Background: Lecithin:cholesterol acyltransferase (LCAT) is the sole enzyme that esterifies cholesterol in plasma. Its role in the supposed protection from atherogenesis remains unclear because mutations in LCAT causing fish-eye disease (FED) or familial LCAT deficiency (FLD) have been reported to be associated with more or instead less carotid atherosclerosis, respectively. This discrepancy may be associated with the loss of cholesterol esterification on only apolipoprotein AI (FED) or on both apolipoprotein AI– and apolipoprotein B–containing lipoproteins (FLD), an aspect that has thus far not been investigated. Methods: Seventy-four heterozygotes for LCAT mutations recruited from Italy and the Netherlands were assigned to FLD (n=33) or FED (n=41) groups and compared with 280 control subjects. Subclinical atherosclerosis was assessed with carotid intima-media thickness. Results: Compared with control subjects, total cholesterol was lower by 16% (−32.9 mg/dL) and 7% (−14.9 mg/dL) and high-density lipoprotein cholesterol was lower by 29% (−16.7 mg/dL) and 36% (−20.7 mg/dL) in the FLD and FED groups, respectively. Subjects with FLD displayed a significant 18% lower low-density lipoprotein cholesterol compared with subjects with FED (101.9±35.0 versus 123.6±47.4 mg/dL; P =0.047) and control subjects (122.6±35.0 mg/dL; P =0.003). Remarkably, all 3 intima-media thickness parameters were lower in subjects with FLD compared with FED and control subjects (accounting for age, sex, body mass index, smoking, hypertension, family history of cardiovascular disease, and plasma lipids). After additional correction for nationality and ultrasonographic methods, average and maximum intima-media thickness remained significantly lower when subjects with FLD were compared with those with FED (0.59 versus 0.73 mm, P =0.003; and 0.87 versus 1.24 mm, P <0.001, respectively). In contrast, the common carotid intima-media thickness (corrected for age, sex, body mass index, smoking, hypertension, family history of cardiovascular disease, and plasma lipids) was higher in subjects with FED compared with control subjects (0.69 versus 0.65 mm; P =0.05), but this significance was lost after adjustment for nationality and ultrasonographic machine. Conclusions: In this head-to-head comparison, FLD and FED mutations were shown to be associated with decreased and increased atherosclerosis, respectively. We propose that this discrepancy is related to the capacity of LCAT to generate cholesterol esters on apolipoprotein B–containing lipoproteins. Although this capacity is lost in FLD, it is unaffected in FED. These results are important when considering LCAT as a target to decrease atherosclerosis.

Reactive oxygen species (ROS) induce nuclear factor erythroid 2–related factor 2 (Nrf2) activation as an adaptive defense mechanism, determining the synthesis of antioxidant molecules, including heme-oxygenase-1 (HO-1). HO-1 protects cells against oxidative injury, degrading free heme and inhibiting ROS production. HO-1 is highly expressed in macrophages during plaque growth. Macrophages are morpho-functionally heterogeneous, and the prevalence of a specific phenotype may influence the plaque fate. This heterogeneity has also been observed in monocyte-derived macrophages (MDMs), a model of macrophages infiltrating tissue. The study aims to assess oxidative stress status and Nrf2/HO-1 axis in MDM morphotypes obtained from healthy subjects and coronary artery disease (CAD) patients, in relation to coronary plaque features evaluated in vivo by optical coherence tomography (OCT). We found that MDMs of healthy subjects exhibited a lower oxidative stress status, lower Nrf2 and HO-1 levels as compared to CAD patients. High HO-1 levels in MDMs were associated with the presence of a higher macrophage content, a thinner fibrous cap, and a ruptured plaque with thrombus formation, detected by OCT analysis. These findings suggest the presence of a relationship between in vivo plaque characteristics and in vitro MDM profile, and may help to identify patients with rupture-prone coronary plaque.

Background: In acute myocardial infarction, acute hyperglycemia is a predictor of acute kidney injury ( AKI ), particularly in patients without diabetes mellitus. This emphasizes the importance of an acute glycemic rise rather than glycemia level at admission. We investigated whether, in diabetic patients with acute myocardial infarction, the combined evaluation of acute and chronic glycemic levels may have better prognostic value for AKI than admission glycemia. Methods and Results: At admission, we prospectively measured glycemia and estimated average chronic glucose levels (mg/dL) using glycosylated hemoglobin (HbA _1c ), according to the following formula: 28.7×HbA _1c (%)−46.7. We evaluated the association with AKI of the acute/chronic glycemic ratio and of the difference between acute and chronic glycemia (Δ _A−C ). We enrolled 474 diabetic patients with acute myocardial infarction. Of them, 77 (16%) experienced AKI . The incidence of AKI increased in parallel with the acute/chronic glycemic ratio (12%, 14%, 22%; P =0.02 for trend) and Δ _A−C (13%, 13%, 23%; P =0.01) but not with admission glycemic tertiles ( P =0.22). At receiver operating characteristic analysis, the acute/chronic glycemic ratio (area under the curve: 0.62 [95% confidence interval, 0.55–0.69]; P =0.001) and Δ _A−C (area under the curve: 0.62 [95% confidence interval, 0.54–0.69]; P =0.002) accurately predicted AKI , without difference in the area under the curve between them ( P =0.53). At reclassification analysis, the addition of the acute/chronic glycemic ratio and Δ _A−C to acute glycemia allowed proper AKI risk prediction in 16% of patients. Conclusions: In diabetic patients with acute myocardial infarction, AKI is better predicted by the combined evaluation of acute and chronic glycemic values than by assessment of admission glycemia alone.

Despite the fact that American Heart Association (AHA) recommended a systematic screening for depression in cardiovascular inpatients, poor attention has been given to this issue. Furthermore, no specific guidelines exist for anxiety screening in cardiovascular inpatients. Thus, the aims of this study were to verify the feasibility of a depressive and anxiety symptoms screening protocol in an Italian hospital specializing in cardiovascular diseases and to evaluate both anxiety and depressive symptoms prevalence. A group of 2009 consecutive inpatients completed the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder (GAD-7). The rates of depressive and anxiety symptoms were almost 9% and 16% respectively. Men were less likely than women to experience both depressive and anxiety symptoms. Patients who were admitted to the heart failure unit reported higher risk of experiencing both symptoms compared to patients in other wards. Similarly, patients admitted to the cardiac surgery unit showed a higher risk of experiencing anxiety symptoms compared to other patients. The proposed screening procedure showed a good feasibility and acceptance. This study highlighted the importance of implementing a short screening procedure in hospitals dealing with cardiovascular inpatients to identify those individuals who require specific attention and interventions.