Adult outcomes of childhood kidney replacement therapy in Europe from 2008 to 2019: an ERA Registry study.

BACKGROUND AND HYPOTHESIS: Young adults starting kidney replacement therapy (KRT) during childhood and reaching their 18th birthday (i.e. adult survivors of childhood KRT) form a challenging population of interest to nephrologists treating adults, as during this period there will be a transition to adult renal centres. Nonetheless, few studies have focused on the epidemiology of KRT in this group. We aimed to provide an update on these patients' characteristics, treatment history, graft and patient survival, to report their 5-year prognosis, and expected remaining lifetime. METHODS: Data on KRT patients reaching their 18th birthday in 2008-2019 were collected from 21 European countries/regions providing individual patient data to the European Renal Association (ERA) Registry. Patient characteristics and treatment trajectories were examined before and after turning 18 years. Kaplan-Meier and Cox proportional hazards regression were used for patient and graft survival analyses. RESULTS: In total, 2944 patients were included. The proportion of adult survivors initiating KRT at a very young age (0-4 years), and undergoing pre-emptive kidney transplantation increased. Unadjusted 5-year patient survival was 96.9% (95% CI: 96.2-97.5). Dialysis patients had a higher risk of death than kidney transplant recipients (adjusted hazard ratio 5.44 (95% CI: 3.34-8.86)). Between ages 18 and 23 years, about 21% of the adult survivors lost their kidney transplant and 34% of the dialysis patients continued this treatment. Compared with the general population, life expectancy for eighteen-year-old kidney transplant and dialysis patients was 17 and 40 years shorter, respectively. CONCLUSION: Life expectancy of 18-year-old kidney transplant recipients was lower compared with the general population. Yet, having a functioning kidney graft at age 18 years resulted in better outcomes than being on dialysis. Nevertheless, between ages 18 and 23 years, about one-fifth of the kidney grafts failed and one-third of the patients remained on dialysis.

Cost-effectiveness of applying high-sensitivity troponin I to a score for cardiovascular risk prediction in asymptomatic population.

INTRODUCTION: Risk stratification scores such as the European Systematic COronary Risk Evaluation (SCORE) are used to guide individuals on cardiovascular disease (CVD) prevention. Adding high-sensitivity troponin I (hsTnI) to such risk scores has the potential to improve accuracy of CVD prediction. We investigated how applying hsTnI in addition to SCORE may impact management, outcome, and cost-effectiveness. METHODS: Characteristics of 72,190 apparently healthy individuals from the Biomarker for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project were included into a discrete-event simulation comparing two strategies for assessing CVD risk. The standard strategy reflecting current practice employed SCORE (SCORE); the alternative strategy involved adding hsTnI information for further stratifying SCORE risk categories (S-SCORE). Individuals were followed over ten years from baseline examination to CVD event, death or end of follow-up. The model tracked the occurrence of events and calculated direct costs of screening, prevention, and treatment from a European health system perspective. Cost-effectiveness was expressed as incremental cost-effectiveness ratio (ICER) in € per quality-adjusted life year (QALYs) gained during 10 years of follow-up. Outputs were validated against observed rates, and results were tested in deterministic and probabilistic sensitivity analyses. RESULTS: S-SCORE yielded a change in management for 10.0% of individuals, and a reduction in CVD events (4.85% vs. 5.38%, p<0.001) and mortality (6.80% vs. 7.04%, p<0.001). S-SCORE led to 23 (95%CI: 20-26) additional event-free years and 7 (95%CI: 5-9) additional QALYs per 1,000 subjects screened, and resulted in a relative risk reduction for CVD of 9.9% (95%CI: 7.3-13.5%) with a number needed to screen to prevent one event of 183 (95%CI: 172 to 203). S-SCORE increased costs per subject by 187€ (95%CI: 177 € to 196 €), leading to an ICER of 27,440€/QALY gained. Sensitivity analysis was performed with eligibility for treatment being the most sensitive. CONCLUSION: Adding a person's hsTnI value to SCORE can impact clinical decision making and eventually improves QALYs and is cost-effective compared to CVD prevention strategies using SCORE alone. Stratifying SCORE risk classes for hsTnI would likely offer cost-effective alternatives, particularly when targeting higher risk groups.

Serum Concentrations of Matrix Metalloproteinase-1 and Procollagen Type I Carboxy Terminal Propeptide Discriminate Infarct-Like Myocarditis and Non-ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Biomarkers simplifying the diagnostic workup by discriminating between non-ST-segment-elevation myocardial infarction (NSTEMI) and infarct-like myocarditis are an unmet clinical need. METHODS AND RESULTS: A total of 105 subjects were categorized into groups as follows: ST-segment-elevation myocardial infarction (n=36), NSTEMI (n=22), infarct-like myocarditis (n=19), cardiomyopathy-like myocarditis (n=18), and healthy control (n=10). All subjects underwent cardiac magnetic resonance imaging, and serum concentrations of matrix metalloproteinase-1 (MMP-1) and procollagen type I carboxy terminal propeptide (PICP) were measured. Biomarker concentrations in subjects presenting with acute coronary syndrome and non-ST-segment-elevation, for example NSTEMI or infarct-like myocarditis, categorized as the non-ST-segment-elevation acute coronary syndrome-like cohort, were of particular interest for this study. Compared with healthy controls, subjects with myocarditis had higher serum concentrations of MMP-1 and PICP, while no difference was observed in individuals with myocardial infarction. In the non-ST-segment-elevation acute coronary syndrome-like cohort, MMP-1 concentrations discriminated infarct-like myocarditis and NSTEMI with an area under the receiver operating characteristic curve (AUC) of 0.95 (95% CI, 0.89-1.00), whereas high-sensitivity cardiac troponin T performed inferiorly (AUC, 0.74 [95% CI, 0.58-0.90]; P=0.012). Application of an optimal MMP-1 cutoff had 94.4% sensitivity (95% CI, 72.7%-99.9%) and 90.9% specificity (95% CI, 70.8%-98.9%) for the diagnosis of infarct-like myocarditis in this cohort. The AUC of PICP in this context was 0.82 (95% CI, 0.68-0.97). As assessed by likelihood ratio tests, incorporating MMP-1 or PICP with age and C-reactive protein into composite prediction models enhanced their diagnostic performance. CONCLUSIONS: MMP-1 and PICP could potentially be useful biomarkers for differentiating between NSTEMI and infarct-like myocarditis in individuals with non-ST-segment-elevation acute coronary syndrome-like presentation, though further research is needed to validate their clinical applicability.

Impact of Lipoprotein(a) Level on Low-Density Lipoprotein Cholesterol- or Apolipoprotein B-Related Risk of Coronary Heart Disease.

BACKGROUND: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities. OBJECTIVES: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDLLp(a)corr) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events. METHODS: Among 68,748 CHD-free subjects at baseline LDLLp(a)corr was calculated as "LDL-C-Lp(a)-C," where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDLLp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile). RESULTS: Similar risk estimates for incident CHD were found for LDL-C and LDL-CLp(a)corr30 or LDL-CLp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; Pinteraction0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (Pinteraction0.49). CONCLUSIONS: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels.

Time-restricted eating affects human adipose tissue fat mobilization.

OBJECTIVE: Time-restricted eating (TRE), a dietary approach that confines food intake to specific time windows, has shown metabolic benefits. However, its impact on body weight loss remains inconclusive. The objective of this study was to investigate the influence of early TRE (eTRE) and delayed TRE (dTRE) on fat mobilization using human adipose tissue (AT) cultures. METHODS: Subcutaneous AT was collected from 21 participants with severe obesity. We assessed fat mobilization by measuring glycerol release in AT culture across four treatment conditions: control, eTRE, dTRE, and 24-h fasting. RESULTS: TRE had a significant impact on lipolysis (glycerol release [mean (SD)] in micromoles per hour per gram: control, 0.05 [0.003]; eTRE, 0.10 [0.006]; dTRE, 0.08 [0.005]; and fasting, 0.17 [0.008]; p < 0.0001). Both eTRE and dTRE increased lipolysis compared with the control group, with eTRE showing higher glycerol mobilization than dTRE during the overall 24-h time window, especially at the nighttime/habitual sleep episode (p < 0.0001). Further analysis of TRE based on fasting duration revealed that, independently of the time window, glycerol release increased with fasting duration (in micromoles per hour per gram: 8 h = 0.08 [0.001]; 12 h = 0.09 [0.008]; and 16 h of fasting = 0.12 [0.011]; p < 0.0001). CONCLUSIONS: This study provides insights into the potential benefits of TRE on fat mobilization and may guide the design of future dietary strategies for weight management and metabolic health.

Efficacy and Safety of Habitual Consumption of a Food Supplement Containing Miraculin in Malnourished Cancer Patients: The CLINMIR Pilot Study.

Taste disorders (TDs) are common among systemically treated cancer patients and negatively impact their nutritional status and quality of life. The novel food approved by the European Commission (EFSA), dried miracle berries (DMB), contains the natural taste-modifying protein miraculin. DMB, also available as a supplement, has emerged as a possible alternative treatment for TDs. The present study aimed to evaluate the efficacy and safety of habitual DMB consumption in malnourished cancer patients undergoing active treatment. An exploratory clinical trial was carried out in which 31 cancer patients were randomized into three arms [standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry)] for three months. Patients consumed a DMB tablet or placebo daily before each main meal (breakfast, lunch, and dinner). Throughout the five main visits, electrochemical taste perception, nutritional status, dietary intake, quality of life and the fatty acid profile of erythrocytes were evaluated. Patients consuming a standard dose of DMB exhibited improved taste acuity over time (% change right/left side: -52.8 ± 38.5/-58.7 ± 69.2%) and salty taste perception (2.29 ± 1.25 vs. high dose: 2.17 ± 1.84 vs. placebo: 1.57 ± 1.51 points, p < 0.05). They also had higher energy intake (p = 0.075) and covered better energy expenditure (107 ± 19%). The quality of life evaluated by symptom scales improved in patients receiving the standard dose of DMB (constipation, p = 0.048). The levels of arachidonic (13.1 ± 1.8; 14.0 ± 2.8, 12.0 ± 2.0%; p = 0.004) and docosahexaenoic (4.4 ± 1.7; 4.1 ± 1.0; 3.9 ± 1.6%; p = 0.014) acids in erythrocytes increased over time after DMB intake. The standard dose of DMB increased fat-free mass vs. placebo (47.4 ± 9.3 vs. 44.1 ± 4.7 kg, p = 0.007). Importantly, habitual patients with DMB did not experience any adverse events, and metabolic parameters remained stable and within normal ranges. In conclusion, habitual consumption of a standard 150 mg dose of DMB improves electrochemical food perception, nutritional status (energy intake, fat quantity and quality, fat-free mass), and quality of life in malnourished cancer patients receiving antineoplastic treatment. Additionally, DMB consumption appears to be safe, with no changes in major biochemical parameters associated with health status. Clinical trial registered (NCT05486260).

Distribution of papA and papG Variants among Escherichia coli Genotypes: Association with Major Extraintestinal Pathogenic Lineages.

The pyelonephritis-associated fimbria (P fimbria) is one of the most recognized adhesion determinants of extraintestinal pathogenic Escherichia coli strains (ExPECs). Twelve variants have been described for the gene encoding the P fimbria major structural subunit PapA and three variants for the gene encoding the adhesin subunit PapG. However, their distribution among the ExPEC diversity has not been comprehensively addressed. A complete landscape of that distribution might be valuable for delineating basic studies about the pathogenicity mechanisms of ExPECs and following up on the evolution of ExPEC lineages, particularly those most epidemiologically relevant. Therefore, we performed a massive descriptive study to detect the papA and papG variants along different E. coli genotypes represented by genomic sequences contained in the NCBI Assembly Refseq database. The most common papA variants were F11, F10, F48, F16, F12, and F7-2, which were found in significant association with the most relevant ExPEC genotypes, the phylogroups B2 and D, and the sequence types ST95, ST131, ST127, ST69, ST12, and ST73. On the other hand, the papGII variant was by far the most common followed by papGIII, and both were also found to have a significant association with common ExPEC genotypes. We noticed the presence of genomes, mainly belonging to the sequence type ST12, harboring two or three papA variants and two papG variants. Furthermore, the most common papA and papG variants were also detected in records representing strains isolated from humans and animals such as poultry, bovine, and dogs, supporting previous hypotheses of potential cross-transmission. Finally, we characterized a set of 17 genomes from Chilean uropathogenic E. coli strains and found that ST12 and ST73 were the predominant sequence types. Variants F7-1, F7-2, F8, F9, F11, F13, F14, F16, and F48 were detected for papA, and papGII and papGIII variants were detected for papG. Significant associations with the sequence types observed in the analysis of genomes contained in the NCBI Assembly Refseq database were also found in this collection in 16 of 19 cases for papA variants and 7 of 9 cases for the papG variants. This comprehensive characterization might support future basic studies about P fimbria-mediated ExPEC adherence and future typing or epidemiological studies to monitor the evolution of ExPECs producing P fimbria.

Prognostic impact of vasopressor test in transcatheter edge-to-edge repair of secondary mitral regurgitation: The PETIT study.

BACKGROUND: Vasopressor test (VPT) might be useful in patients with functional mitral regurgitation (MR) and left ventricular dysfunction (MITRA-FR-like patients) during transcatheter edge-to-edge repair (TEER). AIMS: We aimed to evaluate the prognostic impact of VPT. METHODS: MR treated with TEER were included in a multicenter prospective registry. VPT was used intraprocedurally in patients with left ventricular dysfunction and/or hypotension. The 1-year echocardiographic and clinical outcomes were compared according to the use of VPT. The primary endpoint was a combination of mortality + heart failure (HF) readmission at 1-year. RESULTS: A total of 1115 patients were included, mean age was 72.8 ± 10.5 years and 30.4% were women. VPT was performed in 128 subjects (11.5%), more often in critically ill patients with biventricular dysfunction. Postprocedurally the VPT group had greater rate of MR ≥ 2+ (46.9% vs. 31.7%, p = 0.003) despite greater number of devices (≥2 clips, 52% vs. 40.6 p = 0.008) and device repositioning or new clip in 12.5%. At 1-year, the primary endpoint occurred more often in the VPT group (27.3% vs. 16.9%, p = 0.002) as well as all-cause mortality (21.9% vs. 8.1%, p ≤ 0.001) but no differences existed in HF readmission rate (14.8% vs. 13.2%, p = 0.610), cardiovascular mortality (4.4% vs. 3.9%, p = 0.713) or residual MR ≥ 2+ (51.1% vs 51.7%, p = 0.371). CONCLUSIONS: Dynamic evaluation of MR during TEER procedure through VPT was performed in patients with worse baseline risk who also presented higher all-cause mortality at 1-year follow-up. However, 1-year residual MR, cardiovascular mortality and HF readmission rate remained comparable suggesting that VPT might help in the management of MITRA-FR-like patients.

New race-free creatinine- and cystatin C-based equations for the estimation of glomerular filtration rate and association with cardiovascular mortality in the AtheroGene study.

Renal function is associated with cardiovascular outcomes and mortality. Among equations used to eGFR, CKD-EPI equations show more accurate association with cardiovascular risk and mortality than MDRD. Recently, new CKD-EPI equations were proposed which do not include race and would be considered sufficiently accurate to estimate eGFR in clinical practice. It is unknown if these new race-free equations are comparably well associated with cardiovascular outcomes in high-risk individuals. The analysis was performed in the AtheroGene Study cohort including patients at high cardiovascular risk. eGFR was determined using the established as well as the recently developed formulas which are calculated without the otherwise existing coefficient for black race. The outcome was cardiovascular death. Analyses included Cox-proportional hazard regression and area-under-the-curve calculation. The analysis included 2089 patients followed up for a median of 3.8 years with a maximum of 6.9 years, corresponding to an overall period of 7701 patient-years. Cardiovascular death occurred in 93 (4.45%), corresponding to an annualized rate of 1.2/100 person-years. In all Cox regression analyses, the estimated adjusted GFR was an independent predictor of cardiovascular death. The equations which included cystatin C showed higher C-index compared to those which did not include cystatin C (0.75-0.76 vs. 0.71, respectively). The equations for the estimation of eGFR which include cystatin C are better associated with cardiovascular death compared to the race-free equations which include only creatinine. This finding adds on the related literature which supports the elimination of race in GFR-estimating equations, and promotion of the use of cystatin C.

Unrecognized myocardial scar by late-gadolinium-enhancement cardiovascular magnetic resonance: Insights from the population-based Hamburg City Health Study.

BACKGROUND: The presence of myocardial scar is associated with poor prognosis in several underlying diseases. Late-gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging reveals clinically silent "unrecognized myocardial scar" (UMS), but the etiology of UMS often remains unclear. This population-based CMR study evaluated prevalence, localization, patterns, and risk factors of UMS. METHODS: The study population consisted of 1064 consecutive Hamburg City Health Study participants without a history of coronary heart disease or myocarditis. UMS was assessed by standard-phase-sensitive-inversion-recovery LGE CMR. RESULTS: Median age was 66 [quartiles 59, 71] years and 37% (388/1064) were females. UMS was detected in 244 (23%) participants. Twenty-five participants (10%) had ischemic, and 217 participants (89%) had non-ischemic scar patterns, predominantly involving the basal inferolateral left-ventricular (LV) myocardium (75%). Two participants (1%) had coincident ischemic and non-ischemic scar. The presence of any UMS was independently associated with LV ejection fraction (odds ratios (OR) per standard deviation (SD) 0.77 (confidence interval (CI) 0.65-0.90), p = 0.002) and LV mass (OR per SD 1.54 (CI 1.31-1.82), p < 0.001). Ischemic UMS was independently associated with LV ejection fraction (OR per SD 0.58 (CI 0.39-0.86), p = 0.007), LV mass (OR per SD 1.74 (CI 1.25-2.45), p = 0.001), and diabetes (OR 4.91 (CI 1.66-13.03), p = 0.002). Non-ischemic UMS was only independently associated with LV mass (OR per SD 1.44 (CI 1.24-1.69), p < 0.001). CONCLUSION: UMS, in particular with a non-ischemic pattern, is frequent in individuals without known cardiac disease and predominantly involves the basal inferolateral LV myocardium. Presence of UMS is independently associated with a lower LVEF, a higher LV mass, and a history of diabetes.

C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project.

BACKGROUND AND AIMS: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population. METHODS: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L). RESULTS: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024). CONCLUSIONS: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.

Inflammatory burden, lifestyle and atherosclerotic cardiovascular disease: insights from a population based cohort study.

The inflammatory burden as measured by high-sensitivity C-reactive Protein (hsCRP) is recognized as a cardiovascular risk factor, which can however be affected by lifestyle-related risk factors (LRF). Up-to-date the interplay between hsCRP, LRF and presence and extent of atherosclerotic disease is still largely unknown, which we therefore sought to investigate in a contemporary population-based cohort. We included participants from the cross-sectional population-based Hamburg City Health Study. Affected vascular beds were defined as coronary, peripheral, and cerebrovascular arteries. LRF considered were lack of physical activity, overweight, active smoking and poor adherence to a Mediterranean diet. We computed multivariable analyses with hsCRP as the dependent variable and LRF as covariates according to the number of vascular beds affected. In the 6765 individuals available for analysis, we found a stepwise increase of hsCRP concentration both according to the number of LRF present as well as the number of vascular beds affected. Adjusted regression analyses showed an independent association between increasing numbers of LRF with hsCRP levels across the extent of atherosclerosis. We demonstrate increasing hsCRP concentrations according to both the number of LRF as well as the extent of atherosclerosis, emphasizing the necessity of lifestyle-related risk factor optimization.

Calibrating machine learning approaches for probability estimation: A comprehensive comparison.

Statistical prediction models have gained popularity in applied research. One challenge is the transfer of the prediction model to a different population which may be structurally different from the model for which it has been developed. An adaptation to the new population can be achieved by calibrating the model to the characteristics of the target population, for which numerous calibration techniques exist. In view of this diversity, we performed a systematic evaluation of various popular calibration approaches used by the statistical and the machine learning communities for estimating two-class probabilities. In this work, we first provide a review of the literature and, second, present the results of a comprehensive simulation study. The calibration approaches are compared with respect to their empirical properties and relationships, their ability to generalize precise probability estimates to external populations and their availability in terms of easy-to-use software implementations. Third, we provide code from real data analysis allowing its application by researchers. Logistic calibration and beta calibration, which estimate an intercept plus one and two slope parameters, respectively, consistently showed the best results in the simulation studies. Calibration on logit transformed probability estimates generally outperformed calibration methods on nontransformed estimates. In case of structural differences between training and validation data, re-estimation of the entire prediction model should be outweighted against sample size of the validation data. We recommend regression-based calibration approaches using transformed probability estimates, where at least one slope is estimated in addition to an intercept for updating probability estimates in validation studies.

Spanish cardiac catheterization and coronary intervention registry. 32nd official report of the Interventional Cardiology Association of the Spanish Society of Cardiology (1990-2022).

INTRODUCTION AND OBJECTIVES: This article presents the annual activity report of the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC) for the year 2022. METHODS: All Spanish centers with catheterization laboratories were invited to participate. Data were collected online and were analyzed by an external company in collaboration with the members of the board of the ACI-SEC. RESULTS: A total of 111 centers participated. The number of diagnostic studies increased by 4.8% compared with 2021, while that of percutaneous coronary interventions (PCI) remained stable. PCIs on the left main coronary artery increased by 22%. The radial approach continued to be preferred for PCI (94.9%). There was an upsurge in the use of drug-eluting balloons, as well as in intracoronary imaging techniques, which were used in 14.7% of PCIs. The use of pressure wires also increased (6.3% vs 2021) as did plaque modification techniques. Primary PCI continued to grow and was the most frequent treatment (97%) in ST-segment elevation myocardial infarction. Most noncoronary procedures maintained their upward trend, particularly percutaneous aortic valve implantation, atrial appendage closure, mitral/tricuspid edge-to-edge therapy, renal denervation, and percutaneous treatment of pulmonary arterial disease. CONCLUSIONS: The Spanish cardiac catheterization and coronary intervention registry for 2022 reveals a rise in the complexity of coronary disease, along with a notable growth in procedures for valvular and nonvalvular structural heart disease.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

An arrhythmogenic metabolite in atrial fibrillation.

BACKGROUND: Long-chain acyl-carnitines (ACs) are potential arrhythmogenic metabolites. Their role in atrial fibrillation (AF) remains incompletely understood. Using a systems medicine approach, we assessed the contribution of C18:1AC to AF by analysing its in vitro effects on cardiac electrophysiology and metabolism, and translated our findings into the human setting. METHODS AND RESULTS: Human iPSC-derived engineered heart tissue was exposed to C18:1AC. A biphasic effect on contractile force was observed: short exposure enhanced contractile force, but elicited spontaneous contractions and impaired Ca2+ handling. Continuous exposure provoked an impairment of contractile force. In human atrial mitochondria from AF individuals, C18:1AC inhibited respiration. In a population-based cohort as well as a cohort of patients, high C18:1AC serum concentrations were associated with the incidence and prevalence of AF. CONCLUSION: Our data provide evidence for an arrhythmogenic potential of the metabolite C18:1AC. The metabolite interferes with mitochondrial metabolism, thereby contributing to contractile dysfunction and shows predictive potential as novel circulating biomarker for risk of AF.

Shared gene expression signatures between visceral adipose and skeletal muscle tissues are associated with cardiometabolic traits in children with obesity.

Obesity in children is related to the development of cardiometabolic complications later in life, where molecular changes of visceral adipose tissue (VAT) and skeletal muscle tissue (SMT) have been proven to be fundamental. The aim of this study is to unveil the gene expression architecture of both tissues in a cohort of Spanish boys with obesity, using a clustering method known as weighted gene co-expression network analysis. For this purpose, we have followed a multi-objective analytic pipeline consisting of three main approaches; identification of gene co-expression clusters associated with childhood obesity, individually in VAT and SMT (intra-tissue, approach I); identification of gene co-expression clusters associated with obesity-metabolic alterations, individually in VAT and SMT (intra-tissue, approach II); and identification of gene co-expression clusters associated with obesity-metabolic alterations simultaneously in VAT and SMT (inter-tissue, approach III). In both tissues, we identified independent and inter-tissue gene co-expression signatures associated with obesity and cardiovascular risk, some of which exceeded multiple-test correction filters. In these signatures, we could identify some central hub genes (e.g., NDUFB8, GUCY1B1, KCNMA1, NPR2, PPP3CC) participating in relevant metabolic pathways exceeding multiple-testing correction filters. We identified the central hub genes PIK3R2, PPP3C and PTPN5 associated with MAPK signaling and insulin resistance terms. This is the first time that these genes have been associated with childhood obesity in both tissues. Therefore, they could be potential novel molecular targets for drugs and health interventions, opening new lines of research on the personalized care in this pathology. This work generates interesting hypotheses about the transcriptomics alterations underlying metabolic health alterations in obesity in the pediatric population.