Cholesterin und Atherosklerose - landläufige Irrtümer und wissenschaftliche Erkenntnisse

Der Zusammenhang zwischen Cholesterin und Atherosklerose ist eine der bestbelegten Hypothesen in der Medizin. Genetik, Epidemiologie und Interventionsstudien zeigen, dass hohes Cholesterin zu Atherothrombose führt und umgekehrt LDL-Cholesterinsenkung das Risiko von kardiovaskulären Ereignissen erheblich reduziert. Nichtsdestotrotz zirkulieren immer noch viele Stereotypen und Behauptungen, die Patienten mit Dyslipidämie verunsichern. So wird beispielsweise der Einfluss der Ernährung und des Lebensstils überschätzt. Heute verfügen wir über fundierte und bessere Kenntnisse der verschiedenen Arten von Cholesterin und seiner Wirkung auf das Herzkreislaufsystem, aber die Unterscheidung zwischen «bösem» und «gutem» Cholesterin ist eine grobe Vereinfachung. Aktuell gibt es mehrere pharmakologische Therapien, die sicher und effizient Gefässe vor den negativen Effekten von Cholesterin schützen können. Doch jedes Medikament hat Nebenwirkungen, so dass ein wichtiger Aspekt der Kunst der Medizin die Personalisierung der Therapie für jeden einzelnen Patienten ist – nicht nur hinsichtlich Risikoprofiloptimierung, sondern auch hinsichtlich der Verträglichkeit und des Krankheitsverständnisses

Secondary hypertension as a cause of treatment resistance

In secondary hypertension, elevated blood pressure is caused by a known and/or potentially treatable underlying disease.Although the prevalence of secondary hypertension depends on the patient population and the thoroughness of applied diagnostic approaches, arterial hypertension is classified in 90 to 95% as primary in nature. In young patients, individuals without a family history of hypertension, late onset of hypertension or worsening of a previous well-controlled hypertension as well as in patients who have a difficult to treat hypertension, the prevalence of secondary hypertension is significantly higher.Because the identification and the specific therapy of secondary hypertension may result in normalisation or improvement of elevated blood pressure in many cases, a targeted diagnostics is of great importance

Arterial age as a substitute for chronological age in the AGLA risk function could improve coronary risk prediction

PRINCIPLES: As a result of the relatively low sensitivity of coronary risk charts, such as the Swiss coronary risk calculator (Arbeitsgruppe Lipide und Atherosklerose, AGLA), for detecting subjects with future myocardial infarction, the performance of arterial age (aa) as a surrogate marker for chronological age (ca) was tested. METHODS: In a practice based sample, burden of carotid plaque was obtained with ultrasound, using total plaque area (TPA). In this derivation cohort, sex-specific 5-year groups of mean TPA were calculated in subjects aged between 35 and 79 years. The arterial age formula was found by fitting an exponential function on these data. AGLAca and AGLAaa were tested externally for their ability to detect 13 myocardial infarctions in 684 subjects (validation cohort). RESULTS: The derivation cohort included 1,500 subjects (mean age 59 ± 9 years, mean TPA 54 ± 52 mm2, 5% diabetics, 43% women). Arterial age was found to be y = 5.4175e0.0426x in men and y = 4.1942e0.0392x in women. Mean 10-year AGLAca coronary risk was comparable to AGLAaa (8% ± 9% vs 9% ± 15%). Receiver operating characteristic (ROC) analysis of AGLAca and AGLAaa results showed areas under the curve of 0.65 (p = 0.041) and 0.78 (p \u3c0.0001), respectively, (p = 0.041 for the difference = 0.13). This finding was also confirmed by a Cox proportional hazards regression model on patients\u27 event-free survival (p = not significant for AGLAca, p = 0.0003 for AGLAaa). CONCLUSIONS: Arterial age derived from TPA could be used instead of chronological age in the AGLA coronary risk function. Further studies on the external validity and cost effectiveness of the additional ultrasound imaging study are necessary

Extensive carotid atherosclerosis and the diagnostic accuracy of coronary risk calculators

Preventive therapy in primary care is guided by risk thresholds for future cardiovascular events. We aimed to assess whether the sensitivity of various risk calculators for the detection of subclinical carotid atherosclerosis (TPA80) could be improved by lowering risk thresholds in younger age groups. We compared sensitivity, specificity, and discriminatory performance of SCORE, SCORE-HDL, PROCAM, AGLA, FRAM and PCE coronary risk calculators to detect total plaque area > 80 mm2 (TPA80), a coronary risk equivalent, in age groups 40-55, 56-65, 66-75 from Germany (DE, N = 2942) and Switzerland (CH, N = 2202) during the years 2002 to 2016. All calculators showed good to moderate discriminatory performance to detect TPA80 with AUC ranging from 0.74 (CH-AGLA) to 0.87 (DE- SCORE), but the sensitivity of high risk risk thresholds varied widely from 39% for DE-FRAM-CVD to 5% for CH-AGLA. Lowering of the risk threshold increased sensitivity substantially at the expense of minor losses in specificity, but the sensitivity generally remained < 45% at the 90% specificity threshold. Current risk thresholds of American and European coronary risk calculators have a low sensitivity to detect TPA80 in younger individuals

Kardiologischer Check-up bei Frauen in den Wechseljahren

Kardiovaskuläre Erkrankungen, insbesondere atherothrombotische Ereignisse, verursachen jährlich über 4 Mio. Todesfälle in Europa. Herz-Kreislauf-Erkrankungen enden insgesamt tödlicher für die Frauen (2,2 Mio.) als für die Männer (1,8 Mio.), wohingegen kardiovaskuläre Todesfälle vor dem 65. Lebensjahr vorwiegend Männer betreffen (490.000 vs. 193.000). Das Herz-Kreislauf-Risiko ist nach der Menopause erhöht, das Risiko steigt weiter bei vorzeitiger oder früher Menopause. Risikofaktoren wie arterielle Hypertonie sollen spätestens ab dem 18. Lebensjahr abgeklärt werden, bei Verdacht auf eine familiäre Hypercholesterinämie soll eine Abklärung bereits im Kindesalter erfolgen. Frauen mit erhöhtem Risiko sollten deshalb früher zur Vorsorgeuntersuchung gehen. Für alle anderen Frauen ist ein kardialer Check-up generell nach der Menopause bzw. ab dem 50. Lebensjahr empfohlen. Welche kardiologischen Vorsorgeuntersuchungen für eine Frau in den Wechseljahren sinnvoll sind, hängt von individuellen Faktoren wie Krankheiten in der Familie, Alter, Vorerkrankungen oder kardiovaskulären Risikofaktoren ab. Zudem zählen als wichtige Aspekte die Lebensstilfaktoren (Konsum von Tabak oder Nikotin, Ernährung, körperliche Aktivität, Stress, Konsum von illegalen Drogen) sowie die familiäre und berufliche Situation. Ein kardiologischer Check-up bietet die Gelegenheit, Lebensgewohnheiten zu besprechen und individuelle Ratschläge zu erteilen. Auf Basis der Untersuchungsresultate werden gezielte, nach Alter und individuellen Risikofaktoren angepasste Präventivmassnahmen mit bewiesener Wirksamkeit empfohlen

Blood pressure target attainment in the background of guidelines: the very elderly in Swiss primary care

Background There are only a few trials for the very elderly population (>79 years). No consensus, which blood pressure (BP) goals and substances should be applied, has been found yet. This survey was undertaken to investigate how octogenarians are treated and attain BP targets in the Swiss primary care. Methods Data from 4594 hypertensive patients were collected within 7 days. Eight hundred and seventy-seven patients met the requirement to be >79 years. We assessed substances/combinations and investigated pulse pressure and target blood pressure attainment (TBPA) using three different recommendations [Canadian Hypertension Education Program (CHEP), Swiss Society of Hypertension (SSH), European Society of Hypertension-European Society of Cardiology (ESH-ESC)]. Secondarily, we compared TBPA attained by angiotensin-converting enzyme inhibitor (ACEI)/diuretic (D), angiotensin receptor blocker (ARB)/D and calcium channel blocker (CCB)/D with any other dual therapy and investigated whether Ds/beta-blockers (BBs) or Ds/renin angiotensin-converting enzyme inhibitors (RAAS-Is) lead to higher TBPA. Finally, we assessed the impact of drug administration, practical work experience, location and specialization of GPs on TBPA. Results Octogenarians attained target blood pressure (TBP) between 44% (ESH-ESC) and 74% (SSH). Optimal/normal BP was reached in 22.8% of patients. Pulse pressure <65 mmHg was shown in 66.4% of patients. Monotherapy was most commonly applied followed by dual single-pill combination with ARB/D (46.5%) or ACEI/D (36.0%). No benefit in TBPA was found comparing a RAASI/D and CCB/D treatment with any other dual combination. There was also no difference between BB/D and RAAS-I/D combination therapy and between single-pill combination and dual free combinations. Conclusions GPs adhere to the use of substances proven in outcome trials and attain high TBP. No difference in meeting BP goals could be found using different drug classes. There is an unmet need to harmonize recommendations and to add additional information for the treatment of octogenarian

Arrhythmic Manifestations of Cardiac Amyloidosis: Challenges in Risk Stratification and Clinical Management

Amyloidosis is a systemic disease characterized by extracellular deposits of insoluble amyloid in various tissues and organs. Cardiac amyloidosis is a frequent feature of the disease, causing a progressive, restrictive type of cardiomyopathy, and is associated with adverse clinical outcomes and increased mortality. The typical clinical presentation in patients with cardiac amyloidosis is heart failure (HF) with preserved ejection fraction. Most patients present with typical symptoms and signs of HF, such as exertional dyspnea, pretibial edema, pleural effusions and angina pectoris due to microcirculatory dysfunction. However, patients may also frequently encounter various arrhythmias, such as atrioventricular nodal block, atrial fibrillation and ventricular tachyarrhythmias. The management of arrhythmias in cardiac amyloidosis patients with drugs and devices is often a clinical challenge. Moreover, predictors of life-threatening arrhythmic events are not well defined. This review intends to give a deepened insight into the arrhythmic features of cardiac amyloidosis by discussing the pathogenesis of these arrhythmias, addressing the challenges in risk stratification and strategies for management in these patients

Endocrine hormone imbalance in heart failure with reduced ejection fraction: A cross-sectional study

BACKGROUND AND AIMS Sustained neurohormonal activation plays a central role in the progression of heart failure (HF). Other endocrine axes may also be affected. It was the aim of this study to examine the endocrine profile (thyroid, parathyroid, glucocorticoid, and sex hormones) in a contemporary sample of patients with HF and reduced ejection fraction (EF) on established disease-modifying therapy. METHODS This study prospectively measured morning fasting hormones in 52 ambulatory and stable HF patients with EF < 50% on disease-modifying therapy (mean age 63 ± 11 years, 29% female, mean LVEF 32 ± 9.6%) and compared them to 54 patients at elevated risk for HF (61 ± 12 years, 28% female) and 62 healthy controls (HC; 61 ± 13 years, 27% female). Main comparisons were performed using one-way analysis of variance. Associations with biomarkers were studied with linear regression. RESULTS HF patients showed a reduced free triiodothyronine (fT3)/free thyroxine (fT4) ratio compared to HC (0.30 ± 0.06 vs. 0.33 ± 0.05, p = 0.046). Parathyroid hormone (PTH) and cortisol were increased in HF compared to both HC (median [IQR] 59 [50-84] vs. 46 [37-52] ng/L, p < 0.001 and 497 ± 150 vs. 436 ± 108 nmol/L, p = 0.03, respectively) and patients at risk (both p < 0.001). Total testosterone was reduced in male HF compared to HC (14.4 ± 6.6 vs. 18.6 ± 5.3 nmol/L; p = 0.01). No differences in TSH, estradiol, progesterone, and prolactin were found. Lower fT3 levels were found in HF with EF < 40% versus EF 40%-49% (4.6 ± 0.3 vs. 5.2 ± 0.7 pmol/L, p = 0.009). In HF patients, fT3 was an independent predictor of NT-proBNP and high-sensitivity troponin T in multiple regression analysis. PTH was positively associated with NT-proBNP. CONCLUSION There is evidence of endocrine hormonal imbalance in HF with reduced EF beyond principal neurohormones and despite the use of disease-modifying therapy

Diverging role of epicardial adipose tissue across the entire heart failure spectrum

AIMS Epicardial adipose tissue (EAT) is a metabolically highly active tissue modulating numerous pathophysiological processes. The aim of this study was to investigate the association between EAT thickness and endothelial function in patients with heart failure (HF) across the entire ejection fraction spectrum. METHODS AND RESULTS A total of 258 patients with HF with an ejection fraction across the entire spectrum [HF with reduced ejection fraction (HFrEF), n = 168, age 60.6 ± 11.2 years; HF with preserved ejection fraction (HFpEF), n = 50, mean age 65.1 ± 11.9 years; HF with mildly reduced ejection fraction (HFmrEF), n = 32, mean age 65 ± 12] were included. EAT was measured with transthoracic echocardiography. Vascular function was assessed with flicker-light-induced vasodilation of retinal arterioles (FIDart%) and flow-mediated dilatation (FMD%) in conduit arteries. Patients with HFrEF have less EAT compared with patients with HFpEF (4.2 ± 2 vs. 5.3 ± 2 mm, respectively, P < 0.001). Interestingly, EAT was significantly associated with impaired microvascular function (FIDart%; r = -0.213, P = 0.012) and FMD% (r = -0.186, P = 0.022), even after multivariate correction for confounding factors (age, body mass index, hypertension, and diabetes; standardized regression coefficient (SRC) = -0.184, P = 0.049 for FIDart% and SRC = -0.178, P = 0.043 for FMD%) in HFrEF but not in HFpEF. CONCLUSIONS Although less EAT is present in HFrEF than in HFpEF, only in HFrEF EAT is associated with vascular dysfunction. The diverging role of EAT in HF and its switch to a functionally deleterious tissue promoting HF progression provide the rationale to specifically target EAT, in particular in patients with reduced ejection fraction