Lp Values Research Articles

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.

P192 LONG TERM PROGNOSTIC EFFECT OF LIPROTEIN(A) IN PATIENTS WITH AND WITHOUT DIABETES MELLITUS AFTER MYOCARDIAL INFARCTION

Abstract Aims To describe the baseline clinical, laboratory and angiographic characteristics of patients with acute myocardial infarction (MI) according to the presence or not of diabetes mellitus (DM), and to evaluate if DM may influence the effect of lipoprotein(a) [Lp(a)] serum level on long–term outcome in this very high–risk population. Methods This was a retrospective, single–center, study including consecutive patients admitted with MI diagnosis between January 1, 2017, and December 31, 2020. The availability of data on baseline Lp(a) serum level was considered as an inclusion criterion. The study population was divided into two groups according to the presence or not of DM. The Lp(a) value of 50 mg/dL was used to test the hypothesis of a different effect of Lp(a) on the clinical outcome of patients with or without DM. The primary study outcome was all–cause death at 3–year follow–up. Results The study population included 997 patients (mean age 63.7±13.5 years; 75.7% were males). Diabetes was reported in 280 (28.1%) patients. DM patients were older than those without DM (67.8±12.1 vs. 62.0±13.7 years, p &amp;lt; 0.001) and showed a significantly higher prevalence of dyslipidemia, hypertension, obesity, prior MI and prior coronary revascularization (p &amp;lt; 0.001). DM patients showed higher SYNTAX score value (19.8 vs. 15.1, p &amp;lt; 0.001) and a higher prevalence of left main involvement (6.3 vs. 3.1, p = 0.023). At Kaplan–Meier analysis, in the group without DM, patients with Lp(a)≥50 mg/dL showed a significantly lower long–term survival compared with those with Lp(a)&amp;lt;50 mg/dL (Log–Rank=0.004). In DM patients DM, conversely, no survival difference was found between patients with Lp(a)≥50 mg/dL vs. those with Lp(a)&amp;lt;50 mg/dL. At multivariable Cox regression analysis, in patients without DM, Lp(a) serum level (HR: 2.68, 95% CI 1.23–5.83; p = 0.013) and age (HR: 1.06, 95% CI 1.04–1.09; p &amp;lt; 0.001) were independent predictors of mortality at 3–year follow–up. Among DM patients, only age was independently associated with 3–year mortality (HR: 1.07, 95% CI 1.03–1.10; p &amp;lt; 0.001) (Table). Conclusion In this MI population, Lp(a) was independently associated with long–term mortality in patients without DM, but not in patients with DM. Whether DM can modify the effect of Lp(a) on clinical outcome after MI requires confirmation by larger prospective studies.

Moderately elevated lipoprotein (a) levels are associated with an earlier need for percutaneous coronary intervention in recurrent cardiovascular disease.

A significant number of cardiovascular disease (CVD) patients, with the target lipid levels, as set by the guidelines, achieved, continue to remain at risk. In this setting, lipoprotein (Lp) a role in CVD prognosis is regaining interest. Although Lp(a) is related to the arteriosclerotic process, there is not currently an adequate amount of data for the inclusion of Lp(a) levels as a primary therapeutic target in the treatment of coronary artery disease (CAD) patients. In this framework, the current retrospective study aims to investigate the association of Lp(a) levels with the adverse cardiovascular (CV) events presented in a 10 year follow-up of CVD patients with dyslipidemia and its association with the major CV risk factors. A statistically significant reduction in Lp(a) levels was observed during the follow-up period (72.8±45.6 vs. 68.3±41.8 mg/dl; McNemar test; P<0.001). The vast majority of patients who suffered a new acute myocardial infarction during the follow up period had Lp(a) levels >30 mg/dl (24/28 patients, mean ± standard deviation Lp(a), 83.1±36.6 mg/dl, P=0.001). Kaplan-Meier survival analysis did not find statistically significant differences in a percutaneous coronary intervention (PCI) time occurrence during the follow-up period between patients with low (≤30 mg/dl) and high (>30 mg/dl) Lp(a) levels (log-rank P=0.305). On the other hand, when a second and third PCI conducted during the monitoring period were included in the Kaplan Meier analysis as events, the mean time for a PCI was significantly shorter (7.2%; P=0.01) for patients with Lp(a) levels >30 mg/dl. In conclusion, the current study reported that patients with high Lp(a) values are more prone to the occurrence of new myocardial infarction, while the Lp(a) cut-off value of 30 mg/dl was linked in CVD patients to an earlier need for PCI, especially in the most vulnerable group of patients with more than one (recurrent) revascularizations.

Association of lipoprotein (a) with coronary artery disease in a South Asian population: A case-control study.

Coronary artery disease (CAD), the leading cause of mortality worldwide, is characterised by an earlier onset and more severe disease in South Asians as compared to Western populations. This is an observational study on 928 individuals who attended three tertiary care centres in Kerala, India from 2014-to 2017. The demographic, anthropometric, behavioural factors and the lipoprotein (Lp(a)) and cholesterol values were compared between the two groups and across disease severity. The Chi-square test was used to compare the categorical variables and independent sample t-test for the continuous variables. Multivariable logistic regression was performed to investigate the association of demographic, clinical and behavioural factors with the disease. Odds ratios are presented with a 95% confidence interval. In individuals below 50 years, two logistic regression models were compared to investigate the improvement in modelling the association of the independent factors and Lp(a) with the occurrence of the disease. We included 682 patients in the diseased group and 246 patients treated for non-coronary conditions in the control group. Those in the control group were significantly younger than in the diseased group(p<0.002). Significantly more patients were diabetic, hypertensive, tobacco users and consumers of alcohol in the diseased group. Multivariable logistic regression on data from all age groups showed that age (OR = 2.55, 95% CI 1.51-4.33, p = 0.01), diabetes (OR = 3.71, 95% CI 2.42-5.70, p = 0.01), hypertension (OR = 3.03, 95% CI 2.12-4.34, p = 0.01) and tobacco use (OR = 5.44, 95% CI 3.39-8.75, p = 0.01) are significantly associated with the disease. Lp(a) (OR = 1.22, 95% CI 0.87-1.72) increased the odds of the disease by 22% but was not statistically significant. In individuals below 50 years, Lp(a) significantly increased the likelihood of CAD (OR = 3.52, 95% CI 1.63-7.57, p = 0.01). Those with diabetes were seven times more likely to be diseased (OR = 7.06, 95% CI 2.59-19.21, p = 0.01) and the tobacco users had six times the likelihood of disease occurrence (OR = 6.38, 95% CI 2.62-15.54, p = 0.01). The median Lp(a) values showed a statistically significant increasing trend with the extent/severity of the disease in those below 50 years. Age, diabetes, hypertension and tobacco use appear to be associated more with the occurrence of coronary artery disease in adults of all ages. Lipoprotein(a), cholesterol and BMI categories do not seem to be related to disease status in all ages. However, in individuals below 50 years, diabetes, tobacco use and lipoprotein (a) are significantly associated with the occurrence of the disease.

Elevated lipoprotein (a) levels and risk of peripheral artery disease outcomes: A systematic review

Despite strong association of elevated lipoprotein (a) (Lp(a)) levels with incident coronary and cerebrovascular disease, data for incident peripheral artery disease (PAD) are less robust. The main objective of the present systematic review was to analyze the association between elevated Lp(a) levels and PAD outcomes. This systematic review was performed according to PRISMA guidelines. A literature search was performed to detect randomized clinical trials or observational studies with a cohort design that evaluated the association between Lp(a) levels and PAD outcomes. Fifteen studies including 493,650 subjects were identified and considered eligible for this systematic review. This systematic review showed that the vast majority of the studies reported a significant association between elevated Lp(a) levels and the risk of PAD outcomes. The elevated Lp(a) levels were associated with a higher risk of incident claudication (RR: 1.20), PAD progression (HR: 1.41), restenosis (HR: 6.10), death and hospitalization related to PAD (HR: 1.37), limb amputation (HR: 22.75), and lower limb revascularization (HR: 1.29 and 2.90). In addition, the presence of elevated Lp(a) values were associated with a higher risk of combined PAD outcomes, with HRs in a range between 1.14 and 2.80, despite adjusting for traditional risk factors. Heterogeneity of results can be explained by different patient populations studied and varying Lp(a) cut-off points of Lp(a) analyzed. This systematic review suggests that evidence is available to support an independent positive association between Lp(a) levels and the risk of future PAD outcomes. PROSPERO Registration No.: 289253.

The relationship between lipoprotein(a) and cardiovascular events in acute coronary syndrome patients with and without chronic kidney disease

Background and aimsPatients with chronic kidney disease (CKD) have high residual risk of cardiovascular events, whether the residual risk is associated with elevated level of lipoprotein(a) [Lp(a)] is unascertained. We aimed to explore the impact of Lp(a) levels on the risk of major adverse clinical events (MACEs) in CKD patients hospitalized for acute coronary syndrome (ACS) compared to those without CKD. MethodsThe data of patients hospitalized for ACS were collected at the China-Japan Friendship Hospital from January 2015 to December 2019. Patients were divided into 2 groups according to renal function: non-CKD group (eGFR≥60 ml/min/1.73 m2) and CKD group (eGFR <60 ml/min/1.73 m2). Multivariate Cox regression analysis and restricted cubic splines were performed to explore the relationship between Lp(a) levels and MACEs. ResultsA total of 1306 patients were enrolled. Patients with CKD had higher Lp(a) concentrations compared with those without CKD. During a median follow-up of 3.9 years, an elevated Lp(a) value was an independent predictor for MACEs in the overall population. Patients with a high Lp(a) level had higher risk of MACEs than those with a low Lp(a) level, regardless of renal function. The association between higher Lp(a) levels and MACEs remained consistent using the cut-off value of median (11.57 mg/dL), 30 mg/dL and 50 mg/dL in patients with CKD. On the contrary, Lp(a) higher than 50 mg/dL was associated with significantly higher risk of MACEs in patients without CKD. ConclusionsWe confirmed that a high Lp(a) level was associated with long term adverse outcomes in ASC patients, especially in those with CKD.

Impact of Lipoprotein(a) concentrations on long-term cardiovascular outcomes in patients undergoing percutaneous coronary intervention: A large cohort study

Background and aimsTill now, the prognostic value of lipoprotein(a) [Lp(a)] in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) remains controversial. We therefore conducted this study to evaluate the effect of Lp(a) levels on clinical outcomes in this population. Methods and resultsA total of 10,059 CAD patients who underwent PCI were prospectively enrolled in this cohort study, of which 6564 patients had Lp(a) ≤30 mg/dl and 3495 patients had Lp(a) > 30 mg/dl. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction, stroke or unplanned revascularization. Multivariate Cox regression analysis and propensity-score matching analysis were performed. After propensity-score matching, 3449 pairs of patients were identified, and post-matching absolute standardized differences were <10% for all the covariates. At 2.4 years, the risk of MACCE was significantly higher in patients with elevated Lp(a) levels than those with normal Lp(a) levels in both overall population (13.0% vs. 11.4%; adjusted hazard ratio [HR] 1.142, 95% confidence interval [CI] 1.009–1.293; P = 0.040) and propensity-matched cohorts (13.0% vs. 11.2%; HR 1.167, 95%CI 1.019–1.337; P = 0.026). Of note, the predictive value of Lp(a) levels on MACCE tended to be more evident in individuals >65 years or those with left main and/or three-vessel disease. On the contrary, elevated Lp(a) levels had almost no effect on clinical outcomes in patients ≤65 years (P interaction = 0.021) as well as those who had one- or two-vessel coronary artery disease (P interaction = 0.086). ConclusionIn CAD patients who underwent PCI, elevated Lp(a) levels were positively related to higher risk of MACCE at 2.4-year follow-up, especially in patients >65 years and those with left main and/or three-vessel disease. Registration numbernot applicable.

Elevated lipoprotein(a) levels as an independent predictor of long-term recurrent events in patients with acute coronary syndrome: an observational, retrospective cohort study.

BackgroundWhether lipoprotein(a) [Lp(a)] is associated with recurrent cardiovascular events (RCVEs) still remains controversial. The present study aimed to investigate the prognostic value of Lp(a) for long-term RCVEs and each component of it in people with acute coronary syndrome (ACS).MethodsThis multicenter, observational and retrospective study enrolled 765 ACS patients at 11 hospitals in Chengdu from January 2014 to June 2019. Patients were assigned to low-Lp(a) group [Lp(a) < 30 mg/dl] and high-Lp(a) group [Lp(a) ≥ 30 mg/dl]. The primary and secondary endpoints were defined as RCVEs and their elements, including all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke and unplanned revascularization.ResultsOver a median 17-month follow-up, 113 (14.8%) patients presented with RCVEs were reported, among which we observed 57 (7.5%) all-cause deaths, 22 (2.9%) cases of nonfatal stroke, 13 (1.7%) cases of nonfatal MI and 33 (4.3%) cases of unplanned revascularization. The incidences of RCVEs and revascularization in the high-Lp(a) group were significantly higher than those in the low-Lp(a) group (P < 0.05), whereas rates of all-cause death, nonfatal stroke and nonfatal MI were not statistically different (P > 0.05). Kaplan–Meier analysis also revealed the same trend. Multivariate Cox proportional hazards analysis showed that 1-SD increase of Lp(a) was independently associated with both the primary endpoint event [hazard ratio (HR), 1.285 per 1-SD; 95% confidence interval (CI), 1.112–1.484; P < 0.001] and revascularization (HR, 1.588 per 1-SD; 95% CI, 1.305–1.932; P < 0.001), but not with the other secondary events.ConclusionIncreased Lp(a) is an independent predictor of RCVEs and unplanned revascularization in patients with ACS.

A general mathematical model for the in vitro assembly dynamics of intermediate filament proteins

Intermediate filament (IF) proteins assemble into highly flexible filaments that organize into complex cytoplasmic networks: keratins in all types of epithelia, vimentin in endothelia, and desmin in muscle. Since IF elongation proceeds via end-to-end annealing of unit-length filaments and successively of progressively growing filaments, it is important to know how their remarkable flexibility, i.e., their persistence length lp, influences the assembly kinetics. In fact, their lp ranges between 0.3 μm (keratin K8/K18) and 1.0 μm (vimentin and desmin), and thus is orders of magnitude lower than that of microtubules and F-actin. Here, we present a unique mathematical model, which implements the semiflexible nature of the three IF types based on published semiflexible polymers theories and depends on a single free parameter k0. Calibrating this model to filament mean length dynamics of the three proteins, we demonstrate that the persistence length is indeed essential to accurately describe their assembly kinetics. Furthermore, we reveal that the difference in flexibility alone does not explain the significantly faster assembly rate of keratin filaments compared with that of vimentin. Likewise, desmin assembles approximately six times faster than vimentin, even though both their filaments exhibit the same lp value. These data strongly indicate that differences in their individual amino acid sequences significantly impact the assembly rates. Nevertheless, using a single k0 value for each of these three key representatives of the IF protein family, our advanced model does accurately describe the length distribution and mean length dynamics and provides effective filament assembly rates. It thus provides a tool for future investigations on the impact of posttranslational modifications or amino acid changes of IF proteins on assembly kinetics. This is an important issue, as the discovery of mutations in IF genes causing severe human disease, particularly for desmin and keratins, is steadily increasing.

Distribution of the critically endangered javan blue-banded kingfisher Alcedo euryzona along the Welo River flow in the Petungkriyono forest

This research was aimed to determine the ecological factors that can affect the distribution of Alcedo euryzona and its relationship with the quantification of human anthropogenic activities in the vicinity. The research was conducted using the point count method with 7 observation points along the Welo River (±5,096 km). Based on the analysis, the distribution pattern of Alcedo euryzona is uniformly based on Morisita’s index with a value of lp < 0 (-0,033). Whereas the relationship between the existence of species and anthropogenic activity based on hypothesis test in binary logistic analysis partially has no significant effect with a value > 0,05 (0,999). The ecological factors that influence the existence of the species include river shoulders, temperature, and altitude.

Value of repeated measurements of lipoprotein (a) to assess cardiovascular risk: a retrospective study

Background: High plasma concentrations of lipoprotein (a) [Lp(a)] are associated with an increased cardiovascular risk. Current guidelines recommend measurement of only a single Lp(a) in an individual’s lifetime under specific circumstances to improve cardiovascular risk prediction. Accordingly, the question raised is the number of false positives and negatives missed through only a single measurement. Methods: All Lp(a) measurements between 2004 and March 2021 were retrieved from the laboratory database of the Erasme hospital. Only patients with repeated measurement were included. The first and subsequent Lp(a) measurement were compared. Two different cohorts were studied as a result of a change in Lp(a) determination methodology (n = 2049 and n = 309, respectively). The effects of a third Lp(a) measurement were assessed through binary analyses (n = 678). The 180 mg/dl (430 nmol/L) threshold recommended in the ESC guidelines was assessed first. Analysis was repeated for 100, 70 and 50 mg/dl thresholds of raised Lp(a) levels. Results: A low rate of false negatives (0.8%–1%) and false positives (0.6–0.3%) were revealed with two Lp(a) measurements. There was no difference in regards to the divergent Lp(a) thresholds nor the measurement of Lp(a) on two or three occasions. Conclusion: The present study showed Lp(a) determination to be reproducible. A single measurement is sufficient to assess if a patient exceeds various cut-off values of elevated Lp(a) levels.

Assessing the Accuracy of Estimated Lipoprotein(a) Cholesterol and Lipoprotein(a)‐Free Low‐Density Lipoprotein Cholesterol

BackgroundAccurate measurement of the cholesterol within lipoprotein(a) (Lp[a]‐C) and its contribution to low‐density lipoprotein cholesterol (LDL‐C) has important implications for risk assessment, diagnosis, and treatment of atherosclerotic cardiovascular disease, as well as in familial hypercholesterolemia. A method for estimating Lp(a)‐C from particle number using fixed conversion factors has been proposed (Lp[a]‐C from particle number divided by 2.4 for Lp(a) mass, multiplied by 30% for Lp[a]‐C). The accuracy of this method, which theoretically can isolate “Lp(a)‐free LDL‐C,” has not been validated.Methods and ResultsIn 177 875 patients from the VLDbL (Very Large Database of Lipids), we compared estimated Lp(a)‐C and Lp(a)‐free LDL‐C with measured values and quantified absolute and percent error. We compared findings with an analogous data set from the Mayo Clinic Laboratory. Error in estimated Lp(a)‐C and Lp(a)‐free LDL‐C increased with higher Lp(a)‐C values. Median error for estimated Lp(a)‐C <10 mg/dL was −1.9 mg/dL (interquartile range, −4.0 to 0.2); this error increased linearly, overestimating by +30.8 mg/dL (interquartile range, 26.1–36.5) for estimated Lp(a)‐C ≥50 mg/dL. This error relationship persisted after stratification by overall high‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol subtypes. Similar findings were observed in the Mayo cohort. Absolute error for Lp(a)‐free LDL‐C was +2.4 (interquartile range, −0.6 to 5.3) for Lp(a)‐C<10 mg/dL and −31.8 (interquartile range, −37.8 to −26.5) mg/dL for Lp(a)‐C≥50 mg/dL.ConclusionsLp(a)‐C estimations using fixed conversion factors overestimated Lp(a)‐C and subsequently underestimated Lp(a)‐free LDL‐C, especially at clinically relevant Lp(a) values. Application of inaccurate Lp(a)‐C estimations to correct LDL‐C may lead to undertreatment of high‐risk patients.

S-PRG-based toothpastes compared to NaF toothpaste and NaF varnish on dentin permeability in vitro.

ObjectivesTo analyze the effect of 5 toothpastes containing different percentages of S-PRG fillers compared to NaF toothpaste and NaF varnish on the dentin hydraulic conductance (Lp).MethodologyDentin disks (1.0±0.2 mm thickness) were cut from third molars, and their Lp values were evaluated using Flodec. The specimens were allocated into 7 groups (n=8). The minimum (smear layer) and the maximum (after acid etching) Lp values were recorded. Lp was also assessed after treatment with either a 0wt.%, 1wt.%, 5wt.%, 20wt.%, or 30wt.% S-PRG toothpaste, a NaF toothpaste, or a NaF varnish. Toothpastes were applied by brushing for 15 s, allowing it to settle for 1 min, and rinsing with deionized water. The NaF varnish was applied for 4 min and was removed with a probe. Specimens were exposed to citric acid (6%, pH 2.1, 1 min) and their final Lp was recorded. The pH of all products was recorded (n=3) and specimens from each group were analyzed by Laser Scanning Confocal Microscopy (LSCM). Data were subjected to 2-way repeated measures ANOVA and post-hoc Bonferroni (a=0.05).ResultsThe highest Lp reduction was noticed for the 5wt.% S-PRG toothpaste, NaF toothpaste, and NaF varnish. However, the toothpastes containing 5wt.%, 20wt.%, and 30wt.% of S-PRG were similar to all toothpastes but differed from the NaF varnish. After erosion, all groups retrieved their maximum Lp values, except for the NaF varnish. The LSCM evidenced deposits on the surface of specimens treated with 5%, 20%, and 30% S-PRG-based toothpastes and NaF toothpaste. Even more deposits were observed for the NaF varnish. After the erosive challenge, the deposits were diminished in all groups.ConclusionToothpastes containing 5wt.%, 20wt.%, and 30wt.% of S-PRG fillers behaved similarly to a conventional NaF toothpaste, even after an erosive challenge. The NaF varnish promoted better reduction of the Lp, but its effect was also diminished after erosion.

The Correlation between Serum Lipoprotein(a) and Risk of Mortality in Patients on Peritoneal Dialysis.

Patients with peritoneal dialysis commonly have severe disorders of lipid metabolism, with particularly severe changes in serum lipoprotein(α) [Lp(α)]. Serum Lp(α) may play a role in the risk of mortality in peritoneal dialysis patients. The aim was to investigate the correlation between high serum Lp(α) levels and all-cause mortality and death from cardiovascular events and infection in peritoneal dialysis patients. Three hundred and ninety-two patients with end-stage kidney disease who started peritoneal dialysis treatment between March 1, 2007 and May 31, 2020, were selected. Clinical data of all enrolled patients after 3 months of peritoneal dialysis were collected. Based on the median value of serum Lp(α) level, all enrolled patients were divided equally into a high serum Lp(α) level group (> 275.95 mg/L, n = 196) and a low serum Lp(α) level group (< 275.95 mg/L, n = 196). SPSS25.0 statistical software was used to analyze the factors affecting serum Lp(α) levels and the correlation between high serum Lp(α) levels and all-cause mortality and death from cardiovascular events and infection in peritoneal dialysis patients. Binary multivariate logistic regression analysis showed that higher low-density lipoprotein (LDL) levels (OR = 1.614, 95% CI: 1.261 - 2.068, p = 0.000) and high Body Mass Index (BMI) levels (OR = 1.063, 95% CI: 1.004 - 1.126, p = 0.036) were the risk factors for the high serum Lp(α) levels. High serum albumin levels (OR = 0.959, 95% CI: 0.927 - 0.991, p = 0.014) and high parathyroid hormone levels (OR = 0.999, 95% CI: 0.997 - 1.000, p = 0.010) were protective factors for the high serum Lp(α) levels. The cumulative survival of patients in the high serum Lp(α) level group was lower in death from cardiovascular events as shown by Kaplan-Meier survival analysis (Log-rank test χ2 = 4.348, p = 0.037). Multivariate Cox regression analysis showed that high serum Lp(α) levels were an independent risk factor for death from cardiovascular events in peritoneal dialysis patients (HR = 1.002, 95% CI: 1.001 - 1.003, p = 0.001). The occurrence of high serum Lp(α) levels in peritoneal dialysis patients was positively associated with LDL and BMI, and negatively associated with serum albumin and parathyroid hormone levels. High serum Lp(α) levels were related to the risk of death from cardiovascular events in peritoneal dialysis patients.

Genetic Testing in Patients with High Lipoprotein(a): Experience from the UCSD Lipoprotein(a) Specialty Clinic†

Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synopsis Lipoprotein(a) (Lp(a)) is an inherited and likely causal risk factor for cardiovascular disease (CVD) and aortic stenosis. LPA variants rs10455872 and rs3798220 are present in ∼15% and ∼3% of Caucasians, respectively, and are associated with elevated Lp(a) levels. Genetic testing in clinical practice is emerging as a tool for personalizing risk assessment and treatment decisions [1-3]. Objective/Purpose To explore the role of genetic testing for LPA SNPs and other genetic mutations in patients with elevated Lp(a). Methods In the UC San Diego Lipoprotein(a) Specialty Clinic, next-generation DNA sequencing was performed using the GBinsight Comprehensive Dyslipidemia Panel (GB Lifesciences, San Diego, CA, USA) in 26 patients with Lp(a) ³ 50 mg/dL, evaluating 327 exons and selected single-nucleotide polymorphisms (SNPs) in 129 genes known or suspected to be associated with CVD. Known LPA SNPs and high impact variants in other genes associated with lipid abnormalities were reported as pathogenic/likely pathogenic. Given non-normality, Lp(a) values were compared using a Mann-Whitney U test. Results Among the 26 patients (mean age 61 yrs, 50% women), 14 (53.8%) had LPA SNPs that have been shown to be associated with elevated Lp(a): rs10455872 (minor allele frequency (MAF) 2.2%) occurred in 9 patients (34.6%), and rs3798220 (MAF 5.1%) occurred in 7 patients (26.9%). Two patients (7.7%) had both rs10455872 and rs3798220 LPA SNPs. LPA SNP rs41272112 (MAF 2.2%) was present in 1 patient (3.8%), and rs186696265 (MAF 0.3%) was present in 4 patients (15.4%). Thus, 12 patients (46.2%) with elevated Lp(a) had no known LPA SNPs. Three of those 12 patients had other potential genetic explanations for elevated Lp(a) (compound heterozygote LDLR, APOE e4 homozygote, and a heterozygous likely pathogenic variant in LDLRAP1) (Table). Patients with elevated Lp(a) and at least 1 LPA variant had Lp(a) 166 +/- 92 mg/dL (mean+/-SD) (131.5, 106.75-243 mg/dL (median, IQR)), and those with elevated Lp(a) but without an LPA variant had Lp(a) 105.9 +/- 46 mg/dL (mean+/-SD) (100.5, 65.5-127.25 mg/dL (median, IQR) (p=0.08)). Conclusions Real-world testing for LPA SNPs in a referral Lp(a) specialty practice demonstrates genetic associations of elevated Lp(a) in approximately half of the patients, which is substantially higher than the general population. However, a significant proportion of patients have no known LPA SNPs despite highly elevated Lp(a), suggesting they harbor small apo(a) isoforms. The role of genetic testing at the bedside in such patients is evolving. A dedicated Lp(a) specialty clinic may allow optimal evaluation and management of patients with elevated Lp(a). Nothing to disclose.

Characterisation of Lipoprotein(a) in Patients Undergoing Percutaneous Coronary Intervention (PCI): Results From a Large Multi-Centre Registry

Elevated lipoprotein(a) [Lp(a)] is an independent inherited cardiovascular risk factor, causal in premature CVD and estimated to be elevated in 20% of the global population. Given the mounting evidence, GenesisCare is embarking on a Lp(a) prevalence and distribution study of its cardiology patients. Here we present a sub-cohort study wherein retrospective patients in our PCI registry with a documented Lp(a) value were assessed for clinical characteristics and outcomes.

Association of Lipoprotein(a) With Atherosclerotic Plaque Progression

BackgroundLipoprotein(a) [Lp(a)] is associated with increased risk of myocardial infarction, although the mechanism for this observation remains uncertain. ObjectivesThis study aims to investigate whether Lp(a) is associated with adverse plaque progression. MethodsLp(a) was measured in patients with advanced stable coronary artery disease undergoing coronary computed tomography angiography at baseline and 12 months to assess progression of total, calcific, noncalcific, and low-attenuation plaque (necrotic core) in particular. High Lp(a) was defined as Lp(a) ≥ 70 mg/dL. The relationship of Lp(a) with plaque progression was assessed using linear regression analysis, adjusting for body mass index, segment involvement score, and ASSIGN score (a Scottish cardiovascular risk score comprised of age, sex, smoking, blood pressure, total and high-density lipoprotein [HDL]–cholesterol, diabetes, rheumatoid arthritis, and deprivation index). ResultsA total of 191 patients (65.9 ± 8.3 years of age; 152 [80%] male) were included in the analysis, with median Lp(a) values of 100 (range: 82 to 115) mg/dL and 10 (range: 5 to 24) mg/dL in the high and low Lp(a) groups, respectively. At baseline, there was no difference in coronary artery disease severity or plaque burden. Patients with high Lp(a) showed accelerated progression of low-attenuation plaque compared with low Lp(a) patients (26.2 ± 88.4 mm3 vs −0.7 ± 50.1 mm3; P = 0.020). Multivariable linear regression analysis confirmed the relation between Lp(a) and low-attenuation plaque volume progression (β = 10.5% increase for each 50 mg/dL Lp(a), 95% CI: 0.7%-20.3%). There was no difference in total, calcific, and noncalcific plaque volume progression. ConclusionsAmong patients with advanced stable coronary artery disease, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core). This may explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis.

Theoretical approaches to determination of optimal cryopreservation regimens for cell spheroids of different cultivation terms

Background: Three-dimensional culture systems are unique platforms for studying complex biological processes in vitro. Cell-cell and cell-extracellular matrix interactions form a communication network of biochemical and mechanical signals, bring spheroids (SP) closer to native tissues and significantly distinguish them from monolayer cultures. It is important for cell technologies to develop methods for cryopreservation of 3D cultures, that allows creating the stocks of valuable cell samples, save time and materials, and prevent the loss of cultures due to technical failures, contamination, phenotype drift and aging. Objectives: Development of approaches to cellular spheroids cryopreservation. Determination of the permeability parameters of L929 cells spheroids at different cultivation periods for the theoretical assessment of optimal freezing regimens. Materials and methods: We have used L929 cells, which form SPs of different diameters and can be maintained for a long time in 3D conditions. To determine the integral filtration Lp and permeability for DMSO kp coefficients for SP at different periods of cultivation, the volumetric method was used. The study of the changes in the spheroids volume in time was carried out with a confocal microscope LSM 510 META. The numerical values of the integral SF permeability coefficients were determined by approximating the experimental data on the change in the relative volume of the SP versus the exposure time in the test solution with theoretical curves calculated on the basis of a physical and mathematical model for passive mass transfer between the spheroid and the environment, provided that they coincide as much as possible. Prediction of the osmotic behavior of spheroids under cooling conditions was carried out based on the differential equation describing the kinetics of changes in the relative cell volume during extracellular crystallization of a cryoprotective solution, substituting determined values of integral permeability coefficients Lp and kp and activation energies EAL and EAk into the model equations. The kinetics of changes in the extracellular solution concentration during freezing was set analytically by approximating the phase melting diagram of the DMSO solution. Results: The filtration and permeability for DMSO molecules coefficients in SP were determined and their significant decrease with a cultivation duration was shown. The activation energy values for the penetration of water and DMSO molecules into the SP were calculated and their dependence on the cultivation time was determined. Proceeding from the determined parameters of permeability, the dynamic of changes in the volume of SPs for different periods of cultivation at different rates of cooling was calculated. Conclusions: The optimal cooling modes of SP from L929 cells were in theory determined: for 7 days of cultivation — 1,5-2 °C/min with cooling to -80°C and subsequent immersion in nitrogen; for 14 and 21 days of cultivation — 0.5 °C/min to -40°C and subsequent immersion in nitrogen.

Abstract 13099: Correlation of Lipoprotein(a) Levels With Coronary Plaque Morphological Features and Vulnerability: An Optical Coherence Tomography Study

Introduction: High lipoprotein(a) level is a potential independent risk factor for coronary artery disease (CAD). However, the relationship between the Lp(a) value and the morphological characteristics of plaque defined by optical coherence tomography (OCT) has not been completely clarified so far. Meanwhile, no evidence has been raised for a clear cut-off value of Lp(a) for preventing the process of CAD. Hypothesis: Based on the biological properties of Lp(a), We assessed the hypothesis that the Lp(a) levels may relate to the vulnerable features of lipid plaque defined by OCT. Methods: 420 CAD patients who had undergone OCT scan to at least 1 main coronary vessel during 2013-2018 were enrolled. Patients were first stratified into 3 levels according to the values of Lp(a) at admission: Lp(a)&lt;30 mg/dl (Group A), 30-60 mg/dl(Group B), and &gt;60 mg/dl(Group C). After enrolled the cases with Lp(a) &gt;60mg/dl, we chose cases of the other 2 groups matching according to traditional risk factors of CAD to our current analysis. OCT pullbacks of the target vessels were collected and analyzed at every 0.4 mm by 2 independent observers blinded to the clinical data and angiographies with QIVUS software. Results: A total of 90 cases were enrolled into the current study, with 30 cases in each group. Lipid plaque in Group B and Group C had a thinner minimum fibrous cap thickness, wider maximum lipid arc, longer lipid length, and greater lipid index than Group A. The Lp(a) levels significantly correlated with lipid length (r=0.283), the maximum arc of lipid(r=0.293), lipid index(r=0.357), and inversely correlated with minimum fibrous cap thickness (r =-0.403). Multivariate analysis demonstrated that the Lp(a) level was independently associated with TCFA (odds ratio 1.035, 95% confidence interval 1.014-1.057). In addition, the ROC curve analysis results (AUC =0.694, p &lt; 0.001) indicated the Lp(a) is a good diagnostic indicator for detecting TCFA, and the optimal cut-off was 33.65 mg/dl. Conclusions: Our current study indicates that CAD patients with higher Lp(a) level(&gt;30 mg/dl) exhibited a higher prevalence of TCFA and had more other typical vulnerable characteristics defined by OCT. New Lp(a) lowering therapy could aim at a level of &lt; 33.65mg/dl for stabilizing coronary plaque.

Abstract 10921: The Relationship Between Lipoprotein(a) and Cardiovascular Events in Chronic Kidney Disease Patients Hospitalized for Acute Coronary Syndrome

Introduction: Patients with chronic kidney disease (CKD) have the high risk of residual cardiovascular events after statin therapy, hence whether elevated lipoprotein(a) [Lp(a)] levels leading to worse outcomes is unclear. Hypothesis: High Lp(a) levels are associated with higher risk of major adverse clinical events (MACE) in patients with CKD and acute coronary syndrome (ACS). Methods: Patients with CKD (estimated glomerular filtration rate &lt; 60mL/min/1.73m 2 ) hospitalized for ACS were enrolled in China-Japan Friendship Hospital from January 2015 to December 2019. Patients were divided into 2 groups according to median levels of Lp(a). The MACE were a composite endpoint of cardiac death, non-fatal myocardial infarction, and non-fatal ischemia stroke. Multivariate Cox regression analysis and restricted cubic spline curve were performed to explore the relationship between Lp(a) levels and MACE. Results: A total of 434 ACS patients with CKD were enrolled, with 37.8% were women. The median Lp(a) concentration was 16.7mg/dL. During a median follow-up of 2.8 years, patients had higher risk of MACE (45.2% vs. 14.7%, log rank p &lt; 0.001) in the high Lp(a) group than the low Lp(a) group. The relationship between Lp(a) and MACE appeared to be nonlinear. Multivariable Cox regression analysis showed that high Lp(a) value was an independent predictor of MACE compared with low Lp(a) value (HR = 3.33, 95% CI 2.20-5.05, p &lt; 0.001). The receiver operating characteristic curve analysis showed that adding Lp(a) concentration to original risk model improved the prognostic model, with area under the curve increasing from 0.69 to 0.74. Conclusions: In ACS patients with CKD, high Lp(a) concentrations predict the risk of cardiac death, non-fatal myocardial ischemia and non-fatal ischemia stroke at 2-years follow-up.