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- Rossignol, P, et al.
(författare)
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NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients
- 2022
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Ingår i: European Heart Journal Open. - : Oxford University Press. - 2752-4191. ; 2:6
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Tidskriftsartikel (refereegranskat)abstract
- Aimas: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine.Methods and Results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths.Conclusions: Our findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.
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- Coiro, S., et al.
(författare)
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Diuretic therapy as prognostic enrichment factor for clinical trials in patients with heart failure with reduced ejection fraction
- 2021
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Ingår i: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 110, s. 1308-1320
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Tidskriftsartikel (refereegranskat)abstract
- Background Loop diuretics are the mainstay of congestion treatment in patients with heart failure (HF). We assessed the association between baseline loop diuretic use and outcome. We also compared the increment in risk related to diuretic dose with conventional prognostic enrichment criteria used in the EMPHASIS-HF trial, which included patients with systolic HF and mild symptoms, such as prior hospitalization and elevated natriuretic peptides. Methods Individual analyses were performed according to baseline loop diuretic usage (furosemide-equivalent dose > 40 mg, 1-40 mg, and no furosemide), and according to enrichment criteria adopted in the trial [i.e. recent hospitalization (< 30 days or 30 to 180 days prior to randomization) due to HF or other cardiovascular cause, or elevated natriuretic peptides]. The primary endpoint was a composite of cardiovascular death or HF hospitalization. Results Loop diuretic usage at baseline (HR for > 40 mg furosemide-equivalent dose = 3.16, 95% CI 2.43-4.11; HR for 1-40 mg = 2.06, 95% CI 1.60-2.65) was significantly associated with a higher risk for the primary endpoint in a stepwise manner when compared to no baseline loop diuretic usage. In contrast, the differences in outcome rates were more modest when using history of hospitalization and/or BNP: all HR ranged from 1 (reference, non-HF related CV hospitalization > 30 days) to 2.04 (HF hospitalization < 30 days). The effect of eplerenone on the primary endpoint was consistent across subgroups in both analyses (P for interaction >= 0.2 for all). Conclusions Loop diuretic usage (especially at doses > 40 mg) identified patients at higher risk than history of HF hospitalization and/or high BNP blood concentrations. Graphic abstract
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- Ferreira, J. P., et al.
(författare)
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Impact of Insulin Treatment on the Effect of Eplerenone: Insights From the EMPHASIS-HF Trial
- 2021
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Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 14:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, including those treated with insulin in the EMPHASIS-HF trial (Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms). METHODS: The primary outcome was the composite of heart failure hospitalization or cardiovascular death. Cox models with treatment-by-diabetes subgroup interaction terms were used. RESULTS: The median follow-up was 21 (10-33) months. Of the 2737 patients included, 623 (23%) had non-insulin-treated diabetes, 236 (9%) had insulin-treated diabetes and 1878 did not have diabetes. Patients with insulin-treated diabetes were younger, more often women, with higher body mass index, waist circumference, more frequent ischemic heart failure cause, impaired kidney function, and longer diabetes duration. Compared with patients without diabetes, those with insulintreated diabetes had a 2-fold higher risk of having a primary outcome event. The hazard ratio (95% CI) for the effect of eplerenone, compared with placebo, on the primary outcome was 0.31 (0.19-0.50) in insulin-treated diabetes, 0.69 (0.500.93) in non-insulin-treated diabetes, and 0.72 (0.58-0.88) in patients without diabetes; interaction P=0.007. The annualized number needed-to-treat-to-benefit with regards to the primary outcome was 3 (95% CI, 3-4) in patients with insulin-treated diabetes, 16 (13-19) in patients with diabetes not receiving insulin, and 26 (24-28) in patients without diabetes. CONCLUSIONS: Patients with insulin-treated diabetes experienced a greater benefit from eplerenone than those with diabetes not treated with insulin and people without diabetes.
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- Holm, H., et al.
(författare)
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Ventricular–arterial coupling (VAC) in a population-based cohort of middle-aged individuals: The STANISLAS cohort
- 2023
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Ingår i: Atherosclerosis. - 1879-1484. ; 374, s. 11-20
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Tidskriftsartikel (refereegranskat)abstract
- Background and aimsData exploring normal values of different ventricular–arterial coupling (VAC) parameters and their association with anthropometric and cardiovascular (CV) factors are scarce. We aim to report values of two different methods of VAC assessment according to age and sex and explore their association with CV factors within a large population-based cohort of middle-aged individuals.MethodsFor 1333 (mean age 48 ± 14) individuals participating in the 4th visit of the STANISLAS cohort, VAC was assessed by two methods [1]: arterial elastance (Ea)/end-systolic elastance (Ees) and [2] Pulse wave velocity (PWV)/Global longitudinal strain (GLS).ResultsThe mean values of Ea/Ees and PWV/GLS were 1.06 ± 0.20 and 0.42 ± 0.12, respectively. The two methods of VAC assessment were poorly correlated (Pearson's correlation coefficient r = 0.14 (0.08; 0.19)). Increased PWV/GLS was associated with older age and a higher degree of cardiovascular risk factors (i.e., BMI, blood pressure, LDL, diabetes, hypertension) in the whole population as well as in the parent generation. In contrast, higher Ea/Ees were associated with decreasing age, and lower prevalence of risk factors in the whole cohort but neutrally associated with risk factors in the parent generation.ConclusionsHigher PWV/GLS is significantly associated with CV factors regardless of age. In contrast, worse Ea/Ees is associated with a better CV risk profile when considering individuals aged 30 to 70 but neutrally associated with CV factors when considering only older patients. These results may suggest that PWV/GLS should preferably be used to explore VAC. In addition, age-individualized threshold of Ea/Ees should be used.
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| 8. |
- Olivier, A., et al.
(författare)
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Effect of eplerenone in patients with heart failure and reduced ejection fraction: potential effect modification by abdominal obesity: Insight from the EMPHASIS-HF trial
- 2017
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 19:9, s. 1186-1197
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: An excessive production of aldosterone influences outcome in patients with heart failure (HF) and in obese patients. Findings from laboratory studies suggest that chronic aldosterone blockade maybe more beneficial in abdominally obese HF-prone rats. In the current study, we investigated if the clinical response to a mineralocorticoid receptor antagonist in mildly symptomatic HF patients varied by abdominal obesity. METHODS AND RESULTS: A total of 2587 NYHA class II, reduced ejection fraction HF (HFrEF) patients enrolled in the EMPHASIS-HF trial were randomly assigned to eplerenone and placebo. In this post hoc analysis, patients were categorized according to waist circumference (WC) (normal if WC < 102 cm in men and < 88 cm in women; abdominal obesity if WC >/= 102 cm in men and >/= 88 cm women). The potential statistical interaction between the treatment and WC was assessed on the primary endpoint of death from cardiovascular causes or hospitalization for HF and other secondary endpoints. Over a median follow-up of 21 months, a significant benefit of eplerenone for the primary outcome was noted in both normal [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61-0.98, P = 0.03] and increased (HR 0.48, 95% CI 0.37-0.63, P < 0.0001) WC subgroups, but the latter patients appeared to receive greater benefit than patients with normal WC (P for interaction = 0.01). This suggests a significant quantitative (treatment effect varies in magnitude by subgroup, but is always in same direction) rather than a qualitative interaction (direction of the treatment effect varies by subgroup) between eplerenone and WC in the adjusted analysis. Mean doses of eplerenone, blood pressure and serum potassium changes and adverse events were similar between WC subgroups. CONCLUSION: In EMPHASIS-HF, eplerenone improved outcomes in HFrEF patients with and without abdominal obesity, although the benefit appeared to be more pronounced among those with abdominal obesity. The findings are potentially hypothesis generating and need to be replicated in other HFrEF populations.
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