Assignment of Tangier disease to chromosome 9q31 by a graphical linkage exclusion strategy.

A low level of high density lipoprotein (HDL) cholesterol is a strong predictor of ischaemic heart disease (IHD) and myocardial infarction. One cause of low HDL-cholesterol is Tangier disease (TD), an autosomal codominant inherited condition first described in 1961 in two siblings on Tangier Island in the United States of America. Apart from low HDL-cholesterol levels and an increased incidence of atherosclerosis, TD is characterized by reduced total cholesterol, raised triglycerides, peripheral neuropathy and accumulation of cholesteryl esters in macrophages, which causes enlargement of the liver, spleen and tonsils. In contrast to two other monogenic HDL deficiencies in which defects in the plasma proteins apoA-I and LCAT interfere primarily with the formation of HDL (refs 7-10), TD shows a defect in cell signalling and the mobilization of cellular lipids. The genetic defect in TD is unknown, and identification of the Tangier gene will contribute to the understanding of this intracellular pathway and of HDL metabolism and its link with IHD. We report here the localization of the genetic defect in TD to chromosome 9q31, using a genome-wide graphical linkage exclusion strategy in one pedigree, complemented by classical lod score calculations at this region in a total of three pedigrees (combined lod 10.05 at D9S1784). We also provide evidence that TD may be due to a loss-of-function defect.

The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease.

Tangier disease (TD) is an autosomal recessive disorder of lipid metabolism. It is characterized by absence of plasma high-density lipoprotein (HDL) and deposition of cholesteryl esters in the reticulo-endothelial system with splenomegaly and enlargement of tonsils and lymph nodes. Although low HDL cholesterol is associated with an increased risk for coronary artery disease, this condition is not consistently found in TD pedigrees. Metabolic studies in TD patients have revealed a rapid catabolism of HDL and its precursors. In contrast to normal mononuclear phagocytes (MNP), MNP from TD individuals degrade internalized HDL in unusual lysosomes, indicating a defect in cellular lipid metabolism. HDL-mediated cholesterol efflux and intracellular lipid trafficking and turnover are abnormal in TD fibroblasts, which have a reduced in vitro growth rate. The TD locus has been mapped to chromosome 9q31. Here we present evidence that TD is caused by mutations in ABC1, encoding a member of the ATP-binding cassette (ABC) transporter family, located on chromosome 9q22-31. We have analysed five kindreds with TD and identified seven different mutations, including three that are expected to impair the function of the gene product. The identification of ABC1 as the TD locus has implications for the understanding of cellular HDL metabolism and reverse cholesterol transport, and its association with premature cardiovascular disease.

[Cardiac rehabilitation: current status and future challenges]. / Kardiologische Rehabilitation: Aktueller Stand und zukünftige Anforderungen.

The goal of cardiac rehabilitation is to support heart patients using a multidisciplinary team in order to obtain the best possible physical and mental health and achieve long-term social reintegration. In addition to improving physical fitness, cardiac rehabilitation restores self-confidence, thus better equipping patients to deal with mental illness and improving their social reintegration ("participation"). Once the causes of disease have been identified and treated as effectively as possible, drug and lifestyle changes form the focus of cardiac rehabilitation measures. In particular diseases, rehabilitation offers the opportunity for targeted educational courses for diabetics or drug dose escalation, as well as special training for heart failure patients. A nationwide network of outpatient heart groups is available for targeted follow-up. Cardiac patients predominantly rehabilitated in follow-up rehabilitation are older and have greater morbidity than in the past; moreover, they generally come out of acute clinical care earlier and are discharged from hospital more quickly. The proportion of severely ill and multimorbid patients presents a diagnostic and therapeutic challenge in cardiac rehabilitation, although cardiac rehabilitation was not initially conceived for this patient group. The benefit of cardiac rehabilitation has been a well documented reduction in morbidity and mortality. However, hurdles remain, partly due to the patients themselves, partly due to the health insurers. Some insurance providers still refuse rehabilitation for non-ST-segment elevation infarction. In principle rehabilitation can be carried out in an inpatient or an outpatient setting. Specific allocation criteria have not yet been established, but the structure and process quality of outpatient rehabilitation should correspond to that of the inpatient setting. The choice between the two settings should be based on pragmatic criteria. Both settings should be possible for an individual patient. Cardiac rehabilitation is already focusing on older, sicker and polymorbid patients; this will become ever more the case in the future. There is still a need for future clinical research for these patients.

Comparison of skeletal muscle strength between cardiac patients and age-matched healthy controls.

The purpose of the present study was to compare muscular strength of knee extensors and arm flexor muscles of cardiac patients (n = 638) and healthy controls (n = 961) in different age groups. Isometric torques were measured in a sitting position with the elbow, hip, and knee flexed to 90(0). For statistical analysis, age groups were pooled in decades from the age of 30 to 90 years. Additionally, the influence of physical lifestyle prior to disease on muscular strength was obtained in the patients. For statistical analysis three-way ANOVA (factors age, gender, and physical activity level) was used.Both in patients and in controls a significant age-dependent decline in maximal torque could be observed for arm flexors and knee extensors. Maximal leg extensor muscle showed statistically significant differences between healthy controls and cardiac patients as well as between subgroups of patients: Physically inactive patients showed lowest torques (male: 148 +/- 18 Nm; female: 82 +/- 25 Nm) while highest values were measured in control subjects (male: 167 +/- 16 Nm; female: 93 +/- 17 Nm). In contrast, arm flexor muscles did not show any significant influence of health status or sports history.This qualitative difference between weight-bearing leg muscles and the muscle group of the upper extremity suggest that lower skeletal muscle strength in heart patients is mainly a consequence of selective disuse of leg muscles rather than any pathological skeletal muscle metabolism. Since a certain level of skeletal muscle strength is a prerequisite to cope with everyday activities, strength training is recommended as an important part of cardiac rehabilitation.

Draft Genome Sequences of Klebsiella oxytoca Isolates Originating from a Highly Contaminated Liquid Hand Soap Product.

In 2013, contaminated liquid soap was detected by routine microbiological monitoring of consumer products through state health authorities. Because of its high load of Klebsiella oxytoca, the liquid soap was notified via the European Union Rapid Alert System for Dangerous Non-Food Products (EU-RAPEX) and recalled. Here, we present two draft genome sequences and a summary of their general features.

The significance of high levels of lipoprotein (a) compared with established risk factors in premature coronary artery disease: differences between men and women.

It was shown in a series of studies that increased lipoprotein (a) concentration is a strong and independent risk factor for coronary artery disease. The goal of this study was to determine the significance of elevated lipoprotein (a) levels for the existence and the early manifestation of coronary artery disease by systematically recording cardiovascular risk factors in diagnostic coronary angiographies in a larger group of patients, whereby particular attention was paid to sex-specific differences. In 1011 consecutive patients who underwent coronary angiography (731 men, 280 women, mean age 59 +/- 10 years), fasting blood samples were taken immediately before the angiographies to determine the levels of cholesterol, low density lipoprotein-, high density lipoprotein-cholesterol, triglycerides and lipoprotein (a). In addition, further risk factors were qualitatively recorded. The data evaluation was carried out using the SPSSx software package univariately and multivariately with stepwise discriminant analysis. In 231 patients (144 men, 87 women) either no or only discrete coronary findings appeared, while in 780 cases (587 men, 193 women) coronary artery disease with stenoses > 50% were found. Women with coronary artery disease were significantly older than men and demonstrated higher lipoprotein levels. Women as well as men with coronary artery disease differed from healthy controls by having higher levels of lipoprotein (a) and other lipoproteins, lipoprotein (a) having the smallest error probability (P < 0.0005). The early manifestation of coronary artery disease (below the 18th age percentile) in men (< 50 years) was connected with significantly higher levels of cholesterol, triglycerides and lipoprotein (a), which emphasized their atherogenic significance in the general view. The most striking finding was that in young women (< 53 years), compared to older women with coronary artery disease--corresponding to the age-determined prevalence--significantly lower concentrations of cholesterol, triglycerides and lipoprotein (a) were found. Possible explanations include later manifestation of coronary artery disease, a steeper increase of the lipids with age, particularly of lipoprotein (a), but also a different valence of the risk factors in women.

Effects of fenofibrate on angiographically examined coronary atherosclerosis and left ventricular function in hypercholesterolemic patients.

Within the framework of a prospective lipid-lowering intervention study 44 patients were treated over a period of 3 years with a lipid-lowering diet and 200-400 mg fenofibrate daily. The intervention led to statistically significant decreases in total cholesterol (Chol), low density lipoprotein cholesterol (LDL-Chol) and triglycerides levels, and to a significant increase in high density lipoprotein cholesterol (HDL-Chol) levels. Despite intervention, in 8 patients the HDL-Chol levels decreased by up to 20 mg/dl, where these were mainly patients with high initial values. Likewise, the triglycerides of 4 patients whose initial levels were relatively low increased (up to 49 mg/dl) and the LDL-Chol levels of 8 patients whose initial levels were also low increased (up to 49 mg/dl). Only minor success was achieved through the 6-week diet, but this was still slightly significant for Chol and LDL-Chol levels. A total of 21 patients underwent repeat angiography within 3 years for clinical reasons. For the evaluation of the angiographic progress a total of 98 minor and moderate stenoses was measured using digital image processing and automatic contour finding. The change in the angiographic parameters 'percent diameter reduction' (%DR) and 'percent plaque area' (%PA) correlated with on-treatment LDL-Chol levels (%DR change with LDL-Chol: r = 0.67, P = 0.0005; %DR change with Chol: r = 0.61, P = 0.002; %PA change with LDL-Chol: r = 0.40, P = 0.037; %PA change with Chol: r = 0.38, P = 0.044), while for HDL-Chol and triglycerides no influence on the angiographic progress could be demonstrated. On the basis of the reproducibility of the measuring methods the patients were classified in the categories 'regression', 'unchanged' and 'progression'. The patients classified as 'regression' (parameter: %DR change) showed an LDL-Chol mean value of 162 +/- 9 mg/dl, whereas those classified as 'unchanged' or 'progression' showed values of 189 +/- 25 mg/dl and 199 +/- 21 mg/dl, respectively (P = 0.014). A negative correlation appeared between the angiographic progress parameters and the initial degree of stenosis. The left ventricular ejection fraction in the second angiography showed relationships to lipoprotein levels and angiographic progress parameters.

Progression and regression of minor coronary arterial narrowings by quantitative angiography after fenofibrate therapy.

To study the effects of fenofibrate, a lipid-lowering medication, on patients with coronary artery disease, 191 minor coronary narrowings in 42 patients with coronary artery disease were analyzed by quantitative coronary angiography using computer-assisted contour detection. Computed parameters were percent diameter reduction and percent plaque area. A prospectively formed intervention group of 21 patients treated with special diet and fenofibrate (200 to 400 mg/day) was checked every 6 weeks with regard to risk factors. After a mean interval of 21 months, coronary angiography was repeated, using the same x-ray system and nearly identical projections. The intervention group was angiographically compared at follow-up with an untreated comparison group, also comprising 21 patients. Both groups had high initial serum cholesterol (mean 311 mg/dl) and low-density lipoprotein (LDL) cholesterol levels (mean 235 mg/dl). Only among the treated patients did lipid levels change significantly: cholesterol, -19%; LDL cholesterol, -20%; high-density lipoprotein cholesterol, +19%; and triglycerides, -30%. At angiographic follow-up, the changes in percent diameter reduction and percent plaque area correlated positively with the mean serum and LDL cholesterol levels of the intervention group. Significant differences were found in the change in percent plaque area between both groups. The intervention subgroup with angiographic regressions (11 patients) had significantly lower serum and LDL cholesterol levels than the intervention subgroup with angiographic progressions (10 patients). These results indicate the beneficial effect of fenofibrate on minor coronary narrowings. Because of its high reproducibility in measuring minor narrowings, quantitative coronary angiography proved to be a suitable method for angiographic follow-up.

Gamma-glutamyltransferase and prognosis in patients with stable coronary heart disease followed over 8 years.

OBJECTIVES: Serum gamma-glutamyltransferase (gamma-GT) predicts incident cardiovascular disease and mortality. The present study examined whether gamma-GT also is associated with prognosis in patients with stable coronary heart disease. METHODS AND RESULTS: This study included 1152 participants (aged 30-70 years at baseline) of an in-patient rehabilitation programme after acute coronary syndrome, recruited in two rehabilitation clinics in Germany in the years 1999-2000 (KAROLA study). Until year 8 follow-up, 147 participants had experienced a non-fatal or fatal secondary cardiovascular disease event. Confounder-adjusted Cox proportional hazards models revealed an increase in risk for secondary events over ascending gamma-GT quartiles, with hazard ratios (95% confidence interval) of 1.21 (0.72-2.03), 1.32 (0.80-2.16) and 1.75 (1.08-2.83) for the 2nd, 3rd and 4th in reference to the lowest quartile (Ptrend=0.024). The association with all-cause mortality examined as a secondary outcome was slightly stronger (hazard ratio of 4th quartile: 1.97 [1.15-3.36]; Ptrend=0.017). CONCLUSIONS: In patients with stable coronary heart disease, serum gamma-GT was associated with prognosis independent of a variety of established risk markers. The association appeared similar to that reported for primary cardiovascular disease, which should motivate additional studies of its clinical utility in cardiovascular patient care.

Effect of APOE genotype on lipid levels in patients with coronary heart disease during a 3-week inpatient rehabilitation program.

It has been suggested that the apolipoprotein E (APOE) genotype modifies the effect of dietary and pharmacological interventions for lowering lipid levels. We wanted to determine whether APOE genotyping information would be useful in making lipid-lowering treatment decisions in clinical practice. We included 981 patients with coronary heart disease (CHD) enrolled in an inpatient 3-week standardized rehabilitation program. Of these, 555 (57%) patients received continued statin therapy and 232 (24%) patients received newly initiated statin therapy. Dietary intervention was part of the program only for 194 (20%) patients. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels decreased in all the groups of patients during rehabilitation. The decreases were less pronounced among the APOE E2 carriers. However, the observed variation among the groups with respect to reduction of lipid levels was accounted for mainly by the initial lipid levels (30-47%) and only marginally on the APOE genotype (1%) . We therefore found no evidence that APOE genotyping will be useful in guiding dietary or pharmacological lipid-lowering treatment decisions.

Validation of the EuroQol questionnaire in cardiac rehabilitation.

OBJECTIVE: To analyse the psychometric properties of the EuroQol questionnaire (EQ-5D) applied to patients with acute coronary syndromes (ACS). SETTING: Rehabilitation hospital. PATIENTS AND DESIGN: 106 consecutive patients with ACS (51% myocardial infarction, 42% coronary artery bypass grafting, 7% angina) completed the EQ-5D, the 36 item short form health survey (SF-36), and the MacNew questionnaire at admission, at discharge, and three months after inpatient cardiac rehabilitation. Acceptance, validity, reliability, and responsiveness of the EQ-5D were tested. RESULTS: The EQ-5D was highly accepted. The EQ-5D index showed substantial ceiling effects after rehabilitation. As expected the EQ-5D visual analogue scale (VAS) score (70.3 v 57.1) and EQ-5D index (77.8 v 64.5) were significantly better for patients with myocardial infarction than for patients who underwent surgery (both p < or = 0.001). Significant correlations were found between the EQ-5D VAS score, EQ-5D index, and domains of the SF-36 (r = 0.21 to r = 0.74). The correlation with the MacNew subscores and with the global score ranged between 0.55 and 0.78. With repeated measurement the EQ-5D showed reasonable reliability in stable patients with intraclass correlation ranging between 0.91 and 0.54. EQ-5D was responsive in patients who indicated improvement in health states between admission and discharge (effect size 0.74-0.82). CONCLUSION: The psychometric properties of the EQ-5D were satisfying. It is a reasonably valid, reliable, and responsive instrument for patients with ACS. It may be useful in clinical research and epidemiological studies to generate preference based valuations of health related quality life.

Long term adherence to dietary recommendations after inpatient rehabilitation: prospective follow up study of patients with coronary heart disease.

OBJECTIVE: To evaluate the adherence to nutritional recommendations in inpatient rehabilitation and the long term maintenance of dietary changes among patients with coronary heart disease. DESIGN: Prospective cohort study. SETTING: Two rehabilitation clinics in Germany. PARTICIPANTS: A cohort of 1206 patients undergoing inpatient rehabilitation after an acute manifestation of coronary heart disease. MAIN OUTCOME MEASURES: Self reported dietary intake before, during, and one and three years after rehabilitation measured with a semiquantitative food frequency questionnaire and summarised to a nutritional index, which was used to categorise patients as having a poor, fair, or good diet. RESULTS: During rehabilitation the proportion of patients whose dietary intake was categorised as good increased strongly from 30% to 91%. One and three years after rehabilitation a still increased proportion of 49% and 42%, respectively, in the good category was observed. The strong increase in intake of low fat and wholemeal products that was achieved during rehabilitation was followed after rehabilitation discharge by a backslide to the intake observed before rehabilitation admission. The avoidance of unfavourable food items, such as French fries or eggs, was at least partly maintained during the follow up period. CONCLUSION: During inpatient rehabilitation most patients do have to make major changes in their dietary intake to comply with recommendations. Although some proportion of patients continue to adhere to dietary recommendations in the long run, further research into strategies to improve maintenance of dietary changes is needed to enhance further the long term benefits from cardiac rehabilitation.

[Changes of risk factors in patients with coronary heart disease after in-patient rehabilitation]. / Veränderungen von Risikofaktoren nach stationärer Rehabilitation bei Patienten mit koronarer Herzkrankheit.

BACKGROUND AND OBJECTIVE: Rehabilitation therapy of patients with coronary heart disease (CHD) aims at reducing cardiovascular risk factors and at maintaining reduced risk factor levels. The aim of this analysis was to assess to what degree current in-patient rehabilitation and subsequent out-patient care by general practitioners (GPs) achieve these goals. PATIENTS AND METHODS: As part of the KAROLA-Study (Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung = Long-term success of cardiological rehabilitation therapy) 1206 patients between 30 and 70 years of age (mean age: male: 58.3 years, female: 60.8 years) who underwent in-patient rehabilitation due to CHD between January 1999 and May 2000 were recruited. Risk factor levels were assessed at the beginning and at the end of in-patient rehabilitation, and patients were re-examined one year after discharge using a standardised exam conducted by the GPs. RESULTS: Patients with increased risk factor levels at the time of admission showed significant improvements in the following risk factors during rehabilitation: Body mass index (-0.7 kg/m(2)), diastolic blood pressure (-10 mmHg), systolic blood pressure (-10 mmHg), total cholesterol (-73 mg/dl), LDL-cholesterol (-63 mg/dl), HDL-cholesterol (+ 3 mg/dl), triglycerides (-70 mg/dl). One year after discharge, however, all but one of the parameters (LDL-cholesterol) had re-increased significantly. The prescription of lipid lowering drugs rose from 56 % to 76 % during rehabilitation therapy and remained constant during the first year after discharge. CONCLUSIONS: During in-patient rehabilitation therapy important risk factors of CHD improved on average, but these improvements are only partly sustained in the long term. To ensure long-term success of rehabilitation measures more effective maintenance of risk factor modification in subsequent out-patient care is needed.

[Incidence and significance of angina pectoris in aortic valve disease]. / Häufigkeit und diagnostische Bedeutung von Angina pectoris bei Aortenklappenfehlern.

To determine the incidence and significance of angina pectoris in aortic valve disease, clinical, haemodynamic, and angiographic data concerning 111 consecutive patients aged 27-68 years (mean 52) were retrospectively analysed. 14.4% (group A) had significant, 85.6% (group B) had no coronary heart disease. There was a significant difference between the groups regarding the incidence of typical angina pectoris (62.5% vs 31.6%, p less than 0.01) and freedom from chest pain (12.5% vs 32.6%, p less than 0.05). No difference, however, could be found concerning the incidence of atypical chest pain (25% vs 35.8%). Of 12 patients aged over 50 years with coronary artery disease, no patient was free of angina pectoris. 83% had typical, 17% had atypical angina pectoris. Of 4 patients below 45 years with coronary artery disease, however, none had typical angina pectoris, 2 patients had atypical angina, and 2 patients had none. These results demonstrate that typical angina pectoris in patients with aortic valve disease is not a specific indicator of concomitant significant coronary artery disease. On the other hand, absence of chest pain does not predict absence of coronary artery disease, especially in younger patients. We therefore suggest that coronary angiography be carried out in all adult patients in whom aortic valve surgery is being considered.

[Effects of inpatient rehabilitation on cardiovascular risk factors in patients with coronary heart disease. PIN-Study Group]. / Auswirkung stationärer Rehabilitation auf kardiovaskuläre Risikofaktoren bei Patienten mit koronarer Herzerkrankung. PIN-Studiengruppe.

BACKGROUND AND OBJECTIVE: The prognostically favourable effect of secondary prevention in patients with proven coronary heart disease (CHD: documented myocardial infarction, angiographically proven coronary artery stenosis > 60% and/[or] status after coronary artery surgery) has been demonstrated. But it has not been adequately shown to what extent the guidelines laid down by specialist societies is being followed in routine clinical practice. Nor have there been any large-size standardized investigations of whether in-hospital rehabilitation decreases cardiovascular risk factors. It was the aim of this study to investigate the acute effects on cardiovascular risk factors of in-hospital post-infarction rehabilitation. PATIENTS AND METHODS: From January to May 1997, at 18 rehabilitation clinics, 2441 consecutive patients (22% women, aged 65 +/- 10 years, 78% men, aged 60 +/- 10 years) with proven CHD were included in this post-infarction after-care (PIN) study. During their hospital stay (26 +/- 5 days) they undertook physical training appropriate for cardiological follow-up treatment, as well as various other modes of treatment to affect risk factors. Diagnosis, treatment and standardized data were prospectively recorded on admission and discharge. RESULTS: At discharge the proportions of patients with conventionally defined risk factors were significantly lower than on admission (P < 0.001). The proportion was 8% in patients with arterial blood pressure > 140/90 mm Hg (vs. 24% on admission), 5% in smokers (vs. 39% on admission), 30% vs. 60% in patients with cholesterol levels > 200 mg/dl, 67% vs. 87% in those with low density lipids > 100 mg/dl, 15% vs. 22%, in those with serum triglyceride levels > 200 mg/dl, 11% vs. 14% in those with glucose levels > 140 mg/dl, and 15% vs. 18% in patient with a body/mass index > 30 kg/m2. There was an increase in the proportion of patients who during their hospital stay were prescribed additional drugs: from 85% to 86% for acetylsalicylic acid (P < 0.05), 61% to 77% for beta-adrenergic receptor blockers, 33% to 67% for cholesterol synthesis enzyme (CSE) inhibitors, and 51% to 57% for angiotensin converting enzyme (ACE) inhibitors. CONCLUSION: Modifiable cardiovascular risk factors can be reduced by various methods of rehabilitation and more intensive drug treatment during hospitalization. By taking account of evidence-based medicine favourable conditions can be created for longterm ambulant after-care.

Determination of free apolipoprotein(a) in serum by immunoassay and its significance for risk assessment in patients with coronary artery disease.

This paper describes a new enzyme-linked ligand sorbent assay (ELLSA) to quantify free apolipoprotein(a) (apo(a)). The new test immobilizes free apo(a) utilizing a specific peptide that carries the amino acid sequence of a non-covalent apo(a) binding site on apoB3375-3405 (ligand-peptide). The ligand-peptide coupled to Sepharose was used in affinity chromatography to separate free apo(a) from whole serum. Isolated free apo(a) consisted of full length apo(a) and smaller apo(a). Additionally, free apo(a) levels determined by ELLSA as well as by electroimmunodiffusion correlated moderately well. Significantly increased serum concentrations of free apo(a) were found in coronary artery disease. The mean value of free apo(a) was three times higher in patients than in controls while the lipoprotein(a) (Lpla)) concentration was doubled. Utilizing receiver operating characteristic diagrams, it was shown that the free apo(a)-ELLSA had a better diagnostic test performance in atherosclerotic risk assessment than the Lp(a)-test: specificity free apo(a)-ELLSA 0.77, Lp(a)-test 0.81 [with (a:a)-enzyme immunoassay (EIA)] to 0.83 [with (a:B)-EIA]; sensitivity free apo(a)-ELLSA 0.57, Lp(a)-test 0.36 to 0.40. In conclusion, the new free apo(a)-ELLSA allows for the specific quantification of free apo(a). This provides an interesting indicator for atherosclerotic risk assessment.

[Quantitative coronary angiography: progression and regression of coronary stenoses--an intervention study with fenofibrate]. / Quantitative Koronarangiographie: Progression und Regression von Koronarstenosen--Eine Interventionsstudie mit Fenofibrat.

In order to examine the effect of fenofibrate on coronary narrowings, within the framework of a prospective intervention study, we treated a total of 44 hypercholesterolemic patients (who were in our clinic to undergo PTCA) with diet and fenofibrate (200-400 mg/day) over a period of 3 years. After a mean interval of 21 months, control angiographies were performed in nearly identical projections for 21 patients on clinical grounds. The minor and medium-grade narrowings of the reangiographed patients at the beginning and at the end of the intervention interval were measured by means of digital image processing and automatic contour detection. The measuring parameters were percent diameter reduction (% DR) and percent plaque area (%PA). With regard to their angiographic progression, the 21 reangiographed patients of the intervention group were compared to a comparison group consisting likewise of 21 patients of similar age and sex distribution and persistently high lipid and lipoprotein levels. During the intervention period, the reangiographed patients of the intervention group showed the following changes of the lipid and lipoprotein levels in contrast to the outset values: cholesterol -19 +/- 8%, LDL -20 +/- 14%, HDL +19 +/- 44%, triglycerides -30 +/- 31%.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac risk factors, medication, and recurrent clinical events after acute coronary disease; a prospective cohort study.

AIMS: Systematic data are sparse on clinical outcome after acute coronary disease followed by cardiac rehabilitation therapy. Therefore, our objective was to determine the long-term development of cardiac risk factors, recurrent clinical events, and cardiac medication in patients undergoing routine in hospital cardiac rehabilitation therapy. METHODS AND RESULTS: In the prospective PIN Study (Post Infarct Care), 2441 consecutive patients (78% men, 60+/-10 years, 22% women, 65+/-10 years) were enrolled in 18 inpatient rehabilitation centres in Germany following myocardial infarction (56%), coronary artery bypass graft (38%) or percutaneous transluminal coronary angioplasty (6%). Cardiac risk factors, pre-specified clinical end-points, and the prescription of cardiac medication were prospectively documented on admission to and at discharge from rehabilitation therapy, and 3, 6 and 12 months later by obtaining information with standardized questionnaires from the patients and their physicians. The cardiac risk factors improved initially during cardiac rehabilitation therapy, but deteriorated within the following 12 months: 39% patients smoked at the beginning vs 5% at the end of in hospital rehabilitation vs 10% at 12 months follow-up (P<0.001). The respective numbers for patients with blood pressure >140 and/or 90 mmHg were 24 vs 8 vs 25% (P<0.01) and with plasma cholesterol >200 mg. dl(-1)57 vs 29 vs 51% (P<0.01). A total of 886 patients experienced one or more recurrent clinical events during the first year, 69% of those within the initial 6 months. At 12 months follow-up, 77% of patients received aspirin, 70% beta-blockers, 62% lipid lowering medication, and 53% angiotensin converting enzyme inhibitors. CONCLUSION: The present results indicate that the benefit of cardiac rehabilitation therapy following acute coronary events is only partially maintained during the following year. Continuous strategies of medical care need to be developed to improve the long-term outcome in coronary patients.

[Isovolemic hemodilution in patients with coronary heart disease]. / Isovolämische Hämodilution bei Patienten mit koronarer Herzkrankheit.

In the age of cellsavers patients suffering from coronary heart disease are diluted to a hematocrit of 20% or even less during a surgical intervention in the coronaries and they leave the operating room with a hematocrit of 30%. On the other hand, a hemodilution to a level of 30% in patients with coronary heart disease represents a contraindication due to the limited coronary reserve. On the occasion of the collection of autologue blood, before vascular surgery or for therapeutical hemodilution, the hematocrit was reduced from 45 to 35% by means of an isovolemic hemodilution with 500 ml of Haes 200/0.5 10% in 50 patients. In the load-ECG the pressure X frequency-product and the dyspnoe decreased significantly. The microcirculation in the nailfold and the systemical blood fluidity increased significantly. As in 22% of the patients a deterioration was stated, we propose to dilute all the patients who have to undergo a coronary vessel operation without exclusion criteria once isovolemically and to stress them before and afterwards. The patients having a clinical defict should be diluted intraoperatively only to 30% and postoperatively not under 35%.