| 1. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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| 2. |
- Asselbergs, Folkert W., et al.
(författare)
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Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci
- 2012
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:5, s. 823-838
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.
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| 3. |
- Ganesh, Santhi K., et al.
(författare)
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Loci influencing blood pressure identified using a cardiovascular gene-centric array
- 2013
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
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| 4. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 5. |
- de Boer, Rudolf A, et al.
(författare)
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The WAP four-disulfide core domain protein HE4 : a novel biomarker for heart failure.
- 2013
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Ingår i: JACC. Heart failure. - : Elsevier BV. - 2213-1787 .- 2213-1779. ; 1:2, s. 164-169
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study investigated clinical determinants and added prognostic value of HE4 as a biomarker not previously described in heart failure (HF).BACKGROUND: Identification of plasma biomarkers that help to risk stratify HF patients may help to improve treatment.METHODS: Plasma HE4 levels were determined in 567 participants of the COACH (Coordinating study evaluating outcomes of Advising and Counseling in Heart failure). Patients had been hospitalized for HF and were followed for 18 months. The primary endpoint of this study was a composite of all-cause mortality and HF hospitalization.RESULTS: HE4 showed a strong correlation with HF severity, according to New York Heart Association functional class and brain natriuretic peptide (BNP) levels (p < 0.001). HE4 also showed a positive correlation with GDF15 (p < 0.001) and, in addition, correlated with kidney function (estimated glomerular filtration rate [eGFR]; p < 0.001). Cox regression analysis revealed that a doubling of HE4 levels was associated with a hazard ratio (HR) of 1.73 (95% confidence interval [CI]: 1.53 to 1.95) for the primary outcome (p < 0.001). After correction for age, gender, BNP, and eGFR, the HR was 1.46 (95% CI: 1.23 to 1.72; p < 0.001), and after additional adjustment for GDF15, the HR lowered to 1.30 (95% CI: 1.07 to 1.59; p = 0.009). The area under the curve in the receiver-operating characteristic curve analysis increased from 0.727 to 0.752 when HE4 was included in the clinical evaluation (p = 0.051). The integrated discrimination improvement and net reclassification index for reclassification showed significant improvements when HE4 was added to the clinical model, and this remained significant after BNP inclusion in the model.CONCLUSIONS: HE4 plasma levels are correlated with markers of HF severity, show prognostic value, and can improve risk assessment in HF.
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| 6. |
- Debono, Bertrand, et al.
(författare)
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Consensus statement for perioperative care in lumbar spinal fusion : Enhanced Recovery After Surgery (ERAS®) Society recommendations
- 2021
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Ingår i: The spine journal. - : Elsevier. - 1529-9430 .- 1878-1632. ; 21:5, s. 729-752
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Enhanced Recovery After Surgery (ERAS) evidence-based protocols for perioperative care have led to improvements in outcomes in numerous surgical areas, through multimodal optimization of patient pathway, reduction of complications, improved patient experience and reduction in the length of stay. ERAS represent a relatively new paradigm in spine surgery.PURPOSE: This multidisciplinary consensus review summarizes the literature and proposes recommendations for the perioperative care of patients undergoing lumbar fusion surgery with an ERAS program.STUDY DESIGN: This is a review article.METHODS: Under the impetus of the ERAS (R) society, a multidisciplinary guideline development group was constituted by bringing together international experts involved in the practice of ERAS and spine surgery. This group identified 22 ERAS items for lumbar fusion. A systematic search in the English language was performed in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Systematic reviews, randomized controlled trials, and cohort studies were included, and the evidence was graded according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Consensus recommendation was reached by the group after a critical appraisal of the literature.RESULTS: Two hundred fifty-six articles were included to develop the consensus statements for 22 ERAS items; one ERAS item (prehabilitation) was excluded from the final summary due to very poor quality and conflicting evidence in lumbar spinal fusion. From these remaining 21 ERAS items, 28 recommendations were included. All recommendations on ERAS protocol items are based on the best available evidence. These included nine preoperative, eleven intraoperative, and six postoperative recommendations. They span topics from preoperative patient education and nutritional evaluation, intraoperative anesthetic and surgical techniques, and postoperative multi-modal analgesic strategies. The level of evidence for the use of each recommendation is presented.CONCLUSION: Based on the best evidence available for each ERAS item within the multidisciplinary perioperative care pathways, the ERAS (R) Society presents this comprehensive consensus review for perioperative care in lumbar fusion.
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| 7. |
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| 8. |
- Ljungqvist, Olle, 1954-, et al.
(författare)
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Enhanced Recovery After Surgery and Elderly Patients : Advances
- 2023
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Ingår i: Anesthesiology clinics. - : Elsevier. - 1932-2275. ; 41:3, s. 647-655
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Forskningsöversikt (refereegranskat)abstract
- Enhanced recovery after surgery (ERAS) is a new way of working where evidence-based care elements are assembled to form a care pathway involving the patient's entire journey through surgery. Many elements included in ERAS have stress-reducing effects on the body or helps avoid side effects associated with alternative treatment options. This leads to less overall stress from the injury caused by the operation and helps facilitate recovery. In old, frail patients with concomitant diseases and less physical reserves, this may help explain why the ERAS care is reported to be beneficial for this specific patient group.
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| 9. |
- Ljungqvist, Olle, 1954-, et al.
(författare)
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Opportunities and Challenges for the Next Phase of Enhanced Recovery After Surgery : A Review
- 2021
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Ingår i: JAMA Surgery. - : American Medical Association. - 2168-6254 .- 2168-6262. ; 56:8, s. 775-784
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Forskningsöversikt (refereegranskat)abstract
- Importance: Enhanced Recovery After Surgery (ERAS) is a global surgical quality improvement initiative now firmly entrenched within the field of perioperative care. Although ERAS is associated with significant clinical outcome improvements and cost savings in numerous surgical specialties, several opportunities and challenges deserve further discussion.Observations: Uptake and implementation of ERAS Society guidelines, together with ERAS-related research, have increased exponentially since the inception of the ERAS movement. Opportunities to further improve patient outcomes include addressing frailty, optimizing nutrition, prehabilitation, correcting preoperative anemia, and improving uptake of ERAS worldwide, including in low- and middle-income countries. Challenges facing enhanced recovery today include implementation, carbohydrate loading, reversal of neuromuscular blockade, and bowel preparation. The COVID-19 pandemic poses both a challenge and an opportunity for ERAS.Conclusions and Relevance: To date, ERAS has achieved significant benefit for patients and health systems; however, improvements are still needed, particularly in the areas of patient optimization and systematic implementation. During this time of global crisis, the ERAS method of delivering care is required to take surgery and anesthesia to the next level and bring improvements in outcomes to both patients and health systems.
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| 10. |
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| 11. |
- Oodit, Ravi, et al.
(författare)
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Guidelines for Perioperative Care in Elective Abdominal and Pelvic Surgery at Primary and Secondary Hospitals in Low-Middle-Income Countries (LMIC's) : Enhanced Recovery After Surgery (ERAS) Society Recommendation
- 2022
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Ingår i: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 46:8, s. 1826-1843
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Forskningsöversikt (refereegranskat)abstract
- Background: This is the first Enhanced Recovery After Surgery (ERAS (R)) Society guideline for primary and secondary hospitals in low-middle-income countries (LMIC's) for elective abdominal and gynecologic care.Methods: The ERAS LMIC Guidelines group was established by the ERAS (R) Society in collaboration with different representatives of perioperative care from LMIC's. The group consisted of seven members from the ERAS (R) Society and eight members from LMIC's. An updated systematic literature search and evaluation of evidence from previous ERAS (R) guidelines was performed by the leading authors of the Colorectal (2018) and Gynecologic (2019) surgery guidelines (Gustafsson et al in World J Surg 43:6592-695, Nelson et al in Int J Gynecol Cancer 29(4):651-668). Meta-analyses randomized controlled trials (RCTs), prospective and retrospective cohort studies from both HIC's and LMIC's were considered for each perioperative item. The members in the LMIC group then applied the current evidence and adapted the recommendations for each intervention as well as identifying possible new items relevant to LMIC's. The Grading of Recommendations, Assessment, Development and Evaluation system (GRADE) methodology was used to determine the quality of the published evidence. The strength of the recommendations was based on importance of the problem, quality of evidence, balance between desirable and undesirable effects, acceptability to key stakeholders, cost of implementation and specifically the feasibility of implementing in LMIC's and determined through discussions and consensus.Results: In addition to previously described ERAS (R) Society interventions, the following items were included, revised or discussed: the Surgical Safety Checklist (SSC), preoperative routine human immunodeficiency virus (HIV) testing in countries with a high prevalence of HIV/AIDS (CD4 and viral load for those patients that are HIV positive), delirium screening and prevention, COVID 19 screening, VTE prophylaxis, immuno-nutrition, prehabilitation, minimally invasive surgery (MIS) and a standardized postoperative monitoring guideline.Conclusions: These guidelines are seen as a starting point to address the urgent need to improve perioperative care and to effect data-driven, evidence-based care in LMIC's.
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| 12. |
- Vergaro, Giuseppe, et al.
(författare)
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Cardiac biomarkers retain prognostic significance in patients with heart failure and chronic obstructive pulmonary disease
- 2021
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Ingår i: Journal of Cardiovascular Medicine. - : Wolters Kluwer. - 1558-2027 .- 1558-2035. ; 23:1, s. 28-36
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with heart failure (HF). We assessed the influence of COPD on circulating levels and prognostic value of three HF biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), and soluble suppression of tumorigenesis-2 (sST2).Methods: Individual data from patients with chronic HF, known COPD status, NT-proBNP and hs-TnT values (n = 8088) were analysed. A subgroup (n = 3414) had also sST2 values.Results: Patients had a median age of 66 years (interquartile interval 57–74), 77% were men and 82% had HF with reduced ejection fraction. NT-proBNP, hs-TnT and sST2 were 1207 ng/l (487–2725), 17 ng/l (9–31) and 30 ng/ml (22–44), respectively. Patients with COPD (n = 1249, 15%) had higher NT-proBNP (P = 0.042) and hs-TnT (P < 0.001), but not sST2 (P = 0.165). Over a median 2.0-year follow-up (1.5–2.5), 1717 patients (21%) died, and 1298 (16%) died from cardiovascular causes; 2255 patients (28%) were hospitalized for HF over 1.8 years (0.9–2.1). NT-proBNP, hs-TnT and sST2 predicted the three end points regardless of COPD status. The best cut-offs from receiver-operating characteristics analysis were higher in patients with COPD than in those without. Patients with all three biomarkers higher than or equal to end-point- and COPD-status-specific cut-offs were also those with the worst prognosis.Conclusions: Among patients with HF, those with COPD have higher NT-proBNP and hs-TnT, but not sST2. All these biomarkers yield prognostic significance regardless of the COPD status.
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| 13. |
- Vergaro, Giuseppe, et al.
(författare)
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NT-proBNP for Risk Prediction in Heart Failure : Identification of Optimal Cutoffs Across Body Mass Index Categories
- 2021
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Ingår i: JACC. Heart failure. - : American College of Cardiology. - 2213-1779 .- 2213-1787. ; 9:9, s. 653-663
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe goal of this study was to assess the predictive power of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and the decision cutoffs in heart failure (HF) across body mass index (BMI) categories.BackgroundConcentrations of NT-proBNP predict outcome in HF. Although the influence of BMI to reduce levels of NT-proBNP is known, the impact of obesity on prognostic value remains uncertain.MethodsIndividual data from the BIOS (Biomarkers In Heart Failure Outpatient Study) consortium were analyzed. Patients with stable HF were classified as underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), and mildly (BMI 30-34.9 kg/m2), moderately (BMI 35-39.9 kg/m2), or severely (BMI ≥40 kg/m2) obese. The prognostic role of NT-proBNP was tested for the endpoints of all-cause and cardiac death.ResultsThe study population included 12,763 patients (mean age 66 ± 12 years; 25% women; mean left ventricular ejection fraction 33% ± 13%). Most patients were overweight (n = 5,176), followed by normal weight (n = 4,299), mildly obese (n = 2,157), moderately obese (n = 612), severely obese (n = 314), and underweight (n = 205). NT-proBNP inversely correlated with BMI (β = –0.174 for 1 kg/m2; P < 0.001). Adding NT-proBNP to clinical models improved risk prediction across BMI categories, with the exception of severely obese patients. The best cutoffs of NT-proBNP for 5-year all-cause death prediction were lower as BMI increased (3,785 ng/L, 2,193 ng/L, 1,554 ng/L, 1,045 ng/L, 755 ng/L, and 879 ng/L, for underweight, normal weight, overweight, and mildly, moderately, and severely obese patients, respectively) and were higher in women than in men.ConclusionsNT-proBNP maintains its independent prognostic value up to 40 kg/m2 BMI, and lower optimal risk-prediction cutoffs are observed in overweight and obese patients.
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