Relationship between Lipid Phenotypes, Overweight, Lipid Lowering Drug Response and KIF6 and HMG-CoA Genotypes in a Subset of the Brisighella Heart Study Population.

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.

Middle-Term Dietary Supplementation with Red Yeast Rice Plus Coenzyme Q10 Improves Lipid Pattern, Endothelial Reactivity and Arterial Stiffness in Moderately Hypercholesterolemic Subjects.

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.

Risk Factors for Lacunar Strokes with Visible Cerebral Lesions on Computed Tomography Scan.

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.

Maternal cardiac evaluation during uncomplicated twin pregnancy with emphasis on the diastolic function.

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.

Short-term effects of a combined nutraceutical of insulin-sensitivity, lipid level and indexes of liver steatosis: a double-blind, randomized, cross-over clinical trial.

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.

Serum LDL cholesterol levels and new onset of arterial hypertension: an 8-year follow-up.

BACKGROUND: Serum cholesterol has been demonstrated to correlate with blood pressure values; therefore, abnormal levels of serum cholesterol might contribute to the development of hypertension. The aim of this study was to assess the new onset of hypertension over a period of 8 years in a pharmacologically untreated population sample in normo- and hypercholesterolemic individuals. DESIGN: 1864 Caucasian subjects with baseline blood pressure values <140/90 mmHg were subdivided into two different groups, according to LDL cholesterol changes observed over a period of 8 years. Group 1 included subjects whose LDL cholesterol levels remained or decreased within the normal range, while Group 2 included those whose LDL cholesterol levels were persistently increased above the normal range. The 8-year incidence of new-onset hypertension was 7·1% in Group 1 and 13·8% in Group 2 (P = 0·02), after adjustment for the main confounding risk factors. The difference between Groups 1 and 2 was confirmed in men (8·2 vs. 13·1%, P = 0·04) and women (6·1. vs. 14·5%, P = 006), as well as in subjects younger than 65 years (5·7 vs. 10·9%; P = 0·011), but not in older ones. CONCLUSIONS: Baseline serum LDL cholesterol levels are related to the rate of new-onset hypertension in patients with normal or marginally elevated blood pressure values.

Blood pressure and metabolic effect of a combination of lercanidipine with different antihypertensive drugs in clinical practice.

The aim of this study is to assess the blood pressure (BP) and metabolic effects of lercanidipine when combined with other classes of first-line antihypertensive drugs in day-to-day clinical practice. For this study, we consecutively enrolled 162 patients with uncomplicated primary hypertension, who are partial responders to the treatment with lercanidipine over a period of 24 months. Patients were then allocated to the combination of lercanidipine (10-20 mg/day) with ß-blockers, diuretics, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers according to compelling indications (if any) and/or suggestions of European Society of Hypertension-European Society of Cardiology (ESH-ESC) guidelines. All the enrolled patients completed the study and no adverse drug reaction was registered during the research period. The association of a second drug with lercanidipine determined an additional BP decrease of either systolic BP or diastolic BP independently from the type of drug added (P always <.05). The additional effect of lercanidipine appears widely distributed with no significant differences in the size of BP decrease. From the metabolic point of view, the addition of a second drug did not determine a significant variation in the serum levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (P always >.05). Conversely, a significant decrease in fasting plasma glucose and serum levels of triglycerides has been observed in patients where lercanidipine has been combined with an angiotensin-converting enzyme inhibitor or an angiotensin-II receptor blocker. In conclusion, in our study we observed that lercanidipine-based protocols are well tolerated and efficacious in reducing BP. Moreover, the association of lercanidipine with renin-angiotensin system blockers is also associated with significant improvements in triglycerides and fasting plasma glucose.

Differences in Diagnosis and Management of Hypertensive Urgencies and Emergencies According to Italian Doctors from Different Departments Who Deal With Acute Increase in Blood Pressure-Data from Gear (Gestione Dell'emergenza e Urgenza in ARea Critica) Study.

Background: Diagnosis and treatment of hypertension emergency (HE) and urgency (HU) may vary according to the physicians involved and the setting of the treatment. The aim of this study was to investigate differences in management of HE and HU according to the work setting of the physicians. Methods: The young investigators of the Italian Society of Hypertension developed a 23-item questionnaire spread by email invitation to the members of Italian Scientific societies involved in the field of emergency medicine and hypertension. Results: Six-hundred and sixty-five questionnaires were collected. No differences emerged for the correct definitions of HE and HU or for the investigation of possible drugs that may be responsible for an acute increase in BP. The techniques used to assess BP values (p < 0.004) and the sizes of cuffs available were different according to the setting. Cardiologists more frequently defined epistaxis (55.2% p = 0.012) and conjunctival hemorrhages (70.7%, p < 0.0001) as possible presentation of HE, and rarely considered dyspnea (67.2% p = 0.014) or chest pain (72.4%, p = 0.001). Intensive care (IC) unit doctors were more familiar with lung ultrasound (50% p = 0.004). With regard to therapy, cardiologists reported the lowest prescription of i.v. labetalol (39.6%, p = 0.003) and the highest of s.l. nifedipine (43.1% p < 0.001). After discharge, almost all categories of physicians required home BP assessment or referral to a general practitioner, whereas hypertensive center evaluation or ambulatory BP monitoring were less frequently suggested. Conclusion: Management and treatment of HE and HU may be different according to the doctor's specialty. Educational initiatives should be done to standardize treatment protocols and to improve medical knowledge.

Evaluation of Unattended Automated Office, Conventional Office and Ambulatory Blood Pressure Measurements and Their Correlation with Target Organ Damage in an Outpatient Population of Hypertensives: Study Design and Methodological Aspects.

Accurate measurement of blood pressure (BP) has a pivotal role in the management of patients with arterial hypertension. Recently, introduction of unattended office BP measurement has been proposed as a method allowing more accurate management of hypertensive patients and prediction of hypertension-mediated target organ damage (HMOD). This approach to BP measurement has been in particular proposed to avoid the white coat effect (WCE), which can be easily assessed once both attended and unattended BP measurements are obtained. In spite of its interest, the role of WCE in predicting HMOD remains largely unexplored. To fill this gap the Young Investigator Group of the Italian Hypertension Society (SIIA) conceived the study "Evaluation of unattended automated office, conventional office and ambulatory blood pressure measurements and their correlation with target organ damage in an outpatient population of hypertensives". This is a no-profit multicenter observational study aiming to correlate attended and unattended BP measurements for quantification of WCE and to correlate WCE with markers of HMOD, such us left ventricular hypertrophy, left atrial dilatation, and peripheral atherosclerosis. The Ethical committee of the Federico II University hospital has approved the study.

A meta-analysis of Italian and Estonian individuals shows an effect of common variants in HMGCR on blood apoB levels.

Aim: The aim of the study was to explore the effects of variants at HMGCR-KIF6loci on a range of cardio-metabolic phenotypes. Methods: We analyzed the range of variants within Genetics in Brisighella Health Study and KIF6 genes using an additive genetic model on 18 cardiometabolic phenotypes in a sample of 1645 individuals from the Genetics in Brisighella Health Study and replicated in 10,662 individuals from the Estonian Genome Center University of Tartu. Results: We defined directly the effects of rs3846662:C>A at HMGCR on apoB levels. The analysis also confirmed effects of on low-density lipoprotein-cholesterol and total cholesterol levels. Variants in KIF6 gene did not reveal any associations with cardiometabolic phenotypes. Conclusion: This study highlights effect of HMGCR locus on assay-determined apoB levels, an infrequent measure of blood lipids in large studies.

Correction to: Effect of a short-term dietary supplementation with phytosterols, red yeast rice or both on lipid pattern in moderately hypercholesterolemic subjects: a three-arm, double-blind, randomized clinical trial.

[This corrects the article DOI: 10.1186/s12986-017-0214-2.].

Serum uric acid predicts incident metabolic syndrome in the elderly in an analysis of the Brisighella Heart Study.

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 < 0.000001], even there were sex-related differences in the best cut-off values (5.5 mg/dL for men; 4.2 mg/dL for women). Prospectively, SUA appeared predictive of middle-term (4-year) MetS incidence in the whole population (AUC = 0.604, 95%C.I.[0.518, 0.690], P = 0.029, best cut-off value = 4.7 mg/dL) and in the female group (AUC = 0,641, 95%C.I.[0.519, 0.762], P = 0.039, best cut-off value = 3.9 mg/dL) though not in the male one (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.

Fatty liver index is associated to pulse wave velocity in healthy subjects: Data from the Brisighella Heart Study.

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 < 28 and no diabetes), intermediate-risk (BMI ≥ 28 or diabetes), high-risk (BMI ≥ 28 and diabetes). Multiple Linear Regression analysis was assessed for predictors of AS. RESULTS: We studied 1731 volunteers. In subjects with low metabolic risk, HSI (RR = 0.138, 95%CI 0.105-0.170, p < 0.001), FLI (RR = 0.024, 95%CI 0.016-0.032, p < 0.001), LAP (RR = 0.014, 95%CI 0.008-0.020, p < 0.001) and Serum Uric Acid (RR = 0.150, 95%CI 0.024-0.275, p = 0.019) were significant predictors of AS. HSI and FLI emerged as predictors of PWV in intermediate risk group (RR = 0.116, 95%CI 0.071-0.160, p < 0.001; RR = 0.010, 95%CI 0.001-0.020, p = 0.041). In volunteers with high risk, FLI and Uric Acid were related to PWV (RR = 0.049, 95%CI 0.011-0.087, p = 0.013; RR = 0.632, 95% CI 0.222-1.041, p = 0.003). CONCLUSION: Fatty liver indirect indexes were associated to AS in subjects with different metabolic risk profiles.

LDL-oxidation, serum uric acid, kidney function and pulse-wave velocity: Data from the Brisighella Heart Study cohort.

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.

Effects of a Combined Nutraceutical on Lipid Pattern, Glucose Metabolism and Inflammatory Parameters in Moderately Hypercholesterolemic Subjects: A Double-blind, Cross-over, Randomized Clinical Trial.

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.

High serum uric acid is associated to poorly controlled blood pressure and higher arterial stiffness in hypertensive subjects.

INTRODUCTION: Serum uric acid (SUA) has been associated to incident hypertension and increased risk of cardiovascular diseases. MATERIALS AND METHODS: 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. RESULTS: 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 (p<0.001) 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. CONCLUSION: 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.

Circulating Levels of Proprotein Convertase Subtilisin/Kexin Type 9 and Arterial Stiffness in a Large Population Sample: Data From the Brisighella Heart Study.

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 PCSK9 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 PCSK9 plasma circulating levels and pulse wave velocity. Postmenopausal women showed higher PCSK9 levels (309.9±84.1 ng/mL) compared with the other groups (P<0.001). Older men had significant higher levels than younger men (283.2±75.6 versus 260.9±80.4 ng/mL; 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<0.001), PCSK9 (B=0.014, 95% CI 0.011-0.016, P<0.001), and serum uric acid (B=0.313, 95% 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 PCSK9 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 PCSK9 is significantly related to arterial stiffness, independent of sex and menopausal status in women.

Effect of a short-term dietary supplementation with phytosterols, red yeast rice or both on lipid pattern in moderately hypercholesterolemic subjects: a three-arm, double-blind, randomized clinical trial.

BACKGROUND: Phytosterols and red yeast rice are largely studied cholesterol-lowering nutraceuticals, respectively inhibiting the bowel absorption and liver synthesis of cholesterol. Our aim was to test the effect on lipid profile of phytosterols, red yeast rice and their association. METHODS: We performed a three parallel arms, double blind, clinical trial randomizing 90 moderately hypercholesterolemic subjects to treatment with phytosterols 800 mg (group 1), red yeast rice standardized to contain 5 mg monacolins from Monascus purpureus (group 2), or both combined nutraceuticals (group 3). RESULTS: After 8 weeks of treatment, in group 1 no significant variation of lipid parameters has been detected. In group 2 a significant reduction (p < 0.001) of LDL-Cholesterol (-20.5% vs. baseline) and Apolipoprotein B (-14.4% vs. baseline) as it occurred in group 3 (LDL-Cholesterol vs. baseline: -27.0%, Apolipoprotein B vs. baseline: -19.0%) (P < 0.001). LDL-Cholesterol and Apolipoprotein B changes were significantly different comparing group 2 with group 1 (P < 0.05), and group 3 with group 1 (P < 0.05). LDL-Cholesterol change was also significantly higher in group 3 than in group 2 (P < 0.05). CONCLUSION: The association of phytosterol and red yeast rice seems to have additive cholesterol lowering effect, reaching a clinically significant LDL-Cholesterol reduction in mildly hypercholesterolemic patients. TRIAL REGISTRATION: ClinicalTrial.gov ID: NCT02603276, Registered 27/08/2015.

Serum lipoprotein(a) level as long-term predictor of cardiovascular mortality in a large sample of subjects in primary cardiovascular prevention: data from the Brisighella Heart Study.

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 56-69years (regardless of gender) and women aged 40-55years with a low CV risk profile who had lower Lp(a) levels showed a significant benefit on CV mortality (P<0.05 always) and, indicatively, on the estimated survival time (even P<0.05). The ROC curves constructing for each CV risk group using Lp(a) as test-variable and death as state-variable identified serum Lp(a) as an independent long-term CV mortality prognosticator for subjects at high CV risk (AUC=0.63, 95%CI [0.50-0.76], P=0.049) and women with an intermediate CV risk profile (AUC=0.7, 95%CI [0.52-0.79], P=0.034). CONCLUSIONS: In the light of our finding and at the best of the previous knowledge, dosing Lp(a) is confirmed as important in subjects at high or medium risk (even if in primary prevention for CV diseases), especially in women.

Serum uric acid change and modification of blood pressure and fasting plasma glucose in an overall healthy population sample: data from the Brisighella heart study.

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.