Polygenic risk score adds to a clinical risk score in the prediction of cardiovascular disease in a clinical setting DOI Creative Commons
Nilesh J. Samani,

Emma Beeston,

Chris Greengrass

et al.

European Heart Journal, Journal Year: 2024, Volume and Issue: 45(34), P. 3152 - 3160

Published: June 7, 2024

Abstract Background and Aims A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of risk, but whether the addition a CVD-PRS to clinical scores improves identification at increased in real-world setting is unknown. Methods The Genetics Vascular Health Check Study (GENVASC) was embedded within UK National Service (NHSHC) programme which invites between 40–74 years age without known CVD attend an assessment general practice where factors are measured (QRISK2) calculated. Between 2012–2020, 44,141 (55.7% females, 15.8% non-white) who attended NHSHC 147 participating practices across two counties England were recruited followed. When 195 (cases) had suffered major event (CVD death, myocardial infarction or acute coronary syndrome, revascularisation, stroke), 396 propensity-matched controls with similar profile identified, nested case-control genetic study undertaken see if QRISK2 form integrated tool (IRT) combined would have identified more time their as high (QRISK2 10-year ≥10%), compared alone. Results distribution standardised significantly cases (cases mean .32; controls, −.18, P = 8.28×10−9). 61.5% (95% confidence interval [CI]: 54.3%–68.4%) subsequently developed being NHSHC, while combination IRT 68.7% CI: 61.7%–75.2%), relative increase 11.7% (P 1×10−4). odds ratio (OR) up-classified 2.41 1.03–5.64, .031) for controls. In aged 40–54 years, 26.0% 16.5%–37.6%) those event, 38.4% 27.2%–50.5%), indicating stronger 47.7% younger group .001). proportion additional similarly women men, non-white ethnicities white ethnicity. findings when added atherosclerotic pooled cohort equations (ASCVD-PCE) SCORE2 scores. Conclusions setting, information improved went on especially among individuals. provide important evidence potential value implementing health systems.

Language: Английский

Reversal agents for current and forthcoming direct oral anticoagulants DOI Open Access
Nick van Es, Raffaele De Caterina, Jeffrey I. Weitz

et al.

European Heart Journal, Journal Year: 2023, Volume and Issue: 44(20), P. 1795 - 1806

Published: March 29, 2023

Over the past 20 years, there has been a shift from vitamin K antagonists to direct oral anticoagulants (DOACs), which include thrombin inhibitor dabigatran and factor Xa inhibitors apixaban, edoxaban, rivaroxaban. Although DOACs are associated with less serious bleeding than antagonists, still occurs DOACs, particularly in elderly those comorbidities. Reversal of anticoagulant effects may be needed patients requiring urgent surgery or intervention. can effected specific agents, such as idarucizumab for andexanet alfa rivaroxaban, non-specific prothrombin complex concentrates, activated concentrate, recombinant VII. This paper (i) provides an update on when how reverse (ii) describes new reversal agents under development, (iii) strategic framework XI currently investigation phase three clinical trials.

Language: Английский

Citations

32
COVID-19 Is a Coronary Artery Disease Risk Equivalent and Exhibits a Genetic Interaction With ABO Blood Type DOI
James R. Hilser, N. Sṕencer,

Kimia Moeeni Afshari

et al.

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2024, Volume and Issue: 44(11), P. 2321 - 2333

Published: Oct. 9, 2024

BACKGROUND: COVID-19 is associated with acute risk of major adverse cardiac events (MACE), including myocardial infarction, stroke, and mortality (all-cause). However, the duration underlying determinants heightened cardiovascular disease MACE post–COVID-19 are not known. METHODS: Data from UK Biobank was used to identify cases (n=10 005) who were positive for polymerase chain reaction (PCR + )-based tests SARS-CoV-2 infection (n=8062) or received hospital-based International Classification Diseases version-10 (ICD-10 ) codes (n=1943) between February 1, 2020 December 31, 2020. Population controls (n=217 730) propensity score—matched (n=38 860) also drawn during same period. Proportional hazard models evaluate association long-term (>1000 days) as a coronary artery equivalent. Additional analyses examined whether interacted genetic affect its components. RESULTS: The elevated in at all levels severity (HR, 2.09 [95% CI, 1.94–2.25]; P <0.0005) greater extent hospitalized 3.85 3.51–4.24]; <0.0005). Hospitalization represented equivalent since incident among without history even higher than that observed patients 1.21 1.08–1.37]; <0.005). A significant interaction ABO locus hospitalization ( =0.01), thrombotic being increased subjects non-O blood types 1.65 1.29–2.09]; =4.8×10 −5 type O 0.96 0.66–1.39]; =0.82). CONCLUSIONS: represents equivalent, post–acute infarction stroke particularly types. These results may have important clinical implications represent, our knowledge, one first examples gene-pathogen exposure events.

Language: Английский

Citations

14
Sex-specific genetic architecture of blood pressure DOI
Min‐Lee Yang, Chang Xu, Trisha Gupte

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(3), P. 818 - 828

Published: March 1, 2024

Language: Английский

Citations

13
Drug-target Mendelian randomization analysis supports lowering plasma ANGPTL3, ANGPTL4, and APOC3 levels as strategies for reducing cardiovascular disease risk DOI Creative Commons
Fredrik Landfors, Peter Henneman, Elin Chorell

et al.

European Heart Journal Open, Journal Year: 2024, Volume and Issue: 4(3)

Published: April 30, 2024

Abstract Aims APOC3, ANGPTL3, and ANGPTL4 are circulating proteins that actively pursued as pharmacological targets to treat dyslipidaemia reduce the risk of atherosclerotic cardiovascular disease. Here, we used human genetic data compare predicted therapeutic adverse effects inactivation. Methods results We conducted drug-target Mendelian randomization analyses using variants in proximity genes associated with protein levels drug targets. obtained exposure outcome from large-scale genome-wide association studies generalized least squares correct for linkage disequilibrium-related correlation. evaluated five primary cardiometabolic endpoints screened potential side across 694 disease-related endpoints, 43 clinical laboratory tests, 11 internal organ MRI measurements. Genetically lowering reduced odds coronary artery disease (CAD) [odds ratio, 0.57 per s.d. (95% CI 0.47–0.70)] Type 2 diabetes (T2D) 0.73 0.57–0.94)]. APOC3 also CAD 0.90 0.82–0.99)]. lowered ANGPTL3 via common were not CAD. However, meta-analysis protein-truncating revealed inactivation protected against (odds 0.71 allele [95%CI, 0.58–0.85]). Analysis ANGPTL4, did identify important safety concerns. Conclusion Human evidence suggests therapies aimed at reducing may T2D.

Language: Английский

Citations

13
Polygenic risk score adds to a clinical risk score in the prediction of cardiovascular disease in a clinical setting DOI Creative Commons
Nilesh J. Samani,

Emma Beeston,

Chris Greengrass

et al.

European Heart Journal, Journal Year: 2024, Volume and Issue: 45(34), P. 3152 - 3160

Published: June 7, 2024

Abstract Background and Aims A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of risk, but whether the addition a CVD-PRS to clinical scores improves identification at increased in real-world setting is unknown. Methods The Genetics Vascular Health Check Study (GENVASC) was embedded within UK National Service (NHSHC) programme which invites between 40–74 years age without known CVD attend an assessment general practice where factors are measured (QRISK2) calculated. Between 2012–2020, 44,141 (55.7% females, 15.8% non-white) who attended NHSHC 147 participating practices across two counties England were recruited followed. When 195 (cases) had suffered major event (CVD death, myocardial infarction or acute coronary syndrome, revascularisation, stroke), 396 propensity-matched controls with similar profile identified, nested case-control genetic study undertaken see if QRISK2 form integrated tool (IRT) combined would have identified more time their as high (QRISK2 10-year ≥10%), compared alone. Results distribution standardised significantly cases (cases mean .32; controls, −.18, P = 8.28×10−9). 61.5% (95% confidence interval [CI]: 54.3%–68.4%) subsequently developed being NHSHC, while combination IRT 68.7% CI: 61.7%–75.2%), relative increase 11.7% (P 1×10−4). odds ratio (OR) up-classified 2.41 1.03–5.64, .031) for controls. In aged 40–54 years, 26.0% 16.5%–37.6%) those event, 38.4% 27.2%–50.5%), indicating stronger 47.7% younger group .001). proportion additional similarly women men, non-white ethnicities white ethnicity. findings when added atherosclerotic pooled cohort equations (ASCVD-PCE) SCORE2 scores. Conclusions setting, information improved went on especially among individuals. provide important evidence potential value implementing health systems.

Language: Английский

Citations

13