Institution
Clinical Trial Service Unit
About: Clinical Trial Service Unit is a based out in . It is known for research contribution in the topics: Population & Stroke. The organization has 428 authors who have published 1387 publications receiving 181920 citations.
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TL;DR: Two LPA variants were strongly associated with both an increased level of Lp(a) lipoprotein and an increased risk of coronary disease, and the association between the LPA genotype score and the risk of heart disease was abolished.
Abstract: BACKGROUND: An increased level of Lp(a) lipoprotein has been identified as a risk factor for coronary artery disease that is highly heritable. The genetic determinants of the Lp(a) lipoprotein level and their relevance for the risk of coronary disease are incompletely understood. METHODS: We used a novel gene chip containing 48,742 single-nucleotide polymorphisms (SNPs) in 2100 candidate genes to test for associations in 3145 case subjects with coronary disease and 3352 control subjects. Replication was tested in three independent populations involving 4846 additional case subjects with coronary disease and 4594 control subjects. RESULTS: Three chromosomal regions (6q26-27, 9p21, and 1p13) were strongly associated with the risk of coronary disease. The LPA locus on 6q26-27 encoding Lp(a) lipoprotein had the strongest association. We identified a common variant (rs10455872) at the LPA locus with an odds ratio for coronary disease of 1.70 (95% confidence interval [CI], 1.49 to 1.95) and another independent variant (rs3798220) with an odds ratio of 1.92 (95% CI, 1.48 to 2.49). Both variants were strongly associated with an increased level of Lp(a) lipoprotein, a reduced copy number in LPA (which determines the number of kringle IV-type 2 repeats), and a small Lp(a) lipoprotein size. Replication studies confirmed the effects of both variants on the Lp(a) lipoprotein level and the risk of coronary disease. A meta-analysis showed that with a genotype score involving both LPA SNPs, the odds ratios for coronary disease were 1.51 (95% CI, 1.38 to 1.66) for one variant and 2.57 (95% CI, 1.80 to 3.67) for two or more variants. After adjustment for the Lp(a) lipoprotein level, the association between the LPA genotype score and the risk of coronary disease was abolished. CONCLUSIONS: We identified two LPA variants that were strongly associated with both an increased level of Lp(a) lipoprotein and an increased risk of coronary disease. Our findings provide support for a causal role of Lp(a) lipoprotein in coronary disease.
1,272 citations
Clinical Trial Service Unit1, Johns Hopkins University School of Medicine2, University of Cambridge3, University of Bristol4, University of Wisconsin-Madison5, University of London6, Queen Mary University of London7, The George Institute for Global Health8, Imperial College London9, Brigham and Women's Hospital10, University of Edinburgh11, University of North Carolina at Chapel Hill12, National Institutes of Health13, National Health and Medical Research Council14, Population Health Research Institute15
TL;DR: The large-scale evidence from randomised trials indicates that it is unlikely that large absolute excesses in other serious adverse events still await discovery, and any further findings that emerge about the effects of statin therapy would not be expected to alter materially the balance of benefits and harms.
1,245 citations
TL;DR: The epidemiological and clinical evidence on CHD and Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus, as well as possible mechanisms are reviewed.
1,213 citations
TL;DR: Most deep-vein thromboses are subclinical and resolve completely when mobility is restored, although some do produce permanent valvular damage and chronic venous insufficiency, and a few, however, may travel to the lungs and, depending on how much of the pulmonary circulation is.
Abstract: DURING prolonged general anesthesia and any period of limited mobility following surgery, thrombus formation may be initiated in the deep veins of the legs. Studies employing Radio-labeled fibrinogen or venography have revealed deep-vein thrombosis in 20 to 30 percent of patients who have undergone general surgery and in an even larger proportion of patients who have had orthopedic surgery.1 2 3 Most such thromboses are subclinical and resolve completely when mobility is restored, although some do produce permanent valvular damage and chronic venous insufficiency. A few, however, may travel to the lungs and, depending on how much of the pulmonary circulation is . . .
1,203 citations
Auckland University of Technology1, Institute for Health Metrics and Evaluation2, National Institutes of Health3, Clinical Trial Service Unit4, Columbia University Medical Center5, University of Miami6, Washington State Institute for Public Policy7, Copenhagen University Hospital8, National University of Ireland, Galway9, National University of Singapore10, University of Auckland11, Imperial College London12
TL;DR: Worldwide, the burden of ischaemic and haemorrhagic stroke increased significantly between 1990 and 2010 in terms of the absolute number of people with incident ischaemia and haelopathy, number of deaths, and disability-adjusted life-years lost, and DALYs lost.
1,031 citations
Authors
Showing all 428 results
| Name | H-index | Papers | Citations |
|---|---|---|---|
| Salim Yusuf | 231 | 1439 | 252912 |
| Richard Peto | 183 | 683 | 231434 |
| Cornelia M. van Duijn | 183 | 1030 | 146009 |
| Rory Collins | 162 | 489 | 193407 |
| Naveed Sattar | 155 | 1326 | 116368 |
| Timothy J. Key | 146 | 808 | 90810 |
| John Danesh | 135 | 394 | 100132 |
| Andrew J.S. Coats | 127 | 820 | 94490 |
| Valerie Beral | 114 | 471 | 53729 |
| Mike Clarke | 113 | 1037 | 164328 |
| Robert Clarke | 111 | 512 | 90049 |
| Robert U. Newton | 109 | 753 | 42527 |
| Richard Gray | 109 | 808 | 78580 |
| Braxton D. Mitchell | 102 | 558 | 49599 |
| Naomi E. Allen | 101 | 364 | 37057 |