Daniel J Rader

Treatment Research Institute, Philadelphia PA, Philadelphia, Pennsylvania, United States

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Publications (610)5284.48 Total impact

  • Sumeet A Khetarpal, Daniel J Rader
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    ABSTRACT: A wealth of novel lipid loci have been identified through a variety of approaches focused on common and low-frequency variation and collaborative metaanalyses in multiethnic populations. Despite progress in identification of loci, the task of determining causal variants remains challenging. This work will undoubtedly be enhanced by improved understanding of regulatory DNA at a genomewide level as well as new methodologies for interrogating the relationships between noncoding SNPs and regulatory regions. Equally challenging is the identification of causal genes at novel loci. Some progress has been made for a handful of genes and comprehensive testing of candidate genes using multiple model systems is underway. Additional insights will be gleaned from focusing on lowfrequency and rare coding variation at candidate loci in large populations. This article is part of a Special Issue entitled: From Genome to Function.
    Biochimica et biophysica acta. 06/2014;
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    ABSTRACT: Background Obesity and obstructive sleep apnea tend to coexist and are associated with inflammation, insulin resistance, dyslipidemia, and high blood pressure, but their causal relation to these abnormalities is unclear. Methods We randomly assigned 181 patients with obesity, moderate-to-severe obstructive sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg per liter to receive treatment with continuous positive airway pressure (CPAP), a weight-loss intervention, or CPAP plus a weight-loss intervention for 24 weeks. We assessed the incremental effect of the combined interventions over each one alone on the CRP level (the primary end point), insulin sensitivity, lipid levels, and blood pressure. Results Among the 146 participants for whom there were follow-up data, those assigned to weight loss only and those assigned to the combined interventions had reductions in CRP levels, insulin resistance, and serum triglyceride levels. None of these changes were observed in the group receiving CPAP alone. Blood pressure was reduced in all three groups. No significant incremental effect on CRP levels was found for the combined interventions as compared with either weight loss or CPAP alone. Reductions in insulin resistance and serum triglyceride levels were greater in the combined-intervention group than in the group receiving CPAP only, but there were no significant differences in these values between the combined-intervention group and the weight-loss group. In per-protocol analyses, which included 90 participants who met prespecified criteria for adherence, the combined interventions resulted in a larger reduction in systolic blood pressure and mean arterial pressure than did either CPAP or weight loss alone. Conclusions In adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss intervention did not reduce CRP levels more than either intervention alone. In secondary analyses, weight loss provided an incremental reduction in insulin resistance and serum triglyceride levels when combined with CPAP. In addition, adherence to a regimen of weight loss and CPAP may result in incremental reductions in blood pressure as compared with either intervention alone. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT0371293 .).
    New England Journal of Medicine 06/2014; 370(24):2265-2275. · 51.66 Impact Factor
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    ABSTRACT: Rationale: Individuals with naturally occurring loss-of-function PCSK9 mutations experience reduced blood low-density lipoprotein cholesterol (LDL-C) levels and protection against cardiovascular disease. Objective: The goal of this study was to assess whether genome editing using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system can efficiently introduce loss-of-function mutations into the endogenous PCSK9 gene in vivo. Methods and Results: We used adenovirus to express Cas9 and a CRISPR guide RNA targeting Pcsk9 in mouse liver, where the gene is specifically expressed. We found that within three to four days of administration of the virus, the mutagenesis rate of Pcsk9 in the liver was as high as >50%. This resulted in decreased plasma PCSK9 levels, increased hepatic LDL receptor levels, and decreased plasma cholesterol levels (by 35%-40%) in the blood. No off-target mutagenesis was detected in 10 selected sites. Conclusions: Genome editing with the CRISPR-Cas9 system disrupts the Pcsk9 gene in vivo with high efficiency and reduces blood cholesterol levels in mice. This approach may have therapeutic potential for the prevention of cardiovascular disease in humans.
    Circulation Research 06/2014; · 11.86 Impact Factor
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    ABSTRACT: The period following an acute coronary syndrome (ACS) represents a critical time frame with a high risk for recurrent events and death. The pathogenesis of this increase in clinical cardiovascular disease events after ACS is complex, with molecular mechanisms including increased thrombosis and inflammation. Dyslipoproteinemia is common in patients with ACS and predictive of recurrent cardiovascular disease events after presentation with an ACS event. Although randomized clinical trials have provided fairly convincing evidence that high-dose statins reduce the risk of recurrent cardiovascular events after ACS, there remain questions about how aggressively to reduce low-density lipoprotein cholesterol levels in ACS. Furthermore, no other lipid-related interventions have yet been proven to be effective in reducing major cardiovascular events after ACS. Here, we review the relationship of lipoproteins as biomarkers to cardiovascular risk after ACS, the evidence for lipid-targeted interventions, and the potential for novel therapeutic approaches in this arena.
    Circulation Research 06/2014; 114(12):1880-9. · 11.86 Impact Factor
  • Daniel J Rader
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    ABSTRACT: The development of new therapies for coronary artery disease (CAD) poses a substantial challenge, and several recent approaches have failed for lack of efficacy. Human genetics has the potential to identify new targets for which the likelihood of therapeutic success is considerably greater. The intense focus on the genetics of CAD will revitalize the field and lead to future therapies for this common disease.
    Science translational medicine 06/2014; 6(239):239ps4. · 10.76 Impact Factor
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    ABSTRACT: We report a novel apolipoprotein (apo) A-I truncation (apoA-IMytilene) due to a heterozygous nonsense mutation (c.718C > T, p.Gln216*) in a 68-year-old male proband with premature coronary heart disease (CHD), corneal arcus, and very low plasma concentrations of HDL cholesterol (HDL-C) and apoA-I. Two family members also had the same mutation. Our objectives were to characterize the kindred and to examine the kinetics of apoA-I, as well as cellular cholesterol efflux capacity in the proband.
    Atherosclerosis 06/2014; 235(2):470-476. · 3.71 Impact Factor
  • Ali Javaheri, Daniel J Rader
    Circulation Research 05/2014; 114(11):1681-3. · 11.86 Impact Factor
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    ABSTRACT: Hyperlipidemia is common in patients with CKD. The objective of this study was to evaluate whether measures of plasma lipids and lipoproteins predict progression of kidney disease in patients with CKD.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prospective cohort study in adults (n=3939) with CKD aged 21-74 years recruited between 2003 and 2008 and followed for a median of 4.1 years. At baseline, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), apoA-I , apoB, and lipoprotein(a) [Lp(a)] were measured. The outcomes were composite end point of ESRD or 50% decline in eGFR from baseline (rate of change of GFR).RESULTS: Mean age of the study population was 58.2 years, and the mean GFR was 44.9 ml/min per 1.73 m(2); 48% of patients had diabetes. None of the lipid or lipoprotein measures was independently associated with risk of the composite end point or rate of change in GFR. However, there were significant (P=0.01) interactions by level of proteinuria. In participants with proteinuria<0.2 g/d, 1-SD higher LDL-C was associated with a 26% lower risk of the renal end point (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.59 to 0.92; P=0.01), and 1-SD higher total cholesterol was associated with a 23% lower risk of the renal end point (HR, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In participants with proteinuria>0.2 g/d, neither LDL-C (HR, 0.98; 95% CI, 0.98 to 1.05) nor total cholesterol levels were associated with renal outcomes. Treatment with statins was reported in 55% of patients and was differential across lipid categories.CONCLUSIONS: In this large cohort of patients with CKD, total cholesterol, triglycerides, VLDL-C, LDL-C, HDL-C, apoA-I, apoB, and Lp(a) were not independently associated with progression of kidney disease. There was an inverse relationship between LDL-C and total cholesterol levels and kidney disease outcomes in patients with low levels of proteinuria.
    Clinical Journal of the American Society of Nephrology 05/2014; · 5.07 Impact Factor
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    ABSTRACT: Hepatic lipase (HL) and endothelial lipase (EL) share overlapping and complementary roles in lipoprotein metabolism. The deletion of HL and EL alleles in mice raises plasma total cholesterol and phospholipid concentrations. However, the influence of HL and EL in vivo on individual molecular species from each class of lipid is not known. We hypothesized that the loss of HL, EL, or both in vivo may affect select molecular species from each class of lipids. To test this hypothesis, we performed lipidomic analyses on plasma and livers from fasted female wild-type, HL-knockout, EL-knockout, and HL/EL-double knockout mice. Overall, the loss of HL, EL, or both resulted in minimal changes to hepatic lipids; however, select species of CE were surprisingly reduced in the livers of mice only lacking EL. The loss of HL, EL, or both reduced the plasma concentrations for select molecular species of triacylglycerol, diacylglycerol, and free fatty acid. On the other hand, the loss of HL, EL, or both raised the plasma concentrations for select molecular species of phosphatidylcholine, cholesteryl ester, diacylglycerol, sphingomyelin, ceramide, plasmanylcholine, and plasmenylcholine. The increased plasma concentration of select ether phospholipids was evident in the absence of EL, thus suggesting that EL might exhibit a phospholipase A2 activity. Using recombinant EL, we showed that it could hydrolyse the artificial phospholipase A2 substrate 4-nitro-3-(octanoyloxy)benzoic acid. In summary, our study shows for the first time the influence of HL and EL on individual molecular species of several classes of lipids in vivo using lipidomic methods.
    Lipids 04/2014; · 2.56 Impact Factor
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    ABSTRACT: For a more complete understanding of pharmacodynamic, metabolic, and pathophysiologic effects, protein kinetics, such as production rate and fractional catabolic rate, can offer substantially more information than protein concentration alone. Kinetic experiments with stable isotope tracers typically require laborious sample preparation and are most often used for studying abundant proteins. Here we describe a practical methodology for measuring isotope enrichment into low-abundance proteins that uses an automated procedure and immunoaffinity enrichment (IA) with LC-MS. Low-abundance plasma proteins cholesteryl ester transfer protein (CETP) and proprotein convertase subtilisin/kexin type 9 (PCSK9) were studied as examples.METHODS: Human participants (n = 39) were infused with [(2)H3]leucine, and blood samples were collected at multiple time points. Sample preparation and analysis were automated and multiplexed to increase throughput. Proteins were concentrated from plasma by use of IA and digested with trypsin to yield proteotypic peptides that were analyzed by microflow chromatography-mass spectrometry to measure isotope enrichment.RESULTS: The IA procedure was optimized to provide the greatest signal intensity. Use of a gel-free method increased throughput while increasing the signal. The intra- and interassay CVs were <15% at all isotope enrichment levels studied. More than 1400 samples were analyzed in <3 weeks without the need for instrument stoppages or user interventions.CONCLUSIONS: The use of automated gel-free methods to multiplex the measurement of isotope enrichment was applied to the low-abundance proteins CETP and PCSK9.
    Clinical Chemistry 04/2014; · 7.15 Impact Factor
  • Sony Tuteja, Daniel J Rader
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    ABSTRACT: High-density lipoprotein cholesterol (HDL-C) has been identified in population studies as an independent, inverse predictor of cardiovascular events. Though the causal nature of this association has been questioned, HDL and its major protein apoA-I have been shown to prevent and reverse atherosclerosis in animal models. In addition, HDL and apoA-I have several putatively atheroprotective functions, such as ability to promote efflux of cholesterol from macrophages in the artery wall, inhibit vascular inflammation, and enhance endothelial function. Therefore, HDL-C and apoA-I have been investigated as therapeutic targets for coronary heart disease (CHD). However, recent clinical trials with drugs that raise HDL-C, such as niacin and cholesteryl ester transfer protein (CETP) inhibitors, have been disappointing. Here we review the current state of the science regarding HDL as a therapeutic target.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 8 April 2014; doi:10.1038/clpt.2014.79.
    Clinical Pharmacology &#38 Therapeutics 04/2014; · 6.85 Impact Factor
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    ABSTRACT: Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) are secreted proteins that inhibit lipoprotein lipase in vitro. Genetic variants at the ANGPTL3 and ANGPTL4 gene loci are significantly associated with plasma lipid traits. The aim of this study was to evaluate the association of plasma ANGPTL3 and ANGPTL4 concentrations with lipid and metabolic traits in a large community-based sample. Plasma ANGPTL3 and ANGPTL4 levels were measured in 1770 subjects using a validated ELISA assay. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, sex, and race were performed. ANGPTL3 levels were significantly positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels (both P<2×10(-5)) but not triglycerides. In contrast, ANGPTL4 levels were significantly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (both P<2×10(-5)) and positively associated with triglycerides (P=0.003). In addition, ANGPTL4, but not ANGPTL3, levels were significantly positively associated with fasting blood glucose and metabolic syndrome. Despite having similar biochemical effects in vitro, plasma ANGPTL3 and ANGPTL4 concentrations have nearly opposite relationships with plasma lipids. ANGPTL4 is strongly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and positively with multiple features of the metabolic syndrome including triglycerides, whereas ANGPTL3 is positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and not with metabolic syndrome traits including triglycerides. Although ANGPTL3 and ANGPTL4 both inhibit lipoprotein lipase in vitro and influence lipoprotein metabolism in vivo, the physiology of these related proteins and their effects on lipoproteins is clearly divergent and complex.
    Arteriosclerosis Thrombosis and Vascular Biology 03/2014; · 6.34 Impact Factor
  • Daniel J Rader, John J P Kastelein
    Circulation 03/2014; 129(9):1022-32. · 15.20 Impact Factor
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    ABSTRACT: Familial hypercholesterolemia (FH) is a hereditary condition caused by various genetic mutations that lead to significantly elevated low-density lipoprotein cholesterol levels and resulting in a 20-fold increased lifetime risk for premature cardiovascular disease. Although its prevalence in the United States is 1 in 300 to 500 individuals, <10% of FH patients are formally diagnosed, and many are not appropriately treated. Contemporary data are needed to more fully characterize FH disease prevalence, treatment strategies, and patient experiences in the United States. The Familial Hypercholesterolemia Foundation (a patient-led nonprofit organization) has established the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE FH) Registry as a national, multicenter initiative to identify US FH patients, track their treatment, and clinical and patient-reported outcomes over time. The CASCADE FH will use multiple enrollment strategies to maximize identification of FH patients. Electronic health record screening of health care systems will provide an efficient mechanism to identify undiagnosed patients. A group of specialized lipid clinics will enter baseline and annual follow-up data on demographics, laboratory values, treatment, and clinical events. Patients meeting prespecified low-density lipoprotein or total cholesterol criteria suspicious for FH will have the opportunity to self-enroll in an online patient portal with information collected directly from patients semiannually. Registry patients will be provided information on cascade screening and will complete an online pedigree to assist with notification of family members. The Familial Hypercholesterolemia Foundation CASCADE FH Registry represents a novel research paradigm to address gaps in knowledge and barriers to comprehensive FH screening, identification, and treatment.
    American heart journal 03/2014; 167(3):342-349.e17. · 4.65 Impact Factor
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    ABSTRACT: Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
    The American Journal of Human Genetics 02/2014; · 11.20 Impact Factor
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    ABSTRACT: Context: Women with PCOS have a high prevalence of cardiovascular disease (CVD) risk factors including dyslipidemia. Lipoproteins are heterogeneous and measurement of serum lipids provides only the size of the pool and does not predict their function or composition. Recently, HDL-C function as determined by cholesterol efflux capacity from macrophages, has been shown to be an independent predictor of subclinical CVD. Objective: To comprehensively evaluate lipoprotein profile including lipid particle size and number and cholesterol efflux capacity in PCOS to better define CVD risk. Design: Case control study Setting: Academic PCOS center Patients: Women with PCOS (n=124) and geographically matched controls (n=67). Main Outcome measure: The primary outcome was to measure HDL-C efflux capacity by an ex vivo system involving the incubation of macrophages with apolipoprotein B-depleted serum from subjects and the secondary outcome was to measure lipid particle size and number using NMR spectroscopy. Results: Women with PCOS had significantly higher BMI and BP but similar HDL-C and LDL-C levels compared to controls. The mean ApoA1 levels were lower and ApoB/ ApoA1 ratio was higher in PCOS subjects compared to controls (p<0.01). There were no differences in ApoB levels. Women with PCOS had an 11% decrease in normalized cholesterol efflux capacity compared to controls (p<0.05). Cholesterol efflux capacity in PCOS correlated with BMI, ApoA1, HDL-C and presence of metabolic syndrome. In a multivariable regression model, PCOS was significantly associated with diminished cholesterol efflux. PCOS was also associated with an atherogenic profile including an increase in large VLDL particles, VLDL size and small LDL-C particles (p<0.01). Conclusions: Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population.
    The Journal of clinical endocrinology and metabolism 02/2014; · 6.50 Impact Factor
  • Ali Javaheri, Daniel J Rader, Shahrokh Javaheri
    Hypertension 02/2014; · 6.87 Impact Factor
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    ABSTRACT: Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121(∗)], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.
    The American Journal of Human Genetics 02/2014; 94(2):223-32. · 11.20 Impact Factor
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    ABSTRACT: Cardiovascular disease poses a major challenge for the 21st century, exacerbated by the pandemics of obesity, metabolic syndrome and type 2 diabetes. While best standards of care, including high-dose statins, can ameliorate the risk of vascular complications, patients remain at high risk of cardiovascular events. The Residual Risk Reduction Initiative (R3i) has previously highlighted atherogenic dyslipidaemia, defined as the imbalance between proatherogenic triglyceride-rich apolipoprotein B-containing-lipoproteins and antiatherogenic apolipoprotein A-I-lipoproteins (as in high-density lipoprotein, HDL), as an important modifiable contributor to lipid-related residual cardiovascular risk, especially in insulin-resistant conditions. As part of its mission to improve awareness and clinical management of atherogenic dyslipidaemia, the R3i has identified three key priorities for action: i) to improve recognition of atherogenic dyslipidaemia in patients at high cardiometabolic risk with or without diabetes; ii) to improve implementation and adherence to guideline-based therapies; and iii) to improve therapeutic strategies for managing atherogenic dyslipidaemia. The R3i believes that monitoring of non-HDL cholesterol provides a simple, practical tool for treatment decisions regarding the management of lipid-related residual cardiovascular risk. Addition of a fibrate, niacin (North and South America), omega-3 fatty acids or ezetimibe are all options for combination with a statin to further reduce non-HDL cholesterol, although lacking in hard evidence for cardiovascular outcome benefits. Several emerging treatments may offer promise. These include the next generation peroxisome proliferator-activated receptoralpha agonists, cholesteryl ester transfer protein inhibitors and monoclonal antibody therapy targeting proprotein convertase subtilisin/kexin type 9. However, long-term outcomes and safety data are clearly needed. In conclusion, the R3i believes that ongoing trials with these novel treatments may help to define the optimal management of atherogenic dyslipidaemia to reduce the clinical and socioeconomic burden of residual cardiovascular risk.
    Cardiovascular Diabetology 01/2014; 13(1):26. · 4.21 Impact Factor
  • Daniel J Rader, Emil M Degoma
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    ABSTRACT: The cholesteryl ester transfer protein (CETP) plays an integral role in the metabolism of plasma lipoproteins. Despite two failures, CETP inhibitors are still in clinical development. We review the genetics of CETP and coronary disease, preclinical data on CETP inhibition and atherosclerosis, and the effects of CETP inhibition on cholesterol efflux and reverse cholesterol transport. We discuss the two failed CETP inhibitors, torcetrapib and dalcetrapib, and attempt to extract lessons learned. Two CETP inhibitors, anacetrapib and evacetrapib, are in phase III development, and we attempt to differentiate them from the failed drugs. Whether pharmacologic CETP inhibition will reduce the risk of cardiovascular disease is one of the most fascinating and important questions in the field of cardiovascular medicine.
    Annual review of medicine 01/2014; 65:385-403. · 9.94 Impact Factor

Publication Stats

28k Citations
5,284.48 Total Impact Points


  • 2011–2014
    • Treatment Research Institute, Philadelphia PA
      Philadelphia, Pennsylvania, United States
    • Universität zu Lübeck
      Lübeck Hansestadt, Schleswig-Holstein, Germany
    • The University of Western Ontario
      London, Ontario, Canada
    • University of Utah
      Salt Lake City, Utah, United States
  • 1998–2014
    • University of Pennsylvania
      • • Perelman School of Medicine
      • • Division of Translational Medicine and Human Genetics
      • • Cardiovascular Institute
      • • Institute for Translational Medicine and Therapeutics
      • • Department of Medicine
      • • Department of Pharmacology
      • • Department of Pathology and Laboratory Medicine
      Philadelphia, Pennsylvania, United States
  • 1993–2014
    • Hospital of the University of Pennsylvania
      • • Division of Cardiovascular Medicine
      • • Department of Medicine
      Philadelphia, Pennsylvania, United States
  • 2013
    • Vanderbilt University
      • Department of Medicine
      Nashville, MI, United States
    • CGH Medical Center
      Sterling, Illinois, United States
  • 2008–2013
    • Harvard Medical School
      Boston, Massachusetts, United States
    • Wistar Institute
      Philadelphia, Pennsylvania, United States
    • Temple University
      • Section of Hospital Medicine
      Philadelphia, PA, United States
    • Stanford University
      • Division of Pediatric Cardiology
      Stanford, CA, United States
  • 2003–2013
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
    • Hanson Institute
      Tarndarnya, South Australia, Australia
    • University of Adelaide
      • Discipline of Medicine
      Adelaide, South Australia, Australia
  • 1990–2013
    • National Heart, Lung, and Blood Institute
      • Hematology Branch
      Maryland, United States
  • 2012
    • Columbia University
      • Department of Medicine
      New York City, NY, United States
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
    • Wellcome Trust Sanger Institute
      Cambridge, England, United Kingdom
  • 2010–2012
    • University of Groningen
      • Department of Pediatrics
      Groningen, Province of Groningen, Netherlands
    • Massachusetts General Hospital
      • • Center for Human Genetic Research
      • • Cardiovascular Research Center
      Boston, MA, United States
    • Emory University
      Atlanta, Georgia, United States
    • The Rockefeller University
      • Laboratory of Biochemical Genetics and Metabolism
      New York City, NY, United States
    • University of Michigan
      • Department of Biostatistics
      Ann Arbor, MI, United States
  • 2004–2012
    • The Children's Hospital of Philadelphia
      • • Division of Endocrinology and Diabetes
      • • Division of Gastroenterology, Hepatology and Nutrition
      • • Department of Pediatrics
      Philadelphia, Pennsylvania, United States
  • 2009
    • Chestnut Hill College
      Philadelphia, Pennsylvania, United States
  • 2007–2009
    • Thomas Jefferson University Hospitals
      • Division of Cardiology
      Philadelphia, Pennsylvania, United States
  • 2004–2009
    • Tufts University
      • • Cardiovascular Nutrition Research Laboratory
      • • Lipid Metabolism Research Laboratory
      • • Division of Endocrinology, Diabetes and Metabolism
      Boston, GA, United States
  • 2006–2008
    • deCODE genetics, Inc.
      Reikiavik, Capital Region, Iceland
  • 2004–2007
    • Heart Research Institute
      Newtown, New South Wales, Australia
  • 1994–2006
    • University of Delaware
      • Department of Biological Sciences
      Newark, DE, United States
  • 2005
    • Ludwig-Maximilian-University of Munich
      • Department of Internal Medicine II
      München, Bavaria, Germany
    • University of Massachusetts Amherst
      • Department of Public Health
      Amherst Center, MA, United States
    • University of Toronto
      • Department of Medicine
      Toronto, Ontario, Canada
  • 2002
    • The Jikei University School of Medicine
      • Department of Cardiology
      Tokyo, Tokyo-to, Japan
  • 2000
    • Merck
      Whitehouse Station, New Jersey, United States
    • Universität Heidelberg
      • Department of Internal Medicine I, Endocrinology and Metabolism
      Heidelberg, Baden-Wuerttemberg, Germany
  • 1997
    • University of Washington Seattle
      • Department of Medicine
      Seattle, WA, United States
  • 1993–1995
    • Bristol-Myers Squibb
      • Department of Metabolic Diseases
      New York City, NY, United States
  • 1992
    • University of Hamburg
      • Department of Internal Medicine II and Clinic (Oncology Center)
      Hamburg, Hamburg, Germany