From Survey Results to a Decision-Making Matrix for Strategic Planning in Healthcare: The Case of Clinical Pathways.

BACKGROUND: It is a well-known fact that the information obtained from a survey can be used in a healthcare organizational analysis; however, it is very difficult to compare the different results found in the literature to each other, even through the use of metanalysis, as the methodology is often not consistent. METHODS: Data from a survey analyzing the organizational and managerial responses adopted in pathology-specific clinical pathways (CPs) during the first two waves of the COVID-19 pandemic were used for constructing a decisional matrix, a tool called SPRIS system, consisting of four different sheets. The first sheet reports the results of the survey and, using a streetlight color system, identifies strengths and weaknesses; the second one, by assigning a priority score, establishes the priority of intervention on each of the strengths and weaknesses identified; the third sheet reports the subjective items of the questionnaire in order to identify threats and opportunities and their probability of happening; in the last sheet, a SWOT Analysis is used to calculate the performance index of the whole organization. RESULTS: The SPRIS system, applied to data concerning the adaptation of four CPs to the COVID-19 pandemic, showed that, whereas all the CPs had a good performance index, some concerns remained unsolved and need be addressed. CONCLUSIONS: The SPRIS system showed to be an easily constructed tool that is able to give an overview of the organization analyzed by the survey and to produce an index that can be used in a direct quality comparison between different services or organizations.

Impact of the COVID-19 Pandemic on Clinical Pathways for Non-SARS-CoV-2 Related Diseases in the Lazio Region, Italy.

Clinical pathways (CPs) are multidisciplinary clinical governance tools necessary for the care management of the patients, whose aim is to outline the best practicable path within a health organization related to an illness or to a complex clinical situation. The COVID-19 pandemic emergency has created the need for an organizational renewal of care pathways based on the principles of "primary health care" recommended by the WHO. In Italy, the Hospitals and Local Health Authorities (ASL) have tried to guarantee the continuity of non-deferrable treatments and the maximum safety of both patients and health professionals. This study analyzes the organizational and managerial responses adopted in pathology-specific care pathways to assess how CPs as diagnostic tools responded to the COVID-19 pandemic in the first two waves. Twenty-four referents of Operational Units (UU OO) from Hospitals (AO) and Local Health Authorities (ASL) of the Lazio Region (Central Italy) that apply four different CPs responded to a survey, which analyzes the managerial and organizational responses of CPs in regard to different contexts. Results show that the structural and organizational adjustments of the CPs have made it possible to maintain an adequate level of care for specific treatment processes, with some common critical aspects that require improvement actions. The adjustments found could be useful for dealing with new outbreaks and/or new epidemics in order to try to mitigate the potential negative impact, especially on the most vulnerable patient categories.

Anti-Inflammatory Effects of Immunostimulation in Patients with COVID-19 Pneumonia.

BACKGROUND: The effects of immunomodulators in patients with Coronavirus Disease 2019 (COVID-19) pneumonia are still unknown. We investigated the cellular inflammatory and molecular changes in response to standard-of-care + pidotimod (PDT) and explored the possible association with blood biomarkers of disease severity. METHODS: Clinical characteristics and outcomes, neutrophil-to-lymphocyte ratio (NLR), plasma and cell supernatant chemokines, and gene expression patterns after SARS-CoV-2 and influenza (FLU) virus in vitro stimulation were assessed in 16 patients with mild-moderate COVID-19 pneumonia, treated with standard of care and PDT 800 mg twice daily (PDT group), and measured at admission, 7 (T1), and 12 (T2) days after therapy initiation. Clinical outcomes and NLR were compared with age-matched historical controls not exposed to PDT. RESULTS: Hospital stay, in-hospital mortality, and intubation rate did not differ between groups. At T1, NLR was 2.9 (1.7-4.6) in the PDT group and 5.5 (3.4-7.1) in controls (p = 0.037). In the PDT group, eotaxin and IL-4 plasma concentrations progressively increased (p < 0.05). Upon SARS-CoV-2 and FLU-specific stimulation, IFN-γ was upregulated (p < 0.05), while at genetic transcription level, Pathogen Recognition Receptors (TRLs) were upregulated, especially in FLU-stimulated conditions. CONCLUSIONS: Immunomodulation exerted by PDT and systemic corticosteroids may foster a restoration in the innate response to the viral infection. These results should be confirmed in larger RCTs.

Changes in quality of life and dyspnoea after hospitalization in COVID-19 patients discharged at home.

BACKGROUND: To date, the effects of COVID-19 pneumonia on health-related quality of life (HRQoL) and dyspnoea are unknown. METHODS: In a real-life observational study, 20 patients with COVID-19-related pneumonia received usual care plus erdosteine (300 mg twice daily) for 15 days after hospital discharge following local standard operating procedures. At discharge (T0) and on Day 15 (T1), participants completed the St George's Respiratory Questionnaire (SGRQ), the modified Medical Research Council (mMRC) scale of dyspnoea during daily activity, the BORG scale for dyspnoea during exertion, and Visual Analogue Scale (VAS) for dyspnoea at rest. Paired t-tests compared scores at T0 and T1. RESULTS: The mean (SD) SGRQ total score decreased from 25.5 (15.5) at T0 to 16.9 (13.2) at T1 (p<0.01); 65% of patients achieved a clinically important change of ≥4 points. SGRQ domain scores (symptoms, activity, and impact) were also significantly reduced (all p<0.01). The mean (SD) VAS score decreased from 1.6 (1.7) to 1.4 (2.5); p<0.01. The mean mMRC score decreased significantly (p=0.031) and 30% of patients achieved a clinically important change of ≥1 point. The mean (SD) Borg score increased from 12.8 (4.2) to 14.3 (2.4); p<0.01. CONCLUSION: The present proof of concept study is the first to report HRQoL in patients with COVID-19. During 15 days after hospital discharge, patients reported significant improvements in HRQoL and dyspnoea at rest and during daily activities.

Application of tRNS to improve multiple sclerosis fatigue: a pilot, single-blind, sham-controlled study.

We evaluated the effects of transcranial random noise stimulation (tRNS) on fatigue in 17 subjects with relapsing-remitting multiple sclerosis with low physical disability. Two different patient groups underwent real or sham stimulation for 10 days, targeting the primary motor cortex of the dominant side or contralateral to the most compromised limb. In the 'real group', beneficial effects were observed using the Modified Fatigue Impact Scale (p = 0.04; physical subscale: p = 0.03), the subscales 'change in health' (p = 0.006) and 'role limitations due to physical problems' (p = 0.001) of the Multiple Sclerosis Quality of Life-54, and by assessing the patient impression of perceived fatigue (p = 0.005).

Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study.

BACKGROUND AND AIMS: Blood lysosomal acid lipase (LAL) is reduced in non-alcoholic steatohepatitis, which is the major cause of cryptogenic cirrhosis (CC); few data on LAL activity in CC do exist. We investigated LAL activity in a cohort of patients with liver cirrhosis. METHODS: This is a multicentre cohort study including 274 patients with liver cirrhosis of different aetiology from 19 centres of Internal Medicine, Gastroenterology and Hepatology distributed throughout Italy. Blood LAL activity (nmol/spot/h) was measured with dried blood spot extracts using Lalistat 2. RESULTS: Overall, 133 patients had CC, and 141 patients had cirrhosis by other causes (61 viral, 53 alcoholic, 20 alcoholic + viral, 7 autoimmune). Mean age was 64.2 ± 13.4 years, and 28.5% were women. Patients with CC were older compared to other aetiology-cirrhosis, with a lower Child-Turcotte-Pugh (CTP, p=0.003) and MELD (p=0.009) score, and a higher prevalence of cardio-metabolic risk factors and previous ischemic events. In the whole cohort, median LAL activity value was 0.58 nmol/spot/h, 0.49 and 0.65 in the groups of CC and known-aetiology cirrhosis, respectively (p=0.002). The difference remained significant after adjustment for white blood cells count (p=0.001). Multivariable linear regression analysis showed that CC (vs. known aetiology, Beta = -0.144, p=0.018), platelet count (Beta = 0.398, p < 0.001) and CTP score (Beta = -0.133, p=0.022) were associated with log-LAL activity. Similar results were found using MELD as covariate. CONCLUSIONS: We found a marked reduction of LAL activity in patients with cryptogenic cirrhosis compared to the other known aetiologies. A prospective study will clarify the role of LAL in chronic liver diseases.

Epidemiological study of an outbreak of Norovirus in a rest home in Italy.

A Norovirus GII.4 (variant 2006) epidemic occurred in a rest home in the Abruzzo region of Italy between January and March 2009. Rest homes are typologically exposed to Norovirus infections as often reported in the literature. The investigation proposed in this article focused on identifying the source of infection and the route of propagation of the virus in the infected rest home. Microbiological, chemical and hygiene/health investigations were conducted on residents and employees of the home and on its water supply. A questionnaire was designed and distributed to identify the habits of the subjects who promoted the spread of the virus, in order to obtain a retrospective view of the event.

Flavonoids, vascular function and cardiovascular protection.

A large body of evidence supports that the dietary intake of polyphenols - particularly of flavonoids and the specific class of flavonoids named flavanols - might be able to exert some beneficial vascular effects and reduce the risk for cardiovascular morbidity and mortality. The review of epidemiological and mechanistic studies supports the role of flavonoids, particularly cocoa and tea flavanols, in protecting the cardiovascular system against cardiovascular disease. Nevertheless, flavonoids are an heterogeneous group of natural molecules differently represented in fruit and vegetables and definitive data on cardiovascular benefits are lacking. The weakness of the available data include few and very small studies, no crossover designed studies and a wide range of dose and type of flavonoids tested. Thus, although flavonoid-rich foods and beverages are likely to protect cardiovascular system, further research is needed to characterize the mechanism of action on flavanol-rich foods. Long-term clinical trials are also needed to definitively clarify the benefits deriving from long-term consumption of flavanol-rich foods, particularly focussing on the lowest effective levels as well as synergism or antagonistic actions between different classes of flavonoids commonly found in foods.

Different effects of angiotensin converting enzyme inhibitors on endothelin-1 and nitric oxide balance in human vascular endothelial cells: evidence of an oxidant-sensitive pathway.

Angiotensin converting enzyme inhibitors (ACE-I) are able to reduce the formation of the potent vasoconstrictor endothelin-1 and increase nitric oxide bioavailability in human vascular endothelial cells (HUVECs). We tested the effects of two sulfhydryl-containing ACE-I, zofenoprilat, and captopril, and two nonsulfhydryl containing ACE-I, enalaprilat and lisinopril, on endothelin-1/nitric oxide balance and oxidative stress in HUVECs. All the four tested ACE-I reduced endothelin-1 secretion and increased nitric oxide metabolite production by HUVECs. However, zofenoprilat (-42% after 8 hours of incubation) was more effective (P < .05) than enalaprilat (-25%), lisinopril (-21%), and captopril (-30%) in reducing endothelin-1 secretion. Similarly, zofenoprilat (+110% after 8 hours of incubation) was more effective (P < .05) than enalaprilat (+64%), lisinopril (+63%), and captopril (+65%) in increasing nitric oxide metabolite production. The effect of ACE-I on endothelin-1 and nitric oxide metabolite production is mediated by the activation of bradykinin B(2) receptor being counteracted, at least in part, by a specific antagonist. Zofenoprilat and, to a lesser extent, captopril also reduced oxidative stress in HUVECs. In conclusion, among the four tested ACE-I, zofenoprilat was more effective in improving endothelin-1/nitric oxide balance in HUVECs likely because of its greater antioxidant properties.

Cardiovascular risk and cardiometabolic protection: role of glitazones.

Thiazolidinediones (TZDs) are widely used in the type 2 diabetes mellitus (DMT2) treatment but have also been tested in cardiovascular prevention. DMT2 is associated with a marked increment in cardiovascular risk, and its prevention represents a main target in cardiometabolic protection. Both Troglitazone (Troglitazone in Prevention of Diabetes study) and Rosiglitazone (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication study) significantly reduced new-onset diabetes. A similar topic will be investigated with pioglitazone (Actos Now for Prevention of Diabetes). In the Prospective Pioglitazone Clinical Trial in Macrovascular events the primary end point (all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndromes, endovascular or surgical intervention in the coronary/leg arteries and amputation above ankles) was unaffected, whereas the secondary one (all-cause mortality, nonfatal myocardial infarction and stroke) was reduced by pioglitazone (-16%, p=0.027) compared to placebo in 5,238 patients with DMT2 and macrovascular disease. In contrast, a meta-analysis (Nissen and Wolski, N Engl J Med. 2007;356:2457-2471) reported that rosiglitazone treatment is associated with a significant increase in myocardial infarction risk (p=0.03) and a borderline significant increase in the risk of death from cardiovascular causes (p=0.06). Nevertheless, the possibility that rosiglitazone might affect cardiovascular events should be evaluated by the ongoing trial Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD). Interim findings early from RECORD did not show significant differences between the rosiglitazone and the control group regarding myocardial infarction and death from cardiovascular and any cause. Additional large-scale trials are awaited to clarify the of role TZDs in cardiovascular outcomes.

Tea, flavonoids, and nitric oxide-mediated vascular reactivity.

Epidemiological evidence supports the concept that diets rich in fruits and vegetables promote health and attenuate or delay the onset of cardiovascular disease (CVD). Although a variety of factors contribute to the beneficial effects of plant foods, much attention has been addressed to plant polyphenols. In this regard, in the daily Western diet, both black and green teas contribute to a relevant proportion of total phenol intake. The more abundant class of flavonoids that is present in teas is represented by flavanols, i.e., catechin, epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate. Studies using animal models of atherosclerosis indicate that dietary flavonoid consumption delays atherosclerotic plaque development. Accordingly, an inverse association between tea intake and CVD has been demonstrated. Further, flavonoids can reduce endothelial dysfunction, i.e., the key step in the development of atherosclerosis. Concordantly, human data suggest that tea may reduce blood pressure levels. Despite this, although they often show that tea may have cardiovascular protective effects, results from epidemiological studies exploring the association between tea and health are controversial. Conflicting results may be caused by disparate study designs and flavonoid contents in different kinds of tea. Thus, because tea is a popular beverage worldwide, and several studies have shown that it is protective against CVD, further studies are needed to determine the role of tea in primary and secondary cardiovascular prevention.

Role of combination therapy in the treatment of hypertension: focus on valsartan plus amlodipine.

Hypertension control is rare in clinical practice, particularly in high-risk patients. A large factor is therapeutic inertia deriving from poorly prescribed lifestyle changes, excess monotherapy use, and scarce on-treatment modifications. The use of drug combinations significantly improves blood pressure (BP) control; in particular, fixed combinations improve therapy without increasing daily pill intake, thereby favouring patient compliance and therapy continuation. The most widely used fixed combination is based on thiazide diuretics added to either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). Several large-scale clinical trials have been conducted showing that these combinations are effective in lowering BP. However, thiazide diuretics can reduce the metabolic benefits derived from renin-angiotensin-aldosterone system (RAAS) inhibitors in high metabolic risk patients. In contrast, ACE inhibitors or ARBs combined with dihydropyridine calcium channel antagonists (DHPCAs) exert a marked antihypertensive effect without decreasing metabolic protection by RAAS blockade. In the recent JIKEI heart study, approximately 60% of patients affected by hypertension, heart failure, coronary heart disease or their combination in the valsartan arm were simultaneously treated with DHPCAs. Of note, a 39% reduction in the primary endpoint of combined morbidity and mortality was reported in the valsartan compared with the non-valsartan arm. Furthermore, in a recent multinational study, 83% of 3161 hypertensive patients treated with valsartan and the DHCPA amlodipine reported a concontrolled BP after 8 weeks of treatment. As expected, amlodipine did not negatively influence the metabolic profile of patients, thereby supporting the role of ARB+DHPCA combinations as effective and promising tools in hypertension treatment. In summary, the combination of ARBs with DHPCAs is an effective strategy in hypertension treatment through synergy between their antihypertensive and vascular protective actions, persistent metabolic benefits deriving from RAAS inhibition, and reduced incidence of side effects.

Nifedipine improves the migratory ability of circulating endothelial progenitor cells depending on manganese superoxide dismutase upregulation.

BACKGROUND: Migratory ability of resident endothelial cells and their circulating progenitors, that is endothelial progenitor cells (EPCs), represent a crucial event in vascular repairing processes. Although oxidants are known to counteract the migratory ability of resident endothelial cells, their possible role in modulating EPC motility is unknown. EPCs exhibit stronger resistance to oxidants than mature endothelial cells mainly because of higher expression of manganese (Mn) superoxide dismutase (SOD). As nifedipine is a dihydropyridine calcium antagonist known to enhance MnSOD expression in mature endothelial cells, we investigated the effects of nifedipine on MnSOD expression and motility in EPCs. METHODS AND RESULTS: EPCs were isolated from peripheral blood of healthy donors and cultured in fibronectin-coated flasks. Nifedipine improved both motility of cultured EPCs (+55% vs. control, P = 0.007) and their adhesion to tumor necrosis factor-alpha-activated mature endothelial cells (+33% vs. control, P = 0.03). Reduction of EPC dichlorofluorescein content (-32% vs. control, P = 0.009) and a parallel increase in nitrite plus nitrate concentration in EPC supernatants (+25% vs. control, P = 0.009) were also observed. The study of SOD showed a nifedipine-dependent upregulation of MnSOD in a time-dependent and dose-dependent manner. MnSOD expression blockade by RNA interference abolished nifedipine effect on EPC motility. Although nifedipine also increased vascular endothelial growth factor (VEGF) release from EPCs, its effect on EPC motility was unaffected by an anti-VEGF antibody. CONCLUSION: Nifedipine improves EPC motility due to MnSOD upregulation. The capability of this dihydropyridine calcium antagonist to reduce cardiovascular events might also be related to improved EPC function.

C-reactive protein: interaction with the vascular endothelium and possible role in human atherosclerosis.

C-reactive protein (CRP) is the first acute phase protein that has been described in the literature. It is phylogenetically ancient and - with serum amyloid P - belongs to proteins named as "pentraxin". After being considered a marker of acute inflammation for several decades and fruitfully used in clinical practice, CRP has been recently considered as a potential contributor to inflammatory diseases including atherosclerosis as well as a marker of cardiovascular risk. With regard to the first topic, inflammation is now believed to represent the underlying mechanism leading to the formation of human atheroma and favouring both the destabilization of vulnerable plaques and the formation of occlusive thrombi. In this regard, numerous studies indicated that modest changes in circulating CRP levels, as detected by highly sensitive methods, can be extremely useful in predicting cardiovascular and perhaps cerebrovascular diseases in apparently healthy individuals as well as in patients affected by atherosclerosis. Subjects manifesting with identical low density cholesterol and/or blood pressure levels have different rates of cardiovascular accidents on the basis of different circulating CRP concentrations. In addition, women with identical cardiovascular risk profiles developed more type 2 diabetes in the presence of higher circulating CRP levels and thereby are expected to display divergent cardiovascular prognosis. Therefore, even slight changes in circulating CRP concentrations - assuming that blood is collected appropriately and CRP is measured with correct methods - could help clinicians in defining individual cardiovascular risk. In this review, we have firstly described the current understanding of the structure of CRP, its function, and interaction with the vascular endothelial cell. Then, we have discussed how to measure circulating CRP and the more recent findings on the suggested role of circulating CRP as a novel cardiovascular risk factor.

Enhanced plasma soluble CD40 ligand levels in essential hypertensive patients with blunted nocturnal blood pressure decrease.

BACKGROUND: Hypertensives with a blunted nocturnal blood pressure (BP) decrease have increased risk of developing atherosclerotic disease. Soluble CD40 ligand (sCD40L) is involved in the pathogenesis of risk factor-related vascular damage. Therefore, we evaluated the relationship between circulating sCD40L levels, circadian BP profile, and early carotid atherosclerosis in essential hypertensives. METHODS: Plasma sCD40L concentrations were assessed in two groups of 25 never-treated hypertensives, without additional cardiovascular risk factors, differentiated on the basis of a nocturnal decrease of BP either of >10% (dippers) or <10% (nondippers) of daytime values, and in 25 matched normotensives. Carotid intima-media thickness (IMT) was also measured in all participants. RESULTS: Plasma sCD40L concentrations were higher in nondippers (4.9 +/- 1.2 ng/mL) than in dippers (3.7 +/- 0.7, P = .0005) and controls (1.6 +/- 0.6, P < .0001). These latter had lower sCD40L concentrations than dippers (P < .0001). The IMT was higher in both hypertensive groups than in normotensives (P < .0001). In the entire hypertensive population IMT directly correlated with circulating levels of sCD40L (r = 0.365, P = .01) and inversely correlated with nocturnal systolic BP decreases (r = -0.286, P = .043). In a multivariate regression analysis sCD40L was the main determinant of IMT (r(2) = 0.157, P = .004). CONCLUSIONS: Nondippers have enhanced plasma sCD40L levels, which may contribute to their increased susceptibility to develop vascular damage.

Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives.

Consumption of flavanol-rich dark chocolate (DC) has been shown to decrease blood pressure (BP) and insulin resistance in healthy subjects, suggesting similar benefits in patients with essential hypertension (EH). Therefore, we tested the effect of DC on 24-hour ambulatory BP, flow-mediated dilation (FMD), and oral glucose tolerance tests (OGTTs) in patients with EH. After a 7-day chocolate-free run-in phase, 20 never-treated, grade I patients with EH (10 males; 43.7+/-7.8 years) were randomized to receive either 100 g per day DC (containing 88 mg flavanols) or 90 g per day flavanol-free white chocolate (WC) in an isocaloric manner for 15 days. After a second 7-day chocolate-free period, patients were crossed over to the other treatment. Noninvasive 24-hour ambulatory BP, FMD, OGTT, serum cholesterol, and markers of vascular inflammation were evaluated at the end of each treatment. The homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and insulin sensitivity index (ISI) were calculated from OGTT values. Ambulatory BP decreased after DC (24-hour systolic BP -11.9+/-7.7 mm Hg, P<0.0001; 24-hour diastolic BP -8.5+/-5.0 mm Hg, P<0.0001) but not WC. DC but not WC decreased HOMA-IR (P<0.0001), but it improved QUICKI, ISI, and FMD. DC also decreased serum LDL cholesterol (from 3.4+/-0.5 to 3.0+/-0.6 mmol/L; P<0.05). In summary, DC decreased BP and serum LDL cholesterol, improved FMD, and ameliorated insulin sensitivity in hypertensives. These results suggest that, while balancing total calorie intake, flavanols from cocoa products may provide some cardiovascular benefit if included as part of a healthy diet for patients with EH.

Early activation of vascular endothelial cells and platelets in obese children.

Obesity in adulthood is combined with vascular endothelial cell and platelet activation. In this study we evaluated whether or not such activation is already present in obese children. Forty obese (10.3 +/- 2.5 yr) and 40 nonobese (10.3 +/- 2.3 yr) children were studied. Circulating levels of soluble (s) intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, as indices of vascular endothelial cell activation, were assessed in both groups. Plasma concentrations of sP-selectin and sCD40 ligand, as indices of platelet activation, were also measured. Circulating levels of highly sensitive C-reactive protein (hs-CRP) and the lipid peroxidation product 8-iso-prostaglandin (PG)F(2alpha) were evaluated because of their ability to promote vascular endothelial cell and platelet activation. Circulating levels of all of the assessed markers were higher in obese than in nonobese children (sICAM-1, +38.8 +/- 13.3%; sVCAM-1, +26.5 +/- 13.7%; sE-selectin, +31.3 +/- 17.3%; sP-selectin, +31.7 +/- 16.9%; sCD40 ligand, +36.9 +/- 22.1%; total 8-iso-PGF(2alpha), +24.0 +/- 20.2%; hs-CRP, +76.6 +/- 12.9%; P < 0.0001). Significant correlations (P < 0.004) between plasma total 8-iso-PGF(2alpha) levels and circulating sICAM-1 (r = 0.485), sVCAM-1 (r = 0.506), sP-selectin (r = 0.449), sCD40 ligand (r = 0.498), and hs-CRP (r = 0.520) concentrations were found in obese children. In conclusion, an early activation of vascular endothelial cells and platelets was present in obese children. Increased lipid peroxidation was also present in these children and likely contributed to the observed proinflammatory phenotype.

Effects of bezafibrate and simvastatin on endothelial activation and lipid peroxidation in hypercholesterolemia: evidence of different vascular protection by different lipid-lowering treatments.

Hypercholesterolemia is combined with enhanced lipid peroxidation, which can promote atherogenesis by inducing endothelial adhesion molecule expression. Statins may protect vascular endothelium in hypercholesterolemia by reducing enhanced plasma levels of low-density lipoprotein and decreasing oxidative stress. Herein, we describe increased circulating levels of soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin and total 8-iso-prostaglandin F(2 alpha) (8-iso-PGF(2 alpha)) concentrations, as indexes of endothelial activation and lipid peroxidation, respectively, in 67 hypercholesterolemic patients compared with 32 normocholesterolemic subjects. Significant cholesterol reductions were achieved in hypercholesterolemic patients after 6 months under either simvastatin (40 mg/d) or bezafibrate (800 mg/d) treatment, given according to a randomized double-blind trial. Simvastatin but not bezafibrate simultaneously reduced soluble adhesin and total 8-iso-PGF(2 alpha) concentrations also. Vitamin E supplementation (400 IU/d) further reduced indexes of endothelial activation and lipid peroxidation in simvastatin-treated patients and significantly reduced the above indexes in bezafibrate-treated patients. Changes in circulating soluble adhesion molecule levels were directly correlated with changes in total 8-iso-PGF(2 alpha) concentrations in simvastatin-treated patients also receiving vitamin E supplementation. All together, our data demonstrated that hypercholesterolemia was combined with endothelial activation and lipid peroxidation, which were efficaciously counteracted by simvastatin but not bezafibrate treatment. Thus, a different vascular protection can be achieved by different lipid-lowering treatments.