| 1. |
- Girerd, Sophie, et al.
(författare)
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Arteriovenous fistula thrombosis is associated with increased all-cause and cardiovascular mortar in haemodialysis patients from the AURORA trial
- 2020
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 13:1, s. 116-122
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Tidskriftsartikel (refereegranskat)abstract
- Background. The impact of arteriovenous fistula (AVF) or graft (AVG) thrombosis on mortality has been sparsely studied. This study investigated the association between AVF/AVG thrombosis and all-cause and cardiovascular mortality.Methods. The data from 2439 patients with AVF or AVG undergoing maintenance haemodialysis (HD) included in the A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events trial (AURORA) were analysed using a time-dependent Cox model. The incidence of vascular access (VA) thrombosis was a pre-specified secondary outcome.Results. During follow-up, 278 AVF and 94 AVG thromboses were documented. VA was restored at 22 +/- 64 days after thrombosis (27 patients had no restoration with subsequent permanent central catheter). In multivariable survival analysis adjusted for potential confounders, the occurrence of AVF/AVG thrombosis was associated with increased early and late allcause mortality, with a more pronounced association with early all-cause mortality {hazard ratio [HR] < 90 days 2.70 [95% confidence interval (CI) 1.83-3.97], P < 0.001; HR > 90 days 1.47 [1.20-1.80], P < 0.001). In addition, the occurrence of AVF thrombosis was significantly associated with higher all-cause mortality, whether VA was restored within 7 days [HR 1.34 (95% CI 1.02-1.75), P = 0.036] or later than 7 days [HR 1.81 (95% CI 1.29-2.53), P = 0.001].Conclusions. AVF/AVG thrombosis should be considered as a major clinical event since it is strongly associated with increased mortality in patients on maintenance HD, especially in the first 90 days after the event and when access restoration occurs >7 days after thrombosis. Clinicians should pay particular attention to the timing of VA restoration and the management of these patients during this high-risk period. The potential benefit of targeting overall patient risk with more aggressive treatment after AVF/AVG restoration should be further explored.
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| 2. |
- Bäck, Magnus, et al.
(författare)
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Fatty acid desaturase genetic variations and dietary omega-3 fatty acid intake associate with arterial stiffness
- 2022
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Ingår i: European Heart Journal Open. - : Oxford University Press. - 2752-4191. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Long-chain polyunsaturated fatty acids (PUFAs) generate diverse bioactive lipid mediators, which tightly regulate vascular inflammation. The effects of omega-3 PUFA supplementation in cardiovascular prevention however remain controversial. In addition to direct dietary intake, fatty acid desaturases (FADS) determine PUFA levels. Increased arterial stiffness represents an independent predictor of mortality and cardiovascular events. The aim of the present study was to determine the association of PUFA intake, FADS1 genotype, and FADS expression with arterial stiffness.METHODS AND RESULTS: A cross-sectional population-based cohort study of 1464 participants without overt cardiovascular disease was conducted. Dietary intake was assessed using a food frequency questionnaire. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV), and the FADS1 locus variant was determined. Blood cell transcriptomics was performed in a subset of 410 individuals. Pulse wave velocity was significantly associated with the FADS1 locus variant. Differential associations between PWV and omega-3 PUFA intake were observed depending on the FADS1 genotype. High omega-3 PUFA intake attenuated the FADS1 genotype-dependent associations. Carriers of the minor FADS1 locus variant exhibited increased expression of FADS2, which is associated with PWV.CONCLUSION: Taken together, these findings point to FADS1 genotype-dependent associations of omega-3 PUFA intake on subclinical cardiovascular disease. These findings may have implications for identifying responders and non-responders to omega-3 PUFA supplementation and open up for personalized dietary counselling in cardiovascular prevention.
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| 3. |
- Chau, Kénora, et al.
(författare)
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Obesity and metabolic features associated with long-term developing diastolic dysfunction in an initially healthy population-based cohort
- 2018
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Ingår i: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 107:10, s. 887-896
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diastolic dysfunction (DD) is increasingly common. However, its metabolic determinants are poorly known. This study aims to determine which metabolic and inflammatory features predict DD in initially healthy adults. Methods: We prospectively analyzed the association between metabolic features and DD in 728 initially healthy adults aged 30–60 from Eastern France enrolled in the STANISLAS population-based cohort. Clinical and biological cardiovascular features were collected at baseline (1994–1995). DD was assessed twenty years later (2011–2016) by echocardiography using current international guidelines. For replication purposes, 1463 subjects from the Malmö Preventive Project cohort were analyzed. Results: In the STANISLAS cohort, 191 subjects (26.2%) developed DD. In age-sex-adjusted logistic models, significant predictors of DD were body mass index (BMI, odds ratio for 1-standard-deviation increase (OR) 1.28, 95% CI 1.08–1.52), waist circumference (WC, OR 1.48, 95% CI 1.18–1.84), waist-hip ratio (OR 1.53, 95% CI 1.16–2.02), systolic blood pressure (OR 1.19, 95% CI 1.00–1.43) and triglycerides (TG, OR 1.18, 95% CI 1.00–1.40). Subjects with elevated WC (> 80th percentile) and TG (> 50th percentile) had a twofold higher DD risk (age-sex-adjusted odds ratio 2.00, 95% CI 1.20–3.31, P = 0.008), whereas no such interplay was observed for BMI. In the Malmö cohort, BMI was similarly associated with DD; participants with both elevated BMI and TG were at higher DD risk (age-sex-adjusted odds ratio 1.61, 95% CI 1.18–2.20, P = 0.002). Conclusions: Subjects with elevated WC and TG may have a higher long-term DD risk. Prevention targeting visceral obesity may help reduce the incidence of DD.
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| 4. |
- de Gonzalo-Calvo, David, et al.
(författare)
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Improved cardiovascular risk prediction in patients with end-stage renal disease on hemodialysis using machine learning modeling and circulating microribonucleic acids
- 2020
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Ingår i: Theranostics. - : IVYSPRING INT PUBL. - 1838-7640. ; 10:19, s. 8665-8676
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: To test whether novel biomarkers, such as microribonucleic acids (miRNAs), and nonstandard predictive models, such as decision tree learning, provide useful information for medical decision-making in patients on hemodialysis (HD). Methods: Samples from patients with end-stage renal disease receiving HD included in the AURORA trial were investigated (n=810). The study included two independent phases: phase I (matched cases and controls, n=410) and phase II (unmatched cases and controls, n=400). The composite endpoint was cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. miRNA quantification was performed using miRNA sequencing and RT-qPCR. The CART algorithm was used to construct regression tree models. A bagging-based procedure was used for validation. Results: In phase I, miRNA sequencing in a subset of samples (n=20) revealed miR-632 as a candidate (fold change=2.9). miR-632 was associated with the endpoint, even after adjusting for confounding factors (HR from 1.43 to 1.53). These findings were not reproduced in phase II. Regression tree models identified eight patient subgroups with specific risk patterns. miR-186-5p and miR-632 entered the tree by redefining two risk groups: patients older than 64 years and with hsCRP<0.827 mg/L and diabetic patients younger than 64 years. miRNAs improved the discrimination accuracy at the beginning of the follow-up (24 months) compared to the models without miRNAs (integrated AUC [iAUC]=0.71). Conclusions: The circulating miRNA profile complements conventional risk factors to identify specific cardiovascular risk patterns among patients receiving maintenance HD.
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| 5. |
- Girerd, Nicolas, et al.
(författare)
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Hypotension in heart failure is less harmful if associated with high or increasing doses of heart failure medication: Insights from the Swedish Heart Failure Registry
- 2023
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844.
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Tidskriftsartikel (refereegranskat)abstract
- Aims Heart failure (HF) medication may reduce blood pressure (BP). Low BP is associated with worse outcomes but how this association is modified by HF medication has not been studied. We evaluated the association between BP and outcomes according to HF medication dose in HF with reduced ejection fraction (HFrEF). Methods and results We studied HFrEF patients from the Swedish HF registry (2000-2018). Associations between systolic BP (SBP) and cardiovascular death (CVD) and/or HF hospitalization (HFH) were analysed according to doses of renin-angiotensin system (RAS) inhibitors, beta-blockers and mineralocorticoid receptor antagonists (MRA). Among 42 040 patients (median age 74.0), lower baseline SBP was associated with higher risk of CVD/HFH (adjusted hazard ratio [HR] per 10 mmHg higher SBP: 0.92, 95% confidence interval [CI] 0.92-0.93), which was less high risk under optimized RAS inhibitor and beta-blocker doses (10% decrease in event rates per 10 mmHg SBP increase in untreated patients vs. 7% decrease in patients at maximum dose, both adjusted p < 0.02). Among the 13 761 patients with repeated measurements, 9.9% reported a SBP decrease >10 mmHg when HF medication doses were increased, whereas 24.6% reported a SBP decrease >10 mmHg with stable/decreasing doses. Decreasing SBP was associated with higher risk of CVD/HFH in patients with stable (HR 1.10, 95% CI 1.04-1.17) or decreasing (HR 1.29, 95% CI 1.18-1.42) HF medication dose but not in patients with an increase in doses (HR 0.94, 95% CI 0.86-1.02). Conclusions The association of lower SBP with higher risk of CVD/HFH is attenuated in patients with optimized HF medication. These results suggest that low or declining SBP should not limit HF medication optimization.
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| 6. |
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| 7. |
- Holm, Hannes, et al.
(författare)
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Ventricular-arterial coupling and cardiovascular risk among young adults : The African-PREDICT study
- 2023
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Ingår i: American Journal of Physiology - Heart and Circulatory Physiology. - 1522-1539. ; 325:2, s. 362-371
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Tidskriftsartikel (refereegranskat)abstract
- Ventricular-arterial coupling (VAC) has independent diagnostic and prognostic value for cardiovascular (CV) risk stratification, but studies on its association with anthropometric and CV factors are sparse in young individuals without overt CV disease. We aim to provide descriptive data regarding VAC and its associations with CV risk factors in young adults without overt CV disease. For 631 (mean age, 24 ± 3 yr; 51% female) individuals, VAC was determined by carotid-femoral pulse wave velocity (PWV)/global longitudinal strain (GLS). Multivariable logistic and linear regression models were performed to explore the association between PWV/GLS and CV risk factors. A P-value < 0.05 was considered statistically significant. The mean PWV/GLS was 0.33 ± 0.07 m/s%. Higher ratios of PWV/GLS associated with older age, male sex, and a higher prevalence of CV risk factors (i.e., higher blood pressure, prevalent hypertension, higher waist circumference, active smoking, higher plasma triglycerides, lower high-density lipoprotein cholesterol, and an adverse urine albumin/creatinine ratio). Furthermore, higher PWV/GLS was associated with echocardiographic measures such as lower ejection fraction and higher left ventricle mass index. In expanded logistic regression models, higher ratios of PWV/GLS were significantly associated with the prevalence of active smoking [odds ratio (OR), 1.88; confidence interval (CI) 1.36-2.58, P < 0.001] and hypertension (OR 1.98; CI 1.40-2.80, P < 0.001). We demonstrated that worse VAC reflected by higher values of PWV/GLS are significantly associated with CV risk factors in young adults. The results suggest that PWV/GLS might serve as a tool to improve the profiling of cardiovascular risk in young adults. NEW & NOTEWORTHY Assessing VAC is especially useful in heart failure and valvular heart disease, but less is known about VAC in the pathophysiology of CV disease risk in younger individuals. In young individuals without overt CV disease, we showed descriptive data regarding VAC, determined by PWV/GLS ratio, and explored the associations of VAC with clinical CV disease risk factors. Worse VAC, reflected by higher values of PWV/GLS, associated with high blood pressure and smoking in young adults.
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| 8. |
- Karason, Kristjan, 1962, et al.
(författare)
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Heart failure in obesity: insights from proteomics in patients treated with or without weight-loss surgery.
- 2022
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Ingår i: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 46, s. 2088-2094
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with incident heart failure (HF), but the underlying mechanisms are unclear.We performed a nested case-control study within the Swedish-Obese-Subjects study, by identifying 411 cases who developed HF and matched them with respect to age, sex, weight-loss-surgery and length of follow-up with 410 controls who did not develop HF. In analyses corrected for multiple testing, we studied 182 plasma proteins known to be related to cardiovascular disease to investigate whether they could add to the understanding of the processes underlying obesity-related HF.A total of 821 subjects were followed for 16±6 years. Multivariable analysis adjusted for matching variables revealed that 32 proteins were significantly associated with HF. Twelve proteins were related to HF≥80% of the time using a bootstrap resampling approach (false-discovery-rate [FDR]<0.05): 11 were associated with increased HF-risk: TNFRSF10A*, ST6GAL1, PRCP, MMP12, TIMP1, CCL3, QPCT, ANG, C1QTNF1, SERPINA5 and GAL-9; and one was related to reduced HF-risk: LPL. An further 20 proteins were associated with onset of HF 50-80% of the time using bootstrap resampling (FDR<0.05). A pathway analysis including all significant 32 proteins suggested that these biomarkers were related to inflammation, matrix remodeling, cardiometabolic hormones and hemostasis. Three proteins, C1QTNF1, FGF-21 and CST3, reflecting dyslipidemia and kidney disease, displayed a higher association with HF in patients who did not undergo weight-loss-surgery and maintained with obesity.Pathways associated with HF in obesity include inflammation, matrix remodeling, cardiometabolic hormones and hemostasis; three protein biomarkers predicting HF appeared to be obesity-specific.
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| 9. |
- Kobayashi, Masatake, et al.
(författare)
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Machine Learning-Derived Echocardiographic Phenotypes Predict Heart Failure Incidence in Asymptomatic Individuals
- 2022
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Ingår i: JACC: Cardiovascular Imaging. - : Elsevier BV. - 1876-7591 .- 1936-878X. ; 15:2, s. 193-208
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study sought to identify homogenous echocardiographic phenotypes in community-based cohorts and assess their association with outcomes.BACKGROUND: Asymptomatic cardiac dysfunction leads to a high risk of long-term cardiovascular morbidity and mortality; however, better echocardiographic classification of asymptomatic individuals remains a challenge.METHODS: Echocardiographic phenotypes were identified using K-means clustering in the first generation of the STANISLAS (Yearly non-invasive follow-up of Health status of Lorraine insured inhabitants) cohort (N = 827; mean age: 60 ± 5 years; men: 48%), and their associations with vascular function and circulating biomarkers were also assessed. These phenotypes were externally validated in the Malmö Preventive Project cohort (N = 1,394; mean age: 67 ± 6 years; men: 70%), and their associations with the composite of cardiovascular mortality (CVM) or heart failure hospitalization (HFH) were assessed as well.RESULTS: Three echocardiographic phenotypes were identified as "mostly normal (MN)" (n = 334), "diastolic changes (D)" (n = 323), and "diastolic changes with structural remodeling (D/S)" (n = 170). The D and D/S phenotypes had similar ages, body mass indices, cardiovascular risk factors, vascular impairments, and diastolic function changes. The D phenotype consisted mainly of women and featured increased levels of inflammatory biomarkers, whereas the D/S phenotype, consisted predominantly of men, displayed the highest values of left ventricular mass, volume, and remodeling biomarkers. The phenotypes were predicted based on a simple algorithm including e', left ventricular mass and volume (e'VM algorithm). In the Malmö cohort, subgroups derived from e'VM algorithm were significantly associated with a higher risk of CVM and HFH (adjusted HR in the D phenotype = 1.87; 95% CI: 1.04 to 3.37; adjusted HR in the D/S phenotype = 3.02; 95% CI: 1.71 to 5.34).CONCLUSIONS: Among asymptomatic, middle-aged individuals, echocardiographic data-driven classification based on the simple e'VM algorithm identified profiles with different long-term HF risk. (4th Visit at 17 Years of Cohort STANISLAS-Stanislas Ancillary Study ESCIF [STANISLASV4]; NCT01391442).
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| 10. |
- Leierer, Johannes, et al.
(författare)
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Identification of endophenotypes supporting outcome prediction in hemodialysis patients based on mechanistic markers of statin treatment
- 2024
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundStatins are widely used to reduce the risk of cardiovascular disease (CVD). Patients with end-stage renal disease (ESRD) on hemodialysis have significantly increased risk of developing CVD. Statin treatment in these patients however did not show a statistically significant benefit in large trials on a patient cohort level.MethodsWe generated gene expression profiles for statins to investigate the impact on cellular programs in human renal proximal tubular cells and mesangial cells in-vitro. We subsequently selected biomarkers from key statin-affected molecular pathways and assessed these biomarkers in plasma samples from the AURORA cohort, a double-blind, randomized, multi-center study of patients on hemodialysis or hemofiltration that have been treated with rosuvastatin. Patient clusters (phenotypes) were created based on the identified biomarkers using Latent Class Model clustering and the associations with outcome for the generated phenotypes were assessed using Cox proportional hazards regression models. The multivariable models were adjusted for clinical and biological covariates based on previously published data in AURORA.ResultsThe impact of statin treatment on mesangial cells was larger as compared with tubular cells with a large overlap of differentially expressed genes identified for atorvastatin and rosuvastatin indicating a predominant drug class effect. Affected molecular pathways included TGFB-, TNF-, and MAPK-signaling and focal adhesion among others. Four patient clusters were identified based on the baseline plasma concentrations of the eight biomarkers. Phenotype 1 was characterized by low to medium levels of the hepatocyte growth factor (HGF) and high levels of interleukin 6 (IL6) or matrix metalloproteinase 2 (MMP2) and it was significantly associated with outcome showing increased risk of developing major adverse cardiovascular events (MACE) or cardiovascular death. Phenotype 2 had high HGF but low Fas cell surface death receptor (FAS) levels and it was associated with significantly better outcome at 1 year.ConclusionsIn this translational study, we identified patient subgroups based on mechanistic markers of statin therapy that are associated with disease outcome in patients on hemodialysis.
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