High Levels Of Lp Research Articles

Association between lipoprotein(a) and peripheral arterial disease in coronary artery bypass grafting patients.

Peripheral arterial disease (PAD) affects a large population and is associated with various adverse clinical outcomes. Lipoprotein(a) has proatherogenic properties and is associated with PAD incidence and severity. The aim of this study is to explore the association betweenLP(a) and PAD in coronary artery bypass grafting (CABG) patients. A total of 1001 patients were included and divided into two groups: low Lp(a) group [LP(a) < 30 mg/dL] and high Lp(a) group [LP(a) ≥ 30 mg/dL]. A comparison of PAD incidencediagnosed by ultrasoundwas made between the groups. Multivariate logistic regression was conducted to explore the risk factors for PAD. During the analysis,the influence of diabetes mellitus (DM) and gender on LP(a) serum level was taken into consideration. DM history (odds ratio [OR], 2.330, p = .000 for males; OR, 2.499, p = .002 for females) and age (OR, 1.101, p = .000 for males; OR, 1.071, p = .001 for females) were risk factors for PAD. LP(a) ≥ 30 mg/dL was a risk factor for PAD only in female patients (OR, 2.589, p = .003), while smoking history was a risk factor only in male patients (OR, 1.928, p = .000). LP(a) level was not associated with PAD severity inDM patients of both gender. As for female patients without DM, PAD was more severe in the high LP(a) group. In CABG patients,DM history and age were risk factors for PAD. But a high level of LP(a) was a significant risk factor only in female patients. In addition, we are the first to propose a gender deviation in the correlation betweenLP(a) serum level and severity of PAD diagnosed by ultrasound.

High lipoprotein(a) levels and mitral valve disease: A systematic review

AimsThe role of lipoprotein(a) [Lp(a)] as a possibly causal risk factor for atherosclerotic artery disease and aortic valve stenosis has been well established. However, the information available on the association between Lp(a) levels and mitral valve disease is limited and controversial. The main objective of the present study was to assess the association between Lp(a) levels and mitral valve disease. Data synthesisThis systematic review was performed according to PRISMA guidelines (PROSPERO CRD42022379044). A literature search was performed to detect studies that evaluated the association between Lp(a) levels or single-nucleotide polymorphisms (SNPs) related to high levels of Lp(a) and mitral valve disease, including mitral valve calcification and valve dysfunction. Eight studies including 1,011,520 individuals were considered eligible for this research. The studies that evaluated the association between Lp(a) levels and prevalent mitral valve calcification found predominantly positive results. Similar findings were reported in two studies that evaluated the SNPs related to high levels of Lp(a). Only two studies evaluated the association of Lp(a) and mitral valve dysfunction, showing contradictory results. ConclusionsThis research showed disparate results regarding the association between Lp(a) levels and mitral valve disease. The association between Lp(a) levels and mitral valve calcification seems more robust and is in line with the findings already demonstrated in aortic valve disease. New studies should be developed to clarify this topic.

Relationship of apolipoprotein(a) isoform size with clearance and production of lipoprotein(a) in a diverse cohort

Lipoprotein(a) [Lp(a)] has two main proteins, apoB100 and apo(a). High levels of Lp(a) confer an increased risk for atherosclerotic cardiovascular disease. Most people have two circulating isoforms of apo(a) differing in their molecular mass, determined by the number of Kringle IV Type 2 repeats. Previous studies report a strong inverse relationship between Lp(a) levels and apo(a) isoform sizes. The roles of Lp(a) production and fractional clearance and how ancestry affects this relationship remain incompletely defined. We therefore examined the relationships of apo(a) size with Lp(a) levels and both apo(a) fractional clearance rates (FCR) and production rates (PR) in 32 individuals not on lipid-lowering treatment. We determined plasma Lp(a) levels and apo(a) isoform sizes, and used the relative expression of the two isoforms to calculate a “weighted isoform size” (wIS). Stable isotope studies were performed, using D3-leucine, to determine the apo(a) FCR and PR. As expected, plasma Lp(a) concentrations were inversely correlated with wIS (R2 = 0.27; P = 0.002). The wIS had a modest positive correlation with apo(a) FCR (R2 = 0.10, P = 0.08), and a negative correlation with apo(a) PR (R2 = 0.11; P = 0.06). The relationship between wIS and PR became significant when we controlled for self-reported race and ethnicity (SRRE) (R2 = 0.24, P = 0.03); controlling for SRRE did not affect the relationship between wIS and FCR. Apo(a) wIS plays a role in both FCR and PR; however, adjusting for SRRE strengthens the correlation between wIS and PR, suggesting an effect of ancestry.

Predictive effect of different blood lipid parameters combined with carotid intima-media thickness on coronary artery disease.

Blood lipids disorder and atherosclerosis are closely related to coronary artery disease (CAD). This study aims to compare different blood lipid parameters combined with carotid intima-media thickness (cIMT) in predicting CAD. This was a retrospective study including patients who underwent coronary angiography for highly suspected CAD. Blood samples were taken for lipid profile analysis and cIMT was evaluated by carotid ultrasound. Logistic analysis was used to establish different models of different lipid parameters in predicting CAD. The area under the receiver operating characteristic curve (AUC) was used to examine the predictive value. The optimal lipid parameter was also used to explore the relationship with multi-vessel CAD. Patients were classified into two groups based on whether CAD existed. Compared with non-CAD patients, the CAD group had higher lipoprotein (a) [Lp (a)], apolipoprotein B/apolipoprotein A, total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C and LDL-C/HDL-C. According to the AUCs, Lp (a) combined with cIMT (AUC: 0.713, P < 0.001) had the best performance in predicting CAD compared to other lipid parameters. High level of Lp (a) was also associated with multi-vessel CAD (odds ratio: 1.41, 95% confidence interval: 1.02-1.95, P = 0.036). For patients with highly suspected CAD, Lp (a) better improved the predictive value of CAD rather than most of blood lipid indices, especially in the absence of high levels of LDL-C. Lp (a) also can be used to predict the multi-vessel CAD.

‘Use of lipid-lowering therapy: the guidelines, the drugs or the patient?’

The current step up approach in the therapy of dyslipidemias aims to reduce the amount of LDL cholesterol below a threshold that varies according to the patient's risk category, with a pharmacological approach that sees statins as a fundamental cornerstone. Although absolutely functional in reducing cardiovascular events, this therapeutic algorithm does not yet take into consideration the innumerable phenotypic variables that we can find in dyslipidemic subjects. The ever finer understanding of the pathophysiological mechanisms underlying dyslipidemias in combination with the novelties obtained through DNA genotyping will allow, in the near future, the development of a 'tailor-made' therapy for each category of patients. This article will summarize the most recent evidence regarding the therapy of dyslipidemias, with particular attention to the concept of cumulative exposure and some hypotheses on possible initial therapeutic proposals in patients with diabetes, vasculopathy, with hypertriglyceridaemia and with high levels of Lp (a).

Abstract 10296: Relation of Lipoprotein(a) to Progression of Coronary Artery Calcium: Results From a Pooled Cohort of Mesa, Cardia, and Framingham Offspring Studies

Background: Lipoprotein(a) [Lp(a)] levels and coronary artery calcium (CAC) are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events. Progression of CAC is also associated with greater ASCVD risk. Less well-established is the relation of Lp(a) with progression of atherosclerosis as assessed by progression of CAC. Methods: We included a pooled cohort of 9454 persons without ASCVD at baseline (mean age 55.6 years, 53.5% female, and 31% black) and with multiple measures of CAC (up to 4 over a mean of 7.3 + 3.3 years from baseline CAC measures) from the Multiethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, and Framingham Offspring Studies. Lp(a) was assessed continuously and by category (&lt;15 mg/dL [reference], 15-29 mg/dL, 30-49 mg/dL, 50-69 mg/dL, 70-89 mg/dL, and &gt; 90 mg/dL) in relation to progression of CAC (annualized change in Agatston score) incorporating multiple CAC measures utilizing mixed model regression with time (in years), adjusted for age, sex, race, baseline CAC, and other covariates. Subgroup analyses were done separately in those with baseline CAC. Results: A 50 mg/dL increment of Lp(a) was associated with an adjusted annualized change in CAC score of 3.97 units. Compared to those with Lp(a) levels of &lt;15 mg/dL, those with levels of 50-69 mg/dL, 70-89 mg/dL, and &gt; 90 mg/dL had a statistically significant annualized progression of CAC that was 3.09, 8.70, and 9.46 units greater in adjusted analyses. Progression was greater in those with baseline CAC&gt;0 (Table). Conclusions: Higher levels of Lp(a) are associated with greater progression of atherosclerosis as measured by CAC scores.

The nonlinear correlation between lipoprotein (a) and the prevalence of aortic valve calcification in patients with new-onset acute myocardial infarction

Background Growing studies show that lipoprotein (a) [Lp(a)] is related to calcified aortic valve diseases in general population, while the relationship between Lp(a) and aortic valve calcification (AVC) in patients with new-onset acute myocardial infarction (AMI) remains unclear. Therefore, this study was to evaluate the correlation between Lp(a) and AVC in patients with new-onset AMI. Methods This cross-sectional study included 410 patients with new-onset AMI who were hospitalised in Zhongda Hospital affiliated to Southeast University from January 1, 2020 to December 31, 2021. Multivariable logistic regression, subgroup analysis, generalised additive model, threshold and saturation effect and receiver operator characteristic (ROC) curve were used to explore the association between Lp(a) and AVC. Results Patients with AVC had higher levels of Lp(a) than those without AVC. Multivariable logistic regression analysis showed that higher Lp(a) was still associated with higher risk of AVC after adjusting for confounding factors, and this correlation was robust in most subgroups and sensitivity analyses (p < 0.05). Additionally, the generalised additive model showed that there was a nonlinear correlation between Lp(a) and AVC (P for nonlinearity = 0.037). Threshold and saturation effect analysis indicated that when Lp(a) < 840 mg/L, it was positively correlated with the prevalence of AVC (p < 0.05), but when Lp(a) ≥ 840 mg/L, this correlation no longer existed. Besides, ROC curve analysis demonstrated that Lp(a) had a good diagnostic performance for AVC. Conclusion Lp(a) was independently associated with the prevalence of AVC in patients with new-onset AMI.

Elevated Lipoprotein(a) Linked to Recurrent Cardiovascular Events – A Case Report

Abstract The role of lipoprotein(a) [Lp(a)] in the development of atherosclerosis has been recently recognized, and the current recommendation is to measure Lp(a) once in a lifetime in all individuals, in order to identify those at risk for developing an acute coronary syndrome or recurrent events, even in the absence of other cardiovascular risk factors. We present the case of a middle-aged patient with recurrent cardiovascular events, in whom we identified high levels of Lp(a) as a possible explanation of the recurrent events.

Association of lipoprotein(a) with aortic dissection.

BackgroundLipoprotein(a) [Lp(a)] is associated with coronary atherosclerotic heart disease, aortic stenosis, stroke, and heart failure. We aimed to determine the relationship between Lp(a) and aortic dissection (AD).MethodsTwo hundred patients with AD were included in our case group. The control group consisted of 200 non‐AD people who were age‐ (±5 years) and gender‐matched to the case group. Data were collected retrospectively, including hypertension, smoking, coronary artery disease, diabetes mellitus, Lp(a), total cholesterol, triglyceride, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol. The association between Lp(a) and AD was studied using univariate and multivariate logistic regression analysis.ResultsPatients with AD had greater median Lp(a) concentrations than non‐AD people (152.50 vs. 81.75 mg/L). Lp(a) was associated with AD in a multivariate logistic regression analysis (odds ratio, 8.03; 95% confidence interval, 2.85–22.62), comparing those with Lp(a) quartile 4 with those with Lp(a) quartile 1. Stratified analysis showed that this relationship was observed in both men and women, as well as in older and younger individuals.ConclusionsHigh levels of Lp(a) are strongly associated with AD, independent of other cardiovascular risk factors.

Lipoprotein(a) cholesterol contribution to “LDL-C” lowers the ability of a statin to reduce “LDL-C”

Background and Aims : In patients with high levels of Lp(a), the Lp(a)-Cholesterol is a significant component of the “LDL-C”. This affects the ability of a statin to lower “LDL-C” because statins cannot lower this Lp(a)-Cholesterol component. We provide a method to calculate this effect.Methods: Lp(a)-Cholesterol(mg/dL) equals Lp(a)(nmoles/L) divided by 7.5 based on accepted conversion factors. With Lp(a)-Cholesterol calculated the % of Lp(a)-Cholesterol in the "LDL-C" can be calculated. Then the % of actual LDL-C in the "LDL-C" is known. The % reduction of “LDL-C” by statin therapy is linearly proportional to the % of actual LDL in the “LDL-C” . For example if 20% of "LDL-C" is Lp(a)-Cholesterol then 80% is actual LDL-C. Thus the 50% lowering of "LDL-C" expected with a high intensity statin would be only 80% of 50% which is 40%Tabled 1Lp(a) Level nmoles/L (mg/dL)Lp(a)-C mg/dL%Lp(a)-C of "LDL-C"%actual LDL-C of "LDL-C"%Reduction of "LDL-C of "LDL-C"25 (10)3.33%97%48.5%125 (50)16.715%85%42,5%175 (70)23.321%79%39.5%250 (100)33.330%70%35.0%300 (120)40,036%64%32.0% Open table in a new tab Conclusions: If a Lp(a) level is determined before statin therapy, this method allows the actual percentage reduction expected with statin therapy to be determined. The appropriate level of intensity can thus be chosen. Early repeating of Lp(a) and "LDL-C" may be indicated. Background and Aims : In patients with high levels of Lp(a), the Lp(a)-Cholesterol is a significant component of the “LDL-C”. This affects the ability of a statin to lower “LDL-C” because statins cannot lower this Lp(a)-Cholesterol component. We provide a method to calculate this effect. Methods: Lp(a)-Cholesterol(mg/dL) equals Lp(a)(nmoles/L) divided by 7.5 based on accepted conversion factors. With Lp(a)-Cholesterol calculated the % of Lp(a)-Cholesterol in the "LDL-C" can be calculated. Then the % of actual LDL-C in the "LDL-C" is known. The % reduction of “LDL-C” by statin therapy is linearly proportional to the % of actual LDL in the “LDL-C” . For example if 20% of "LDL-C" is Lp(a)-Cholesterol then 80% is actual LDL-C. Thus the 50% lowering of "LDL-C" expected with a high intensity statin would be only 80% of 50% which is 40% Conclusions: If a Lp(a) level is determined before statin therapy, this method allows the actual percentage reduction expected with statin therapy to be determined. The appropriate level of intensity can thus be chosen. Early repeating of Lp(a) and "LDL-C" may be indicated.

Elevated lipoprotein(a) as a predictor for coronary events in older men

Elevated circulating lipoprotein (a) [Lp(a)] is associated with an increased risk of first and recurrent cardiovascular events; however, the effect of baseline Lp(a) levels on long-term outcomes in an elderly population is not well understood. The current single-center prospective study evaluated the association of Lp(a) levels with incident acute coronary syndrome to identify populations at risk of future events. Lp(a) concentration was assessed in 755 individuals (mean age of 71.9 years) within the community and followed for up to 8 years (median time to event, 4.5 years; interquartile range, 2.5–6.5 years). Participants with clinically relevant high levels of Lp(a) (>50 mg/dl) had an increased absolute incidence rate of ASC of 2.00 (95% CI, 1.0041) over 8 years (P = 0.04). Moreover, Kaplan-Meier cumulative event analyses demonstrated the risk of ASC increased when compared with patients with low (<30 mg/dl) and elevated (30–50 mg/dl) levels of Lp(a) over 8 years (Gray’s test; P = 0.16). Within analyses adjusted for age and BMI, the hazard ratio was 2.04 (95% CI, 1.0–4.2; P = 0.05) in the high versus low Lp(a) groups. Overall, this study adds support for recent guidelines recommending a one-time measurement of Lp(a) levels in cardiovascular risk assessment to identify subpopulations at risk and underscores the potential utility of this marker even among older individuals at a time when potent Lp(a)-lowering agents are undergoing evaluation for clinical use.

The Ability of Lipoprotein (a) Level to Predict Early Carotid Atherosclerosis Is Impaired in Patients With Advanced Liver Fibrosis Related to Metabolic-Associated Fatty Liver Disease.

Hepatic fibrosis reduces the serum level of lipoprotein (a) (Lp(a)) and may affect its accuracy in cardiovascular disease prediction of metabolic-associated fatty liver disease (MAFLD). We aimed to estimate the association between Lp(a) levels and the risk of carotid atherosclerosis in MAFLD patients with advanced fibrosis. This was a cross-sectional study enrolling 4,348 consecutive individuals (1,346 patients with MAFLD and 3,002 non-MAFLD patients) who were admitted to the First Affiliated Hospital, Sun Yat-sen University, and underwent abdominal and carotid ultrasonography from 2015 to 2021. Lp(a) levels, liver biochemical markers, metabolic indices, and anthropometric parameters were measured. Liver fat content and fibrosis severity were assessed by MRI-PDFF, using the NAFLD fibrosis score (NFS) and liver stiffness measurement (LSM) of two-dimensional shear wave elastography, respectively. There was an L-shaped relationship between Lp(a) levels and LSMs in patients with MAFLD, and Lp(a) levels had a different relationship with liver fat content in MAFLD patients with F1-2 versus those with F3-4. Non-MAFLD patients had higher levels of Lp(a) than MAFLD patients with or without advanced fibrosis (both P < 0.05). Lp(a) levels and degree of liver fibrosis were both positively correlated with carotid atherosclerosis in patients with MAFLD. Lp(a) levels performed well on carotid atherosclerosis risk prediction for non-MAFLD patients with an area under the curve (AUC) of 0.819, which was significantly better than the carotid atherosclerosis risk prediction for MAFLD patients with NFS ≤ -1.836 (AUC: 0.781), NFS > -1.836 (AUC: 0.692), and LSM ≥ 9.0 kPa (AUC: 0.635) (all P < 0.05). Advanced liver fibrosis significantly reduces the predictive value of Lp(a) levels for the risk of carotid atherosclerosis in patients with MAFLD.

Cascade testing for elevated lipoprotein(a) in relatives of probands with high lipoprotein(a)

ObjectiveElevated lipoprotein(a) [Lp(a)] is a common inherited condition associated with cardiovascular disease. This study investigated whether cascade testing for Lp(a) was effective in detecting new cases of elevated Lp(a) in families. MethodsRelatives from adult probands with Lp(a) concentration ≥100 mg/dL were tested for elevated Lp(a) (≥50 mg/dL) via a cascade testing program in a tertiary hospital setting. The prevalence and yield of detecting new cases of elevated Lp(a) among the relatives were assessed. ResultsOf the 83 probands, 43.4% had familial combined hyperlipidemia (FCHL) and 34.9% common hypercholesterolemia (CH). Among 182 relatives tested (151 adults and 31 children), elevated Lp(a) was found in 68.1%, with 32.9% having Lp(a) between 50 and 99 mg/dL and 35.2% having Lp(a) ≥100 mg/dL. One new case of elevated Lp(a) ≥50 mg/dL was identified for every 1.5 relatives tested and 1 new case of elevated Lp(a) ≥100 mg/dL for every 2.8 relatives tested. The proportion of relatives detected with elevated Lp(a) was significantly higher when tested from probands with Lp(a) >150 mg/dL compared with those with Lp(a) between 100 and 150 mg/dL (81.1% vs. 55.5%; P = 0.001). The concordance rates (kappa coefficient) for the detection of elevated Lp(a) with FCHL and CH were 34.8% (0.026) and 53.2% (0.099), respectively. ConclusionCascade testing for elevated Lp(a) from affected probands with phenotypic dyslipidemia is highly effective in identifying new cases of high Lp(a) in families. The yield of detecting elevated Lp(a) is greater when probands have higher levels of Lp(a) and exceeds the detection of relatives with FCHL and CH.

Assessment of the role of lipoprotein a level in the development of cardiovascular diseases

A comparative trial within 2 groups of patients with cardiovascular diseases who have high and normal levels of lipoprotein (a) was conducted to determine the link between high levels of Lp (a) and the nature of the development of cardiovascular events. According to the results of the study, conclusions about the significance of the level of Lp(a), as well as hypolipidemic therapy in patients with cardiovascular pathology were made. The features of the population of patients with an expected increase in Lp(a) and the predominance of lesions of the brachiocephalic arteries among individuals with increased Lp(a) were revealed. Hypolipidemic statin therapy with a passable correction of the lipid spectrum does not always allow to control the increase in Lp(a)

Abstract MP47: Assessment Of Atherosclerosis In A Novel Transgenic Mouse Expressing Pathogenic Levels Of Human Lipoprotein(a)

Studying the role of elevated plasma levels of lipoprotein(a) (Lp(a)) in atherogenesis is challenging given that the LPA gene encoding apo(a) is absent in typical animal models. As such we created a novel transgenic mouse line expressing both human apolipoprotein(a) (apo(a)) and human apoB100 ((Tg(LPA +/0 ;APOB +/0 )) . The LPA transgene, assembled in the pLIV vector, produces a physiologically relevant 12-kringle apo(a) isoform. The APOB transgene contains the entire human APOB gene with a mutation preventing APOB editing. In our atherosclerosis model, male and female mice were injected weekly with an antisense oligonucleotide targeting the mouse LDL receptor (IONIS Pharmaceuticals), and fed a high-fat, high-cholesterol diet for 12 weeks. High plasma Lp(a) levels were observed in both male and female Tg(LPA +/0 ;APOB +/0 ) mice (219.0±11.9 and 133.7±12.1 mg/dL, respectively; n=12/group). Importantly, high levels of Lp(a) in plasma did not result in metabolic alterations, including differences in weight gain, energy expenditure, activity, RER, VO 2 /VCO 2 consumption/output, and glucose tolerance compared to Tg(APOB +/0 ) control mice. Both male and female Tg(LPA +/0 ;APOB +/0 ) and Tg(APOB +/0 ) mice exhibited enhanced proatherogenic lipoprotein profiles with the majority of the cholesterol and TG present in the VLDL and LDL fractions. Complex lesions developed in all transgenic mice, including large, lipid-rich necrotic cores, with overlying fibrous caps and intimal calcium deposition. Immunohistochemistry with a monoclonal apo(a) antibody revealed the presence of Lp(a) in the plaques of Tg(LPA +/0 ;APOB +/0 ) mice. Analysis of aortic sinus lesions revealed a 23% increase in total plaque area in female Tg(LPA +/0 ;APOB +/0 ) mice compared to female Tg(APOB +/0 ) mice (p=0.0836). Moreover, atherosclerotic plaques in female Tg(LPA +/0 ;APOB +/0 ) mice contained significantly more calcium deposition than female Tg( APOB +/0 ) mice (1.79±0.4% vs. 2.96 ±0.3% of total plaque area (p&lt;0.05)). No differences in plaque area or calcium were observed in male mice. In this ongoing study, detailed analyses of atherosclerotic plaque components in Tg(LPA +/0 ;APOB +/0 ) mice will be required to uncover the unique contribution of Lp(a) to atherogenesis.

Lipoprotein(a) Where Do We Stand? From the Physiopathology to Innovative Terapy.

A number of epidemiologic studies have demonstrated a strong association between increasing lipoprotein a [Lp(a)] and cardiovascular disease. This correlation was demonstrated independent of other known cardiovascular (CV) risk factors. Screening for Lp(a) in the general population is not recommended, although Lp(a) levels are predominantly genetically determined so a single assessment is needed to identify patients at risk. In 2019 ESC/EAS guidelines recommend Lp(a) measurement at least once a lifetime, fo subjects at very high and high CV risk and those with a family history of premature cardiovascular disease, to reclassify patients with borderline risk. As concerning medications, statins play a key role in lipid lowering therapy, but present poor efficacy on Lp(a) levels. Actually, treatment options for elevated serum levels of Lp(a) are very limited. Apheresis is the most effective and well tolerated treatment in patients with high levels of Lp(a). However, promising new therapies, in particular antisense oligonucleotides have showed to be able to significantly reduce Lp(a) in phase II RCT. This review provides an overview of the biology and epidemiology of Lp(a), with a view to future therapies.

Evaluation of cardiovascular events and progression to end-stage renal disease in patients with dyslipidemia and chronic kidney disease from the North-Eastern area of Romania.

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 ± 10.9years, 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 12months 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 > 220ng/mL was a predictor of cardiovascular events, while the EF < 50% was a predictor for renal outcomes. For CKD patients with PCSK9 > 220ng/mL and hsCRP > 3mg/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 > 220ng/mL was predictor for cardiovascular events, while EF < 50% was predictor for CKD progression to ESRD. PCSK9 > 220ng/mL and hsCRP > 3mg/L were associated with the occurrence of renal and cardiovascular events earlier.

Associations of Lipoprotein(a) With Coronary Atherosclerotic Burden and All-Cause Mortality in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention.

Background: The coronary atherosclerotic burden in patients with ST-segment elevation myocardial infarction (STEMI) has been identified as the main predictor of prognosis. However, the association of lipoprotein(a) [Lp(a)], a well-established proatherogenic factor, with atherosclerotic burden in patients with STEMI is unclear.Methods: In total, 1,359 patients who underwent percutaneous coronary intervention (PCI) for STEMI were included in analyses. Three prespecified models with adjustment for demographic parameters and risk factors were evaluated. Generalized additive models and restricted cubic spline analyses were used to assess the relationships of Lp(a) with Gensini scores and the no-reflow phenomenon. Kaplan–Meier curves were generated to explore the predictive value of Lp(a) for long-term all-cause mortality. Furthermore, mRNA expression levels of LPA in different groups were compared using the GEO database.Results: Patients in the highest tertile according to Lp(a) levels had an increased incidence of heart failure during hospitalization. Furthermore, patients with high levels of Lp(a) (>19.1 mg/dL) had sharply increased risks for a higher Gensini score (Pfor trend = 0.03) and no-reflow (Pfor trend = 0.002) after adjustment for demographic parameters and risk factors. During a median follow-up of 930 days, 132 deaths (9.95%) were registered. Patients with high levels of Lp(a) (>19.1 mg/dL) had the worst long-term prognosis (Pfor trend < 0.0001). In a subgroup analysis, patients with higher Lp(a) still had the highest all-cause mortality. Additionally, the mRNA expression levels of LPA in patients with STEMI with lower cardiac function were higher than those in other groups (P = 0.003). A higher coronary atherosclerotic burden was correlated with higher LPA expression (P = 0.01).Conclusion: This study provides the first evidence that Lp(a) (at both the protein and mRNA levels) is independently associated with coronary atherosclerotic lesions and prognosis in patients with STEMI treated with PCI.Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier: ChiCTR1900028516.

Mental health is correlated with lipoprotein(a) levels in male patients with premature coronary heart disease.

High levels of lipoprotein(a) (Lp(a)) is an independent risk factor for premature coronary heart disease (PCHD). It is also considered a residual risk for controlled low density lipoprotein cholesterol (LDL-C). Dietary control, exercise, and drugs have limited effects on the levels of Lp(a). Recently, mental health was found to be associated with lipid levels and increased risk of PCHD. However, the relationship between mental health and Lp(a) is still unknown. This study explored the association between mental health and Lp(a) levels in men with PCHD. A retrospective, observational study was conducted. A total of 226 male patients with PCHD, aged 49.65±3.68 years, was included in this study. The control group consisted of 230 age-matched healthy male volunteers. Serum Lp(a) levels ≥30 mg/dL, as measured by the immunoturbidimetry method, were considered high. All participants received health related quality of life (HRQoL) scores using the self-assessed 36-Item Short Form Health Survey (SF-36). The HRQoL includes both a physical component summary (PCS) and a mental component summary (MCS). Patients with PCHD were found to have higher levels of Lp(a) (51.61±33.39 vs. 26.42±21.93, P<0.001), and lower MCS (35.83±4.21 vs. 39.85±4.12) and PCS scores (38.02±3.73 vs. 39.63±3.21) compared to healthy volunteers. The MCS score was negatively correlated with Lp(a) levels in the PCHD group (R=-0.295, P<0.001), but no correlation was detected in the control group. There was no relationship between the PCS score and Lp(a) levels in neither the PCHD group nor the healthy control group. Multivariate logistic regression analysis indicated that the MCS and PCS scores were negatively correlated with the risk of PCHD. These findings suggested that poor mental health may be associated with high levels of Lp(a) and increased risk of PCHD in men. Therefore, improving the mental state in men with PCHD may be crucial.

300-OR: Association of Raised Lipoprotein(a) Levels with Micro- and Macrovascular Complications in Patients with Type 1 Diabetes

Background: Raised levels of lipoprotein(a) [Lp(a)] are causally associated with incident macroangiopathy and aortic valvular calcification in (non)diabetic subjects. Objective: In type 2 diabetes (T2DM), there is an inverse, J-shaped relationship between elevated Lp(a) and prevalent microangiopathies. This work assessed whether this inverse association also exists in type 1 diabetes (T1DM). Methods: The cardiometabolic phenotype of 357 patients with T1DM was determined, alongside routine lipids, Lp(a), non-Lp(a)-LDL-C, apolipoprotein B100, apolipoprotein A-I, and atherogenic dyslipidemia. Patients in the 1st tertile of Lp(a) ([TI]; n=119; median Lp(a) 6 nmol/L) were compared to those in the 3rd tertile of Lp(a) ([TIII]; n=119; median Lp(a) 100 nmol/L). Results: There were no significant differences between [TI] and [TIII] patients regarding gender, diabetes duration, HbA1c, smoking, BMI, hypertension, GFR, (micro)albuminuria, cerebrovascular disease, routine lipids (total C; LDL-C; HDL-C; TG), apolipoprotein B100, apolipoprotein A-I, non-Lp(a)-LDL-C, and frequency/intensity of statin use. Compared to [TIII], [TI] patients were younger (48 vs. 53 years), had lower body fat (24 vs. 27%), and higher muscle mass (36 vs. 34%; all p&amp;lt;0.05). After adjusting for age, [TIII] had more overall microangiopathy (+37%; 57 vs. 45%) and diabetic retinopathy (+34%; 51 vs. 38%; 0.0441). They also had an increased prevalence of overall macroangiopathy (+211%; 19 vs. 9%; p 0.0265) and coronary artery disease (+250%; 15 vs. 6%; p 0.0238). Among [TIII] patients, 35% were in the highest CV risk category, vs. 16% of [TI] (p 0.0008). Conclusion: In addition to the risk of macrovascular complications, a high level of Lp(a) is associated with an increased frequency of retinal microangiopathy in T1DM patients, contrary to what was observed in T2DM. On the other hand, the frequency of macroangiopathy was increased in T1DM just like in T2DM and nondiabetic patients. Disclosure S. Van haare heijmeijer: None. M. P. Hermans: None.