Nutraceuticals for the Control of Dyslipidaemias in Clinical Practice

Dyslipidaemias result in the deposition of cholesterol and lipids in the walls of blood vessels, chronic inflammation and the formation of atherosclerotic plaques, which impede blood flow and (when they rupture) result in acute ischaemic episodes. Whilst recent years have seen enormous success in the reduction of cardiovascular risk using conventional pharmaceuticals, there is increasing interest amongst patients and practitioners in the use of nutraceuticals to combat dyslipidaemias and inflammation in cardiovascular disease. Nutraceutical is a portmanteau term: ‘ceutical’ indicate pharmaceutical-grade preparations, and ‘nutra’ indicates that the products contain nutrients from food. Until relatively recently, little high-quality evidence relating to the safety and efficacy of nutraceuticals has been available to prescribers and policymakers. However, as a result of recent randomised-controlled trials, cohort studies and meta-analyses, this situation is changing, and nutraceuticals are now recommended in several mainstream guidelines relating to dyslipidaemias and atherosclerosis. This article will summarise recent clinical-practice guidance relating to the use of nutraceuticals in this context and the evidence which underlies them. Particular attention is given to position papers and recommendations from the International Lipid Expert Panel (ILEP), which has produced several practical and helpful recommendations in this field

RNA Silencing in the Management of Dyslipidemias

PURPOSE OF REVIEW: Remarkable reductions in cardiovascular morbidity and mortality have been achieved in recent decades through the widespread use of ‘small-molecule’ hypolipidaemic drugs such as statins and ezetimibe. An alternative approach is to perturb the production of proteins through ribonucleic acid (RNA) silencing, leading to long-lasting knock-down of specific biological molecules. This review describes the scientific basis of RNA silencing, and critically evaluates the evidence relating to inclisiran, a small interfering RNA against proprotein convertase subtilisin kexin 9 (PCSK9). RECENT FINDINGS: Pooled analysis of three recent ORION trials has demonstrated that twice-yearly administration of inclisiran reduces LDL-C by 50% in a range of patient groups, with only mild adverse effects. SUMMARY: Inclisiran provides safe, effective and long-lasting reductions in PCSK9 and LDL-C. The results of the phase-3 ORION-4 outcomes study are eagerly awaited. Further promising RNA silencing technologies have the potential to improve the management of dyslipidaemia

Curcumin-The Nutraceutical With Pleiotropic Effects? Which Cardiometabolic Subjects Might Benefit the Most?

Despite continuous advances in pharmacotherapy, atherosclerotic cardiovascular disease remains the world's leading killer. Atherosclerosis relates not only to an increased level of cholesterol, but involves the development of atherosclerotic plaques, which are formed as a result of processes including inflammation and oxidative stress. Therefore, in addition to the classical risk factors for ASCVD (such as type 2 diabetes, overweight, obesity, hypertension and metabolic syndrome), residual risk factors such as inflammation and oxidative stress should also be reduced. The most important intervention in ASCVD is prevention, which includes promoting a healthy diet based on products of natural origin. Curcumin, which is often present in the diet, has been demonstrate to confer several benefits to health. It has been shown in numerous clinical trials that curcumin exhibited anti-diabetic, lipid-lowering, antihypertensive, antioxidant and anti-inflammatory effects, as well as promoting weight loss. All this means that curcumin has a comprehensive impact on the most important risk factors of ASCVD and may be a beneficial support in the treatment of these diseases. Recently, it has also been shown that curcumin may have a beneficial effect on the course of SARS-CoV-2 infection and might be helpful in the prevention of long-COVID complications. The aim of this review is to summarize the current knowledge regarding the safety and efficacy of curcumin in the prevention and treatment of cardiometabolic diseases

Personalized management of dyslipidemias in patients with diabetes-it is time for a new approach (2022)

Dyslipidemia in patients with type 2 diabetes (DMT2) is one of the worst controlled worldwide, with only about 1/4 of patients being on the low-density lipoprotein cholesterol (LDL-C) target. There are many reasons of this, including physicians' inertia, including diabetologists and cardiologists, therapy nonadherence, but also underusage and underdosing of lipid lowering drugs due to unsuitable cardiovascular (CV) risk stratification. In the last several years there is a big debate on the risk stratification of DMT2 patients, with the strong indications that all patients with diabetes should be at least at high cardiovascular disease (CVD) risk. Moreover, we have finally lipid lowering drugs, that not only allow for the effective reduction of LDL-C and do not increase the risk of new onset diabetes (NOD), and/or glucose impairment; in the opposite, some of them might effectively improve glucose control. One of the most interesting is pitavastatin, which is now available in Europe, with the best metabolic profile within statins (no risk of NOD, improvement of fasting blood glucose, HOMA-IR, HbA1c), bempedoic acid (with the potential for the reduction of NOD risk), innovative therapies-PCSK9 inhibitors and inclisiran with no DMT2 risk increase, and new forthcoming therapies, including apabetalone and obicetrapib-for the latter one with the possibility of even decreasing the number of patients diagnosed with prediabetes and DMT2. Altogether, nowadays we have possibility to individualize lipid lowering therapy in DMT2 patients and increase the number of patients on LDL-C goal without any risk of new onset diabetes and/or diabetes control worsening, and in consequence to reduce the risk of CVD complications due to progression of atherosclerosis in this patients' group

CRISPR Gene Editing in Lipid Disorders and Atherosclerosis: Mechanisms and Opportunities

Elevated circulating concentrations of low-density lipoprotein cholesterol (LDL-C) have been conclusively demonstrated in epidemiological and intervention studies to be causally associated with the development of atherosclerotic cardiovascular disease. Enormous advances in LDL-C reduction have been achieved through the use of statins, and in recent years, through drugs targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of the hepatic LDL-receptor. Existing approaches to PCSK9 targeting have used monoclonal antibodies or RNA interference. Although these approaches do not require daily dosing, as statins do, repeated subcutaneous injections are nevertheless necessary to maintain effectiveness over time. Recent experimental studies suggest that clustered regularly interspaced short palindromic repeats (CRISPR) gene-editing targeted at PCSK9 may represent a promising tool to achieve the elusive goal of a ‘fire and forget’ lifelong approach to LDL-C reduction. This paper will provide an overview of CRISPR technology, with a particular focus on recent studies with relevance to its potential use in atherosclerotic cardiovascular disease

Clinical Features of Familial Hypercholesterolemia in Children and Adults in EAS-FHSC Regional Center for Rare Diseases in Poland

Background: Familial hypercholesterolemia (FH) is a genetic autosomal co-dominant metabolic disorder leading to elevated circulating concentrations of low-density lipoprotein cholesterol (LDL-C). Early development of atherosclerotic cardiovascular disease (ASCVD) is common in affected patients. We aimed to evaluate the characteristics and differences in the diagnosis and therapy of FH children and adults. Methods: All consecutive patients who were diagnosed with FH, both phenotypically and with genetic tests, were included in this analysis. All patients are a part of the European Atherosclerosis Society FH-Study Collaboration (FHSC) regional center for rare diseases at the Polish Mother’s Memorial Hospital Research Institute (PMMHRI) in Lodz, Poland. Results: Of 103 patients with FH, there were 16 children (15.5%) at mean age of 9 ± 3 years and 87 adults aged 41 ± 16; 59% were female. Children presented higher mean levels of total cholesterol, LDL-C, and high-density lipoprotein cholesterol (HDL-C) measured at the baseline visit (TC 313 vs. 259 mg/dL (8.0 vs. 6.6 mmol/L), p = 0.04; LDL 247 vs. 192 mg/dL (6.3 vs. 4.9 mmol/L), p = 0.02, HDL 53 vs. 48 mg/dL (1.3 vs. 1.2 mmol/L), p = 0.009). Overall, 70% of adult patients and 56% of children were prescribed statins (rosuvastatin or atorvastatin) on admission. Combination therapy (dual or triple) was administered for 24% of adult patients. Furthermore, 13.6% of adult patients and 19% of children reported side effects of statin therapy; most of them complained of muscle pain. Only 50% of adult patients on combination therapy achieved their treatment goals. None of children achieved the treatment goal. Conclusions: Despite a younger age of FH diagnosis, children presented with higher mean levels of LDL-C than adults. There are still urgent unmet needs concerning effective lipid-lowering therapy in FH patients, especially the need for greater use of combination therapy, which may allow LDL-C targets to be met in most of the patients

Pharmacist-led intervention for older people with atrial fibrillation in long-term care (PIVOTALL study): a randomised pilot and feasibility study.

BackgroundOlder care home residents are a vulnerable group of people with atrial fibrillation (AF) at high risk of adverse health events. The Atrial Fibrillation Better Care (ABC: Avoid stroke; Better symptom management; Cardiovascular and other comorbidity management) pathway is the gold-standard approach toward integrated AF care, and pharmacists are a potential resource with regards to its' implementation. The aim of this study was to determine the feasibility of pharmacist-led medicines optimisation in care home residents, based on the ABC pathway compared to usual care.MethodsIndividually randomised, prospective pilot and feasibility study of older (aged ≥ 65 years) care home residents with AF (ISRCTN14747952); residents randomised to ABC pathway optimised care versus usual care. The primary outcome was a description of study feasibility (resident and care home recruitment and retention). Secondary outcomes included the number and type of pharmacist medication recommendations and general practitioner (GP) implementation.ResultsTwenty-one residents were recruited and 11 (mean age [standard deviation] 85.0 [6.5] years, 63.6% female) were randomised to receive pharmacist-led medicines optimisation. Only 3/11 residents were adherent to all three components of the ABC pathway. Adherence was higher to 'A' (9/11 residents) and 'B' (9/11 residents) components compared to 'C' (3/11 residents). Four ABC-specific medicines recommendations were made for three residents, and two were implemented by residents' GPs. Overall ABC adherence rates did not change after pharmacist medication review, but adherence to 'A' increased (from 9/11 to 10/11 residents). Other ABC recommendations were inappropriate given residents' co-morbidities and risk of medication-related adverse effects.ConclusionsThe ABC pathway as a framework was feasible to implement for pharmacist medication review, but most residents' medications were already optimised. Low rates of adherence to guideline-recommended therapy were a result of active decisions not to treat after assessment of the net risk-benefit

Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales:a routine data linkage study 2003-2018

OBJECTIVE: To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents. METHODS: Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality. RESULTS: There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8–90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1–17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9–17.9) in 2010 to 17.0% (16.1–18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17–1.37], P < 0.001), all-cause mortality (adjusted HR 1.14 [1.11–1.17], P < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36–1.76], P < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22–1.34], P < 0.001). CONCLUSIONS: Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy

Validation study of a web-based assessment of functional recovery after radical prostatectomy

<p>Abstract</p> <p>Background</p> <p>Good clinical care of prostate cancer patients after radical prostatectomy depends on careful assessment of post-operative morbidities, yet physicians do not always judge patient symptoms accurately. Logistical problems associated with using paper questionnaire limit their use in the clinic. We have implemented a web-interface ("STAR") for patient-reported outcomes after radical prostatectomy.</p> <p>Methods</p> <p>We analyzed data on the first 9 months of clinical implementation to evaluate the validity of the STAR questionnaire to assess functional outcomes following radical prostatectomy. We assessed response rate, internal consistency within domains, and the association between survey responses and known predictors of sexual and urinary function, including age, time from surgery, nerve sparing status and co-morbidities.</p> <p>Results</p> <p>Of 1581 men sent an invitation to complete the instrument online, 1235 responded for a response rate of 78%. Cronbach's alpha was 0.84, 0.86 and 0.97 for bowel, urinary and sexual function respectively. All known predictors of sexual and urinary function were significantly associated with survey responses in the hypothesized direction.</p> <p>Conclusions</p> <p>We have found that web-based assessment of functional recovery after radical prostatectomy is practical and feasible. The instrument demonstrated excellent psychometric properties, suggested that validity is maintained when questions are transferred from paper to electronic format and when patients give responses that they know will be seen by their doctor and added to their clinic record. As such, our system allows ready implementation of patient-reported outcomes into routine clinical practice.</p

Serum antinuclear autoantibodies are associated with measures of oxidative stress and lifestyle factors:analysis of LIPIDOGRAM2015 and LIPIDOGEN2015 studies

Introduction: Oxidative stress is one of many factors suspected to promote antinuclear autoantibody (ANA) formation. Reactive oxygen species can induce changes in the antigenic structure of macromolecules, causing the immune system to treat them as “neo-antigens” and start production of autoantibodies. This study was designed to evaluate the relationship between oxidative stress markers, lifestyle factors and the detection of ANA. Material and methods: We examined measures of oxidative stress indices of free-radical damage to lipids and proteins, such as total oxidant status (TOS), concentration of protein thiol groups (PSH), and malondialdehyde (MDA), activity of superoxide dismutase (SOD) in 1731 serum samples. The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid (UA) concentration, were also measured and the oxidative stress index (OSI-index) was calculated. All samples were tested for the presence of ANA using an indirect immunofluorescence assay (IIFA). Results: The presence of ANA in women was associated with lower physical activity (p = 0.036), less frequent smoking (p = 0.007) and drinking of alcohol (p = 0.024) accompanied by significant changes in SOD isoenzymes activity (p &lt; 0.001) and a higher uric acid (UA) concentration (p &lt; 0.001). In ANA positive males we observed lower concentrations of PSH (p = 0.046) and increased concentrations of MDA (p = 0.047). Conclusions: The results indicate that local oxidative stress may be associated with increased probability of ANA formation in a sex-specific manner.</p