High Lipoprotein Levels Research Articles

Extremely high levels of lipoprotein(a) in Argentina

Extremely high levels of lipoprotein(a) in Argentina

Serum Lipoproteins Are Associated With Coronary Atherosclerosis in Asymptomatic U.S. Adults Without Traditional Risk Factors

BackgroundThe relationship between atherogenic lipoproteins and subclinical coronary atherosclerosis has not been thoroughly evaluated in low-risk adults. ObjectivesThe purpose of this study was to assess the association of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (apoB) with coronary atherosclerosis in adults without traditional risk factors. MethodsWe assessed atherosclerosis on coronary computed tomography angiography among asymptomatic adults in the Miami Heart Study not taking lipid-lowering therapy and without hypertension, diabetes, or active tobacco use. Prevalence of atherosclerosis was evaluated based on serum LDL-C, non-HDL-C, and apoB, and multivariable logistic regression with forward selection was used to assess variables associated with coronary plaque. ResultsAmong 1,033 adults 40 to 65 years of age, 55.0% were women and 86.3% had estimated 10-year atherosclerotic cardiovascular disease risk <5%. Coronary atherosclerosis prevalence was 35.9% (50.6% in men; 23.8% in women) and 3.4% had ≥1 high-risk plaque feature. Atherosclerosis prevalence increased with LDL-C, ranging from 13.2% in adults with LDL-C <70 mg/dL up to 48.2% with ≥160 mg/dL. Higher LDL-C (adjusted OR [aOR]: 1.13 [95% CI: 1.08-1.18] per 10 mg/dL), age (aOR: 1.43 [95% CI: 1.28-1.60] per 5 years), male sex (aOR: 3.81 [95% CI: 2.86-5.10]), and elevated lipoprotein(a) (aOR: 1.46 [95% CI: 1.01-2.09]) were associated with atherosclerosis. Higher serum non-HDL-C and apoB were similarly associated with atherosclerosis. In adults with optimal risk factors, 21.2% had atherosclerosis with greater prevalence at higher lipoprotein levels. ConclusionsAmong asymptomatic middle-aged adults without traditional risk factors, coronary atherosclerosis is common and increasingly prevalent at higher levels of atherogenic lipoproteins. These findings emphasize the importance of lipid-lowering strategies to prevent development and progression of atherosclerosis regardless of risk factors.

Determination of Vitamin K2, Lipoprotein (a) and N-Terminal pro Brain Natriuretic Biomarkers in Diabetic Hypertensive Patients with Acute Myocardial Infarction for Clinical Intervention

Background: Severe Myocardial Infarction is a highly stark manifestation of heart illness, often accompanied with additional complications such as diabetes mellitus (DM) and hypertension (HTN). The hormone within the body enables glucose to enter the cells and burn them up as fuel. HTN is a common vascular disorder that represents a major cardiovascular condition. Methods: The study was conducted at the Biochemistry Department of the College of Medicine from April 2022 to May 2023 and used the Human Vit K2 ELISA Kit, Human Lp(a) ELISA Kit, and Human N-terminal ProBST ELISA Kit to estimate the serum levels of vitamin K2, lipoprotein (a) (Lp(a)), and N-terminal of the Pro brain natriuretic peptide (NT-proBNP). Results: The results showed a important decrease in VK2 levels in AMI patients with DM and HTN than the other two groups (less than AMI patients group with and without HDL-c). On the other hand, Lp(a), and NT-pro BNP levels were significantly increased in AMI patients with DM and HTN than the other two groups (less than AMI patients group with no DM and HTN). As the diagnostic accuracy of tests increased, the area under the ROC curve for NTproBNP for diagnosing AMI achieved the highest 0.988. NTproBNP showed a promising ability to differentiate AMI patients from DM+ HTN group with 0.971 (AUC). Conclusions: In diabetic hypertensive patients with acute myocardial infarction, a low level of vitamin K2 and a high level of lipoprotein(a) might be risk markers for the onset of myocardial infarction.

An Evaluation of Anti-hyperlipidemic Activity of Ethanolic Extract of Coccinia grandis Leaves in High Fat Induced Rodent Model

In the realm of health research, hyperlipidemia is a condition that has lately become prevalent and is a serious issue. Elevated lipid levels in an individual's body are the primary indicator of hyperlipidemia, a condition defined by increased levels of low-density lipoprotein (LDL), total cholesterol, triglycerides, and high lipoprotein levels. Several pharmacological agents are accessible for the treatment of hyperlipidemia. Nevertheless, human beings throughout the globe also thrive on nature-derived therapeutic items. Coccinia grandis is a noteworthy plant known for its antihyperlipidemic properties among them. In this study, we provided a high-fat diet for the experimental rats to generate hyperlipidemia conditions in this rat model. As per our research methodology, Coccnia grandis was administered to all the rats in the treatment group at three (low, medium and high) distinct dosages. It is eventually revealed that Coccnia grandis may successfully lower (p&lt;0.05) the hyperlipidemic state in both medium and high dosages. Elevated and unusual Triglyceride and Total Cholesterol were observed to be restored following Coccnia grandis medication. However, in the case of HDL and LDL, no substantial drop was detected. A considerable restoration was noted similarly in both instances of SGPT and SGOT. These findings show that our plant has components with antihyperlipidemic action, however the concentrations did not meet the necessary threshold. So, additional investigations are needed to examine the chemical structure and the quantities of the molecule as well as find out about genetic alterations.

Higher prevalence of coronary microvascular dysfunction in asymptomatic individuals with high levels of lipoprotein(a) with and without heterozygous familial hypercholesterolaemia

Background and aimsMicrovascular dysfunction underlies many cardiovascular disease conditions; little is known regarding its presence in individuals with high levels of lipoprotein(a) [Lp(a)]. The aim of the present study was to determine the frequency of microvascular dysfunction among such subjects with and without concomitant familial hypercholesterolemia (FH). MethodsFour groups of asymptomatic individuals aged 30–59 years, without manifest cardiovascular disease, were recruited (n = 30 per group): controls with Lp(a) < 30 nmol/L, mutation-confirmed FH with Lp(a) < 30 nmol/L, or >125 nmol/L, and individuals with isolated Lp(a) > 125 nmol/L. Participants underwent evaluation of myocardial microvascular function by measuring coronary flow reserve (CFR) using transthoracic Doppler echocardiography, and of peripheral microvascular endothelial function by peripheral arterial tonometry. ResultsThe groups were balanced in age, sex, and body mass index. Each of the three dyslipoproteinaemic groups had a greater proportion of individuals with impaired coronary flow reserve, 30%, compared to 6.7% of controls (p = 0.014). The median CFR levels did not differ significantly between the four groups, however. Cholesterol-lowering treatment time was longer in the individuals with normal than in those with impaired CFR in the FH + Lp(a) > 125 group (p = 0.023), but not in the group with FH + Lp(a) < 30 (p = 0.468). There was no difference in peripheral endothelial function between the groups. ConclusionsCoronary microvascular dysfunction is more prevalent in asymptomatic individuals with isolated Lp(a) elevation and in heterozygous FH both with and without high Lp(a) compared to healthy controls. Cholesterol-lowering treatment could potentially prevent the development of microvascular dysfunction.

Myocardial microvascular dysfunction in asymptomatic patients with hereditary dyslipidemia

Abstract Introduction Microvascular dysfunction underlies the pathophysiology of many cardiovascular disease (CVD) conditions and is strongly associated with future cardiovascular events. Hereditary forms of dyslipidaemia such as familial hypercholesterolemia (FH) and high levels of lipoprotein(a) [Lp(a)] are associated with premature atherosclerotic CVD but the degree of microvascular dysfunction in asymptomatic individuals is not fully explored. Purpose To evaluate the presence of microvascular dysfunction in asymptomatic individuals with the hereditary dyslipidaemias FH and high Lp(a). Methods Asymptomatic individuals without manifest CVD were recruited to four groups with 30 subjects in each; 1) controls with Lp(a)&amp;lt;30 nmol/L, 2) FH+Lp(a)&amp;lt;30 nmol/L, 3) FH+Lp(a)&amp;gt;125 nmol/L, and 4) isolated Lp(a)&amp;gt;125 nmol/L without FH. FH diagnoses were confirmed by genetic analysis. Transthoracic doppler echocardiography was used to record coronary flow in the distal part of the left anterior descending artery at rest and during hyperaemia induced by intravenous infusion of adenosine. Coronary flow reserve (CFR) was calculated by dividing hyperaemic to basal flow. Peripheral microvascular endothelial function was determined by recording reactive hyperaemia index (RHI) by peripheral arterial tonometry in the index fingers of both hands. CFR and RHI were considered impaired if values were &amp;lt;2.5 and &amp;lt;1.67, respectively. Results The four groups were balanced in age (mean 42.6±8.4 years), sex (50% females), BMI (mean 25.0±4.7 kg/m2), and smoking status (5.0% current smokers). Low-density lipoprotein cholesterol was also similar across the four groups (mean 2.8±1.1 mmol/L) with the two FH groups being on cholesterol lowering treatment while the other two were pharmacologically naïve. The three groups with hereditary dyslipidaemia had a higher proportion of subjects with impaired CFR, 30.0% in each group compared to 6.6% in controls (p=0.014) (Figure 1A). The FH+Lp(a)&amp;lt;30 nmol/L and FH+Lp(a)&amp;gt;125 nmol/L groups had received cholesterol lowering treatment for a median (inter quartile range, IQR) of 4.0 (8.0) and 11.0 (11.0) years respectively (p&amp;lt;0.001). In the FH+Lp(a)&amp;gt;125 nmol/L group individuals with normal CFR had received significantly longer treatment (p=0.006) but not in the FH+Lp(a)&amp;lt;30 nmol/L group (p=0.568) (Figure 1B). There were no major differences in median CFR (p=0.550) (Figure 2A) or median RHI (p=0.341) (Figure 2B) levels between the four groups. Conclusion Asymptomatic individuals with the hereditary dyslipidaemias FH and/or high Lp(a) have a higher degree of coronary microvascular dysfunction compared to healthy controls. For individuals with combined traits FH and high Lp(a), the total treatment years of cholesterol lowering is associated with preserved coronary microvascular function suggesting CFR as a potential useful non-invasive tool for cardiovascular risk-stratification in patients with hereditary dyslipidaemias.Figure 1Figure 2

PB1020 Simultaneous Generation of Thrombin and Plasmin in Patients with Deep Vein Thrombosis and High Levels of Lipoprotein (a)

PB1020 Simultaneous Generation of Thrombin and Plasmin in Patients with Deep Vein Thrombosis and High Levels of Lipoprotein (a)

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) as a marker of hereditary lipid metabolism disorders in patients with early manifestation of coronary artery disease

Background: The clinical phenotype of familial hypercholesterolemia (FH) combined with the classical genetic defects of this disease increase the risk of coronary artery disease (CAD) in the case of a high level of lipoprotein (a) (Lp(a)). Aim: To assess the association of hereditary disorders of lipid metabolism with a high level of Lp(a) in the case of an early manifestation of CAD in the absence of the FH phenotype. Methods: We studied 81 patients with premature CAD (at the age up to 55 years in men and up to 60 years in women). Lp(a) was measured in the blood serum by the immunoturbidimetric method. We performed the molecular genetic testing, using massively parallel sequencing, which included the following panel of genes: ABCA1, ABCG1, ABCG5, ABCG8, ANGPTL3, APOA1, APOA2, APOA4, APOA5, APOB, APOC1, APOC2, APOC3, APOE, APOH, CETP, CH25H, CIDEC, CREB3L3, GPD1, GPIHBP1, LCAT, LDLR, LDLRAP1, LIPA, LIPC, LIPE, LIPG, LMF1, LPA, LPL, MTTP, MYLIP, NPC1, NPC1L1, NPC2, PCSK9, PLTP, PPP1R17, SAR1B, SCARB1, STAP1. Results: 24 (29.6%) patients had Lp(a) 30 mg/dl and were more likely to have a family history of CAD (70.8% vs 42.1%, p=0.05). In patients with a confirmed FH phenotype, there were no pathogenic variants associated with hereditary disorders of lipid metabolism. 4 patients with Lp(a) 30 mg/dl without a confirmed FH phenotype appeared to be carriers of pathogenic variants in the genes of lipid metabolism (LDLR p.Glu763Asp, ABCA1 p.Arg1128His, APOA5 p.His321Le), as well as of a not previously registered variant in the LIPE gene NM_005357.4:c. 2312TC. Conclusions: Lp(a) can be an appropriate marker for revealing pathogenic variants in the genes of the lipid metabolism system in patients without the clinical FH phenotype with an early CAD manifestation.

High levels of lipoprotein(a) in transgenic mice exacerbate atherosclerosis and promote vulnerable plaque features in a sex-specific manner

Background and aimsDespite increased clinical interest in lipoprotein(a) (Lp(a)), many questions remain about the molecular mechanisms by which it contributes to atherosclerotic cardiovascular disease. Existing murine transgenic (Tg) Lp(a) models are limited by low plasma levels of Lp(a) and have not consistently shown a pro-atherosclerotic effect of Lp(a). MethodsWe generated Tg mice expressing both human apolipoprotein(a) (apo(a)) and human apoB-100, with pathogenic levels of plasma Lp(a) (range 87–250 mg/dL). Female and male Lp(a) Tg mice (Tg(LPA+/0;APOB+/0)) and human apoB-100-only controls (Tg(APOB+/0)) (n = 10–13/group) were fed a high-fat, high-cholesterol diet for 12 weeks, with Ldlr knocked down using an antisense oligonucleotide. FPLC was used to characterize plasma lipoprotein profiles. Plaque area and necrotic core size were quantified and immunohistochemical assessment of lesions using a variety of cellular and protein markers was performed. ResultsMale and female Tg(LPA+/0;APOB+/0) and Tg(APOB+/0) mice exhibited proatherogenic lipoprotein profiles with increased cholesterol-rich VLDL and LDL-sized particles and no difference in plasma total cholesterol between genotypes. Complex lesions developed in the aortic sinus of all mice. Plaque area (+22%), necrotic core size (+25%), and calcified area (+65%) were all significantly increased in female Tg(LPA+/0;APOB+/0) mice compared to female Tg(APOB+/0) mice. Immunohistochemistry of lesions demonstrated that apo(a) deposited in a similar pattern as apoB-100 in Tg(LPA+/0;APOB+/0) mice. Furthermore, female Tg(LPA+/0;APOB+/0) mice exhibited less organized collagen deposition as well as 42% higher staining for oxidized phospholipids (OxPL) compared to female Tg(APOB+/0) mice. Tg(LPA+/0;APOB+/0) mice had dramatically higher levels of plasma OxPL-apo(a) and OxPL-apoB compared to Tg(APOB+/0) mice, and female Tg(LPA+/0;APOB+/0) mice had higher plasma levels of the proinflammatory cytokine MCP-1 (+3.1-fold) compared to female Tg(APOB+/0) mice. ConclusionsThese data suggest a pro-inflammatory phenotype exhibited by female Tg mice expressing Lp(a) that appears to contribute to the development of more severe lesions with greater vulnerable features.

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

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

Lipoprotein (a), Inflammation, and Atherosclerosis

Growing evidence has shown that high levels of lipoprotein (a) (Lp(a)) and chronic inflammation may be responsible for the residual risk of cardiovascular events in patients managed with an optimal evidence-based approach. Clinical studies have demonstrated a correlation between higher Lp(a) levels and several atherosclerotic diseases including ischemic heart disease, stroke, and degenerative calcific aortic stenosis. The threshold value of Lp(a) serum concentrations associated with a significantly increased cardiovascular risk is >125 nmol/L (50 mg/dL). Current available lipid-lowering drugs have modest-to-no impact on Lp(a) levels. Chronic inflammation is a further condition potentially implicated in residual cardiovascular risk. Consistent evidence has shown an increased risk of cardiovascular events in patients with high sensitivity C reactive protein (>2 mg/dL), an inflammation biomarker. A number of anti-inflammatory drugs have been investigated in patients with or at risk of cardiovascular disease. Of these, canakinumab and colchicine have been found to be associated with cardiovascular risk reduction. Ongoing research aimed at improving risk stratification on the basis of Lp(a) and vessel inflammation assessment may help refine patient management. Furthermore, the identification of these conditions as cardiovascular risk factors has led to increased investigation into diagnostic and therapeutic strategies targeting them in order to reduce atherosclerotic cardiovascular disease burden.

Correction: High levels of lipoprotein(a) – assessment and treatment

Correction: High levels of lipoprotein(a) – assessment and treatment

Lipoprotein(a): Cardiovascular Disease, Aortic Stenosis and New Therapeutic Option

Atherosclerosis is a chronic and progressive inflammatory process beginning early in life with late clinical manifestation. This slow pathological trend underlines the importance to early identify high-risk patients and to treat intensively risk factors to prevent the onset and/or the progression of atherosclerotic lesions. In addition to the common Cardiovascular (CV) risk factors, new markers able to increase the risk of CV disease have been identified. Among them, high levels of Lipoprotein(a)-Lp(a)-lead to very high risk of future CV diseases; this relationship has been well demonstrated in epidemiological, mendelian randomization and genome-wide association studies as well as in meta-analyses. Recently, new aspects have been identified, such as its association with aortic stenosis. Although till recent years it has been considered an unmodifiable risk factor, specific drugs have been developed with a strong efficacy in reducing the circulating levels of Lp(a) and their capacity to reduce subsequent CV events is under testing in ongoing trials. In this paper we will review all these aspects: from the synthesis, clearance and measurement of Lp(a), through the findings that examine its association with CV diseases and aortic stenosis to the new therapeutic options that will be available in the next years.

CORRELATION OF SEVERITY OF CORONARY ARTERY DISEASE WITH LIPOPROTEIN A LEVEL IN YOUNG ADULTS

Objectives: To address the association between Lipoprotein (a) and coronary artery disease risk in young patients &amp; to evaluate whether high levels of lipoprotein (a) is a predictor of risk and is related to the severity of coronary artery disease.&#x0D; Methodology: This retrospective study was carried out at Cardiology Deptt of Hayatabad Medical Complex Peshawar between June and December 2021. Total 160 patients referred to the cardiac catheterization lab of either gender, aged 20-45 years who underwent coronary angiography for various clinical indications were enrolled in the study. Lipoprotein (a) level, lipid profile, fasting blood glucose, anthropometric and clinical parameters of the patients were analyzed.&#x0D; Results: Statistically significant differences were observed in the mean of serum lipoprotein (a) concentrations between group “A” (58.6 ± 3.20 mg/ dl) and group “B” (19.6+0.10 mg/ dl) P value &lt;0.001. Mean HDL was 32.6 ± 0.30 in group “A” and in group B it was 40.4 ± 0.39 (p value &gt;0.005), total cholesterol was 199 ± 2.00 in group “A” &amp; 152 ± 1.80 in group “B” (p value &lt;0.005), triglycerides (TGL) in group “A” (182.76 ± 43.86 mg/dl) &amp; in group “B” (124.14 ± 44.01 mg/dl) P value &lt;0.001, LDL in group “A” was (130±4.28 &amp; in group “B” (84.4±3.00) p value &lt;0.001, VLDL between group “A” (36.03 ± 9.19mg/dl) and group B (24.68 ± 8.89 mg/dl) P value &gt; 0.003. However total Cholesterol / HDL was significantly lower in group “B” 3.5 as compared to group “A” 5.8 P value &lt; 0.002.&#x0D; Conclusion: Irrespective of other traditional risk factors, increase in Lipoprotein (a) is an independent risk factor for coronary artery disease in young adults with positive family history. Thus elevated levels of Lipoprotein (a) may serve as an important criterion to identify the individuals who need to undergo lipoprotein (a) lowering treatment, thereby preventing them from myocardial infarction.

Lipoprotein(a) levels in children with suspected familial hypercholesterolaemia: a cross-sectional study.

Familial hypercholesterolaemia (FH) predisposes children to the early initiation of atherosclerosis and is preferably diagnosed by DNA analysis. Yet, in many children with a clinical presentation of FH, no mutation is found. Adult data show that high levels of lipoprotein(a) [Lp(a)] may underlie a clinical presentation of FH, as the cholesterol content of Lp(a) is included in conventional LDL cholesterol measurements. As this is limited to adult data, Lp(a) levels in children with and without (clinical) FH were evaluated. Children were eligible if they visited the paediatric lipid clinic (1989-2020) and if Lp(a) measurement and DNA analysis were performed. In total, 2721 children (mean age: 10.3 years) were included and divided into four groups: 1931 children with definite FH (mutation detected), 290 unaffected siblings/normolipidaemic controls (mutation excluded), 108 children with probable FH (clinical presentation, mutation not detected), and 392 children with probable non-FH (no clinical presentation, mutation not excluded). In children with probable FH, 32% were found to have high Lp(a) [geometric mean (95% confidence interval) of 15.9 (12.3-20.6) mg/dL] compared with 10 and 10% [geometric means (95% confidence interval) of 11.5 (10.9-12.1) mg/dL and 9.8 (8.4-11.3) mg/dL] in children with definite FH (P = 0.017) and unaffected siblings (P = 0.002), respectively. Lp(a) was significantly higher and more frequently elevated in children with probable FH compared with children with definite FH and unaffected siblings, suggesting that high Lp(a) may underlie the clinical presentation of FH when no FH-causing mutation is found. Performing both DNA analysis and measuring Lp(a) in all children suspected of FH is recommended to assess possible LDL cholesterol overestimation related to increased Lp(a).

Methodological considerations for circulating long noncoding RNA quantification.

In the past decade, significant resources have been invested in long noncoding RNA (lncRNA) research. Despite the knowledge available, we are far from incorporation of lncRNA into clinical practice. Here, we emphasize the technical challenges in the field, hoping to provoke a response leading to new consensus and guidelines.

Double trouble: Pathogenic LDLR and SCARB1 variants in the same family

Background and Aims : LDLR and SCARB1 are the key membrane receptors LDL and HDL. Mutations in the LDLR and SCARB1 genes are identified in 80% of patients with familial hypercholesterolemia and in <<< 1% of patients with hyperalphalipoproteinemia. Mutations in the both genes act co-dominantly, heterozygous carriers demonstrate intermediate levels of LDL-C or HDL-C between wild-type and homozygous individuals. Here we describe a family with extremely high levels of lipoproteins (above the 90th percentile for age and sex) with a rare variant in one or both genes.Methods: NGS was performed by Ion S5 system. Variant validation was performed by PCR-direct sequencing.Results: The proband was admitted to the cardiology department with recurrent fainting and elevated LDL-C levels. We identified two pathogenic variants in a heterozygous state – LDLR(NM_000527.5):c.986G>A (p.Cys329Tyr) (HGMD - CM981186) and SCARB1(NM_005505.5):c.727-2A>C (rs201068540, according to the ACMG criteria the variant is pathogenic). We then determined that sibling is also the carrier of both mutations, the mother has only the SCARB1 variant, the father has only the LDLR variant. Segregation of variants correlates with the lipid profile of patients. The mutation in the SCARB1 gene correlates with a high HDL-C phenotype, and the LDLR mutation with a high LDL-C phenotype.Conclusions: Our findings suggest mutations in the SCARB1 gene are a rare but recurring cause of elevated HDL-C levels. The finding of the combined variants in LDLR/SCARB1 genes triggering hypercholesterolemia and hyperalphalipoproteinemia phenotypes is essential to elaborate the spectrum of variants causing dyslipidemia and to understand the genotype-phenotype correlation. Background and Aims : LDLR and SCARB1 are the key membrane receptors LDL and HDL. Mutations in the LDLR and SCARB1 genes are identified in 80% of patients with familial hypercholesterolemia and in <<< 1% of patients with hyperalphalipoproteinemia. Mutations in the both genes act co-dominantly, heterozygous carriers demonstrate intermediate levels of LDL-C or HDL-C between wild-type and homozygous individuals. Here we describe a family with extremely high levels of lipoproteins (above the 90th percentile for age and sex) with a rare variant in one or both genes. Methods: NGS was performed by Ion S5 system. Variant validation was performed by PCR-direct sequencing. Results: The proband was admitted to the cardiology department with recurrent fainting and elevated LDL-C levels. We identified two pathogenic variants in a heterozygous state – LDLR(NM_000527.5):c.986G>A (p.Cys329Tyr) (HGMD - CM981186) and SCARB1(NM_005505.5):c.727-2A>C (rs201068540, according to the ACMG criteria the variant is pathogenic). We then determined that sibling is also the carrier of both mutations, the mother has only the SCARB1 variant, the father has only the LDLR variant. Segregation of variants correlates with the lipid profile of patients. The mutation in the SCARB1 gene correlates with a high HDL-C phenotype, and the LDLR mutation with a high LDL-C phenotype. Conclusions: Our findings suggest mutations in the SCARB1 gene are a rare but recurring cause of elevated HDL-C levels. The finding of the combined variants in LDLR/SCARB1 genes triggering hypercholesterolemia and hyperalphalipoproteinemia phenotypes is essential to elaborate the spectrum of variants causing dyslipidemia and to understand the genotype-phenotype correlation.

Effect of lipoprotein(a) levels on long-term outcome in octogenarians with coronary artery disease after drug-eluting stent implantation.

High levels of lipoprotein(a) [Lp(a)] are linked to adverse cardiovascular events. The significance of Lp(a) for the survival of octogenarians with coronary artery disease (CAD) after drug-eluting stent (DES) insertion is, however, not known. The purpose of the study is to investigated the connection between Lp(a) and outcome in octogenarians with CAD after DES implantation. We retrospectively enrolled a total of 506 consecutive octogenarians with CAD and DES implantation in our institution between January 2015 to August 2018. Two patient groups were established: a low group with plasma Lp(a) lower than 50 mg/dL (n = 408) and a high group with values above 50 mg/dL (n = 98). After following up for a median of 31.53 ± 8.22 months, Kaplan-Meier curves indicated that poorer outcome censored for major cardiovascular events (MACE), myocardial infarction (MI), and target vessel revascularization (TVR) in the high group relative to the low group (log-rank test p = 0.001, p = 0.008, and p < 0.001, respectively). High Lp(a) independently predicted MACE (hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.28-2.84; p = 0.002), MI (HR 2.74; 95% CI 1.23-6.11; p = 0.014), and TVR (HR 3.65; 95% CI 1.99-6.69; p < 0.001) after covariate adjustment. High Lp(a) was also significantly related to poor long-term outcome in octogenarians with CAD after DES implantation.

Lipoprotein(a) as Part of the Diagnosis of Clinical Familial Hypercholesterolemia.

Individuals with familial hypercholesterolemia have very high risk of cardiovascular disease due to lifelong elevations in LDL cholesterol. Elevated lipoprotein(a) is a risk factor for cardiovascular diseases such as myocardial infarction and aortic valve stenosis. It has been proposed to include elevated lipoprotein(a) in the diagnosis of clinical familial hypercholesterolemia. Lipoprotein(a) is co-measured in LDL cholesterol, and up to one-quarter of all diagnoses of clinical familial hypercholesterolemia are due to high levels of lipoprotein(a). Further, individuals with both familial hypercholesterolemia and elevated lipoprotein(a) have an extremely high risk of myocardial infarction. We discuss the background for familial hypercholesterolemia and elevated lipoprotein(a) as risk factors for cardiovascular disease and the consequences of the fact that LDL cholesterol measurements/calculations include the cholesterol present in lipoprotein(a). Finally, we discuss the potential of including lipoprotein(a) as part of the diagnosis of familial hypercholesterolemia and in consequence possible treatments.