Background: Observational studies suggested that residual risk of cardiovascular events after LDL (low-density lipoprotein) cholesterol lowering may be linked to remnant cholesterol (RC). We conducted a large-scale Mendelian randomization study to investigate the causal role of RC to predict coronary artery disease (CAD), myocardial infarction (MI), and stroke risk. Methods: We extracted single-nucleotide polymorphisms for RC and LDL from large-scale genome-wide association databases. We estimated the genetic association with outcomes from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Plus the Coronary Artery Disease Genetics), the Metastroke consortium, as well as the GLGC (Global Lipids Genetics Consortium). Genetic variants were used as instruments, thereby minimizing residual confounding and reverse causation biases of observational studies. Results: By leveraging data from a combined sample of 958 434 participants, we found evidence for a significant causal effect of RC on the risk of CAD (odds ratio [OR], 1.51 per SD unit increase in RC [95% CI, 1.42–1.60]; P =5.3×10 ^-5 ), MI (OR, 1.57 [95% CI, 1.21–2.05]; P =9.5×10 ^-4 ), and stroke (OR, 1.23 [95% CI, 1.12–1.35]; P =3.72×10 ^-6 ). There was no evidence of pleiotropy. The effect of RC on CAD and MI remained consistent after accounting for the effects of RC-associated genetic variants on LDL cholesterol: OR, 1.49 (95% CI, 1.37–1.61) for CAD and OR, 1.80 (95% CI, 1.70–19.1) for MI without a meaningful indirect effect exerted on these outcomes via the LDL cholesterol mediator. Conclusions: This large-scale Mendelian randomization study showed a robust genetic causal association between RC and cardiovascular outcomes. The effect on CAD and MI is independent of LDL cholesterol. Early screening for RC along with long-term inhibition of RC should be the focus of future therapeutic interventions.

Aims The coronavirus disease-2019 (COVID-19) pandemic has changed the landscape of medical care delivery worldwide. We aimed to assess the influence of COVID-19 pandemic on hospital admissions and in-hospital mortality rate in patients with acute heart failure (AHF) in a retrospective, multicentre study. Methods and results From 1 January 2019 to 31 December 2020, a total of 101 433 patients were hospitalized in 24 Cardiology Departments in Poland. The number of patients admitted due to AHF decreased by 23.4% from 9853 in 2019 to 7546 in 2020 (P < 0.001). We noted a significant reduction of self-referrals in the times of COVID-19 pandemic accounting 27.8% (P < 0.001), with increased number of AHF patients brought by an ambulance by 15.9% (P < 0.001). The length of hospital stay was overall similar (7.7 ± 2.8 vs. 8.2 ± 3.7 days; P = not significant). The in-hospital all-cause mortality in AHF patients was 444 (5.2%) in 2019 vs. 406 (6.5%) in 2020 (P < 0.001). A total number of AHF patients with concomitant COVID-19 was 239 (3.2% of AHF patients hospitalized in 2020). The rate of in-hospital deaths in AHF patients with COVID-19 was extremely high accounting 31.4%, reaching up to 44.1% in the peak of the pandemic in November 2020. Conclusions Our study indicates that the COVID-19 pandemic led to (i) reduced hospital admissions for AHF; (ii) decreased number of self-referred AHF patients and increased number of AHF patients brought by an ambulance; and (iii) increased in-hospital mortality for AHF with very high mortality rate for concomitant AHF and COVID-19.

Huntington’s disease (HD) is a highly common inherited monogenic neurodegenerative disease, and the gene responsible for its development is located in the 4p16.3 chromosome. The product of that gene mutation is an abnormal huntingtin (Htt) protein that disrupts the neural conduction, thus leading to motor and cognitive disorders. The disease progresses to irreversible changes in the central nervous system (CNS). Although only a few drugs are available to symptomatic treatment, ‘dopamine stabilizers’ (as represented by the pridopidine) may be the new treatment options. The underlying causes of HD are dopaminergic conduction disorders. Initially, the disease is hyperkinetic (chorea) until it eventually reaches the hypokinetic phase. Studies confirmed a correlation between the amount of dopamine in the CNS and the stage of the disease. Pridopidine has the capacity to be a dopamine buffer, which could increase or decrease the dopamine content depending on the disease phase. A research carried out on animal models demonstrated the protective effect of pridopidine on nerve cells thanks to its ability to alter the cortical glutamatergic signaling through the N-methyl-D-aspartate (NMDA) receptors. Studies on dopamine stabilizers also reported that pridopidine has a 100-fold greater affinity for the sigma-1 receptor than for the D2 receptor. Disturbances in the activity of sigma-1 receptors occur in neurodegenerative diseases, including HD. Their interaction with pridopidine results in the neuroprotective effect, which is manifested as an increase in the plasticity of synaptic neurons and prevention of their atrophy within the striatum. To determine the effectiveness of pridopidine in the treatment of HD, large multicenter randomized studies such as HART, MermaiHD, and PRIDE-HD were carried out.

Background: The identification of parameters that would serve as predictors of prognosis in COVID-19 patients is very important. In this study, we assessed independent factors of in-hospital mortality of COVID-19 patients during the second wave of the pandemic. Material and methods: The study group consisted of patients admitted to two hospitals and diagnosed with COVID-19 between October 2020 and May 2021. Clinical and demographic features, the presence of comorbidities, laboratory parameters, and radiological findings at admission were recorded. The relationship of these parameters with in-hospital mortality was evaluated. Results: A total of 1040 COVID-19 patients (553 men and 487 women) qualified for the study. The in-hospital mortality rate was 26% across all patients. In multiple logistic regression analysis, age ≥ 70 years with OR = 7.8 (95% CI 3.17–19.32), p < 0.001, saturation at admission without oxygen ≤ 87% with OR = 3.6 (95% CI 1.49–8.64), p = 0.004, the presence of typical COVID-19-related lung abnormalities visualized in chest computed tomography ≥40% with OR = 2.5 (95% CI 1.05–6.23), p = 0.037, and a concomitant diagnosis of coronary artery disease with OR = 3.5 (95% CI 1.38–9.10), p = 0.009 were evaluated as independent risk factors for in-hospital mortality. Conclusion: The relationship between clinical and laboratory markers, as well as the advancement of lung involvement by typical COVID-19-related abnormalities in computed tomography of the chest, and mortality is very important for the prognosis of these patients and the determination of treatment strategies during the COVID-19 pandemic.

Background: Post-COVID-19 syndrome (PCS) may affect a substantial proportion of patients who have had COVID-19. The rehabilitation program might improve the physical capacity, functioning of the cardiopulmonary system, and mental conditions of these patients. This study aimed to investigate the effectiveness of personalized rehabilitation in patients with PCS according to gender. Methods: Adults who underwent a 6-week personalized PCS rehabilitation program were enrolled in a prospective post-COVID-19 Rehabilitation (PCR-SIRIO 8) study. The initial visit and the final visit included the hand-grip strength test, the bioimpedance analysis of body composition, and the following scales: modified Borg’s scale, Modified Fatigue Impact Scale (MFIS), Functioning in Chronic Illness Scale (FCIS), modified Medical Research Council (mMRC) dyspnea scale, and tests: 30 s chair stand test (30 CST), Six-Minute Walk Test (6MWT), Short Physical Performance Battery test (SPPB)e. Results: A total of 90 patients (54% female) underwent the rehabilitation program. Rehabilitation was associated with an increase in skeletal muscle mass (24.11 kg vs. 24.37 kg, p = 0.001) and phase angle (4.89° vs. 5.01°, p = 0.001) and with a reduction in abdominal fat tissue volume (3.03 L vs. 2.85 L, p = 0.01), waist circumference (0.96 m vs. 0.95 m, p = 0.001), and hydration level (83.54% vs. 82.72%, p = 0.001). A decrease in fat tissue volume and an increase in skeletal muscle mass were observed only in females, while an increase in grip strength was noticed selectively in males. Patients’ fatigue (modified Borg’s scale, MFIS), physical capacity (30 CST, 6MWT), balance (SPPB), dyspnea (mMRC), and functioning (FICS) were significantly improved after the rehabilitation regardless of gender. Conclusions: Personalized rehabilitation improved the body composition, muscle strength, and functioning of patients diagnosed with PCS. The beneficial effect of rehabilitation on body composition, hydration, and phase angle was observed regardless of gender.

Hyperlipidemia is the most prevalent cardiovascular (CV) risk factors. We aimed to analyze the distribution of lipid parameters and clinical variables associated with elevated and non-elevated selected lipid factors in a cohort of all consecutive patients whose lipid profile was assessed at a multi-specialist clinical center. This cross-sectional study analyzed electronic medical records of consecutive patients treated between March and November 2024. Lipid parameters measured included: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (apoB), and lipoprotein (a) [Lp(a)]. Non-high-density lipoprotein cholesterol (non-HDL-C) was calculated as TC–HDL-C. We used multivariate analysis to identify factors associated with LDL-C, TG, and Lp(a) concentrations. A total of 10,597 patients were included in the analysis. The median lipid concentrations (mg/dL) were: TC 162 (IQR 132–198), LDL-C 94 (IQR 69–129), non-HDL-C 112 (IQR 88–146), apoB 78 (IQR 63–99), and Lp(a) 11 (IQR 5–29). Elevated LDL-C > 100 mg/dL was observed in 45.7% of patients, non-HDL-C > 130 mg/dL in 35.1%, and apoB > 100 mg/dL in 23.2%. A discordance between LDL-C and apoB concentrations was present in 23.7% of patients (p < 0.001), while LDL-C/non-HDL-C and apoB/non-HDL-C discordance rates were 13% and 12.6%, respectively (p < 0.001). Patients at very high CV risk had lower TC, LDL-C, non-HDL-C, and apoB concentrations compared to those with low-to-moderate and high CV risk (p < 0.001) and showed the highest median Lp(a) concentration of 13 mg/dL (IQR 5–31; p = 0.01). Goal achievements of LDL-C < 100 mg/dL, TG < 150 mg/dL, and Lp(a) < 30 mg/dL were associated with lipid-lowering treatment [OR 1.32 (95% CI 1.12–1.52)], atrial fibrillation [OR 1.31 (95% CI 1.11–1.54)], chronic coronary syndromes [OR 1.27 (95% CI 1.05–1.52)], smoking [OR 0.78 (95% CI 0.65–0.95)], BMI [OR 0.98 (95% CI 0.96–0.99)], and age [OR 1.006 (95% CI 1.002–1.009)]. The highest proportion of patients with results within the normal range was observed for apoB and the lowest for LDL-C. The highest discordance was observed between apoB/LDL-C, with similar discordance rates between LDL-C/non-HDL-C and apoB/non-HDL-C. Lipid profile control was associated with BMI, atrial fibrillation, age, chronic coronary syndrome, aortic stenosis, diabetes, male gender, lipid-lowering therapy, and smoking. These findings highlight the complexity of lipid management.