Therapie der Hypercholesterinämie in der Primärprävention

2019 ◽  
Vol 144 (05) ◽  
pp. 322-328 ◽  
Author(s):  
Veronika Sanin ◽  
Wolfgang Koenig

AbstractAtherosclerotic cardiovascular disease is the leading cause of premature mortality and morbidity worldwide. Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. The causality of plasma low-density lipoprotein-cholesterol (LDL-C) in the pathophysiology of cardiovascular disease has been established beyond any reasonable doubt. In this context, individual risk estimation, the determination of target values and lipid-lowering strategies represent an essential part and a challenge in the daily clinical practice to prevent cardiovascular events. Statins are recommended as first-line therapy for patients with hypercholesterolemia in secondary prevention. Controversies remain in the context of primary prevention, however, as to which kind of subjects to treat, the magnitude of the benefit, and potential harm. This article gives a brief overview of the current evidence, guideline recommendations and strategies for lowering of LDL-C in the primary prevention of cardiovascular disease.

2017 ◽  
Vol 25 (4) ◽  
pp. 420-431 ◽  
Author(s):  
Jelena Pavlović ◽  
Philip Greenland ◽  
Jaap W Deckers ◽  
Maryam Kavousi ◽  
Albert Hofman ◽  
...  

Background The purpose of this study was to determine how American College of Cardiology/American Heart Association (ACC/AHA) 2013 and European Society of Cardiology 2016 guidelines for the primary prevention of atherosclerotic cardiovascular disease (CVD) compare in reflecting the totality of accrued randomised clinical trial evidence for statin treatment at population level. Methods From 1997–2008, 7279 participants aged 45–75 years, free of atherosclerotic cardiovascular disease, from the population-based Rotterdam Study were included. For each participant, we compared eligibility for each one of 11 randomised clinical trials on statin use in primary prevention of CVD, with recommendations on lipid-lowering therapy from the ACC/AHA and European Society of Cardiology (ESC) guidelines. Atherosclerotic cardiovascular disease incidence and cardiovascular disease mortality rates were calculated. Results The proportion of participants eligible for each trial ranged from 0.4% for ALLHAT-LLT to 30.8% for MEGA. The likelihood of being recommended for lipid-lowering treatment was lowest for those eligible for low-to-intermediate risk RCTs (HOPE-3, MEGA, and JUPITER), and highest for high-risk individuals with diabetes (MRC/BHF HPS, CARDS, and ASPEN) or elderly PROSPER. Eligibility for an increasing number of randomised clinical trials correlated with a greater likelihood of being recommended lipid-lowering treatment by either guideline ( p < 0.001 for both guidelines). Conclusion Compared to RCTs done in high risk populations, randomised clinical trials targeting low-to-intermediate risk populations are less well-reflected in the ACC/AHA, and even less so in the ESC guideline recommendations. Importantly, the low-to-intermediate risk population targeted by HOPE-3, the most recent randomised clinical trial in this field, is not well-captured by the current European prevention guidelines and should be specifically considered in future iterations of the guidelines.


2020 ◽  
Vol 9 ◽  
pp. 204800402094932
Author(s):  
Jack Stewart ◽  
Katherine Addy ◽  
Sarah Campbell ◽  
Peter Wilkinson

Cardiovascular disease remains a substantial concern in terms of global mortality and morbidity, while prevalence of cardiovascular disease is increasing as treatment modalities improve survival. With an ageing population and increasing costs of chronic medical care, primary prevention of cardiovascular disease is an important target for healthcare providers. Since the previous iteration of this paper, new international guidelines have been produced regarding hypertension and lipid lowering therapies, whilst there is a growing body of evidence and new therapies emerging in other areas of lifestyle and pharmacotherapeutic intervention. This review outlines emerging evidence in the field and compares and contrasts contemporary recommendations from European and American guidelines.


Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 690
Author(s):  
Jennifer Behbodikhah ◽  
Saba Ahmed ◽  
Ailin Elyasi ◽  
Lora Kasselman ◽  
Joshua De Leon ◽  
...  

Apolipoprotein (apo) B, the critical structural protein of the atherogenic lipoproteins, has two major isoforms: apoB48 and apoB100. ApoB48 is found in chylomicrons and chylomicron remnants with one apoB48 molecule per chylomicron particle. Similarly, a single apoB100 molecule is contained per particle of very-low-density lipoprotein (VLDL), intermediate density lipoprotein, LDL and lipoprotein(a). This unique one apoB per particle ratio makes plasma apoB concentration a direct measure of the number of circulating atherogenic lipoproteins. ApoB levels indicate the atherogenic particle concentration independent of the particle cholesterol content, which is variable. While LDL, the major cholesterol-carrying serum lipoprotein, is the primary therapeutic target for management and prevention of atherosclerotic cardiovascular disease, there is strong evidence that apoB is a more accurate indicator of cardiovascular risk than either total cholesterol or LDL cholesterol. This review examines multiple aspects of apoB structure and function, with a focus on the controversy over use of apoB as a therapeutic target in clinical practice. Ongoing coronary artery disease residual risk, despite lipid-lowering treatment, has left patients and clinicians with unsatisfactory options for monitoring cardiovascular health. At the present time, the substitution of apoB for LDL-C in cardiovascular disease prevention guidelines has been deemed unjustified, but discussions continue.


2020 ◽  
Vol 41 (31) ◽  
pp. 3005-3015 ◽  
Author(s):  
Martin Bødtker Mortensen ◽  
Børge Grønne Nordestgaard

Abstract Aims The 2019 vs. 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) dyslipidaemia guidelines contains new recommendations for primary prevention with statins; however, the potential impact of these changes is unclear. We compared the 2019 and 2016 guidelines regarding statin eligibility and potential impact on prevention of atherosclerotic cardiovascular disease (ASCVD) in the general population. Methods and results We examined 45 750 individuals aged 40–75 from the Copenhagen General Population Study, all free of ASCVD and statin use at baseline. During the 9.2-year follow-up, 3337 experienced ASCVD (myocardial infarction, stroke, and cardiovascular death). For Class I/A recommendations, 32.3% (95% confidence interval: 31.8–32.7) and 15.4% (15.1–15.7) of individuals were statin eligible according to the 2019 and 2016 guidelines. The increased statin eligibility by the 2019 guidelines was explained by lower low-density lipoprotein cholesterol (LDL-C) thresholds alone (explaining 33.2%), older age range alone (49.4%), older age range in combination with lower LDL-C thresholds (14.7%), and updated SCORE risk algorithm (2.8%). If fully implemented, the estimated percentage of ASCVD events that can be prevented by using high-intensity statins for 10 years were 25% and 11% with the 2019 and 2016 guidelines. Mainly because of older age range in the 2019 guidelines, the corresponding estimated numbers needed to treat (NNT) to prevent one ASCVD event were 19 and 20. Conclusion Due to lower LDL-C threshold and older age range, the 2019 vs. 2016 ESC/EAS guidelines doubles the number of individuals eligible for primary prevention with statins. This considerably improves the potential for ASCVD prevention in the general population, with similar NNT to prevent one event.


Author(s):  
Suzanne V. Arnold ◽  
Christopher P. Cannon ◽  
James A. de Lemos ◽  
Robert S. Rosenson ◽  
Christie M. Ballantyne ◽  
...  

Background Because of an increasing number and complexity of treatment options for lipid‐lowering therapy in patients with atherosclerotic cardiovascular disease, guidelines recommend greater active involvement of patients in shared decision‐making. However, patients' understanding and perceptions of the benefits, risks, and treatment objectives of lipid‐lowering therapy are unknown. Methods and Results Structured questionnaires were conducted in 5006 US outpatients with atherosclerotic cardiovascular disease and suboptimal low‐density lipoprotein cholesterol (LDL‐C) control (LDL‐C ≥70 mg/dL) or on a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor and in 113 physician providers as a part of the GOULD (Getting to an Improved Understanding of Low‐Density Lipoprotein Cholesterol and Dyslipidemia Management) Registry. Mean age of the patients was 68±10 years, 60% were men, and 86% were White race. Across all patients, 63% believed heart disease was the leading cause of death in men and 46% the leading cause of death in women. Only 28% of patients thought the primary reason they were taking lipid‐lowering medication was to lower the risk of heart attack or stroke, 68% did not know their approximate LDL‐C level, and 69% did not know their LDL‐C goal. Patients on PCSK9 inhibitors (versus LDL‐C cohort), younger patients (versus age ≥65 years), and men (versus women) were somewhat more knowledgeable about their disease and its management. Most physicians (66%) felt that a lack of understanding of the importance and efficacy of statins was the primary factor contributing to nonadherence, as opposed to costs (9%) or side effects (1%). More education was the most commonly used strategy to address patient‐reported side effects. Conclusions A large proportion of patients with atherosclerotic cardiovascular disease remain unaware of their underlying atherosclerotic cardiovascular disease risk, reasons for taking lipid‐lowering medications, current LDL‐C levels, or treatment goals. These data highlight a large education gap which, if addressed, may improve shared decision‐making and treatment adherence. Registration URL: https://www.clinicaltrials.org ; Unique identifier: NCT02993120.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Christopher P Cannon ◽  
James A De Lemos ◽  
Christie M Ballantyne ◽  
Robert S Rosenson ◽  
Shushama Alam ◽  
...  

Background: Atherosclerotic cardiovascular disease (ASCVD) treatment guidelines recommend intensive statin therapy and adding non-statin therapy if LDL-C ≥70 mg/dL. Methods: We designed the GOULD registry to assess lipid-lowering therapy (LLT) over time: At 120 U.S. centers, 5006 ASCVD patients on any (LLT) were enrolled in 1 of 3 cohorts: 1) currently on PCSK9 inhibitor (PCSK9i), 2) no PCSK9i and LDL-C ≥100 mg/dL, and 3) no PCSK9i and LDL-C 70-99 mg/dL. Results: Over the two years, only 16.8% had some type of LLT intensification, In the cohorts of patients with baseline LDL-C ≥ 100 and 70-99 mg/dL, LLT intensification was present in 21.9% and 14.3% respectively: statin dose was intensified in 6.1% and 6.1%, ezetimibe was added in 6.8% and 4.3% and PCSK9i was added in 6.3% and 2.2% respectively. Conversely, out of the total population, statins were discontinued in 246/4275 (5.8%), ezetimibe in 81/535 (15.1%), and PCSK9i in 47/544 (8.6%). At 24 months, 83.7% were on statin (43.4% high-intensity), with 14.2% on ezetimibe. Lipid panels were measured in 73% by 1 year and 84% by 2 years. Among Pts in the LDL-C ≥100 and 70-99 mg/dL cohorts, 18.6% and 30.4% achieved an LDL-C <70 mg/dL by 1 year, with little further change by 2 years: 21.3% and 33.5% respectively. In the PCSK9 cohort, 53.2% had LDL-C<70 mg/dl. Overall, only 31.7% had LDL-C <70 mg/dL at 2 years (an increase from 6.7% at baseline), while 25.0% had LDL-C >100 mg/dL. Conclusion: Of ASCVD patients with suboptimal LDL-C at baseline, even after 2 years of follow up, strikingly only 16% had LLT intensification, and thus most remained uncontrolled. Further intensive efforts are needed to achieve optimal LDL management in patients with ASCVD.


2019 ◽  
Vol 33 (6) ◽  
pp. 882-894 ◽  
Author(s):  
Barbara S. Wiggins ◽  
Dave Dixon ◽  
Jessica Bellone ◽  
Nicole Gasbarro ◽  
Joel C. Marrs ◽  
...  

Although the mortality from cardiovascular disease has declined, it remains the leading cause of morbidity and mortality in the United States. Dyslipidemia is a modifiable risk factor that plays a significant role in the development of atherosclerotic cardiovascular disease. Treating dyslipidemia by lowering cholesterol, predominately low-density lipoprotein cholesterol, has been shown to reduce cardiovascular events. The first article that provided dyslipidemia bibliographies was published in 2006. Since this time, new therapies have become available and older therapies that were once thought to provide benefit have since been shown to lack positive outcomes and have therefore fallen out of favor for routine use. As the body of evidence continues to expand, clinicians are faced with reevaluating their treatment strategies to ensure optimal outcomes and appropriate use of lipid-lowering therapies. Therefore, this compilation was created to serve as a resource for clinicians. This publication provides an update of key articles in dyslipidemia management including various guidelines and practice-changing randomized controlled trials.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Renato Quispe ◽  
Seth S Martin ◽  
Erin D Michos ◽  
Isha Lamba ◽  
Roger S Blumenthal ◽  
...  

Introduction: Emerging evidence suggests that remnant cholesterol (RC) promotes future atherosclerotic cardiovascular disease (ASCVD) events. Our aim was to estimate the risk associated with RC beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB). Hypothesis: RC provides incremental prognostic information regarding incident ASCVD, independent of LDL-C and apoB. Methods: We pooled data from 17,532 individuals from Atherosclerosis Risk in Communities study (n=9,748), Multi-Ethnic Study of Atherosclerosis (n=3,049) and Coronary Artery Risk Development in Young Adults (n=4,735), who were ASCVD-free at baseline and had measurements of lipids, apoB and apolipoprotein A1. RC was calculated as non-high-density cholesterol (non-HDL-C) minus LDL-C estimated by the Martin/Hopkins equation. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in discordant/concordant groups of RC and LDL-C across median cutpoints and cutpoints of percentile equivalence to LDL-C targets (70 and 100 mg/dL). Results: Mean age of participants was 52.3±17.9 years, 56.7% women and 34% black. There were 2,143 ASCVD events over median follow-up of 18.7 years. After multivariable adjustment including apoB and HDL-C, logRC was associated with higher ASCVD risk [HR 1.42, 95% CI (1.23-1.63)]. In discordance analyses, the high RC and low LDL-C group (≥/<median) was associated with increased ASCVD risk compared to the low/low concordant group [1.17, (1.01-1.35)] but the low RC and high LDL-C group was not. Similar results were shown when examining discordance across lower cutpoints. Conclusion: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors and LDL-C and apoB levels. RC assessment and management in primary prevention, beyond LDL-C and apoB, is useful and requires further scrutiny.


Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 857
Author(s):  
Josep Julve ◽  
Joan Carles Escolà-Gil

Epidemiological studies have shown that low levels of plasma high-density lipoprotein cholesterol (HDL-C) are associated with increased atherosclerotic cardiovascular disease (CVD) [...]


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