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Biomedical subjects

L U Gerdes

Publications and source records attributed to L U Gerdes.

At least 55 records · Page 3Linked to original sources
PubMed1993

Apolipoprotein(a) polymorphism predicts the increase of Lp(a) by pravastatin in patients with familial hypercholesterolaemia treated with bile acid sequestration.

HMG-CoA reductase inhibitors effectively reduce the concentration of low density lipoproteins (LDL) in plasma. Lipoprotein(a) [Lp(a)] may be as atherogenic as LDL. A few studies, only one of which was placebo controlled, suggest that the HMG CoA reductase inhibitors either do not affect Lp(a) or they increase Lp(a). The response of Lp(a) to HMG-CoA reductase inhibition has not been related to apolipoprotein(a) phenotypes in previous studies. We conducted a double-blind, placebo controlled study of pravastatin in 51 patients with familial hypercholesterolemia (FH) (n = 43) or probable FH (n = 8). All patients had LDL-cholesterol concentration above 4.1 mmol l-1 despite treatment with diet and bile acid sequestration. In patients assigned to pravastatin (n = 34), the mean concentrations of total cholesterol and LDL cholesterol fell significantly (P < 0.01) when compared to placebo. Lp(a) increased (P < 0.01) from a mean (+/- SD) of 33.6 +/- 40.8 mg dl-1 to 41.1 +/- 46.1 mg dl-1 on pravastatin but was unchanged during placebo treatment. The percentage increase in Lp(a) was the same in patients with different apo(a) phenotypes, and hence the absolute increase in Lp(a) was greatest in patients with the low molecular weight apo(a) phenotypes.

Adult↗
PubMed1992

[A marked decline in the mortality from ischemic heart disease among middle aged Danish men in the 1980's and simultaneous changes of mortality because of other causes].

The mortality from ischaemic heart disease (IHD) in 35-64 year old Danish men has declined by 27% from 1981 to 1989. In the same period, a lesser increase in mortality from all other causes was observed. However, this is a heterogenous phenomenon, since the mortality from (in particular) infectious diseases (AIDS), diabetes mellitus, and a number of diseases related to heavy drinking has increased, whereas the suicide rate and mortality from lung cancer (in 1985-89) have decreased. It is not possible to evaluate the contribution of improved treatment of IHD cases and a decreasing incidence of disease, respectively, to the decline in mortality from IHD. A decreasing incidence is very probable, however, since both the percentage of smokers and the plasma cholesterol levels in middle-aged men have declined significantly since mid-1970s and leisure time physical activity has increased. The trend in IHD mortality in the 1980s points to a sustained decline in the 1990s and a levelling off in the increase in mortality from other causes. Thus total mortality is expected to decrease more rapidly in the 1990s, resulting in an increase in life expectancy of Danish men.

Adult↗
PubMed1992

Effects of perindopril on insulin sensitivity and plasma lipid profile in hypertensive non-insulin-dependent diabetic patients.

About 40% of patients with non-insulin-dependent diabetes (NIDDM) have hypertension, which in turn may contribute to their enhanced risk for cardiovascular diseases. However, a number of antihypertensive agents tend to cause a deterioration in the control of diabetes. The present study was designed to elucidate whether treatment with perindopril (a new angiotensin-converting enzyme [ACE] inhibitor) affects plasma lipid metabolism, glucose homeostasis, and insulin sensitivity. Ten patients with NIDDM and moderate hypertension were studied in a double-blind, placebo-controlled, crossover study encompassing 6 weeks of placebo treatment and 6 weeks of perindopril treatment given in random order. Mean systolic/diastolic blood pressure was 162/94 +/- 6/3 mm Hg during placebo treatment versus 157/91 +/- 5/2 mm Hg during perindopril therapy. Plasma levels of free fatty acids, triglycerides, high density lipoprotein (HDL) cholesterol, and total cholesterol were similar during placebo and perindopril treatment. Oral glucose tolerance tests showed similar responses of plasma glucose, serum insulin, and serum C peptide following placebo and perindopril treatment. Insulin sensitivity estimated with an intravenous insulin tolerance test (IVITT) was unchanged by perindopril therapy (KIVITT: 0.014 +/- 0.001 min-1 [placebo] versus 0.015 +/- 0.003 min-1 [perindopril], difference not significant. In conclusion, treatment with perindopril in NIDDM patients had no adverse effects on plasma lipids, glucose tolerance, or insulin sensitivity.

Aged↗
PubMed1992

Generation of analytic plasma lipoprotein profiles using two prepacked superose 6B columns.

A simple, low-priced chromatographic system to generate plasma lipoprotein profiles from total human plasma was tested with plasma from normolipidemic subjects and patients with heterozygous familial hypercholesterolemia, hyper-alpha-lipoproteinemia, lipoprotein lipase deficiency, familial dysbetalipoproteinemia and familial lecithin-cholesterol-acyl-transferase deficiency. The system appears to be a good alternative to more expensive high-pressure liquid chromatography systems, notably in lipoprotein laboratories already provided with equipment for column chromatography. If a microplate photometer and a computer is available in the laboratory, the measurement of various lipids in 70-80 eluant fractions from the columns can be simplified.

Adult↗
PubMed1992

Apolipoprotein E polymorphism in a Danish population compared to findings in 45 other study populations around the world.

Apolipoprotein E (apoE) phenotypes were determined in a random sample of 466 Danish men born in 1948. The frequencies of the common alleles of the apoE gene were (with 95% confidence intervals) epsilon 2 = 0.085 (0.068-0.105), epsilon 3 = 0.741 (0.712-0.769), and epsilon 4 = 0.174 (0.150-0.200). These frequencies were compared to findings in 45 other study populations around the world (n greater than 100). The Danish population was found to cluster with populations from Iceland, Norway, Iceland, Scotland, the Netherlands, Germany, France (Paris), and Caucasian populations in Canada and the USA. The compiled data further show that dissimilarities in apoE allele frequencies among Caucasian populations are comparable to dissimilarities between some Caucasian and Asian populations. Notably, the frequency of epsilon 4 appears to be higher in northern regions of Europe (the Nordic countries, Scotland, Germany, and the Netherlands) than in southern regions (Switzerland, Tyrol, France [Nancy], Italy, and Spain).

Adult↗
PubMed1992

Differences in apolipoprotein (a) polymorphism in west Greenland Eskimos and Caucasian Danes.

Previous studies in Greenland suggest that death rates from ischemic heart disease [IHD] are lower in Eskimos than in Danes and other Caucasian populations. This has been explained by a high intake of n-3 polyunsaturated fatty acids with beneficial effects on blood lipids and hemostasis. In other populations, lipoprotein(a) [Lp(a)] is associated with IHD, plasma concentrations of Lp(a) being genetically determined to a major extent. We have compared Lp(a) concentrations and apo(a) phenotypes in 120 Greenlandic Eskimos with those in 466 Danish men. The median Lp(a) concentration in Eskimos (8.7 mg/dl;[95% CI 6.5-10.7]) was not significantly different from that in Danes (6.3 mg/dl; [95% CI 5.2-7.0]), whereas the 90th percentile was significantly higher among Danes: 46.36 mg/dl; [95% CI 43.0-54.3] vs. 27.6 mg/dl [95% CI 20.7-36.9]. In 20% of the Danes, but in only 8% of the Eskimos (P = 0.009), the concentration of Lp(a) exceeded 30 mg/dl. The difference is probably explained by a low frequency of the low molecular weight apo(a) phenotypes among Eskimos, since the apo(a) isoforms F and B were absent, and the S1 and S2 types were present in only 3.3% of Eskimos. In contrast, these apo(a) isoforms were present in 26.6% of the Danes in either single-band or double-band phenotypes. The pattern of apo(a) polymorphism found in this study could provide part of a genetic explanation for the putative low rates of IHD in Eskimo populations.

Adult↗
PubMed1992

Treatment of hypothyroidism reduces low-density lipoproteins but not lipoprotein(a).

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apo B) is attached to a large plasminogen-like protein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated. LDL and apo B levels are often elevated in untreated hypothyroidism and lowered by thyroxine (T4) treatment, probably due to an increase in LDL receptors. We measured plasma concentrations of LDL, apo B, and Lp(a) in 13 patients with symptomatic primary hypothyroidism before and during T4 therapy. The mean concentration of LDL decreased significantly (P = .006) from 6.05 mmol/L to 4.07 mmol/L, and the mean concentration of apo B decreased significantly (P = .005) from 1.42 g/L to 1.12 g/L. Median Lp(a) concentrations remained unchanged (P = .77); they were 17.05 mg/dL before and 16.59 mg/dL during T4 treatment. In both the untreated condition and during substitution therapy, Lp(a) levels were higher in patients than in healthy controls, probably due to a relatively high frequency of the small Lp(a) phenotypes in our patients. Since Lp(a) contains apo B, which is a ligand for the LDL receptor, it is surprising that Lp(a) is not reduced along with LDL and apo B. These findings suggest that the catabolism of LDL and Lp(a) differ in some respect, and that thyroid hormones have little, if any, effect on Lp(a).

Female↗
PubMed1992

Placebo-controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non-insulin-dependent diabetic patients with primary hypertension.

The antihypertensive effect of captopril, metoprolol, and hydrochlorothiazide was compared in 23 non-insulin-dependent (NIDDM) diabetic patients less than or equal to 75 years of age, with borderline to moderate primary hypertension. In a double blind, placebo-controlled cross-over trial the patients were treated with 25 to 50 mg captopril, 50 to 100 mg metoprolol, 12.5 to 25 mg hydrochlorothiazide, and placebo, each given twice daily for 8 weeks. Antidiabetic treatment remained unchanged during the study. After receiving placebo for a 4 week run-in period, arterial blood pressure was 168/101 +/- 93/10 (mean +/- SEM) mm Hg. Diastolic blood pressure was lowered significantly during all active treatment periods compared to the placebo value of 97 +/- 2 mm Hg: captopril, 92 +/- 1 mm Hg; metoprolol, 90 +/- 1 mm Hg; hydrochlorothiazide, 91 +/- 1 mm Hg. Metabolic variables were not significantly altered by captopril and metoprolol, while hydrochlorothiazide treatment increased hemoglobin A1c from 7.5 +/- 0.3 to 8.2 +/- 0.4% (P less than .001), decreased high-density lipoprotein-cholesterol from 1.19 +/- 0.08 to 1.10 +/- 0.06 mmol/L (P less than .05). Glomerular filtration rate, urinary albumin excretion, orthostatic blood pressure response, and digital systolic blood pressure in the lower limb remained unchanged during the active treatment periods. The frequency of subjective adverse effects was acceptable during active treatment and not significantly different compared to placebo. We conclude that antihypertensive treatment for 8 weeks with captopril or metoprolol in NIDDM patients is well-tolerated and causes no deterioration in metabolic control and kidney function, while hydrochlorothiazide causes a slight deterioration in glycemic control and lipid profile.

Aged↗
PubMed1992

Normal lipoprotein(a) concentrations and apolipoprotein(a) isoforms in patients with insulin-dependent diabetes mellitus.

Lipoprotein(a) [Lp(a)] is an LDL particle in which apoliporotein B-100 is attached to a large plasminogen-like protein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated, and plasma Lp(a) concentrations above 20-30 mg dl-1 are an independant risk factor for ischaemic heart disease (IHD). To investigate whether Lp(a) could be important for the high cardiovascular mortality rate in patients with insulin dependent diabetes mellitus (IDDM), we determined Lp(a) concentrations and phenotypes in a group of 108 men (median age 32 years) with IDDM without nephropathy. A group of 40-year-old men (n = 466) served as controls. The median Lp(a) concentration was 7.4 mg dl-1 [95% CI 4.9 to 11.7] in the diabetic patients and 6.3 mg dl-1 [95% CI 5.2 to 7.0] in controls. The Lp(a) concentration exceeded 30 mg dl-1 in 22% of IDDM patients and in 20% of controls (P = 0.13). Moreover, the distribution of apo(a) phenotypes did not differ between patients and control. Lp(a) levels and apo(a) phenotypes are thus apparently the same in IDDM patients without nephropathy and controls. These findings do not exclude the possibility that Lp(a) may be increased in patients with nephropathy in whom coronary artery disease frequently co-exist or that Lp(a) in a given concentration is more atherogenic in IDDM patients than in persons without IDDM.

Apolipoproteins↗
PubMed1992

Significant association between low-molecular-weight apolipoprotein(a) isoforms and intermittent claudication.

The role of lipoprotein(a) (Lp[a]) and apolipoprotein(a) (apo[a]) isoforms in symptomatic peripheral atherosclerosis was studied in 100 randomly selected middle-aged (45-69 years) men with intermittent claudication (IC) and 100 randomly selected healthy control (C) subjects. IC and C subjects were matched pairwise for sex, age, and smoking habits. Plasma Lp(a) concentrations were significantly higher in IC subjects, with a median value of 20.12 mg/dl, compared with 11.11 mg/dl in C subjects (p less than 0.0009). The elevated Lp(a) concentration was to a great extent due to a significant difference in the frequency distribution of apo(a) isoforms between IC and C subjects (p less than 0.029). Low-molecular-weight apo(a) isoforms were more prevalent in IC than C subjects. Also, IC subjects with apo(a) S2 and S3 phenotypes had higher Lp(a) concentrations than control subjects with the same phenotypes: S2:60.70 mg/dl (IC) and 48.69 mg/dl (C), p less than 0.038; and S3: 30.18 mg/dl (IC) and 12.01 mg/dl (C), p less than 0.042, so other still-unknown factors, genetic or nongenetic, may be important. Stepwise logistic regression analysis demonstrated that Lp(a) concentration contributed significantly (p less than 0.0002) to IC, independent of age, smoking, hypertension, diabetes mellitus, plasma total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, apo B, and plasma total triglycerides. Apo(a) isoforms grouped according to molecular weight were also independent of the above risk factors associated (p = 0.016) with the occurrence of IC because of their low-molecular-weight but were not independent of Lp(a) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Variation of apolipoprotein B gene is associated with myocardial infarction and lipoprotein levels in Danes.

Three DNA polymorphisms (XbaI, EcoRI, MspI) in the 3'-end of the apolipoprotein B gene were studied in relation to atherosclerosis, lipoprotein levels and age in three groups of atherosclerotic individuals and in nonatherosclerotic controls. The atherosclerotic groups comprised a postmyocardial infarction group with a mean age of 48 years, a group of individuals operated on for carotid stenosis with a mean age of 62 years, and a group of 85-year-olds with clinical coronary artery disease, peripheral arterial disease, or both. All 311 individuals were unrelated Caucasians of Danish ancestry. For the XbaI polymorphism, the X- allele was an independent predictor for myocardial infarction on multivariate analysis, but did not distinguish between patients and controls on univariate analysis. Additionally, this polymorphism was associated with variation in lipoprotein levels, but there was no clear evidence of a gene dosage effect. For the EcoRI polymorphism, the E- allele was associated with elevated levels of VLDL cholesterol, plasma triglycerides and VLDL triglycerides. Similar, but weaker associations were found for the MspI polymorphism. There were no significant differences in allele frequencies as a function of age for any of the DNA polymorphisms. In conclusion, while variation associated with the EcoRI polymorphism appears to be involved in the regulation of VLDL metabolism, variation associated with the XbaI polymorphism may determine susceptibility to coronary artery disease independent of other conventional risk factors, but it also appears to affect variation in lipoprotein levels.

Adult↗
PubMed1991

Functional properties in vitro of systemic small arteries from rabbits fed a cholesterol-rich diet for 12 weeks.

1. Recent evidence has suggested that the impairment of endothelium-dependent cholinergic relaxation in vitro, which is seen in atherosclerotic large arteries of animals and man, could be part of a general deleterious effect to the endothelium of hypercholesterolaemia. 2. This possibility has been investigated in vitro by measuring the response to acetylcholine, sodium nitroprusside, 5-hydroxytryptamine and noradrenaline in segments of aorta and of femoral, mesenteric and cerebral small arteries (internal diameter approximately 200 microns) from control rabbits (n = 12) and from rabbits fed a 1% (w/w) cholesterol and 3% (w/w) coconut oil diet (n = 12) for 12 weeks. 3. Thoracic aorta segments from the control rabbits exhibited a maximal relaxation in response to acetylcholine of 64 +/- 11% compared with 10 +/- 5% (P less than 0.01) for thoracic segments from cholesterol-fed animals. Cerebral, femoral and mesenteric small arteries exposed to acetylcholine (10(-9)-10(-4) mol/l) relaxed to the same degree as arteries from control rabbits. The responses to sodium nitroprusside and bradykinin of the small arteries from the cholesterol-fed rabbits remained unaffected. 5-Hydroxytryptamine evoked comparable contractions in the small arteries, while the sensitivity to noradrenaline of the femoral small arteries was significantly decreased and the response of cerebral small arteries to noradrenaline in cholesterol-fed rabbits slightly increased compared with control rabbits. 4. Aorta from the cholesterol-fed rabbits had extensive atheromatous lesions. Morphological measurements and histological examination showed unchanged thickness and light microscopic appearance of intima and media of small arteries from cholesterol-fed animals compared with control animals. 5. The present study indicates that hypercholesterolaemia in this rabbit model is followed by atherosclerotic lesions and changed function of large arteries, but that both function and structure of systemic small arteries are largely unaffected.

Animals↗
PubMed1991

The psychosocial work environment of younger men surviving acute myocardial infarction.

In a retrospective, consecutive case-control study, the psychosocial work environment of 52 men younger than 55 years, who had survived an acute myocardial infarction, was analysed with respect to workload and work quality using a comprehensive self-administered questionnaire. Patients more frequently reported exhaustion after work, had less responsibility at their job, held less well esteemed positions, and had less possibility of social contact during working hours. These differences bore no simple relationship to social class or conventional risk factor distribution, although higher workloads were associated with a significantly higher frequency of smoking. The study suggests that the ideal cardioprotective job is a well esteemed job at a certain responsibility level with good conditions for social interaction during working hours, in which the experienced job demands are reasonable, and where extra resources are available if needed.

Adult↗
PubMed1990

[Threshold values for hypercholesterolemia: single values or percentiles?].

The distribution of serum cholesterol in the population depends on sex and age. By analyzing data for men and women aged 20-69 from the Copenhagen City Heart Study 1981-1983, it is shown that this dependence is of major importance for the sex and age distribution of subjects classified as hypercholesterolaemic, when single threshold values are used to define the condition (7 mmol/l; 6 mmol/l for subjects less than 30 years): 56% are women, and 38% of these are women aged 50-59. Men between 30 and 59 years of age, for whom the association between hypercholesterolemia and ischaemic heart disease is most pronounced, only constitute 28%. As an alternative to single threshold values, one can use sex- and age-specific percentiles for cholesterol. The advantage appears from the explained cumulative percentage distribution curves in Figures 1 and 2. With the 90-percentiles, it is possible to identify the "cholesterol top-10" of the entire population, and although the use may seem more complicated, it has several advantages, notably the possibility of identifying younger hypercholesterolaemic subjects and making more appropriate use of the available resources for treatment.

Adult↗
PubMed1990

[Measurement of cholesterol in capillary blood using the Reflotron system. Results from approximately 1,000 comparisons with reference measurements of cholesterol in venous serum].

The results of 969 measurements of total cholesterol in capillary blood from fingerstick, performed with the Reflotron-system in the field, were compared with measurements of total cholesterol in venous serum. The comparison allows an evaluation of the combined effect of differences in sample material, working place, stability of methods and staff training. The mean values for all measurement were nearly identical with the two methods, and approximately 95% of the Reflotron-measurements were within an interval of +/- 0.7 mmol/l around the estimated true value. However, values below approximately 6 mmol/l were systematically underestimated, and values above approximately 7 mmol/l were overestimated with the Reflotron-system. The coefficient of variation of the system is below 5%, but both this precision and the accuracy appear to be unstable. Evaluated as a tool in screening for hypercholesterolemia, measurements with the system resulted in a modest extent of erroneous classification of subjects, but the positive diagnostic predictive value of the statement "cholesterol above 7 mmol/l" is only approximately 76%. Simulations of likely variations in the accuracy and precision of the method show a significant influence on the extent of errors. It is recommended that measurements with the system are routinely controlled by measuring an appropriate control material, at the start of each run and after every 30 samples.

Adult↗
PubMed1990

[A comparison of results of simple evaluation of the risk of ischemic heart disease with calculations based on a multiplicative model].

A simple model for detection of subjects at risk of ischaemic heart disease, based on the addition of scores for different risk factors (Anggaard EE, Land JM, Lenihan J et al. Br Med J 1986; 293: 177-80), is at present widely applied in Denmark. The model could be tested in a prospective study, or a historical follow-up study, but we do not have the possibilities to do so. Instead we have compared the risk score of the model with the estimated five-year coronary mortality risk (ECR) in 742 men aged 40-44 years, calculated on the basis of data from the Seven Countries Study. There is a reasonable consistency in this comparison, in spite of the different principles of calculation, the consideration of different risk factors and/or weighting of risk factors. For example, the model has a sensitivity of 71%, a specificity of 89% and a positive predictive value of 68% in detecting 40-44 year old men in the upper quartile of ECR. The "false positives" are often men, who for other reasons may require preventive medical attention (obese heavy smokers), and the "false negatives" are often men with isolated hypertension.

Adult↗
PubMed1990

[Occurrence of cardiovascular risk factors among working Danish men 20-59 years of age].

The prevalence of risk factors for ischaemic heart disease (IHD) was recorded in 1,365 men aged 20-59 years in active employment. The purpose was to evaluate the implications of a high-risk strategy based on the rather conservative Danish guidelines for treatment of hypercholesterolemia. The prevalence of various risk factors depends on age, but in all, 1% had diabetes mellitus, 5% had a family history of premature IHD, 50% were smokers, 21% were obese, 12% had systolic blood pressure greater than or equal to 160 mmHg, 8% had diastolic blood pressure greater than or equal to 100 mmHg and 14% had serum cholesterol greater than 7 mmol/l. Only 24% had none of these risk factors and there was a considerable clustering of risk factors in certain subgroups. Approximately 34%, varying from 17% of the younger to 49% of the older, required medical follow-up as part of the high risk strategy. We have estimated the required number of visits to a general practitioner, if all Danish men aged 20-59 years were screened within three years and approximately 30% required follow-up for five years, with three visits in the first year and one thereafter. The number of visits peaks at 450 visits per year during the third year, and a number of circumstances could reduce this figure considerably. Multifactorial models to estimate risk in connection with screening should be adopted to the Danish guidelines for treatment of hypercholesterolemia and hypertension, and future guidelines for intervention should probably be integrated in such a multifactorial model. To practice preventive medicine, many physicians will need greater knowledge of dietary counselling.

Adult↗