Reduced incidence of cardiovascular events in hyper-Lp(a) patients on lipoprotein apheresis. The G.I.L.A. (Gruppo Interdisciplinare Aferesi Lipoproteica) pilot study.

BACKGROUND: Lipoprotein apheresis (LA) is the elective therapy for homozygous and other forms of Familial Hypercholesterolemia, Familial Combined Hypercholesterolemia, resistant/intolerant to lipid lowering drugs, and hyper-lipoproteinemia(a). Lipoprotein(a) [Lp(a)] has been classified as the most prevalent genetic risk factor for coronary artery disease and aortic valve stenosis. AIM: Our multicenter retrospective study has the aim to analyze the incidence of adverse cardiovascular events (ACVE) before and during the LA treatment, in subjects with elevated level of Lp(a) (>60 mg/dL) [hyper-Lp(a)] and chronic ischemic heart disease. METHODS: We collected data of 23 patients (mean age 63 ± 9 years, male 77%; from hospital of Pisa 11/23, Pistoia 7/23, Verona 2/23, Padova 2/23 and Ferrara 1/23), with hyper-Lp(a), pre-apheresis LDL-cholesterol <100 mg/dL, cardiovascular disease, on maximally tolerated lipid lowering therapy and LA treatment (median 7 years, interquartile range 3-9 years). The LA treatment was performed by heparin-induced LDL precipitation apheresis (16/23), dextran-sulphate (4/23), cascade filtration (2/23) and immunoadsorption (1/23). The time lapse between first cardiovascular event and beginning of apheresis was 6 years (interquartile range 1-12 years). RESULTS: The recorded ACVE, before and after the LA treatment inception, were 40 and 10 respectively (p < 0.05), notably, the AVCE rates/year were 0.43 and 0.11 respectively (p < 0.05) with a 74% reduction of event occurrence. CONCLUSIONS: Our data confirm long-term efficacy and positive impact of LA on morbidity in patients with hyper-Lp(a) and chronic ischemic heart disease on maximally tolerated lipid lowering therapy.

Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients.

Metformin, the drug of choice in the treatment of type 2 diabetes mellitus (DM2), in addition to aspirin (ASA), the drug prescribed for cardioprotection of diabetic and non-diabetic patients, have an inhibitory effect on cancer cell survival. The present population-based study conducted in the province of Trieste (Italy), aimed to investigate the prevalence of DM2 in patients with colorectal adenocarcinoma (CRC) and survival for CRC in diabetic and nondiabetic patients. All permanent residents diagnosed with a CRC between 2004 and 2007 were ascertained through the regional health information system. CRC-specific and relative survival probabilities were computed for each group of patients defined by CRC stage, presence or absence of DM2 treated with metformin, and presence or absence of daily ASA therapy. A total of 515 CRC patients without DM2 and 156 with DM2 treated with metformin were enrolled in the study. At the time of CRC diagnosis, 71 (14%) nondiabetic and 39 (25%) diabetic patients were taking ASA daily. The five-year relative survival for stage III CRC was 101% [95% confidence interval (CI)=76-126] in the 18 patients with DM2 treated with metformin and ASA, 55% (95% CI=31-78) in the 23 without DM2 treated with ASA, 55% (95% CI=45-65) in the 150 without DM2 not taking ASA, and 29% (95% CI=13-45) in the 43 with DM2 treated with metformin, however not with ASA. The findings support the hypothesis of a possible inhibitory effect of metformin and ASA on CRC cells. Randomized controlled trials are required to verify this hypothesis.

Gender-Specific Association of Desacylated Ghrelin with Subclinical Atherosclerosis in the Metabolic Syndrome.

OBJECTIVE: Ghrelin, a gastric hormone with pleiotropic effects modulates vascular function and may influence atherosclerosis. Plasma ghrelin is reduced in the metabolic syndrome (MS), which is also characterized by early atherosclerosis. Ghrelin circulates in acylated (AG) and desacylated (DAG) forms. Their relative impact and that of gender on subclinical atherosclerosis in MS is unknown. AIM OF THE STUDY: To investigate potential associations of total, AG and DAG with carotid atherosclerosis and with gender in the MS. METHODS: Plasma total ghrelin, AG, DAG and carotid artery IMT (cIMT) were measured in 46 MS patients (NCEP-ATP III criteria, 22M/24F). RESULTS: Compared with males, females had higher (p <0.05) total and DAG. In the association analysis, age and plasma glucose were positively (p <0.05) correlated with cIMT in all MS patients. The positive (p <0.05) association between cIMT and age was also confirmed in males, while that between cIMT and glucose was significant in women. In contrast, neither total ghrelin nor AG and DAG were associated with cIMT in all MS patients nor in the male subgroup. In females, a negative (p <0.05) association between carotid artery IMT, DAG and glucose was detected, but not between cIMT, total ghrelin and AG. In multivariate modeling, DAG remained negatively (p <0.05) associated with cIMT after adjusting for plasma glucose and cardiovascular risk factors. CONCLUSIONS: These data indicate a negative independent association between DAG and cIMT in middle-aged women with the MS and suggest a gender-specific modulatory function of DAG in the development of atherosclerosis.

Lack of Fibronectin Extra Domain A Alternative Splicing Exacerbates Endothelial Dysfunction in Diabetes.

Glucose-induced changes of artery anatomy and function account for diabetic vascular complications, which heavily impact disease morbidity and mortality. Since fibronectin containing extra domain A (EDA + FN) is increased in diabetic vessels and participates to vascular remodeling, we wanted to elucidate whether and how EDA + FN is implicated in diabetes-induced endothelial dysfunction using isometric-tension recording in a murine model of diabetes. In thoracic aortas of EDA-/-, EDA+/+ (constitutively lacking and expressing EDA + FN respectively), and of wild-type mice (EDAwt/wt), streptozotocin (STZ)-induced diabetes impaired endothelial vasodilation to acetylcholine, irrespective of genotype. However STZ + EDA-/- mice exhibited increased endothelial dysfunction compared with STZ + EDA+/+ and with STZ + EDAwt/wt. Analysis of the underlying mechanisms revealed that STZ + EDA-/- mice show increased oxidative stress as demonstrated by enhanced aortic superoxide anion, nitrotyrosine levels and expression of NADPH oxidase NOX4 and TGF-ß1, the last two being reverted by treatment with the antioxidant n-acetylcysteine. In contrast, NOX1 expression and antioxidant potential were similar in aortas from the three genotypes. Interestingly, reduced eNOS expression in STZ + EDA+/+ vessels is counteracted by increased eNOS coupling and function. Although EDA + FN participates to vascular remodelling, these findings show that it plays a crucial role in limiting diabetic endothelial dysfunction by preventing vascular oxidative stress.

Omega-3 Polyunsaturated Fatty Acids: Structural and Functional Effects on the Vascular Wall.

Omega-3 polyunsaturated fatty acids (n-3 PUFA) consumption is associated with reduced cardiovascular disease risk. Increasing evidence demonstrating a beneficial effect of n-3 PUFA on arterial wall properties is progressively emerging. We reviewed the recent available evidence for the cardiovascular effects of n-3 PUFA focusing on structural and functional properties of the vascular wall. In experimental studies and clinical trials n-3 PUFA have shown the ability to improve arterial hemodynamics by reducing arterial stiffness, thus explaining some of its cardioprotective properties. Recent studies suggest beneficial effects of n-3 PUFA on endothelial activation, which are likely to improve vascular function. Several molecular, cellular, and physiological pathways influenced by n-3 PUFA can affect arterial wall properties and therefore interfere with the atherosclerotic process. Although the relative weight of different physiological and molecular mechanisms and the dose-response on arterial wall properties have yet to be determined, n-3 PUFA have the potential to beneficially impact arterial wall remodeling and cardiovascular outcomes by targeting arterial wall stiffening and endothelial dysfunction.

[Achieving optimal cholesterol levels in patients with chronic ischemic heart disease: from guidelines to the real world]. / Il raggiungimento dei target raccomandati di profilo lipidico in una popolazione con cardiopatia ischemica cronica: dalle linee guida al mondo reale.

BACKGROUND: It is known that less than half of patients with coronary heart disease reaches the target of LDL cholesterol (LDL-C) <100 mg/dl. According to the latest international guidelines, this target has been lowered to <70 mg/dl in very high-risk patients. METHODS: From November 1, 2009 to December 31, 2012, 4953 patients with coronary heart disease were enrolled in the Cardiovascular Registry of Trieste (Italy). We assessed clinical data, LDL-C levels, statin prescription and medium-term outcome in patients with coronary heart disease. RESULTS: At first clinical evaluation, LDL-C values were available for only 61.5% of patients. The target level of LDL-C <70 mg/dl was reached in 17% of cases and LDL-C <100 mg/dl in 53%. Patients with lower LDL-C levels were more frequently males, with higher cardiovascular risk profile, more comorbidity and more frequent polypharmacy. LDL-C levels influenced statin prescription: in patients with LDL-C ≥ 100 mg/dl, cardiologists started or modified the dosage of statin therapy twice more than in patients with LDL-C <100 mg/dl, even if only in less than 20% of cases. Patients with LDL-C <100 mg/dl in statin therapy had better prognosis, whereas patients with low LDL-C levels without statin therapy had the worst prognosis. Other prognostic factors in this population with LDL-C <100 mg/dl were age, presence of heart failure, comorbidities (evaluated with Charlson index) and polypharmacy. CONCLUSIONS: In our population of outpatients with coronary heart disease, the target of LDL-C <100 mg/dl was reached in 53% of cases. LDL-C levels influenced statin prescription and modification of dosages. The medium-term outcome is closely influenced by the achievement of target LDL-C levels and statin prescription.

Sudden hearing loss and Crohn disease: when Cogan syndrome must be suspected.

Cogan's syndrome is a rare systemic vasculitis of unknown origin. It is characterized by the presence of worsening audiovestibular and ocular symptoms that may manifest simultaneously or sequentially. No specific diagnostic laboratory tests or imaging studies exist. The diagnosis is clinical and should be established as early as possible so as to initiate prompt treatment with steroids and prevent rapid progression to deafness or blindness and potentially fatal systemic involvement. We report a case of association between Cogan's syndrome and ileal Crohn's disease which we believe deserves attention since, after an accurate review of the literature, we have found approximately 250 reports of patients with Cogan's syndrome, only 13 of whom with concurrent chronic inflammatory bowel disease; of these 13 cases, none experienced improvement after therapy. In the light of the good outcome obtained in our case, we proposed a valid treatment option with boluses of steroids, combined with early systemic immunosuppression and intra-tympanic steroid injections.

Pulmonary artery aneurysm and sarcoidosis.

Pulmonary artery aneurysm unassociated to congenital heart disease and pulmonary hypertension is exceedingly rare. Its pathogenesis and correct management remain unknown. Sarcoidosis is a systemic disease that can exceptionally involve large vessels, leading to stenosis and dilatation. Pulmonary artery aneurysm has never been described in association with sarcoidosis. Surgical approach should prevent aneurysm rupture, but it is not known when surgery should be preferred to strict medical follow-up. In this report we present a case of large pulmonary artery aneurysm associated to systemic sarcoidosis underlining problematic management of diseases 'forgotten' by evidence based medicine.

HELP LDL apheresis reduces plasma pentraxin 3 in familial hypercholesterolemia.

BACKGROUND: Pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, is secreted by vascular cells in response to injury, possibly aiming at tuning arterial activation associated with vascular damage. Severe hypercholesterolemia as in familial hypercholesterolemia (FH) promotes vascular inflammation and atherosclerosis; low-density lipoprotein (LDL) apheresis is currently the treatment of choice to reduce plasma lipids in FH. HELP LDL apheresis affects pro- and antiinflammatory biomarkers, however its effects on PTX3 levels are unknown. We assessed the impact of FH and of LDL removal by HELP apheresis on PTX3. METHODS: Plasma lipids, PTX3, and CRP were measured in 19 patients with FH undergoing chronic HELP LDL apheresis before and after treatment and in 20 control subjects. In the patients assessment of inflammation and oxidative stress markers included also plasma TNFα, fibrinogen and TBARS. RESULTS: At baseline, FH patients had higher (p = 0.0002) plasma PTX3 than matched control subjects. In FH PTX3 correlated positively (p≤0.05) with age, gender and CRP and negatively (p = 0.01) with HELP LDL apheresis vintage. The latter association was confirmed after correction for age, gender and CRP. HELP LDL apheresis acutely reduced (p≤0.04) plasma PTX3, CRP, fibrinogen, TBARS and lipids, but not TNFα. No association was observed between mean decrease in PTX3 and in LDL cholesterol. PTX3 paralleled lipids, oxidative stress and inflammation markers in time-course study. CONCLUSION: FH is associated with increased plasma PTX3, which is acutely reduced by HELP LDL apheresis independently of LDL cholesterol, as reflected by the lack of association between change in PTX3 and in LDL levels. These results, together with the finding of a negative relationship between PTX3 and duration of treatment suggest that HELP LDL apheresis may influence both acutely and chronically cardiovascular outcomes in FH by modulating PTX3.

Inflammation impairs eNOS activation by HDL in patients with acute coronary syndrome.

AIMS: The aim of the present study was to evaluate the high-density lipoprotein (HDL) structure and endothelial NO synthase (eNOS) activation capacity in ST-elevation myocardial infarction (STEMI) patients with different acute-phase inflammatory response (APR). METHODS AND RESULTS: Forty-five STEMI patients were stratified in quartiles according to the delta CRP level, calculated by subtracting the CRP value at admission from the CRP peak value (APR peak). The HDL structure and HDL capacity to stimulate NO production were evaluated at admission and at APR peak. STEMI patients with a low APR had a completely preserved HDL structure and HDL ability to activate eNOS and promote NO production, which did not change during STEMI. On the contrary, HDL from STEMI patients developing a significant APR had compromised ability to stimulate eNOS and promote NO production, and underwent a significant particle remodelling during STEMI. The defective capacity to stimulate NO production of HDL isolated from STEMI patients with high APR was explained, at least in part, by the reduced PON-1 and S1P content. The HDL ability to promote cell cholesterol efflux through different pathways was preserved in ACS patients independently of the inflammatory response. CONCLUSION: The present results extend previous studies reporting an impaired eNOS-activating capacity of HDL from ACS patients, showing that only a subset of patients undergoing STEMI, and in particular those developing an important inflammatory response, have circulating HDL defective in stimulating endothelial eNOS and NO production.

Nonalcoholic fatty liver and metabolic syndrome in Italy: results from a multicentric study of the Italian Arteriosclerosis society.

Nonalcoholic fatty liver disease (NAFLD) is associated with all the components of metabolic syndrome (MS) and might to be considered an additional component of MS itself. The Italian Society for the Study of Atherosclerosis (SISA) in 2005 started a research project aimed to study the NAFLD, using ultrasound (US), in nondiabetic MS subjects matching at least one of the ATP III criteria for HDL-C or triglycerides [TG]. Prevalence of US-NAFLD and its associated risk factors and prevalence of hypertransaminasemia and its possible determinants were evaluated. NAFLD prevalence was 0.78. Men with steatosis compared to men without steatosis were younger (P < 0.05) with higher TG (P < 0.03), homeostasis model assessment insulin resistance (HOMA-R) (P < 0.003), and visceral fat thickness (VFT) (P < 0.0001). Women with steatosis showed higher TG (P < 0.05), HOMA-R (P < 0.04), VFT (P < 0.0001), and lower age (P < 0.05). At multivariate analyses, VFT (P < 0.0001), HOMA-R (P < 0.02), and TG/HDL (P < 0.05) were associated with severity of NAFLD. Age (P < 0.05), LogTG (P < 0.005), and VFT (P < 0.01) were associated with higher ALT. The US prevalence of steatosis in this study (0.78) is the highest reported in patients with MS. Considering the exclusion of severe obese and diabetic patients and the recruitment criteria, this finding highlights the prominent role played by the alterations of lipid metabolism in the pathogenesis of NAFLD.

[Dyslipidemia: news in diagnosis and drug therapy]. / Dislipidemie: attualita' in diagnosi e terapia farmacologica.

Plasma lipid levels are to a large extent determined by genetic factors. In its more extreme forms this is manifested as familial hyperlipidemias, which are an important cause of premature coronary heart disease. It has been demonstrated that rigorous treatment of familial forms reduces the burden of ischemic heart disease. Statins are among the most studied drugs in cardiovascular prevention; a number of large-scale clinical trials have demonstrated that statins substantially reduce cardiovascular morbidity and mortality in both primary and secondary prevention. The currently available evidence suggests that the clinical benefit is largely independent of the type of statin, but depends on the extent of LDL-C lowering. When the most potent statins are insufficient, LDL-C apheresis should be used.

High-fat diet with acyl-ghrelin treatment leads to weight gain with low inflammation, high oxidative capacity and normal triglycerides in rat muscle.

Obesity is associated with muscle lipid accumulation. Experimental models suggest that inflammatory cytokines, low mitochondrial oxidative capacity and paradoxically high insulin signaling activation favor this alteration. The gastric orexigenic hormone acylated ghrelin (A-Ghr) has antiinflammatory effects in vitro and it lowers muscle triglycerides while modulating mitochondrial oxidative capacity in lean rodents. We tested the hypothesis that A-Ghr treatment in high-fat feeding results in a model of weight gain characterized by low muscle inflammation and triglycerides with high muscle mitochondrial oxidative capacity. A-Ghr at a non-orexigenic dose (HFG: twice-daily 200-µg s.c.) or saline (HF) were administered for 4 days to rats fed a high-fat diet for one month. Compared to lean control (C) HF had higher body weight and plasma free fatty acids (FFA), and HFG partially prevented FFA elevation (P<0.05). HFG also had the lowest muscle inflammation (nuclear NFkB, tissue TNF-alpha) with mitochondrial enzyme activities higher than C (P<0.05 vs C, P = NS vs HF). Under these conditions HFG prevented the HF-associated muscle triglyceride accumulation (P<0.05). The above effects were independent of changes in redox state (total-oxidized glutathione, glutathione peroxidase activity) and were not associated with changes in phosphorylation of AKT and selected AKT targets. Ghrelin administration following high-fat feeding results in a novel model of weight gain with low inflammation, high mitochondrial enzyme activities and normalized triglycerides in skeletal muscle. These effects are independent of changes in tissue redox state and insulin signaling, and they suggest a potential positive metabolic impact of ghrelin in fat-induced obesity.

Exercise and glycemic imbalances: a situation-specific estimate of glucose supplement.

PURPOSE: The purposes of this study were to describe a newly developed algorithm that estimates the glucose supplement on a patient- and situation-specific basis and to test whether these amounts would be appropriate for maintaining blood glucose levels within the recommended range in exercising type 1 diabetic patients. METHODS: The algorithm first estimates the overall amount of glucose oxidized during exercise on the basis of the patient's physical fitness, exercise intensity, and duration. The amount of supplemental CHO to be consumed before or during the effort represents a fraction of the burned quantity depending on the patient's usual therapy and insulin sensitivity and on the time of day the exercise is performed. The algorithm was tested in 27 patients by comparing the estimated amounts of supplemental CHO with the actual amounts required to complete 1-h constant-intensity walks. Each patient performed three trials, each of which started at different time intervals after insulin injection (81 walks were performed overall). Glycemia was tested every 15 min. RESULTS: In 70.4% of the walks, independent of the time of day, the amount of CHO estimated by the algorithm would be adequate to allow the patients to complete the exercise with a glucose level within the selected thresholds (i.e., 3.9-10 mmol·L(-1)). CONCLUSIONS: The algorithm provided a satisfactory estimate of the CHO needed to complete the exercises. Although the performance of the algorithm still requires testing for different exercise intensities, durations, and modalities, the results indicate its potential usefulness as a tool for preventing immediate exercise-induced glycemic imbalances (i.e., during exercise) in type 1 diabetic patients, in particular for spontaneous physical activities not planned in advance, thus allowing all insulin-dependent patients to safely enjoy the benefits of exercise.

Insulin downregulates SIRT1 and AMPK activation and is associated with changes in liver fat, but not in inflammation and mitochondrial oxidative capacity, in streptozotocin-diabetic rat.

BACKGROUND & AIMS: Involvement of insulin in diabetes-associated liver triglyceride deposition and its potential pathways remain incompletely defined. SIRT1 may negatively modulate lipogenesis and liver triglyceride accumulation, involving AMP-activated protein kinase (AMPK) activation. In streptozotocin-diabetic rats, we hypothesized that insulin negatively modulates liver SIRT1 and activates AMPK-inhibited lipogenic mediators leading to triglyceride accumulation. The impact of insulin deprivation (INS-) and replacement (INS+) on liver inflammation and mitochondrial oxidative capacity (also potentially regulating triglyceride deposition) was also measured. METHODS: Streptozotocin-diabetic rats under chronic (8-week) INS- and INS+. RESULTS: Compared to INS- (P < 0.05), INS+ had low liver SIRT1 with low AMPK activating phosphorylation, low inactivating phosphorylation of its lipogenic target acetyl-CoA carboxylase and high tissue triglycerides. INS- (P < 0.05 vs Control) had liver inflammation and high mitochondrial oxidative capacity, but neither was modulated by INS+. Pair-feeding showed no influence of spontaneous overeating on insulin-induced changes. CONCLUSIONS: Insulin replacement downregulates SIRT1 and AMPK activation in vivo in streptozotocin-diabetic rat liver, likely contributing to insulin-induced liver triglyceride accumulation. Under the current experimental conditions, insulin-deprived diabetes is associated with liver inflammation and high mitochondrial oxidative capacity, that are not affected by insulin replacement and are therefore unlikely to contribute to tissue triglyceride changes in this model.

Prolonged inactivity up-regulates cholesteryl ester transfer protein independently of body fat changes in humans.

CONTEXT: Physical inactivity is associated with insulin resistance and decreased high-density lipoprotein (HDL) cholesterol. Cholesteryl ester transfer protein (CETP) is involved in cholesterol metabolism, being responsible for the transfer of cholesteryl esters from HDL to very low- and low-density lipoproteins. OBJECTIVE: We hypothesized that physical inactivity could decrease HDL cholesterol through changes in CETP availability. DESIGN AND PARTICIPANTS: Twenty-four healthy, male volunteers (aged 23.1 +/- 0.5 yr) were investigated in eucaloric conditions before and at the end of 35 d of experimental bed rest. MEASURES: Changes in body composition were monitored by bioimpedance throughout the study. Before and at the end of the experimental period, plasma insulin and glucose and plasma lipid pattern as well as CETP concentrations were determined. RESULTS: Our results demonstrated that during bed rest, fat mass did not change significantly, whereas fat-free mass decreased by 3.9 +/- 0.4% (P < 0.01). The homeostatic model assessment index of insulin resistance significantly (P < 0.001) increased by 47 +/- 11% after bed rest. Bed rest decreased HDL cholesterol by 12 +/- 3% (P < 0.05), increased triglycerides by 51 +/- 10% (P < 0.05), whereas it did not change significantly low-density lipoprotein cholesterol. Plasma CETP concentration increased after bed rest by 27 +/- 9% (P < 0.01). Bed rest-induced changes in CETP concentrations inversely correlated with changes in the ratio between HDL and non-HDL cholesterol (n = 24; R = -0.43; P < 0.05). CONCLUSIONS: Physical inactivity decreases HDL cholesterol, at least in part, through CETP up-regulation.

Functional lecithin: cholesterol acyltransferase is not required for efficient atheroprotection in humans.

BACKGROUND: Mutations in the LCAT gene cause lecithin:cholesterol acyltransferase (LCAT) deficiency, a very rare metabolic disorder with 2 hypoalphalipoproteinemia syndromes: classic familial LCAT deficiency (Online Mendelian Inheritance in Man No. 245900), characterized by complete lack of enzyme activity, and fish-eye disease (Online Mendelian Inheritance in Man No. 136120), with a partially defective enzyme. Theoretically, hypoalphalipoproteinemia cases with LCAT deficiency should be at increased cardiovascular risk because of high-density lipoprotein deficiency and defective reverse cholesterol transport. METHODS AND RESULTS: The extent of preclinical atherosclerosis was assessed in 40 carriers of LCAT gene mutations from 13 Italian families and 80 healthy controls by measuring carotid intima-media thickness (IMT). The average and maximum IMT values in the carriers were 0.07 and 0.21 mm smaller than in controls (P=0.0003 and P=0.0027), respectively. Moreover, the inheritance of a mutated LCAT genotype had a remarkable gene-dose-dependent effect in reducing carotid IMT (P=0.0003 for average IMT; P=0.001 for maximum IMT). Finally, no significant difference in carotid IMT was found between carriers of LCAT gene mutations that cause total or partial LCAT deficiency (ie, familial LCAT deficiency or fish-eye disease). CONCLUSIONS: Genetically determined low LCAT activity in Italian families is not associated with enhanced preclinical atherosclerosis despite low high-density lipoprotein cholesterol levels. This finding challenges the notion that LCAT is required for effective atheroprotection and suggests that elevating LCAT expression or activity is not a promising therapeutic strategy to reduce cardiovascular risk.

Circulating pentraxin 3 levels are higher in metabolic syndrome with subclinical atherosclerosis: evidence for association with atherogenic lipid profile.

Metabolic syndrome is characterized by increased cardiovascular risk. Pentraxin 3 (PTX3), an acute phase protein, is involved in atherosclerosis. No information is available on PTX3 plasma concentrations in metabolic syndrome and on its associations with metabolic alterations and subclinical atherosclerosis. The aim of this study was to assess PTX3 plasma levels in metabolic syndrome patients compared to control subjects and their potential associations with anthropometric and clinical components of the syndrome as well as with carotid artery intima-media thickness (cIMT), a marker of subclinical atherosclerosis. Plasma was obtained from metabolic syndrome patients (NCEP-ATP III criteria n = 41, 20 M/21F) and by age-matched control subjects (n = 32, 16 M/16F). PTX3 was measured using sandwich ELISA and cIMT with ultrasound. Compared to those of the control subjects, plasma levels of PTX3 were higher (? * 100%, P = 0.0009) in metabolic syndrome patients. In univariate analysis, plasma PTX3 was negatively (P = 0.005) associated with high-density lipoprotein (HDL) cholesterol and positively (P = 0.046) with plasma triglycerides and with cIMT (P = 0.045) in the patients (n = 41). In multivariate analysis the direct association between PTX3 and cIMT was no longer significant after correction for HDL. None of these associations were detected in the control patients. These data demonstrate that PTX3, a novel marker of vascular disease, is higher in patients with metabolic syndrome associated with subclinical atherosclerosis. In addition, PTX3 is significantly independently correlated with low HDL cholesterol, but not with cIMT, suggesting a novel association between PTX3 and atherogenic lipid profile.