24
Monday 10 October 1994: Poster Abstracts Risk factors
and after treatment. Analysis of covariance was done using age, body mass index and smoking as covatiables. OEHF’ had a lower K (1.42f0.50 vs 1.96f0.74min-‘, P c O.Ol), IMGU (4.42% 2.15 vs 7.28 f 4.44 mg/K min, P = 0.01) and AUC (5508 f 2849 vs 8402 f 5267 @U/ml f min. P= 0.02) than controls. IR did not differ significantly (3.11 f 1.90 vs 3.63 f 2.38 min-l@U/ml)-‘). Quinaptil decreased blood pressure (163/104 vs 149/97 mmHg, P < 0.01) but glucose tolerance (Kg 1.57 f 0.47 vs 1.54 f 0.45), IR (3.89 + 2.96 vs 3.36 f 2.52) and lipid metabolism did not change significantly. Serum uric acid levels were similar before and after treatment (5.6 f 1.8 vs 5.6 f 1.7 mg/dl). Our results show that OEHF have a lower glucose tolerance because of reduced insulin secretion, hypertension does not increase the severity of insulin resistance already present in obesity, and quinapril does not increase the risk for coronary heart disease. Prevalence of and risk factors for uitrasoundquantified atherosclerosis in a free-living representative middle-aged population: the ‘MaImiI Diet and Disease Study’ Berglund LG, Janzon L, Elmstil S, Wallmark A, &j&i_&
1
Dept. of Community Health Sciences, MalmcY General Hospital, Lund Univ. 214 01 Malmii, Sweden
In a study of the association between cardiovascular risk indicators and atherosclerosis a random sample of 4490 men and women aged 45-65 were investigated ultrasonographically in the right carotid artery, in a pre-defined ‘window’ extending 3 cm proximal and 1 cm distal to the bifurcation. Common carotid intima-media thickness (IMT, a measure of early atherosclerosis) was calculated off-line as the distance between the leading edges of the inner and outer echoes of the double-line pattern of the far wall. Plaque occurrence. (late atherosclerosis) within this window was determined semiquantitatively. Mean age was 58 It 6 years for both sexes. IMT was greater for men (0.78 lt0.17) than women (0.74*0.13), P
m,
Apolipoprotein E genotype as a risk factor for coronary heart disease mortality among men aged 6584 years: the Finnish cohorts of the Seven Countries Study Pekkanen J, Ehnholm C, Nissinen A, Sing CF. Na-
tional Public Health Inst.. Mannerheimintie 166, 00300 Helsinki, Finland
Earlier we reported that allelic variation of the gene coding for apolipoprotein (apo) E is a significant predictor of risk from coronary heart disease (CHD) death in a longitudinal 5-year follow-up of two cohorts of elderly Finnish men aged 65-84 years, one in Eastern (n = 297) and the other in South-Western Finland
(n = 369). Here we address whether the apo E polymorphism confers information about risk of CHD death after adjustment for other putative CHD risk factors. The two most frequent genotypes were ~33 (68% in the East and 57% in the South-West) and ~34 (23% in the East and 3 1% in the South-West). Five-year CHD mortality in the men who had the ~33 genotype was 7.9% in the East and 7.6% in the SouthWest. For ~34 men the respective percentages were 11.6% and 19.5%. In the South-Western cohort relative risk of CHD death, adjusted for age, total and HDL cholesterol, systolic and diastolic blood pressure, BMI, and smoking status, was significantly higher in the ~34 men (odds ratio (OR) = 2.5,95% CI 1.7-3.7) than in the ~33 men. This was not true in the Eastern cohort (OR = 1.4, 95% CI 0.8-2.3). In contrast, the OR for the group of rare genotypes (~24(n = 6) and ~44 (n = 3) combined) was higher (OR = 5.1,95% CI 3.0-12.0) in the East. In the South-West the OR for ~24 (n = 16, no EM recorded in the South-West) was 1.4 (95% CI 0.6 3.3). We conclude that the apo E polymorphism is a significant risk factor for CHD death in these cohorts of elderly Finnish men, after adjustment for other CHD risk-factors. Is the serum concentration of apolipoprotein B a more suitable parameter than chotesterolemia for the screening of children at risk of coronary artery disease? &&g@& Dept. of Pediatrics, Charles Univ., E. BeneSe 13, 305
1
99 Plzen, Czech Republic 437 first-grade. students from Plzefi (age 6 years) were chosen to test the relation between cholesterolemia and semm concentration of apolipoprotein B (apo B) and an early myocardial infarction (MI) in the family history of these students. A questionnaire formulated to gain information about the family history of premature cardiovascular disease was returned by the parents of 365 children. 57 of these children had parents or grandparents with documented early MI. On the basis of the completed questionnaires, 177 boys and 188 girls were tested for TC and semm apo B from samples from the finger capillary blood. In 100 of these children, the concentration of apo B from capillary blood was compared to that from venous blood and blood obtained by dried blood spot. Hypercholesterolemia was observed in 89 children. Of these children, 37 had healthy parents and 52 had parents or grandparents that had suffered MI. Apo B levels greater than 0.8 g/l (95th percentile) were experienced by 54 children. Only 4 of them had healthy parents, but 50 children had parents or grandparents who had suffered MI. Our results suggest that within the pediatric population, apo B level obtained from dried blood spot is a more suitable screening parameter than total cholesterol level for the detection of individuals with a high risk for the development of ischemic coronary artery disease.
1 mAF,
The cardiovascular toll of cigarette smoking in dyslipidemic patients in the United Kingdom Butowski P, Turner K, Royal Free Hosp. Med. Sch.,
London NW3 2QG, UK; Medical Dept., Bristol Myers Squibb, London, UK The Lipid Clinics Programme’s computerized database manage-
ment system has been installed in 71 lipid and related cardiovascular clinics in the UK. Information on 23 483 patients entered has been analyzed for relationships between smoking habits at first presentation and the subsequent development at mean follow-up of 1.8 years of hypertension and other cardiovascular disease, expressed and recorded as: angina; myocardial infarction; arrhythmias; coronary artery bypass graft; cerebrovascular disease; non-coronary artery surgery; angiography performed; pe-
Atherosclerosis X, Montreal, October 1994
Monday 10 October 1994: Poster Abstracts Risk factors
ripheral vascular disease; unspecified other cardiovascular disease. ‘Never smokers’ were 3601 men mean age 44.7 years, 4883 women mean age 53.1 years; cunent smokers were 3077 men mean age 46.3 years, 2275 women mean age 50.3 years; ‘ever’, i.e. current and ex-smokers were 7210 men mean age 49.2 years, 4559 women mean age 53.3 years. TC and LDL-C were similar between groups, but TG was lower and HDLC was higher in never-smokers, particularly women. The development of new hypertension was not consistently related to smoking habits. In contrast, the expression of newly recorded cardiovascular disease was greater and in some cases doubled in current or ‘ever’ smokers for 1508 male/female categories (not for a very small female group with arrhythmias, or for CABG procedures where selection bias may apply). These marked differences emphasize the risk of development and progression of clinical cardiovascular disease in dyslipoproteinemic smokers, and the serious inadequacy of stopsmoking support. Carotid and femoral atherosclerosis in patients un1 dereoine hemodialvsis my Niihizawa Y,“Konishi T, Kawasaki K, Tabata T, Inoue T, Morii H, 2nd Dept. of Internal Medicine, Osaka City Univ. Med. Sch., I-5-7, Asakimachi, Abenoku, Osaka, 545, Japan
The aim of the present study was to investigate the risk factors for carotid and femoral atherosclerosis and to compare the impact of the major coronary risk factors for early atherosclerosis between the two arteries in patients undergoing hemodialysis. Highresolution ultrasonography was used to determine non-invasively the mean maximal intima-media thickness (IMT) in the far wall of the common carotid artery and common femoral artery in 200 patients on hemodialysis and 100 age-matched healthy control subjects. The IMTs of both carotid and femoral arteries in patients under hemodialysis were greater than in control subjects (carotid, 0.85 + 0.03 mm vs 0.75 f 0.02 mm; femoral, 1.07 f 0.04 mm vs 0.90 * 0.05 mm, P < 0.01). There was a significant correlation between the carotid and femoral IMT in all subjects (r=0.323, P < 0.001). Multiple regression analysis showed that age, period of hemodialysis, BMI, and cigarette smoking were independent risk factors for carotid atherosclerosis in patients under hemodialysis. On the other hand, those for the femoral atherosclerosis were cigarette smoking, serum m-PTH, period of hemodialysis, serum LDL-C and age. The results indicate that patients undergoing hemodialysis show advanced atherosclerosis with different risk factor profiles in their carotid and femoral arteries. It is suggested that femoral atherosclerosis in patients on hemodialysis might be associated in part with secondary hyperparathyroidism. The amino acid homocysteine as a possible important primary atherogenic risk factor: a mechanistic proposition &ydom AJC, Dept. of Chemical Pathology G3, Faculty of
1
Medicine, PO Box 339, Bloemfontein 9300, South Africa
The amino acid homocysteine (HSH) is metabolically, structurally and chemically related to the biologically more abundant cysteine (CSH). Because of its relatively low pK, value, the free sulfhydryl group of CSH is chemically also more reactive than the corresponding group of HSH, and in addition the ‘normal’ free plasma concentration of reduced CSH is about 100 times that of HSH. However, HSH could still be more atherogenic than CSH, for the following reasons. The amino and thiol groups of CSH are structurally close so there can be a proton tautomerism interaction between the nitrogen and sulfur atoms. This interaction is reflected in the observed ionization heterogeneity of CSH, which is
25
structurally not possible for HSH. An important deduction is that in a sulfhydryl-disulfide exchange reaction, CSH will be much mom readily reversible than HSH, which implies that HSH may selectively damage structural proteins in the arterial system, e.g. proteoglycans, link proteins and fibronectin. At high levels, HSH could cause de-endothelialization, while at ‘normal’ to moderately elevated plasma levels it could lead to increased permeability, an important initial phase of atherosclerosis. Furthermore, there is a good correlation between ultrast.ructural data regarding the development of atherosclerosis and the above-mentioned delineation of HSH’s reaction with the arterial wall which implicate HSH as an important primary atherogenic risk factor. Fibrinogen and Bbrinolysis kinetics in rat during the j intake of a lipid-rich diet Villaverde CA, Peiia E, Tibau N, Joan 0, Villaverde CJ, Unidad de Trombosis y Aterioscierosis, CSIC, Jordi Girona 18-26, Barcelona, Spain
Epidemiologic studies have shown that blood increases in tibrinogen (tbg) and librinolysis inhibitors are independent risk factors in myocardial infarction and other cardiovascular processes, but frequently coincide with increases in cholesterol (chol) or triacylglycerides (TG). Purposes: To study whether the increases in plasma fbg induced by a high-lipid diet are related to overall levels of tibrinolysis activators and inhibitors and to those of chol and TG. Material and methods: Five groups of SpragueDawley rats were used: group 1, baseline (n = 30); the other groups (n = 10) were continuously fed a high-lipid diet ad libitum for 25 days and sacrificed. Blood levels of the following were evaluated at 10, 12, 15 and 25 days: chol, TG, fbg and, by a thromboelastographic technique developed in our department, fibrinolysis activators, euglobulin (eug) in plaque, and fibrinolysis inhibitors. Results: The high-lipid diet caused a progressive increase in all the parameters studied, but with a differing evolution over time. On day 10, all the parameters had increased with regard to baseline and in a statistically significant manner: between day 10 and day 15, fbg and activators showed no significant change, but TG and chol did. Values reached on day 25 were: fbg, 4 f 0.6 g/l; TG, 616 f 147 mg/dl; chol, 1307 f 129 mg/dl; activators, 0.46 * 0.08 PU/ml; and inhibitors, 1815 f 273 mm* arbitrary units. Conclusions: The curve for the increase in lbg is not related to those for chol or TG and appears to depend on the balance of fibrinolysis activators and inhibitors, although the latter two are related to the increase in TG. This suggests the existence of an independent mechanism for the increases in chol, TG and fibrinogen Serum HDL-cholesterol after a fat/cholesterol re1 stricted meal &iner JW, Jenkins RM, Shand DL, Connell JM, Zyruk H, DuPont Merck Pharmaceutical Co., PO Box 80026, Wilmington, DE 1988m26, USA
The enhanced risk for coronary heart disease (CHD) associated with elevated total or LDL cholesterol is modified by serum HDLC level. The sensitivity of this level to a non-fasting state could influence perceived CHD risk. 72 men with mild to moderate hypercholesterolemia followed a fat- and cholesterol-restricted diet for 3 weeks, the last week while sequestered in a study unit. They then received a generous ‘usual fare’ but fat- and cholesterol-restricted brunch. Serum lipoprotein levels were determined fasting, 4 h after the meal and again the following day, fasting. On the test-meal day post-prandial HDL-C declined to 36.0 + 8.3 mg/dl from a preprandial value of 41.7 f 9.3, a 13.6 f 5.4% decline (range -22.5% to +3.0%). 68 of the 72 subjects exhibited an HDL decline. Pre-meal to post-meal change in HDL
Atherosclerosis X, Montreal, October 1994