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- Valenzuela, Pedro L., et al.
(författare)
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Lifestyle interventions for the prevention and treatment of hypertension
- 2021
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Ingår i: Nature Reviews Cardiology. - : Springer Science and Business Media LLC. - 1759-5002 .- 1759-5010. ; 18:4, s. 251-275
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Forskningsöversikt (refereegranskat)abstract
- Hypertension affects approximately one third of the world’s adult population and is a major cause of premature death despite considerable advances in pharmacological treatments. Growing evidence supports the use of lifestyle interventions for the prevention and adjuvant treatment of hypertension. In this Review, we provide a summary of the epidemiological research supporting the preventive and antihypertensive effects of major lifestyle interventions (regular physical exercise, body weight management and healthy dietary patterns), as well as other less traditional recommendations such as stress management and the promotion of adequate sleep patterns coupled with circadian entrainment. We also discuss the physiological mechanisms underlying the beneficial effects of these lifestyle interventions on hypertension, which include not only the prevention of traditional risk factors (such as obesity and insulin resistance) and improvements in vascular health through an improved redox and inflammatory status, but also reduced sympathetic overactivation and non-traditional mechanisms such as increased secretion of myokines.
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- Bakris, George L, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease Trial.
- 2019
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Ingår i: American Journal of Nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 50:5, s. 333-344
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Among diabetics, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality, and progression of their underlying disease. Finerenone is a novel, non-steroidal, selective mineralocorticoid-receptor antagonist which has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD), while revealing only a low risk of hyperkalemia. However, the effect of finerenone on renal and CV outcomes has not been investigated in long-term trials yet.METHODS: The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease -(FIDELIO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important renal and CV outcomes in T2D patients with CKD. FIDELIO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 5.5 years. FIDELIO-DKD randomized 5,734 patients with an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30-≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death.CONCLUSION: FIDELIO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of renal and CV events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen.
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- Bakris, George L, et al.
(författare)
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Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes
- 2020
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 383:23, s. 2219-2229
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. However, its long-term effects on kidney and cardiovascular outcomes are unknown.METHODS: In this double-blind trial, we randomly assigned 5734 patients with CKD and type 2 diabetes in a 1:1 ratio to receive finerenone or placebo. Eligible patients had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300, an estimated glomerular filtration rate (eGFR) of 25 to less than 60 ml per minute per 1.73 m2 of body-surface area, and diabetic retinopathy, or they had a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of 25 to less than 75 ml per minute per 1.73 m2. All the patients were treated with renin-angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer's label that did not cause unacceptable side effects. The primary composite outcome, assessed in a time-to-event analysis, was kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. The key secondary composite outcome, also assessed in a time-to-event analysis, was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.RESULTS: During a median follow-up of 2.6 years, a primary outcome event occurred in 504 of 2833 patients (17.8%) in the finerenone group and 600 of 2841 patients (21.1%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.93; P = 0.001). A key secondary outcome event occurred in 367 patients (13.0%) and 420 patients (14.8%) in the respective groups (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P = 0.03). Overall, the frequency of adverse events was similar in the two groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with finerenone than with placebo (2.3% and 0.9%, respectively).CONCLUSIONS: In patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo. (Funded by Bayer; FIDELIO-DKD ClinicalTrials.gov number, NCT02540993.).
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- Fiuza-Luces, Carmen, et al.
(författare)
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Exercise benefits in cardiovascular disease : beyond attenuation of traditional risk factors
- 2018
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Ingår i: Nature Reviews Cardiology. - : Springer Science and Business Media LLC. - 1759-5002 .- 1759-5010. ; 15:12, s. 731-743
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Tidskriftsartikel (refereegranskat)abstract
- Despite strong scientific evidence supporting the benefits of regular exercise for the prevention and management of cardiovascular disease (CVD), physical inactivity is highly prevalent worldwide. In addition to merely changing well-known risk factors for systemic CVD, regular exercise can also improve cardiovascular health through non-traditional mechanisms. Understanding the pathways through which exercise influences different physiological systems is important and might yield new therapeutic strategies to target pathophysiological mechanisms in CVD. This Review includes a critical discussion of how regular exercise can have antiatherogenic effects in the vasculature, improve autonomic balance (thereby reducing the risk of malignant arrhythmias), and induce cardioprotection against ischaemia–reperfusion injury, independent of effects on traditional CVD risk factors. This Review also describes how exercise promotes a healthy anti-inflammatory milieu (largely through the release of muscle-derived myokines), stimulates myocardial regeneration, and ameliorates age-related loss of muscle mass and strength, a frequently overlooked non-traditional CVD risk factor. Finally, we discuss how the benefits of exercise might also occur via promotion of a healthy gut microbiota. We argue, therefore, that a holistic view of all body systems is necessary and useful when analysing the role of exercise in cardiovascular health.
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- Rossing, Peter, et al.
(författare)
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Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Sodium-Glucose Cotransporter 2 Inhibitor Treatment : The FIDELITY Analysis.
- 2022
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:12, s. 2991-2998
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Finerenone reduced the risk of kidney and cardiovascular events in people with chronic kidney disease (CKD) and type 2 diabetes in the FIDELIO-DKD and FIGARO-DKD phase 3 studies. Effects of finerenone on outcomes in patients taking sodium-glucose cotransporter 2 inhibitors (SGLT2is) were evaluated in a prespecified pooled analysis of these studies.RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes and urine albumin-to-creatinine ratio (UACR) ≥30 to ≤5,000 mg/g and estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 were randomly assigned to finerenone or placebo; SGLT2is were permitted at any time. Outcomes included cardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney composite (kidney failure, sustained ≥57% eGFR decline, or renal death) end points, changes in UACR and eGFR, and safety outcomes.RESULTS: Among 13,026 patients, 877 (6.7%) received an SGLT2i at baseline and 1,113 (8.5%) initiated one during the trial. For the cardiovascular composite, the hazard ratios (HRs) were 0.87 (95% CI 0.79-0.96) without SGLT2i and 0.67 (95% CI 0.42-1.07) with SGLT2i. For the kidney composite, the HRs were 0.80 (95% CI 0.69-0.92) without SGLT2i and 0.42 (95% CI 0.16-1.08) with SGLT2i. Baseline SGLT2i use did not affect risk reduction for the cardiovascular or kidney composites with finerenone (Pinteraction = 0.46 and 0.29, respectively); neither did SGLT2i use concomitant with study treatment.CONCLUSIONS: Benefits of finerenone compared with placebo on cardiorenal outcomes in patients with CKD and type 2 diabetes were observed irrespective of SGLT2i use.
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- Zannad, Faiez, et al.
(författare)
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Prevention of cardiovascular disease guided by total risk estimations - challenges and opportunities for practical implementation: highlights of a CardioVascular Clinical Trialists (CVCT) Workshop of the ESC Working Group on CardioVascular Pharmacology and Drug Therapy.
- 2012
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 19:6, s. 1454-1464
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Forskningsöversikt (refereegranskat)abstract
- This paper presents a summary of the potential practical and economic barriers to implementation of primary prevention of cardiovascular disease guided by total cardiovascular risk estimations in the general population. It also reviews various possible solutions to overcome these barriers. The report is based on discussion among experts in the area at a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy that took place in September 2009. It includes a review of the evidence in favour of the 'treat-to-target' paradigm, as well as potential difficulties with this approach, including the multiple pathological processes present in high-risk patients that may not be adequately addressed by this strategy. The risk-guided therapy approach requires careful definitions of cardiovascular risk and consideration of clinical endpoints as well as the differences between trial and 'real-world' populations. Cost-effectiveness presents another issue in scenarios of finite healthcare resources, as does the difficulty of documenting guideline uptake and effectiveness in the primary care setting, where early modification of risk factors may be more beneficial than later attempts to manage established disease. The key to guideline implementation is to improve the quality of risk assessment and demonstrate the association between risk factors, intervention, and reduced event rates. In the future, this may be made possible by means of automated data entry and various other measures. In conclusion, opportunities exist to increase guideline implementation in the primary care setting, with potential benefits for both the general population and healthcare resources.
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- Zannad, Faiez, et al.
(författare)
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Risk stratification in cardiovascular disease primary prevention - scoring systems, novel markers, and imaging techniques
- 2012
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Ingår i: Fundamental and Clinical Pharmacology. - : Wiley. - 0767-3981 .- 1472-8206. ; 26:2, s. 163-174
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Forskningsöversikt (refereegranskat)abstract
- The aim of this paper is to review and discuss current methods of risk stratification for cardiovascular disease (CVD) prevention, emerging biomarkers, and imaging techniques, and their relative merits and limitations. This report is based on discussions that took place among experts in the area during a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy in September 2009. Classical risk factors such as blood pressure and low-density lipoprotein cholesterol levels remain the cornerstone of risk estimation in primary prevention but their use as a guide to management is limited by several factors: (i) thresholds for drug treatment vary with the available evidence for cost-effectiveness and benefit-to-risk ratios; (ii) assessment may be imprecise; (iii) residual risk may remain, even with effective control of dyslipidemia and hypertension. Novel measures include C-reactive protein, lipoprotein-associated phospholipase A 2, genetic markers, and markers of subclinical organ damage, for which there are varying levels of evidence. High-resolution ultrasound and magnetic resonance imaging to assess carotid atherosclerotic lesions have potential but require further validation, standardization, and proof of clinical usefulness in the general population. In conclusion, classical risk scoring systems are available and inexpensive but have a number of limitations. Novel risk markers and imaging techniques may have a place in drug development and clinical trial design. However, their additional value above and beyond classical risk factors has yet to be determined for risk-guided therapy in CVD prevention. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.
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