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Copyright of Herz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Herz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Herz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Herz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cardiovascular diseases are the most frequent cause of disability and death. Evidence-based pharmacotherapy is the basis for successful treatment of common diseases, such as hypertension, heart failure, coronary artery disease, and atrial fibrillation. The proportion of older people with several diseases (multimorbidity) who need five or more drugs daily (polypharmacy) is steadily increasing. Evidence on the efficacy and safety of drugs in these patients is, however, limited because they are often excluded or underrepresented in clinical trials. In addition, clinical guidelines mostly focus on single diseases and only occasionally deal with the challenges in the pharmacotherapy of older multimorbid patients with polypharmacy. This article describes the options and special features of pharmacotherapy for hypertension, chronic heart failure and dyslipidemia, as well as antithrombotic treatment in (very) old people., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Lowering of low-density lipoprotein (LDL) cholesterol represents one of the most effective interventions in cardiovascular prevention. Besides the oral treatment with statins, ezetimibe and bempedoic acid, subcutaneously administered inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK9) have been established as further cornerstones of lipid-lowering treatment. The antibodies evolocumab and alirocumab are administered subcutaneously every 2-4 weeks and lower LDL cholesterol by around 60%, independent of pre-treatment with very good tolerability. Both drugs successfully reduced cardiovascular endpoints in large outcome trials. A novel principle of PCSK9 inhibition is RNA interference, which is exploited by the novel compound inclisiran. Inclisiran is a double-stranded modified RNA molecule, which neutralizes the mRNA of PCSK9 and thus inhibits PCSK9 protein synthesis intracellularly. Inclisiran only needs to be administered every 6 months. The cardiovascular outcome trial ORION‑4 is currently ongoing. In Germany, prescription of PCSK9 inhibitors is regulated by the decision of the Federal Joint Committee. Novel strategies to inhibit PCSK9 function are under development and include orally available drugs and animal experiment concepts on gene editing, which are in different states of evaluation., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Lipoprotein apheresis is an extracorporeal procedure for the treatment of patients with homozygous familial hypercholesterolemia, patients with severe treatment-resistant hypercholesterolemia and patients with lipoprotein(a) hypercholesterolemia, who show progressive atherosclerotic cardiovascular disease despite optimal treatment. This article reports on the historical developments of the procedures, the most frequently used methods for apheresis as well as the data situation on efficacy and tolerability. Randomized prospective studies on clinical outcomes are not available. Furthermore, the article reports on a patient with homozygous familial hypercholesterolemia and 34 years of treatment with heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) apheresis, the longest treatment of this kind worldwide. A second patient with combined heterozygous familial hypercholesterolemia and 31 years of liposorber and HELP apheresis is also described. The observational studies and the case reports demonstrate the safety and long-term tolerability of the procedure., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Statins are among the best studied drugs. Due to the extensive evidence regarding efficacy and safety, they are the cornerstone of lipid-lowering therapy. While the tolerability of statins in large blinded studies is at the placebo level, so-called statin intolerance (SI) is a frequent and complex problem in everyday clinical practice. Statin-associated muscular pain (SAMS) is most commonly reported. In many cases SI is associated with inadequate lowering of low-density lipoprotein (LDL) cholesterol (LDL-C), thereby increasing the cardiovascular risk. The diagnosis of SAMS is based on the exclusion of possible alternative causes of muscular symptoms and the exclusion of nocebo effects through a diagnostic strategy of discontinuation of statin treatment, observation and assessment of symptoms, followed by renewed administration of a different statin initially at a low dose with subsequent dose increase. A large proportion of patients with SI and SAMS can take statins permanently and without discomfort by this approach. If LDL‑C lowering is insufficient, combination therapies are used. It is an important task of the prescribing physicians and all those involved in the treatment to increase the adherence to statins through appropriate communication. Numerous questions on SI remain open and are being addressed by an ongoing register., (© 2022. The Author(s).)

Coronary artery disease (CAD) is the most frequent cause of morbidity and mortality worldwide. Lifestyle modifications and drug treatment of cardiovascular risk factors are able to effectively prevent CAD. The basis of prevention is the assessment of the individual cardiovascular risk, e.g. by using a validated risk score. Documented evidence for prevention of CAD is available for the control of hypertension using angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB) and calcium antagonists, for the treatment of hypercholesterolemia using statins, ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK-9) inhibitors and for the treatment of type 2 diabetes mellitus with metformin, sodium-glucose transporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists. There is no positive benefit-risk ratio for people with a low risk in the use of acetylsalicylic acid in primary prevention, in contrast to the positive recommendations for secondary prevention. There is no evidence for the efficacy of primary prevention with beta blockers, dipeptidyl peptidase 4 (DPP-4) inhibitors, glitazones, sulfonylureas or insulin. Similarly, there is no evidence for drug treatment of obesity, any supplementation with vitamins or hormone preparations or omega‑3 fatty acids.

In August 2019 the updated dyslipidemia guidelines of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) were published. Since the last version from 2016, important large randomized trials especially with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and new genetic analyses have become available that show additional reduction of atherosclerotic cardiovascular disease (ASCVD) risk on top of the previously recommended treatments. Based on these data the main concept of the recommendations is achieving an early and as large as possible absolute reduction of low-density lipoprotein cholesterol (LDL-C). As a result of this knowledge and the extended pharmaceutical treatment options the LDL‑C goals are amended to lower values. Patients at very high cardiovascular risk are recommended to achieve LDL‑C <1.4 mmol/l (55 mg/dl). For patients with high, moderate, and low cardiovascular risks, LDL‑C goals are set at <1.8 mmol/l (70 mg/dl), <2.6 mmol/l (100 mg/dl) and <3.0 mmol/l (116 mg/dl), respectively. A new classification of patients with recurrent cardiovascular events despite maximum tolerated statin-based therapy is introduced. For these patients the LDL‑C goal is <1.0 mmol/l (40 mg/dl). Novel recommendations comprise a more precise classification of patients at low or moderate risk based on cardiovascular imaging, recommendations for familial hypercholesterolemia, screening for increased lipoprotein(a) and determination of apolipoprotein B as diagnostic and therapeutic goal.

Background: The multifactorial origin of cardiovascular diseases has led to polypharmacy in primary and secondary prophylaxis with evidence-based medications, such as statins, antihypertensive drugs and platelet aggregation inhibitors. The number of prescribed drugs correlates inversely to adherence and can lead to treatment failure. Fixed-dose combination drugs (polypills) could increase the medication adherence of patients, reduce risks and prevent cardiovascular events., Methods: This review is based on publications that were retrieved from Medline (via PubMed) and The Cochrane Library. The clinical database ClinicalTrials.gov. was also considered., Results: In the studies on primary prevention conducted to date, fixed-dose combinations showed a superior control of risk factors, e.g. hypertension and low-density lipoprotein (LDL) cholesterol compared to placebo and at least non-inferiority compared to usual care. In secondary prevention, the effect of the polypill is mostly on the reduction of blood pressure and LDL cholesterol in non-adherent patients; however, evidence that fixed-drug combinations reduce cardiovascular morbidity and mortality compared to standard therapy is lacking., Conclusion: The polypill can be considered as an alternative to polypharmacy after a risk-benefit assessment, especially in non-adherent patients. Ongoing studies are investigating the effect of the polypill on cardiovascular events. Current polypills are limited by the lack of sufficient dosages of the individual components to avoid overtreatment and undertreatment at the individual treatment level.

Backround: Each year 16-17 million determinations of high-density lipoprotein cholesterol (HDL-C) are conducted and interpreted in Germany. Recently acquired data have led to a fundamental reassessment of the clinical significance of HDL-C., Method: This review article is based on a selective literature search., Results: Low HDL‑C levels usually indicate an increased cardiovascular risk, particularly in primary prevention but the epidemiological relationship between HDL‑C and the risk is complex. The HDL plays a role in the back transport and excretion of cholesterol; however, the biological functions of HDL are dependent on the protein and lipid composition, which is not reflected by the HDL‑C concentration. If the composition of HDL is pathologically altered it can also exert negative vascular effects., Conclusion: Compared with low-density lipoprotein cholesterol (LDL-C), HDL‑C is of secondary importance for cardiovascular risk stratification and the calculation of the LDL-C:HDL‑C ratio is not useful for all patients. Low HDL‑C levels should prompt a search for additional metabolic and inflammatory pathologies. An increase in HDL‑C through lifestyle changes (e.g. smoking cessation and physical exercise) has positive effects and is recommended; however, HDL‑C is currently not a valid target for drug therapy.

The 2 or 4‑week subcutaneous therapy with the recently approved antibodies alirocumab and evolocumab for inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) reduces low-density lipoprotein cholesterol (LDL-C) in addition to statins and ezetimibe by 50-60 %. The therapy is well-tolerated. The safety profile in the published studies is comparable to placebo. Outcome data and information on long-term safety and the influence on cardiovascular events are not yet available but the results of several large trials are expected in 2016-2018. At present (spring 2016) PCSK9 inhibitors represent an option for selected patients with a high cardiovascular risk and high LDL-C despite treatment with the maximum tolerated oral lipid-lowering therapy. This group includes selected patients with familial hypercholesterolemia and high-risk individuals with statin-associated muscle symptoms (SAMS).

Lipid disorders play an essential role in the pathogenesis of atherosclerotic diseases. An integral part of the clinical evaluation is the estimation of the individual cardiovascular risk using risk scores and patient history. Due to the long established prognostic relevance, reduction of low-density lipoproteins (LDL) using statins remains beyond doubt the central intervention both in primary and secondary prevention of atherosclerotic diseases. Indispensible components of treatment in all patients with elevated triglyceride levels are lifestyle changes contributing to a reduction of accompanying risk factors, in particular physical activity and smoking cessation.

A large number of patients fall into a category at the interface between heart or brain and are expected to require thorough clinical knowledge from both the cardiological as well as the neurological point of view for further patient-oriented treatment. The current article therefore addresses this important issue and aims to provide important information for clinical decision making for those patients at the interface between heart and brain. Due to the clinical impact, patients with carotid stenosis, a patent foramen ovale or non-valvular atrial fibrillation are described in more detail in this article.

Myocardial remodeling comprises changes in cardiac shape, mass, diameter, and function in response to changes in hemodynamic load, cardiac damage, or neurohumoral stimulation. Adaptive remodeling is a consequence of physiological stimuli such as physical activity. Maladaptive remodeling results from pathologic conditions such as myocardial ischemia and cardiac valve disease. Since regular vigorous endurance exercise can result in cardiac remodeling cardiologic screening is recommended for athletes to identify individuals with cardiomyopathies. Moderate physical activity is cornerstone of primary and secondary prevention of cardiovascular diseases. In secondary prevention, individual training recommendations need to be adapted to the underlying myocardial disease and individual risk factors. Experimental and clinical studies show that specific training interventions exert cardioprotective effects and reverse remodeling. However, clinical and basic science studies are needed to understand the mechanisms of adaptive and maladaptive remodeling and to better utilize this powerful therapeutic tool in the treatment of myocardial diseases.

The main treatment goals of conservative treatment of patients with stable coronary heart disease are prevention of symptoms, prevention of myocardial infarction, and heart failure and reduction of mortality. Lifestyle changes (smoking cessation, physical activity) are essential to reduce risk factors. For symptomatic treatment and prevention of angina pectoris, beta-blockers, calcium channel blockers, nitrates, I((f)) (funny channel) blockers and ranolazine are effective. Cornerstones of pharmacological prevention are drugs with prognostic effects, specifically aspirin and statins, as well as treatment of co-existing disorders such as hypertension and diabetes.