Kidney Disease Research Articles

Intracranial haemorrhage following treatment for pulmonary embolism: analysis of the german nationwide inpatient sample

Abstract Background Intracranial haemorrhage (ICH) can be a life-threatening complication of pulmonary embolism (PE) and its treatment during the acute phase. Purpose To characterize patients hospitalized with PE and ICH by identifying risk factors across different treatment groups, and to detect temporal trends in a large nationwide sample. Methods The German nationwide inpatient sample was screened for patients admitted with PE during the period 2005-2020. All hospitalizations were stratified based on the occurrence of ICH and accordingly, risk factors for ICH were investigated (source: Research data center [RDC] of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005-2020, own calculations). Results Overall, 816,653 hospitalizations were included in the present study; among them, 2516 (0.3%) experienced an ICH event and 84,810 (10.4%) died in-hospital. The annual number of hospitalizations of patients admitted due to PE increased steadily from 38,749 in 2005 to 54,966 in 2020, whereas the incidence of ICH remained, despite annual fluctuations, largely stable over time, both in the entire study population and in the subgroup of patients with severe PE as defined by clinical and haemodynamic parameters (n=270,980 [33.2%]). ICH was overall more frequent after the seventh decade of life but, interestingly, no correlation with age was found amongst patients with severe PE (Figure 1). ICH in hospitalized PE patients was associated with an aggravated comorbidity burden mirrored by a higher Charlson Comorbidity Index (5.0 [interquartile range 4.0-7.0] vs. 4.0 [2.0-5.0], P<0.001). This was mainly driven by the higher prevalence of heart failure (27.3% vs. 19.4%, P<0.001) and acute or chronic kidney disease (27.6% vs. 18.1%, P<0.001) in patients with ICH. In addition, severe PE (OR 3.09 [95% CI 2.84-3.35], P<0.001), acute kidney injury (OR 3.60 [3.09-4.18], P<0.001), and particularly ischaemic stroke (OR 14.64 [12.61-17.00], P<0.001) were identified as independent predictors of ICH by multivariable logistic regressions. Overall, 27% of the ICH cases were related to systemic thrombolysis. In PE patients treated with systemic thrombolysis, age ≥70 years as well as female sex were independent predictors of ICH. Finally, ICH was independently associated with a substantial increase in case-fatality in patients hospitalized with PE (univariate OR: 5.38 [4.97-5.84], P<0.001; multivariable OR: 6.16 [5.64-6.72], P<0.001). Conclusions In this healthcare dataset of the German nationwide inpatient sample, the overall incidence of ICH remained low at 0.3% over the 15-year study period. Severe PE, age, comorbidity burden, kidney disease, heart failure and ischaemic stroke were independent risk factors for ICH.

Association of lipid target achievement and cardiovascular outcomes following statin initiation: a population-based cohort study

Abstract Introduction Non-high density lipoprotein cholesterol (non-HDL-C) is increasingly incorporated into clinical practice guidelines along with low density lipoprotein cholesterol (LDL-C) to guide lipid-lowering therapy decisions. We aimed to examine patterns of LDL-C and non-HDL-C levels after statin initiation for primary prevention of cardiovascular disease (CVD), and their association with incident CV events. Methods We conducted a population-based cohort study of Ontario, Canada residents age ≥66 years who initiated a statin for primary prevention between January 1, 2012 and December 31, 2019. For those surviving 1-year after statin initiation, we determined the proportion with a lipid panel in the 1-year period after a statin was started. For those with a lipid panel, we used the lipid panel closest to the end of the 1-year period to categorize individuals based on the LDL-C and non-HDL-C thresholds in the 2021 Canadian Cardiovascular Society dyslipidemia guidelines (Table 1). We stratified by diabetes/chronic kidney disease (CKD) status. We evaluated the association between LDL-C/non-HDL-C category and a composite of all-cause mortality or hospitalization for myocardial infarction, stroke or revascularization (primary outcome). We also investigated the association between each category and each component of the primary outcome. The index date was the 365 days after a statin was initiated and follow-up was until December 31, 2020. We used a cause-specific hazards model for analysis, adjusted for clinical and sociodemographic confounders. Results Our cohort comprised 173,127 people. In the 1-year period after statin initiation, 72% of people had a follow-up lipid panel performed. Median follow-up after that was 2.5 years. Compared with those meeting both LDL-C and non-HDL-C targets, being above both targets was associated with an increased rate of the primary outcome for people without diabetes/CKD (HR 1.10, 95% CI 1.05 to 1.15) and those with diabetes/CKD (HR 1.16, 95% CI 1.09 to 1.23). Being at LDL-C target but above non-HDL-C target was associated with an increased rate of the primary outcome for people with diabetes/CKD (HR 1.16, 95% CI 1.03 to 1.30) but not for those without diabetes/CKD (HR 1.05, 95% CI 0.93 to 1.17). Conclusions In this population-based cohort, having an LDL-C and non-HDL-C above guideline-recommended targets after statin initiation was associated with an increased rate of adverse outcomes. These findings support the residual risk associated with incompletely controlled LDL-C or non-HDL-C levels after initiating statin therapy for primary prevention.Primary outcome associationsComponents of primary outcome

Research examining microcirculatory dynamics in diseases that cause oedema using skin blood flow and skin reperfusion pressure

Oedema is a build-up of fluid in the tissues in the body. It can develop due to diseases including heart failure and kidney disease. It usually occurs in the limbs, where it can cause discomfort, joint stiffness or pain. However, fluid can also accumulate in the brain, which is called cerebral oedema or in the blood vessels serving the lungs, called pulmonary oedema. A type of oedema called pitting oedema is more prevalent than the other type, non-pitting oedema. In order to treat the condition, the underlying cause must be resolved. Treatment can involve diuretics to help the release of fluids, positioning to encourage draining or compression to force fluids away. Researchers at the Faculty of Rehabilitation at Reiwa Health Sciences University led by Dr Haruki Kogo are examining the microcirculatory dynamics of diseases that cause oedema using skin blood flow and skin reperfusion pressure. They have developed a device that can diagnose oedema and confirmed the reproducibility and validity of the device. They have registered the trademark and plan to commercialise the device for use in clinical and research settings. The device is able to measure the depth of the surface imprint in pitting oedema patients, simplifying the evaluation of pitting oedema, which will be extremely useful in clinical settings. The researchers tested the device across two hospitals, comparing the results with results obtained from the popular circumference measurement method and ultrasound imaging measurement. The team found that there was a strong correlation between measurements from the device and the tissue thickness measurement derived from the ultrasound. This confirmed that the device is a reliable gauge for the measurement of oedema.

Pericoronary adipose tissue computed tomography attenuation (PCAT) as a marker of premature CVD in asymptomatic people living with HIV (PLWH) without traditional risk factors: H-ART to heart study

Abstract Background Controversy exists regarding the contribution of HIV, ART or traditional risk factors to CVD risk in PLWH. The H-ART to Heart study investigates the prevalence of subclinical CVD in asymptomatic PLWH without cardiovascular risk factors compared to negative controls(-). Vascular inflammation inhibits local adipogenesis in pericoronary adipose tissue (PCAT) and thus can be detected on coronary computed tomography angiography (CTCA) as an increase in CT attenuation of PCAT surrounding the proximal right coronary artery (RCA). Methods This cross-sectional study compared PLWH aged 35-55yrs (diagnosed >10 yrs, on ART) to matched controls. Included were Caucasian men who have sex with men(MSM) and Black African/Caribbean women (BW) with traditional risk factors excluded (hypertension, hyperlipidaemia, diabetes, kidney disease, smoking, depression, inflammatory conditions, etc.). Detailed vitals, 10 year CVD risk calculation (Q-RISK 3) were recorded. CTCA were performed with novel analysis using PCAT to assess for coronary inflammation (Figure 1.) Results 98 participants were recruited (49M; 51 PLWH). Mean Q Risk 3 (10yr CVD risk - %) was low across the groups (HIV+MSM 4.65±2.1, HIV-MSM 3.88±2.7;p=0.29; HIV+BW 2.03±1.3, HIV-BW 1.38±0.98 p=0.66). 79 participants (42 PLWH; 37 controls) completed a CTCA with only 2 PLWH having clinically significant disease (CAD-RAD 3+ ie. >50% luminal stenosis) and none in the control group. (p=0.49) The CT scans of 69 patients were assessed for peri-coronary adipose tissue (PCAT) density, 2 were ruled out due to a small non-dominant RCA. The PCAT density of PLWH was higher than that of the controls (-71.2±27.6 vs -75.5±30.3 P=<0.05). Multivariate linear regression demonstrated that HIV status was an independent predictor of coronary inflammation (p=0.037) after adjusting for age, gender and BMI. Conclusion PWLH without traditional CV risk factors did not have significant evidence of more clinically relevant stenosis than controls on CTCA. However PCAT demonstrated a higher signal of coronary inflammation, despite stable disease, compliance with ART and low CVD risk scores. PLWH remain at risk of CV disease, this study supports the rationale for early preventative strategies for CVD prevention in PLWH.PCAT showing HIV inflammation Vs Control

Undiagnosed Diabetes Mellitus is an important risk factor in secondary prevention after an acute coronary syndrome and warrants active screening

Abstract Background/Introduction Previous studies have shown that patients with Diabetes Mellitus (DM) undergoing percutaneous coronary intervention (PCI) for an acute coronary syndrome (ACS) have an increased ischemic risk compared to non-diabetics. This has led to the recommendation to take DM into account when considering extended dual antiplatelet therapy (DAPT) to prevent ischemic events. Although screening for DM can simply be conducted by measuring HbA1c values, the ACS guidelines do not yet recommend to screen for DM de novo. This may lead to undertreatment. Purpose We aimed to determine the ischemic risk of previously diagnosed DM and of DM de novo compared to patients without DM in a real world ACS population. Methods We included patients from the South East (Zuid Oost) Netherlands Heart Registry (ZON-HR) undergoing PCI for ACS without using oral anticoagulants and compared outcomes between DM and non-DM patients. In a subgroup of patients without previously diagnosed DM with available HbA1c measurements at baseline, we compared outcomes between patients with or without DM de novo (HbA1c ≥48 mmol/mol). All analyses were performed using Cox regression analysis. We used multivariate analysis to adjust for known ischemic risk factors. Results Of the 2406 patients included, 426 were previously diagnosed with DM. Additional ischemic risk factors, such as a history of myocardial infarction (MI), multivessel disease and kidney disease, were significantly more often present in patients with DM. Patients with DM showed numerically more major adverse cardiac and cerebral events (MACCE). However, this was not significant (HR: 1.24, 95% CI: 0.92-1.66). All-cause mortality was higher in patients with DM at 30 days (HR: 1.51, 95% CI 1.00-2.29) and 1 year (HR: 1.55, 95% CI 1.10-2.18), which remained significant at 1 year when corrected for additional risk factors. The HbA1c values at baseline were available in 387 patients without previously diagnosed DM. In this subgroup, 69 (18%) patients showed an elevated HbA1c level of ≥48 mmol/mol. Outcomes within this subgroup are presented in table 1. Patients with de novo DM showed significant more ischemic events after one month and one year follow-up compared to patients without DM de novo. Figure 1 depicts the survival from MACCE over time in these subgroups. Conclusion In our real world population of ACS patients undergoing PCI, we found no significant difference in ischemic risk between patients with previously diagnosed DM compared to non-DM. However, all-cause mortality was significant higher in DM patients. Active screening for DM resulted in a large proportion of patients with DM de novo who showed a major increase in ischemic risk. These results demonstrate the importance of screening for DM in ACS patients undergoing PCI.

Large scale OECD health valuation study to estimate the economic benefits of chemical regulation

Abstract Chemical regulation aims at protecting human health and the environment from the risks of chemicals, while recognizing the economic importance of the use of chemicals. Assessment of the societal impacts of chemical regulation and different policy options requires information on both costs and benefits. So far, regulators assessing chemicals regulations has not had access to high quality and internationally comparable data on the full monetary benefit of reducing health and environmental risk. The OECD has implemented a multi-country stated preference valuation project that covers ten chemicals-related health conditions (e.g. asthma, kidney disease, infertility, etc.) with more than 80 surveys with large samples in 22 countries. The OECD Surveys on Willingness-to-Pay to Avoid Negative Chemicals-Related Health Impacts (SWACHE) project aims to establish internationally comparable values for the willingness-to-pay (WTP) to avoid negative health effects due to exposure to chemicals. The values can be used to demonstrate and measure the economic benefits of minimising the morbidity impacts of chemical regulations, environmental policies and public policies in general. The latest valuation results of the project will be presented, along with key aspects of the joint methodology used and the plans to further expand this work. In addition, the OECD is collaborating with other intergovernmental organisations via the Inter-Organization Programme for the Sound Management of Chemicals (IOMC) to update the cost of inaction estimates for chemicals as part of the Global Framework on Chemicals. An update on this initiative, that can benefit from the results of the SWACHE project, will be provided.

Much ado about nothing: the impact of coronary angiography on kidney function in individuals with chronic kidney disease

Abstract Background and Objectives Chronic kidney disease (CKD) is associated with premature coronary artery disease and an increased risk of cardiovascular morbidity and mortality (1). Historically, there has been a tendency to delay or even avoid coronary angiography (CA) in those with CKD due to an increased risk of contrast-induced nephropathy or concern over precipitating the need for chronic dialysis. Such "renal nihilism" may account for the poorer outcomes observed in CKD patients who present with acute coronary syndromes (2). The role of this retrospective analysis was to evaluate the impact of CA on the temporal trend in kidney function in individuals with CKD over a 24-month period. Methods The clinical details of 120 individuals under long-term local follow-up by various Nephrology clinics (CKD clinic, low creatine clearance, polycystic kidney disease, transplant and immunosuppression clinics) was collected. All underwent CA locally. Kidney function was observed at set intervals of 12-, 9-, 6- and 3-months prior to CA, immediately post-CA, and at 3-, 6-, 9- and 12-months post-CA. Only results obtained after the desired time point but within 28 days were included. All CAs regardless of either their indication (elective or urgent) or whether percutaneous intervention (PCI) was performed, were included. Patients already on dialysis at the time of the CA were excluded. Statistical analysis was performed via one-way ANOVA. Results Patient characteristics are summarised in table 1. The average age of patients was 67, with a male preponderance (72%). 22% had CKD 3, 24% had CKD 4 and 12% had CKD 5. 9% were kidney transplant recipients. 37% underwent urgent CA whilst a total of 22% had PCI. 27% progressed to requiring renal replacement therapy (RRT). The mean length to RRT was 2.8 years. The rate of decline in kidney function in the last 12 months prior to CA was 7.7% and 6.3% in the year after CA (figure 1). There was no statistically significant difference in kidney function after CA (p = 0.395). This was replicated in analyses focussing on CKD classes 3, 4 and 5 individually, within stable kidney transplant recipients, and within analysis comparing PCI vs non-intervention CAs. Conclusion The results demonstrate CA does not accelerate the decline in kidney function in those with known CKD over a 12-month period, and suggests where appropriate, an invasive treatment strategy should be consider and utilised more often in this population.Table 1:Patient characteristicsFigure 1:Trend in eGFR relative to CA

Mizhuo Guanchangye enema delays the decline of renal function in rats with chronic kidney disease by intervening in the TLR4/MyD88/NF-κB pathway

BackgroundChronic kidney disease (CKD) is a prevalent chronic condition that poses a significant threat to human health. There is a close connection between the gut and kidneys, jointly influencing the onset and progression of CKD through the “gut-kidney axis.” Traditional Chinese medicine has shown potential in CKD treatment, but the specific mechanisms require further investigation.ObjectivesThis study aims to explore the protective effects of Mizhuo Enema (MZGCY) on kidney function in CKD rats by regulating the TLR4/MyD88/NF-κB signaling pathway.MethodsThe researcher employed a CKD rat model, which was divided into four groups: Control, Model, half-dose Mizhuo Guanchangye (1/2 MZGCY), and full-dose Mizhuo Guanchangye (MZGCY). Post enema administration, assessments were conducted on kidney function indicators, which included blood urea nitrogen (BUN), serum creatinine (SCR), and 24-h urinary protein. Additionally, measurements were taken for intestinal toxic substances such as indoxyl sulfate (IS) and lipopolysaccharide (LPS), as well as inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Examinations of pathological changes in both the intestines and kidneys were also performed. During this process, immunofluorescence was utilized to detect the expression levels of proteins toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor kappa B (NF-κB) in the intestinal tissues.ResultsIt was found that after enema treatment, the BUN, SCR, and 24-h urinary protein levels in the MZGCY and 1/2 MZGCY groups significantly decreased, indicating notable improvement in kidney function. Compared to the model group, the IS, LPS, IL-6, and TNF-α levels in the MZGCY and 1/2 MZGCY groups were significantly reduced. Immunofluorescence showed a marked decrease in the expression of TLR4, MyD88, and NF-κB proteins in the intestines of the MZGCY group.ConclusionMZGCY significantly reduces the levels of intestinal toxins and inflammatory factors in the serum of CKD rats by interfering with the TLR4/MyD88/NF-κB signaling pathway, thereby improving intestinal and renal pathological changes and delaying CKD progression. This study demonstrates that MZGCY has significant renal protective effects, providing a new potential approach for CKD treatment.

The incidence of death and risk factors for mortality following major bleeding in patients anticoagulated with factor Xa inhibitors: an observational study in the UK clinical setting (AXIOM UK)

Abstract Background Major bleeding (MB) in association with anticoagulant use results in significant mortality. Mortality can be directly attributed to bleeding, or may follow bleeding complications such acute kidney injury, myocardial infarction, stroke and other cardiovascular events. Most real-world data relating to bleeding mortality is derived from cohorts receiving vitamin-K antagonists. We investigated all-cause mortality (ACM) after MB in a large cohort anticoagulated with Factor Xa inhibitors (FXai), e.g. direct oral anticoagulants (DOAC) rivaroxaban, apixaban and low-molecular-weight heparins (LMWH). Purpose To describe incidence rates of and risk factors for ACM following MB in patients receiving FXai. To investigate MB related ACM by bleeding site, treatment indication, treatment subgroups and individual and cumulative time periods. Methods Retrospective cohort analysis of new users of FXai, between 2012-2020, for therapeutic indications including atrial fibrillation (AF), venous thromboembolism, bioprosthetic cardiac valves or adult congenital heart disease was conducted. MB was defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. Incidence rates were reported per 100 person-years. Sub-distribution hazard ratios with 95% confidence intervals (95% CI) were estimated from Fine and Gray regression models accounting for competing risks. Results In 240,357 new users of FXai, 88% used an oral FXai. The most common FXai indication was AF (72%). There were 10,163 patients (4.2%) hospitalised for bleeding events during FXai use. Of these, 3,873 MB events (38%) fulfilled the ISTH definition of MB and 1312 died during 3,542 person years of follow-up (Table 1). ACM incidence rates varied by time, indication, bleeding subtype, and drug type. ACM occurred in 926 patients (23.9%) in the first month. Mortality rates were highest in the first month 607 (95% CI 568-647) per 100 person years, the rates then decreased over the year but remained elevated throughout the first year compared with subsequent years. Those receiving LMWH had higher ACM than those receiving a DOAC, but this was not significant in the adjusted risk factor analysis. Risk factors for ACM following bleeding included age ≥80, and a history of current smoking, myocardial infarction, congestive heart failure, peripheral artery disease, Stage 4 or 5 kidney disease, metastatic cancer, and intracranial haemorrhage. Age<60, bleeding following major trauma, and a history of anaemia were associated with lower risk of ACM (Table 2). Conclusions There is a significant incidence of ACM following MB among FXai users. The incidence rate of ACM in patients treated with FXai was highest in the first month after FXai initiation, declined during the first year and then plateaued. Multiple risk factors associated with ACM have been recognised and these could guide urgent therapies such as antidotes.

Association of pulsatile venous waveform pattern in the venous studies of lower extremities to 2d-echocardiographic parameters for right heart function and right atrial pressure

Abstract Introduction To date, the detection of pulsatile venous waveform (PVW) pattern in venous duplex scans are read as suggestive of increased central venous pressure (CVP) and/or right-sided heart failure. In the advent of point of care ultrasound, non-invasive measures can be used to determine systemic hemodynamics in emergent clinical settings. Purpose This study aims to determine the association of PVW pattern to echocardiographic parameters of right ventricular (RV) function and right atrial pressure (RAP). Methods A single center retrospective study of adult patients with venous studies of the lower extremities and 2d-echocardiogram done from January 2019 to October 2023. Logistic regression analyses were performed to determine the association of PVW pattern with RV dysfunction based on TAPSE, S’ and FAC, as well as with increased RAP. Results A total of 2086 adult patients were included with median for age of 67 years of which 1141 (55%) were females, and 728 (35%) were hypertensive. PVW pattern was noted from 163 participants (7.8%) of which a higher proportion had heart failure, kidney disease, COVID-19, pneumonia and valvular heart disease. Patients with PVW pattern had a significantly lower median TAPSE [18 (IQR 15-20) vs 20 (IQR 18-22)] and median S’ [11.1 (IQR 8.6-13.20) vs 12.3 (IQR 10.6-14.40)] with FAC 27.1 + 11.9%. Increased RAP was noted in 7% of the study population. Patients with PVW pattern had a higher median inferior vena cava (IVC) diameter [1.9 ( IQR 1.5-2.3) vs 1.5 (IQR 1.3-1.8)] and lower median IVC collapsibility [39.9 (IQR 23.5-51.4) vs 50 (IQR 38.9-58.80]. PVW pattern is significantly associated with TAPSE (crude OR 3.89; CI 2.67-5.66, p<0.0001), S’ (crude OR 3.26, CI 2.30-4.62, p<0.0001) and increased RAP (adjusted OR 6.06, CI 4.02-9.14, p<0.0001). Conclusion Patients with PVW pattern had about 4 times and 3 times higher odds of developing RV systolic dysfunction based on TAPSE and S’, respectively. Its presence confers about 6 times higher odds of developing increased RAP. These parameters can direct further diagnostic work-up and guide assessment of response to decongestive therapy in critical units and other areas where 2d-echocardiogram is not readily accessible.

Future of Uremic Toxin Management

During the progression of chronic kidney disease (CKD), the retention of uremic toxins plays a key role in the development of uremic syndrome. Knowledge about the nature and biological impact of uremic toxins has grown exponentially over the past decades. However, the science on reducing the concentration and effects of uremic toxins has not advanced in parallel. Additionally, the focus has remained for too long on dialysis strategies, which only benefit the small fraction of people with CKD who suffer from advanced kidney disease, whereas uremic toxicity effects are only partially prevented. This article reviews recent research on alternative methods to counteract uremic toxicity, emphasizing options that are also beneficial in the earlier stages of CKD, with a focus on both established methods and approaches which are still under investigation or at the experimental stage. We will consequently discuss the preservation of kidney function, the prevention of cardiovascular damage, gastro-intestinal interventions, including diet and biotics, and pharmacologic interventions. In the final part, we also review alternative options for extracorporeal uremic toxin removal. The future will reveal which of these options are valid for further development and evidence-based assessment, hopefully leading to a more sustainable treatment model for CKD than the current one.

Torsemide versus furosemide in patients with heart failure: a systematic review and meta-analysis

Abstract Introduction Loop diuretics are essential agents in the management of fluid overload conditions, heart failure and renal dysfunction. Despite their widespread use, there is ongoing debate regarding the relative efficacy, safety, and clinical outcomes associated with furosemide and torsemide. By systematically analyzing existing literature, this study seeks to provide a comprehensive evaluation of the comparative effectiveness and safety profiles of these two medications , Helping to inform clinical decision-making and contribute to the optimization of diuretic therapy in patients with heart and kidney diseases. Methods We searched PubMed, Scopus, WOS, and Cochrane until February 2024 for relevant studies comparing the torsemide and furosemide in Heart failure patients. Outcomes of interest were all-cause mortality, cardiovascular mortality, all-cause hospitalization, hospitalization for HF, and improvement of ≥ 1 in NYHA functional class. Results 16 studies were included in this meta-analysis with a total of 12545 patients, There were no significant results between the two drugs in all-cause mortality, cardiovascular mortality or all-cause hospitalization, torsemide showed a reduction in hospitalization from heart failure (RR 0.85, 95% CI [0.71 to 1.02]), torsemide showed a significant improvement of ≥ 1 in NYHA functional class (OR 1.60, 95% CI [1.18, 2.17]). Conclusion There was no difference between torsemide and furosemide when it comes to all-cause and cardiovascular mortality, but torsemide showed better results in reducing hospitalization rates and and improving quality of life.Hospitalization from heart failureImprovement ≥ 1 in NYHA class

Bidirectional relationship between kidney disease progression and cardiovascular events in type 2 diabetes: new Insights from the CANVAS Program and CREDENCE trial

Abstract Background The extent to which chronic kidney disease (CKD) progression increases cardiovascular risk, and whether different types of cardiovascular events affect risk of CKD progression, is incompletely understood. Purpose We sought to explore risk of cardiovascular events before and after CKD progression, and CKD progression before and after different cardiovascular events in patients with type 2 diabetes. Methods We conducted a pooled individual participant data analysis of the CANVAS Program and CREDENCE trial. Using Poisson regression, we assessed the incidence of major adverse cardiovascular events ([MACE] stroke, myocardial infarction, or cardiovascular death) and hospitalised heart failure (HHF) or cardiovascular death before and after CKD progression (defined as 40% decline in estimated glomerular filtration rate [eGFR] or kidney failure), and CKD progression before and after nonfatal cardiovascular events, with no adjustment for confounding related to subgroups defined by post-randomization variables. We estimated the cumulative incidence of all-cause mortality after different nonfatal cardiovascular and kidney outcomes, including different thresholds of CKD progression (kidney failure, 40% or 50% decline in eGFR or doubling of serum creatine) using Cox regression models. Results Among 14,464 participants (mean age 63.7 years, 35.3% female, mean eGFR 55mL/min/1.73m2 and median urinary albumin:creatinine ratio 34mg/g) over a median follow-up of 2.5 years, 1,482, 1,076 and 1,020 experienced MACE, HHF or cardiovascular death, and CKD progression, respectively. After (vs. before) CKD progression, there was an approximate 3-fold increase in incidence of MACE (30.2 vs. 93.8 per 1000-patient-years) and 4-fold increase in HHF or cardiovascular death (21.0 vs. 79.3 per 1000-patient-years). Conversely, the incidence of CKD progression was approximately 1.5-fold higher after (vs. before) nonfatal myocardial infarction or stroke (21.7 vs. 34.1 per 1000-patient-years) and 5-fold higher after HHF (21.2 vs. 108.2 per 1000-patient-years). These patterns were consistent in both treatment arms, with unadjusted incidence rates for clinical events appearing numerically lower in canagliflozin compared to placebo-treated participants (Figure 1). Of all non-fatal cardio-kidney outcomes, HHF and doubling of serum creatine or kidney failure conferred the highest risk of death (Figure 2). Conclusion Atherosclerotic and heart failure risk increases substantially after CKD progression. CKD progression was accelerated after cardiovascular events, particularly HHF. Treatment with canagliflozin was associated with lower event rates before and after a serious cardio-kidney outcome, suggesting continued use of canagliflozin may be beneficial even after cardiovascular events and CKD progression.Figure 1.Figure 2.

The prevalence, patients characteristics and risk factors of hyper-Lp(a)-emia in the Polish population. The first results from the PMMHRI-Lp(a) Registry

Abstract Background Based on the recent data and existing guidelines Lp(a) is recognized, independent CVD risk factor. However, the knowledge on the prevalence of elevated Lp(a) levels, patients characteristics as well as non-genetic risk factors is scarce from some world regions including from Poland, the largest CEE country. Purpose We aim to present the first results from the Lp(a) registry established in the 2nd largest hospital in Poland - Polish Mother’s Memorial Hospital Research Institute (PMMHRI). Methods The PMMHRI-Lp(a)-Registry was established in 2022. The indications for Lp(a) measurement in the registry are based on the 2021 Polish Lipid Guidelines and new Polish recommendations on the management with elevated Lp(a) (2024). The PMMHRI-Lp(a)-Registry is a part of the being founded Lp(a) National Registry of the Polish Lipid Association. Results Based on the data from 302 consecutive patients (mean age 52.18 years; women 53%) the mean Lp(a) level was 30.3±39.4 mg/dl; it was numerically higher in woman (32.8 mg/dl), but there were no significant sex differences (men: 27.5 mg/dl; p=0.245). There were also no significant differences between those with and without CAD, stroke, HF, cancer, diabetes, kidney disease, and thyroid disease. The significant Lp(a) level difference was observed in those with diagnosed dyslipidemia in comparison to those without (31.9±40.6 vs 17.7±25.8 mg/dl, p=0.044) and in those with the history of myocardial infarction (MI) vs those without (50.1±50.3 vs 28.1±37.5 mg/dl, p=0.004). However, when we divided those with MI on premature vs no premature, no significant difference in Lp(a) level was observed (41,6±41.9 vs 57.6±56.7 mg/dl, p=0.39). Lipid lowering therapy did not significantly affect Lp(a) level, with only significant differences in those treated with ezetimibe (as a part of the combination therapy; 39.5±47.6 vs 27.5±36.3 mg/dl, p=0.027). For selected patients (n=31; 10.3%) with two Lp(a) measurements (mean time distance: 7±5 months) we did not observe any significant visit-to-visit variability (mean difference: 0.81 mg/dl; z=0.256, p=0.262) (Fig. 1). We did not also observe any percentage differences in variables (besides MI history, p=0.017) for different Lp(a) risk groups: 0-30, >30-50, >50-180 and >180 mg/dl. While dividing the population on those with Lp(a) ≤30 mg/dl vs >30 mg/dl, the only differences were seen for dyslipidemia diagnosis (p=0.044) and MI occurrence (6.98 vs 17.24%; p=0.007). Similar pattern was observed while dividing the whole population on those with Lp(a) ≤50 vs >50 mg/dl (Fig. 2). Conclusions These results strongly emphasize that Lp(a) should be measured commonly, as its high level is highly prevalent in patients at the risk both in primary and secondary prevention, what require risk re-stratification and treatment optimization. This is especially important in the regions that characterize of baseline high CVD risk, what refers to most of the CEE countries, including Poland.

Prediction of incident major adverse cardiac events in patients starting haemodialysis for end stage kidney disease, using clinical laboratory cardiac biomarkers - a real world analysis.

Abstract Background and Aims Despite its many advantages, haemodialysis (HD) is associated with increased cardiovascular mortality and morbidity, with some studies reporting 48% higher mortality within 2 years of starting HD. Cardiac biomarkers provide insight into cardiac structure and function, including myocyte stress, inflammation and fibrosis. We aimed to investigate the prognostic significance of routine cardiac biomarkers (troponin and natriuretic peptides) in the prediction of incident major adverse cardiac events (MACE) within 5 years if commencing HD. Methods A retrospective cohort study was performed using electronic medical records from a global federated research network from the US. The network was searched on 26th February 2023. The cohorts commenced HD post-diagnosis of end-stage kidney disease. Data censoring for MACE was invoked prior to the index event of HD. Cardiac biomarkers were the first reported result within 3 months of starting HD. Cohorts were grouped according to biomarker-specific thresholds and 1:1 propensity-score matched for age, gender and co-morbidities (hypertension, diabetes mellitus and smoking status). Logistical regression produced odds ratios with 95%CI for 5-year incident MACE. MACE was defined, a priori, as a composite of ischaemic heart disease, angina pectoris, acute myocardial infarction, heart failure, AF, stroke and all-cause mortality. All statistical analysis was performed on the online platform. Results The results are shown Tables 1(Troponin I and BNP alone) and 2 (Combined Troponin I and BNP). Results that reached statistical significance (p<0.05) are shown. Conclusion Routinely available cardiac biomarkers can predict MACE and cardiac outcomes in incident HD, although results differ between markers of myocyte injury (troponin) and stress (BNP). A combined approach may prove most beneficial. The results suggest the clinical need for CV mortality and morbidity risk profiling in incident dialysis using a combination of clinical and laboratory variables and the need for prospective validation.Table 1Table 2

A 3-year retrospective exploration of predictors for cardiac arrest in atrial fibrillation

Abstract Background An increasing correlation between atrial fibrillation (AF) and a heightened risk of cardiac arrest is emerging. Yet, the specific predictors of cardiac arrest in hospitalized patients with AF remain unclear. Purpose This study aims to identify these predictors, providing essential insights for refined risk assessment and targeted clinical interventions. Methods Adult patients hospitalized between 2018 and 2020 with a primary diagnosis of AF with or without cardiac arrest were identified using the International Classification of Diseases, Tenth Revision (ICD-10) code. Demographics and comorbidities were recorded. Logistic regression was employed to identify predictors of increased cardiac arrest. Results In a study of 272,028 hospitalizations with AF, 2,352 patients suffered cardiac arrest, and 523 died during hospitalization. Factors associated with increased odds of cardiac arrest include heart failure (OR = 1.79, 95% CI: 1.60–2.00), cardiogenic shock (OR = 2.95, 95% CI: 2.35–3.71), history of coronary angioplasty or bypass (OR = 1.79, 95% CI: 1.59–2.02), chronic kidney disease (OR = 1.26, 95% CI: 1.12–1.42), end-stage kidney disease (OR = 2.34, 95% CI: 1.98–2.77), and septic shock (OR = 6.50, 95% CI: 4.80–8.80). Chronic obstructive pulmonary disease (COPD) and infection were associated with a 13% (OR = 1.13, 95% CI: 1.02–1.26) and 45% (OR = 1.45, 95% CI: 1.25–1.68) increase in odds for cardiac arrest, respectively. Increased age (OR = 0.99, 95% CI: 0.98–0.99) and female sex (OR = 0.83, 95% CI: 0.76–0.91) showed an inverse relation with cardiac arrest. Hypertension and obesity exhibited protective effects against cardiac arrest, with odds ratios of 0.85 (95% CI: 0.74–0.97) and 0.83 (95% CI: 0.75–0.93), respectively. Conclusion Our study underscores the intricate web of factors influencing cardiac arrest risk in AF patients. A personalized approach to risk assessment in the context of AF might be needed.

Impact of chronic kidney disease on patients with Myocardial Infarction with Non Obstructive Coronary Arteries (MINOCA)

Abstract Background Chronic kidney disease (CKD) in patients with myocardial infarction (MI) is associated with more advanced disease, a higher risk of complications and poorer prognosis, as well as increased mortality. The aim of this study is to assess the impact of CKD in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) and its influence on the prognosis of these patients. Methods it was an observational, prospective and analytic study. We analyzed all consecutive patients with MI who underwent coronary angiography admitted to our Hospital between 2016 and 2023; MINOCA patients were classified following the 2023 ESC Guidelines definition. The patients were divided into two groups depending on whether they had CKD or not. Median follow-up was 43 months [20-71]. Results we included 136 patients with MINOCA, of whom 11 (8.1%) had CKD. Patients with impaired kidney function were older and mostly male. They also exhibited a higher prevalence of classic cardiovascular risk factors such as hypertension, diabetes, or dyslipidemia. However, there were fewer smokers in this group. We did not find significant differences in coronary artery anatomy (smooth or small plaques) between both groups. Additionally, the majority of patients in both groups had preserved left ventricular function. Despite that, patients with CKD typically had ST segment elevation in the ECG and higher myocardial injury biomarkers’ levels as well as NT-proBNP. During hospitalization, patients without renal dysfunction had more complications (11.2% vs 0%, p=0.062) such as inotropic requirements, stroke or cardiogenic shock, but overall there were very few. In terms of treatment, it was fairly similar in both groups, although patients with kidney disease received diuretics significantly more often. Throughout the follow up, there were no significant differences in MACE (major adverse cardiovascular events) between death (27.3% vs 7.4%, p=0.06), readmission (10% vs 10.8%, p=1) or MI (0% vs 3.4%, p=1), but patients with CKD suffered more frequently from stroke (40% vs 4.2%, p<0.01). Conclusions 1) Patients with MINOCA and CKD are typically older and predominantly male with a high prevalence of cardiovascular comorbidities (hypertension, diabetes, dyslipidaemia). 2) The severity of MI appears to be slightly higher in this group, as evidenced by more ST-segment elevation upon admission and higher hs Troponine T levels. However, they experience fewer cardiovascular complications and maintain normal left ventricular function. 3) Although we found no significant differences in major adverse cardiovascular events (MACE), patients with CKD were more likely to suffer from stroke.Table 1Table 1

Acute kidney injury (AKI) in cardiac intensive care unit patients: a real challenge to overcome

Abstract Introduction Acute kidney injury (AKI) is a major cause of morbidity and mortality in intensive care units (ICUs), but in cardiac intensive care unit (CICU), despite the evidence of a causal link between cardiac illness and AKI, few data are available (1). Purpose We analyzed the predictive factors of AKI in CICU, as well as the impact of AKI on the long-term prognosis of patients admitted to CICU. Methods We reviewed the medical data of patients admitted to our CICU over a 2-year period. We excluded patients with chronic kidney disease prior to admission. We defined AKI according to the KDIGO (Kidney Disease Improving Global Outcomes) classification based on serum creatinine and urine output. To determine the predictive factors, we performed a logistic regression analysis, and to determine the prognostic impact of AKI, we performed a Cox proportional hazards regression, taking all-cause mortality at 30 months as the main study outcome. p-values less than 0.05 were considered statistically significant Results We included in our study 1581 patients hospitalized in our unit over a 2-year period, 70.4% of whom were men and 29.6% women. Among these patients, 291 presented with AKI (18.4%), 35.5% classified as KDIGO 1, 42% as KDIGO 2, and 22.5% as KDIGO 3. For the admission diagnosis of patients with AKI, STEMI came first at 56.3%, followed by NSTEMI at 17.3%, acute heart failure at 9.3%, pulmonary embolism at 2.1%, severe arrhythmias at 7.9%, and valvular disease at 1.1%. Among patients in the KDIGO 3 group, 54% benefited from a renal replacement strategy. La morta For factors predictive of AKI, and after adjustment for variables significant in univariate analysis, we objectified the following factors: arterial hypertension (OR=1.92, p<0.001), Diabetes (OR=1.50, p=0.007), KILLIP>2 at admission (OR=1.75, p=0.003), Ejection fraction<40% at admission (OR=1. 93, p<0.001), right ventricular systolic dysfunction (OR=2.95, p<0.001), anemia with Hb<10g/dl (OR=2.95, p<0.001), cardiogenic shock (OR=3.02, p<0.001), high-grade conduction disorder (OR=2.7, p=0.003) and bleeding events (OR=5.93, p<0.001) (Table 1-figure 1). For all-cause mortality at 30 months, 204 events were observed, 104 in the AKI group (35%), and 100 in the non-AKI group (7.75%) (p<0.001), and AKI was independently associated with the outcome studied for all KDIGO classes with for stage 1 (HR = 1.33; p=0.03), stage 2 (HR = 2.28; p<0. 001), and stage 3 (HR = 5.71; p<0.001), adding to this diabetes (HR = 1.96; p<0.001), cardiogenic shock (HR = 2.27; p<0.001) and finally EF<35% at discharge (HR = 1.53; p=0.001) (Table 2-figure 1). The Kaplein-Meier survival analysis showed a significant difference between the rates of mortality between the different KDIGO at 30-months, with a log-rank test p<0.001 (Figure 2). Conclusion We can conclude that AKI remains a real challenge for admitted patients, since long-term mortality in this group is very high.Figure 1.Figure 2.

Chronic kidney disease in patients with heart failure in German primary care practices: the InspeCKD study

Abstract Background Chronic kidney disease (CKD) is, alongside type 2 diabetes mellitus, the most common comorbidity in patients with heart failure (HF), with a prevalence of 40-50%. HF patients should therefore be screened, monitored, and treated according to international Kidney Disease Improving Global Outcomes (KDIGO) conclusions for early identification and intervention of CKD, with annual determination of eGFR to monitor kidney function and annual urine albumin-to-creatinine ratio (UACR) testing as appropriate. Early diagnosis is important as therapeutic options can be offered to slow the progression of CKD and reduce the risk of cardiovascular complications and mortality. Purpose Currently, there are only limited data available regarding screening, diagnosis and treatment of CKD for HF patients in German primary care physician (PCP) practices. Therefore, this analysis of the InspeCKD study was designed to examine the frequency of use of CKD-specific laboratory diagnostics in HF patients in routine PCP care. Methods In the current data analysis, fully anonymized patient data from German PCP practices were evaluated. In accordance with the screening recommendation of the KDIGO guideline, adult patients with diabetes, hypertension and/or cardiovascular disease, including HF, with at least one year of observation period were included in the analysis. Results The overall patient cohort comprised 448.837 patients from 1.244 German PCP practices. Of the 7.9% HF patients, 6.1% participated in a disease management program (DMP) for coronary heart disease. The average age of HF patients was 74 years. The prevalence of diagnosed CKD in HF patients during the observational period (mean: 1.7 years) was 26.8%. Within the subgroup of patients with HF, serum creatinine to estimate GFR was measured at least once in 48.5% of patients. Urine dipstick testing for albuminuria was performed in 7.4% of patients and UACR was measured at least once in 0.3% of patients. In patients with at least one documented measurement, eGFR and UACR were checked 2.2 and 0.9 times, respectively, per patient and year. Of the HF patients with laboratory-confirmed CKD according to KDIGO criteria, 81.8% were not diagnosed with CKD. Conclusion The analysis shows that, given the high prevalence of CKD in HF patients and the current KDIGO recommendations for early identification and intervention of CKD, a substantial proportion of HF patients in German PCP practices did not receive adequate laboratory diagnostics for early diagnosis of CKD. In addition, the majority of patients with laboratory-confirmed CKD were not diagnosed. Early detection of CKD and the use of evidence-based therapeutic options can significantly reduce the risk of CKD progression. In conclusion, there is an urgent need to raise awareness among PCPs about secondary and tertiary prevention of CKD in patients with HF and to include coordinated CKD screening recommendations in HF guidelines.

Life course cumulative PM2.5 exposure since childhood and albuminuria in midlife: a 30-year prospective cohort study

Abstract Background Previous studies have confirmed the adverse effect of ambient fine particulate matter (PM2.5) on kidney and cardiovascular diseases. However, the effects of long-term cumulative PM2.5 exposure on albuminuria, particularly from childhood to middle age, remains uncertain. Purposes We aimed to investigate the association between cumulative PM2.5 exposure and albuminuria across three distinct time frames using data from the 30-year population-based cohort study. Methods Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 1643 children and adolescents were followed with 6 visits over 30 years. The annual mean PM2.5 concentration for the period 1987-2017, at the address of each participant, was obtained from the MERRA-2 and CHAP datasets in China. We assessed cumulative PM2.5 exposure as the area under the curve (AUC) and used the linear regression models to estimate the association between cumulative PM2.5 exposure and urinary albumin-to-creatinine ratio (uACR) in 2017. Results In full adjustment for potential confounders, childhood and life course cumulative PM2.5 exposure was positively associated with uACR in midlife [childhood: β=0.103 (95%CI: 0.003, 0.202); life course: β=0.078 (95%CI: 0.004, 0.153)]. However, the relationship between adulthood cumulative PM2.5 exposure and uACR in middle age was not statistically significant. In addition, the associations of adulthood and life course cumulative PM2.5 exposure with uACR in middle age were only observed in non-smokers [β=0.109 (95% CI: 0.002, 0.216)], but not in smokers. Conclusions Cumulative PM2.5 exposure during childhood and over the life course is associated with higher uACR in midlife, especially for children and non-smokers. Lowering PM2.5 pollution early in life could prevent the development of renal dysfunction and cardiovascular disease in later life.