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

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

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

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

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

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

Age-dependent impairment of the erythropoietin response to reduced central venous pressure in HFpEF patients

Despite growing research interest in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), it remains unknown whether central hemodynamic alterations inherently present in this condition do affect blood pressure and blood volume (BV) regulation. The present study sought to determine hemodynamic and endocrine responses to prolonged orthostatic stress in HFpEF patients. Central venous pressure (CVP) assessed via the internal jugular vein (IJV) aspect ratio with ultrasonography, arterial pressure and heart rate were determined at supine rest and during 2 hours of moderate (25-30°) head-up tilt (HUT) in 18 stable HFpEF patients (71.2 ± 7.3 years), 14 elderly (EC), and 10 young (YC) healthy controls. Parallel endocrine measurements comprised main BV-regulating hormones: pro-atrial natriuretic peptide, copeptin, aldosterone, and erythropoietin (EPO). At supine rest, the IJV aspect ratio was higher (>30%) in HFpEF patients compared with EC and YC, while mean arterial pressure was elevated in HFpEF patients (98.0 ± 13.1 mm Hg) and EC (95.6 ± 8.3 mm Hg) versus YC (87.3 ± 5.0 mm Hg) (P < 0.05). HUT increased heart rate (+10%) and reduced the IJV aspect ratio (-52%), with similar hemodynamic effects in all groups (P for interaction ≥ 0.322). The analysis of endocrine responses to HUT revealed a group×time interaction for circulating EPO, which was increased in YC (+10%) but remained unaltered in HFpEF patients and EC. The EPO response to a given reduction in CVP is similarly impaired in HFpEF patients and elderly controls, suggesting an age-dependent dissociation of EPO production from hemodynamic regulation in the HFpEF condition

Vascular lesions induced by renal nerve ablation as assessed by optical coherence tomography: pre- and post-procedural comparison with the Simplicity® catheter system and the EnligHTN™ multi-electrode renal denervation catheter

Aims Catheter-based renal nerve ablation (RNA) using radiofrequency energy is a novel treatment for drug-resistant essential hypertension. However, the local endothelial and vascular injury induced by RNA has not been characterized, although this importantly determines the long-term safety of the procedure. Optical coherence tomography (OCT) enables in vivo visualization of morphologic features with a high resolution of 10-15 µm. The objective of this study was to assess the morphological features of the endothelial and vascular injury induced by RNA using OCT. Methods and results In a prospective observational study, 32 renal arteries of patients with treatment-resistant hypertension underwent OCT before and after RNA. All pre- and post-procedural OCT pullbacks were evaluated regarding vascular changes such as vasospasm, oedema (notches), dissection, and thrombus formation. Thirty-two renal arteries were evaluated, in which automatic pullbacks were obtained before and after RNA. Vasospasm was observed more often after RNA then before the procedure (0 vs. 42%, P < 0.001). A significant decrease in mean renal artery diameter after RNA was documented both with the EnligHTN™ (4.69 ± 0.73 vs. 4.21 ± 0.87 mm; P < 0.001) and with the Simplicity® catheter (5.04 ± 0.66 vs. 4.57 ± 0.88 mm; P < 0.001). Endothelial-intimal oedema was noted in 96% of cases after RNA. The presence of thrombus formations was significantly higher after the RNA then before ablation (67 vs. 18%, P < 0.001). There was one evidence of arterial dissection after RNA with the Simplicity® catheter, while endothelial and intimal disruptions were noted in two patients with the EnligHTN™ catheter. Conclusion Here we show that diffuse renal artery constriction and local tissue damage at the ablation site with oedema and thrombus formation occur after RNA and that OCT visualizes vascular lesions not apparent on angiography. This suggests that dual antiplatelet therapy may be required during RN