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Biomedical subjects

C von Schacky

Publications and source records attributed to C von Schacky.

At least 19 recordsLinked to original sources

[Total risk for cardiovascular disease. At what point is medical prophylactic medication useful?].

Despite the epidemiological importance of coronary artery disease: cardiovascular events are rare from the individual viewpoint. There is considerable uncertainty when to start medical treatment. A given risk factor modification results in a relative risk reduction independent of the global risk. Therefore the global risk determines the absolute benefit of a preventive measure. The global risk can be estimated using different scoring systems. Using the global risk and the expected relative risk reduction, the number needed to treat (NNT) to avoid one event or cardiac death can be calculated. The NNT is a measure for the usefulness of a preventive intervention. A NNT of <200 appears acceptable for primary prevention. This can be achieved with pharmacological preventive strategies if the global risk of 10 years is > or =20%. As age is one of the most important risk predictors the need for treatment at comparable risk factor constellations is age dependent. Risk stratification with estimation of the NNT is therefore important for the decision to treat or not to treat.

Cardiotonic Agents↗

[Role of hormone-replacement therapy for prevention of coronary artery disease in women].

The postmenopausal increase in the incidence of coronary artery disease implied a protective effect of estrogens. Nonrandomized, clinical and experimental studies have supported this notion. In the first randomized study (HERS 1998) no protective effect on prognosis of postmenopausal women with coronary artery disease was demonstrated. Also, in healthy postmenopausal women no beneficial effect of a hormone-replacement therapy on coronary events was shown (WHI-Study 2002, 2004). Therefore, hormone-replacement therapy is not recommended for prophylaxis of cardiovascular disease in healthy women or in women with documented coronary artery disease (Recommendation class I, evidence-level A). The continuation or the start of a hormone- replacement therapy is only justified for therapy of severe menopausal symptoms. Women should be informed that changes in lifestyle including not smoking, a heart healthy diet, and regular exercise are the most important measures to prevent cardiovascular diseases.

Clinical Trials as Topic↗

[Cardiovascular prevention and rehabilitation].

The distinction between primary and secondary prevention has been abandoned in favor of cardiovascular prevention, mandating individual risk assessment. First, the individual cardiovascular risk of a person is determined by index diseases like myocardial infarction, peripheral arterial disease or other, or, if absent, by a score consisting of a number of conventional risk factors. According to current guidelines, cardiovascular prevention is indicated, as soon as the risk for fatal cardiovascular disease is > or = 5 %, equivalent to a risk for a major cardiovascular event of > or = 20 %. Non-pharmaceutical approaches are: refraining from smoking, mediterranean diet with fatty fish, physical activity and normal body weight. Blood pressure and diabetes mellitus are optimized. In addition, the following agents are used: platelet inhibitors, beta-blockers, ACE-inhibitors, statins and omega-3 fatty acids. A number of structural problems add to individual factors impeding optimal implementation of cardiovascular prevention in Germany.

Adrenergic beta-Antagonists↗

[Secondary prevention of coronary heart disease].

The target group for "secondary prevention"--better "risk-adapted prevention"--of CHD are individuals who have suffered a myocardial infarction or have indicator diseases or other risk factor constellations with a cardiovascular risk of > 20% in ten years. The indisputably effective measures include cessation of smoking, blood pressure control with appropriate medications, a Mediterranean diet, maritime omega-3 fatty acids, endurance sports, statin-based lipid management (LDL < 100 mg/dl, triglycerides < 200 mg/dl), a target BMI of 18.5-25, optimized diabetes management, use of platelet aggregation inhibitors, beta blockers and ACE inhibitors. Hormone replacement therapy or vitamin supplementation has been identified as ineffective or mildly dangerous. Other measures have either not become established, or only poorly so. Currently, implementation of the effective measures leaves much to be desired. Quality-controlled close cooperation by the family doctor and cardiologist arguably provides the best long-term care in the area of secondary prevention, but still remains utopian.

Adrenergic beta-Antagonists↗

[Omega-3-fatty acids, Mediterranean cooking, low-fat diet. What really prevents myocardial infarct?].

The strength of evidence in support of dietary measures in the secondary prevention of coronary artery disease is variable (Table 1). The most impressive data available concern the impact of omega-3 fatty acids found in sea-fish at an intake of about 1.0 g/day, but the data underscoring the value of a Mediterranean diet are also convincing. No comparable data are available for low-fat and fat-modified diets. For diabetics, an HbA1c of < 7% should be achieved. There is indirect evidence that a body mass index of between 18.5 and 23.9 kg is optimal, and can be achieved by physical exercise and weight control. Weight reduction also lowers blood pressure, a goal that can equally be reached by a low-salt diet rich in fruit and vegetables, and the practice of endurance sports. The results of ongoing studies on the use of vitamin supplements are as yet unavailable.

Animals↗

The effect of n-3 fatty acids on coronary atherosclerosis: results from SCIMO, an angiographic study, background and implications.

According to the model of "response to injury," the arterial endothelium is occasionally injured in hyperlipidemia, hypertension, diabetes mellitus and in other states known as risk factors. The ensuing inflammatory response is modulated by cytokines and growth factors, among them platelet-derived growth factor (PDGF), and monocyte chemoattractant protein-1 (MCP-1). In two independent studies, we demonstrated that mRNA levels for PDGF-A and -B and for MCP-1 are reduced after ingestion of n-3 fatty acids by human volunteers. This reduction persists after monocyte stimulation/differentiation by adherence. Moreover, the reduction is brought about only by dietary n-3 fatty acids and not by other classes of unsaturated fatty acids (n-6 or n-9). This appears to be one major mechanism of action of reduced progression/increased regression of established coronary artery disease by ingestion of 1.5 g/d n-3 fatty acids, as assessed by coronary angiography in a randomized placebo-controlled double-blind intervention study in 223 patients. The study was conducted according to "Good Clinical Practice," comprehensive rules regulating investigations with pharmaceutical compounds. Together, our investigations lend support to the importance of PDGF-A, PDGF-B, and MCP-1 in the pathogenesis of atherosclerosis, and the beneficial role of n-3 fatty acids therein.

Angiography↗

Endothelial function of the popliteal artery in patients with coronary artery disease.

Coronary artery disease (CAD) is associated more closely with atherosclerosis in the popliteal than in the brachial artery. This case-control study aimed at clarifying whether endothelial dysfunction of patients with CAD can be detected non-invasively in the popliteal artery by means of ischemia-induced flow-mediated dilation (FMD) and cold pressor reaction (CPR), and how it compares with the brachial artery. We further investigated a new mode of evaluation of the CPR. Eleven cases with CAD were compared with 16 matched healthy controls. Popliteal and brachial arterial diameter was monitored by ultrasound for 20 min following ischemia and cold pressor. For CPR, the difference between maximum and minimum diameter was defined as maximum vasomotion. In the popliteal artery, maximum vasomotion and FMD were significantly smaller in cases than in controls, the difference being more pronounced than in the brachial artery, where only maximum vasomotion was significantly smaller. After exclusion of current smokers, only the difference in maximum vasomotion of both arteries remained significant. We conclude that maximum vasomotion may be more sensitive for detection of endothelial dysfunction than FMD. Endothelial dysfunction in patients with CAD is more pronounced in the popliteal artery than in the brachial artery.

Adult↗

Influence of 17beta-oestradiol on blood pressure of postmenopausal women at high vascular risk.

OBJECTIVES: It remains an unsolved issue whether hormone replacement therapy (HRT) lowers blood pressure. This randomized trial examined the effect of 17beta-oestradiol combined cyclically with gestodene on blood pressure of postmenopausal women who were not on antihypertensive medication. All subjects had an increased risk for adverse vascular events as indicated by intima-media thickness of carotid arteries and standard risk factors. DESIGN AND SETTING: Two hundred and twenty-six postmenopausal women were randomized to oral treatment for 48 weeks with 1 mg of 17beta-oestradiol per day continuously, plus 0.025 mg gestodene on days 17-28 of each 4-week cycle (HRT 1), or plus gestodene in each third cycle only (HRT 2), or no HRT. According to predefined criteria, four subjects in HRT 1, 12 in HRT 2 and 13 in no HRT who were started on antihypertensive medication were excluded from the analysis. Thirty subjects ended participation prematurely for other reasons. Resting blood pressure was measured at baseline and after 12, 22 and 48 weeks. RESULTS: During treatment diastolic blood pressure changed significantly in both HRT groups compared to no HRT, by -3.7 +/- 9.8 mmHg, -3.0 +/- 8.8 mmHg and 1.0 +/- 9.9 mmHg at week 48 in groups HRT 2, HRT 1 and no HRT, respectively (P = 0.008 for HRT 2 versus no HRT, P = 0.027 for HRT 1 versus no HRT). The higher the diastolic blood pressure was at beginning the greater was the decrease. The decrease of systolic blood pressure was not significantly different between groups. CONCLUSIONS: For postmenopausal women with high cardiovascular risk but without antihypertensive medication, long-term treatment with 17beta-oestradiol combined with gestodene lowers diastolic blood pressure.

Blood Pressure↗

Effect of oral postmenopausal hormone replacement on progression of atherosclerosis : a randomized, controlled trial.

-Postmenopausal hormone replacement therapy (HRT) is associated with low cardiovascular morbidity and mortality in epidemiological studies. Yet, no randomized trial has examined whether HRT is effective for prevention of coronary heart disease (CHD) in women with increased risk. The objective of this study was to determine whether HRT can slow progression of atherosclerosis, measured as intima-media thickness (IMT) in carotid arteries. Carotid IMT is an appropriate intermediate end point to investigate clinically relevant effects on atherogenesis. This randomized, controlled, observer-blind, clinical, single-center trial enrolled 321 healthy postmenopausal women with increased IMT in >/=1 segment of the carotid arteries. For a period of 48 weeks, subjects received either 1 mg/d 17ss-estradiol continuously plus 0.025 mg gestodene for 12 days every month (standard-progestin group), or 1 mg 17ss-estradiol plus 0.025 mg gestodene for 12 days every third month (low-progestin group), or no HRT. Maximum IMT in 6 carotid artery segments (common, bifurcation, and internal, both sides) was measured by B-mode ultrasound before and after intervention. HRT did not slow IMT progression in carotid arteries. Mean maximum IMT in the carotid arteries increased by 0.02+/-0.05 mm in the no HRT group and by 0.03+/-0.05 and 0.03+/-0.05 mm, respectively, in the HRT groups (P:>0.2). HRT significantly decreased LDL cholesterol, fibrinogen, and follicle-stimulating hormone. In conclusion, 1 year of HRT was not effective in slowing progression of subclinical atherosclerosis in postmenopausal women at increased risk.

Carotid Arteries↗

Impact of social support, cynical hostility and anger expression on progression of coronary atherosclerosis.

OBJECTIVES: This prospective cohort study of patients with coronary artery disease (CAD) sought to determine the impact of social support, anger expression and cynical hostility on progression of coronary atherosclerosis as shown by angiography. BACKGROUND: Low social support, high levels of expressed anger and cynical hostility are correlated to increased CAD morbidity and mortality. However, the impact of these factors, alone or together, on progression of human coronary atherosclerosis is unknown. METHODS: Of 223 patients with CAD documented by standardized angiography at baseline, 162 had a second angiogram after two years. An expert panel who had no knowledge of the patients' characteristics evaluated the films pairwise to determine disease progression. At baseline, all patients were asked to answer three self-report questionnaires: questions concerning emotional social support, the State-Trait-Anger-Expression Inventory (STAXI) and the Cook-Medley cynical hostility scale. Each patient's clinical and laboratory status was followed. RESULTS: Questionnaires and angiographic follow-up data were available for 150 patients. Bivariate analysis of the psychological variables showed a higher risk of progression only for patients who scored high on STAXI anger-out or low on social support. In the multivariate analysis, when adjusting for confounding variables and examining the interaction between psychological variables, only patients with both high anger-out and low social support were at highly increased risk for progression (odds ratio 30, confidence interval [CI] 5.5 to 165.1; RR 3.19). CONCLUSIONS: Patients with CAD and low emotional social support who express anger outwardly are at a highly increased risk of disease progression, independent of medication or other risk factors.

Anger↗

Hormone replacement therapy and distensibility of carotid arteries in postmenopausal women: a randomized, controlled trial.

OBJECTIVES: The study objective was to clarify in a randomized, controlled, observer-blind trial whether hormone replacement therapy (HRT) improves elastic properties of the common carotid artery in women with signs of subclinical atherosclerosis, especially in subgroups with increased risk, and whether less progestin enhances the effect. BACKGROUND: Previous observational studies have yielded conflicting results on the influence of HRT on central arteries. Some studies reported improvement of distensibility by estrogen alone or in the subgroup of smokers. METHODS: A total of 321 postmenopausal women were randomized to 1 mg 17beta-estradiol plus 0.025 mg gestodene for 12 days every month (HRT 1), or 1 mg 17beta-estradiol plus 0.025 mg gestodene for 12 days every third month (HRT 2), or no-HRT, during 48 weeks. In 173 women, distensibility of the common carotid artery was determined before and after therapy by M-mode ultrasound and brachial blood pressure measurement. RESULTS: Change of distensibility was small and similar in the three treatment groups. In the subgroup of current smokers, HRT 2 (low progestin) increased distensibility by 32% (HRT 2: 8.2+/-11.7; HRT 1:0.6+/-6.0; no HRT: -1.8+/-6.8 x 10(-3)/kPa, p = 0.025 for no-HRT vs. HRT 2). In the subgroups with elevated blood pressure, high low density lipoprotein (LDL) cholesterol, or high age, no effect of HRT was detected. CONCLUSIONS: This randomized intervention study demonstrates that long-term HRT with estrogen and progestin does not substantially influence distensibility of central arteries. Yet, in currently smoking postmenopausal women, HRT with low progestin seems to improve distensibility; this merits further study in a specifically designed trial.

Adult↗

Bone sialoprotein is a specific biochemical marker of bone metabolism in postmenopausal women: a randomized 1-year study.

Accelerated bone remodeling after the menopause is associated with increased bone loss that can be abolished using hormone replacement therapy (HRT). Biochemical markers of bone metabolism are known to correlate closely with changes in bone histomorphometry and osteodensitometry. Bone sialoprotein (BSP), a major constituent of bone matrix, is almost exclusively found in mineralized tissues and therefore considered a potential marker of bone metabolism. In 82 postmenopausal women, randomly allocated to either low-dose sequential HRT or no HRT, serum BSP was measured and compared with established specific biochemical markers of bone resorption [urinary deoxypyridinoline (DPD), pyridinoline (PYD) and amino-terminal telopeptide (NTx)] and markers of bone formation [serum osteocalcin (Oc) and bone-specific alkaline phosphatase (bALP)]. Longitudinal analysis showed a marked response of BSP levels following commencement of HRT, resulting in a 52% reduction after 12 months compared with initial values. The changes of BSP levels over time were at least as strong as in conventional markers of bone formation and resorption and paralleled their changes. A moderate to close correlation was found between BSP and both markers of bone resorption (r = 0.57 for NTx; r = 0.38 for DPD) and formation (r = 0.55 for Oc; r = 0.39 for bALP; p < 0.0001, respectively). Our data demonstrate a cause and effect relationship between commencement of HRT and a change in serum BSP. In conclusion, serum BSP circumvents some of the limitations of urinary measurements and appears valuable for the quantitative monitoring of the skeletal response to HRT in healthy postmenopausal women.

Aged↗

n-3 fatty acids and the prevention of coronary atherosclerosis.

Epidemiologic studies have shown an inverse correlation between consumption of fish or other sources of dietary n-3 fatty acids and cardiovascular events. Numerous mechanisms of action for the favorable effect of dietary n-3 fatty acids on factors implicated in the pathogenesis of atherosclerosis have been described. Studies in dogs, swine, and nonhuman primates have consistently shown beneficial effects in various models of vasoocclusive diseases. Studies published currently do not indicate that dietary n-3 fatty acids prevent restenosis after percutaneous coronary angioplasty or induce regression of coronary atherosclerosis. However, in a recent study, occlusion of aortocoronary venous bypass grafts was reduced after 1 y by daily ingestion of 4 g fish-oil concentrate. In the Diet and Reinfarction Trial, 2-y overall mortality was reduced by 29% in survivors of a first myocardial infarction after consumption of n-3 fatty acid-rich fatty fish at least twice a week had been advised (Lancet 1989;2:757-61). When n-3 fatty acids were integrated into a diet resembling a traditional Mediterranean diet, 5-y cardiovascular mortality after a first myocardial infarction was reduced by 70% (Lancet 1994; 343:1454-9). Preliminary studies indicate that cardiac transplant patients could be an interesting focus of investigation. Currently, food sources rich in n-3 fatty acids are thought to be beneficial in secondary prophylaxis after a myocardial infarction. Large-scale clinical studies with endpoints such as morbidity and mortality are needed to more precisely define the role of n-3 fatty acids in primary and secondary prophylaxis of coronary atherosclerosis.

Coronary Angiography↗

n-3 polyunsaturated fatty acids and the cardiovascular system.

n-3 Polyunsaturated fatty acids, mainly those contained in fish oils, are candidates for inclusion in secondary prevention programmes for coronary heart disease, based on the results of recent randomized trials in humans. Marine n-3 polyunsaturated fatty acids retard coronary atherosclerosis and appear to prevent fatal arrhythmias; and they decrease mortality subsequent to myocardial infarction.

Arteriosclerosis↗

n-3 polyunsaturated fatty acids and the cardiovascular system.

n-3 Polyunsaturated fatty acids, mainly those contained in fish oils, are candidates for inclusion in secondary prevention programmes for coronary heart disease, based on the results of recent randomized trials in humans. Marine n-3 polyunsaturated fatty acids retard coronary atherosclerosis and appear to prevent fatal arrhythmias; and they decrease mortality subsequent to myocardial infarction.

Arteriosclerosis↗

The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Epidemiologic studies, studies of mechanisms of action, and many animal studies indicate that dietary intake of omega-3 fatty acids has antiatherosclerotic potential. Few trials in humans have examined this potential. OBJECTIVE: To determine the effect of dietary intake of omega-3 fatty acids on the course of coronary artery atherosclerosis in humans. DESIGN: Randomized, double-blind, placebo-controlled, clinically controlled trial. SETTING: University preventive cardiology unit. PATIENTS: 223 patients with angiographically proven coronary artery disease. INTERVENTION: Fish oil concentrate (55% eicosapentaenoic and docosahexaenoic acids) or a placebo with a fatty acid composition resembling that of the average European diet, 6 g/d for 3 months and then 3 g/d for 21 months. MEASUREMENTS: The results of standardized coronary angiography, done before and after 2 years of treatment, were evaluated by an expert panel (primary end point) and by quantitative coronary angiography. Patients were followed for clinical and laboratory status. RESULTS: Pairs of angiograms (one taken at baseline and one taken at 2 years) were evaluated for 80 of 112 placebo recipients and 82 of 111 fish oil recipients. At the end of treatment, 48 coronary segments in the placebo group showed changes (36 showed mild progression, 5 showed moderate progression, and 7 showed mild regression) and 55 coronary segments in the fish oil group showed changes (35 showed mild progression, 4 showed moderate progression, 14 showed mild regression, and 2 showed moderate regression) (P = 0.041). Loss in minimal luminal diameter, as assessed by quantitative coronary angiography, was somewhat less in the fish oil group (P > 0.1). Fish oil recipients had fewer cardiovascular events (P = 0.10); other clinical variables did not differ between the study groups. Low-density lipoprotein cholesterol levels tended to be greater in the fish oil group. CONCLUSION: Dietary intake of omega-3 fatty acids modestly mitigates the course of coronary atherosclerosis in humans.

Adult↗