[Modern genetic counselling : Practical aspects exemplified by hypertrophic cardiomyopathy]. / Moderne humangenetische Beratung : Praktische Aspekte am Beispiel der hypertrophen Kardiomyopathie.

Genetic counselling and subsequent molecular genetic testing should be performed in patients when an inherited monogenic form of heart disease is suspected. For the individual patient as well as for the (possibly asymptomatic) relatives, molecular diagnostics is important for an early diagnosis, (preventive) therapy and prognosis assessment. Using the example of hypertrophic cardiomyopathy (HCM), the most common monogenic form of structural heart disease, essential aspects of modern genetic counselling are elucidated. Specific examples of one case with a classical form of hypertrophic obstructive cardiomyopathy and one case of congenital HCM with Noonan's syndrome are discussed.

Increased proatherogenic monocyte-platelet cross-talk in monocyte subpopulations of patients with stable coronary artery disease.

BACKGROUND: Monocytes and platelets are important cellular mediators of atherosclerosis. Human monocytes can be divided into CD14(++) CD16(-) , CD14(++) CD16(+) and CD14(+) CD16(++) cells, which differ in their functional properties. The aim of this study was to examine monocyte subset distribution, monocyte-platelet aggregate (MPA) formation and expression of CCR5, the receptor of the platelet-derived chemokine CCL5, and to determine whether these parameters are altered in individuals with coronary atherosclerosis. METHODS: Peripheral blood cells from 64 healthy blood donors (HBDs) and 60 patients with stable coronary artery disease (CAD) were stained with antibodies against CD14, CD16, CD42b and CCR5 and analysed by flow cytometry. Circulating CCL5 levels were determined using an enzyme-linked immunosorbent assay. RESULTS: In patients with CAD, the relative proportion of the CD14(++) CD16(-) monocyte subset was elevated (P < 0.05) and of the CD14(+) CD16(++) subset was reduced (P < 0.001) compared with the HBD group. Furthermore, MPA formation significantly increased in patients with CAD in all three monocyte subsets. In both study groups, the majority of CCR5(+) cells was detected in CD14(++) CD16(+) monocytes (P < 0.001 versus CD14(++) CD16(-) and CD14(+) CD16(++) ), although the CCR5(+) monocyte number was reduced in patients with CAD (CD14(++) CD16(-) /CD14(+) CD16(++) , P < 0.001; CD14(++) CD16(+) , P < 0.05) compared with the HBD group, particularly in those who were not taking statins. Ex vivo incubation of monocytes from HBDs with plasma from patients with CAD also decreased CCR5(+) expression (P < 0.05 versus plasma from HBDs). Serum CCL5 levels were similar in both groups. CONCLUSIONS: The increased monocyte-platelet cross-talk in patients with CAD might have contributed to atherosclerosis progression. The decreased CCR5(+) monocyte numbers in patients with CAD could have resulted from CCR5(+) cell recruitment into atherosclerotic lesions or CCR5 downregulation in response to circulating factors.

[New pharmaceuticals in cardiology. Heart failure, anticoagulation, dyslipidemia]. / Neue Medikamente in der Kardiologie. Herzinsuffizienz, Antikoagulation, Dyslipidämien.

Three innovative pharmaceuticals which might play an important role in the field of cardiology in the near future were recently tested in large clinical studies. Serelaxin, a vasoactive hormone peptide that is produced during pregnancy, reduces vessel resistance, increases cardiac output, and improves renal function. Lately, it was demonstrated that serelaxin significantly reduces congestion symptoms in patients with acute heart failure. As a secondary endpoint the mortality at day 180 was reduced. Therefore, serelaxin seems to be a promising new drug for the treatment of acute heart failure which might have a prognostic impact. Edoxaban is a selective factor Xa inhibitor, which inhibits thrombin production and thrombus formation. Two recently published studies reported that edoxaban is at least as effective as the vitamin K antagonist warfarin in prevention and treatment of venous thromboembolism and in the prevention of stroke and systemic embolism due to nonvalvular atrial fibrillation. Compared to warfarin, edoxaban significantly exhibited less frequent severe bleeding complications. Edoxaban will probably soon be the fourth new oral anticoagulant available for patients. The serine protease proprotein convertase subtilisin/kexin 9 (PCSK9) reduces the ability of the liver to bind low-density lipoprotein cholesterol (LDL-C) and to remove it from the circulation. Recently, a monoclonal antibody for PCSK9 was developed which induces a LDL-C plasma level reduction up to 73 % and also decreases lipoprotein(a) and apolipoprotein B. PCSK9 inhibition is a promising new mechanism for LDL-C reduction and the corresponding drug will be presumably approved soon by the regulatory authorities.

Hypercholesterolaemia impairs monocyte function in CAD patients.

OBJECTIVES: Hypercholesterolaemia (HC) impairs arteriogenesis, i.e. collateral artery growth. Monocytes are crucial mediators of arteriogenesis. We investigated the impact of the cardiovascular risk factor HC on ligand-induced monocyte chemotaxis. SUBJECTS: The migratory response of monocytes towards the arteriogenic ligands vascular endothelial growth factor-A (VEGF-A) and monocyte chemoattractant protein-1 (MCP-1) in hypercholesterolaemic coronary artery disease (CAD) patients (n = 14), hypercholesterolaemic controls (n = 8) and age-matched healthy controls (n = 19) was analysed. Furthermore, the serum VEGF-A level was determined in all individuals. RESULTS: VEGF-A-induced monocyte chemotaxis was severely impaired in hypercholesterolaemic CAD patients when compared with age-matched healthy controls (P < 0.001). The same was true for the migratory response towards MCP-1 (P < 0.001). VEGF-A- and MCP-1-induced monocyte chemotaxis of hypercholesterolaemic controls was also decreased in comparison with the healthy control group, but not as severe as observed in the hypercholesterolaemic CAD patients. VEGF-A serum levels did not differ between the three study groups. CONCLUSIONS: Hypercholesterolaemia severely impairs monocyte function in hypercholesterolaemic CAD patients. Monocyte dysfunction is probably connected to impaired collateral artery growth. The duration of the cardiovascular risk factor HC seems to influence the extent of monocyte dysfunction, as there exists a continuum of diminished monocyte chemotaxis in the three study groups. Further trials are warranted in order to determine whether statins can reverse the negative influence of HC on cell function.