Lipoprotein(a) and the Risk for Recurrent Atherosclerotic Cardiovascular Events Among Adults With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study

Poudel, Bharat; Rosenson, Robert S.; Kent, Shia T.; Bittner, Vera; Gutiérrez, Orlando M.; Anderson, Amanda H.; Woodward, Mark; Jackson, Elizabeth A.; Monda, Keri L.; Bajaj, Archna; Huang, Lei; Kansal, Mayank; Rahman, Mahboob; He, Jiang; Muntner, Paul; Colantonio, Lisandro D.

doi:10.1016/j.xkme.2023.100648

Cited by 4 publications

(1 citation statement)

References 43 publications

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“… 7 However, in the 2023 Chronic Renal Insufficiency Cohort Study, lipoprotein(a) was not associated with increased CVD risk, suggesting that other factors may be more important in patients with end‐stage renal disease. 87 …”

Section: Nongenetic Determinants Of Plasma Lipoprotein(a) Levelsmentioning

confidence: 99%

Genetics and Pathophysiological Mechanisms of Lipoprotein(a)‐Associated Cardiovascular Risk

Volgman,

Koschinsky,

Mehta

et al. 2024

JAHA

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Elevated lipoprotein(a) is a genetically transmitted codominant trait that is an independent risk driver for cardiovascular disease. Lipoprotein(a) concentration is heavily influenced by genetic factors, including LPA kringle IV‐2 domain size, single‐nucleotide polymorphisms, and interleukin‐1 genotypes. Apolipoprotein(a) is encoded by the LPA gene and contains 10 subtypes with a variable number of copies of kringle ‐2, resulting in >40 different apolipoprotein(a) isoform sizes. Genetic loci beyond LPA , such as APOE and APOH , have been shown to impact lipoprotein(a) levels. Lipoprotein(a) concentrations are generally 5% to 10% higher in women than men, and there is up to a 3‐fold difference in median lipoprotein(a) concentrations between racial and ethnic populations. Nongenetic factors, including menopause, diet, and renal function, may also impact lipoprotein(a) concentration. Lipoprotein(a) levels are also influenced by inflammation since the LPA promoter contains an interleukin‐6 response element; interleukin‐6 released during the inflammatory response results in transient increases in plasma lipoprotein(a) levels. Screening can identify elevated lipoprotein(a) levels and facilitate intensive risk factor management. Several investigational, RNA‐targeted agents have shown promising lipoprotein(a)‐lowering effects in clinical studies, and large‐scale lipoprotein(a) testing will be fundamental to identifying eligible patients should these agents become available. Lipoprotein(a) testing requires routine, nonfasting blood draws, making it convenient for patients. Herein, we discuss the genetic determinants of lipoprotein(a) levels, explore the pathophysiological mechanisms underlying the association between lipoprotein(a) and cardiovascular disease, and provide practical guidance for lipoprotein(a) testing.

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Section: Nongenetic Determinants Of Plasma Lipoprotein(a) Levelsmentioning

confidence: 99%

Genetics and Pathophysiological Mechanisms of Lipoprotein(a)‐Associated Cardiovascular Risk

Volgman,

Koschinsky,

Mehta

et al. 2024

JAHA

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Association of Lipoprotein(a) With Major Adverse Cardiovascular Events Across hs-CRP

Alebna,

Han,

Ambrosio

et al. 2024

JACC: Advances

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Lipoprotein(a) concentrations and cardiovascular disease in patients with chronic kidney disease: Results from the German Chronic Kidney Disease study

Gruber,

Kollerits,

Forer

et al. 2024

J Intern Med

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BackgroundLipoprotein(a) (Lp(a)) is a causal, genetically determined risk factor for cardiovascular disease (CVD) in the general population. Patients with chronic kidney disease (CKD) have an increased CVD risk and elevated Lp(a) concentrations. Only a few studies on Lp(a) were performed in persons with mild‐to‐moderate CKD; none of them used genetic variants to explore potential causal associations.ObjectivesThis study aims to investigate the association of measured and genetically predicted Lp(a) concentrations on prevalent and incident CVD events in the German Chronic Kidney Disease (GCKD) study.MethodsThe study included 5043 participants of European ancestry with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2 or an eGFR >60 mL/min/1.73 m2 in the presence of overt albuminuria with a follow‐up of 6.5 years.ResultsWith each 10 mg/dL higher Lp(a) concentration, odds for prevalent CVD (1290 events) increased 1.065‐fold (95%CI: 1.042–1.088, p < 0.001). The risk was significantly higher in patients with Lp(a) ≥50 mg/dL but most pronounced in Lp(a) ≥70 mg/dL (odds ratio = 1.775 [1.409–2.231], p < 0.001) compared to Lp(a) <30 mg/dL. Each 10 mg/dL higher Lp(a) concentration and Lp(a) ≥70 mg/dL increased the risk for incident 3‐point major adverse cardiovascular events (MACEs) (474 events): hazard ratio [HR] = 1.037 [1.009–1.067], p = 0.009 and HR = 1.335 [1.001–1.781], p = 0.050), respectively. Similar results were obtained for 4‐point MACE (653 events). Analyses based on apo(a) isoforms and genetically predicted Lp(a) concentrations led to even stronger associations.ConclusionsIn patients with mild‐to‐severe CKD, elevated Lp(a) concentrations and genetic determinants of Lp(a) concentrations are significantly associated with CVD at baseline and during follow‐up, independent of traditional risk factors.

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Lipoprotein(a) and the Risk for Recurrent Atherosclerotic Cardiovascular Events Among Adults With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study

Cited by 4 publications

References 43 publications

Genetics and Pathophysiological Mechanisms of Lipoprotein(a)‐Associated Cardiovascular Risk

Genetics and Pathophysiological Mechanisms of Lipoprotein(a)‐Associated Cardiovascular Risk

Association of Lipoprotein(a) With Major Adverse Cardiovascular Events Across hs-CRP

Lipoprotein(a) concentrations and cardiovascular disease in patients with chronic kidney disease: Results from the German Chronic Kidney Disease study

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