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Biomedical subjects

G Assmann

Publications and source records attributed to G Assmann.

At least 91 records · Page 5Linked to original sources

Lipoprotein(a) is an independent risk factor for myocardial infarction at a young age.

We quantified lipoprotein(a) [Lp(a)] immunochemically in young (less than 46 y) male survivors of myocardial infarction and in age-matched controls recruited from participants of the Prospective Cardiovascular Münster (PROCAM) study. We further determined apolipoprotein E polymorphism and measured triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol (HDL and LDL), and apolipoproteins AI, AII, and B in the serum of these subjects. Lp(a) concentrations in serum were not correlated with other well-recognized risk factors for early myocardial infarction such as apolipoproteins AI and B, LDL cholesterol, and HDL cholesterol. Apolipoprotein E polymorphism did not affect Lp(a) concentrations, but had a major influence on apolipoprotein B concentration. Lp(a) concentrations were not influenced by age. Our data suggest that (a) an increased concentration of Lp(a) constitutes an independent risk factor for early myocardial infarction and (b) the concentrations of Lp(a) and LDL cholesterol (apolipoprotein B) in serum are under separate metabolic control.

Age Factors

Diabetes mellitus and hypertension in the elderly: concomitant hyperlipidemia and coronary heart disease risk.

Age is an important factor in predicting risk of myocardial infarction (MI). Age is currently treated as an independent variable in assessing risk, but it is also related to other major risk factors including hyperlipidemia, hypertension and diabetes, all of which increase in prevalence with age. Current evidence indicates that a combination of 2 or more of the major risk factors predisposes a person to a high risk of MI. In the experience of the Prospective Cardiovascular Munster study, patients with diabetes alone have twice the risk of MI, but those with diabetes and hyperlipidemia have about a 15-fold increased risk. Similarly, patients with hypertension alone have twice the risk of MI, but those with hypertension combined with hyperlipidemia have approximately a 15-fold increased risk.

Adult

European lipid guidelines: therapeutic recommendations. European Atherosclerosis Society.

The European Consensus Conference has classified persons with hyperlipidemia into 5 groups on the basis of cholesterol and triglyceride levels. Plasma cholesterol concentration alone is not sufficient for the assessment of myocardial infarction risk; other risk factors must be considered for a more sensitive prediction. Guidelines for risk assessment of coronary heart disease and treatment regimens for each of the 5 hyperlipidemia groups, as outlined in the Policy Statement on coronary heart disease of the European Atherosclerosis Society, are described. It is emphasized that therapeutic goals for patients with hyperlipidemia depend to some extent on the presence or absence of other risk factors; plasma cholesterol and low-density lipoprotein cholesterol target levels may be lower in those with associated risk factors.

Age Factors

Apolipoprotein A-I variants. Naturally occurring substitutions of proline residues affect plasma concentration of apolipoprotein A-I.

Six unrelated families with genetically determined structural variants of apo A-I were found in the course of an electrophoretic screening program for apo A-I variants in dried blood samples of newborns. The following structural variations were identified by the combined use of HPLC, time-of-flight secondary ion mass spectrometry (TOF-SIMS), and automated gas phase sequencing: Pro3----Arg (1x), Pro4----Arg (1x), and Pro165----Arg (4x). All variant carriers were heterozygous for their mutant of apo A-I. Subjects heterozygous for apo A-I(Pro165----Arg) (n = 12) were found to exhibit lower mean values for apo A-I (109 +/- 16 mg/dl) and HDL cholesterol (37 +/- 9 mg/dl) than unaffected family members (n = 9): 176 +/- 41 and 64 +/- 18 mg/dl, respectively (P less than 0.001). In 9 of 12 apo A-I(Pro165----Arg) variant carriers the concentrations of apo A-I were below the fifth percentile of sex-matched controls. By two-dimensional immunoelectrophoresis as well as by densitometry the relative concentration of the variant apo A-I in heterozygous carriers of apo A-I(Pro165----Arg) was determined to account for only 30% of the total plasma apo A-I mass instead of the expected 50%. Thus, the observed apo A-I deficiency may be largely a consequence of the decreased concentration of the variant apo A-I. In the case of the apo A-I(Pro3----Arg) mutant, densitometry of HDL apolipoproteins demonstrated a distinctly increased concentration of the variant proapo A-I relative to normal proapo A-I. This phenomenon was not observed in the apo A-I(Pro4----Arg) mutant or in other mutants. This suggests that the interspecies conserved proline residue in position 3 of mature apo A-I is functionally important for the regular enzymatic conversion of proapo A-I to mature apo A-I.

Amino Acid Sequence

Comparison of the reflectance method (Reflotron reflectance photometer) with the absorbance method (automatic analysers) for the determination of cholesterol.

The European Atherosclerosis Society (1) and the Expert Panel of the US National Cholesterol Education Program (2) have issued detailed guide values for recognition and management of hyperlipidaemia in adults. In these guidelines, the diagnosis of dyslipidaemia based on the measurements of total cholesterol, triacylglycerols, HDL and LDL cholesterol plays an important role. A prerequisite for the desired success of interventive measures is the reliability of the analytical data. The aim of this study was to investigate the precision and accuracy of Reflotron Cholesterol, a method based on the dry chemistry principle. Accuracy was assessed by establishing the correlation with the standardized automated methods used in routine lipid diagnosis. In addition, it was also examined whether the Reflotron Cholesterol results in plasma and blood are comparable. The Reflotron cholesterol (sample: blood) showed a good correlation with the CHOD/PAP method on a Hitachi 737 instrument (sample: plasma). The median value of the differences of the test results was -0.4%. Similarly, the method comparison of Reflotron Cholesterol (sample: blood) versus CHOD/PAP method on a SMAC instrument (sample: plasma) showed that Reflotron produces slightly (1.8%) higher results. The Reflotron Cholesterol values obtained from blood samples were slightly lower than those from plasma samples (median value of the differences: -2.2%). The results suggest that for routine purposes Reflotron Cholesterol provides results which are in good agreement with those obtained by standardized wet chemistry methods.

Autoanalysis

[Results of the "Munster Prospective Cardiovascular" study].

In the 'Prospective Cardiovascular Münster' (PROCAM) study since 1979 employees have been examined for cardiovascular risk factors and held under observation for the onset of clinically significant signs of atherosclerosis (myocardial infarction, stroke, coronary death). Until the end of recruitment (end of 1985) 20,060 male and female employees aged 17-65 from 52 industrial companies in Westfalia have participated. The voluntary examination at the start of the observation period includes a standardised questionnaire, a physical examination, blood pressure measurements and an ECG. Blood samples are taken after an overnight fast. The data presented here describe the longitudinal evaluation of initially healthy men aged 40 to 65 who had suffered no myocardial infarction or stroke before the examination. In an uniform follow-up period of four years 73 myocardial infarctions and coronary deaths were observed while 2681 men had survived without myocardial infarction or stroke. By far the best single parameter for establishing a risk group was HDL cholesterol. Using the characteristic hyper/dyslipoproteinemia which means cholesterol greater than = 300 mg/dl or HDL cholesterol less than 35 mg/dl combined with cholesterol greater than = 200 mg/dl and/or triglyceride greater than = 200 mg/dl or a multiple logistic function including age, cholesterol, HDL cholesterol, systolic blood pressure, cigarette smoking, diabetes mellitus, angina pectoris and a family history of myocardial infarction patients at high risk for coronary heart disease could be identified. More than two thirds of new events happened in each of these high risk subgroups, which comprise less than 20 percent of men under consideration each.

Adolescent

The Prospective Cardiovascular Münster (PROCAM) study: prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease.

The ongoing Prospective Cardiovascular Münster (PROCAM) study was initiated in 1979. The objectives of this trial were to determine the prevalence of coronary heart disease (CHD) risk factors in the German population, improve the prediction and early detection of CHD, and derive recommendations for the primary prevention of vascular disease from the trial results. Of male PROCAM trial participants, ages 40 to 65 years, who had been free of myocardial infarction or stroke at the time of entry and had been followed up for 4 years, longitudinal data analysis shows that hypertension, diabetes mellitus, and hyperlipidemia are independent risk factors for CHD. The concomitant occurrence of these factors leads to a cumulative increase in CHD risk. Hyperlipidemia is a more significant risk factor for CHD than hypertension or diabetes mellitus. Ongoing data from 4043 men and 1333 women, ages 50 to 65 years, show that more than 50% of all diabetics are hypertensive. Cholesterol is slightly increased in male hypertensives and diabetics of either sex, whereas low-density lipoprotein cholesterol is slightly raised in male hypertensives and female diabetics only. The serum triglyceride concentrations are higher for hypertensives and markedly higher for diabetics of both sexes. High-density lipoprotein cholesterol concentrations are decreased in hypertensives, especially in hypertensive women, and even more so in diabetics. The European Consensus Conference for primary prevention of CHD has classified hyperlipidemia into five groups (A to E). For hypertensives, the proportion of patients in group D (cholesterol between 200 and 300 mg/dl and triglyceride levels between 200 and 500 mg/dl) is 20.4% for men and 6.2% for women, about twice as high as those in the control groups. The occurrence of combined (group D) or massive hyperlipidemia (group E: cholesterol greater than 300 mg/dl and/or triglycerides greater than 500 mg/dl) is prevalent in more than 30% of all diabetics: two to three times more frequently than in nondiabetic patients. When concomitant hypertension is included, this prevalence increases to more than 40% for diabetic men. Among those patients endangered by three risk factors, approximately 40% of all men and 60% of all women have the particularly atherogenic combination that includes lowered high-density lipoprotein cholesterol.

Adult

[The tumor marker CA 15-3 in breast cancer in serum and cell compartments as an additional prognostic criterion].

In 86 woman patients having a histologically confirmed carcinoma of the breast we examined during primary treatment the CA 15-3 data in the compartments serum, cytosol and a membrane fraction. Low CA 15-3 levels in the serum combined with high concentrations in cytosol and the membrane fraction were associated with a good prognosis, whereas a poor prognosis was seen in case of high serum values and simultaneously low values in the cytosol and the membrane fraction. Hence, it seems that prognoses of the future course of the disease are possible if the CA 15-3 values are simultaneously determined in the serum, in cytosol and in a membrane fraction.

Adult

Apolipoprotein A-I (Glu 198----Lys): a mutant of the major apolipoprotein of high-density lipoproteins occurring in a family with dyslipoproteinemia.

To detect genetic mutants of apo A-I, the major structural protein of human HDL, we screened 530 unrelated Austrian probands (168 children, 362 adults). An apo A-I mutant characterized by an exchange of the acidic amino acid Glu in position 198 with the basic amino acid Lys was identified in the serum of the mother of a hyperlipoproteinemic girl. So far only two patients with this mutant, referred to as apo A-I (Glu 198----Lys) have been described. We detected six new patients (two children and four adults) with apo A-I (Glu 198----Lys) among 20 members in three generations of the affected family. An autosomal codominant inheritance of the apolipoprotein variant could be established. All affected individuals were heterozygous for the mutant. Among the six new subjects with apo A-I (Glu 198----Lys) two children and one adult presented with high-density lipoprotein (HDL) cholesterol concentrations below the fifth percentile for age and sex and with low serum apo A-I and A-II. Although there was no consistent relationship of the mutant with low serum HDL in this family, a moderate effect of apo A-I (Glu 198----Lys) on HDL levels cannot be ruled out. Hyperlipoproteinemia of types IIa, IIb, and IV was observed in eight of the 20 family members studied, but did not cosegregate with the mutant apo A-I. There was no association of apo A-I (Glu 198----Lys) with premature clinical manifestations of atherosclerosis. The mutation occurred in a part of the apo A-I molecule, which is thought to be involved in lipid binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent