Lipoprotein(a) concentrations and secondary outcomes following first-time acute coronary syndrome: The Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS).

The aim of this study was to assess the independent contributions of plasma levels of lipoprotein(a) (Lp(a)), Lp(a) cholesterol, and of apo(a) isoform size to prospective coronary heart disease (CHD) risk. Plasma Lp(a) and Lp(a) cholesterol levels, and apo(a) isoform size were measured at examination cycle 5 in subjects participating in the Framingham Offspring Study who were free of CHD. After a mean follow-up of 12.3 years, 98 men and 47 women developed new CHD events. In multivariate analysis, the hazard ratio of CHD was approximately two-fold greater in men in the upper tertile of plasma Lp(a) levels, relative to those in the bottom tertile (P < 0.002). The apo(a) isoform size contributed only modestly to the association between Lp(a) and CHD and was not an independent predictor of CHD. In multivariate analysis, Lp(a) cholesterol was not significantly associated with CHD risk in men. In women, no association between Lp(a) and CHD risk was observed. Elevated plasma Lp(a) levels are a significant and independent predictor of CHD risk in men. The assessment of apo(a) isoform size in this cohort does not add significant information about CHD risk. In addition, the cholesterol content in Lp(a) is not a significant predictor of CHD risk.

Long-term prognostic implications of PCI in ACS patients without ischemia on the basis of computational pressure-flow dynamics derived fractional flow reserve

ObjectiveThis study aimed to investigate the linear association between lipoprotein(a) [Lp(a)] levels and all-cause and cardiovascular mortality in patients with acute coronary syndrome (ACS).MethodsThis retrospective cohort study included 578 patients with ACS who were hospitalized at Henan Provincial People’s Hospital between January 2020 and January 2024. Patients were categorized into two groups: lower Lp(a) group (≤ 300 mg/L) and higher Lp(a) group (> 300 mg/L). Kaplan-Meier survival analysis, Cox regression models, subgroup and sensitivity analyses were used to evaluate the association between Lp(a) and all-cause and cardiovascular mortality. Restricted cubic spline (RCS) analysis was conducted to explore nonlinear associations.ResultsDuring a median follow-up of 27.5 months, a total of 124 all-cause deaths occurred (21.5%), of which 79 cases (13.7%) were classified as cardiovascular deaths. Compared to the lower Lp(a) group, the higher Lp(a) group exhibited a significantly increased risk of all-cause and cardiovascular mortality across all models. In the fully adjusted model (Model 3), the hazard ratio (HR) for all-cause mortality was 1.719 (95% confidence interval [CI]: 1.197–2.470, P = 0.003), while the HR for cardiovascular mortality was 2.505 (95% CI: 1.529-4.102, P < 0.001). In an additional analysis using a 500 mg/L cut-off, patients with Lp(a) > 500 mg/L had a significantly higher risk of cardiovascular mortality (HR = 2.209, P = 0.001), while the association with all-cause mortality (P = 0.284) was not statistically significant in the fully adjusted model. When Lp(a) was analyzed as a continuous variable, each 90 mg/L increase in Lp(a) was associated with a 5% higher risk of all-cause mortality (HR = 1.052, 95% CI: 1.003-1.104, P = 0.038), and each 45 mg/L increase was associated with a 5% higher risk of cardiovascular mortality (HR = 1.054, 95% CI: 1.026-1.084, P < 0.001). For log10-transformed Lp(a), the HR was 1.954 (95% CI: 1.252-3.050, P = 0.003) for all-cause mortality and 3.913 (95% CI: 2.108-7.265, P < 0.001) for cardiovascular mortality. Similarly, for standardized Lp(a) (Z-score), the HR was 1.178 (95% CI: 1.009-1.375, P = 0.038) for all-cause mortality and 1.408 (95% CI: 1.179-1.681, P < 0.001) for cardiovascular mortality. Most subgroup analyses showed that elevated Lp(a) levels were significantly associated with an increased risk of all-cause and cardiovascular mortality (P < 0.05). Sensitivity analyses confirmed the robustness of the findings, with significant associations persisting after excluding patients with early mortality or without stent implantation. Kaplan-Meier analysis showed that both all-cause and cardiovascular survival rates were significantly lower in the high Lp(a) group compared to the low Lp(a) group (P < 0.001 for both). RCS analyses revealed a linear positive association between Lp(a) levels and both all-cause and cardiovascular mortality.ConclusionsHigher Lp(a) levels were independently and linearly associated with an increased risk of all-cause and cardiovascular mortality in ACS patients.

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.

Clinical registry-derived data are widely used to represent patient populations. In New Zealand (NZ), a national registry - the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry - aims to include all patients undergoing coronary angiography; other acute coronary syndrome (ACS) patients are also registered but without complete capture. This study compares national hospitalisation data of all first-time ACS admissions in NZ with patients in the ANZACS-QI registry, to investigate the use of clinical registry-derived data in research and in assessing clinical care. Patients admitted with first-time ACS in the NZ National Hospitalisation Dataset between 01/01/2015-31/12/2016 were included. Clinical characteristics and time to 12-month clinical outcomes were compared between patients captured and not-captured in the registry. 16,569 patients were admitted with first-time ACS, median age 69 years, 61% male; 60% (n = 9918) were enrolled in ANZACS-QI. Registry-captured patients were younger, more often male, and with a lower comorbidity burden than non-captured patients. Overall, 16% patients died within 12 months, 15% experienced a non-fatal cardiovascular readmission and 28% either died or were readmitted. Patients not captured in the registry were more than twice as likely to have experienced death or a non-fatal cardiovascular readmission within 12 months as captured patients. First-time ACS patients captured in the ANZACS-QI registry had very different clinical characteristics and outcomes than those not captured. Cardiovascular registry-derived data is dependent on registry design and may not be representative of the wider patient population; this must be considered when using registry-derived data.

It is postulated that lipoprotein (a) [Lp(a)] inhibits fibrinolysis, but this hypothesis has not been tested in humans due to the lack of specific Lp(a) lowering agents. Patients with elevated Lp(a) were randomized to antisense oligonucleotide [IONIS-APO(a)Rx] directed to apo(a) (n = 7) or placebo (n = 10). Ex vivo plasma lysis times and antigen concentrations of plasminogen, factor XI, plasminogen activator inhibitor 1, thrombin activatable fibrinolysis inhibitor, and fibrinogen at baseline, day 85/92/99 (peak drug effect), and day 190 (3 months off drug) were measured. The mean ± SD baseline Lp(a) levels were 477.3 ± 55.9 nmol/l in IONIS-APO(a)Rx and 362.1 ± 89.9 nmol/l in placebo. The mean± SD percentage change in Lp(a) for IONIS-APO(a)Rx was -69.3 ± 12.2% versus -5.4 ± 6.9% placebo (P < 0.0010) at day 85/92/99 and -15.6 ± 8.9% versus 3.2 ± 12.2% (P = 0.003) at day 190. Clot lysis times and coagulation/fibrinolysis-related biomarkers showed no significant differences between IONIS-APO(a)Rx and placebo at all time points. Clot lysis times were not affected by exogenously added Lp(a) at concentrations up to 200 nmol/l to plasma with very low (12.5 nmol/l) Lp(a) levels, whereas recombinant apo(a) had a potent antifibrinolytic effect. In conclusion, potent reductions of Lp(a) in patients with highly elevated Lp(a) levels do not affect ex vivo measures of fibrinolysis; the relevance of any putative antifibrinolytic effects of Lp(a) in vivo needs further study.

Acute coronary syndromes

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

General population studies have shown that elevated Lp(a) (lipoprotein[a]) levels are an emerging risk factor for cardiovascular disease and subsequent cardiovascular events. The role of Lp(a) for the risk of secondary MACE in patients undergoing carotid endarterectomy (CEA) is unknown. Our objective is to assess the association of elevated Lp(a) levels with the risk of secondary MACE in patients undergoing CEA. Lp(a) concentrations were determined in preoperative blood samples of 944 consecutive patients with CEA included in the Athero-Express Biobank Study. During 3-year follow-up, major adverse cardiovascular events (MACE), consisting of myocardial infarction, stroke, and cardiovascular death, were documented. After 3 years follow-up, Kaplan-Meier cumulative event rates for MACE were 15.4% in patients with high Lp(a) levels (>137 nmol/L; >80th cohort percentile) and 10.2% in patients with low Lp(a) levels (≤137 nmol/L; ≤80th cohort percentile; log-rank test: P=0.047). Cox regression analyses adjusted for conventional cardiovascular risk factors revealed a significant association between high Lp(a) levels and 3-year MACE with an adjusted hazard ratio of 1.69 (95% CI, 1.07-2.66). One-third of MACE occurred within 30 days after CEA, with an adjusted hazard ratio for the 30-day risk of MACE of 2.05 (95% CI, 1.01-4.17). Kaplan-Meier curves from time point 30 days to 3 years onward revealed no significant association between high Lp(a) levels and MACE. Lp(a) levels were not associated with histological carotid plaque characteristics. High Lp(a) levels (>137 nmol/L; >80th cohort percentile) are associated with an increased risk of 30-day MACE after CEA. This identifies elevated Lp(a) levels as a new potential risk factor for secondary cardiovascular events in patients after carotid surgery. Future studies are required to investigate whether Lp(a) levels might be useful in guiding treatment algorithms for carotid intervention.

Role of LipoprotEin(a) in CardiovascuLar diseases and premature acute coronary syndromes (RELACS study): Impact of Lipoprotein(a) levels on the premature coronary event and the severity of coronary artery disease.

Introduction Lipoprotein (a) [Lp(a)] is an atherogenic, procoagulant, and inflammatory particle. It is a genetic risk factor for cardiovascular disease, with up to 80% of its concentration inherited in an autosomal dominant manner. Purpose The objective is to determine the levels of Lp(a) in family members of patients with acute coronary syndrome (ACS) and elevated Lp(a). Methods We present the cohort of patients from our center included in the study HER(A) SCA, a multicenter, observational, and prospective study. Patients with acute coronary syndrome and elevated Lp(a), defined as ≥ 50 mg/dl, were included, and Lp(a) levels along with lipid profiles were determined in their first-degree relatives. Results A total of 96 individuals were included, 36 patients and 60 relatives. The mean age was 50.5 years. Of them, 54.4% were women, 25% were smokers, 24% were hypertensive, 12% were diabetic, and 31% were dyslipidemic. All risk factors were more frequent among ACS patients. 47,6% of ACS patients were previously on lipid-lowering treatment, most of them with statins, and only 36% with ezetimibe; none were receiving iPCSK9 treatment. Only 8% of the relatives were previously on lipid-lowering medications. The baseline characteristics of the population are found in Table. 1; all risk factors were more frequent in ACS patients. Relatives have a worse lipid profile than the index cases, with higher levels of total cholesterol and LDL, although with higher HDL levels. However, ACS patients have higher levels of Lp(a) (90.4 mg/dl vs. 54.3 mg/dl, p=0.001) and CRP (18.3 vs. 2.9, p=0.001). None of our patients had Lp(a) values above 180 mg/dl, although the highest levels were found in the index cases (Fig 2). Conclusions As supported by evidence, in our cohort, 51% of relatives of patients with ACS and elevated Lp(a) also have levels of Lp(a) &amp;gt; 50 mg/dl, although relatives have lower values. Elevated Lp(a) in relatives is associated with a worse overall lipid profile, suggesting the need for effective primary prevention to avoid future cardiovascular events. Only a small percentage of relatives with elevated Lp(a) receive lipid-lowering treatment.Table 1- The baseline charasteristicsFig. 2(Lp(a) event vs. Lp(a) relatives)

Impact of Lp(a) on lipid control in patients with acute coronary syndrome

Recently, interest has been growing in lipoprotein(a) (Lp[a]) as an independent risk factor for cardiovascular diseases. European Society of Cardiology recommends a single measurement of Lp(a) concentration as a guide to determine cardiovascular risk group and appropriate treatment. Although initially assumed to be genetically determined, a growing number of reports indicate that Lp(a) concentration may change over time. The aim of the study was to compare changes in the concentration of Lp(a) in patients with acute coronary syndrome (ACS) at the moment of ACS and 3 months later. Forty patients with ACS were enrolled and divided into ST‑segment elevation myocardial infarction (STEMI) and non‑STEMI (NSTEMI) + unstable angina (UA) groups. The levels of lipids, C‑reactive protein, high‑sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and Lp(a) were determined using routine laboratory methods, with interleukin‑33 levels measured using an enzyme‑linked immunosorbent assay. Among all ACS patients, 9 (22.5%) had elevated Lp(a) levels (>75 nmol/l). This proportion was higher in the STEMI (n = 8; 35%) than NSTEMI+UA (n = 2; 13%) patients. All patients with ACS showed significantly higher serum Lp(a) levels 3 months after ACS. The Lp(a) level at the moment of ACS and 3 months later differed markedly in the STEMI patients (P = 0.03), all patients with ACS (P = 0.003), and NSTEMI+UA individuals (P = 0.003). Measuring Lp(a) level during ACS may be insufficient for accurate diagnosis and effective treatment, as its concentration increases 3 months post‑ACS. Therefore, ACS may be regarded as another nongenetic factor influencing Lp(a) concentration.

To analyze the correlation of lipoprotein(a) [Lp(a)] with the clinical stability and severity of coronary artery stenosis in patients with coronary artery disease (CAD). A total of 531 patients undergoing coronary angiography in Nanfang Hospital between January, 2013 and December, 2016 were enrolled in this study. At the cutoff Lp(a) concentration of 300 mg/L, the patients were divided into high Lp(a) group (n=191) and low Lp(a) group (n=340). In each group, the patients with an established diagnosis of CAD based on coronary angiography findings were further divided into stable angina pectoris (SAP) group and acute coronary syndrome (ACS) group. The correlation between the severity of coronary artery stenosis and Lp(a) was evaluated. The patients in high and low Lp(a) groups showed no significant differences in age, gender, body mass index, smoking status, hypertension, or diabetes (P&gt;0.05). Multivariate logistic regression analysis revealed that age, gender, and serum levels of low-density lipoprotein cholesterol (LDL-C) and Lp(a) were independent risk factors for CAD in these patients. A high Lp(a) level was associated with an increased risk of CAD (OR=2.443, 95%CI: 1.205-4.951, P=0.013). The patients with a high Lp(a) level were at a significantly higher risk of CAD than those with a low Lp(a) level irrespective of a low or high level of LDL-C (P=0.006 and 0.020). In the patients with CAD, the ACS group had a significantly higher Lp(a) level than the SAP group (P &lt; 0.001); the proportion of the patients with high Gensini scores was significantly greater in high Lp(a) group than in low Lp(a) group (17.3% vs 5.6%, P=0.026), and a linear relationship was found between Lp(a) level and Gensini score (R=0.130, P=0.006). Serum level of Lp(a) is an independent risk factor for CAD, and an increased Lp(a) is the residual risk for CAD. In patients with CAD, a high Lp(a) level is associated with the clinical instability and severity of coronary artery stenosis.

Lipoprotein(a) in various conditions: To keep a sense of proportions