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O Faergeman

Publications and source records attributed to O Faergeman.

At least 19 recordsLinked to original sources
PubMed2006

Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel.

There is abundant evidence that the risk of atherosclerotic vascular disease is directly related to plasma cholesterol levels. Accordingly, all of the national and transnational screening and therapeutic guidelines are based on total or LDL cholesterol. This presumes that cholesterol is the most important lipoprotein-related proatherogenic risk variable. On the contrary, risk appears to be more directly related to the number of circulating atherogenic particles that contact and enter the arterial wall than to the measured concentration of cholesterol in these lipoprotein fractions. Each of the atherogenic lipoprotein particles contains a single molecule of apolipoprotein (apo) B and therefore the concentration of apo B provides a direct measure of the number of circulating atherogenic lipoproteins. Evidence from fundamental, epidemiological and clinical trial studies indicates that apo B is superior to any of the cholesterol indices to recognize those at increased risk of vascular disease and to judge the adequacy of lipid-lowering therapy. On the basis of this evidence, we believe that apo B should be included in all guidelines as an indicator of cardiovascular risk. In addition, the present target adopted by the Canadian guideline groups of an apo B <90 mg dL(-1) in high-risk patients should be reassessed in the light of the new clinical trial results and a new ultra-low target of <80 mg dL(-1) be considered. The evidence also indicates that the apo B/apo A-I ratio is superior to any of the conventional cholesterol ratios in patients without symptomatic vascular disease or diabetes to evaluate the lipoprotein-related risk of vascular disease.

Apolipoproteins B↗
PubMed2006

Danish singles have a twofold risk of acute coronary syndrome: data from a cohort of 138 290 persons.

STUDY OBJECTIVE: Atherosclerosis of the coronary and other arteries is an important health problem in virtually all countries of the world, and thus there is a persisting need for the development of preventive programmes including population risk group identification. The aim of the study was to identify sociodemographic population risk indicators of an initial episode of acute coronary syndrome (ACS), including unstable angina pectoris (UAP), myocardial infarction (MI), and sudden cardiac death (SCD). DESIGN: Cohort study of 138 290 residents of the municipality of Aarhus, Denmark, aged 30-69 years. Information on population members' individual age, sex, social background, and eventual death was obtained from Danish Population Registers. SETTING: University hospital. PATIENTS: The study prospectively identified 646 victims of ACS from 1 April 2000 to 31 March 2002. MAIN RESULTS: Based on multiple logistic regression, age and single living were found to be positively associated with incident ACS in both sexes. Women >60 years living alone and men >50 years living alone were at especially high risk. They constituted only 5.4% and 7.7% of the source population, respectively, but they accounted for 34.3% and 62.4% of ACS patients dying within 30 days. CONCLUSIONS: Single living is associated with an increased risk of ACS. Thus, risk groups identified by use of information on their age and family structure may be targets for future more focused and cost effective preventive strategies. In Western populations, such high risk groups will constitute comparatively limited parts of the population, and in Denmark they are easily identifiable in routine population registers.

Acute Disease↗
PubMed2002

LDL receptor mutation genotype and vascular disease phenotype in heterozygous familial hypercholesterolaemia.

Patients with homozygous familial hypercholesterolaemia (FH) caused by receptor-negative, low-density lipoprotein (LDL) receptor gene mutations have higher concentrations of LDL-cholesterol in plasma and earlier onset of cardiovascular disease (CVD) than patients homozygous for receptor-defective, LDL receptor mutations. In contrast, it is uncertain whether the severity of atherosclerotic disease differs in heterozygous FH caused by receptor-negative and receptor-defective mutations. The present authors investigated the influence of LDL receptor mutation type on the clinical phenotype in 31 patients with heterozygous FH caused by the receptor-negative, Trp23-stop mutation and in 31 patients heterozygous for the receptor defective Trp66-Gly mutation. Untreated levels of plasma LDL-cholesterol and calculated cholesterol-years score did not differ significantly between the two groups of patients. Detection of vascular disease was based on two approaches: (1) measurement of coronary calcification by spiral computed tomography (CT) scanning; and (2) ultrasonic measurement of carotid intima-media thickness (IMT). Age was significantly correlated to the presence of coronary calcification, but controlling for relevant cofactors, there was no evidence that the receptor-negative mutation caused more calcification than the receptor-defective mutation. Furthermore, carotid IMT was significantly influenced by plasma concentrations of Lp(a) and triglycerides, as well as by age, sex and smoking status, but again, there was no statistically significant effect of LDL receptor gene mutational type. The similarity in vascular phenotypes was probably caused by a similar life-long burden of LDL-cholesterol in the two groups of patients.

Adult↗
PubMed2002

Methods for detecting coronary disease: epidemiology and clinical management.

The epidemic of atherosclerotic disease in wealthy countries had probably begun by 1900. Although a few physicians understood how atherosclerosis/thrombosis of the coronary arteries caused angina pectoris and myocardial infarction, the medical community did not accept that relationship until the 1920s. In wealthy countries, the epidemic peaked in mid-century, and it is now advancing in poor countries and in countries becoming affluent. Two recent developments in methods for disease detection, however, will profoundly affect not only our understanding of the epidemic of atherosclerotic disease, but also our management of patients. A redefinition of the clinical diagnosis of myocardial infarction, a well-used but imperfect measure of the epidemic, was published in September 2000. Criteria employed for about 50 years have now been replaced by criteria based on sensitive biochemical markers of necrosis of as little as 1 g of myocardium, accompanied by chest discomfort or electrocardiographic (ECG) changes, or following coronary artery intervention. The new criteria, adopted by the major societies of cardiology in Europe and the United States, is likely to increase the apparent incidence and prevalence of coronary heart disease (CHD). In the beginning of the twentieth century, diagnosis of CHD required an autopsy. In the end it was carried out by angiography as well, but it could not be applied to large proportions of the population. That has now been changed by new, non-invasive methods of computer tomography (CT) and magnetic resonance imaging (MRI), and patients, however, asymptomatic, will expect treatment for a disease that physicians have detected. Coronary artery disease (CAD) will be to CHD what occult cancer is to cancer.

Coronary Disease↗
PubMed2001

The atherosclerosis epidemic: methodology, nosology, and clinical practice.

An electronic search shows that there is a small but respectable amount of research on psychiatric and neurologic nosology. There is a also a small body of literature on endocrinologic nosology, but cardiologists almost never write about the nosology of heart disease. It does not keep them awake at night. Our understanding of the 20th-century epidemic of coronary artery disease (CAD), which dominates cardiology, has nevertheless been frustrated by problems of nosology. One of the purposes of this article is to discuss how our understanding of the epidemic has depended on classification of disease events and on the methods used to detect them. The other purpose is to show how current reclassifications of CAD and the major metabolic condition conducive to CAD, type 2 diabetes, each affect the practice of cardiology and medicine.

Adult↗
PubMed2001

LDL-receptor gene mutations and the hypocholesterolemic response to statin therapy.

Studies of the cholesterol lowering effect of statin therapy as a function of low-density lipoprotein (LDL)-receptor mutation type have not produced a clear picture, possibly because they included patients with several different kinds of LDL-receptor mutations. We studied the response to treatment with fluvastatin in 28 patients with heterozygous familial hypercholesterolemia as a result of a receptor-negative mutation (Trp23-stop) and in 30 patients with a receptor-binding defective mutation (Trp66-Gly) to test the hypothesis that response to treatment depends on the type of mutation. Patients were randomized to 12 weeks of treatment with fluvastatin 40 mg daily and 12 weeks of placebo treatment, preceded by a placebo run-in period of 8 weeks in a double-blind, cross-over design. Untreated plasma concentrations of lipids and lipoproteins were similar in the two groups of patients. Plasma cholesterol and LDL cholesterol response to therapy tended to be less marked in receptor-binding defective patients, but the differences were not statistically significant. A tabulation of the results of the present and earlier studies suggests that differences in treatment response as an apparent function of LDL-receptor gene mutational type occur mainly in populations with recent genetic admixture (<400 years). In such populations, persons with the same mutation in the LDL-receptor gene are more likely to share other but undetermined genetic variations affecting the pharmacology of statins.

Adult↗
PubMed2000

Follow-up study of patients randomized in the Scandinavian simvastatin survival study (4S) of cholesterol lowering.

The Scandinavian Simvastatin Survival Study (4S) and other randomized clinical trials have demonstrated that cholesterol-lowering treatment with statins improves prognosis in patients with coronary atherosclerosis compared with placebo. The effect of therapy with statins beyond the typical 5 to 6 years' duration of the trials, in particular regarding the risk of cancer, has not been investigated. This study examines the long-term effects of simvastatin for up to 8 years on cause-specific mortality in patients with coronary heart disease (CHD). We performed an observational, government registry-based study of mortality in the groups originally randomized to simvastatin or placebo in the 4S over an additional 2-year follow-up period, so that the median total follow-up period was 7.4 years (range 6.9 to 8.3 in surviving patients). Randomization took place at outpatient clinics at 94 clinical centers in Denmark, Finland, Iceland, Norway, and Sweden from 1988 to 1989. Of 4,444 patients with CHD, 2,223 and 2,221 were randomized to treatment with placebo or simvastatin therapy, respectively. Patients received treatment with simvastatin, starting at 20 mg/day, with titration to 40 mg/day at 12 or 24 weeks if total cholesterol was >5.2 mmol/L (200 mg/dl), or placebo. After the double-blind period, most patients in both treatment groups received simvastatin as open-label prescription. Of the 1,967 patients originally treated with placebo and surviving the double-blind period, 97 (4.9%) died during the following 2 years. In the group randomized to simvastatin the corresponding number was 74 of the 2, 039 survivors (3.6%). Adding these deaths to those occurring during the original trial, the total was 353 (15.9%) and 256 (11.5%) deaths in the groups originally randomized to placebo and simvastatin, respectively. The relative risk was 0.70 (95% confidence interval 0. 60 to 0.82, p = 0.00002). The total number of cancer deaths was 68 (3.1%) in the placebo group and 52 (2.3%) in the simvastatin group (relative risk 0.73, 95% confidence interval 0.51 to 0.05, p = 0. 087), and the numbers of noncardiovascular and other deaths were similar in both groups. We therefore conclude that treatment with simvastatin for up to 8 years in patients with CHD is safe and yields continued survival benefit.

Adult↗
PubMed2000

The apolipoprotein epsilon4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction : a substudy of the Scandinavian simvastatin survival study.

BACKGROUND: Carriers of the epsilon4 allele of the apolipoprotein E gene are at a higher risk of coronary heart disease than individuals with other genotypes. We examined whether the risk of death or a major coronary event in survivors of myocardial infarction depended on apolipoprotein E genotype and whether the benefits of treatment with simvastatin differed between genotypes. METHODS AND RESULTS: Cox proportional hazards models were used to analyze 5.5 years of follow-up data from 966 Danish and Finnish myocardial infarction survivors enrolled in the Scandinavian Simvastatin Survival Study. A total of 16% of the 166 epsilon4 carriers in the placebo group died compared with 9% of the 312 patients without the allele, which corresponds to a mortality risk ratio of 1.8 (95% confidence interval, 1.1 to 3.1). The risk ratio was unaffected by considerations of sex, age, concurrent angina, diabetes, smoking, and serum lipids in multivariate analyses. Simvastatin treatment reduced the mortality risk to 0.33 (95% confidence interval, 0.16 to 0.69) in epsilon4 carriers and to 0.66 (95% confidence interval, 0. 35 to 1.24) in other patients (P=0.23 for treatment by genotype interaction). Apolipoprotein E genotype did not predict the risk of a major coronary event. Baseline serum levels of lipoprotein(a) also predicted mortality risk and could be combined with epsilon4-carrier status to define 3 groups of patients with different prognoses and benefits from treatment. CONCLUSIONS: Myocardial infarction survivors with the epsilon4 allele have a nearly 2-fold increased risk of dying compared with other patients, and the excess mortality can be abolished by treatment with simvastatin.

Adult↗
PubMed2000

The revised joint guidelines.

There is a wealth of scientific evidence that lifestyle interventions and the use of drug therapies in patients with coronary heart disease (CHD) and individuals at high risk for developing CHD can reduce cardiovascular morbidity and mortality. In the revised guidelines of the European Joint Task Force for the prevention of CHD in clinical practice, these individuals remain the priority for prevention. The new guidelines have been formulated as a result of evidence from numerous epidemiological, observational and clinical trials and define specific goals of therapy for the management of lipids, blood pressure and diabetes. The intensity of lifestyle intervention and need for drug therapy should be determined by the absolute risk of a major ischemic event, based on an assessment of all risk factors. Implementation of these recommendations in clinical practice will ensure a common approach to CHD prevention throughout Europe and improve patients' quality of life.

Blood Pressure↗
PubMed2000

Functional characterization of two low density lipoprotein receptor gene mutations by fluorescence flow cytometric assessment of receptor activity in stimulated human T-lymphocytes.

We report a functional characterization of the W23X and W66G low density lipoprotein (LDL) receptor gene mutations. The authors used two-color fluorescence flow cytometry to measure LDL receptor activity in stimulated T-lymphocytes, prepared from patients heterozygous for the W23X or W66G mutation, and compared the results with measurements of LDL receptor activity in stimulated T-lymphocytes prepared from unrelated healthy control subjects. It was found that the W23X mutation significantly reduced LDL receptor expression and LDL binding and internalization, and that the W66G mutation significantly reduced LDL receptor expression and LDL binding. LDL internalization in patients heterozygous for the W66G mutation was not significantly reduced. The data support the concepts that the W23X mutation prevents production of LDL receptors (class I) and that the W66G mutation produces LDL receptors unable to recycle normally in cells (class V).

Adult↗