High Lp Research Articles

Lipoprotein a Combined with Fibrinogen as an Independent Predictor of Long-Term Prognosis in Patients with Acute Coronary Syndrome: A Multi-Center Retrospective Study.

Background: Patients with acute coronary syndrome (ACS) still have a high risk of recurrence of major adverse cardiovascular and cerebrovascular events (MACCE). However, there are rare studies on the prediction of MACCE in patients with ACS using lipoprotein a [Lp(a)] combined with fibrinogen. The aim of this study was to analyze the predictive value of Lp(a) combined with fibrinogen for the long-term prognosis of patients with ACS. Methods: 804 patients with ACS admitted to 11 tertiary general hospitals in Chengdu from January 2017 to June 2019 were included in the study. According to the Lp(a) 300 mg/L, patients were assigned to the non-high Lp(a) group and high Lp(a) group. Patients were assigned to the non-high or high fibrinogen groups using the fibrinogen level of 3.08 g/L. Subsequently, patients were divided into group A, B, or C by Lp(a) combined with fibrinogen. The study endpoints were MACCE, including all-cause death, non-fatal myocardial infarction, non-fatal stroke, and revascularization. The incidences of MACCE among groups were compared. Lp(a), fibrinogen, Lp(a) combined with fibrinogen classifications were each added into the basic model to construct three new models. The C-index, net reclassification index (NRI) and integrated discrimination improvement (IDI) of the three new models were then compared. Results: The median follow-up was 16 months. During follow-up, the cumulative incidence of MACCE in group C was significantly higher than that measured in group A and B (p < 0.001). The results of the multivariate Cox regression analysis of MACCE showed that Lp(a) ≥300 mg/L with fibrinogen ≥3.08 g/L was an independent predictor of MACCE. According to the GRACE score and the statistical analyses, the basic model was constructed, which had a C-index of 0.694. The C-index, NRI, and IDI of the new model constructed using the basic model + Lp(a) combined with fibrinogen classification were 0.736, 0.095, and 0.094 respectively. Conclusions: Single Lp(a), single fibrinogen and Lp(a) combined with fibrinogen were independent predictors of MACCE in patients with ACS. The predictive value of Lp(a) combined with fibrinogen in patients with ACS was better than that of single Lp(a) and single fibrinogen.

Lipoprotein(a) levels and risk of adverse events after myocardial infarction in patients with and without diabetes

Introduction: The aim of this study was to evaluate the association of lipoprotein(a) [Lp(a)] levels with long-term outcome in patients with recent history of myocardial infarction (MI), and to investigate if diabetes may influence this association.Methods: Consecutive MI patients who underwent urgent/emergent coronary angiography from February 2013 to June 2019 were prospectively collected. The primary outcome was the composite of MI recurrence and all-cause death. The propensity score weighting technique was used to account for covariates potentially influencing the relationship between Lp(a) levels and the study outcomes.Results: The study population consisted of 1018 post-MI patients (median age 63 years). Diabetes was reported in 280 patients (27.5%), who showed lower Lp(a) levels than patients without diabetes (p = 0.026). At a median follow-up of 1121 days, the primary outcome was reported in 182 patients (17.9%). At univariable Cox regression analysis, Lp(a) was associated with the risk of the primary outcome in the overall population and in non-diabetic patients, but not in diabetics. The adjusted Cox regression analysis confirmed the independent association between Lp(a) values and the primary outcome in non-diabetic patients, but not in diabetics.Lp(a) levels > 70 mg/dL were independently associated with the risk of the primary outcome in non-diabetic patients (adjusted HR: 2.839; 95% CI, 1.382–5.832), but not in diabetics.Conclusions: In this real-world post-MI population, increasing Lp(a) levels were significantly associated with the risk of recurrent MI and all-cause death, and very high Lp(a) serum concentration independently predicted long-term outcome in non-diabetic patients, but not in diabetics.

Association of lipoprotein(a) with all-cause and cause-specific mortality: A prospective cohort study

BackgroundA growing number of studies have demonstrated a causal association between lipoprotein(a) [Lp(a)] and atherosclerotic cardiovascular diseases (ASCVDs), but its association with all-cause and cause-specific mortality remains unclear. Therefore, this study aimed to explore the association of Lp(a) with all-cause and cause-specific mortality. MethodsThis prospective cohort study included 8,525 participants from the third National Health and Nutrition Examination Survey. Lp(a) was considered an exposure variable, all-cause and cause-specific mortality were used as outcome variables, and all participants were followed from the interview date until death or December 31, 2015. COX proportional hazards regression models, stratified analysis, sensitivity analysis, restricted cubic spline plots and Kaplan-Meier survival curves were used to analyze the association of Lp(a) with all-cause and cause-specific mortality. ResultsAfter adjusting for traditional cardiovascular risk factors, Lp(a) remained strongly associated with all-cause and CVDs-related mortality (P for trend = 0.007 and < 0.001). Subgroup analyses showed that higher Lp(a) remained associated with higher risk of all-cause mortality in those > 60 years of age, with a BMI < 30 kg/m2, and without diabetes, whereas the association between Lp(a) and CVDs-related mortality remained stable in participants ≤ 60 years of age, male, with a BMI < 30 kg/m2, with hypertension, without diabetes, or without CVDs (P < 0.05). In sensitivity analyses, we found that the association of Lp(a) with all-cause and CVDs-related mortality remained robust after excluding individuals who died within one year of follow-up (P for trend = 0.041 and 0.002). ConclusionsLp(a) was associated with the risk of all-cause and CVDs-related mortality.

New Horizons: Revival of Lipoprotein (a) as a Risk Factor for Cardiovascular Disease.

The status of lipoprotein (a) [Lp(a)] as a cardiovascular risk factor has been resurrected by advances in genetics. Mendelian randomization studies show a causal link of Lp(a) with coronary artery disease (CAD), peripheral artery disease (PAD), and calcific aortic valve stenosis (CAVS). The genetics of Lp(a) is complex and extends beyond the kringle-IV type 2, as it is also dependent on ancestry. The plasma concentration of Lp(a) is determined by the hepatic production of apolipoprotein(a) [apo(a)] component of Lp(a), supporting the use of nucleic acids that inhibit the messenger RNA (mRNA) gene transcript for apo(a). Analytical barriers to measurement of Lp(a) are being addressed using isoform independent assays and a traceable standard. The association of Lp(a) and atherosclerotic cardiovascular disease is higher for myocardial infarction than PAD and CAVS. Increased risk of type 2 diabetes mellitus associated with low Lp(a) levels is perplexing and requires further investigation. The greatest advancement in Lp(a)-lowering therapies is based on using RNA therapeutics that are now being investigated in clinical trials. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition lowers Lp(a) modestly, but whether cardiovascular benefit is independent of low-density lipoprotein lowering remains unclear. Opportunistic and selective testing for Lp(a) is supported by moderate evidence, with the case for universal screening premature. Modification of behavioral and clinical risk factors may be targeted to mitigate Lp(a)-mediated risk of cardiovascular disease. Clinical practice guidelines have been developed to address gaps in care of high Lp(a), but full implementation awaits the findings of clinical outcome trials using RNA-directed therapies currently underway.

Lipoprotein (a) levels and vulnerable characteristics in nonculprit plaque in patients with acute coronary syndrome.

High plasma levels of Lp(a) are associated with a worse prognosis in patients with coronary artery disease. The aim of the present study is to clarify the association between high lipoprotein a [Lp(a)] levels and vulnerable characteristics of nonculprit plaques in patients with acute coronary syndrome (ACS). A total of 185 consecutive patients with ACS who underwent optical coherence tomography imaging of nonculprit plaques in the culprit vessels were enrolled. Patients were divided into the high Lp(a) group (≥30mg/dL; 50 nonculprit plaques in 49 patients) or the low Lp(a) group (<30mg/dL; 139 nonculprit plaques in 136 patients). The prevalence of thin-cap fibroatheroma (TCFA) was significantly higher in the high Lp(a) group than in the low Lp(a) group (38.0 vs. 21.6%, p=0.034). Multivariate logistic analysis demonstrated that a high Lp(a) level was independently associated with the prevalence of TCFA (odds ratio, 1.18; 95% confidence interval, 1.01-1.36; p=0.033). The prevalence of TCFA was significantly higher in the high Lp(a) group than in the low Lp(a) group among patients with plaque erosion (50.0 vs. 9.4%, respectively; p=0.027), although the difference was not statistically significant between the two groups in patients with plaque rupture. High Lp(a) levels were associated with a high prevalence of TCFA in nonculprit plaques among patients with ACS, particularly in patients with plaque erosion. The present results may partly explain the pathogenesis of worse clinical outcomes in patients with ACS and a high Lp(a) level as shown in clinical studies.

Predictive value of lipoprotein(a) for assessing the prevalence and severity of lower-extremity peripheral artery disease among patients with acute coronary syndrome.

Lipoprotein(a) [Lp(a)] is a reliable lipid marker for atherosclerosis. However, the clinical relevance of Lp(a) to lower-extremity peripheral artery disease (LE-PAD) and coronary artery disease (CAD) in the same patient has not been investigated. Patients who received primary percutaneous coronary intervention for the acute coronary syndrome (ACS) were enrolled. Patients who received hemodialysis, required multidisciplinary treatments, or had incomplete medical history were excluded. A total of 175 patients were divided into two groups according to whether they had LE-PAD (n = 21) or did not (n = 154), and three multivariable logistic regression models were used to assess if Lp(a) level is associated with LE-PAD prevalence. In addition, serum Lp(a) levels were compared among three groups according to the severity of LE-PAD (none, unilateral, or bilateral) and CAD. Serum Lp(a) levels were significantly higher in patients with LE-PAD than in those without (31.0mg/dL vs. 13.5mg/dL, p = 0.002). After adjusting for confounding factors, higher Lp(a) levels were independently associated with the prevalence of LE-PAD in all three models (p < 0.001 for all). With respect to LE-PAD severity, serum Lp(a) levels were significantly higher in the bilateral LE-PAD groups than in the group with no LE-PAD (p = 0.005 for all), whereas Lp(a) was not associated with CAD severity. Though Lp(a) levels are associated with the prevalence and severity of LE-PAD, are not associated with the severity of CAD among patients with ACS.

Association between lipoprotein(a) and thromboembolism in patients with non-valvular atrial fibrillation: a cross-sectional study

BackgroundLipoprotein(a) [Lp(a)] is a recognized risk factor for ischemic stroke (IS); however, its role in thromboembolism in patients with non-valvular atrial fibrillation (NVAF) remains controversial. We aimed to assess the association of Lp(a) and IS and systemic embolism (SEE) in NVAF patients.MethodsIn total, 16,357 patients with NVAF were recruited from the First Affiliated Hospital of Xinjiang Medical University from January 1, 2009, to December 31, 2021, and were divided into groups based on Lp(a) quartiles. Logistic regression models analyzed the association between Lp(a), IS, and SEE. The restriction cubic spline was used to assess the potential nonlinear relationship between Lp(a), IS, and SEE. We conducted subgroup analyses and estimated the multiplicative interaction between the stratified variables and Lp(a) to investigate whether the association between Lp(a) and IS and SEE was affected by age, sex, anticoagulants, and CHA2DS2-VASc score.ResultsWe identified 1319 IS and 133 SEE events. After correcting for CHA2DS2-VASc score and other potential confounders, each 1-standard deviation (SD) increase in log-Lp(a) was related to a 23% increased risk of IS (odds ratios [OR], 1.23; 95% confidence intervals [CI], 1.07–1.41). NVAF patients in the highest Lp(a) quartile were 1.23-fold more likely to have IS than those in the lowest quartile (OR, 1.23; 95% CI, 1.04–1.45). A positive linear relationship between Lp(a) and IS risk was observed (P for nonlinear = 0.341). In the fully adjusted model, subjects had a 1.78-fold increased risk of SEE for each 1-SD increase in log-Lp(a) (OR, 2.78; 95% CI, 1.78–4.36). Subjects in the highest Lp(a) quartile had a 2.38-fold elevated risk of SEE (OR, 3.38; 95% CI, 1.85–6.19) compared with the lowest quartile. Furthermore, Lp(a) had a nonlinear relationship with the risk of SEE (P for nonlinear = 0.005).ConclusionsElevated Lp(a) concentration was significantly associated with IS and SEE, suggesting that Lp(a) may be an emerging biomarker that can help clinicians identify patients at high risk of thromboembolism in this population.

Serum Lipoprotein(a) and 3-Year Outcomes in Patients Undergoing Percutaneous Coronary Intervention

We aimed at addressing the association between serum lipoprotein (a) levels and clinical outcomes of consecutive patients undergoing PCI. We used consecutive patients undergoing PCI at the Heart Center University of Freiburg, Bad Krozingen in Germany between January 2005 and November 2013. A total of 6679 patients (men [n = 5391] and women [n = 1288]) with mean age of 67.5 (± 11.1) years were assessed at baseline and prospectively followed for 3 years. Lp(a) measurement was performed at hospital admission as a routine laboratory parameter. Approximately 30% of PCI patients showed an elevated Lp(a) value of more than 50 mg/dL. In total, 736 Patients died during the follow-up, thereof 189 (11.3%) in the first quartile, 186 (10.7%) in the second quartile, 183 (11.5%) in the third quartile and 178 (10.7%) in the last quartile (P value 0.843 from LogRank test). The MACE rate showed consistent results with 409 (24.4%), 385 (22.1%), 395 (24.7%) and 419 (25.3%) in the different respective quartiles (P value 0.125 from LogRank test). In this large non-selected cohort of patients undergoing PCI followed by moderate intensity statin therapy, higher Lp(a) levels were not associated with worse clinical outcomes during a follow-up of 3 years.

Novel metabolic classification for extrahepatic complication of metabolic associated fatty liver disease: A data-driven cluster analysis with international validation

BackgroundTraditional classification systems of metabolic-associated fatty liver disease (MAFLD) do not account for the high rate of extrahepatic complications. To create a new classification of MAFLD using metabolic parameters to identify risks of complications more accurately. MethodsThe retrospective study included MAFLD patients from the First Affiliated Hospital of Sun Yat-sen University for model development, and the model was validated respectively using Chinese cohort and UK Biobank database. Cluster analysis with k-means cluster was built using age, body mass index (BMI), glycosylated hemoglobin (HbA1c), total cholesterol/high density lipoprotein cholesterol (HDL-C) ratio, triglyceride, and lipoprotein(a) [Lp(a)] levels. Cox regression models were used to compare the risk of type 2 diabetes (T2DM), chronic heart disease (CHD), stroke and mortality between the clusters. Results1038 MAFLD patients from cross-sectional population were recruited for the model derivation, with 10,451 cases (33.4 % of MAFLD) from Chinese cohort and 304,141 cases (34.9 % of MAFLD, 1010 cases with magnetic resonance imaging proton density fat fraction measurement [MRI-PDFF]) from the international cohort validated. Five replicable clusters of MAFLD patients were identified: Cluster 1(mild obesity and dyslipidemia-related), Cluster 2 (age related), Cluster 3 (severe insulin resistance-related), Cluster 4[high Lp(a)-related], and Cluster 5 (severe mixed hyperlipidemia-related). Patients in different clusters exhibited differences in the development of T2DM, CHD, stroke and all-causes mortality. Patients in Cluster 3 had significantly worst survival outcomes and higher risks of T2DM and CVD than those in other clusters. ConclusionThe novel classification offers improved discrimination of new-onset MAFLD patients with different metabolic complications.

The association between serum lipid levels and histological type of breast cancer

BackgroundStudies have investigated the association between serum lipids level or apolipoprotein levels and breast cancer (BC) risk. However, the relationship between serum lipids level and apolipoprotein levels and histological type of breast cancer remains unclear. This study was aimed to explore the association between serum lipids level and the histological type of BC, particularly to estrogen receptor (ER) and progesterone receptor (PR) positive BC.Materials and methods220 cases of pathology-confirmed BC were retrospectively collected in this study. Patients’ demographic information, clinical data, and pathological features were obtained from medical records. Serum levels including high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), ApoB, ApoE and lipoprotein a(LP(a)) were collected before treatment. Logistic regression analyses were used to show the association between serum lipids and subtypes of BC. Receiver operating characteristic (ROC) curves were generated to analyze the predictive performance.ResultsThere were 70 ER-negative and 73 PR-negative BC. Patients with ER-negative BC had higher HDL-c, higher LDL-c, and higher LP(a) than those in ER-positive one (p < 0.05). Patients with PR-negative BC were more likely to have high LDL-c and high LP(a) levels than patients with PR-positive one (p < 0.05). Multivariate logistic regression analysis showed that serum HDL-c (odds ratio (OR): 0.27, 95% confidence interval (CI) 0.10–0.76), LDL-c (OR: 0.19, 95%CI 0.04–0.93) and LP(a) (OR: 0.23,95%CI 0.07–0.80) levels were negatively associated with ER-positive BC, and serum HDL-c and LDL-c levels were significantly negatively associated with PR-positive BC (OR: 0.32, 95%CI 0.12–0.82; OR: 0.14, 95%CI 0.03–0.77). In addition, ER and PR positive BC was negatively associated with serum HDL-c and LDL-c levels (OR = 0.39, 95% CI 0.17–0.91; OR = 0.22, 95% CI 0.06–0.85) after adjusting with confounders. Serum HDL-c level (OR = 0.13, 95% CI 0.02–0.87) was still independently associated with ER and PR positive BC in postmenopausal women. The area under the curves (AUCs) of HDL-c to identify ER-positive BC, PR-positive BC, and ER and PR positive BC were 0.65 (95%CI 0.58–0.73, P < 0.01), 0.62 (95%CI 0.54–0.69, P < 0.01) and 0.64 (95%CI 0.56–0.72, P < 0.01), respectively.ConclusionsSerum HDL-c and LDL-c levels were related to ER or PR positive BC. Lipid levels may also have acceptable performance in identifying BC histological type.

Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement.

This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do not support Lp(a) as a risk factor for venous thrombotic events and impaired fibrinolysis. Very low Lp(a) levels may associate with increased risk of diabetes mellitus meriting further study. Lp(a) has pro-inflammatory and pro-atherosclerotic properties, which may partly relate to the oxidized phospholipids carried by Lp(a). This panel recommends testing Lp(a) concentration at least once in adults; cascade testing has potential value in familial hypercholesterolaemia, or with family or personal history of (very) high Lp(a) or premature ASCVD. Without specific Lp(a)-lowering therapies, early intensive risk factor management is recommended, targeted according to global cardiovascular risk and Lp(a) level. Lipoprotein apheresis is an option for very high Lp(a) with progressive cardiovascular disease despite optimal management of risk factors. In conclusion, this statement reinforces evidence for Lp(a) as a causal risk factor for cardiovascular outcomes. Trials of specific Lp(a)-lowering treatments are critical to confirm clinical benefit for cardiovascular disease and aortic valve stenosis.

Smoking and diabetes attenuate beneficial effects of PSCK9 inhibitors on arterial wall properties in patients with very high lipoprotein (a) levels

Background and aimsElevated lipoprotein (a) (Lp(a)) and low-density lipoprotein cholesterol levels (LDL-C) are significant residual risk factors for cardiovascular events. Treatment with protein convertase subtilisin kexin type 9 (PCSK9) inhibitors reduces the levels of both. Less is known about effects of PCSK9 inhibitors on functional and morphological properties of the arterial wall. The aim of the present study was to determine whether other factors besides decreased LDL-C and Lp(a) are associated with functional (flow-mediated dilation [FMD]) and morphological (carotid intima-media thickness [c-IMT], pulse-wave velocity [PWV]) changes of the arterial wall properties in patients with coronary artery disease (CAD) treated with alirocumab and evolocumab. MethodsOne hundred patients with CAD after myocardial infarction before 55 years and with high Lp(a) were randomised to lipid-lowering therapies without PCSK9 inhibitors (control; N = 31), or with alirocumab 150 mg SC (N = 35) or evolocumab 140 mg SC (N = 34), every 2 weeks. All patients underwent blood sampling for biochemical analyses and ultrasound measurements for FMD, c-IMT and PWV. ResultsThere were no significant changes in FMD for the control (10.7% ± 6.6%–11.1% ± 4.4%, p = 0.716) and alirocumab (10.7% ± 5.9%–11.2% ± 5.3%, p = 0.547) groups, while evolocumab promoted significant increase (11.2% ± 6.8%–14.1% ± 6.6%, p < 0.0001). Only in non-smokers and non-diabetics significant improvements in FMD (p < 0.0001) after treatment with PCSK9 inhibitors were observed. ConclusionThese data show that for patients with CAD and high Lp(a) levels, beneficial effects of PCSK9 inhibitors on the arterial wall properties can be attenuated by specific risk factors, such as smoking and diabetes.

Management of significantly elevated lipoprotein(a) in patients without established ASCVD

Background and Aims : EAS/ESC and Canadian Cardiovascular Society (CCS) Guidelines recommend that everyone should have a determination of Lp(a) level once in a lifetime. 20% of the population will be found to have elevated Lp(a) above 50mg/dL (125nmoles/L) {high Lp(a)}. High Lp(a) produces significant risk of ASCVD particularly CAD. The majority of high Lp(a) patients will not have established ASCVD but need recommendations.

LPA genotypes and haplotypes influence lipoprotein(a) levels but not arterial wall properties, in stable post-coronary event patients with very high lipoprotein(a) levels

Background and Aims: Lipoprotein (a) [Lp(a)] levels are an independent risk factor for coronary artery disease. Two single nucleotide polymorphisms (rs1045587, rs10455872) and KIV-2 repeats in the gene encoding Lp(a) (LPA) are strongly associated with increased Lp(a) levels and coronary artery disease. The aim was to initially investigate whether in stable patients following myocardial infarction and with very high Lp(a) levels these genetic variants are associated with increased Lp(a) levels. We then also investigated the functional and morphological characteristics of the arterial wall in these patients.

Elevated Lipoprotein(a) prevalence and association with family history of premature cardiovascular disease in general population with moderate cardiovascular risk and increased LDL cholesterol.

BackgroundElevated Lipoprotein(a) [Lp(a)] is independently associated with increased cardiovascular disease (CVD) risk. There are discrepancies regarding its epidemiology due to great variability in different populations. This study aimed to evaluate the prevalence of elevated Lp(a) in people with moderate CVD risk and increased LDL-c and to determine the association between family history of premature CVD and elevated Lp(a).MethodsRandom subjects from the CESCAS population-based study of people with moderate CVD risk (Framingham score 10–20 %) and LDL-c ≥ 130 mg/dL, were selected to evaluate Lp(a) by immunoturbidimetry independent of the Isoforms variability. The association between family history of premature CVD and elevated Lp(a) was evaluated using multivariate logistic regression models. Elevated Lp(a) was defined as Lp(a) ​​≥ 125 nmol/L.ResultsLp(a) was evaluated in 484 samples; men = 39.5 %, median age = 57 years (Q1-Q3: 50–63), mean CVD risk = 14.4 % (SE: 0.2), family history of premature CVD = 11.2 %, Lp(a) median of 21 nmol/L (Q1-Q3: 9–42 nmol/L), high Lp(a) = 6.1 % (95 % CI = 3.8–9.6). Association between family history of premature CVD and elevated Lp(a) in total population: OR 1.31 (95 % CI = 0.4, 4.2) p = 0.642; in subgroup of people with LDL-c ≥ 160 mg%, OR 4.24 (95 % CI = 1.2, 15.1) p = 0.026.ConclusionsIn general population with moderate CVD risk and elevated LDL-c from the Southern Cone of Latin America, less than one over ten people had elevated Lp(a). Family history of premature CVD was significantly associated with the presence of elevated Lp(a) in people with LDL-c ≥ 160 mg/dL.

Impact of lipoprotein(a) levels on primary patency after endovascular therapy for femoropopliteal lesions.

Lipoprotein(a) [Lp(a)] is a risk factor for peripheral artery disease (PAD). However, the relationship between Lp(a) levels and clinical events after endovascular therapy (EVT) for the femoropopliteal artery in PAD patients remains unclear. Thus, this study aimed to assess the impact of Lp(a) levels on primary patency after EVT for de novo femoropopliteal lesions in PAD patients. A retrospective analysis was conducted on 109 patients who underwent EVT for de novo femoropopliteal lesions, and Lp(a) levels were measured before EVT between June 2016 and December 2019. Patients were divided into low Lp(a) [Lp(a) < 30mg/dL; 78 patients] and high Lp(a) [Lp(a) ≥ 30mg/dL; 31 patients] groups. The main outcome was primary patency following EVT. Loss of primary patency was defined as a peak systolic velocity ratio > 2.4 on a duplex scan or > 50% stenosis on angiography. Cox proportional hazards analysis was performed to determine whether high Lp(a) levels were independently associated with loss of primary patency. The mean follow-up duration was 28months. The rates of primary patency were 83 and 76% at 1year and 75 and 58% at 2years in the low and high Lp(a) groups, respectively (P = 0.02). After multivariate analysis, High Lp(a)[Lp(a) ≥ 30mg/dL] (hazard ratio 2.44; 95% CI 1.10-5.44; P = 0.03) and female sex (hazard ratio 2.65; 95% CI 1.27-5.51; P < 0.01) were independent predictors of loss of primary patency. Lp(a) levels might be associated with primary patency after EVT for de novo femoropopliteal lesions.

Lipid Parameters and Proprotein Convertase Subtilisin/Kexin Type 9 in Healthy Lebanese Adults.

Background: High levels of non-HDL cholesterol (non-HDL-C), triglycerides (TG), lipoprotein (a) (Lp(a)), and Proprotein convertase subtilisin/kexin type 9 (PCSK9) as well as low levels of HDL-C are strongly associated with cardiovascular disease (CVD). Our study aims to estimate the prevalence of dyslipidemia and high Lp(a) in the Lebanese population and to study the relationship of these variables with gender, age, body mass index (BMI), and PCSK9. Methods: This cross-sectional study was carried out on a sample of healthy volunteers aged 18 to 65. Blood samples were drawn from volunteers for total cholesterol (TC), HDL-C, TG, PCSK9, and Lp(a) measurements. Non-HDL-C was calculated by subtracting HDL-C from TC. Results: In total, 303 volunteer subjects with an average age of 38.9 years were included in the study. Respectively, 44%, 29.8%, and 44% of men had high non-HDL-C and TG with low HDL-C versus 23.5%, 8%, and 37% in women. Non-HDL-C and TG were significantly higher in men than in women, while the reverse was observed for HDL-C (p < 0.0001 for the three comparisons). Non-HDL-C and TG were significantly correlated with age and BMI (p< 0.0001 for all correlations), while HDL-C was inversely correlated with BMI (p < 0.0001) but not with age. Abnormal Lp(a) levels (≥75 nmol/L) were found in 19.1% of the population, predominantly in women (24.1% versus 13.4% in men, p = 0.004). The median PCSK9 and its interquartile was 300 (254–382) ng/L with no gender difference (p = 0.18). None of the following factors: gender, age, BMI, non-HDL-C, HDL-C, or TG, were independently associated with Lp(a), while PCSK9 was significantly correlated with age, non-HDL-C, and TG in both men and women and inversely correlated with HDL-C in men. Dyslipidemia is very common in the Lebanese population and is associated with age, high BMI, and male sex. Lp(a) is higher in women without any correlation with the lipid profile, whereas PCSK9 is associated with non-HDL-C and TG. Further studies are needed to evaluate the potential role of Lp(a) and PCSK9 in predicting CVD in healthy populations.

Lipoprotein(a) is associated with the onset but not the progression of aortic valve calcification.

Lipoprotein(a) [Lp(a)] is a potential causal factor in the pathogenesis of aortic valve disease. However, the relationship of Lp(a) with new onset and progression of aortic valve calcium (AVC) has not been studied. The purpose of the study was to assess whether high serum levels of Lp(a) are associated with AVC incidence and progression. A total of 922 individuals from the population-based Rotterdam Study (mean age 66.0±4.2 years, 47.7% men), whose Lp(a) measurements were available, underwent non-enhanced cardiac computed tomography imaging at baseline and after a median follow-up of 14.0 [interquartile range (IQR) 13.9-14.2] years. New-onset AVC was defined as an AVC score >0 on the follow-up scan in the absence of AVC on the first scan. Progression was defined as the absolute difference in AVC score between the baseline and follow-up scan. Logistic and linear regression analyses were performed to evaluate the relationship of Lp(a) with baseline, new onset, and progression of AVC. All analyses were corrected for age, sex, body mass index, smoking, hypertension, dyslipidaemia, and creatinine. AVC progression was analysed conditional on baseline AVC score expressed as restricted cubic splines. Of the 702 individuals without AVC at baseline, 415 (59.1%) developed new-onset AVC on the follow-up scan. In those with baseline AVC, median annual progression was 13.5 (IQR = 5.2-37.8) Agatston units (AU). Lipoprotein(a) concentration was independently associated with baseline AVC [odds ratio (OR) 1.43 for each 50 mg/dL higher Lp(a); 95% confidence interval (CI) 1.15-1.79] and new-onset AVC (OR 1.30 for each 50 mg/dL higher Lp(a); 95% CI 1.02-1.65), but not with AVC progression (β: -71 AU for each 50 mg/dL higher Lp(a); 95% CI -117; 35). Only baseline AVC score was significantly associated with AVC progression (P < 0.001). In the population-based Rotterdam Study, Lp(a) is robustly associated with baseline and new-onset AVC but not with AVC progression, suggesting that Lp(a)-lowering interventions may be most effective in pre-calcific stages of aortic valve disease.

High lipoprotein(a) levels predict severity of coronary artery disease in patients hospitalized for acute myocardial infarction. Data from the French RICO survey

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) and >100 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.

Long-term tracking and population characteristics of lipoprotein (a) in the Cardiovascular Risk in Young Finns Study

Background and aimsLipoprotein (a) (Lp(a)) is a causal risk factor for cardiovascular diseases and its levels are under strict genetic control. Therefore, it is hypothesized that the concentration of Lp(a) remains stable throughout life. Finns have lower Lp(a) levels than central Europeans, but it is unknown whether there are differences within Finland, especially between the eastern and western parts of the country with known genetic duality and persistent differences in cardiovascular disease rates. We have examined the long-term stability of Lp(a) levels over 25 years in the Cardiovascular Risk in Young Finns Study (YFS), and the characteristics of individuals with different Lp(a) levels, including their geographical origin within Finland. MethodsIn YFS, the first large baseline examination was conducted in 1980 (baseline age, 3–18 years). Several follow-ups during the past 40 years have been conducted to investigate the determinants of cardiometabolic health. Lp(a) levels have been measured in study years 1986 (N = 2464, ages 9–24 years), 2001 (N = 2281, ages 24–39 years), 2007 (N = 2204, ages 35–45 years) and 2011 (N = 2044, ages 39–49 years). Tracking of Lp(a) was estimated by calculating Spearman's rank order correlations between the study years, and by cross-tabulating how many individuals diagnosed with either elevated or non-elevated Lp(a) levels in 1986, 2001 and 2007 remained in the same category in the latest follow-up in 2011. ResultsSpearman's correlation coefficients varied between r = 0.84–0.96. Most individuals (87–94%) who had a high Lp(a) level (>30 mg/dl) in any of the previous study years had a high level also in 2011. On average, the median Lp(a) levels were consistently ∼20% higher in the individuals originating from eastern Finland compared to those from western Finland, but there were no differences in the distribution of known genetic determinants between eastern and western Finns that would have explained the observed difference. ConclusionsThese data confirm that Lp(a) levels remain very stable over the life-course. In line with the genetic duality between eastern and western parts of Finland, we observed about 20% higher Lp(a) levels in individuals originating from eastern Finland compared to those originating from western Finland.