Lipoprotein(a) and oxidized phospholipids in calcific aortic valve stenosis

Lipoprotein(a; Lp[a]) and its associated oxidized phospholipids are causal, genetic risk factors for calcific aortic valve stenosis (CAVS). We determined the prevalence of Lp(a) measurement among 2710 patients with CAVS and 1369 control patients (∼50% of study group) without CAVS with an echocardiogram between January 2010 and February 2016 in an academic echocardiography laboratory. Lipoprotein(a) measurements were performed at a referral laboratory using an isoform-independent assay. The prevalence of any Lp(a) measurement was 4.6% (124 of the 2710) in patients with CAVS and 3.1% (42 of the 1369) in the control group ( P = .021). In patients with CAVS, mean (standard deviation) Lp(a) levels were 38 (54) mg/dL and median (interquartile range) Lp(a) levels were 14 (6-48) mg/dL. Of the 124 patients with CAVS having Lp(a) measurements, 83 (66.9%) had Lp(a) <30 mg/dL and 41 (33.1%) had Lp(a) ≥30 mg/dL. This study reflects low physician testing of Lp(a) levels in CAVS. Given the role of Lp(a) as a causal risk factor for CAVS, and the ongoing development of therapies to normalize Lp(a) levels, our results suggest that Lp(a) measurements in CAVS should be more widely obtained in clinical practice.

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Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2015.07.020 ◽

2015 ◽

Vol 66 (11) ◽

pp. 1236-1246 ◽

Cited By ~ 159

Author(s):

Romain Capoulade ◽

Kwan L. Chan ◽

Calvin Yeang ◽

Patrick Mathieu ◽

Yohan Bossé ◽

...

Keyword(s):

Aortic Valve ◽

Aortic Valve Stenosis ◽

Oxidized Phospholipids ◽

Lipoprotein A

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P2748Lipoprotein(a) and autotaxin in patients with stenotic atherosclerosis of coronary arteries and aortic valve stenosis

European Heart Journal ◽

10.1093/eurheartj/ehz748.1065 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

O Afanasieva ◽

N Tmoyan ◽

O Razova ◽

E Klesareva ◽

M Afanasieva ◽

...

Keyword(s):

Aortic Valve ◽

Aortic Valve Stenosis ◽

Odds Ratio ◽

Control Group ◽

Elevated Concentration ◽

Oxidized Phospholipids ◽

Lipoprotein A ◽

Group I ◽

Group Ii

Abstract Background Lipoprotein(a) [Lp(a)] is an independent risk factor of coronary heart disease (CHD) and calcific aortic valve stenosis (CAVS). It has been recently shown that autotaxin (ATX), which breaks down lysophosphatidylcholine, derived from oxidized phospholipids, to lysophosphatidic acid, was strongly associated with CAVS. Purpose The aim of the study was to investigate the role of Lp(a) and ATX in CHD patients with and without CAVS. Methods The study included 438 patients (average age 66±11 years, men 310), 332 had CHD with ≥50% stenosis in at least one coronary artery according to angiography. CAVS was diagnosed with ultrasound. The control group consisted of 106 patients without CHD and CAVS. The concentrations of Lp(a), ATX, lipids and blood cells were measured for all the patients. Results CHD without CAVS (group I) was diagnosed in 287 patients, 45 patients had CHD and CAVS (group II). Patients in both groups were older than patients in the control group (75±8, 66±10 and 61±13 years respectively). ATX level was lower in group I (median [25; 75%]: 493 [406; 583] ng/ml) than in control group (544 [412; 655] ng/ml, p=0.02) or group II (553 [475; 609] ng/ml, p=0.003). Lp(a) was lower in control group (14.5 [5.5; 36.0] mg/dl) than in group I (25.6 [9.7; 58.5] mg/dl, p=0.0004) and group II (23.8 [9.9; 79.1] mg/dl, p=0.02). Elevated level of ATX was positively associated with CAVS in CHD patients, but negatively with CHD in patients without CAVS. We have shown that age, glucose level and neutrophil-lymphocytes index (NLI) could be predictors of CAVS in patients with CHD according to results of logistic regression analysis. Odds ratio of high (QIV) vs. low (QI) Odds ratio (95% confidence interval) Groups Autotaxin Lipoprotein(a) Neutrophil-lymphocytes index I vs. control 0.5 (0.3–0.9)* 2.7 (1.3–5.2)** 2.4 (1.3–4.6)* II vs. control 8.6 (1.1–70.1)* 3.4 (1.2–9.4)* 6.2 (2.2–16.9)** II vs. I 16.6 (2.1–131.1)** 1.3 (0.5–3.2) 2.5 (1.0–6.37)* *p<0.05, **p<0.005. Conclusion Elevated Lp(a) level is a predictor of CHD regardless of calcific aortic valve stenosis, whereas elevated concentration of autotoxin in CHD patients was associated with calcific aortic valve stenosis.

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Lipoprotein(A), Oxidized Phospholipids, And Aortic Valve Microcalcification Assessed By 18f-Naf Pet/Ct

Atherosclerosis ◽

10.1016/j.atherosclerosis.2019.06.322 ◽

2019 ◽

Vol 287 ◽

pp. e110-e111

Author(s):

A.A. Després ◽

N. Perrot ◽

L. Tastet ◽

A. Pouliot ◽

M. Shen ◽

...

Keyword(s):

Aortic Valve ◽

Oxidized Phospholipids ◽

Lipoprotein A ◽

Pet Ct

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Lipoprotein(a)-Associated Molecules Are Prominent Components in Plasma and Valve Leaflets in Calcific Aortic Valve Stenosis

JACC Basic to Translational Science ◽

10.1016/j.jacbts.2017.02.004 ◽

2017 ◽

Vol 2 (3) ◽

pp. 229-240 ◽

Cited By ~ 27

Author(s):

Michael Torzewski ◽

Amir Ravandi ◽

Calvin Yeang ◽

Andrea Edel ◽

Rahul Bhindi ◽

...

Keyword(s):

Aortic Valve ◽

Aortic Valve Stenosis ◽

Lipoprotein A

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Elevated Lipoprotein(a) and Risk of Aortic Valve Stenosis in the General Population

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2013.09.038 ◽

2014 ◽

Vol 63 (5) ◽

pp. 470-477 ◽

Cited By ~ 251

Author(s):

Pia R. Kamstrup ◽

Anne Tybjærg-Hansen ◽

Børge G. Nordestgaard

Keyword(s):

Aortic Valve ◽

General Population ◽

Aortic Valve Stenosis ◽

Lipoprotein A

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Abstract 235: Prevalence of Lipoprotein(a) Measurements and Extent of Lipoprotein(a) Elevations in 2,266 Patients with Aortic Stenosis: Results from an Academic Echocardiography Laboratory Practice Setting

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.235 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Michael J Wilkinson ◽

Gary S Ma ◽

Calvin Yeang ◽

Monet Strachan ◽

Joel Wilson ◽

...

Keyword(s):

Aortic Valve ◽

Practice Setting ◽

Oxidized Phospholipids ◽

Laboratory Practice ◽

Lipoprotein A ◽

Causal Risk Factor ◽

Number Of Patients ◽

Echocardiography Laboratory ◽

Ongoing Development ◽

The University

Background: The LPA gene causes elevated lipoprotein(a) (Lp(a)) levels and causally mediates calcific aortic valve stenosis (AS). Elevated Lp(a) and its associated oxidized phospholipids (OxPL-apoB) predict the progression of pre-existing AS and need for aortic valve replacement and are targets of therapy. Methods: We determined the prevalence and the extent of Lp(a) elevation in patients with AS diagnosed by echocardiography performed at the University of California San Diego between 2010-2015. Severity of AS was classified as critical, severe, moderate, mild, or trace. Lp(a) levels were organized as Lp(a) <30 mg/dL, 30-50 mg/dL, 50-100 mg/dL and >100 mg/dL. Results: 2,266 patients with AS were found, with 130 critical, 333 severe, 477 moderate, 1318 mild, and 8 cases of trace AS. Mean age was 75.0 and range 18-106 years. 51% of patients were male. Prevalence of any Lp(a) measurement was 159/2,266 patients (7.02%). The number (%) of patients with an Lp(a) level was: 1) critical (n=4, 3.1%), 2) severe (n=28, 8.4%), 3) moderate (n=56, 11.7%), 4) mild (n=71, 5.4%), and 5) trace (n=0). The extent of Lp(a) elevation within each AS category is in Table 1: 55/159 (34%), 35/159 (22%) and 19/159 (12%) of patients had Lp(a) >30 mg/dL, >50 mg/dL and >100 mg/dL, respectively. Conclusion: Lp(a) was measured in only 7.0% of patients with AS in an academic setting. Given the ongoing development of therapies to lower Lp(a) in patients with AS, educational efforts are needed to raise awareness of Lp(a) as a causal risk factor for AS.

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