Background Pro‐protein convertase subtilisin/kexin 9 (PCSK9) is a proenzyme primarily known to regulate low‐density lipoprotein receptor re‐uptake on hepatocytes. Whether PCSK9 can concurrently trigger inflammation or not remains unclear. Here, we investigated the potential association between circulating levels of PCSK9 and mortality in patients with severe sepsis or septic shock. Methods Plasma PCSK9 levels at days 1, 2 and 7 were measured in 958 patients with severe sepsis or septic shock previously enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. Correlations between levels of PCSK9 and pentraxin 3 (PTX3), a biomarker of disease severity, were evaluated with ranked Spearman’s coefficients. Cox proportional hazards models were used to assess the association of PCSK9 levels at day 1 with 28‐ and 90‐day mortality. Results Median plasma PCSK9 levels were 278 [182–452] ng mL−1 on day 1. PCSK9 correlated positively with PTX3 at the three time‐points, and patients with septic shock within the first quartile of PCSK9 showed higher levels of PTX3. Similar mortality rates were observed in patients with severe sepsis across PCSK9 quartiles. Patients with septic shock with lower PCSK9 levels on day 1 (within the first quartile) showed the highest 28‐ and 90‐day mortality rate as compared to other quartiles. Conclusion In our sub‐analysis of the ALBIOS trial, we found that patients with septic shock presenting with lower plasma PCSK9 levels experienced higher mortality rate. Further studies are warranted to better evaluate the pathophysiological role of PCSK9 in sepsis.

Background: Inflammation, overweight and other cardiovascular risk factors might negatively impact on hypertension remission in metabolic syndrome (MetS), independently of the pharmacological treatment. Here, the potential influence of systemic inflammation (assessed by serum high-sensitivity C-reactive protein [hs-CRP]) on hypertension remission will be investigated in a cohort of hypertensive patients with MetS. Material and Methods: Hypertensive patients with MetS (n = 100) were enrolled, treated under current behavior/dietary/pharmacological recommendations and followed up for 12 months. All patients received medications and nutritional advice based on Mediterranean-like dietary pattern in addition to psychological and physicalactivity counselling. At baseline (T0), 6 (T1) and 12 (T2) months of follow-up, clinical data, haematological and biochemical profiles and serum hs-CRP were measured. Results: As compared to T0, at T2 patients displayed improvements in anthropometric and metabolic profiles. At T2, the hypertension remission rate was 13.0%. Serum hs-CRP did not change overtime in the overall cohort. Surprisingly, patients who experienced hypertension remission were less treated with antihypertensive drugs, but developed a weak improvement in anthropometric measures during follow-up.The hypertension remission group had lower baseline levels of hs-CRP as compared to non-remission. Low baseline hs-CRP (<2 µg/mL, cut-off value identified by ROC curve) predicted hypertension remission, independently of antihypertensive treatment implementation, baseline systolic blood pressure and waist circumference improvement. Conclusions: Remission of hypertension in MetS is independently associated with baseline low CRP levels, which might suggest a critical role for inflammation in sustaining high blood pressure levels. K E Y W O R D SC-reactive protein, hypertension, inflammation, metabolic syndrome, obesity, overweight

Although coronary thrombosis (CT) is integral to cardiovascular outcomes, the underlying pathophysiological mechanisms remain unclear. CT may occur in case of atherosclerotic plaque erosion/rupture, or even after stenting implantation. Platelets (PLT) activation is the keystone of atherothrombosis and depends on many dysregulated elements, including endothelial dysfunction, oxidized lipoproteins, and immune response. Besides the classical view of PLT as an effector of hemostatic response, a new repertoire of PLT activities is emerging. PLT lipidome oxidation is a self‐maintaining process which promotes PLT reactivity, coagulation cascade, and inflammatory cell activation. PLT‐innate immune cell interaction is also sustained by neutrophil extracellular traps and NLRP3 inflammasome pathways. Other noteworthy emerging mechanisms are implicated in the crosstalk between PLT and surrounding cells. Especially, microvesicles (MVs) released from PLT may extend their signaling network far beyond the classical cell−cell interactions. Moreover, the recognition of noncoding RNA in PLT MVs introduce another layer of complexity in terms of intercellular signaling by a direct regulation of messenger RNA profile and gene expression in the recipient cells. The aim of this narrative review is to update the recent advance in CT and intracoronary stent thrombosis, including causal factors and potential translation of experimental evidence into the clinical setting.

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Background: Inflammatory biomarkers are useful in detecting patients with sepsis. The prognostic role of resistin and myeloperoxidase (MPO) has been investigated in sepsis. Materials and Methods: Plasma resistin and MPO were measured on days 1, 2 and 7 in 957 patients enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. The association between resistin and MPO levels on day 1, 2 and 7 and 90-day mortality was assessed. Results: Plasma resistin and MPO concentrations were higher at day 1 and decreased until day 7. Both biomarkers were positively correlated with each other and with physiological parameters. Higher levels of resistin and MPO on day 1 were associated with the development of new organ failures. Patients experiencing death at 90 days showed higher levels of resistin and MPO compared with survivors. At day 1, only MPO in the 4th quartile (Q4), but not resistin, was found to predict 90-day death (adjusted hazard ratio [aHR] 1.55 vs Q1). At day 2, resistin in the Q3 and Q4 2 of 13 | BONAVENTURA ET Al.

Abstract Aims  A 5-year survival of patients with unprotected left main (ULM) stenosis according to the choice of revascularization (percutaneous vs. surgical) remains to be defined. Methods and results  Randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) vs. coronary artery bypass graft (CABG) with a follow-up of at least 5 years were included. All-cause death was the primary endpoint. MACCE [a composite endpoint of all-cause mortality, myocardial infarction (MI), stroke, and repeat revascularization] along with its single components and cardiovascular (CV) death were the secondary ones. Analyses were stratified according to the use of first- vs. last-generation coronary stents. Subgroup comparisons were performed according to SYNTAX score (below or above 33) and to age (using cut-offs of each trial’s subgroup analysis). Four RCTs with 4394 patients were identified: 2197 were treated with CABG, 657 with first generation, and 1540 with last-generation stents. At 5-year rates of all-cause death did not differ [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.71–1.21], as those of CV death and stroke. Coronary artery bypass graft reduced rates of MACCE (OR 0.69, 95% CI 0.60–0.79), mainly driven by MI (OR 0.48, 95% CI 0.36–0.65) and revascularization (OR 0.53, 95% CI 0.45–0.64). Benefit of CABG for MACCE was consistent, although with different extent, across values of SYNTAX score (OR 0.76, 95% CI 0.59–0.97 for values &lt; 32 and OR 0.63, 95% CI 0.47–0.84 for values ≥ 33) while was not evident for ‘younger’ patients (OR 0.83, 95% CI 0.65–1.07 vs. OR 0.65, 95% CI 0.51–0.84 for ‘older’ patients). Conclusion  For patients with ULM disease followed-up for 5 years, no significant difference was observed in all-cause and cardiovascular death between PCI and CABG. Coronary artery bypass graft reduced risk of MI, revascularization, and MACCE especially in older patients and in those with complex coronary disease and a high SYNTAX score.

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