High Extra Virgin Olive Oil Consumption Is Linked to a Lower Prevalence of NAFLD with a Prominent Effect in Obese Subjects: Results from the MICOL Study.

Extra virgin olive oil (EVOO) has healthy benefits for noncommunicable diseases (NCDs). However, limited evidence is available about the effects of liver disease and non-alcoholic fatty liver disease (NAFLD). We evaluate whether dose-increased consumption of EVOO is associated with a lower prevalence of NAFLD and if these effects vary based on body weight. The study included 2436 subjects with a 33% NAFLD prevalence. Daily EVOO was categorized into tertiles: low (0-24 g/day), moderate (25-37 g/day), and high consumption (>37 g/day). Subjects were also classified by body mass index (BMI) as normo-weight (18.5-24.9), overweight (25-29.9), and obese (≥30). Logistic regression analysis was applied to calculate odds ratios (ORs) for NAFLD, considering a 20-gram increment in EVOO intake and accounting for EVOO categories combined with BMI classes. The ORs were 0.83 (0.74;0.93) C.I. p = 0.0018 for continuous EVOO, 0.89 (0.69;1.15) C.I. p = 0.37, and 0.73 (0.55;0.97) C.I. p = 0.03 for moderate and high consumption, respectively, when compared to low consumption. Overall, the percent relative risk reductions (RRR) for NAFLD from low to high EVOO consumption were 18% (16.4%;19.2%) C.I. and 26% (25%;27.4%) C.I. in overweight and obese subjects. High EVOO consumption is associated with a reduced risk of NAFLD. This effect is amplified in overweight subjects and even more in obese subjects.

Circulating Small Extracellular Vesicles Reflect the Severity of Myocardial Damage in STEMI Patients.

Circulating small extracellular vesicles (sEVs) contribute to inflammation, coagulation and vascular injury, and have great potential as diagnostic markers of disease. The ability of sEVs to reflect myocardial damage assessed by Cardiac Magnetic Resonance (CMR) in ST-segment elevation myocardial infarction (STEMI) is unknown. To fill this gap, plasma sEVs were isolated from 42 STEMI patients treated by primary percutaneous coronary intervention (pPCI) and evaluated by CMR between days 3 and 6. Nanoparticle tracking analysis showed that sEVs were greater in patients with anterior STEMI (p = 0.0001), with the culprit lesion located in LAD (p = 0.045), and in those who underwent late revascularization (p = 0.038). A smaller sEV size was observed in patients with a low myocardial salvage index (MSI, p = 0.014). Patients with microvascular obstruction (MVO) had smaller sEVs (p < 0.002) and lower expression of the platelet marker CD41-CD61 (p = 0.039). sEV size and CD41-CD61 expression were independent predictors of MVO/MSI (OR [95% CI]: 0.93 [0.87-0.98] and 0.04 [0-0.61], respectively). In conclusion, we provide evidence that the CD41-CD61 expression in sEVs reflects the CMR-assessed ischemic damage after STEMI. This finding paves the way for the development of a new strategy for the timely identification of high-risk patients and their treatment optimization.

GALAD outperforms aMAP and ALBI for predicting HCC in patients with compensated advanced chronic liver disease: A 12-year prospective study.

BACKGROUND AND AIMS: Surveillance programs are strongly recommended in patients with liver cirrhosis for early detection of HCC development. Six-monthly ultrasound sonography is the most reliable and commonly used technique, especially when associated with serum determination of α-fetoprotein, but different score systems have been proposed to overcome the unsatisfactory diagnostic accuracy of α-fetoprotein. The aim of this 12-year prospective study is to compare the gender, age, AFP-L3, AFP, des-gamma-carboxy prothrombin (GALAD) versus age, gender, bilirubin, albumin, and platelets and albumin-bilirubin scores in predicting HCC onset. APPROACH AND RESULTS: A cohort of 545 consecutive patients with compensated advanced chronic liver disease without suspected focal lesions was followed up every 6 months by liver imaging and α-fetoprotein to detect HCC occurrence. Harrell's C-index for censored data was employed to evaluate the performance of any parameters or scores helping to predict HCC development. ROC curve analysis showed that the GALAD score was more accurate in evaluating HCC development than albumin-bilirubin and age, gender, bilirubin, albumin, and platelets. The AUC ranged from 0.7268 to 0.6851 at 5 and 10 years, both in the total cohort and in the sub-cohorts (viral hepatitis, NASH, and alcohol). The HCC Risk model was constructed using univariate and multivariate Cox proportional hazard regression analysis, showing a strong association of GALAD with HR > 1, p < 0.05, in the total and sub-cohorts, and a better risk prediction in the alcohol cohort, both alone and standardized with other blood parameters. CONCLUSIONS: GALAD is the most reliable and accurate score system to detect HCC risk of development in patients with compensated advanced chronic liver disease.

Migraine in Patients Undergoing PFO Closure: Characterization of a Platelet-Associated Pathophysiological Mechanism: The LEARNER Study.

The association between migraine and patent foramen ovale (PFO) has been documented. We aimed to investigate platelet activation, prothrombotic phenotype, and oxidative stress status of migraineurs with PFO on 100 mg/day aspirin, before and 6 months after PFO closure. Data show that, before PFO closure, expression of the classical platelet activation markers is comparable in patients and aspirin-treated healthy subjects. Conversely, MHA-PFO patients display an increased prothrombotic phenotype (higher tissue factorpos platelets and microvesicles and thrombin-generation potential), sustained by an altered oxidative stress status. This phenotype, which is more controlled by P2Y12-blockade than by aspirin, reverted after PFO closure together with a complete migraine remission. (pLatelEts And MigRaine iN patEnt foRamen Ovale [LEARNER]; NCT03521193).

Mercaptoalbumin Is Associated with Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting.

Coronary artery bypass graft (CABG) surgery still represents the gold standard for patients with complex multivessel coronary artery disease. However, graft occlusion still occurs in a significant proportion of CABG conduits, and oxidative stress is currently considered to be a potential contributor. Human serum albumin (HSA) represents the main antioxidant in plasma through its reduced amino acid Cys34, which can efficiently scavenge several oxidants. In a nested case-control study including 36 patients with occluded grafts and 38 age- and sex-matched patients without occlusion, we assessed the levels of the native mercaptoalbumin (HSA-SH) and oxidized thiolated form of albumin (Thio-HSA) in relation with graft occlusion within 5 years after CABG. We found that the plasma level of preoperative HSA-SH was significantly lower in patients with occluded graft at 5 years follow-up than in patients with graft patency. Furthermore, low HSA-SH remained independently associated with graft occlusion even after adjusting for preoperative D-dimer, a well-known marker of activated coagulation recently found to be associated with graft occlusion. In conclusion, the preoperative level of HSA-SH is independently associated with graft occlusion in CABG and represents a measurable and potentially druggable predictor.

Comparison between PtCO2 and PaCO2 and Derived Parameters in Heart Failure Patients during Exercise: A Preliminary Study.

Evaluation of arterial carbon dioxide pressure (PaCO2) and dead space to tidal volume ratio (VD/VT) during exercise is important for the identification of exercise limitation causes in heart failure (HF). However, repeated sampling of arterial or arterialized ear lobe capillary blood may be clumsy. The aim of our study was to estimate PaCO2 by means of a non-invasive technique, transcutaneous PCO2 (PtCO2), and to verify the correlation between PtCO2 and PaCO2 and between their derived parameters, such as VD/VT, during exercise in HF patients. 29 cardiopulmonary exercise tests (CPET) performed on a bike with a ramp protocol aimed at achieving maximal effort in ≈10 min were analyzed. PaCO2 and PtCO2 values were collected at rest and every 2 min during active pedaling. The uncertainty of PCO2 and VD/VT measurements were determined by analyzing the error between the two methods. The accuracy of PtCO2 measurements vs. PaCO2 decreases towards the end of exercise. Therefore, a correction to PtCO2 that keeps into account the time of the measurement was implemented with a multiple regression model. PtCO2 and VD/VT changes at 6, 8 and 10 min vs. 2 min data were evaluated before and after PtCO2 correction. PtCO2 overestimates PaCO2 for high timestamps (median error 2.45, IQR -0.635-5.405, at 10 min vs. 2 min, p-value = 0.011), while the error is negligible after correction (median error 0.50, IQR = -2.21-3.19, p-value > 0.05). The correction allows removing differences also in PCO2 and VD/VT changes. In HF patients PtCO2 is a reliable PaCO2 estimation at rest and at low exercise intensity. At high exercise intensity the overall response appears delayed but reproducible and the error can be overcome by mathematical modeling allowing an accurate estimation by PtCO2 of PaCO2 and VD/VT.

Plasma Exosome Profile in ST-Elevation Myocardial Infarction Patients with and without Out-of-Hospital Cardiac Arrest.

The identification of new biomarkers allowing an early and more accurate characterization of patients with ST-segment elevation myocardial infarction (STEMI) is still needed, and exosomes represent an attractive diagnostic tool in this context. However, the characterization of their protein cargo in relation to cardiovascular clinical manifestation is still lacking. To this end, 35 STEMI patients (17 experiencing resuscitated out-of-hospital cardiac arrest (OHCA-STEMI) and 18 uncomplicated) and 32 patients with chronic coronary syndrome (CCS) were enrolled. Plasma exosomes were characterized by the nanoparticle tracking analysis and Western blotting. Exosomes from STEMI patients displayed a higher concentration and size and a greater expression of platelet (GPIIb) and vascular endothelial (VE-cadherin) markers, but a similar amount of cardiac troponin compared to CCS. In addition, a difference in exosome expression of acute-phase proteins (ceruloplasmin, transthyretin and fibronectin) between STEMI and CCS patients was found. GPIIb and brain-associated marker PLP1 accurately discriminated between OHCA and uncomplicated STEMI. In conclusion, the exosome profile of STEMI patients has peculiar features that differentiate it from that of CCS patients, reflecting the pathophysiological mechanisms involved in STEMI. Additionally, the exosome expression of brain- and platelet-specific markers might allow the identification of patients experiencing ischemic brain injury in STEMI.

Modulation of soluble receptor for advanced glycation end products isoforms and advanced glycation end products in long-living individuals.

Background: Circulating levels of soluble receptor for advanced glycation end products (sRAGE) and advanced glycation end products (AGEs) correlate with aging/cardiovascular risk, which is delayed in long-living individuals (LLIs). AGEs/sRAGE isoforms (cleaved RAGE [cRAGE] and secretory RAGE [esRAGE]) ratio is a valuable marker for disease risk. Results: We evaluated circulating sRAGE isoforms, and AGEs in LLIs (n = 95; 90-105 years) and controls (n = 94; 11-89 years). cRAGE decreased with age in controls and further declined in LLIs. esRAGE increased in LLIs. AGEs rose with age in controls and decreased in LLIs that were characterized by a lower AGEs/sRAGE ratio. Notably, cRAGE and AGE/esRAGE ratio better discriminated controls from LLIs. Conclusion: circulating cRAGE could be considered a reliable marker of chronological age while esRAGE a protective factor for longevity.

Lay abstract Aging is the major risk factor for disease development. Long-living individuals (LLIs) are subjects older than 90 years that represent an invaluable model to study mechanisms underpinning longevity and healthy aging. Circulating levels of soluble receptor for advanced glycation end products (sRAGE) change with aging and can forecast the cardiovascular risk, which is reduced in centenarians. sRAGE is composed of two isoforms, the cleaved RAGE (cRAGE) and the secretory RAGE (esRAGE), that are known to inhibit the oxidative stress and inflammatory activities of their ligands such the advanced glycation end products (AGEs). In this study, we measured the plasmatic levels of both sRAGE isoforms and AGEs in LLIs (90­105 years) and control subjects (11­89 years). We found that cRAGE decreases with age in controls and LLIs. esRAGE increases in LLIs and AGEs increase in controls with age but decrease in LLIs. AGEs/esRAGE ratio and cRAGE were able to discriminate controls from LLIs. Hence, LLIs are characterized by a lower AGEs/sRAGE ratio, due to esRAGE increase and AGEs reduction that may explain their reduced cardiovascular and metabolic risk. Besides, circulating cRAGE could be considered a reliable marker of chronological age, while esRAGE a protective factor associated with longevity.

Potential Relation between Plasma BDNF Levels and Human Coronary Plaque Morphology.

Coronary artery disease (CAD) patients are at high ischemic risk, and new biomarkers reflecting atherosclerotic disease severity and coronary plaque vulnerability are required. The Brain-Derived Neurotrophic Factor (BDNF) affects endothelial and macrophage activation suggesting its involvement in atherosclerotic plaque behavior. To investigate whether plasma BDNF is associated with in vivo coronary plaque features, assessed by optical coherence tomography (OCT), in both acute myocardial infarction (AMI) and stable angina (SA) patients, we enrolled 55 CAD patients (31 SA and 24 AMI), and 21 healthy subjects (HS). BDNF was lower in CAD patients than in HS (p < 0.0001), and it decreased with the presence, clinical acuity and severity of CAD. The greater BDNF levels were associated with OCT features of plaque vulnerability in overall CAD as well as in SA and AMI patients (p < 0.03). Specifically, in SA patients, BDNF correlated positively with macrophages' infiltration within atherosclerotic plaque (p = 0.01) and inversely with minimal lumen area (p = 0.02). In AMI patients a negative correlation between BDNF and cap thickness was found (p = 0.02). Despite a small study population, our data suggest a relationship between BDNF and coronary plaque vulnerability, showing that vulnerable plaque is positively associated with plasma BDNF levels, regardless of the clinical CAD manifestation.

Soluble Receptor for Advanced Glycation End-products regulates age-associated Cardiac Fibrosis.

Myocardial aging increases the cardiovascular risk in the elderly. The Receptor for Advanced Glycation End-products (RAGE) is involved in age-related disorders. The soluble isoform (sRAGE) acts as a scavenger blocking the membrane-bound receptor activation. This study aims at investigating RAGE contribution to age-related cardiac remodeling. We analyzed the cardiac function of three different age groups of female Rage-/- and C57BL/6N (WT) mice: 2.5- (Young), 12- (Middle-age, MA) and 21-months (Old) old. While aging, Rage-/- mice displayed an increase in left ventricle (LV) dimensions compared to age-matched WT animals, with the main differences observed in the MA groups. Rage-/- mice showed higher fibrosis and a larger number of α-Smooth Muscle Actin (SMA)+ cells with age, along with increased expression of pro-fibrotic Transforming Growth Factor (TGF)-ß1 pathway components. RAGE isoforms were undetectable in LV of WT mice, nevertheless, circulating sRAGE declined with aging and inversely associated with LV diastolic dimensions. Human cardiac fibroblasts stimulated with sRAGE exhibited a reduction in proliferation, pro-fibrotic proteins and TGF-beta Receptor 1 (TGFbR1) expression and Smad2-3 activation. Finally, sRAGE administration to MA WT animals reduced cardiac fibrosis. Hence, our work shows that RAGE associates with age-dependent myocardial changes and indicates sRAGE as an inhibitor of cardiac fibroblasts differentiation and age-dependent cardiac fibrosis.

Very Long-term Outcome of Minimally Invasive Direct Coronary Artery Bypass.

BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) is a well-established, low-impact surgical procedure for revascularization of the left descending coronary artery with the left internal mammary artery. This study aimed to evaluate safety, overall survival, and freedom from major adverse cardiocerebral-related events (MACCE) after 20 years of MIDCAB. METHODS: This study retrospectively collected a series of 141 patients who underwent MIDCAB between 1997 and 2017, to assess long-term outcome. A total of 133 patients who underwent revascularization of the left descending coronary artery with the left mammary artery through a full median sternotomy were analyzed. RESULTS: Actuarial survival rates on a Kaplan-Meier curve were 100%, 95%, 90%, 83%, and 70% at 1, 5, 10, 15, and 20 years, respectively. Freedom from MACCE, defined as myocardial infarction, stroke, and cardiac death, was 97%, 90%, 79%, 75%, and 61% at 1,5,10,15, and 20 years, respectively. At Cox multivariable analysis, age, cancer, and chronic renal insufficiency were found to be independent predictors affecting long-term survival, with a hazard ratio of 1.12 (P = .007), 17.63 (P < .001), and 5.16 (P = .03), respectively. The MIDCAB group showed a significantly shorter hospital length of stay and significantly lower rates of blood transfusions, cardiac-related events, and all-cause events compared with the full sternotomy group (P = .02 and P = .001, respectively). CONCLUSIONS: The very long-term clinical outcome of MIDCAB is satisfactory in terms of survival and freedom from MACCE. MIDCAB significantly reduces hospital length of stay and blood transfusions when compared with full sternotomy bypass surgery on the left descending coronary artery and appears to improve prognosis in terms of cardiac-related events and all-cause events effectively.

The microRNA-34a-Induced Senescence-Associated Secretory Phenotype (SASP) Favors Vascular Smooth Muscle Cells Calcification.

The senescence of vascular smooth muscle cells (VSMCs), characterized by the acquisition of senescence-associated secretory phenotype (SASP), is relevant for VSMCs osteoblastic differentiation and vascular calcification (VC). MicroRNA-34a (miR-34a) is a driver of such phenomena and could play a role in vascular inflammaging. Herein, we analyzed the relationship between miR-34a and the prototypical SASP component IL6 in in vitro and in vivo models. miR-34a and IL6 levels increased and positively correlated in aortas of 21 months-old male C57BL/6J mice and in human aortic smooth muscle cells (HASMCs) isolated from donors of different age and undergone senescence. Lentiviral overexpression of miR-34a in HASMCs enhanced IL6 secretion. HASMCs senescence and calcification accelerated after exposure to conditioned medium of miR-34a-overexpressing cells. Analysis of miR-34a-induced secretome revealed enhancement of several pro-inflammatory cytokines and chemokines, including IL6, pro-senescent growth factors and matrix-degrading molecules. Moreover, induction of aortas medial calcification and concomitant IL6 expression, with an overdose of vitamin D, was reduced in male C57BL/6J Mir34a-/- mice. Finally, a positive correlation was observed between circulating miR-34a and IL6 in healthy subjects of 20-90 years. Hence, the vascular age-associated miR-34a promotes VSMCs SASP activation and contributes to arterial inflammation and dysfunctions such as VC.

Association of Microvesicles With Graft Patency in Patients Undergoing CABG Surgery.

BACKGROUND: Graft patency is one of the major determinants of long-term outcome following coronary artery bypass graft surgery (CABG). Biomarkers, if indicative of the underlying pathophysiological mechanisms, would suggest strategies to limit graft failure. The prognostic value of microvesicles (MVs) for midterm graft patency has never been tested. OBJECTIVES: The aim of this study was to evaluate whether MV pre-operative signature (number, cellular origin, procoagulant phenotype) could predict midterm graft failure and to investigate potential functional role of MVs in graft occlusion. METHODS: This was a nested case-control substudy of the CAGE (CoronAry bypass grafting: factors related to late events and Graft patency) study that enrolled 330 patients undergoing elective CABG. Of these, 179 underwent coronary computed tomography angiography 18 months post-surgery showing 24% graft occlusion. Flow cytometry MV analysis was performed in 60 patients (30 per group with occluded [cases] and patent [control subjects] grafts) on plasma samples collected the day before surgery and at follow-up. RESULTS: Before surgery, cases had 2- and 4-fold more activated platelet-derived and tissue-factor positive MVs respectively than control subjects. The MV procoagulant capacity was also significantly greater. Altogether this MV signature properly classified graft occlusion (area under the curve 0.897 [95% confidence interval: 0.81 to 0.98]; p < 0.0001). By using an MV score (0 to 6), the odds ratio for occlusion for a score above 3 was 16.3 (95% confidence interval: 4.1 to 65.3; p < 0.0001). CONCLUSIONS: The pre-operative signature of MVs is independently associated with midterm graft occlusion in CABG patients and a cumulative MV score stratifies patients' risk. Because the MV signature mirrors platelet activation, patients with a high MV score could benefit from a personalized antiplatelet therapy.

Montelukast Use Decreases Cardiovascular Events in Asthmatics.

Cysteinyl leukotrienes are proinflammatory mediators with a clinically established role in asthma and a human genetic and preclinical role in cardiovascular pathology. Given that cardiovascular disease has a critical inflammatory component, the aim of this work was to conduct an observational study to verify whether the use of a cysteinyl leukotriene antagonist, namely, montelukast, may protect asthmatic patients from a major cardiovascular event and, therefore, represent an innovative adjunct therapy to target an inflammatory component in cardiovascular disease. We performed an observational retrospective 3-year study on eight hundred adult asthmatic patients 18 years or older in Albania, equally distributed into two cohorts, exposed or nonexposed to montelukast usage, matched by age and gender according to information reported in the data collection. Patients with a previous history of myocardial infarction or ischemic stroke were excluded. In summary, 37 (4.6%) of the asthmatic patients, 32 nonexposed, and five exposed to montelukast suffered a major cardiovascular event during the 3-year observation period. All the cardiovascular events, in either group, occurred among patients with an increased cardiovascular risk. Our analyses demonstrate that, independent from gender, exposure to montelukast remained a significant protective factor for incident ischemic events (78% or 76% risk reduction depending on type of analysis). The event-free Kaplan-Meier survival curves confirmed the lower cardiovascular event incidence in patients exposed to montelukast. Our data suggest that there is a potential preventative role of montelukast for incident cardiac ischemic events in the older asthmatic population, indicating a comorbidity benefit of montelukast usage in asthmatics by targeting cysteinyl leukotriene-driven cardiac disease inflammation.

Data on the association between a simplified Mediterranean diet score and the incidence of combined, cardio and cerebro vascular events.

Data presented in this article are related to the research article entitled "A priori-defined Mediterranean-like dietary pattern predicts cardiovascular events better in north Europe than in Mediterranean countries" [Veglia et al., 2018]. Data contain information about the incidence of cardiovascular events in a high-risk European population (IMPROVE study) [Baldassarre et al., 2010, 2012, 2013]. Combined vascular events, as well as cardio- and cerebro-vascular events were stratified according to a priori-defined simple Mediterranean Diet (MD) score, based on just seven nutritional items (minimal adherence was 0 and maximal adherence was 7).

Modulation of soluble receptor for advanced glycation end-products (RAGE) isoforms and their ligands in healthy aging.

The receptor for advanced glycation end-products (RAGE) recognizes several ligands involved in inflammatory diseases. Two circulating soluble isoforms exist: esRAGE derived from alternative splicing and cRAGE generated by the membrane-bound RAGE (FL-RAGE) proteolysis. Together, esRAGE and cRAGE constitute sRAGE and function as decoy receptors preventing FL-RAGE/ligands binding.We determined serum concentration of both, esRAGE and cRAGE, and their ligands AGEs, HMGB1 and S100A8/A9 in a healthy population of 169 subjects aged 20-90 years. cRAGE showed a negative (r=-0.375, P<0.0001) while AGEs (r=0.160, P=0.0384) and S100A8/A9 (r=0.207, P=0.0091) a positive correlation with age. esRAGE did not change during aging and inversely correlated with Hemoglobin, ALT, insulin, HOMA index, Waist-Hip ratio (W/H), Waist Circumference (WC) and positively with AGEs. cRAGE exhibited also an inverse correlation with WC, W/H, PAI-1, HMGB1, AGEs and S100A8/A9. Age, W/H, HMGB1, S100A8/A9 and AGEs are independent predictors of cRAGE, whereas W/H and AGEs associate with esRAGE. Treatment of cells with glycated albumin reduced cRAGE production and upregulated FL-RAGE.These results indicate that in a healthy population cRAGE is a biomarker of aging while esRAGE represents a more reliable marker of obesity and insulin resistance. Hence, sRAGE isoforms levels could be differentially associated with age-related diseases risk factors.

A priori-defined Mediterranean-like dietary pattern predicts cardiovascular events better in north Europe than in Mediterranean countries.

BACKGROUND: The Mediterranean Diet (MD) is a model of healthy eating contributing to a favorable health status, but its clinical usefulness is still debated. The aim of this study was to relate the adherence to MD with the incidence of cardio/cerebro-vascular events (VEs) in north and south European participants of the IMPROVE study. METHODS: IMPROVE is an observational, longitudinal, prospective cohort study involving 3703 individuals from five European countries (Finland, Sweden, Netherlands, France and Italy). The study end-point was the incidence of the first combined cardio/cerebro-vascular event occurring during 36-months follow-up. At baseline, a dietary questionnaire about the usual intake during the year preceding enrollment was administered. Based on 7 nutritional items, a MD Score was constructed in which minimal adherence was 0 and maximal adherence was 7. RESULTS: Latitude was the strongest determinant of MD score (p < 0.001). VEs occurred in 215 participants. The incidence of VEs was the highest in subjects with MD score 0-1, lower in those with score 2-3 and the lowest in those with score ≥ 4. MD score remained significantly associated with subsequent VEs after adjustment for confounders (hazard ratio for one-point increment of the score = 0.75, p < 0.001) and the association was stronger in northern than in southern countries (p = 0.04 for MD Score × latitude interaction). CONCLUSIONS: The MD adherence score based on a simple dietary questionnaire detects changes of risk of VEs. According to our findings north Europeans appear to benefit most from VE-prevention when their diet is altered to the MD diet.

Association of lifelong occupation and educational level with subclinical atherosclerosis in different European regions. Results from the IMPROVE study.

BACKGROUND AND AIMS: We aimed to examine the association between socioeconomic status (SES) and subclinical atherosclerosis, as assessed by carotid intima-media-thickness (C-IMT) and to investigate whether the effect of social inequality on C-IMT is mediated by cardiovascular (CV) risk factors and whether it is dissimilar in men and women, and in different European countries. METHODS: We assessed the association of lifelong occupation and educational level with C-IMT in the IMPROVE study cohort including 3703 subjects (median age 64.4 years; 48% men) from Southern (Italy), Western (France and the Netherlands) and Northern Europe (Finland and Sweden). Three summary measures of C-IMT (IMTmean, IMTmax, IMTmean-max), obtained from four segments of both carotids, were considered. RESULTS: After adjusting for conventional CV risk factors, current employment status and diet, C-IMT was higher in manual workers than in white collars (+7.7%, +5.3%, +4.6% for IMTmax, IMTmean-max and IMTmean, respectively; all p<.0001). Similar results were obtained by stratification for educational level. The effect of occupation on C-IMT was comparable in men and women and in different age groups, and was only partially mediated by differences in CV risk factors. Of note, the association of C-IMT with occupation was significant in Western and Northern Europe but not in Italy, with a significant statistical interaction (p = .0005). CONCLUSIONS: Low SES was associated with subclinical atherosclerosis in subjects with at least three CV risk factors. Such association was stronger in Northern and Western Europe than in Italy. This difference was not completely explained by inequalities in CV risk factors and behavioural variables.

Carotid plaque-thickness and common carotid IMT show additive value in cardiovascular risk prediction and reclassification.

BACKGROUND AND AIMS: Carotid plaque size and the mean common carotid intima-media thickness measured in plaque-free areas (PF CC-IMTmean) have been identified as predictors of vascular events (VEs), but their complementarity in risk prediction and stratification is still unresolved. The aim of this study was to evaluate the independence of carotid plaque thickness and PF CC-IMTmean in cardiovascular risk prediction and risk stratification. METHODS: The IMPROVE-study is a European cohort (n = 3703), where the thickness of the largest plaque detected in the whole carotid tree was indexed as cIMTmax. PF CC-IMTmean was also assessed. Hazard Ratios (HR) comparing the top quartiles of cIMTmax and PF CC-IMTmeanversus their respective 1-3 quartiles were calculated using Cox regression. RESULTS: After a 36.2-month follow-up, there were 215 VEs (125 coronary, 73 cerebral and 17 peripheral). Both cIMTmax and PF CC-IMTmean were mutually independent predictors of combined-VEs, after adjustment for center, age, sex, risk factors and pharmacological treatment [HR (95% CI) = 1.98 (1.47, 2.67) and 1.68 (1.23, 2.29), respectively]. Both variables were independent predictors of cerebrovascular events (ischemic stroke, transient ischemic attack), while only cIMTmax was an independent predictor of coronary events (myocardial infarction, sudden cardiac death, angina pectoris, angioplasty, coronary bypass grafting). In reclassification analyses, PF CC-IMTmean significantly adds to a model including both Framingham Risk Factors and cIMTmax (Integrated Discrimination Improvement; IDI = 0.009; p = 0.0001) and vice-versa (IDI = 0.02; p < 0.0001). CONCLUSIONS: cIMTmax and PF CC-IMTmean are independent predictors of VEs, and as such, they should be used as additive rather than alternative variables in models for cardiovascular risk prediction and reclassification.

A meta-analysis of randomized controlled trials on statins for the prevention of contrast-induced acute kidney injury in patients with and without acute coronary syndromes.

OBJECTIVES: We assessed whether short-term, pre-procedural, intensive statin treatment may reduce contrast-induced acute kidney injury (CI-AKI) incidence in patients with and without acute coronary syndromes (ACS) undergoing coronary angiography (CA) and percutaneous coronary intervention (PCI). BACKGROUND: Statins may exert renal-protective effects through their pleiotropic properties. However, there have been conflicting reports on the CI-AKI preventive effect of pre-procedural statin administration. METHODS: Randomized controlled trials published between January 1st, 2003 and February 28th, 2014 comparing the preventive effects against CI-AKI of pre-procedural statins vs. control (lower statin dose, no statin, or placebo) in patients undergoing CA/PCI were included. RESULTS: Data were combined from 9 clinical trials enrolling 5212 patients (age 65 ± 5 years, 63% males). Pooled analysis showed that intensive, short-term statin pre-treatment significantly reduced the risk of CI-AKI as compared to control (relative risk [RR] 0.50; 95% confidence interval [CI] 0.39 to 0.64; P<0.001). Pre-specified subgroup analysis showed that intensive statin pre-treatment significantly reduced CI-AKI risk in patients with ACS (RR 0.37; 95% CI 0.25 to 0.55; P<0.0001), with only a non-significant positive trend in patients without ACS (RR 0.65; 95% CI 0.41 to 1.03; P=0.07). No evidence of publication bias was detected. CONCLUSIONS: Short-term, pre-procedural, intensive statin treatment significantly reduced CI-AKI incidence in ACS patients, and may contribute to the overall clinical benefit associated with the early use of these drugs in this clinical setting. Its role in non-ACS patients warrants further investigation.