| 1. |
- Aragam, KG, et al.
(författare)
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Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:12, s. 1803-1815
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR–Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.
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| 2. |
- Aragam, KG, et al.
(författare)
-
Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants
- 2022
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:12, s. 1803-1815
-
Tidskriftsartikel (refereegranskat)abstract
- The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR–Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.
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| 3. |
- Koeckerling, D., et al.
(författare)
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Endovascular revascularization strategies for aortoiliac and femoropopliteal artery disease: a meta-analysis
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 44:11, s. 935-950
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Tidskriftsartikel (refereegranskat)abstract
- Aims Optimal endovascular management of intermittent claudication (IC) remains disputed. This systematic review and meta-analysis compares efficacy and safety outcomes for balloon angioplasty (BA), bare-metal stents (BMS), drug-coated balloons (DCB), drug-eluting stents (DES), covered stents, and atherectomy. Methods and results Electronic databases were searched for randomized, controlled trials (RCT) from inception through November 2021. Efficacy outcomes were primary patency, target-lesion revascularization (TLR), and quality-of-life (QoL). Safety endpoints were all-cause mortality and major amputation. Outcomes were evaluated at short-term (<1 year), mid-term (1-2 years), and long-term (>= 2 years) follow-up. The study was registered on PROSPERO (CRD42021292639). Fifty-one RCTs enrolling 8430 patients/lesions were included. In femoropopliteal disease of low-to-intermediate complexity, DCBs were associated with higher likelihood of primary patency [short-term: odds ratio (OR) 3.21, 95% confidence interval (CI) 2.44-4.24; long-term: OR 2.47, 95% CI 1.93-3.16], lower TLR (short-term: OR 0.33, 95% CI 0.22-0.49; long-term: OR 0.42, 95% CI 0.29-0.60) and similar all-cause mortality risk, compared with BA. Primary stenting using BMS was associated with improved short-to-mid-term patency and TLR, but similar long-term efficacy compared with provisional stenting. Mid-term patency (OR 1.64, 95% CI 0.89-3.03) and TLR (OR 0.50, 95% CI 0.22-1.11) estimates were comparable for DES vs. BMS. Atherectomy, used independently or adjunctively, was not associated with efficacy benefits compared with drug-coated and uncoated angioplasty, or stenting approaches. Paucity and heterogeneity of data precluded pooled analysis for aortoiliac disease and QoL endpoints. Conclusion Certain devices may provide benefits in femoropopliteal disease, but comparative data in aortoiliac arteries is lacking. Gaps in evidence quantity and quality impede identification of the optimal endovascular approach to IC.
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| 4. |
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| 5. |
- Capodanno, Davide, et al.
(författare)
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Defining Strategies of Modulation of Antiplatelet Therapy in Patients With Coronary Artery Disease : A Consensus Document from the Academic Research Consortium
- 2023
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 147:25, s. 1933-1944
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Tidskriftsartikel (refereegranskat)abstract
- Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.
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