EJPC @ a glance: focus issue on heart failure and kidney disease

This issue of European Journal of Preventive Cardiology focuses on heart failure (HF) and kidney disease, a rapidly evolving area of research in cardiology. When exploring HF in our patients, peak VO2 is an important functional and prognostic marker. According to the Fick principle, oxygen uptake (V̇O2) is equal to the product of cardiac output (Qc) and arterial-venous O2 content difference (ΔCa-vO2). V̇O2 is however also dependent on blood flow distribution, an important variable which is not accounted for in the Fick equation. Increased peripheral vascular resistance because of vasomotor dysregulation and endothelial dysfunction acts as a catalyst for blood flow divergence. Blood flow distribution plays a key role in V̇O2, which is why it should be measured, rather than estimated with the Fick’s equation. In their research paper titled ‘Deceived by the Fick principle: blood flow distribution in heart failure’, Agostoni et al.1 explored the relationship of all three components of the Fick principle (V̇O2, Qc, and ΔCa-vO2) following HF management (exercise training, cardiac resynchronization therapy, or percutaneous edge-to-edge mitral valve repair). The cohort consisted of 273 stable HF patients and New York Heart Association (NYHA II or III) on optimal medical therapy. The variables were directly evaluated with cardiopulmonary exercise testing at baseline and at 6 months after either intervention. Qc was also measured non-invasively at rest and at peak exercise using inert gas rebreathing technique. All three interventions displayed a correlation between peak V̇O2 and peakQc (R2 = 0.47) and workload (R2 = 0.70). Post-procedure changes however showed a reverse correlation. This became even stronger in patients with a significantly improved peakVO2. PeakQc and ΔCa-vO2 changes diverged in 76% of patients, regardless of the treatment options. As nicely illustrated in his editorial, Van Iterson2 reaffirms the mystery of the complex interplay between the Fick principle components. Physicians should move away from focusing on peakVO2, encouraging a detailed analysis of all Fick principle components following HF management. Awareness about gender inequality in cardiovascular care has been under the spotlight over the past few years. Gender-targeted outcome data in HF patients are however at times conflicting. Besides, females are frequently under-represented in randomized controlled trials (RCTs). In a report entitled ‘Sex differences in long-term heart failure prognosis: a comprehensive meta-analysis’, Qiu et al.3 explore the impact of sex in the long-term prognosis differences in HF. Ninety-four studies were included, including 706 247 participants (43.5% women). All-cause and cardiovascular mortality, hospitalization for HF, and the composite endpoints were all lower in females (Figure 1). The lower mortality found was especially more pronounced in those with a long HF history (defined as a follow-up period of >2 years) or in those patients who were recruited in RCTs. Admittedly, heterogeneity in study design, old-fashioned therapies presented in older trials, and different management pathways and healthcare resources across different regions makes a head-to-head comparison difficult. This pooled analysis underscores the necessity for a gender-balanced representation of both sexes in RCTs. Sex differences in the long-term prognosis of heart failure: a systematic review and meta-analysis.3 Acute HF is a multi-faced disorder, traditionally linked to different triggers in individuals mostly with a background of chronic HF. Among triggers, the impact of environmental factors such as ambient temperature and seasonal variation can also play an important role. The dynamic impact of common risk factors and age in relation to temperature has however not been well explored in HF patients. In their research paper entitled ‘The cold temperature associated with new-onset heart failure after incorporating dynamic status of multimorbidity: nationwide cohort, Taiwan 2012–2019’, Chen et al.4 investigate the relationship between ambient temperature and new-onset HF by risk strata (Figure 2). This nationwide cohort study consisted of 148 709 patients diagnosed with new-onset heart HF over 152.52 million person-years. Patients were grouped into three different strata according to their age and comorbidities. Most patients were in stratum 1 (89.9%), including young patients and those without comorbidities. Stratum 3 (1.1%) consisted of HF patients aged 70+ with four or more risk factors. Poisson regression analysis revealed that age, diabetes, chronic obstructive pulmonary disease, coronary artery disease, chronic kidney disease (CKD), hypertension, myocardial infarction, and atrial fibrillation were all significantly associated with new-onset HF. The risk of HF appeared to increase as ambient temperatures decreased. Rate ratios of HF (a winter median temperature of 17°C vs. the summer median temperature of 29°C) were quite similar for each strata (in ascending fashion: 1.45, 1.58, and 1.49).4 The authors conclude that low ambient temperatures appear to play an important role in new HF hospitalization. These findings will certainly have important implications for future public health policies and preventive strategies, specifically targeting individuals at risk of developing new HF. Cold temperature associated with new-onset heart failure after incorporating dynamic status of multimorbidity: nationwide cohort, Taiwan 2012–19.4 Exercise capacity assessment is universally recommended in all HF guidelines. The 6 min walk test (6MWT) is a well-established validated tool that has been widely adopted. The 6 min walking distance is also an important prognostic marker in HF. In the study entitled ‘Prognostic value of Borg scale following 6-min walk test in hospitalized older patients with heart failure’, Saito et al.5 explored the interest of the Borg score to assess dyspnoea after 6MWT and to investigate its prognostic value in HF patients. This multicentre observational study recruited 1185 hospitalized individuals with HF in Japan, as a post hoc sub-analysis of the FRAGILE-HF cohort. Patients older than 65 years with HF and who could ambulate prior to hospital discharge were included. Those with myocarditis, presence of left ventricular assist device, previous heart transplant, and patients on end-stage renal replacement therapy were excluded. All HF-recruited patients performed a 6MWT prior to discharge, with 2-year mortality set as the primary outcome for the study. Patients were split into low and high Borg score groups. The Meta-analysis Global Group in Chronic Heart Failure risk score, log-transformed brain natriuretic peptide values, and 6MWT were used as adjustment variables in the hazard model. Following adjustment, the Borg score remained an independent predictor of the primary outcome, irrespective of LVEF. A higher Borg score was also independently associated with a higher 6MWT.5 Conclusions from this research paper support the widespread introduction of post 6MWT dyspnoea evaluation with the Borg score. Further studies may be warranted to explore these associations. In kidneys, the glomerular filtration barrier is primary responsible for filtering out excretory products that are smaller than 6–8 nm. Persistent proteinuria often represents significant nephropathy with alteration of this barrier. The presence of albuminuria is linked to glomerular pathology and failure of proximal tubular catabolism and reabsorption. A high urinary albumin-to-creatinine ratio (UACR) above 30 mg/g is often present in CKD, regarded as a well-established risk factor for cardiovascular mortality. In the manuscript entitled ‘The relationship between low levels of albuminuria and mortality among adults without major cardiovascular risk factors’, Claudel et al.6 explore the relationship between low (<30) UACR with cardiovascular disease and mortality in healthy adults without traditional cardiovascular risk factors. Study participants were recruited between 1999 and 2014 as part of the National Health and Nutrition Examination Survey (NHANES), with the final sample size consisting of 12 835 individuals (mean age 37.7 years, 53.5% female, 70.1% non-Hispanic white). HbA1c and food insecurity were the strongest clinical correlates of UACR. Every 1% increase in HbA1c led to a 7.4% increase in the UACR (P = 0.002), while food insecurity was associated with a 5.6% increase in the UACR (P = 0.002). Over a median follow-up of 12.3 years, 4.8% died, including 0.9% cardiovascular mortality. The doubling of the UACR led to a 36% increased risk of cardiovascular mortality and 24% increased risk of mortality.6 These findings support the notion that low levels of albuminuria remain an important and independent predictor for cardiovascular events, even in the absence of traditional risk factors. In their elegant editorial, Moreno Velásquez and Gigante7 suggest the regular use of UACR as an emerging cardiovascular biomarker, which may be useful during risk stratification in combination with other modalities like cardiovascular risk scores and CT calcium scoring. Finally, in a clinical study entitled ‘Associations of uric acid with the risk of cardiovascular disease and all-cause mortality among individuals with chronic kidney disease: the Kailuan study’, Li et al.8 studied the impact of uric acid (UA) concentrations on different cardiovascular diseases and all-cause mortality in patients with CKD. In this large prospective cohort study conducted in China, 27 707 individuals with CKD at baseline were recruited. Those with a history of cardiovascular disease, dialysis patients, or renal transplant patients were excluded. After adjusting for potential confounders, UA conferred a greater risk of myocardial infarction [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.13–1.67], heart failure (HR 1.60, 95% CI 1.38–1.85), and mortality (HR 1.29, 95% CI 1.21–1.38) in a dose-response manner (P < 0.001). No association was observed between UA and stroke. The association between UA and HF and mortality was even stronger in those with an estimated glomerular filtration rate < 45 mL/min/1.73 m2 (P < 0.05).8 The findings from this study certainly support previous reports that UA is a risk marker for cardiovascular disease—the novelty here is the demonstration in a large cohort of individuals with CKD patients. In their accompanying editorial, Trimaille and Wells9 emphasize that while the conclusions of this study are limited to a specific population, UA could potentially be a therapeutic target in CKD patients. Large randomized trials are needed to evaluate the potential benefits of UA lowering in cardiovascular outcomes. The editors invite the readers to discover further rapid communications and letters in this EJPC issue. We hope this issue will be of interest for all our readers and stimulate further research around heart failure and kidney disease to help better implement scientific results into clinical practice for cardiovascular management and prevention.