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Background and aim: General population awareness about cardiovascular risk factors is usually low. The aim of the present study was to evaluate the vascular aging of subjects aware and not aware to be hypertensive, hypercholesterolemic, hypertriglyceridemic or diabetics in a general population sample. Methods and results: We interviewed 1652 subjects without atherosclerotic cardiovascular diseases (M: 46.6%, F: 53.4%) about their awareness of hypertension, hypercholesterolemia, hypertriglyceridemia or type 2 diabetes. Then we compared the augmentation index and pulse wave velocity of subjects aware and not aware of the investigated cardiovascular risk factors. 1049 participants declared not to be hypertensive, while 32 were not sure. Among them, respectively, 23.5% and 50% were hypertensive. Subjects not aware of their hypertension had significantly higher aortic blood pressure than aware ones (p < 0.001). 841 participants declared not to be hypercholesterolemic, while 60 were not sure. Among them, respectively, 18.1% and 40% were hypercholesterolemic. Subjects not aware of their hypercholesterolemia had significantly higher augmentation index than the aware ones (p < 0.05). 1226 participants declared not to be hypertriglyceridemic, while 200 were not sure. Among them, respectively, 19.2% and 44% were hypertriglyceridemic. Subjects not aware of their hypertriglyceridemia had significantly higher TG levels aware ones (p < 0.05), although this seemed to not related to increased arterial stiffness. 1472 participants declared not to be diabetic, while 20 were not sure. Among them, respectively, 2.0% and 25.0% were diabetics. Subjects not aware of their diabetes had significantly higher augmentation index than the aware ones (p < 0.05). Conclusions: In conclusion, the lack of awareness of hypertension and hypercholesterolemia is relatively frequent in the general population and is associated to significantly higher arterial stiffness.

Several epidemiological studies report a positive correlation between hyperuricemia and metabolic syndrome (MetS) in adults, which hyperuricemic subjects seem to more easily develop. We aimed to verify if serum uric acid (SUA) concentrations were positively associated with MetS prevalence and middle-term (4-year) incidence in older overall healthy subjects. We also purposed to identify which SUA cut-off values could be functional in MetS diagnosis in addition to the traditionally used parameters. For this reason, we selected from the historical cohort of the Brisighella Heart Study 923 older healthy subjects repeatedly visited during the 2008 and 2012 population surveys. In our sample, MetS was more frequent for higher SUA concentrations rather than the population’s mean in both men [OR = 2.12, 95%C.I.(1.55, 2.90)] and women [OR = 2.69,95%C.I.(1.91, 3.78)]. ROC analysis showed SUA was predictive of MetS in the whole population [AUC = 0.647, 95%C.I.(0.609, 0.686), P = 0.000001] and in both sex subgroups [men: AUC = 0.592, 95%C.I.(0.529, 654); P = 0.004; women: AUC = 0.758, 95%C.I.(0.711, 0.806), P 0.05). In conclusion, in our cohort, SUA is a frequent component of MetS, other than a middle-term predictor of newly diagnosed MetS in older women.

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulating levels are significantly associated with an increased risk of cardiovascular events. This study aimed to evaluate the relationship between circulating levels of PCSK 9 and arterial stiffness, an early instrumental biomarker of cardiovascular disease risk, in a large sample of overall healthy participants. Methods and Results From the historical cohort of the Brisighella Heart Study, after exclusion of active smokers, participants in secondary prevention for cardiovascular disease, and patients in treatment with statins or vasodilating agents, we selected 227 premenopausal women and 193 age‐matched men and 460 postmenopausal women and 416 age‐matched men. In these participants, we evaluated the correlation between PCSK 9 plasma circulating levels and pulse wave velocity. Postmenopausal women showed higher PCSK 9 levels (309.9±84.1 ng/mL) compared with the other groups ( P P =0.008). In the whole sample, pulse wave velocity was predicted mainly by age (B=0.116, 95% CI 0.96–0.127, P PCSK 9 (B=0.014, 95% CI 0.011–0.016, P CI 0.024–0.391, P =0.026). Physical activity, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and estimated glomerular filtration rate were not associated with pulse wave velocity ( P >0.05).By considering the subgroups described, age and PCSK 9 levels were mainly associated with pulse wave velocity, which also correlated with serum uric acid in postmenopausal women. Conclusions In the Brisighella Heart Study cohort, circulating PCSK 9 is significantly related to arterial stiffness, independent of sex and menopausal status in women.

Aim: The aim of our study was to investigate whether treatment with red yeast rice added with Coenzyme Q10 is associated with changes in endothelial function and arterial stiffness. Methods: This double blind, placebo-controlled, randomized clinical trial was carried out on 40 non-smoker moderately hypercholesterolemic subjects (ClinicalTrial.gov ID NCT02492464). After 4 weeks of diet and physical activity, patients were allocated to treatment with placebo or with an active product containing 10 mg monacolins and 30 mg Coenzyme Q10, to be assumed for 6 months. Endothelial reactivity and arterial stiffness have been measured through the validated Vicorder® device. Results: During monacolin treatment, patients experienced a more favorable percentage change in low density lipoprotein (LDL)-cholesterol (after monacolin treatment: -26.3%; after placebo treatment: +3.4%, p < 0.05). Endothelial reactivity (pulse volume displacement after monacolin treatment: +6.0%; after placebo treatment: -0.3%, p < 0.05), and arterial stiffness (pulse wave velocity (PWV) after monacolin treatment: -4.7%; after placebo: +1.1%, p < 0.05) also significantly improved only after monacolin treatment. Conclusion: The long-term assumption of the tested dietary supplement is associated with an improvement in LDL-cholesterolemia, endothelial reactivity and PWV in moderately hypercholesterolemic subjects.

Background: Serum uric acid (SUA) and oxidized LDL (oxLDL) may be associated with arterial aging. The aim of our study was to evaluate the relationship between SUA, oxLDL and arterial stiffness in subjects with normal renal function and in patients with mild or moderate renal impairment. Methods: From the database of the 2012 Brisighella Heart Study, we compared age-matched adult, non-smoker subjects without cardiovascular disease and with normal renal function (n = 205), subjects with stage II chronic kidney disease (CKD) (n = 118) and subjects with stage III CKD (n = 94). All subjects underwent a determination of the LDL oxidative susceptibility, oxLDL levels, SUA and Pulse Wave Velocity (PWV). Results: By univariate analysis, PWV correlated with a large number of clinical, haemodynamic and metabolic parameters, including estimated glomerular filtration rate (eGFR) in subjects with normal renal function and in those with stage II or III CKD. Stepwise multiple regression analyses showed that in the presence of normal renal function or stage II CKD, the main predictors of PWV were age, systolic blood pressure (SBP), ox-LDL, apolipoprotein B and SUA (p < 0.05), while in the presence of stage III CKD only age, SBP and apolipoprotein B remained significant (p < 0.05). Conclusion: Both ox-LDL and SUA independently predicts PWV only in subjects with normal or mildly reduced renal function, but not in the subjects with more compromised eGFR. This study confirms the complex relationship of SUA with cardiovascular and metabolic disease in the patient with established renal disease.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is associated to increased risk of cardiovascular disease. Our aim was to evaluate association of indexes of fatty liver with arterial stiffness (AS). METHODS: We analyzed data of adult volunteers visited during the last Brisighella survey. We evaluated the Pulse Wave Velocity (PWV) and the following non-invasive indexes of liver steatosis: Fatty Liver Index (FLI), Lipid Accumulation Product (LAP), Hepatic Steatosis Index (HSI). We compared patients according to the risk of Non-Alcoholic Steatohepatitis (NASH): low-risk (BMI

The existence of genetic traits might explain the susceptibility to develop hypercholesterolemia and the inter-individual differences in statin response. This study was performed to evaluate whether individuals’ polymorphisms in HMG-CoA and KIF6 genes are independently associated with hypercholesterolemia, other lipid-associated traits, and statin response in unselected individuals enrolled in the Brisighella heart study (Survey 2012). A total of 1622 individuals, of which 183 under statin medication, were genotyped for a total of five polymorphisms (KIF6 rs20455, rs9471077, rs9462535; HMG-CoA rs3761740, rs3846662). The relationships between the five loci and clinical characteristics were analyzed. The principal basic parameters calculated on 12 h fasting blood included total cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low-Density Lipoprotein Cholesterol (LDL-C), and triglycerides (TG). Hypercholesterolemia was defined as a TC >200 mg/dL or use of lipid-lowering medication. 965 individuals were characterized by hypercholesterolemia; these subjects were significantly older (p < 0.001), with body mass index (BMI) and waist circumference significantly higher (p < 0.001) compared to the others. HMG-CoA rs3846662 GG genotype was significantly over-represented in the hypercholesterolemic group (p = 0.030). HMG-CoA rs3846662 genotype was associated with the level of TC and LDL-C. Furthermore, in the same subset of untreated subjects, we observed a significant correlation between the KIF6 rs20455 and HDL-C. KIF6 variants were associated with a significantly lower (rs20455) or higher (rs9471077 and rs9462535) risk of obesity, in males only. No association between responsiveness to statins and the polymorphisms under investigation were observed. Our results showed associations between HMG-CoA rs3846662 and KIF6 rs20455 and lipid phenotypes, which may have an influence on dyslipidemia-related events. Moreover, this represents the first study implicating KIF6 variants with obesity in men, and point to the possible involvement of this genetic locus in the known gender-related differences in coronary artery disease.

Background: There is an increasing interest for combined nutraceuticals that can act on several points of lipid and glucose metabolism with preventive purposes. However, the simple assemblage of nutraceuticals with potentially additive mechanism of action need to be clinically tested. Methods: To assess the effects of a combination of nutraceuticals based on artichoke, red yeast rice, banaba, and coenzyme Q10, we performed a double bind, cross-over designed trial versus placebo in 30 adults with LDL cholesterol suboptimal in primary prevention of cardiovascular disease. After a period of 3 weeks of dietary habits correction, patients began a period of 6 weeks of treatment with nutraceutical or placebo, followed by 2 weeks of washout and finally 6 weeks in cross-over. Data related to lipid pattern, insulin resistance, renal function, liver and CPK have been obtained at each visit. Results: In particular, the after the nutraceutical treatment the enrolled patients experienced a significant improvement in total cholesterol (-13.6 %), LDL-C (-18.2 %), non-HDL-C (-15 %), glutamic oxaloacetic transaminase (-10 %), glutamate-pyruvate transaminase (-30.9 %), and hs-CRP (-18.2 %) versus placebo. No changes have been observed in the other investigated parameters in both groups. Conclusions: The tested combination of nutraceuticals has shown clinical efficacy in the reduction of total cholesterol, non-HDL, LDL and triglycerides, while improving the level of liver transaminases and high sensitivity C-reactive protein. Further confirmation are needed to verify these observations on the middle and long term with a larger number of subjects

Serum uric acid (SUA) has been associated to incident hypertension and increased risk of cardiovascular diseases.Among the 2191 subjects enrolled during the last population survey of the Brisighella Heart Study, we identified 146 new cases of arterial hypertension and 394 treated but uncontrolled hypertensive patients with different levels of SUA. Their hemodynamic characteristics have been compared with those of age- and sex-matched normotensive (N. 324) and controlled hypertensive (N. 470) subjects. Then, by logistic regression analysis, we evaluated which factors were associated with a worse BP control under pharmacological treatment.SUA levels were significantly higher in untreated hypertensive and uncontrolled hypertensive patients when compared to normotensives and controlled hypertensive patients. Pulse wave velocity (PWV) was significantly higher (p0.001) in undiagnosed and uncontrolled hypertensive patients, while controlled hypertensive patients had PWV values comparable to normotensive controls. A similar trend has been observed for the augmentation index (AI). A worse BP control was associated with SUA levels (OR 1277, 95% CI 1134-1600 per mg/dL), AI (OR 1066, 95%CI 1041-1092 per unit), and PWV (OR 1201, 95% CI 1089-1423, per m/s), but not with age, body mass index, nor estimated glomerular filtration rate.Based on our data, SUA seems to be associated with an inadequate BP control in subjects treated with antihypertensive drugs, and subjects with both uncontrolled BP and relatively high SUA levels have also an increased arterial stiffness that (per se) could be a cause of worse BP control under treatment.

INTRODUCTION: One of the most frequent side effect of oral contraceptives use is a stable alteration of the lipid profile. This could be even more relevant in women affected by polycystic ovary syndrome (PCOS). AIM: Considering the importance of a balanced lipid profile in cardiovascular prevention and that the exposure to the drugs could be many years long, our aim was to investigate the possible beneficial effect of a largely tested low-dosed combined lipid-lowering nutraceutical on dyslipidemias induced by oestroprogestins prescribed to young women for different indications. METHODS: We prospectively enrolled 84 patients in primary cardiovascular disease prevention, with low estimated cardiovascular disease risk (130 mg/dL) after the use of at least two different oral oestroprogestins treatments. Forty-four women were prescribed oral oestroprogestins for PCOS, while 40 for pure contraception. The tested nutraceutical contained berberine 500 mg/tab and monacolins 3 mg/tab was prescribed to all enrolled patients, associated the previously prescribed standard lipid-lowering diet. RESULTS: After 3 months of nutraceutical treatment, we observed a significant improvement in BMI (-1.5 ± 0.8 %, p < 0.001), FPG (-6.9 ± 5.8 %, p < 0.001), HOMA index (-3.5 ± 5.6 %, p < 0.001), TC (-20.1 ± 6.6 %, p < 0.001), LDL-C (-25.3 ± 8.9 %, p < 0.001), HDL-C (+14.1 ± 2.2 %, p < 0.001), TG (-29.9 ± 25.2 %, p < 0.001) and hsCRP (-2.5 ± 2.4 %, p = 0.019). Similar results have been obtained even repeating the analysis by subgroups, beyond hsCRP that significantly improved in PCOS patients compared to both the baseline and the non-PCOS group. CONCLUSION: It appears that the tested combined lipid-lowering nutraceutical is able to equally improve lipid metabolism in oral contraceptive induced hypercholesterolemia in women affected or not by PCOS.

INTRODUCTION: A large number of epidemiological trials clearly show the impact of the main cardiovascular disease risk factors in term of hospitalization and related cost, but relatively less frequently if this reflect the health needs of a given population. AIM: To develop a model for the health needs-assessment that will be applied to verify if and how the prevalence of some classical risk factors for cardiovascular disease predicts mortality and hospitalisation episodes at 3 years, and if it could express the health need of that population. The long-life clinical record of 1,704 subjects, recruited during the 2004 Brisighella Heart Study survey, has been monitored. We defined the health profile of these subjects at 2004 (based on clinical history, smoking and dietary habits, physical activity, drug use, anthropometric data, blood pressure, and hematological data) and then sampled data relative to their hospitalisations, mortality, and general medical assistance. RESULTS: Our results shows that age over 65 years (OR 4.08; 95 % CI 2.74-6.08), hypertension (OR 3.44; 95 % CI 2.36-5.01) and hypercholesterolemia (OR 1.33; 95 % CI 0.92-1.94) increase the probability to get hospitalised. Furthermore, the burden of care was defined and computed for our sample. Vascular and respiratory diseases [Burden of health care (Bc) = 24.5 and 36.5, respectively] are the most costly DRGs which means that the biggest part of our resources directed to cardiovascular patients were provided for these diagnoses. CONCLUSION: The application of the proposed model could help policy makers and researchers in directing resources and workforce in the treatment of cardiovascular diseases.

Background: Serum uric acid (SUA) is an emerging risk factor for incident hypertension and type 2 diabetes. It is less clear if changes in SUA are associated to different incidence in these main cardiovascular risk factors. Methods: From the cohort of the Brisighella Heart Study, we selected non-diabetic subjects that in 2008 were untreated with SUA-lowering drugs nor antihypertensive ones. Then we divided the subjects in four main groups: the ones that maintained their SUA level unchanged during the next 4 years, the ones that increased it >1 mg/dL without treatment, the ones that reduced it >1 mg/dL without drug treatment and the ones that reduced it >1 mg/dL with the continuous use of allopurinol. Results: Compared with 2008, SBP significantly increased in subjects with worsened (and untreated) SUA level, while improved in subjects treated with allopurinol (p < 0.05). In 2012, subjects with worsened (and untreated) SUA level had a significantly higher SBP compared with subjects with unchanged SUA and those with SUA improved after allopurinol treatment (p < 0.05). An identical trend has been observed as it regards FPG. Conclusion: It seems that SUA improvement could positively influence the age-related worsening of SBP and FPG in general population.Key messages Serum uric acid (SUA) is an emerging risk factor for incident hypertension and type 2 diabetes. SUA improvement could positively influence the age-related worsening of SBP and FPG in general population.

Background High lipoprotein(a) [Lp(a)] levels have been re-evaluated as an independent risk factor for atherosclerotic vascular diseases. Methods We assessed whether serum Lp(a) levels can significantly influence long-term survival in subjects with an equal general cardiovascular (CV) risk profile. We prospectively evaluated a sample of 1215 adult subjects from the Brisighella Heart Study cohort (M: 608; F: 607; aged 40–69) who had no cardiovascular disease at enrolment. According to the CUORE project risk-charts (Italian-specific risk-charts), individuals were stratified into a low—(n = 865), an intermediate—(n = 275) and a high—(n = 75) cardiovascular risk groups. Kaplan–Meier 25-year survival analysis was carried out examining apart each class of risk and the log-rank statistic was used to estimate, when statistically possible, the survival time of the subjects stratified into quartiles of Lp(a). Results Subjects at high and intermediate CV risk aged 56–69 years (regardless of gender) and women aged 40–55 years with a low CV risk profile who had lower Lp(a) levels showed a significant benefit on CV mortality (PÂ

Introduction: The prevalence of systemic arterial hypertension in young adults is increasing worldwide in association with modifiable risk factors. Aim: To assess the prevalence of high blood pressure (BP) in young adults participating to a screening campaign during the World Hypertension Day (17/05/2014), and to determine the possible association with lifestyle factors. Methods: 493 individuals aged 18–35 years were selected in 13 Italian cities. All participants underwent BP measurement together with the administration of a questionnaire exploring: medical and drug history; traditional cardiovascular risk factors and diseases; dietary pattern; salt intake; sleep habits; mood disorders. Results: High BP (≥140/90 mmHg) was found in 54 individuals, with a prevalence of 11 % and awareness of 28 %. Those with high BP values were more frequently men, reported a higher BMI and a greater use of corticosteroids and non-steroidal anti-inflammatory drugs, and had a lower anxiety score. Concerning dietary habits, they were more likely to eat cheese/cold cuts ≥3 times/week, to have their meals out ≥1/day and to eat in fast foods ≥1/week. In the multiple logistic regression analysis, male sex [OR 3.19, 95 % CI (1.33–7.63)], BMI [OR 1.14 95 % CI (1.04–1.25)], eating in fast foods [OR 3.10 95 % CI (1.21–7.95)], and anxiety [OR 0.85 95 % CI (0.75–0.97)], were independently associated with high BP. Conclusions: High BP values were found in 11 % young adults. Male sex, adiposity and alimentary habits were the main determinants of high BP values, indicating that young men are a suitable target for healthy lifestyle interventions.

Background: Lactotripeptides (LTPs) have a mild antihypertensive effect in hypertensive subjects. The main aim of our clinical trial was to test if LTPs could have some influence on blood pressure (BP) and related hemodynamic parameters in a sample of outpatients affected by metabolic syndrome. Methods: A randomized, double-blind, placebo-controlled, crossover clinical trial was conducted in a group of 40 nonsmoking volunteers with metabolic syndrome. The treatment periods were 4 weeks long and were separated by a 4-week washout period. The dietary supplementation was made by daily administration of LTPs from casein, 10.2 mg/day, and compared with placebo. Results: During the LTP treatment, patients experienced a significant mean decrease in systolic BP (SBP; -3.4 ± 4.4 mmHg, P = 0.041), diastolic BP (DBP; -3.1 ± 3.2 mmHg, P = 0.049), and pulse wave velocity (PWV; -0.7 ± 0.3 m/sec, P = 0.001). After LTP treatment, delta SBP, DBP, and PP were all significantly improved (P < 0.01 for all) compared with placebo. PWV also improved significantly after LTP treatment with respect to the end of the treatment with placebo (-0.8 ± 0.4 vs. -0.1 ± 0.3 m/sec, P = 0.009). The square root of the ratio of peak:baseline pulse volume during hyperemia (V2/V1) improved after LTP treatment only (1.2 ± 0.4 vs. 1.4 ± 0.5, P = 0.04). Through the evaluation of the hemodynamic parameters that were measured by the 24-hr ambulatory monitoring, we observed that SBP, MBP, and the percentage of time with SBP over the normal were significantly reduced only after the LTP treatment (P < 0.05). These parameters were also significantly improved when compared with the ones measured after the placebo treatment (P < 0.05). Conclusion: In our trial, during LTP treatment, patients affected by metabolic syndrome experienced a mild but significant improvement in office and 24-hr BP, PWV, and endothelial function compared with placebo treatment.

Our aim was to evaluate the predictors of Isoleucine-Proline-Proline/Valine-Proline-Proline (IPP-VPP) lactotripeptides (LTPs) antihypertensive effect in the context of a short-term large double-blind randomized clinical trial involving 164 pharmacologically untreated subjects in primary prevention for cardiovascular disease. When compared with the baseline, office systolic blood pressure (SBP) (-3.42 mm Hg, P < .001) and diastolic blood pressure (DBP) (-2.35 mm Hg, P < .001) significantly decreased, in the LTP-treated patients only. No significant change in predictors during the study of ambulatory blood pressure measurement (ABPM) parameters was observed. A short-term supplementation with LTPs significantly improves the office SBP and DBP, especially in male subjects. The main predictor of LTP antihypertensive effect was the baseline BP.

Background The aim of this study was the detection of risk factors for lacunar strokes with visible lesions on computed tomography (CT) scan, considering in particular clinical characteristics, echocardiographic parameters, and carotid–femoral pulse wave velocity (PWV, a marker of large-artery stiffness). Lacunar strokes with very small or nonvisible lesions may have different risk factors. Methods We examined 106 patients (mean age 66.9 ± 12.3 years, 60 men), including 55 patients with clinically lacunar stroke associated with deep ischemic lesions of .3-1.5 cm on brain CT scan, and 51 control patients with cortical ischemic stroke, with lesions of 2.5-10.0 cm. Results In multiple logistic regression, with respect to cortical strokes, the following variables were independently associated with lacunar strokes: tricuspid regurgitation velocity (inverse relationship, odds ratio [OR] .13, 95% confidence interval [CI] .04-.43, P = .0007, cutoff at 228 cm/s), mean systolic blood pressure (SBP) (OR 3.98, 95% CI 2.78-7.79, P = .008, cutoff at 145 mmHg), ever-smoker status (OR 2.68, 95% CI 1.06-6.80, P = .04), and atrial fibrillation (inverse relationship, OR .11, 95% CI .01-1.00, P = .0496). In univariate analysis, the patients with lacunar stroke also had a lower prevalence of mitral regurgitation. There were no differences between the 2 groups in relation to diabetes, cholesterol, left ventricular mass and dimensions, and PWV. Conclusions The patients with lacunar strokes with visible cerebral lesions on CT scan, compared with the patients with cortical infarct, had a lower tricuspid regurgitation velocity, a higher mean SBP, a greater prevalence of ever-smokers, and a lower prevalence of atrial fibrillation.

The correlation of both obstructive sleep apnoea syndrome (OSAS) and snoring with cardiovascular risk is well known, but its investigation is complex and not suitable for studying large cohorts of subjects. Thus, we prospectively evaluated 1476 non-pharmacologically treated subjects selected from the last survey of the Brisighella Heart Study. Snoring and sleep apnoea were investigated asking the subjects if they were aware of snoring during the night, and if this was associated with episodes of apnoea. A full set of clinical and laboratory parameters were evaluated, while augmentation index (AIx), and pulse wave velocity (PWV) were recorded with the Vicorder(®) apparatus. A logistic regression analysis identifies as main independent predictors of AIx age (OR 1.058, 95% CI 1.043-1.065, p < 0.001), Body Mass Index (OR 1.046, 95% CI 1.014-1.079, p = 0.005), and apolipoprotein B (OR 1.014, 95% CI 1.004-1.023, p = 0.001). The main independent predictors of PWV are snoring (OR 1.215, 95% CI 1.083-1.390, p < 0.001), and snoring with apnoea (OR 1.351, 95% CI 1.135-1.598, p = 0.014), age (OR 1.078, 95% CI 1.052-1.089, p < 0.001), serum uric acid [SUA] (OR 1.093, 95% CI 1.026-1.151, p < 0.001) and mean arterial pressure (OR 1.042, 95% CI 1.024-1.056, p < 0.001). In conclusion, in our cohort of overall healthy subjects, self-reported snoring and sleep apnoea are independently associated with a higher PVW, and AIx is statistically significantly higher in snorers with or without sleep apnoea than in non-snorers. Body Mass Index and apolipoprotein B are associated with AIx, while SUA and mean arterial pressure are related to PWV.

Background: Overweight subjects easily develop alterations of the glucose and lipid metabolism and are exposed to an increased cardiometabolic risk. This condition is potentially reversible through the improvement of dietary and behavioural habits. However, a well-assembled nutraceutical would be a useful tool to better improve the metabolic parameters associated to overweight and insulin resistance. Methods: To evaluate the effect of a combined nutraceutical containing berberine, chlorogenic acid and tocotrienols, we performed a double blind, cross-over designed trial versus placebo, in 40 overweight subjects with mixed hyperlipidaemia. After the first 8 weeks of treatment (or placebo), patients were asked to observe a 2-week washout period, and they were then assigned to the alternative treatment for a further period of 8 weeks. Clinical and laboratory data associated to hyperlipidaemia and insulin resistance have been obtained at the baseline, at the end of the first treatment period, after the washout, and again after the second treatment period. Results: Both groups experienced a significant improvement of anthropometric and biochemical parameters versus baseline. However, total cholesterol, LDL cholesterol, triglycerides, non-HDL cholesterol, fasting insulin, HOMA-IR, GOT and Lipid Accumulation Product decreased more significantly in the nutraceutical group versus placebo. Conclusions: This combination seems to improve a large number of metabolic and liver parameters on the short-term in overweight subjects. Further studies are needed to confirm these observations on the middle- and long-term.

The aim of this retrospective study was to evaluate the main independent prognostic factors of negative maternal and fetal outcomes in a relatively large sample of pregnant outpatients (N=906) who were normotensive or affected by chronic hypertension, gestational hypertension, or preeclampsia. Among the studied parameters, the ones significantly associated with negative maternal outcomes were a diagnosis of preeclampsia (vs other forms of hypertension or normotension) and higher serum uric acid level, while antihypertensive treatment, number of previous deliveries, and blood pressure (BP) control at deliveries seemed to be protective. Regarding negative fetal outcomes, the parameters significantly associated with a negative maternal outcome were a diagnosis of preeclampsia (vs other forms of hypertension or normotension) and mother pre‐pregnancy body mass index, while antihypertensive treatment and BP control at delivery seemed to be protective. Specific patient characteristics should help to predict the risk of negative maternal and fetal outcomes.

Introduction Recent studies show that serum uric acid (SUA) is a predictor of atrial fibrillation, while its association with other kinds of arrhythmias is not yet established. We aimed to evaluate the incidence of the most common electrocardiographic alterations in a relatively large sample of general population and their association with SUA. Materials and methods We selected a Brisighella Heart Study cohort sample of 1557 subjects, consecutively visited in the 2004 and 2008 surveys, in a setting of primary prevention for cardiovascular disease and without a known diagnosis of arrhythmia or left ventricular hypertrophy, excluding subjects affected by gout or taking any antihyperuricemic agent or drugs able to interfere with the QT interval. A step-wise Cox regression analysis was used to determine the independent prognostic significance of age, gender, physical activity, smoking, body mass index (BMI), fasting plasma glucose, mean arterial pressure (MAP), heart rate, LDL-cholesterol, HDL-cholesterol, triglycerides, SUA and eGFR on ECG alterations during a 4-year follow-up. Results No one of the considered variables was associated with the incident diagnosis of sinus tachycardia and sinus bradycardia. SUA predicted incident tachyarrhythmias, Q waves and ECG signs of left ventricular hypertrophy; age, female sex and active smoking predicted incident tachyarrhythmias; male sex, active smoking and LDL-cholesterol predicted incident ECG signs of previous myocardial infarction; BMI and MAP predicted incident ECG-diagnosed left ventricular hypertrophy. Conclusion In a cohort of general population, SUA seems to be a significant middle-term predictor of electrocardiographically diagnosed myocardial infarction, left ventricular hypertrophy and tachyarrhythmias.

To propose a test to evaluate endothelial function, based on VO(2) on-transition kinetics in sub-anaerobic threshold (AT) constant load exercise, we tested healthy subjects and patients with ischemic-hypertensive cardiopathy by two cardiopulmonary tests on a cycle ergometer endowed with an electric motor to overcome initial inertia: a pre-test and, after at least 24 h, one 6 min constant load exercise at 90 % AT. We measured net phase 3 VO(2)-on kinetics and, by phase 2 time constant (tau), valued endothelial dysfunction. We found shorter tau in repeated tests, shorter time between first and second test, by persisting endothelium-dependent arteriolar vasodilatation and/or several other mechanisms. Reducing load to 80 % and 90 % AT did not produce significant changes in tau of healthy volunteers, while in heart patients an AT load of 70 %, compared to 80 % AT, shortened tau (delta=4.38+/-1.65 s, p=0.013). In heart patients, no correlation was found between NYHA class, ejection fraction (EF), and the two variables derived from incremental cycle cardio-pulmonary exercise, as well as between EF and tau; while NYHA class groups were well correlated with tau duration (r=0.92, p=0.0001). Doxazosin and tadalafil also significantly reduced tau. In conclusion, the O(2) consumption kinetics during the on-transition of constant load exercise below the anaerobic threshold are highly sensitive to endothelial function in muscular microcirculation, and constitute a marker for the evaluation of endothelial dysfunction.

INTRODUCTION: Serum uric acid (SUA) levels, an inexpensive and standardized marker of systemic oxidative stress, has been recently associated with the risk of atherosclerotic cardiovascular events. OBJECTIVES: The main objective of the study was to evaluate the possible relationship between SUA, oxidized low-density lipoproteins (oxLDLs) and LDL susceptibility to oxidation in a sample of nonsmoking healthy subjects. PATIENTS AND METHODS: From the general database of the Brisighella Heart Study, we selected a sample of 354 nonsmoking and pharmacologically untreated adult subjects, in primary prevention for cardiovascular disease, with normal renal function, and without known allergic or rheumatic diseases, who were visited during the 2008 population survey. A full set of clinical and hematochemical parameters was evaluated together with oxidative susceptibility of LDL and oxLDL levels. RESULTS: In a multivariate analysis, the oxLDL level was positively correlated with apolipoprotein B (ApoB; B = 0.077; 95% confidence interval [CI], 0.015-0.139; P = 0.016), triglicerydes (B = 0.050; 95% CI, 0.032-0.069; P

Serum uric acid is representative for xanthine-oxidase, the key enzyme involved in the production of uric acid, which is up-regulated in the failing heart, and may play an important role in the pathophysiologic process that leads to heart failure. In our study, we investigated the relation between stroke volume, cardiac output and serum uric acid in a large sample of overall healthy pharmacologically untreated subjects. The Brisighella Heart Study included 2,939 men and women between the ages of 14-84 without prior coronary heart disease or cerebrovascular disease who were not taking antihypertensive therapy at baseline. For this study, we selected 734 adult subjects enrolled in the last Brisighella population survey not taking antihypertensive, antidiabetic, lipid-lowering and uric acid-lowering drugs, and who were also not affected by chronic heart failure or by gout. The main predictors of cardiac functionality parameters were mean arterial pressure (MAP), HR, SUA and age (all p < 0.001), while gender, BMI, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting plasma glucose, creatinine, estimated glomerular filtration rate, physical activity and smoking habit were not significantly associated (all p > 0.05). In particular, there is a strong relation between estimated cardiac output and serum uric acid (B = -0.219, p < 0.001) and between stroke volume and serum uric acid (B = -3.684, p < 0.001). These observations might have an impact on future considerations about serum uric acid as an early inexpensive marker of heart function decline in the general population

Contrasting evidence shows a possible association between serum uric acid (SUA) and cognitive function in elderly subjects. We aimed at evaluating the impact of circulating SUA levels on cognitive function in a cohort of pharmacologically untreated young elderly subjects. For this study, we selected 288 healthy young elderly participants from the historical cohort of the Brisighella Heart Study (M: 108, F: 180; mean age: 69 ± 6 years old). Exclusion criteria were limitation of activities of daily living, depression, chronic pharmacological treatment, patients in secondary prevention for cardiovascular disease, known neurodegenerative disorders, confirmed diabetes or gout, and ultrasonic evaluated carotid atherosclerosis. Cognitive functions were assessed by scholarship-adjusted mini-mental state examination (MMSE). A stepwise multiple regression analysis was carried out including a large set of clinical and laboratory parameters, carotid intima-media thickness, and the Beck Depression scale score. The analysis was then repeated by gender. In the multiple regression analysis, the only factors associated with the MMSE score were: age (B = −0.058, 95 % CI −0.108, −0.009, p = 0.022), LDL-C (B = −0.639, 95 % CI −0.912, −0.411, p = 0.034) and SUA (B = −0.527, 95 % CI −0.709, −0.344, p = 0.022). Repeating the analysis by low or high SUA level (based on the gender specific SUA distribution 50th percentile), it appears that in subjects with a low SUA, cognitive decline is only associated with age, while in those with high SUA it is associated with LDL-C (OR 1.18, 95 % CI 1.07–1.33, p = 0.019) and SBP (OR 1.02, 95 % CI 1.001–1.048, p = 0.039). Our data demonstrate a positive association between circulating levels of uric acid and cognitive dysfunction in a sample of pharmacologically untreated young elderly subjects.

OBJECTIVE The objective is to evaluate the relationship between cholesterolemia, serum apolipoprotein B (apoB) level and blood pressure in a large sample of general population. METHODS The Brisighella Heart Study (BHS) is a prospective, population-based longitudinal epidemiological investigation. For this study, we analysed the data sampled in the 2008 BHS population survey, excluding those participants treated with antihypertensive and/or lipid lowering drugs (N: 2473). RESULTS In a sex, BMI, smoking habit, physical activity level and serum creatinine adjusted model, low-density lipoprotein-cholesterol (LDL-C) appears to be significantly related to SBP (P

Contrasting data partially support a certain antihypertensive efficacy of lactotripeptides (LTPs) derived from enzymatic treatment of casein hydrolysate. Our aim was to evaluate this effect on a large number of hemodynamic parameters. We conducted a prospective double-blind randomized clinical trial, which included 52 patients affected by high-normal blood pressure (BP) or first-degree hypertension. We investigated the effect of a 6-week treatment with the LTPs isoleucine-proline-proline and valine-proline-proline at 3 mg per day, assumed to be functional food, on office BP, 24-h ambulatory BP monitoring (ABPM) values, stress-induced BP increase and cardiac output-related parameters. In the LTP-treated subjects, we observed a significant reduction in office systolic BP (SBP; -5±8 mm Hg, P=0.013) and a significant improvement in pulse wave velocity (PWV; -0.66±0.81 m s(-1), P=0.001; an instrumental biomarker of vascular rigidity). No effect on 24-h ABPM parameters and BP reaction to stress was observed from treatment with the combined LTPs. LTPs, but not placebo, were associated with a mild but significant change in the stroke volume (SV), SV index (markers of cardiac flow), the acceleration index (ACI) and velocity index (VI) (markers of cardiac contractility). No effect was observed on parameters related to fluid dynamics or vascular resistance. LTPs positively influenced the office SBP, PWV, SV, SV index, ACI and VI in patients with high-normal BP or first-degree hypertension.

Contrasting data partially support a certain antihypertensive efficacy of lactotripeptides derived from enzymatic treatment of casein hydrolysate. We carried out a randomized, double-blind, crossover clinical study to investigate the antihypertensive efficacy of a short-term treatment with lactotripeptides in Mediterranean subjects with normal or high-normal blood pressure (BP). We consecutively enrolled 55 untreated subjects (men:women = 30:25), 40.3 ± 9.8 years old, with normal or high-normal BP. After 4 weeks of dietary standardization, they were allocated to treatment with a fruit juice containing 3 mg of added Ile-Pro-Pro/Val-Pro-Pro lactotripeptides or with placebo for 4 weeks. After a 4-week washout period, they were then assigned to the alternative treatment for a further period of 4 weeks. Overall, no significant difference has been observed in office BP comparing baseline data with those posttreatment. Repeating the analysis by basal BP level, a mild but significant reduction in systolic BP (-1.7 ± 2.3 mm Hg; t = 3.5, P = .002) has been observed only in subjects with high-normal BP after treatment with lactotripeptides. With regard to 24-hour BP measurement, after lactotripeptide treatment only, the subjects experienced a significant reduction in diurnal diastolic BP (-1.6 ± 5.4 mm Hg; P = .042), diurnal mean BP (-2.1 ± 5.9 mm Hg; P = .19), and 24-hour (-5.4 ± 14.2 mm Hg; P = .011) and diurnal (-7.1 ± 19.2%; P = .014) diastolic BP value measurements relative to normal values. No modification has been observed in relation to plasma renin activity and aldosteronemia. In conclusion, diurnal diastolic BP is significantly reduced by lactrotripeptide supplementation in untreated Mediterranean subjects with normal or high-normal BP. Office systolic BP is reduced only in subjects with high-normal BP.

none 10 no OBJECTIVE: The objective of the study was to evaluate the longitudinal changes in maternal systolic and diastolic function in a series of women carrying an uncomplicated twin pregnancy. STUDY DESIGN: A series of women carrying a twin pregnancy underwent standard M-mode, 2-dimensional color Doppler, and tissue Doppler transthoracic echocardiography during the first (11-13 weeks), the second (20-23 weeks), the third (28-32 weeks) trimesters, and the postpartum (6 months after delivery). RESULTS: From January 2012 to September 2013, 30 women with an uncomplicated twin pregnancy were included in this prospective study. All the pregnancies were diamniotic including 24 dichorionic and 6 monochorionic sets. Overall, 60 live births were observed with a mean gestational age at delivery of 37 ± 1 weeks and a mean birthweight of 2532 ± 313 g. During pregnancy a significant worsening of left ventricle systolic function expressed by ejection fraction, fractional shortening and S1 longitudinal contractility decrease was observed. These findings also persisted at postpartum assessment. Regarding diastolic function, our data showed a significant progressive reduction of pulsed Doppler E-wave velocity and an increase of A-wave from the first to the third trimester. Similar changes were documented for tissue Doppler E1 and A1 peak velocities assessed at the level of the mitral and tricuspid annulus. After delivery diastolic findings returned to values comparable with those obtained in the first trimester. CONCLUSION: In uncomplicated twin gestations, significant changes in maternal systolic and diastolic function occur from the first to the third trimester. Moreover, although diastolic parameters normalize after pregnancy, a relative systolic dysfunction seems to persist after delivery mixed Ghi, Tullio; Degli Esposti, Daniela; Montaguti, Elisa; Rosticci, Martina; Tancredi, Sonia; Youssef, Aly; Di Giovanni, Maria Valentina; Pilu, Gianluigi; Borghi, Claudio; Rizzo, Nicola Ghi, Tullio; Degli Esposti, Daniela; Montaguti, Elisa; Rosticci, Martina; Tancredi, Sonia; Youssef, Aly; Di Giovanni, Maria Valentina; Pilu, Gianluigi; Borghi, Claudio; Rizzo, Nicola