Which Statin is Best for the Kidneys? E Penson, Peter; Banach, Maciej; McCloskey, Alice P
Current vascular pharmacology,
2023, Letnik:
21, Številka:
1
Journal Article
Display omitted
Statins beside their main effect on reducing the progression of cardiovascular disease through pharmacological inhibition of the endogenous cholesterol synthesis, have additional ...pleiotropic effects including antiinflammatory effects mediated through the induction of suppressor regulatory T cells (Tregs). Statin-induced expansion of Tregs reduces chronic inflammation and may have beneficial effects in autoimmune diseases. However, statins could represent a double-edged sword in immunomodulation. Drugs that act by increasing the concentration of Tregs could enhance the risk of cancers, particularly in the elderly and may have adverse effects in neurodegenerative disorders and infectious diseases. In the present paper, we review the experimental studies that evaluate the effects of statins on Treg cells in autoimmune and inflammatory diseases and we discuss potential therapeutic applications of statins in this setting.
Elevated circulating concentrations of lipoprotein(a) Lp(a) is strongly associated with increased risk of atherosclerotic cardiovascular disease (CVD) and degenerative aortic stenosis. This ...relationship was first observed in prospective observational studies, and the causal relationship was confirmed in genetic studies. Everybody should have their Lp(a) concentration measured once in their lifetime. CVD risk is elevated when Lp(a) concentrations are high i.e. > 50 mg/dL (≥100 mmol/L). Extremely high Lp(a) levels >180 mg/dL (≥430 mmol/L) are associated with CVD risk similar to that conferred by familial hypercholesterolemia. Elevated Lp(a) level was previously treated with niacin, which exerts a potent Lp(a)-lowering effect. However, niacin is currently not recommended because, despite the improvement in lipid profile, no improvements on clinical outcomes have been observed. Furthermore, niacin use has been associated with severe adverse effects. Post hoc analyses of clinical trials with proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors have shown that these drugs exert clinical benefits by lowering Lp(a), independent of their potent reduction of low-density lipoprotein cholesterol (LDL-C). It is not yet known whether PCSK9 inhibitors will be of clinical use in patients with elevated Lp(a). Apheresis is a very effective approach to Lp(a) reduction, which reduces CVD risk but is invasive and time-consuming and is thus reserved for patients with very high Lp(a) levels and progressive CVD. Studies are ongoing on the practical application of genetic approaches to therapy, including antisense oligonucleotides against apolipoprotein(a) and small interfering RNA (siRNA) technology, to reduce the synthesis of Lp(a).
In addition to their cholesterol-lowering effects, statins are associated with pleiotropic effects including improvements in heart failure (HF), reduced blood pressure, prevention of the rupture of ...atherosclerotic plaques and improved angiogenesis. In addition to these cardiovascular benefits, statins have been implicated in the treatment of neurological injuries, cancer, sepsis, and cirrhosis. These cholesterol-independent beneficial effects of statins are predominantly mediated through signaling pathways leading to increased production and bioavailability of nitric oxide (NO). In this review, the mechanistic pathways and therapeutic effects of statin-mediated elevations of NO are described and discussed.
Purpose of Review
We aimed to summarize recent guidelines, position papers, and high-quality clinical research relating the use of nutraceuticals in the management of individuals at high risk of ...atherosclerotic cardiovascular disease.
Recent Findings
It is essential that individuals at high risk of cardiovascular disease receive guideline-directed evidence-based therapies to reduce their risk of morbidity and mortality from cardiovascular events. Compared with conventional therapeutics, nutraceuticals have undergone relatively little investigation in randomized controlled trials. Thus, recommendations for nutraceuticals in international guidelines are rare, and nutraceuticals should not be used preferentially in place of statins. Nevertheless, recent position papers from the International Lipid Expert Panel and clinical evidence from studies of triglyceride reduction by polyunsaturated fatty acid administration demonstrate that nutraceuticals do have an important role in optimizing therapy in individuals at high risk of cardiovascular disease. Roles for nutraceuticals include as follows: (1) managing residual risk associated with lipids other than low-density lipoprotein cholesterol (LDL-C); (2) managing non-lipid-mediated residual risk; (3) optimizing LDL-C treatment in statin intolerance; (4) optimizing LCL-C treatment when add-on therapies for statins are not available; (5) as adjuncts to lifestyle for individuals at high lifetime risk of atherosclerotic cardiovascular disease (ASCVD). The strength of evidence for each of these applications is variable.
Summary
In addition to guideline-directed therapeutics, nutraceuticals may have roles in optimizing preventative therapy and targeting residual risk in individuals at high risk of ASCVD. Application of Good Manufacturing Practice and randomized controlled trials when producing and evaluating nutraceuticals will expand the armoury of evidence-based agents for the prevention of ASCVD.
Purpose of Review
Recent studies have demonstrated an important role for inflammation in the pathogenesis of atherosclerotic cardiovascular disease. Several studies have investigated the efficacy of ...colchicine (a widely used and safe anti-inflammatory drug) in patients with atherosclerosis. This review explains the rationale for the use of colchicine in this setting and critically appraises recent outcome trials.
Recent Findings
Two large randomised-controlled trials LoDoCo2 (included patients with chronic coronary syndromes) and COLCOT (acute coronary syndromes) have demonstrated reductions in atherosclerotic cardiovascular events, but not mortality. A smaller study (COPS) found no beneficial effect of colchicine but was probably underpowered.
Summary
Colchicine is effective at reducing cardiovascular events in chronic and acute coronary syndromes, although reductions in all-cause mortality have not been demonstrated during the period of follow-up in trials to date. Mild gastrointestinal symptoms are the most commonly reported adverse effects, although in well-designed randomised controlled trials these are relatively uncommon.
PDF
