Lipoprotein(a) is a strong risk factor for Aortic Valve Calcium

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Kaiser ◽  
S.S Singh ◽  
K.H Zheng ◽  
R Verbeek ◽  
M Kavousi ◽  
...  
Keyword(s):  
Aortic Valve ◽  
The Netherlands ◽  
Medical Center ◽  
Density Lipoprotein ◽  
Population Based ◽  
Public Institution ◽  
Western World ◽  
Funding Source ◽  
Linear Regression Models ◽  
Lipoprotein A

Abstract Background Aortic valve calcium (AVC) is an important hallmark of aortic valve stenosis, which is the most common valvular heart disease in the Western world. Studies suggesting an important role for lipoprotein(a) [Lp(a)] in the etiology of AVC are accumulating, yet population-based evidence is scarce. Therefore, we investigated the association of Lp(a) with the presence of AVC in two large cohorts. Methods A total of 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3), and 859 asymptomatic persons from the Amsterdam Medical Center outpatient clinic for familial premature (non-valvular) atherosclerosis (57%women, mean age=45.9±11.6) underwent blood sampling to determine serum Lp(a) and non-enhanced cardiac CT-scan to assess AVC. We combined both cohorts and investigated the association of Lp(a) with the presence and amount of AVC using logistic and linear regression models, adjusting for age, sex, smoking, body mass index, non-high density lipoprotein cholesterol and use of antihypertensive medication. Results Out of a total of 3271 subjects with an average age of 63.4±7.98, AVC was present in 844 (25.8%) individuals. Higher levels of Lp(a) were associated with the presence of AVC, independent of age, sex and cardiovascular risk factors [Odds ratio (OR) per 1-SD increase in Lp(a): 1.39 (95% CI:1.27; 1.51). In persons with AVC, a higher level of Lp(a) was also related to larger volume of AVC [β per 1-SD increase in Lp(a): 0.76 (95% CI:1.27; 1.51)]. All findings were similar across both cohorts. Conclusion Lp(a) is a prominent and independent marker of the presence and amount of AVC in the general population. Future studies investigating the effect of Lp(a) lowering on the progression of AVC are warranted. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): NESTOR program for geriatric research, the Netherlands Heart Foundation, the Netherlands Organization for Scientific Research, the Health Research and Development Council (28-2975 and 97-1-364), and the Municipality of Rotterdam

scholarly journals Lipoprotein(a) is associated with incidence but not progression of aortic valve calcium

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Y Kaiser ◽  
J E Van Der Toorn ◽  
K H Zheng ◽  
M Kavousi ◽  
M W Vernooij ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Density Lipoprotein ◽  
Public Institution ◽  
Lipid Lowering ◽  
Regression Analyses ◽  
Rotterdam Study ◽  
Lipoprotein A ◽  
Relationship Of ◽  
The Relationship

Abstract Background Lipoprotein(a) [Lp(a)] has been implicated in the etiology of aortic valve stenosis. Although Lp(a) is strongly associated with the presence of aortic valve calcium (AVC), there are no data evaluating the relationship of Lp(a) with AVC incidence and AVC progression. Purpose To assess whether high Lp(a) levels are associated with AVC incidence and progression. Methods In 922 individuals from the population-based Rotterdam Study (mean age 66.0±4.2 years, 47.7% men) for whom Lp(a) measurements were available, non-enhanced cardiac CT imaging was performed at baseline and after a median follow-up of 14.0 [13.9–14.2] years. AVC incidence was defined as an AVC score >0 on the second scan, in absence of AVC on the first scan. We performed logistic regression analyses to evaluate the relationship of Lp(a) with AVC incidence and linear regression analyses to assess the relationship between Lp(a) and AVC progression. All analyses were corrected for age, sex, body mass index, smoking, non-high-density lipoprotein cholesterol, use of lipid-lowering medication, and hypertension. Additionally, we analyzed the progression conditional on the baseline AVC-score. Results Of the 702 (76.1%) individuals without AVC at baseline, 415 (59.1%) showed incident AVC at follow-up. The 220 (23.9%) individuals with AVC on baseline had a median AVC score of 52 [15–131], with a median yearly progression of 13 [5–38]. Lp(a) concentration was independently associated with AVC incidence (OR 1.32 for each 105 nmol/L Lp(a) increase; 95% CI: 1.03–1.68), but not with AVC progression (β −4.3 AU/year for each 105 nmol/L Lp(a) increase; 95% CI: −12.3–3.7). Conclusions Lp(a) is associated with AVC incidence but not AVC progression, suggesting that Lp(a)-lowering interventions may be futile after AVC has been established. Future studies should focus on whether Lp(a) lowering interventions can prevent the development of AVC in high-risk individuals. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Rotterdam Study is supported by Erasmus MC and Erasmus University Rotterdam and the Netherlands Organization for Scientific Research

High levels of lipoprotein(a) are associated with the severity of coronary disease in patients with acute myocardial infarction. Data from the RICO survey

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Farnier ◽  
H Yao ◽  
N Hounton ◽  
M Maza ◽  
F Chague ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Coronary Angiography ◽  
Public Institution ◽  
Syntax Score ◽  
Funding Source ◽  
Lipoprotein A ◽  
History Of ◽  
Acute Mi ◽  
Very High

Abstract Background High level of Lipoprotein(a), Lp(a), is a well-recognised independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, limited data are available on the prevalence of high Lp(a) levels and on the threshold associated to coronary artery disease (CAD) burden in patients with acute myocardial infarction (MI). Methods We aim at assessing CAD burden in 651 consecutive patients hospitalized for an acute MI from January 2019 to September 2019 who underwent coronary angiography. Patients characteristics and angiographic features were compared for patients with Lp(a) <50 mg/dL (normal), ≥50 mg/dL (high) and >80 mg/dL (i.e >90th percentile) (very high). Results The prevalence of Lp(a) ≥50 mg/dL was elevated (19.0%) and 65 patients (10.0%) were in the >90th percentile. Median (IQR) age was similar across the 3 groups (normal: 68 (59–79)y; high: 74 (63–80)y; very high: 71 (57–82)y, p=0.239). When compared with patients with normal Lp(a), patients with very high levels (≥80 mg/dL) had higher prevalence of personal history of ASCVD (29 vs 16%, p=0.021) and family history of CAD (37 vs 19%, p=0.005), and were more frequently women (43 vs 29%, p=0.009). At coronary angiography, patients with very high Lp(a) levels had increased extent of CAD (Median SYNTAX score 17 (5–25) vs 10 (5–17), p=0.002) and more frequent multivessel disease (69 vs 54%, p=0.02). Conclusion Among real world patients hospitalized for an acute MI, Lp(a) levels >80 mg/dL are associated with an increased CAD burden and this threshold identifies a subset of patients with features of high ASCVD risk. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): ARS Bourgogne Franche Comté; CHU Dijon Bourgogne

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

scholarly journals Correlations between lipoprotein(a) gene polymorphisms and calcific aortic valve disease and coronary heart disease in Han Chinese

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096535
Author(s):  
Hongzhi Dong ◽  
Hongliang Cong ◽  
Jing Wang ◽  
Yiyao Jiang ◽  
Chao Liu ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Density Lipoprotein ◽  
Han Chinese ◽  
Valve Disease ◽  
Calcific Aortic Valve Disease ◽  
Lipoprotein A ◽  
Minor Alleles

Objective To investigate the relationship between lipoprotein(a) gene ( LPA) polymorphisms and calcific aortic valve disease (CAVD) and coronary heart disease (CHD) in Han Chinese. Methods A total of 148 patients were recruited (n = 71 with CAVD and n = 77 with CHD) based on a diagnosis achieved using color Doppler echocardiography, coronary angiography, or computed tomography angiography. Seventy-one control individuals without CAVD or CHD were also recruited. Biomarkers including levels of lipoprotein(a) [Lp(a)], low-density lipoprotein and high-density lipoprotein cholesterol, apolipoprotein A1, and apolipoprotein B were tested. LPA polymorphisms rs10455872, rs6415084, rs3798221, and rs7770628 were analyzed using SNaPshot SNP. Results Lp(a) levels were significantly higher in CAVD and CHD groups compared with controls. There was no significant difference in the allelic frequency distribution of rs3798221, rs7770628, or rs6415084 between CHD, CAVD, and control groups. Linear regression showed that rs3798221, rs7770628, and rs6415084 were associated with increased Lp(a) concentrations. Two CAVD patients among the 219 participants carried AG minor alleles at rs10455872, while the remainder carried AA minor alleles. Conclusion rs3798221, rs6415084, and rs7770628 polymorphisms within LPA are associated with higher Lp(a) plasma levels, which correlate with increased CAVD and CHD risks.

scholarly journals A genetic sum score of effect alleles associated with serum lipid concentrations interacts with educational attainment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carina Emmel ◽  
Mirjam Frank ◽  
Nico Dragano ◽  
Markus M. Nöthen ◽  
Raimund Erbel ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Genetic Effect ◽  
Population Based ◽  
Lipoprotein Cholesterol ◽  
Linear Regression Models ◽  
Interaction Terms ◽  
Education Group ◽  
Sum Score ◽  
Study Participants

AbstractHigh-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) levels are influenced by both genes and the environment. The aim was to investigate whether education and income as indicators of socioeconomic position (SEP) interact with lipid-increasing genetic effect allele scores (GES) in a population-based cohort. Using baseline data of 4516 study participants, age- and sex-adjusted linear regression models were fitted to investigate associations between GES and lipids stratified by SEP as well as including GES×SEP interaction terms. In the highest education group compared to the lowest stronger effects per GES standard deviation were observed for HDL-C (2.96 mg/dl [95%-CI: 2.19, 3.83] vs. 2.45 mg/dl [95%-CI: 1.12, 3.72]), LDL-C (6.57 mg/dl [95%-CI: 4.73, 8.37] vs. 2.66 mg/dl [95%-CI: −0.50, 5.76]) and TC (8.06 mg/dl [95%-CI: 6.14, 9.98] vs. 4.37 mg/dl [95%-CI: 0.94, 7.80]). Using the highest education group as reference, interaction terms showed indication of GES by low education interaction for LDL-C (ßGES×Education: −3.87; 95%-CI: −7.47, −0.32), which was slightly attenuated after controlling for GESLDL-C×Diabetes interaction (ßGES×Education: −3.42; 95%-CI: −6.98, 0.18). The present study showed stronger genetic effects on LDL-C in higher SEP groups and gave indication for a GESLDL-C×Education interaction, demonstrating the relevance of SEP for the expression of genetic health risks.

scholarly journals Lipoprotein(a) is robustly associated with aortic valve calcium

Heart ◽  
2021 ◽  
pp. heartjnl-2021-319044
Author(s):  
Yannick Kaiser ◽  
Sunny S Singh ◽  
Kang H Zheng ◽  
Rutger Verbeek ◽  
Maryam Kavousi ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Population Based ◽  
Agatston Score ◽  
Study Cohort ◽  
Rotterdam Study ◽  
Lipoprotein A ◽  
Medical Centers ◽  
End Stage ◽  
Age Range ◽  
Apparently Healthy

ObjectivesTo investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC.MethodsWe included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC.ResultsThe prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (β 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase).ConclusionsLp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.

Low-density lipoprotein cholesterol <50 mg/dL is an appropriate target after acute coronary syndrome: propensity score-matched analysis of the ODYSSEY OUTCOMES trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G.G Schwartz ◽  
M Szarek ◽  
D.L Bhatt ◽  
V.A Bittner ◽  
R Diaz ◽  
...  
Keyword(s):  
Propensity Score ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Target Range ◽  
Funding Source ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein A

Abstract Background New ESC/EAS guidelines advise a low-density lipoprotein cholesterol (LDL-C) target level &lt;55 mg/dL for patients with acute coronary syndromes (ACS), and a level &lt;40 mg/dL for those with recurrent events. Previous analyses of clinical trials have sought to define an optimal LDL-C target range to prevent major adverse cardiovascular events (MACE). However, those analyses are limited because patients who achieve lower versus higher LDL-C levels on lipid-lowering therapy differ in other characteristics that are prognostic for MACE, including baseline LDL-C, lipoprotein(a), and medication adherence. Aim To overcome these limitations, we performed a propensity score-matching (PSM) analysis of the ODYSSEY OUTCOMES trial, which compared the PCSK9 inhibitor alirocumab with placebo in 18,924 patients with recent ACS. Methods Patients on alirocumab were classified in 1 of 3 pre-specified categories according to Month 4 LDL-C &lt;25 (n=3357), 25–50 (n=3692) or &gt;50 mg/dL (n=2197). Within each category, MACE after Month 4 was compared with patients on placebo using 1:1 PSM on demographic, clinical, and adherence variables. Because the trial design involved blinded substitution of placebo for alirocumab when consecutive LDL-C levels were &lt;15 mg/dL on alirocumab, we also evaluated MACE in those patients (n=730) in comparison with patients chosen from the placebo group by 1:3 PSM. Results Patients in the three achieved LDL-C categories of the alirocumab group differed by baseline age, sex, geographic region; history of diabetes, smoking, peripheral artery disease, cerebrovascular disease, coronary revascularization, heart failure, obstructive pulmonary disease, or malignancy; type of index ACS event; baseline LDL-C, lipoprotein(a), estimated glomerular filtration rate, body mass index, systolic blood pressure; use of intensive statin therapy; and adherence with study medication. After PSM, patients in each LDL-C category on alirocumab were well matched to patients on placebo for these characteristics. Treatment hazard ratios (HRs) for MACE (Figure) were similar in those with achieved LDL-C &lt;25 mg/dL or 25–50 mg/dL. Patients with achieved LDL-C &gt;50 mg/dL achieved less benefit. Patients who achieved consecutive LDL-C levels &lt;15 mg/dL and were switched to placebo nonetheless had a robust HR (0.71, 95% CI 0.52–0.98) and thus did not dilute efficacy of alirocumab among those in the &lt;25 mg/dL achieved LDL-C category. Conclusion After accounting for differences in baseline characteristics and adherence, reduction in risk of MACE with alirocumab was similar in patients who achieved LDL-C &lt;25 or 25–50 mg/dL. These data suggest that an LDL-C target of less than 50 mg/dL may be reasonable after ACS and is essentially congruent with new ESC/EAS guidelines. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi and Regeneron Pharmaceuticals, Inc

Risk factors for silent and symptomatic atrial fibrillation in an elderly population screening programme:a report from the noninvasive monitoring for early detection of atrial fibrillation (NOMED-AF)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Mitrega ◽  
B Sredniawa ◽  
J Stokwiszewski ◽  
A Sokal ◽  
J Boidol ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
General Population ◽  
Population Sample ◽  
Population Based ◽  
Public Institution ◽  
Elderly Subjects ◽  
Funding Source ◽  
Cross Sectional ◽  
Independent Risk Factors

Abstract Background It is important to determine the risk factors that predispose elderly subjects from the general population for symptomatic atrial fibrillation and atrial flutter (AF/AFl), but population-based data for silent AF (SAF) are limited. Aim To study risk factors for symptomatic AF and SAF in a general population screen for subjects age ≥65 where continuous monitoring was performed up to 30 days with a vest-based monitor. Methods The NOMED-AF study was a cross-sectional study based on a representative population sample (n=3014; mean age 77.5±7.9 years; F=1479). In 680 subjects AF/AFl (including 279 with SAF) was diagnosed. Independent risk factors for AF/AFl and SAF were determine on weighted data using multiple logistic regression. Results The independent risk factors for AF/AFl and SAF are summarised in the Table. There are nine independent risk factors for AF/AFl and eight for SAF. Revascularization and obesity were independently associated with patients with (symptomatic) AF/AFl, and CKD was associated with SAF. Other risk factors are common for AF/AFl and SAF. Conclusions AF/AFl and SAF have slightly different associated clinical risk factors in this representative population sample aged ≥65 years. This may facilitated targeted screening programmes for high risk subgroups, particularly for SAF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The research has received funding from the National Centre for Research and Development under grant agreement (STRATEGMED2/269343/18/NCBR/2016)

scholarly journals Association Between HDL Cholesterol and QTc Interval: A Population-Based Epidemiological Study

2019 ◽  
Vol 8 (10) ◽  
pp. 1527 ◽  
Author(s):  
Rosaria Del Giorno ◽  
Sofia Gabutti ◽  
Chiara Troiani ◽  
Kevyn Stefanelli ◽  
Raffaele Falciano ◽  
...  
Keyword(s):  
Regression Models ◽  
Reference Group ◽  
Experimental Studies ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Population Based ◽  
Antiarrhythmic Effect ◽  
Qtc Interval ◽  
Linear Regression Models ◽  
Cross Sectional

Previous experimental studies showed that increasing high-density lipoprotein cholesterol (HDL) cholesterol shortens cardiac ventricular repolarization and the QT interval corrected for heart rate (QTc). However, little is known about the epidemiological relationship between HDL and QTc. The potential antiarrhythmic effect of HDL cholesterol remains a speculative hypothesis. In this cross-sectional population based study in adults living in the Italian-speaking part of Switzerland, we aimed to explore the association between HDL cholesterol and the QTc interval in the general population. A total of 1202 subjects were screened. electrocardiogram (ECG) recordings, measurements of lipid parameters and other laboratory tests were performed. QTc was corrected using Bazett’s (QTcBaz) and Framingham (QTcFram) formulas. HDL was categorized according to percentile distributions: <25th (HDL-1; ≤1.39 mmol/L); 25th–<50th (HDL-2; 1.40–1.69 mmol/L); 50th–<75th (HDL-3; 1.69–1.99 mmol/L); and ≥75th (HDL-4; ≥2.0 mmol/L). After exclusion procedures, data of 1085 subjects were analyzed. Compared with the HDL reference group (HDL-1), HDL-2 and HDL-3 were associated with a reduction of QTcBaz and QTcFram duration in crude (HDL-2, QTcBaz/QTcFram: β-11.306/–10.186, SE 4.625/4.016; p = 0.016/0.012; HDL-3, β-12.347/–12.048, SE 4.875/4.233, p = 0.012/<0.001) and adjusted (HDL-2: β-11.697/–10.908, SE 4.333/4.151, p < 0.001/0.010; HDL-3 β-11.786/–11.002, SE 4.719/4.521, p = 0.014/0.016) linear regression models in women. In adjusted logistic regression models higher HDL, were also associated with lower risk of prolonged QTcBaz/QTcFram (HDL-2: OR 0.16/0.17, CI 0.03–0.83/0.47–0.65; HDL-3: OR 0.10/0.14, CI 0.10–0.64/0.03–0.63) in women. Restricted cubic spline analysis confirmed a non linear association (p < 0.001). The present findings indicate an epidemiological association between HDL cholesterol and QTc duration. To draw firm conclusions, further investigations in other populations and with a prospective cohort design are needed.

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