Mannose as a biomarker of coronary artery disease: Angiographic evidence and clinical significance.

BACKGROUND: High mannose has previously associated with insulin resistance and cardiovascular disease (CVD). Our objective is to establish whether mannose is associated with anatomical evidence of coronary artery disease (CAD). METHODS: Plasma mannose concentrations were measured by liquid chromatography/tandem mass spectrometry in a discovery cohort (n = 513) and a validation cohort (n = 221) of carefully phenotyped individuals. In both cohorts CAD was quantitated using state-of-the-art imaging techniques (coronary computed coronary tomography angiography (CCTA), invasive coronary angiography and optical coherence tomography). Information on subsequent CVD events/death was collected. Associations of mannose with angiographic variables and biomarkers were tested using univariate and multivariate regression models. Survival analysis was performed using the Kaplan-Meier estimator. RESULTS: Mannose was related to indices of CAD and features of plaque vulnerability. In the discovery cohort, mannose was a marker of quantity and quality of CCTA-proven CAD and subjects with a mannose level in the top quartile had a significantly higher risk of CVD events/death (p = 3.6e-5). In the validation cohort, mannose was significantly associated with fibrous cap thickness < 65 µm (odds ratio = 1.32 per each 10 µmol/L mannose change [95% confidence interval, 1.05-1.65]) and was an independent predictor of death (hazard ratio for mannose≥vs < 84.6 µmol/L: 4.0(95%CI, 1.4-11.3), p = 0.006). CONCLUSION: The current data add novel evidence that high mannose is a signature of CAD with a vulnerable plaque phenotype, consistently across measures of severity of vessel involvement and independent of the traditional correlates of CVD, and that it is an independent predictor of incident adverse outcomes.

Metabolomic correlates of coronary atherosclerosis, cardiovascular risk, both or neither. Results of the 2 × 2 phenotypic CAPIRE study.

BACKGROUND: Traditional cardiovascular risk factors (RFs) and coronary artery disease (CAD) do not always run parallel. We investigated functional-metabolic correlations of CAD, RFs, or neither in the CAPIRE (Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation) 2 × 2 phenotypic observational study. METHODS: Two hundred and fortyone subjects were included based on RF burden, presence/absence of CAD (assessed by computed tomography angiography), age and sex. Participants displayed one of four phenotypes: CAD with ≥3 RFs, no-CAD with ≥3 RFs, CAD with ≤1 RF and no-CAD with ≤1 RF. Metabolites were identified by gas chromatography-mass spectrometry and pathways by metabolite set enrichment analysis. RESULTS: Characteristic patterns and specific pathways emerged for each phenotypic group: amino sugars for CAD/high-RF; urea cycle for no-CAD/high-RF; glutathione for CAD/low-RF; glycine and serine for no-CAD/low-RF. Presence of CAD correlated with ammonia recycling; absence of CAD with the transfer of acetyl groups into mitochondria; high-risk profile with alanine metabolism (all p < 0.05). The comparative case-control analyses showed a statistically significant difference for the two pathways of phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism in the CAD/Low-RF vs NoCAD/Low-RF comparison. CONCLUSIONS: The present 2 × 2 observational study identified specific metabolic pathways for each of the four phenotypes, providing novel functional insights, particularly on CAD with low RF profiles and on the absence of CAD despite high-risk factor profiles.

Family history in first degree relatives of patients with premature cardiovascular disease.

BACKGROUND: Family history (FH) of cardiovascular disease (CVD) in first degree relatives (FDR) is a major risk factor, especially for premature events. Data are sparse on FH of different manifestations of CVD among FDRs of patients with premature myocardial infarction (MI), chronic stable angina (CSA) or peripheral vascular disease (PVD). METHODS: We obtained FHs from first degree relatives (parents or siblings) of 230 consecutive patients with premature (men < 60 and women < 65 years) CVD, including 79 wth MI, 39 CSA, 51 PVD and 61 blood donors. Among 1225 parents or siblings, 421 had MI, 222 CSA, 261PVD and 321 were among blood donors. RESULTS: FH of MI were 5.6% (18/321) among blood donors, 14.0% (59/421) among patients with premature MI, 14.4% (32/222) CSA, and 8.0% (21/261) PVD. (all p < 0.05). For FH of CSA the corresponding frequencies were 3.7% 5.2%, 11.3%, and 6.9%. (all p < 0.05). For PVD, the corresponding frequencies were 2.1%, 3.4%, 0.9% and 0.7%, respectively. (p = ns). CONCLUSIONS: These data are compatible with the hypothesis that FH of MI, CSA and PVD are significantly different for patients with premature MI or CSA but not PVD.

Differential Proteomics of Cardiovascular Risk and Coronary Artery Disease in Humans.

BACKGROUND: Proteomics of atypical phenotypes may help unravel cardiovascular disease mechanisms. AIM: We aimed to prospectively screen the proteome of four types of individuals: with or without coronary artery disease (CAD), each with or without multiple risk factors. Associations with individual risk factors and circulating biomarkers were also tested to provide a functional context to the protein hits. MATERIALS AND METHODS: The CAPIRE study (ClinicalTrials.gov Identifier: NCT02157662) is a cross-sectional study aimed at identifying possible new mechanisms promoting or protecting against atherothrombosis. Quantification (by aptamer technology), ranking (using partial least squares), and correlations (by multivariate regression) of ~5000 plasma proteins were performed in consecutive individuals aged 45-75 years, without previous cardiovascular disease, undergoing computed tomography angiography for suspected CAD, showing either >5/16 atherosclerotic segments (CAD+) or completely clean arteries (CAD-) and either ≤ 1 risk factor (RF+) or ≥3 risk factors (RF-) (based on history, blood pressure, glycemia, lipids, and smoking). RESULTS: Of 544 individuals, 39% were atypical (93 CAD+/RF-; 120 CAD-/RF+) and 61% typical (102 CAD+/RF+; 229 CAD-/RF-). In the comparison with CAD+/RF- adjusted for sex and age, CAD-/RF+ was associated with increased atrial myosin regulatory light chain 2 (MYO) and C-C motif chemokine-22 (C-C-22), and reduced protein shisa-3 homolog (PS-3) and platelet-activating factor acetylhydrolase (PAF-AH). Extending the analysis to the entire cohort, an additional 8 proteins were independently associated with CAD or RF; by logistic regression, the 12-protein panel alone discriminated the four groups with AUCROC's of 0.72-0.81 (overall p = 1.0e-38). Among them, insulin-like growth factor binding protein-3 is positively associated with RF, lower BMI, and HDL-cholesterol, renin with CAD higher glycated hemoglobin HbA1c, and smoking. CONCLUSIONS: In a CCTA-based cohort, four proteins, involved in opposing vascular processes (healing vs. adverse remodeling), are specifically associated with low CAD burden in high CV-risk individuals (high MYO and C-C-22) and high CAD burden in low-risk subjects (high PS-3 and PAF-AH), in interaction with BMI, smoking, diabetes, HDL-cholesterol, and HbA1c. These findings could contribute to a deeper understanding of the atherosclerotic process beyond traditional risk profile assessment and potentially constitute new treatment targets.

Association of high-risk coronary atherosclerosis at CCTA with clinical and circulating biomarkers: Insight from CAPIRE study.

BACKGROUND: High-risk coronary atherosclerosis features evaluated coronary CT angiography (CCTA) were suggested to have a prognostic role. The present study aimed to evaluate the association of circulating biomarkers with high-risk plaque features assessed by CCTA. METHODS: A consecutive cohort of subjects who underwent CCTA because of suspected CAD was screened for inclusion in the CAPIRE study. Based on risk factors (RF) burden patients were defined as having a low clinical risk (0-1 RF with the exclusion of patients with diabetes mellitus as single RF) or an high clinical risk (≥3 RFs). In all patients, measurement of inflammatory biomarkers and CCTA analysis focused on high-risk plaque features were performed. Univariate and multivariate logistic regression analysis were used to evaluate the relationship between clinical and biological variables with CCTA advanced plaque features. RESULTS: 528 patients were enrolled in CAPIRE study. Older age and male sex appeared to be predictors of qualitative high-risk plaque features and associated with the presence of elevated total, non-calcified and low-attenuation plaque volume. Among circulating biomarkers only hs-CRP was found to be associated with qualitative high-risk plaque features (OR 2.02, p = 0.004 and 2.02, p = 0.012 for LAP and RI > 1.1, respectively) with borderline association with LAP-Vol (OR 1.52, p = 0.076); HbA1c and PTX-3 resulted to be significantly associated with quantitative high-risk plaque features (OR 1.71, p = 0.003 and 1.04, p = 0.002 for LAP-Vol, respectively). CONCLUSIONS: Our results support the association between inflammatory biomarkers (hs-CRP, PTX- 3), HbA1c and high-risk atherosclerotic features detected by CCTA. Male sex and older age are significant predictors of high-risk atherosclerosis.

Short-term prognosis of unstable angina in the era of high-sensitivity cardiac troponin: insights for early rule-out strategies.

BACKGROUND: It is unclear if strategies to rule-out myocardial infarction (MI) based on a single high-sensitivity troponin T (hsTnT) measurement at the emergency department (ED) presentation may also exclude unstable angina. METHODS: We measured hsTnT ex-post on the admission frozen blood sample of 644 subjects with Braunwald IIIB CK-MB-negative unstable angina. This analysis included the 240 patients with hsTnT value ≤99th percentile reference limit (UA). We evaluated the clinical outcome of UA patients and the applicability of two rule-out strategies based on the combination of a non-ischemic ECG with (1) a single hsTnT value below the Limit-of-Detection (LoD), (2) a TIMI risk score ≤1. RESULTS: UA patients with hsTnT ≤99th percentile reference limit had a favorable 30-day outcome [0.8% MI, 0% cardiovascular death (CVD)], but the rate of CVD/MI at 180-day was 4.7%. Sensitivities for UA were 94.6% according to the 'TIMI ≤1-strategy' and 75.4% according to 'hsTnT-below-LoD-strategy', accounting for 5.4 and 24.6% missed diagnoses, respectively. A prognostic risk stratification to guide appropriate outpatient assessment in potential discharged unrecognized UA patients was developed: a risk score based on the combination of age >60 years and C-reactive protein >4.5 mg/L effectively stratified the 180-day CVD/MI occurrence: 0, 2.5 and 12.7% for score 0, 1 and 2 (log-rank = 0.001, C-statistic = 0.776). CONCLUSION: Single measurement hsTnT strategies, successfully tested to rule-out MI, may allow safe ED discharge of patients with a suspected acute coronary syndrome: even if UA may not be excluded, its short-term prognosis is favorable. UA patients with a C-reactive protein >4.5 mg/L and older than 60 years have a substantial medium-term cardiovascular risk and may benefit from a timely outpatient diagnostic assessment.

Impact of adherence to a Mediterranean Diet pattern on patients with first acute myocardial infarction.

BACKGROUND AND AIMS: The Mediterranean diet (MD) affects the risk of myocardial infarction and long-term prognosis after a coronary event. Limited data are available regarding the influence of MD on short-term prognosis. We assessed the impact of the MD adherence on in-hospital and short-term outcome in patients with first ST-elevation Myocardial Infarction (STEMI). METHODS AND RESULTS: As many as 533 European patients with STEMI and no previous history of coronary artery disease were included in this analysis. Previous dietary habits of each patient were collected with a food frequency questionnaire from which we calculated the FAMI Mediterranean Diet Score (FAMI MD Score), according to the MD adherence. A blood sample was drawn to each patient within 6 h of symptoms onset. Levels of high-sensitivity C-Reactive Protein (hsCRP), Interleukin-6 (IL-6) were measured. Clinical outcome at 180 days and myocardial reperfusion were assessed. Patients with higher FAMI MD Score had lower levels of hsCRP; there were no differences between IL-6 level among FAMI MD Score quintiles. There were no associations between adherence to MD and 180-day adverse events. Lower FAMI MD Score was associated with a higher risk of ineffective myocardial reperfusion after thrombolysis or percutaneous coronary intervention. Similar results were observed for daily consumption of ≥4 portions of fruit and vegetable. CONCLUSIONS: A positive effect of the Mediterranean diet, and fruit and vegetable intake was observed on hsCRP and the occurrence of effective myocardial reperfusion. These findings confirm the favorable impact of Mediterranean diet adherence not only in primary but also in secondary prevention.

Coronary Artery Disease and Type 2 Diabetes: A Proteomic Study.

OBJECTIVE: Coronary artery disease (CAD) is a major challenge in patients with type 2 diabetes (T2D). Coronary computed tomography angiography (CCTA) provides a detailed anatomic map of the coronary circulation. Proteomics are increasingly used to improve diagnostic and therapeutic algorithms. We hypothesized that the protein panel is differentially associated with T2D and CAD. RESEARCH DESIGN AND METHODS: In CAPIRE (Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation-a cohort of 528 individuals with no previous cardiovascular event undergoing CCTA), participants were grouped into CAD- (clean coronaries) and CAD+ (diffuse lumen narrowing or plaques). Plasma proteins were screened by aptamer analysis. Two-way partial least squares was used to simultaneously rank proteins by diabetes status and CAD. RESULTS: Though CAD+ was more prevalent among participants with T2D (HbA1c 6.7 ± 1.1%) than those without diabetes (56 vs. 30%, P < 0.0001), CCTA-based atherosclerosis burden did not differ. Of the 20 top-ranking proteins, 15 were associated with both T2D and CAD, and 3 (osteomodulin, cartilage intermediate-layer protein 15, and HTRA1) were selectively associated with T2D only and 2 (epidermal growth factor receptor and contactin-1) with CAD only. Elevated renin and GDF15, and lower adiponectin, were independently associated with both T2D and CAD. In multivariate analysis adjusting for the Framingham risk panel, patients with T2D were "protected" from CAD if female (P = 0.007), younger (P = 0.021), and with lower renin levels (P = 0.02). CONCLUSIONS: We concluded that 1) CAD severity and quality do not differ between participants with T2D and without diabetes; 2) renin, GDF15, and adiponectin are shared markers by T2D and CAD; 3) several proteins are specifically associated with T2D or CAD; and 4) in T2D, lower renin levels may protect against CAD.

Coronary Plaque Features on CTA Can Identify Patients at Increased Risk of Cardiovascular Events.

OBJECTIVES: This study sought to assess whether coronary atherosclerosis analysis by coronary computed tomography angiography (CTA) may improve prognostic stratification among patients with diffuse coronary artery disease (CAD) BACKGROUND: Coronary CTA has recently emerged as a promising noninvasive tool for advanced analysis of coronary atherosclerosis. METHODS: The multicenter CAPIRE (Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation) study is part of the GISSI Outlier Project. A prospective cohort of subjects who underwent coronary CTA for suspected CAD was enrolled. Based on risk factor (RF) burden, patients were defined as having a low clinical risk (0 to 1 RF with the exclusion of patients with diabetes mellitus as single RF) or at high clinical risk (3 or more RFs). Patients with 2 RFs were not enrolled in the study. Coronary CTA advanced plaque assessment was performed. Outcome measures were 3 combined endpoints: acute coronary syndrome (ACS), cardiac death + ACS, and cardiac death + ACS + late revascularization. RESULTS: Among the 544 patients enrolled in the CAPIRE study, in 522 patients, a mean follow-up of 37 ± 10 months was obtained (16 patients were excluded due to 1 < segment involvement score <5 at core lab coronary CTA analysis and 6 patients were lost at follow-up). Higher atherosclerotic burden was found in patients with higher clinical risk, but prevalence of elevated noncalcified plaque volume did not significantly differ between low- versus high-risk patients. Quantitative plaque parameters by coronary CTA were associated with composite endpoints at multivariable analysis when corrected for univariate predictors. Elevated noncalcified plaque volume, expressed as dichotomic variable, was associated with all combined endpoints. Even if the low absolute number of events represents a limitation to the present study, patients with low noncalcified plaque volume had similar risk of cardiac events independently from the presence of multivessel disease, while patients with high noncalcified plaque volume had higher rates of cardiac events. CONCLUSIONS: The CAPIRE study confirmed the prognostic value of atherosclerosis assessment by coronary CTA, demonstrating high noncalcified plaque volume as the most ACS-predictive parameter in patients with extensive CAD. (GISSE Outliers CAPIRE [CAPIRE]; NCT02157662).

Sequencing of NOTCH1 gene in an Italian population with bicuspid aortic valve: Preliminary results from the GISSI OUTLIERS VAR study.

BACKGROUND: Bicuspid aortic valve (BAV) formation is genetically determined, with reduced penetrance and variable expressivity. NOTCH1 is a proven candidate gene and its mutations have been found in familial and sporadic cases of BAV. METHODS: 66 BAV patients from the GISSI VAR study were genotyped for the NOTCH1 gene. RESULTS: We identified 63 variants, in heterozygous and homozygous states. Fifty-two are common polymorphisms present in almost all patients. Eleven variants are new and never yet reported: two are non-synonymous substitutions, Gly540Asp in exon 10 and Glu851Gln in exon 16; one is in the 3'UTR region and seven in introns, one corresponds to a T allele insertion in intron 27. We selected four statistically noteworthy and seven new variants identified in six BAV patients and correlated them with clinical and demographic variables and with imaging and histological parameters. Preliminary data show that four were BAV patients with isolated stenosis in patients over 60 aged. These variants may correlate with a later need for surgery for the presence of stenosis and not aortic valve regurgitation or ascending aortic aneurysm. CONCLUSIONS: Completing the genotyping of 62 BAV patients we found 11 new variants in the NOTCH1 gene never yet reported. These findings confirm that the identification of new, clinically remarkable biomarkers for BAV requires a deeper genetic understanding of the NOTCH1 gene variants, which could be targeted by future diagnostic and therapeutic strategies.

Effect of adherence to Mediterranean diet on first ST-elevation myocardial infarction: Insights from multiethnic case-control study.

OBJECTIVE: This study aimed to assess the protective role of dietary habits and Mediterranean diet adherence in first acute myocardial infarction in patients enrolled in the multicenter and multiethnic FAMI (First Acute Myocardial Infarction) study. METHODS: In this study we analyzed a multiethnic case-control population of 1478 individuals (858 from Europe and 620 from China): 739 patients with ST-elevation myocardial infarction (STEMI) without previous history of coronary artery disease who were admitted to the Emergency Department within 6 h of symptoms onset, and 739 age- and sex-matched healthy controls. Dietary habits were collected with a food frequency questionnaire from which we calculated the FAMI Mediterranean Diet Score, according to the adherence to Mediterranean diet. RESULTS: European patients with STEMI had significantly lower adherence to Mediterranean diet than controls. Among Chinese populations, there was no association between FAMI Mediterranean Diet Score and STEMI prevalence. The distribution of the main food types suggested that our questionnaire was not an effective tool to study dietary habits in the Chinese population. In the European population, higher adherence to Mediterranean dietary pattern was associated with a protective effect on the risk of STEMI, independently of global cardiovascular risk factor profile. Furthermore, high fruit and vegetable consumption was associated with a significant reduction of STEMI risk. CONCLUSIONS: The study found a protective effect of the Mediterranean diet and high fruit and vegetable consumption on the risk of first STEMI, regardless of traditional cardiovascular risk factors in the European population.

Modes of death and prognostic outliers in chronic heart failure.

BACKGROUND: The impact of incident sudden cardiac death (SCD) on the predictive accuracy of prognostic risk scores for patients with chronic heart failure (HF) has rarely been examined. We assessed the relationship between estimated probability of death and modes of death in this population, as well as the predictors of death and survival in prognostic outliers. METHODS AND RESULTS: The MAGGIC 3-year probability of death was estimated in 6,859 participants of the GISSI-HF trial (mean age 67±11 years, 78% men, 91% with ejection fraction <40%, mean follow-up 3.5±1.3 years, observed mortality 28.4%). The incidence of SCD progressively decreased with increased probability of death, and occurred in 52.5% of patients estimated at low-risk (N = 61 with probability <14%) vs. in 23.5% of the high-risk ones (N = 375 with probability >56%, P < .0001). On the contrary, death from worsening HF was significantly more frequent in the latter group (19.7% vs. 46.1%, P < .0001). The overall predictive accuracy of the MAGGIC model improved after excluding deaths from SCD (AUC from 0.731 to 0.760, P = .0034). Among patients estimated at low-risk (N = 61 dead, 743 alive), independent predictors of death were older age, longer history of HF, higher serum uric acid and chronic obstructive pulmonary disease. The only predictor of survival in patients estimated at high-risk (N = 210 alive, 375 dead) was higher systolic blood pressure. CONCLUSIONS: The MAGGIC risk score demonstrated its scarce ability to capture SCD, particularly in chronic HF patients estimated at low risk of death. Newer and better prognostic tools in the evolving horizon of HF are needed.

Prognostic implications of high-sensitivity cardiac troponin T assay in a real-world population with non-ST-elevation acute coronary syndrome.

BACKGROUND: High-sensitivity cardiac troponin T (hsTnT) was recently approved for clinical use by the Food and Drug Administration. The transition from contemporary to hsTnT assays requires a thorough understanding of the clinical differences between these assays. HYPOTHESIS: HsTnT may provide a more accurate prognostic stratification than contemporary cardiac troponin I (cTnI) in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS: HsTnT and cTnI were measured in 644 patients with CK-MB negative NSTE-ACS who were enrolled in the prospective multicenter SPAI (Stratificazione Prognostica dell'Angina Instabile) study. Patients were stratified at the 99th percentile reference limit for each assay. The primary endpoint was cardiovascular death (CVD) or non-fatal myocardial infarction (MI); the secondary endpoint was the occurrence of unstable angina (UA). Follow-up lasted 180 days. RESULTS: Patients with hsTnT ≥99th percentile were at higher risk of CVD/MI (30-day: 5.9% vs 0.8%, p = 0.001; 180-day: 11.1% vs 4.7%, p = 0.004), also after adjusting for TIMI Risk Score. No significant difference in CVD/MI at 180-day was found between hsTnT-positive/cTnI-negative and hsTnT-negative/cTnI-negative patients (adjHR 1.61, 95% CI 0.74-3.49, p = 0.232). Occurrence of UA was not differently distributed between hsTnT groups dichotomized at the 99th percentile (12.4% vs 12.5% p = 0.54). CONCLUSIONS: Our investigation on a real-world NSTE-ACS population showed good prognostic performance of hsTnT in the risk stratification of the hard endpoint, but did not demonstrate the improved prognostic ability of hsTnT over contemporary cTn. Neither troponin assay predicted the recurrence of UA, suggesting the acute rise of cardiac troponin as a marker of severity, but not the occurrence of future coronary instability.

"Summer Shift": A Potential Effect of Sunshine on the Time Onset of ST-Elevation Acute Myocardial Infarction.

BACKGROUND: ST-elevation acute myocardial infarction (STEMI) represents one of the leading causes of death. The time of STEMI onset has a circadian rhythm with a peak during diurnal hours, and the occurrence of STEMI follows a seasonal pattern with a salient peak of cases in the winter months and a marked reduction of cases in the summer months. Scholars investigated the reason behind the winter peak, suggesting that environmental and climatic factors concur in STEMI pathogenesis, but no studies have investigated whether the circadian rhythm is modified with the seasonal pattern, in particular during the summer reduction in STEMI occurrence. METHODS AND RESULTS: Here, we provide a multiethnic and multination epidemiological study (from both hemispheres at different latitudes, n=2270 cases) that investigates whether the circadian variation of STEMI onset is altered in the summer season. The main finding is that the difference between numbers of diurnal (6:00 to 18:00) and nocturnal (18:00 to 6:00) STEMI is markedly decreased in the summer season, and this is a prodrome of a complex mechanism according to which the circadian rhythm of STEMI time onset seems season dependent. CONCLUSIONS: The "summer shift" of STEMI to the nocturnal interval is consistent across different populations, and the sunshine duration (a measure related to cloudiness and solar irradiance) underpins this season-dependent circadian perturbation. Vitamin D, which in our results seems correlated with this summer shift, is also primarily regulated by the sunshine duration, and future studies should investigate their joint role in the mechanisms of STEMI etiogenesis.

ANMCO/ISS/AMD/ANCE/ARCA/FADOI/GICR-IACPR/SICI-GISE/SIBioC/SIC/SICOA/SID/SIF/SIMEU/SIMG/SIMI/SISA Joint Consensus Document on cholesterol and cardiovascular risk: diagnostic-therapeutic pathway in Italy.

Atherosclerotic cardiovascular disease still represents the leading cause of death in Western countries. A wealth of scientific evidence demonstrates that increased blood cholesterol levels have a major impact on the outbreak and progression of atherosclerotic plaques. Moreover, several cholesterol-lowering pharmacological agents, including statins and ezetimibe, have proved effective in improving clinical outcomes. This document focuses on the clinical management of hypercholesterolaemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors discuss in detail the role of hypercholesterolaemia in the genesis of atherosclerotic cardiovascular disease. In addition, the implications for high cholesterol levels in the definition of the individual cardiovascular risk profile have been carefully analysed, while all available therapeutic options for blood cholesterol reduction and cardiovascular risk mitigation have been explored. Finally, this document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolaemia.

Serum uric acid on admission predicts in-hospital mortality in patients with acute coronary syndrome.

BACKGROUND: Despite the association between uric acid and cardiovascular disease has been known for decades, the prognostic value of serum uric acid (UA) in all clinical manifestations of acute coronary syndrome (ACS), namely ST-elevation myocardial infarction (STEMI), NSTEMI and unstable angina, has not been definitively assessed. METHODS: This retrospective analysis included patients from previous SPAI and FAMI studies with the aim to investigate the association between serum uric acid and major adverse cardiovascular events at 180days from hospital admission. RESULTS: 1548 patients were considered and divided in four groups, according UA concentration. Uricemia was significantly associated with gender, BMI, arterial hypertension, HDL-cholesterol, triglycerides, metabolic syndrome and glomerular filtration rate in univariate analysis. Multivariate logistic regression indicated that UA >6.0mg/dL on admission increased the risk of in-hospital mortality in overall population (OR 2.9, 95%CI 1.4-6.1; p=0.0057) and in patients with de novo ACS (OR 3.2, 95%CI 1.5-6.8; p=0.0033). Comparable results were also obtained after adjusting the model for age, gender, body mass index, glomerular filtration rate, metabolic syndrome, acute revascularization and ethnicity. A positive correlation was observed between UA and C reactive protein concentrations in in-hospital deaths only (rho 0.41, p=0.027). CONCLUSION: In patients with acute coronary syndrome, uricemia levels above the current international reference limit (6.0mg/dl) were associated with in-hospital mortality, independently from ethnicity and renal function.

[ANMCO/ISS/AMD/ANCE/ARCA/FADOI/GICR-IACPR/SICI-GISE/SIBioC/SIC/SICOA/SID/SIF/SIMEU/SIMG/SIMI/SISA Consensus document. Hypercholesterolemia and cardiovascular risk: diagnostic and therapeutic pathways in Italy]. / Documento di consenso intersocietario ANMCO/ISS/AMD/ANCE/ARCA/FADOI/ GICR-IACPR/SICI-GISE/SIBioC/SIC/SICOA/ SID/SIF/SIMEU/SIMG/SIMI/SISA Colesterolo e rischio cardiovascolare: percorso diagnostico-terapeutico in Italia.

Atherosclerotic cardiovascular disease still represents the leading cause of death in western countries. A wealth of scientific evidence demonstrates that increased blood cholesterol levels have a major impact on the outbreak and progression of atherosclerotic plaques. Moreover, several cholesterol-lowering pharmacological agents, including statins and ezetimibe, have proven effective in improving clinical outcomes. This document is focused on the clinical management of hypercholesterolemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors have considered with particular attention the role of hypercholesterolemia in the genesis of atherosclerotic cardiovascular disease. Besides, the implications of high cholesterol levels in the definition of the individual cardiovascular risk profile have been carefully analyzed, while all available therapeutic options for blood cholesterol reduction and cardiovascular risk mitigation have been considered. Finally, this document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolemia.