Lipoprotein(a) as a risk factor for calcific aortic valvulopathy in heterozygous familial hypercholesterolemia

Alpo Vuorio, Gerald F. Watts, Petri T. Kovanen

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

A large number of epidemiological studies in ethnically diverse populations show that lipoprotein(a) [Lp(a)] levels above 30-50 mg/dL are significantly associated with calcific aortic valve stenosis, although less so in African Americans. Patients with heterozygous familial hypercholesterolemia (he-FH) have a marked lifelong elevation of serum low-density lipoprotein cholesterol (LDL-C) level, and the prevalence of aortic valve calcification (AVC) is at least two-fold higher among adult he-FH patients compared with healthy controls. Additionally, Lp(a) levels above 50 mg/dL were recently found to be an independent risk factor for AVC among asymptomatic statin-treated he-FH patients. Given that worldwide an estimated 1.4 billion people have an Lp(a) level over 50 mg/dL, and that one out of 250 individuals has he-FH, then globally about 5 million he-FH patients should have an Lp(a) level higher than 50 mg/dL. However, because Lp(a) levels are, on average, significantly higher in he-FH patients than the general population, the actual number of he-FH patients with such high Lp(a) levels must be even higher.

We proposed recently that Lp(a) life-years is a useful metric of cumulative burden of risk for atherosclerotic cardiovascular disease (ASCVD), and now posit that this metric may be extended to the development of AVC. The Lp(a) life-years illustrates the age-dependent exposure to a given Lp(a) level (years x mg/dL). Effective novel pharmacotherapies using apo(a) antisense oligonucleotides (ASOs) or small interfering RNA (siRNA)-based therapies targeting the hepatic expression of apo(a) offer unprecedented potential for significant reduction in the cumulative exposure of the aortic valves to Lp(a), and need to be tested in controlled clinical trials on the progression of AVC.

Original languageEnglish
Pages (from-to)25-30
Number of pages6
JournalAtherosclerosis
Volume281
DOIs
Publication statusPublished - Feb 2019

Cite this

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title = "Lipoprotein(a) as a risk factor for calcific aortic valvulopathy in heterozygous familial hypercholesterolemia",
abstract = "A large number of epidemiological studies in ethnically diverse populations show that lipoprotein(a) [Lp(a)] levels above 30-50 mg/dL are significantly associated with calcific aortic valve stenosis, although less so in African Americans. Patients with heterozygous familial hypercholesterolemia (he-FH) have a marked lifelong elevation of serum low-density lipoprotein cholesterol (LDL-C) level, and the prevalence of aortic valve calcification (AVC) is at least two-fold higher among adult he-FH patients compared with healthy controls. Additionally, Lp(a) levels above 50 mg/dL were recently found to be an independent risk factor for AVC among asymptomatic statin-treated he-FH patients. Given that worldwide an estimated 1.4 billion people have an Lp(a) level over 50 mg/dL, and that one out of 250 individuals has he-FH, then globally about 5 million he-FH patients should have an Lp(a) level higher than 50 mg/dL. However, because Lp(a) levels are, on average, significantly higher in he-FH patients than the general population, the actual number of he-FH patients with such high Lp(a) levels must be even higher.We proposed recently that Lp(a) life-years is a useful metric of cumulative burden of risk for atherosclerotic cardiovascular disease (ASCVD), and now posit that this metric may be extended to the development of AVC. The Lp(a) life-years illustrates the age-dependent exposure to a given Lp(a) level (years x mg/dL). Effective novel pharmacotherapies using apo(a) antisense oligonucleotides (ASOs) or small interfering RNA (siRNA)-based therapies targeting the hepatic expression of apo(a) offer unprecedented potential for significant reduction in the cumulative exposure of the aortic valves to Lp(a), and need to be tested in controlled clinical trials on the progression of AVC.",
keywords = "Familial hypercholesterolemia, lipoprotein(a), Atherosclerosis, Valvulopathy, Aortic calcification, Aortic stenosis, VALVE STENOSIS, OXIDIZED PHOSPHOLIPIDS, CARDIOVASCULAR-DISEASE, TARGETING APOLIPOPROTEIN(A), DENSITY-LIPOPROTEINS, HEART-DISEASE, DOUBLE-BLIND, DIAGNOSIS, ATHEROSCLEROSIS, MANAGEMENT",
author = "Alpo Vuorio and Watts, {Gerald F.} and Kovanen, {Petri T.}",
year = "2019",
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language = "English",
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pages = "25--30",
journal = "Atherosclerosis",
issn = "0021-9150",
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Lipoprotein(a) as a risk factor for calcific aortic valvulopathy in heterozygous familial hypercholesterolemia. / Vuorio, Alpo; Watts, Gerald F.; Kovanen, Petri T.

In: Atherosclerosis, Vol. 281, 02.2019, p. 25-30.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Lipoprotein(a) as a risk factor for calcific aortic valvulopathy in heterozygous familial hypercholesterolemia

AU - Vuorio, Alpo

AU - Watts, Gerald F.

AU - Kovanen, Petri T.

PY - 2019/2

Y1 - 2019/2

N2 - A large number of epidemiological studies in ethnically diverse populations show that lipoprotein(a) [Lp(a)] levels above 30-50 mg/dL are significantly associated with calcific aortic valve stenosis, although less so in African Americans. Patients with heterozygous familial hypercholesterolemia (he-FH) have a marked lifelong elevation of serum low-density lipoprotein cholesterol (LDL-C) level, and the prevalence of aortic valve calcification (AVC) is at least two-fold higher among adult he-FH patients compared with healthy controls. Additionally, Lp(a) levels above 50 mg/dL were recently found to be an independent risk factor for AVC among asymptomatic statin-treated he-FH patients. Given that worldwide an estimated 1.4 billion people have an Lp(a) level over 50 mg/dL, and that one out of 250 individuals has he-FH, then globally about 5 million he-FH patients should have an Lp(a) level higher than 50 mg/dL. However, because Lp(a) levels are, on average, significantly higher in he-FH patients than the general population, the actual number of he-FH patients with such high Lp(a) levels must be even higher.We proposed recently that Lp(a) life-years is a useful metric of cumulative burden of risk for atherosclerotic cardiovascular disease (ASCVD), and now posit that this metric may be extended to the development of AVC. The Lp(a) life-years illustrates the age-dependent exposure to a given Lp(a) level (years x mg/dL). Effective novel pharmacotherapies using apo(a) antisense oligonucleotides (ASOs) or small interfering RNA (siRNA)-based therapies targeting the hepatic expression of apo(a) offer unprecedented potential for significant reduction in the cumulative exposure of the aortic valves to Lp(a), and need to be tested in controlled clinical trials on the progression of AVC.

AB - A large number of epidemiological studies in ethnically diverse populations show that lipoprotein(a) [Lp(a)] levels above 30-50 mg/dL are significantly associated with calcific aortic valve stenosis, although less so in African Americans. Patients with heterozygous familial hypercholesterolemia (he-FH) have a marked lifelong elevation of serum low-density lipoprotein cholesterol (LDL-C) level, and the prevalence of aortic valve calcification (AVC) is at least two-fold higher among adult he-FH patients compared with healthy controls. Additionally, Lp(a) levels above 50 mg/dL were recently found to be an independent risk factor for AVC among asymptomatic statin-treated he-FH patients. Given that worldwide an estimated 1.4 billion people have an Lp(a) level over 50 mg/dL, and that one out of 250 individuals has he-FH, then globally about 5 million he-FH patients should have an Lp(a) level higher than 50 mg/dL. However, because Lp(a) levels are, on average, significantly higher in he-FH patients than the general population, the actual number of he-FH patients with such high Lp(a) levels must be even higher.We proposed recently that Lp(a) life-years is a useful metric of cumulative burden of risk for atherosclerotic cardiovascular disease (ASCVD), and now posit that this metric may be extended to the development of AVC. The Lp(a) life-years illustrates the age-dependent exposure to a given Lp(a) level (years x mg/dL). Effective novel pharmacotherapies using apo(a) antisense oligonucleotides (ASOs) or small interfering RNA (siRNA)-based therapies targeting the hepatic expression of apo(a) offer unprecedented potential for significant reduction in the cumulative exposure of the aortic valves to Lp(a), and need to be tested in controlled clinical trials on the progression of AVC.

KW - Familial hypercholesterolemia

KW - lipoprotein(a)

KW - Atherosclerosis

KW - Valvulopathy

KW - Aortic calcification

KW - Aortic stenosis

KW - VALVE STENOSIS

KW - OXIDIZED PHOSPHOLIPIDS

KW - CARDIOVASCULAR-DISEASE

KW - TARGETING APOLIPOPROTEIN(A)

KW - DENSITY-LIPOPROTEINS

KW - HEART-DISEASE

KW - DOUBLE-BLIND

KW - DIAGNOSIS

KW - ATHEROSCLEROSIS

KW - MANAGEMENT

U2 - 10.1016/j.atherosclerosis.2018.11.040

DO - 10.1016/j.atherosclerosis.2018.11.040

M3 - Review article

VL - 281

SP - 25

EP - 30

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

ER -