| 1. |
- Kato, Norihiro, et al.
(författare)
-
Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
-
Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
|
|
| 2. |
- van der Harst, Pim, et al.
(författare)
-
Seventy-five genetic loci influencing the human red blood cell
- 2012
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
-
Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
|
|
| 3. |
- Jaarsma, Tiny, et al.
(författare)
-
Effect of moderate or intensive disease management program on outcome in patients with heart failure : Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH).
- 2008
-
Ingår i: Archives of Internal Medicine. - : American Medical Association (AMA). - 0003-9926 .- 1538-3679. ; 168:3, s. 316-24
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Heart failure (HF) disease management programs are widely implemented, but data about their effect on outcome have been inconsistent. METHODS: The Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH) was a multicenter, randomized, controlled trial in which 1023 patients were enrolled after hospitalization because of HF. Patients were assigned to 1 of 3 groups: a control group (follow-up by a cardiologist) and 2 intervention groups with additional basic or intensive support by a nurse specializing in management of patients with HF. Patients were studied for 18 months. Primary end points were time to death or rehospitalization because of HF and the number of days lost to death or hospitalization. RESULTS: Mean patient age was 71 years; 38% were women; and 50% of patients had mild HF and 50% had moderate to severe HF. During the study, 411 patients (40%) were readmitted because of HF or died from any cause: 42% in the control group, and 41% and 38% in the basic and intensive support groups, respectively (hazard ratio, 0.96 and 0.93, respectively; P = .73 and P = .52, respectively). The number of days lost to death or hospitalization was 39 960 in the control group, 33 731 days for the basic intervention group (P = .81), and 34 268 for the intensive support group (P = .49). All-cause mortality occurred in 29% of patients in the control group, and there was a trend toward lower mortality in the intervention groups combined (hazard ratio, 0.85; 95% confidence interval, 0.66-1.08; P = .18). There were slightly more hospitalizations in the 2 intervention groups (basic intervention group, P = .89; and intensive support group, P = .60). CONCLUSIONS: Neither moderate nor intensive disease management by a nurse specializing in management of patients with HF reduced the combined end points of death and hospitalization because of HF compared with standard follow-up. There was a nonsignificant, potentially relevant reduction in mortality, accompanied by a slight increase in the number of short hospitalizations in both intervention groups. Clinical Trial Registry http://trialregister.nl Identifier: NCT 98675639.
|
|
| 4. |
- Jonkman, Nini H., et al.
(författare)
-
Do self-management interventions work in patients with heart failure? An individual patient data meta-analysis
- 2016
-
Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 133:12, s. 1189-1198
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: -Self-management interventions are widely implemented in care for patients with heart failure (HF). Trials however show inconsistent results and whether specific patient groups respond differently is unknown. This individual patient data meta-analysis assessed the effectiveness of self-management interventions in HF patients and whether subgroups of patients respond differently.METHODS AND RESULTS: -Systematic literature search identified randomized trials of self-management interventions. Data of twenty studies, representing 5624 patients, were included and analyzed using mixed effects models and Cox proportional-hazard models including interaction terms. Self-management interventions reduced risk of time to the combined endpoint HF-related hospitalization or all-cause death (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.71-0.89), time to HF-related hospitalization (HR, 0.80; 95%CI, 0.69-0.92), and improved 12-month HF-related quality of life (standardized mean difference 0.15; 95%CI, 0.00-0.30). Subgroup analysis revealed a protective effect of self-management on number of HF-related hospital days in patients <65 years (mean number of days 0.70 days vs. 5.35 days; interaction p=0.03). Patients without depression did not show an effect of self-management on survival (HR for all-cause mortality, 0.86; 95%CI, 0.69-1.06), while in patients with moderate/severe depression self-management reduced survival (HR, 1.39; 95%CI, 1.06-1.83, interaction p=0.01).CONCLUSIONS: -This study shows that self-management interventions had a beneficial effect on time to HF-related hospitalization or all-cause death, HF-related hospitalization alone, and elicited a small increase in HF-related quality of life. The findings do not endorse limiting self-management interventions to subgroups of HF patients, but increased mortality in depressed patients warrants caution in applying self-management strategies in these patients.
|
|
| 5. |
|
|
| 6. |
- Wong, Liza S M, et al.
(författare)
-
Anaemia is associated with shorter leucocyte telomere length in patients with chronic heart failure.
- 2010
-
Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 12:4, s. 348-53
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: Anaemia is highly prevalent and associated with poor prognosis in patients with chronic heart failure (CHF). Reduced erythroid proliferation capacity of haematopoietic progenitor cells is associated with reduced telomere length, a marker of cellular ageing. We hypothesize that short telomere length contributes to the susceptibility to develop anaemia in patients with CHF. METHODS AND RESULTS: We studied 875 CHF patients, of whom 254 (29%) fulfilled the WHO criteria of anaemia. Telomere length in DNA from peripheral leucocytes was measured with real-time quantitative polymerase chain reaction. Age, gender, and baseline differences adjusted telomere length was correlated with haemoglobin levels (partial r = 0.130; P = 0.011). One standard deviation shorter telomere length was associated with an increased risk of having anaemia [odds ratio (OR), 1.31; 95% confidence interval (CI), 1.12-1.53; P = 0.001]. This observation was not affected by adjustment for potential confounders (OR, 1.38; 95% CI, 1.05-1.81; P = 0.021 after adjustment for age, gender, erythropoietin levels, renal function, left ventricular ejection fraction, age of CHF onset, blood pressure, history of stroke, diabetes, and B-type natriuretic peptide levels). CONCLUSION: Shorter telomere length increases the odds of having anaemia in CHF patients. This finding supports the hypothesis that cellular ageing in CHF contributes to the susceptibility to develop anaemia.
|
|
| 7. |
- de Boer, Rudolf A, et al.
(författare)
-
Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction
- 2011
-
Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 43:1, s. 60-68
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: galectin-3 is an emerging biomarker which has been studied in relatively small heart failure (HF) cohorts with predominantly systolic HF. We studied the prognostic value of base-line galectin-3 in a large HF cohort, with preserved and reduced left ventricular ejection fraction (LVEF), and compared this to other biomarkers. METHODS: we studied 592 HF patients who had been hospitalized for HF and were followed for 18 months. The primary end-point was a composite of all-cause mortality and HF hospitalization. RESULTS: a doubling of galectin-3 levels was associated with a hazard ratio (HR) of 1.97 (1.62-2.42) for the primary outcome (P < 0.001). After correction for age, gender, BNP, eGFR, and diabetes the HR was 1.38 (1.07-1.78; P = 0.015). Galectin-3 levels were correlated with higher IL-6 and CRP levels (P < 0.002). Changes of galectin-3 levels after 6 months did not add prognostic information to the base-line value (n = 291); however, combining plasma galectin-3 and BNP levels increased prognostic value over either biomarker alone (ROC analysis, P < 0.05). The predictive value of galectin-3 was stronger in patients with preserved LVEF (n = 114) compared to patients with reduced LVEF (P < 0.001). CONCLUSIONS: galectin-3 is an independent marker for outcome in HF and appears to be particularly useful in HF patients with preserved LVEF.
|
|
| 8. |
- Huzen, Jardi, et al.
(författare)
-
Telomere length and psychological well-being in patients with chronic heart failure.
- 2010
-
Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 39:2, s. 223-7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: psychological stress and depressive symptoms have been implicated with accelerated ageing and increased progression of diseases. Shorter telomere length indicates a more advanced biological age. It is unknown whether psychological well-being is associated with telomere length in patients with the somatic condition of chronic heart failure (CHF). DESIGN: a cross-sectional analysis was used. SETTING: patients were admitted to the hospital with signs and symptoms of CHF. OBJECTIVE: the study aimed to assess the association between telomere length and psychological well-being in patients with CHF. METHODS: telomere length was determined by quantitative polymerase chain reaction in 890 patients with New York Heart Association functional class II to IV CHF. We evaluated the perceived mental health by the validated RAND-36 questionnaire. Depressive symptoms were assessed by the Centre for Epidemiologic Studies Depression scale (CES-D), and the presence of type D personality was evaluated by the DS14. RESULTS: a lower perceived mental health on the RAND-36 score was associated with shorter telomere length. Adjustment for age and gender did not change our findings (standardised beta, 0.11; P-value, 0.002). Telomere length was not associated with the CES-D or DS14 score. CONCLUSION: decreased perceived mental health is associated with shorter leukocyte telomere length in patients with CHF. Future work should determine whether psychological stress accelerates biological ageing.
|
|
| 9. |
- Lok, Dirk J., et al.
(författare)
-
Prognostic value of N-terminal pro C-type natriuretic peptide in heart failure patients with preserved and reduced ejection fraction
- 2014
-
Ingår i: European Journal of Heart Failure. - : Oxford University Press (OUP): Policy B / Wiley. - 1388-9842 .- 1879-0844. ; 16:9, s. 958-966
-
Tidskriftsartikel (refereegranskat)abstract
- AimsA-type and B-type natriuretic peptides are established markers in chronic heart failure (HF). C-type natriuretic peptide (CNP) belongs to the same peptide family, but is predominantly localized in the endothelium. The prognostic role of CNP in heart failure has not been established. The aim of the study was to determine the prognostic power and clinical correlates of the N-terminal part of pro CNP (NT-proCNP) in patients with chronic HF. Methods and resultsIn 567 hospitalized heart failure patients, NT-proCNP levels were measured at hospital discharge. The primary endpoint was a combined endpoint of all-cause mortality and HF hospitalization after 18 months. Heart failure with a preserved ejection fraction (HFpEF) was pre-defined as an LVEF greater than40%. Mean (SD) age was 71 +/- 11years, 62% were male, mean LVEF was 32 +/- 14%, and 23% had HFpEF. In multivariate linear regression, NT-proCNP levels showed a positive correlation with NT-proBNP levels and parameters of renal function, whereas a negative correlation with female sex and vascular endothelial growth factor was observed. After 18 months follow-up, 240 patients reached the combined endpoint. We observed interaction between NT-proCNP and LVEF for outcome (P=0.046). Multivariate analyses revealed NT-proCNP to be strongly predictive for the primary endpoint [hazard ratio (HR) 1.78, 95% confidence interval (CI) 1.18-2.67, P=0.006) in patients with HFpEF, but not in patients with a reduced ejection fraction (HFrEF) (HR 1.07, 95% CI 0.81-1.43, P=0.616). Finally, reclassification showed significant additive value in patients with HFpEF (Pless than0.001), but not in those with HFrEF (P=0.453). Conclusionless thanp id="ejhf140-para-0003"greater thanNT-proCNP is a strong independent marker for outcome in patients with HFpEF, but not in those with HFrEF.
|
|
| 10. |
- Luttik, Marie Louise A., et al.
(författare)
-
Long-term follow-up in optimally treated and stable heart failure patients: primary care vs. heart failure clinic. Results of the COACH-2 study
- 2014
-
Ingår i: European Journal of Heart Failure. - : Oxford University Press (OUP): Policy B / Wiley: 12 months. - 1388-9842 .- 1879-0844. ; 16:11, s. 1241-1248
-
Tidskriftsartikel (refereegranskat)abstract
- AimsIt has been suggested that home-based heart failure (HF) management in primary care may be an alternative to clinic-based management in HF patients. However, little is known about adherence to HF guidelines and adherence to the medication regimen in these home-based programmes. The aim of the current study was to determine whether long-term follow-up and treatment in primary care is equally effective as follow-up at a specialized HF clinic in terms of guideline adherence and patient adherence, in HF patients initially managed and up-titrated to optimal treatment at a specialized HF clinic. Methods and resultsWe conducted a multicentre, randomized, controlled study in 189 HF patients (62% male, age 72 11 years), who were assigned to follow-up either in primary care (n = 97) or in a HF clinic (n = 92). After 12 months, no differences between guideline adherence, as estimated by the Guideline Adherence Indicator (GAI-3), and patient adherence, in terms of the medication possession ratio (MPR), were found between treatment groups. There was no difference in the number of deaths (n = 12 in primary care and n = 8 in the HF clinic; P = 0.48), and hospital readmissions for cardiovascular (CV) reasons were also similar. The total number of unplanned non-CV hospital readmissions, however, tended to be higher in the primary care group (n = 22) than in the HF clinic group (n = 10; P = 0.05). Conclusionsless thanp id="ejhf173-para-0003"greater thanPatients discharged after initial management in a specialized HF clinic can be discharged to primary care for long-term follow-up with regard to maintaining guideline adherence and patient adherence. However, the complexity of the HF syndrome and its associated co-morbidities requires continuous monitoring. Close collaboration between healthcare providers will be crucial in order to provide HF patients with optimal, integrated care.
|
|
