Aging and Adherence to the Mediterranean Diet: Relationship with Cardiometabolic Disorders and Polypharmacy.

OBJECTIVES: To investigate the association between adherence to the Mediterranean Diet (Med-Diet), cardiometabolic disorders and polypharmacy. DESIGN: Cross-sectional study. SETTING: Geriatrics outpatient clinic, Policlinico Umberto I, Sapienza University of Rome. PARTICIPANTS: 508 patients (219 male, 289 female) aged 50 to 89 who were evaluated for cardiovascular and metabolic disorders. METHODS AND MEASUREMENTS: Patients underwent a comprehensive medical assessment including medical history and the use of medications. Adherence to Med-Diet was assessed using the validated Med-Diet 14-item questionnaire; for the analysis, patients were divided in high (≥8) and medium-low (<8) adherence. Polypharmacy was defined as taking ≥5 medications. RESULTS: 476 patients completed the study. Mean age was 70.4 years; 58% female. Median Med-Diet score was 8 (interquartile range, 6-9). Patients with medium-low adherence had higher body mass index (p=0.029) and higher prevalence of arterial hypertension (p<0.001), previous coronary (p=0.002) and cerebrovascular events (p=0.011), diabetes, (p<0.001) and dyslipidemia (p=0.001) compared to those at high adherence. Med-Diet score decreased with the number of cardiometabolic disorders (p<0.001). The prevalence of polypharmacy was 39%. Consumption of olive oil (p=0.005), vegetables, (p<0.001), wine (p=0.017), legumes (p=0.028), fish (p=0.046) and nuts (p=0.045) were all inversely associated with the overall number of medications. In a multivariable regression model, medium-low adherence to Med-Diet was independently associated to polypharmacy (O.R.:1.859; 95% CI 1.142 to 3.025; p=0.013), after adjusting for possible confounding factors. CONCLUSION: Med-Diet was inversely associated with cardiometabolic disorders and with polypharmacy, suggesting that improved Med-Diet adherence might potentially delay the onset of age-related health deterioration and reduce the need of multiple medications.

Low-grade endotoxemia, gut permeability and platelet activation in patients with impaired fasting glucose.

BACKGROUND AND AIM: Impaired fasting glucose (IFG) is associated with an increased risk of cardiovascular disease but the underlying mechanisms are still unclear. Aim of the study was to investigate the interplay between platelet activation, lipopolysaccharides (LPS) and markers of oxidative stress in patients with IFG and control subjects. METHODS AND RESULTS: We performed a cross-sectional study including 35 patients with IFG and 35 control subjects who were well comparable for age, sex, body mass index and smoking history. Serum levels of LPS, zonulin (a marker of gut permeability), oxidized LDL and plasma levels of soluble P-selectin, were measured. Patients with IFG had significantly higher levels of sP-selectin, LPS, zonulin and oxLDL compared to control subjects. The IFG status (beta coefficient: 0.518, p < 0.001), higher LPS (beta coefficient: 0.352, p = 0.001) and female sex (beta coefficient: 0.179, p = 0.042) were independently associated with higher sP-selectin; in addition, oxLDL was positively associated with sP-selectin (r = 0.530, p < 0.001) and LPS (r = 0.529, p = 0.001). In IFG patients, we found a significant association between LPS and zonulin (r = 0.521, p = 0.001); this association was confirmed at multivariable analysis (beta coefficient: 0.512, p = 0.007). CONCLUSION: Our study provides evidence that patients with IFG have increased platelet activation, and suggests LPS as a potential trigger for in vivo platelet activation in this patient population.

Under-prescription of statins in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with high cardiovascular risk. Management of dyslipidaemia plays a pivotal role in the prevention of CV events and statins have proved to be safe in these patients. However, in everyday clinical practice statin prescription is sometimes limited because of the concern of physicians about side-effects. The aim of the study was to investigate if the presence of NAFLD affects the prescription of lipid-lowering treatment in a large series of patients with cardio-metabolic disorders. METHODS AND RESULTS: Cardiovascular risk and LDL-C targets were defined according to ESC/EAS Guidelines in 605 consecutive adult subjects referred for screening of suspected metabolic diseases. Liver steatosis was assessed by ultrasound Hamaguchi criteria. In the whole cohort, 442 patients had indication for cholesterol-lowering treatment. Lack of statin prescription was present in 230 (52.0%) patients. Of these, 77 (33.5%) were very high-risk, 48 (20.8%) high-risk, and 105 (45.6%) moderate risk patients. Only 44% of the NAFLD patients with indication for statin treatment were on therapy. NAFLD patients on statin treatment had significantly lower ALT values as compared to those not on treatment (p < 0.05). CONCLUSIONS: Our findings show that about 50% of patients with indication to statin treatment do not receive any cholesterol-lowering medication. Statin under-use was particularly high in subjects with NAFLD. Use of statin treatment should be encouraged in the context of NAFLD, as it may improve lipid profile and reduce the cardiovascular risk in this setting.

Short-term in vivo modifications of platelet NADPH oxidase 2 (NOX2) and prostaglandin F2α in HIV-1 patients on abacavir-based therapies.

OBJECTIVES: The aim of the study was to investigate the in vivo effect of abacavir (ABC) on platelet oxidative stress. METHODS: We performed a randomized pilot study including 39 HIV-1-infected patients, 17 on zidovudine/lamivudine (ZDV/3TC) and 22 on tenofovir/emtricitabine (TDF/FTC). Ten patients on ZDV/3TC and eight patients on TDF/FTC were randomly allocated to switching the nucleoside backbone to ABC/3TC. At baseline and after 6 months, platelet oxidative stress was assessed by platelet NADPH oxidase 2 (NOX2)-derived peptide (sNOX2-dp), a marker of NOX2 activation, and platelet prostaglandin F2α (8-iso-PGF2α ). Platelet activation was measured by soluble CD40L (sCD40L). RESULTS: At baseline, no differences between ZDV/3TC or TDF/FTC recipients were found. After 6 months, patients switching from ZDV/3TC showed a decrease of sNOX2-dp (from 20.9±5.7 to 12.5±3.8 pg/ml, p=0.002) and 8-iso-PGF2α (from 154.3±41.9 to 122.9±28.0 pmol/l, p=0.025). No effects on platelet oxidative stress biomarkers were observed in subjects from TDF/FTC, who showed a significant increase in blood glucose (p=0.043) and total cholesterol (p=0.027). ABC showed no effect on sCD40L levels in both groups. CONCLUSIONS: ABC reduced platelet sNOX2-dp and 8-iso-PGF2α in HIV-1 subjects switching from ZDV/3TC but not in those from TDF/FTC after 6 months. No changes in platelet activation were found in both groups.

Extra virgin olive oil use is associated with improved post-prandial blood glucose and LDL cholesterol in healthy subjects.

OBJECTIVES: Extra virgin olive oil (EVOO) is a key component of the Mediterranean diet and seems to account for the protective effect against cardiovascular disease. However, the underlying mechanism is still elusive. DESIGN: We tested the effect of EVOO, added to Mediterranean-type meal, on post-prandial glycemic and lipid profile. SUBJECTS: Post-prandial glycemic and lipid profile were investigated in 25 healthy subjects who were randomly allocated in a cross-over design to a Mediterranean-type meal added with or without 10 g EVOO (first study), or Mediterranean-type meal with EVOO (10 g) or corn oil (10 g; second study). Glycemic profile, which included glucose, insulin, dipeptidyl-peptidase-4 (DPP-4) protein and activity, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and lipid profile, which included, low-density lipoprotein (LDL) cholesterol (LDL-C), oxidized LDL (ox-LDL), triglycerides and high-density lipoprotein (HDL) cholesterol (HDL-C), were analyzed before and 2 h after the meal. RESULTS: In the first study, 2 h after meal, subjects who assumed a meal with EVOO had significantly lower blood glucose (P<0.001), DPP-4 protein (P<0.001) and activity (P<0.001), LDL-C (P<0.001) and ox-LDL (P<0.001) and higher insulin (P<0.05), GLP-1 (P<0.001) and GIP (P<0.05) compared with those without EVOO. The second study showed that compared with corn oil, EVOO improved both glycemic and lipid profile. Thus, a significantly smaller increase of glucose (P<0.05), DPP4 protein (P<0.001) and activity (P<0.05) and higher increase of insulin (P<0.001) and GLP-1 (P<0.001) were observed. Furthermore, compared with corn oil, EVOO showed a significantly less increase of LDL-C (P<0.05) and ox-LDL (P<0.001). CONCLUSIONS: We report for the first time that EVOO improves post-prandial glucose and LDL-C, an effect that may account for the antiatherosclerotic effect of the Mediterranean diet.

Non-alcoholic fatty liver disease, metabolic syndrome and patatin-like phospholipase domain-containing protein3 gene variants.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease was traditionally interpreted as a condition which may progress to liver-related complications. However, the increased mortality is primarily a result of cardiovascular diseases. It has been suggested that fatty liver can be considered as the hepatic consequence of the metabolic syndrome. The aim was to describe the different clinical presentations of non-alcoholic fatty liver disease on the basis of the patatin-like phospholipase domain-containing protein3 (PNPLA3) rs738409 gene variant. METHODS: Fatty liver was defined by ultrasonographic Hamaguchi's criteria in 211 consecutive subjects with non-alcoholic fatty liver disease. The rs738409 polymorphism was determined by TaqMan assays. Metabolic syndrome was defined according to ATPIII modified criteria. RESULTS: Prevalence of PNPLA3-148II, PNPLA3-148IM, and PNPLA3-148MM genotypes was 45.0%, 40.7%, and 14.3% respectively. Prevalence of metabolic syndrome progressively increased with the severity of liver steatosis (from 52.5% to 65.2%, and 82.3% respectively, p<0.01). The PNPLA3-148MM group had significantly lower mean serum triglycerides (p<0.001), Framingham cardiovascular risk score (p<0.01) and lower prevalence of metabolic syndrome (p<0.05) and its components. Age and HOMA-IR were positive independent predictors of metabolic syndrome, while a negative independent association was found between metabolic syndrome and the homozygotes PNPLA3 I148M variant. CONCLUSIONS: We suggest a lower prevalence of MetS and reduced cardiovascular risk in NAFLD patients with PNPLA3MM genotype.

Undifferentiated connective tissue disease - an unsolved problem:revision of literature and case studies.

In clinical practice, patients with a range of signs and symptoms suggestive of connective tissue disease, but who do not fulfil the classification criteria for a defined disease are often found. This condition is defined as, Undifferentiated Connective Tissue Disease (UCTD). Most of the authors consider UCTD as a distinct clinical entity, generally stable during follow-up. Despite this, no mutual agreement regarding criteria for its diagnosis has been reached. The clinical, serological, therapeutical and evolutional patterns of 41 patients initially diagnosed as having early UCTD during a 3-year followup are described in this study. At the end of the observational period, 21 percent of the enrolled patients, followed throughout the follow-up, demonstrated clinical evolution to a defined connective tissue disease (CTD), whereas 52 percent of the observed subjects maintained an undifferentiated profile with variable clinical findings and presenting a generally stable disease over time. The remaining patients showed clinical improvement or complete regression of the symptoms associated with normalization of the inflammatory indexes. The role of therapy in these different clinical courses is discussed.