Prevalence Of Cardiovascular Disease Research Articles

NT-proBNP in severe aortic valve stenosis: necessity for higher cut-off values regarding congestive heart failure detection in atrial fibrillation

Abstract Background NT-proBNP is an established biomarker for the determination of fluid overload. Patients suffering from atrial fibrillation seem to have higher serum levels of NT-proBNP than patients in sinus rhythm, independent from fluid overload. However, there is no established alternative cut-off for patients with atrial fibrillation, especially in patients with severe aortic valve stenosis. Aim The aim of the current study was to evaluate the levels of serum NT-proBNP for patients with atrial fibrillation (AF) and sinus rhythm (SR) for the determination of fluid overload in patients with severe aortic valve stenosis. Methods 167 Patient suffering from severe aortic valve stenosis undergoing evaluation for TAVR at our hospital were included in this study. Upon recruitment blood samples from every patient were collected and an ECG was documented for each patient. Serum NT-proBNP was measured and volume overload was objectivated by calculation of plasma volume status (PVS), an already published method to estimate fluid overload or depletion by using a formula including weight and haematocrit. Results 37 patients (22.2%) suffered from AF upon recruitment. 47 patients (28.1%) showed fluid overload, indicated by increased PVS (PVS > 0, SR n=37, AF n=10). 94 patients (56.3%) were male and mean age was 80 years. Patients with and without AF showed no significant difference in age, sex or prevalence of cardiovascular diseases, except for gradients across the aortic valve (SR 47mmHg vs. AF 38mmHg; p<0.05) and left ventricular ejection fractions (SR 57% vs. AF 55%; p<0.05). Patients suffering from atrial fibrillation showed significantly higher serum levels of NT-proBNP (4843 ng/L vs. 1226 ng/L, p<0.001). ROC-analyses in patients with SR and severe aortic valve stenosis, showed satisfying results for NT-proBNP (AUC 0.72; sensitivity 0.81; specificity 0.58) to detect fluid overload. Comparable results were evident in patients with AF (AUC 0.77; sensitivity 0.70; specificity 0.78), but cut-off-values in patients suffering from atrial fibrillation were more than six times as much as in patients with sinus rhythm (6575 ng/L vs. 1053 ng/L). Conclusion NT-proBNP proved itself as a sufficient marker to determine volume overload in patients with severe aortic valve stenosis. Cut-offs for accurate determination of fluid overload deviate greatly in patients with sinus rhythm and atrial fibrillation, therefore different cut-offs might be required.

#1920 The impact of kidney function on cardiac diastolic dysfunction trajectories: insights from a longitudinal study

Abstract Background and Aims Although the association between kidney dysfunction and cardiac diastolic dysfunction has been investigated in cross-sectional studies, we currently lack a complete understanding of how the diastolic dysfunction changes over time in individuals with different kidney functions. Exploring the diastolic dysfunction trajectories is crucial as it can provide valuable insights into how kidney function influences cardiac health and which patients are at the highest cardiovascular risk. E/e’ is an echocardiography measure that estimates left ventricular filling pressure and diastolic dysfunction. This study evaluates how kidney function impacts changes in E/e′ over time. Method We identified patients from the Utrecht Patient Oriented Database (UPOD) who visited the outpatient clinic of Utrecht University Medical Center between January 2012 and April 2022. Patients who had received at least three echocardiography reports with a minimum of 12 months between them and had recorded serum creatinine measurements in their electronic health records were included. The estimated glomerular filtration rate (eGFR [mL/min/1.73 m2]) was calculated using the CKD-EPI 2021 creatinine formula without ethnicity and categorized as follows: eGFR ≥ 90, eGFR ≥ 60 - <90, eGFR < 60. Linear mixed-effect models were utilized to determine the impact of kidney function on changes in E/e′ over time. Results A total of 436 patients were included of whom 34.7% were women. The total number of echocardiography examination was 1308. Overall, the median eGFR for all patients was 78.2 mL/min/1.73 m2 [IQR: 61.9, 90.7]. Among them, 26.6%, 51.4%, and 22.0%, had an eGFR ≥ 90, eGFR ≥ 60 - < 90, and eGFR < 60, respectively. Patients with an eGFR < 60 had a higher prevalence of hypertension (64.6%) and cardiovascular disease (84.4%) compared to those with an eGFR ≥ 90, where the prevalence of hypertension and cardiovascular disease was 49.1% and 67.2%, respectively. Additionally, patients with an eGFR < 60 had the lowest mean ejection fraction of 44.9% ± 18.5% and the highest median E/e′ of 12.84 [10.10, 16.16]. The linear mixed model analysis showed that the estimated change in E/e′ per year depended on the level of kidney function. For patients with eGFR ≥ 60 - <90, E/e′ did not significantly change per year (p-value: 0.927). However, for patients with eGFR < 60, a statistically significant (p = 0.014) increase in the E/e′ of 0.45 (0.09, 0.81) was observed per year. Hypertension, diabetes mellitus, and cardiovascular disease were found to affect the change in E/e′, with estimates of 0.95 (0.41, 1.49), 1.82 (0.82, 2.89), and 1.25 (0.54, 1.97), respectively. Conclusion The trajectory of changes in E/e′ over time was significantly affected by varying levels of kidney function. Patients with impaired kidney function (eGFR < 60) have a higher E/e’ compared to those with normal kidney function (eGFR ≥ 90) and presented a significant increase of E/e’ per year.

#2752 Decline of residual renal function in peritoneal patients: in search of the lost kidney?

Abstract Background and Aims The latest (2020) recommendations of the International Society of Peritoneal Dialysis have proposed a new paradigm of adequacy. In this context, preserving residual renal function (RRF) is considered one of the most important therapeutic targets to reduce cardiovascular risk and mortality. Incremental peritoneal dialysis can contribute to preserving RRF. The goal of this study is to evaluate factors which are associated with a decline in RRF in APD patients. Method We conducted a retrospective study of incidental peritoneal dialysis patients between 2020 and 2022. We started considering 62 patients who underwent APD. 23 were excluded due to lack of data, follow-up of less than 1 year, need for haemodialysis sessions before or during follow-up, interfering surgery (bariatric surgery and nephrectomy) and treatment using the CAPD technique. We analyzed data from 39 APD patients (see Table 1) and classified them into two groups based on their RRF decline using the cut-off of 1 ml/min/year (calculated as the mean of urea and creatinine clearance). They were distinguished into slow progressors and fast progressors and we identified any differences in clinical and dialysis parameters at baseline and 12-month follow-up. We calculated dialytic, renal and total Kt/V in both groups and looked for possible predictors of faster RRF loss. For statistical analysis, we used ANOVA for continuous variables, Kruskal-Wallis for non-continuous variables and Fisher for qualitative variables. Finally, predictive data were extracted using logistic regression. Results We found 22 slow progressors and 17 fast progressors. A significant difference was found in the prevalence of cardiovascular disease (18.2% vs 47.1%, p 0.028), residual renal function (5.71 ml/min vs 6.85 ml/min, p 0,03) and dialysing solution volumes (13.2 L vs 14.1 L, p 0.05) between the two groups, with higher values in the fast progressors. In this group, more male patients were also observed (p 0.11), treated with 2 or more antihypertensive drugs (p 0.30) and exposed to higher weekly dialysate glucose (p 0.23) and daily ultrafiltration rates (p 0.23). At the 12-month follow-up, the mean decline in renal function was -1, 56 ml/min in the entire sample, -3.03 ml/min in the fast progressors group and -0.43 ml/min in the slow progressors group; the change in daily Uf inversely correlated with the change in RRF (p 0.025; r -0.35, Fig. 1). There was a mean reduction in ultrafiltrate volume (-22.7 ml vs +123.5 ml, p 0.028) and in the amount of glucose in the dialysing solutions (-138.6 g vs +100.5 g, p 0.007) compared to baseline values in patients who preserved RRF. In contrast, the difference between the two groups in the number of patients who started PD with<5 sessions per week is borderline (p 0.099). Weekly dialysis Kt/V is higher in fast-progressor patients (1 vs 0.88; p 0.205) with a total weekly Kt/V in both cases above the recommended target of 1.7. On multivariate regression analysis, baseline renal function and the presence of heart disease correlate with a more rapid decline in RRF (p 0.047; p 0.021 respectively). Conclusion With the limitations of low sample size and short follow-up time, we observed that ultrafiltration and peritoneal exposure to dialysate glucose may play a role in RRF loss, but more research is needed to confirm this. We found that patients with heart disease and higher baseline RRF were more likely to experience a faster decline in RRF. Overall findings suggest that maintaining RRF is crucial in APD patients, and incremental dialysis can help preserve it. We recommend further studies with longer follow-up times to better understand the relationship between RRF and APD.

#2775 ERCOS multicenter Spanish study: clinical profile of patients with chronic kidney disease G3a-G5D and osteoporosis

Abstract Background and Aims Fracture risk evaluation has recently been integrated into the 2017 KDIGO CKD-MBD (Chronic Kidney Disease- Mineral and Bone Disorder) guideline and its 2021 Spanish endorsement. It is now suggested to test bone mineral density (BMD) to assess fracture risk “if results will impact treatment decisions”. In fact, multiple new prospective studies have now documented that lower BMD predicts incident fractures in patients with CKD G3a–G5D. However, we scarcely know current real clinical practice in this population. Thus, the aim of the ERCOS (“Enfermedad Renal Crónica OSteoporosis”) study was to describe the clinical profile of patients with CKD who had been diagnosed of osteoporosis in outpatient Nephrology and Rheumatology clinics in Spain. Method ERCOS is a descriptive, observational, and multicenter Spanish study. Patients were recruited by consecutive sampling from 15 different Spanish hospitals. Osteoporosis characteristics (history of fragility fracture, BMD and other fracture risk factors), associated comorbidities, biochemical parameters and treatment were analyzed. Results A total of 163 patients (median age 77 years old) were included. Most were women (71.2%) and 98.3% of them were postmenopausal. Hypertension was the most frequent comorbidity (87.1%) and “attributed” cause of CKD (43.2%). Diabetes mellitus and cardiovascular disease were present in 35.6% and 29.4% of patients, respectively. Median estimated glomerular filtration rate was 36 ml/min/1.73 m2 [creatinine 1.48 mg/dl (95% CI 1,2-2)]. 38% of patients were G5D CKD patients (95.2% undergoing hemodialysis). 37.7% of patients had had a fragility fracture after the diagnosis of CKD (vertebral 52.5%, hip 24.6%, wrist 21.3%, humerus 16.4%, among others). Importantly, despite the diagnosis of osteoporosis, only 60.1% of the patients received specific treatment (mainly bisphosphonates or denosumab). Moreover, antiosteoporotic treatment was much more frequently prescribed by rheumatologists (46.9%), internal medicine physicians (23.5%), and only 13.3% was prescribed by nephrologists. 19.4% of patients suffered from fragility fractures even after initiating specific treatment. Conclusion Most patients with moderate and severe CKD with osteoporosis were old postmenopausal women with a high prevalence of diabetes or cardiovascular disease. Although about 40% had even suffered a fragility fracture, there is a high treatment gap, especially relevant among nephrologists. A call to action and to avoid existing therapeutic nihilism seems necessary, expanding the knowledge of the new more proactive guidelines and homogenizing the care and therapeutic approach in these patients.

#2219 Glycemic control and adverse outcomes in patients with diabetes and CKD stage 4-5: a nationwide cohort study

Abstract Background and Aims Although poor glycemic control is strongly associated with adverse clinical outcomes, few studies have evaluated their risk across the full glycemic spectrum in patients with moderate to advanced chronic kidney disease (CKD). Guidelines for HbA1c targets are mainly derived from extrapolation of trials conducted in people with normal or mildly reduced kidney function. In non-dialysis CKD individualized targets are recommended, often aiming for less strict glycemic control, due to lack of evidence for the efficacy of lower HbA1c, and potentially greater harm. In this study, we analyzed long-term outcomes across the full spectrum of HbA1c in CKD stage 4-5. Method Using data from the Swedish Renal Registry, we included patients with diabetes and CKD stages 4-5. Adjusted cause-specific Cox models were used to analyze associations between the one-year baseline mean HbA1c level (<43, 43-52 [reference], 53-64, 65-74, 75-89, ≥90 mmol/mol) and the occurrence of major adverse cardiovascular events (MACE, a composite of cardiovascular death, hospitalization for myocardial infarction or stroke), kidney replacement therapy (KRT), all-cause mortality, and hospitalization/death due to hypoglycemia. Results We included 2571 patients (71 years, 64% men, eGFR 20 mL/min per 1.73m², HbA1c 59.7 mmol/mol [7.6%], 75% insulin users). At baseline, patients with a higher HbA1c level were younger, had a higher prevalence of cardiovascular disease and were more likely prescribed insulin. Kidney function and malnutrition-inflammation markers were, however, not different between groups. Over a median follow-up of 4.9 [4.6;5.2] years, 939 (37%) KRT, 1078 (42%) MACE, and 1523 (59%) deaths occurred. Increasing HbA1c was gradually associated with the risk of MACE (adjusted HR from 0.76 [95% CI: 0.60-0.96] for HbA1c <43 mmol/mol to 1.39 [1.01-1.92] for HbA1c ≥ 90 mmol/mol) (Fig.). In contrast, a J-shaped relationship was observed for the risk of all-cause mortality. Compared to the reference group (43-52 mmol/mol; 5-year absolute risk 52% [48-56]), a HbA1c <43 mmol/mol was not associated with a higher mortality (adjusted HR 1.03 [0.86-1.23], 5-year absolute risk 57% [51-63]), while any HbA1c above 75 mmol/mol was associated with a higher risk of death. The risks of KRT and severe hypoglycemia were not different across HbA1c levels. Conclusion In CKD stage 4-5, HbA1c above the general recommendation for non-CKD patients (43-52 mmol/mol) is associated with a higher risk of MACE and all-cause mortality, but not KRT, without increased risk of severe hypoglycemia. This suggests that targeting a lower HbA1c, together with other cardio-reno-metabolic prevention strategies, might contribute to improve health outcomes in this very high-risk population.

#1804 Long-term outcomes of CKD patients with lupus nephritis: a nationwide cohort study

Abstract Background and Aims Health trajectories of patients with lupus nephritis (LN) are poorly understood in the setting of moderate and advanced chronic kidney disease (CKD). Furthermore, data on comparison of outcomes of LN to other forms of CKD are scarce. Therefore, the aim of this study was to compare long-term outcomes between LN and CKD from other etiologies. Method Using data from the Swedish Renal Registry (2006-2021), we compared clinical outcomes between patients with moderate and advanced CKD related to LN (LN-CKD), and patients with CKD due to primary glomerular diseases (PGD-CKD, i.e. IgA nephropathy, focal segmental glomerulosclerosis, membranous nephropathy), and due to other common CKD etiologies with high cardiovascular risk (Other-CKD, mostly diabetes and nephrosclerosis). Cox proportional hazard models were used to estimate the adjusted hazard ratios of mortality, major cardiovascular events (MACE), heart failure (HF), kidney replacement therapy (KRT) and acute kidney injury (AKI). Models were adjusted for age, sex, comorbidities, clinical and biological data including kidney function, medications and healthcare utilization. Results At baseline, patients with LN-CKD (N = 317, 61 years, 76% women, median eGFR 30 mL/min per 1.73 m²) and PGD-CKD (N = 2296, 57 years, 30% women, eGFR 29 mL/min per 1.73 m²), were younger and had lower prevalence of cardiovascular disease than patients with Other-CKD (N = 34778, 75 years, 36% women, eGFR 25 mL/min per 1.73 m²). Over a median follow-up of 6.2 [3.3; 9.8] years, 19029 deaths (51%), 15768 (42%) MACE and 8390 (22%) KRT events occurred. The unadjusted 5-year absolute risks of death and MACE were high both in patients with LN-CKD (27% and 25%) and Other-CKD (50% and 44%), but lower in those with PGD-CKD (16% and 14%), whereas the 5-year absolute KRT risk was higher in patients with PGD-CKD (PGD-CKD: 37%, LN-CKD: 23%, Other-CKD: 23%). In multivariable analyses and as compared to PGD-CKD, patients with LN-CKD had a higher risk of death (adjusted HR: 1.63 [95% CI: 1.32-2.02]), MACE (1.65 [1.31-2.08]), HF (1.68 [1.31-2.14]) and AKI (1.45 [1.02-2.05]) and showed a lower risk of KRT (HR: 0.81 [0.64-1.02]), although the 95% CI slightly overlapped (Figure, panel A). In contrast, the risks of adverse events were similar between patients with LN-CKD and those with Other-CKD (Figure, panel B). Conclusion While LN-CKD had a lower risk of KRT than PGD-CKD, they exhibited a higher risk of death, MACE, KRT, HF and AKI, reaching the risk magnitude of patients with high cardiovascular burden (Other-CKD). Our findings may inform decisions for care planning in patients with advanced CKD and LN.

#2812 Continuous blood pressure monitoring with a finger cuff is unreliable in chronic hemodialysis patients

Abstract Background and Aims Intradialytic hypotension (IDH) is the most common complication of hemodialysis (HD), which is often related to ultrafiltration. Due to the high prevalence of cardiovascular disease (CVD), compensatory mechanisms often fail. In clinical practice, BP is measured 2x/hour, while additional readings are only performed when symptoms arise. However, since IDH defined by a nadir systolic BP (SBP)<90 mmHg or <100 mmHg (depending on pre-dialysis SBP), regardless of symptoms, is most strongly associated with mortality, current BP measurement frequency may severely underestimate the true incidence of IDH. Continuous BP-monitoring may offer a solution to this issue. The Clearsight device (CSD) is a non-invasive continuous BP-monitoring system that measures arterial pressure and waveforms through a finger cuff by photoplethysmography. Yet, a compromised peripheral circulation may hamper its reliability in HD patients. This study aims to assess the agreement between intradialytic CSD-monitoring and standard oscillometric brachial arterial pressure (oBAP) assessment. Methods 40 Chronic HD patients were cross-over randomized to 4 modalities, each for 2 weeks: [standard HD (S-HD), cool HD (C-HD), low volume hemodiafiltration (LV-HDF) and high-volume HDF (HV-HDF)]. During one session of each second week, BP and heart rate (HR) were continuously recorded with the CSD (BMEYE/Edwards Lifesciences) and every 15 minutes with a brachial arterial cuff (contralateral of the fistula or graft, if applicable). Simultaneous measurements of SBP, diastolic BP (DBP) and HR were compared with descriptive statistics (mean difference [bias, BAP minus CSD], standard deviation (SD) and range) and Bland-Altman analysis. Bias was defined as the mean difference between oBAP and CSD, and 95% limits of agreement (LA) as the mean difference ±1.96 SD. Post-hoc, patients were stratified into tertiles of unexplained missing CSD-readings, to explore whether specific patient characteristics explain failed readings. Results 75% of patients was male, with a mean age 69.7 (±13.5 years) and median dialysis vintage 3.0 years (IQR 1.0-5.8). Diabetes mellitus and CVD were present in 48% and 73%, resp. Of the 2720 paired BP-measurements, 42% CSD and 6% of oBAP-readings were missing, leaving 36% of absent CSD-readings unexplained. Bland-Altman analysis, comparing oBAP and CSD-measurements, revealed a mean bias ± LA of 13.3 ± 44.5 mmHg for SBP, a mean bias ± LA of 13.3 ± 25.5 for DBP, and a mean bias ± LA of −0.03 ± 22.9 for HR. Surprisingly, the group with a high (>38%) proportion of unexplained missing CSD-values was significantly younger compared to the low (<21%) and intermediate group (21-38%) (p = 0.015), whereas no significant differences were observed with respect to dialysis vintage, diabetes mellitus or CVD. Conclusions 1) Compared to the oBAP method, finger cuff-monitoring shows poor precision and accuracy in BP-measurements, but good accuracy and poor precision in HR-readings; 2) 1/3 of readings failed for unknown reasons. Thus, CSD-monitoring is unsuitable for intradialytic hemodynamic monitoring in chronic HD patients.

#2985 Gut microbiome-dependent systemic alterations in experimental chronic kidney disease

Abstract Background and Aims Patients diagnosed with Chronic Kidney Disease (CKD) undergo a notable decline in both quality of life and life expectancy, primarily attributable to the heightened prevalence of cardiovascular diseases (CVD). These conditions not only contribute to the initiation of CKD but are also a consequence of inflammation associated with CKD. Despite optimal kidney replacement therapies, irreversible alterations of the CV system may persist. The responsible mechanisms in CKD leading to CVD are incompletely understood. CKD is characterized by gut microbial dysbiosis, with a significant proportion of uremic toxins suspected to have microbial origin. We hypothesize that the gut microbiota promotes inflammation and CV risk in states of impaired kidney function. Method Experimental CKD was induced in 129sv mice by 5/6 nephrectomy. Prior to nephrectomy, mice were assigned to receive either glucose (Ctrl) or a non-absorptive antibiotic cocktail (comprising Ampicillin, Metronidazole, Neomycin, and Vancomycin, Abx) via the drinking water to deplete their microbiomes throughout the 13-week study period. Ctrl and Abx-treated Sham-operated mice served as controls. Plasma, feces, and urine specimens were systematically collected at diverse time intervals, facilitating the longitudinal exploration of metabolite dynamics and CKD progression through an untargeted Nuclear Magnetic Resonance (NMR) approach. Simultaneously, echocardiography assessments were conducted at identical time points to assess cardiac function. Results Abx-treated CKD mice displayed improved kidney function, demonstrated by significantly reduced levels of plasma Cystatin C (0.2913 ± 0.1850 mg/L) compared to Ctrl (0.9133 ± 0.6616 mg/L)(p = 0.0256). Hearts from Abx-treated CKD mice exhibited significantly less remodeling, independent of their blood pressure (radiotelemetry measurements). The ratio of left ventricular (LV) mass to tibia length was 4.858 ± 0.3453 in the Abx-treated group compared to Ctrl (8.198 ± 0.3542) (p < 0.0001). Sirius red stained hearts revealed significantly less fibrosis in Abx-treated CKD mice (5.784 ± 5.465%) compared to Ctrl (11.98 ± 3.741%) (p = 0.0218). The cardiac expression of several damage-associated genes (Npbb, Ctgf, and Ngal) portrayed the same trend. To elucidate the interplay between the microbiome and the immune system underlying these observed effects, we provide a comprehensive atlas of the immune landscape in different organs (blood, spleen, heart, intestine), along with a catalogue of gut-derived metabolites, shedding light on the systemic alterations induced by microbiome-dependent mechanisms in CKD. Conclusion Our findings suggest that microbiome-dependent mechanisms drive kidney function decline and cardiac remodeling in experimental CKD. These results underscore the interplay between microbial alterations, metabolite dynamics, immune response, and cardiovascular complications in the context of CKD.

#3011 Pathophysiological link between renal and cardiovascular disease in patients with type 2 diabetes mellitus: preliminary results from a proteomic study

Abstract Background and Aims Diabetic kidney disease (DKD) affects nearly 40% of people with diabetes and is the leading cause of chronic kidney disease (CKD). A high prevalence of cardiovascular disease (CVD) is known in this population. Indeed, DKD and CVD are often related and lead to worse outcomes in type 2 diabetes mellitus (T2D), i.e. cardiac fibrosis and CV events are frequently described in patients with DKD. However, specific associations and accurate prediction biomarkers for DKD and CVD progression in T2D are still lacking as various proteins may play a multi-mechanistic role. Lipocalin-2 (LCN2) is involved in several pathophysiological processes (inflammation, renal disease and cardiometabolic complications in CKD). Its leukocyte-chemoattractant effect has shown to reduce CVD in experimental models of cardiomyopathy when suppressed. Excess LCN2 in CKD is a determinant of disease progression, but also a potent mediator of cardiac injury in CKD. Insulin-like growth factor binding proteins (IGFBPs) also play an important role in cell homeostasis by regulating cell transcription, migration, and apoptosis. IGFBP-3 down-regulation has demonstrated to be a predictor of rapid renal progression in T2DM. On the other hand, IGFBP-6 increases when GFR drops, being involved in the pathophysiological process of CKD as an apoptosis-inducing protein In this context, a proteomic-based approach would optimise the clinical utility of multiple plasma biomarkers. The aim was to identify proteins associated with DKD, cardiac fibrosis (estimated by the PICP biomarker) and the presence of a new CV event. Method A prospective cohort of 91 T2D patients, with a minimum follow-up of 3 years (mean: 4 years) was analysed. We evaluated the association between rates of change in GFR and PICP during follow-up (fold-change: end/initial) and their interaction with the development of a composite of cardiovascular (CV) events: CV death, stroke, ischaemic heart disease, atrial fibrillation, valvular heart disease and CV-related hospitalisation. In addition, ninety-two proteins were quantified in serum samples using a multiplex proximity extension assay with high-throughput protein detection technology (Olink proteomics, Cardiometabolic panel). Associations between variations in these proteins and changes in PICP and eGFR (all expressed as fold change from baseline) were assessed using linear regression analyses adjusted for their respective baseline values. All analyses were adjusted by multiple testing (Benjamini-Hochberg, FDR = 0.05%) using R software. Results Sixty-eight (74.7%) men and 23 (25.3%) women were included in the analysis. The mean age at baseline was 65.8 years, and the mean follow-up was 4 years (minimum 3 years). Sixteen cardiovascular events were recorded. An inverse association was observed between GFR and PICP (p = 0.003). Interaction analysis showed that this correlation occurred only in patients with incident CV events (p for interaction <0.001) (Fig. 1). By proteomic analysis (Fig. 2) several proteins were found to be significantly related to one of the three parameters studied (change in GFR, change in PICP and change with cardiovascular event), of which 3 proteins presented an overlap for all the parameters analysed: Lipocalin 2 (LCN2) and Insulin-like growth factor binding proteins 3 and 6 (IGFBP3 and IGFBP6). Interestingly, LCN2 and IGFBP6 were more highly expressed in patients with CV events whereas IGFBP3 was downregulated in these patients. Conclusion In patients with DKD, worsening enal function is associated with elevated circulating levels of the collagen synthesis biomarker PICP, particularly in those who developed at least one CV event. The link shown with LCN2, IGFBP-6 and IGFBP-3 shed light on possible multi-mechanistic pathways involved in DKD and narrow the scope towards a common pathway involving an interaction between pro-apoptotic and local inflammatory factors.

The pattern of cardiovascular disease in River Nile State (October 2019-April 2020)

Background: The rise of cardiovascular diseases poses a significant global threat, not only in terms of morbidity and mortality but also due to their substantial economic burden. Understanding the specific patterns of CVDs within various populations is crucial for effective prevention, early diagnosis, and management. Objective: This study aimed to determine the pattern of cardiovascular disease using echocardiography in River Nile State. Methods: This prospective cross-sectional hospital-based study conducted from October 2019 to April 2020 aimed to ascertain the pattern of cardiovascular diseases using echocardiography in River Nile State. A sample of 1000 participants from Atbara Teaching Hospital, Atbara Complex, and Shendi Teaching Hospital was included. The study population comprised all Sudanese patients undergoing echocardiography in the region. Inclusion criteria involved patients presenting for echocardiography who consented to participate, while refusal to participate constituted exclusion criteria. Data collection involved obtaining written consent from patients and recording echocardiographic findings, including age, gender, and patterns of heart disease, using standardized data sheets. Results: The findings revealed a mean age of 72±6.8 years, with females comprising 64.7% of the sample. Hypertensive heart disease (31.5%) and valvular lesions (29.8%) emerged as the most prevalent cardiovascular diseases. Ischemic heart disease (11.2%), rheumatic heart disease (8.3%), and cardiomyopathy (5.7%) were also notable. Patterns of cardiovascular diseases showed significant associations with age and gender, with hypertensive heart disease and valvular lesions more prevalent in older age groups, while congenital heart disease was more prevalent among younger individuals (20–40 years). Conclusion: The study revealed that hypertensive heart disease (31.5%) and valvular lesions (29.8%) as the dominant CVD patterns. Focusing on these conditions with tailored prevention, early diagnosis, and management is crucial, especially for older individuals. Keywords: Cardiac diseases, Comorbidity, Nile State, Pattern.

Self-Supervised Machine Learning to Characterise Step Counts from Wrist-Worn Accelerometers in the UK Biobank.

Step count is an intuitive measure of physical activity frequently quantified in health-related studies; however, accurate step counting is difficult in the free-living environment, with error routinely above 20% in wrist-worn devices against camera-annotated ground truth. This study aims to describe the development and validation of step count derived from a wrist-worn accelerometer and assess its association with cardiovascular and all-cause mortality in a large prospective cohort. We developed and externally validated a self-supervised machine learning step detection model, trained on an open-source and step-annotated free-living dataset. 39 individuals will free-living ground-truth annotated step counts were used for model development. An open-source dataset with 30 individuals was used for external validation. Epidemiological analysis was performed using 75,263 UK Biobank participants without prevalent cardiovascular disease (CVD) or cancer. Cox regression was used to test the association of daily step count with fatal CVD and all-cause mortality after adjustment for potential confounders. The algorithm substantially outperformed reference models (free-living mean absolute percent error of 12.5%, versus 65-231%). Our data indicate an inverse dose-response association, where taking 6,430-8,277 daily steps was associated with 37% [25-48%] and 28% [20-35%] lower risk of fatal CVD and all-cause mortality up to seven years later, compared to those taking fewer steps each day. We have developed an open and transparent method that markedly improves the measurement of steps in large-scale wrist-worn accelerometer datasets. The application of this method demonstrated expected associations with CVD and all-cause mortality, indicating excellent face validity. This reinforces public health messaging for increasing physical activity and can help lay the groundwork for the inclusion of target step counts in future public health guidelines.

Predicting heart failure symptoms from the apnoea-hypopnoea index determined by full- night polysomnography.

Sleep-disordered breathing (SDB) is closely related to cardiovascular diseases. The higher the apnoea-hypopnoea index (AHI), the higher the prevalence of cardiovascular diseases. Despite these findings suggesting a close link between SDB and heart failure, the relationship between the severity of SDB and the onset of heart failure symptoms in individuals without apparent heart failure symptoms (Heart Failure Stage A+B) remains poorly understood. Between December 2010 and June 2017, we conducted full-night polysomnography (PSG) at the Nippon Medical School Chiba Hokusoh Hospital, extracting patients who were at risk of heart failure (Stage A or B in the Heart Failure Guidelines). Using a median cut-off of AHI≥41.6 events/hour, we divided the patients into two groups and examined the composite endpoint of all-cause mortality plus hospitalization due to heart failure as the primary endpoint. We included 230 patients (mean age 63.0±12.5years, 78.3% males) meeting the selection criteria. When comparing the two groups, those with AHI<41.6 events/hour (L group, n=115) and those with AHI≥41.6 events/hour (H group, n=115), the H group had higher body mass index and higher serum triglyceride, and lower the frequency of acute coronary syndrome and lower estimated glomerular filtration rate than did the L group, but no other patient characteristics differed significantly. The H group had a significantly higher incidence of the composite endpoint than did the L group (10.6% vs. 2.6%, P=0.027). Factors associated with the composite endpoint were identified through multivariate analyses, with AHI, haemoglobin, and left atrial dimension emerging as significant factors (hazard ratio [HR]=1.02, 95% confidence interval [CI]=1.00-1.04, P=0.024; HR=0.71, 95% CI=0.54-0.94, P=0.017; and HR=1.10, 95% CI=1.03-1.18, P=0.006, respectively). Conversely, the minimum SpO2 during PSG (<80%) was not associated with the composite endpoint. In patients with SDB who are at risk of heart failure, severe SDB is associated with a high risk of all-cause mortality and the development of heart failure. Additionally, combining cardiac echocardiography and PSG data may improve risk stratification, offering potential assistance for early intervention. Further examination with a validation cohort is necessary.

Examining the relationship between Life’s Essential 8 and atherosclerotic cardiovascular disease among Adults in the United States: Insights from the National Health and Nutrition Examination Surveys (2017-2020)

The American Heart Association recently updated the assessment of cardiovascular health (CVH) with the Life&amp;rsquo;s Essential 8 (LE8) score. Our cross-sectional analytical study utilized data from 5042 adults in the United States (US) from the 2017 to 2020 NHANES surveys to examine the relationship between CVH assessed by LE8 metrics and the prevalence of atherosclerotic cardiovascular disease (ASCVD). Multivariate linear regressions were utilized to explore the relationship between CVH metrics and ASCVD, while linear probability models were used to predict ASCVD prevalence based on achieved LE8 scores. Controlling for relevant covariates revealed an inverse association between LE8 metrics and ASCVD prevalence. Improvements in LE8 were linked to a 29% reduction in ASCVD prevalence, with transitions to higher LE8 quartiles predicting a 4.8% reduction in ASCVD prevalence. Subgroup analysis indicated significant effects of age, education, and gender on ASCVD prevalence, with younger age, college education, and the female gender being associated with lower prevalence (P &lt; 0.05). Higher LE8 scores correlated with decreased ASCVD prevalence, while factors such as younger age, college education, and the female gender were also associated with lower ASCVD prevalence. Conversely, transitioning from married to divorced/widowed/separated status was linked to increased ASCVD prevalence (P &lt; 0.01).

Cardiometabolic factors and population risks of cardiovascular disease in community-dwelling adults with varied blood pressure statuses.

To examine the differential associations between cardiometabolic risk factors and cardiovascular disease (CVD), and to evaluate the population-attributable fractions (PAFs) for CVD among community-dwelling adults with varied blood pressure (BP) statuses. This prospective cohort study included participants without prevalent CVD from a subcohort of the China Patient-Centred Evaluative Assessment of Cardiac Events Million Persons Project. Participants were divided into four BP groups according to the American College of Cardiology/American Heart Association guidelines. The study exposure comprised the selected cardiometabolic risk factors, including waist circumference (WC), body mass index, (BMI) heart rate, fasting blood glucose (FBG), low-density lipoprotein cholesterol, and remnant cholesterol. The outcome was hospitalizations for CVD. Cox proportional hazard models were conducted, and the PAFs were calculated in the analysis. Among the 94 183 participants (39.0% were men, mean age: 54.2 years), 26.6% had Stage 1 hypertension and 30.8% had Stage 2 hypertension. A total of 6065 hospitalizations for CVD were captured after a median follow-up of 3.5 years. BP (per 1-standard deviation [SD]: hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.29, 1.40), FBG (per 1-SD: HR 1.16, 95% CI 1.14, 1.19) and WC (per 1-SD: HR 1.41, 95% CI 1.36, 1.47) were three major contributors to CVD events. BP status significantly modified the associations of abdominal obesity, suboptimal BMI, suboptimal heart rate and abnormal FBG with CVD, with stronger associations with CVD observed in optimal BP groups compared to hypertensive groups (p for risk factor-by-BP group interaction <0.05). Participants with all cardiometabolic risk factors were at the highest risk for CVD, accounting for 35.6% (95% CI 30.0, 40.8) of the PAF for CVD. Among the risk factors, BP control explained the highest PAF for CVD (15.1%, 95% CI 8.2, 21.4) The overall PAFs of cardiometabolic risk factors for CVD were higher among the normotensive participants compared to the hypertensive participants. The awareness and control rates of hypertension were extremely low among Southern Chinese adults. BP status significantly modified the associations between cardiometabolic risk factors and CVD, and the overall PAFs for CVD were higher among people with normal BP. Dedicated efforts are needed to improve the management of cardiometabolic factors.

Automatic multi-label diagnosis of single-lead ECG using novel hybrid residual recurrent convolutional neural networks

Arrhythmia is a prevalent cardiovascular disease that can unveil various heart health issues. In recent times, the rise of wearable devices has garnered attention towards the advantages of portable single-lead ECG devices in heart health monitoring. Achieving end-to-end ECG automatic diagnosis through deep learning is essential due to the time-consuming and labour-intensive characteristics of manual diagnosis of ECG records. This paper presents the design of a hybrid residual recurrent convolutional neural network (HRRCNN) for automatically diagnosing single-lead ECG with multiple labels. Firstly, the convolutional layers and residual networks extract the spatial and short-term temporal features. Subsequently, a hybrid recurrent neural network (RNN) comprised of a double-layer bidirectional gated recurrent unit (GRU) and a bidirectional long short-term memory (LSTM) is employed to capture long and short-term temporal features. Finally, an output layer, comprising an attention layer and a fully connected layer, converts the extracted features into classification results. To evaluate the performance of HRRCNN, a dataset from the Shanghai First People’s Hospital Affiliated to Shanghai JiaoTong University(Shanghai General Hospital, SGH) is utilized. The experimental results demonstrate that HRRCNN achieves an accuracy of 95.08 %, F1-macro of 87.22 %, Sensitivity of 88.51 %, and a positive prediction rate of 86.13 %. Comparative analysis with existing methods underscores the superior performance of HRRCNN, thereby establishing its potential as an out-of-hospital heart health monitoring tool and an auxiliary tool in clinical settings.

The association between the triglyceride–glucose index and the risk of cardiovascular disease in US population aged ≤ 65 years with prediabetes or diabetes: a population-based study

BackgroundThe relationship between the triglyceride–glucose (TyG) index and the risk of cardiovascular disease (CVD) in the U.S. population under 65 years of age with diabetes or prediabetes is unknown. The purpose of this study was to investigate the relationship between baseline TyG index and CVD risk in U.S. patients under 65 years of age with diabetes or prediabetes.MethodsWe used data from the 2003–2018 National Health and Nutrition Examination Survey (NHANES). Multivariate regression analysis models were constructed to explore the relationship between baseline TyG index and CVD risk. Nonlinear correlations were explored using restricted cubic splines. Subgroup analysis and interaction tests were also conducted.ResultsThe study enrolled a total of 4340 participants with diabetes or pre-diabetes, with a mean TyG index of 9.02 ± 0.02. The overall average prevalence of CVD was 10.38%. Participants in the higher TyG quartiles showed high rates of CVD (Quartile 1: 7.35%; Quartile 2: 10.04%; Quartile 3: 10.71%; Quartile 4: 13.65%). For CVD, a possible association between the TyG index and the risk of CVD was observed. Our findings suggested a linear association between the TyG index and the risk of CVD. The results revealed a U-shaped relationship between the TyG index and both the risk of CVD (P nonlinear = 0.02583) and CHF (P nonlinear = 0.0208) in individuals with diabetes. Subgroup analysis and the interaction term indicated that there was no significant difference among different stratifications. Our study also revealed a positive association between the TyG index and comorbid MetS in the U.S. population under 65 years of age with prediabetes or diabetes.ConclusionsA higher TyG index was linked to an increased likelihood of CVD in the U.S. population aged ≤ 65 years with prediabetes and diabetes. Besides, TyG index assessment will contribute to more convenient and effective screening of high-risk individuals in patients with MetS. Future studies should explore whether interventions targeting the TyG index may improve clinical outcomes in these patients.

Health Outcome Comparison Based on Dietary Inflammatory Levels among Sample of Korean Elderly.

The aim of this study was to investigate the effect of a senior-friendly diet based on the dietary inflammatory index (DII) on the nutritional status and health indicators of older people. A total of 256 participants were classified into tertiles based on their DII values and split into intervention (n = 201) and control (n = 55) groups. The intervention group was provided with a senior-friendly diet, and the control group was allowed to eat their usual diet. Before and after the trial, anthropometric measurements, blood analyses, and questionnaires were completed for both groups. The mean age of the participants was 82.49 years, and 66.4% were female. On average, participants had 2.5 medical conditions, with a notable prevalence of cardiovascular disease. Following the intervention, the energy, carbohydrate, protein, and fat intakes significantly increased in the intervention group compared to pre-intervention levels. Tertile 3 exhibited substantial improvements in total nutrition score, NQ-E balance, and DII total score, as well as in triglycerides and blood glucose, attributed to this dietary intervention compared to other groups. In comparison with Tertile 1, nutrient intake and nutritional status in Tertile 3 were closely associated with significant influencing factors of the dietary intervention. For the group with the worst DII (Tertile 3), this dietary intervention greatly improved nutritional status, nutrient intake, and clinical indicators; thus, this senior-friendly diet appears to be beneficial for elderly people with nutritional vulnerabilities.

Evaluation of Socio-demographic Factors and Comorbidities in Adult Hemophilia Patients

Purpose: The association between socio-demographic factors and hemophilia status and the prevalence of comorbidities were evaluated. Material and Methods: Patients with hemophilia A (n=111) and B (n=24) who were filled a questionnaire form about their sociodemographic factors were included in our study. Factor and inhibitor levels, comorbidities, factor replacement therapies, hemophilic arthropathy, viral status and annual bleeding episodes were recorded. Results: Median age was 39 years in 135 hemophilia patients and 63.1 % of all the patients had severe hemophilia which was significantly higher among hemophilia A patients (p=0.002). Most of the patients (74.8%) were treated with prophylactic factor replacement therapy. Inhibitor status was positive in 8.9% of all patients. Unemployment rate was found 33.3%. Annual bleeding episodes were higher in patients who had a job. Most of the patients (60 %) were graduated from at least high school. The prevalence of cardiovascular disease, hypertension, diabetes mellitus and obesity were 6.7%; 17.8%, 13.3%, 11.9% respectively. Although there is no association between the obesity and annual bleeding episodes, right ankle was the most affected joint in overweight/obese patients. Conclusion: Age-related comorbidities and the relation of hemophilia status and social life are needed to be more investigated.

Cardiovascular calcification in hemodialysis patients: A Qatar-based prevalence and risk factors study.

Patients with end-stage kidney disease on hemodialysis (HD) have an increased risk of death due to the high prevalence of cardiovascular disease. Vascular calcification (VC) is predictive of cardiovascular disease and mortality. We conducted a study to evaluate the prevalence and risk factors for VC in dialysis patients in Qatar. This is a retrospective nationwide study including all chronic ambulatory dialysis patients in Qatar from 2020 to 2022. We used our national electronic medical record to track demographics, clinical characteristics, comorbidities, laboratory values, and diagnostic data for each patient. Calcifications were assessed by echocardiography (routinely done for all our dialysis population per national protocol), computed tomography, X-ray, and ultrasound. The study protocol was approved by the local medical research ethics committee (MRC-01-20-377). 842 HD patients were included in this study. Vascular calcifications (VC) were prevalent in 52.6% of patients. The main site of VC was Mitral valve calcifications in 55.5% of patients. Patients with VC were significantly older and had more prevalence of diabetes mellitus (p = 0.001 and p = 0.006, respectively). There was no statistically significant difference between patients with calcifications and patients without calcifications regarding serum calcium, phosphorus, and PTH level. In multivariate analysis, age and diabetes significantly increased the risk factor for calcification (95% CI 1.033-1.065, p < 0.0001, and 95% CI 1.128-2.272, p < 0001, respectively). Moreover, higher vitamin D levels and higher doses of IV Alfacalcidol were significant risk factors for calcifications (95% CI 1.005-1.030, p < 0.007, and 95% CI 1.092-1.270, p < 0.0001, respectively). Our study found that vascular calcification was widespread among our dialysis population in Qatar. Implementing the practice of echocardiography in dialysis patients was extremely helpful and the most productive in detecting vascular calcification. Diabetes mellitus almost doubles the risk for vascular calcifications in dialysis patients. These results are beneficial in identifying risk factors for vascular calcification, which can help stratify dialysis patients' risk of cardiovascular disease and optimize prevention efforts.

Trends and Disparities in Treatment and Control of Atherosclerotic Cardiovascular Disease in US Adults, 1999 to 2018.

Although cardiovascular mortality continued declining from 2000 to 2019, the rate of this decrease decelerated. We aimed to assess the trends and disparities in risk factor control and treatment among US adults with atherosclerotic cardiovascular disease to find potential causes of the deceleration. A total of 55 ,021 participants, aged ≥20 years, from the 1999 to 2018 National Health and Nutrition Examination Survey were included, of which 5717 were with atherosclerotic cardiovascular disease. Risk factor control was defined as hemoglobin A1c <7%, blood pressure <140/90 mm Hg, and non-high-density lipoprotein cholesterol <100 mg/dL. The prevalence of atherosclerotic cardiovascular disease oscillated between 7.3% and 8.9% from 1999 to 2018. A significant increasing trend was observed in the prevalence of diabetes, obesity, heavy alcohol consumption, and self-reported hypertension within the population with atherosclerotic cardiovascular disease (Ptrend≤0.001). Non-high-density lipoprotein cholesterol <100 mg/dL increased from 7.1% in 1999 to 2002 to 15.7% in 2003 to 2006, before plateauing. Blood pressure control (<140/90 mm Hg) increased until 2011 to 2014, but declined to 70.1% in 2015 to 2018 (Ptrend<0.001, Pjoinpoint=0.14). Similarly, the proportion of participants achieving hemoglobin A1c control began to decrease after 2006 (Pjoinpoint=0.05, Ptrend=0.001). The percentage of participants achieving all 3 targets increased significantly from 4.5% to 18.6% across 1999 to 2018 (Ptrend=0.02), but the increasing trend decelerated after 2005 to 2006 (Pjoinpoint<0.001). Striking disparities in risk factor control and medication use persisted between sexes, and between different racial and ethnic populations. Worsened control of glycemia, blood pressure, obesity, and alcohol consumption, leveled lipid control, and persistent socioeconomic disparities may be contributing factors to the observed deceleration in decreasing cardiovascular mortality trends.