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Background Bempedoic acid (BA) is a novel lipid-lowering drug. We performed a systematic review and meta-analysis on efficacy and safety of BA compared with standard treatment in patients with hypercholesterolemia. Methods and Results Studies were systematically searched in the PubMed, Web of Science, Scopus, and EMBASE databases. Efficacy outcome was represented by percentage changes (mean difference [MD] with pertinent 95% CIs) in total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein B, non-high-density lipoprotein cholesterol, and hs-CRP (high-sensitivity C-reactive protein) in BA patients and controls. Seven studies were included (2767 BA-treated patients and 1469 controls), showing a more significant reduction in low-density lipoprotein cholesterol (MD, -17.5%; 95% CI, -22.9% to -12.0%), total cholesterol (MD, -10.9%; 95% CI, -13.3% to -8.5%), non-high-density lipoprotein cholesterol (MD, -12.3%; 95% CI, -15.3% to -9.20%), apolipoprotein B (MD, -10.6%; 95% CI, -13.2% to -8.02%), and hs-CRP (MD, -13.2%; 95% CI, -16.7% to -9.79%) in BA-treated patients compared with controls. Results were confirmed when separately analyzing studies on patients with high cardiovascular risk, studies on statin-intolerant patients, and studies on patients with hypercholesterolemia on maximally tolerated lipid-lowering therapy. BA-treated subjects reported a higher rate of treatment discontinuation caused by adverse effects, of gout flare, and of increase in uric acid compared with controls. On the other hand, BA-treated patients showed a lower incidence of new-onset diabetes mellitus than controls. Conclusions BA is associated with a significant reduction in low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, and hs-CRP compared with standard treatment. Documented efficacy is accompanied by an acceptable safety profile.

Background: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril/valsartan (S/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients., Methods: Patients with HFrEF admitted to outpatients' services were screened out for study inclusion. S/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up., Results: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 ± 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% ± 5.8% to 31.8% ± 7.3%, p < 0.0001), peak exercise oxygen consumption (VO 2peak ) (from 15.3 ± 3.7 to 17.8 ± 4.2 mL/kg/min, p < 0.0001), the slope of increase in ventilation over carbon dioxide output (VE/VCO 2 slope )(from 33.4 ± 6.2 to 30.3 ± 6.5, p < 0.0001), and HRR (from 11.4 ± 9.5 to 17.4 ± 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE/VCO 2slope ( r = -0.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE/VCO 2slope (Beta (B) = -0.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = -0.304, p = 0.009). S/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p < 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = -2.065, SE = 0.354, p < 0.001)., Conclusions: In HFrEF patients, S/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.

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 T 0 to 21.8, IQR: 16.6-31.8 kPA -1  × 10 -3  at T12 w ) 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®., Competing Interests: Declaration of Competing Interest All the Authors have nothing to declare., (Copyright © 2020. Published by Elsevier B.V.)

Despite an increasing access to prophylaxis with clotting factor concentrates, arthropathy still represents the main chronic complication of hemophilia. Whereas previous studies described hemophilic arthropathy (HA) as a degenerative arthropathy, somehow resembling osteoarthritis (OA), most recent evidence suggests that complex inflammatory and immunologic mechanisms are also involved in the pathophysiology of HA. In the present review, we described available data on major mechanisms leading to arthropathic changes in patients with hemophilia, with a specific focus on the role of synovium. The presence of hemosiderin in the joint space induces synovium proliferation, thus leading to formation of several lytic enzymes determining chondrocytes apoptosis and proteoglycans levels reduction. This leads to a direct joint "chemical" damage representing early damages in the pathogenesis of HA (first hit). In parallel, synovial membrane and synovial endothelial cells become a dynamic reservoir of inflammatory cells and mediators, and propagate the inflammatory response (second hit), switching the process from a chemical damage to an inflammatory damage. Overall, consistent data pointed out synovitis as the keystone in HA pathophysiology. This opens novel potential therapeutic targets in this clinical setting., (Copyright © 2020 Calcaterra, Iannuzzo, Dell’Aquila and Di Minno.)

Oxidative stress and mitochondrial dysfunction are hallmarks of heart failure (HF). Coenzyme Q10 (CoQ10) is a vitamin-like organic compound widely expressed in humans as ubiquinol (reduced form) and ubiquinone (oxidized form). CoQ10 plays a key role in electron transport in oxidative phosphorylation of mitochondria. CoQ10 acts as a potent antioxidant, membrane stabilizer and cofactor in the production of adenosine triphosphate by oxidative phosphorylation, inhibiting the oxidation of proteins and DNA. Patients with HF showed CoQ10 deficiency; therefore, a number of clinical trials investigating the effects of CoQ10 supplementation in HF have been conducted. CoQ10 supplementation may confer potential prognostic advantages in HF patients with no adverse hemodynamic profile or safety issues. The latest evidence on the clinical effects of CoQ10 supplementation in HF was reviewed.

We report a case of a recurrence of 5 cardiac myxomas in both atria with atypical anatomical features difficult to image. Although a multimodality imaging was performed, three-dimensional echocardiography (3DE) was the only technique able to correctly identify all the recurrences and the anatomical characteristics of the myxomas. MRI detected the blood supply of the mass but even after careful review was able to identify only 4 of the 5 lesions. Even though it was already reported the usefulness of 3DE to better delineate the site of attachment of cardiac tumors, it was never reported its sensibility in the setting of multiple myxomas; this case highlights the ability of the 3DE in this challenging scenario and its potential for being considered the key adjunctive modality for the anatomy when advanced surgical plan is required.

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 ± 2.9 mmol/L. LDL-cholesterol levels decreased to 7.2 ± 1.8 mmol/L when treated with statin/ezetimibe and to 5.1 ± 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.

In previous decades, extensive and disfiguring transfacial and/or transcranial approaches were used to reach the sellar and parasellar areas. However, these surgical routes were burdened by severe complications and high mortality rates. Recently, the development of endoscopic endonasal techniques has revolutionized the surgical strategies for approaching the sella and adjacent areas and increased the development of transsphenoidal surgery. With these techniques, surgeons have been able to overcome the visual limitations of the open surgical approaches and access areas previously hidden from view. After the contributions of the Pittsburgh duo, Carrau and Jho, pioneers of pure endoscopic surgery, our school began to implement this technique, introducing technical innovations and variations, describing the anatomical details and defining new routes, and playing a key role in its widespread clinical application., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Lipoprotein (a) (Lp [a]) is associated with premature atherosclerosis in menopausal women without metabolic syndrome (MS). MS is the main confounder in the relationship between Lp(a) and atherosclerosis in menopausal women. We have evaluated the relationship between Lp(a) and small dense-low density lipoprotein (sd-LDL) in 228 menopausal women participating to Progetto Atena. Methods: Lp(a) was measured and LDL particle separation was performed: mean LDL diameter and LDL score (% of sd-LDL) particles calculated. Results: Women without MS and elevated Lp(a) have increased number of sd-LDL ( p  < .05) and higher LDL score compared with those below the median of the studied population ( p  < .05). The association between Lp(a) and sd-LDL was evaluated taking into account different adjustment models. Women with elevated levels of Lp(a) show the following OR of having a small LDL diameter (in the lowest quartile): 1.02, p  = .003; adjusted for age; 1.02, p  = .002; adjusted for age, and triglycerides, or a high LDL score (in the highest quartile): 1.02, p  = .006; adjusted for age; 1.02, p  = .002; adjusted for age and triglycerides. Conclusions: In this group of menopausal women without MS, the independent association of Lp(a) with sd-LDL might explain at least in part the association of Lp(a) with premature atherosclerosis.

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 ( r 2 = .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.

Context: Vitamin D deficiency patients have an increased cardiovascular (CV) morbidity and mortality. Contrasting data are available about the association between peripheral arterial disease (PAD) and Vitamin D status., Objective: To perform a meta-analysis of studies evaluating the association between Vitamin D status and PAD., Data Sources: Studies were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases., Results: Ten studies with data on Vitamin D levels in 2,079 PAD patients and 18,233 non-PAD controls and 6 studies on the prevalence of PAD in 23,171 subjects with Vitamin D deficiency (<20 ng/ml), 48,311 subjects with Vitamin D insufficiency (20-30 ng/ml) and 27,910 with normal Vitamin D levels (>30 ng/ml) were included. Compared to controls, PAD patients showed significantly lower Vitamin D levels (MD: -2.24 ng/ml; 95%CI: -3.38, -1.10; p<0.001, I2=86.5%; p<0.001). Moreover, a higher prevalence of PAD was found both in subjects with Vitamin D insufficiency (OR: 1.098, 95%CI: 1.010-1.195, p=0.029, I2: 0%, p=0,600) and in subjects with Vitamin D deficiency (OR: 1.484, 95%CI: 1.348-1.635, p<0.001, I2: 7.65%, p=0,367) compared with controls with normal Vitamin D levels. Sensitivity analyses and the analysis of data on the cumulative risk of PAD according to Vitamin D levels derived from multivariate analysis consistently confirmed results., Conclusions: PAD patients have lower vitamin D levels than controls and both Vitamin D deficiency and Vitamin D insufficiency are significantly associated with PAD. Reduced Vitamin D levels might represent an independent risk factor for PAD and, in turn, for CV events.

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 (m 11/6  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., Competing Interests: No potential conflicts of interest were disclosed.

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.

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 < 0.001) in triglycerides values (119.3 ± 52.0 vs 90.7 ± 40.7 mg/dL), Apo B (1.1 ± 0.2 vs 0.9 ± 0.1 g/L), insulin (8.9 ± 4.9 vs 5.8 ± 3.2 mU/L), HOMA (2.2 ± 1.7 vs 1.3 ± 0.8), BMI (27.7 ± 3.3 vs 25.8 ± 3.8). LDL score is significantly higher in PsA as compared to control (9.0 ± 10.7 vs 2.9 ± 4.7 mg/dL); and mean LDL size is significantly lower in PsA than control (268.1 ± 4.6 vs 271.2 ± 2.7 Å). These differences were confirmed when stratifying PsA patients for treatment and for disease activity. LDL score and LDL diameter significantly were correlated with the carotid IMT in patients with PsA. These findings show a novel relationship between LDL score and mean LDL size with PsA diagnosis and with sub-clinical atherosclerosis. Sd-LDL gives potentially useful information in the risk assessment for atherosclerotic disease in PsA patients.

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.

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., (© 2013 Elsevier B.V. All rights reserved.)

Introduction: The relationship between anger and sexual behavior has never been thoroughly addressed, although it may deserve special attention because of its theoretical and practical consequences., Aim: We were interested in determining the extent in which trait anger was associated with dysfunctional sexual behavior, taking into account possible gender differences., Method: In this correlational study, 410 volunteers (199 men and 211 women) recruited from the students of the University of Messina, Italy, participated in the study. Median age of participants was 24 years. Men and women did not differ significantly in age (U = 18996, P = 0.606)., Main Outcome Measures: The individuals' sexual behavior was assessed using the Sex and the Average Woman (or Man) questionnaire., Results: We found no association between trait anger and either measure of sexual motivation: sexual excitement, r (396) = 0.11, P = 0.016, and sexual fulfillment, r (396) = -0.06, P = 0.134. Also, gender had no effect on either of these two variables. Trait anger had a positive significant correlation with neurotic sex, r (396) = 0.29, P < 0.002, impersonal sex, r (396) = 0.20, P < 0.002, and aggressive sex, r (396) = 0.28, P < 0.002. As we predicted, the associations between trait anger and these last three variables were stronger for men than for women (although only aggressive sex had a significant result). In multivariate analyses, impersonal sex ceased to be a significant correlate of trait anger., Conclusions: Trait anger has a negative effect on sexual behavior. It seems to exert its worst effects on the nature of sexual interpersonal behavior rather than on sexual motivation. We found no effect of gender on sexual motivation. However, the positive correlation between anger and relational sexual behavior was stronger for men than for women., (© 2010 International Society for Sexual Medicine.)

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<0.0001, respectively). Values of the LDL score above the 90th and the 95th percentile of the control group resulted to be significantly related to FCHL status, even after adjustment for the components of MS (p=0.006 and p=0.001, respectively). Among FCHL patients, values of the LDL score above 95th percentile of the values in the control group were found to be significantly related to personal and/or family history of CVD events, independently of age, gender, total cholesterol, apolipoprotein (apo) B, and MS status (p=0.016). The same significant relationship was found adjusting for all components of MS (p=0.034)., Conclusions: High concentrations of sdLDL are highly specific markers of FCHL, independently of concomitant MS. In FCHL patients high levels of sdLDL are related to history of CVD events, independently of MS, total cholesterol and apo B.

It is unclear whether an association between familial combined hyperlipidemia (FCHL) and inflammatory markers exists, independently of age, sex, body weight, insulin resistance, and metabolic syndrome. Serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), monocyte chemoattractant protein 1, interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and high-sensitive C-reactive protein were determined in 135 probands with FCHL and in 146 normolipidemic, normotensive, normoglycemic healthy subjects. Insulin resistance was evaluated using homeostasis model assessment (HOMA). All inflammatory parameters, except interleukin 6, were significantly higher in FCHL according to medians or mean comparisons. After adjustment for age, sex, body mass index, and HOMA, only TNF-alpha remained an independent predictor of FCHL status by binary logistic regression (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.07-1.31; P = .001). In particular, elevated levels of TNF-alpha (above the 90th and 95th percentiles of the value observed in the control group, 9.6 and 9.8 pg/mL, respectively) were independent predictors of FCHL status: for TNF-alpha above the 90th percentile, OR was 7.91 (95% CI, 3.27-19.13; P < .001), and for TNF-alpha above 95th percentile, OR was 13.08 (95% CI, 4.60-37.15; P < .0001). The independent role of TNF-alpha as predictor of FCHL status was confirmed after adjustment for components of the metabolic syndrome (P = .007 and P = .003, for TNF-alpha values above 90th and 95th percentiles, respectively). In conclusion, among the inflammatory markers most commonly measured, only TNF-alpha was associated with FCHL independently of age, sex, body mass index, and HOMA. The association of TNF-alpha with FCHL was also independent of the metabolic syndrome.

Objective: The purpose of this study was to examine the association between body mass index (BMI), venous capacitance, and clinical evidence of varicose veins after adjustment for sex hormones in postmenopausal women., Methods: This study group of the DIANA (DIet and ANdrogens) project (a randomized controlled trial on the effect of some dietary changes on sex hormone pattern in women with elevated androgenic hormone levels in Italy) was comprised of 104 healthy volunteer postmenopausal women, aged 48 to 65 years. The main outcome measures were physical examination to determine the presence and severity of varicose veins and plethysmographic measurement of lower limb venous capacitance and outflow., Results: Women in the upper quartile of BMI (>30 kg/m(2)) showed a positive association with clinical evidence of varicose veins (odds ration, 5.8; 95% CI, 1.2 to 28.2) after adjustment for age, estradiol, testosterone, and sex hormone binding globulin. No association was found between BMI and plethysmographic measurements of venous parameters., Conclusion: Obesity is associated with clinical evidence of varicose veins independently from the influence of sex hormones in postmenopausal women and is not associated with venous capacitance. Increased body weight increases the risk of varicose veins.

Objective: The purpose of this study was to determine if there is an association between elevated sex hormones (ie, serum estradiol, sex hormone binding globulin [SHBG], testosterone) and increased venous distension and clinical evidence of varicose veins in menopausal women., Methods: Participants were 104 healthy volunteer menopausal women, aged 48 to 65 years, who were not undergoing hormonal treatment. Of these 104, 14 were excluded from analyses because their estradiol levels were compatible with a premenopausal condition (4), because they had missing values for insulin concentration (5), and because they did not show up at venous vessel examination (5). Patients underwent a physical examination to determine the presence of varicose veins; a venous strain-gauge plethysmographic examination to compute instrumental measures of venous distensibility; and laboratory analyses of blood so serum testosterone, estradiol, SHBG, glucose, and insulin could be measured. There were also prevalence ratios and odds ratios used to test the presence of an association between biochemical and instrumental variables., Results: Serum levels of estradiol in the upper tertile of the frequency distribution were significantly associated with clinical evidence of varicose veins (prevalence odds ratios 3.6; 95% CI 1.1-11.6) and with increased lower limb venous distensibility (prevalence odds ratios 4.4; 95% CI 1.2-15.5). No association was found for SHBG and testosterone., Conclusions: Our finding that high serum levels of estradiol are associated with clinical evidence of varicose veins and instrumental measurements indicating increased venous distensibility in menopausal women suggests that endogenous estrogens may play a role in the development of this very common venous vessel abnormalities.

To evaluate the effects of short-term cholesterol-lowering treatment on myocardial effort ischemia, 22 patients with stable effort ischemia and mild to moderate hypercholesterolemia (low density lipoprotein [LDL] cholesterol 160 to 220 mg/dl) were randomly allocated at baseline (TO) in 2 groups. Group A included 12 patients treated with simvastatin 10 mg bid; group B included 10 patients treated with placebo. All patients underwent a treadmill electrocardiography (ECG) test; total cholesterol, HDL and LDL cholesterol, triglycerides, plasma, and blood viscosity were measured. All tests were repeated after 4 and 12 weeks. For 18 of the same patients (11 taking simvastatin, 7 receiving placebo), forearm strain-gouge plethysmography was performed at baseline and after 4 weeks, both at rest and during reactive hyperemia. At 4 and 12 weeks, group A showed a significant reduction in total cholesterol (p <0.05) and LDL (p <0.05), with unchanged HDL, triglycerides, blood, and plasma viscosity. Effort was unmodified, ST-segment depression at peak effort and ischemic threshold were significantly improved after 4 and 12 weeks (all p <0.05) with unchanged heart rate x systolic blood pressure product. A significant increase in the excess flow response to reactive hyperemia was detected in group A (p <0.03); group B showed no changes in hematochemical and ergometric parameters. These data suggest that cholesterol-lowering treatment is associated with an improvement in myocardial effort ischemia; this might be explained by a more pronounced increase of coronary blood flow and capacity of vasodilation in response to effort.

The literature on the relationship between season of birth and schizophrenia is reviewed. Analysis of the available data suggests that various factors may be involved in causing the phenomenon. The hypotheses that have been formulated on this epidemiological discovery are analysed and a possible interaction between relational and environmental factors presumably implicated in the explanation of the connection in question is suggested.

The role of information systems and particularly that of expert systems in medicine is analysed in brief. It is pointed out that, unlike other branches of medicine, in mental sciences the role of expert systems has so far been more limited because of certain intrinsic problems of programming on the one hand, and the scientific models of the psychiatrist on the other. An improvement in information technology and programming languages and better empirical classification of mental disturbances could provide useful bases for the realisation of computerised consultancy systems in mental sciences.