[Lipid-lowering therapy in the elderly : Who profits from which target values?] / Lipidsenkende Therapie im Alter : Wer profitiert von welchem Zielwert?

Lowering low-density lipoprotein (LDL) cholesterol levels has been proven to reduce the incidence of cardiovascular and cerebrovascular events and mortality. So far recommendations have not provided information as to a meaningful duration of cholesterol-lowering therapy and were largely guided by economic constraints and limited therapeutic options. In light of the decline in the price of statins, the essential therapeutic agent and the increased efficacy of therapeutic options, treatment can nowadays be geared to target values that can be expected to have an optimal effect even in old age. The most favorable level of LDL-cholesterol for primary prevention is around and below 100 mg/dl, provided continuous adherence to these low levels from adolescence onwards. With later onset of cholesterol reduction the existence of initial atheromatous deposits must be expected. Therefore, with age and the manifestation of other risk factors the optimal treatment targets increasingly converge to those for which experience has been gained from secondary prevention. Both measurements of the effect of cholesterol lowering on the volume of atheromatous plaques and of the incidence of vascular events indicate a target for LDL-cholesterol well below 70 mg/dl and in the range 50-60 mg/dl. At the onset of cholesterol lowering in advanced age, a smaller effect has to be expected but due to the increasing incidence rate of vascular events a higher number of events may be avoided; thus, the efficiency does not necessarily decrease; however, long-term studies indicate that earlier cholesterol lowering provides an advantage for more than a decade, in terms of preventing vascular disease, which tends to increase. Therefore, optimal cardiovascular prevention involves moderate measures to maintain the LDL-cholesterol below 100 mg/dl lifelong from childhood on.

Cholesterol-lowering therapy: Old evidence, new guidelines--Which one to follow? A critical appraisal.

Current guidelines of the European Society of Cardiology and the European Atherosclerosis Society (ESC/EAS), of the American College of Cardiology and the American Heart Association (ACC/AHA), and of the International Atherosclerosis Society (IAS) are all based on the same body of evidence, but come to strikingly different conclusions with regard to lipid lowering therapy. While the ESC/EAS guidelines assign appropriate treatments to distinct lipid disorders, the ACC/AHA guidelines focus exclusively on evidence from randomized controlled trials for statins, but lack advice for those lipid disorders without evidence from randomized trials. Thus, evidence based medicine in its strict sense may leave a clinically significant gap. In striking contrast, the position paper of the IAS suggests the most advanced evidence-based innovative concept of a goal of one and the same healthy cholesterol level for anyone.

[New AHA and ACC guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk : Statement of the D•A•CH Society for Prevention of Cardiovascular Diseases, the Austrian Atherosclerosis Society and the Working Group on Lipids and Atherosclerosis (AGLA) of the Swiss Society for Cardiology]. / Neue AHA- und ACC-Leitlinie zur Risikoreduktion von Herz-Kreislauf-Erkrankungen durch Cholesterinsenkung : Stellungnahme der D•A•CH-Gesellschaft Prävention von Herz-Kreislauf-Erkrankungen e. V., der Österreichischen Atherosklerose Gesellschaft und der Arbeitsgruppe Lipide und Atherosklerose (AGLA) der Schweizer Gesellschaft für Kardiologie.

Guidelines for the reduction of cholesterol to prevent atherosclerotic vascular events were recently released by the American Heart Association and the American College of Cardiology. The authors claim to refer entirely to evidence from randomized controlled trials, thereby confining their guidelines to statins as the primary therapeutic option. The guidelines derived from these trials do not specify treatment goals, but refer to the percentage of cholesterol reduction by statin medication with low, moderate, and high intensity. However, these targets are just as little tested in randomized trials as are the cholesterol goals derived from clinical experience. The same applies to the guidelines of the four patient groups which are defined by vascular risk. No major statin trial has included patients on the basis of their global risk; thus the allocation criteria are also arbitrarily chosen. These would actually lead to a significant increase in the number of patients to be treated with high or maximum dosages of statins. Also, adhering to dosage regulations instead of cholesterol goals contradicts the principles of individualized patient care. The option of the new risk score to calculate lifetime risk up to the age of 80 years in addition to the 10-year risk can be appreciated. Unfortunately it is not considered in the therapeutic recommendations provided, despite evidence from population and genetic studies showing that even a moderate lifetime reduction of low-density lipoprotein (LDL) cholesterol or non-HDL cholesterol has a much stronger effect than an aggressive treatment at an advanced age. In respect to secondary prevention, the new American guidelines broadly match the European guidelines. Thus, the involved societies from Germany, Austria and Switzerland recommend continuing according to established standards, such as the EAS/ESC guidelines.

DELIGHT (delay of impaired glucose tolerance by a healthy lifestyle trial) - a feasibility study on implementing a program of sustainable diabetes prevention in German companies.

BACKGROUND: Ca. 50% of Germans develop prediabetes in their lifetime. Though diabetes type 2 has been proven preventable, no screening for prediabetes has been implemented. DELIGHT was designed to assess if screening for individuals at risk and long-standing diabetes prevention is feasible in the setting of companies within the scope of the German legal health system. MATERIALS AND METHODS: In 5 companies employees with a waist circumference of ≥ 94 (men) and ≥ 80 cm (women) were offered a check-up. Those with fasting plasma glucose ≥ 100 mg/dl (IFG) or ≥ 140 mg/dl 2 h after oral glucose load (IGT) were followed for 3 years with an optional moderate lifestyle program during the first year and quarterly assistance for another 2 years. RESULTS: In 241 of 300 participants the self-measured waist circumference was confirmed as elevated. 3% had type 2 diabetes, while 37% had IFG (isolated in 96%) or IGT, of whom 91.4% (men) and 76.1% (women) had a metabolic syndrome. Within 3 years in those who had lost ≥ 1 kg, weight was reduced by 3.9 kg, risk factors were improved, and no case of diabetes had developed, while among those with weight loss of < 1 kg or weight gain, 10% of men and 5% of women had developed diabetes type 2. Screening for prediabetes did not increase the number or costs of drug prescriptions. CONCLUSIONS: Companies provide a suitable setting for screening for prediabetes. Long-term diabetes prevention is successfully feasible within the narrow financial frame of a legal insurance system without rise of costs.

[Familial hypercholesterolemia]. / Familiäre Hypercholesterinämie.

Familial hypercholesterolemia is one of the most common hereditary metabolic disorders, untreated with grave cardiovascular consequences. A general practitioner will see at least one affected individual each month, but will rarely be aware of the diagnosis, though it is easily suspected: an LDL-cholesterol ≥ 190 mg/dl, a family history of premature cardiovascular disease, or clinical signs as arcus lipoides, tendinous xanthomata, or a thickened Achilles' tendon must draw the attention to familial hypercholesterolemia. Because of the burden of high cholesterol levels from childhood on therapy should be initiated early enough, which has become greatly ameliorated since the introduction of statins. In conjunction with additional risk factors, notably low HDL-cholesterol or elevated lipoprotein(a) the cardiovascular sequelae can be dramatic and may call for more intense therapies. However, often the routine of successful cholesterol lowering covers the diagnosis nowadays, so that a heritable metabolic disorder is not suspected, which, however, prevents an effective prevention in relatives, particularly the children of the patient.

Association between alcohol consumption and carotid intima-media thickness in a healthy population: data of the STRATEGY study (Stress, Atherosclerosis and ECG Study).

BACKGROUND/OBJECTIVES: Epidemiological evidence suggests a protective effect of moderate alcohol consumption on cardiovascular events. However, studies assessing the association between alcohol intake and intima-media thickness (IMT) as a marker of subclinical atherosclerosis have provided inconsistent results. The aim of this analysis of the Stress Atherosclerosis and ECG Study (STRATEGY study) was to investigate the relation between alcohol intake and IMT in a selectively healthy population. SUBJECTS/METHODS: In a cross-sectional study, laboratory values, anthropometric data, nutrition habits and physical activity were assessed in 106 men and 107 women, evenly distributed between 30 and 70 years. Carotid IMT was determined by B-mode ultrasonography according to the standardized protocol of the Study of Health in Pomerania. RESULTS: In men, a significant positive correlation between daily alcohol consumption and IMT was observed (P<0.0001), whereas in women the positive correlation was not significant. The type of beverage consumed did not affect this finding. The mean IMT was significantly higher in men with an alcohol intake above the upper limit of 20 g/day than in men with an alcohol intake <20 g/day (P<0.001). According to a stepwise linear regression model adjusted for age, conventional risk factors, nutrition and physical activity, the IMT increases by 0.0253 mm per 21.4 g/day intake of alcohol in men (P<0.05). CONCLUSIONS: The STRATEGY study revealed a positive association between alcohol consumption and carotid IMT in healthy men aged 30-70 years. This relationship remained significant after adjustment for nutrition, physical activity, anthropometry and conventional cardiovascular risk factors.

Current strategies and recent advances in the therapy of hypercholesterolemia.

Lipid therapy is an option for preventing atherosclerotic vascular disease that has been intensively studied and proved to be effective independent of the underlying risk factors. Since the optimal LDL-cholesterol appears to lie well below 100 mg/dl most potent lipid lowering drugs and adjunctive HDL-raising therapeutics are mandatory. Inhibition of cholesterol synthesis and absorption is currently the preferred measure. However, new developments may substantially increase the efficacy of lipid therapy. One is add-on colesevelam, a synthetic bile-acid sequestrant with increased binding affinity which allows smaller dosages for better tolerability. Alternatively HDL-cholesterol may be increased by 25% using niacin with improved tolerability due to the combination with laropiprant, an inhibitor of the receptor for prostaglandin D2-receptor, which minimizes flushing close to placebo level. Mipomersen, a specific oligonucleotide capable to reduce apolipoprotein B-100 up to 70%, is certainly the most advanced approach to challenge even apheresis as the most effective measure to lower exceptionally elevated cholesterol levels.

Nutrition is a powerful independent risk factor for coronary heart disease in women--The CORA study: a population-based case-control study.

BACKGROUND: It is still common practice to rely mostly on drug treatment for preventing cardiovascular disease, although a healthy nutrition has been defined that may prevent most premature cardiovascular events. OBJECTIVES: This research raises the question of the magnitude of the effect of nutrition on cardiovascular disease independent of that of clinical risk factors, which are the targets of drug therapy. DESIGN: The study of coronary risk factors for atherosclerosis in women compares clinical, biochemical, and lifestyle factors in 200 consecutive pre- and postmenopausal women with incident coronary heart disease (CHD) to those in 255 age-matched population-based controls. RESULTS: Cases reported a higher intake of energy, predominantly through animal fat and protein reflected by a higher consumption of meat and sausage, while controls ate more fruit and vegetables. Multivariate analysis adjusted for clinical risk factors depicted a high intake of meat and sausage and a low consumption of fruit and vegetables as independent risk factors with an odds ratio of 2.5 (95% confidence interval 1.1-5.7) and 0.7 (95% confidence interval 0.5-1.0) for each 100 g per day, respectively. These dietary factors were found to be significantly more pronounced in cases with any clinical risk factor identified in this population as compared to controls with the same risk factors. CONCLUSIONS: The CORA-study clearly indicates a major impact of dietary habits on CHD in women independent of, and additive to, that of conventional risk factors. Thus, in clinical practice, the potential of nutrition as part of a healthy lifestyle is commonly greatly underestimated in favour of drug treatment.

[Cardiovascular risks under hormone replacement therapy]. / Kardiovaskuläres Risiko unter Hormonersatztherapie.

The discussion concerning the cardiovascular safety of hormone replacement therapy calls for a critical evaluation of the results of recent trials. In women arteriosclerotic cardiovascular disease has become the most frequent cause of death. Certainly not only the estrogen deficit can be hold responsible for the increasing cardiovascular risk with the menopause, since the prevalence of classical risk factors (i. e. overweight, metabolic syndrome) increases dramatically during the same period. The positive and negative effects of estrogens on the cardiovascular system are extraordinarily diverse, so that it is not reasonable to transfer isolated in-vitro-results to the situation in vivo. Likewise the results from observational studies or intervention trials in women of advanced age or with coronary heart disease cannot be applied to women in the perimenopause. Unfortunately intervention trials on the effect of hormone replacement therapy on coronary risk are lacking in this crucial period. The data of the Women's Health Initiative do not point to an increased risk at this stage. Therefore low dose estrogens can be reasonably applied for the relieve of menopausal symptoms after controlling the individual cardiovascular risk.

[Primary prevention of cardiovascular diseases. Stepchild of internal medicine]. / Primärprävention von Herz-Kreislauf-Erkrankungen. Ein Stiefkind der Inneren Medizin.

Preventive medicine has not been adequately established in our health care system. Despite growing in-sight into the causes underlying arteriosclerotic cardiovascular disease, half of the population dies and even more suffer from it. Generally the correction of risk factors is regarded as causal therapy. Modification of the lipid and carbohydrate metabolism or the blood pressure are certainly effective, however, intervention trials have also demonstrated the limitations. Mostly an unhealthy lifestyle underlies these risk factors so that correction of the lifestyle is the causal therapy in the true sense. That is the principle basis for primary prevention, while pharmacotherapy can only be an adjunct. Inadequate nutrition, physical inactivity and smoking are considered the true major risk factors in our society. Changes in nutrition in favor of plant products, some physical activity and refraining from smoking can serve an effective contribution to health. In the future not only medical, but also economic requirements will increasingly force us to establish prevention on the basis of lifestyle changes as a mainstay of medicine.