scholarly journals Evaluating bococizumab, a monoclonal antibody to PCSK9, on lipid levels and clinical events in broad patient groups with and without prior cardiovascular events: Rationale and design of the Studies of PCSK9 Inhibition and the Reduction of vascular Events (SPIRE) Lipid Lowering and SPIRE Cardiovascular Outcomes Trials

2016 ◽  
Vol 178 ◽  
pp. 135-144 ◽  
Author(s):  
Paul M. Ridker ◽  
Pierre Amarenco ◽  
Robert Brunell ◽  
Robert J. Glynn ◽  
J. Wouter Jukema ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cardiovascular Events ◽  
Cardiovascular Outcomes ◽  
Lipid Lowering ◽  
Lipid Levels ◽  
Vascular Events ◽  
Clinical Events ◽  
Patient Groups ◽  
Pcsk9 Inhibition

scholarly journals Lipoprotein(a) and Cardiovascular Outcomes after Revascularization of Carotid and Lower Limbs Arteries

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 257
Author(s):  
Marat V. Ezhov ◽  
Narek A. Tmoyan ◽  
Olga I. Afanasieva ◽  
Marina I. Afanasieva ◽  
Sergei N. Pokrovsky
Keyword(s):  
Primary Endpoint ◽  
Cardiovascular Events ◽  
Cardiovascular Outcomes ◽  
Lower Limbs ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Cox Regression Analysis ◽  
Lipoprotein A ◽  
Secondary Endpoints

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.

scholarly journals Cardiovascular outcomes trials with non-statin lipid-lowering drugs in diabetes

2018 ◽  
Vol 18 (3) ◽  
pp. 101-105
Author(s):  
Fariha Naeem ◽  
Gerard McKay ◽  
Miles Fisher
Keyword(s):  
Statin Therapy ◽  
Cardiovascular Events ◽  
Ldl Cholesterol ◽  
Lipid Lowering ◽  
High Dose ◽  
Large Trial ◽  
Pcsk9 Inhibitors ◽  
Vascular Events ◽  
Lipid Lowering Drugs ◽  
Cardiovascular Morbidity And Mortality

Statin therapy is proven to reduce cardiovascular morbidity and mortality in people with diabetes, and high-dose statins are recommended for people with established atherosclerotic vascular disease. In two dedicated studies in people with diabetes, fibrates did not significantly reduce cardiovascular events and were associated with serious side effects. A similar lack of benefit was seen in two large studies of niacin. Ezetimibe, when added to statins, may further reduce LDL cholesterol and non-fatal vascular events. The PCSK9 inhibitors are a new class of subcutaneous lipid- lowering drugs which cause profound reductions in LDL cholesterol when added to statins. Evolocumab reduced non-fatal cardiovascular events when added to background statin therapy in a larger group of subjects and the benefits were confirmed in a diabetes subgroup. In another large trial alirocumab reduced major adverse cardiovascular events and total mortality. The clinical use of ezetimibe and PCSK9 inhibitors is currently limited by cost.

scholarly journals Changes in circulating pro-protein convertase subtilisin/kexin type 9 levels – experimental and clinical approaches with lipid-lowering agents

2019 ◽  
Vol 26 (9) ◽  
pp. 930-949 ◽  
Author(s):  
C Macchi ◽  
M Banach ◽  
A Corsini ◽  
CR Sirtori ◽  
N Ferri ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Cardiovascular Events ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Outcomes ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome

Regulation of pro-protein convertase subtilisin/kexin type 9 (PCSK9) by drugs has led to the development of a still small number of agents with powerful activity on low-density lipoprotein cholesterol levels, associated with a significant reduction of cardiovascular events in patients in secondary prevention. The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) and Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab (ODYSSEY OUTCOMES) studies, with the two available PCSK9 antagonists, i.e. evolocumab and alirocumab, both reported a 15% reduction in major adverse cardiovascular events. Regulation of PCSK9 expression is dependent upon a number of factors, partly genetic and partly associated to a complex transcriptional system, mainly controlled by sterol regulatory element binding proteins. PCSK9 is further regulated by concomitant drug treatments, particularly by statins, enhancing PCSK9 secretion but decreasing its stimulatory phosphorylated form (S688). These complex transcriptional mechanisms lead to variable circulating levels making clinical measurements of plasma PCSK9 for cardiovascular risk assessment a debated matter. Determination of total PCSK9 levels may provide a diagnostic tool for explaining an apparent resistance to PCSK9 inhibitors, thus indicating the need for other approaches. Newer agents targeting PCSK9 are in clinical development with a major interest in those with a longer duration of action, e.g. RNA silencing, allowing optimal patient compliance. Interest has been expanded to areas not only limited to low-density lipoprotein cholesterol reduction but also investigating other non-lipid pathways raising cardiovascular risk, in particular inflammation associated to raised high-sensitivity C-reactive protein levels, not significantly affected by the present PCSK9 antagonists.

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 ◽  
...  
Keyword(s):  
Chest Pain ◽  
Prothrombin Time ◽  
Cardiovascular Events ◽  
Cox Regression ◽  
Cardiovascular Outcomes ◽  
Lipid Lowering ◽  
Thrombin Time ◽  
Proprotein Convertase ◽  
Cox Regression Analysis ◽  
Routine Coagulation

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.

Antithrombotic Therapy in Lower Extremity Artery Disease

2020 ◽  
Vol 18 (3) ◽  
pp. 215-222 ◽  
Author(s):  
Mislav Vrsalovic ◽  
Victor Aboyans
Keyword(s):  
Lower Extremity ◽  
Antiplatelet Therapy ◽  
Antithrombotic Therapy ◽  
Cardiovascular Events ◽  
Cardiovascular Outcomes ◽  
Lower Limbs ◽  
Stent Type ◽  
Increased Risk ◽  
Artery Disease ◽  
Lower Extremity Artery Disease

Lower extremity artery disease (LEAD) is a marker of a more advanced atherosclerotic process often affecting multiple vascular beds beyond the lower limbs, with a consequent increased risk for all-cause and cardiovascular mortality. Antithrombotic therapy is the cornerstone of management of these patients to prevent ischaemic cardiovascular and limb events and death. In patients with symptomatic LEAD, the efficacy of aspirin has been established long ago for the prevention of cardiovascular events. In the current guidelines, clopidogrel may be preferred over aspirin following its incremental ability to prevent cardiovascular events, while ticagrelor is not superior to clopidogrel in reducing cardiovascular outcomes. Dual antiplatelet therapy (DAPT, aspirin with clopidogrel) is currently recommended for at least 1 month after endovascular interventions irrespective of the stent type. Antiplatelet monotherapy is recommended after infra-inguinal bypass surgery, and DAPT may be considered in below-the-knee bypass with a prosthetic graft. In symptomatic LEAD, the addition of anticoagulant (vitamin K antagonists) to antiplatelet therapy increased the risk of major and life-threatening bleeding without benefit regarding cardiovascular outcomes. In a recent trial, low dose of direct oral anticoagulant rivaroxaban plus aspirin showed promising results, not only to reduce death and major cardiovascular events, but also major limb events including amputation. Yet, this option should be considered especially in very high risk patients, after considering also the bleeding risk. Despite all the evidence accumulated since >40 years, many patients with LEAD remain undertreated and deserve close attention and implementation of guidelines advocating the use of antithrombotic therapies, tailored according to their level of risk.

scholarly journals New-Onset Diabetes, Endothelial Dysfunction, and Cardiovascular Outcomes in Hypertensive Patients: An Illness-Event Model Analysis

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 721
Author(s):  
Raffaele Maio ◽  
Edoardo Suraci ◽  
Benedetto Caroleo ◽  
Cristina Politi ◽  
Simona Gigliotti ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Confidence Interval ◽  
Cardiovascular Events ◽  
Forearm Blood Flow ◽  
Cardiovascular Outcomes ◽  
Hazard Ratio ◽  
Baseline Status ◽  
Event Model ◽  
New Onset

Background. Insulin resistance and endothelial dysfunction are common findings in hypertensives, both predisposing to a higher risk of diabetes and cardiovascular events. We designed this study to evaluate the role of endothelial dysfunction in three pathogenetic pathways: (1) from baseline to cardiovascular events, (2) from baseline to diabetes, and (3) from new-onset diabetes to cardiovascular events. Methods. We enrolled 653 Caucasian never-treated hypertensives. Endothelial dysfunction was investigated by strain-gauge plethysmography; incident diabetes and cardiovascular events were evaluated by an illness-event model analysis. Results. During the follow-up (median 113 months), we documented 191 new cardiovascular events and 92 new cases of diabetes. In a multiple Cox regression analysis, acetylcholine-stimulated forearm blood flow [100% decrease, hazard ratio: 2.42 (95% confidence interval = 1.72–3.40)] and serum high-sensitivity C-reactive protein [hazard ratio: 1.30 (95% confidence interval = 1.21–1.40)] had an independent association with cardiovascular outcomes. The incidence rate of cardiovascular outcomes in diabetes-developer patients was higher than in the diabetes-free ones (34.9 vs. 2.5 events per 100 persons-year). In an illness-event model, a 100% decrease in forearm blood flow was associated with a 55.5% hazard ratio increase (hazard ratio: 1.56, 95% confidence interval: 1.33–1.82) of transition 1 (from baseline status to cardiovascular events) and to an almost doubled increase (hazard ratio: 2.54, 95% CI: 2.00–3.25) of the risk of transition 2 (from baseline status to diabetes). No such effects were found in transition 3 (from diabetes to cardiovascular events). Conclusions. Endothelial dysfunction plays a primary role in the pathways leading to diabetes and cardiovascular events in hypertensives. When diabetes is overt, endothelial dysfunction has no predictive value for subsequent cardiovascular events.

Fragmented QRS, a predictor of clinical events in patients on cardiac resynchronization therapy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Martinez Milla ◽  
C Garcia-Talavera ◽  
B Arroyo ◽  
A Camblor ◽  
A Garcia-Ropero ◽  
...  
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Cardiovascular Events ◽  
Hospital Admissions ◽  
Multivariate Logistic Regression Analysis ◽  
Cardiac Resynchronization ◽  
Resynchronization Therapy ◽  
Coronary Syndrome ◽  
Clinical Events ◽  
Increased Risk

Abstract Introduction Cardiac resynchronization therapy with defrilator (CRT-D) has been shown to reduce mortality in HFrEF. The width and morphology of the QRS are essential when deciding on the implantation of these devices. QRS fragmentation (fQRS) has been shown to be a good predictor of cardiovascular events in certain patients, but its role in patients with CRT-D has not been studied. The aim of this study is to determine whether the presence of a fQRS at the time of CRT-D implantation can predict clinical events. Methods All patients who underwent CRT-D implantation from 2010 to 2017 were included. Patients' ECG were evaluated at the time of implantation, and the incidence of clinical events during follow-up was also assessed. fQRS was defined as the presence of an RSR' pattern with a notch in the R wave or in the ascending or descending branch of the S wave in two continuous leads on the ECG. Results We studied 131 patients (mean age 73 years, 76.5% male). The mean follow-up period was 37±26 months. No difference in baseline characteristics was found (Table 1); the proportion of fQRS was 48.9%. 25 patients (19.1%) had hospital admissions secondary to cardiovascular causes (heart failure, arrhythmic events, acute coronary syndrome, and death from other causes). We performed a multivariate logistic regression analysis aiming at an association between the presence of fQRS and the increased risk of hospital admissions due to cardiovascular causes OR 2.92 (95% CI: 1.04–8.21, P=0.04). Conclusion The presence of a fQRS at the time of implantation of a CRT-D is an independent predictor of hospital admissions due to cardiovascular causes. Therefore this could be a useful marker to identify the population at high risk of cardiovascular events, for this we consider necessary to conduct future studies and thus assess the value of the fQRS for the selection of patients requiring closer monitoring thus avoiding further hospital admissions. Funding Acknowledgement Type of funding source: None

Risk prediction for subclinical carotid atherosclerosis in rotational shift workers in the arctic

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Shurkevich ◽  
A Vetoshkin ◽  
L Gapon ◽  
A Simonyan ◽  
V Kuznetsov
Keyword(s):  
Blood Pressure ◽  
Early Diagnosis ◽  
Cardiovascular Events ◽  
Carotid Arteries ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
The Arctic ◽  
Lipid Lowering ◽  
Correct Prediction ◽  
Shift Workers

Abstract Introduction High prevalence of cardiovascular events at northern latitudes determines the necessity of studying mechanisms of formation and early diagnosis of atherosclerotic process. Purpose To determine the most unfavorable prognostic factors that provide the percentage of correct prediction and high accuracy in detection of atherosclerotic plaque (ASP) in common carotid arteries (CCA) in rotational shift workers in the Arctic. Methods Within 2010–2012 a study of 424 males aged 30–59 years at the medical unit “Gazprom dobycha Yamburg” (Yamburg settlement, 68°N) was performed. Patients were randomized into 2 groups according to blood pressure (BP). Gr.I included 294 people with BP more than 140/90 mmHg, arterial hypertension (AH) of 1,2 stage and Gr.II included 130 people with BP less than 140/90 mmHg. Groups did not differ in age (46.9±5.8 years, p=0.435); total work experience in the Arctic: 16.5±6.8 years (p=0.512) and rotational shiftwork duration: 12.5±4.6 years (p=0.597). Office BP was 149.4±13.3/97.1±7.3 mmHg in Gr.I and 123.4±7.5/80.5±5.5 mmHg in Gr.II. Ultrasound examination of carotid arteries with determination of presence or absence of ASP in CCA and estimation of stenosis using NASCET method were performed; ambulatory blood pressure monitoring was conducted; blood glucose levels, total cholesterol, high-density lipoprotein cholesterol, low density lipoprotein cholesterol were determined. Statistical analysis was carried out using R (v. 3.6.1) programming language for statistical data processing of R Studio application package (v. 1.2.1335). Results Signs of CCA atherosclerosis were revealed in 56% of patients with AH and in 25% of those without AH. According to multivariate analysis, three variables with the most significant set of predictors, associated with ASP in CCA with the percentage of correct prediction of 75.9% were selected by step-by-step method: diastolic BP24 (&lt;0.0001), glucose (0.0167) and cholesterol (0.0439). Based on the obtained model, it was concluded that 1 mmHg increase in diastolic BP24 increases the risk for developing ASP by 5.9%, Exp. (Beta) = 1.059, 1 mmol/l increase in glucose and cholesterol escalates the risk by 44.1% and 25.2%, respectively: Exp. (Beta) = 1.441 and Exp. (Beta) = 1.252. Conclusion The data obtained will improve accuracy for the early diagnosis of subclinical atherosclerosis of CCA, allow to prescribe lipid-lowering therapy timely and reduce the risk of adverse cardiovascular events in rotational shift workers in the Arctic. Funding Acknowledgement Type of funding source: None

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