Year: 2019
Type: editorial
Abstract: Screening for High Lipoprotein(a)The Time Is Now Articles, see p 1472 and p 1483 I n 1994, the landmark 4S trial (Scandinavian Simvastatin Survival Study) reported that lowering low-density lipoprotein (LDL) cholesterol with simvastatin reduced cardiovascular events in patients with coronary artery disease and hypercholesterolemia. 1 This seminal trial crystallized our understanding of the causal role of LDL cholesterol in atherosclerosis and launched the modern era of preventive cardiology.Today, the evidence in favor of LDL cholesterol as a modifiable causal driver of atherosclerosis has never been stronger, and current therapies, such as PCSK9 inhibitors (PCSK9i), can now lower LDL cholesterol to levels never previously seen.But despite achieving very low levels of LDL cholesterol, many patients continue to have recurrent events.Although the residual risk for cardiovascular events is likely multifactorial, in certain patients a key component is a high residual burden of atherogenic lipid particles attributable to high lipoprotein(a) [Lp(a)].Lp(a) is a curious lipoprotein particle, first discovered in 1963, that consists of a lipid-rich apolipoprotein (apo) B lipoprotein covalently linked to an apo(a) moiety. 2 The apo(a) component is encoded by the LPA gene, and levels of Lp(a) are almost entirely explained by genetics.Indeed, elevated Lp(a) is the most common genetic dyslipidemia, with nearly 1 in 5 individuals affected in the United States [ie, based on Lp(a) >50 mg/dL or >120 nmol/L].Epidemiological evidence has linked Lp(a) to several cardiovascular diseases, including myocardial infarction (MI), 3 stroke, 3 and aortic valve stenosis, 4 and genetic evidence, using Mendelian randomization, has provided supportive evidence that these associations are causal.4,5 Causality is a key criterion in evaluating whether circulating biomarkers are possible therapeutic targets, and the evidence in support of Lp(a) appears quite favorable.Several agents are currently in development to specifically lower Lp(a), and these appear highly effective in lowering plasma Lp(a), with an excellent safety profile.6 However, to date, there remains no strong clinical evidence that lowering Lp(a) has any beneficial effects in preventing cardiovascular disease.Lp(a) still waits for its "4S" moment, but that moment appears imminent, with at least 1 trial in the final planning stages for post-acute coronary syndrome patients.In the context of these developments, Lp(a) is experiencing a resurgence in interest by the cardiovascular research community, and with good reason: there remain many unanswered questions about Lp(a) and its role in cardiovascular disease.In this issue of Circulation, 2 articles are presented that provide answers to some of these outstanding questions.In the first, Paré et al, 7 using data from the large, multiethnic INTERHEART study, evaluate the associations between Lp(a) levels and isoform size difference with MI across 7 ethnic groups in 6086 cases of first MI and 6857 control subjects.The authors should be commended for using this rich, multiethnic dataset to examine the role of Lp(a) across ethnicities using state-of-the-
Source: Circulation
Author: George Thanassoulis
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2922495129