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Biomedical subjects

Steen Stender

Publications and source records attributed to Steen Stender.

At least 19 recordsLinked to original sources

A trans world journey.

A high intake of industrially produced trans fatty acids (IP-TFA) is associated with increased risk of coronary heart disease (CHD), and a daily intake as low as possible is required to minimize health risks. To achieve this at the individual level in Denmark, legislation limited IP-TFA in foods to a maximum of 2% of fat content from 2004. We assessed the potential exposure of consumers to IP-TFA by analysing popular foods in Denmark, and in 25 other countries. Fifty-five servings of French fries and chicken nuggets, 87 packages of microwave popcorn, and 393 samples of biscuits/cakes/wafers with "partially hydrogenated vegetable fat" listed high on the food label were bought between November 2004 and February 2006. The content of IP-TFA was analysed by standardized methodology. We defined a "high trans menu" as a large size serving of French fries and nuggets, 100 g of microwave popcorn, and 100 g of biscuits/wafers/cakes. The amounts of IP-TFA in a "high trans menu" was 30 g in 2001 in Denmark, but was reduced to less than 1g in 2005. By contrast, a "high trans menu" provided more than 20 g in 17 out of 18 countries, with Hungary, Czech Republic, Poland, Bulgaria, and USA, ranking highest with 42, 40, 38, 37, and 36 g, respectively. The legislation in Denmark has reduced the exposure of IP-TFA at the individual level without noticeable effect on availability, price, and quality of foods previously containing high amounts of IP-TFA. The findings of high concentrations of IP-TFA in popular foods outside Denmark suggest that millions of people inside and outside EU have intakes of IP-TFA that may increase their risk of CHD. The Danish experience demonstrates that this risk can be eliminated.

Coronary Disease↗

Trans, and n-3 polyunsaturated fatty acids and vascular function-a yin yang situation?

Trans fatty acids (TFA) and n-3 polyunsaturated fatty acids (n-3 PUFA) have opposite effects on several biological functions. We report a study on the effects on risk markers for cardiovascular disease. Eighty-seven healthy males were randomly assigned to 8 weeks of daily intake of either 20 g of industrially produced TFA (IP-TFA), 4 g n-3 PUFA, or control fat, incorporated in bakery products as part of the daily food. High-density lipoprotein cholesterol decreased in the TFA-group, triglycerides and mean arterial blood pressure decreased in the n-3 group. Heart rate variability (HRV), arterial dilatory capacity, flow mediated vasodilation, compliance, and distensibility were unchanged. Post hoc, we did a subgroup analysis of the results from the subjects with normal initial HRV. In these, 24-h heart rate (HR) was significantly increased by approximately three beats/min in the TFA group, with a decrease of the same magnitude in the n-3 group. A high HR is associated to an increased mortality and vice versa. Our results thus support the notion that IP-TFA and n-3 PUFA affect risk for cardiovascular mortality via mechanisms not only related to changes in plasma concentrations of lipids and lipoproteins.

Adult↗

[High levels of industrially produced trans fatty acids in popular fast food - but not in Denmark--secondary publication].

An intake of trans-fatty acids of 5 grams per day is associated with an increase of 25% in the risk of ischemic heart disease. In 2004 Denmark, as the first country in the world, introduced a limitation on the content of industrially produced trans-fatty acids in foods. The amount in a "high-trans menu" consisting of popular foods was, from 2001 to 2005, reduced in Denmark from 30 g to <1 g. The amount in the same menu bought in countries within and outside the European Union is 20-40 g. During a period of just a few years, Denmark has thus eliminated a risk factor for ischemic heart disease without noticeable side effects for consumers. This risk factor is, however, still present in many other countries.

Animals↗

Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction.

AIMS: To study initiation, dosages, and compliance with beta-blockers, angiotensin-converting enzyme (ACE)-inhibitors, and statins in patients after acute myocardial infarction (AMI) and to identify likely targets for improvement. METHODS AND RESULTS: Patients admitted with first AMI between 1995 and 2002 were identified by linking nationwide administrative registers. A total of 55 315 patients survived 30 days after discharge and were included; 58.3% received beta-blockers, 29.1% ACE-inhibitors, and 33.5% statins. After 1, 3, and 5 years, 78, 64, and 58% of survivors who had started therapy were still receiving beta-blockers, 86, 78, and 74% were receiving ACE-inhibitors, and 85, 80, and 82% were receiving statins, respectively. Increased age and female sex were associated with improved compliance. The dosages prescribed were generally 50% or less of the dosages used in clinical trials, and dosages did not increase during the observation period. Patients who did not start treatment shortly after discharge had a low probability of starting treatment later. CONCLUSION: The main problem with underuse of recommended treatment after AMI is that treatment is not initiated at an appropriate dosage shortly after AMI. A focused effort in the immediate post-infarction period would appear to provide long-term benefit.

Adrenergic beta-Antagonists↗

Nationwide trends in the prescription of beta-blockers and angiotensin-converting enzyme inhibitors after myocardial infarction in Denmark, 1995-2002.

OBJECTIVES: To study the use of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) in Denmark from 1995 to 2002. DESIGN: Information about patients with first AMI aged > or = 30 years and the dispensing of beta-blockers and ACE inhibitors from pharmacies within 30 d from discharge was obtained from the National Patient Registry and the Danish Registry of Medicinal Product Statistics. RESULTS: Beta-blocker use increased from 38.1% of patients in 1995 to 67.9% in 2002 (OR = 3.85, CI: 3.58-4.13). Women, elderly patients and patients taking loop-diuretics and antidiabetic drugs received beta-blockers less frequently, but patients taking loop-diuretics or antidiabetic drugs had the greatest increase. ACE inhibitor use increased from 24.5 to 35.5% (OR = 1.86, CI: 1.72-2.01). Women, patients aged < 60 years or > or = 80 years and patients not taking loop-diuretics received ACE inhibitors less frequently, but patients not taking loop-diuretics had the greatest increase. CONCLUSIONS: Beta-blocker use increased markedly post-AMI from 1995 to 2002, whereas ACE inhibitor use increased modestly. The results suggested undertreatment of women, elderly patients and people with diabetes.

Adrenergic beta-Antagonists↗

Effect of sucrose on inflammatory markers in overweight humans.

BACKGROUND: Observational studies have found that dietary glycemic load is positively associated with C-reactive protein (CRP) concentrations in healthy humans, which suggests that the type of carbohydrate ingested influences inflammatory activity. OBJECTIVE: We investigated the effect of a diet with a high content of sucrose or artificial sweeteners on the inflammatory markers CRP, haptoglobin, and transferrin in overweight subjects. DESIGN: Overweight men and women consumed daily food and drink supplements containing either sucrose [n = 21; body mass index (BMI, in kg/m2): 28.0] or artificial sweeteners (n = 20; BMI: 27.6), predominantly from soft drinks (70%; average approximately 1.3 L/d) for 10 wk. RESULTS: During the intervention, sucrose intake increased by 151% in the sucrose group and decreased by 42% in the sweetener group, resulting in a 1.6-kg weight gain in the sucrose group and a 1.2-kg weight loss in the sweetener group over 10 wk (P < 0.001). Concentrations of haptoglobin, transferrin, and CRP increased by 13%, 5%, and 6%, respectively, in the sucrose group and decreased by 16%, 2%, and 26%, respectively, in the sweetener group (between-group differences: P = 0.006, P = 0.01, and P = 0.1, respectively). Adjustment for changes in body weight and energy intake did not substantially influence this outcome. CONCLUSIONS: The study shows that in the present group of overweight subjects a high consumption of sugar-sweetened foods and drinks increased haptoglobin and transferrin but had, at best, only a limited influence on CRP.

Adult↗

Statin use after acute myocardial infarction: a nationwide study in Denmark.

AIMS: To study outpatient statin use after first acute myocardial infarction (AMI) in Denmark between 1995 and 2002 and to determine the predictors of statin use. METHODS: This is a nationwide population-based study using administrative registries. Patients with first AMI between 1995 and 2002 older than 30 years of age and alive 6 months after discharge (n = 45 219) were identified through the National Patient Registry. The statins purchased by these patients within 6 months after discharge were determined using the Registry of Medicinal Product Statistics, a nationwide prescription database. RESULTS: Statin use following AMI increased from 13% in 1995 to 61% in 2002. In 2002, 81% of patients aged 30-64 years used statins. Older patients used fewer statins, but use increased more among patients aged 75-84 years: from 1.3% to 43%. Use in elderly patients did not differ according to gender in 2000-02, but young men used more than younger women. In 2000-02, patients with diabetes (odds ratio (OR): 0.84; 95% confidence interval (CI): 0.74-0.95) and with heart failure (OR: 0.70; 95% CI: 0.64-0.76) were undertreated; this trend was present throughout the period. CONCLUSIONS: In this nationwide study, younger patients after AMI had high statin use in 2002, but high-risk patients such as those with diabetes and heart failure were still being undertreated.

Adult↗

Regression of coronary atherosclerosis by simvastatin: a serial intravascular ultrasound study.

BACKGROUND: Angiography of the coronary arteries reflects only changes in luminal dimensions. With intravascular ultrasound, cross-sectional images can be obtained and area measurements can be added to calculate volumes of the external elastic membrane (EEM), plaque plus media (P+M), and lumen. The aim of this study was to investigate the effect of lipid lowering by simvastatin on coronary atherosclerotic P+M as changes in volumes of EEM, P+M, and lumen. METHODS AND RESULTS: In 40 male patients with hypercholesterolemia, ischemic heart disease, and a nonsignificant coronary artery lesion in a not previously revascularized coronary artery, serial intravascular ultrasound studies with an ECG-triggered pullback were performed at baseline, after 3 months on a lipid-lowering diet, and after another 12 months on simvastatin 40 mg/d. Mean length of the analyzed atherosclerotic segments was 5.9+/-3.3 mm. After 12 months on simvastatin, a significant reduction in P+M volume of 6.3% (P=0.002) was observed, whereas only a nonsignificant reduction in EEM volume of 1.8% was seen without any concomitant change in lumen volume. A significant reduction in total cholesterol of 31.0% (6.1+/-0.8 versus 4.2+/-0.7 mmol/L, P<0.001) and LDL cholesterol of 42.6% (4.0+/-0.8 versus 2.2+/-0.6 mmol/L, P<0.001) was obtained. CONCLUSIONS: Lipid-lowering therapy with simvastatin for 12 months is associated with a significant P+M regression in coronary arteries measured as reduction in P+M and EEM volumes without any concomitant change in lumen volume.

Coronary Angiography↗

Effects of switching statins on achievement of lipid goals: Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study.

BACKGROUND: In a multinational trial (4522IL/0081), we assessed the effects of switching to low doses of rosuvastatin from commonly used doses of atorvastatin, simvastatin, and pravastatin on low-density lipoprotein cholesterol (LDL-C) goal achievement in high-risk patients. METHODS: Hypercholesterolemic patients (n = 3140) with coronary heart disease, atherosclerosis, or type 2 diabetes were randomized to open-label rosuvastatin 10 mg, atorvastatin 10 or 20 mg, simvastatin 20 mg, or pravastatin 40 mg for 8 weeks. Patients either remained on these treatments for another 8 weeks or switched treatments from atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg to rosuvastatin 10 mg or from atorvastatin 20 mg to rosuvastatin 10 or 20 mg. The primary efficacy measure was the proportion of patients reaching the Joint European Societies' LDL-C goal (<116 mg/dL) at week 16. For measures of cholesterol goal achievement, treatment arms were compared using logistic-regression analysis. RESULTS: Significant improvement in LDL-C goal achievement was found for patients who switched to rosuvastatin 10 mg, compared with patients who remained on atorvastatin 10 mg (86% vs 80%, P <.05), simvastatin 20 mg (86% vs 72%, P <.0001), and pravastatin 40 mg (88% vs 66%, P <.0001), and between patients switched to rosuvastatin 20 mg and those who remained on atorvastatin 20 mg (90% vs 84%, P <.01). Similar results were found for achievement of the European combined LDL-C and total cholesterol goals and National Cholesterol Education Program Adult Treatment Panel III LDL-C goals. All statins were well tolerated over 16 weeks. CONCLUSIONS: We demonstrated that switching to a more efficacious statin is an effective strategy to improve lipid goal achievement in patients requiring lipid-lowering therapy.

Aged↗

Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin.

BACKGROUND: Despite the efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C) levels, many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction. The cholesterol absorption inhibitor, ezetimibe, has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins. This study was performed to compare the efficacy and safety of ezetimibe (10 mg) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease (CHD) and are not at their LDL-C goal on the starting dose of atorvastatin. METHODS: This was a 14-week, multicenter, randomized, double-blind, active-controlled study conducted in 113 clinical research centers in 21 countries. Participants were adults with heterozygous familial hypercholesterolemia (HeFH), CHD, or multiple (> or =2) cardiovascular risk factors, and a LDL-C level > or =130 mg/dL after a 6- to 10-week dietary stabilization and atorvastatin (10 mg/day) open-label run-in period. Eligible subjects continued to receive atorvastatin (10 mg) and were randomized to receive blinded treatment with ezetimibe (10 mg/day; n = 305) or an additional 10 mg/day of atorvastatin (n = 316). The atorvastatin dose in both groups was doubled after 4 weeks, 9 weeks, or both when the LDL-C level was not at its goal (< or =100 mg/dL), so that patients receiving combined therapy could reach 40 mg/day and patients receiving atorvastatin alone could reach 80 mg/day. The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14. A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy. RESULTS: The proportion of subjects reaching their target LDL-C level goal of < or =100 mg/dL was significantly higher in the co-administration group than in the atorvastatin monotherapy group (22% vs 7%; P <.01). At 4 weeks, levels of LDL-C, triglycerides, and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin (LDL-C -22.8% versus -8.6%; P <.01). The combination regimen had a safety and tolerability profile similar to that of atorvastatin alone. CONCLUSIONS: The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone.

Adolescent↗

Reduced endothelial nitric oxide synthase activity and concentration in fetal umbilical veins from maternal cigarette smokers.

OBJECTIVE: This study aimed to investigate the effect of maternal cigarette smoking on endothelial nitric oxide synthase (eNOS) activity and concentration in the fetal umbilical vein, and subsequently, to relate the findings to the size of the newborn. STUDY DESIGN: Forty-four nonsmoking and 30 smoking women were included in the study. Umbilical vein endothelial cells were isolated immediately after delivery. The eNOS activity was determined in the samples by the conversion of (14)C-L-arginine to (14)C-L-citrulline, and the eNOS concentration was determined by a human eNOS immunoassay. RESULTS: Newborns of smokers had a lower weight (P=.014) and a smaller head circumference (P=.002) than those newborns of nonsmokers. The eNOS activity in fetal umbilical veins exposed to maternal smoking was 40% lower (P=.006), and the eNOS concentration 32% lower (P=.053) in newborns of smokers than in nonsmokers. CONCLUSION: The findings suggest that maternal smoking reduces nitric oxide production in the fetal circulation. This may contribute to retarded fetal growth caused by the subsequent endothelial dysfunction with reduction of dilatory capacity of the vessels.

Adult↗

Low variation and high reproducibility in plaque volume with intravascular ultrasound.

BACKGROUND: Intravascular ultrasound (IVUS) has several advantages compared to angiography when evaluating coronary atherosclerosis in the vessel wall. METHODS: The accuracy, reproducibility, and short-time spontaneous variation in volume of vessel, plaque and lumen were studied by electrocardiographic-gated three-dimensional (3D) IVUS in 20 male patients with ischaemic heart disease (IHD). RESULTS: The study lesions were angiographically insignificant, with a length of the analysed segment on 11.4+/-5.9 mm. At baseline the mean minimal lumen diameter was 2.41+/-0.59 mm, minimal lumen area 4.82+/-2.38 mm2, and maximal plaque burden 65.61+/-9.57%. Mean reference diameter was 3.1+/-0.6 mm. No significant changes were observed in volumes of total vessel, lumen or plaque. The coefficient of variation (CV) for two volume measurements at baseline was: vessel 0.8%, plaque 1.3%, and lumen 1.4%. For measurements recorded at baseline and after 12.6+/-1.5 weeks, CV was respectively 3.5%, 3.3% and 6.6%. Reproducibility and interobserver and intraobserver variation showed very high correlations. A linear correlation was present in percent changes over 12.6+/-1.5 weeks between vessel volume and lumen volume (r=0.804; p<0.001) and between percent changes in plaque volume and vessel volume (r=0.581; p=0.007). No correlation was found between changes in plaque volume and lumen volume (r=0.015; p=0.950). CONCLUSION: ECG-gated 3D IVUS is a highly reproducible method when applied on coronary artery atherosclerosis. CV for lumen volume over 12.6+/-1.5 weeks is twice that of plaque volume indicating the superiority of the 3D IVUS compared to coronary angiography (CAG).

Aged↗

Influence of trans fatty acids on health.

The contribution of dietary trans fatty acids (TFAs) on the risk of ischemic heart disease (IHD) has recently gained further support due to the results from large, prospective, population-based studies. Compared to saturated fat, TFAs are, gram to gram, associated with a considerably (2.5- to >10-fold) higher risk increment for IHD. A negative effect on the human fetus and on newborns and an increase in colon cancer risk in adults are possible but, however, still equivocal. Recent findings justify further studies concerning the effect of TFAs on allergic diseases in children and on the risk of type-2 diabetes in adults. The intake of industrially produced TFAs in European countries is decreasing. However, determination of the TFA content in various popular food items collected in Danish shops showed that it is likely that persons with a frequent intake of, e.g., French fries, microwave oven popcorn, chocolate bars, fast food, etc., consume industrially produced TFAs in amounts far exceeding the average intake, and are thereby exposed to an unnecessary health risk. The Danish government has decided that oils and fats containing more than 2% industrially produced TFAs will not be sold in Denmark after the January 1, 2004.

Animals↗