European Journal of Clinical Investigation最新文献

Background: Low-density lipoprotein (LDL) is a central player in atherogenesis and has long been referred to as 'bad cholesterol.' However, emerging evidence indicates that LDL functions in multifaceted ways beyond cholesterol transport that include roles in inflammation, immunity, and cellular signaling. Understanding LDL's structure, metabolism and function is essential for advancing cardiovascular disease research and therapeutic strategies.

Methods: This narrative review examines the history, structural properties, metabolism and functions of LDL in cardiovascular health and disease. We analyze key milestones in LDL research, from its early identification to recent advancements in molecular biology and omics-based investigations. Structural and functional insights are explored through imaging, proteomic analyses and lipidomic profiling, providing a deeper understanding of LDL heterogeneity.

Results: Low-density lipoprotein metabolism, from biosynthesis to receptor-mediated clearance, plays a crucial role in lipid homeostasis and atherogenesis. Beyond cholesterol transport, LDL contributes to plaque inflammation, modulates adaptive immunity and regulates cellular signaling pathways. Structural studies reveal its heterogeneous composition, which influences its pathogenic potential. Evolving perspectives on LDL redefine its clinical significance, affecting cardiovascular risk assessment and therapeutic interventions.

Conclusions: A holistic understanding of LDL biology challenges traditional perspectives and underscores its complexity in cardiovascular health. Future research should focus on further elucidating LDL's structural and functional diversity to refine risk prediction models and therapeutic strategies, ultimately improving cardiovascular outcomes.

Objective: Ankle-brachial index (ABI) and carotid-femoral pulse-wave velocity (cfPWV) are well-established surrogate markers of overall cardiovascular risk. However, their prognostic value towards short- and long-term mortality in an emergency medicine setting is yet unknown.

Approach and results: Acutely ill medical patients systematically underwent cfPWV and ABI measurements at the emergency department of a tertiary care hospital. Patients' survival was analysed in relation to their ABI and cfPWV values at initial presentation. In total, 1080 individuals (43.7% females; 59.6 ± 17.4 years old) were enrolled. Over a median follow-up period of 24.4 months, 112 (10%) deaths were observed. 30-day mortality was 4.9% in patients with a pathological ABI and 1.4% with a normal ABI (p = .003). There was also a significant difference over the entire observational period regarding cumulative mortality (p < .001). Thirty-day mortality was 2.4% in patients with a cfPWV ≥10 m/s and .7% with a cfPWV <10 m/s (p = .025), and cumulative mortality over the whole period differed between a cfPWV ≥10 m/s and <10 m/s as well (p < .001).

Conclusion: In acutely ill medical patients, the noninvasive ABI and cfPWV assessment at triage level facilitates initial risk stratification in the emergency setting for short- and long-term mortality. Patients with pathological ABI and cfPWV values could thus be seen as a proxy of a sicker cohort with an overall worse polyvascular situation.

Background: This investigation had two main objectives: (1) to compare the triglyceride-glucose (TyG) index with the homeostasis model assessment of insulin resistance (HOMA-IR) in relation to insulin-stimulated myocardial glucose metabolic rate (MrGlu), measured by a dynamic positron emission tomography (PET) scan using 18F-fluorodeoxyglucose (18F-FDG) coupled with a euglycemic-hyperinsulinemic clamp; and (2) to assess whether the TyG index correlates with myocardial mechano-energetic efficiency (MEE).

Methods: We evaluated MrGlu in 46 participants who had no prior diagnosis of coronary heart disease. Myocardial MrGlu was quantified by 18F-FDG PET during a euglycemic-hyperinsulinemic clamp. In a larger cohort of 1820 individuals, myocardial MEE per gram of left ventricular mass (MEEi) was measured echocardiographically. The TyG index was computed as the Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2].

Results: When compared to HOMA-IR, the TyG index exhibited a stronger correlation with myocardial MrGlu (Pearson's r = -.566 for TyG vs. -.471 for HOMA-IR). Within the larger cohort, individuals in the highest TyG quartile showed significantly reduced MEEi compared to those in the lowest quartile (p < .001). Stepwise multivariate linear regression confirmed that the TyG index was the most significant determinant of MEEi, independent of traditional cardio-metabolic risk factors.

Conclusions: Our findings suggest that the TyG index is superior to HOMA-IR as an indicator of cardiac insulin resistance and that it independently correlates with MEEi. Thus, the TyG index may serve as a valuable, readily available tool to identify subjects at elevated cardiovascular risk.

Background: Patients with inferior ST-segment elevation myocardial infarction face a substantial risk for cardiovascular death. While left ventricular function is known to be associated with clinical outcomes in these patients, we evaluated the prognostic impact of tricuspid annular plane systolic excursion (TAPSE) and advanced measures of right ventricular function (free wall strain [FWS] and global longitudinal strain [RVGLS]).

Methods: Consecutive patients presenting with acute inferior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention between 01/2012 and 08/2015 were retrospectively analysed. Associations between RV strain measurements and all-cause mortality were evaluated using Cox regression analysis.

Results: 207 patients (69.6% male, median 59.0 [IQR: 52.1-70.7] years) were followed for 8.3 (IQR: 7.4-9.3) years, during which 49 patients (23.7%) deceased. Median right ventricular function parameters were significantly better in surviving patients (RVGLS: -17.5% vs. -13.3%, p < .001; FWS: -20.5% vs. -14.8%, p < .001; TAPSE 1.8 cm vs. 1.3 cm, p < .001). All 3 parameters were associated with mortality in univariate and multivariable analysis adjusted for age, sex and the number of comorbidities (chronic kidney disease, hypercholesterinaemia, diabetes mellitus) (adj. hazard ratio [HR] per 1 standard deviation: RVGLS: 1.68 [95% CI: 1.27-2.23, p < .001], FWS: 1.56 [95% CI: 1.56-2.00, p < .001], TAPSE: 1.55 [95% CI: 1.17-2.05, p = .002]). Additionally, right ventricular function was inversely associated with peak troponin T and creatine kinase levels.

Conclusions: Among patients with inferior ST-segment myocardial infarction, RVGLS, FWS and TAPSE convey crucial prognostic information and might help to identify patients at increased risk requiring intensified monitoring and therapy.

Background: Recent evidence suggests that Alzheimer's amyloid-beta (1-40) (Αβ1-40), an emerging biomarker of cardiovascular disease, may be involved in the heart-brain-renal axis. We aimed to comprehensively explore the association between circulating Aβ1-40 levels and renal function and its clinical relevance.

Methods: Consecutively recruited subjects in the Athens Angiometabolic Registry with measured Aβ1-40 plasma levels (n = 811) were analysed. Αβ1-40 was measured by enzyme-linked immunosorbent assay and glomerular filtration rate (GFR) was calculated using the abbreviated four-variable Modification of Diet in Renal Disease (MDRD) formula. All-cause mortality was the main clinical endpoint across a median follow-up of 47 months.

Results: Cross-sectionally, a bidirectional association between Αβ1-40 [adjusted odds ratio (adjOR) = 3.67 for highest tertile of Αβ1-40 and chronic kidney disease (CKD) stage ≥3, p < .001] and CKD stage ≥3 (adjOR = 3.52 for association with highest Aβ1-40 tertile, p < .001) was observed. Longitudinally, increased Αβ1-40 at baseline was associated with decline in renal function at follow-up (adjOR for CKD stage ≥3 = 2.26, p = .033). Similarly, longitudinal changes in Aβ1-40 were inversely associated with changes in GFR (OR = .77 per 1 SD increase in Aβ1-40, p = .006). Aβ1-40 was associated with all-cause mortality, independently of traditional risk factors (hazard ratio = 1.20 per 1 SD increase in Aβ1-40, p = .016). An indirect effect of GFR on the association between Aβ1-40 and mortality (p < .05) with an estimated indirect-to-total effect ratio of .334, but not of Αβ1-40 on GFR with mortality, was observed.

Conclusions: In a population with a wide range of GFR, we found a bidirectional association between Αβ1-40 levels and renal function. The association of Αβ1-40 with all-cause mortality was partly mediated by lower GFR.

Besides the well-known role of hormonal factors in mineral and bone metabolism, the sympathetic nervous system participates in this regulation by inhibiting bone formation and promoting bone resorption, primarily via β-adrenergic receptors expressed on osteoblasts. Conversely, the parasympathetic system, through cholinergic signalling, inhibits osteoclast activity, promoting bone formation and maintaining skeletal homeostasis. This review presents the role of the autonomic nervous system, with particular focus on the potential role of β-blockers, especially β1-selective blockers, in modulating bone health in people with normal kidney function and those with CKD. While early studies with non-selective β-blockers like propranolol showed mixed results, recent findings in postmenopausal women suggested that β1-selective β-blockers could enhance bone density by modulating sympathetic activity. Trial emulation using large databases and eventually randomized controlled trials are needed to test the hypothesis that β-blockade can favourably impact bone disease in patients with kidney failure.

Background: Atrial fibrillation (AF) and low body weight (BW, <60 kg) are common in patients with heart failure (HF). However, the safety and effectiveness of direct oral anticoagulants (DOACs) in this group remain unclear. This study compares the efficacy and safety of apixaban versus vitamin K antagonists (VKAs) in patients with nonvalvular AF, low BW and HF.

Methods: We analysed 155,152 patients with HF and AF, weighing ≤100 kg and treated with oral anticoagulants (apixaban 86,493; VKA 68,659), from the TriNetX Global Research Network. Outcomes included ischaemic stroke/systemic embolism (SEE), clinically relevant bleedings, intracranial haemorrhage (ICH), all-cause death and net clinical benefit (composite of stroke/SEE, bleedings and all-cause death) across three BW categories: 60-100 kg (reference), 50-60 kg (low BW) and ≤50 kg (very low BW). Propensity score matching was used to balance the treatment groups.

Results: Patients with low BW had a higher risk of adverse events compared to those with reference BW, regardless of treatment. Apixaban consistently reduced the risk of ischaemic stroke/SEE and bleeding (including ICH) across all BW ranges (all p-interaction >.10), and improved net clinical benefit compared to VKA (reference BW: HR .82 [95% CI: .80-.84]; low BW: HR .79 [95% CI: .74-.85]; very low BW: HR .86 [95% CI: .78-.95], p-interaction = .366). However, a significant BW-treatment interaction was observed for all-cause mortality, indicating reduced relative effectiveness of apixaban vs. VKA as BW decreases.

Conclusion: In this large real-world analysis, treatment with apixaban was associated with a superior effectiveness and safety profile compared to VKA in patients with AF, HF and low BW. These results remained consistent, albeit slightly attenuated, in patients with very low BW. These findings provide preliminary evidence supporting the use of apixaban in this high-risk population.