Lp Concentrations Research Articles

Influence of triglyceride concentration in lipoprotein(a) as a function of dyslipidemia

BackgroundRecently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)-TG association in patients treated at the Lipid Units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias. Patients and methodsFive thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included. ResultsThe mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0–210) and Lp(a) 55.0 nmol/L (IQR 17.9–156). Lp(a) concentration showed a negative association with TG concentration when TG values ​​exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)-TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300–399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL. ConclusionsOur results show an inverse Lp(a)-TG relationship in TG concentrations >300 mg/dL in subjects without diabetes, obesity and without familial hypercholesterolemia. Our results suggest that, in those hypertriglyceridemias due to hepatic overproduction of VLDL, the formation of Lp(a) is reduced, unlike those in which the peripheral catabolism of TG-rich lipoproteins is reduced.

Lipoprotein(a) serum concentrations in children in relation to body mass index, age and sex

BackgroundLipoprotein(a) (Lp(a)) is an inherited risk factor for atherosclerotic cardiovascular disease (ASCVD). Limited data exist on Lp(a) values in children. We aimed to evaluate whether Lp(a) concentrations in youth are influenced by BMI.Methods756 blood samples of 248 children with obesity and 264 matched healthy children aged 5 and 18 years, enrolled in the population-based LIFE Child (German civilization diseases cohort) study, were analyzed. Repeat measurements were available in 154 children (1–4 follow ups, ~1 year apart).ResultsThe median Lp(a) concentration in the total cohort (n = 512) at first visit was 9.7 mg/dL (IQR 4.0–28.3). Lp(a) concentrations between 30–50 mg/dL were observed in 11.5%, while 12.5% exhibited Lp(a) ≧50 mg/dL. There was no association of Lp(a) with body mass index (BMI) (ß = 0.004, P = 0.49). Lp(a) levels did not correlate with age or sex, while Lp(a) was associated positively with low-density lipoprotein cholesterol (ß = 0.05, P < 0.0001). The Lp(a) risk category remained stable in 94% of all children in repeated measurements.ConclusionsThe data showed no association of Lp(a) levels in children with BMI, age or sex. Measurement of Lp(a) in youth may be useful to identify children at increased lifetime risk for ASCVD.ImpactIn youth, Lp(a) levels are not affected by age, sex and BMI.Lp(a) risk categories remain stable over time in repeated measurements in children.Measurement of Lp(a) in children may be useful as an additional factor to identify children at increased lifetime risk for ASCVD and for reverse family screening.

Lipoprotein apheresis affects the concentration of extracellular vesicles in patients with elevated lipoprotein (a)

Lipoprotein apheresis (LA) is a therapeutic option for hyperlipoproteinemia(a) (hyper-Lp(a)) and atherosclerotic cardiovascular disease (ASCVD). LA improves blood rheology, reduces oxidative stress parameters and improves endothelial function. The underlying molecular mechanisms of LA beneficial effects are unknown, but it has been suggested that LA exhibits multiple activities beyond simply removing lipoproteins. We hypothesized that LA removes not only lipoproteins, but also extracellular vesicles (EVs). To test this hypothesis, we performed a prospective study in 22 patients undergoing LA for hyper-Lp(a) and ASCVD. Different EVs subtypes were measured before and directly after LA, and after 7 days. We used calibrated flow cytometry to detect total particle concentration (diameter > ~ 100 nm), total lipoproteins concentration (diameter > 200 nm, RI > 1.51), total EV concentration (diameter > 200 nm, RI < 1.41), concentrations of EVs derived from erythrocytes (CD235a+; diameter > 200 nm, RI < 1.41), leukocytes (CD45+; diameter > 200 nm, RI < 1.41) and platelets (CD61+, PEVs; diameter > 200 nm, RI < 1.41). LA reduced the concentrations of all investigated EVs subtypes and lipoproteins. Lp(a) concentration was lowered by 64.5% [(58% – 71%); p < 0.001]. Plasma concentrations of EVs > 200 nm in diameter derived from platelets (CD61 +), leukocytes (CD45+) and erythrocytes (CD235a+) decreased after single LA procedure by 42.7% [(12.8–54.7); p = 0.005], 42.6% [(29.7–54.1); p = 0.030] and 26.7% [(1.0–62.7); p = 0.018], respectively, compared to baseline. All EV subtypes returned to the baseline concentrations in blood plasma after 7 days. To conclude, LA removes not only Lp(a), but also cell-derived EVs, which may contribute to LA beneficial effects.

Lipoprotein(a) is associated with DNA damage in patients with heterozygous familial hypercholesterolemia

Heterozygous familial hypercholesterolemia (HeFH) is a common autosomal-dominant inherited disorder associated with atherosclerotic cardiovascular disease (ASCVD). HeFH subjects have a higher lipoprotein(a), i.e. Lp(a), concentration than the general population. Patients with FH are exposed to elevated levels of LDL from birth and ox-LDL may induce other oxidation pathways. The aim of the study was to determine the levels of markers of oxidative stress and DNA damage in patients with HeFH and describe the effect of Lp(a) on the resulting damage. Higher DNA damage was identified in patients with HeFH compared to the normolipidemic ones, and ASCVD was associated with greater damage. Oxidative stress markers were elevated in HeFH patients; however, only ox-LDL was higher in the ASCVD group and its level correlated with DNA damage. A positive correlation was found between DNA damage and Lp(a) concentration in the HeFH patients. Higher levels of Lp(a) were associated with greater DNA damage, especially in patients with HeFH and ASCVD. In HeFH patients, the optimal Lp(a) cut-off point associated with ASCVD is > 23.45 nmol/L, i.e. much lower than for the general population; however this cut-off point needs validation in a larger group of HeFH patients.

Lipoprotein(a): from Causality to Treatment.

This paper reviews the evidence why lipoprotein(a) (Lp(a)) is a causal risk factor for cardiovascular disease and how high Lp(a) concentrations should be managed now and with an outlook to the future. No optimal and widely available animal models exist to study the causality of the association between Lp(a) and cardiovascular disease. This has been a major handicap for the entire field. However, genetic studies turned the page. Already in the early 1990s, the principle of Mendelian randomization studies was applied for the first time ever (even if they were not named so at that time). Genetic variants of the LPA gene such as the apolipoprotein(a) isoform size, the number and sum of kringle IV repeats and later single nucleotide polymorphisms are strongly associated with life-long exposure to high Lp(a) concentrations as well as cardiovascular outcomes. This evidence provided a basis for the development of specific Lp(a)-lowering drugs that are currently in clinical testing phase. Lp(a) is one of the most important genetically determined risk factors for cardiovascular disease. With the specific Lp(a)-lowering therapies, we might get tools to fight this common risk factor in case the outcome trials will be positive.

Predictive value of lipoprotein(a) for left atrial thrombus or spontaneous echo contrast in non-valvular atrial fibrillation patients with low CHA2DS2-VASc scores: a cross-sectional study

ObjectiveCurrent guidelines are debated when it comes to starting anticoagulant therapy in patients with non-valvular atrial fibrillation (NVAF) and low CHA2DS2-VASc scores (1–2 in women and 0–1 in men). However, these individuals still have a high likelihood of developing left atrial thrombus/spontaneous echo contrast (LAT/SEC) and experiencing subsequent thromboembolism. Recent research has demonstrated that lipoprotein(a) [Lp(a)] may increase the risk of thrombosis, but the relationship between Lp(a) and LAT/SEC in NVAF patients is not clearly established. Therefore, this study sought to evaluate the predictive ability of Lp(a) for LAT/SEC among NVAF patients with low CHA2DS2-VASc scores.MethodsNVAF patients with available transesophageal echocardiography (TEE) data were evaluated. Based on the TEE results, the subjects were classified into non-LAT/SEC and LAT/SEC groups. The risk factors for LAT/SEC were examined using binary logistic regression analyses and were validated by using 1:1 propensity score matching (PSM). Subsequently, novel predictive models for LAT/SEC were developed by integrating the CHA2DS2-VASc score with the identified factors, and the accuracy of these models was tested using receiver operating characteristic (ROC) analysis.ResultsIn total, 481 NVAF patients were enrolled. The LAT/SEC group displayed higher Lp(a) concentrations. It was found that enlarged left atrial diameter (LAD), high concentrations of Lp(a), and a history of coronary heart disease (CHD) were independent predictors of LAT/SEC. Lp(a) and LAD still had predictive values for LAT/SEC after adjusting for PSM. In both the highest quartile groups of Lp(a) (>266 mg/L) and LAD (>39.5 mm), the occurrence of LAT/SEC was higher than that in the corresponding lowest quartile. By incorporating Lp(a) and the LAD, the predictive value of the CHA2DS2-VASc score for LAT/SEC was significantly improved.ConclusionElevated Lp(a) and enlarged LAD were independent risk factors for LAT/SEC among NVAF patients with low CHA2DS2-VASc scores. The prediction accuracy of the CHA2DS2-VASc score for LAT/SEC was significantly improved by the addition of Lp(a) and LAD. When evaluating the stroke risk in patients with NVAF, Lp(a) and LAD should be taken into account together with the CHA2DS2-VASc score.Trial registrationRetrospectively registered.

High lipoprotein(a) concentration is associated with moyamoya disease

BackgroundMoyamoya disease (MMD) has attracted the attention of scholars because of its rarity and unknown etiology.MethodsData for this study were sourced from the Second Affiliated Hospital of Nanchang University. Regression analyses were conducted to examine the association in Lipoprotein [Lp(a)] and MMD. R and IBM SPSS were conducted.ResultsA cohort comprising 1012 MMD patients and 2024 controls was established through the propensity score matching method. Compared with controls, MMD patients showed higher median Lp(a) concentrations [18.5 (9.6–37.8) mg/dL vs. 14.9 (7.8–30.5) mg/dL, P < 0.001]. The odds ratios and 95% confidence intervals for Lp(a) were calculated in three models: unadjusted model, model 1 (adjusted for body mass index and systolic blood pressure), and model 2 (adjusted for model 1 plus triglyceride, C-reactive protein, homocysteine, and low-density lipoprotein cholesterol). Results were [1.613 (1.299–2.002), P < 0.001], [1.598 (1.286–1.986), P < 0.001], and [1.661 (1.330–2.074), P < 0.001], respectively. Furthermore, age, sex, or hypertension status had nothing to do with this relationship.ConclusionsPositive relationship exists between Lp(a) and MMD.

Circulating culprit or therapeutic bullseye: lipoprotein(a) in cardiovascular risk assessment and novel therapeutic prospects

Lipoprotein(a) [Lp(a)] has emerged as a significant player in the realm of cardiovascular disease (CVD), exerting a pivotal role in atherosclerotic cardiovascular disease (ASCVD), aortic valve stenosis (AVS), and overall cardiovascular (CV) and all-cause mortality. Since its discovery in 1963 by Kåre Berg, our understanding of Lp(a) has undergone significant evolution. This comprehensive review delves into the genetics, structure, assembly, and inter-population differences of Lp(a), shedding light on its intricate involvement in CVD. Genetically, Lp(a) is primarily influenced by variations in the LPA gene. The LPA gene encodes apo(a) and the variation in the kringle domains is the main determinant of plasma Lp(a) levels. Other genetic variants, such as SNPs in the LPA gene region, the pentanucleotide repeat polymorphism, and specific SNPs in the coding sequences of kringle domains, have also been associated with varying Lp(a) concentrations. Additionally, genes outside the LPA locus, including APOE, APOH, and CEPT gene regions, contribute to Lp(a) variability across different populations. Inter-population differences in Lp(a) levels are evident, with ethnicity and sex playing significant roles. Racial disparities in median Lp(a) concentration have been observed, with black individuals often displaying higher levels compared to their white counterparts. The review underscores Lp(a) as an independent, heritable CV risk factor in both primary and secondary settings. High Lp(a) levels are closely linked to the recurrence of myocardial infarction, AVS, and CV events. The necessity of measuring Lp(a) concentration at least once in life to assess an individual's absolute global CV risk is emphasized. Despite substantial progress, many questions remain unanswered about Lp(a), including its physiological role in the cardiovascular system and its involvement in inflammatory and thrombotic processes. Ongoing research holds promise for the development of therapeutic interventions, such as pharmacological agents and apheresis, to mitigate the cardiovascular risks associated with elevated Lp(a) levels. This review highlights the multifaceted nature of Lp(a) in the context of cardiovascular health, emphasizing the importance of continued research efforts to unravel its complexities and develop innovative strategies for managing its associated risks.

Haplotype of the Lipoprotein(a) Gene Variants rs10455872 and rs3798220 Is Associated with Parameters of Coagulation, Fibrinolysis, and Inflammation in Patients after Myocardial Infarction and Highly Elevated Lipoprotein(a) Values.

Lipoprotein(a) (Lp(a)) is an independent risk factor for future coronary events. Variants rs10455872 and rs3798220 in the gene encoding Lp(a) are associated with an increased Lp(a) concentration and risk of coronary artery disease. We aimed to determine whether in high-risk coronary artery disease patients these two genetic variants and the kringle IV type 2 (KIV-2) repeats are associated with impairment of inflammatory and hemostatic parameters. Patients after myocardial infarction with elevated Lp(a) levels were included. Blood samples underwent biochemical and genetic analyses. In carriers of the AC haplotype, the concentrations of tumor necrosis factor (TNF)-α (4.46 vs. 3.91 ng/L, p = 0.046) and plasminogen activator inhibitor-1 (PAI-1) (p = 0.026) were significantly higher compared to non-carriers. The number of KIV-2 repeats was significantly associated with the concentration of high-sensitivity C-reactive protein (ρ = 0.251, p = 0.038) and overall fibrinolytic potential (r = -0.253, p = 0.038). In our patients, a direct association between the AC haplotype and both TNF-α and PAI-1 levels was observed. Our study shows that the number of KIV-2 repeats not only affects proatherosclerotic and proinflammatory effects of Lp(a) but is also associated with its antifibrinolytic properties.

Lipoprotein(a): Levels and Reference Intervals Among People in Saudi Arabia.

Blood Lp(a) concentration is recognized as an independent risk factor for cardiovascular disease (CVD). Population-based lipoprotein(a) (Lp[a]) research in Saudi Arabia is rare. Thus, the primary goal of this pilot study was to identify age- and sex-specific reference ranges for Lp(a) levels, in addition to the associations between Lp(a) levels and other atherosclerotic markers in Saudi individuals. A five-year retrospective study of Lp(a) and lipid markers in Saudi patients was conducted using the Al-Borg diagnostics database (2015-2020). The population sample consisted of 361 Saudi individuals aged 18-93 years (162 males, 199 females). An immunoturbidimetric technique was used to determine Lp(a) concentration. The mean and median Lp(a) levels in the study population were 35 nmol/L and 50 nmol/L, respectively. Sex and age did not influence Lp(a) values. Lp(a) values showed a minor correlation with other atherosclerotic markers when the Pearson correlation coefficient was used. In Saudi Arabia, the distribution of Lp(a) concentrations is skewed to the left, favoring lower values. Lp(a) levels in individuals residing in Saudi Arabia were comparable to those observed in other ethnic groups. Additionally, standardizing Lp(a) measurements according to sex and age may enhance broader applicability and facilitate comparisons across different populations. However, larger studies are required to provide more comprehensive data for comparison.

Association between lipoprotein(a) plasma levels and diabetic nephropathy in Han Chinese patients with type 2 diabetes mellitus.

The goal of this study was to evaluate the relationship between serum lipoprotein(a) [Lp(a)] levels and diabetic nephropathy (DN) among Han Chinese individuals with type 2 diabetes mellitus (T2DM). This retrospective analysis comprised a consecutive case series of 767 grown-up patients with T2DM (199 among them with DN) hospitalized in the Department of Endocrinology at the The First Affiliated Hospital of Anhui Medical University from February 20220 to February 2021. Clinical data and other laboratory measurements, such as glycated hemoglobin (HbA1c), were extracted from medical records and compared among groups. Clinical characteristics according to Lp(a) quartiles were also studied. Univariate and multivariate regression analysis were used to examine the relationship between serum Lp(a) and DN. Patients with DN had a longer disease duration, higher HbA1c, higher level of Lp(a), and were more likely to have diabetic retinopathy (DR) than those without DN (P < 0.005 for each). With regard to the Lp(a) quartile group, patients with a higher Lp(a) concentration were more likely to have DN and have higher level of HbA1c during the study (P for trend < 0.005 for each). After adjusting for several confounding factors, the development of DN was significantly associated with the serum Lp(a) level (P = 0.026, comparing the 4th vs 1st quartile of Lp(a)) according to multivariate regression analysis. The receiver operating characteristic (ROC) curves for DN development using serum Lp(a) showed that the area under the receiver operating characteristic curves (AUC) was 0.590 (P < 0.001). Findings from this study demonstrated that the DN was independently associated with the serum Lp(a) level in patients with T2DM in this retrospective study.

Assessment of Lipoprotein (a) Levels in Patients with Atherosclerotic Cardiovascular Disease: Single Center Experience from Türkiye.

This study aims to evaluate the role of elevated lipoprotein (a) [Lp(a)] levels as a potential contributor to residual risk in individuals with atherosclerotic cardiovascular disease (ASCVD). Considering that approximately 90% of Lp(a) levels are genetically determined and can vary regionally, we assessed Lp(a) levels in a cohort of ASCVD patients from the Turkish population, where data is currently limited. We conducted a retrospective analysis of data and Lp(a) measurements collected from individuals diagnosed with ASCVD at a single center. The analysis included Lp(a) levels of 1193 consecutive individuals. The mean Lp(a) level was 28.2 mg/dL, with a median of 16 mg/dL and an interquartile range (IQR) from the 25th to the 75th percentile, 7 mg/dL to 39 mg/dL. The highest recorded Lp(a) level was 326 mg/dL. Among the cases, 18.7% exhibited Lp(a) levels ≥ 50 mg/dL, 10.8% had levels ≥ 70 mg/dL, and 5.8% had levels ≥ 90 mg/dL. The mean levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were 132 ± 47 mg/dL and 212 ± 54 mg/dL, respectively. Lp(a) levels were significantly higher in females compared to males. Furthermore, the proportion of females with Lp(a) levels ≥ 90 mg/dL was higher than in males (11.4% vs. 1.4%; P < 0.01). Additionally, a modest but significant correlation was observed between Lp(a) levels and TC (r = 0.075, P = 0.01) as well as LDL-C (r = 0.106, P < 0.01). This study revealed that Lp(a) concentrations were higher in women and statin users among ASCVD patients and identified a weak but significant correlation between Lp(a) levels and both TC and LDL-C.

Influencia de la concentración de triglicéridos en la lipoproteína(a) en función de la dislipidemia

BackgroundRecently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)–TG association in patients treated at the lipid units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias. Patients and methodsFive thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included. ResultsThe mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0–210) and Lp(a) 55.0 nmol/L (IQR 17.9–156). Lp(a) concentration showed a negative association with TG concentration when TG values exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)–TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300–399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL. ConclusionsOur results show an inverse Lp(a)–TG relationship in TG concentrations > 300 mg/dL in subjects without diabetes, obesity and without familial hypercholesterolemia. Our results suggest that, in those hypertriglyceridemias due to hepatic overproduction of VLDL, the formation of Lp(a) is reduced, unlike those in which the peripheral catabolism of TG-rich lipoproteins is reduced.

Why and when should be lipoprotein(a) level measured?

Lipoprotein(a) [Lp(a)] is composed of a low-density lipoprotein (LDL) and glycoprotein (a)—apo(a). The size and concentration of Lp(a) in serum can vary among individuals and is determined by genetic factors. The environmental factors, diet, and physical activity have a negligible effect on Lp(a) level. Observational, epidemiological, and genetic studies improved that high levels of Lp(a) &gt; 50 mg/dL (&gt; 125 nmol/L) have been associated with an increased risk of myocardial infarction (MI), stroke, and calcific aortic valve stenosis (CAVS). It is recommended to measure Lp(a) at least once in adults to identify individuals with a high cardiovascular risk. This screening is particularly important in certain populations, including: youth with a history of ischemic stroke or a family history of premature atherosclerotic cardiovascular disease (CVD; ASCVD) or high Lp(a), individuals with recurrent cardiovascular events despite optimal hypolipemic treatment and no other identifiable risk factors or patients with familial hypercholesterolemia (FH). Considering Lp(a) levels in the evaluation of cardiovascular risk can provide valuable information for risk stratification and management decisions. However, it’s important to note that the treatments of elevated level of Lp(a) are limited. In recent years, there has been ongoing research and development of new drugs targeting Lp(a): pelacarsen—antisense oligonucleotide (ASO), and olpasiran—a small interfering RNA (siRNA).

Associations of Lipoprotein(a) Level with Cerebral Small Vessel Disease in Patients with Alzheimer's Disease.

This study aimed to examine the association of lipoprotein(a) [Lp(a)] level with the burden of cerebral small vessel disease (CSVD) in patients with Alzheimer's disease (AD). Data from 111 consecutive patients with AD admitted to Nanjing First Hospital from 2015 to 2022 were retrospectively analyzed in this study. Serum Lp(a) concentrations were grouped into tertiles (T1-T3). Brain magnetic resonance imaging (MRI) was rated for the presence of CSVD, including enlarged perivascular spaces (EPVS), lacunes, white-matter lesions, and cerebral microbleeds (CMBs). The CSVD burden was calculated by summing the scores of each MRI marker at baseline. A binary or ordinal logistic regression model was used to estimate the relationship of serum Lp(a) levels with CSVD burden and each MRI marker. Patients with higher tertiles of Lp(a) levels were less likely to have any CSVD (T1, 94.6%; T2, 78.4%; T3, 66.2%; p = 0.013). Multivariable analysis found that Lp(a) levels were inversely associated with the presence of CSVD (T2 vs. T1: adjusted odds ratio [aOR] 0.132, 95% confidence interval [CI] 0.018-0.946, p = 0.044; T3 vs. T1: aOR 0.109, 95% CI 0.016-0.737, p = 0.023) and CSVD burden (T3 vs. T1: aOR 0.576, 95% CI 0.362-0.915, p = 0.019). The independent relationship between Lp(a) levels and individual CSVD features was significant for moderate-to-severe EPVS in the centrum semiovale (T2 vs. T1: aOR 0.059, 95% CI 0.006-0.542, p = 0.012; T3 vs. T1: aOR 0.029, 95% CI 0.003-0.273, p = 0.002) and CMBs (T3 vs. T1: aOR 0.144, 95% CI 0.029-0.716, p = 0.018). In this study, serum Lp(a) level was inversely associated with CSVD in AD patients.

Aggressive course of atherosclerosis in hyperlipoproteinemia (a): a case series

Currently, worldwide interest in lipoprotein(a) (LP(a) as one of the most important markers of premature and aggressive atherosclerosis is steadily growing. This trend is due to both the new data on the pathogenesis of hyperlipoproteinemia (a) and the development of novel treatment methods in the near future. The variety of clinical manifestations of atherosclerosis associated with high LP(a) concentrations leads such patients to specialists of various profiles. The aim of this paper was to demonstrate, using examples from the practice of two lipid centers in Krasnodar, the diversity of clinical scenarios of atherosclerosis as a systemic disease in patients with very high LP(a) levels, as well as to highlight the current and future options for the treatment of hyperlipoproteinemia (a).

Study on the 5-year trend and influencing factors of lipoprotein (a) concentration in community-based population

Objective: To explore the trend and influencing factors of serum lipoprotein (a) (Lp(a)) concentration over time in Chinese community populations. Methods: This study is a prospective cohort study. The participants were enrolled from Chinese Multi-provincial Cohort Study- Beijing projects, completed the cardiovascular disease risk factor surveys in 2002 and 2007, and the serum Lp (a) concentration were measured. Based on the Lp(a) concentration at baseline (2002) and follow-up (2007), the participants were classified into subgroups of <30.0 mg/dl (1 mg/dl=0.01 g/L) group, 30.0 to 49.9 mg/dl group, and ≥50.0 mg/dl group, respectively. Multivariable logistic regression analysis was used to identify influencing factors associated with Lp (a) absolute change (≥20 mg/dl) and relative change (≥20%) within 5 years. Results: Among 1 955 participants with age of (56.5±8.0) years old and 821 male (42.0%) at baseline, there were 1 657 (84.8%), 184 (9.4%) and 114 (5.8%) participants in Lp(a)<30.0 mg/dl group, 30.0 to 49.9 mg/dl group and ≥50.0 mg/dl group, respectively. Among the baseline Lp(a) concentration of 30.0-49.9 mg/dl group, 68 (37.0%) participants progressed to Lp(a) ≥50.0 mg/dl after 5 years follow-up, and 102 (55.4%) remained at this level. Participants with baseline Lp(a)<30.0 mg/dl (92%, 1 524/1 657) or Lp(a)≥50.0 mg/dl (94.7%, 108/114) tended to be maintained at their respective levels. The results of the multivariate logistic regression analysis showed that, in addition to the high level of baseline Lp(a) concentration, family history of cardiovascular disease, elevated fasting blood glucose and usage of oral lipid-lowering drugs were the influencing factors of Lp(a) changes over time (P<0.05). Conclusions: Adults with borderline-high Lp(a) concentrations (30.0 to 49.9 mg/dl) could be considered for repeated testing, especially for those with a family history of cardiovascular disease, elevated fasting blood glucose and usage of statins.

Association between serum lipoprotein(a) and mildly reduced eGFR: a cross-sectional study

Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease (CVD) and aortic stenosis. However, the data on the relationship between Lp(a) and mildly reduced estimated glomerular filtration rate (eGFR) has been disputed. This study was conducted to assess the relationship between Lp(a) concentrations and mildly reduced eGFR in healthy subjects.This community-based, cross-sectional study enrolled 1,064 volunteers aged ≥ 40 years who lived in Yonghong Community, Zhonglou District, Changzhou, China, between December 2016 and December 2017. A mildly reduced eGFR was defined as eGFR between 60 and 90 mL/min/1.73m2. A standardized questionnaire and biochemical measurements were used to gather information about participants. The serum concentration of Lp(a) was determined using the latex-enhanced immunoturbidimetric test. Of the total study population, 34.8% (n = 370) were men, and the mean age was 66.8 ± 8.5 years. A significant association existed between Lp(a) levels and the risk of mildly reduced eGFR. Individuals with the highest tertile of Lp(a) had higher odds of mildly reduced eGFR after adjusting for various confounders (adjusted odds ratio [OR]: 1.80, 95% confidence interval [CI]: 1.24–2.60, P = 0.0025) compared to those with the lowest tertile of Lp(a). Multivariable logistic regression of studies in which Lp(a) was presented as continuous variables showed consistent results (adjusted OR: 1.23 for 1-SD increment of Ln-Lp(a), 95% CI: 1.05–1.43). Subgroup analyses showed that study characteristics such as age, sex, obesity, diabetes, and hypertension status did not significantly affect the association (P for all interactions > 0.05). These results suggest that higher serum Lp(a) level was an independent risk factor for mildly reduced eGFR.

The role of serum lipoprotein(a) levels in bioprosthetic aortic valve degeneration

Abstract Introduction Lipoprotein(a) [Lp(a)] is associated with an increased incidence of aortic stenosis. Bioprosthetic aortic valve degeneration and native aortic stenosis share similar pathological mechanisms. Evidence regarding the role of serum Lp(a) concentrations in bioprosthetic aortic valve degeneration is lacking. Purpose To evaluate the association between serum Lp(a) concentrations and bioprosthetic aortic valve degeneration. Methods In this retrospective multicenter study, consecutive patients who underwent a bioprosthetic aortic valve replacement between Jan-2010 and Dec-2020 and had a preoperatory serum Lp(a) measurement were included. A baseline transthoracic echocardiography (TTE) was performed following the aortic valve replacement and a follow-up TTE was performed at least 24 months after the baseline study to determine the presence of bioprosthetic valve degeneration. Significant degeneration was defined as: (a) an increase &amp;gt;10 mmHg in mean bioprosthetic aortic valve gradient from baseline status + a decrease in effective orifice area + a decrease in Doppler velocity index + exclusion of clinically thrombotic leaflet thickening, OR (b) new moderate or severe prosthetic aortic regurgitation (if the main component was periprosthetic, then it was not considered). Lp(a) concentrations were compared between patients with and without degeneration and regression analysis was conducted to investigate the association between bioprosthetic valve degeneration and Lp(a) levels. Results In total, 211 cases were included (mean age 74.1 ±9.4 years, 72.0% males, 29.9% transcatheter aortic valve replacements) (Figure 1). Median time between baseline and follow-up TTE was 5.0 (IQR 3.7) years. Bioprostheses degeneration was observed in 33 (15.6%) patients at follow-up. Median serum levels of Lp(a) were significantly higher in the patients affected by degeneration versus non-affected cases (50.0 vs 15.7 mg/dl, p=0.003). In the regression analysis, high Lp(a) levels (≥30 mg/dl) were associated with degeneration both in a univariate analysis (OR 4.8, 95%CI 2.2-10.9, p&amp;lt;0.001) and multivariate analysis adjusted by other risk factors for bioprostheses degeneration (age, sex, hypertension, smoking, patient prosthesis mismatch, creatinine levels, and body surface area) (OR 5.2, 95%CI 2.1-12.8, p&amp;lt;0.001). Conclusion Serum Lp(a) concentrations seem to be a risk factor for bioprosthetic aortic valve degeneration (Figure 2). There is an increasing need to accurately predict bioprosthetic aortic valve degeneration and to develop novel methods and treatments to increase their durability. Prospective studies are needed to confirm these findings and to investigate whether lowering Lp(a) could slow bioprostheses degradation.Population characteristicsLp(a) and bioprostheses degeneration

Two of a kind: mass and molar immunoassay-based lipoprotein (a) concentrations are similarly prognostic for MACE risk and predictive of alirocumab benefit in ODYSSEY OUTCOMES

Abstract Background Lipoprotein (a) (Lp(a)) is a risk factor for incident and recurrent ischemic cardiovascular (CV) events and may modify the benefit of PCSK9 inhibitors (PCSK9i). While Lp(a) concentration can be measured in either mass or molar units, to date there has been no direct, large-scale comparison of the relationships of mass vs. molar Lp(a) with CV risk and response to treatment. Purpose Using samples from ODYSSEY OUTCOMES where 18,924 patients with recent acute coronary syndrome were randomized 1:1 to the PCSK9i alirocumab (ALI) or placebo (PBO), baseline mass vs. molar Lp(a) were compared in terms of prognosis for first major adverse CV event (MACE, consisting of coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) in the placebo group and associations with ALI risk reduction. Methods Lp(a) mass and molar tests were the Siemens N latex immunonephelometric test and the Roche TinaQuant immunoturbidimetric assay, respectively. Both tests use polyclonal anti-apo(a) antibodies but are designed to be relatively apo(a)-size independent within allowable measurement uncertainty. Absolute risk of MACE at 4 years in the PBO group and treatment risk ratios (RR) by continuous Lp(a) concentrations were estimated by natural cubic splines from Poisson regression models with log follow-up time as an offset and adjustment for baseline LDL-C. For comparative modeling purposes Lp(a) values were transformed into percentiles; due to ties at the lower limits of quantification, minimum percentiles were 8th and 6th for mass and molar, respectively. All analyses were intention-to-treat. Results Baseline mass and molar Lp(a) concentrations, available in 11943 patients, were correlated (r=0.94). ALI MACE reduction in evaluable patients (1324 events; RR [95% CI] = 0.83 [0.74, 0.92]) was similar to the total population (1955 events; RR [95% CI] = 0.85 [0.78, 0.93]). Relationships with risk of MACE in the PBO group were nearly identical for mass (spline p=0.0001) and molar (spline p=0.0002) concentrations (Figure 1). Of note, the confidence boundaries around the splines were nearly superimposable, indicating similar precision of the estimated Lp(a)-associated risk with both measurement techniques. Risk reductions with ALI were similarly related to mass (spline p&amp;lt;0.0001) and molar (spline p&amp;lt;0.0001) concentrations (Figure 2). Conclusion Baseline mass and molar Lp(a) concentrations were similarly prognostic for MACE risk in the PBO group after adjustment for LDL-C. Mass and molar Lp(a) also similarly modified the ALI treatment effect on MACE, with trends towards less treatment benefit at lower concentrations. These results suggest that, at the treatment group level, the prognostic and predictive value of immunoassay-based Lp(a) tests for ischemic CV events in patients with recent acute coronary syndrome is not meaningfully different for the mass or molar concentration essays that were evaluated.Figure 1Figure 2