Low Lp Research Articles

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.

Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis.

Lipoprotein(a) (Lp(a)) is one of the most important risk factors for the development of calcific aortic valve stenosis (CAVS). However, the mechanisms through which Lp(a) causes CAVS are currently unknown. Our objectives were to characterize the Lp(a) proteome and to identify proteins that may be differentially associated with Lp(a) in patients with versus without CAVS. Our second objective was to identify genes that may be differentially regulated by exposure to high versus low Lp(a) levels in explanted aortic valves from patients with CAVS. We isolated Lp(a) from the blood of 21 patients with CAVS and 22 volunteers and performed untargeted label-free analysis of the Lp(a) proteome. We also investigated the transcriptomic signature of calcified aortic valves from patients who underwent aortic valve replacement with high versus low Lp(a) levels (n = 118). Proteins involved in the protein activation cascade, platelet degranulation, leukocyte migration, and response to wounding may be associated with Lp(a) depending on CAVS status. The transcriptomic analysis identified genes involved in cardiac aging, chondrocyte development, and inflammation as potentially influenced by Lp(a). Our multi-omic analyses identified biological pathways through which Lp(a) may cause CAVS, as well as key molecular events that could be triggered by Lp(a) in CAVS development.

Effect of lycopene on environmental toxicity and pollution induced by PFOS

Objective: Intend to observe the effect of lycopene on reproductive toxicity induced by PFOS in male rats and its possible mechanism. Methods: 30 male SD rats were randomly divided into 5 groups with 6 rats in each group. The control group was given CMC-Na solution. At the same time, the PFOS group and the low, middle and high dose LP protection groups were fed with poisoned feed (32mg/kg PFOS-K).In the meanwhile, the lycopene protection groups were given LP every other day according to their designed dose, and were killed continuously for 3 months. In addition, the sperm motility, number, LDH-X, CAT, GSH-Px, SOD enzyme activity and MDA content were detected and observed. Results: The sperm motility was 44.00%, 53.68% and 58.37%, respectively.The rate of sperm deformity decreased, and the levels of LDH-X and serum testosterone (T) recovered in varying degrees. Moreover, low, middle and high doses of LP could significantly restore the activities of SOD and CAT and reduce the content of MDA, which was significantly different from that of PFOS group (P<0.05). Conclusion: 10∼20mg/kg LP can protect against reproductive damage induced by subchronic low dose PFOS. In addition, antioxidant damage and regulation of testosterone secretion are important mechanisms for LP to protect reproductive damage induced by PFOS.

Effect of Lipoprotein (a) Levels on Long-term Cardiovascular Outcomes in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries

The association between elevated lipoprotein(a) [Lp(a)] and poor outcomes in coronary artery disease (CAD) has been addressed for decades. However, little is known about the prognostic value of Lp(a) in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA). A total of 1179 patients with MINOCA were enrolled and divided into low, medium, and high Lp(a) groups based on the cut-off value of 10 and 30mg/dL. The primary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier and Cox regression analyses were performed. Accuracy was defined as area under the curve (AUC) using a receiver-operating characteristic analysis. Patients with higher Lp(a) levels had a significantly higher incidence of MACE (9.5%, 14.6%, 18.5%; p=0.002) during the median follow-up of 41.7 months. The risk of MACE also increased with the rising Lp(a) levels even after multivariate adjustment [low Lp(a) group as reference, medium group: hazard ratio (HR) 1.55, 95% confidence interval (CI): 1.02-2.40, p=0.047; high group: HR 2.07, 95% CI: 1.32-3.25, p=0.001]. Further, clinically elevated Lp(a) defined as Lp(a) ≥30 mg/dL was closely associated with an increased risk of MACE in overall and in subgroups (all p <0.05). When adding Lp(a) (AUC 0.61) into the Thrombolysis in Myocardial Infarction (TIMI) score (AUC 0.68), the combined model (AUC 0.73) yielded a significant improvement in discrimination for MACE (ΔAUC 0.05, p=0.032). In conclusion, elevated Lp(a) was strongly associated with a poor prognosis in patients with MINOCA. Adding Lp(a) to traditional risk score further improved risk prediction. Our data, for the first time, confirmed the Lp(a) as a residual risk factor for MINOCA.

Lipoprotein (a), hypertension, and cardiovascular outcomes: a prospective study of patients with stable coronary artery disease.

Although emerging data suggest that circulating lipoprotein (a) [Lp (a)] could predict cardiovascular events (CVEs) in patients with cardiovascular disease, no study is currently available regarding the prognostic linkage of Lp (a) and hypertension in patients with coronary artery disease (CAD). This study sought to evaluate the association of Lp (a), hypertension and cardiovascular outcomes in patients with stable CAD. A total of 8668 patients with stable CAD were consecutively enrolled. Baseline Lp (a) concentrations were measured. All subjects were categorized according to Lp (a) levels of <10 (low), 10-30 (medium) and ≥30 mg/dL (high) and were further stratified by hypertension status. They were regularly followed-up for the occurrence of cardiovascular death, nonfatal myocardial infarction, and stroke. Over an average of 54.81 ± 18.60 months of follow-up, 584 (6.7%) CVEs occurred. Kaplan-Meier and multivariate Cox regression analyses showed that elevated Lp (a) levels had a significant association with CVEs in hypertensive patients, regardless of the control status of blood pressure, but not in normotensive subjects. Moreover, when analyzed by subgroups according to both Lp (a) category and hypertension status, the risk of CVEs was only significantly elevated in the high Lp (a) plus hypertension group compared with the reference group with low Lp (a) levels and normotension (hazard ratio: 1.80, 95% confidence interval: 1.11-2.91). Elevated Lp (a) was associated with an increased risk of CVEs in stable CAD patients with hypertension. Moreover, the coexistence of high Lp (a) concentrations and hypertension greatly worsened the clinical prognosis in patients with CAD, which may suggest a prognostic correlation between Lp (a) and hypertension.

Very low lipoprotein(a) and increased mortality risk after myocardial infarction

BackgroundInconclusive data exist on risk associated with Lp(a) in patients after myocardial infarction (MI). Aims of the present study were to evaluate the association of Lp(a) level with total mortality and recurrent cardiovascular events. Design and methodsSingle center prospective registry of consecutive patients hospitalized for acute myocardial infarction between June 2017 and June 2020 at a large tertiary cardiac center with available blood samples drawn <24h of admission. ResultsData from 851 consecutive patients hospitalized for MI were evaluated. During the median follow-up of 19 months (interquartile range 10–27), 58 (6.8%) patients died. Nonlinear modelling revealed a U-shaped association between Lp(a) and total mortality risk. Compared to patients with Lp(a) ranging between 10-30 nmol/L and after multivariate adjustment, total mortality risk was increased both in patients with Lp(a)<7 nmol/L (hazard ratio (HR) 4.08, 95% confidence interval (CI) 1.72–9.68) and Lp(a) ≥125 nmol/L (HR 2.92, 95% CI 1.16–7.37), respectively. Similarly, the risk of combined endpoint of acute coronary syndrome recurrence or cardiovascular mortality was increased both in patients with low (sub-HR 2.60, 95% CI 1.33–5.08) and high (sub-HR 2.10, 95% CI 1.00–4.39) Lp(a). Adjustment for heart failure signs at the time of hospitalization weakened the association with total mortality and recurrent cardiovascular events. ConclusionsIn the present analysis, both high and low concentrations of Lp(a) were associated with an increased risk of total mortality and recurrent cardiovascular events after MI. The excess of mortality associated with Lp(a) was partially attributable to more prevalent heart failure.

Relationship of Plasma ApolipoproteinC3 with Plasma Lipoprotein(a)

Introduction ApoliproteinC3 (ApoC3) is a small (~8.8kDa) protein, made in the liver. It is an inhibitor of lipoprotein lipase as well as the uptake of triglyceride (TG) rich lipoproteins and remnants by the liver. Overexpression contributes to atherosclerosis by increasing plasma concentration of TG-rich lipoproteins. Recent genetic studies suggest that ApoC3-lowering treatments may have cardiovascular benefit. ApoC3 is also known to participate in the inflammation cascade; it facilitates the interaction between monocytes and endothelial cells leading to their activation and monocyte adhesion, promoting further development of atherosclerosis. A recent study reported the presence of ApoC3 on lipoprotein(a) [Lp(a)] particles in subjects with mild to moderate aortic stenosis. Lp(a) is an ApoB100 containing lipoprotein and a causal factor of ASCVD. Most individuals have two isoforms of Apo(a), varying in the number of KIV2 repeats, and hence, have two different circulating Lp(a) molecules. High levels of Lp(a) are inversely associated with the isoform size. Our goal was to investigate relationships between ApoC3 and Lp(a) in a racially diverse healthy population. Methods We analyzed data from 39 healthy subjects who completed studies of lipoprotein metabolism at the Columbia University Medical Center. Subjects were 18 – 75 years old, and 49% were female. Fifty-one percent were Black, 23% Hispanic, 21% White, and 5% mixed race. Lipids (total Cholesterol (C), TG, HDLC, LDLC) were measured by a CDC standardized automatic analyzer. Plasma ApoC3 and Lp(a) levels were measured via validated ELISA assays. Lp(a) particles were isolated from plasma by immunoprecipitation (IP) with a monoclonal antibody (Abcam). Isolated Lp(a) samples were processed for proteomic analysis at the CUIMC – Proteomics Core. We calculated iBAQ value (total intensities/identified peptides for one protein). Excel and R-program were used for statistical analysis. Results Unlikeprevious studies, our group of healthy volunteers did not have an association between Lp(a) and ApoC3 levels. Previous studies were completed in subjects with high Lp(a). In a sub-group analysis of participants (N=15) in our study, with Lp(a) levels >100nmol/L, we found a trend in the association of ApoC3 and Lp(a) plasma concentration (R = -0.48, p=0.068). However, unlike in previous reports, it was not a positive correlation. Based on the proteomic analysis of our IP Lp(a) particles from 2 subjects with high (~ 128nmol/L) and 2 subjects with low (~ 23nmol/L) Lp(a), ApoC3/Apo(a) iBAQ ratios were similar in subjects with low Lp(a) levels, however there was not a clear relationship between ApoC3/Apo(a) ratios in subjects with high Lp(a). Conclusion and Future Direction In healthy subjects, there is no association of ApoC3 with Lp(a) plasma levels. In a subset of subjects (high Lp(a)), we observed a trend towards lower ApoC3 levels associated with high Lp(a). Our small data set suggests possible distinct roles for ApoC3 in healthy individuals with high Lp(a) level. ApoC3 may be associated with specific circulating isoform sizes of Lp(a). Future studies will focus on analysis of larger cohorts, examining the ApoC3 and Apo(a) relationships.

A Look at the Proteome of Lp(a) Isolated by Immunoprecipitation

Introduction Lipoprotein [Lp)(a)] is composed of an apoB100 containing lipoprotein bound to a glycoprotein, apolipoprotein (a). Epidemiological, genome-wide association, and Mendelian randomization studies show high Lp(a) plasma levels as causal in the development of atherosclerotic cardiovascular disease (ASCVD). Plasma Lp(a) levels are 70-90% determined by the number of DNA-base repeats coding a highly polymorphic sequence of the LPA gene called Kringle IV Type 2 (KIV-2). Most individuals have two Lp(a) isoforms that differ in apo(a) size. The pathways regulating Lp(a) clearance and secretion in humans are not well understood and are currently being studied by our group using stable isotopes. The latter may be regulated by the different proteins carried by the Lp(a) particle. However, these studies have concentrated on small cohorts and subjects with high levels of plasma Lp(a). Our goal was to examine the effect of Lp(a) levels (low vs. high) on Lp(a) protein composition, and in addition examine if the proteins carried by large size apo(a) isoforms (associated with low Lp(a) levels) and low size apo(a) isoforms (associated with high Lp(a) levels) were similar. We hypothesize that the protein expression of isolated Lp(a) particles from subjects with high and low Lp(a) will be enriched with different proteins. Methods: We enrolled 13 healthy volunteers (7 male, 6 female), obtained fasting bloods and isolated plasma samples from EDTA-containing tubes. We measured plasma Lp(a) levels via a validated and standardized ELISA assay. Isoform sizes were obtained via SDS-page electrophoresis and standardized to a known KIV-2 repeat in 9 of the 13 subjects. We compared the proteomic profiles of isolated Lp(a) in 6 subjects with high Lp(a) levels (>75nmol/L) to that of 7 subjects with low Lp(a) levels (<40nmol/L). Lp(a) was isolated from 500uL of plasma by immunoprecipitation. The proteome of eluent was obtained by gel-based protein identification. The use of proteome software Scaffold4 enabled the detection of protein biomarkers that may be related to functional abnormalities involved in the pathophysiology of Lp(a).Results: We found similar protein expression in subjects with high and low levels of Lp(a), these proteins are listed in Table 1. Additionally, protein expression counts for apo(a) and apoB100 were higher in subjects with high Lp(a) levels when compared with subjects with low Lp(a) levels. Lp(a) levels are inversely correlated to isoform size, i.e. subjects with small isoforms have high levels and vice versa. We examined the protein composition of Lp(a) in a small sub-cohort of subjects expressing >24 repeats (low Lp(a) levels), n=6 and <24 (high Lp(a) levels), n=3. We found that subjects with >24 repeats (Table 2-A) presented with higher protein expression counts of apoE and Von W factor while subjects with <24 (Table 2 -B) presented with higher protein expression of complement C3. Conclusion: We did not find differences in the proteome of subjects with high and low levels of Lp(a). Although protein expressions are similar across Lp(a) levels, Lp(a) circulating isoforms may be linked to higher or lower levels of certain proteins. The latter may link isoforms to specific roles in Lp(a) disease.

Optimization of Dephosphorization Parameter in Consteel Electric Arc Furnace Using Rule Set Model

The proper process parameter of dephosphorization is a key problem in actual steelmaking production. This article presents a rule set model combining a k‐means method and a decision tree model, which can extract the rule set from the actual production data to optimize the dephosphorization process. The industrial data from Consteel electric arc furnace are selected as the sample data, and then, the phosphorus partition ratio (Lp) is calculated based on the selected data. The k‐means method is used to divide the calculated Lp into two classes (high Lp and low Lp), and meanwhile, through the data statistic, the importance variables, including oxygen consumption, lime weight, dolomite weight, smelting temperature, and scrap ratio (ratio of scrap weight and hot metal weight), are extracted and merged with the classified Lp data into the new data set. Then, the decision tree is used to extract the valuable information to obtain the rule set from new data set. From the rule set, the optimum range of scrap ratio and oxygen consumption under different smelting conditions is obtained, which can guide the adjustment of process parameters in the actual production to enhance the dephosphorization effect.

Association Between Lipoprotein(a) and Peri-procedural Myocardial Infarction in Patients With Diabetes Mellitus Who Underwent Percutaneous Coronary Intervention.

BackgroundHigh lipoprotein(a) (Lp[a]) levels are associated with increased risks of cardiovascular events in Percutaneous Coronary Intervention (PCI) patients with diabetes mellitus (DM). Peri-procedural myocardial infarction (PMI) occurs commonly during the PCI, whereas the relationship between Lp(a) and PMI remains unclear. Our study aimed to evaluate the association between Lp(a) value and the incidence of PMI in a larger-scale diabetic cohort undergoing PCI throughout 2013.MethodsA total of 2,190 consecutive patients with DM were divided into two groups according to the median Lp(a) level of 175 mg/L: Low Lp(a) group (N = 1095) and high Lp(a) group (N = 1095). PMI was defined based on the 2018 universal definition of myocardial infarction.ResultsPatients with high Lp(a) levels exhibited higher rates of PMI compared to those with low Lp(a) levels (2.3% versus 0.8%, P = 0.006). The multivariable logistic analysis showed that PMI was independently predicted by Lp(a) as a dichotomous variable (OR 2.64, 95%CI 1.22–5.70) and as a continuous variable (OR 1.57, 95% CI 1.12–2.20). However, further investigation found that this association was only maintained in men, whose Lp(a) levels were significantly associated with the frequency of PMI, both as a dichotomous variable (OR 3.66, 95%CI 1.34–10.01) and as a continuous variable (OR 1.81, 95%CI 1.18–2.78). Lp(a) wasn’t a risk factor of PMI in women.ConclusionsHigh Lp(a) levels had forceful correlations with the increased frequency of PMI in male diabetic patients undergoing PCI. Lp(a) might act as a marker of risk stratification and a therapeutic target to reduce PCI-related ischemic events.

Subjects with familial hypercholesterolemia have lower aortic valve area and higher levels of inflammatory biomarkers

BackgroundReduction of the aortic valve area (AVA) may lead to aortic valve stenosis with considerable impact on morbidity and mortality if not identified and treated. Lipoprotein (a) [Lp(a)] and also inflammatory biomarkers, including platelet derived biomarkers, have been considered risk factor for aortic stenosis; however, the association between Lp(a), inflammatory biomarkers and AVA among patients with familial hypercholesterolemia (FH) is not clear. ObjectiveWe aimed to investigate the relation between concentration of Lp(a), measurements of the aortic valve including velocities and valve area and circulating inflammatory biomarkers in adult FH subjects and controls. MethodsIn this cross-sectional study aortic valve measures were examined by cardiac ultrasound and inflammatory markers were analyzed in non-fasting blood samples. The study participants were 64 FH subjects with high (n = 29) or low (n = 35) Lp(a), and 14 healthy controls. ResultsAortic valve peak velocity was higher (p = 0.02), and AVA was lower (p = 0.04) in the FH patients compared to controls; however, when performing multivariable linear regression, there were no significant differences. Furthermore, there were no significant differences between the high and low FH Lp(a) groups regarding the aortic valve. FH subjects had higher levels of platelet-derived markers CD40L, PF4, NAP2 and RANTES compared to controls (0.003 ≤ P ≤ 0.03). This result persisted after multiple linear regression. ConclusionsMiddle-aged, intensively treated FH subjects have higher aortic valve velocity, lower AVA, and higher levels of the platelet-derived markers CD40L, PF4, NAP2 and RANTES compared to healthy control subjects. The aortic valve findings were not significant after multiple linear regression, whereas the higher levels of platelet-derived markers were maintained.

Association of Serum Lipoprotein (a) Levels and Coronary Atheroma Volume by Intravascular Ultrasound.

BackgroundLp(a) (lipoprotein (a)) is a risk factor for cardiovascular events, but the mechanism of increased risk is uncertain. This study evaluated the relationship between Lp(a) and coronary atheroma volume by intravascular ultrasound.Methods and ResultsThis was a post hoc analysis of 6 randomized trials of coronary atheroma by intravascular ultrasound. The population was stratified into high (≥60 mg/dL) and low (<60 mg/dL) baseline serum Lp(a). The primary outcome was baseline coronary percent atheroma volume. A mixed model adjusted for baseline low density lipoprotein, ApoB (apoliporotein B100), non‐high density lipoprotein, sex, age, race, history of myocardial infarction, statin use, and intravascular ultrasound study was used to provide estimates of baseline plaque burden. Of 3943 patients, 17.3% (683) had Lp(a) ≥ 60 mg/dL and 82.7% (3260) had Lp(a) < 60 mg/dL. At baseline, uncorrected low density lipoprotein level (107.7 ± 32.0 versus 99.1 ± 31.5) and statin therapy (99.0% versus 97.0%) were higher in patients with high Lp(a) levels, but low density lipoprotein corrected for Lp(a) was lower (80.6 ± 32.0 versus 94.0 ± 31.4) in patients with high Lp(a) levels. Percent atheroma volume was significantly higher in the high Lp(a) group in unadjusted (38.2% [32.8, 43.6] versus 37.1% [31.4, 43.1], P=0.01) and risk‐adjusted analyses (38.7%±0.5 versus 37.5%±0.5, P<0.001). There was a significant association of increasing risk‐adjusted percent atheroma volume across quintiles of Lp(a) (Lp(a) quintiles 1‐5; 37.3 ± 0.5%, 37.2 ± 0.5%, 37.3 ± 0.5%, 38.0 ± 0.5%, 38.5 ± 0.5%, P=0.002).ConclusionsElevated Lp(a) is independently associated with increased percent atheroma volume. Further work is needed to clarify the relationship of Lp(a)‐lowering treatment with cardiovascular outcomes.

Association of lipoprotein (a) and in-hospital outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention

ABSTRACT Objective: The current study was to evaluate the association of Lipoprotein (a) [Lp(a)] and in-hospital outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods: ACS patients undergoing PCI were retrospectively enrolled. Based on Lp(a) level, patients were divided into low (<30 mg/dL) and high (≥30 mg/dL) Lp(a) groups. Results: Compared to those with low Lp(a), patients with high Lp(a) had larger numbers of coronary arteries ≥70% stenosis and had longer coronary artery lesion (P < 0.05). After adjustment for covariates, high Lp(a) remained associated with higher odds of having coronary artery ≥70% stenosis, type C coronary lesion and pre-PCI TIMI flow grade 1/0. Patients with high Lp(a) had a higher unadjusted odds of acute stent thrombosis (odds ratio [OR] 1.10 and 95% confidence interval [CI] 1.01–2.27), congestive heart failure (OR 1.24 and 95% CI 1.15–2.38) and composite in-hospital outcomes (OR 1.28 and 95% CI 1.18–2.42). After adjustment for covariates, patients with high Lp(a) still had a higher odds of congestive heart failure (OR 1.08 and 95% CI 1.01–1.78) and composite in-hospital outcomes (OR 1.12 and 95% CI 1.04–1.81). Conclusion: In ACS patients undergoing PCI, compared to those with low Lp(a), patients with high Lp(a) had more severe coronary artery lesion, higher risk of congestive heart failure and composite in-hospital outcomes.

Abstract 15487: Combined Effects of Lipoprotein(a) and Hypertension in Predicting Cardiovascular Outcomes in Patients With Coronary Artery Disease

Introduction: Although emerging data have suggested that circulating lipoprotein(a) [Lp(a)] could predict cardiovascular events (CVEs) in patients with cardiovascular disease, no study is currently available regarding the prognostic significance of Lp(a) in patients with hypertension. Hypothesis: We assessed the hypothesis that there is a prognostic linkage between hypertension and Lp(a) concentrations in patients with coronary artery disease (CAD). Methods: A total of 8668 patients with stable CAD were consecutively enrolled. Baseline Lp(a) concentrations of them were measured. All subjects were categorized according to Lp(a) levels of &lt;10 (low), 10-30 (medium) and 30 mg/dL (high) and were further stratified by hypertension status. They were regularly followed-up for the occurrence of cardiovascular death, non-fatal myocardial infarction and stroke. Results: Over an average of 54.81±18.60 months follow-up, 584 (6.7%) CVEs occurred. Kaplan-Meier and multivariate Cox regression analyses showed that elevated Lp(a) levels had a significant association with CVEs in hypertensive patients, regardless of the control status of blood pressure, but not in normotensive subjects. Moreover, when subgrouping according to both Lp(a) categories and hypertension status, the risk for CVEs was only significantly elevated in high Lp(a) plus hypertension group compared with the reference group with low Lp(a) levels and normotension (hazard ratio: 1.85, 95% confidence interval: 1.19-2.85). Conclusions: In conclusion, elevated Lp(a) was associated with higher risk for CVEs in CAD patients with hypertension and the coexistence of high Lp(a) concentrations and hypertension greatly worsened the clinical prognosis. Our findings may present a prognostic linkage between hypertension and Lp(a) concentrations in patients with CAD.

Abstract 14328: Relation of Lipoprotein(a) Levels to Incident Diabetes and Modification by Alirocumab Treatment: An Analysis of the Odyssey Outcomes Trial

Background: Cohort studies and clinical trials have shown a greater prevalence of diabetes among subjects with lower levels of lipoprotein(a) [Lp(a)]. Some healthy cohort studies have shown a greater incidence of new onset diabetes (NOD) among those with lower Lp(a). It is unknown whether the risk of NOD associates with Lp(a) levels in patients (pts) with established cardiovascular disease or whether pharmacologic reduction of Lp(a) with PCSK9 inhibitors modulates this risk. Objective: Using data from the ODYSSEY OUTCOMES trial that compared the PCSK9 inhibitor alirocumab (ALI) with placebo (PBO) in pts with recent acute coronary syndrome, we examined whether NOD was related to baseline Lp(a) level and whether any such relationship was modified by ALI treatment. Methods and Results: Lp(a) was measured with a mass assay in 13,480 trial pts without diabetes at baseline; median (IQR) baseline Lp(a) was 21.9 mg/dL (6.9-61.1); median follow-up was 2.7 years. Intensive statin therapy was utilized in 89%. In the PBO group, NOD was greatest in Quartile 1 and least in Quartile 4 of baseline Lp(a) ( Figure , 4.6 vs 3.1 cases per 100 pt-years, P trend 0.0003). ALI lowered Lp(a) by a median of 23% from baseline. Absolute median reduction in Lp(a) with ALI ranged from nil in baseline Lp(a) Quartile 1 to 15 mg/dL in Quartile 4. Treatment HR (ALI/PBO) for NOD was neutral overall (0.95, 95% CI 0.85-1.05) but varied across baseline Lp(a) quartiles from 0.79 (0.64-0.96) in Quartile 1 to 1.09 (0.87-1.38) in Quartile 4 ( Figure , P trend =0.025). Conclusion: In pts with recent acute coronary syndrome, there is greater NOD among those with lower baseline Lp(a) levels. ALI has an overall neutral effect on NOD: In pts with low baseline Lp(a), ALI has minimal effect on Lp(a) levels and tends to reduce NOD. In pts with high baseline Lp(a), ALI reduces Lp(a) levels with a non-significant excess of NOD. The findings may have implications for emerging therapies that reduce Lp(a) more substantially than PCSK9 inhibitors.

Impact of lipoprotein(a) levels on angiographic severity of femoropopliteal lesions

Abstract Background High lipoprotein(a) [Lp(a)] levels are a risk factor for peripheral artery disease (PAD). However, the association between Lp(a) levels and angiographic severity of PAD has not been systematically studied. Purpose The aim of this study was to assess the impact of Lp(a) levels on angiographic severity of femoropopliteal lesions in patients with PAD. Methods We retrospectively analyzed a single-center database including 108 patients (74±8 years, 69% male) who underwent endovascular therapy for de novo femoropopliteal lesions and measured Lp(a) levels before therapy between June 2016 and September 2019. Patients were divided into low Lp(a) [LP(a) &amp;lt;30 mg/dL; 77 patients] and high Lp(a) [LP(a) ≥30 mg/dL; 31 patients] groups. Trans-Atlantic Inter-Society Consensus (TASC) II classification, calcification [referring to peripheral arterial calcium scoring system (PACSS) classification] and lesion length were compared between the groups. Results Median Lp(a) was 16 (7–31) mg/dL.The prevalence of TASC II class D (13% vs 38%, P&amp;lt;0.01) and severe calcification (PACSS 4) (6% vs 23%, P=0.02) was significantly higher and lesion length was longer (123±88 mm vs 175±102 mm, P&amp;lt;0.01) in the high Lp(a) group than in the low Lp(a) group.(Table and Figure) In multivariate analysis, Lp(a)≥30 was an independent predictor for TASC II class D (HR=3.67, P=0.02) and PACSS 4 (HR=4.97, P=0.02) prevalence. Conclusion Lp(a) was associated with angiographic severity of femoropopliteal lesions in patients with PAD. Comparison of angiographic severity Funding Acknowledgement Type of funding source: None

Serum Lipoprotein(a) levels on clinical outcomes after endovascular therapy

Abstract Background While lipoprotein (a) (Lp(a)) is an independent predictor of atherosclerotic diseases involving the coronary and cerebrovascular arteries, its prognostic value in patients with peripheral artery disease (PAD) remains still unclear. Objective The aim of study is to determine the role of Lp(a) levels after endovascular therapy (EVT). Methods This study was prospective observational study. From September 2016 to April 2019, 676 the patients (873 limbs) who underwent EVT for de-novo PAD were enrolled. We divided into Lp(a) levels ≥40 mg/dl (high Lp(a) group; n=129) and &amp;lt;40 mg/dl (low Lp(a) group; n=547). Outcome measures were major adverse cardiovascular events (MACE; all-cause death, myocardial infarction and stroke), and major adverse limb events (MALE; repeat revascularization for limb and major amputation) at 1 year. Major amputation defined as above forefoot amputation due to vascular cause. Results The mean follow-up period was 14.3±8.9 months. Serum Lp(a) levels before EVT were 27.2 (10.0–36.0 mg/dl). High Lp (a) group was significantly older, higher prevalence of history of stroke, chronic kidney disease, and multi-vessel lesions. Cumulative incidence of MACE at 1 year was not significantly between two groups (p=0.53, log-rank test), whereas cumulative incidence of MALE at 1 year was significantly higher in high Lp (a) group (p=0.04, log-rank test). However, after adjusting for prespecified risk factors, high Lp (a) group was not independent predictor in MALE at 1 year. Conclusion High Lp (a) might not be associated with cardiovascular events and limb prognosis after EVT for PAD in early phase. Funding Acknowledgement Type of funding source: None

Elevated Lp(a) (Lipoprotein[a]) Levels Increase Risk of 30-Day Major Adverse Cardiovascular Events in Patients Following Carotid Endarterectomy.

General population studies have shown that elevated Lp(a) (lipoprotein[a]) levels are an emerging risk factor for cardiovascular disease and subsequent cardiovascular events. The role of Lp(a) for the risk of secondary MACE in patients undergoing carotid endarterectomy (CEA) is unknown. Our objective is to assess the association of elevated Lp(a) levels with the risk of secondary MACE in patients undergoing CEA. Lp(a) concentrations were determined in preoperative blood samples of 944 consecutive patients with CEA included in the Athero-Express Biobank Study. During 3-year follow-up, major adverse cardiovascular events (MACE), consisting of myocardial infarction, stroke, and cardiovascular death, were documented. After 3 years follow-up, Kaplan-Meier cumulative event rates for MACE were 15.4% in patients with high Lp(a) levels (>137 nmol/L; >80th cohort percentile) and 10.2% in patients with low Lp(a) levels (≤137 nmol/L; ≤80th cohort percentile; log-rank test: P=0.047). Cox regression analyses adjusted for conventional cardiovascular risk factors revealed a significant association between high Lp(a) levels and 3-year MACE with an adjusted hazard ratio of 1.69 (95% CI, 1.07-2.66). One-third of MACE occurred within 30 days after CEA, with an adjusted hazard ratio for the 30-day risk of MACE of 2.05 (95% CI, 1.01-4.17). Kaplan-Meier curves from time point 30 days to 3 years onward revealed no significant association between high Lp(a) levels and MACE. Lp(a) levels were not associated with histological carotid plaque characteristics. High Lp(a) levels (>137 nmol/L; >80th cohort percentile) are associated with an increased risk of 30-day MACE after CEA. This identifies elevated Lp(a) levels as a new potential risk factor for secondary cardiovascular events in patients after carotid surgery. Future studies are required to investigate whether Lp(a) levels might be useful in guiding treatment algorithms for carotid intervention.

Relationship Between Lipoprotein(a) and Angiographic Severity of Femoropopliteal Lesions.

Aim: High levels of lipoprotein(a) [Lp(a)] are a risk factor for peripheral artery disease (PAD). However, the relationship between Lp(a) levels and the severity of femoropopliteal lesions in patients with PAD has not been systematically studied. This study aimed to assess the impact of Lp(a) levels on angiographic severity of femoropopliteal lesions in patients with PAD. Methods: We retrospectively analyzed a single-center database including 108 patients who underwent endovascular therapy for de novo femoropopliteal lesions and measured the Lp(a) levels before therapy between June 2016 and September 2019. Patients were divided into low Lp(a) [Lp(a) ＜30 mg/dL; 77 patients] and high Lp(a) [Lp(a) ≥ 30 mg/dL; 31 patients] groups. Trans-Atlantic Inter-Society Consensus (TASC) II classification, calcification [referring to the peripheral arterial calcium scoring system (PACSS) classification], and lesion length were compared between the groups. Results: The prevalence of TASC II class D (13% vs 38%, P ＜0.01) and severe calcification (PACSS 4) (6% vs 23%, P =0.02) was significantly higher and the lesion length longer (123±88 mm vs 175±102 mm, P ＜0.01) in the high Lp(a) group than in the low Lp(a) group. In multivariate analysis, Lp(a) ≥ 30 was an independent predictor for the prevalence of TASC II class D (HR=3.67, 95% CI 1.27–10.6, P =0.02) and PACSS 4 (HR=4.97, 95% CI 1.27–19.4, P =0.02). Conclusion: The prevalence of TASC II class D and severe calcification of femoropopliteal lesions was higher in patients with high Lp(a) than those with low Lp(a).

Serum lipoprotein(a) levels and insulin resistance have opposite effects on fatty liver disease

Background and aimsHigh lipoprotein(a) [Lp(a)] levels are associated with increased risk of cardiovascular disease. However, the association between Lp(a) and fatty liver disease (FLD) remains controversial. Therefore, we analyzed the relationship between FLD and serum Lp(a) levels in Korean adults. MethodsA total of 22,534 participants who underwent a routine health screening program at Kangbuk Samsung Hospital in 2010 and 2014 were enrolled. Anthropometric and biochemical parameters, including Lp(a), were measured. The presence of FLD was assessed using abdominal ultrasonography. Odds ratios (ORs) for the presence of FLD were analyzed in quartile groups of serum Lp(a) levels using logistic regression. We divided the participants into four groups according to the median values of Lp(a) and homeostasis model assessment for insulin resistance (HOMA-IR). ResultsAmong the total study population, 3030 (13.4%) participants had fatty liver disease. The mean Lp(a) level was lower in subjects with FLD than in those without (70.0 vs 73.8 nmol/L, p < 0.001). The OR for FLD was the lowest in the fourth Lp(a) quartile group, using the first quartile group as the reference group after adjusting for confounding factors [0.815; 95% confidence interval (CI) 0.725–0.916]. When the OR for FLD was analyzed in four groups divided by the median values of Lp(a) and HOMA-IR, the low Lp(a)-high HOMA-IR group had the greatest OR for FLD, using the high Lp(a)-low HOMA-IR group as the reference (1.903; 95% CI 1.679–2.158). ConclusionsSerum Lp(a) levels were inversely associated with the presence of FLD. Subjects with low Lp(a) and high insulin resistance (IR) showed higher risk of FLD than those with high Lp(a) and low IR, suggesting the opposite associations of Lp(a) and IR with FLD.