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.

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.

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.].

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.

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.

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.

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.

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.

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.

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.

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.

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.

Lipid-lowering and anti-inflammatory effects of omega 3 ethyl esters and krill oil: a randomized, cross-over, clinical trial.

INTRODUCTION: Polyunsaturated fatty acids (PUFAs) derived from different sources could have different lipid-lowering effects in humans. The main aim of our study was to compare the short-term triglyceride-lowering efficacy of krill oil and purified omega 3 ethyl ester PUFAs in mildly overweight hypertriglyceridemic subjects. MATERIAL AND METHODS: This double-blind, randomized clinical trial was carried out in 25 moderately hypertriglyceridemic subjects (TG = 150-500 mg/dl). After a 4-week run-in, participants were allocated to treatment with similar pills containing omega 3 ethyl ester PUFAs 1000 mg twice a day vs. krill oil 500 mg twice a day. After 4 weeks of treatment, participants were asked to observe a 4-week wash-out period, and they were then assigned to the alternative treatment for a further period of 4 weeks. RESULTS: Although both PUFA sources were able to improve TG plasma levels, esterified omega 3 PUFAs were more efficacious than krill oil (p < 0.05). Nonetheless, only krill oil treatment was able to significantly improve high-density lipoprotein cholesterol and apolipoprotein AI levels, compared to both baseline (p < 0.05) and end of treatment with esterified omega 3 PUFAs (p < 0.05) values. Both treatments were able to significantly reduce high-sensitivity C-reactive protein (hs-CRP) levels from the baseline (p < 0.05), but krill oil improved it more efficaciously than esterified omega 3 PUFAs (p < 0.05). CONCLUSIONS: Krill oil has lipid-lowering effects comparable with those obtained through a 4-fold higher dose of purified omega 3 ethyl ester PUFAs in mildly overweight hypertriglyceridemic subjects, while more efficaciously reducing hs-CRP.

Additional therapy for cholesterol lowering in ezetimibe-treated, statin-intolerant patients in clinical practice: results from an internal audit of a university lipid clinic.

OBJECTIVE: The aim of our study was to evaluate the tolerability and efficacy of alternative approaches to improve cholesterolemia control in patients with statin-related myalgia treated with ezetimibe. RESEARCH DESIGN AND METHODS: We retrospectively evaluated 3534 Clinical Report Forms (CRFs) filled in the period June 2012-June 2015 for first visits to the lipid clinic of the University of Bologna. For this study, we selected 252 CRFs based on the following criteria: statin-related myalgia, previous failed treatment with at least two low-dosed statins, well tolerated treatment with ezetimibe. Then, the following lipid-lowering treatments were added in order to improve the ezetimibe low density lipoprotein cholesterol (LDL-C) lowering efficacy, based on clinical judgment: fenofibrate 145 mg, rosuvastatin 5 mg 1 tablet/week, rosuvastatin 5 mg 2 tablets/week, red yeast rice (standardized in monacolin K 3 mg) + berberine 500 mg, berberine 500 mg b.i.d., phytosterols 900 mg + psyllium fiber 3.5 g b.i.d. Patients continuing to claim a tolerable myalgia were then treated with coenzyme Q10 nanoemulsions 200 mg/day. RESULTS: The treatment with standard lipid-lowering diet plus ezetimibe alone was associated with a mean LDL-C reduction of 17 ± 2%. The additive LDL-lowering effect with the various tested treatment was: -16 ± 2% with fenofibrate 145 mg/day, -13 ± 1% with rosuvastatin 5 mg 1 tablet/week, -17 ± 3% with rosuvastatin 5 mg 2 tablets/week, -19 ± 4% with red yeast rice + berberine, -17 ± 4% with berberine b.i.d. and -10 ± 3% with phytosterols + psyllium b.i.d.; 11% of the patients treated with fenofibrate required treatment modification because of myalgia recurrence, while the percentage was negligible for the other tested treatments. In patients with residual tolerable myalgia, treatment with coenzyme Q10 for 8 weeks was associated with a mean improvement of the graduated myalgia score from 4.8 ± 1.9 to 2.9 ± 1.3 (p = 0.013). CONCLUSIONS: Some alternative treatments seems to be effective and well tolerated, thus improving the ezetimibe effect on cholesterolemia.

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.

Effect of red yeast rice combined with antioxidants on lipid pattern, hs-CRP level, and endothelial function in moderately hypercholesterolemic subjects.

Our aim was to test, through a crossover, double-blind, placebo-controlled randomized clinical trial, if a short-term treatment with 10 mg monacolins combined with antioxidants could improve lipid pattern, high-sensitivity C-reactive protein (hs-CRP), and endothelial function in a small cohort of moderately hypercholesterolemic subjects. Thus, 25 healthy, moderately hypercholesterolemic subjects were consecutively enrolled and, after 4 weeks of stabilization diet, were randomized to the sequence placebo followed by a washout, monacolins or monacolins followed by a washout, placebo, with each period being 4 weeks long. At each study step, a complete lipid pattern, safety parameters, hs-CRP, and endothelial function have been measured. When compared to the placebo phase, during monacolin treatment, patients experienced a more favorable percentage change in total cholesterol (TC) (TC after monacolin treatment, -18.35%; TC after placebo treatment, -5.39%), low-density lipoprotein cholesterol (LDL-C) (LDL after monacolin treatment, -22.36%; LDL after placebo treatment, -1.38%), non-high-density lipoprotein cholesterol (HDL-C) (non-HDL after monacolin treatment, -22.83%; non-HDL after placebo treatment: -7.15%), hs-CRP (hs-CRP after monacolin treatment: -2.33%; hs-CRP after placebo treatment, 2.11%), and endothelial function (pulse volume displacement after monacolin treatment, 18.59%; pulse volume displacement after placebo treatment, -6.69%). No significant difference was observed with regard to triglycerides, HDL-cholesterol, and safety parameters. On the basis of our data, we could demonstrate that a 10 mg monacolin nutraceutical treatment appears to safely reduce cholesterolemia, hs-CRP, and markers of vascular remodeling in moderately hypercholesterolemic subjects. These results need to be confirmed in larger patient samples and in studies with longer duration.