Role of lipoprotein(a) and its autoantibodies in polyvascular atherosclerotic disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Tmoyan ◽  
O Afanasieva ◽  
M Ezhov ◽  
U Chubykina ◽  
E Klesareva ◽  
...  
Keyword(s):  
Risk Factor ◽  
Independent Risk Factor ◽  
Lower Limbs ◽  
Public Institution ◽  
Funding Source ◽  
Lipoprotein A ◽  
National Medical ◽  
Vascular Beds ◽  
Relationship Of

Abstract Background Lipoprotein(a) [Lp(a)] is an independent risk factor of cardiovascular disease. The role of Lp(a) and its autoantibodies in the development of atherosclerosis, depending on the severity of lesion, is uncertain. Purpose To define the relationship of Lp(a) level and autoantibodies to Lp(a) with atherosclerosis of different vascular beds. Methods The study included 1288 patients older than 18 years with instrumental examination of three vascular beds (coronary, carotid and lower limbs arteries). Patients were divided according to the number of affected vascular beds (stenosis ≥50%): 0 (n=339), 1 (n=470), 2 (n=315), 3 (n=164). Levels of lipids, Lp(a) and autoantibodies to Lp(a) were measured in serum of all patients. Results Lp(a) concentration steadily increased and the level of IgM autoantibodies decreased with the number of affected vascular beds (Figure). There was no any association between IgG autoantibodies to Lp(a) and stenotic atherosclerosis. In logistic regression analysis adjusted for age, sex, hypertension, diabetes mellitus, smoking, elevated Lp(a) level was an independent predictor of stenotic atherosclerosis and it was associated with severity of lesions (table). Conclusions Lipoprotein(a) is an independent risk factor of stenotic atherosclerosis and its concentration increases with the number of affected vascular beds, while IgM autoantibodies to Lp(a) possess cardioprotective properties. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Medical Research Center of Cardiology of Ministry of Health of the Russian Federation

Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3364-3368 ◽  
Author(s):  
Mario von Depka ◽  
Ulrike Nowak-Göttl ◽  
Roswith Eisert ◽  
Christian Dieterich ◽  
Monika Barthels ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Protein C ◽  
Independent Risk Factor ◽  
Elevated Serum ◽  
Prothrombin G20210a ◽  
Control Group ◽  
Healthy Controls ◽  
Lipoprotein A

Elevation of serum lipoprotein (a) (Lp[a]) is a known risk factor predisposing to cardiovascular and cerebrovascular disease. However, little is known about the role of increased Lp(a) in venous thromboembolism (VTE). This study evaluated the role of Lp(a) among a panel of established hereditary thrombogenic defects in patients with VTE. A total of 685 consecutive patients with at least one episode of VTE and 266 sex- and age-matched healthy controls were screened with regard to activated protein C resistance, protein C, protein S, and antithrombin deficiency, elevated serum levels of Lp(a), and the factor V G1691A, MTHFR C677T, and prothrombin G20210A mutations. Elevated Lp(a) levels above 30 mg/dL were found in 20% of all patients, as compared to 7% among healthy controls (P < .001, odds ratio [OR] 3.2, 95% confidence interval [CI], 1.9-5.3). The coexistence of FV G1691A and elevated Lp(a) was significantly more prevalent among patients with VTE than in the control group (7% versus 0.8%; P < .001, OR 9.8, 95% CI, 2.4-40.7). No other established prothrombotic risk factor was found to be significantly combined with increased Lp(a). These data suggest that Lp(a) concentrations greater than 30 mg/dL are a frequent and independent risk factor for VTE. Furthermore, elevated Lp(a) levels might contribute to the penetrance of thromboembolic disease in subjects being affected by other prothrombotic defects, such as FV G1691A mutation.

Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3364-3368 ◽  
Author(s):  
Mario von Depka ◽  
Ulrike Nowak-Göttl ◽  
Roswith Eisert ◽  
Christian Dieterich ◽  
Monika Barthels ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Protein C ◽  
Independent Risk Factor ◽  
Elevated Serum ◽  
Prothrombin G20210a ◽  
Control Group ◽  
Healthy Controls ◽  
Lipoprotein A

Abstract Elevation of serum lipoprotein (a) (Lp[a]) is a known risk factor predisposing to cardiovascular and cerebrovascular disease. However, little is known about the role of increased Lp(a) in venous thromboembolism (VTE). This study evaluated the role of Lp(a) among a panel of established hereditary thrombogenic defects in patients with VTE. A total of 685 consecutive patients with at least one episode of VTE and 266 sex- and age-matched healthy controls were screened with regard to activated protein C resistance, protein C, protein S, and antithrombin deficiency, elevated serum levels of Lp(a), and the factor V G1691A, MTHFR C677T, and prothrombin G20210A mutations. Elevated Lp(a) levels above 30 mg/dL were found in 20% of all patients, as compared to 7% among healthy controls (P &lt; .001, odds ratio [OR] 3.2, 95% confidence interval [CI], 1.9-5.3). The coexistence of FV G1691A and elevated Lp(a) was significantly more prevalent among patients with VTE than in the control group (7% versus 0.8%; P &lt; .001, OR 9.8, 95% CI, 2.4-40.7). No other established prothrombotic risk factor was found to be significantly combined with increased Lp(a). These data suggest that Lp(a) concentrations greater than 30 mg/dL are a frequent and independent risk factor for VTE. Furthermore, elevated Lp(a) levels might contribute to the penetrance of thromboembolic disease in subjects being affected by other prothrombotic defects, such as FV G1691A mutation.

The neuro-cardiac junction defines an extracellular microdomain required for neurotrophic signaling

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Mongillo ◽  
M Franzoso ◽  
V Prando ◽  
L Dokshokova ◽  
A Di Bona ◽  
...  
Keyword(s):  
Culture Medium ◽  
Heart Diseases ◽  
Sympathetic Neurons ◽  
Confocal Imaging ◽  
Public Institution ◽  
Mdx Mice ◽  
Mouse Heart ◽  
Funding Source ◽  
Neurotrophic Signaling

Abstract Background Sympathetic neurons (SNs) innervate the myocardium with a defined topology that allows physiological modulation of cardiac activity. Neurotrophins released by cardiac cells control SN viability and myocardial distribution, which are impaired in heart diseases with reduced (e.g. heart failure) or heterogenous sympathetic stimulation (e.g. arrhythmias). We previously demonstrated that SNs interact directly with cardiomyocytes (CMs) at neuro-cardiac junctions (NCJ), and such structured contact sites allow neurons to efficiently activate β-adrenoceptors on the myocyte membrane. Aims We here asked whether NCJs are functional for retrograde (myocyte to neuron) neurotrophic signaling. Methods and results Electron microscopy and immunofluorescence on mouse heart slices and SN/CM co-cultures showed that the NGF receptor, TrkA, is preferentially found in correspondence of the NCJ. Consistently, neurons taking structured contact with CMs showed fast TrkA activation and its retrograde transport to the soma, which was monitored using live confocal imaging in cells expressing TrkA-RFP. In accord with NGF dependent effects, CM-contacted SN showed larger synaptic varicosities and did not require NGF supplementation in the culture medium. In support that NGF locally released at NCJs sustains SN viability, the neurotrophin concentration in the culture medium was 1.61 pg/mL, and did not suffice to maintain neuronal viability, which was also perturbed (66% decrease of neuronal density) by silencing NGF expression in CMs. These results support that the NCJ is essential for intercellular neurotrophin signaling. Consistently, by applying competitive inhibition of TrkA with increasing doses of K252a, we estimated NGF concentration at the contact site to be about 1000-fold higher than that released by CM in the culture medium. To seek for the structural determinants of the NCJ, we focused on dystrophin, based on the finding that the protein accumulates on the CM membrane portion contacted by SNs, as observed in mouse heart slices, and co-cultured CMs. In support of a role of CM-expressed dystrophin in neurotrophic signaling, hearts from dystrophin-KO (mdx) mice showed 74.36% decrease of innervation, with no significant changes of NGF expression. In line with the purported role of NCJs, in co-cultures between wild type SNs and mdx CMs, TrkA activation (TrkA movements toward SN soma (%): WTCM-WTSN=18±4; MDXCM-WTSN= 12±3; p&lt;0,05) and neuronal survival were reduced. Conclusions Taken together, our results suggest that NGF-dependent signaling to SNs requires a direct and specialized interaction with myocytes, and that loss of dystrophin at the CM membrane impairs retrograde signaling to the neurons leading to cardiac sympathetic dys-innervation. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): University of Padova

scholarly journals Serum High Lipoprotein(a) Levels in Patients with Type 2 Diabetes May Be an Independent Risk Factor for Hypertension

2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Lingfen Zeng ◽  
Jieming Sun ◽  
Ming Cui
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Risk Factor ◽  
Independent Risk Factor ◽  
Glycosylated Hemoglobin ◽  
Serum Triglyceride ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Lipoprotein A

Objective — To investigate whether serum lipoprotein(a) [Lp(a)] is an independent risk factor for abnormal blood pressure in patients with type 2 diabetes mellitus. Method — Analyzed data collected from diabetes patients and epidemiological survey from January 1,2020 to May 01,2021, with hypertension as a dependent variable, metabolic index such as glycosylated hemoglobin, serum total cholesterol, serum triglyceride and Lp(a) were independent variables, established logistic regression equation, analyze the influence of their variables on dependent variables. Results — The OR value of Lp(a) is 1.020, 95% confidence intervals (1.006, 1.035), p 0.006; The OR value of age is 1.073, 95% confidence interval (1.028, 1.119); and OR of the remaining parameters were tested no statistically different, p>0.05. Conclusions — The abnormal elevated Lp(a) level in the serum of type 2 diabetic patients may be related to the occurrence of hypertension. For patients with high Lp(a), Monitoring blood pressure may help to better detect and diagnose hypertension. At the same time, it is suggested that reducing serum Lp(a) level may reduce the risk of hypertension.

scholarly journals THE RISK OF FALLS IN PATIENTS WITH RHEUMATOID ARTHRITIS

2017 ◽  
Vol 54 (6) ◽  
pp. 705-711 ◽  
Author(s):  
N. V. Toroptsova ◽  
A. Yu. Feklistov
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Risk Factor ◽  
Independent Risk Factor ◽  
Risk Of Falls ◽  
Relationship Of ◽  
The Relationship

The paper discusses the materials of investigations dealing with falls as an independent risk factor for fractures in patients with rheumatoid arthritis (RA). It gives data on the incidence and possible risk factors of falls in this category of patients. According to the data obtained, the prevalence of falls in different countries varies from 10 to 50%, which may be related to differences in the methods of collecting information, and the relationship of the investigated factors with the risk of falls in patients with RA is uniquely unproven and calls for further investigations.

Lipids, lipoproteins, and atherogenesis

2011 ◽  
pp. 11-24
Author(s):  
Joanna Gouni-Berthold ◽  
Wilhelm Krone
Keyword(s):  
Risk Factor ◽  
High Density Lipoprotein ◽  
Independent Risk Factor ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Apolipoprotein A ◽  
Low Hdl ◽  
Lipids And Lipoproteins

• Lipids and lipoproteins have a central role in the pathogenesis of atherosclerosis. • The concentration of low-density lipoprotein (LDL) is strongly and directly related to risk of atherosclerosis whereas high-density lipoprotein (HDL) is inversly related, low HDL being an independent risk factor. • The role of plasma triglycerides is less well defined. • The ratio of apolipoprotein B (the major apolipoprotein of LDL) to apolipoprotein A-1 (the major apolipoprotein of HDL) is emerging as the best predictor of atherosclerotic risk.

P6196Lipoprotein (a) and cardiovascular risk: are women at increased risk?

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M R Santos ◽  
A Pereira ◽  
F Mendonca ◽  
J Sousa ◽  
M Neto ◽  
...  
Keyword(s):  
Risk Factor ◽  
Coronary Stenosis ◽  
Independent Risk Factor ◽  
Arterial Disease ◽  
Cardiac Events ◽  
Male Population ◽  
Female Population ◽  
Lipoprotein A ◽  
Increased Risk ◽  
Peripheral Arterial

Abstract Introduction Coronary artery disease (CAD) is the leading cause of death worldwide, placing a major economic and resource burden on health and public health systems, so efforts are being made to accurately predict risk for major adverse cardiac events (MACE). The field of risk prediction and CAD prevention continues to evolve with the identification of novel risk factors and biomarkers, such as lipoprotein a [Lp)a]. Almost 20% of the population has elevated circulating levels of Lp(a), which is recognized as an independent risk factor for CAD, stroke, peripheral arterial disease, and aortic stenosis. Importantly, studies showed that this was particularly true for women. Objective To evaluate if the elevation of Lp(a) is associated with MACE in female, male or both. Materials and methods Case control study of 3050 subjects from the GENEMACOR study population. In female population (n=676): cases were 341 patients with at least one >75% coronary stenosis (median age 55.7±7.2) and 335 normal controls (median age 55.8±6) adjusted by age with cases. In male population (n=2374): 1278 patients with at least one >75% coronary stenosis (median age 52.7±8) and 1096 controls (median age 51.9±8) also adjusted by age. χ2 and T student tests were used to analyze the demographic, laboratorial, angiographic and anthropometric characteristics of the population. Lipoprotein (a) was determined by immunoturbidimetry. High Lp(a) level was considered if superior to 30 mg/dl. Logistic regression was used to evaluate Lp(a) as a risk factor for CAD in total, female and male populations. Results In female population 44.0% patients vs 21.2% controls (p<0.000) had Lp(a)>30mg/dl. In male population 39.4% patients vs 23.8% controls (p<0.000) had Lp(a)>30mg/dl. In total population Lp(a)>30mg/dl was a predictor for CAD (OR 2.24, 95% CI: 1.91–2.62, p<0.0001). Analyzing by gender, Lp(a)>30mg/dl was also a predictor for CAD either in male (OR 2.08, 95% CI: 1.74–2.5, p<0.0001) or female population (OR 2.92, 95% CI: 2.08–4.09, p<0.0001). Conclusions As opposed to other studies, in our population elevated Lp(a) levels (>30mg/dl) were associated with elevated CAD risk, in both men and women. We conclude that Lp(a) can be considered an independent risk factor for CAD disease in our population, and further strategies for Lp(a) reduction may indeed translate in improved outcomes in CAD disease.

scholarly journals Lipoprotein(a) Is an Independent Risk Factor for Cardiovascular Disease in Heterozygous Familial Hypercholesterolemia

2005 ◽  
Vol 51 (11) ◽  
pp. 2067-2073 ◽  
Author(s):  
Daniel T Holmes ◽  
Brian A Schick ◽  
Karin H Humphries ◽  
Jiri Frohlich
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Familial Hypercholesterolemia ◽  
Independent Risk Factor ◽  
Independent Predictor ◽  
Cvd Risk ◽  
Lipoprotein A ◽  
Heterozygous Familial Hypercholesterolemia ◽  
Lipid Clinic

Abstract Background: The role of lipoprotein(a) [Lp(a)] as a predictor of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolemia (HFH) is unclear. We sought to examine the utility of this lipoprotein as a predictor of CVD outcomes in the HFH population at our lipid clinic. Methods: This was a retrospective analysis of clinical and laboratory data from a large multiethnic cohort of HFH patients at a single, large lipid clinic in Vancouver, Canada. Three hundred and eighty-eight patients were diagnosed with possible, probable, or definite HFH by strict clinical diagnostic criteria. Multivariate Cox regression analysis was used to study the relationship between several established CVD risk factors, Lp(a), and the age of first hard CVD event. Results: An Lp(a) concentration of 800 units/L (560 mg/L) or higher was a significant independent risk factor for CVD outcomes [hazard ratio (HR) = 2.59; 95% confidence interval (CI), 1.53–4.39; P &lt;0.001]. Other significant risk factors were male sex [HR = 3.19 (1.79–5.69); P &lt;0.001] and ratio of total to HDL-cholesterol [1.18 (1.07–1.30); P = 0.001]. A previous history of smoking or hypertension each produced HRs consistent with increased CVD risk [HR = 1.55 (0.92–2.61) and 1.57 (0.90–2.74), respectively], but neither reached statistical significance (both P = 0.10). LDL-cholesterol was not an independent predictor of CVD risk [HR = 0.85 (0.0.71–1.01); P = 0.07], nor was survival affected by the subcategory of HFH diagnosis (i.e., possible vs probable vs definite HFH). Conclusion: Lp(a) is an independent predictor of CVD risk in a multiethnic HFH population.

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