[The role of lipid metabolism in the prevention of coronary heart disease]. / Die Rolle des Lipidstoffwechsels in der Prävention der koronaren Herzerkrankung.

Prevention of cardiovascular disease should be considered as a continuum from low to high risk: those at the highest risk are patients with clinically manifest cardiovascular disease, followed by subjects without known cardiovascular disease at different levels of risk from high to low. Today there is clear evidence that an independent relationship exists between plasma LDL cholesterol levels and the risk for coronary heart disease. The relationship between other plasma lipoproteins and atherosclerosis is more complex. The threshold for individuals requiring LDL cholesterol reduction is determined by epidemiological data, randomized controlled trials, and economic considerations. Patients with familial dyslipidemia suffer early coronary morbidity and mortality. For these patients, consequent lowering of LDL cholesterol should be the primary objective. For patients with established coronary heart disease or other atherosclerotic disease and for those with diabetes, there is significant evidence that reducing LDL cholesterol, irrespective of the initial values, reduces the risk of further coronary events, stroke, and total mortality. For asymptomatic individuals, the treatment of plasma lipids should be based on their absolute coronary risk, including other cardiovascular risk factors. The goals for plasma LDL cholesterol have been set in national and international recommendations. The goals for LDL cholesterol in patients with low, moderate and high coronary risk are <160, <130 and 100 mg/dl, respectively. In some very high risk patients LDL level markedly below 100 mg/dl should be aimed at. HDL cholesterol and triglyceride measurements should be used to identify individuals at high multifactorial risk of cardiovascular disease and used as additional considerations in the selection of lifestyle and drug interventions.

[Value of coronary artery calcium measurements in primary prevention]. / Bedeutung der Koronarkalkbestimmung in der Primärprävention.

Frequently, myocardial infarction or sudden coronary death are the index manifestations of coronary artery disease. In view of the high out-of-hospital mortality of acute myocardial infarction, medical care is unable to provide a benefit for many patients. Against this background, it is an important aim of measuring coronary calcium to identify asymptomatic subjects with an increased coronary risk who are likely to derive a benefit from risk-modifying therapy. Coronary calcium is a largely specific expression of coronary atherosclerosis and is correlated with overall coronary plaque volume. Due to the complex biology of the vessel wall and its ability to undergo compensatory remodelling, coronary calcium does not necessarily indicate significant stenosis. Coronary calcium is found in 70-80% of plaque ruptures but only in a minority of plaque erosions. It neither indicates a "vulnerable" nor a "stable" plaque. Six independent studies including healthy self-referred and physician-referred volunteers consistently describe the predictive value of coronary calcium with regard to coronary and cardiovascular clinical events. After adjusting for coronary risk factors, increased amounts of coronary calcium are associated with a 5- to 10-times elevated relative risk. Only recently have the first results from strictly unselected, population-based cohorts been reported which confirm the predictive ability of coronary calcium measurements. Concordant with actual guidelines issued by US-American and European expert panels, coronary calcium measurements can be used especially in patients with an indeterminate risk on the basis of clinical assessment and risk factor analysis. Substantially elevated coronary calcium scores provide a rationale for intensified risk-modifying therapy. This is also true for elderly patients in whom the established risk factors lose some of their predictive power. The use of coronary calcium measurements in self-referred patients or as a primary means for risk stratification is not encouraged.

[Cholesterol: blood levels or total risk as a guide to preventive treatment?]. / Cholesterin: Serum-Werte oder Gesamtrisiko als Entscheidungshilfe für medikamentöse Prophylaxe?

The results of a cholesterol lowering therapy with statins do belong to the best documented steps in medical treatment. The newer studies like HPS and LIPID have shown a therapeutic benefit across all serum-cholesterol levels, nearly obviating the need for a prior determination of the cholesterol values. Why not using the serum-cholesterol level as the only guide to therapy? Since there is no threshold indicating the need for treatment, there is the danger of an unlimited inflation of the indications for therapy, possibly leading to a collapse of the health care system. At the upper extreme, therapy would have to start at a very young age, and no one can predict the side effects of a statin therapy over many decades. Improving the target for therapy can only be achieved via determination of the total risk of cardiovascular disease. Several algorithms like PROCAM ( www.chd-taskforce.de), the risk chart of the European Society of Cardiology or the Framingham risk-scores will come to similar results. In this manner, one can differentiate further, and persons with a low risk of cardiovascular disease like women and young adults do not have to be treated unnecessarily. However, it must not be overlooked that the sensitivity of these risk-scores is rather low. The majority of myocardial infarctions occur in the average risk population, because of sheer numbers. Independent indicators of cardiovascular risk, such as the CRP, the intima-media thickness of the carotid artery and in particular the determination of the coronary calcium score via EBT or ultrafast scan can lead to more clarity. To improve the estimation of the individual risk, we will need a combination of risk-factors and -indicators.

Do students with and without lexical retrieval weaknesses respond differently to instruction?

Deficits in phonological processing are theorized to be responsible for at least some reading disabilities. A considerable amount of research demonstrates that many students can be taught one of these phonological processes-phonemic awareness. However, not all students have responded favorably to this instruction. Research has suggested that these nonresponders may be unable to retrieve phonological codes quickly from long-term memory. The purpose of this study was to examine whether such a deficiency, which we refer to as lexical retrieval weakness, blunts the effectiveness of combined phonemic awareness and decoding training. To this end, we compared the effectiveness of phonemic awareness and decoding training for students with and without severe lexical retrieval weaknesses. All students in both groups demonstrated poor phonemic awareness. The results suggested that students with relatively strong lexical retrieval skill responded more favorably to beginning reading instruction than did students with weak lexical retrieval skill. In other words, lexical retrieval weakness may influence reading development independently of the effects of phonemic awareness. Implications for instruction are discussed.

[Lipid intervention and coronary heart disease in men less than 56 years of age. The Coronary Intervention Study: CIS]. / Lipid-Intervention und koronare Herzkrankheit bei Männern unter 56 Jahren. Die Coronare Interventions-Studie: CIS.

UNLABELLED: The CIS was undertaken with the aim to evaluate the effects of lipid modifications on angiographic progression and regression of CAD in patients with CAD and hypercholesterolemia. The design included a multicenter randomized, double-blind, parallel, placebo-controlled comparison, with target and safety limits for adjusting the trial medication depending on the LDL cholesterol level (LDL-C) achieved, i.e., up to 40 mg of simvastatin (S) or placebo (P) daily, add-on medication (up to 3 x 4 g Colestyramin), and diet counselling. Male patients, average age 49 (< or = 56) years, were included with angiographic CAD and a screening total cholesterol of 207-350 mg/dl, who were not due to undergo coronary bypass surgery or PTCA, who did not suffer from serious other disease (e.g., diabetes mellitus), and who had not undergone coronary bypass surgery previously. RESULTS: All baseline variables were comparable in the treatment groups, with 129 patients taking S and 125 taking P. Of these 254 patients 217 had their final study visit and 207 underwent a second angiography after an average treatment time of 2.3 years under an average daily dose of 37 mg S. 205 pairs of films were available for analysis. Vital information was obtained of all patients until closure of the data bank, half a year after the last study angiography. Five deaths occurred within the study period, 12 through March 15, 1995 (S: 1/6, P: 4/6). 37 patients (S: 18, P: 19) discontinued trial drug and protocol. Concomitant CAD medication was comparable in both groups, except lipid-lowering add-on medication which was significantly higher in the P group (38% versus 13%). Significant changes in lipid levels, on treatment, were observed in the S group amounting to a mean difference in LDL-C of -35%, in Apo-Protein B (ApoB) of -30%, in VLDL-C of -37%, and in triglycerides (TG) of -27%, and in HDL-C of +6%, in comparison to the control group; these differences were even greater in 137 fully compliant patients: -41, -36, -39, -31, and +7%, respectively. Progression in the S group was significantly less, as defined by the two primary target criteria: 1) the minimum obstruction diameter (MOD), determined by quantitative coronary angiography (QCA), decreased about five times less in comparison to the control group (S: by -0.017; P: -0.0954 mm), and 2) the standardized visual global change score (GCS) deteriorated almost three times less in the S group (by +0.20) than in the P group (+0.58). Of the secondary target criteria, the mean lumen diameter (QCA) also developed a significant difference (S: -0.20; P: +0.23 mm; p = 0.0006) with a trend toward regression in the S group. The QCA-%-stenosis deteriorated three- to four-times less in the S group as compared to the control group (S: by 0.69%; P: by 2.73%; p = 0.0022), and the number of patients with angiographic progression was nearly halved (S: 30%; P: 56%; p < 0.0000). These differences were determined by intention to treat analysis (ITT), and they were obtained in spite of lipid lowering add-on medication in 38% of the P patients; they turned out to be more pronounced in 137 fully compliant patients, in an analysis "as treated". The mean decrease in LDL-C serum level caused by S was significantly correlated to the decrease in progression, and multivariate regression analysis of both treatment groups identified LDL-C (or ApoB) and TG as independent predictors of progression. Progression appeared to be most pronounced in low and medium sized lesions, and the beneficial effect of lipid intervention dominated in lesions with 12-56% QCA stenosis severity. A small fraction of patients who suffered from exercise-induced angina, with ST-segment-depression at the beginning of the study, experienced a significant improvement under S as compared to P treatment. Although the study was not designed to show differences in clinical events, the combined number of all major cardiovascular events tended to be less frequent in the S than in the C gr

[Partial inpatient cardiologic rehabilitation in an urban satellite center of a rehabilitation clinic: the Munich model]. / Teilstationäre kardiologische Rehabilitation im innerstädtischen Satellitenzentrum einer Rehabilitationsklinik: das Münchner Modell.

In April 1996 the Munich Rehabilitation Center was founded by the Social Security Agency as a "satellite center" of the "Klinik Höhenried for Cardiovascular Diseases", which is located 50 km south of Munich near the lake Starnberg and performs in-patient rehabilitation since 1967. The Munich Rehabilitation Center is exclusively designated for outpatient rehabilitation for patients in the Munich area. Monday to Friday from 9 a.m. to 4 p.m. up to 50 patients are treated according to the same standards as in residential centers. About 40% of patients treated are in WHO phase II, e.g. after coronary artery bypass grafting, acute myocardial infarction or a percutaneous transluminal coronary angioplasty. 60% have a chronic stable cardiac disease or risk factors for arteriosclerosis. After almost 3 years of experience we see some specific advantages in outpatient compared to the in-patient setting. Ambulatory treatment seems to be more than the residential center "minus a bed". For example: a "holiday feeling" can be avoided by the location in a city area, so the patients are focusing on medical rehabilitation. Outpatient rehabilitation makes an easy transition from a cardiological center to every day life possible. Some patients would refuse any further treatment far away from home because of personal or occupational reasons. Anxiety can be reduced and self-confidence increased by the outpatient setting. There is a daily feedback about the ability to transfer therapeutic advices home. We learned to appreciate outpatient rehabilitation as a cost-effective supplement to the proven in-patient setting for patients in municipal areas.

Preparing students with special needs for reintegration: curriculum-based measurement's impact on transenvironmental programming.

The original intent of special education pull-out services was to remove students from general education temporarily for intensive, individualized instruction in deficit areas. In many school districts, however, it seems that once students participate in pull-out services, there is little effort to return them to general education. One explanation for this is that not much is known about how best to prepare students for movement up the cascade of services, including reintegration into the mainstream. A promising reintegration approach is transenvironmental programming (TP). Research suggests that supplementing TP with continuous progress monitoring, specifically via curriculum-based measurement (CBM), better prepares students for reintegration than either TP or CBM alone. Findings from the present study provide a possible explanation: Results suggest that special educators using TP who receive CBM information about their students' academic progress are more likely to plan and implement academic interventions in preparation for students' transition than are those special educators who do not receive this information. This supports the hypothesis that the relatively greater success of TP + CBM is due to increased attention to academic preparation. Implications for practice and future research are discussed.

Plasma total homocysteine levels in patients with early-onset coronary heart disease and a low cardiovascular risk profile.

Mild hyperhomocysteinemia has been associated with an increased risk to develop premature coronary heart disease. Recently, the homocysteine concentration has been positively correlated with several main cardiovascular risk factors. We addressed the issue as to whether patients with coronary heart disease and a low cardiovascular risk profile also have a higher prevalence of hyperhomocysteinemia than matched controls. Ninety-five patients (aged 50.5 +/- 6.6 years) and 34 controls (50.0 +/- 6.7 years) less than 60 years of age were selected from a sample of patients after coronary angiography. Subjects with hypertension, diabetes, and moderate or severe hyperlipidemia were excluded. We determined plasma aminothiols (total homocysteine, cysteine, and glutathione), lipoprotein fractions, fibrinogen, and uric acid, the body mass index (weight in kilograms divided by height in meters squared), and the waist to hip ratio. Furthermore, 37 healthy subjects aged 30.8 +/- 7.5 years underwent aminothiol determinations. Patients and controls were similar with regard to age and primary cardiovascular risk factors. Total homocysteine concentrations in the patient group (9.2 +/- 2.4 micromol/L) were significantly higher than in the healthy subjects (8.0 +/- 2.0 micromol/L). However, they did not differ from the levels in the age-matched controls (9.3 +/- 3.0 micromol/L). Neither total cysteine nor glutathione concentrations were significantly different between patients and controls. Male patients (n = 85) had higher mean very-low-density lipoprotein (VLDL) triglycerides (1.36 +/- 0.90 mmol/L) and lower high-density lipoprotein 3 (HDL3) cholesterol (0.75 +/- 0.21 mmol/L) than male controls (n = 28; 1.01 +/- 0.62 and 0.88 +/- 0.26 mmol/L, respectively). Female patients did not have any significant differences in lipoprotein concentrations versus the controls. Among further cardiovascular risk factors, we found a higher prevalence of central obesity in male patients. In conclusion, there was not a higher incidence of hyperhomocysteinemia among patients with premature coronary heart disease and a low cardiovascular risk profile. The higher prevalence of hyperhomocysteinemia found in other studies may be related to the primary risk factors seen in these populations, and may therefore be an indicator of the global cardiovascular risk.

The effect of simvastatin on progression of coronary artery disease. The Multicenter coronary Intervention Study (CIS).

BACKGROUND: In several angiographic trials, HMG-CoA reductase inhibitors have shown a beneficial effect on the progression of coronary artery disease. Using 20 mg simvastatin, day-1, a treatment period of up to 4 years was necessary to show a significant reduction in coronary artery disease progression. The question remains however whether higher dosages of simvastatin would be more advantageous in respect to the magnitude of the effect and the required time interval to demonstrate treatment efficacy. METHODS AND RESULTS: In the Coronary Intervention Study (CIS), a multicentre randomized double-blind placebo-controlled study, the effects of lipid-lowering therapy with simvastatin on progression of coronary artery disease in 254 men with documented coronary artery disease and hypercholesterolaemia were investigated. Following a period of lipid-lowering diet, treatment with 40 mg simvastatin or placebo was maintained for an average of 2.3 years. Two primary angiographic endpoints were chosen: the global change score (visual evaluation according to the method of Blankenhorn) and the per patient mean change of minimum lumen diameter (evaluated by the CAAS I system). The mean simvastatin dose was 34.5 mg day-1. In the placebo group, the serum lipids remained unchanged; in comparison to the placebo group the simvastatin group showed a 35% LDL-cholesterol decrease. Coronary angiography was repeated in 205 patients (81%) and 203 film pairs (80%,) were evaluable by quantitative coronary angiography. In the simvastatin and placebo groups, the mean global change scores were +0.20 and +0.58 respectively, demonstrating a significantly slower progression of coronary artery disease in the treatment group (P = 0.02). The change in minimum lumen diameter assessed by computer-assisted quantitative evaluation with the CAAS I system was -0.02 mm in the simvastatin group and -0.10 mm in the placebo group (P = 0.002). In the simvastatin group, there was a significant correlation between the LDL cholesterol levels achieved therapeutically and the per patient mean loss of minimum lumen diameter (r = 0.29; P = 0.003). During the study period, there was no significant difference in the incidence of serious cardiac events (15 of 129 patients in the simvastatin group and 19 of 125 patients in the placebo group, ns). CONCLUSION: Treatment with 40 mg simvastatin day-1 reduces serum cholesterol and slows the progression of coronary artery disease significantly within a short period of treatment time. In the treatment group, retardation of progression is inversely correlated to the LDL-cholesterol levels achieved.

Trimetazidine: a new concept in the treatment of angina. Comparison with propranolol in patients with stable angina. Trimetazidine European Multicenter Study Group.

1. Trimetazidine has a direct anti-ischaemic effect on the myocardium without altering the rate x pressure product or coronary blood flow. 2. The effects of trimetazidine (20 mg three times daily) were compared with those of propranolol (40 mg three times daily) in a double-blind parallel group multicentre study in 149 men with stable angina. 3. Reproducibility of exercise performance was verified during a 3 week run-in placebo washout period. All patients had > 1 mm ST-depression on exercise test. 4. After 3 months, similar anti-anginal efficacy was observed between the trimetazidine (n = 71) and propranolol (n = 78) groups. No significant differences were observed between trimetazidine and propranolol as regards anginal attack rate per week (mean difference P-TMZ: 2; 95% CI: -4.4, 0.5) and exercise duration (mean difference P-TMZ: 0 s; 95% CI: -33, 34) or time to 1 mm ST segment depression (mean difference P-TMZ: 13 s; 95% CI: -24, 51). Heart rate and rate x pressure product at rest and at peak exercise remained unchanged in the trimetazidine group but significantly decreased with propranolol (P < 0.001 in all cases). With both drugs there was a trend to decreased ischaemic episodes in the 46% patients who experienced ambulatory ischaemia on Holter monitoring. Six patients stopped trimetazidine and 12 propranolol. Of these, five in each group were withdrawn because of deterioration in cardiovascular status. 5. The results suggest that trimetazidine and propranolol at the doses studied have similar efficacy in patients with stable angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS)

[An increased risk of kinesitherapy in silent myocardial ischemia?]. / Erhöhtes Risiko der Bewegungstherapie bei stummer Myokardischämie?

The effect of three-week standardized physical training on exercise-induced ischaemia was investigated in patients with silent ischaemia after myocardial infarction. 24-hour monitoring and exercise ECGs before and after the period of physical training, were undertaken in 32 men (mean age 53.6 +/- 8.1 years) with angiographically proven coronary heart disease. The protocol of the standardized exercise included bicycle ergometry, gymnastics, breathing and movement exercises, as well as nonstandardized walking or hiking. Following the training period the number of ischaemic episodes fell from 90 to 72 for the group as a whole and that of the asymptomatic episodes from 79 to 64. The number and severity of ventricular arrhythmias were similar during silent and symptomatic ischaemia. There was a significant increase in duration of exercise until reaching the ischaemia threshold (mean exercise duration 4.7 +/- 2.1 vs 5.9 +/- 2.5 min; P = 0.0007). There was no increased risk concerning ventricular arrhythmias.