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Background and Aims Familial hypercholesterolemia (FH) is an autosomal dominant disease that leads to cardiovascular (CV) disease. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-I) demonstrated efficacy in low-density lipoprotein cholesterol (LDL-C) reduction and in prevention of CV events. The aim of our study is to evaluate the relationship between LDL receptor (LDLR) mutations and response to PCSK9-I therapy. Methods and Results We evaluated total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in consecutive patients with FH before PCSK9-I treatment and after 12 (T12w) and 36 (T36w) weeks of treatment. We evaluated LDL-C target achievement according to different mutations in LDLR. Eighty FH subjects (mean age:54±13.3 years), 39 heterozygous (He) with defective LDLR gene mutations, 30 He with null mutations and 11 compound-He or homozygotes (Ho) were recruited. At baseline, 69 subjects were under maximal lipid lowering therapy (MLLT) and 11 subjects had statin-intolerance. From baseline to T36w we observed an overall 51% reduction in LDL-C. We found no difference in LDL-C changes between subjects with He-defective mutation and He-null mutations both at T12w (p=1.00) and T36w (p=0.538). At T36w, LDL-C target was achieved in 59% of He-defective mutations subjects and in 36% of He-null mutations subgroup (p=0.069), whereas none of compound-He/Ho-FH achieved LDL-C target. Conclusions After 36 weeks there were no differences in response to PCSK9-I therapy between different groups of He-FH subjects. Response to PCSK9-I was significantly lower in carriers of compound-He/Ho mutations. Registration number for clinical trials: NCT04313270 extension.

The association between early atherosclerosis (IMT) and Atherogenic index of plasma (AIP), a marker of atherogenicity (log triglycerides/HDL Cholesterol) was evaluated in a population-based cohort study in women, aged 30-69, living in the metropolitan area of Naples, Southern Italy (Progetto ATENA). Serum cholesterol, HDL-cholesterol, LDL-cholesterol, Triglyceride, Insulin, HOMA, Apo B, hs-CPR were measured in 390 menopausal women, as a part of 5.062 participants of the cohort. Women in the second and third tertile of AIP showed an increased common carotid intima-media thickness compared with those in the first tertile: II vs I tertile (O.R. = 2.24, p = 0.007), III vs I tertile (O.R. = 2.29, p = 0.005), adjusted for age and Systolic pressure or II vs I tertile (O.R. = 2.19, p = 0.014), III vs I tertile (O.R. = 2.13, p = 0.026), adjusted for age, Systolic pressure, Body mass index and Apo B. Women in the second and third tertile of AIP compared to those in the first tertile, showed an OR of 2.14 (p = 0.016) and 1.99 (p = 0.033) respectively, of having elevates level of IMT, adjusted for traditional cardiovascular risk factor (age, Systolic Pressure, BMI, LDL Cholesterol, Diabetes diagnosis). This finding shows that in this group of menopausal women increased IMT is associated with elevated AIP independently of age and different cardiovascular risk factors. These results are in line with the hypothesis that AIP may be an useful clinical tools to give additional information in the risk assessment for atherosclerotic disease, in particular in postmenopausal women.

BACKGROUND: Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null-null) or impaired (non-null) LDL-receptor activity. Loss-of-function variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo. The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24. RESULTS: The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy. At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of -49.0 percentage points (95% confidence interval [CI], -65.0 to -33.1; P

Carotid artery plaques are considered a measure of atherosclerosis and are associated with an increased risk of atherosclerotic cardiovascular disease, particularly ischemic strokes. Monitoring of patients with an elevated risk of stroke is critical in developing better prevention strategies. Non-invasive imaging allows us to directly see atherosclerosis in vessels and many features that are related to plaque vulnerability. A large body of evidence has demonstrated a strong correlation between some lipid parameters and carotid atherosclerosis. In this article, we review the relationship between lipids and atherosclerosis with a focus on carotid ultrasound, the most common method to estimate atherosclerotic load.

Background and aim: Protein convertase subtilisin kexin type 9 (PCSK-9) inhibitors demonstrated efficacy in cholesterol reduction and in the prevention of cardiovascular events. We evaluated changes in lipid profile and carotid stiffness in patients with familial hypercholesterolemia during 12 weeks of treatment with a PCSK-9 inhibitor, Evolocumab®. Methods and results: Patients with familial hypercholesterolemia starting a treatment with Evolocumab® were included. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), small dense LDL (assessed by LDL score) and carotid stiffness were evaluated before starting treatment with Evolocumab® and during 12 weeks of treatment. Twenty-five subjects were enrolled (52% males, mean age 51.5 years). TC and LDL-C were reduced of 38% and 52%, respectively during treatment, with LDL score reduced of 46.1%. In parallel, carotid stiffness changed from 8.8 (IQR: 7.0–10.4) m/sec to 6.6 (IQR: 5.4–7.5) m/sec, corresponding to a median change of 21.4% (p < 0.001), with a significant increase in carotid distensibility (from 12.1, IQR: 8.73–19.3 kPA−1 × 10−3 at T0 to 21.8, IQR: 16.6–31.8 kPA−1 × 10−3 at T12w) corresponding to a median change of 62.8% (p < 0.001). A multivariate analysis showed that changes in LDL score were independently associated with changes in carotid stiffness (β = 0.429, p = 0.041). Conclusion: Small dense LDL reduction, as assessed by LDL score, is associated with changes in carotid stiffness in patients with familial hypercholesterolemia treated with Evolocumab®.

Purpose of review In the US anterior ocular inflammatory disease (AOID) composed of the spectrum of ocular allergies, different forms of infectious conjunctivitis, and dry eye diseases, affects over 40% of the population. This review evaluates the current economic costs for AOID associated pharmacotherapies. Recent findings In recent years, with improved understanding in pathophysiology of the AOID, providing novel targets for pharmacotherapy, have led to considerable improvements in outcomes for patients. Despite these advances, there continues to be a need for interventions that inhibit key inflammatory mediators or pathways in the ophthalmic space. In 2018, AOID drugs market represents ∼40% of the costs for the total ophthalmic drugs: dry eye (43%), antiinfectives (15%), antiallergics (13%), and antiinflammatory agents (29%). With increasing treatment costs, the need for improved, cost-effective modalities persists along with treatment algorithms to derive optimal benefits for patients. Summary There has been a dramatic increase in the economic burden of AOID with the annual expenditure for the prescription drugs approaching close to $11 billion in 2018. With increasing prevalence of ocular disease, further investment is required to provide more effective treatment options and deliver improved public health and economic outcomes.

In this study, we aimed at disclosing the main features of paroxysmal nocturnal hemoglobinuria (PNH) clones, their association with presentation syndromes, and their changes during follow-up. A large-scale, cooperative collection (583 clones from 529 patients) of flow cytometric and clinical data was entered into a national repository. Reason for testing guidelines were provided to the 41 participating laboratories, which followed the 2010 technical recommendations for PNH testing by Borowitz. Subsequently, the 30 second-level laboratories adopted the 2012 guidelines for high-resolution PNH testing, both upon order by the local clinicians and as an independent laboratory initiative in selected cases. Type3 and Type2 PNH clones (total and partial absence of glycosyl-phosphatidyl-inositol-anchor, respectively) were simultaneously present in 54 patients. In these patients, Type3 component was sevenfold larger than Type2 (p 0.001). Frequency distribution analysis of solitary Type3 clone size (N = 442) evidenced two discrete patterns: small (20% of peripheral neutrophils) and large ( 70%) clones. The first pattern was significantly associated with bone marrow failure and myelodysplastic syndromes, the second one with hemolysis, hemoglobinuria, and thrombosis. Pediatric patients (N = 34) showed significant preponderance of small clones and bone marrow failure. The majority of PNH clones involved neutrophils, monocytes, and erythrocytes. Nevertheless, we found clones made exclusively by white cells (N = 13) or erythrocytes (N = 3). Rare cases showed clonal white cells restricted only to monocytes (6 cases) or neutrophils (3 cases). Retesting over 1-year follow-up in 151 cases showed a marked clone size increase in 4 cases and a decrease in 13, demonstrating that early breaking-down of PNH clones is not a rare event (8.6% of cases). This collaborative nationwide study demonstrates a clear-cut difference in size between Type2 and Type3 clones, emphasizes the existence of just two classes of PNH presentations based on Type3 clone size, depicts an asymmetric cellular composition of PNH clones, and documents the possible occurrence of changes in clone size during the follow-up.

Small dense LDL particles (sd-LDL) and body shape index (ABSI), were evaluated in 228 women, living in Naples, Italy (Progetto ATENA). Serum cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, insulin, HOMA, Apo B, hs-CPR and sd-LDL were measured. LDL particle separation was performed by Lipoprint System: seven LDL subfractions were obtained and LDL score (% of sd-LDL particles) calculated. ABSI was calculated according to Krakauer’s formula: ABSI (m11/6 kg−2/3). The association between sd-LDL and ABSI was evaluated taking into account different adjustment models. Women with elevated levels of ABSI show the following OR of having high LDL score: 2.39, p = 0.002; unadjusted; 2.47, p = 0.002; adjusted for age; 2.13, p = 0.011; adjusted for age and Apo B; 1.93, p = 0.026; adjusted for age and Apo B and triglycerides. ABSI was associated with elevated LDL score independently of age, Systolic pressure, Apo B and triglycerides. Median of LDL diameter decreased among ABSI quartiles: quartile I: 271.5 nm, quartile II: 270.7 nm, quartile III 270.5 nm, quartile IV 269.4 nm; Kruskall Wallis Test: p = 0.016. These results are in line with the hypothesis that ABSI could be a marker of visceral abdominal associated to adverse metabolic changes including presence of elevated sd-LDL, a risk factor for premature cardiovascular disease.

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .).

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Evinacumab, a fully human monoclonal antibody against angiopoietin-like protein 3, has demonstrated approximately 50% reductions in LDL-C in HoFH patients when added to maximally tolerated lipid-lowering therapies. Objective: In this post-hoc analysis, we assessed the effect of evinacumab on the eligibility for apheresis using predefined US and EU apheresis criteria. Methods: This was a double-blind, placebo-controlled, 24-week phase 3 trial (NCT03399786) that randomized patients 2:1 to evinacumab 15 mg/kg intravenously every 4 weeks (Q4W; n=43) or placebo (n=22). We assessed the proportion of patients who met per protocol US apheresis criteria (LDL-C ≥300 mg/dL), newer US criteria for FH (LDL-C ≥300 mg/dL or LDL-C ≥160 mg/dL with coronary heart disease or peripheral artery disease) and per protocol EU apheresis criteria (LDL-C >160 mg/dL [primary prevention] or >120 mg/dL [secondary prevention]) at baseline and week 24. Results: Under the newer US criteria (2018), 62.8% (n=27) of evinacumab-treated patients and 54.5% (n=12) placebo-treated patients qualified for apheresis at baseline (Table). Following 24 weeks of treatment, 48.8% of all evinacumab versus 9.1% of all placebo patients no longer qualified for apheresis. Similar results were observed using EU apheresis criteria, where 46.5% of evinacumab-treated patients shifted from qualifying for apheresis at baseline to not qualifying at week 24, compared with 4.5% of placebo-treated patients. The majority of evinacumab (65.1%) and placebo (68.2%) patients did not qualify for per protocol US apheresis at baseline, however a shift of 27.9% and 9.1% was observed, respectively. Conclusions: Evinacumab has the potential to reduce the need for apheresis in patients with HoFH.

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder characterized by markedly elevated LDL-C and premature ASCVD. For HoFH patients (pts) with complete loss of low-density lipoprotein receptor (LDLR) function in both copies of the LDLR gene (null mutations) and some other HoFH pts, statins and PCSK9 inhibitors have limited to no efficacy, presenting a great unmet medical need. The efficacy and safety of evinacumab (EVIN; an angiopoietin-like protein 3 inhibitor) in HoFH pts was assessed during the double-blind treatment period (DBTP) of a phase 3 trial (NCT03399786). Objective: To examine longer-term efficacy and safety of EVIN in pts with HoFH who participated in the subsequent open-label treatment period (OLTP) of this phase 3 study. Methods: Patients with HoFH on stable lipid-lowering therapies (± lipoprotein apheresis) and screening LDL-C ≥70 mg/dL who completed the 24-week DBTP entered the 24-week OLTP and received IV EVIN 15 mg/kg every 4 weeks. Results: In total, 64 pts completed the DBTP and received open-label EVIN. Mean (standard deviation [SD]) baseline LDL-C at DBTP entry was 250.5 (162.3) mg/dL. From baseline to Week 48, EVIN reduced mean LDL-C by 46.3% (mean [SD] reduction of 134.3 [117.3] mg/dL). At Week 48, mean LDL-C reductions with open-label EVIN were 42.7% and 55.8% for pts who received EVIN (n=44) vs placebo (n=20) during the DBTP, respectively ( Figure ). LDL-C reduction observed at Week 48 was similar for pts with null/null mutations (n=19; 47.2%) versus non-null/null mutations (n=39; 45.9%). Adverse events (AEs) occurred in 47 pts (73.4%) during the OLTP; the most common were nasopharyngitis (9.4%) and headache (9.4%). During the OLTP, serious AEs occurred in 7 pts (10.9%; all pts received EVIN during the DBTP); none were considered related to study treatment. Conclusions: In pts with HoFH, EVIN showed substantial and sustained LDL-C reduction regardless of LDLR function and was generally well tolerated.

Background: Homozygous familial hypercholesterolemia (HoFH) is characterized by very premature atherosclerotic cardiovascular disease due to profoundly elevated levels of LDL-C. Attempts to lower LDL-C in patients with HoFH often require multiple lipid-lowering medications (LLMs). Evinacumab, an angiopoietin-like protein 3 inhibitor, has been shown to reduce LDL-C in patients with HoFH by approximately 50% when added to maximally tolerated background LLMs. Objective: In this post-hoc analysis we assessed efficacy of evinacumab in patients with HoFH according to background LLM type. Methods: This was a double-blind, placebo-controlled, 24-week phase 3 trial (NCT03399786) that randomized patients 2:1 to receive intravenous (IV) evinacumab 15 mg/kg (n=43) or IV placebo (n=22) every 4 weeks. The effect of background LLMs on the efficacy of evinacumab to lower LDL-C was assessed for the following subgroups: high intensity-statin, low-intensity statins, lomitapide, triple therapy (ezetimibe + PCSK9 inhibitor + statin), and quadruple therapy (triple therapy + lomitapide). Primary endpoint was % LDL-C reduction from baseline to week 24. Results: At baseline, 55.4% (evinacumab, 58.1%; placebo, 50.0%) of HoFH patients were on triple therapy. Overall, 93.8% were on statins (76.9% on high intensity statins). Across LLM subgroups, mean baseline LDL-C levels ranged from 166.8 mg/dL to 281.8 mg/dL (Table). From baseline to week 24, marked reductions in LDL-C occurred with evinacumab treatment, which were observed in all groups: quadruple therapy (66.8%), triple therapy (56.0%), lomitapide (49.6%), high-intensity statins (48.6%) and low-intensity statins (41.0%). Evinacumab was generally well-tolerated. Conclusions: Evinacumab substantially lowers LDL-C levels in patients with HoFH irrespective of background LLM.

Background PCSK-9-i demonstrated efficacy in cholesterol reduction and prevention of cardiovascular events. Purpose Changes in lipid-profile, oxidative stress and subclinical atherosclerosis markers in patients with familial hypercholesterolemia (FH) during 12 weeks of treatment with PCSK-9-i. Methods Patients with FH starting a treatment with Evolocumab® were included. TC, LDL-C, Lp(a), small dense LDL (assessed byLDL score), 11-dehydro-thromboxane (11-TXB2), 8-iso-prostaglandin-2alpha (8-iso-PGF2α),FMD, RHI and carotid stiffness were evaluated at baseline and after 12weeks of treatment. Results 25 subjects were enrolled (52% males, mean age 51.5 years). At the 12-week, the median reduction was 38% for TC, 52% for LDL-C, 7% for Lp(a) and 46% for LDL score; 11-TXB2 and 8-iso-PGF2α were reduced of 18% and 17%, respectively. FMD changed from4.78%±2.27 to10.6%±5.89 (p Conclusions Small dense LDL reduction is related to changes in oxidative stress and in subclinical atherosclerosis markers in FH patients treated with Evolocumab®. Changes in endothelial function Funding Acknowledgement Type of funding source: None

Introduction Familial hypercholesterolemia (FH) is an autosomal dominant disease that leads to premature cardiovascular disease (CAD). The availability of ab-PCSK9 has changed the approach to therapy. Purpose To evaluate the relationship between different types of mutations in LDLR gene and response to ab-PCSK9. Methods 73 FH patients, 33 women and 40 men (53.9±13. yrs), in primary prevention (N=46) and secondary prevention (N=27), were recruited. This sample included patients with mutations in LDLR gene: heterozygotes for missense mutations (N=31), for null mutations (N=31), compound heterozygotes or homozygotes (N=11). At baseline, the whole sample had a maximally tolerated lipid lowering therapy (MT-LLT) without ab-PCSK9; 16 patients had MT-LLTs intolerance. After 160 days with ab-PCSK9 therapy we evaluated the achievement of a goal (LDL-C Results After 160 days of therapy with ab-PCSK9 (45 patients on Alirocumab, 28 patients on Evolocumab) and MT-LLT, 29/73 patients (39.7%) of the whole sample achieve the goal of LDL-C. Of them 14/29 (48.2%) were in primary prevention, 15/29 (51.7%) in secondary prevention, no difference in achievement of the goal. We then evaluated the percent of patients achieving the goal of LDL-C: 15/31 (48.3%) patients with missense mutation and 14/31 (45.1%) patients with null mutation, no significant difference among groups; 0/11 compound heterozygotes or homozygotes; 3/16 (18.7%) MT-LLTs intolerance. The other main cardiovascular risk factors did not influence of the achievement the goal of LDL cholesterol. Conclusions Lack of correlation between type of mutation in heterozygous FH patients and ab-PCSK9 therapy response; response was significantly poorest in patients with compound heterozygosis or homozygosis mutation as compared to heterozygotes; the intolerance to MT-LLT was significant in the achievement of the goal of LDL-C. Different between guideline 2016 vs 2019 Funding Acknowledgement Type of funding source: None

Background The European Reference Network on Rare Disease (ERN) is focused on providing more equitable care across Europe and creates a network of both medical specialists and patient experts. One relevant objective of the activities planned into the ERNs is to address the economic dimensions of rare diseases in order to develop strategies to improve research and patients' access to orphan drugs (ODs) and highly specialized health technologies. The themes built in these preliminary years were directed toward guidelines and policies concerning reimbursement of ODs and direct provision by the healthcare system. Methods to proceed further in humanization of care we establish involvement of patients' associations in decision making and implementation of clinical practice guidelines. We built in Federico II University Hospital where 12 ERN were aligned a front office corner shared between patients association and hospital direction in order to face the patient difficulties along the pathway. The corner is open three times a week on the morning, with a dedicated phone number. Results Main issues regarded the understanding of the disease and the diagnosis (ie, lack of familiarity with the rare disease, disease heterogeneity, lack of established diagnostic criteria, misdiagnosis,) the development of effective treatments and the need for efficacy along the path way of care (ie, geographical limitations, disease coding systems, ethical and privacy issues). Fewer concerns were about the equity of access and other social pressures. Conclusions In general, in ERN context, few people declared to work in human and social issues, including research on patient's quality of life, patient's awareness, or methods for social support. Our findings demonstrated that Patients were positively affected from the corner initiative: this may ameliorate the use of infrastructures offering services, also that rarely known as national and international biobanking platforms, registries and networks. Key messages Humanization of care issues and strategies are nowadays mandatory in rare diseases. Patients are positively affected from shared initiatives.

Aims Oncological disease need a system of care involving hospital staff and informal caregivers. Care-givers are subjected to stressful factors (burden) with repercussions on psycho-physical balance. The project, carried out together with the ONLUS Travel Companions Association and the Multidisciplinary Oncological Groups (GOM) of Brain and Breast Cancers, intends to offer supportive training experiences for care-givers and health workers, offering emotional and practical preparation for the treatments that they will find themselves providing the cancer relative by helping to improve the quality of care and the relationship between the subjects. The professionals participating in the project (doctors, nurses) take part in a training held by professionals from the Association. The care givers, divided into groups, carry out a CBI test (Caregiver Burden Inventory) and training meetings on medical, psychological and social assistance issues. After 3 months from the end of the course, the care-giver carries out the interview with the psychologist and recompiles the CBI. Furthermore, on 30 selected patients of Breast Cancers, GOM, an emotional evaluation questionnaire of their life experience was administered with respect to the stages of the disease pathway. Results The answers were then analyzed by the word cloud method and summarized in a synthetic map for each question. The most used words to describe the mood during the illness are 'anger, pain, anguish and worry'; while waiting before the visit they are 'long, exhausting, anxious'; towards the doctor 'availability, humanity, kindness, friendliness, professionalism'; with regard to 'excellent, availability' assistance; about social life during the 'unchanged, serene' illness; towards the return home 'joy'. Conclusions The project is a starting point towards a continuous and progressive humanization of the integrated pathways from 'to cure' to 'to care' in oncology. Key messages Patients are positively affected from shared initiatives. Word cloud may resume patients moods and thei main issues concerninthe path.

Background In the era of personalized therapy liquid biopsy is considered an important diagnostic tool in the clinical management of cancer patients. Tissue specimen represents “gold standard” for molecular evaluation of specific gene targets alterations that lead cancer patients to benefit of a “tailed therapy” based on molecular features of the tumor. This innovative source of nucleic acids was introduced in clinical setting only for NSCLC patients to test Epidermal Grow Factor Receptor (EGFR) mutations when tissue is not available or to monitor acquired resistance mutation after a first line of treatment. The study aimed at assessing the diagnostic potential of liquid biopsy in balanced tertiary screening modeling. Methods The cases relating to 5 years of activity regarding to molecular diagnostics performed on liquid biopsy specimens in the Predictive Diagnostic laboratory of AOU Federico II were reviewed. Laboratory data were collected in SPSS. Non parametric analysis were performed in order to test the differences between patients WILD TYPE or not. A multivariate logistic model was performed in order to assess the effect of mutation, age and sex, on the tumor progression. The results of the revision concern 515 total cases (almost of all plasma or peripheral blood) allowed to evaluate the liquid biopsies for women and men. The average age of the Patients is 66.3 years, and the 25 percentile is 59 years. Results The cases are 221 basal and 294 by progression. The cases with mutation, as expected, have an OR 4,15 compared to the basal to have a tumor progression (95% IC: 2,7 - 6,3) regardless of sex and age. The mutations detected were 131 from different types of pulmonary carcinomas. Conclusions Working on case data, specifying the characteristics of the Patients with mutations will drive a further estimate in tertiary prevention screening designs. Key messages In the last five years, the liquid biopsy has been used for different purposes in oncology. To specify the characteristics of the Patients with mutations will drive a further estimate in tertiary prevention screening designs.

Aim: The association between Lipoprotein (a) (Lp [a]) and common carotid intima media thickness (IMT) has been evaluated in 222 menopausal women. Material & methods: Lp (a) and IMT were measured, carotid ultrasound examination (B-Mode imaging) was performed and mean max IMT was calculated. Results: Lp (a) was significantly lower in women with metabolic syndrome (MS). In a multivariate analysis Lp (a) showed the following odds ratio (OR; all p < 0.05) of having common carotid IMT (≥1.30 mm): 1.03, adjusted for age, low-density lipoprotein cholesterol (LDL) and waist circumference; 1.02, adjusted for age LDL, homeostatic assessment model (HOMA). In women without MS, after controlling for age, LDL and waist circumference, we found the following OR for increased IMT (≥1.30; OR: 1.03; for Lp [a]); 1.02 adjusted for age, LDL and HOMA (all p < 0.05). In women with MS these relationships were not statistically significant. Conclusion: Lp (a) gives additional information in the risk assessment for atherosclerotic cardiovascular disease, especially in menopausal women without MS.

Background and aims: Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). Methods: Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationwide DNA diagnostic centers. Results and conclusions: From 2012 to October 2016, available biochemical and clinical information of 3480 subjects with familial hypercholesterolemia identified according to the Dutch Lipid Clinic Network (DLCN) score were included in the database and genetic analysis was performed in 97.8% of subjects, with a mutation detection rate of 92.0% in patients with DLCN score >= 6. The establishment of the LIPIGEN network will have important effects on clinical management and it will improve the overall identification and treatment of primary dyslipidemias in Italy. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.

Aim: The aim of this study was to test small dense LDL changes with Armolipid Plus treatment in patients with familial combined hyperlipidemia (FCHL). Methods: After 4 weeks, 30 patients with FCHL were included in an 8-week, randomized, double-blind study and were taking, in addition to the standard diet, either placebo or Armolipid Plus. Results: The placebo group showed no statistically significant differences in the studied parameters; instead, in the Armolipid Plus group, statistically significant reduction differences were detected in BMI (p = 0.010), LDL score (p = 0.035) and an increase in mean LDL particle diameter (p = 0.040). Conclusion: The combination of a standard diet with Armolipid Plus is able to reduce LDL score and increase LDL particle diameter in a group of FCHL after 8 weeks of treatment.

This review reports our experience in evaluating the progression from asymptomatic to symptomatic atherosclerosis in an evidence-based context. In particular, studies published in the last 5 years were analyzed in more detail and their relevance to cardiovascular prevention in women and children is discussed. The evaluation of carotid artery intima–media thickness by ultrasonography and the measurement of coronary artery calcification using computed tomography scanning can provide evidence for the presence and extent of atherosclerosis in adults. Intima–media thickness was demonstrated to predict prognosis and help in clinical decision making. Computed tomography estimates of advanced coronary atherosclerosis are markers of advanced atherosclerosis and are of value for screening adult men, but their value in women and children is doubtful owing to radiation risk. Intima–media thickness measurement, even when acknowledging its limitations, is a preferred approach, with the promising perspective of the availability of portable devices of lower cost in the near future. Further evaluation of the potential role for the emerging biomarkers and imaging techniques could clarify the clinical relevance of emerging risk profiles such as the metabolic syndrome. Ultrasound methods provide information regarding the extent and progression of early atherosclerotic abnormalities in women and in children and predict cardiovascular prognosis.

Homozygous familial hypercholesterolemia (HoFH), the severest form of familial hypercholesterolemia (FH), is characterized by very high LDL-cholesterol levels and a high frequency of coronary heart disease. The disease is caused by the presence of either a pathogenic variant at homozygous status or of two pathogenic variants at compound heterozygous status in the LDLR, APOB, PCSK9 genes. We retrospectively analyzed data of 23 HoFH patients (four children and 19 adults) identified during the genetic screening of 724 FH patients. Genetic screening was performed by sequencing FH causative genes and identifying large rearrangements of LDLR. Among the HoFH patients, four out of 23 (17.4%) were true homozygotes, whereas 19 out of 23 (82.6%) were compound heterozygotes for variants in the LDLR gene. Basal LDL-cholesterol was 12.9 &plusmn, 2.9 mmol/L. LDL-cholesterol levels decreased to 7.2 &plusmn, 1.8 mmol/L when treated with statin/ezetimibe and to 5.1 &plusmn, 3.1 mmol/L with anti-PCSK9 antibodies. Homozygous patients showed higher basal LDL-cholesterol and a poorer response to therapy compared with compound heterozygotes. Since 19 unrelated patients were identified in the Campania region (6,000,000 inhabitants) in southern Italy, the regional prevalence of HoFH was estimated to be at least 1:320,000. In conclusion, our results revealed a worse phenotype for homozygotes compared with compound heterozygotes, thereby highlighting the role of genetic screening in differentiating one genetic status from the other.

BACKGROUND: Severe hypertriglyceridemia is a rare disease characterized by triglyceride levels higher than 1000 mg/dl (11.3 mmol/L) and acute pancreatitis. The disease is caused by pathogenic variants in genes encoding lipoprotein lipase (LPL), apolipoprotein A5 (APOA5), apolipoprotein C2 (APOC2), glycosylphosphatidylinositol-anchored high density lipoproteinbinding protein 1 (GPIHBP1) and lipase maturation factor 1 (LMF1). OBJECTIVE: We aim to identify the genetic cause of severe hypertriglyceridemia and characterize the new variants in a patient with severe hypertriglyceridemia. METHODS: The proband was a male showing severe hypertriglyceridemia (triglycerides 1416 mg/dL, 16.0 mmol/L); proband’s relatives were also screened. Genetic screening included direct sequencing of the above genes and identification of large rearrangements in the LPL gene. Functional characterization of mutant LMF1 variants was performed by complementing LPL maturation in transfected Lmf1-deficient mouse fibroblasts. RESULTS: The proband and his affected brother were compound heterozygotes for variants in the LMF1 gene never identified as causative of severe hypertriglyceridemia c.[157delC;1351C>T];[410C>T], p.[(Arg53Glyfs*5)];[(Ser137Leu)]. Functional analysis demonstrated that the p.(Arg53Glyfs*5) truncation completely abolished and the p.(Ser137Leu) missense variant dramatically diminished the lipase maturation activity of LMF1. CONCLUSIONS: In addition to a novel truncating variant, we describe for the first time a missense variant functionally demonstrated affecting the lipase maturation function of LMF1. This is the first case in which compound heterozygous variants in LMF1 was functionally demonstrated as causative of severe hypertriglyceridemia.

Background and aims Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification. Methods This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH. Results The DLCN score was applied on a sample of 1377 adults (mean age 42.9 ± 14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3–5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score. Conclusions Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects.

The aim of the study was to evaluate the relationship between cholesterol contained in very-low-density lipoproteins (VLDL-C), intermediate-density lipoproteins (IDL-C), low-density lipoproteins, high-density lipoproteins, and carotid intima–media thickness (cIMT) and carotid plaques in 228 postmenopausal women (63.1 ± 8.2 years) who participated in the ATENA Project and underwent clinical, biochemical (including the assay of lipoproteins using the Lipoprint system), and carotid ultrasound tests. Very-low-density lipoprotein cholesterol had a statistically significant linear association with cIMT ( P < .001), which remained significant after adjustment for age, smoking, systolic blood pressure, glucose, and body mass index ( r2 = .20, P < .05). Higher concentrations of IDL-C and cholesterol contained in triglyceride-rich lipoproteins (TRL-C, ie, VLDL-C + IDL-C) were associated with plaques in the common carotid (tertile III/tertile I: odds ratio [OR] = 2.52, 95% confidence interval [CI] = 1.21-5.32, P < .02; OR = 2.30, 95% CI = 1.05-5.01, P < .05, respectively), after adjustment for main cardiovascular risk factors. In conclusion, high concentrations of VLDL-C and TRL-C are independently associated with the presence of carotid plaques. Their assay represents a useful tool for improving our knowledge on the role of different classes of lipoproteins in atherosclerosis.

Background Familial hypercholesterolemia is a common autosomal dominant disease, caused by mutations leading to elevated low-density lipoprotein (LDL) cholesterol and, if untreated, to premature cardiovascular disease. Methods Patients (young adults with a family history of hypercholesterolaemia or premature cardiovascular disease) with LDL cholesterol concentration ≥4.9 mmol/l, after excluding Familial Combined Hyperlipidaemia, were evaluated for causative mutations, Dutch Lipid Clinic Network score calculation and non-invasive ultrasound examination of carotid arteries. Results Of the 263 patients, 210 were heterozygotes for LDL receptor ( LDLR) mutations, four had APOB gene mutations, one PCSK9 gene mutation, while 48 had no evidence of mutations. Among 194 unrelated index cases 149 had mutations (77%). Among patients with LDLR mutations ( n = 145), there were five compound heterozygotes, 75 patients with null mutations and 65 with missense mutations. As many as 178 patients underwent a follow-up and treatment (statin ± ezetimibe), achieving a mean reduction of 49% in LDL cholesterol, with 21% of patients reaching the LDL goal of 2.6 mmol/l. In a multivariate analysis, carotid plaques, at ultrasound examination, were associated with the presence of genetic mutation ( p = 0.001), LDL cholesterol ( p 0.001), Dutch Lipid Clinic Network score ( p 0.001), independently of age, gender, smoking habits and systolic blood pressure. The presence of carotid plaque ( p = 0.017), LDL cholesterol ( p 0.003), Dutch Lipid Clinic Network score ( p 0.001) were independently associated with premature cardiovascular disease. Conclusions We identified patients with causative mutations in 82% of the cases under study. In addition to LDL cholesterol and Dutch Lipid Clinic Network score, carotid plaques in ultrasound evaluation provide direct evidence of premature vascular disease and are associated with high risk for cardiovascular events.

This research objective is to describe the process and model of harmonious communication among religious adherents and the supporting and inhibiting factors for the occurrence of harmonious communication in Sorong, West Papua. This research uses a qualitative approach with descriptive research to understand the process and model of communication between religious adherents. The research subject of interfaith leaders in Sorong amounted to 7 informant. The data collection method was done by interview and documentation techniques. Furthermore, the research result is a description of the process of harmonious communication among religious adherents carried out through the stages of structuring harmony and productivity. While, the stages of structuring harmony are carried out through the process of instilling mutual understanding, tolerance, and mutual respect among the adherents of the religion. The steps have resulted in productivity, namely; the realization of harmony among religious communities, and rised to a harmonious communication model that was built based on peace, tolerance, and cooperation. Supporting factors for harmonious communication are the role of the "Forum on Religious Harmony" (FKUB) and the role of religion and culture. The factor of inhibiting is the existence of socio-economic inequality and ineffective communication between local leaders and communities and national leaders.

Background: atherosclerotic process inexorably advances in patients reaching low-density lipoprotein cholesterol (LDL-C) targets. An attractive hypothesis is that lipoprotein particles (very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL)), could contribute to residual risk. The present study aims to investigate the relationship between carotid intima-media thickness (IMT) and different lipoprotein subfractions in a cohort of healthy postmenopausal women. Methods: 75 postmenopausal women, at LDL-C target levels without overt cardiovascular disease, underwent biochemical analyses (including subfraction assay of plasma lipoproteins) and carotid ultrasound examination. Results: a statistically significant correlation between VLDL and carotid IMT (p &lt, 0.001) was found. No significant correlation was found between carotid IMT and LDL-C (p = 0.179), IDL-C (p = 0.815), high-density lipoprotein (HDL) (p = 0.855), and LDL score (p = 0.240). Moreover, IMT is significantly correlated to LDL particle diameter (p = 0.044). After adjusting for age, systolic blood pressure, body mass index, smoking habits, glucose plasma concentration, and Lipoprotein(a) (Lpa) levels, multivariate analysis showed that women in the third tertile of VLDL-C, compared with those in the first tertile, were significantly associated to the highest IMT (p = 0.04). Conclusions: in this cohort of postmenopausal women, VLDL-C was significantly associated to carotid IMT, independent of main cardiovascular risk factors. These findings pave the way for targeting circulating concentrations of VLDL-C to reduce cardiovascular events in patients with target LDL-C levels.

Psoriatic arthritis (PsA) is an inflammatory rheumatic disorder occurring in patients with psoriasis. Several studies have shown an association between Psa and traditional atherosclerotic risk factors. We evaluated the relationship between small dense low-density lipoproteins particles (sd-LDL) a risk marker for atherosclerosis, sub-clinical atherosclerosis and PsA in a group of 50 patients with PsA and in 100 controls. Cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, insulin, homeostasis model assessment (HOMA), Apo B, and sd-LDL have been measured. LDL particle separation was performed and seven LDL subfractions were obtained, LDL score (percentage of sd-LDL) and mean LDL particle size were calculated. PsA patients and control group differ significantly (p

Paolo Rubba, Gennaro Marotta, Marco GentileDepartment of Clinical and Experimental Medicine, Federico II University of Naples, ItalyAbstract: Rosuvastatin is a synthetic statin that represents an advance in the pharmacologic and clinical properties of statins. Relative to other statins, rosuvastatin possesses a greater number of binding interactions with HMG-CoA reductase and has a high affinity for the active site of the enzyme. As with other statins, serious adverse effects with rosuvastatin therapy are uncommon and primarily involve effects on the liver and skeletal muscle. The risk increases with increasing dosages and coadministration with other drugs interacting with the same metabolic pathway. The degree of LDL reduction is important to achieve the treatment goals suggested by international guidelines. Among the most potent statins, rosuvastatin is capable of getting the majority of patients to their LDL cholesterol goals. In addition, rosuvastatin has been found effective in reducing small-dense LDL, C-reactive protein and in increasing HDL cholesterol levels. Controlled clinical trials using vascular end-points have been performed. In particular, a study demonstrated that rosuvastatin therapy could slow progression and/or cause regression of carotid intima-media thickness over 2 years in middle-aged individuals with a low Framingham risk score (FRS) and mild to moderate subclinical atherosclerosis. A primary prevention study (JUPITER) was stopped before the programmed end of the study, because of excess benefit for high-risk individuals receiving rosuvastatin treatment. It is suggested that pronounced LDL reduction, in association with significant HDL cholesterol increase, are the bases of a marked preventive action of rosuvastatin. The results from JUPITER support the use of rosuvastatin for primary cardiovascular prevention, in overweight men and women, with near to normal LDL cholesterol and high CRP. There is now evidence of benefit from rosuvastatin treatment for a wide segment of the general population at intermediate cardiovascular risk. In absolute numbers, this segment represents the main source of cardiovascular events: on the basis of JUPITER results, it is expected that treatment target and potential candidates to statin therapy will be revaluated and redefined.Keywords: cardiovascular prevention, cholesterol, high-density lipoprotein, C-reactive protein, vascular end-point, overweight

1. Atherosclerosis. 2009 Mar;203(1):320-4. Epub 2008 Jul 12. Small dense low-density lipoprotein in familial combined hyperlipidemia: Independent of metabolic syndrome and related to history of cardiovascular events. Pauciullo P, Gentile M, Marotta G, Baiano A, Ubaldi S, Jossa F, Iannuzzo G, Faccenda F, Panico S, Rubba P. Department of Clinical and Experimental Medicine, University Federico II Medical School, Nuovo Policlinico, Edificio 1, Via Pansini 5 - 80131 - Naples, Italy. pauciull@unina.it INTRODUCTION: It is unclear whether small dense low-density lipoprotein (sdLDL) are associated with familial combined hyperlipidemia (FCHL), independently of the metabolic syndrome (MS). It is also unclear whether sdLDL are related to history of cardiovascular (CVD) events in FCHL patients, independently of MS. PATIENTS AND METHODS: Serum levels of sdLDL, expressed as percentage of total LDL cholesterol (LDL score), were determined in 137 probands with FCHL and in 133 normolipidemic, normotensive, normoglycemic healthy subjects. RESULTS: In binary logistic regression age- and gender-adjusted LDL score values above the 90th and 95th percentiles of the values in the control group (10.23 and 13.11%, respectively) were found to be significant predictors of FCHL status, independently of MS diagnosis (p=0.007 and p

1. Heart. 2007 Jan;93(1):78-81. Epub 2006 Jun 28. Impaired endothelium-dependent vascular reactivity in patients with familial combined hyperlipidaemia. De Michele M, Iannuzzi A, Salvato A, Pauciullo P, Gentile M, Iannuzzo G, Panico S, Pujia A, Bond GM, Rubba P. Division of Cardiology, Moscati Hospital, Aversa, Italy. BACKGROUND: Familial combined hyperlipidaemia (FCHL) is associated with a markedly increased risk of premature coronary artery disease. This study was designed to evaluate whether preclinical atherosclerotic functional abnormalities are detectable in the arteries of patients with FCHL. METHODS: 60 subjects were recruited for the study: 30 probands of families with FCHL (mean (standard deviation (SD)) age 48 (10) years, 77% men), defined by fasting total plasma cholesterol or triglyceride concentration >250 mg/dl (>6.5 mmol/l cholesterol, >2.8 mmol/l triglyceride) and by the occurrence of multiple lipoprotein phenotypes within a family, and 30 age-matched and sex-matched healthy controls. All subjects underwent high-resolution B-mode ultrasound examination and the brachial arterial reactivity, a marker of endothelial function, was measured by a semiautomated computerised program. Lipid profile, resting blood pressure, body mass index (BMI), smoking status, insulin and homocysteine levels were also determined. RESULTS: Compared with controls, patients with FCHL had significantly higher BMI, diastolic blood pressure and insulin levels. No difference was observed in baseline brachial diameter between the two groups (mean (SD) 3.45 (0.51) mm for FCHL v 3.60 (0.63) mm for controls; p = 0.17). In response to flow increase, the arteries of the controls dilated (mean (SD) 8.9% (4.9%), range 2.3-20.8%), whereas in the patients with FCHL, brachial arterial reactivity was significantly impaired (5.5% (2.5%), range 0-10.1%; p = 0.002). In multivariate linear regression analysis, apolipoprotein B and BMI were independent determinants of brachial artery response to reactive hyperaemia. CONCLUSIONS: The findings of our study suggest that vascular reactivity is impaired in the arteries of patients with FCHL. PMCID: PMC1861336 PMID: 16807271 [PubMed - indexed for MEDLINE]

Methods: A thorough search has been conducted using various databases, ie, Cochrane library, PubMed, EMBASE, Federico II University Open Archive. The evidence was considered following the Effective Practice and Organization of Care Group checklist. Prevalent organizational attitudes and areas were assessed, and various scenarios were analyzed. Initially, all titles and abstracts were screened. In the next phase, the full text of all abstracts considered potentially relevant by at least one of the reviewers was evaluated. Inconsistencies in decision-making within this second phase were solved based on consensus between both reviewers. In this phase, for every study we defined whether the organization was considered relevant and what the scenario was. The information was extracted from each study based on bibliographic details (author, journal, year of publication, and language). As many as 1,071 studies were analyzed, and 81 were selected as potentially relevant. Results: We found three prevalent areas of interest focused on organizational elements: global organizational strategies scenario, clinical hospital organization, and citizenship and social scenario. Conclusion: We reached the conclusion that organization has a central role in different scenarios of procurement and transplantation in a continuum from government to hospital (the core of the system) and finally among citizens. A standardized hospital pathway definitely remains the essential step in order to ameliorate either procurement or transplantation. Introduction: The growing disparity between organ availability for transplantation and the number of patients in need has challenged the donation and transplantation community to develop innovative processes, ideas, and techniques to bridge this gap. Advances in the sharing of best practices in the donation community have contributed greatly to this aim over the past 5 years. Studies published during the past five years (2010–2014) were analyzed to gain insight on the evolving organizational areas and tools that the procurement and transplantation pathways have been focused on. The hypothesis assessed is that networking and efficacious handling of this complex path may be ameliorated by an adaptive organizational toolbox

Obesity in children may lead to insulin resistance and impaired glucose regulation over time. The aim of this study was to investigate the insulin resistance status and the frequency of impaired glucose regulation in obese children and adolescents from the Campania region (Southern Italy), where the prevalence of obesity is among the highest in Europe.We studied 100 (62 male) Italian obese children and adolescents (mean age 10.1+/-2.7 years) and 50 (27 male) normal weight healthy subjects (mean age 10.2+/-2.7 years). Anthropometric measures and biochemical tests were performed in all subjects. In obese patients an oral glucose tolerance test was also performed. The estimate of insulin resistance was calculated by a homeostasis model assessment (HOMA) index. A cut-off HOMA level of2.5 in children and4.0 in adolescents was used to identify an insulin-resistance status. Insulin resistance was found in 40.8% of obese children and 41.2% of obese adolescents, whereas it was found in 3.0% of normal children and none of the 17 normal adolescents (p0.0001 and p0.002, respectively). None of the subjects had impaired fasting glucose or diabetes, while 4 obese patients had impaired glucose tolerance (4%).Impaired glucose tolerance is still rare whereas insulin-resistance is already detectable in more than 40% of obese children and adolescents in Southern Italy. Our observations confirm that metabolic risk factors can be found at a very early age and strengthen the case for implementing programmes for prevention and treatment of childhood obesity.

OBJECTIVE The aim of this study was to evaluate whether overweight and obesity are associated with arterial abnormalities in postmenopausal women and the contribution of the metabolic syndrome. METHODS A total of 390 postmenopausal women (mean age, 63.1 ± 7.7 y) living in the metropolitan area of Naples, Southern Italy, and participating in a population-based cohort study (Progetto Atena) were offered an ultrasound examination of the carotid arteries; 370 women accepted. Blood pressure, serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting glucose, insulin, apolipoprotein B, and high-sensitivity C-reactive protein were measured in all participants. RESULTS Women in the second and third tertiles of body mass index showed a greater common carotid intima-media thickness compared with those in the first tertile (tertile II vs I, odds ratio, 2.15; P = 0.013; tertile III vs I, odds ratio, 2.24; P = 0.018), adjusted for age and metabolic syndrome. Obese and overweight postmenopausal women showed greater common carotid lumen diameters as compared with lean postmenopausal women (mean ± SD, 6.36 ± 0.86, 6.16 ± 0.65, and 5.96 ± 0.59 mm, respectively; P < 0.001 [obese vs lean] and P = 0.04 [overweight vs lean]); no statistical difference in carotid lumen diameter was found between obese and overweight postmenopausal women. The statistical significance between obese and lean postmenopausal women was retained even after adding the components of the metabolic syndrome as covariates. CONCLUSIONS These findings indicate an association between overweight, obesity, and preclinical carotid artery abnormalities, independently of the metabolic syndrome, in a population of postmenopausal women.

Background and aim The relationships between high Creatinine (Cr) levels or low estimated Glomerular Filtration Rate (eGFR) and common carotid Intima Media thickness (IMT) have been evaluated in a population-based cohort study in women, aged 30–69 (Progetto ATENA). Methods and results Serum Cr and eGFR were measured in 310 women, as a part of 5.062. In this group carotid ultrasound examination (B-Mode imaging) was performed and mean max IMT was calculated. Women were classified by Cr levels >1 mg/dL or eGFR Women with Cr > 1 mg/dL (90th percentile of creatinine distribution) or eGFR less than 56 ml/min (5th percentile of eGFR distribution) had relatively more carotid plaques as compared to the rest of the cohort. Multivariate logistic analysis, after adjustment for age, demonstrated a significant association between Cr (>1 mg/dL) and IMT (≥1.2 mm): OR 4.12 (C.I 1.22–13.86), p = 0.022; or eGFR ( p = 0.019. Conclusions These findings on an independent relationship between Cr and common carotid plaques in this population of middle aged women, independently of age, suggest the value of screening for early carotid disease in asymptomatic middle aged-women with mild renal insufficiency, in order to predict those at relatively higher risk for future cardiovascular events.

The association between small dense LDL particles and early atherosclerosis has been evaluated in a sample of middle-aged women. We analysed the relation between sd-LDL and common carotid intima media thickness in 228 menopausal women. LDL separation was performed by Lipoprint System: 7 LDL subfractions were obtained, mean LDL size and LDL score (% of sd-LDL) were calculated. Multivariate analysis showed a significant association between IMT (≥ 1.30 mm) and mean LDL size after controlling for age (OR 7.80; 95% CI 1.47-41.39; p = 0.016 for mean LDL particle size). IMT remained significantly related to mean LDL particle size after controlling for age and Apo B. In a subsequent multivariate analysis, after controlling for age, IMT (≥ 1.30 mm) was significantly related to LDL score (OR 12.15; 95% CI 1.29-114.36; p = 0.029 for LDL score), or age and Apo B (OR 10.13; 95% CI 1.07-95.71; p = 0.043 for LDL score). Our results suggest an association between sd-LDL and IMT, independently of age and Apo B. This data may indicate that sd-LDL are markers of early carotid atherosclerosis, and suggest that measurement of sd-LDL-C gives useful information in the risk assessment for atherosclerotic disease in menopausal women.

The current study sought to investigate the role of low-density lipoprotein receptor (LDLr) mutations in assessing the risk profile of familial hypercholesterolemia (FH) patients, independently of major cardiovascular risk factors. FH due to LDLr mutations is associated with premature atherosclerosis. The variable clinical severity of the disease in heterozygotes has been related to cholesterol levels and the coexistence of other cardiovascular risk factors, but the independent role of different LDLr mutations is still unclear. cDNA of LDL gene was sequenced in 102 patients with clinical features of heterozygous FH. Carotid artery intima-media thickness (IMT) was measured by B-mode ultrasound imaging in all patients. Sixteen different mutations (5 never described) were found in 82 patients (49 families; mean age, 39 years; 53% women). One of the newly described mutations, the 2312-3 C→A, was found in 24 patients (13 families). The mean of maximum thicknesses was significantly higher in the 2312-3 C→A group than in patients with other LDLr mutations ( P = .004 after adjustment for major cardiovascular risk factors). Similar results ( P = .001) were obtained in the adjusted comparisons of probands only, and of the patients with similar baseline cholesterol ( P = .002). This study indicates that the identification of an LDLr mutation can help to assess the risk profile of FH patients independently of the major cardiovascular risk factors.