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Abstract: Lipoprotein(a)(Lp[a]) is a low-density lipoprotein-cholesterol (LDL-C)-like particle with potent pro-atherothrombotic properties. The association of Lp(a) with several circulating factors, including vitamins, remains unresolved. We performed an observational analysis using the National Health and Nutrition Examination Survey III cohort, a cohort used to monitor the nutrition status of US-citizens. We used multivariable linear regression to test associations of Lp(a) and LDL-C with levels of serum vitamins and minerals and whole-blood lead. Analyses controlled for factors known to associate with Lp(a) (age, sex, race/ethnicity, statin use, hemoglobin A1c, body mass index, hypertension, diabetes, glomerular filtration rate, alcohol intake, and saturated fat intake). LDL-C was corrected for Lp(a) mass. Multiple sensitivity tests were performed, including considering factors as categorical variables (deficient, normal, elevated). Among 7,662 subjects, Lp(a) correlated (β-coefficient) positively (change per 1 conventional unit increase) with carotenoids (lycopene (0.17(0.06,0.28), p=0.005), lutein (0.19(0.07,0.30), p=0.002), β-cryptoxanthin (0.21(0.05,0.37), p=0.01), β-carotene (0.05(0.02,0.09), p=0.003), and α-carotene (0.15(0.01,0.30), p=0.04)) and lead (0.54(0.03,1.05), p=0.04) levels when tested as continuous variables. LDL-C had similar associations. Lp(a) did not associate with vitamins A, B12, C, or E retinyl esters, folate, RBC-folate, selenium, ferritin, transferrin saturation, or calcium. With factors as categorical variables, Lp(a) but not LDL-C negatively associated with elevated vitamin B12 (−5.41(−9.50, −1.53), p=0.01) and folate (−2.86(−5.09, −0.63), p=0.01). In conclusion, Lp(a) associated similarly to LDL-C when vitamins, minerals, and lead were tested as continuous variables, while only Lp(a) correlated with vitamin B12 and folate when tested as categorical variables. These observations are hypotheses generating and require further studies to determine causality.

Lipoprotein(a) (Lp(a)) is a well-recognized independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, limited data are available on the relationship between coronary artery disease (CAD) burden and Lp(a) levels in patients with acute myocardial infarction (MI).The objective of this study was to assess the severity of CAD according to Lp(a) levels from a French regional registry of acute MI.CAD burden was assessed in 1213 consecutive patients hospitalized for acute MI in 2019-2020 who underwent coronary angiography. Patients were compared according to their Lp(a) levels:50 mg/dL (normal), ≥50 mg/dL and ≤100 mg/dL (high) and100 mg/dL (very high).The prevalence of high and very high Lp(a) was 13% and 6%, respectively. Median age, and rates of diabetes and smoking were similar in all groups. Patients with high or very high Lp(a) were more often under statin therapy, their corrected LDL-cholesterol levels were lower and previous ASCVD rates higher. When compared with lower levels, patients with very high Lp(a) levels had more elevated SYNTAX scores and more frequent multivessel disease. By multivariate logistic regression analysis, the odd ratio for the estimate of multivessel disease was the highest for patients with Lp(a)100 mg/dL. Moreover, there was a gradual increase in the number of in-hospital deaths across the three Lp(a) groups (p=0.028).In real-world patients hospitalized for acute MI in France, very high Lp(a) levels are independently associated with a severe CAD burden, supporting the need for systematic screening of Lp(a) in these patients.

Increased risk of coronary artery disease (CAD) in familial hypercholesterolaemia (FH) is modified by factors beyond defects in the low-density lipoprotein receptor pathway. The rs1250229-T single nucleotide polymorphism (SNP) in the FN1 gene is associated with CAD in genome-wide association studies and is in linkage disequilibrium with another SNP (rs1250259-T) in FN1 that is associated with decrease fibronectin secretion.We investigated whether rs1250229-T was also associated with prevalent CAD in patients with genetically confirmed FH.We collected clinical data from 256 patients with genetically confirmed FH. The FN1 rs1250229 SNP was genotyped on a SEQUENOM platform. The association between rs1250229-T and prevalent CAD was assessed using simple and multiple regression analyses.In patients with FH, the FN1 rs1250229-T (minor) allele was a significant negative predictor of prevalent CAD (odds ratio [OR] 0.353; 95% confidence interval [CI] 0.193 - 0.647; P = 0.001). FN1 rs1250229-T remained a significant predictor of prevalent CAD after adjusting for age, sex, obesity, hypertension, smoking status and lipoprotein(a) concentration (OR 0.200; 95% CI 0.091 - 0.441; P 0.001).The FN1 rs1250229-T allele is inversely associated with CAD in patients with genetically confirmed FH, independently of traditional risk factors. While this finding requires replication, it suggests that the biology of fibronectin may contribute to variation in the risk of CAD in FH.

Homozygous familial hypercholesterolaemia (HoFH) is a life-threatening disorder characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels. Untreated, severe atherosclerotic cardiovascular disease (ASCVD), including aortic valve stenosis (AVS), may already occur in childhood. Another important genetic risk factor for ASCVD and AVS is elevated lipoprotein(a) [Lp(a)], which is highly prevalent in the general paediatric population. However, data on Lp(a) in children with HoFH are scarce. Therefore, we performed a cross-sectional study to evaluate Lp(a) levels in children with HoFH and compared them to children with heterozygous FH (HeFH) and unaffected children. Adjusted least-square mean (95% CI) Lp(a) levels in HoFH (n=29), HeFH (n=101) and unaffected children (n=102) were 18.7 (12.0-29.1), 15.3 (11.8-19.8) and 10.5 (8.3-13.2) mg/dL, respectively (p-for-trend=0.007). Lp(a) levels in children with HoFH were higher than in children with HeFH and in unaffected children. Given the very high ASCVD risk with HoFH, identifying other risk factors such as elevated Lp(a) in these children is important. Therefore, Lp(a) levels should be measured at least once in all children with HoFH.

The role of Lp(a) in multi-ethnic Asian populations with coronary artery disease (CAD) has not been well established. The aims of this study were (i) to investigate whether Lp(a) is a predictor of CAD, and (ii) amongst patients with CAD, to ascertain whether Lp(a) is a predictor of acute myocardial infarction (AMI) and severity of CAD.We compared three cardiovascular phenotypes from patients recruited at coronary angiography. CAD was defined as ≥50% coronary artery stenosis and subdivided into a group with AMI history (CAD+AMI+) and a group without (CAD+AMI-). Minimal CAD group (CAD-) was defined as normal or30% coronary artery stenosis and no AMI. The severity of CAD was defined using the modified Gensini score.We studied 2025 patients comprising 94.5% men and 61.4% of Chinese ethnicity. The median Lp(a) level was highest in CAD+AMI+, followed by CAD+AMI- and CAD- (26.2, 20.1, and 15.8 nmol/L respectively). Similarly, the frequency of patients with Lp(a) ≥120 nmol/L were in the same order (11.8%, 9.1% and 2.4%). Lp(a) levels were highest among Asian Indians, followed by Malays and Chinese patients (p 0.001). Lp(a) levels and Lp(a) ≥120 nmol/L were significant predictors of CAD (Odds ratio (OR) = 1.12 per 10 nmol/L increment, p 0.001, and OR = 5.41 p = 0.004 respectively). Among patients with CAD, higher Lp(a) levels were associated with increased AMI risk (OR = 1.02 per 10 nmol/L increment, p = 0.024). Lp(a) ≥120 nmol/L was positively associated with CAD severity (p = 0.020).Plasma Lp(a) concentration is a positive predictor of CAD and AMI in a mostly male South East Asian population.

Aims Lipoprotein(a) [Lp(a)] is a causal and independent risk factor for cardiovascular disease (CVD). People with elevated Lp(a) are often prescribed statins as they also often show elevated low-density lipoprotein cholesterol (LDL-C) levels. While statins are well-established in lowering LDL-C, their effect on Lp(a) remains unclear. We evaluated the effect of statins compared to placebo on Lp(a) and the effects of different types and intensities of statin therapy on Lp(a). Methods and results We conducted a systematic review and meta-analysis of randomized trials with a statin and placebo arm. Medline and EMBASE were searched until August 2019. Quality assessment of studies was done using Cochrane risk-of-bias tool (RoB 2). Mean difference of absolute and percentage changes of Lp(a) in the statin vs. the placebo arms were pooled using a random-effects meta-analysis. We compared effects of different types and intensities of statin therapy using subgroup- and network meta-analyses. Certainty of the evidence was determined using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Overall, 39 studies (24 448 participants) were included. Mean differences (95% confidence interval) of absolute and percentage changes in the statin vs. the placebo arms were 1.1 mg/dL (0.5–1.6, P Conclusion Statin therapy does not lead to clinically important differences in Lp(a) compared to placebo in patients at risk for CVD. Our findings suggest that in these patients, statin therapy will not change Lp(a)-associated CVD risk.

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) or lipoprotein "little a" is an under-recognized causal risk factor for cardiovascular (CV) disease (CVD), including coronary atherosclerosis, aortic valvular stenosis, ischemic stroke, heart failure and peripheral arterial disease. Elevated plasma Lp(a) (≥50 mg/dL or ≥100 nmol/L) is commonly encountered in almost 1 in 5 individuals and confers a higher CV risk compared to those with normal Lp(a) levels, although such normal levels have not been generally agreed upon. Elevated Lp(a) is considered a cause of premature and accelerated atherosclerotic CVD. Thus, in patients with a positive family or personal history of premature coronary artery disease (CAD), Lp(a) should be measured. However, elevated Lp(a) may confer increased risk for incident CAD even in the absence of a family history of CAD, and even in those who have guideline-lowered LDL-cholesterol (

Lipid-driven cardiovascular disease (CVD) risk is caused by atherogenic apolipoprotein B (apoB) particles containing low-density lipoprotein cholesterol (LDL-C), triglycerides and lipoprotein(a) [Lp(a)] and resembles a large and modifiable proportion of the total CVD risk. While a surplus of novel lipid-lowering therapies has been developed in recent years, management of lipid-driven CVD risk in the Netherlands remains suboptimal. To lower LDL‑C levels, statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibiting antibodies are the current standard of therapy. With the approval of bempedoic acid and the silencing RNA inclisiran, therapeutic options are expanding continuously. Although the use of triglyceride-lowering therapies remains a matter of debate, post hoc analyses consistently show a benefit in subsets of patients with high triglyceride or low high-density lipoprotein cholesterol levels. Pemafibrate and novel apoC-III could be efficacious options when approved for clinical use. Lp(a)-lowering therapies such as pelacarsen are under clinical investigation, offering a potent Lp(a)-lowering effect. If proven effective in reducing cardiovascular endpoints, Lp(a) lowering holds promise to be the third axis of effective lipid-lowering therapies. Using these three components of lipid-lowering treatment, the contribution of apoB-containing lipid particles to the CVD risk may be fully eradicated in the next decade.

Background. We developed a new nomogram combining serum biomarkers with clinicopathological features to improve the accuracy of prediction of nonsentinel lymph node (SLN) metastases in Chinese breast cancer patients. Methods. We enrolled 209 patients with breast cancer who underwent SLN biopsy and axillary lymph node dissection. We evaluated the relationships between non-SLN metastases and clinicopathologic features, as well as preoperative routine tests of blood indexes, tumor markers, and serum lipids, including lipoprotein a (Lp(a)). Risk factors for non-SLN metastases were identified by logistic regression analysis. The nomogram was created using the R program to predict the risk of non-SLN metastases in the training set. Receiver operating characteristic (ROC) analysis was applied to assess the predictive value of the nomogram model in the validation set. Results. Lp(a) was significantly associated with non-SLN metastasis status. Compared with the MSKCC model, the predictive ability of our new nomogram that combined Lp(a) level and clinical variables (pathologic tumor size, lymphovascular invasion, multifocality, and positive/negative SLN numbers) was significantly greater (AUC: 0.732, 95% CI: 0.643–0.821) (C-index: 0.703, 95% CI: 0.656–0.791) in the training cohorts and also performed well in the validation cohorts (C-index: 0.773, 95% CI: 0.681–0.865). Moreover, the new nomogram with Lp(a) improved the accuracy (12.10%) of identification of patients with non-SLN metastases (NRI: 0.121; 95% CI: 0.081–0.202; P = 0.011 ). Conclusions. This novel nomogram based on preoperative serum indexes combined with clinicopathologic features facilitates accurate prediction of risk of non-SLN metastases in Chinese patients with breast cancer.

AIMS/INTRODUCTION Diabetic kidney disease (DKD) exacerbates dyslipidemia and increases the incidence of atherosclerotic cardiovascular disease. DKD is a concept that includes typical diabetic nephropathy and an atypical phenotype without proteinuria. We investigated dyslipidemia in different DKD phenotypes that have not been fully studied. MATERIALS AND METHODS Fasting plasma was obtained from 1,073 diabetes patients enrolled in the regional diabetes cohort (ViNA cohort). Non-proteinuric and proteinuric DKD were defined as an estimated glomerular filtration rate 300 mg/g. Novel lipid risk factors, low-density lipoprotein (LDL) triglyceride (TG) and small dense LDL cholesterol were measured using our established homologous assay. RESULTS The proportion of atherosclerotic cardiovascular disease patients was higher in non-proteinuric DKD and even higher in proteinuric DKD than in non-DKD. Increased estimated glomerular filtration rate grade and albuminuric stage were independently correlated with higher TG, TG-rich lipoprotein cholesterol and apolipoprotein CIII. Therefore, proteinuric DKD had the highest of these levels. Small dense LDL cholesterol and LDL-TG were higher in the proteinuria without renal dysfunction group in the lipid-lowering drug-free subset. Lipoprotein(a) was higher in DKD regardless of proteinuria. CONCLUSIONS Proteinuria was associated with an atherogenic subspecies of LDL, whereas renal dysfunction was associated with increased lipoprotein(a). Proteinuria and renal dysfunction independently exacerbated TG-rich lipoprotein-related dyslipidemia. This is in good agreement with the results of large-scale clinical studies in which proteinuria and renal dysfunction synergistically increased the risk of atherosclerotic cardiovascular disease in populations with diabetes.

Familial hypercholesterolemia (FH), familial combined hyperlipidemia (FCHL), and elevated lipoprotein (a) (Lp[a]) increase risk of premature coronary artery disease (CAD). The objective of this study was to assess the prevalence of FH, FCHL, elevated Lp(a) and their impact on management in patients with premature CAD.We prospectively recruited men ≤ 50 years and women ≤ 55 with obstructive CAD. FH was defined as Dutch Lipid Clinic Network scores ≥ 6. FCHL was defined as apolipoprotein B1.2 g/L, triglyceride and total cholesterol90th population percentile, and family history of premature cardiovascular disease. Lp(a) ≥ 50 mg/dL was considered to be elevated.Among 263 participants, 9.1% met criteria for FH, 12.5% for FCHL, and 19.4% had elevated Lp(a). Among patients with FH, 37.5% had FH-causing DNA variants. Patients with FH, but not other dyslipidemias, were more likely than nondyslipidemic patients to have received lipid-lowering therapy before presenting with CAD (33.3% vs 12.3%, P = 0.04) and combined lipid-lowering therapy after the presentation (41.7% vs 7.7%, P0.001). One year after presentation, 58.3%, 54.5%, and 58.8% of patients with FH, FCHL, and elevated Lp(a) had low-density lipoprotein cholesterol (LDL-C)1.8 mmol/L, respectively, compared with 68.0 % in reference group. Patients with FCHL were more likely to have non-high-density lipoprotein (HDL) and apolipoprotein B above recommended lipid goals (70.0% and 87.9%, respectively).FH, FCHL, and elevated Lp(a) are common in patients with premature CAD and have differing impact on treatment and achievement of lipid targets. Assessment for these conditions in patients with premature CAD provides valuable information for individualized management.

Introduction The combination of biochemical markers, together with the design and implementation of diagnostic algorithms in laboratory computer systems could become very powerful tools in the stratification of cardiovascular risk. Objectives To implement new biochemical markers and diagnostic algorithms not yet available, in order to provide an estimation of cardiovascular risk and the diagnostic orientation of lipid alterations. Material and methods Study of the implementation of Apolipoprotein B and Lipoprotein (a), as well as the inclusion of different diagnostic algorithms. This was carried out jointly by the different Lipid Units of the Spanish Society of Atherosclerosis, Hospital Virgen Macarena in Seville, Hospital Juan Ramon Jimenez, Hospital Infanta Elena, and Hospital de Rio Tinto during 2018 and 2019. Results The four diagnostic algorithms entered into the Laboratory Information System (LIS), showed a total of 9985 patients with c-LDL >200 mg/dL. The diagnostic algorithm was extended to include Apo B, with 8182 determinations showing an Apolipoprotein B > 100 mg/dL). A total of 747 lipoprotein (a) were determined, of which 30.65% were >50 mg/dL. More than two-thirds (71.80%) showed results compatible with small and dense LDL particles. Conclusions The implementation of new analytical parameters and algorithms in Primary Care laboratory results can identify a considerable number of patients with different alterations in lipid metabolism. This, together with the classic risk factors, could contribute to a correct risk stratification in preventing the progression of CVD.

Background Comorbidities including ischemic heart disease (IHD) worsen outcomes after SARS‐CoV‐2 infections. High lipoprotein(a) [Lp(a)] concentrations are a strong risk factor for IHD and possibly for thromboembolic events. We therefore evaluated whether SARS‐CoV‐2 infections modify the risk of high Lp(a) concentrations for IHD or thromboembolic events during the first 8.5 months follow‐up of the pandemic. Method Cohort study using data from the UK Biobank during the SARS‐CoV‐2 pandemic. Baseline Lp(a) was compared between SARS‐CoV‐2 positive patients and the population controls. UK Biobank received ethical approval from the North West Multi‐Centre Research Ethics Committee (REC reference: 11/NW/0382). All participants gave written informed consent before enrolment in the study, which was conducted in accordance with the principles of the Declaration of Helsinki. Results SARS‐CoV‐2 positive patients had Lp(a) concentrations similar to the population controls. The risk for IHD increased with higher Lp(a) concentrations in both, the population controls (n = 435,104) and SARS‐CoV‐2 positive patients (n = 6,937). The causality of the findings was supported by a genetic risk score for Lp(a). A SARS‐CoV‐2 infection modified the association with a steeper increase in risk for infected patients (interaction P‐value = 0.03). Although SARS‐CoV‐2 positive patients had a 5‐times higher frequency of thromboembolic events compared to the population controls (1.53% vs. 0.31%), the risk was not influenced by Lp(a). Conclusions SARS‐CoV‐2 infections enforce the association between high Lp(a) and IHD but the risk for thromboembolic events is not influenced by Lp(a). This article is protected by copyright. All rights reserved

Background and Objective High lipoprotein(a) is a genetically determined causal risk factor for cardiovascular disease, and 20% of the adult population has high levels (ie, >42 mg/dL, >88 nmol/L). We investigated whether early life lipoprotein(a) levels measured in cord blood may serve as a proxy for neonatal venous blood levels, whether lipoprotein(a) birth levels (ie, cord or venous) predict levels later in life, and whether early life and parental levels correlate. Methods The Compare study is a prospective cohort study of newborns (N = 450) from Copenhagen, Denmark, including blood sampling of parents. Plasma lipoprotein(a) was measured in cord blood (N = 402), neonatal venous blood (N = 356), and at 2 (N = 320) and 15 months follow-up (N = 148) of infants, and in parents (N = 705). Results Mean lipoprotein(a) levels were 2.2 (95% CI, 1.9-2.5), 2.4 (2.0-2.7), 4.1 (3.4-4.9), and 14.6 (11.4-17.9) mg/dL in cord, neonatal venous, and 2- and 15-month venous samples, respectively. Lipoprotein(a) levels in cord blood correlated strongly with neonatal venous blood levels (R2 = 0.95, P 42 mg/dL at 15 months with positive predictive values of 89% and 85% for neonatal venous and cord blood. Neonatal and infant levels correlated weakly with parental levels, most pronounced at 15 months (R2 = 0.22, P Conclusions Lipoprotein(a) levels are low in early life, cord blood may serve as a proxy for neonatal venous blood, and birth levels ≥ 90th percentile can identify newborns at risk of developing high levels.

Lipoprotein(a) (Lp(a)) is a prothrombotic and anti-fibrinolytic lipoprotein, whose role has not been clearly defined in the pathogenesis of coronavirus disease 2019 (COVID-19). In this prospective observational study, serum Lp(a) as well as outcomes were measured in 50 COVID-19 patients and 30 matched sick controls. Lp(a) was also assessed for correlation with a wide panel of biomarkers. Serum Lp(a) did not significantly differ between COVID-19 patients and sick controls, though its concentration was found to be significantly associated with severity of COVID-19 illness, including acute kidney failure stage (r = 0.380, p = 0.007), admission disease severity (r = 0.355, p = 0.013), and peak severity (r = 0.314; p = 0.03). Lp(a) was also positively correlated with interleukin (IL)-8 (r = 0.308; p = 0.037), fibrinogen (r = 0.344; p = 0.032) and creatinine (r = 0.327; p = 0.027), and negatively correlated with ADAMTS13 activity/VWF:Ag (r = − 0.335; p = 0.021); but not with IL-6 (r = 0.241; p = 0.106). These results would hence suggest that adverse outcomes in patients with COVID-19 may be aggravated by a genetically determined hyper-Lp(a) state rather than any inflammation induced elevations. Supplementary Information The online version contains supplementary material available at 10.1007/s11239-021-02597-y.

Patients with genetically associated elevated lipoprotein(a) [Lp(a)] levels are at greater risk for coronary artery disease, heart attack, stroke, and peripheral arterial disease. To date, there are no US FDA-approved drug therapies that are designed to target Lp(a) with the goal of lowering the Lp(a) level in patients who have increased risk. The American College of Cardiology (ACC) has provided guidelines on how to use traditional lipid profiles to assess the risk of atherosclerotic cardiovascular disease (ASCVD); however, even with the emergence of statin add-on therapies such as ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, some populations with elevated Lp(a) biomarkers remain at an increased risk for cardiovascular (CV) disease. Residual CV risk has led researchers to inquire about how lowering Lp(a) can be used as a potential preventative therapy in reducing CV events. This review aims to present and discuss the current clinical and scientific evidence pertaining to pelacarsen.

The natural history of most thrombi undergoes total or near total resolution, but the thrombi in chronic thromboembolic pulmonary hypertension (CTEPH) do not resolve completely and subsequently increase the pulmonary vascular resistance. We hypothesised that the elevated lipoprotein A in acute pulmonary embolism could lessen the autoresorption of the emboli and ultimately lead to CTEPH.

Objectives This study evaluated the association between elevated levels of lipoprotein(a) [Lp(a)] and risk of recurrent ischemic events in patients who underwent percutaneous coronary intervention (PCI). Background Elevated levels of Lp(a) have been identified as an independent, possibly causal, risk factor for atherosclerotic cardiovascular disease in a general population study. Methods A prospective single-center registry was used to identify 12,064 patients with baseline Lp(a) measurements who underwent PCI between 2003 and 2013. The primary outcomes were a composite of cardiovascular death, spontaneous myocardial infarction, and ischemic stroke. Results From the registry, 3,747 (31.1%) patients had high Lp(a) (>30 mg/dL) and 8,317 (68.9%) patients had low Lp(a) (≤30 mg/dL). During a median follow-up of 7.4 years, primary outcomes occurred in 1,490 patients, and the incidence rates of primary outcomes were 2.0 per 100 person-years in the high-Lp(a) group and 1.6 per 100 person-years in the low-Lp(a) group (adjusted hazard ratio [aHR]: 1.17; 95% confidence interval [CI]: 1.05-1.30; P = 0.004). Increased risk of recurrent ischemic cardiovascular events in the high-Lp(a) group was consistent in various subgroups including patients receiving statin treatment at discharge (aHR: 1.18; 95% CI: 1.03-1.34; P = 0.011). In addition, the risk of repeated revascularization was significantly higher in the high-Lp(a) group (aHR: 1.13; 95% CI: 1.02-1.25; P = 0.022). Conclusions Elevated levels of Lp(a) were significantly associated with the recurrent ischemic events in patients who underwent PCI. This study provides a rationale for outcome trials to test Lp(a)-lowering therapy for secondary prevention in patients undergoing PCI.

ObjectivesTo investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC.MethodsWe included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC.ResultsThe prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (β 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase).ConclusionsLp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.

Background Little is known about the relationship between lipoprotein (a) [Lp(a)] and high-sensitivity C-reactive protein (hsCRP) and their joint association with atherosclerotic cardiovascular disease (ASCVD). Objectives The purpose of this study was to assess whether Lp(a)-associated ASCVD risk is modified by hsCRP in the context of primary prevention. Methods The current study included 4,679 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) Apolipoprotein ancillary data set. Cox proportional hazards models and Kaplan-Meier curves were used to assess the association among Lp(a), hsCRP, and time to cardiovascular disease (CVD) events. Results During a mean follow-up of 13.6 years, 684 CVD events occurred. A significant interaction was observed between Lp(a) and hsCRP (P = 0.04). With hsCRP 100 mg/dL. However, with hsCRP ≥2 mg/L, a significant CVD risk was observed with Lp(a) of 50-99.9 mg/dL (HR: 1.36; 95% CI: 1.02-1.81) and Lp(a) ≥100 mg/dL (HR: 2.09; 95% CI: 1.40-3.13). Isolated elevations of either Lp(a) or hsCRP were not associated with increased CVD risk. In contrast, the combination of elevated Lp(a) (≥50 mg/dL) and hsCRP (≥2 mg/L) was independently associated with significant CVD risk (HR: 1.62; 95% CI: 1.25-2.10) and all-cause mortality (HR: 1.39; 95% CI: 1.12-1.72). Conclusions Lp(a)-associated ASCVD risk is observed only with concomitant elevation of hsCRP. Individuals with concomitant presence of elevated Lp(a) and systemic inflammation have greater ASCVD risk and all-cause mortality, and thus may merit closer surveillance and more aggressive ASCVD risk management.

Background Lipoprotein(a)[Lp(a)] has been considered as an independent risk factor for coronary artery disease (CAD). The present study aimed to evaluate the association between baseline serum Lp(a) and CAD progression determined by angiographic score. Methods A total of 814 patients who had undergone two or more coronary computed tomography angiography at least 6 months apart were consecutively enrolled and the coronary severity was determined by the Gensini score system. Patients were stratified into two groups according to Lp(a)>300 mg/L and Lp(a) ≤ 300 mg/L or classified as “progressors” and “non‐progressors” based on the Gensini score rate of change per year. The association of continuous Lp(a) and Lp(a)>300 mg/L with CAD progression were respectively assessed by logistic regression analysis. Moreover, further evaluation of those association was performed in subgroups of the study population. Results Patients in the “progressors” group had significant higher Lp(a) levels. Furthermore, the multivariate logistic regression analysis showed that elevated Lp(a) (odds ratio [OR]: 1.451, 95% confidence interval [CI]: 1.177–1.789, p300 mg/L (OR:1.642, 95% CI:1.018–2.649, p = .042) were positively associated with CAD progression after adjusting for confounding factors. In addition, those relation seemed to be more prominent in subjects with lower body mass index (OR: 1.880, 95% CI: 1.224–2.888, p for interaction = .060). Conclusions Elevated baseline serum Lp(a) is positively and independently associated with angiographic progression of CAD, particularly in participants with relatively low body mass index. Therefore, Lp(a) could be a potent risk factor for CAD progression, assisting in early risk stratification in cardiovascular patients.

Aims To investigate plasma lipoprotein(a) [Lp(a)] levels measured in routine clinical care and their association with mortality and cardiovascular disease. Methods and results This retrospective registry-based observational cohort study includes all individuals with plasma Lp(a) results measured at the Karolinska University Laboratory 2003–17. Outcome data were captured in national outcome registries. Levels of Lp(a) expressed in mass or molar units were examined separately. In adjusted Cox regression models, association between deciles of plasma Lp(a) concentrations, mortality, and cardiovascular outcomes were assessed. A total of 23 398 individuals [52% females, mean (standard deviation) age 55.5 (17.2) years, median Lp(a) levels 17 mg/dL or 19.5 nmol/L] were included. Individuals with an Lp(a) level >90th decile (>90 mg/dL or >180 nmol/L) had hazard ratios (95% confidence interval) of 1.25 (1.05–1.50) for major adverse cardiovascular events (P = 0.013), 1.37 (1.14–1.64) for atherosclerotic cardiovascular disease (P = 0.001), and 1.62 (1.28–2.05) for coronary artery disease (P ≤ 0.001), compared to individuals with Lp(a) ≤50th decile. No association between Lp(a) and mortality, peripheral artery disease, or ischaemic stroke was observed. Conclusion High Lp(a) levels are associated with adverse cardiovascular disease outcomes also in individuals with Lp(a) measured in routine clinical care. This supports the 2019 ESC/EAS recommendation to measure Lp(a) at least once during lifetime to assess cardiovascular risk and implies the need for intensive preventive therapy in patients with elevated Lp(a).

The association between elevated lipoprotein(a) [Lp(a)] and poor outcomes in coronary artery disease (CAD) has been addressed for decades. However, little is known about the prognostic value of Lp(a) in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA). A total of 1179 patients with MINOCA were enrolled and divided into low, medium, and high Lp(a) groups based on the cut-off value of 10 and 30mg/dL. The primary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier and Cox regression analyses were performed. Accuracy was defined as area under the curve (AUC) using a receiver-operating characteristic analysis. Patients with higher Lp(a) levels had a significantly higher incidence of MACE (9.5%, 14.6%, 18.5%; p = 0.002) during the median follow-up of 41.7 months. The risk of MACE also increased with the rising Lp(a) levels even after multivariate adjustment [low Lp(a) group as reference, medium group: hazard ratio (HR) 1.55, 95% confidence interval (CI): 1.02-2.40, p = 0.047; high group: HR 2.07, 95% CI: 1.32-3.25, p = 0.001]. Further, clinically elevated Lp(a) defined as Lp(a) ≥30 mg/dL was closely associated with an increased risk of MACE in overall and in subgroups (all p0.05). When adding Lp(a) (AUC 0.61) into the Thrombolysis in Myocardial Infarction (TIMI) score (AUC 0.68), the combined model (AUC 0.73) yielded a significant improvement in discrimination for MACE (ΔAUC 0.05, p = 0.032). In conclusion, elevated Lp(a) was strongly associated with a poor prognosis in patients with MINOCA. Adding Lp(a) to traditional risk score further improved risk prediction. Our data, for the first time, confirmed the Lp(a) as a residual risk factor for MINOCA.

[EN] [Introduction and objectives] Our objective was to approximate the prevalence of mutations in candidate genes for familial hypercholesterolemia (FH) in a middle-aged Spanish population and to establish the predictive value of criteria for clinical suspicion in the detection of causative mutations., [EN] [Methods] Unrelated individuals aged ≥ 18 years from the Aragon Workers’ Health Study (AWHS) with high low-density lipoprotein cholesterol (LDL-C) and clinical suspicion of FH (participants with LDL-C concentrations above the 95th percentile, participants with premature cardiovascular disease and/or participants with high LDL-C [130 mg/dL] under statin therapy), assuming that any participant with FH exhibits at leats 1 trait, were selected and the LDLR, APOB, PCSK9, APOE, STAP1 and LDLRAP1 genes were sequenced by next generation sequencing technology., [EN] [Results] Of 5400 individuals from the AWHS, 4514 had complete data on lipid levels and lipid-lowering drugs, 255 participants (5.65%) met the criteria for suspicion of FH, 24 of them (9.41%) were diagnosed with hyperlipoproteinemia(a), and 16 (6.27% of those sequenced) were found to carry causative mutations in candidate genes: 12 participants carried 11 different pathogenic LDLR alleles and 4 participants carried 1 pathogenic mutation in PCSK9. LDL-C concentrations > 220 mg/dL and LDL-C > 130 mg/dL despite statin therapy showed the strongest association with the presence of mutations (P = .011)., [EN] [Conclusions] Our results show that the prevalence of FH in Spain is 1:282 and suggest that the combination of high untreated LDL-C and high levels of LDL-C despite statin therapy are the best predictors of a positive FH genetic test., [ES] [Introducción y objetivos] Nuestro objetivo fue aproximar la prevalencia de mutaciones en los genes candidatos de hipercolesterolemia familiar (HF) en una población española de mediana edad, y determinar el valor predictivo de los criterios clínicos de sospecha de HF en la detección de mutaciones causales., [ES] [Métodos] Se seleccionaron individuos mayores de 18 años no relacionados de la cohorte Estudio de Salud de los Trabajadores de Aragón (AWHS) con colesterol unido a lipoproteínas de baja densidad (cLDL) > percentil 95, con enfermedad cardiovascular prematura o con cLDL > 130 mg/dl con tratamiento hipolipemiante, asumiendo que al menos una de las características estará presente en todos los individuos con HF. En estos participantes se secuenciaron los genes LDLR, APOB, PCSK9, APOE, STAP1 y LDLRAP1 mediante secuenciación masiva., [ES] [Resultados] De 5.400 individuos del AWHS, 4.514 tenían datos lipídicos y registro farmacológico hipolipemiante completo, 255 participantes (5,65%) cumplían los criterios de sospecha de HF, 24 de ellos (9,41%) fueron diagnosticados de hiperlipoproteinemia(a) y 16 (6,27% de los secuenciados) presentaron alguna mutación causal en genes candidatos: 12 participantes portaban 11 alelos patogénicos diferentes en LDLR y 4 participantes portaban una mutación patogénica en PCSK9. Las concentraciones de cLDL > 220 mg/dl y el cLDL > 130 mg/dl a pesar del tratamiento con estatinas mostraron la mayor asociación con la presencia de mutación (p = 0,011)., [ES] [Conclusiones] Nuestros resultados muestran que la prevalencia española de HF es 1:282 y sugieren que una concentración de cLDL elevado, y niveles altos de cLDL a pesar de la terapia con estatinas son los mejores predictores para un diagnóstico genético positivo de HF., Este trabajo contó con el apoyo de subvenciones del Gobierno de Aragón, B14-7R, España y del Ministerio de Economía y Competitividad de España PI15/01983, PI18/01777 y CIBERCV. Estos proyectos son cofinanciados por el Instituto de Salud Carlos III y el Fondo Europeo de Desarrollo Regional (FEDER) de la Unión Europea «Una manera de hacer Europa».

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.

Purpose of review Calcific aortic stenosis (CAVS) is the most common form of valvular heart disease in developed countries, increasing in prevalence with the aging population. Surgical or transcatheter aortic valve replacement is the only treatment available for CAVS. However, these interventions are typically reserved for severe symptomatic aortic stenosis (AS). The purpose of this review is to summarize the recent literature in uncovering the underlying pathophysiology of CAVS in the setting of lipoprotein (a) [Lp(a)] and emerging therapies targeting Lp(a) which may help halt disease progression in CAVS. Recent findings Pathophysiologic, epidemiological, and genetic studies over the past two decades have provided strong evidence that Lp(a) is an important mediator of calcific aortic valvular disease (CAVD). Studies suggest that Lp(a) is a key carrier of pro-calcifying oxidized phospholipids (OxPL). The metabolism of OxPL results in a pro-inflammatory state and subsequent valvular thickening and mineralization through pro-osteogenic signaling. The identification of Lp(a) as a causal mediator of CAVD has allowed for opportunities for emerging therapeutic agents which may slow the progression of CAVD (Fig. 1JOURNAL/cocar/04.03/00001573-202109000-00007/figure1/v/2021-08-04T080204Z/r/image-jpeg). Summary This review summarizes the current knowledge on the association of Lp(a) with CAVD and ongoing studies of potential Lp(a)-lowering therapies. Based on the rate-limiting and causal role of Lp(a) in progression of CAVS, these therapies may represent novel pharmacotherapies in AS and inform the developing role of Lp(a) in the clinical management of CAVD.

The aim of this prospective cohort study was: to identify the association between different biomarkers [proprotein convertase subtilisin/kexin 9-PCSK9, lipoprotein(a)-Lp(a) and high-sensitivity C-reactive protein-hsCRP] and the cardiovascular events; to evaluate the relationship between the 3 biomarkers mentioned above and the renal outcomes that contributed to end-stage renal disease (ESRD).We studied 110 patients with chronic kidney disease (CKD) stages 2 to 4. The identification of the new cardiovascular events and the renal outcomes were performed by clinical and paraclinical explorations.350 patients were examined and 110 (31.4%) were included in this study. The mean age was 55.6 ± 10.9 years, with a higher number of men compared to women. The CKD patients with de novo cardiovascular events and new renal outcome during the study, had significantly increased values of total cholesterol (TC), low density cholesterol lipoprotein (LDL-C) at 6 and 12 months and higher levels of Lp(a), PCSK9, hsCRP and low ankle-brachial index (ABI) and ejection fraction (EF) values compared to patients without cardiovascular and renal events. In CKD patients, PCSK9 220 ng/mL was a predictor of cardiovascular events, while the EF 50% was a predictor for renal outcomes. For CKD patients with PCSK9 220 ng/mL and hsCRP 3 mg/L levels, the time-interval for the new cardiovascular and renal events occurrence were significantly decreased compared to patients displaying low values of these biomarkers.The results of this study show that PCSK9 220 ng/mL was predictor for cardiovascular events, while EF 50% was predictor for CKD progression to ESRD. PCSK9 220 ng/mL and hsCRP 3 mg/L were associated with the occurrence of renal and cardiovascular events earlier.

Elevated levels of lipoprotein(a) [Lp(a)] have been identified as an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and, more recently, calcific aortic valve disease (CAVD). CAVD is a slow, progressive disorder presenting as severe trileaflet calcification known as aortic valve stenosis (AS) that impairs valve motion and restricts ventricular outflow. AS afflicts 2% of the aging population (≥ 65 years) and tends to be quite advanced by the time it presents clinical symptoms of exertional angina, syncope, or heart failure. Currently, the only effective clinical therapy for AS patients is surgical or transcatheter aortic valve replacement. Evidence is accumulating that Lp(a) can exacerbate pathophysiological processes in CAVD, specifically, endothelial dysfunction, formation of foam cells, and promotion of a pro-inflammatory state. In the valve milieu, the pro-inflammatory effects of Lp(a) are manifested in valve thickening and mineralization through pro-osteogenic signaling and changes in gene expression in valve interstitial cells that is primarily facilitated by the oxidized phospholipid content of Lp(a). In AS pathogenesis, an incomplete understanding of the role of Lp(a) at the molecular level and the absence of appropriate animal models are barriers for the development of specific and effective clinical interventions designed to mitigate the role of Lp(a) in AS. However, the advent of effective therapies that dramatically lower Lp(a) provides the possibility of the first medical treatment to halt AS progression.

Background Lipoprotein (a) [Lp(a)] is a proven independent risk factor for coronary heart disease. It is also associated with type 2 diabetes mellitus (T2DM). However, the correlation between Lp(a) and T2DM has not been clearly elucidated. Methods This was a retrospective cohort study involving 9248 T2DM patients and 18,496 control individuals (1:2 matched). Patients were randomly selected from among inpatients in the Second Affiliated Hospital of Nanchang University between 2006 and 2017. Clinical characteristics were compared between the two groups. Spearman rank-order correlation coefficients were used to evaluate the strength and direction of monotonic associations of serum Lp(a) with other metabolic risk factors. Binary logistic regression analysis was used to establish the correlation between Lp(a) levels and T2DM risk. Results The median Lp(a) concentration was lower in T2DM patients than in controls (16.42 vs. 16.88 mg/dL). Based on four quartiles of Lp(a) levels, there was a decrease in T2DM risk from 33.7% (Q1) to 31.96% (Q4) (P for trend 28.72 mg/dL (Q4) were associated with a significantly lower T2DM risk in the unadjusted model [0.924 (0.861, 0.992), P = 0.030]. Similar results were obtained in adjusted models 1 [Q4, 0.925 (0.862, 0.993), P = 0.031] and 2 [Q4, 0.919 (0.854, 0.990), P = 0.026]. Furthermore, in the stratified analysis, Q4 of Lp(a) was associated with a significantly lower T2DM risk among men [0.813 (0.734, 0.900), P 60 years [0.819 (0.737, 0.910), P Conclusions There is an inverse association between Lp(a) levels and T2DM risk in the Chinese population. Male patients, especially those aged more than 60 years with Lp(a) > 28.72 mg/dL, are low-risk T2DM individuals, regardless of LDL-C levels and CHD status.

Amaç: Tip II diabetes mellitus (tip II DM) günümüzde çok sık görülmekte olup önemli mortalite nedenleri arasındadır. Bu çalışmadaki amacımız komplikasyon gelişmiş ve gelişmemiş tip II DM hastalarında paraoksonaz1 (PON1), arilesteraz (ARE), lipoprotein(a) [Lp(a)] ve diğer lipit parametreleri arasındaki ilişkiyi belirlemektir.Gereç ve Yöntemler: Fırat Üniversitesi Hastanesi Endokrinoloji kliniğine başvuran 20 komplikasyon gelişmeyen, ve 20 komplikasyon gelişmiş olmak üzere 40 tip II DM hastasının serum PONl, ARE, Lp(a), apo A, apo B ve diğer lipid parametreleri araştırıldı. Kontrol grubu kardiyovasküler hastalığı, diyabeti veya serum lipid düzeyini etkileyen bir hastalığı olmayan sağlıklı 40 bireyden oluşmaktadır. Bulgular: Tip II DM komplikasyon gelişmiş olan hastalarda serum PONl, ARE, total kolesterol, trigliserid, HDL-K, LDL-K, VLDL-K, Lp(a), apo A ve apo B düzeyleri sağlıklı kontrol grubuna göre anlamlı farklılık bulundu (p0.05). Sonuç: Tip II DM hastalarında PONl, ARE, total kolesterol, trigliserid, HDL-K, LDL-K, VLDL-K, Lp(a), apo A ve apo B bu parametrelerin kontrolünün yapılması komplikasyonların önlenmesini ve hastalığın seyrini olumlu yönde etkileyecektir.

Lipid metabolism is often disrupted in liver cirrhosis. The present study aimed to evaluate the impact of lipid profile on decompensation events, severity of liver dysfunction, and death in patients with liver cirrhosis.In a cross-sectional study, 778 patients with lipid profile data were enrolled, and then were divided into 240 and 538 patients with and without liver cirrhosis, respectively. In a cohort study, 314 cirrhotic patients with lipid profile data, who were prospectively followed, were enrolled. Lipid profile included total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), triglycerides (TG), and lipoprotein(a).In the cross-sectional study, cirrhotic patients with decompensation events had significantly lower levels of TC and lipoprotein(a) than those without; and cirrhotic patients with Child-Pugh class B and C had significantly lower levels of TC, HDL-c, LDL-c, and lipoprotein(a) than those with Child-Pugh class A. In the cohort study, there was an inverse association of survival with TC, HDL-c, and lipoprotein(a) levels; after adjusting for MELD score, TC (Hazard Ratio [HR] = 1.703, P = 0.034) and HDL-c (HR = 2.036, P = 0.005), but not lipoprotein(a) (HR = 1.377, P = 0.191), remained a significant predictor of death; when TC, HDL-c, lipoprotein(a), and MELD score were included in the multivariate Cox regression analysis, HDL-c (HR = 1.844, P = 0.024) was the only independent predictor of death.Decreased levels in specific components of lipid profile indicate more decompensation events, worse liver function, and reduced survival in liver cirrhosis. MELD score combined with HDL-c should be promising for the assessment of outcomes of cirrhotic patients.

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.

We evaluated the lipidomic profile of patients with very high-risk atherosclerotic cardiovascular disease (ASCVD) by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-MS). A total of 64 patients with a very high risk of ASCVD were recruited and randomLy divided into the atorvastatin group (20 mg, every night, 4 weeks) or the combined group (evolocumab, 140 mg, once every 2 weeks on top of atorvastatin (20 mg per day)). The level of serum lipids was detected before and after treatment for 4 weeks. The lipid classes of triacylglycerols, cholesteryl esters, and sphingomyelins were analyzed using an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry system. There were 32 patients in each group. After 4 weeks of treatment, the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in both groups and the level of lipoprotein-a (Lp-a) in the combined group were lower. In the combined treatment group, the levels of TC, LDL-C, and Lp-a decreased significantly (P < 0.05) after 4 weeks of treatment. Most of the lipid classes in plasma decreased in the combined group at 4 weeks, especially sphingolipids. Only 1 patient had an adverse event (a rash) in the combined group, which improved after anti-allergic treatment. PCSK9 inhibitors can rapidly and effectively reduce most lipid classes in patients with very-high-risk ASCVD.

Background/ Synopsis: Cholesterol plays an important role in sustaining tumor growth and metastasis in a large variety of cancers. New and powerful cholesterol-lowering drugs are being used in combination to treat cardiovascular diseases. Thus, it becomes intuitive to verify whether these drugs could be combined to induce a cholesterol shortage sufficient to impede tumor progression. Circulating levels of the targets of a new generation of lipid-lowering drugs have not been fully investigated in cancers. Given that drugs directed against PCSK9 (evolocumab, alirocumab, inclisiran), ANGPTL3 (evinacumab) and Lp(a) (pelacarsen) are available, it becomes important to assess circulating levels of these drug targets and their role in cancers. Objective/Purpose: To compare circulating levels of PCSK9, ANGPTL3, and Lp(a) in women with stage III breast cancer versus women with premalignant or benign breast lesions. Methods: Twenty-three plasma samples from women diagnosed with a stage III breast cancer (ductal, lobular or mixed) were matched for age with twenty-three plasma samples from women bearing premalignant (stage 0, n=9) or benign (n= 14) breast lesions. The lipid profile (Apo B, total cholesterol, HDL cholesterol and triglycerides levels) and Lp(a) were measured on a Roche Modular analytical platform, whereas LDL levels were calculated with the Friedewald formula. ANGPTL3 and PCSK9 plasma levels were quantitated by ELISA. All statistical analyses were performed using SAS software version 9.4. Results: PCSK9 levels were significantly higher in women with stage III breast cancer compared to age-matched counterparts presenting a benign lesion (95.9 +/- 27.1 ng/mL vs. 78.5 +/- 19.3 ng/mL, pConclusion: In this cohort of 46 women, PCSK9 levels increased along with the severity of breast disease. Given that PCSK9 plays an important role in maintaining cholesterolemia and has been shown to degrade MHC-I on tumor cells, impeding immune T-cells response to tumors, the association between PCSK9 levels and breast disease severity needs to be further investigated in larger studies.

Objective Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor. We present real-life characteristics of patients with increased Lp(a) levels attending a University Lipid Clinic. Methods We retrospectively studied patients attending the University of Ioannina Hospital Lipid Clinic with Lp(a) levels ≥30 mg/dL who were followed-up for a median of 22 months. Results One hundred eight patients (median age 59 years, 49% females) were included with median Lp(a) levels 67 mg/dL (30–320). Of patients, 25.1% had established atherosclerotic cardiovascular disease (ASCVD): 11.1 and 5.6% positive personal history of myocardial infarction (MI) and stroke, respectively, 6.5% carotid artery disease and 1.9% lower extremities arterial disease (LEAD). In addition, 35.2% of participants had heterozygous familial hypercholesterolemia (heFH), 37.9% positive family history of premature ASCVD, 29.6% hypertension, 12.0% diabetes and 5.5% chronic kidney disease (CKD). Of patients, 67.6% were receiving statin therapy and 16.6% additional ezetimibe at baseline visit, and 83 and 35% were receiving statin treatment and additional ezetimibe, respectively, during follow-up. Low-density cholesterol (LDL-C) levels and LDL-Ccorrected for Lp(a) levels were significantly reduced in lipid-lowering therapy naive patients by 37 and 40% (p 0.05), respectively, during follow-up. Lp(a) levels increased by 9% (p Conclusion Our data confirm the high prevalence of established ASCVD, hFH and positive familial history of premature ASCVD in patients with elevated Lp(a) levels. Lp(a) levels slightly increased during follow-up.

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

Background Lipoprotein(a) (Lp[a]) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Proprotein convertase subtilisin/kexin‐9 monoclonal antibodies (PCSK9mAbs) can lower Lp(a) levels in clinical trials, but their effects in patients with elevated Lp(a) in clinical practice remain unclear. Aims To investigate the effectiveness and safety of PCSK9mAbs in lowering plasma Lp(a) in patients with elevated Lp(a) concentrations in a lipid clinic. Methods This was an open‐label study of 53 adult patients with elevated Lp(a) concentration (≥0.5 g/L). Clinical, biochemical, and safety data were collected before and on treatment with evolocumab or alirocumab over a mean period of 11 months. Results Treatment with a PCSK9mAb resulted in a significant reduction of 0.29 g/L (−22%) in plasma Lp(a) concentration (p.05 in all). 7.5% and 47% of the patients attained a target concentration of Lp(a)

BACKGROUND Lipoprotein(a) has been suggested as an independent risk factor for cardiovascular events in patients with coronary heart disease (CHD). OBJECTIVE This study aimed to investigate the association of lipoprotein(a) with long-term poor prognosis following acute coronary syndromes (ACS) in advanced-age patients. METHODS We enrolled 536 patients aged ≥80 years hospitalized for ACS and plasma lipoprotein(a) concentrations were measured at admission. The primary outcomes were hard CHD events (a composite of fatal or non-fatal myocardial infarction, and CHD death). The secondary outcomes included major adverse cardiovascular events (MACEs), all-cause death and cardiac death. RESULTS During a median 66-month follow-up, 89 hard CHD events occurred. The optimal cutoff points of lipoprotein(a) levels were obtained from ROC curve analyses. Kaplan-Meier curves showed a significantly higher cumulative incidence of hard CHD events, MACEs, all-cause death and cardiac death in high lipoprotein(a) group than that in low lipoprotein(a) group. Multivariate Cox proportional hazards analyses revealed that elevated lipoprotein(a) levels were independently associated with an increased risk of hard CHD events [hazard ratio (HR): 1.714, 95% confidence interval (95%CI): 1.114-2.638], MACEs (HR 1.354, 95%CI: 1.024-1.790), all-cause death (HR 1.804, 95%CI: 1.286-2.532) and cardiac death (HR 1.891, 95%CI: 1.112-3.217). Furthermore, adding lipoprotein(a) to the prognostic model for hard CHD events improved the C-statistic value (P CONCLUSION Elevated lipoprotein(a) levels were associated with an increased risk of hard CHD events, MACEs, all-cause death and cardiac death in the advanced-age patients with ACS, which indicated that routine screening for lipoprotein(a) might aid prognosis and risk assessment.

Background: Lipoprotein(a) (Lp[a]), which consists of a low-density lipoprotein (LDL) bound to apolipoprotein(a), is one of the strongest genetic risk factors for atherosclerotic cardiovascular diseases. Few studies have performed hypothesis-free direct comparisons of the Lp(a) and the LDL proteomes. Our objectives were to compare the Lp(a) and the LDL proteomic profiles and to evaluate the effect of lifelong exposure to elevated Lp(a) or LDL cholesterol levels on the plasma proteomic profile. Methods: We performed a label-free analysis of the Lp(a) and LDL proteomic profiles of healthy volunteers in a discovery (n = 6) and a replication (n = 9) phase. We performed inverse variance weighted Mendelian randomization to document the effect of lifelong exposure to elevated Lp(a) or LDL cholesterol levels on the plasma proteomic profile of participants of the INTERVAL study. Results: We identified 15 proteins that were more abundant on Lp(a) compared with LDL (serping1, pi16, itih1, itih2, itih3, pon1, podxl, cd44, cp, ptprg, vtn, pcsk9, igfals, vcam1, and ttr). We found no proteins that were more abundant on LDL compared with Lp(a). After correction for multiple testing, lifelong exposure to elevated LDL cholesterol levels was associated with the variation of 18 plasma proteins whereas Lp(a) did not appear to influence the plasma proteome. Conclusions: Results of this study highlight marked differences in the proteome of Lp(a) and LDL as well as in the effect of lifelong exposure to elevated LDL cholesterol or Lp(a) on the plasma proteomic profile. Résumé: Contexte: La lipoprotéine(a) (Lp[a]), qui est constituée d’une lipoprotéine de basse densité (LDL) liée à une apolipoprotéine(a), est l’un des plus importants facteurs de risque génétiques de survenue d’une maladie cardiovasculaire athéroscléreuse. Peu d’études comparatives directes sans hypothèse ont porté sur le protéome de la Lp(a) et celui des LDL. Nos objectifs étaient de comparer les profils protéomiques de la Lp(a) et des LDL et d’évaluer l’effet d’une exposition à vie à un taux élevé de Lp(a) ou de cholestérol LDL sur le profil protéomique plasmatique. Méthodologie: Nous avons réalisé une analyse sans marquage des profils protéomiques de la Lp(a) et des LDL chez des volontaires en bonne santé dans le cadre d’une phase de découverte (n = 6) et d’une phase de réplication (n = 9). Pour rendre compte de l’effet d’une exposition à vie à un taux élevé de Lp(a) ou de cholestérol des LDL sur le profil protéomique plasmatique des participants de l’étude INTERVAL, nous avons utilisé une analyse de randomisation Mendélienne avec pondération par l’inverse de la variance. Résultats: Nous avons relevé 15 protéines associées en plus grande abondance à la Lp(a) qu’aux LDL (serping1, pi16, itih1, itih2, itih3, pon1, podxl, cd44, cp, ptprg, vtn, pcsk9, igfals, vcam1 et ttr). Nous n’avons noté aucune protéine associée en plus grande abondance aux LDL qu’à la Lp(a). Après correction pour tenir compte de la multiplicité des tests, l’exposition à vie à un taux élevé de cholestérol LDL a été associée à la variation de 18 protéines plasmatiques, tandis que le taux de Lp(a) ne semblait pas influencer le protéome plasmatique. Conclusions: Les résultats de notre étude font ressortir les différences marquées entre le protéome de la Lp(a) et celui des LDL, ainsi qu’entre l’effet sur le profil protéomique plasmatique de l’exposition à vie à un taux élevé de cholestérol LDL et celui de l’exposition à vie à un taux élevé de Lp(a).

Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as an important regulator of low-density lipoprotein (LDL) receptor processing. Evolocumab and alirocumab are PCSK9 inhibitors; however, little is known about the association between PCSK9 levels and lipid profiles in a general population. Because PCSK9 inhibitors have LDL-C lowering effects, we investigated whether there is a positive correlation between serum PCSK9 levels and LDL-C or lipoprotein(a) [Lp(a)]. Methods: In Uku town, 674 residents (mean age; 69.2 ± 8.3 years) received health check-ups. The participants underwent a physical examination and blood tests, including PCSK9 and Lp(a). Serum PCSK9 and Lp(a) were measured by ELISA and Latex methods, respectively. HOMA-IR was calculated by fasting plasma glucose × insulin levels/405. Results: The mean (range) of PCSK9 and Lp(a) were 211.2 (49–601) ng/mL and 60 (1–107) mg/dL, respectively. Because of a skewed distribution, the log-transformed values were used. With univariate linear regression analysis, PCSK9 levels were associated with Lp(a) (p = 0.028), triglycerides (p < 0.001), and HOMA-IR (p < 0.001), but not with LDL-C (p = 0.138) levels. Multiple stepwise regression analysis revealed that serum PCSK9 levels were independently associated with triglycerides (p < 0.001), Lp(a) (p = 0.033) and HOMA-IR (p = 0.041). Conclusions: PCSK-9 is independently associated with triglycerides, Lp(a) levels, and HOMA-IR, but not LDL-C, in a relatively large general population sample.

Supplemental Digital Content is available in the text., Background: Recent international guidelines have lowered recommended target levels of low-density lipoprotein cholesterol (LDL-C) for patients at very high risk for major adverse cardiovascular events (MACE). However, uncertainty persists whether additional benefit results from achieved LDL-C levels below the conventional targets. Inferences from previous analyses are limited because patients who achieve lower versus higher LDL-C on lipid-lowering therapy differ in other characteristics prognostic for MACE and because few achieved very low LDL-C levels. To overcome these limitations, we performed a propensity score–matching analysis of the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) which compared alirocumab with placebo in 18 924 patients with recent acute coronary syndrome receiving intensive or maximum-tolerated statin treatment. Methods: Patients on alirocumab were classified in prespecified strata of LDL-C achieved at 4 months of treatment: 50 mg/dL (n=2197). For each stratum, MACE (coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) after month 4 was compared in patients receiving placebo with similar baseline characteristics and adherence by using 1:1 propensity score matching. Results: Across achieved LDL-C strata of the alirocumab group, patients differed by baseline LDL-C, lipoprotein(a), use of intensive statin therapy, study medication adherence, and other demographic, medical history, biometric, and laboratory criteria. After propensity score matching, characteristics were similar in corresponding patients of the alirocumab and placebo groups. Treatment hazard ratio, 95% CI, and absolute risk reduction (number per 100 patient-years) for MACE were similar in those with achieved LDL-C 50 mg/dL had poorer adherence and derived less benefit (hazard ratio, 0.87 [95% CI, 0.73–1.04]; absolute risk reduction, 0.62). No safety concerns were associated with a limited period of LDL-C levels

Lipoprotein(a) [Lp(a)] is a cardiovascular factor, for which there is no approved specific lowering treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to have lowering effects on Lp(a). Aim of this systematic review is to synthesize the current literature and quantify the effects of PCSK9 inhibitors on the serum Lp(a) levels in human subjects. Double-blind, phase 2 or 3, randomized-controlled trials comparing PCSK9 inhibitors (alirocumab or evolocumab) to placebo and/or ezetimibe and/or other lipid-lowering therapy were deemed eligible for inclusion. We searched MEDLINE (via PubMed), CENTRAL, Scopus, and Web of Science as of 17 June 2020. Quality assessment was performed using the Revised Cochrane risk-of-bias tool for randomized trials. Forty-three studies were identified (64,107 patients randomized) and 41 studies were included in the quantitative analysis. PCSK9 inhibitors reduced Lp(a) levels by -26.7% (95% CI, -29.5% to -23.9%) with a significant heterogeneity within studies. There was significant difference in Lp(a) change from baseline according to comparator (placebo: mean -27.9%; 95% CI, -31.1% to -24.6% vs. ezetimibe: mean, -22.2%; 95% CI, -27.2% to -17.2%; P = 0.04) and duration of treatment (≤12 weeks: mean, -30.9%; 95% CI, -34.7% to -27.1% vs. >12 weeks: mean, -21.9%; 95% CI, -25.2% to -18.6%; P < 0.01). Meta-regression analysis showed that only the mean percentage change from baseline low-density lipoprotein cholesterol due to the intervention is significantly associated with the effect size difference (P < 0.0001). PCSK9 inhibitors reduced low-density lipoprotein cholesterol by -54% (95% CI -57.6% to -50.6%). There is substantial efficacy of the currently approved PCSK9 inhibitors in the lowering of Lp(a) levels. Dedicated randomized controlled trials are needed to establish the benefit of this intervention.

Background Obesity is associated with adverse cardiovascular outcomes and this is improved following bariatric surgery. Oxidised phospholipids (OxPL) are thought to reflect the pro-inflammatory effects of lipoprotein(a) [Lp(a)], and both are independent predictors of cardiovascular disease. Objective Our study sought to determine the impact of bariatric surgery on OxPL, biomarkers of oxidised LDL (OxLDL) and Lp(a). Methods This is a prospective, observational study of 59 patients with severe obesity undergoing bariatric surgery. Blood samples were obtained prior to surgery and at 6 and 12 months after. Sixteen patients attending the tertiary medical weight management clinic at the same centre were also recruited for comparison. Lipid and metabolic blood parameters, OxLDL, OxPL on apolipoprotein B-100 (OxPL-apoB), IgG and IgM autoantibodies to MDA-LDL, IgG and IgM apoB-immune complexes and Lp(a) were measured. Results Reduction in body mass index (BMI) was significant following bariatric surgery, from median 48 kg/m2 at baseline to 37 kg/m2 at 6 months and 33 kg/m2 at 12 months. OxPL-apoB levels decreased significantly at 12 months following surgery [5.0 (3.2–7.4) to 3.8 (3.0–5.5) nM, p = 0.001], while contrastingly, Lp(a) increased significantly [10.2 (3.8–31.9) to 16.9 (4.9–38.6) mg/dl, p = 0.002]. There were significant post-surgical decreases in IgG and IgM biomarkers, particularly at 12 months, while OxLDL remained unchanged. Conclusions Bariatric surgery results in a significant increase in Lp(a) but reductions in OxPL-apoB and other biomarkers of oxidised lipoproteins, suggesting increased synthetic capacity and reduced oxidative stress. These biomarkers might be clinically useful to monitor physiological effects of weight loss interventions.

High consumption of trans-fatty acids (TFAs) linked with obesity, disorders of lipoproteins, type 2 Diabetes Mellitus (T2DM), risk factors of coronary heart disease, and development of atherosclerosis. The intent of our trials was to assess the possible bad impact of TFAs on the lipid status and focusing on characterizing the physiological alters in an animal model comparing with cis fatty acids. Sixty male albino rats, with nearly similar average weight 170±5wereassignedinto 4 main groups (15 rats per group) and kept on a standard diet set for 12 weeks. All groups received different diet treatment for successive 12 weeks. Group A: control group received a conventional diet, group B received a diet contained 360 gm TFAs inform of partially hydrogenated vegetable oil (PHVO) l kg of diet, group C was fed a High Fat Diet (HFD) contained 360 gm beef tallow l kg of diet for, and group D received a diet containing 360 gm linseed oil l kg of diet. Both feeding of TFAs and HFD resulted in a marked increase in the body weight in reach to the obesity grade with a significant increase (P≤0.05) in leptin and leptin receptor gene expression. Also, a significant increase in Malondialdehyde (MDA) and Lipoprotein-a (Lp-a) and a marked decrease in total antioxidant capacity (TAC). It could be concluded that TFAs induce combined increased body weight, with imbalance in oxidative stress, dyslipidemia, and elevated atherogenic Lipoprotein-a may be leading to development of atherosclerosis and coronary heart disease.

Background: Psoriasis is a chronic inammatory disease with multisystem involvement. Psoriasis is an immune mediated skin disease characterized by hyperproliferation of keratinocytes9 which is initiated and maintained by inammatory mediators. Objective: To determine the serum lipid disturbances in psoriasis. To assess the signicance of lipoprotein (a) levels in psoriasis. Materials And Methods: 30 Number of cases of patients suffering from Psoriasis in the age group of 15-75 was included in the study.30 age and sex matched healthy volunteers served as controls. Results: Signicant elevation in levels of fasting glucose, creatinine, total cholesterol.triglycrides, VLDL, LDL, Lipoprotein (a), and Malondialdehyde (MDA) was observed in cases compared with controls. Conclusions: It is important to measure serum lipid level particularly cholesterol, LDL and TG in psoriatic patients for early screening of hyperlipidemia to evaluate risk to atherosclerosis and vascular obstructive disorders and its complications.