Eliminate LDL cholesterol after heart attack but only for a while.

There is a clear demonstration of the inverse linear correlation between LDL cholesterol levels and clinical benefit. However, the timing of the action of lipid-lowering drugs is not clear. According to animal studies with recombinant lipoprotein A-1, the composition of atherosclerosis changes within 40 h (with variations in lipid and inflammatory contents). Progression-regression studies of atherosclerosis in humans confirm the data, highlighting a rapid change in the plaque over 5 weeks. The data are also in line with what emerges from the survival curves of the old study comparing atorvastatin 80 mg vs. placebo (Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering). The spacing of the curves occurs after only 4 weeks, indicating the precociousness of the favourable effects of powerful statins. Finally, a recent Odyssey post hoc analysis compared the risk of cardiac death and coronary revascularization between a group in which alirocumab lowered LDL cholesterol to below 15 mg (Group 1 and in which the drug was therefore stopped) against the subjects in the placebo group (Group 2), applying a propensity score matching. The primary endpoint occurred in a lower percentage of patients in Group 1 (6.4 vs. 8.4%). Furthermore, patients in Group 1 had a significantly lower hazard ratio (HR) for major adverse cardiovascular events [0.72; 95% confidence interval (CI) 0.51-0.997; P = 0.047] compared with the entire alirocumab group vs. placebo (HR 0.85; 95% CI 0.78-0.93; P < 0.001). According to these preliminary observations, aggressive and early treatment of hypercholesterolaemia in subjects with acute coronary syndrome translates into improved clinical results compared with a strategy that provides for more gradual control. These data will need to be confirmed through further prospective clinical studies and ideally with early conducted atherosclerosis regression studies.

Cardiovascular Effects of Cosmic Radiation and Microgravity.

Recent spaceflights involving nonprofessional people have opened the doors to the suborbital space tourism business. However, they have also drawn public attention to the safety and hazards associated with space travel. Unfortunately, space travel involves a myriad of health risks for people, ranging from DNA damage caused by radiation exposure to the hemodynamic changes that occur when living in microgravity. In fact, the primary pathogenetic role is attributed to cosmic radiation, since deep space lacks the protective benefit of Earth's magnetic shielding. The second risk factor for space-induced pathologies is microgravity, which may affect organ function and cause a different distribution of fluid inside the human body. Both cosmic radiation and microgravity may lead to the alteration of cellular homeostasis and molecular changes in cell function. These, in turn, might have a direct impact on heart function and structure. The aim of this review is to draw attention to the fact that spaceflights constitute a novel frontier in biomedical research. We summarize the most important clinical and experimental evidence regarding the cardiovascular effects of cosmic radiation and microgravity. Finally, we highlight that unraveling the mechanisms underlying how space radiation and microgravity affect the cardiovascular system is crucial for identifying potential countermeasures and developing effective therapeutic strategies.

Prediction of new onset atrial fibrillation in patients with acute coronary syndrome undergoing percutaneous coronary intervention using the C2HEST and mC2HEST scores: A report from the multicenter REALE-ACS registry.

BACKGROUND: New onset atrial fibrillation (NOAF) is associated with worse clinical outcomes after acute coronary syndrome (ACS). Identification of ACS patients at risk of NOAF remains challenging. To test the value of the simple C2HEST score for predicting NOAF in patients with ACS. METHODS: We studied patients from the prospective ongoing multicenter REALE-ACS registry of patients with ACS. NOAF was the primary endpoint of the study. The C2HEST score was calculated as coronary artery disease or chronic obstructive pulmonary disease (1 point each), hypertension (1 point), elderly (age ≥ 75 years, 2 points), systolic heart failure (2 points), thyroid disease (1 point). We also tested the mC2HEST score. RESULTS: We enrolled 555 patients (mean age 65.6 ± 13.3 years; 22.9% women), of which 45 (8.1%) developed NOAF. Patients with NOAF were older (p < 0.001) and had more prevalent hypertension (p = 0.012), chronic obstructive pulmonary disease (p < 0.001) and hyperthyroidism (p = 0.018). Patients with NOAF were more frequently admitted with STEMI (p < 0.001), cardiogenic shock (p = 0.008), Killip class ≥2 (p < 0.001) and had higher mean GRACE score (p < 0.001). Patients with NOAF had a higher C2HEST score compared with those without (4.2 ± 1.7 vs 3.0 ± 1.5, p < 0.001). A C2HEST score > 3 was associated with NOAF occurrence (odds ratio 4.33, 95% confidence interval 2.19-8.59, p < 0.001). ROC curve analysis showed good accuracy of the C2HEST score (AUC 0.71, 95%CI 0.67-0.74) and mC2HEST score (AUC 0.69, 95%CI 065-0.73) in predicting NOAF. CONCLUSIONS: The simple C2HEST score may be a useful tool to identify patients at higher risk of developing NOAF after presentation with ACS.

Optical coherence tomography-derived lipid core burden index and clinical outcomes: results from the CLIMA registry.

AIMS: The aim of this study was to assess the morphological characteristics and prognostic implications of the optical coherence tomography (OCT)-derived lipid core burden index (LCBI). METHODS AND RESULTS: OCT-LCBI was assessed in 1003 patients with 1-year follow-up from the CLIMA multicentre registry using a validated software able to automatically obtain a maximum OCT-LCBI in 4 mm (maxOCT-LCBI4mm). Primary composite clinical endpoint included cardiac death, myocardial infarction, and target-vessel revascularization. A secondary analysis using clinical outcomes of CLIMA study was performed. Patients with a maxOCT-LCBI4mm ≥ 400 showed higher prevalence of fibrous cap thickness (FCT) <75 µm [odds ratio (OR) 1.43, 95% confidence interval (CI) 1.03-1.99; P = 0.034], lipid pool arc >180° (OR 3.93, 95%CI 2.97-5.21; P < 0.001), minimum lumen area <3.5 mm2 (OR 1.5, 95%CI 1.16-1.94; P = 0.002), macrophage infiltration (OR 2.38, 95%CI 1.81-3.13; P < 0.001), and intra-plaque intimal vasculature (OR 1.34, 95%CI 1.05-1.72; P = 0.021). A maxOCT-LCBI4mm ≥400 predicted the primary endpoint [adjusted hazard ratio (HR) 1.86, 95%CI 1.1-3.2; P = 0.019] as well as the CLIMA endpoint (HR 2.56, 95%CI 1.24-5.29; P = 0.011). Patients with high lipid content and thin FCT < 75 µm were at higher risk for adverse events (HR 4.88, 95%CI 2.44-9.72; P < 0.001). CONCLUSIONS: A high maxOCT-LCBI4mm was related to poor outcome and vulnerable plaque features. This study represents a step further in the automated assessment of the coronary plaque risk profile.

Non-Invasive Treatments for Failed Back Surgery Syndrome: A Systematic Review.

STUDY DESIGN: Systematic Review. OBJECTIVES: The aim of this systematic review is to evaluate the efficacy of non-invasive procedures in relieving chronic pain due to Failed Back Surgery Syndrome (FBSS). METHODS: Since patients who suffered from FBBS are often non-responders to analgesics, we compared Visual Analogical Scale for low back and leg pain, Oswestry Disability Index, trial success rate, adverse events and complications between conservative treatment groups and control groups. RESULTS: The included studies were 15. Spinal Cord Stimulation (SCS) was performed in 11 trials; 4 studies assessed the efficacy of different epidural injections; one study evaluated repetitive Transcranial Magnetic Stimulation. All the studies reported back and leg pain relief after treatment with SCS, with a significant superiority in high frequences (HFS) group, compared to low frequences (LFS) group. Moreover, disability decreased with each non-invasive treatment evaluated. Epidural injections of steroids and hyaluronidase have shown controversial results. Adverse events were described in 7 studies: lead migration, hardware-related events, infection and incisional pain were the most reported. Finally, trial success rate showed better outcomes for HFS. CONCLUSIONS: Our systematic review highlights the efficacy of conservative treatments in FBSS patients, with an improvement in pain scores and a decrease in disability index, especially after SCS with HFS. However, due to the lack of homogeneity among trials and population characteristics, further studies are needed to confirm the effectiveness of non-invasive interventions in patients affected by FBSS.

Sex-specific features of optical coherence tomography detected plaque vulnerability related to clinical outcomes: insights from the CLIMA study.

PURPOSE: To investigate the different impact of optical coherence tomography (OCT)-derived vulnerable plaque features on future adverse events (AEs) according to the biological sex. METHODS: The prospective multicenter CLIMA study (ClinicalTrials.gov: NCT02883088) enrolled 1003 patients with OCT plaque analysis of non-treated coronary plaques located in the proximal left anterior descending artery. Sex-specific differences in plaque composition and vulnerable features were described. We investigated the incidence of AEs, including cardiac death, any myocardial infarction and target vessel revascularization at 1-year. RESULTS: Among 1003 patients, 24.6% were women. Women were older and more frequently affected by chronic kidney disease. Dyslipidemia, prior MI and smoking habit were more common in men. At OCT analysis, women had shorter plaque length (p < 0.001), ticker fibrous cap (p = 0.001), smaller maximum lipid arc (p = 0.019), lower macrophage infiltration (p < 0.001) and intra-plaque layered tissue (p = 0.007). During follow-up, 65 AEs were registered. The presence of a thin fibrous cap and a large macrophage infiltration (> 67°) predicted AEs in both sexes. The presence of macrophages (HR 3.38, p = 0.018) and a small minimum lumen area (HR 4.97, p = 0.002) were associated with AEs in women but not in men, while a large lipid arc (> 180°) was associated with AEs in men (HR 2.56, p = 0.003) but not in women. CONCLUSION: This subanalysis of the CLIMA study investigated for the first-time sex-specific OCT features of plaque vulnerability associated with AEs. Local inflammation was associated with AEs in women and a large lipid arc was predictive in men. OCT may help develop sex-specific risk stratification strategies.

Relationship between non-invasively detected liver fibrosis and in-hospital outcomes in patients with acute coronary syndrome undergoing PCI.

BACKGROUND: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) still experience a high rate of in-hospital complications. Liver fibrosis (LF) is a risk factor for mortality in the general population. We investigated whether the presence of LF detected by the validated fibrosis 4 (FIB-4) score may indicate ACS patients at higher risk of poor outcome. METHODS: In the prospective ongoing REAl-world observationaL rEgistry of Acute Coronary Syndrome (REALE-ACS), LF was defined by a FIB-4 score > 3.25. We repeated the analysis using an APRI score > 0.7. The primary endpoint was in-hospital adverse events (AEs) including a composite of in-hospital cardiogenic shock, PEA/asystole, acute pulmonary edema and death. RESULTS: A total of 469 consecutive ACS consecutive patients were enrolled. Overall, 21.1% of patients had a FIB-4 score > 3.25. Patients with LF were older, less frequently on P2Y12 inhibitors (p = 0.021) and admitted with higher serum levels of white blood cells (p < 0.001), neutrophils to lymphocytes ratio (p < 0.001), C-reactive protein (p = 0.013), hs-TnT (p < 0.001), creatine-kinase MB (p < 0.001), D-Dimer levels (p < 0.001). STEMI presentation and higher Killip class/GRACE score were more common in the LF group (p < 0.001). 71 patients experienced 110 AEs. At the multivariate analysis including clinical and laboratory risk factors, FIB-4 > 3.25 (OR 3.1, 95%CI 1.4-6.9), admission left ventricular ejection fraction% below median (OR 9.2, 95%CI 3.9-21.7) and Killip class ≥ II (OR 6.3, 95%CI 2.2-18.4) were the strongest independent predictors of in-hospital AEs. Similar results were obtained using the APRI score. CONCLUSION: LF detected by FIB-4 score > 3.25 was associated with more severe ACS presentation and worse in-hospital AEs irrespective of clinical and laboratory variables.

[From regression to stabilization: new insights into the evolution of coronary atherosclerotic plaque]. / Dalla regressione alla stabilizzazione: l'evoluzione della placca aterosclerotica coronarica secondo le nuove evidenze.

Coronary artery atherosclerosis is a constantly evolving disease. Over the years, new drug therapies have been shown to reduce adverse cardiovascular events and improve the survival of patients with coronary artery disease. New intracoronary imaging modalities, including intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy, have been introduced to detect the anatomic changes which follow an effective lipid-lowering therapy in human coronary plaques. Particularly, the use of optical coherence tomography made it possible to evaluate plaque composition and showed how an intensive lipid-lowering therapy can stabilize atherosclerosis by improving vulnerable plaque features. Future non-invasive applications are required for large-scale use of these findings.