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BACKGROUND: Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but tailored tools for cardiovascular risk prediction remain unavailable. OBJECTIVES: To assess a broad panel of cardiovascular biomarkers and risk factors for the prediction of MACE and cardiovascular death in cancer patients. METHODS: In total, 2192 patients with newly diagnosed or recurrent cancer were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death. Univariable and multivariable risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with adverse outcomes, and a risk score was developed. RESULTS: Traditional cardiovascular risk factors and selected cancer types were linked to higher MACE risk. While levels of Lp(a), CRP, and GDF-15 did not associate with MACE, levels of ICAM-1, P-/E-/L-selectins, and NT-proBNP were independently linked to 2-year MACE risk. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age of ≥60 years and +2 points for atherosclerotic disease, yielding a bootstrapped C-statistic of 0.76 (95% CI: 0.71-0.81) for the prediction of 2-year MACE. Implementation of biomarker data conferred improved performance (0.83, 95% CI: 0.78-0.88), with a simplified model showing similar performance (0.80, 95% CI: 0.74-0.86). The biomarker-enhanced and simplified prediction models achieved a C-statistic of 0.82 (95% CI: 0.71-0.93) and 0.74 (95% CI: 0.64-0.83) for the prediction of 5-year cardiovascular death. CONCLUSION: Biomarker-enhanced risk prediction strategies allow the identification of cancer patients at high risk of MACE and cardiovascular death. While external validation studies are ongoing, this first-of-its-kind risk score may provide the basis for personalized cardiovascular risk assessment across cancer entities.

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Objective: This study aimed to explore the relationship between serum lipoprotein(a) (LP(a)) levels and early neurological deterioration (END) in patients with acute ischemic stroke (AIS) after thrombolysis. Methods: In total, 236 patients with AIS after thrombolysis were enrolled in this study. Serum LP(a) levels were measured on admission after thrombolysis. END was defined as an increase of at least two points in the NIHSS score within 48 hours after thrombolysis. Binary logistic regression analysis was used to assess the association between serum LP(a) levels and END. Results: Overall, patients with END had higher LP(a) than those without END (high LP(a): 38.3% vs 22.2%, intermediate LP(a): 40.3% vs 41.8%, low LP(a): 21.3% vs 36.0%, p<0.005). In the multivariate analysis, high LP(a) (defined as LP(a) level≥ 300 mg/L) was an independent risk factor for END post-thrombolysis (OR=3.154, 95% CI=1.067-9.322, p=0.038). Conclusion: Our findings demonstrated that LP(a) was an independent risk factor for END post-thrombolysis and that LP(a) level≥ 300 mg/L could be associated with END post-thrombolysis in this study population.

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Genetic variations among people mainly determine the blood levels of lipoprotein (a) (Lp(a)), and it is relatively stable throughout one's lifetime. Nevertheless, there could still be other factors that control the Lp(a) level. Thyroid hormones are known to influence the serum lipid level by regulating the expression of key enzymes that are involved in lipid metabolism. Both hypo and hyperthyroidism are associated with changes in lipid levels. Even though thyroid hormone abnormalities have been shown to alter traditional lipid parameters like low-density lipoprotein (LDL-C), its influence on Lp(a) has not been established. This review aims to identify the relationship between Lp(a) and thyroid hormones by reviewing data from correlative studies and observing treatment-related Lp(a) level changes in thyroid disorders from interventional studies. We searched MEDLINE, Cochrane, and Google Scholar databases with predefined search criteria and search strategies for paper identification. Individual reviewers reviewed identified papers for selection. Finalized papers were reviewed for Lp(a) levels and their responses to treatment in patients with thyroid disorders to establish the relationship between Lp(a) and thyroid hormone. We concluded that the data were limited and sometimes contradicted one another to establish a clear relationship between Lp(a) and thyroid hormones. Even though correlative studies data showed strong indications that overt-hypothyroidism was associated with high Lp(a) levels, thyroid hormone replacement studies did not show any significant changes in Lp(a) levels compared to pre-treatment in patients with both overt-hypothyroidism and subclinical hypothyroidism. More clinical trials focusing on Lp(a) with longer periods of treatment and follow-up in thyroid patients are needed to establish the relationship between the two. The possibility of dose-related Lp(a) responses to thyroid hormone treatment should also be explored.

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INTRODUCTION: Lipoprotein(a) [Lp(a)] is an established independent causal risk factor for cardiovascular disease and atherosclerosis. However, its association with young-onset ischemic stroke is not well-established. A systematic review and meta-analysis was performed to investigate the association of elevated Lp(a) with young ischemic stroke. METHODS: Four electronic databases: PubMed (MEDLINE), EMBASE, Scopus and Cochrane Library were systematically searched, profiling studies from inception till 6 Mar 2024. We included studies investigating the relationship between stratified Lp(a) levels and young ischemic stroke. We compared the odds of young stroke patients (age <65 years) having elevated Lp(a) compared to age-matched controls without stroke or transient ischemic attack. RESULTS: Five case-control studies comprising a total of 1345 patients were included; 57.7 % (776/1345) were females, with a mean age of 41.5 years. Among them, 22.5 % (264/1171) were smokers. Additionally, 16.8 % (197/1171) had hypertension, 5.9 % (69/1171) had diabetes, and 29.2 % (284/971) had hyperlipidemia. Young stroke patients were more likely to have high Lp(a) level than age-matched controls (OR 1.61, 95 %CI 1.24-2.10). Four studies defined a high Lp(a) level as ≥30mg/dL, whilst one study used a Lp(a) level of >23.2mg/dL as the cut-off. A sensitivity analysis excluding this study showed that young stroke patients were still more likely to have Lp(a) ≥30mg/dL than controls (OR 1.43, 95 %CI 1.08-1.88). CONCLUSION: Young stroke patients are more likely to have elevated Lp(a) compared to age-matched controls, suggesting an association between elevated Lp(a) and young stroke. Further research is warranted to evaluate the causal relationships between Lp(a) and young-onset ischemic stroke, as well as to conduct a cost-benefit analysis of Lp(a) screening in young adults as part of a primary prevention strategy.

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INTRODUCTION: Lipoprotein(a) [Lp(a)] is linked to higher risks of atherosclerotic cardiovascular disease (ASCVD). Current guideline recommendations are quite liberal on measuring Lp(a) (Class IIa, Level C), and may lead to underuse among (interventional) cardiologists. AREAS COVERED: This case-based narrative review outlines four clinical cases of patients with elevated Lp(a) to illustrate its pathophysiological impact on coronary artery disease (CAD). The expert consensus statements from the American Heart Association (AHA) and European Atherosclerosis Society (EAS) served as the basis of this review. More recent publications, from 2023 to 2024, were accessed through the MEDLINE online library. EXPERT OPINION: We highlighted the importance of routine Lp(a) measurement in identifying patients at high risk for atherosclerosis, necessitating potent risk mitigation. Measuring Lp(a) helps clinicians identify which patients are at highest residual risk, who require potent pharmacological treatment and special attention during catheter interventions. As noninvasive and advanced intravascular imaging modalities evolve, future catheterization laboratories will integrate advanced imaging, diagnostics, and treatment, facilitating tailored patient care. Knowing Lp(a) levels is crucial in this context. While Lp(a)-lowering drugs are currently investigated in clinical trials, it is of paramount importance to know Lp(a) levels and strive toward aggressive management of other modifiable risk factors in patients with elevated Lp(a) and established symptomatic CAD being diagnosed or treated in catheterization laboratories.

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BACKGROUND AND AIMS: The short-term (within 6 weeks) effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on lipid plaques have not been adequately evaluated. We aimed to investigate whether a single dose of a PCSK9 inhibitor before percutaneous coronary intervention (PCI) could reduce the abundance of lipid-core plaques identified via near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) at target lesions within a very short period. METHODS: This prospective, single-arm, single-center interventional study enrolled 27 consecutive patients with coronary artery disease. These patients underwent NIRS-IVUS during coronary angiography and repeat NIRS-IVUS during PCI performed between 2 and 6 weeks after the single-dose administration of 420 mg evolocumab. Changes in lesion lipid-core burden index (LCBI) and maximal LCBI over any 4-mm segment (max-LCBI4mm) were assessed using NIRS at the target lesions, along with lipid profile. RESULTS: The max-LCBI4mm significantly decreased from 387 before PCSK9 inhibitor administration to 315 after its administration (interquartile range [IQR]: 268-572 and 221-488, respectively; p = 0.02) within a very short period. The lesion LCBI also decreased from 161 to 117 (IQR: 105-263 and 65-226, respectively; p = 0.02). No significant changes were observed in the minimum lumen area and diameter. After PCSK9 inhibitor administration, low-density lipoprotein (LDL) cholesterol (p < 0.001), lipoprotein(a) (p = 0.001), and malondialdehyde-modified LDL (p < 0.001) levels decreased compared with those before its administration. CONCLUSIONS: A single dose of the PCSK9 inhibitor administered before PCI reduced the abundance of lipid-core plaques identified via NIRS-IVUS at target lesions within a very short period of 2-6 weeks.

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BACKGROUND: Predictors of neoatherosclerosis in patients who received primary percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear. OBJECTIVE: The aim of this study is to investigate the frequency and risk factors of neoatherosclerosis 1-year after the onset of ACS. METHODS: This study investigated 83 patients who underwent PCI for ACS followed by 1-year follow-up optical coherence tomography. The patients were categorized into the neoatherosclerosis (n = 11) and non-neoatherosclerosis groups (n = 72). Baseline characteristics, PCI procedures, medical therapies, and blood tests at 1-year, including detailed lipid profiles, were compared between the two groups. RESULTS: Diabetes mellitus was more prominent in the neoatherosclerosis than in the non-neoatherosclerosis group (45% vs. 17 %, respectively, p = 0.03). Total cholesterol (171 ± 37 mg/dL vs. 145 ± 25 mg/dL, respectively, p < 0.01), non-high-density lipoprotein cholesterol (HDL-C) (124 ± 36 mg/dL vs. 94 ± 24 mg/dL, respectively, p < 0.01), low-density lipoprotein cholesterol (94 ± 36 mg/dL vs. 72 ± 19 mg/dL, respectively, p < 0.01), and lipoprotein (a) (Lp[a]) (70 [19-112] mg/dL vs. 10 [3-25] mg/dL, respectively, p = 0.03) at follow-up were significantly higher in the neoatherosclerosis group. Multivariate analysis revealed that neoatherosclerosis was associated with high serum non-HDL-C (odds ratio [OR]: 1.075; 95 % confidence interval [CI]: 1.011-1.144; p < 0.01) and high serum Lp(a) levels (>30 mg/dL) (OR: 11.0; 95 % CI: 1.492-81.02; p = 0.02). CONCLUSION: Poorly controlled non-HDL-C and Lp(a) would be risk factors of neoatherosclerosis in patients 1-year after ACS.

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BACKGROUND: Recently, the effect of Lipoprotein(a) [Lp(a)] on thrombogenesis has aroused great interest, while inflammation has been reported to modify the Lp(a)-associated risks through an unidentified mechanism. PURPOSE: This study aimed to evaluate the association between platelet reactivity with Lp(a) and high-sensitivity C-reactive protein (hs-CRP) levels in percutaneous intervention (PCI) patients treated with clopidogrel. METHODS: Data were collected from 10,724 consecutive PCI patients throughout the year 2013 in Fuwai Hospital. High on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) were defined as thrombelastography (TEG) maximum amplitude of adenosine diphosphate-induced platelet (MAADP) > 47 mm and < 31 mm, respectively. RESULTS: 6615 patients with TEG results were finally enrolled. The mean age was 58.24 ± 10.28 years and 5131 (77.6%) were male. Multivariable logistic regression showed that taking Lp(a) < 30 mg/dL and hs-CRP < 2 mg/L as the reference, isolated Lp(a) elevation [Lp(a) ≥ 30 mg/dL and hs-CRP < 2 mg/L] was not significantly associated with HTPR (P = 0.153) or LTPR (P = 0.312). However, the joint elevation of Lp(a) and hs-CRP [Lp(a) ≥ 30 mg/dL and hs-CRP ≥ 2 mg/L] exhibited enhanced association with both HTPR (OR:1.976, 95% CI 1.677-2.329) and LTPR (OR:0.533, 95% CI 0.454-0.627). CONCLUSIONS: The isolated elevation of Lp(a) level was not an independent indicator for platelet reactivity, yet the concomitant elevation of Lp(a) and hs-CRP levels was significantly associated with increased platelet reactivity. Whether intensified antiplatelet therapy or anti-inflammatory strategies could mitigate the risks in patients presenting combined Lp(a) and hs-CRP elevation requires future investigation.

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BACKGROUND: Lipoprotein(a) [Lp(a)] plasma level is a well-known risk factor for coronary artery disease (CAD). Existing data regarding the influence of sex on the Lp(a)-CAD relationship are inconsistent. OBJECTIVE: To investigate the relationship between Lp(a) and CAD in men and women and to elucidate any sex-specific differences that may exist. METHODS: Data of patients with Lp(a) measurements who were admitted to a tertiary university hospital, Koc University Hospital, were analyzed. The relationship between Lp(a) levels and CAD was explored in all patients and in subgroups created by sex. Two commonly accepted Lp(a) thresholds ≥ 30 and ≥ 50 mg/dL were analyzed. RESULTS: A total of 1858 patients (mean age 54 ± 17 years; 53.33% females) were included in the analysis. Lp(a) was an independent predictor of CAD according to the multivariate regression model for the entire cohort. In all cohort, both cut-off values (≥ 30 and ≥ 50 mg/dL) were detected as independent predictors of CAD (p < 0.001). In sex-specific analysis, an Lp(a) ≥ 30 mg/dL was an independent predictor of CAD only in women (p < 0.001), but Lp(a) ≥ 50 mg/dL was a CAD predictor both in men and women (men, p = 0.004; women, p = 0.047). CONCLUSION: The findings of this study may suggest that different thresholds of Lp(a) level can be employed for risk stratification in women compared to men.

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Objective: Apolipoprotein B (ApoB) and lipoprotein (a) (Lp[a]) are predictors of cardiovascular disease (CVD) risk; therefore, current recommendations for CVD risk assessment and management advocate that patients receive testing for ApoB and Lp(a) in addition to the standard lipid panel. However, US guidelines around ApoB and Lp(a) testing have evolved over time and vary slightly by expert committee. The objective of this analysis was to estimate the number of insured individuals in the USA who received any component of a lipid test, or ApoB and/or Lp(a) testing, during 2019. Methods: We conducted a cross-sectional analysis to estimate the prevalence of any component of a lipid test, ApoB, and/or Lp(a) in the USA using four different claim data sources (including Medicaid, Medicare, and commercially insured enrollees). Prevalence estimates were age-, sex-, payor-, and region-standardized to the 2019 US Annual Social and Economic Supplement of the Current Population Survey. We also described the clinical profile of patients who received lipid testing between 2019 and 2021 (cohort analysis) in Optum claims database. Enrollees were grouped into four non-mutually exclusive cohorts based on their completion of any component of the lipid panel, ApoB, Lp(a), or ApoB and Lp(a). Results: In the prevalence cohort, over a third (38 %) of insured adults in the USA underwent testing for any component of a lipid panel in 2019. This proportion was higher for individuals aged ≥65 years compared to younger adults (62% vs 31 %). The proportion of ApoB and Lp(a) testing represented only <1 % of testing for any component of a lipid panel. In the cohort analysis, we found that lipid testing increased with age and comorbidities. Conclusion: These data should be considered by guideline-issuing agencies and organizations to develop education campaigns encouraging more frequent use of tests beyond the standard lipid panel.

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Background and aims: Different lipoprotein(a) [Lp(a)] assays may affect risk stratification of individuals and thus clinical decision-making. We aimed to investigate how transitioning between Lp(a) assays at a large central laboratory affected the proportion of individuals with Lp(a) result above clinical thresholds. Methods: We studied nationwide clinical laboratory data including 185,493 unique individuals (47.7 % women) aged 18-50 years with 272,463 Lp(a) measurements using Roche (2000-2009) and Siemens Lp(a) assay (2009-2019). Results: While the majority of individuals (66-75 %) had low levels of Lp(a) (<30 mg/dL) independent of the assay used, the Roche assay detected 20 % more individuals with Lp(a) >50 mg/dL, 40 % more individuals with Lp(a) >100 mg/dL and 80 % more individuals with Lp(a) > 180 mg/dL than the currently used Siemens assay, likely due to calibration differences. Conclusion: Transitioning from one Lp(a) immunoassay to another had significant impact on Lp(a) results, particularly in individuals approaching clinically relevant Lp(a) thresholds.

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BACKGROUND AND OBJECTIVE: High Lp(a) levels are a risk factor for ASCVD, however Lp(a) ordering in clinical practice is low. This study examines how race/ethnicity and socioeconomic status influence Lp(a) ordering. METHODS: This is a single center, retrospective study (2/1/2020-6/30/2023) using electronic medical records of adults with at least one personal ICD-10 diagnosis of ASCVD, aortic valve stenosis, resistant hypercholesterolemia (LDL-C >160 mg/dL on statin therapy), and family history of ASCVD or high Lp(a). We evaluated Lp(a) level differences among racial/ethnic groups and sexes. We also assessed associations between diagnosis type, diagnosis number, age at diagnosis, race/ethnicity, socioeconomic score (based on zip codes), public health coverage and the presence of Lp(a) orders. RESULTS: 4 % of our cohort (N=2,249 in 56,833) had an Lp(a) order (17.3 % of whom identified as Hispanic, 8.7 % non-Hispanic Black, 47.5 % non-Hispanic White, and 27 % Asian/other). Non-Hispanic Black and Hispanic patients had lower rates of Lp(a) orders (0.17 % and 0.28 %, respectively) when compared to non-Hispanic White patients (2.35 %), p < 0.001, however, their median Lp(a) levels were higher, p < 0.001. Individuals on Medicaid or belonging to deprived socioeconomic groups were less likely to have an Lp(a) order (IRR = 0.40, p < 0.001 and IRR = 0.39, p < 0.001 respectively). Certain diagnosis (carotid stenosis, family history of ASCVD and FH) and multiple diagnoses (>2) resulted in more Lp(a) orders compared to only one diagnosis (p < 0.001). CONCLUSIONS: Lp(a) ordering is low in patients with or at risk for ASCVD. Non-Hispanic Black and Hispanic patients are less likely to have an Lp(a) order. Individuals on Medicaid and residing in socioeconomically deprived neighborhoods are less like have an Lp(a) order. Lp(a) orders depend on the type and number of patients' diagnoses.

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Guidelines recommend checking lipoprotein(a) [Lp(a)] levels in patients at high-risk for cardiovascular disease, with more recent recommendations advocating for universal screening in all adults. A brief electronic survey was distributed to select groups of University of Pennsylvania Health System (UPHS) providers, including Internal Medicine and Cardiology physicians and advance practice providers, to understand the current attitudes and barriers to testing for Lp(a). Of the 126 survey respondents, only 31 % answered that they test for Lp(a) regularly in their practice. Presence of ASCVD and a family history of ASCVD were the most common reasons for testing. Most survey respondents (69 %) replied that they do not currently check Lp(a) levels in patients. The most common reasons provided included lack of familiarity with Lp(a), insurance/ billing concerns, lack of clinical trial outcomes data, and lack of available pharmaceutical interventions. Results from ongoing clinical trials of novel Lp(a)-lowering therapies, if successful, may address provider hesitation toward Lp(a)-testing, but there remains a large gap to fill in awareness of Lp(a).

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Atherosclerotic cardiovascular disease represents the most common cause of death worldwide. Altered cholesterol metabolism and inflammation are major cardiovascular risk factors that underpin atherosclerotic plaque growth and destabilization. While initial evidence considered dyslipidemia and inflammation as independent atherogenic actors, growing evidence has revealed that several molecular mechanisms implicated in cholesterol metabolism participate in multiple inflammatory signalling pathways. In particular, proprotein convertase subtilisin/kexin type 9, adenosine monophosphate-activated protein kinase pathway, oxidized low-density lipoproteins, and lipoprotein (a) have been demonstrated to share concurrent atherogenic and inflammatory properties. Novel lipid-lowering therapies targeting these molecular pathways have been implemented. Mechanistic and clinical studies have addressed their hypolipidemic potential and explored their role in atherosclerosis-related vascular inflammation, and ongoing randomized clinical trials are investigating their prognostic role. The purpose of this review was to dive into the signalling pathways linking cholesterol metabolism and inflammation and outline the current evidence on the anti-inflammatory activities of the novel lipid-lowering drugs.

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BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is a well-recognized risk factor for atherosclerotic cardiovascular disease (ASCVD). Few data are available on the distribution of Lp(a) levels among subjects at different cardiovascular risk and in subjects with monogenic and polygenic dyslipidemias (familial hypercholesterolemia, FH and familial hypobetalipoproteinemia type 1, FHBL1). The aim of this study was to investigate the distribution of Lp(a) plasma levels in subjects with high and low LDL-C levels (FH and FHBL1) and in the general population. METHODS AND RESULTS: The study cohorts included 356 hypercholesterolemic patients, 212 carrying a FH causative mutation, 144 with clinical FH (mutation negative - FHneg), 52 FHBL1 and 797 free-living subjects. Lp(a) levels were significantly higher in FH subjects (both FH and FHneg) (median 12.46 mg/dl and 14.0 mg/dl, respectively) compared with FHBL1 and free-living subjects (7.68 mg/dl and 7.18 mg/dl, respectively). More, Lp(a) levels were similar in FH subjects carrying LDLR defective and null mutations and FHneg. Subjects at high and very high CV risk exhibited significant higher Lp(a) levels (median 10.68 mg/dl and 9.20 mg/dl, respectively) compared with low and moderate CV risk (median 5.72 mg/dl and 7.80 mg/dl, respectively) (p < 0.0008). CONCLUSIONS: FH subjects exhibit higher Lp(a) levels than FHBL1 and general population. Lp(a) slightly contribute to hypercholesterolemia in FH patients. Subjects at high and very high CV risk exhibited significant higher Lp(a) levels compared with low and moderate CV risk. Combined evaluation of Lp(a) levels in FH subjects with other traditional risk factors could identify very high-risk individuals who may benefit from early aggressive treatments to avoid premature CV events.

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Background: Limited observational reports link elevated lipoprotein(a) (Lp[a]) levels to aortic stenosis (AS) or to disease progression. Data on large cohorts of verified severe AS patients are lacking. Objectives: The purpose of the study was to characterize Lp(a) levels of severe AS patients referred to transcatheter aortic valve implantation (TAVI) and compare them to a large cohort of Lp(a) samples derived from the general population. Methods: Lp(a) levels obtained from frozen serum samples of TAVI patients between 2012 and 2017 were compared to a control group for whom Lp(a) levels were obtained for any reason and stratified by gender. Multivariable binary logistic regression analyses were conducted to investigate associations between younger age at TAVI and an Lp(a) cutoff of 50 mg/dL. Results: Lp(a) levels of 503 TAVI were compared to 25,343 controls. Patients in the AS group had mildly higher median Lp(a) levels compared to controls (20.5 vs 18.7 mg/dL, P = 0.04). Lp(a) levels in males with severe AS were higher than controls (19.9 vs 16.6 mg/dL, P = 0.04). Females had a nonsignificant difference (22.1 vs 21.3 mg/dL, P = 0.87). In multivariable analysis, an Lp(a) cutoff of above 50 mg/dL was not associated with an earlier age at TAVI (beta: 1.04; 95% CI: 0.42-2.57; P = 0.94). Conclusions: Median Lp(a) levels were only mildly higher in severe AS patients undergoing TAVI in comparison to a large control group, mainly driven by higher Lp(a) levels in males. Higher Lp(a) levels were not associated with an earlier age at TAVI, rejecting its association with an accelerated disease progression.

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There is a well-established and strong link between high lipoprotein(a) concentration and coronary heart disease, but the evidence regarding peripheral artery disease and carotid atherosclerosis is not as conclusive. This review aims to summarize the relationships between lipoprotein(a), peripheral artery disease and carotid atherosclerosis, in order to try to understand the weight of lipoprotein(a) in determining the development, progression and any complications of atherosclerotic plaque at the carotid and peripheral artery level. There is currently no effective therapy to reduce lipoprotein(a) concentration, but understanding its significance as a vascular risk factor is the starting point to then explore (when effective therapies become available) if there is the possibility, even in patients with peripheral artery disease and carotid atherosclerosis, to achieve better control of the residual vascular risk that is ultimately induced by lipoprotein(a).

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BACKGROUND: The role of lipoprotein (a), or Lp(a), in the development of obstructive coronary artery disease (CAD) and high-risk plaque (HRP) among primary prevention patients with stable chest pain is unknown. We sought to evaluate the relationship of Lp(a), independent of low-density lipoprotein cholesterol (LDL-C), with the presence of obstructive CAD and HRP in an attempt to improve understanding of the residual risk imparted by Lp(a) on CAD. METHODS: We performed a secondary analysis among PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) Trial participants who had coronary computed tomographic angiography (CTA) performed and Lp(a) data available. Lp(a) concentration was analyzed as a binary variable with elevated Lp(a) defined as ≥50 mg/dL. "Stenosis ≥ 50%" was defined as ≥50% coronary artery stenosis in any epicardial vessel, and "Stenosis ≥ 70%" was defined as ≥70% coronary artery stenosis in any epicardial vessel and/or ≥50% left main coronary artery stenosis. HRP was defined as presence of plaque on CTA imaging with evidence of positive remodeling, low CT attenuation, or napkin ring sign. Multivariate logistic regression models were constructed to evaluate the association between Lp(a) and the outcomes of obstructive CAD and HRP stratified by LDL-C ≥100 mg/dL vs. <100 mg/dL. RESULTS: Of the 1,815 patients who underwent CTA and had Lp(a) data available, those with elevated Lp(a) were more commonly female and Black than those with lower Lp(a). Elevated Lp(a) was associated with both Stenosis ≥ 50% (OR 1.57, 95% CI 1.14-2.15, p=0.005) and Stenosis ≥ 70% (OR 2.05, 95% CI 1.34-3.11, p=0.0008) in multivariate models, and this relationship was not modified by LDL-C ≥100 mg/dL vs. <100 mg/dL (interaction p>0.4). Elevated Lp(a) was not associated with HRP when adjusted for obstructive CAD. CONCLUSIONS: This study of patients without known CAD found that elevated Lp(a) ≥50 mg/dL was independently associated with the presence of obstructive CAD regardless of controlled vs. uncontrolled LDL-C, but was not independently associated with HRP when Stenosis ≥ 50% or ≥ 70% was accounted for. Further research is warranted to delineate the role of Lp(a) in the residual risk for ASCVD that patients may have despite optimal LDL-C lowering.

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Background: High circulatory lipoprotein(a) [Lp(a)] concentration promotes atherosclerosis; however, its efficacy in predicting the extent of atherosclerotic coronary heart disease (CHD) with coronary artery obstruction and major adverse cardiovascular events (MACEs) in diabetic patients remains questionable. This study aimed to examine whether elevated circulating Lp(a) levels exacerbate CHD and to assess their utility in predicting MACEs in individuals diagnosed with type 2 diabetes mellitus (T2DM). Methods: In total, 4332 patients diagnosed with T2DM who underwent coronary angiography (CAG) were included and categorized into two groups (CHD and non-CHD) based on the CAG results. We used a correlation analysis to explore the potential links between the levels of circulating Lp(a) and CHD severity. Cox regression analysis was performed to evaluate MACEs. Results: The concentrations of circulating Lp(a) were markedly elevated in the CHD group and positively correlated with disease severity. Our results indicate that elevated circulating Lp(a) is a crucial risk factor that significantly contributes to both the progression and severity of CHD. The differences between the two groups are evident in the risk of CHD occurrence [odds ratio (OR) = 1.597, 95 % confidence interval (CI): 1.354-1.893, p < 0.001], the different levels of vessel involvement (OR = 1.908 for triple-vessel vs. single-vessel disease, 95 % CI: 1.401-2.711, p < 0.001), and their relation to the Gensini Score (OR = 2.002 for high vs. low GS, 95 % CI: 1.514-2.881, p < 0.001). Over the course of the 7-year follow-up period, the multivariate Cox regression analysis indicated that increased levels Lp(a) levels are independently associated with the occurrence of MACEs [hazard ratio (HR) = 1.915, 95 % CI: 1.571-2.493, p < 0.001]. Conclusion: We confirmed a positive correlation among circulating Lp(a) levels, CHD lesions count, and Gensini scores. Moreover, Lp(a) levels have predictive significance for the occurrence of MACEs in T2DM patients.

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BACKGROUND: Elevated lipoprotein (Lp(a)) levels are associated with increased risk of atherosclerotic processes and cardiovascular events in adults. The amount of Lp(a) is mainly genetically determined. Therefore, it is important to identify individuals with elevated Lp(a) as early as possible, particularly if other cardiovascular risk factors are present. The purpose of the study was to investigate whether, in a population of children and adolescents already followed for the presence of one or more cardiovascular risk factors (elevated blood pressure (BP), and/or excess body weight, and/or dyslipidemia), the measurement of Lp(a) can be useful for better stratifying their risk profile. METHODS: In a sample of 195 children and adolescents, height, body weight, waist circumference and systolic (SBP) and diastolic (DBP) BP were measured. Body Mass Index (BMI) and SBP and DBP z-scores were calculated. Plasma Lp(a), total cholesterol, high-density lipoprotein (HDL), triglycerides, glucose, insulin, uric acid and creatinine were assessed. Low-density lipoprotein (LDL) cholesterol was calculated with the Friedewald formula. High Lp(a) was defined as ≥ 75 nmol/L and high LDL cholesterol as ≥ 3.37 mmol/L. RESULTS: Our sample of children and adolescents (54.4% males, mean age 11.5 years) had median LDL cholesterol and Lp(a) values equal to 2.54 (interquartile range, IQR: 2.07-3.06) mmol/L and 22 (IQR: 7.8-68.6) nmol/L respectively. 13.8% of children had LDL cholesterol ≥ 3.37 mmol/L and 22.6 Lp(a) values ≥ 75 nmol/L. Lp(a) values were higher in children of normal weight than in those with excess weight (p = 0.007), but the difference disappeared if normal weight children referred for dyslipidemia only were excluded from the analysis (p = 0.210). 69.4% of children had normal Lp(a) and LDL cholesterol values and only 6.2% showed both elevated Lp(a) and LDL cholesterol levels. However, 16.6% of the sample, despite having normal LDL cholesterol, had elevated Lp(a) values. Multivariable analyses showed a significant association of LDL cholesterol both with Lp(a) values, and with the presence of elevated Lp(a) levels. For each mmol/L increase in LDL cholesterol the risk of having an elevated Lp(a) value increased by 73%. There was an inverse correlation between BMI z-score and Lp(a). Neither BP z-scores, nor other biochemical parameters were associated with Lp(a). CONCLUSIONS: In our population more than one out of five children had elevated Lp(a) values, and in about 17% of children elevated Lp(a) values were present in the absence of increased LDL cholesterol. Our results suggest that Lp(a) measurement can be useful to better define the cardiovascular risk profile in children and adolescents already followed for the presence of other cardiovascular risk factors such as elevated BP, excess body weight and high LDL cholesterol.

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