[Therapeutic options in hyperlipidemia]. / Therapieoptionen von Fettstoffwechselstörungen.

Treatment of lipid disorders (dyslipidemia) is the cornerstone of atherosclerosis prevention and reduction of progression. Lifestyle modification is the first step to improve the plasma lipid profile. Statins play a central role in the reduction of LDL cholesterol. Whether and to what extent other lipids such as triglycerides or lipoprotein(a) should also be treated depends on the extent of atherosclerotic disease and its progression over time. Especially in residential cardiac rehabilitation we have the opportunity to encourage adherence and adapt medication as necessary due to a face to face contact over 4 weeks. Moreover, the prescription for a PCSK9-inhibitor could be resolved or the indication for a lipoprotein apheresis could be considered.

Molecular imaging of atherosclerotic lesions by positron emission tomography - can it meet the expectations?

Early non-invasive imaging of atherosclerosis and in particular the detection of lesions at risk with high specificity could significantly affect cardiovascular morbidity and mortality. Conventional nuclear medicine approaches, in particular using autologous radiolabeled lipoproteins, can be related to histopathological findings; however, they fail to identify lesions at risk. Positron emission tomography (PET) tracers with much better physical properties have been examined, the most detailed information being available for F-18-deoxyglucose (FDG) and F-18-sodium fluoride (NaF). These two approaches are sensitive to different biochemical mechanisms, i.e. inflammation and microcalcification. Initial enthusiasm, in particular for F-18-FDG, has disappeared, although for F-18-NaF there is some hope, but this is not a breakthrough. No tracer is available so far that is able to identify a specific characteristic of a lesion prone to rupture. Other PET tracers in the pipeline have been examined, mainly in experimental models and only a few in patients, but they failed to contribute significantly to early lesion discovery and do not support great expectations. The key question is: Do we understand what we see? Moreover, methodological problems, a lack of standardization of imaging protocols and aspects of quantification provide a wide range for potential future improvements. While monitoring a therapeutic intervention seems to be possible for both F-18-FDG and F-18-NaF, highly specific early identification of lesions at risk by PET imaging is still far away. As of today, PET is not ready for routine clinical judgment of atherosclerotic lesions at risk to rupture. Even if all these problems can be solved, radiation exposure will still remain a concern, in particular for repeated studies.

In-111 polyclonal HIG identifies patients but not atherosclerotic lesions at risk - a 5 years follow-up.

There is a strong need for non-invasive detection of human atherosclerotic lesions. One of the radioisotopic approaches using Indium-111-HIG has been shown to accumulate in oxidized LDL-rich foam cells and inflammatory vascular lesions. Earlier human studies in 200 patients, 100 with peripheral vascular disease and 100 with carotid artery disease comparing In-111-HIG scintigraphy with sonographic data revealed a high sensitivity (70%-77%) but a very low specificity (33%-41%). At this time we concluded the approach "not promising" for human studies. However, clinical follow-up over 5 years now shows that those patients with positive In-111-HIG scintigraphy exhibited a significantly higher vascular morbidity (P<0,01) and mortality (P<0,01), especially in the immediate follow-up period. Retrospective analysis discovered higher CRP and isoprostane (8-epi-prostaglandin (PG) F2α) levels in HIG-positive patients at the time of scintigraphy. These findings indicate that In-111-HIG reflecting vascular lesions with a high inflammatory component, probably more prone to rupture, may identify a population at high vascular risk rather than a lesion at risk. The clinical impact of this finding should be assessed in prospective studies.

Effects of hiking at moderate and low altitude on cardiovascular parameters in male patients with metabolic syndrome: Austrian Moderate Altitude Study.

OBJECTIVE: Physical activity is a cornerstone in therapy for patients with metabolic syndrome. Walking and hiking in a mountain scenery represents an ideal approach to make them move. The Austrian Moderate Altitude Study (AMAS) 2000 main study is a randomized controlled trial to investigate the cardiovascular effects of hiking at moderate altitude on patients with metabolic syndrome compared with a control group at low altitude, to assess a potential altitude-specific effect. METHODS: Seventy-one male patients with metabolic syndrome were randomly assigned to a moderate altitude group (at 1700 m), with 36 participants, or to a low altitude group (at 200 m), with 35 participants. The 3-week vacation program included 12 hiking tours (4 per week, average duration 2.5 hours, intensity 55% to 65% of heart rate maximum). Physical parameters, performance capacity, 24-hour blood pressure, and heart rate profiles were obtained before, during, and after the stay. RESULTS: In both groups, we found a significant mean weight loss of -3.13 kg; changes in performance capacity were minor. Systolic, diastolic, and mean arterial pressures and circadian heart rate profiles were significantly reduced in both groups, with no differences between them. Consequently, the pressure-rate product was reduced as well. All study participants tolerated the vacation well without any adverse events. CONCLUSIONS: A 3-week hiking vacation at moderate or low altitude is safe for patients with metabolic syndrome and provides several improvements in their cardiovascular parameters. The cardiovascular benefits achieved are more likely to be the result of regular physical activity than the altitude-specific effect of a mountain environment.

Scintigraphic perfusion defects due to right ventricular apical pacing: a pitfall in clinical cardiology.

Right ventricular apical pacing (RVAP) with a left bundle branch block on the electrocardiogram may result in regional wall motion abnormalities and decreased left ventricular function (LVF). Furthermore, perfusion defects in dipyridamole technetium-99m-methoxisobutylisonitrile ((99m)Tc-MIBI) myocardial perfusion imaging may occur despite a normal coronary angiogram. In a 68 years old patient, RVAP resulted in regional wall motion abnormalities, markedly decreased LVF and perfusion defects in dipyridamole (99m)Tc-MIBI myocardial perfusion imaging by single photon emission tomography (SPET). Coronary angiography excluded coronary heart disease. Reprogramming of the pacemaker resulted in physiologic activation of the ventricles. Echocardiography showed a normal LV systolic function. Repeated myocardial perfusion imaging was unremarkable. In conclusion, our case confirms thatRVAP may lead to scintigraphic perfusion defects and wall motion abnormalities despite a normal coronary angiogram and this differentiate between ischemia-induced perfusion defects.

Platelet function in the postprandial period.

BACKGROUND: Postprandial hyperlipidemia and hyperglycemia have been related to cardiovascular events. Among different underlying mechanisms platelet activation seems to be responsible too. No comparable data between various tests in normo- vs. hyperlipidemics before and at different time intervals are available after a fat meal. We aimed to compare 9 of them within the same patients at several time points in postprandial hyperlipidemia. RESULTS: For some tests baseline values between the groups were significantly different (TXB2, platelet sensitivity, sedimentation and WU-test). However, hyperlipidemia revealed a variable influence on the tests examined. Some of the available tests apparently sensitive to show platelet activation reflect the increase in triglycerides (TG), such as the sedimentation index. ADP-induced platelet aggregatory activity in count adjusted washed isolated platelet samples during postprandial hyperlipidemia indicates mildly enhanced platelet activity, but does not seem to induce significant changes in aggregation. In patients with severe hypertriglyceridemia (> 400 mg/dl fasting) changes in platelet function are more pronounced due to delayed decay and may last up to 16 hours paralleling TG reaching the prevalue. The overwhelming majority of platelet function tests do not significantly respond to postprandial hyperlipidemia. The correlation between the tests applied is poor. For standardization purpose, platelet aggregation tests, aimed to examine proaggregatory capacity in atherosclerosis, should only be performed at the same time of the day after a fasting period > 6 hours. The great variation in preanalytical work-up on comparison of various tests, large number of platelet tests available and their respective potential value are discussed. CONCLUSIONS: At present, the suspicion that platelet function is significantly activated in the postprandial period cannot be supported by any of the tests used. The information provided is valuable to know for which test and group of patients a fasting period of which duration is recommendable.

Resistance training dose response in combined endurance-resistance training in patients with cardiovascular disease: a randomized trial.

OBJECTIVE: To compare the effectiveness of 2 different volumes of resistance training (RT) combined with aerobic training in residential cardiac rehabilitation (CR). DESIGN: Randomized prospective cohort study. SETTING: Center for inpatient CR. PARTICIPANTS: Patients (N=295) with a mean age ± SD of 62.7±11.7 years participated in the study. INTERVENTIONS: Patients were randomly divided into 2 groups (group 1 and group 2) with different volumes of RT; 2 sets × 12 repetitions (REPS) (group 1) and 3 sets × 15 REPS (group 2) per session, 2 times per week; each RT session consisting of 10 different resistance exercises. In addition, patients also completed continuous moderate intensity aerobic training composed of cycle ergometry 6 times per week for 17±4 minutes (mean ± SD) and walking 5 times per week for 45 minutes. MAIN OUTCOME MEASURES: At entry and after 26±4 (mean ± SD) days of CR, blood pressure, heart rate, maximal oxygen consumption, and maximal power determined during cycle ergometry, strength determined via RT, and blood biochemistries were assessed. Data were analyzed via a 2-way (group × time) repeated measures analysis of variance. RESULTS: Statistical analysis revealed equivalent improvements in exercise capacity, muscular strength, hemodynamics, and blood chemistries regardless of RT volume (comparison-wise type I error rate, α<.01). CONCLUSIONS: Our results show that nearly doubling (3 sets × 15 REPS vs 2 sets × 12 REPS) the volume of RT as part of a residential CR program does not yield further improvement in strength and cardiovascular risk factors.