVE studies , *ATHEROSCLEROSIS , *CARDIAC research , *ATHEROSCLEROSIS prevention , *ANTILIPEMIC agents , *DISEASES , *LONGITUDINAL method , *RESEARCH methodology , *MEDICAL cooperation , *MEDICAL protocols , *PREVENTIVE health services , *RESEARCH , *RISK assessment , *EVALUATION research , *RANDOMIZED controlled trials , *TREATMENT effectiveness - Abstract
Background: Guidelines recommend initiating primary prevention for atherosclerotic cardiovascular disease (ASCVD) with statins based on absolute ASCVD risk assessment. Recently, alternative trial-based and hybrid approaches were suggested for statin treatment eligibility.Objectives: This study compared these approaches in a direct head-to-head fashion in a contemporary population.Methods: The study used the CGPS (Copenhagen General Population Study) with 37,892 subjects aged 40 to 75 years recruited in 2003 to 2008, all free of ASCVD, diabetes, and statin use at baseline.Results: Among the population studied, 42% were eligible for statin therapy according to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) risk assessment and cholesterol treatment guidelines approach, versus 56% with the trial-based approach and 21% with the hybrid approach. Among these statin-eligible subjects, the ASCVD event rate per 1,000 person-years was 9.8, 6.8, and 11.2, respectively. The ACC/AHA-recommended absolute risk score was well calibrated around the 7.5% 10-year ASCVD risk treatment threshold and discriminated better than the trial-based or hybrid approaches. Compared with the ACC/AHA risk-based approach, the net reclassification index for eligibility for statin therapy among 40- to 75-year-old subjects from the CGPS was -0.21 for the trial-based approach and -0.13 for the hybrid approach.Conclusions: The clinical performance of the ACC/AHA risk-based approach for primary prevention of ASCVD with statins was superior to the trial-based and hybrid approaches. Our results indicate that the ACC/AHA guidelines will prevent more ASCVD events than the trial-based and hybrid approaches, while treating fewer people compared with the trial-based approach. [ABSTRACT FROM AUTHOR]- Published
- 2015
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4. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
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Ridker, Paul M, Danielson, Eleanor, Fonseca, Francisco A.H., Genest, Jacques, Gotto, Antonio M., Kastelein, John J.P., Koenig, Wolfgang, Libby, Peter, Lorenzatti, Alberto J., MacFadyen, Jean G., Nordestgaard, Børge G., Shepherd, James, Willerson, James T., Glynn, Robert J., Gotto, Antonio M Jr, Nordestgaard, Børge G, and JUPITER Study Group
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MEDICAL research , *STATINS (Cardiovascular agents) , *CARDIOVASCULAR diseases , *C-reactive protein , *CHOLESTEROL , *MYOCARDIAL infarction treatment , *CARDIOVASCULAR disease prevention , *CORONARY heart disease prevention , *STROKE prevention , *ANTILIPEMIC agents , *COMPARATIVE studies , *CONFIDENCE intervals , *DIABETES , *FLUOROHYDROCARBONS , *GLYCOSYLATED hemoglobin , *HETEROCYCLIC compounds , *LONGITUDINAL method , *LOW density lipoproteins , *RESEARCH methodology , *MEDICAL cooperation , *MUSCLE diseases , *MYOCARDIAL infarction , *RESEARCH , *STROKE , *SULFONAMIDES , *EVALUATION research , *RANDOMIZED controlled trials , *PROPORTIONAL hazards models , *BLIND experiment , *KAPLAN-Meier estimator , *ROSUVASTATIN , *PHARMACODYNAMICS , *THERAPEUTICS ,CARDIOVASCULAR disease related mortality ,SULFONAMIDE drugs - Abstract
Background: Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment.Methods: We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes.Results: The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes.Conclusions: In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, NCT00239681.) [ABSTRACT FROM AUTHOR]- Published
- 2008
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5. Pericardial Adipose Tissue Volume Is Independently Associated With Human Immunodeficiency Virus Status and Prior Use of Stavudine, Didanosine, or Indinavir.
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Knudsen, Andreas D, Krebs-Demmer, Lisanne, Bjørge, Natascha I D, Elming, Marie B, Gelpi, Marco, Sigvardsen, Per E, Lebech, Anne-Mette, Fuchs, Andreas, Kühl, Jørgen T, Køber, Lars, Lundgren, Jens, Nordestgaard, Børge G, Kofoed, Klaus F, and Nielsen, Susanne D
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HIV , *ADIPOSE tissues , *HIV infections , *CARDIOVASCULAR diseases , *COMPARATIVE studies , *RESEARCH methodology , *MEDICAL cooperation , *PERICARDIUM , *RESEARCH , *VIRAL load , *EVALUATION research , *HUMAN research subjects , *DIDANOSINE (Drug) , *STAVUDINE , *ANTI-HIV agents , *HIV protease inhibitors , *INDINAVIR - Abstract
Background: Increased pericardial adipose tissue is associated with higher risk of cardiovascular disease. We aimed to determine whether human immunodeficiency virus (HIV) status was independently associated with larger pericardial adipose tissue volume and to explore possible HIV-specific risk factors.Methods: Persons with HIV (PWH) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study and matched 1:1 on age and sex to uninfected controls. Pericardial adipose tissue volume was measured using cardiac computed tomography.Results: A total of 587 PWH and 587 controls were included. Median age was 52 years, and 88% were male. Human immunodeficiency virus status was independently associated with 17 mL (95% confidence interval [CI], 10-23; P < .001) larger pericardial adipose tissue volume. Larger pericardial adipose tissue volume was associated with low CD4+ nadir and prior use of stavudine, didanosine, and indinavir. Among PWH without thymidine analogue or didanosine exposure, time since initiating combination antiretroviral treatment (per 5-year use) was associated with l6 mL (95% CI, -6 to -25; P = .002) lower pericardial adipose tissue volume.Conclusions: Human immunodeficiency virus status was independently associated with larger pericardial adipose tissue volume. Severe immunodeficiency, stavudine, didanosine, and indinavir were associated with larger pericardial adipose tissue volume. Persons with HIV with prior exposure to these drugs may constitute a distinct cardiovascular risk population. [ABSTRACT FROM AUTHOR]- Published
- 2020
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6. Lipoprotein(a) Reduction in Persons with Cardiovascular Disease.
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Tsimikas, Sotirios, Karwatowska-Prokopczuk, Ewa, Gouni-Berthold, Ioanna, Tardif, Jean-Claude, Baum, Seth J., Steinhagen-Thiessen, Elizabeth, Shapiro, Michael D., Stroes, Erik S., Moriarty, Patrick M., Nordestgaard, Børge G., Xia, Shuting, Guerriero, Jonathan, Viney, Nicholas J., O'Dea, Louis, Witztum, Joseph L., and AKCEA-APO(a)-LRx Study Investigators
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CARDIOVASCULAR diseases , *DISEASE risk factors , *AORTIC stenosis , *PLATELET count , *ANTILIPEMIC agents , *CHOLESTEROL , *COMPARATIVE studies , *DOSE-effect relationship in pharmacology , *LIPOPROTEINS , *RESEARCH methodology , *MEDICAL cooperation , *NUCLEOTIDES , *REGRESSION analysis , *RESEARCH , *EVALUATION research , *RANDOMIZED controlled trials , *BLIND experiment - Abstract
Background: Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels.Methods: We conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter). Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx, referred to here as APO(a)-LRx (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or saline placebo subcutaneously for 6 to 12 months. The lipoprotein(a) level was measured with an isoform-independent assay. The primary end point was the percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in the groups that received monthly doses and week 27 in the groups that received more frequent doses).Results: The median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter. Administration of APO(a)-LRx resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001). There were no significant differences between any APO(a)-LRx dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms. The most common adverse events were injection-site reactions.Conclusions: APO(a)-LRx reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease. (Funded by Akcea Therapeutics; ClinicalTrials.gov number, NCT03070782.). [ABSTRACT FROM AUTHOR]- Published
- 2020
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