Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening

Objectives  We investigated whether qualitative or quantitative alterations of the endothelial progenitor cell (EPC) pool predict age-related structural vessel wall changes. Background  We have previously shown that age-related endothelial dysfunction is accompanied by qualitative rather than quantitative changes of EPCs. Animal studies suggest that impaired EPC functions lead to accelerated arterial intimal thickening. Methods  Intima-media thickness (IMT) was measured in the common carotid artery in our previously published groups of younger (25 ± 1 years, n = 20) and older (61 ± 2 years, n = 20) healthy non-smoking volunteers without arterial hypertension, hypercholesterolemia, and diabetes mellitus. Endothelial progenitor cells (EPCs, KDR⁺/CD34⁺ and KDR⁺/CD133⁺) were counted in peripheral blood using flow cytometry. In ex vivo expanded EPCs, the function was determined as chemotaxis to VEGF, proliferation, and survival. Results  We observed thicker IMT in older as compared to younger subjects (0.68 ± 0.03 mm Vs. 0.48 ± 0.02 mm, P < 0.001). Importantly, there were significant inverse univariate correlations between IMT, EPC chemotaxis, and survival (r = −0.466 P < 0.05; r = −0.463, P < 0.01). No correlation was observed with numbers of circulating EPCs. Multivariate regression analysis revealed that age, mean arterial pressure and migration of EPCs were independent predictors of IMT (R ² = 0.58). Conclusion  Impaired EPC function may lead to accelerated vascular remodeling due to chronic impairment of endothelial maintenance. Returned for 1. Revision: 13 December 2007 1. Revision received: 16 June 2008 Returned for 2. Revision: 20 June 2008 2. Revision received: 17 July 2008     

Hypertrophic cardiomyopathy: Management issues in the new millennium

Hypertrophic cardiomyopathy is an inherited cardiac disorder. Sudden cardiac death frequently occurs in otherwise healthy individuals, and accounts for nearly 35% of all sudden deaths within this age group. Although symptoms occur commonly, they often go unreported. Despite this, a degree of functional limitation is often seen on objective assessment. Management of hypertrophic cardiomyopathy is aimed at relieving symptoms, identifying and treating those individuals at increased risk of sudden death, and screening family members.     

High Dose Adenosine Stress Echocardiography for Noninvasive Detection of Coronary Artery Disease

Objectives. The aim of this study was to assess the tolerability and incremental diagnostic value of high adenosine doses in stress echocardiography testing in patients with coronary artery disease (CAD).

Background. In comparison with other pharmacologic stress echocardiography tests, standard dose adenosine stress has suboptimal sensitivity for detecting milder forms of CAD.

Methods. Adenosine stress echocardiography was performed in 58 patients using a starting dose of 100 μg/kg body weight per min over 3 min followed by 140 μg/kg per min over 4 min (standard dose). If no new wall motion abnormality appeared, the dose was increased to 200 μg/kg per min over 4 min (high dose). All patients underwent coronary angiography. Significant CAD was defined as ≥50% diameter stenosis in at least one major coronary artery. Thirty-three patients had one-vessel and seven had multivessel CAD. Coronary angiographic findings were normal in 18 patients.

Results. The high adenosine dose caused a slight but significant increase over baseline values in rate-pressure product. Limiting side effects occurred in two patients during the standard dose protocol and in one patient receiving the high dose regimen. The test was stopped in 30 patients after the standard adenosine dose regimen because of a provoked new wall motion abnormality. The sensitivity of adenosine echocardiography with the standard dose was 75% (95% confidence interval [CI] 63% to 87%). After completion of the standard dose protocol, 28 patients continued testing with the high dose adenosine protocol. The overall sensitivity of adenosine echocardiography, calculated as cumulative, increased to 92% (95% CI 84% to 100%) with the high dose (p < 0.05). The specificity of adenosine testing was 100% and 88%, respectively, with the standard and high dose regimen (p = 0.617).

Conclusions. We believe that use of a higher than usual adenosine dose protocol for stress testing may improve the diagnostic value of adenosine echocardiography, mainly by increasing sensitivity in patients with single-vessel disease without deterioration of the safety profile and with only a mild reduction in specificity.

(J Am Coll Cardiol 1996;28:1689–95)>     

Empfehlungen der Projektgruppe Prävention der DGK zur risikoadjustierten Prävention von Herz- und Kreislauferkrankungen

Dyslipidemia

There is a strong correlation between low-density lipoproteins (LDL) cholesterol level and cardiovascular risk. Risk adjusted treatment, predominantly with statins, improves prognosis (Class I recommendation, evidence level A). The LDL targets depend on the individual risk. For HDL und triglycerides no target levels but only levels below (for HDL-C) or above which an increased cardiovascular risk is documented are defined. The guideline conforming LDL lowering with the defined LDL target levels requires the availability of highly effective statins for all patients.

Arterial hypertension

Arterial hypertension is one of the major cardiovascular risk factors leading to myocardial infarction, stroke or dementia. Repeated blood pressure readings of 140/90 mmHg or more confirm the diagnosis hypertension and should lead to further investigations to exclude secondary forms of hypertension or already established end organ damage. Antihypertensive drugs are prescribed according to the individual cardiovascular risk and additional diseases. Life style modifications markedly reduce blood pressure even in patients receiving blood pressure lowering drugs. A combination of drugs is needed in most cases and fixed combinations are recommended. Follow-up has to be performed regularly to control blood pressure response, possible side effects and patient adherence to therapy.

Glucosemetabolism and diabetes

The stages in the manifestation of type 2 diabetes mellitus develop over several years ranging from impaired fasting glucose to impaired glucose metabolism and manifest diabetes mellitus. Cardiovascular complications can occur early and the earlier the diagnosis is confirmed with subsequent near normal blood glucose adjustment, the more favorable the prognosis. The glycated hemoglobin (HbA1c) target for patients with established type 2 diabetes is less than 7% (53 mmol/mol). In individual cases particularly with new onset diabetes lower values can be attempted. Particular care should be taken to avoid hypoglycemic episodes because of the high associated risk. Statins should be prescribed to reach the LDL-C target of <70 mg/dl (1.8 mmol/l). Additional cardiovascular risk factors increase cardiovascular risk and are to be treated according to the evidence-based therapy recommendations.     

Katheterablation des Vorhofflimmerns

Atrial fibrillation (AF), the most frequently encountered sustained cardiac arrhythmia, contributes significantly to population morbidity and mortality and is associated with heart failure and stroke. Catheter ablation of AF is an effective tool to treat symptomatic paroxysmal AF. In patients with persistent AF and/or cardiac disease, however, ablation tends to be more challenging with substrate modification strategies playing a major role in many cases. Novel technologies and concepts (e.g., alternative energy sources, remote robotic catheter navigation, elimination of localized re-entrant waves or “rotors”, and gene therapy) have been developed to reduce the AF recurrence rate and are currently under evaluation at different stages of clinical and experimental studies. Long-term continuation of oral anticoagulant therapy is required post-ablation irrespective of the procedural success in all patients with a CHA₂DS₂-VASc score of ≥?2. Finally, ongoing clinical trials are investigating potential effects of AF ablation on morbidity and mortality and on left ventricular ejection fraction in patients with heart failure.