In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.
1 December 2021 in Current Atherosclerosis Reports
Familial hypercholesterolemia (FH) is one of the most common monogenic diseases, leading to an increased risk of premature atherosclerosis and its cardiovascular complications due to its effect on plasma cholesterol levels. Variants of three genes (LDL-R, APOB and PCSK9) are the major causes of FH, but in some probands, the FH phenotype is associated with variants of other genes. Alternatively, the typical clinical picture of FH can result from the accumulation of common cholesterol-increasing alleles (polygenic FH). Although the Czech Republic is one of the most successful countries with respect to FH detection, approximately 80% of FH patients remain undiagnosed. The opportunities for international collaboration and experience sharing within international programs (e.g., EAS FHSC, ScreenPro FH, etc.) will improve the detection of FH patients in the future and enable even more accessible and accurate genetic diagnostics.
12 April 2016 in European Heart Journal Supplements
A panel of European experts on lipids and cardiovascular disease discussed clinical approaches to managing cardiovascular risk in clinical practice, including residual cardiovascular risk associated with lipid abnormalities, such as atherogenic dyslipidaemia (AD). A simplified definition of AD was proposed to enhance understanding of this condition, its prevalence, and its impact on cardiovascular risk. Atherogenic dyslipidaemia can be defined by high fasting triglyceride levels (≥2.3 mmol/L) and low high-density lipoprotein cholesterol (HDL-c) levels (≤1.0 and ≤1.3 mmol/L in men and women, respectively) in statin-treated patients at high cardiovascular risk. The use of a single marker for the diagnosis and treatment of AD, such as non-HDL-c, was advocated. Interventions including lifestyle optimization and low-density lipoprotein (LDL)-lowering therapy with statins (±ezetimibe) are implemented by all experts. Treatment of residual AD can be performed with the addition of fenofibrate, since it can improve the complete lipoprotein profile and reduce the risk of cardiovascular events in patients with AD. Specific clinical scenarios in which fenofibrate may be prescribed are discussed, and include patients with very high triglycerides (≥5.6 mmol/L), patients who are intolerant or resistant to statins, and patients with AD and at high cardiovascular risk. The fenofibrate–statin combination was considered by the experts to benefit from a favourable benefit–risk profile. Cardiovascular experts adopt a multifaceted approach to the prevention of atherosclerotic cardiovascular disease, with lifestyle optimization, LDL-lowering therapy, and treatment of AD with fenofibrate routinely used to help reduce a patient's overall cardiovascular risk.
Alpha-lipoic acid (ALA) is a natural short-chain fatty acid that has attracted great attention in recent years as an antioxidant molecule. However, some concerns have been recently raised regarding its safety profile. To address the issue, we aimed to assess ALA safety profile through a systematic review of the literature and a meta-analysis of the available randomized placebo-controlled clinical studies. The literature search included EMBASE, PubMed Medline, SCOPUS, Google Scholar, and ISI Web of Science by Clarivate databases up to 15th August 2020. Data were pooled from 71 clinical studies, comprising 155 treatment arms, which included 4749 subjects with 2558 subjects treated with ALA and 2294 assigned to placebo. A meta-analysis of extracted data suggested that supplementation with ALA was not associated with an increased risk of any treatment-emergent adverse event (all p > 0.05). ALA supplementation was safe, even in subsets of studies categorized according to smoking habit, cardiovascular disease, presence of diabetes, pregnancy status, neurological disorders, rheumatic affections, severe renal impairment, and status of children/adolescents at baseline.