Atherogenic markers in predicting cardiovascular risk and targeting residual cardiovascular risk

Abstract Low-density lipoprotein (LDL) cholesterol (LDL-C) is the primary target in cardiovascular (CV) disease prevention and is commonly used in estimating CV risk; however, alternative markers may be needed when LDL-C is not an appropriate marker (e.g. in the presence of low LDL-C levels or elevated triglyceride [TG] levels). Non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (apoB) are markers of atherogenic lipoproteins with evidenced associations with CV risk and are, therefore, recommended as secondary targets, appropriate for use in the presence of elevated TG levels. The reported strength of the associations of non-HDL-C and apoB in comparison to LDL-C is conflicting between studies, potentially due to discordance of the markers which can alter their predictive pattern. Although LDL-C levels are commonly managed with statin treatment, a residual risk of CV events still remains, and an abnormal lipid profile can persist. Combination therapy to further reduce LDL-C levels can be beneficial; a statin therapy combined with other LDL-C-lowering therapy further reduced the number of CV events. In addition, targeting other markers, including non-HDL-C, apoB, total cholesterol and TGs may also be beneficial, specifically in patients with low HDL-C and elevated TG levels. More clinical evidence is required before definitive recommendations can be made; however, a statin–fenofibrate combination demonstrated favourable reductions in major CV events in these specific patients

Pharmaceutical strategies for reducing LDL-C and risk of cardiovascular disease

Abstract A key strategy in preventing cardiovascular (CV) disease is the reduction of low-density lipoprotein cholesterol (LDL-C). Statins are a crucial therapy for achieving LDL-C reductions, with the highest tolerated dose often prescribed, especially for patients who are at the greatest risk of CV disease. However, statin intolerance, heterogeneous responses to statins and non-adherence make alternative therapies necessary in some cases. Statins can be combined with a multitude of therapies with synergistic mechanisms of action to effectively manage lipid profiles, while improving safety and tolerability profiles. Addition of a cholesterol absorption inhibitor, bile acid sequestrant or fibrate to statin therapy leads to greater numbers of patients achieving and maintaining LDL-C goals. Furthermore, combination therapies can alter the plasma profiles of other molecules involved in hypercholesterolaemia, including triglycerides and high-density lipoprotein cholesterol. An additional strategy is proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition therapy, for use in patients who are statin intolerant, patients with heterozygous or homozygous familial hypercholesterolaemia, and patients at very high CV risk, as a potential means for achieving large LDL-C reductions and maintaining LDL-C goals. Clinical trials have demonstrated that PCSK9 inhibition therapy is not only effective but can also be combined with statin therapy to ensure greater reductions in LDL-C. Current, ongoing studies are investigating the efficacy of novel therapies, including selective peroxisome proliferator-activated receptor (PPAR) alpha modulators, PCSK9-specific ribonucleic acid (RNA) interference and anti-inflammatory therapies

Atherosclerosis

Atherosclerosis, the formation of fibrofatty lesions in the artery wall, causes much morbidity and mortality worldwide, including most myocardial infarctions and many strokes, as well as disabling peripheral artery disease. Development of atherosclerotic lesions probably requires low-density lipoprotein, a particle that carries cholesterol through the blood. Other risk factors for atherosclerosis and its thrombotic complications include hypertension, cigarette smoking and diabetes mellitus. Increasing evidence also points to a role of the immune system, as emerging risk factors include inflammation and clonal haematopoiesis. Studies of the cell and molecular biology of atherogenesis have provided considerable insight into the mechanisms that link all these risk factors to atheroma development and the clinical manifestations of this disease. An array of diagnostic techniques, both invasive (such as selective coronary arteriography) and noninvasive (such as blood biomarkers, stress testing, CT and nuclear scanning), permit assessment of cardiovascular disease risk and targeting of therapies. An expanding armamentarium of therapies that can modify risk factors and confer clinical benefit is available; however, we face considerable challenge in providing equitable access to these treatments and in maximizing adherence. Yet, the clinical application of the fruits of research has advanced preventive strategies, enhanced clinical outcomes in affected individuals, and improved their quality of life. Rapidly accelerating knowledge and continued research promise to provide further progress in combating this common chronic disease

Lipid-lowering and anti-thrombotic therapy in patients with peripheral arterial disease:European Atherosclerosis Society/European Society of Vascular Medicine Joint Statement

Patients with peripheral arterial disease (PAD) are at very high risk of cardiovascular events, but risk factor management is usually suboptimal. This Joint Task Force from the European Atherosclerosis Society and the European Society of Vascular Medicine has updated evidence on the management on dyslipidaemia and thrombotic factors in patients with PAD. Guidelines recommend a low-density lipoprotein cholesterol (LDLC) goal of more than 50% reduction from baseline and <1.4 mmol/L (<55 mg/dL) in PAD patients. As demonstrated by randomized controlled trials, lowering LDL-C not only reduces cardiovascular events but also major adverse limb events (MALE), including amputations, of the order of 25%. Addition of ezetimibe or a PCSK9 inhibitor further decreases the risk of cardiovascular events, and PCSK9 inhibition has also been associated with reduction in the risk of MALE by up to 40%. Furthermore, statin- based treatment improved walking performance, including maximum walking distance, and pain-free walking distance and duration. This Task Force recommends strategies for managing statin-associated muscle symptoms to ensure that PAD patients benefit from lipid-lowering therapy. Antiplatelet therapy, either daily clopidogrel 75 mg or the combination of aspirin 100 mg and rivaroxaban (2×2.5 mg) is also indicated to prevent cardiovascular events. Dual pathway inhibition (aspirin and rivaroxaban) may be considered following revascularization, taking into account bleeding risk. This Joint Task Force believes that adherence with these recommendations for lipid-lowering and antithrombotic therapy will improve the morbidity and mortality in patients with PAD

Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement

This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do not support Lp(a) as a risk factor for venous thrombotic events and impaired fibrinolysis. Very low Lp(a) levels may associate with increased risk of diabetes mellitus meriting further study. Lp(a) has pro-inflammatory and pro-atherosclerotic properties, which may partly relate to the oxidized phospholipids carried by Lp(a). This panel recommends testing Lp(a) concentration at least once in adults; cascade testing has potential value in familial hypercholesterolaemia, or with family or personal history of (very) high Lp(a) or premature ASCVD. Without specific Lp(a)-lowering therapies, early intensive risk factor management is recommended, targeted according to global cardiovascular risk and Lp(a) level. Lipoprotein apheresis is an option for very high Lp(a) with progressive cardiovascular disease despite optimal management of risk factors. In conclusion, this statement reinforces evidence for Lp(a) as a causal risk factor for cardiovascular outcomes. Trials of specific Lp(a)-lowering treatments are critical to confirm clinical benefit for cardiovascular disease and aortic valve stenosis

2017 Update of ESC/EAS Task Force on practical clinical guidance for proprotein convertase subtilisin/kexin type 9 inhibition in patients with atherosclerotic cardiovascular disease or in familial hypercholesterolaemia

A correction has been published: European Heart Journal, Volume 39, Issue 22, 7 June 2018, Pages 2105Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017.info:eu-repo/semantics/publishedVersio

Explaining the decline in coronary heart disease mortality in Turkey between 1995 and 2008.

BACKGROUND: Coronary heart disease (CHD) mortality rates have been decreasing in Turkey since the early 1990s. Our study aimed to determine how much of the CHD mortality decrease in Turkey between 1995 and 2008 could be attributed to temporal trends in major risk factors and how much to advances in medical and surgical treatments. METHODS: The validated IMPACT CHD mortality model was used to combine and analyse data on uptake and effectiveness of CHD treatments and risk factor trends in Turkey in adults aged 35-84 years between 1995 and 2008.Data sources were identified, searched and appraised on population, mortality and major CHD risk factors for adults those aged 35-84 years. Official statistics, electronic databases, national registers, surveys and published trials were screened from 1995 onwards. RESULTS: Between 1995 and 2008, coronary heart disease mortality rates in Turkey decreased by 34% in men and 28% in women 35 years and over. This resulted in 35,720 fewer deaths in 2008.Approximately 47% of this mortality decrease was attributed to treatments in individuals (including approximately 16% to secondary prevention, 3% angina treatments, 9% to heart failure treatments, 5% to initial treatments of acute myocardial infarction, and 5% to hypertension treatments) and approximately 42% was attributable to population risk factor reductions (notably blood pressure 29%; smoking 27%; and cholesterol 1%). Adverse trends were seen for obesity and diabetes (potentially increasing mortality by approximately 11% and 14% respectively). The model explained almost 90% of the mortality fall. CONCLUSION: Reduction in major cardiovascular risk factors explained approximately 42% and improvements in medical and surgical treatments explained some 47% of the CHD mortality fall. These findings emphasize the complimentary value of primary prevention and evidence-based medical treatments in controlling coronary heart disease

Perspectives from the European Society of Cardiology Congress 2014

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