Elevated lipoprotein (a) levels and risk of peripheral artery disease outcomes: A systematic review

Masson, Walter; Lobo, Martín; Barbagelata, Leandro; Molinero, Graciela; Bluro, Ignacio; Nogueira, Juan Patricio

doi:10.1177/1358863x221091320

Cited by 13 publications

(8 citation statements)

References 46 publications

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“…Elevated lipoprotein(a) is a well‐established risk factor for multiple cardiovascular diseases (CVDs), especially coronary artery disease and aortic stenosis (AS). 1 Lipoprotein(a) is also associated with ischemic stroke, 2 , 3 peripheral vascular disease (PVD), 4 and heart failure (HF). 5 The accumulation of epidemiologic and genetic studies strongly supports a causal role for lipoprotein(a) in CVD in diverse populations, even with low levels of low‐density lipoprotein cholesterol.…”

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confidence: 99%

Lipoprotein(a) Testing Trends in a Large Academic Health System in the United States

Bhatia,

Hurst,

Desai

et al. 2023

JAHA

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Background Despite its high prevalence and clinical significance, clinical measurement of lipoprotein(a) is rare but has not been systematically quantified. We assessed the prevalence of lipoprotein(a) testing overall, in those with various cardiovascular disease (CVD) conditions and in those undergoing cardiac testing across 6 academic medical centers associated with the University of California, in total and by year from 2012 to 2021. Methods and Results In this observational study, data from the University of California Health Data Warehouse on the number of individuals with unique lipoprotein(a) testing, unique CVD diagnoses (using International Classification of Diseases, Tenth Revision [ ICD‐10 ], codes), and other unique cardiac testing were collected. The proportion of total individuals, the proportion of individuals with a given CVD diagnosis, and the proportion of individuals with a given cardiac test and lipoprotein(a) testing any time during the study period were calculated. From 2012 to 2021, there were 5 553 654 unique adults evaluated in the University of California health system, of whom 18 972 (0.3%) had lipoprotein(a) testing. In general, those with lipoprotein(a) testing were more likely to be older, men, and White race, with a greater burden of CVD. Lipoprotein(a) testing was performed in 6469 individuals with ischemic heart disease (2.9%), 836 with aortic stenosis (3.1%), 4623 with family history of CVD (3.3%), 1202 with stroke (1.7%), and 612 with coronary artery calcification (6.1%). For most conditions, the prevalence of testing in the same year as the diagnosis of CVD was relatively stable, with a small upward trend over time. Lipoprotein(a) testing was performed in 10 753 individuals (1.8%) who had lipid panels, with higher rates with more specialized testing, including coronary computed tomography angiography (6.8%) and apolipoprotein B (63.0%). Conclusions Lipoprotein(a) testing persists at low rates, even among those with diagnosed CVD, and remained relatively stable over the study period.

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confidence: 99%

Lipoprotein(a) Testing Trends in a Large Academic Health System in the United States

Bhatia,

Hurst,

Desai

et al. 2023

JAHA

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“…In a systematic review including 15 studies and 493,650 patients, most studies confirmed a significant association between high Lp(a) levels and the risk of PAD. High Lp(a) levels have also been found to be associated with increased PAD progression, risk of intermittent claudication, recurrence of significant stenosis and risk of hospitalisation and death [ 55 ]. Higher levels of Lp(a) have been shown to be independently associated with an increased risk of major adverse limb events (MALE) [ 56 ].…”

Section: Lipoprotein(a) and Cardiovascular Diseasementioning

confidence: 99%

Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels

Sosnowska,

Stepinska,

Mitkowski

et al. 2024

Arch Med Sci

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Elevated Lp(a) levels ≥50 mg/dl are estimated to occur in more than 1.5 billion people worldwide. However, determination of Lp(a) levels is performed far too rarely, including Poland, where, in fact, it is only since the 2021 PoLA guidelines that Lp(a) measurements have begun to be performed. Determination of Lp(a) concentrations is not easy due to, among other things, the different sizes of the apo(a) isoforms; however, the currently available certified tests make it possible to distinguish between people with low and high cardiovascular risk with a high degree of precision. In 2022, the first guidelines for the management of patients with elevated Lp(a) levels were published by the EAS and the AHA. The first Polish guidelines are the result of the work of experts from the two scientific societies and their aim is to provide clear, practical recommendations for the determination and management of elevated Lp(a) levels.

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“…A recent systematic review analyzed 15 studies involving 493,650 patients, and the majority of these studies supported a significant association between high Lp(a) levels and the risk of PAD, according to the authors. High Lp(a) levels were also found to be linked to an increased risk of claudication, PAD progression, restenosis, hospitalization, and death [ 121 ] ( Figure 2 ).…”

Section: Lp(a) In Vascular Diseasesmentioning

confidence: 99%

Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives

Vinci,

Di Girolamo,

Panizon

et al. 2023

IJERPH

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Cardiovascular disease (CVD) is still a leading cause of morbidity and mortality, despite all the progress achieved as regards to both prevention and treatment. Having high levels of lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease that operates independently. It can increase the risk of developing cardiovascular disease even when LDL cholesterol (LDL-C) levels are within the recommended range, which is referred to as residual cardiovascular risk. Lp(a) is an LDL-like particle present in human plasma, in which a large plasminogen-like glycoprotein, apolipoprotein(a) [Apo(a)], is covalently bound to Apo B100 via one disulfide bridge. Apo(a) contains one plasminogen-like kringle V structure, a variable number of plasminogen-like kringle IV structures (types 1–10), and one inactive protease region. There is a large inter-individual variation of plasma concentrations of Lp(a), mainly ascribable to genetic variants in the Lp(a) gene: in the general po-pulation, Lp(a) levels can range from <1 mg/dL to >1000 mg/dL. Concentrations also vary between different ethnicities. Lp(a) has been established as one of the risk factors that play an important role in the development of atherosclerotic plaque. Indeed, high concentrations of Lp(a) have been related to a greater risk of ischemic CVD, aortic valve stenosis, and heart failure. The threshold value has been set at 50 mg/dL, but the risk may increase already at levels above 30 mg/dL. Although there is a well-established and strong link between high Lp(a) levels and coronary as well as cerebrovascular disease, the evidence regarding incident peripheral arterial disease and carotid atherosclerosis is not as conclusive. Because lifestyle changes and standard lipid-lowering treatments, such as statins, niacin, and cholesteryl ester transfer protein inhibitors, are not highly effective in reducing Lp(a) levels, there is increased interest in developing new drugs that can address this issue. PCSK9 inhibitors seem to be capable of reducing Lp(a) levels by 25–30%. Mipomersen decreases Lp(a) levels by 25–40%, but its use is burdened with important side effects. At the current time, the most effective and tolerated treatment for patients with a high Lp(a) plasma level is apheresis, while antisense oligonucleotides, small interfering RNAs, and microRNAs, which reduce Lp(a) levels by targeting RNA molecules and regulating gene expression as well as protein production levels, are the most widely explored and promising perspectives. The aim of this review is to provide an update on the current state of the art with regard to Lp(a) pathophysiological mechanisms, focusing on the most effective strategies for lowering Lp(a), including new emerging alternative therapies. The purpose of this manuscript is to improve the management of hyperlipoproteinemia(a) in order to achieve better control of the residual cardiovascular risk, which remains unacceptably high.

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Elevated lipoprotein (a) levels and risk of peripheral artery disease outcomes: A systematic review

Cited by 13 publications

References 46 publications

Lipoprotein(a) Testing Trends in a Large Academic Health System in the United States

Lipoprotein(a) Testing Trends in a Large Academic Health System in the United States

Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels

Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives

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