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Aims This review aims to provide an update of available methods for imaging calcification activity and potential therapeutic options. Data Synthesis: Aortic valve calcification represents the most common heart valve condition requiring treatment among adults in Western societies. No medical therapies are proven to be effective in treating symptoms or reducing disease progression. Therefore, surgical or transcatheter aortic valve replacement remains the only available treatment option. Elevated circulating concentrations of lipoprotein(a) is strongly associated with degenerative aortic stenosis. This relationship was first observed in prospective observational studies, and the causal relationship was confirmed in genetic studies. Conclusions: new therapeutic targets have been identified and new imaging techniques could be used to test the effectiveness of new agents and further clarify the pathophysiology of AVS. No therapy that specifically lowers Lp (a) levels has been approved for clinical use.

Lipoprotein(a) forms a subfraction of the lipid profile and is characterized by the addition of apolipprotein(a) (apo(a)) to apoB100 derived particles. Its levels are mostly genetically determined inversely related to the number of protein domain (kringle) repeats in apo(a). In epidemiological studies, it shows consistent association with cardiovascular disease (CVD) and most recently with extent of aortic stenosis. Issues with standardizing the measurement of Lp(a) are being resolved and consensus statements favor its measurement in patients at high risk of, or with family histories of CVD events. Major lipid-lowering therapies such as statin, fibrates, and ezetimibe have little effect on Lp(a) levels. Therapies such as niacin or cholesterol ester transfer protein (CETP) inhibitors lower Lp(a) as well as reducing other lipid-related risk factors but have failed to clearly reduce CVD events. Proprotein convertase subtilisin kexin-9 (PCSK9) inhibitors reduce cholesterol and Lp(a) as well as reducing CVD events. New antisense therapies specifically targeting apo(a) and hence Lp(a) have greater and more specific effects and will help clarify the extent to which intervention in Lp(a) levels will reduce CVD events.

Early-onset dementia is defined as dementia occurring prior to the age of 65. Given its impact on physical, mental, and socioeconomic well-being, it is crucial to identify modifiable risk factors. Here, we report a 43-year-old man with early-onset dementia associated with elevated lipoprotein (a) and a missense variant in the DNAJC5 gene. He presented to the hospital with memory loss and multiple cerebrovascular infarcts. Eight months prior, an MRI revealed small acute and subacute infarcts involving the left PCA for which he was treated with antiplatelet agents and a statin. Three months later, he was readmitted for progressive memory loss. CT imaging showed evolving and new infarcts compared to prior scans. A cardiac echocardiogram excluded thrombus and PFO, and he was diagnosed with early vascular dementia. He was readmitted again 5 months later with additional evaluation revealing multifocal moderate to severe stenosis and irregularities involving the bilateral ICA and bilateral PCAs. MRI showed more pronounced infarcts compared to a previous MRI as well as new infarcts. CSF studies, VDRL, RF, ANA, ANCA, homocysteine, and MMA levels were normal. Lipoprotein (a) was found to be markedly elevated, and genetic testing revealed a missense variant of the DNAJC5 gene, the mutation of which is associated with ceroid lipofuscinosis. In conclusion, in patients with early-onset dementia and evidence of accelerated atherosclerosis, it is reasonable to measure Lp(a) and consider testing for variants in genes such as DNAJC5 and others, particularly when disease severity appears unexplained by known risk factors or circumstances.

Background There is a well-documented empirical relationship between lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD); however, causal evidence, especially from the Chinese population, is lacking. Therefore, this study aims to estimate the causal association between variants in genes affecting Lp(a) concentrations and CVD in people of Han Chinese ethnicity. Methods Two-sample Mendelian randomization analysis was used to assess the causal effect of Lp(a) concentrations on the risk of CVD. Summary statistics for Lp(a) variants were obtained from 1256 individuals in the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei. Data on associations between single-nucleotide polymorphisms (SNPs) and CVD were obtained from recently published genome-wide association studies. Results Thirteen SNPs associated with Lp(a) levels in the Han Chinese population were used as instrumental variables. Genetically elevated Lp(a) was inversely associated with the risk of atrial fibrillation [odds ratio (OR), 0.94; 95% confidence interval (95%CI), 0.901–0.987; P = 0.012)], the risk of arrhythmia (OR, 0.96; 95%CI, 0.941–0.990; P = 0.005), the left ventricular mass index (OR, 0.97; 95%CI, 0.949–1.000; P = 0.048), and the left ventricular internal dimension in diastole (OR, 0.97; 95%CI, 0.950–0.997; P = 0.028) according to the inverse-variance weighted method. No significant association was observed for congestive heart failure (OR, 0.99; 95% CI, 0.950–1.038; P = 0.766), ischemic stroke (OR, 1.01; 95%CI, 0.981–1.046; P = 0.422), and left ventricular internal dimension in systole (OR, 0.98; 95%CI, 0.960–1.009; P = 0.214). Conclusions This study provided evidence that genetically elevated Lp(a) was inversely associated with atrial fibrillation, arrhythmia, the left ventricular mass index and the left ventricular internal dimension in diastole, but not with congestive heart failure, ischemic stroke, and the left ventricular internal dimension in systole in the Han Chinese population. Further research is needed to identify the mechanism underlying these results and determine whether genetically elevated Lp(a) increases the risk of coronary heart disease or other CVD subtypes.

Lipoprotein (a) [Lp(a)] is characterized by an LDL-like composition in terms of lipids and apoB100, and by one copy of a unique glycoprotein, apo(a). The apo(a) structure is mainly based on the repetition of tandem kringle domains with high homology to plasminogen kringles 4 and 5. Among them, kringle IV type 2 (KIV-2) is present in a highly variable number of genetically encoded repeats, whose length is inversely related to Lp(a) plasma concentration and cardiovascular risk. Despite it being the major component of apo(a), the actual function of KIV-2 is still unclear. Here, we describe the first high-resolution crystallographic structure of this domain. It shows a general fold very similar to other KIV domains with high and intermediate affinity for the lysine analog, ε-aminocaproic acid. Interestingly, KIV-2 presents a lysine binding site (LBS) with a unique shape and charge distribution. KIV-2 affinity for predicted small molecule binders was found to be negligible in surface plasmon resonance experiments; and with the LBS being nonfunctional, we propose to rename it “pseudo-LBS”. Further investigation of the protein by computational small-molecule docking allowed us to identify a possible heparin-binding site away from the LBS, which was confirmed by specific reverse charge mutations abolishing heparin binding. This study opens new possibilities to define the pathogenesis of Lp(a)-related diseases and to facilitate the design of specific therapeutic drugs.

Introduction Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease (CAD). To the best of our knowledge, this is the first study addressing the relationship between Lp(a) and platelet reactivity in primary and secondary prevention. Methods Lp(a) was evaluated in 396 individuals with (82.3%) and without (17.7%) obstructive CAD. The population was divided into two groups according to Lp(a) concentrations with a cutoff value of 50 mg/dL. The primary objective was to evaluate the association between Lp(a) and adenosine diphosphate (ADP)-induced platelet reactivity using the VerifyNow™ P2Y12 assay. Platelet reactivity was also induced by arachidonic acid and collagen–epinephrine (C-EPI) and assessed by Multiplate™, platelet function analyzer™ 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD. Results Overall, 294 (74.2%) individuals had Lp(a) 0.05). Finally, multivariable analysis did not show a significant association between ADP-induced platelet reactivity and Lp(a) ≥ 50 mg/dL [adjusted OR = 1.00 [(95% CI 0.99–1.01), P = 0.590]. Conclusion In individuals with or without CAD, Lp(a) ≥ 50 mg/dL was not associated with higher platelet reactivity. Electronic supplementary material The online version of this article (10.1007/s12325-020-01483-y) contains supplementary material, which is available to authorized users.

Lipoprotein (a) [Lp(a)] is a risk factor for CVD and a target of therapy, but Lp(a) measurements are not globally standardized. Commercially available assays generally use polyclonal antibodies that detect multiple sites within the kringle (K)IV(2) repeat region of Lp(a) and may lead to inaccurate assessments of plasma levels. With increasing awareness of Lp(a) as a cardiovascular risk factor and the active clinical development of new potential therapeutic approaches, the broad availability of reagents capable of providing isoform independence of Lp(a) measurements is paramount. To address this issue, we generated a murine monoclonal antibody that binds to only one site on apo(a). A BALB/C mouse was immunized with a truncated version of apo(a) that contained eight total KIV repeats, including only one copy of KIV(2). We generated hybridomas, screened them, and successfully produced a KIV(2)-independent monoclonal antibody, named LPA-KIV9. Using a variety of truncated apo(a) constructs to map its binding site, we found that LPA-KIV9 binds to KIV(9) without binding to plasminogen. Fine peptide mapping revealed that LPA-KIV9 bound to the sequence (4076)LETPTVV(4082) on KIV(9). In conclusion, the generation of monoclonal antibody LPA-KIV9 may be a useful reagent in basic research studies and in the clinical application of Lp(a) measurements.

International audience; Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDLsubclasses, and thus potential atherogenicity? What is the effect of statin treatment? Obese hypertriglyceridemic hypercholesterolemicmales [n = 12; lipoprotein (a)

Background: The pathophysiology of coronary artery ectasia (CAE) is under investigated and not well understood. Atherosclerosis is considered as the main etiologic factor for CAE in adults where more than 50% of CAE patients have atherosclerosis. Recently, lipoprotein (a) (Lp(a)) has emerged as a powerful risk factor for atherosclerosis and coronary artery disease (CAD). Serum levels of Lp(a) in patients with CAE have not been investigated. We assumed that Lp(a) may play a role in the pathogenesis of CAE. Principally, our study aims to identify whether Lp(a) is an independent risk factor for CAE. Methods: Our study is a prospective pilot study. Study population was collected prospectively from pool of patients referred for elective cardiac catheterization at Jordan University Hospital (JUH) in the period extending from February 17, 2018 to June 31, 2018. Patients were referred for elective coronary angiography after being interviewed and physically examined by a cardiologist (HA). Patients with known history of CAD or who are already on anti-lipidemic drugs either documented in the medical records or by interviewing patients for history of revascularization were excluded from the study. Results: Regarding the primary outcome, there was no significant difference in Lp(a) concentrations between normal and ectasia groups in the general sample (median: 17.5mg/dL vs. 20.4 mg/dL, P value = 0.38). Conclusions: Our study concludes that there is no detected relationship between elevated Lp(a) levels and developing CAE. CAE was more common in patients with low high-density lipoprotein (HDL) level (compared with patients with normal coronaries), higher total cholesterol level (compared with patients with non-obstructive stenosis) and higher hemoglobin A1c (HbA1c). Cardiol Res. 2020;11(1):50-55 doi: https://doi.org/10.14740/cr992 Â

Background The current study aimed to evaluate the relationship between baseline serum lipoprotein (a) [Lp(a)] level and heart failure with reduced ejection fraction (HFrEF) development. Methods This was a retrospective study, and participants were enrolled from the outpatient clinic. All data were extracted from the electronic health record of the outpatient clinic system. The follow‐up was performed through reviewing the clinical notes at the outpatient clinic system, and study outcome of the current study was the first diagnosis of HFrEF. Participants were divided into low Lp(a) (, After stepwise adjusting for covariates, per 10 mg/dl increase in baseline Lp(a) remained significantly associated with HFrEF, with odds ratio of 1.17 (95% CI 1.05, 1.46). In addition, the magnitude of the association between baseline Lp(a) level and HFrEF was greater in men and in individuals with diabetes mellitus (DM) or coronary heart disease (CHD), while it was weaker in individuals treated with beta‐blocker at baseline.

Background: Lipoprotein(a) [Lp(a)] is an LDL-like molecule that is likely causal for cardiovascular events and Lp(a) variability has been shown to be mostly of genetic origin. Exogenous hormones (hormone replacement therapy) seem to influence Lp(a) levels, but the impact of endogenous hormone levels on Lp(a) is still unknown. The aim of the study was to assess the effect of endogenous steroid hormone metabolites on Lp(a). Methods: Lipoprotein(a) levels were measured in 1,021 participants from the Swiss Kidney Project on Genes in Hypertension, a family-based, multicentre, population-based prospective cohort study. Endogenous levels of 28 steroid hormone precursors were measured in 24-h urine collections from 883 individuals. Of the participants with Lp(a) data, 1,011 participants had also genotypes available. Results: The participants had an average age of 51 years and 53% were female. Median Lp(a) levels were 62 mg/L, and the 90thpercentile was 616 mg/L. The prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. Forty-three per cent of Lp(a) variability was explained respectively by: age (2%, p-16). Of the 28 endogenous steroid hormones assessed, androstenetriol, androsterone, 16α-OH-DHEA and estriol were nominatively associated with serum Lp(a) levels in univariable analyses and explained 0.4%-1% of Lp(a) variability, but none of them reached significance in multivariable models. Conclusions: In this contemporary population-based study, the prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. The effect of endogenous steroid hormone levels of Lp(a) variability was small at best, suggesting a negligible impact on the wide range of Lp(a) variability.

ContextElevated levels of lipoprotein(a) (Lp[a]) is an independent risk factor for atherosclerotic cardiovascular disease especially in patients with diabetes. Adult levels of Lp(a) are thought to be is expressed by the second year of life.ObjectiveWe hypothesized that Lp(a) would be influenced by low density lipoprotein cholesterol (LDL-C), race, and HbA1C.MethodsRetrospective electronic medical record review of children and adolescents with type 1 diabetes (T1D) (n = 607) and type 2 diabetes (T2D) (n = 93).ResultsTotal of 700 subjects, ages 12-19 years with T1D (n = 607) and T2D (n = 93), 49% were male, mean age was 13.2 ± 3.08 years, and the median Lp(a) was 8.00 mg/dL, IQR 5.00-12.00. The Black subjects had an increased relative risk (RR) of higher Lp(a) compared with White subjects (RR 1.25, P ConclusionOur data suggest that Lp(a) is associated with LDL-C in children with diabetes. Lp(a) is differentially increased at higher concentrations of LDL-C. Black children with diabetes have a significant burden of Lp(a) concentrations compared with White children.

The pharmacologic inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) lowers lipoprotein (a) [Lp(a)] concentrations. However, the impact of genetic PCSK9 loss-of-function variants (LOFVs) on Lp(a) is uncertain. We determined the association of PCSK9 LOFVs with Lp(a) measures among black adults. Genotyping for PCSK9 LOFVs was conducted in 10,196 black Reasons for Geographic and Racial Differences in Stroke study participants. Among 241 participants with and 723 randomly selected participants without PCSK9 LOFVs, Lp(a) concentations, apo(a) kringle IV (KIV) repeats (a proxy for isoform size), and oxidized phospholipid (OxPL) apoB levels were measured using validated methods. Median Lp(a) concentrations among participants with and without PCSK9 LOFVs were 63.2 and 80.4 nmol/l, respectively (P = 0.016). After adjusting for age, sex, estimated glomerular filtration rate, LDL cholesterol, and statin use, participants with versus without a PCSK9 LOFV had a lower median Lp(a) concentration [Δ = -18.8 nmol/l (95% CI: -34.2, -3.3)]. Median apo(a) isoform sizes were 24 and 23 KIV repeats (P = 0.12) among participants with and without PCSK9 LOFVs, respectively [Δ = 1.1 (95% CI: 0.2, 2.0) after adjustment]. Median OxPL-apoB levels among participants with and without PCSK9 LOFVs were 3.4 and 4.1 nM (P = 0.20), respectively [Δ = -1.2 nM (95% CI -2.4, -0.04) after adjustment]. Among black adults, PCSK9 LOFVs were associated with lower Lp(a) concentration and OxPL-apoB levels.

Heritability of LPA allele, apo(a) isoform sizes, and isoform-associated lipoprotein(a) [Lp(a)] levels was studied in 82 Caucasian and African-American families with two parents and two children (age: 6-74 years). We determined: 1) Lp(a) levels; 2) LPA allele sizes; 3) apo(a) isoform sizes; and 4) isoform-specific apo(a) levels (ISLs), the amount of Lp(a) carried by an individual apo(a) isoform. Trait heritability was estimated by mid-parent-offspring analysis. The ethnicity-adjusted heritability estimate for Lp(a) level was 0.95. Heritability for ISLs corresponding to the smaller LPA allele in a given allele-pair was higher than that corresponding to the larger LPA allele (0.91 vs. 0.59, P = 0.017). Although not statistically different, heritability for both apo(a) isoforms (0.90 vs. 0.70) and LPA alleles (0.98 vs. 0.82) was higher for the smaller versus larger sizes. Heritability was generally lower in African-Americans versus Caucasians with a 4-fold difference for the larger LPA allele (0.25 vs. 0.94, P = 0.001). In Caucasians, an overall higher heritability pattern was noted for the older (≥47 years) versus younger (

Background Previous studies have observed that high level of lipoprotein (a) [Lp(a)] was common in the phenotypic familial hypercholesterolemia (FH) and may explain part of the clinical diagnosis of FH. Hypothesis We aim to develop a modified model including Lp(a) and compare its diagnostic performance with Dutch Lipid Clinic Network (DLCN) criteria. Methods Data of 10 449 individuals were utilized for the model establishment (7806 for derivation and 2643 for validation) from January 2011 to March 2018. The novel score model was modified on the basis of DLCN. Furthermore, 718 patients were screened for LDLR, APOB, and PCSK9 gene mutations. Results The novel modified model consisted of untreated low‐density lipoprotein cholesterol (LDL‐C) level, Lp(a), personal premature coronary heart disease (CHD), tendon xanthomas and family history of CHD and/or hypercholesterolemia. It has shown high discrimination (area under curve [AUC] 0.991, 95% confidence interval [CI[ 0.988‐0.994, P

BACKGROUND In Chronic Kidney Disease (CKD) patients, comprehensive care of patients involves not only the management of renal disease, but also the appropriate management of its complications. The study of Lipoprotein (a) levels (LP(a)) in CKD patients becomes important as it expresses the link between Chronic Renal Failure (CRF) and cardiovascular complications. In our study, Lipoprotein(a) is analysed in relation to various criteria in CRF to evaluate the risk group for complications. MATERIALS AND METHODS This study was done for a period of 1 year from April 2017 to March 2018 at Medicine OPD, ward, Nephrology OP and wards, Government KAPV medical college hospital, Trichy. During this period, 50 patients admitted with chronic renal failure of both sexes, irrespective of age were selected and enrolled for the study. RESULTS 37 out of 50 patients had elevated LP(a) levels. Age and sex were not found to be significant factors affecting LP(a). Increased LP(a) levels were seen in patients with severe anaemia, elevated seem creatinine levels, increased diastolic BP and ECG changes. CONCLUSION Elevated serum LP(a) level is very much useful in assessing the risk in CRF as accelerated atherosclerosis, uncontrolled hypertension, coronary artery disease and end stage renal disease.

BACKGROUND Prevalence of Coronary Artery Disease (CAD) is increasing in India. Acute myocardial infarction has very high morbidity and mortality, hence economically a big burden. However, established risk factors alone do not explain this excess of coronary artery disease, emerging risk factors like Hyperhomocysteinaemia and Lipoprotein (a) have been recognized as independent risk factors for CAD in many retrospective case control studies. This study is done to analyse plasma homocysteine and lipoprotein(a) levels in patients admitted to the hospital with Coronary Heart Disease for its role and its relation to other known risk factors. MATERIALS AND METHODS This study was conducted in 50 patients of acute ST elevation myocardial infarction (STEMI). Patients visiting OPD and inpatients in the department of medicine, Meenakshi Medical College Hospital and Research Institute during the period of February 2018 to August 2018 were included in the study. This study also included 50 people as control group. Patients were screened to look for traditional risk factors, and the homocysteine and lipoprotein(a) levels were documented. RESULTS When the association of both elevated lipoprotein (a) and homocysteine were compared with case and control group, it was seen that there is a high statistical significance with p-value of

Background: Disorders of thyroid gland are common in general population, and it’s the most common affecting the endocrine system after diabetes mellitus. Thyroid function regulates a wide range of metabolic parameters, as well as affects some cardiovascular disease risk factors. Fructosamine is produced by a reaction between albumin (protein) and glucose; it is used to monitor patients with diabetes for short-term glycemic changes. H-FABP is present in the cytoplasm of cardiac myocytes, and delivers fatty acids into these cells. It has been shown to increase in myocardial injury. Lipoprotein LP(a) is consist of a special apolipoprotein called apoprotein (a), and it’s recognized as a cardiovascular disease independent risk factor. Objective: To study whether certain metabolic and cardiovascular markers (fructosamine, H-FABP and lipoprotein (a) are changed in hypothyroid patients. Methods: The current study included 280 overt hypothyroid, 272 with subclinical hypothyroidism compared with 270 healthy individuals of matched age and gender. For all subjects serum (TSH, T4, T3, FBS, HbA1c, fructosamine, triglycerides, cholesterol, lipoprotein (a), and Heart-type Fatty Acid-Binding Protein (H-FABP)) was measured. Results: Serum fructosamine level significantly elevated (p value

Familial hypercholesterolemia (FH) is one of the most common genetic disorders in humans. It is an extremely atherogenic metabolic disorder characterized by lifelong elevations of circulating LDL-C levels often leading to premature cardiovascular events. In this review, we discuss the clinical phenotypes of heterozygous and homozygous FH, the genetic variants in four genes (LDLR/APOB/PCSK9/LDLRAP1) underpinning the FH phenotype as well as the most recent in vitro experimental approaches used to investigate molecular defects affecting the LDL receptor pathway. In addition, we review perturbations in the metabolism of lipoproteins other than LDL in FH, with a major focus on lipoprotein (a). Finally, we discuss the mode of action and efficacy of many of the currently approved hypocholesterolemic agents used to treat patients with FH, with a special emphasis on the treatment of phenotypically more severe forms of FH., K. C. received a scholarship from the European Union (European Regional Development Fund INTERREG V) and the Région Réunion (Saint-Denis, Réunion, France); J. G.-N. is a recipient of a Ramón y Cajal fellowship from the Spanish Ministerio de Ciencia, Innovación y Universidades; A. G. has received a postdoctoral fellowship from the Fondation pour la Recherche Médicale; C. M. has received research grants from the Basque Government Grupos Consolidados IT-1264-19; GL Research Group is funded by the Agence Nationale de la Recherche (Paris, France) Program Grant CHolesterol Personalized Innovation ANR-16-RHUS-0007 and project grant KRINGLE2 ANR-20-CE14-0009 as well as from La Fondation de France (project grant: 00096274).

After training as a gastroenterologist in the UK, the author became interested in lipidology while he was a research fellow in the USA and switched careers after returning home. Together with Nick Myant, he introduced the use of plasma exchange to treat familial hypercholesterolemia (FH) homozygotes and undertook non-steady state studies of LDL kinetics, which showed that the fractional catabolic rate of LDL remained constant irrespective of pool size. Subsequent steady-state turnover studies showed that FH homozygotes had an almost complete lack of receptor-mediated LDL catabolism, providing in vivo confirmation of the Nobel Prize-winning discovery by Goldstein and Brown that LDL receptor dysfunction was the cause of FH. Further investigation of metabolic defects in FH revealed that a significant proportion of LDL in homozygotes and heterozygotes was produced directly via a VLDL-independent pathway. Management of heterozygous FH has been greatly facilitated by statins and proprotein convertase subtilisin/kexin type 9 inhibitors but remains dependent upon lipoprotein apheresis in homozygotes. In a recent analysis of a large cohort treated with a combination of lipid-lowering measures, survival was markedly enhanced in homozygotes in the lowest quartile of on-treatment serum cholesterol. Emerging therapies could further improve the prognosis of homozygous FH; whereas in heterozygotes, the current need is better detection.

Familial hypercholesterolemia (FH), an autosomal dominant disorder of LDL metabolism that is characterized by elevated LDL cholesterol, is commonly encountered in patients with atherosclerotic coronary heart disease. Combinations of cholesterol lowering therapies are often used to lower LDL cholesterol in patients with familial hypercholesterolemia; however, current treatment goals for LDL cholesterol are rarely achieved in patients with homozygous FH, and are difficult to achieve in patients with heterozygous FH. Therapies that lower LDL cholesterol through LDL receptor-mediated mechanisms have thus far been largely ineffective in patients with homozygous FH, particularly in those with negligible (

BackgroundLipoprotein (a) [Lp (a)] has been well recognized as a risk factor of cardiovascular disease. However, the association between serum Lp (a) and diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM) remains unknown. We performed a meta-analysis to comprehensively evaluate the above association.MethodsObservational studies aiming to evaluate the independent association between serum Lp (a) and diabetic nephropathy in T2DM patients were identified by systematic search of PubMed and Embase databases. A random-effect model which incorporated the potential intra-study heterogeneity was used for the meta-analysis.ResultsEleven observational studies with 9304 T2DM patients were included. Results showed that compared to those with the lowest Lp (a), patients with the highest Lp (a) level had higher odds of diabetic nephropathy (adjusted odds ratio [OR]: 1.63, 95% confidence interval [CI]: 1.25–2.14, I2 = 54%, P < 0.001). Meta-analysis of studies in which Lp (a) was presented as continuous variables showed consistent result (adjusted OR: 1.13 for 1 mg/dl increment of Lp (a), 95% CI: 1.03–1.24, I2 = 36%, P = 0.008). Subgroup analyses showed that study characteristics such as definitions of diabetic nephropathy and study design did not significantly affect the association (P for subgroup difference all > 0.05).ConclusionsHigher serum Lp (a) in patients with T2DM is independently associated with higher odds of diabetic nephropathy. Large scale prospective cohort studies are needed to validate this finding. Moreover, the potential influence of Lp (a) lowering on renal function in T2DM patients may be further investigated.

Background Lp(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 Results This 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 (P =0.01) and risk‐adjusted analyses (38.7%±0.5 versus 37.5%±0.5, P P =0.002). Conclusions Elevated 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.

Homozygous familial hypercholesterolemia (HoFH) is a rare, autosomal dominant disease that leads to premature cardiovascular disease (CVD). Since monozygotic twins share the intrauterine environment and have the same age and gene profile, they could represent a very special resource for the investigation of the causes and the natural course of FH. This report is a description of 36-year-old monozygotic twin brothers with almost identical early coronary artery involvement due to FH concomitant with high lipoprotein(a) (Lpa) levels and a review of the literature. Sequence analysis revealed that the twins were homozygous for the LDLR c.1060+10G>A (rs12710260) mutation and heterozygous for the LDLR c.542C>T (rs557344672) mutations. Both were also homozygous for the c.1060+7T>C (rs2738442) and c.1586+53A>G (rs1569372) mutations in the LDLR gene as well as c.4265A>T (rs568413) mutations in the APOB gene. In the literature, there are 7 twin cases with reported FH, but none with high Lpa levels. The HoFH twins in this case report had lower low-density lipoprotein (LDL) cholesterol levels than expected (before treatment 204 and 223 mg/dL), with almost identical coronary involvement. Both had an extremely high Lpa level (308 and 272 nmol/L) with a very low coronary calcium score (16 AU) and a good response to statins (>60%). There was a history of the first CVD event occurring at nearly the same age (32–34 years) in the family. This could be an important aspect of FH families as a result of the similar timing of cumulative LDL exposure exceeding the threshold of CVD events. In conclusion, this first report of monozygotic HoFH twins with elevated Lpa levels and almost identical early coronary artery involvement at the same age provides evidence to substantiate the hypothesis of lifetime cholesterol burden/exposure.

Background Low-density lipoprotein cholesterol (LDL-c) has been proven to be a risk factor for atherosclerotic cardiovascular disease (CVD), while lipoprotein (a) (Lp(a)) is a residual risk factor for CVD, even though LDL-c is well controlled by statin use. Importantly, the role of Lp(a) in atherosclerotic renal artery stenosis (ARAS) is still unknown. Methods For this hospital-based cross-sectional study, patients who simultaneously underwent coronary and renal angiography were examined. ARAS was defined as a 50% reduction in the cross-sectional (two-dimensional plane) area of the renal artery. Data were collected and compared between ARAS and non-ARAS groups, including clinical history and metabolite profiles. Univariate analysis, three tertile LDL-c-based stratified analysis, and multivariate-adjusted logistic analysis were conducted, revealing a correlation between Lp(a) and ARAS. Results A total of 170 hypertensive patients were included in this study, 85 with ARAS and 85 with non-RAS. Baseline information indicated comparability between the two groups. In the univariate and multivariate analysis, common risk factors for atherosclerosis were not significantly different. Stratified analysis of LDL-c revealed a significant increase in the incidence of ARAS in patients who had high Lp(a) concentrations at low LDL-c levels (odds ratio (OR): 4.77, 95% confidence interval (CI): 1.04–21.79, P = 0.044). Further logistic analysis with adjusted covariates also confirmed the result, indicating that high Lp(a) levels were independently associated with ARAS (adjusted OR (aOR): 6.14, 95%CI: 1.03–36.47, P = 0.046). This relationship increased with increasing Lp(a) concentration based on a curve fitting graph. These results were not present in the low and intermediate LDL-c-level groups. Conclusion In hypertensive patients who present low LDL-c, high Lp(a) was significantly associated with atherosclerotic renal artery stenosis and thus is a residual risk factor.

Elevated lipoprotein (a) [Lp(a)] is related to the incidence of lower limb deep vein thrombosis and pulmonary embolism. Its role in portal and/or splenic vein thrombosis (PSVT) is not established. A total of 77 consecutive patients who underwent splenectomy for cirrhotic portal hypertension were prospectively studied between 2014 and 2017. The impact of Lp(a) on preoperative day 1 and postoperative days (PODs) 1, 3, 5, 7, and 14 was analyzed. Color Doppler ultrasound examination was performed for the diagnosis of PSVT. The median interval between surgery and postoperative PSVT was 6 days (range: 2-13 days). The levels of Lp(a) were highly increased in patients with PSVT and significant intergroup differences (vs non-PSVT) were found until day 3 and day 5 after operation, respectively. On POD 3, at a threshold of 309.06 mg/L, Lp(a) was a better predictor of PSVT (area under the curve [AUC] = 0.872) compared to the levels on PODs 1, 5, and 7 (AUC = 0.775, 0.796, and 0.791, respectively). The median Lp(a) values peaked at 382.5 mg/L on POD 5 for patients without PSVT. After POD 5, the Lp(a) decreased with values at 347.4 mg/L on POD 7 and 150.7 mg/L on POD 14. For the first time, Lp(a) was shown to be abnormal in patients with PSVT following splenectomy. Monitoring of serum Lp(a) levels on POD 3 might represent a valuable tool to predict early PSVT after splenectomy in cirrhotic patients.

Lipoprotein (a) (Lp(a)) is considered a genetic factor for cardiovascular disease playing an important role in atherogenesis and thrombosis, but the evidence about its association with sleep duration is controversial. We evaluated the relation between self-reported sleep duration and Lp(a). Among 1600 participants of the population-based sample, we selected 1427 subjects without previously known cardiovascular events, who answered the questions about their sleep duration, had valid lipid profile results (total cholesterol, low- and high-density lipoproteins, Lp(a), apolipoprotein AI (ApoAI), ApoB, and ApoB/ApoAI), and did not take lipid-lowering drugs (mean age 46 &plusmn, 12 years). We performed a structured interview, which included questions about lifestyle, medical history, complaints, and sleep duration (How long have you been sleeping per night during the last month?). Sleep duration was classified as follows: &lt, 6 h/night&mdash, short, 6&ndash, 9 h/night&mdash, normal, and &ge, 10 h/night&mdash, long. Overall, 73 respondents (5.2%) were short-sleepers and 69 (4.8%) long-sleepers. Males were slightly more prevalent among short-sleepers. The groups matched by age, body mass index, blood pressure, diabetes mellitus, and hypertension rate. Short-sleepers had lower rates of high total cholesterol (&ge, 5.0 mmol/L), lower Lp(a) levels and lower rates of increased Lp(a) &ge, 0.5 g/L, and higher insulin and insulin resistance (assessed by the homeostatic model assessment for insulin resistance (HOMA-IR)). ApoAI, ApoB, their ratio, and other lab tests were similar in the groups. The multinomial logistic regression demonstrated that only the short sleep duration was independently (odds ratio (OR) 0.29, 95% confidence interval (CI) (0.09&ndash, 0.91), p = 0.033) associated with Lp(a) (&chi, 2 = 41.58, p = 0.003). Other influencing factors were smoking and HOMA-IR. Such an association was not found for long-sleepers. In conclusion, a short-sleep duration is associated with Lp(a). The latter might mediate the higher insulin resistance and higher cardiometabolic risks in short-sleepers.

Background Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and increased cardiovascular disease (CVD) risk. FH patients often have increased lipoprotein(a) [Lp(a)] levels, which further increase CVD risk. Novel methods for accurately calculating LDL-C have been proposed. Methods Patients with FH were recruited by a network of Greek sites participating in the HELLAS-FH registry. LDL-C levels were calculated using the Friedewald (LDL-CF) and the Martin/Hopkins (LDL-CM/H) equations as well as after correcting LDL-CM/H for Lp(a) levels [LDL-CLp(a)corM/H]. The objective was to compare LDL-C levels and target achievement as estimated by different methods in FH patients. Results This analysis included 1620 patients (1423 adults and 197 children). In adults at diagnosis, LDL-CF and LDL-CM/H levels were similar [235 ± 70 mg/dL (6.1 ± 1.8 mmol/L) vs 235 ± 69 mg/dL (6.1 ± 1.8 mmol/L), respectively; P = NS], while LDL-CLp(a)corM/H levels were non-significantly lower than LDL-CF [211 ± 61 mg/dL (5.5 ± 1.6 mmol/L); P = 0.432]. In treated adults (n = 966) both LDL-CF [150 ± 71 mg/dL (3.9 ± 1.8 mmol/L)] and LDL-CM/H levels [151 ± 70 mg/dL (6.1 ± 1.8 mmol/L); P = 0.746] were similar, whereas LDL-CLp(a)corM/H levels were significantly lower than LDL-CF [121 ± 62 mg/dL (3.1 ± 1.6 mmol/L); P M/H (2.5%) and especially LDL-CLp(a)corM/H methods (10.7%) were significantly different than LDL-CF (2.9%; P In children, all 3 formulas resulted in similar LDL-C levels, both at diagnosis and in treated patients. However, target achievement by LDL-CF was lower compared with LDL-CM/H and LDL-CLp(a)corM/H methods (22.1 vs 24.8 vs 33.3%; P Conclusion LDL-CLp(a)corM/H results in significantly lower values and higher target achievement rate in both treated adults and children. If validated in clinical trials, LDL-CLp(a)corM/H may become the method of choice to more accurately estimate ‘true’ LDL-C levels in FH patients.

Elevated lipoprotein(a) [Lp(a)] is a well-known risk factor for cardiovascular disease. Its role in venous thromboembolism (VTE) is unclear. We present a case of a healthy man presenting with bilateral pulmonary embolism and investigations suggested elevated Lp(a) being the only risk factor. In this case report, we would like to emphasize the role of Lp(a) in VTE without any other clear predisposing factors.

Background The aim of this study was to assess the relationship between serum lipoprotein (a) (Lp[a]) concentration and the requirement for peripheral artery disease ( PAD ) operations or incidence of major adverse cardiovascular events. Methods and Results A total of 1472 people with PAD presenting with intermittent claudication (n=355), abdominal aortic aneurysm (n=989) or critical limb ischemia (n=128) were prospectively recruited from 4 outpatient clinics in Australia. Lp(a) was measured in serum samples collected at recruitment using an immunoassay. Participants were followed for a median (interquartile range) of 2.4 (0.1–6.1) years to record requirement for any PAD operation, defined to include any open or endovascular PAD intervention (lower limb peripheral revascularization, abdominal aortic aneurysm repair, other aneurysm repair, or carotid artery revascularization). Myocardial infarctions, strokes, and deaths were also recorded. The association of Lp(a) with events was assessed using Cox proportional hazard analysis adjusting for traditional risk factors. Participants with Lp(a) ≥30 mg/dL had a greater requirement for any PAD operation (hazard ratio, 1.20, 95% CI , 1.02–1.41) and lower limb peripheral revascularization alone ( hazard ratio 1.33, 95% CI , 1.06–1.66) but no increased risk of major adverse cardiovascular events or all‐cause mortality. Lp(a) ≥50 mg/dL and a 40 mg/dL increase in Lp(a) were also associated with an increased risk of lower limb peripheral revascularization alone but not with other outcomes. Conclusions In participants with PAD referred for hospital management those with high Lp(a) had greater requirement for lower limb peripheral revascularization but Lp(a) was not consistently associated with other clinical events.

Background Possible interaction between Lipoprotein (a) (Lp(a)) and body mass index (BMI) was investigated with regard to the risk of first incident acute myocardial infarction (AMI). Methods Cross-sectional study of 1522 cases with initial AMI and 1691 controls without coronary artery disease (CAD) were retrospectively analyzed using logistic regression model. Subjects were categorized based on Lp(a) and BMI and compared with regard to occurrence of AMI by calculating odds ratios (ORs) with 95% confidence intervals (CIs). A potential interaction between Lp(a) and BMI was evaluated by the measures of effect modification on both additive (Relative excess risk due to interaction, RERI) and multiplicative scales. Results Compared with reference group (BMI 2 and in the first quintile of Lp(a)), multivariable-adjusted analysis revealed that ORs(95%CI) of AMI were 2.27(1.46–3.52) for higher BMI alone; 1.79(1.11–2.90), 1.65(1.05–2.60), 1.96(1.20–3.20) and 2.34(1.47–3.71) for higher Lp(a) alone across its quintiles; and 2.86(1.85–4.40), 3.30(2.14–5.11), 4.43(2.76–7.09) and 5.98(3.72–9.60) for both higher BMI and higher Lp(a), greater than the sum of the both risks each. Prominent interaction was found between Lp(a) and BMI on additive scale (RERI = 2.45 (0.36–4.54) at the fifth quintile of Lp(a)) but not on multiplicative scale. Conclusions This study demonstrates that BMI and Lp(a) levels are important factors affecting the risk of AMI. Significant interaction is found between Lp(a) and BMI in initial AMI on additive scale, indicating that Lp(a) confers greater risk for initial AMI when BMI is elevated. For those whose BMIs are inadequately controlled, Lp(a) lowering may be an option. Trial registration This clinical study was not registered in a publicly available registry because this study was a retrospective study first started in 2015. Data are available via the correspondent.

Cholesterol efflux (CE) capacity has been inversely associated with atherosclerosis and may provide an insight on inflammation occurring in human immunodeficiency virus (HIV) individuals. We address this by studying CE in HIV patients at different stages of HIV disease progression. In this cross-sectional study, CE from ApoB-depleted plasma, lipids levels, viral load (VL), CD4+/CD8+ T-cells, high-sensitive C-reactive protein (hsCRP), and lipoprotein (a) were evaluated in untreated HIV-infected patients (UHIVs; n = 43), elite controllers (ECs; n = 8), HIV-exposed seronegative individuals (HESNs; n = 32), and healthy controls (HCs; n = 14). Among UHIVs, those with CD4+

Lipoprotein(a) [Lp(a)] is composed of a low density lipoprotein (LDL)-like particle to which apolipoprotein (a) [apo(a)] is linked by a single disulfide bridge. Lp(a) is considered a causal risk factor for ischemic cardiovascular disease (CVD) and calcific aortic valve stenosis (CAVS). The evidence for a causal role of Lp(a) in CVD and CAVS is based on data from large epidemiological databases, mendelian randomization studies, and genome-wide association studies. Despite the well-established role of Lp(a) as a causal risk factor for CVD and CAVS, the underlying mechanisms are not well understood. A key role in the Lp(a) functionality may be played by its oxidized phospholipids (OxPL) content. Importantly, most of circulating OxPL are associated with Lp(a); however, the underlying mechanisms leading to this preferential sequestration of OxPL on Lp(a) over the other lipoproteins, are mostly unknown. Several studies support the hypothesis that the risk of Lp(a) is primarily driven by its OxPL content. An important role in Lp(a) functionality may be played by the lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme that catalyzes the degradation of OxPL and is bound to plasma lipoproteins including Lp(a). The present review article discusses new data on the pathophysiological role of Lp(a) and particularly focuses on the functional role of OxPL and Lp-PLA2 associated with Lp(a).

Supplemental Digital Content is available in the text., Objective— Lp(a) [lipoprotein (a)] is composed of apoB (apolipoprotein B) and apo(a) [apolipoprotein (a)] and is an independent risk factor for cardiovascular disease and aortic stenosis. In clinical trials, anacetrapib, a CETP (cholesteryl ester transfer protein) inhibitor, causes significant reductions in plasma Lp(a) levels. We conducted an exploratory study to examine the mechanism for Lp(a) lowering by anacetrapib. Approach and Results— We enrolled 39 participants in a fixed-sequence, double-blind study of the effects of anacetrapib on the metabolism of apoB and high-density lipoproteins. Twenty-nine patients were randomized to atorvastatin 20 mg/d, plus placebo for 4 weeks, and then atorvastatin plus anacetrapib (100 mg/d) for 8 weeks. The other 10 subjects were randomized to double placebo for 4 weeks followed by placebo plus anacetrapib for 8 weeks. We examined the mechanisms of Lp(a) lowering in a subset of 12 subjects having both Lp(a) levels >20 nmol/L and more than a 15% reduction in Lp(a) by the end of anacetrapib treatment. We performed stable isotope kinetic studies using 2H3-leucine at the end of each treatment to measure apo(a) fractional catabolic rate and production rate. Median baseline Lp(a) levels were 21.5 nmol/L (interquartile range, 9.9–108.1 nmol/L) in the complete cohort (39 subjects) and 52.9 nmol/L (interquartile range, 38.4–121.3 nmol/L) in the subset selected for kinetic studies. Anacetrapib treatment lowered Lp(a) by 34.1% (P≤0.001) and 39.6% in the complete and subset cohort, respectively. The decreases in Lp(a) levels were because of a 41% reduction in the apo(a) production rate, with no effects on apo(a) fractional catabolic rate. Conclusions— Anacetrapib reduces Lp(a) levels by decreasing its production. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00990808.

Aim. To evaluate the influence of nicotinic acid (NA) on subfractional spectrum of proand antiatherogenic lipoproteides in hyperlipoproteidemia (a) patients.Material and methods. Totally, 78 patients included, with Lp(a) level more than 20 mg/dL, taking either combinational statin and NA therapy (n=43), or on monotherapy by statins (n=13), or monotherapy by NA (n=22). Lipid profile parameters were analyzed with the assays “Biocon/Analyticon” (Germany), quantitative subfractional contents were assessed with the system Lipoprint® (Quantimetrix,USA), Lp(a) concentriation — with immune enzyme assay.Results. Results. In combinational therapy and monotherapy groups of NA the baseline Lp(a) levels were 98,0±44,8 and 71,3±21,8 mg/dL, respectively, р

General lipoprotein (Lp) (a) screening can help to identify patients at high risk for cardiovascular disease. Non-invasive methods allow early detection of clinically asymptomatic incipient atherosclerotic disease. Medical treatment options are still unsatisfactory. Lp(a) apheresis is an established treatment in Germany for secondary prevention of progressive cardiovascular disease. Statin-based lowering of LDL cholesterol and thrombocyte aggregation inhibitors still represent the basis of medical treatment. Target levels for LDL-cholesterol should be modified in patients with hyperlipoproteinemia (a).

Background Recently it has been demonstrated that elevated lipoprotein (a) (LPA) levels are associated with an increased risk of cardiovascular disease across multiple ethnic groups. However, there is only scanty data about the incidence of elevated LPA levels in different patient cohorts. As a consequence, we aimed to examine whether patients with elevated LPA levels might be seen more often in a cardiovascular center in comparison to the general population. Methods We reviewed LPA concentrations of 52,898 consecutive patients who were admitted to our hospital between January 2004 and December 2014. We subdivided them into different groups according to their LPA levels. Data was compared to available information in medical literature. Results 26.4% of the patients had LPA levels >30 mg/dl which is in line with the data from literature. Mean level of LPA concentration in our study was twice as high in comparison to the general population (25.8% vs. 13.3%). 4.6% had LPA levels >98 mg/dl (general population 30 mg/dl is comparable to the general population but mean levels over all are twice as high and the proportion of patients with LPA levels of >98 mg/dl is extremely higher.

Lipoprotein(a) (Lp(a)) is an independent cardiovascular risk factor playing a causal role for atherosclerotic cardiovascular disease (CVD). Lipoprotein apheresis (LA) is a safe well-tolerated outpatient treatment to lower LDL-C and Lp(a) by 60–70%, and is the ultimate escalating therapeutic option in patients with hyperlipoproteinemias (HLP) involving LDL particles. Major therapeutic effect of LA is preventing cardiovascular events. Lp(a)-HLP associated with progressive CVD has been approved as indication for regular LA in Germany since 2008. The Pro(a)LiFe-study investigated with a prospective multicenter design the long-term preventive effect of LA on incidence rates of cardiovascular events prospectively over a period of 5 years in 170 consecutive patients who commenced regular LA. During a median period of 4.7 years of the pre-LA period, Lp(a) associated progressive CVD became apparent. Apolipoprotein(a) (apo(a)) isoforms and polymorphisms at the apo(a) gene (LPA) were analyzed to assess hypothetical clinical correlations. 154 patients (90.6%) completed 5‑years follow-up. Significant decline of the mean annual major adverse cardiac event (MACE) rate was observed from 0.41 ± 0.45 two years prior to regular LA to 0.06 ± 0.11 during 5 years with regular LA (p < 0.0001). 95.3% of patients expressed at least one small apo(a) isoform. Calculation of isoform specific concentrations allowed to confirm the equivalence of 60 mg/dl or 120 nmol/l as Lp(a) thresholds of the German LA guideline. Results of 5 years prospective follow-up confirmed that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP and afore progressive CVD.

High concentrations of lipoprotein(a) (Lp(a)) represent an important independent and causal risk factor associated with adverse outcome in atherosclerotic cardiovascular disease (CVD). Effective Lp(a) lowering drug treatment is not available. Lipoprotein apheresis (LA) has been proven to prevent cardiovascular events in patients with Lp(a)-hyperlipoproteinemia (Lp(a)-HLP) and progressive CVD. Here we present the course of a male patient with established peripheral arterial occlusive disease (PAOD) at the early age of 41 and coronary artery disease (CAD), who during follow-up developed over 2 years a progressive syndrome of cerebellar and spinal cord deficits against the background of multifactorial cardiovascular risk including positive family history of CVD. Spastic tetraplegia and dependency on wheel chair and nursing care represented the nadir of neurological deficits. All conventional risk factors including LDL-cholesterol had already been treated and after exclusion of other causes, genetically determined Lp(a)-HLP was considered as the major underlying etiologic factor of ischemic vascular disease in this patient including spinal cord ischemia with vascular myelopathy. Treatment with an intensive regimen of chronic LA over 4.5 years now was successful to stabilize PAOD and CAD and led to very impressive neurologic and overall physical rehabilitation and improvement of quality of life. Measurement of Lp(a) concentration must be recommended to assess individual cardiovascular risk. Extracorporeal clearance of Lp(a) by LA should be considered as treatment option for select patients with progressive Lp(a)-associated ischemic syndromes.

Aims: Cardiovascular risk persists despite intensive lipid lowering therapy using statins. Serum levels of lipoprotein (a) [Lp(a)] can be a residual cardiovascular risk for adverse events. Aim of the present study was to evaluate the impact of Lp(a) on long-term clinical outcomes in patients treated with statin after percutaneous coronary intervention. Methods: We prospectively enrolled 3507 consecutive CAD patients who underwent a first percutaneous coronary intervention (PCI) between 1997 and 2011 at our institution. We identified 1768 patients (50.4%) who had treated with statin during PCI. Eligible 1336 patients were stratified to two groups according to Lp(a) levels (median Lp (a) 21.5 mg/dL). The primary outcome was major adverse cardiac events (MACE) including cardiac death and non-fatal acute coronary syndrome. Results: MACE occurred 144 (10.8%) including 34 (2.5%) cardiac death and 110 (8.7%) non-fatal ACS during median follow-up period of 1920 days. The cumulative rate of MACE was significantly higher in group with high Lp(a) group (log-rank p = 0.0460). Multivariate Cox regression analysis showed a significant correlation between Lp (a) levels treated as a natural logarithm-transformed continuous variable and increased MACE (adjusted HR for MACE 1.28, 95%CI 1.04–1.58, p = 0.0184) Conclusion: Elevated levels of Lp(a) is significantly associated with long-term adverse clinical outcomes among CAD patients who received statin therapy after PCI.

Cardiovascular disease (CVD) has consistently been the leading cause of death worldwide. Several clinical and epidemiological studies have demonstrated that an elevated plasma concentration of lipoprotein (a) [Lp(a)] is a causative and independent major risk factor for the development of CVD, as well as calcific aortic valve stenosis. Thus, the therapeutic management of hyperlipoproteinemia (a) has received much attention, as significant reductions in Lp(a) levels may, potentially, favorably affect cardiovascular risk. Aspirin, niacin, estrogens, and statins, which act on different molecular pathways, may be prescribed to patients with mild or modest elevations of Lp(a) levels. Other therapeutic interventions, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, Lp(a) apheresis, and the novel antisense oligonucleotides APO(a)-Rx and APO(a)-LRx, which are being evaluated in ongoing clinical trials, have provided some promising results and can potentially be used in severe cases of hyperlipoproteinemia (a). This review aims to present and discuss the current clinical and scientific data pertaining to the therapeutic options for the management of hyperlipoproteinemia (a).

A considerable body of data from genetic and epidemiological studies strongly support a causal relationship between high lipoprotein(a) [Lp(a)] levels, and the development of atherosclerosis and cardiovascular disease. This relationship is continuous, unrelated to Lp(a) threshold, and independent of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels. Unfortunately, the mechanism(s) through which Lp(a) promotes atherosclerosis are not clarified yet. Suggested hypotheses include: an increased Lp(a)-associated cholesterol entrapment in the arterial intima followed by inflammatory cell recruitment, abnormal upload of proinflammatory oxidized phospholipids, impaired fibrinolysis by inhibition of plasminogen activation, and enhanced coagulation, through inhibition of the tissue factor pathway inhibitor. This review is aimed at summarizing the available evidence on the topic. There are two clinical forms, isolated hyperlipidemia(a) [HyperLp(a)] with acceptable LDL-C levels (

Background We investigated whether or to what extent the interaction of lipoprotein (a) [Lp(a)] with cholesterol-containing lipids was associated with angiographic coronary collateralization in type 2 diabetic patients with chronic total occlusion. Methods Serum levels of Lp(a), total cholesterol, low-density lipoprotein–cholesterol (LDL-C), high-density lipoprotein–cholesterol (HDL-C), and triglyceride were determined and non-HDL-C was calculated in 706 type 2 diabetic and 578 non-diabetic patients with stable coronary artery disease and angiographic total occlusion of at least one major coronary artery. The degree of collaterals supplying the distal aspect of a total occlusion from the contra-lateral vessel was graded as poor (Rentrop score of 0 or 1) or good coronary collateralization (Rentrop score of 2 or 3). Results For diabetic and non-diabetic patients, Lp(a), total cholesterol, LDL-C, and non-HDL-C levels were higher in patients with poor coronary collateralization than in those with good collateralization, whereas HDL-C and triglyceride levels were similar. After adjustment for potential confounding factors, tertiles of Lp(a), total cholesterol, LDL-C and non-HDL-C remained independent determinants for poor collateralization. A significant interaction between Lp(a) and total cholesterol, LDL-C or non-HDL-C was observed in diabetic patients (all P interaction

Background Elevated lipoprotein (a) [Lp(a)] is an under-diagnosed genetically inherited risk factor for coronary heart disease (CHD) and calcific aortic valve stenosis. Premature myocardial infarction (MI) could stem from the association between elevated Lp(a) and other non-traditional cardiovascular risk factors. Case summary Here, we report a male patient with extremely high Lp(a) plasma levels [610 nmol/L (244 mg/dL); normal

Population, genetic, and clinical studies demonstrated a causative and continuous, from other plasma lipoproteins independent relationship between elevated plasma lipoprotein (a) [Lp(a)] concentration and the development of cardiovascular disease (CVD), mainly those related to athe-rosclerotic CVD, and calcific aortic stenosis. Currently, a strong international consensus is still lacking regarding the single value which would be commonly used to define hyperlipoproteinemia (a). Its prevalence in the general population is estimated to be in the range of 10%–35% in accordance with the most commonly used threshold levels (>30 or >50 mg/dL). Since elevated Lp(a) can be of special importance in patients with some genetic disorders, as well as in individuals with otherwise controlled major risk factors, the identification and establishment of the proper therapeutic interventions that would lower Lp(a) levels and lead to CVD risk reduction could be very important. The majority of the classical lipid-lowering agents (statins, ezetimibe, and fibrates), as well as nutraceuticals (CoQ10 and garlic), appear to have no significant effect on its plasma levels, whereas for the drugs with the demonstrated Lp(a)-lowering effects (aspirin, niacin, and estrogens), their clinical efficacy in reducing cardiovascular (CV) events has not been unequivocally proven yet. Both Lp(a) apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors can reduce the plasma Lp(a) by approximately 20%–30% on average, in parallel with much larger reduction of low-density lipoprotein cholesterol (up to 70%), what puts us in a difficulty to conclude about the true contribution of lowered Lp(a) to the reduction of CV events. The most recent advancement in the field is the introduction of the novel apolipoprotein (a) [apo(a)] antisense oligonucleotide therapy targeting apo(a), which has already proven itself as being very effective in decreasing plasma Lp(a) (by even >90%), but should be further tested in clinical trials. The aim of this review was to present some of the most important accessible scientific data, as well as dilemmas related to the currently and potentially in the near future more widely available therapeutic options for the management of hyperlipoproteinemia (a).

Aim. To study the relationship between the concentration of lipoprotein (a) (Lp (a)) and autotaxin (ATX) in patients with and without degenerative aortic valve stenosis (AoS) in the presence of coronary artery disease (CAD).Material and methods. The study included 461 patients (mean age, 66±11 years, men, 323), 354 of whom had CAD with stenosis ≥50% in at least one coronary artery according to angiography. Degenerative AoS was diagnosed with ultrasound. The control group consisted of 107 patients without CAD and degenerative AoS. Concentrations of Lp (a), ATX, lipids and blood cells were measured for all patients.Results. CAD without degenerative AoS (group 1) was diagnosed in 307 patients, while 47 patients had CAD and degenerative AoS (group 2). Patients in both groups were older than patients in the control group (66±10, 74±8, and 61±13 years, respectively). The ATX level was lower in group 1 (median [25; 75%]: 495 [406; 583] ng/ml) than in the control group (545 [412; 654] ng/ml) or group 2 (545 [476; 605] ng/ml) (pConclusion. An elevated Lp (a) level is associated with CAD regardless of the aortic valve involvement, while an increased concentration of ATX and neutrophil to lymphocyte ratio in patients with CAD were associated with degenerative AoS regardless of age and other risk factors.

Lipoprotein a (Lp (a)) and coronary artery calcification (CAC) are markers of coronary artery and cardiovascular diseases. However, the association between Lp (a) and CAC in asymptomatic individuals remains unclear. In this study, we aimed to determine the influence of Lp (a) on CAC in asymptomatic individuals. We included 2019 asymptomatic Korean adults who underwent testing for a coronary artery calcium score (CACS) and Lp (a) at the Gangnam Severance Hospital Health Checkup Center in Korea from January 2017 to August 2019. Participants were divided into 2 groups: CACS = 0 and CACS > 0. Factors affecting the CACS were analyzed by sex. Because age is a major risk factor for atherosclerosis, ≥45 years in men and ≥55 years in women, we further divided participants into 4 subgroups (≥45 and

Two genetic variants (rs3798220 and rs10455872) in the apolipoprotein (a) gene (LPA) have been implicated in cardiovascular disease (CVD), presumably through their association with lipoprotein (a) [Lp(a)] levels. While Lp(a) is recognized as a lipoprotein with atherogenic and thrombogenic characteristics, it is unclear whether or not the two Lp(a)-associated genetic variants are also associated with markers of thrombosis (i.e., plasminogen levels and fibrinolysis). In the present study, we genotyped the two genetic variants in 2919 subjects of the Old Order Amish (OOA) and recruited 146 subjects according to the carrier and noncarrier status for rs3798220 and rs10455872, and also matched for gender and age. We measured plasma Lp(a) and plasminogen levels in these subjects, and found that the concentrations of plasma Lp(a) were 2.62- and 1.73-fold higher in minor allele carriers of rs3798220 and rs10455872, respectively, compared with noncarriers (P = 2.04 × 10−17 and P = 1.64 × 10−6, respectively). By contrast, there was no difference in plasminogen concentrations between carriers and noncarriers of rs3798220 and rs10455872. Furthermore, we observed no association between carrier status of rs3798220 or rs10455872 with clot lysis time. Finally, plasminogen mRNA expression in liver samples derived from 76 Caucasian subjects was not significantly different between carriers and noncarriers of these two genetic variants. Our results provide further insight into the mechanism of action behind two genetic variants previously implicated in CVD risk and show that these polymorphisms are not major modulating factors for plasma plasminogen levels and fibrinolysis.

BACKGROUND Lipoprotein (a) has been identified as an important, independent, causal risk factor for various cardiovascular diseases, but its association with hypertension has shown differing results. The studies regarding this association are limited. AIMS AND OBJECTIVES In the present study, the levels of Lp (a) and other lipid parameters like Serum Total Cholesterol, Serum LDL Cholesterol, Serum HDL Cholesterol, serum triglycerides have been studied in hypertensive and non-hypertensive patients to investigate any significant relationship between the same. MATERIALS AND METHODS 30 essential hypertensive patients were selected and were compared with 30 controls matched in terms of age and sex. Lipid profile including Total cholesterol, LDL- Cholesterol, HDL- Cholesterol, Triglycerides and Lp (a) were studied in both groups. RESULTS Hypertensive patients were observed to have higher levels of Serum Total Cholesterol, Serum Triglycerides, Serum LDL cholesterol, but it was not found to be significant. But lipoprotein (a) was found to be significantly higher (p