Randomized, Double-Blind, Placebo-Controlled Trial to Test the Effects of a Nutraceutical Combination Monacolin K-Free on the Lipid and Inflammatory Profile of Subjects with Hypercholesterolemia.

BACKGROUND: Nutraceutical combinations (NCs) against hypercholesterolemia are increasing in the marketplace. However, the availability of NCs without monacolin K is scarce even though the statin-intolerant population needs it. METHODS: This study is a parallel-group, randomized, placebo-controlled, double-blind trial. We evaluated the effects of the NC containing phytosterols, bergamot, olive fruits, and vitamin K2 on lipid profile and inflammatory biomarkers in 118 subjects (mean age ± SD, 57.9 ± 8.8 years; 49 men and 69 women) with hypercholesterolemia (mean total cholesterol ± SD, 227.4 ± 20.8 mg/dL) without clinical history of cardiovascular diseases. At baseline and 6 and 12 weeks of treatment, we evaluated lipid profile (total, LDL and HDL cholesterol, and triglycerides), safety (liver, kidney, and muscle parameters), and inflammatory biomarkers such as hs-CRP, leukocytes, interleukin-32, and interleukin-38 and inflammatory-microRNAs (miRs) miR-21, miR-126, and miR-146a. RESULTS: Compared to the placebo, at 6 and 12 weeks, NC did not significantly reduce total cholesterol (p = 0.083), LDL cholesterol (p = 0.150), and triglycerides (p = 0.822). No changes were found in hs-CRP (p = 0.179), interleukin-32 (p = 0.587), interleukin-38 (p = 0.930), miR-21 (p = 0.275), miR-126 (p = 0.718), miR-146a (p = 0.206), myoglobin (p = 0.164), and creatine kinase (p = 0.376). Among the two reported, only one adverse event was probably related to the nutraceutical treatment. CONCLUSIONS: The evaluated nutraceutical combination did not change serum lipid profile and inflammatory parameters, at least not with the daily dose applied in the present study.

Effects of a novel nutraceutical combination (BruMeChol™) in subjects with mild hypercholesterolemia: study protocol of a randomized, double-blind, controlled trial.

BACKGROUND: Elevated cholesterol levels and systemic inflammation are considered relevant risk factors for cardiovascular disease (CVD) development and progression. Increasing evidence suggests that cholesterol-lowering and inflammation-lowering nutraceuticals are useful in the management of moderate hypercholesterolemia. Here, we describe the study protocol of a clinical trial aimed to evaluate the cholesterol and inflammatory lowering effect of an innovative dietary supplement (BruMeChol™, Mivell S.r.l., Italy), composed of a mixture of extracts of bergamot and olive fruits in association with vitamin K2 in subjects with mild hypercholesterolemia. METHODS: The study was planned as a randomized, double-blind, placebo-controlled, parallel group clinical trial for 12 weeks at the Cardiology Unit of the IRCCS INRCA of Ancona, Italy. A total of 125 subjects (age ≥ 40 years) with mild hypercholesterolemia (total serum cholesterol levels ≥ 200 and ≤ 250 mg/dl) will be recruited. Intervention arm participants will take one capsule of dietary supplement two times a day, 15 min before the main meal. Control arm participants will receive one capsule of placebo in the same way. The dietary supplement capsule contains the following ingredients: phytosterols, flavonoid-rich extract of bergamot fruit (Citrus bergamia), flavonoid-rich extract of olive fruit (Olea europaea), and vitamin K2. Participants will undergo a medical evaluation and chemical-clinical examinations, which include lipid profile, glycemia, biomarkers of renal, liver and cardiac/muscular functions, interleukins (IL 6, IL-32, IL-37, and IL-38), and innovative mediators of inflammation such as inflamma-miRs (miR-21 and miR-146a), at baseline, and after 6 and 12 weeks of treatment. The decrease in total cholesterol levels and inflammatory biomarkers will be the primary and secondary endpoints of the study. DISCUSSION: This protocol study, planned to verify the effects of BruMeChol™ dietary supplementation in subjects with mild hypercholesterolemia, could also contribute to new study designs for next large-scale multicenter clinical trials. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619000170123 . Retrospectively registered on 5 February 2019.

Clustering of ABCB1 and CYP2C19 Genetic Variants Predicts Risk of Major Bleeding and Thrombotic Events in Elderly Patients with Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy with Aspirin and Clopidogrel.

OBJECTIVE: The clinical efficacy of clopidogrel in secondary prevention of vascular events is hampered by marked inter-patient variability in drug response, which partially depends on genetic make-up. The aim of this pilot prospective study was to evaluate 12-month cardiovascular outcomes in elderly patients with acute coronary syndrome (ACS) receiving dual antiplatelet therapy (aspirin and clopidogrel) according to the clustering of CYP2C19 and ABCB1 genetic variants. METHODS: Participants were 100 consecutive ACS patients who were genotyped for CYP2C19 (G681A and C-806T) and ABCB1 (C3435T) polymorphisms, which affect clopidogrel metabolism and bioavailability, using PCR-restriction fragment length polymorphism. They were then grouped as poor, extensive and ultra-rapid metabolisers based on the combination of CYP2C19 loss-of-function (CYP2C19*2) and gain-of-function (CYP2C19*17) alleles and ABCB1 alleles. The predictive value of each phenotype for acute vascular events was estimated based on 12-month cardiovascular outcomes. RESULTS: The poor metabolisers were at an increased risk of thrombotic events (OR 1.26; 95% CI 1.099-1.45; χ2 = 5.676; p = 0.027), whereas the ultra-rapid metabolisers had a 1.31-fold increased risk of bleeding events compared with the poor and extensive metabolisers (OR 1.31; 95% CI 1.033-1.67; χ2 = 5.676; p = 0.048). Logistic regression model, including age, sex, BMI and smoking habit, confirmed the differential risk of major events in low and ultra-rapid metabolisers. CONCLUSIONS: Our findings suggest that ACS patients classified as 'poor or ultra-rapid' metabolisers based on CYP2C19 and ABCB1 genotypes should receive alternative antiplatelet therapies to clopidogrel.

Surgical bleeding after pre-operative unfractionated heparin and low molecular weight heparin for coronary bypass surgery.

BACKGROUND AND OBJECTIVES: Since the impairment of platelet function may cause excess peri-operative bleeding, pre-operative discontinuation of aspirin and heparin bridging are common for cardiac surgery. We evaluated the impact of pre-operative administration of enoxaparin and unfractionated heparin (UFH) on coagulation parameters and peri-operative bleeding in patients undergoing elective coronary artery bypass grafting (CABG) surgery after discontinuation of aspirin. DESIGN AND METHODS: Forty-three patients with three-vessel coronary artery disease undergoing elective CABG surgery discontinued aspirin and were randomized to receive either UFH 180 UI/Kg x 2/day s.c. or enoxaparin 100 UI/Kg x 2/day s.c. until 12 h before surgery (median pre-operative treatment 8 days, range 6-12 days). Surgery was performed as usual with UFH. Neither UFH nor any low molecular weight heparin was given in the immediate post-operative period. The effects of UFH and enoxaparin were monitored by the activated partial thromboplastin time (aPTT) and the Enox-test (sensitive to factor Xa inhibition) using a Rapidpoint Coagulation Analyzer. aPTT and factor Xa activity were also measured by standard methods. Peri-operative bleeding and the nadirs of hemoglobin concentration, hematocrit and platelet count were monitored post-operatively. RESULTS: Patients in the two groups were similar for number of bypasses, on-pump time, total surgery time, and time from the last heparin administration. Coagulation parameters increased significantly and similarly at 30 min and 6 h with both treatments, but returned within the normal range at 12 h. Hemoglobin, hematocrit and platelet counts significantly decreased to the same extent after CABG and re-normalized at the same time. Transfusional requirements of blood and plasma units were similar in the two groups. INTERPRETATION AND CONCLUSIONS: From the kinetics of coagulation parameters and the evaluation of bleeding, enoxaparin is a safe alternative to UFH as a bridging therapy to CABG after discontinuation of aspirin.