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![Delineation of structural characteristics of Lp(a) and similarity between Lp(a) and plasminogen. (Adapted from [16].)](publication/258703248/figure/fig1/AS:203109860155403@1425436572998/Delineation-of-structural-characteristics-of-Lpa-and-similarity-between-Lpa-and.png)
Delineation of structural characteristics of Lp(a) and similarity between Lp(a) and plasminogen. (Adapted from [16].)
Source publication
Atherosclerotic cardiovascular diseases (CVD) are still the leading cause of morbidity and mortality worldwide, although optimal medical therapy has been prescribed for primary and secondary preventions. Residual cardiovascular risk for some population groups is still considerably high although target low density lipoprotein-cholesterol (LDL-C) lev...
Contexts in source publication
Context 1
... has been well recognized that Lp(a) is composed of two main components, named low density lipoprotein (LDL) and Apo(a). These two moieties are covalently tethered by a disulfide bond, which is established between Apo(a) and apolipoprotein B-100 (ApoB-100) motif of lipid core (see Figure 1) [16,29]. Similar to LDL-C, each Lp(a) is equipped with one molecule of ApoB-100, which is pre- dominantly responsible for the proatherosclerotic feature of Lp(a). ...Context 2
... to LDL-C, each Lp(a) is equipped with one molecule of ApoB-100, which is pre- dominantly responsible for the proatherosclerotic feature of Lp(a). Another important motif, Apo(a), is a glycosylated- rich moiety, and the gene sequence of Apo(a) is highly homologous with that of plasminogen (see Figure 1) [30,31]. Apolipoprotein(a) gene (LPA) locates on chromosome 6q23 and is flanked by plasminogen gene [32]. ...Citations
... In such condition, the levels of LDL-C were comparable in both groups, and the additional effect of Lp (a) could be investigated. Previous studies have shown that patients still have a certain risk of CAD after the treatment for reducing LDL-C, and this residual risk was related to elevated Lp (a) (49)(50)(51)(52)(53). In our study, the mean LDL-C level in CAD group was 2.6 mmol/L, meeting the LDL-C management target at a low level. ...
Background
Blood lipids disorder and atherosclerosis are closely related to coronary artery disease (CAD). This study aims to compare different blood lipid parameters combined with carotid intima-media thickness (cIMT) in predicting CAD.
Methods
This was a retrospective study including patients who underwent coronary angiography for highly suspected CAD. Blood samples were taken for lipid profile analysis and cIMT was evaluated by carotid ultrasound. Logistic analysis was used to establish different models of different lipid parameters in predicting CAD. The area under the receiver operating characteristic curve (AUC) was used to examine the predictive value. The optimal lipid parameter was also used to explore the relationship with multi-vessel CAD.
Results
Patients were classified into two groups based on whether CAD existed. Compared with non-CAD patients, the CAD group had higher lipoprotein (a) [Lp (a)], apolipoprotein B/apolipoprotein A, total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C and LDL-C/HDL-C. According to the AUCs, Lp (a) combined with cIMT (AUC: 0.713, P < 0.001) had the best performance in predicting CAD compared to other lipid parameters. High level of Lp (a) was also associated with multi-vessel CAD (odds ratio: 1.41, 95% confidence interval: 1.02–1.95, P = 0.036).
Conclusion
For patients with highly suspected CAD, Lp (a) better improved the predictive value of CAD rather than most of blood lipid indices, especially in the absence of high levels of LDL-C. Lp (a) also can be used to predict the multi-vessel CAD.
... Most individuals express two distinct Lp(a) isoforms [23]. The LPA gene, located in chromosome 6q23, is evolutionarily derived from the plasminogen (PLG) gene and remains highly homologous to it [23][24][25][26]. The LPA gene, and thus apo(a), consists of two kringle domains: kringle V (KV) and kringle IV (KIV) [23,27]. ...
... Specifically, KIV contains one copy of KIV1 and KIV3-10, but variable copies of KIV2 (1 to >40 on each allele) [23,27]. KIV2 and its different repeats in apo(a) account for the high size apo(a) polymorphism and determine the size of each apo(a) isoform, its formation rate, and serum Lp(a) concentrations [26,27]. ...
Familial hypercholesterolemia (FH) is the most frequent genetic disorder resulting in increased low-density lipoprotein cholesterol (LDL-C) levels from childhood, leading to premature atherosclerotic cardiovascular disease (ASCVD) if left untreated. FH diagnosis is based on clinical criteria and/or genetic testing and its prevalence is estimated as being up to 1:300,000–400,000 for the homozygous and ~1:200–300 for the heterozygous form. Apart from its late diagnosis, FH is also undertreated, despite the available lipid-lowering therapies. In addition, elevated lipoprotein(a) (Lp(a)) (>50 mg/dL; 120 nmol/L), mostly genetically determined, has been identified as an important cardiovascular risk factor with prevalence rate of ~20% in the general population. Novel Lp(a)-lowering therapies have been recently developed and their cardiovascular efficacy is currently investigated. Although a considerable proportion of FH patients is also diagnosed with high Lp(a) levels, there is a debate whether these two entities are associated. Nevertheless, Lp(a), particularly among patients with FH, has been established as a significant cardiovascular risk factor. In this narrative review, we present up-to-date evidence on the pathophysiology, diagnosis, and treatment of both FH and elevated Lp(a) with a special focus on their association and joint effect on ASCVD risk.
... Psychosocial characteristics of study participants before and after the COVID-19 lockdown……………………………………………………………………………………..62 ...
This thesis demonstrated the significant effect psychosocial factors have on cardiovascular risk factors in young adults in Rome, Italy, and how these risk factors could persist into adulthood leading to deteriorating cardiovascular health in the long term. The emergence of the COVID-19 pandemic has taken a massive toll on individuals' physiological and psychological well-being worldwide. Though public health measures ensued to keep the virus at bay and helped protect individuals against potential infections, this study shows that the psychological impact of these measures has proved to be immense.
While several ongoing research is focused on the long-term effect of the SARS-CoV-2 virus on infected individuals who are fully recovered and subsequently vaccinated, the impact of the psychosocial toll of the pandemic on cardiovascular health should not be discredited, especially in emerging adults. The deleterious effect of these cardiovascular risk factors may not be evident in young adults at the moment but could be a major concern in the near future.
... The adverse effects of elevated Lp(a) level on cardiovascular system have been well documented. [13][14][15][16] In general, elevated Lp(a) level is associated with endothelial dysfunction, inflammatory cells migration and infiltration, oxidative stress, and fibrinolysis inhibition. [13][14][15][16] These pathophysiological processes together lead to cardiovascular events. ...
... [13][14][15][16] In general, elevated Lp(a) level is associated with endothelial dysfunction, inflammatory cells migration and infiltration, oxidative stress, and fibrinolysis inhibition. [13][14][15][16] These pathophysiological processes together lead to cardiovascular events. [13][14][15][16] One recent study suggested that in patients with acute coronary syndrome (ACS) undergoing percutaneous coro-nary intervention (PCI), elevated Lp(a) level was associated with a higher risk of in-hospital cardiovascular event, including incident HF. 10 However, whether this association would be modified by baseline systemic inflammation was unknown. ...
... [13][14][15][16] These pathophysiological processes together lead to cardiovascular events. [13][14][15][16] One recent study suggested that in patients with acute coronary syndrome (ACS) undergoing percutaneous coro-nary intervention (PCI), elevated Lp(a) level was associated with a higher risk of in-hospital cardiovascular event, including incident HF. 10 However, whether this association would be modified by baseline systemic inflammation was unknown. Importantly, two recent studies indicated that the relationship between elevated Lp(a) level and cardiovascular event in community populations was modified by baseline high-sensitivity C-reactive protein (Hs-CRP) level. ...
Aim:
Current study was to evaluate relationship between baseline serum lipoprotein (a) [Lp(a)] level and prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and to explore whether the relationship would be modified by baseline high-sensitivity C-reactive protein (Hs-CRP) level.
Methods and results:
This is an observational prospective study. HFrEF patients from outpatient clinic were consecutively recruited (n = 362). Based on Lp(a) cutoff (30 mg/dL), patients were divided into normal and high Lp(a) groups; and based on Hs-CRP cutoff (3 mg/dL), patients were divided into low-degree and high-degree groups. The 1 year rate of HF rehospitalization was similar between these two groups (22.7% vs. 24.1%, P = 0.18), while the 1 year rate of cardiovascular mortality was higher in Lp(a) ≥ 30 mg/dL versus Lp(a) < 30 mg/dL groups (20.3% vs. 13.3%, P = 0.009), as was composite endpoint (44.4% vs. 36.0%, P < 0.001). After adjusting for covariates, elevated Lp(a) level remained associated with a higher risk of cardiovascular mortality [hazard ratio (HR) 1.22 and 95% confidence interval (CI) 1.04-1.64, P = 0.02] and composite endpoint (HR 1.38 and 95% CI 1.16-2.01, P = 0.006). In Hs-CRP ≥ 3 mg/dL group, elevated Lp(a) level was associated with HF rehospitalization, cardiovascular mortality, and composite endpoint, which was not observed in Hs-CRP < 3 mg/dL group. The association was greater for cardiovascular mortality (P-interaction = 0.04) and composite endpoint (P-interaction = 0.02) in Hs-CRP ≥ 3 mg/dL versus Hs-CRP < 3 mg/dL groups.
Conclusion:
Elevated Lp(a) level is associated with higher risk of cardiovascular mortality in HFrEF patients, which might be due to enhanced systemic inflammation.
... In such condition, the levels of LDL-C were comparable in both groups, and the additional effect of Lp (a) could be investigated. Previous studies have shown that patients still have a certain risk of CAD after the treatment for reducing LDL-C, and this residual risk was related to elevated Lp (a) [39][40][41][42][43]. Among patients whose target blood lipids are normal or below the target, Lp (a) will play an important role in the prediction of CAD. ...
Background: Blood lipids disorder and atherosclerosis are closely related to coronary artery disease (CAD). This study aims to compare different blood lipid parameters combined with carotid intima-media thickness (cIMT) in predicting CAD.
Methods: This was a retrospective study including patients who underwent coronary angiography for highly suspected CAD. Blood samples were taken for lipid profile analysis and cIMT was evaluated by carotid ultrasound. Logistic analysis was used to establish different models of different lipid parameters in predicting CAD. The area under the receiver operating characteristic curve (AUC) was used to examine the predictive value. The optimal lipid parameter was also used to explore the relationship with multi-vessel CAD.
Results: Patients were classified into two groups based on whether CAD existed. There was no difference in low-density lipoprotein cholesterol (LDL-C) between the two groups. Compared with non-CAD patients, the CAD group had higher lipoprotein (a) (Lp (a)), apolipoprotein B/apolipoprotein A, total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C and LDL-C/HDL-C. According to the AUCs, Lp (a) combined with cIMT (AUC: 0.713, P < 0.001) had the best performance in predicting CAD compared to other lipid parameters. High levels of Lp (a) was also associated with multi-vessel CAD (odds ratio: 1.41, 95% confidence interval: 1.02–1.95, P = 0.036).
Conclusion: For patients with highly suspected CAD, Lp (a) better improved the predictive value of CAD rather than most of blood lipid indices, especially in the absence of high levels of LDL-C. Lp (a) also can be used to predict the multi-vessel CAD.
... In such condition, the levels of LDL-C were comparable in both groups, and the additional effect of Lp (a) could be investigated. Previous studies have shown that patients still have a certain risk of CAD after the treatment for reducing LDL-C, and this residual risk was related to elevated Lp (a) [39][40][41][42][43]. Among patients whose target blood lipids are normal or below the target, Lp (a) will play an important role in the prediction of CAD. ...
Background
Blood lipids disorder and atherosclerosis are closely related to coronary artery disease (CAD). This study aims to compare different blood lipid parameters combined with carotid intima-media thickness (cIMT) in predicting CAD.
Methods
This was a retrospective study including patients who underwent coronary angiography for highly suspected CAD. Blood samples were taken for lipid profile analysis and cIMT was evaluated by carotid ultrasound. Logistic analysis was used to establish different models of different lipid parameters in predicting CAD. The area under the receiver operating characteristic curve (AUC) was used to examine the predictive value. The optimal lipid parameter was also used to explore the relationship with multi-vessel CAD.
Results
Patients were classified into two groups based on whether CAD existed. There was no difference in low-density lipoprotein cholesterol (LDL-C) between the two groups. Compared with non-CAD patients, the CAD group had higher lipoprotein (a) (Lp (a)), apolipoprotein B/apolipoprotein A, total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C and LDL-C/HDL-C. According to the AUCs, Lp (a) combined with cIMT (AUC: 0.713, P < 0.001) had the best performance in predicting CAD compared to other lipid parameters. High levels of Lp (a) was also associated with multi-vessel CAD (odds ratio: 1.41, 95% confidence interval: 1.02–1.95, P = 0.036).
Conclusion
For patients with highly suspected CAD, Lp (a) better improved the predictive value of CAD rather than most of blood lipid indices, especially in the absence of high levels of LDL-C. Lp (a) also can be used to predict the multi-vessel CAD.
... In such condition, the levels of LDL-C were comparable in both groups, and the additional effect of Lp (a) could be investigated. Previous studies have shown that patients still have a certain risk of CAD after the treatment for reducing LDL-C, and this residual risk was related to elevated Lp (a) [38][39][40][41][42]. Among patients whose target blood lipids are normal or below the target, Lp (a) will play an important role in the prediction of CAD. ...
Background: Blood lipids disorder and atherosclerosis are closely related to coronary artery disease (CAD). This study aims to compare different blood lipid parameters combined with carotid intima-media thickness (cIMT) in predicting CAD.
Methods: This was a retrospective study including patients who underwent coronary angiography for highly suspected CAD. Blood samples were taken for lipid profile analysis and cIMT was evaluated by carotid ultrasound. Logistic analysis was used to establish different models of different lipid parameters in predicting CAD. The area under the receiver operating characteristic curve (AUC) was used to examine the predictive value. The optimal lipid parameter was also used to explore the relationship with multi-vessel CAD.
Results: Patients were classified into two groups based on whether CAD existed. There was no difference in low-density lipoprotein cholesterol (LDL-C) between the two groups. Compared with non-CAD patients, the CAD group had higher lipoprotein (a) (Lp (a)), apolipoprotein B/apolipoprotein A, total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C and LDL-C/HDL-C. According to the AUCs, Lp (a) combined with cIMT (AUC: 0.713, p < 0.001) had the best performance in predicting CAD compared to other lipid parameters. High levels of Lp (a) was also associated with multi-vessel CAD (odds ratio: 1.41, 95% confidence interval: 1.02–1.95, P = 0.036).
Conclusion: For patients with highly suspected CAD, Lp (a) better improved the predictive value of CAD rather than most of blood lipid indices, especially in the absence of high levels of LDL-C. Lp (a) also can be used to predict the multi-vessel CAD.
... Acute coronary syndrome (ACS) is the most leading cause of cardiovascular-related mortality and disability worldwide [1,2]. It is widely acknowledged that low-density lipoprotein cholesterol (LDL-C) is causally associated with development and progression of ACS. ...
... Hence, the level of LDL-C ≤1.8 mmol/L is recommended for patients with established atherosclerotic cardiovascular disease by most treatment guidelines, even a more aggressive target of LDL-C ≤1.4 mmol/L is recommended in recent years [3,4]. The LDL-C level of many individuals can achieve therapeutic goals based on statin therapy, however, the incidence of major adverse cardiovascular events (MACE) is still high [2,5]. Therefore, further risk stratification and identification of high-risk individuals in low-risk patients (LDL-C ≤1.8 mmol/L) are very urgent and necessary. ...
Low-density lipoprotein cholesterol (LDL-C) is a traditional and important risk factor for atherosclerotic cardiovascular disease (CVD). Recently, lipoprotein (a) (lp(a)) attracts considerable attention as a residual risk factor for CVD. However, the roles of lp(a) in acute coronary syndrome (ACS) patients with well-controlled LDL-C (≤1.8mmol/L) after percutaneous coronary intervention (PCI) remain unclear. Current study results demonstrated that occurrence of major adverse cardiovascular events (MACE) and recurrent myocardial infarction (MI) increased with the Lp(a) increasing in patients with LDL-C≤1.8mmol/L at 1-month follow-up. In relatively low-risk patients presented with ACS and underwent PCI (LDL-C ≤1.8mmol/L at 1-month follow-up), lp(a) is still independently related to adverse prognosis. Further researches of targeted therapy against lp(a) are warranted.
... Several studies have demonstrated that Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease due to its proatherosclerotic and pro-thrombotic effects. [9][10][11][12] In addition, high serum Lp(a) level was related to an increased risk of acute ischemic events, incident HF, and cardiovascular mortality. [9][10][11][12][13][14] For example, our prior study has indicated that among individuals with acute coronary syndrome undergoing percutaneous coronary intervention, compared to those with low serum Lp(a) level, individuals with high serum Lp(a) level had a higher risk of developing congestive HF during hospitalization. ...
... [9][10][11][12] In addition, high serum Lp(a) level was related to an increased risk of acute ischemic events, incident HF, and cardiovascular mortality. [9][10][11][12][13][14] For example, our prior study has indicated that among individuals with acute coronary syndrome undergoing percutaneous coronary intervention, compared to those with low serum Lp(a) level, individuals with high serum Lp(a) level had a higher risk of developing congestive HF during hospitalization. 13 Interestingly, results from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort study suggested that increased serum Lp(a) level at baseline was associated with incident HF only in the White but not in the Black, Hispanic, or Chinese populations. ...
Background
The current study aimed to evaluate the relationship between baseline serum lipoprotein (a) [Lp(a)] level and heart failure with reduced ejection fraction (HFrEF) development.
Methods
This was a retrospective study, and participants were enrolled from the outpatient clinic. All data were extracted from the electronic health record of the outpatient clinic system. The follow-up was performed through reviewing the clinical notes at the outpatient clinic system, and study outcome of the current study was the first diagnosis of HFrEF. Participants were divided into low Lp(a) (<30 mg/dl, n = 336) and high Lp(a) (≥30 mg/dl, n = 584) groups.
Results
Individuals in the high Lp(a) group were more likely to be men and have diabetes mellitus (DM) and dyslipidemia. Increased Lp(a) at baseline was positively associated with serum N-terminal pro-B natriuretic peptide level while negatively associated with left ventricular ejection fraction (LVEF) at follow-up. After adjusting for covariates, per 10 mg/dl increase in baseline Lp(a) remained significantly associated with HFrEF, with odds ratio of 1.17 (95% confidence interval of 1.05, 1.46). The magnitude of association between baseline Lp(a) level and HFrEF was greater in men and in individuals with DM or coronary heart disease (CHD), while it was weaker in individuals treated with beta-blocker at baseline.
Conclusion
Increased Lp(a) at baseline was associated with HFrEF development. The adverse effects of Lp(a) were greater on men and individuals with DM or CHD, which were mitigated by beta-blocker therapy. These findings together underscore the possibility and usefulness of Lp(a) as a new risk factor to predict HFrEF.
... Previous studies have demonstrated a strong and independent association between Lp(a) and carotid artery disease [6] and Lp(a) independently predict carotid atherosclerosis progression [7]. However, for a great degree of homology between apo(a) and plasminogen [8], lots of studies considered the Lp(a) fragments showed an anti-angiogenesis role in vitro [9,10]. On the contrast, there are also a great deal of conflicting reports postulated Lp(a) induced angiogenesis [11] while others demonstrated a neutral effect on angiogenesis [12], engendering considerable controversy. ...
... Based on the high degree of homology between apo(a) and plasminogen [8], a number of researches found that some of apo(a) fragments played a role of anti-angiogenesis which was similar to the function of plasminogen [9,10]. Nevertheless, the above results were from the small samples study in vitro, there is still lack of pathophysiological role of the anti-angiogenic or angiogenic activity in humans [22]. ...
Background:
Lipoprotein(a) is genetically determined and increasingly recognized as a major risk factor for arteriosclerotic cardiovascular disease. We examined whether plasma lipoprotein(a) concentrations were associated with intraplaque neovascularization (IPN) grade in patients with carotid stenosis and in terms of increasing plaque susceptibility to haemorrhage and rupture.
Methods:
We included 85 patients diagnosed with carotid stenosis as confirmed using carotid ultrasound who were treated at Guangdong General Hospital. Baseline data, including demographics, comorbid conditions and carotid ultrasonography, were recorded. The IPN grade was determined using contrast-enhanced ultrasound through the movement of the microbubbles. Univariate and multivariate binary logistic regression analyses were used to evaluate the association between lipoprotein(a) and IPN grade, with stepwise adjustment for covariates including age, sex, comorbid conditions and statin therapy (model 1), total cholesterol, triglyceride, low-density lipoprotein cholesterol calculated by Friedwald's formula, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B (model 2), maximum plaque thickness and total carotid maximum plaque thickness, degree of carotid stenosis and internal carotid artery (ICA) occlusion (model 3).
Results:
Lipoprotein(a) was a significant predictor of higher IPN grade in binary logistic regression before adjusting for other risk factors (odds ratio [OR] 1.238, 95% confidence interval [CI] (1.020, 1.503), P = 0.031). After adjusting for other risk factors, lipoprotein(a) still remained statistically significant in predicting IPN grade in all model. (Model 1: OR 1.333, 95% CI 1.074, 1.655, P = 0.009; Model 2: OR 1.321, 95% CI 1.059, 1.648, P = 0.014; Model 3: OR 1.305, 95% CI 1.045, 1.628, P = 0.019). Lp(a) ≥ 300 mg/L is also significantly related to IPN compare to < 300 mg/L (OR 2.828, 95% CI 1.055, 7.580, P = 0.039) as well as in model 1, while in model 2 and model 3 there are not significant difference.
Conclusions:
Plasma lipoprotein(a) concentrations were found to be independently associated with higher IPN grade in patients with carotid stenosis. Lowering plasma lipoprotein(a) levels may result in plaque stabilization by avoiding IPN formation.
