scholarly journals Association of circulating proprotein convertase subtilisin/kexin type 9 concentration, prothrombin time and cardiovascular outcomes: a prospective cohort study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jia Peng ◽  
Ming-Ming Liu ◽  
Hui-Hui Liu ◽  
Yuan-Lin Guo ◽  
Na-Qiong Wu ◽  
...  

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered to have multiple roles in the development of atherosclerosis, which is recently reported to participate in the thrombotic process. We aimed to examine the relationship between PCSK9 concentration, coagulation indexes and cardiovascular events. Methods A total of 2293 consecutive patients with angina-like chest pain and without lipid-lowering drugs treatment were enrolled and followed up for major adverse cardiovascular events (MACEs). Circulating PCSK9 concentration was determined by ELISA. The routine coagulation tests including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time were performed. The associations between PCSK9 concentration, routine coagulation indicators and MACEs were analyzed. Results Patients with high PCSK9 levels had lower PT and APTT levels (all p <  0.05). However, PCSK9 concentration was only independently and negatively correlated with PT (β = − 0.115, p <  0.001). During a mean of 38.3 months, 186 (8.1%) MACEs were occurred. Multiple Cox regression analysis indicated high PCSK9 or low PT levels as risk factors related to MACEs. When the prognosis was analyzed by the combination of PCSK9 and PT levels, patients with high PCSK9 and low PT had higher incidence of MACEs compared to those with low PCSK9 and high PT. Conclusions Our study firstly suggested that PCSK9 concentration was negatively correlated with plasma levels of PT. Furthermore, high PCSK9 and low PT were associated with MACEs and the combination of PCSK9 with PT had an addictive effect on predicting cardiovascular outcomes in patients with chest pain, which was useful for further subdivision of cardiovascular risks.

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 257
Author(s):  
Marat V. Ezhov ◽  
Narek A. Tmoyan ◽  
Olga I. Afanasieva ◽  
Marina I. Afanasieva ◽  
Sergei N. Pokrovsky

Background: Despite high-intensity lipid-lowering therapy, there is a residual risk of cardiovascular events that could be associated with lipoprotein(a) (Lp(a)). It has been shown that there is an association between elevated Lp(a) level and cardiovascular outcomes in patients with coronary heart disease. Data about the role of Lp(a) in the development of cardiovascular events after peripheral revascularization are scarce. Purpose: To evaluate the relationship of Lp(a) level with cardiovascular outcomes after revascularization of carotid and lower limbs arteries. Methods: The study included 258 patients (209 men, mean age 67 years) with severe carotid and/or lower extremity artery disease, who underwent successful elective peripheral revascularization. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The secondary endpoint was the composite of primary endpoint and repeated revascularization. Results: For 36-month follow-up, 29 (11%) primary and 128 (50%) secondary endpoints were registered. There was a greater risk of primary (21 (8%) vs. 8 (3%); hazard ratio (HR), 3.0; 95% confidence interval (CI) 1.5–6.3; p < 0.01) and secondary endpoints (83 (32%) vs. 45 (17%), HR, 2.8; 95% CI 2.0–4.0; p < 0.01) in patients with elevated Lp(a) level (≥30 mg/dL) compared to patients with Lp(a) < 30 mg/dL. Multivariable-adjusted Cox regression analysis revealed that Lp(a) was independently associated with the incidence of cardiovascular outcomes. Conclusions: Patients with peripheral artery diseases have a high risk of cardiovascular events. Lp(a) level above 30 mg/dL is significantly and independently associated with cardiovascular events during 3-year follow-up after revascularization of carotid and lower limbs arteries.


2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Jia Peng ◽  
Ming-Ming Liu ◽  
Jing-Lu Jin ◽  
Ye-Xuan Cao ◽  
Yuan-Lin Guo ◽  
...  

Abstract Background The risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) can be easily evaluated by noninvasive scoring systems, of which the NAFLD fibrosis score (NFS) is the most commonly used. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a new predictor of cardiovascular events, has been reported to be associated with cardiovascular outcomes and NAFLD. However, the relationship of NFS with PCSK9 and their prognostic abilities in cardiovascular risks are unknown. Methods A total of 2008 hospitalized subjects who had chest pain without lipid-lowering therapy were consecutively included. Baseline clinical data were collected, and the NFS was calculated. The circulating PCSK9 concentration was determined by enzyme immunoassay. The major adverse cardiovascular event (MACE) occurrences were recorded in the follow-up period. Associations of PCSK9 concentration with NFS were examined. All of the participants were categorized into three groups according to NFS levels and were further stratified by PCSK9 tertiles to evaluate the MACEs. Results 158 (7.87%) MACEs were observed during a mean of 3.2 years of follow-up. NFS levels were independently related to higher PCSK9 levels according to multivariable linear regression analysis. Furthermore, elevated PCSK9 and NFS concentrations were respectively associated with increased MACE incidence in multivariable Cox regression models. When combining NFS status with PCSK9 tertiles as a stratifying factor, patients with intermediate-high NFS and high PCSK9 levels had higher risks of events than those with low NFS and low PCSK9 levels. Conclusions This study revealed for the first time that NFS is positively related to PCSK9 and that the combination of NFS and PCSK9 greatly increased the risk of MACEs in patients with chest pain, providing a potential link between NFS and PCSK9 for predicting cardiovascular events.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N A Tmoyan ◽  
M V Ezhov ◽  
O I Afanasieva ◽  
E A Klesareva ◽  
M I Afanasieva ◽  
...  

Abstract Background Randomized trials have proved the reduction of cardiovascular events due to LDL-cholesterol level decrease. However, despite high-intensity statin therapy, there is a residual risk, that could be associated with lipoprotein(a) [Lp(a)]. It has been shown that there is an association between elevated Lp(a) level and cardiovascular outcomes in patients with coronary heart disease. Data about the role of Lp(a) in the development of cardiovascular events after revascularization of peripheral arteries are scarce. Purpose To evaluate the relationship of Lp(a) level with cardiovascular outcomes after revascularization of carotid and lower limbs arteries. Methods The study included 258 patients with severe carotid and/or lower extremity artery disease, who underwent successful elective revascularization. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The secondary endpoint was the composite of transitory ischaemic attack, limb amputation, hospitalization for unstable angina, or revascularization surgery. Results During 36 months follow-up 29 (11%) primary and 113 (44%) secondary endpoints were registered. It was noted greater rate of primary (21 [8%] vs. 8 [3%]; hazard ratio [HR], 3.0; 95% confidence interval [CI] 1.5–6.3; p<0.01) and secondary endpoints (72 [28%] vs. 41 (16%], HR, 2.5; 95% CI 1.7–3.7; p<0.01) in patients with elevated Lp(a) level (≥30 mg/dl) compared to patients with Lp(a) <30 mg/dl (Picture). Multivariable-adjusted Cox regression analysis revealed that Lp(a) was independently associated with incidence of cardiovascular outcomes. Conclusions Patients with peripheral artery diseases have a high risk of cardiovascular events and the level of Lp(a) ≥30 mg/dl is an independent predictor of cardiovascular events in prospective 3-year follow-up after revascularization of carotid and lower limbs arteries.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Peng ◽  
J.J Li

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) has multiple roles in the development and progression of atherosclerosis. Recent studies have indicated an association of PCSK9 with thrombotic process. Purpose We aimed to examine whether there exists a relationship between plasma PCSK9 concentration and the most commonly coagulation parameters including prothrombin time (PT) and activated partial thromboplastin time (APTT). Methods A total of 2293 consecutive patients with angina-like chest pain who had no treatment of lipid-lowering drugs were enrolled in this study. The baseline clinical and laboratory data were collected. PT and APTT tests were performed. Circulating PCSK9 concentrations were determined by ELISA and classified into three subgroups according to their levels of PCSK9 tertiles. The relation of PCSK9 concentration to PT or APTT were analyzed. Results Firstly, we found that the patients with high PCSK9 levels trended to have lower PT and APTT (p&lt;0.0001, p=0.003) according to results of PCSK9 tertiles. Then, pearson correlation analysis showed that log-transformed PCSK9 concentration was negatively correlated with PT (r=−0.194, p&lt;0.0001) and was significantly but weakly related with APTT (r=−0.075, p&lt;0.0001). The stepwise multivariable regression analysis revealed that PCSK9 was independently related with PT after adjusting traditional atherosclerotic risk factors and coagulation parameters (β=−0.137, p&lt;0.0001; β=−0.121, p&lt;0.0001, respectively). Conclusion Circulating PCSK9 concentration was independently negative associated with PT, suggesting a potential link between PCSK9 and PT that may be involved in atherogenesis and atherothrombosis. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jasper Jan Brugts ◽  
Nestor Mercado ◽  
Joachim Ix ◽  
Michael G Shlipak ◽  
Simon R Dixon ◽  
...  

Periprocedural bleeding is one of the most frequent complications of percutaneours coronary interventions. We assessed the relation between blood transfusion and all-cause mortality or incident cardiovascular events (death, MI, stroke) among 6103 patients of the Evaluation of Oral Xemilofiban in Controlling Thrombotic Events (EXCITE)-trial. Subjects were followed for 7 months after enrollment for the occurrence of events. Multivariate Cox-regression analysis evaluated the independent association of blood transfusion with each outcome adjusted for age, gender, race, diabetes mellitus, hypertension, hypercholesterolemia, history of MI, PCI, CABG, heart failure, LVEF<30%, use of beta-blockers, statins, ACE-inhibitors, platelet inhibitors and allocation to treatment with xemolifiban. In addition, propensity score analyses were performed (ROC 0.80). Mean age was 59.2 years, 21.7% were female, and 18.9% had diabetes mellitus. Of the169 patients who received blood transfusion, 14 (8.3%) died and 42 (24.9%) experienced a CVD event. Of the 5934 patients without transfusion, 65 (1.1%) died (p-value: <0.001) and 555 (9,4%) experienced a CVD event (p-value: <0.001) In multivariate analysis, blood transfusion was associated with a 5.3 fold increased risk of mortality (HR 5.3; 95% CI 2.8 –10.2), and a 2.5 fold increased risk of incident CVD (HR 2.5; 95% CI 1.7–3.4.) Noteworthy, patients who were US citizens had a higher transfusion rate then non-US citizens (OR 1.45, 95%CI 1.02–2.06) The need of blood transfusion is a strong and independent predictor of all-cause mortality and incident CVD events among patients undergoing PCI.


Heart ◽  
2021 ◽  
pp. heartjnl-2020-318414
Author(s):  
Georgios Giannopoulos ◽  
Sofia Karageorgiou ◽  
Dimitrios Vrachatis ◽  
Ioannis Anagnostopoulos ◽  
Maria S Kousta ◽  
...  

BackgroundAcute myocardial infarction (MI) is a major clinical manifestation of coronary artery disease. Post-MI morbidity and mortality can be reduced by lifestyle changes and aggressive risk factor modification. These changes can be applied more effectively if the patient is actively involved in the process. The hypothesis of this study was that an educational programme in post-MI patients could lead to reduced incidence of cardiovascular events.MethodsPost-MI patients were prospectively randomised into two groups. Patients in the intervention arm were scheduled to attend an 8-week-long educational programme on top of usual treatment, while controls received optimal treatment. The primary endpoint was the composite of all-cause death, MI, cerebrovascular event and unscheduled hospitalisation for cardiovascular causes. Endpoint adjudication was blinded.Results329 patients (238 men) were included, with a mean follow-up time of 17±4 months. In the primary analysis, mean primary end point-free survival time was 597 days (95% CI 571 to 624) in controls, compared with 663 days (95% CI 638 to 687) in the intervention group (p<0.001). The HR in the univariate Cox regression analysis was 0.48 (95% CI 0.32 to 0.73; p=0.001). The raw rates of the primary endpoint were 20.8% (6 deaths, 13 MIs, 2 strokes and 14 hospitalisations) vs 36.6% (8 deaths, 22 MIs, 7 strokes and 22 hospitalisations), respectively (OR 0.46, 95% CI 0.28 to 0.74; p=0.002).ConclusionThese results suggest that a relatively short adult education programme offered to post-MI patients has beneficial effects, resulting in reduced risk of cardiovascular events.Trial registration numberNCT04007887.


2018 ◽  
Vol 119 (02) ◽  
pp. 203-212 ◽  
Author(s):  
Kazuma Yamakawa ◽  
Jumpei Yoshimura ◽  
Takashi Ito ◽  
Mineji Hayakawa ◽  
Toshimitsu Hamasaki ◽  
...  

Background Two different criteria for evaluating coagulopathy in sepsis were recently released: sepsis-induced coagulopathy (SIC) and sepsis-associated coagulopathy (SAC). Although both use universal haemostatic markers of platelet count and pro-thrombin time, significance and usefulness of these criteria remain unclear. Objective This article validates and evaluates the significance of SIC and SAC criteria compared with the International Society on Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) and Japanese Association for Acute Medicine (JAAM) DIC criteria. Methods Clinical characteristics of patients from a nationwide Japanese cohort were classified by SIC, SAC or DIC status and relations between criteria were examined. We evaluated associations between in-hospital mortality and anticoagulant therapy according to the SIC, SAC or DIC status to clarify the significance of criteria for introducing anticoagulants. Intervention effects were analysed by Cox regression analysis adjusted by propensity scoring. Results Incidences of coagulopathy diagnosed by SIC and JAAM DIC were similar, whereas those of SAC and ISTH overt DIC were about half of the former two (61.4%, 60.8% vs. 45.3%, 29.3%). Severity and mortality of all criteria were almost comparable. For validating initiation of anticoagulation, favourable effects of anticoagulant therapy were observed only in sub-sets with, and not without, coagulopathy diagnosed by all four criteria. Slight non-significant differences between anticoagulant groupings were found in ISTH overt DIC- and SAC-negative populations, suggesting that some patients even ‘without’ these criteria may benefit from anticoagulant therapy. Conclusion Newly developed SIC diagnostic criteria for coagulopathy may be valuable in detecting appropriate candidates for anticoagulant therapy in sepsis and a useful alternative to conventional DIC scoring systems.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Z Meiszterics ◽  
T Simor ◽  
R J Van Der Geest ◽  
N Farkas ◽  
B Gaszner

Abstract Introduction Increased aortic pulse wave velocity (PWV) as a strong predictor of major advanced cardiovascular events (MACE) has a prognostic relevance in patients after myocardial infarction (MI). Several non-invasive methods have been proposed for the assessment of arterial stiffness, but the PWV values show significant differences according to the applied techniques. Cardiac magnetic resonance imaging (CMR) provides an accurate method to measure PWV and infarct size in patients after MI. Purpose Calculated PWV values of CMR based phase-contrast (PC) and invasively validated oscillometric methods were compared in this prospective observational study. We aimed to evaluate the cut-off PWV values for each method, while MACE predicted and validated the prognostic value of high PWV in post-infarcted patients in a 6-year follow-up. Methods 3D aortic angiography and PC velocity imaging was performed using a Siemens Avanto 1,5 T CMR device. Oscillometric based Arteriograph (AG) was used to assess PWV using direct body surface distance measurements. The comparison between the two techniques was tested. Patients received follow-up for MACE comprising all-cause death, non-fatal MI, ischemic stroke, hospitalization for heart failure and coronary revascularization. Event-free survival was analysed using Kaplan-Meier plots and log-rank tests. Univariable and multivariable Cox regression analysis was performed to identify outcome predictors. Results 75 patients (56 male, 19 female, average age: 56±13 years) referred for CMR were investigated, of whom 50 had coronary artery disease (CAD) including 35 patients with previous MI developing ischaemic late gadolinium enhancement (LGE) pattern. AG and CMR derived PWV values were significantly correlated (rho: 0,343, p&lt;0,05), however absolute PWV values were significantly higher for AG (median (IQR): 10,4 (9,2–11,9) vs. 6,44 (5,64–7,5); p&lt;0,001). Bland Altman analysis showed an acceptable agreement with a mean difference of 3,7 m/s between the two measures. In patients with CAD significantly (p&lt;0,01) higher PWV values were measured by AG and CMR, respectively. During the median follow-up of 6 years, totally 69 MACE events occurred. Optimized PWV cut-off values for MACE prediction were calculated (CMR: 6,47 m/s; AG: 9,625 m/s) by receiver operating characteristic analysis. Kaplan-Meier analysis in both methods showed a significantly lower event-free survival in case of high PWV (p&lt;0,01, respectively). Cox regression analysis revealed PWV for both methods as a predictor of MACE (PWV CMR hazard ratio (HR): 2,6 (confidence interval (CI) 1,3–5,1), PWV AG HR: 3,1 (CI: 1,3–7,1), p&lt;0,005, respectively). Conclusions Our study showed good agreement between the AG and CMR methods for PWV calculation. Both techniques are feasible for MACE prediction in postinfarcted patients. However, different AG and CMR PWV cut-off values were calculated to improve risk stratification. FUNDunding Acknowledgement Type of funding sources: None. Agreement between the two methods Kaplan-Meier event curves for MACE


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T Nishimura ◽  
K Senoo ◽  
I Hibiki ◽  
T Okura ◽  
T Miki ◽  
...  

Abstract Background Atrial fibrillation (AF) is associated with increased risks of stroke and heart failure. AF risk prediction can facilitate the efficient deployment of diagnosis or interventions to prevent AF. Purpose We sought to assess the combination prediction value of Holter electrocardiogram (Holter ECG) and the CHARGE-AF score (Cohorts for Aging and Research in Genomic Epidemiology-AF) for the new-onset of AF in a single center study. We also investigated the association between clinical findings and the new-onset of cerebral cardiovascular events. Methods From January 2008 and May 2014, 1246 patients with aged≥20 undergoing Holter ECG for palpitations, dizziness, or syncope were recruited. Among them, 350 patients were enrolled in this study after exclusion of 1) AF history at the time of inspection or before, 2) post cardiac device implantation, 3) follow-up duration &lt;1 year, and 4) no 12-lead ECG records within 6 months around Holter ECG. Results During the 5.9-year follow-up, 40 patients (11.4%) developed AF incidence. Multivariate cox regression analysis revealed that CHARGE-AF score (hazard ratio [HR]: 1.59, 95% confidence interval (95% CI): 1.13–2.26, P&lt;0.01), BMI (HR: 0.91, 95% CI: 0.83–0.99, P=0.03), frequent supraventricular extrasystoles (SVEs) ≥1000 beats/day (HR: 4.87, 95% CI: 2.59–9.13, P&lt;0.001) and first-degree AV block (HR: 3.52, 95% CI: 1.63–7.61, P&lt;0.01) were significant independent predictors for newly AF. The area under the ROC curve (AUC) of the combination of the CHARGE-AF score and frequent SVEs (≥1000) was greater than the CHARGE-AF score alone (0.73, 95% CI: 0.64–0.82 vs 0.66, 95% CI: 0.56–0.75, respectively). On the ROC curve, the CHARGE-AF score of 12.9 was optimum cut-off value for newly AF. Patients with both the CHARGE-AF score≥12.9 and SVEs≥1000 developed AF at 129.0/1000 person-years, compared with those with the CHARGE-AF score&lt;12.9 and SVEs≥1000 (48.9), the CHARGE-AF score≥12.9 and SVEs&lt;1000 (40.0) and the CHARGE-AF score&lt;12.9 and SVEs&lt;1000 (7.4), respectively. In multivariate cox regression analysis, age, past history of congestive heart failure and myocardial infarction, and antihypertensive medication were significant predictors of cerebral cardiovascular events (n=43), all of which signifying the components of the CHARGE-AF score. The AUC of the combination of the CHARGE-AF score and frequent SVEs (≥1000) was not different from the CHARGE-AF score alone (0.73, 95% CI: 0.64–0.81 vs 0.73, 95% CI: 0.64–0.82, respectively). Conclusion CHARGE-AF score has higher predictive power of both the new incident AF and cerebral cardiovascular events. The combination of CHARGE-AF score and SVEs≥1000 beats/day in Holter ECG can demonstrate the additional effect of prediction ability for the new incident AF, but not for cerebral cardiovascular events. FUNDunding Acknowledgement Type of funding sources: None.


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