High Lp Research Articles

Healthy lifestyle, lipoprotein (a) levels and the risk of coronary artery disease.

Lipoprotein (a) [Lp(a)] is associated with coronary artery disease (CAD). However, the role of healthy lifestyle against the risk of CAD with consideration of high Lp(a) levels remains unclear. This study examined 4512 participants who underwent serum Lp(a) level assessment at Kanazawa University Hospital from 2008 to March 2016. Their lifestyle habits were examined based on four questionnaires regarding dietary pattern, exercise habits, smoking status and body weight. Logistic regression analyses were performed to identify the association between healthy lifestyle and CAD independent of Lp(a) levels. The Lp(a) levels were significantly associated with CAD (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.08-1.17, p = 1.3 × 10-7 per 10 mg/dL). Under these circumstances, the lifestyle risk score was also significantly associated with CAD (OR: 1.24, 95% CI: 1.12-1.36, p = 2.4 × 10-8 ). Compared with patients with a favourable lifestyle who have Lp(a) levels of <30 mg/dL, those with an intermediate or unfavourable lifestyle were at higher risk for CAD (OR: 1.11, 95% CI: 1.02-1.20, p = 0.003 and OR: 1.40, 95% CI: 1.16-1.54, p = 3.6 × 10-5 , respectively). Further, patients with a favourable, intermediate or unfavourable lifestyle who have Lp(a) levels of ≥30 mg/dL were at high risk for CAD (OR: 1.21, 95% CI: 1.08-1.34, p = 0.0014; OR: 1.31, 95% CI: 1.14-1.48, p = 1.2 × 10-4 ; and OR: 1.81, 95% CI: 1.44-2.18, p = 2.2 × 10-7 , respectively). Healthy lifestyle was associated with a lower risk of CAD regardless of Lp(a) levels.

Generation of an induced pluripotent stem cell line (ITXi012-A) from a patient with genetically determined high-lipoprotein(a) plasma levels

Elevated circulating lipoprotein(a) (Lp(a)) is a genetically determined risk factor for coronary artery disease and aortic valve stenosis (Tsimikas, 2017). Importantly, the LPA gene, which encodes the apolipoprotein(a) (protein-component of Lp(a)), is missing in most species, and human liver cell-lines do not secrete Lp(a). There is a need for the development of human in vitro models suitable for investigating biological mechanisms involved in Lp(a) metabolism. We here generated and characterized iPSCs from a patient with extremely high Lp(a) plasma levels genetically determined (Coassin et al., 2022). This unique cellular model offers great opportunities and new perspectives for investigations on biological mechanisms involved in Lp(a) metabolism.

Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives.

Cardiovascular disease (CVD) is still a leading cause of morbidity and mortality, despite all the progress achieved as regards to both prevention and treatment. Having high levels of lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease that operates independently. It can increase the risk of developing cardiovascular disease even when LDL cholesterol (LDL-C) levels are within the recommended range, which is referred to as residual cardiovascular risk. Lp(a) is an LDL-like particle present in human plasma, in which a large plasminogen-like glycoprotein, apolipoprotein(a) [Apo(a)], is covalently bound to Apo B100 via one disulfide bridge. Apo(a) contains one plasminogen-like kringle V structure, a variable number of plasminogen-like kringle IV structures (types 1-10), and one inactive protease region. There is a large inter-individual variation of plasma concentrations of Lp(a), mainly ascribable to genetic variants in the Lp(a) gene: in the general po-pulation, Lp(a) levels can range from <1 mg/dL to >1000 mg/dL. Concentrations also vary between different ethnicities. Lp(a) has been established as one of the risk factors that play an important role in the development of atherosclerotic plaque. Indeed, high concentrations of Lp(a) have been related to a greater risk of ischemic CVD, aortic valve stenosis, and heart failure. The threshold value has been set at 50 mg/dL, but the risk may increase already at levels above 30 mg/dL. Although there is a well-established and strong link between high Lp(a) levels and coronary as well as cerebrovascular disease, the evidence regarding incident peripheral arterial disease and carotid atherosclerosis is not as conclusive. Because lifestyle changes and standard lipid-lowering treatments, such as statins, niacin, and cholesteryl ester transfer protein inhibitors, are not highly effective in reducing Lp(a) levels, there is increased interest in developing new drugs that can address this issue. PCSK9 inhibitors seem to be capable of reducing Lp(a) levels by 25-30%. Mipomersen decreases Lp(a) levels by 25-40%, but its use is burdened with important side effects. At the current time, the most effective and tolerated treatment for patients with a high Lp(a) plasma level is apheresis, while antisense oligonucleotides, small interfering RNAs, and microRNAs, which reduce Lp(a) levels by targeting RNA molecules and regulating gene expression as well as protein production levels, are the most widely explored and promising perspectives. The aim of this review is to provide an update on the current state of the art with regard to Lp(a) pathophysiological mechanisms, focusing on the most effective strategies for lowering Lp(a), including new emerging alternative therapies. The purpose of this manuscript is to improve the management of hyperlipoproteinemia(a) in order to achieve better control of the residual cardiovascular risk, which remains unacceptably high.

Lipoprotein(a) is a new prognostic factor in patients with psoriasis and coronary artery disease: a retrospective cohort study

BackgroundThe prognostic value of lipoprotein (Lp) (a) in patients who have suffered from coronary artery disease (CAD) has not been fully studied, and the results are inconsistent. This study was conducted to evaluate whether increased Lp(a) concentrations cause differences in clinical adverse outcomes in patients with psoriasis who have already suffered from CAD.MethodsThis retrospective cohort study included consecutive patients with psoriasis and CAD between January 2017 and May 2022 in our hospital. The clinical records were collected, and comparisons were made between patients in the low Lp(a) and high Lp(a) groups. Cox proportional hazard analysis and log-rank tests were used to evaluate the association between variables.ResultsAmong 295 patients, 148 patients were in the low Lp(a) group, and 147 were in the high Lp(a) group. These two groups did not differ significantly in age, gender or body mass index. Compared with the low Lp(a) group, the levels of platelet counts (P = 0.038) and high sensitivity C reactive protein (P = 0.012) were higher in the high Lp(a) group. Patients in the high Lp(a) group had higher total cholesterol levels (P = 0.029) and lower triglyceride levels (P = 0.037). Among the whole cohort, clinical adverse events were not correlated with Lp(a) concentrations after a median follow-up of 3 years. However, in the subgroup analysis, there were significant differences in all-cause death (log rank P = 0.036) and rehospitalization (log rank P = 0.037) between the two groups in patients with diabetes; a difference in rehospitalization (log rank P = 0.042) was also found between the two groups in men.ConclusionsIn patients with psoriasis and CAD, high levels of Lp(a) were related to a poor prognosis, especially in patients with diabetes and in men. These results will provide valuable information for the risk stratification of patients with psoriasis and CAD.

Role of lipoprotein(a) concentrations in bioprosthetic aortic valve degeneration

ObjectivesLipoprotein(a) (Lp(a)) is associated with an increased incidence of native aortic stenosis, which shares similar pathological mechanisms with bioprosthetic aortic valve (bAV) degeneration. However, evidence regarding the role of Lp(a)...

Lipoprotein(a) and functional outcome of acute ischemic stroke when discordant with low-density lipoprotein cholesterol.

Several studies have indicated that residual cardiovascular risk might be associated with elevated lipoprotein(a) [Lp(a)] even in the setting of controlled low-density lipoprotein cholesterol (LDL-C). We aimed to prospectively examine the association between Lp(a) and unfavorable functional outcome among patients with acute ischemic stroke when Lp(a) and LDL-C were discordant. Based on samples from the Infectious Factors, Inflammatory Markers and Prognosis of Acute Ischemic Stroke study, 973 patients with baseline plasma Lp(a) levels were included. The primary outcome was the composite outcome of death or major disability (modified Rankin Scale score of 3-6) at 6months. Logistic regression models were used to estimate the risk for the primary outcome. Discordance analyses were performed, using difference in percentile units (>10units), to detect the relative risk when Lp(a) and LDL-C were discordant. In total, 201 (20.7%) participants experienced major disability or death at 6months. The multivariable-adjusted odds ratio (OR) for the highest quartile was 1.88 [95% confidence interval (CI): 1.16-3.04] compared with the lowest quartile. Each 1-SD higher log-Lp(a) was associated with a 23% increased risk (95% CI: 2%-47%) for the primary outcome. Compared with the concordant group, the high Lp(a)/low LDL-C discordant group was associated with increased risk for the primary outcome (adjusted OR: 1.59, 95% CI: 1.01-2.52). Elevated plasma Lp(a) levels were associated with increased risk of major disability and death at 6months. Discordantly high Lp(a)/low LDL-C was associated with an unfavorable functional outcome, supporting the predictive potential of plasma Lp(a) after ischemic stroke, especially when discordant with LDL-C. Key messages What is already known on this topic Previous studies have indicated that a positive association between increased lipoprotein(a) [Lp(a)] and cardiovascular disease risk remained even in patients who achieved controlled low-density lipoprotein cholesterol (LDL-C) levels. The findings of studies exploring the association between Lp(a) and unfavorable clinical outcomes of stroke were inconsistent, and whether Lp(a) can predict the risk of unfavorable functional outcome in stroke patients when Lp(a) and LDL-C levels are discordant remains unknown. What this study adds Elevated plasma Lp(a) levels were associated with increased risk of major disability and death at 6months beyond LDL-C levels in acute ischemic stroke patients. How this study might affect research, practice, or policy The combination of LDL-C-lowering therapies and Lp(a)-lowering therapies may have better clinical efficacy for patients with ischemic stroke, and it is of great clinical interest to further explore this possibility in dedicated randomized trials.

Predictors of functional and morphological arterial wall properties in coronary artery disease patients with increased lipoprotein (a) levels before and after treatment with proprotein convertase subtilisin-kexin type 9 inhibitors

BackgroundIn addition to proatherogenic properties, lipoprotein (a) (Lp(a)) has also pro-inflammatory, antifibrinolytic and prothrombogenic features. The aim of the current study was to identify the predictors of functional and morphological properties of the arterial wall in patients after myocardial infarction and increased Lp(a) levels at the beginning and after treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors.MethodsSeventy-six post-myocardial infarction patients with high Lp(a) levels were included in the study. Ultrasound measurements of flow-mediated dilation of brachial artery (FMD), carotid intima-media thickness (c-IMT) and pulse wave velocity (PWV) were performed initially and after 6 months of treatment. At the same time points lipids, Lp(a), inflammatory and hemostasis markers were measured in blood samples.ResultsIn linear regression model FMD significantly correlated with age at first myocardial infarction (β = 0.689; p = 0.022), high-sensitivity C-reactive protein (β = -1.200; p = 0.009), vascular cell adhesion protein 1 (VCAM-1) (β = -0.992; p = 0.006), overall coagulation potential (β = 1.428; p = 0.014) and overall hemostasis potential (β = -1.473; p = 0.008). c-IMT significantly correlated with age at first myocardial infarction (β = 0.574; p = 0.033) and Lp(a) (β = 0.524; p = 0.040). PWV significantly correlated with systolic blood pressure (β = 0.332; p = 0.002), tumor necrosis factor alpha (β = 0.406; p = 0.002), interleukin-8 (β = -0.315; p = 0.015) and plasminogen activator inhibitor 1 (β = 0.229; p = 0.031). After treatment FMD reached statistical significance only in univariant analysis with systolic blood pressure (r = -0.286; p = 0.004) and VCAM-1 (r = -0.229; p = 0.024). PWV and c-IMT correlated with age (r = 0.334; p = 0.001 and r = 0.486; p < 0.0001, respectively) and systolic blood pressure (r = 0.556; p < 0.0001 and r = 0.233; p = 0.021, respectively).ConclusionsOur results suggest that age, systolic blood pressure, Lp(a) levels and other biochemical markers associated with Lp(a) are predictors of functional and morphological properties of the arterial vessel wall in post-myocardial patients with high Lp(a) levels initially. However, after 6 months of treatment with PCSK9 inhibitors only age and systolic blood pressure seem to be predictors of these properties.Trial registrationThe protocol for this study was registered with clinicaltrials.gov on November, 3 2020 under registration number NCT04613167.Graphical

Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19

BackgroundPatients with COVID-19 have a higher risk of thrombosis and thromboembolism, but the underlying mechanism(s) remain to be fully elucidated. In patients with COVID-19, high lipoprotein(a) (Lp(a)) is positively associated with the risk of ischemic heart disease. Lp(a), composed of an apoB-containing particle and apolipoprotein(a) (apo(a)), inhibits the key fibrinolytic enzyme, tissue-type plasminogen activator (tPA). However, whether the higher Lp(a) associates with lower tPA activity, the longitudinal changes of these parameters in hospitalized patients with COVID-19, and their correlation with clinical outcomes are unknown. ObjectivesTo assess if Lp(a) associates with lower tPA activity in COVID-19 patients, and how in COVID-19 populations Lp(a) and tPA change post infection. MethodsEndogenous tPA enzymatic activity, tPA or Lp(a) concentration were measured in plasma from hospitalized patients with and without COVID-19. The association between plasma tPA and adverse clinical outcomes was assessed. ResultsIn hospitalized patients with COVID-19, we found lower tPA enzymatic activity and higher plasma Lp(a) than that in non–COVID-19 controls. During hospitalization, Lp(a) increased and tPA activity decreased, which associates with mortality. Among those who survived, Lp(a) decreased and tPA enzymatic activity increased during recovery. In patients with COVID-19, tPA activity is inversely correlated with tPA concentrations, thus, in another larger COVID-19 cohort, we utilized plasma tPA concentration as a surrogate to inversely reflect tPA activity. The tPA concentration was positively associated with death, disease severity, plasma inflammatory, and prothrombotic markers, and with length of hospitalization among those who were discharged. ConclusionHigh Lp(a) concentration provides a possible explanation for low endogenous tPA enzymatic activity, and poor clinical outcomes in patients with COVID-19.

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.

The association between lipoprotein(a) and atrial fibrillation: A systemic review and meta-analysis.

Lipoprotein(a) (Lp[a]) is a particle consisting of a low-density lipoprotein (LDL)-like core connected to an apolipoprotein(a) chain, which is an established risk factor for cardiovascular disease. However, studies addressing the relationship between atrial fibrillation (AF) and Lp(a) demonstrated conflicted results. Thus, we sought to evaluate this relationship by conducting this systemic review and meta-analysis. We performed a comprehensive systematic search of health science databases, including PubMed, Embase, Cochrane Library, Web of Science, MEDLINE, and ScienceDirect, to identify all relevant literature from their inception to March 1, 2023. We identified nine related articles, which were eventually included in this study. Our study showed no association between Lp(a) with new-onset AF (HR = 1.45, 95% confidence interval [CI]: 0.57-3.67, p = .432). In addition, genetically elevated Lp(a) was not associated with the risk of atrial fibrillation (OR = 1.00, 95%CI: 1.00-1.00, p = .461). Different stratification of Lp(a) levels may have different outcomes. Also, higher Lp(a) levels may be inversely associated with the risk of developing AF compared to those with lower levels. Lp(a) levels were not associated with incident AF. Further research is needed to identify the mechanism underlying these results and better understand Lp(a) stratification for AF and the possible inverse association between Lp(a) and AF.

Effect of genetic polymorphisms in LALBA and Prolactin genes on milk traits in Barki ewes

This study investigated the genetic polymorphisms in Alpha-lactalbumin (LALBA) and Prolactin (PRL) genes in the Egyptian Barki sheep. The investigated genes were previously identified to be associated with milk and reproductive traits in several livestock species. Nevertheless, little is known about their contribution to milk traits in Egyptian sheep. Milk traits of daily milk yield (DMY), protein percentage (PP), fat percentage (FP), lactose percentage, and total solid percentage (TSP) were available for 256 and 233 Barki ewes for LALBA and PRL, respectively. The association analysis between the phenotypes of milk traits was carried out using the general linear model implemented in SAS software. The single strand conformation polymorphism identified 3 (A, B and C) and 2 (G and C) distinctive alleles in LALBA and PRL, respectively. Allele frequencies for LALBA variants were 0.73 (A), 0.16 (B) and 0.11 (C), and 0.63 (G), and 0.37 (C) for PRL variants. Results showed that age and parity of the ewe significantly (P < 0.05) influenced the studied milk traits. Additionally, a significant (P < 0.05) effect of LALBA variants was reported on milk composition but not DMY. Likewise, a significant (P < 0.05) effect of PRL variants was observed on DMY and TSP. Interestingly, Animals with BB genotypes of LALBA gene produced milk with high FP (5.65 ± 1.25 %), PP (5.77 ± 1.17 %), LP (7.4 ± 1.22 %) and lower TSP (13.06 ± 5.1 %) compared with animals that carry other genotypes. Regarding the PRL polymorphisms, the heterozygote ewes (GC) tended to significantly produce more milk (368.57 ± 20.39 g/day) with higher TSP (19.81 ± 1.57) compared with the homozygotes. This study reported the LALBA and PRL as candidate genes with significant effects on milk yield and composition, which may be appropriate for a wide range of selection programs with breeding objectives that focus on milk yield and composition in sheep. However, further investigations with larger sample size are recommended to confirm these findings with higher accuracy.

Lipoprotein(a): a Case for Universal Screening in Youth.

Lipoprotein(a) has emerged as a strong independent risk factor for cardiovascular disease. Targeted screening recommendations for Lp(a) measurement exist for adults and youth known to be at high-risk. However, Lp(a) measurements are not included in universal screening guidelines in the US; hence, most families in the US with high Lp(a) levels who are at risk of future atherosclerotic heart disease, stroke, or aortic stenosis are not recognized. Lp(a) measurement included as part of routine universal lipid screening in youth would identify those children at risk of ASCVD and enable family cascade screening with identification and early intervention for affected family members. Lp(a) levels can be reliably measured in children as young as two years of age. Lp(a) levels are genetically determined. The Lp(a) gene is inherited in a co-dominant fashion. Serum Lp(a) attains adult levels by two years of age and is stable for the lifetime of the individual. Novel therapies that aim to specifically target Lp(a) are in the pipeline, including nucleic acid-based molecules such as antisense oligonucleotides and siRNAs. Inclusion of a single Lp(a) measurement performed as part of routine universal lipid screening in youth (ages 9-11; or at ages 17-21) is feasible and cost effective. Lp(a) screening would identify youth at-risk of ASCVD and enable family cascade screening with identification and early intervention for affected family members.

The Association of Lipoprotein(a) and Neutrophil-to-Lymphocyte Ratio Combination with Atherosclerotic Cardiovascular Disease in Chinese Patients.

The association of lipoprotein(a) [Lp(a)] with atherosclerotic cardiovascular disease (ASCVD) risk can be modified by chronic systemic inflammation. The neutrophil-to-lymphocyte ratio (NLR) is a reliable and easily available marker of immune response to various infectious and non-infectious stimuli. The purpose of this study was to assess the combined effects of Lp(a) and NLR in predicting the ASCVD risk and coronary artery plaque traits. This study included 1618 patients who had coronary computed tomography angiography (CTA) with risk assessment of ASCVD. CTA was used to evaluate the traits of coronary atherosclerotic plaques, and the association of ASCVD with Lp(a) and NLR was assessed by multivariate logistic regression models. Plasma Lp(a) and NLR were significantly increased in patients having plaques. High Lp(a) was defined as the plasma Lp(a) level > 75 nmol/L and high NLR as NLR > 1.686. The patients were grouped into four categories according to normal or high NLR and plasma Lp(a) as nLp(a)/NLR-, hLp(a)/NLR-, nLp(a)/NLR+ and hLp(a)/NLR+. The patients in the latter three groups had higher risk of ASCVD compared to the reference group nLp(a)/NLR-, with the highest ASCVD risk in the hLp(a)/NLR+ group (OR = 2.39, 95% CI = 1.49-3.83, P = 0.000). The occurrence of unstable plaques was 29.94% in the hLp(a)/NLR+ group, which was significantly higher than groups nLp(a)/NLR+, hLp(a)/NLR- and nLp(a)/NLR- with 20.83%, 26.54% and 22.58%, respectively, and there was a significantly increased risk of unstable plaque in the hLp(a)/NLR+ group compared to the nLp(a)/NLR- group (OR = 1.67, 95% CI = 1.04-2.68, P = 0.035). The risk of stable plaque was not significantly increased in the hLp(a)/NLR+ group compared to the nLp(a)/NLR- group (OR = 1.73, 95% CI = 0.96-3.10, P = 0.066). The concomitant presence of elevated Lp(a) and higher NLR is associated with increased unstable coronary artery plaques in patients with ASCVD.

Lipoprotein(a) As a Potential Predictive Factor for Earlier Aortic Valve Replacement in Patients with Bicuspid Aortic Valve.

Bicuspid aortic valve (BAV) affects 0.5-2% of the general population and constitutes the major cause of severe aortic valve stenosis (AVS) in individuals ≤70 years. The aim of the present study was to evaluate the parameters that may provide information about the risk of AVS developing in BAV patients, with particular emphasis on lipoprotein(a) (Lp(a)), which is a well-recognized risk factor for stenosis in the general population. We also analyzed the impact of autotaxin (ATX) and interleukin-6 (IL-6) as parameters potentially related to the pathomechanism of Lp(a) action. We found that high Lp(a) levels (>50 mg/dL) occurred significantly more frequently in patients with AVS than in patients without AVS, both in the group below and above 45 years of age (p = 0.036 and p = 0.033, respectively). Elevated Lp(a) levels were also strictly associated with the need for aortic valve replacement (AVR) at a younger age (p = 0.016). However, the Lp(a) concentration did not differ significantly between patients with and without AVS. Similarly, we observed no differences in ATX between the analyzed patient groups, and both ATX activity and concentration correlated significantly with Lp(a) level (R = 0.465, p < 0.001 and R = 0.599, p < 0.001, respectively). We revealed a significantly higher concentration of IL-6 in young patients with AVS. However, this observation was not confirmed in the group of patients over 45 years of age. We also did not observe a significant correlation between IL-6 and Lp(a) or between CRP and Lp(a) in any of the analyzed groups of BAV patients. Our results demonstrate that a high level of Lp(a), greater than 50 mg/dL, may be a significant predictive factor for earlier AVR. Lp(a)-related parameters, such as ATX and IL-6, may be valuable in providing information about the additional cardiovascular risks associated with developing AVS.

Evidence and Uncertainties on Lipoprotein(a) as a Marker of Cardiovascular Health Risk in Children and Adolescents.

Lipoprotein(a) (Lp(a)) is made up of apoprotein(a) (apo(a)) and an LDL-like particle. The LPA gene encodes apo(a) and thus determines the characteristics and amount of apo(a) and Lp(a). The proportion of Lp(a) in each individual is genetically determined and is only minimally modifiable by the environment or diet. Lp(a) has important pro-atherosclerotic and pro-inflammatory effects. It has been hypothesized that Lp(a) also has pro-coagulant and antifibrinolytic actions. For these reasons, high Lp(a) values are an important independent risk factor for cardiovascular disease and calcific aortic valve stenosis. Numerous studies have been performed in adults about the pathophysiology and epidemiology of Lp(a) and research is under way for the development of drugs capable of reducing Lp(a) plasma values. Much less information is available regarding Lp(a) in children and adolescents. The present article reviews the evidence on this topic. The review addresses the issues of Lp(a) changes during growth, the correlation between Lp(a) values in children and those in their parents, and between Lp(a) levels in children, and the presence of cardiovascular disease in the family. Gaining information on these points is particularly important for deciding whether Lp(a) assay may be useful for defining the cardiovascular risk in children, in order to plan a prevention program early.

Combined effect of D-dimer, hs-CRP, and Lp(a) on 5-year clinical outcomes after percutaneous coronary intervention: A large real-world study in China

To reduce cardiovascular risk in patients with established coronary heart disease, the present study investigated the combined effect of D-dimer, high-sensitivity C-reactive protein (hs-CRP), and lipoprotein(a) [Lp(a)] on long-term cardiovascular outcomes from the perspectives of thrombosis, inflammation, and lipid risk simultaneously. Consecutive 10,724 patients with percutaneous coronary intervention (PCI) were enrolled throughout 2013. Over a median follow-up of 5.1 years, each individual elevation of D-dimer, hs-CRP, and Lp(a) was associated with poor ischemic outcomes but not bleeding. Concurrent high D-dimer, hs-CRP, and Lp(a) had even greater risks of all-cause death (hazard ratio [HR] 2.714, 95% confidence interval [CI] 1.742-4.231) and cardiac death (HR 4.152, 95% CI 2.207-7.812) and had incremental value beyond the traditional risk factors model. Concurrent high D-dimer, hs-CRP, and Lp(a) levels had a synergistic effect on adverse 5-year ischemic outcomes, highlighting that the potential utility of simultaneous assessment of multiple cardiovascular risk biomarkers may help to identify high-risk patients after PCI.

Plasma Lipoprotein(a) Levels in Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

The polycystic ovary syndrome (PCOS) may represent an important model of lipid alterations. Lipoprotein(a) [Lp(a)] has emerged as a new marker of cardiovascular risk. The main objective of this meta-analysis was to analyze the available evidence on Lp(a) levels in patients with PCOS compared to a control group. This meta-analysis was performed according to PRISMA guidelines. A literature search was performed to detect studies that have quantified Lp(a) levels in women with PCOS compared to a control group. The primary outcome was Lp(a) levels expressed in mg/dL. Random effects models were used. Twenty-three observational studies including 2,337 patients were identified and considered eligible for this meta-analysis. In the overall analysis, the quantitative analysis showed that patients with PCOS have a higher Lp(a) levels (SMD: 1.1 [95% CI: 0.7 to 1.4]; I2=93%) compared to the control group. The results were similar in the analysis of the subgroups of patients according to body mass index (normal weight group: SMD: 1.2 [95% CI: 0.5 to 1.9], I2=95%; overweight group: SMD: 1.2 [95% CI: 0.5 to 1.8], I2=89%). Sensitivity analysis showed that the results were robust. This meta-analysis shows that women with PCOS had higher levels of Lp(a) compared to healthy women used as a control group. These findings were observed in both overweight and non-overweight women.

Lipoprotein(a), family history of cardiovascular disease, and incidence of heart failure

Lipoprotein(a) (Lp(a)) is a largely genetically determined biomarker for cardiovascular disease (CVD), while its potential interplay with family history (FHx) of CVD, a measure of both genetic and environmental exposures, remains unclear. We examined the associations of Lp(a) in terms of circulating concentration or polygenetic risk score (PRS), and FHx of CVD with risk of incident heart failure (HF). Included were 299,158 adults from the UK Biobank without known HF and CVD at baseline. Hazards ratios (HRs) and 95% Cls were estimated by Cox regression models adjusted for traditional risk factors defined by the Atherosclerosis Risk in Communities study HF risk score. During the 11.8-year follow-up, 5,502 incidents of HF occurred. Higher levels of circulating Lp(a), Lp(a) PRS, and positive FHx of CVD were associated with higher risks of HF. Compared with individuals who had lower circulating Lp(a) and no FHx, HRs (95% CIs) of HF were 1.36 (1.25, 1.49), 1.31 (1.19, 1.43), and 1.42 (1.22, 1.67) for those with higher Lp(a) and a positive history of CVD for all family members, parents, and siblings, respectively; similar results were observed by using Lp(a) PRS. The risk estimates for HF associated with elevated Lp(a) and positive FHx were attenuated after excluding those with incident myocardial infarction (MI) during follow-up. Lp(a) and FHx of CVD were independent risk factors for incident HF, and the highest risk of HF was observed among individuals with both risk factors. The association may be partly mediated by myocardial infarction.

Lipoprotein(a), metabolic profile and new-onset type 2 diabetes in patients with familial combined hyperlipidemia: A 9 year follow-up study

Lipoprotein(a) [Lp(a)] appears to have an inverse association with the risk of type 2 diabetes mellitus in the general population. This study aimed to investigate the prognostic role of Lp(a) regarding the development of type-2 diabetes in the special population of subjects with familial combined hyperlipidemia (FCH). This cohort study included 474 patients (mean age 49.7±11.3 years, 64% males) with FCH, without diabetes at baseline who were followed for a mean period of 8.2±6.8 years. At baseline evaluation venous blood samples were obtained for the determination of lipid profile and Lp(a) levels. The endpoint of interest was the development of diabetes. Patients with increased Lp(a) levels ≥30mg/dl compared to those with low Lp(a) levels <30mg/dl had lower levels of triglycerides (238±113 vs 268±129 mg/dl, p=0.01), greater levels of high-density lipoprotein (HDL) cholesterol (44±10 vs 41±10 mg/dl, p=0.01) and hypertension in a greater percentage (42% vs 32%, p=0.03). The incidence of new-onset diabetes during the follow-up period was 10.1% (n=48). Multiple Cox regression analysis revealed that increased Lp(a) is an independent predictor of lower diabetes incidence (HR 0.39, 95% CI 0.17-0.90, p=0.02) after adjustment for confounders. Among subjects with FCH those with higher Lp(a) levels have lower risk for the development of type 2 diabetes. Moreover, the presence of increased Lp(a) seems to differentiate the expression of metabolic syndrome characteristics in patients with FCH, as increased Lp(a) is related to lower levels of triglycerides, greater prevalence of hypertension and higher levels of HDL cholesterol.

Lipoprotein (a) cholesterol burden predicts atherosclerotic risk in patients with elevated lipoprotein a

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): Mayo Clinic Department of Laboratory Medicine and Pathology. Background Elevated lipoprotein(a) [Lp(a)] is associated with increased risk for atherosclerotic cardiovascular disease (ASCVD). Treatment of patients with elevated Lp(a) usually includes marked reduction in low density lipoprotein cholesterol (LDL-C). However, there are uncertainties about whether all increases in Lp(a) are equivalent in there risk relationship. Purpose The aim of this investigation was to risk stratify patients with elevated Lp(a) mass [Lp(a)-M] based on Lp(a) cholesterol (Lp(a)-C) measurements. We assessed coronary artery disease (CAD) by coronary angiogram and major adverse cardiac events (MACE) in a cohort of patients with elevated Lp(a) mass (≥30mg/dL) over a 15 year followup. Methods Electrophoretic and immunologic assays were used to measure Lp(a)-C and Lp(a)-M, respectively. Univariate and multivariate logistic regression analysis was employed to test for association between Lp(a) and CAD in a cohort patients with elevated Lp(a)-M (≥30mg/dL). The relationship between Lp(a) and time to major cardiac events was evaluated using cox regression analysis. Receiver operator curve (ROC) analyses were used to identify optimal cutoff values for Lp(a)-M and C for predicting CAD in our model. Results We analyzed 179 patients with elevated Lp(a)-M. Cutoff values of 3.3mg/dL for Lp(a)-C and 42.1mg/dL for Lp(a)-M optimally predicted CAD in an ROC analysis. Of these patients, 84 were found to have Lp(a)-C &amp;lt; 3.3mg/dL (low Lp(a)-C), while 95 patients had Lp(a)-C levels ≥ 3.3mg/dL (high Lp(a)-C). High Lp(a)-C was associated with CAD identified on coronary angiography in univariate (OR = 2.17, 95% CI = 1.18 – 4.00, p = 0.013) and multivariate (OR = 3.36, 95% CI = 1.64 – 6.89, p &amp;lt; 0.001) models controlling for traditional risk factors. In univariate analyses high Lp(a)-C was also associated with MACE (HR = 2.38, 95% CI = 1.19 – 4.75, p = 0.01) while Lp(a)-M ≥ 42.1mg/dL (high Lp(a)-M) was not (HR = 1.68, 95% CI = 0.82 – 3.44, p = 0.15) (Table 1, Figure 1). Lp(a)-C remained significantly correlated with MACE after adjusting for traditional risk factors. When included in a model together, Lp(a)-C maintained its significance while Lp(a)-M failed to predict MACE, indicating that Lp(a)-C is a stronger predictor of MACE than Lp(a)-M. Conclusion This study demonstrates that patients with elevated Lp(a)-M and high Lp(a)-C are approximately 2.5 times more likely to encounter MACE over time when compared to patients with elevated Lp(a)-M and low Lp(a)-C. Our investigation suggests that Lp(a)-C can be used to risk stratify patients with elevated Lp(a)-M and identify those at higher risk.