Search Results (69)

Atherosclerotic cardiovascular disease (ASCVD) has long been screened using the traditional lipid profile, mainly focusing on LDL cholesterol. However, despite growing evidence supporting lipoprotein(a) [Lp(a)] as an independent risk factor involved in atherosclerosis, its clinical use remains limited. This review examines the reasons behind the limited use of Lp(a) screening in clinical practice, assessing its role in cardiovascular risk, comparing it to traditional lipid markers and evaluating current assessment methods. It also explores existing and emerging treatments, including gene-silencing therapies, for managing elevated Lp(a) levels. One in four clinicians does not routinely check Lp(a) levels, which proves a lack of awareness amongst them. The reasons for that are implied to be that the cost is too high and that available treatments are scarce. The traditional lipid profile, including LDL, high-density lipoprotein (HDL) and triglycerides, continues to be the gold standard for CV risk assessment. One limitation of using Lp(a) in clinical practice is the significant variability in apo(a) sizes, which results from the presence of multiple isoforms determined by the number of kringle domains. This structural diversity poses challenges in standardizing measurement methods, affecting the accuracy and comparability of results. While statins have a minimal impact on Lp(a), PCSK9-i lowers its levels by 20–25%, although this class is not prescribed primarily for this reason. Lastly, gene-silencing therapies, which achieve the greatest reduction in Lp(a) levels, are still in phase III trials, and there is still a need to examine whether this reduction translates into CV benefits. These limitations should not discourage further research, because ASCVD’s complexity requires a more tailored approach. Current lipid-lowering therapy still fails in a minority of cases, as evidenced by new-onset cardiovascular events in patients with well-controlled LDL levels. There is a need for future interventional studies to assess whether a reduction in Lp(a) by PCSK9-i really translates into CV benefits, independent of LDL. Full article

Background and Clinical Significance: Statins are a widely used drug class associated with a plethora of muscular side effects ranging from the subclinical elevation of creatine kinase to fulminant rhabdomyolysis. Cardiac myopathy secondary to statin treatment is rare and was recently reported as a part of statin-induced necrotizing autoimmune myopathy (SINAM). Its occurrence outside of this context is still debated. Case Presentation: We present the case of a 60-year-old male who developed atorvastatin-induced rhabdomyolysis, without associated hydroxymethyl glutaryl coenzyme A reductase (HMGCR) antibodies, with clinical findings of cardiac failure and severe ECG anomalies. The symptoms slowly regressed with statin withdrawal, and the patient made a full recovery. We discuss the recently proposed statin-associated cardiomyopathy (SACM) and the possible mechanisms. We compare our case to the three other cases of statin-induced cardiac myositis found in the literature. Conclusions: We believe that in vulnerable patients, as was our case, statins can determine significant subacute cardiac toxicity. This would seem to occur in the context of severe skeletal muscle injury, probably due to higher metabolic resistance on the part of the myocardium. Also, the available evidence suggests myocardial involvement should be actively investigated in SINAM patients, preferably by cardiac MRI. Full article

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, often involving a strong genetic background. Polygenic risk scores (PRSs) combine the cumulative effects of multiple genetic variants to quantify an individual’s susceptibility to CVD. Pharmacogenomics (PGx) can further personalize treatment by tailoring medication choices to an individual’s genetic profile. Even with these potential benefits, the extent to which PRS can be integrated into the PGx of CVD remains unclear. Our review provides an overview of current evidence on the application of PRS in the PGx of CVD, examining clinical utility and limitations and providing directions for future research. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews protocol, we conducted a comprehensive literature search in PubMed, EMBASE, and the Web of Science. Studies investigating the relationship between PRS in predicting the efficacy, adverse effects, or cost-effectiveness of cardiovascular medications were selected. Of the 1894 articles identified, 32 met the inclusion criteria. These studies predominantly examined lipid-lowering therapies, antihypertensives, and antiplatelets, although other medication classes (e.g., rate-control drugs, ibuprofen/acetaminophen, diuretics, and antiarrhythmics) were also included. Our findings showed that PRS is most robustly validated in lipid-lowering therapies, especially statins, where studies reported that individuals with higher PRSs derived the greatest reduction in lipids while on statins. Studies analyzing antihypertensives, antiplatelets, and antiarrhythmic medications demonstrated more variable outcomes, though certain PRSs did identify subgroups with significantly improved response rates or a higher risk of adverse events. Though PRS was a strong tool in many cases, we found some key limitations in its applicability in research, such as the under-representation of non-European-ancestry cohorts in the examined studies and a lack of standardized outcome reporting. In conclusion, though PRS offers promise in improving the efficacy of PGx of CVD by enhancing the personalization of medication on an individual level, several obstacles, such as the need for including a broader ancestral diversity and more robust cost-effectiveness data remain. Future research must (i) prioritize validating PRS in ethnically diverse populations, (ii) refine PRS derivation methods to tailor them for drug response phenotypes, and (iii) establish clear and attainable guidelines for standardizing the reporting of outcomes. Full article

Cardiovascular drugs are widely used for the prevention and treatment of various cardiac and vascular disorders. However, some of these drugs can also cause adverse effects on the kidney, leading to acute or chronic renal dysfunction, electrolyte imbalances, and increased mortality. The mechanisms of drug-induced renal toxicity vary depending on the type and class of the drug, the dose and duration of exposure, and the patient’s characteristics and comorbidities. In this review, we summarize the current knowledge on the renal effects of some common cardiovascular drugs, such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta-blockers, antiplatelet agents, anticoagulants, and statins and proton-pump inhibitors. We also discuss the clinical implications and management strategies for preventing or minimizing drug-induced nephrotoxicity, as well as the potential role of oxidative stress in its pathogenesis. Full article

The introduction of anticancer agents has transformed oncology, significantly improving survival rates. However, these therapies have introduced unintended cardiovascular risks, with atherosclerovascular disease (ASCVD) emerging as a leading cause of morbidity and mortality among cancer survivors. The development of ASCVD in this population involves multifactorial mechanisms, including endothelial dysfunction, oxidative stress, systemic inflammation, and disrupted lipid metabolism. This review examines the various mechanisms through which anticancer chemotherapy contributes to ASCVD and highlights strategies for risk assessment and management. Each class of anticancer agents presents distinct cardiovascular challenges: anthracyclines induce oxidative stress and endothelial damage, promoting foam cell formation and plaque progression; taxanes and vascular endothelial growth factor (VEGF) inhibitors impair lipid metabolism and vascular stability; anti-metabolites exacerbate endothelial injury through reactive oxygen species; and mTOR inhibitors, hormonal therapies, tyrosine kinase inhibitors, and immune checkpoint inhibitors disrupt lipid profiles and inflammatory pathways, increasing the risk of plaque rupture and thrombosis. Mitigating chemotherapy-induced ASCVD necessitates a comprehensive, multidisciplinary approach. Detailed pre-treatment cardiovascular risk assessments must address traditional and cancer-specific risk factors, including demographics, pre-existing conditions, and modifiable behaviors such as smoking and inactivity. Pharmacological interventions like statins and angiotensin-converting enzyme (ACE) inhibitors, paired with lifestyle modifications, are essential to reducing ASCVD risk. In resource-limited settings, cost-effective strategies should be prioritized to enhance accessibility. Establishing cardio-oncology units facilitates care coordination, while long-term surveillance enables timely detection and intervention. These strategies collectively improve cardiovascular outcomes and survivorship in diverse patient populations. Full article

Inflammation has been widely recognized as one of the major pathophysiological drivers of the development of atrial fibrillation (AF), which works in tandem with other risk factors of AF including obesity, diabetes, hypertension, and heart failure (HF). Our current understanding of the role of inflammation in the natural history of AF remains elusive; however, several key players, including the NLRP3 (NLR family pyrin domain containing 3) inflammasome, have been acknowledged to be heavily influential on chronic inflammation in the atrial myocardium, which leads to fibrosis and eventual degradation of its electrical function. Nevertheless, our current methods of pharmacological modalities with reported immunomodulatory properties, including well-established classes of drugs e.g., drugs targeting the renin–angiotensin–aldosterone system (RAAS), statins, and vitamin D, have proven effective in reducing the overall risk of developing AF, the onset of postoperative atrial fibrillation (POAF), and reducing overall mortality among patients with AF. This might bring hope for further progress in developing new treatment modalities targeting cellular checkpoints of the NLRP3 inflammasome pathway, or revisiting other well-known anti-inflammatory drugs e.g., colchicine, vitamin C, nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticosteroids, and antimalarial drugs. In our review, we aim to find relevant upstream anti-inflammatory treatment methods for the management of AF and present the most current real-world evidence of their clinical utility. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the novel terminology encompassing liver disease associated with metabolic dysfunction, replacing the previous terminology of non-alcoholic fatty liver disease (NAFLD). This disease is strongly associated with metabolic disorders such as obesity, type 2 diabetes, and dyslipidemia. MASLD and dyslipidemia are deeply interconnected, driven by shared pathophysiological mechanisms. Emerging evidence suggests that statins, a class of lipid-lowering medications, may have beneficial effects on MASLD beyond their primary role in reducing cholesterol levels through several mechanisms, including anti-inflammatory, antioxidant, anti-fibrosis, and immunomodulatory effects. This review aims to summarize the efficacy of statins in the management of MASLD and provide insights into their potential mechanisms of action. It discusses the pathophysiology of MASLD and the role of statins in targeting key aspects of the disease. Additionally, the review examines the clinical evidence supporting the use of different statins in MASLD treatment and highlights their specific effects on liver enzymes, inflammation, and fibrosis. Furthermore, an algorithm for statin therapy in MASLD is proposed based on the current knowledge and available evidence. Full article

Pancreatic lipase serves as a primary trigger for hyperlipidemia and is also a crucial target in the inhibition of hypercholesterolemia. By synthesizing anti-hypercholesterolemic drugs such as atorvastatin, which are used to treat hypercholesterolemia, there were some side effects associated with the long-term use of statins. Based on this idea, in the present study, we identified peptides that inhibited PL by virtual screening and in vitro activity assays. In addition, to delve into the underlying mechanisms, we undertook a dual investigative approach involving both molecular docking analyses and molecular dynamics simulations. The results showed that peptides RK7, KQ7, and TL9, all with molecular weights of <1000 Da and a high proportion of hydrophobic amino acids, inhibited PL well. Molecular docking and molecular dynamics showed that peptides RK7, KQ7, and TL9 bound to important amino acid residues of PL, such as Pro and Leu, through hydrogen bonding, hydrophobic interactions, salt bridges, and π-π stacking to occupy the substrate-binding site, which inhibited PL and identified them as potential PL inhibitors. In vitro tests showed that the IC₅₀ of RK7 and KQ7 on PL were 0.690 mg/mL and 0.593 mg/mL, respectively, and the inhibitory effects of RK7 and KQ7 on PL were significantly enhanced after simulated gastrointestinal digestion. Our results suggested that peptides RK7 and KQ7 from yak milk cheese can be identified as a novel class of potential PL inhibitors. Full article

Hypertriglyceridemia therapy is essential for preventing cardiovascular diseases. Fibrates belong to an important class of lipid-lowering drugs useful for the management of dyslipidaemia. By acting on the peroxisome proliferator-activated receptor (PPAR)-α, these drugs lower serum triglyceride levels and raise high-density lipoprotein cholesterol. Fibrate monotherapy is associated with a risk of myopathy and this risk is enhanced when these agents are administered together with statins. However, whereas gemfibrozil can increase plasma concentrations of statins, fenofibrate has less influence on the pharmacokinetics of statins. Pemafibrate is a new PPAR-α-selective drug considered for therapy, and clinical trials are ongoing. Apart from this class of drugs, new therapies have emerged with different mechanisms of action to reduce triglycerides and the risk of cardiovascular diseases. Full article

Metabolic syndrome prevalence is between 24 and 27% and poses a significant risk for the development of atherosclerotic cardiovascular disease (ASCVD), type 2 diabetes (T2D), or other comorbidities. Currently, no drugs are approved for metabolic syndrome treatment itself, so the risk factors are treated with therapies approved for cardiac and metabolic conditions. These are approved drugs for dyslipidemia treatment such as statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, cornerstone antihypertensive drugs, or novel class glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RA) for T2D and overweight or obesity treatment. We have also evaluated new pharmacological interventions in clinical development that have reached Phase 2 and/or Phase 3 randomized clinical trials (RCTs) for the management of the risk factors of metabolic syndrome. In the pipeline are glucose-dependent insulinotropic polypeptide (GIP), GLP-1, glucagon receptor (GCGR), amylin agonists, and a combination of the latter for T2D and overweight or obesity treatment. Non-entero-pancreatic hormone-based therapies such as ketohexokinase (KHK) inhibitor, growth differentiation factor 15 (GDF15) agonists, monoclonal antibodies (mAbs) as activin type II receptors (ActRII) inhibitors, and a combination of anti-α-myostatin (GFD8) and anti-Activin-A (Act-A) mAbs have also reached Phase 2 or 3 RCTs in the same indications. Rilparencel (Renal Autologous Cell Therapy) is being evaluated in patients with T2D and chronic kidney disease (CKD) in a Phase 3 trial. For dyslipidemia treatment, novel PCSK9 inhibitors (oral and subcutaneous) and cholesteryl ester transfer protein (CETP) inhibitors are in the final stages of clinical development. There is also a surge of a new generation of an antisense oligonucleotide (ASO) and small interfering RNA (siRNA)-targeting lipoprotein(a) [Lp(a)] synthesis pathway that could possibly contribute to a further step forward in the treatment of dyslipidemia. For resistant and uncontrolled hypertension, aldosterone synthase inhibitors and siRNAs targeting angiotensinogen (AGT) messenger RNA (mRNA) are promising new therapeutic options. It would be interesting if a few drugs in clinical development for metabolic syndrome such as 6-bromotryptophan (6-BT), vericiguat, and INV-202 as a peripherally-acting CB1 receptor (CB1r) blocker would succeed in finally gaining the first drug approval for metabolic syndrome itself. Full article

Aims: The aim of this study was to explore the suspected adverse drug reaction (ADR) data of five licensed statins in the UK: atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin. A secondary aim was to determine if there are any associations between the polypharmacological properties of the statins and their associated muscle-related side effects. Methods: The chemical database of bioactive molecules with drug-like properties, European Molecular Biology Laboratory (ChEMBL), was used to obtain data on the pharmacological interactions of statins with human proteins. The Medicines and Healthcare Products Regulatory Agency’s (MHRA) Yellow Card scheme was used to obtain reports of suspected ADRs from 2018 to 2022. The OpenPrescribing database was used to obtain the prescribing rates for statistical interpretation. Results: The study found no significant difference between the statins association with suspected ADRs across all organ classes (X², p > 0.05). Fluvastatin was found to have a higher incidence of ADRs/100,000 R_x across multiple system organ classes. Conclusions: No significant difference was found between the suspected ADR incidence of the statins across all system organ classes. Full article

This report describes major pathomechanisms of disease in which the dysregulation of host inflammatory processes is a major factor, with cardiovascular disease (CVD) as a primary model, and reviews strategies for countermeasures based on synergistic interaction between various agents, including drugs and generally regarded as safe (GRAS) natural medical material (NMM), such as Ginkgo biloba, spice phytochemicals, and fruit seed flavonoids. The 15 well-defined CVD classes are explored with particular emphasis on the extent to which oxidative stressors and associated ischemia-reperfusion tissue injury contribute to major symptoms. The four major categories of pharmaceutical agents used for the prevention of and therapy for CVD: statins, beta blockers (β-blockers), blood thinners (anticoagulants), and aspirin, are presented along with their adverse effects. Analyses of major cellular and molecular features of drug- and NMM-mediated cardioprotective processes are provided in the context of their development for human clinical application. Future directions of the evolving research described here will be particularly focused on the characterization and manipulation of calcium- and calcineurin-mediated cascades of signaling from cell surface receptors on cardiovascular and immune cells to the nucleus, with the emergence of both protective and pathological epigenetic features that may be modulated by synergistically-acting combinations of drugs and phytochemicals in which phytochemicals interact with cells to promote signaling that reduces the effective dosage and thus (often) toxicity of drugs. Full article

Statins are a class of medications primarily used in adults to lower cholesterol levels and reduce the risk of cardiovascular events. However, the use of statins in children is generally limited and carefully considered despite the well-documented anti-inflammatory, anti-angiogenic, and pro-apoptotic effects, as well as their effect on cell signaling pathways. These multifaceted effects, known as pleiotropic effects, encompass enhancements in endothelial function, a significant reduction in oxidative stress, the stabilization of atherosclerotic plaques, immunomodulation, the inhibition of vascular smooth muscle proliferation, an influence on bone metabolism, anti-inflammatory properties, antithrombotic effects, and a diminished risk of dementia. In children, recent research revealed promising perspectives on the use of statins in various conditions including neurological, cardiovascular, and oncologic diseases, as well as special situations, such as transplanted children. The long-term safety and efficacy of statins in children are still subjects of ongoing research, and healthcare providers carefully assess the individual risk factors and benefits before prescribing these medications to pediatric patients. The use of statins in children is generally less common than in adults, and it requires close monitoring and supervision by healthcare professionals. Further research is needed to fully assess the pleiotropic effects of statins in the pediatric population. Full article

Although various guidelines for cardiovascular disease prevention have been established, the optimal drug therapy is often not implemented due to poor medication adherence and the clinical inertia of healthcare practitioners. Polypill strategies are one solution to this problem. Previous studies have established the usefulness of polypills, i.e., combination tablets including three or more medications, for the prevention of cardiovascular disease. For this purpose, the polypills generally contain an antiplatelet medication, an antihypertensive medication, and a statin. For the specific management of hypertension, combination therapy including more than two classes of antihypertensive medications is recommended by most international guidelines. Combination tablets including two classes of antihypertensive medications, such as renin-angiotensin system (RAS) inhibitors (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) and Ca-channel blockers or thiazide diuretics, have been reported to be useful for cardiovascular disease prevention and lowering blood pressure (BP) levels. The use of RAS inhibitors is recommended for a wide range of complications, including diabetes, chronic heart failure, and chronic kidney disease. The combination of an RAS inhibitor and diuretic or Ca-channel blocker is thus recommended for the management of hypertension. Finally, we expect that novel medications such as angiotensin receptor neprilysin inhibitors (ARNIs) and sodium glucose cotransporter 2 inhibitors (SGLT2i), which have a more diverse range of effects in hypertension, heart failure, or diabetes, may be a solution to the problem of polypharmacy. Evidence is accumulating on the benefits of polypill strategies in cardiovascular disease prevention. Combination tablets are also effective for the treatment of hypertension. Full article

We aimed to characterize non-oncologic chronic drug therapy of bladder cancer (BC) patients and evaluate a possible impact on recurrence-free (RFS) and cancer-specific survival (CSS). Patients with a first diagnosis (FD) of BC or radical cystectomy (RC) were included in a prospective, monocentric, observational study. Drugs and medical data was assessed at start and three-monthly for 24 months. Drugs were classified by anatomical-therapeutic-chemical code (ATC). Endpoints for outcome analysis were RFS and CSS in univariate (Kaplan–Meier curves and log-rank test, Cox regression for Hazard Ratio (HR)) and multivariate (Cox regression models) analyses. Of 113 patients, 52 had FD and 78 RC. Median age was 74 and 72 years, 83% and 82% were male. Drugs of 114 ATC classes were taken by 48 (92%) FD patients (median number 4.5/IQR 2–7.5) and 73 (94%) of RC patients (median 5/IQR 2–9). In univariate analysis (log-rank test (p)/Cox regression (HR, 95% CI, p)), polypharmacy (p = 0.036/HR = 2.83, 95% CI = 1.02–7.90, p = 0.047), calcium channel blockers (p = 0.046/HR = 2.47, 95% CI = 0.97–6.27, p = 0.057) and proton pump inhibitors (p = 0.015/HR = 3.16, 95% CI = 1.18–8.41, p = 0.022) had a significant negative impact on RFS in RC patients, statins (p = 0.025/HR = 0.14, 95% CI = 0.02–1.06, p = 0.057) a positive effect on RFS in FD patients, angiotensin-converting enzyme inhibitors (p = 0.008/HR = 10.74, 95% CI = 1.20–96.17, p = 0.034) and magnesium (p = 0.042/HR = 5.28, 95% CI = 0.88–31.59, p = 0.067) a negative impact on CSS in FD patients. In multivariate analysis, the only significant drug effects were the negative impact of angiotensin-converting enzyme inhibitors (HR = 15.20, 95% CI = 1.30–177.67, p = 0.030) and magnesium (HR = 22.87, 95% CI = 1.57–333.81), p = 0.022) on CSS in FD patients, and the positive impact of statins (HR = 0.12, 95% CI = 0.01–0.97, p = 0.047) on RFS in FD patients. Impact of non-oncologic drugs on RFS and CSS was small in this prospective study. Thus, appropriate treatment of comorbidities is encouraged. Full article