Elevated Levels Of Lp Research Articles

Lipoprotein(a) and High-Sensitivity C-Reactive Protein Compound the Risk of Hypoattenuating Leaflet Thickening After Transcatheter Aortic Valve Replacement.

The mechanism for hypoattenuating leaflet thickening (HALT) after transcatheter aortic valve replacement is still not well elucidated, and the role of Lp(a) (lipoprotein[a]) and hs-CRP (high-sensitivity C-reactive protein) has rarely been studied. This study sought to test the hypothesis that the risk of HALT is associated with an elevated level of Lp(a) or hs-CRP. A total of 307 consecutive individuals who underwent a transcatheter aortic valve replacement procedure were included. All patients received their first postoperative computed tomography scans within 12 months, and raw data were analyzed on 3mensio software. HALT was defined as visually identified increased leaflet thickness with typical meniscal appearance and at least 2 different multiplanar reformation projections. Associations of Lp(a) or hs-CRP with the risk of HALT were evaluated using multivariable logistic regression analysis. The incidence of HALT within 12 months after transcatheter aortic valve replacement in this study was 36.2%, and the risk of HALT was associated with higher baseline Lp(a) (the multivariable adjusted odds ratio [OR] for every 10 mg/dL change was 1.18 [95% CI, 1.09-1.29]) and hs-CRP level (the multivariable adjusted OR for every 1 mg/L change was 1.08 [95% CI, 1.00-1.27]). Compared with individuals out of the top 25th percentile for both Lp(a) and hs-CRP, the multivariable adjusted OR for HALT was 4.74 (95% CI, 1.65-14.37) for the top 25th percentile. This result remained consistent after excluding patients receiving anticoagulant therapy. The top 25th percentile of Lp(a) level (≥40 mg/dL) combined with the top 25th percentile of hs-CRP level (≥3.5 mg/L) conferred a 4.74-fold risk of HALT.

IMPACT OF DYSLIPIDEMIA ON CORONARY HEART DISEASE IN WOMEN (REVIEW)

Introduction:The increase in the level of lipids in the blood is one of the risk factors for cardiovascular diseases (due to atherosclerosis and thrombosis) increasing premature morbidity, disability, financial cost and mortality, not only in the EU and the USA, but also in countries developing worldwide. It has been proven that lipid disorders promote the development of atherosclerosis and its clinical consequences such as CVD including (coronary heart disease, acute myocardial infarction, peripheral artery disease, heart failure and sudden death). Combinations of lipoprotein levels and lipid fractions play a major risk role in terms of coronary heart diseases. Purpose: Evidence of dyslipidemia as a risk factor for CVD, especially in obese women who suffer from metabolic syndrome or diabetes and have lipid profiles that negatively affect the risk of coronary heart disease. Methodology: International literature review in PubMed, CINAHL, Am J Cardiology, Int J Public Health; in accordance with the purpose and objectives of the study. Result: Coronary heart diseases are the leading cause of death among women and men although they are less common and appear later in women than in men. Each year 345,000 women suffer from an initial or recurrent myocardial infarction, and 261,000 women die from MI. Compared to men, women, and especially women in the postmenopausal period, remain at high risk for coronary disease. In women, calcification occurs 10 to 15 years later. Multiple angiographic studies of coronary arteries have shown a lower rate of epicardial coronary artery disease in women than in age-matched men. Elevated levels of Lp (a) appear to be more associated with the occurrence of coronary heart disease than with the severity of coronary artery disease in both sexes. Outcome data in women using lipid-lowering medications other than statins are extremely limited. Conclusion: The importance of a healthy lifestyle should begin in childhood and continue throughout life. Although the benefits of lipid-lowering therapy in women with cardiovascular disease are clear, more data are needed in those without cardiovascular disease. Clinical trials for lipid-lowering women with cardiovascular disease to date have used a strategy focused on lowering LDL-cholesterol, which may not be optimal for women who have low HDL-cholesterol or triglyceride levels. which are very important factors affecting coronary heart disease. It remains to be determined whether outcomes among women will improve if treatment strategies are directed toward more aggressive and comprehensive modification of lipoprotein profiles.

Influence of pseudoxanthoma elasticum on the lipid profile and prognostic implications.

Background: Pseudoxanthoma elasticum (PXE) is a rare, inherited disease characterised by specific skin lesions, progressive loss of vision and early onset atherosclerosis. Atherosclerosis in PXE leads to an increased rate of vascular occlusion and severe intermittent claudication. Although genetically determined, the individual course of PXE is highly variable. Up to now, there is no sufficient parameter to identify individuals at risk of rapid disease progression. This present study focused the lipid profile of patients with PXE and its possible influence on the clinical severity of peripheral artery disease (PAD). Patients and methods: 112 patients with PXE were retrospectively screened. Patients without a complete lipid profile consisting of total cholesterol (TC), triglycerides (TGC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and Lipoprotein(a) (Lp[a]) where excluded as well as patients with already initiated lipid-lowering therapy. 52 patients met the inclusion criteria. An age-adjusted ordinal regression model was applied to determine the association of each lipid fraction with the severity of PAD assessed as Fontaine classification. Results: The lipid profile of patients with PXE was unremarkable (TGC: 135.8±105.8 mg/dl; TC: 172.5±44.4 mg/dl; HDL: 63.0±18.2 mg/dl; Lp[a]: 64.7±93.5 nmol/l). Ordinal regression showed a significant association of Lp(a) with the severity of PAD with an odds ratio of 1.01 (1.00-1.02; p = 0.004), whereas the other fractions of the lipid profile had no significant influence. Conclusions: This study provides the largest evaluation of blood lipids up to now and the first characterization of Lp(a) levels in patients with PXE. We were able to provide first evidence of a correlation between elevated levels of Lp(a) and the severity of PAD. The present results suggest that determination of Lp(a) in early stages of PXE could help to identify patients at risk of rapid disease progression and with the need of intensified walking exercise training.

Elevated Levels of Lp(a) are Associated with Circulating Levels of PCSK9 and Coronary Atherosclerosis as Detected by Cardiac Computed Tomography Angiography

Elevated Levels of Lp(a) are Associated with Circulating Levels of PCSK9 and Coronary Atherosclerosis as Detected by Cardiac Computed Tomography Angiography

Exploring the Interplay between Diabetes and Lp(a): Implications for Cardiovascular Risk.

The objective of this manuscript is to review and describe the relationship between Lp(a) and diabetes, exploring both their association and synergy as cardiovascular risk factors, while also describing the current evidence regarding the potential connection between low levels of Lp(a) and the presence of diabetes. Epidemiological studies suggest a potential relationship between low to very low levels of Lp(a) and diabetes. Lipoprotein(a), or Lp(a), is an intriguing lipoprotein of genetic origin, yet its biological function remains unknown. Elevated levels of Lp(a) are associated with an increased risk of cardiovascular atherosclerosis, and coexisting diabetes status confers an even higher risk. On the other hand, epidemiological and genetic studies have paradoxically suggested a potential relationship between low to very low levels of Lp(a) and diabetes. While new pharmacological strategies are being developed to reduce Lp(a) levels, the dual aspects of this lipoprotein's behavior need to be elucidated in the near future.

Статеві та клініко-інструментальні паралелі рівнів ліпопротеїн(а) в пацієнтів з дуже високим серцево-судинним ризиком

In recent years it has been established that elevated levels of Lp(a) are an independent genetic risk factor for the development of atherosclerotic cardiovascular diseases and aortic stenosis, however, issues of gender and age characteristics remain controversial.The aim of study was to analyze the gender characteristics of the relationship between Lp(a) levels and atherogenic changes in the lipid spectrum of the blood, clinical and instrumental characteristics, taking into account damage to the aortic valve and the results of coronary angiography in patients with stable coronary heart disease. Materials and methods. The 106 patients with chronic coronary heart disease (CAD) were examined. The average age of the subjects was 55.00±1.0 years (95% CI 51.11-58.89), among them: 78 men and 28 women.The entire cohort of patients was divided depending on the Lp(a) levels: 1group (n=58) with a Lp(a) level less than 50 mg/dl; 2 group (n=20) with Lp(a) level 50-100 mg/dl; 3 group (n=8) with Lp(a) level 101-150 mg/dl and 4 group (n=20) with Lp(a) level more than 150 mg/dl.Research methods included: 1. General clinical examination; 2. Laboratory characteristics of lipid (with determination of Lp(a)) and carbohydrate metabolism, as well as standard biochemical parameters; 3. Instrumental examination (electrocardiography, echocardiography, ultrasound peripheral vessels examination, coronary angiography); 4. Mathematical and statistical processing of the results obtained.Results and conclusions. In patients with CAD verified by clinical-instrumental and coronary angiographic criteria, it is noted that Lp(a) levels in women are on average significantly higher (P< 0.05) than in men and increase with the onset of menopause.Close correlations have not been recorded between Lp(a) in mg/dL and total cholesterol, LDL cholesterol and non-HDL cholesterol, as well as the concentrations of glucose, glycosylated hemoglobin, serum creatinine, and the concentration of thyroid-stimulating hormone (TSH).Determined that in patients with documented atherosclerotic lesions of the coronary arteries against the Lp(a) levels above 100 mg/dl, there is a greater need for coronary revascularization. A close relationship is observed between the increase in Lp(a) levels and the percentage of detection of aortic stenosis, which confirms the pathogenetic role of this lipoprotein in the formation of this acquired aortic valve disease.

Clinical characteristics associated with elevated levels of lipoprotein(a) in patients with vascular risk.

Lipoprotein(a) (Lp(a)) is increasingly used in the evaluation of patients with vascular risk due to its association with cardiovascular events. The purpose of this study was to identify the clinical characteristics of patients with elevated levels of Lp(a) attended in an outpatient vascular risk unit. An observational, retrospective study was conducted to assess the clinical characteristics of patients with elevated levels of Lp(a) (≥50 mg/dL), as compared to patients with normal values (<50 mg/dL). The sample was composed of 878 patients identified as having a high vascular risk due to a diagnosis of vascular disease, attended in a vascular risk unit between 2021 and 2022. The highest levels of Lp(a) were independently associated with a higher probability of having a history of peripheral arterial disease (p=0.024), polygenic familial hypercholesterolemia (PH, p=0.030) and combined familial hypercholesterolemia (CFH, p=0.015); and using PCSK9 inhibitor treatment (p=0.029) and combination therapy with statins and ezetimibe (p=0.018). In contrast, there were no significant differences in relation to familial history of early cardiovascular disease (p=0.143) or personal history of cardiovascular disease (p=0.063), which contrasts with other series. Elevated levels of Lp(a) were associated with a history of peripheral arterial disease, diagnosis of FHP and CFH, and need for more intense lipid-lowering treatments.

Lipoprotein(a) levels and carotid intima-media thickness in children: A 20-year follow-up study

Elevated lipoprotein(a) [Lp(a)] is independently associated with cardiovascular disease (CVD). In a recent long-term follow-up study involving children with familial hypercholesterolemia (FH), Lp(a) levels contributed significantly to early atherosclerosis, as measured by carotid intima-media thickness (cIMT). To determine if this holds true for children without FH, we conducted a 20-year follow-up study, examining 88 unaffected siblings (mean age: 12.9 years) of children with FH. No significant association was found between Lp(a) and cIMT during follow-up (ß-adjusted [95% confidence interval] = 0.0001 [-0.008 to 0.008] mm per 50 nmol/L increase Lp(a), p = 0.97). In conclusion, our findings suggest that elevated levels of Lp(a) do not play a significant role in arterial wall thickening among children without FH during the 20-year follow-up period. This leads us to consider the possibility that cIMT may not be a suitable marker for detecting potential subtle changes in the arterial wall mediated by Lp(a) in the young, general population. However, it could also be that elevated Lp(a) is only a significant risk factor for atherosclerosis in the presence of other risk factors such as FH.

ApoB-specific CD4+ T cells circulate in human blood and formation of a memory population is driven by coronary artery disease and an elevated cardiovascular risk profile

Abstract Aim Atherosclerosis is a chronic inflammatory disease involving an autoimmune response against Apolioprotein B (ApoB), the core protein of low-density lipoprotein (LDL) cholesterol. Using a translational bench-to-bedside approach, we linked the presence and immuno-phenotype of ApoB-specific CD4+ T cells to clinical risk profiles for cardiovascular disease in humans. Methods Peripheral blood mononuclear cells (PBMCs) from 230 patients that underwent coronary angiography were co-incubated in vitro with a pool of immunodominant peptides from human ApoB for 6h. Reactive ApoB-specific T cells (ApoB+) were defined in flow cytometry by expression of the activation marker CD40L. Partition of ApoBpos into naïve and memory T cells was achieved by extracellular fluorochrome-based staining of CD45RO, CCR7 and CD45RA. Cytokine expression of ApoBpos was determined by intracellular staining. Results We found that a median of 0.69±0.1% of circulating CD4+ T cells were reactive to Apolipoprotein B. We found detectable concentrations of auto reactive ApoB+ T cells in 86,44% of all healthy individuals. However, overall frequencies of ApoB reactive T cells did not correlate with diagnosed coronary artery disease (CAD). Compared to ApoBneg. T cells, we detected a higher fraction of memory T cells in ApoBpos (p&amp;lt;0,0001), suggesting a previously occurred ApoB directed immune response. Accordingly, elevated serum levels of ApoB specific IgG Antibodies associated with high proportions of ApoB specific memory cells. Patients diagnosed with coronary artery disease presented higher percentages of central memory T cells among ApoBpos compared to healthy individuals. Correspondingly, these observations applied to patients with an elevated 10-year risk for cardiovascular events estimated by the ESC-SCORE2. These effects largely grounded on strong associations with the clinical diagnosis of arterial hypertension, elevated levels of Lp(a) and obesity. Interestingly, systolic blood pressure and LDL-serum levels correlated with elevated proportions of memory-status ApoBpos T cells in patients without statin intake, although this was not the case for patients with LDL-lowering medication. Analysis of cytokine expression in ApoBpos CD4+ T cells showed significantly increased expression of anti-inflammatory Il-2 and IL-10 in addition to pro-inflammatory IFNγ. Cytokine secretion was mainly driven by memory-status ApoBpos when compared to naïve ApoBpos T cells. Interestingly, a significant number of patients showed a mixed TH1/Treg phenotype among ApoBpos with simultaneous expression of IL-10 and IFN-γ. Conclusions Our data show for the first time that ApoB-reactive T cells exist even in healthy individuals. Cardiovascular risk factors and clinically relevant atherosclerotic disease drive memory formation and activation of ApoB+ T cells. ApoB+ Memory T cells are prone to secrete pro- and anti-inflammatory cytokines and may modulate systemic inflammation in atherosclerosis.

Lp(a) and inflammation: a new insight into atherosclerosis

AbstractBackgroundLipid‐lowering therapy is of utmost importance in both primary and secondary prevention of atherosclerotic cardio vascular disease (ASCVD). However, the presence of residual risk allows cardiovascular events to occur even when low‐density lipoprotein cholesterol (LDL‐C) levels are very low. A large number of clinical studies have provided evidence confirming the association between elevated plasma Lp(a) and the development of ASCVD. Clinical studies have also suggested that reducing Lp(a) may help decrease the occurrence of cardiovascular events.MainLp(a) consists of LDL‐like particles, apo(a) and OxPL. The level of Lp(a) in thehuman body is predominantly determined by genetics, with external factorshaving minimal impact. Additionally, Lp(a) levels have been found to vary among different ethnicities. There is a notable correlation between elevated levels of Lp(a) and coronary artery disease (CAD), which is independent of other lipoproteins. Furthermore, there exists a linear relationship between Lp(a) levels and the risk of developing ASCVD. It is now wildly believed that Lp(a) primarily contributes to the development of cardiovascular events through pro‐inflammation, pro‐thrombosis and pro‐atherosclerosis. From the perspective of Lp(a) influencing inflammation, it primarily promotes the release of inflammatoryfactors. This, in turn, increases levels of vascular inflammation and facilitates the recruitment of monocytes‐macrophages. Moreover, it also affects the function of endothelial cells during the development process of atherosclerosis. All these aspects complement each other and contribute to the progression of at herosclerosis. Currently, the lipid‐lowering treatment used inclinical practice can partially reduce the levels of Lp(a), but its impact on inflammation is not significant.ConclusionLp(a) is an independent risk factor for CAD, as it promotes inflammation in the body and accelerates theprogression of atherosclerosis. Further research on effective methods to reduce Lp(a) levels can provide new insights for the treatment of atherosclerosis.

Predictive value of lipoprotein(a) in coronary artery calcification among asymptomatic cardiovascular disease subjects: A systematic review and meta-analysis

AimsStudies have indicated inconsistent results regarding the association between plasma levels of Lipoprotein(a) [Lp(a)] and coronary artery calcification (CAC). We performed a systematic review and meta-analysis to investigate the association between elevated levels of Lp(a) and risk of CAC in populations free of cardiovascular disease (CVD) symptoms. Data synthesisPubMed, Web of Science, Embase, and Scopus were searched up to July 2022 and the methodological quality was assessed using Newcastle–Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratio (OR) and 95% confidence interval. Out of 298 studies, data from 8 cross-sectional (n = 18,668) and 4 cohort (n = 15,355) studies were used in meta-analysis. Cohort studies demonstrated a positive significant association between Lp(a) and CAC, so that individuals with Lp(a)≥30–50 exposed to about 60% risk of CAC incidence compared to those with lower Lp(a) concentrations in asymptomatic CVD subjects (OR, 1.58; 95% CI, 1.38–1.80; l2, 0.0%; P, 0.483); Subgroup analysis showed that a cut-off level for Lp(a) measurement could not statistically affect the association, but race significantly affected the relationship between Lp(a) and CAC (OR,1.60; 95% CI, 1.41–1.81). Analyses also revealed that both men and women with higher Lp(a) concentrations are at the same risk for increased CAC. ConclusionsBlood Lp(a) level was significantly associated with CAC incidence in asymptomatic populations with CVD, indicating that measuring Lp(a) may be a useful biomarker for diagnosing subclinical atherosclerosis in individuals at higher risk of CAC score. Prospero registration numberCRD42022350297.

P360 INFLAMMATION AND LIPID METABOLISM IN YOUNG PATIENTS WITH ACUTE CORONARY SYNDROME

Abstract Background Inflammation and lipid metabolism play a central role in pathogenesis of atherosclerosis. High sensitivity C–reactive protein (hsCRP), Lipoprotein(a) [Lp(a)] and other inflammation markers are well–established markers of cardiovascular (CV) diseases and are associated with adverse CV outcome after acute coronary syndrome (ACS). Methods The study enrolled patients ≤ 55 years of age referred to Cardiology Department of Policlinico Casilino with ACS. In order to evaluate inflammation and lipid metabolism in young patients presenting with ACS, we design an acronym to describe biochemical tests measured: ACS–Lip. Biochemical tests include: A – Apolipoprotein A (ApoA), A – Apolipoprotein B (ApoB), C – hsCRP, C – Cystatin C, S – Suppression of tumourigenicity 2 (ST2). Lip – low–density lipoprotein cholesterol (LDL), high–density lipoprotein (HDL) cholesterol and triglycerides (TG), – Lp(a), Interleukin 6 (IL–6), plasma glucose, glycosylated hemoglobin Type A1c (HbA1c) levels were also determined. Results A total of 20 patients (85% males, mean age 45.5 ± 7.7 years old) were enrolled from July 2020 to March 2022. Hs–CRP was ≥3 mg/L in 100 % of patients. Mean LDL cholesterol level at admission was 117 ± 56 mg/dL, while mean HDL cholesterol was 38 ± 11 mg/dL. Mean Lp(a) level was 42.9 ± 36.1 mg/dL. Elevated Lp(a)&amp;gt;30 mg/dL was documented in 55% of patients. Lp(a) level distribution in the study population is reported in Figure 1. Additional parameters are reported in Table 1. Conclusion In our experience, elevated levels of Lp(a) and of markers inflammation display a detailed profile of patients presenting with ACS at a relatively young age, identifying patients with high risk of recurrence of cardiovascular events. This result focus on the potential use in clinical practice of efficacious Lp(a)–lowering drugs and on the role on inflammatory mediators both as indicator and therapeutic target.

P491 YOUNG AND MIDDLE–AGED PATIENTS PRESENTING WITH ACUTE CORONARY SYNDROME: THE ROLE OF LIPOPROTEIN(A)

Abstract Background Lipoprotein(a) [Lp(a)] is a liver–derived lipoprotein with genetically determined concentrations. High level of lipoprotein(a) is a common risk factor for cardiovascular disease and stroke. Higher plasma Lp(a) concentrations are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), through mechanisms associated with increased atherogenesis, inflammation, and thrombosis. Methods The study enrolled patients ≤ 55 years of age referred to Cardiology Department of Policlinico Casilino with acute coronary syndrome (ACS). In order to identify patients with high cardiovascular risk, we measured, according to current guidelines, Lp(a) value. Results A total of 73 patients (84% males, mean age 47±7 years old) were enrolled from July 2020 to March 2022. Mean Lp(a) level was 50.9± 46.7 mg/dL. High Lp(a) &amp;gt; 50 mg/dL was documented in 31.5 % of patients, while the interim grey zone of elevated Lp (a) (30–50 mg/dL) in 27.4%. Conclusion In our experience, elevated levels of Lp(a) was documented in more than half of patients, presenting with ACS at a relatively young age. This support recent guidelines recommendation to measure Lp (a) at least once in adults, preferably in the first lipid profile, to identify patients with high cardiovascular risk of recurrence. This result focus on the potential use in clinical practice of efficacious Lp(a)–lowering drugs.

Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia.

Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH.

Elevated levels of Lp(a) are associated with coronary lesion complexity in patients hospitalized for an acute myocardial infarction: Data from the French RICO Survey

Elevated levels of Lp(a) are associated with coronary lesion complexity in patients hospitalized for an acute myocardial infarction: Data from the French RICO Survey

Elevated levels of Lp(a) are associated with coronary lesion complexity in patients hospitalized for an acute myocardial infarction: data from the French RICO Survey

Abstract Background Although patients with elevated Lp(a) are at high risk of acute myocardial infarction (MI), coronary artery disease (CAD) burden associated with Lp(a) remains poorly investigated. Methods Single center study including all consecutive patients hospitalized for an acute MI in Coronary Care Unit from the RICO database (2019–2021) who underwent coronary angiography and blood sample for Lp(a) assessment on admission. Coronary lesion complexity was retrospectively assessed by SYNTAX score and pre-specified angiographic criteria. Patients were compared according to their Lp(a) levels: &amp;lt;50 mg/dL (normal), ≥50 mg/dL and ≤100 mg/dL (high) and &amp;gt;100 mg/dL (very high). Results 921 patients were included, of whom 177 (19.2%) had elevated Lp(a) &amp;gt;50 mg/dL, including 121 (13.1%) with high and 56 (6.1%) with very high Lp(a). Median (IQR) age was similar across the 3 groups (normal: 68 (58–78)y; high: 70 (60–80)y; very high: 69 (61–78)y, p=0.381). When compared with patients with normal Lp(a), patients with high and very high Lp(a) levels had increased prevalence of personal history of CAD (19%, 28% and 29%, respectively, p=0.026) and family history of CAD (19%, 26% and 29%, p=0.032, respectively). The rate of women was more common in very high Lp(a) level than in high and normal groups (46%, 33%, and 29%, respectively, p=0.016). Rate of ST-segment elevation MI was similar for the 3 groups (p=0.961). At coronary angiography, CAD burden, as assessed by SYNTAX score was much higher in elevated Lp(a) groups (11 (6–19), 15 (8–24), 17 (7–25), p=0.001, respectively). Moreover, patients with elevated Lp(a) had more complex coronary lesions (p=0.034), characterized by left main (p=0.021), and calcified lesions (p=0.002) (figure). In-hospital mortality gradually increased across the 3 groups (2.8%, 6.6%, 8.9%, p=0.010, respectively). Conclusions This retrospective study in patients with acute MI shows that elevated Lp(a) were common, associated with high risk for in-hospital mortality. Patients with high Lp(a) were characterized by severe CAD burden, with complex anatomy features including left main and calcified lesions. The long-term prognostic impact of Lp(a)-associated CAD burden needs to be explored. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): ARS Bourgogne Franche ComtéCHU Dijon BourgogneAssociation de Cardiologie de Bourgogne

Carotid endarterectomy plaques of patients with elevated levels of lipoprotein(a) demonstrate increased intraplaque angiogenesis

Background and Aims : Elevated lipoprotein(a) [Lp(a)] levels have been demonstrated to be a causal risk factor for the development of cardiovascular disease. Previously, we described that patients with elevated Lp(a) levels have an increased risk of major adverse cardiovascular events (MACE), mostly stroke, 30 days after undergoing carotid endarterectomy (CEA). Aim: Unravelling the mechanism underlying this increase in MACE.Methods: We performed targeted plasma proteomics analysis using the proximity extension assay for 276 proteins on complete plasma from patients undergoing CEA with high levels (>195 mg/dl; N=39) and low levels (<7 mg/dl; N=73) of Lp(a).Results: Surprisingly, no differences were observed in the expression of systemic plasma proteins. Hence, we started to assess the local effects of Lp(a) on plaque morphology. Plaque phenotyping demonstrated that patients with high levels (>195 mg/dl; N=57) of Lp(a) had a 33% increase in mean vessel density compared to patients with low levels (<7 mg/dl; N=106), as attested by semi-quantitatively scoring of the plaques. This increase in neovascularization correlates with decreased plaque stability, as was indicated by increased intraplaque haemorrhage. In-vitro stimulation of Human Arterial Endothelial Cells with physiologically relevant levels of Lp(a) (100 mg/dl), results in enhanced collagen degradation capacity, hyper-sprouting in a 3D spheroid assay and increased blood vessel invasion using a 3D collagen-invasiveness assay. Currently, we are elucidating the signalling pathways underlying this Lp(a)-induced angiogenesis, which we strive to present at the EAS 2022.Conclusions: Lp(a)-induced intraplaque angiogenesis can contribute to the increased risk of major adverse cardiovascular events in patients with elevated levels of Lp(a). Background and Aims : Elevated lipoprotein(a) [Lp(a)] levels have been demonstrated to be a causal risk factor for the development of cardiovascular disease. Previously, we described that patients with elevated Lp(a) levels have an increased risk of major adverse cardiovascular events (MACE), mostly stroke, 30 days after undergoing carotid endarterectomy (CEA). Aim: Unravelling the mechanism underlying this increase in MACE. Methods: We performed targeted plasma proteomics analysis using the proximity extension assay for 276 proteins on complete plasma from patients undergoing CEA with high levels (>195 mg/dl; N=39) and low levels (<7 mg/dl; N=73) of Lp(a). Results: Surprisingly, no differences were observed in the expression of systemic plasma proteins. Hence, we started to assess the local effects of Lp(a) on plaque morphology. Plaque phenotyping demonstrated that patients with high levels (>195 mg/dl; N=57) of Lp(a) had a 33% increase in mean vessel density compared to patients with low levels (<7 mg/dl; N=106), as attested by semi-quantitatively scoring of the plaques. This increase in neovascularization correlates with decreased plaque stability, as was indicated by increased intraplaque haemorrhage. In-vitro stimulation of Human Arterial Endothelial Cells with physiologically relevant levels of Lp(a) (100 mg/dl), results in enhanced collagen degradation capacity, hyper-sprouting in a 3D spheroid assay and increased blood vessel invasion using a 3D collagen-invasiveness assay. Currently, we are elucidating the signalling pathways underlying this Lp(a)-induced angiogenesis, which we strive to present at the EAS 2022. Conclusions: Lp(a)-induced intraplaque angiogenesis can contribute to the increased risk of major adverse cardiovascular events in patients with elevated levels of Lp(a).

Association of LPA and levels of HbA1c in patients with diabetes mellitus type 2

Background and Aims : Lipoprotein(a) [Lp(a)], is a well-recognized cardiovascular risk factor. Emerging data support a correlation between elevated levels of Lp(a) and the development of diabetes mellitus type 2. To investigate whether there is correlation between Lp(a) levels and HbA1c, in diabetic patients type 2.

Pathways of lipoprotein(a) catabolism

Lipoprotein(a) [Lp(a)] is a modified form of low-density lipoprotein (LDL) with an additional protein component, apolipoprotein(a). Elevated levels of Lp(a) (>50 mg/dL), which are present in 20% of the population, impart a risk of developing cardiovascular disease similar to LDL. A good understanding of LDL catabolism led to the development of therapies to effectively lower LDL, i.e., statins and the PCSK9 inhibitors which both upregulate the low-density-lipoprotein receptor (LDLR). The pathway for Lp(a) clearance is more complicated with multiple receptors operating via different forms of endocytosis being identified.

Association of Lipoprotein(a) With Recurrent Ischemic Events Following Percutaneous Coronary Intervention.

This study evaluated the association between elevated levels of lipoprotein(a) [Lp(a)] and risk of recurrent ischemic events in patients who underwent percutaneous coronary intervention (PCI). Elevated levels of Lp(a) have been identified as an independent, possibly causal, risk factor for atherosclerotic cardiovascular disease in a general population study. A prospective single-center registry was used to identify 12,064 patients with baseline Lp(a) measurements who underwent PCI between 2003 and 2013. The primary outcomes were a composite of cardiovascular death, spontaneous myocardial infarction, and ischemic stroke. From the registry, 3,747 (31.1%) patients had high Lp(a) (>30mg/dL) and 8,317 (68.9%) patients had low Lp(a) (≤30mg/dL). During a median follow-up of 7.4 years, primary outcomes occurred in 1,490 patients, and the incidence rates of primary outcomes were 2.0 per 100 person-years in the high-Lp(a) group and 1.6 per 100 person-years in the low-Lp(a) group (adjusted hazard ratio [aHR]: 1.17; 95% confidence interval [CI]: 1.05-1.30; P = 0.004). Increased risk of recurrent ischemic cardiovascular events in the high-Lp(a) group was consistent in various subgroups including patients receiving statin treatment at discharge (aHR: 1.18; 95%CI: 1.03-1.34; P = 0.011). In addition, the risk of repeated revascularization was significantly higher in the high-Lp(a) group (aHR: 1.13; 95%CI: 1.02-1.25; P = 0.022). Elevated levels of Lp(a) were significantly associated with the recurrent ischemic events in patients who underwent PCI. This study provides a rationale for outcome trials to test Lp(a)-lowering therapy for secondary prevention in patients undergoing PCI.