A weighty matter

Posters

12. Miscellaneous

104

IP228

LONG TERM LIPID-APHERESIS WiTH SEVERE FAMILIAL

IN THREE CHILDREN IIYPERCHOLESTEROLEMIA

U. Kassner, A. Vogt, H.-P. Thomas, E. Steinhagen-Thiessen. Char&?, firchow-Klinikum, Lipid Department, Humboldt-University of Berlin, Germany

We are reporting about three sisters of turkish descent with severe familial hypercholesterolemia. They all presented in 1990 (age 3, 5 and 7) with multiple xsnthomas, high serum low-density-lipoprotein-cholesterol-levels (LDL-C) (girl 1: 566 mg/dl, girl 2: 852 mg/dl, girl 3: 582 mg/dl) and normal serum triglyceridlevels (TG). They also have a positive family history for premature coronary artery disease (CAD). During standard hypolipemic diet and use of resins serum LDL-C-levels decreased (girl 1: 445 mg/dl, girl 2: 523 mg/dl, girl 3: 423 mg/dl). Since patients with not adequately treatable severe hypercholesterolemia are at very high risk to develop premature CAD extracorporal lipid-apheresis on a weekly basis was initiated. Girl 1 is treated for almost nine years, girl 2 for six years and girl 3 for four years now. All three children tolerate lipid-apheresis very well and serum LDL-C is reduced effectively. The over all.reduction of LDL-C (first visit - last visit) in girl 1 is 64%, in girl 2 70% and in girl 3 56%. A single treatment results in a mean acute decrease of LDL-C in girl 1 of about 70%, in girl 2 of about 61% and in girl 3 of about 66%. In all three children an almost complete regression of xanthomas was achieved. Baaed on annual echocardiograms and duplex ultrasounds of the carotic arteries no aortic valve stenosis or progressive arteriosclerosis were revealed. Conclusion: Lipid-apheresis is safe and highly effective to reduce LDLC-levels, to prevent arteriosclerotic complications and leads to impressive regression of the described xanthomas. IP229

LIPOPROTEINS AS PREDICTORS OF POOR OUTCOME IN ACUTE ISCHEMIC STROKE

L. Denti A. Cecchetti, S. Perelli-Ercolini, F. Ablondi, L. Marchini, -9 ME Merli, A. Giordano, M. Sacco’, G. Valenti. Chair of Gerontology and Geriatrics; University of Parma, Parma, Italy The relation between lipoprotein and risk for ischemic stroke has been exten-

sively investigated in cross-sectional and prospective observational studies. Some lipoprotein fractions, such as Lp(a), Tg and LDLox, which can reportedly affect hemostasis and/or fibrinolysis, could also influence the outcome of acute stroke, by interferring in rivascularization processes. However, data on the predictive value of lipids of stroke outcome are scarce. This study was aimed to assess if serum lipid concentrations, assessed within 24 hours from stroke onset, are predictive of outcome. 74 patients (mean age 82.9 +/- 7.4, range 67-99), consecutively admitted to a Geriatric Ward. Complete clinical and laboratory assessment, comprehensive of neurological evaluation, head CT scan, carotid ultrasonography and ECG to define clinical and etiologic stroke subtype, according to standardized criteria. Fasting blood samples were collected within 48 hours from admission, for assay of TC, TG, HDL-C (enzymatic-colorimetic method), Lp(a) (immuno-enzymatic assay), ApoAI and ApoB (immuno-turbidimetric method). Univariate and multiple logistic regression analysis, with adjustment for other related clinical covariates, was used to assess the relation of lipids to poor outcome, defined as severe disability (Barthel index < 60/100) or death, at 1 month (or at discharge) and at 3 months. Lipids were also related to neurological evolution, assessed at admission and after 1 week and 1 month (or at discharge) by NIHSS. Patients showed significantly lower HDL-C and HDL-C/ApoAI ratio than age and sex-matched controls, while Lp(a) values were similar. However, no significant association was found between any lipid fractions and either poor outcome or neurological improvement. In conclusion, in our study, admission lipid levels did not give any contribution to clinical and functional outcome, both in the short and the long term. This is true also for Lp(a) and TG, in spite of their potential influence on fibrinolysis processes. In addition, these results co&m the independence of neuronal metabolism from circulating cholesterol.

P230 SERUM LEPTIN LEVELS: RELATIONSHIP WITH cl GLUCOSE TOLERANCE AND LIPID PROFILE

BMI,

E.M. Repetto, B. Geloneze, M.R. Picolo, S. Rodovalho-Geloneze, S.G. Pereira, M.A. Tambascia. Endocrine Unit - State University of Campinas, Brazil

Leptin is produced and released by adipose tissue and is directly related to adiposity. In recent studies leptin has been associated with metabolic abnormalities related to cardiovascular risk such as dyslipidemia and diabetes. To assess the relationship of serum leptin levels with the lipid profile in a wide range of BMI and glucose tolerance status. We studied 205 patients: 55 type 2 diabetic (DM) and 150 normotolerant (NGT) according to ADA criteria, with wide range of BMI (2l78 kg/m2). Mean body mass index was: in the NGT = 40fll and in DM = 43fl4 kg/m’). Serum leptin concentration was measured and correlated to glucose tolerance status and to lipid profile (total cholesterol, LDL-chol, HDL-chol and tryglicerides). Our data showed that leptin correlated closely to BMI (r = 0.70) in both groups. There were no differences between NGT and DM groups (Leptin = 42rt27 and 43f37 ng/dL respectively). In a multivarited analysis leptin were not associated with plasma lipid levels in both groups. Serum leptin levels were significantly correlated to BMI, but not to glucose tolerance and plasma lipids. Our data support the hypothesis that leptin is not directly associated to lipid profile in normal and diabetic patients. Ip231(

ROLE OF THE ALCOHOLS GLYCEROL AND CHOLESTEROL IN THE TRANSPORT AND INTRACELLULAR INTERNALIZATION OF FATTY ACIDS. DIAGNOSTIC SIGNIFICANCE OF HYPERCHOLESTEROLEMIA

VN. Titov, D.M. Lisitsin, M.G. Tvorogova. Russian Cardiology Research Center 3& Cherepkovskaya St,: ISA, Moscow 122551; Institute of Chemical Physics, Russian Academy of Medical Sciences, Russia

A method quantitative determination of double bonds (DB, mmol/L) in blood serum pool of fatty acids (FA) has been developed. It consists in ozone titration of lipids extracted from the serum by the method of Folch. Serum DB content correlates with the levels of the alcohol cholesterol (CL) (r = 0.612, p < 0.001) and the alcohol glycerol (CL, r = 0.392, p < 0.001). The BD: (CL + GL) in mmol/L proved to be constant (5.08~tO.11) in adults and children, as well as in ischemic heart disease and myocardial infarction. It is suggested that the alcohol GL and CL are involved in the lipoprotein transport and receptor-mediated uptake of saturated and unsaturated FA (glycerol) and of essential polyenic FA in the form of nonpolar esters (cholesterol). High blood content of the alcohol GL reflects the accumulation of saturated and unsaturated FA in the form of triglycerides as a result of impaired of uptake of these FA by cells. High blood content of the alcohol CL indicates blood accumulation of essential polyenic FA in the form of polyesterified CL (poly-ECL). Lipoproteins separately transport and cell separately internalize saturated and essential poly-FA via apoEiB-100 and apoB-100 receptor-mediated endocytosis. Poly-ECL is functionally nonpolar form of essential poly-FA, mono-ECL is nonpolar form of the alcohol LC. Low-density lipoproteins are the major transportation and internalization form of essential poly-FA as nonpolar poly-ECL. Independent increases in blood contents of the alcohols glycerol and CL indicate two individual pathologies disturbances in cellular uptake of saturated and polyenic FA. Atherosclerosis is a conseguence of blocked apoB-100 ligand-receptor binging and internalization of w-3 and w-6 essential poly-FA, their intracellular deficiency and compensatory synthesis of w-9 eicosanoids. Experiments in various laboratory animal species will show whether the DB/(GL==CL) ratio is a biological constant. 0P232A WEIGHTY

MATTER

P.J. Twomey, M. Ireland. Departments of Clinical Biochemisiry and Nutrition & Dietetics, Royal Infirmary Edinburgh EH3 9rW, UK Following the Joint British recommendations on prevention of coronary, heart disease in clinical practice a retrospective audit was conducted on 76 patients aged ~75 who were discharged in 1999 post an acute admission for a myocardial infarction. The purpose of the audit was to evaluate the discharge summaries provided to general practitioners with respect to dietary risk factors. The following data points were obtained from the discharge summaries in the patients’ hospital case notes: weight, body mass index,

72nd EAS Congress

Posters 12. Miscellaneous including statements describing body habitus, cholesterol level, whether the patients was seen by a dietitian and the advice provided if seen. The dietetic database was checked to see how many patients received dietetic advice. None of the 76 discharge summaries mentioned the patients’ weight or body mass index. 4 discharge summaries mentioned that the patient was obese or overweight. Only 1 discharge summary mentioned that the patient was advised to lose weight. Nineteen of the patients were referred to the dietetic service and were provided with advice for lipid lowering (S), diabetes/lipid lowering (6), lipid lowering/weight reduction (4) and diabetes/high protein diet (1) respectively. None of the patients with a cholesterol < 5.0 mmol/L recorded in the discharge summaries was referred for dietary advice. Requests for lipid lowering advice seems to be the main reason for referral to the dietetic service for patients post myocardial infarction. Obesity does not seem to rate highly as a risk factor in the prevention of coronary heart disease despite its prevalence and metabolic effects. Senior House Officers wrote the majority of discharge summaries. An educational programme outlining the risk factors that should be communicated to the primary healthcare team may thus improve the quality of the discharge summaries. Additionally, the dietetic referral procedures may need to be reviewed. IP233

TIMING

IS IMPORTANT

P.J. ‘Rvomey. Department of Clinical Biochemistry, Edinburgh EH3 4EU, UK

Royal Znjrmary

Following the Joint British recommendations on prevention of coronary heart disease in clinical practice a retrospective audit was conducted on 65 patients aged ~75 who were discharged in 1999 post an acute admission for a myocardial infarction. All patients were followed up by a cardiac rehabilitation sister and were actively encouraged by her to have their cholesterol re-measured in the community. The purpose of the audit was to determine the lipid request pattern for these patients after hospital discharge to assess the implementation of the Joint British recommendations. Data was obtained from the laboratory computer system commencing from the admission date recorded in the patients’ case notes.

Number

of cbcdesterol requests between

6-13 weeks post event

Number

0

37 (56)%

I

27 (42)%

2

I (Z)%

of patients

Approximately half of the patients did not meet the Joint British recommendation criteria of having their cholesterol re-measured between 6 and 13 weeks post myocardial infarction. By six months, more than a quarter of patients still needed their cholesterol to be re-measured. One-fifth of patients had a cholesterol re-measurement that was performed during the acute phase response. It is worrying that 56% of these patients who were actively followed up by a cardiac rehabilitation sister did not meet the criteria set down by the Joint British recommendations. The fact that 28% of patients did not have a recorded cholesterol level by 6 months suggests that an alternative strategy may be needed. The prescription of efficacious statin doses before discharge from the hospital setting may help to overcome the under-treatment of these patients. For such a policy to work, the cholesterol level on samples obtained within 24 hours of the onset of chest pain is necessary to establish the degree of cholesterol lowering that is required to attain target values. The 20% of patients who had samples analysed too soon may have an underestimation of the degree of dyslipidaemia. The result may be the absence of treatment or decreased efficacy of treatment for hypercholesterolaemia. Should be we not spread the message to cardiologists and general practitioners that timing is everything if they want to reduce the burden of ischaemic heart disease? IP234

LET’S NOT FORGET

TIMING

P.J. Twomey. Department of Clinical Biochemistry, Edinburgh EH3 4EU, UK

Royal Znjrmaty

Following the Joint British recommendations on prevention of coronary heart disease in clinical practice a retrospective audit was conducted on 65 patients aged ~75 who were discharged in 1999 post an acute admission for a myocardial infarction. The purpose of the audit was to determine the lipid request pattern while these patients were under the care of the cardiologists.

105

Data was obtained from the laboratory computer system commencing from the time of onset of chest pain or admission time recorded in the patients’ case notes. Aaalyte

No. of samples

Sampler collected < 24 houn

Samples

colkcted

> 24 hours

Cholestenul

89

44 (49%)

45 (51%)

Trt@yceride

75

34 (45%)

41 (55%)

HDL-C LDGC

37 35

14(38%) 13(37%)

23 (62%) 22(63%)

The majorityof lipids analysed were on samples that were collected after 24 hours Approximately half of the patients had a sample collected within 24 hours analysed for cholesterol and random triglycerides with about one-fifth having HDL-cholesterol measured within 24 hours. Serum HDL-cholesterol and total cholesterol continue to be risk factors for recurrent ischaemic heart disease events after a myocardial infarction. In patients acutely post myocardial infarction, serum total cholesterol and LDL-cholesterol as well as serum HDL cholesterol decrease. Thus, lipid measurements on a sample that is collected within 24 hours of the onset of chest pain may give some reflection of the concentration of total cholesterol and HDL cholesterol before the acute event. However, samples collected after this period will lead to an underestimation of the dyslipidaemia. It may be in the laboratory’s and patient’s interest to have a mechanism in place such that patients with a myocardial infarction have one full lipid profile requested automatically on a sample that has been collected within the first 24 hours of the onset of a chest pain. Ideally, further lipid requests would be ignored to avoid artefacts due to the acute phase response. My data suggests that such a mechanism may be more cost effective from the laboratory point of view and would also help to identify risk factors such as low HDL-cholesterol that some cardiologists seem to overlook despite the available evidence.

IP235

BINDING OF NATIYE AND NATURALLY OCCURRED MULTIPLE-MODIFIED LDL WITH ELASTIN OF UNINVOLVED AND ATHEROSCLEROTIC HUMAN AORTA

VV Tertov I.\! Suprun, T.A. Scalbe, L.A. Medvedeva, AN. Orekhov. _> Institute of Experimental Cardiology; Institute for Athewxclemsis Research, Moscow, Russia Several years ago we have found and isolated a subfraction of naturally occurred multiple-modified LDL (nomLDL) which produced lipid accumulation in human aortic intimal smooth muscle cells and macrophages. In present study we studied the comparative binding of native LDL and nomLDL with elastin and proteoglycans from early and developed atherosclerotic lesions to evaluate the possible role of nomLDL in extracellular lipid deposition. Native LDL and nomLDL were isolated by lectin chromatography and iodinated using ICl-procedure. Elastin, collagen and proteoglycans were isolated from proteoglycan-rich and muscle elastic sublayers of intima and media of uninvolved and atherosclerotic human aorta. The binding of nomLDL with elastin from proteoglycan-rich sublayer of normal intima was 2-fold higher as compare to native LDL. NomLDL was bound to elastin from proteoglycan-rich sublayer of initial lesions and fatty streaks 2- and 5 fold efKectively than with normal elastin. The association of nomLDL with elastin from proteoglycan-rich sublayer of fibroatheroma was 2-fold lower than to elastin from fatty streaks. The closed changes in lipoprotein binding was observed for the elastin from muscle etastic sublayer of human aorta. The binding of native and nomLDL with elastin from media of normal and atherosclerotic areas was similar. Retention time for nomLDL in preformed lipoprotein-elastin complexes was longer than for native LDL. Binding of nomLDL was correpondent to positive charged amino acid level in aortic elastin. The binding of nornLDL to proteoglycans from proteoglycan-rich and muscle elastic sublayers of normal intima was 2and 3-fold, correspondently, higher than of native LDL. The binding of native LDL and nomLDL to proteoglycans of both intimal sublayers decreased in order: norma > initial lesions > fatty streaks > fibroatheroma. The similar changes in lipoprotein binding was observed for the proteoglycans from media layer of human aorta. The binding of native LDL and nomLDL correlated possitively with proteoglycan level of chondroitin sulphate A and C, and negatively with derrnathan sulphate content. Binding of nomLDL with collagen from proteoglycan-rich and muscle elastic sublayers of fibroatheroma v+as 2-fold higher than to collagen from normal intima. Complexes of nomLDL with collagen, elastin and proteoglycans stimulated cholesterol accumulation

72nd EAS Congress