scholarly journals Lipoprotein(a) has no major impact on calcification activity in patients with mild to moderate aortic valve stenosis

Heart ◽  
2021 ◽  
pp. heartjnl-2021-319804
Author(s):  
Yannick Kaiser ◽  
Nick S Nurmohamed ◽  
Jeffrey Kroon ◽  
Hein J Verberne ◽  
Evangelos Tzolos ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Low Density Lipoprotein ◽  
Linear Regression Analysis ◽  
Density Lipoprotein ◽  
Calcium Score ◽  
Lipoprotein A ◽  
Positron Emission ◽  
The Mean ◽  
Jet Velocity

ObjectiveTo assess whether patients with aortic valve stenosis (AS) with elevated lipoprotein(a) (Lp(a)) are characterised by increased valvular calcification activity compared with those with low Lp(a).MethodsWe performed 18F-sodium fluoride (18F-NaF) positron emission tomography/CT in patients with mild to moderate AS (peak aortic jet velocity between 2 and 4 m/s) and high versus low Lp(a) (>50 mg/dL vs <50 mg/dL, respectively). Subjects were matched according to age, gender, peak aortic jet velocity and valve morphology. We used a target to background ratio with the most diseased segment approach to compare 18F-NaF uptake.Results52 individuals (26 matched pairs) were included in the analysis. The mean age was 66.4±5.5 years, 44 (84.6%) were men, and the mean aortic valve velocity was 2.80±0.49 m/s. The median Lp(a) was 79 (64–117) mg/dL and 7 (5–11) mg/dL in the high and low Lp(a) groups, respectively. Systolic blood pressure and low-density-lipoprotein cholesterol (corrected for Lp(a)) were significantly higher in the low Lp(a) group (141±12 mm Hg vs 128±12 mm Hg, 2.5±1.1 mmol/L vs 1.9±0.8 mmol/L). We found no difference in valvular 18F-NaF uptake between the high and low Lp(a) groups (3.02±1.26 vs 3.05±0.96, p=0.902). Linear regression analysis showed valvular calcium score to be the only significant determinant of valvular 18F-NaF uptake (β=0.63; 95% CI 0.38 to 0.88 per 1000 Agatston unit increase, p<0.001). Lp(a) was not associated with 18F-NaF uptake (β=0.17; 95% CI −0.44 to 0.88, p=0.305 for the high Lp(a) group).ConclusionAmong patients with mild to moderate AS, calcification activity is predominantly determined by established calcium burden. The results do not support our hypothesis that Lp(a) is associated with valvular 18F-NaF uptake.

Potential pathological roles for oxidized low-density lipoprotein and scavenger receptors SR-AI, CD36, and LOX-1 in aortic valve stenosis

2014 ◽  
Vol 235 (2) ◽  
pp. 398-407 ◽  
Author(s):  
Suvi Syväranta ◽  
Mervi Alanne-Kinnunen ◽  
Katariina Öörni ◽  
Riina Oksjoki ◽  
Markku Kupari ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Scavenger Receptors ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein

Triglycerides and remnant cholesterol associated with risk of aortic valve stenosis: Mendelian randomization in the Copenhagen General Population Study

2020 ◽  
Vol 41 (24) ◽  
pp. 2288-2299 ◽  
Author(s):  
Morten Kaltoft ◽  
Anne Langsted ◽  
Børge G Nordestgaard
Keyword(s):  
Aortic Valve ◽  
General Population ◽  
Aortic Valve Stenosis ◽  
Population Study ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
General Population Study ◽  
Plasma Triglycerides ◽  
Increased Risk ◽  
Remnant Cholesterol

Abstract Aims We tested the hypothesis that higher levels of plasma triglycerides and remnant cholesterol are observationally and genetically associated with increased risk of aortic valve stenosis. Methods and results We included 108 559 individuals from the Copenhagen General Population Study. Plasma triglycerides, remnant cholesterol (total cholesterol minus low-density lipoprotein and high-density lipoprotein cholesterol), and 16 genetic variants causing such increased or decreased levels were determined. Incident aortic valve stenosis occurred in 1593 individuals. Observationally compared to individuals with triglycerides &lt;1 mmol/L (&lt;89 mg/dL), the multifactorially adjusted hazard ratio for aortic valve stenosis was 1.02 [95% confidence interval (CI) 0.87–1.19] for individuals with triglycerides of 1.0–1.9 mmol/L (89–176 mg/dL), 1.22 (1.02–1.46) for 2.0–2.9 mmol/L (177–265 mg/dL), 1.40 (1.11–1.77) for 3.0–3.9 mmol/L (266–353 mg/dL), 1.29 (0.88–1.90) for 4.0–4.9 mmol/L (354–442 mg/dL), and 1.52 (1.02–2.27) for individuals with triglycerides ≥5 mmol/L (≥443 mg/dL). By age 85, the cumulative incidence of aortic valve stenosis was 5.1% for individuals with plasma triglycerides &lt;2.0 mmol/L (77 mg/dL), 6.5% at 2.0–4.9 mmol/L (177–442 mg/dL), and 8.2% for individuals with plasma triglycerides ≥5.0 mmol/L (443 mg/dL). The corresponding values for remnant cholesterol categories were 4.8% for &lt;0.5 mmol/L (19 mg/dL), 5.6% for 0.5–1.4 mmol/L (19–57 mg/dL), and 7.4% for ≥1.5 mmol/L (58 mg/dL). Genetically, compared to individuals with allele score 13–16, odds ratios for aortic valve stenosis were 1.30 (95% CI 1.20–1.42; Δtriglycerides +12%; Δremnant cholesterol +11%) for allele score 17–18, 1.41 (1.31–1.52; +25%; +22%) for allele score 19–20, and 1.51 (1.22–1.86; +51%; +44%) for individuals with allele score 21–23. Conclusion Higher triglycerides and remnant cholesterol were observationally and genetically associated with increased risk of aortic valve stenosis.

Abstract 12822: Increased Expression and Serum Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Patients With Aortic Valve Stenosis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomotaka Yoshiyama ◽  
Kei Yunoki ◽  
Ryushi Komatsu ◽  
Kazuo Haze ◽  
Takahiko Naruko ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Oxidized Low Density Lipoprotein ◽  
Control Subjects ◽  
Density Lipoprotein Receptor

Background: The development of aortic valve stenosis (AS) involves multiple events, including inflammation and lipid deposition and oxidation. Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) play an important role in the development and progression of atherosclerosis. The aims of this study were to investigate the serum levels of sLOX-1 in patients with AS and also examine the expression of LOX-1 immunohistochemically in aortic valve specimens from these patients. Methods: Serum sLOX-1 levels were measured in patients with AS (n=128), stable angina pectoris (SAP, n=343) and in 53 control subjects using a sandwich ELISA method. Frozen aortic valve samples were also obtained surgically from a cohort of 20 AS patients. In addition, frozen aortic valve specimens were obtained at autopsy from individuals who died of non-cardiovascular causes (n = 11, mean age 68 yr) as a reference. Immunostaining of the samples was performed using antibodies against smooth muscle cells, macrophages, T-lymphocytes, neutrophils, microvessels, and LOX-1. Results: Serum sLOX-1 levels were significantly higher in AS patients compared with SAP patients ( P <0.0005) or control subjects ( P <0.0001). There were no differences in serum sLOX-1 levels between AS patients with or without coronary artery disease. Immunohistochemical staining showed that the LOX-1-positive area, as a percentage of the total area, was significantly (P<0.01) higher in AS patients compared with reference cases. Double immunostaining for LOX-1 and macrophages revealed that the vast majority of LOX-1-positive cells were macrophages. Conclusions: This study demonstrates for the first time that serum sLOX-1 levels are elevated in patients with AS, and AS lesions contain a significantly higher percentage of LOX-1-positive macrophages. These findings suggest that LOX-1, a marker of oxidative stress, may play an important role in the development of aortic valve stenosis.

scholarly journals Transcatheter Aortic Valve Implantation Represents an Anti-Inflammatory Therapy Via Reduction of Shear Stress–Induced, Piezo-1–Mediated Monocyte Activation

Circulation ◽  
2020 ◽  
Vol 142 (11) ◽  
pp. 1092-1105 ◽  
Author(s):  
Sara Baratchi ◽  
Maria T.K. Zaldivia ◽  
Maria Wallert ◽  
Julia Loseff-Silver ◽  
Sefaa Al-Aryahi ◽  
...  
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Shear ◽  
High Shear Stress ◽  
Transcatheter Aortic Valve ◽  
Stress Dependent ◽  
Valve Implantation

Background: Aortic valve stenosis is an increasingly prevalent degenerative and inflammatory disease. Transcatheter aortic valve implantation (TAVI) has revolutionized its treatment, thereby avoiding its life-threatening/disabling consequences. Whether aortic valve stenosis is accelerated by inflammation and whether it is itself a cause of inflammation are unclear. We hypothesized that the large shear forces exerted on circulating cells, particularly on the largest circulating cells, monocytes, while passing through stenotic aortic valves result in proinflammatory effects that are resolved with TAVI. Methods: TAVI provides a unique opportunity to compare the activation status of monocytes under high shear stress (before TAVI) and under low shear stress (after TAVI). The activation status of monocytes was determined with a single-chain antibody, MAN-1, which is specific for the activated β 2 -integrin Mac-1. Monocyte function was further characterized by the adhesion of myocytes to stimulated endothelial cells, phagocytic activity, uptake of oxidized low-density lipoprotein, and cytokine expression. In addition, we designed a microfluidic system to recapitulate the shear rate conditions before and after TAVI. We used this tool in combination with functional assays, Ca 2+ imaging, siRNA gene silencing, and pharmacological agonists and antagonists to identify the key mechanoreceptor mediating the shear stress sensitivity of monocytes. Last, we stained for monocytes in explanted stenotic aortic human valves. Results: The resolution of high shear stress through TAVI reduces Mac-1 activation, cellular adhesion, phagocytosis, oxidized low-density lipoprotein uptake, and expression of inflammatory markers in monocytes and plasma. Using microfluidics and pharmacological and genetic studies, we could recapitulate high shear stress effects on isolated human monocytes under highly controlled conditions, showing that shear stress–dependent calcium influx and monocyte adhesion are mediated by the mechanosensitive ion channel Piezo-1. We also demonstrate that the expression of this receptor is shear stress dependent and downregulated in patients receiving TAVI. Last, we show monocyte accumulation at the aortic side of leaflets of explanted aortic valves. Conclusions: We demonstrate that high shear stress, as present in patients with aortic valve stenosis, activates multiple monocyte functions, and we identify Piezo-1 as the mainly responsible mechanoreceptor, representing a potentially druggable target. We demonstrate an anti-inflammatory effect and therefore a novel therapeutic benefit of TAVI.

scholarly journals Aortic valve calcium score in hypercholesterolemic patients with and without low-density lipoprotein receptor gene mutation

PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0209229 ◽  
Author(s):  
Rafal Gałąska ◽  
Dorota Kulawiak-Gałąska ◽  
Magdalena Chmara ◽  
Krzysztof Chlebus ◽  
Michał Studniarek ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Gene Mutation ◽  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Calcium Score ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

Distribution of Serum Lipoprotein (a) Concentrations in a Healthy Turkish Population

1994 ◽  
Vol 31 (4) ◽  
pp. 343-346 ◽  
Author(s):  
Asim Örem ◽  
Orhan Değer ◽  
Ekin Önder ◽  
S Caner Karahan ◽  
Hasan Efe ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Turkish Population ◽  
Serum Lipoprotein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lipoprotein A ◽  
A Value ◽  
Different Populations ◽  
The Mean

Serum lipoprotein (a)[Lp (a)] concentrations are highly skewed in different populations. We measured serum Lp (a) by quantitative enzyme-linked immunosorbent assay (ELISA) in 248 healthy Turkish subjects (127 male, 121 female). The mean Lp (a) value was 0·21 g/L and values did not differ between the sexes. The Lp (a) frequency distribution showed less skewness than those of Asian and Western populations but it clearly deviated from a Gaussian distribution. Plasma Lp (a) concentration did not correlate significantly with age, total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, apolipoprotein A-l and B or triglyceride concentration.

Effect of thyroid function on concentrations of lipoprotein(a)

1993 ◽  
Vol 39 (12) ◽  
pp. 2466-2469 ◽  
Author(s):  
H Engler ◽  
W F Riesen
Keyword(s):  
Thyroid Hormones ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density Lipoprotein Cholesterol ◽  
Apo B ◽  
Thyroid State ◽  
Lipoprotein A ◽  
The Mean ◽  
L 14 ◽  
Rule Out

Abstract The effect of thyroid hormones on concentrations of lipoprotein(a) [Lp(a)] was analyzed in 60 patients with active thyroid dysfunction (hyperthyroidism 30 cases, hypothyroidism 32 cases, and 2 cases with opposite changes) and after normalization of the thyroid state. Treatment of hyperthyroidism increased the mean Lp(a) concentrations by 60% (from 73 to 102 mg/L, P &lt; 0.002); at the same time, low-density lipoprotein cholesterol (LDL-C) increased by 53% (from 2.6 to 3.7 mmol/L, P &lt; 0.0001) and apolipoprotein B (apo B) by 35% (from 0.91 to 1.17 g/L, P &lt; 0.0005). In hypothyroidism, the opposite changes were observed: mean Lp(a) decreased from 136 to 114 mg/L (10%, P &lt; 0.02), LDL-C from 4.6 to 3.9 mmol/L (13%, P &lt; 0.01), and apo B from 1.51 to 1.20 g/L (14%, P &lt; 0.01). Although the changes in Lp(a) concentrations did correlate with changes of LDL-C during treatment of hyperthyroidism (r = 0.43, P &lt; 0.05), and with changes in apo B during thyroxine-substitution therapy for hypothyroidism (r = 0.46, P &lt; 0.05), we observed no associations between Lp(a) and LDL-C or apo B in the euthyroid state. These data cannot rule out the possibility that the thyroid hormone-induced increase in LDL-C receptor activity was responsible for the decreased concentrations of Lp(a) in hyperthyroidism. Given that LDL-C is approximately 30% of the Lp(a) molecule but the changes in Lp(a) concentrations are comparable with those in LDL-C (60% vs 53%), and given that Lp(a) is metabolized by an LDL-C-receptor-independent pathway, the present data suggest a direct effect of thyroid hormones on Lp(a) synthesis.

Quantification of lipoprotein(a) in plasma by assaying cholesterol in lectin-bound plasma fraction

1994 ◽  
Vol 40 (3) ◽  
pp. 400-403 ◽  
Author(s):  
L J Seman ◽  
J L Jenner ◽  
J R McNamara ◽  
E J Schaefer
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Content ◽  
Lipoprotein A ◽  
Apolipoprotein A ◽  
Plasma Fraction ◽  
Chd Risk ◽  
Increased Risk ◽  
The Mean ◽  
High Concentrations

Abstract Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle in which apolipoprotein(a) [apo(a)] is disulfide-linked to apolipoprotein B (apoB). High concentrations of Lp(a) in plasma are associated with an increased risk of coronary heart disease (CHD). Lp(a) has traditionally been measured by immunoassay and expressed as total mass of Lp(a). Measuring Lp(a) by its cholesterol content will provide a way to directly compare Lp(a) with other lipoproteins that are measured by cholesterol. We have developed an assay to quantify Lp(a) by its cholesterol content [Lp(a)-C], using lectin affinity to isolate Lp(a) from other lipoproteins, and then measuring the cholesterol within the isolated fraction. We compared the Lp(a)-C assay with an ELISA for Lp(a) mass in 47 plasma samples from normotriglyceridemic, fasting individuals with high Lp(a) contents (mean +/- SD, 446 +/- 350 mg/L). The mean Lp(a)-C concentration was 110 +/- 89 mg/L and correlated very highly with Lp(a) mass (r = 0.9975). Lp(a)-C measurement is an alternative method to screen for this CHD risk factor.

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