There is an increasing number of nutraceutical combinations (NCs) on the market for hypercholesterolemia, although clinical trials to verify their safety and efficacy are scarce. We selected fourteen ...randomized, placebo-controlled clinical trials (RCTs) on different lipid-lowering NCs in hypercholesterolemic subjects. We described each compound′s mechanism of action and efficacy in the mixtures and summarized the clinical trials settings and NCs safety and efficacy results. Almost all NCs resulted efficient against hypercholesterolemia; only one reported no changes. Interestingly, red yeast rice (RYR) was present in eleven mixtures. It is not clear whether the lipid-lowering efficacy of these combinations derives mainly from the RYR component monacolin K “natural statin” single effect. Up to now, few RCTs have verified the efficacy of every single compound vs. NCs to evaluate possible additive or synergistic effects, probably due to the complexity and the high resources request. In conclusion, to manage the arising nutraceutical tide against hypercholesterolemia, it could be helpful to increase the number and robustness of clinical studies to verify the efficacy and safety of the new NCs.
► Profiling of circulating miRs revealed age-related differences. ► MiR-21 was decreased in centenarians and increased in CVD patients. ► A significant correlation between miR-21 and C-reactive ...protein and fibrinogen was observed. ► MiR-21 appears as circulating biomarker of inflammation in aging process and CVD.
Circulating microRNAs (miRs) have been investigated as diagnostic/prognostic biomarkers in human diseases. However, little is known about their expression throughout the aging process.
Eleven healthy individuals aged 20, 80 and 100years underwent miR plasma profiling. The validation cohort consisted of 111 healthy adults (CTR) aged 20–105years and included 30 centenarians. In addition, 34 patients with cardiovascular disease (CVD) and 15 healthy centenarian offspring (CO) were enrolled.
An exploratory factorial analysis grouped the miRs into three main factors: factor 1 primarily higher in 20-year-old subjects, but these differences did not reach statistical significance, factor 2 primarily higher in octogenarians and factor 3 primarily higher in centenarians. MiR-21, the most highly expressed miR of factors 2 and 3, was further validated, confirming the differences in the age groups. MiR-21 expression was higher in the CVD patients and lower in the CO compared to the age-matched CTR. MiR-21 was correlated with C-reactive protein and fibrinogen levels. TGF-β signaling was the predicted common pathway targeted by miRs of factors 2 and 3. TGF-βR2 mRNA, a validated miR-21 target, showed the highest expression in the leukocytes from a subset of the octogenarians.
Our findings suggest that miR-21 may be a new biomarker of inflammation.
Purpose
Sacubitril/valsartan has been associated with a positive reverse left ventricular remodelling in patients with heart failure with reduced ejection fraction (HFrEF). These patients may also ...benefit from an ICD implant. We aimed to assess EF improvement after 6 months of treatment with sacubitril/valsartan, evaluating when ICD as primary prevention was no longer indicated.
Methods
Multicentre, observational, prospective study enrolling all consecutive patients with HFrEF and EF ≤ 35% with an ICD as primary prevention and starting treatment with sacubitril/valsartan (NCT03935087). Resynchronization therapy and patients experiencing appropriate ICD therapies before sacubitril/valsartan were excluded.
Results
Two-hundred-and-thirty patients were enrolled (73.9% males, mean age 64.3 ± 12.1 years) After 6 months of treatment, a reduction in left ventricular end-diastolic and end-systolic volumes was noted and LVEF increased from 28.3 ± 5.6% to 32.2 ± 6.5% (
p
< 0.001). At 6 months, a non-ischemic aetiology of cardiomyopathy and a final dose of sacubitril/valsartan > 24/26 mg twice daily were associated with a higher probability of an absolute increase of > 5% in LVEF. A total of 5.3% of primary prevention patients still had an arrhythmic event in the first 6 months after treatment with sacubitril/valsartan started.
Conclusions
Sacubitril/valsartan improves systolic function in HFrEF, mainly due to reverse left ventricular remodelling. Improvement in EF after 6 months of treatment could help prevent ICD implantation in nearly one out of four patients, with important clinical and economic implications. However, the risk of sudden cardiac death in this recovered HFrEF population has not been thoroughly studied, and the present data should be interpreted only as hypothesis-generating.
Objectives: Physical exercise significantly impacts the biochemistry of the organism. Ubiquinone is a key component of the mitochondrial respiratory chain and ubiquinol, its reduced and active form, ...is an emerging molecule in sport nutrition. The aim of this study was to evaluate the effect of ubiquinol supplementation on biochemical and oxidative stress indexes after an intense bout of exercise.
Methods: 21 male young athletes (26 + 5 years of age) were randomized in two groups according to a double blind cross-over study, either supplemented with ubiquinol (200 mg/day) or placebo for 1 month. Blood was withdrawn before and after a single bout of intense exercise (40 min run at 85% maxHR). Physical performance, hematochemical parameters, ubiquinone/ubiquinol plasma content, intracellular reactive oxygen species (ROS) level, mitochondrial membrane depolarization, paraoxonase activity and oxidative DNA damage were analyzed.
Results: A single bout of intense exercise produced a significant increase in most hematochemical indexes, in particular CK and Mb while, on the contrary, normalized coenzyme Q
10
plasma content decreased significantly in all subjects. Ubiquinol supplementation prevented exercise-induced CoQ deprivation and decrease in paraoxonase activity. Moreover at a cellular level, in peripheral blood mononuclear cells, ubiquinol supplementation was associated with a significant decrease in cytosolic ROS while mitochondrial membrane potential and oxidative DNA damage remained unchanged.
Discussion: Data highlights a very rapid dynamic of CoQ depletion following intense exercise underlying an increased demand by the organism. Ubiquinol supplementation minimized exercise-induced depletion and enhanced plasma and cellular antioxidant levels but it was not able to improve physical performance indexes or markers of muscular damage.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In this randomized, double-blind, single-center trial (ANZCTR number ACTRN12619000436178) we aimed to investigate changes in endothelium-dependent vasodilation induced by ubiquinol, the reduced form ...of coenzyme Q10 (CoQ10), in healthy subjects with moderate dyslipidemia. Fifty-one subjects with low-density lipoprotein (LDL) cholesterol levels of 130-200 mg/dL, not taking statins or other lipid lowering treatments, moderate (2.5%-6.0%) endothelial dysfunction as measured by flow-mediated dilation (FMD) of the brachial artery, and no clinical signs of cardiovascular disease were randomized to receive either ubiquinol (200 or 100 mg/day) or placebo for 8 weeks. The primary outcome measure was the effect of ubiquinol supplementation on FMD at the end of the study. Secondary outcomes included changes in FMD on week 4, changes in total and oxidized plasma CoQ10 on week 4 and week 8, and changes in serum nitrate and nitrite levels (NOx), and plasma LDL susceptibility to oxidation in vitro on week 8. Analysis of the data of the 48 participants who completed the study demonstrated a significantly increased FMD in both treated groups compared with the placebo group (200 mg/day, +1.28% ± 0.90%; 100 mg/day, +1.34% ± 1.44%;
< 0.001) and a marked increase in plasma CoQ10, either total (
< 0.001) and reduced (
< 0.001). Serum NOx increased significantly and dose-dependently in all treated subjects (
= 0.016), while LDL oxidation lag time improved significantly in those receiving 200 mg/day (
= 0.017). Ubiquinol significantly ameliorated dyslipidemia-related endothelial dysfunction. This effect was strongly related to increased nitric oxide bioavailability and was partly mediated by enhanced LDL antioxidant protection.
The Neutrophil-to-lymphocyte ratio (NLR) is a marker of poor prognosis in hospitalized older patients with different diseases, but there is still no consensus on the optimal cut-off value to identify ...older patients at high-risk of in-hospital mortality. Therefore, in this study we aimed at both validating NLR as a predictor of death in older hospitalized patients and assess whether the presence of specific acute diseases can modify its predictive value.
This prospective cohort study included 5034 hospitalizations of older patients admitted to acute care units in the context of the ReportAge study. NLR measured at admission was considered as the exposure variable, while in-hospital mortality was the outcome of the study. ROC curves with Youden's method and restricted cubic splines were used to identify the optimal NLR cut-off of increased risk. Cox proportional hazard models, stratified analyses, and Kaplan-Meier survival curves were used to analyse the association between NLR and in-hospital mortality.
Both continuous and categorical NLR value (cut-off ≥ 7.95) predicted mortality in bivariate and multivariate prognostic models with a good predictive accuracy. The magnitude of this association was even higher in patients without sepsis, congestive heart failure, and pneumonia, and those with higher eGFR, albumin, and hemoglobin (p < 0.001). A negative multiplicative interaction was found between NLR and eGFR < 45 (p = 0.001).
NLR at admission is a readily available and cost-effective biomarker that could improve identification of geriatric patients at high risk of death during hospital stay independent of admitting diagnosis, kidney function and hemoglobin levels.
Atrial fibrillation (AF) has been associated with higher morbidity and mortality rates, especially in older patients. Subclinical atrial fibrillation (SCAF) is defined as the presence of atrial ...high-rate episodes (AHREs) > 190 bpm for 10 consecutive beats > 6 min and <24 h, as detected by cardiac implanted electronic devices (CIEDs). The selection of eligible patients for anticoagulation therapy among elderly individuals with AHREs detected through CIEDs remains a contentious issue. The meta-analysis of ARTESiA and NOAH-AFNET 6 clinical trials revealed that taking Edoxaban or Apixaban as oral anticoagulation therapy can reduce the risk of stroke by approximately 32% while increasing the risk of major bleeding by approximately 62%. However, it is still unclear which are, among patients with SCAF, those who can take the highest net clinical benefit from anticoagulant therapy. The present review summarizes the current evidence on this intriguing issue and suggests strategies to try to better stratify the risk of stroke and systemic embolism in patients with AHREs. We propose incorporating some parameters including chronic kidney disease (CKD), obesity, enlarged left atrial volume, the efficacy in blood pressure management, and frailty into the traditional CHA2DS2-VASc score. Future trials will be needed to verify the clinical usefulness of the proposed prognostic score mainly in the view of a personalized therapeutic approach in patients with SCAF.
Disorders of lipoprotein metabolism are among the major risk factors for cardiovascular disease (CVD) development. Single nucleotide polymorphisms (SNPs) have been associated with the individual ...variability in blood lipid profile and response to lipid-lowering treatments. Here, we genotyped 34 selected SNPs located in coding genes related to lipid metabolism, inflammation, coagulation, and a polymorphism in the
gene-a microRNA previously linked to CVD-to evaluate the association with lipid trait in subjects with moderate dyslipidemia not on lipid-lowering treatment (Treatment-naïve (TN) cohort,
= 125) and in patients treated with statins (STAT cohort,
= 302). We also explored the association between SNPs and the effect of a novel phytochemical lipid-lowering treatment in the TN cohort. We found that 6 SNPs (in the
, TNFA, CETP, SOD2, and VEGFA genes) were associated with lipid traits in the TN cohort, while no association was found with the response to twelve-week phytochemical treatment. In the STAT cohort, nine SNPs (in the
, CETP, CYP2C9, IL6, ABCC2, PON1, IL10, and VEGFA genes) were associated with lipid traits, three of which were in common with the TN cohort. Interestingly, in both cohorts, the presence of the rs3746444
SNP was associated with a more favorable blood lipid profile. Our findings could add information to better understand the individual genetic variability in maintaining a low atherogenic lipid profile and the response to different lipid-lowering therapies.
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.
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