scholarly journals Management of hypercholesterolemia, appropriateness of therapeutic approaches and new drugs in patients with high cardiovascular risk

2018 ◽  
Vol 12 (3) ◽  
pp. 203-212 ◽  
Author(s):  
Roberto Vettor ◽  
Roberto Serra
Keyword(s):  
Cardiovascular Risk ◽  
Clinical Trial Data ◽  
Statin Treatment ◽  
Clinical Development ◽  
New Drugs ◽  
Risk Category ◽  
Therapeutic Approaches ◽  
High Cardiovascular Risk ◽  
All Cause Mortality ◽  
Receive Treatment

Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Lowering low-density lipoproteins-cholesterol (LDL-C) has been shown to decrease the risk of CVD and of all-cause mortality. For appropriate management, estimation of each individual’s total cardiovascular risk is critical, as patients should receive treatment according to their cardiovascular risk category as well as their LDL-C level. However, available data indicate that a large proportion of patients fail to achieve lipid goals despite treatment, and a significant percentage of patients are not able to tolerate statin treatment. Researchers have therefore focused considerable attention on the development of novel LDL-C-lowering agents that act via different mechanisms. Among the most recent advances in clinical development are the proprotein convertase subtilisin/kexin 9 antibody inhibitors, including alirocumab and evolocumab, which appear particularly promising, with clinical trial data indicating these agents to be both well tolerated and highly efficacious in lowering LDL-C.

Neuroblastoma

2020 ◽  
pp. 241-252
Author(s):  
Angelika Eggert ◽  
Garrett M. Brodeur ◽  
Gudrun Schleiermacher
Keyword(s):  
Histone Deacetylases ◽  
Solid Tumour ◽  
Malignant Neoplasm ◽  
Clinical Development ◽  
New Drugs ◽  
Therapeutic Approaches ◽  
Critical Signal ◽  
Prognostic Utility ◽  
Sympathetic Nervous ◽  
Current Risk

Neuroblastoma, a malignant neoplasm of the sympathetic nervous system, is the most common extracranial solid tumour in childhood. Since its first description in the nineteenth century, its highly heterogeneous clinical presentation has challenged clinicians and fascinated basic researchers. Neuroblastoma serves as a paradigm for the prognostic utility of biological and clinical data and the potential to tailor therapy for patient cohorts at low, intermediate, and high risk for recurrence. This chapter presents an overview of the key genetic, molecular, histological, and clinical features of neuroblastoma, as well as current risk-stratification strategies and therapeutic approaches. It also highlights how our understanding of tumour pathogenesis, coupled with molecular analyses, has illuminated critical signal transduction pathways and key molecules involved in neuroblastoma tumourigenesis, pointing to novel therapeutic targets for clinical development. Future treatment avenues for relapsed neuroblastoma are discussed, including new drugs targeting ALK, MYC/MYCN, histone deacetylases, or MDM2/TP53.

scholarly journals All-cause mortality following low-dose aspirin treatment for patients with high cardiovascular risk in remote Australian Aboriginal communities: an observational study

BMJ Open ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. e030034 ◽  
Author(s):  
Yuejen Zhao ◽  
Kanakamani Jeyaraman ◽  
Paul Burgess ◽  
Christine Connors ◽  
Steven Guthridge ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Outcome Measures ◽  
Low Dose ◽  
Aboriginal People ◽  
Univariate Analysis ◽  
High Cardiovascular Risk ◽  
Aboriginal Communities ◽  
All Cause Mortality ◽  
Benefit And Risk

ObjectivesTo evaluate the benefit and risk of low-dose acetylsalicylic acid (aspirin) in patients from remote Aboriginal communities in the Northern Territory, Australia.DesignRetrospective cohort study using primary care and hospital data routinely used for healthcare. Aspirin users and non-users were compared before and after controlling confounders by matching. Marginal structural models (MSM) were applied to ascertain the benefit and risk.SettingThe benefit and harm of aspirin were investigated in patients aged ≥18 years from 54 remote Aboriginal communities.ParticipantsNone had a previous cardiovascular event or major bleeds. Patients on anticoagulants or other antiplatelets were excluded.InterventionAspirin at a dose of 75–162 mg/day.Outcome measuresEndpoints were all-cause, cardiovascular mortality and incidences of cardiovascular events and major bleeds.Results8167 predominantly Aboriginal adults were included and followed between July 2009 and June 2017 (aspirin users n=1865, non-users n=6302, mean follow-up 4 years with hospitalisations 6.4 per person). Univariate analysis found material differences in demographics, prevalence of chronic diseases and outcome measures between aspirin users and non-users before matching. After matching, aspirin was significantly associated with reduced all-cause mortality (HR=0.45: 95% CI 0.34 to 0.60; p<0.001), but not bleeding (HR=1.13: 95% CI 0.39 to 3.26; p=0.820). After using MSMs to eliminate the effects of confounders, loss of follow-up and time dependency of treatment, aspirin was associated with reduced all-cause mortality (HR=0.60: 95% CI 0.47 to 0.76; p<0.001), independent of age (HR=1.06; p<0.001), presence of diabetes (HR=1.42; p<0.001), hypertension (HR=1.61; p<0.001) and alcohol abuse (HR=1.81; p<0.001). No association between aspirin and major bleeding was found (HR=1.14: 95% CI 0.48 to 2.73; p=0.765). Sensitivity analysis suggested these findings were unlikely to have been the result of unmeasured confounding.ConclusionAspirin was associated with reduced all-cause mortality. Bleeding risk was less compared with survival benefits. Aspirin should be considered for primary prevention in Aboriginal people with high cardiovascular risk.

scholarly journals Guideline Concordance of Statin Treatment Decisions: A Retrospective Cohort Study

2020 ◽  
Vol 9 (11) ◽  
pp. 3719
Author(s):  
Yael Rachamin ◽  
Stefan Markun ◽  
Thomas Grischott ◽  
Thomas Rosemann ◽  
Rahel Meier
Keyword(s):  
Cohort Study ◽  
Cardiovascular Risk ◽  
General Practitioners ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Small Deviation ◽  
Statin Treatment ◽  
Treatment Decisions ◽  
High Cardiovascular Risk ◽  
Very High

Guidelines recommend initiation of statins depending on cardiovascular risk and low-density lipoprotein cholesterol (LDL-C) levels. In this retrospective cohort study, we aimed to assess guideline concordance of statin treatment decisions and to find determinants of undertreatment in Swiss primary care in the period 2016–2019. We drew on electronic medical records of 8060 statin-naive patients (50.0% female, median age 59 years) with available LDL-C levels and cardiovascular risk. Guideline concordance was assessed based on the recommendations of the European Society of Cardiology, and multilevel logistic regression was performed to find determinants of undertreatment. We found that statin treatment was initiated in 10.2% of patients during one year of follow up. Treatment decisions were classified as guideline-concordant in 63.0%, as undertreatment in 35.8% and as overtreatment in 1.2%. Among determinants of undertreatment were small deviation from LDL-C treatment thresholds (odds ratio per decrease by 1 mmol/L: 2.09 [95% confidence interval 1.87–2.35]), high compared with very high cardiovascular risk (1.64 [1.30–2.05]), female sex (1.31 [1.05–1.64]), and being treated by older general practitioners (per 10 year decrease: 0.74 [0.61–0.90]). In conclusion, undertreatment of patients at high or very high cardiovascular risk was common, but general practitioners considered cardiovascular risk and LDL-C in their treatment decisions.

scholarly journals The Lipid Accumulation Product and All-cause Mortality in Patients at High Cardiovascular Risk: A PreCIS Database Study

Obesity ◽  
2010 ◽  
Vol 18 (9) ◽  
pp. 1836-1844 ◽  
Author(s):  
Adriana G. Ioachimescu ◽  
Danielle M. Brennan ◽  
Brian M. Hoar ◽  
Byron J. Hoogwerf
Keyword(s):  
Cardiovascular Risk ◽  
Lipid Accumulation ◽  
Lipid Accumulation Product ◽  
High Cardiovascular Risk ◽  
Database Study ◽  
All Cause Mortality

scholarly journals Role of colchicine in stroke prevention: an updated meta-analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L.M Lobo ◽  
G Masson ◽  
G Molinero ◽  
G Masson ◽  
A Lavalle Cobo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Clinical Trials ◽  
Cardiovascular Risk ◽  
Cardiovascular Mortality ◽  
Meta Analysis ◽  
The Body ◽  
High Cardiovascular Risk ◽  
Stroke Incidence ◽  
All Cause Mortality ◽  
Colchicine Therapy

Abstract Background Colchicine is a microtubule inhibitor with anti-inflammatory proprieties. As the body and quality of evidence regarding the efficacy of colchicine for cardiovascular prevention is controversial, the aims of this study was to evaluate the effect of colchicine therapy on vascular events. Methods A meta-analysis was performed of randomized controlled clinical trials of colchicine on high cardiovascular risk populations, reporting data from stroke, myocardial infarction, cardiovascular mortality and all-cause mortality, after searching the PubMed/MEDLINE, Embase and Cochrane Controlled Trials databases. A random-effects meta-analysis model was then applied. Results Nine eligible trials of colchicine therapy, involving a total of 6630 patients, were considered eligible for analysis (3359 subjects were allocated to receive colchicine while 3271 subjects were allocated to the respective control arms). The stroke incidence was lower in the colchicine group compared with placebo arm (OR, 0.33; 95% CI, 0.15–0.70; six studies evaluated). We did not find a significant reduction in the incidence of myocardial infarction, cardiovascular mortality or all-cause mortality. Conclusion Our data suggest that in a population with high cardiovascular risk, the use of colchicine results in significantly reduction on stroke risk. Colchicine is an accessible drug that could be successfully utilized for the prevention of atherosclerotic cerebrovascular disease. The tolerability and benefits should be confirmed in ongoing clinical trials. Forest Plot Primary endpoint Funding Acknowledgement Type of funding source: None

Testosterone, sex hormone-binding globulin and risk of cardiovascular events: A report from the Outcome Reduction with an Initial Glargine Intervention trial

2018 ◽  
Vol 26 (8) ◽  
pp. 847-854 ◽  
Author(s):  
Anne Wang ◽  
Stefan Arver ◽  
Kurt Boman ◽  
Hertzel C Gerstein ◽  
Shun Fu Lee ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Cardiovascular Events ◽  
Free Testosterone ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
High Cardiovascular Risk ◽  
All Cause Mortality ◽  
Low Levels

Aims: Testosterone and its binding protein sex hormone-binding globulin have been associated with cardiovascular disease and dysglycaemia. However, information on the prognostic implication in patients at high cardiovascular risk with dysglycaemia is inconsistent. The study objective was to determine whether testosterone and/or sex hormone-binding globulin predict cardiovascular events or death in dysglycaemic patients. Methods: Dysglycaemic males at high cardiovascular risk ( n = 5553) who participated in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial and provided baseline blood samples were studied. Testosterone and sex hormone-binding globulin were measured at baseline and used to estimate free testosterone. Low levels of total and free testosterone were defined as ≤300 ng/dl and ≤7 ng/dl, respectively. Patients were followed for six years for cardiovascular events (defined as the composite of cardiovascular death, non-fatal myocardial infarction or stroke) and all-cause mortality. Results: The mean total and free testosterone levels were 416.6 ng/dl and 8.4 ng/dl, and low levels were present in 13% and 37% of the patients. The median sex hormone-binding globulin level was 35 nmol/l. In Cox regression models adjusted for age, previous diseases and pharmacological treatment, neither total nor free testosterone predicted cardiovascular events. However, a one-standard-deviation increase in sex hormone-binding globulin predicted both cardiovascular events (hazard ratio 1.07; 95% confidence interval 1.00–1.14; p = 0.03) and all-cause mortality (hazard ratio 1.13; 95% confidence interval 1.06–1.21; p < 0.01). Conclusion: Sex hormone-binding globulin, but not total testosterone, predicts cardiovascular disease and all-cause mortality in dysglycaemic males at high cardiovascular risk.

P3400Definition of extremely high cardiovascular risk in patients after acute myocardial infarction - Data from the TERCET Registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Dyrbus ◽  
M Gasior ◽  
P Desperak ◽  
T Osadnik ◽  
M Banach
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Multivariate Analysis ◽  
Cardiovascular Risk ◽  
High Risk ◽  
Density Lipoprotein ◽  
Cardiovascular Prevention ◽  
Risk Category ◽  
High Cardiovascular Risk

Abstract Background The latest guidelines from the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) introduced a new “ultra-high risk” category of patients, for whom a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dL (1.4 mmol/L) is advised. Purpose Therefore we aimed at identification of the risk factors in patients after acute myocardial infarction (MI), which increased the risk most, and might help to define the group of individuals at extremely high cardiovascular (CV) risk. Methods We analyzed consecutive patients included in the TERCET Registry admitted to the Polish tertiary cardiovascular centre due to MI between 2006 and 2018. According to the guidelines of the European Society of Cardiology (ESC), all patients included in the analysis are considered as of very high CV risk. All patients included in the registry underwent coronary angiography during the hospital stay. On the basis of multivariate analysis, we determined the subgroup of patients with the most unfavourable 12-month outcome (all-cause mortality). Results Finally, 4,562 patients admitted due to STEMI or NSTEMI and discharged from our centre were included in the analysis. According to the results of multivariate analysis performed with stepwise backward regression model, the following risk factors in patients after MI: LVEF<35% (odds ratio [OR]=3.83, 95% confidence interval [CI]: 3.14–4.67), age>75 years (OR=1.91, 95% CI: 1.55–2.35), lack of PCI of culprit vessel (OR=1.66, 95% CI: 1.26–2.20), multivessel CAD (OR=1.60, 95% CI: 1.30–1.99), atrial fibrillation (OR=1.53, 95% CI: 1.21–1.94), diabetes mellitus (OR=1.34, 95% CI: 1.11–1.64), increased LDL-C level (OR=1.09 per 1 mmol/L, 95% CI: 1.01–1.19) and increased creatinine level (OR=1.04 per 10 μmol/L, 95% CI: 1.04–1.05), might help to define the group of patients at extremely-high cardiovascular risk (all p<0.05). The aggregate summary of risk factors associated with extremely high risk is presented in the attached Figure. Next, the effect of the combination of the aforementioned risk factors will be investigated, and SCORE applied for patients in secondary prevention after MI will be prepared. Multivariate analysis results Conclusions To our knowledge, the presented study is the first such an analysis conducted on the population of patients after myocardial infarction gathered in the registry of secondary cardiovascular prevention. In patients after MI, potential risk factors were identified that might help to define the group of patients at ultra-high/extremely-high risk, what might contribute to significantly higher 12-month mortality. Acknowledgement/Funding None

Sign in / Sign up

Export Citation Format

Share Document