[Risk factors of coronary heart disease in women].
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Biomedical subjects
Publications and source records attributed to E Chotkowska.
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The low density lipoproteins (LDL) is one of the important risk factor of coronary heart disease. Evaluation of LDL by direct method of ultracentrifugation (U-LDL), which is the most proper one, is not available in standard laboratories. Instead the Friedewald's formula is commonly used (F-LDL), which calculates level of LDL applying the values of fasting total cholesterol (CH), cholesterol of high density lipoproteins (HDL) and triglicerydes (TG). This formula can be used only in these samples, in which the level TG is below 4.5 mmol/l (400 mg/dl). The aim of the study was the examination of the accuracy of Friedewald's formula while compared with the concentration of LDL cholesterol determined by ultracentrifugation method and evaluate the possibility of extending the range of triglyceride concentration above 4.5 mmol/l (400 mg/dl) in this formula. The data of the study included 2213 samples of the fasting blood serum of consecutive patients in whom the direct measurement of lipoprotein fraction and calculation by Friedewald's formula were performed in years 1992-1999. All serum samples were analysed by the same standardized procedures according to National Heart, Lung and Blood Institute (NHLBI) guidelines. The data of 29 samples with extremely high value of triglyceride level (TG > 5.6 mmol/l, it is 500 mg/dl) were excluded from analysis. The main results showed that agreement between two methods of LDL evaluation was satisfactory also in extended range of TG 4.5-5.6 mmol/l (400-500 mg/dl). The mean values of U-LDL were significant higher than F-LDL (by mean 0.07 mmol/l it is 2.6 mg/dl) in group with TG < or = 4.5 mmol/l, but non significantly lower (by mean 0.13 mmol/l it is 4.9 mg/dl) in group with TG 4.5-5.6 mmol/l. Linear Pearson's and interclass correlations between U-LDL and F-LDL were high and significant in all analyses.
The aim of the study was to evaluate the level of lipid risk factors in a random sample of Warsaw population aged 35-64 years, 764 men and 775 women, were screened within framework of the Pol-MONICA Warsaw Study. The lipids were determined by enzymatic methods in laboratory controlled by CDC Lipid Standardization Program in Atlanta. In the screened sample the observed levels of total cholesterol (5.76 +/- 1.01 and 5.68 +/- 1.03 mmol/l respectively in men and in women) and LDL cholesterol (3.67 +/- 0.90 and 3.56 +/- 0.94 mmol/l respectively) were rather high what can indicate on rather high coronary risk of Warsaw population. On the other hand the high mean level of HDL cholesterol (1.36 +/- 0.36 and 1.53 +/- 0.35 mmol/l respectively) and its subfractions HDL2 (0.24 in men and 0.39 mmol/l in women) as well as HDL3 (1.12 and 1.14 mmol/l respectively) observed in this sample can decrease this global risk. The compared mean level of cholesterol in lipoprotein fractions in the group of investigated persons with and without clinical manifestations of coronary heart disease confirm the observed in the other studies the higher mean levels of total cholesterol and LDL cholesterol in persons with coronary heart disease.
The aim of the study was searching for explanatory variables of high mortality from coronary heart disease (CHD) observed in Poland, with special regards to lipid risk factors, which were determined in a population of Warsaw Pol-MONICA Project. From the randomly selected cohort of Warsaw population, consisted of 348 men and 351 women, aged 35-64 at baseline, the fasting lipid levels were determined three times in 270 men and 266 women. The first study was performed in 1984 year, second in 1988 and third in 1993. The plasma level of triglycerides (TG), total cholesterol (CH) and HDL cholesterol (HDL), after VLDL and LDL precipitation, were measured by standardized enzymatic methods. LDL cholesterol (LDL) was calculated according to Friedewald's formula. Our laboratory was systematically controlled by WHO Lipid Reference Laboratory in Prague and CDC NHLBI Lipid Standardization Program in Atlanta. After ten years of following up total plasma CH increased significantly by 5% in women (from 5.66 to 5.94 mmol/l i.e. 219 to 230 mg/dl) and did not increase significantly in men (increase by 2%, from 5.63 to 5.75 mmol/l i.e. 218 to 222 mg/dl. LDL fraction increased significantly in both sex groups: by 11% in women (from 3.43 to 3.79 mmol/l i.e. 133 to 147 mg/dl) and by 9% in men (from 3.42 to 3.73 mmol/l i.e. 132 to 144 mg/dl). HDL fraction level changed only within the limits of the accuracy of method. Plasma TG decreased significantly in both sex groups; by 12% in women (from 1.58 to 1.39 mmol/l i.e. 140 to 123 mg/dl) and by 19% in men (from 1.93 to 1.57 mmol/l i.e. 171 to 139 mg/dl). The significant increase in percentage of subjects with elevated atherogenic lipoprotein fraction LDL (LDL >or= 4.1 mmol/l i.e. 160 mg/dl) in both gender groups and prevalence of hypercholestrolemia (CH >or= 6.5 mmol/l i.e. 250 mg/dl) in women only was observed during ten years. Simultaneously the significant decrease in the percentage of subjects with elevated level of triglycerides (TG > or = 2.3 mmol/l i.e. 200 mg/dl) in both gender groups was noticed. The relationship between lipid risk factors and age and relative body mass in all subjects was analyzed. In Polish population the levels of lipids and of atherogenic lipoproteins fractions were very high and during ten years of follow up almost all lipid risk factors, except TG, showed disadventage direction of change.
We investigated the effects of long-term testosterone replacement in hypogonadal and elderly men on lipids and lipoproteins. Twenty-two men with initial serum testosterone concentrations below 3.5 ng/ml took part in the study: 11 with hypopituitarism (1st group) and 11 otherwise healthy elderly men with low testosterone levels (2nd group). Testosterone deficiency was replaced by intramuscular injections of testosterone enanthate 200 mg every second week. Plasma levels of sex hormones, gonadotropins, SHBG, lipids and lipoproteins were determined before the treatment and after 3, 6 and 12 months of treatment. During the treatment serum testosterone and estradiol increased significantly, reaching normal levels. This was associated with a decrease in total cholesterol (from 225 +/- 16.9 mg/dl to 202 +/- 13.6 mg/dl after 6 months and 198 +/- 12.8 mg/dl after 1 year of testosterone administration, P < 0.0001 in men with hypoandrogenism associated with aging and from 255 +/- 12.1 mg/dl to 214 +/- 10.6 mg/dl after 6 months and 206 +/- 9 mg/dl after 1 year of treatment, P < 0.0001 in men with hypopituitarism) and LDL-cholesterol concentrations (from 139 +/- 12.5 mg/dl to 126 +/- 10.7 mg/dl after 6 months and 118 +/- 9.8 mg/dl after 1 year of testosterone administration, P < 0.0001 in men with hypoandrogenism associated with aging and from 178 +/- 10.3 mg/dl to 149 +/- 10.2 mg/dl after 6 months and 140 +/- 7.3 mg/dl after 1 year of treatment, P < 0.001 in men with hypopituitarism). However, no significant decrease in HDL-cholesterol levels or HDL2- and HDL3-cholesterol subfractions was observed. The effects of testosterone replacement therapy on lipids and lipoproteins were similar in both groups with different aetiology of hypogonadism. No side effects on the prostate were observed. The results of this study indicate that testosterone replacement therapy in hypogonadal and elderly men may have a beneficial effect on lipid metabolism through decreasing total cholesterol and atherogenic fraction of LDL-cholesterol without significant alterations in HDL-cholesterol levels or its subfractions HDL2-C and HDL3-C.
OBJECTIVES: The purpose of the study was to establish plasma levels of insulin, ovarian sex hormones and dehydroepiandrosterone sulfate (DHEA-S) and to evaluate their correlations with lipids in premenopausal women with angiographically demonstrated coronary stenosis. DESIGN: Differences in plasma levels of insulin, ovarian sex hormones, DHEA-S and lipids between groups were compared by analysis of variance. SETTING: From January 1993 until December 1993 patients were diagnosed in the Outpatient Clinic of the Department of Endocrinology Medical Centre for Postgraduate Education, Warsaw. SUBJECTS: Premenopausal women with normal oral glucose tolerance test (OGTT) results, with and without coronary stenosis were studied: 21 women after acute myocardial infarction with angiographically demonstrated coronary stenosis (women with CHD), and 14 women with chest pain, a positive exercise test without significant changes of coronary arteries on coronarography (women with normal coronarography, NC). The control group consisted of nine, healthy women with no risk factors for CHD. MAIN OUTCOME MEASURES: In premenopausal women with CHD, the decreased plasma level of DHEA-S and hyperinsulinaemia were anticipated. RESULTS: In women with CHD, the plasma levels of DHEA-S (926.5 +/- 83 ng mL-1) were significantly lower than those in women with NC (1375.7 +/- 181 ng mL-1) and in healthy controls (1984 +/- 127 ng mL-1), P < 0.02 and P < 0.001, respectively. The fasting insulin and insulin response to an OGTT in women with CHD and with NC was higher than in healthy subjects. A significant decrease of high-density lipoprotein (HDL) cholesterol, HDL-2 cholesterol and apolipoprotein A-I, and an increase of total cholesterol, low-density lipoprotein cholesterol C and apolipoprotein B levels in women with CHD compared to healthy controls were observed. A negative correlation between fasting insulin and the plasma levels of DHEA-S was established. CONCLUSION: In premenopausal women, hyperinsulinaemia and decreased DHEA-S levels may contribute to the development of coronary atherosclerosis.
Analysis of the efficacy and tolerability of gemfibrozil (Gevilon-Parke Davis) was performed including 29 patients aged 19-69 years with primary hyperlipoproteinemia (HLP) type IIb-16 persons, IV-13 persons. All patients got dietary recommendations and received gemfibrozil 450-900 mg/day for 3 months. In both types of HLP a significant reduction of serum cholesterol (TCh)--15.5% triglycerides (TG)--32.1% VLDL-Ch--34.9% and VLDL-TG concentration--36.6% was observed as well as an increase of HDL3 fraction-16.3%. The greatest reduction of serum TCh concentration and VLDL-Ch were observed in type IIb, while that of TG and VLDL-TG in type IV HLP. The best therapeutic effect was obtained during the first month of treatment. The percent of TCh, TG, VLDL-Ch, VLDL-TG reduction correlated with their initial level. Tolerability of gemfibrozil was very good. Only in 2 patients transient abdominal pain was observed.
OBJECTIVES: The purpose of the study was to evaluate the effect of transdermal 17 beta-oestradiol with oral progestogen on the plasma levels of lipids, lipoproteins and apolipoproteins in hypercholesterolaemic postmenopausal women. DESIGN: During 6 months of replacement therapy with transdermal 17 beta-oestradiol combined with oral progestogen, plasma lipids, lipoproteins and apolipoproteins after 3 and 6 months were measured and compared with pretreatment values by Student's t-test. SETTING: From January 1992 until September 1992 patients were diagnosed and treated in an out-patient clinic of the Department of Endocrinology Medical Centre for Postgraduate Education, Warsaw. SUBJECTS: The patients studied were 11 non-obese postmenopausal women with hypercholesterolaemia based on the World Health Organization criteria. INTERVENTIONS: Venous blood samples were obtained before and 3 and 6 months after the beginning of cyclic replacement therapy with transdermal 17 beta-oestradiol (E2 100 micrograms day-1 combined with oral chlormadinone acetate (2 mg day-1 for 7 days in each cycle). MAIN OUTCOME MEASURES: The antiatherogenic effect of transdermal oestrogen replacement therapy exerted by increased levels of high-density lipoprotein subfraction 2 cholesterol (HDL2-C) leading to the decrease of the total cholesterol level was anticipated. RESULTS: After 6 months of the treatment the concentrations of HDL2 cholesterol (HDL2-C) increased from 0.45 +/- 0.07 mmol l-1 to 0.73 +/- 0.03 mol l-1 (P < 0.05) but the levels of HDL3 cholesterol (HDL3-C) decreased from 1.15 +/- 0.06 mmol l-1 to 0.89 +/- 0.07 mmol l-1 (P < 0.05). The concentrations of total cholesterol decreased from 6.9 +/- 0.13 mmol l-1 to 6.2 +/- 0.2 mmol l-1 (P < 0.05). No changes were observed in the plasma levels of total triglycerides, HDL cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, VLDL triglycerides, apolipoproteins A-I and B. CONCLUSIONS: In hypercholesterolaemic postmenopausal women, transdermally administered 17 beta-oestradiol 100 micrograms daily in combination with oral chlormadinone acetate has a beneficial effect through raising the level of the antiatherogenic HDL2-C subfraction and decreasing the level of total cholesterol.
The aim of the study was to investigate the effect of a new selective alpha 1-adrenoreceptor blocker doxazosin on blood pressure, serum lipids and lipoproteins in patients with essential hypertension. The study was done in 32 out-patients with mild-to-moderate hypertension (22 men and 10 women, mean age 45.6 +/- 10.1). After 2-week placebo period the patients were given doxazosin in increasing doses from 1 to 8 mg daily for 6 to 14 weeks (mean daily dose 2.24 +/- 1.6 mg). Twenty-nine patients completed the study. The active treatment caused highly significant drop in systolic and diastolic blood pressure both in supine and standing positions. No orthostatic hypertension was noted. There was also a statistically significant decrease in serum total cholesterol, VLDL-cholesterol, and triglyceride levels and increase in the positive prognostic lipid indicators. HDL3-cholesterol and apolipoprotein AI levels as well as HDL/total cholesterol ratio. Accordingly, the statistically significant decrease of the so called atherogenic index was noted. The drug was well tolerated and only one patient dropped from the study because of side effects. The authors conclude that doxazosin appears to be an effective and well tolerated antihypertensive drug with a favorable effect on lipid metabolism. It may be particularly useful in hypertensive patients with coexisting lipid abnormalities.
The effect of six months' treatment with bezafibrate (400-600 mg daily) on serum lipids, lipoproteins and apolipoproteins concentrations was investigated in 32 patients with primary hyperlipoproteinemia (HLP) type IIa, IIb and IV. In all types of HLP the reduction of serum cholesterol (CH), triglycerides (TG), very low density lipoprotein (VLDL) fraction and increase in high density lipoprotein (HDL) cholesterol, HDL3-CH and apolipoprotein AI concentrations was observed. In type IIa and IIb HLP low density lipoprotein (LDL) cholesterol and apolipoprotein B levels decreased while in type IV increased. The greatest fall of serum CH concentrations was observed in type IIb while of serum TG level--in type IV. In 15 (46.9%) patients the side effects were noted. They were: abdominal pain, skin rash, myalgia, moderate increase in CPK and aminotransferase activities. Most of there side effects disappeared spontaneously without treatment cessation.
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The results of 12 weeks treatment of primary hyperlipidemias with Lovastatin are presented. This drug belonging to a new generation of hypercholesterolemic drugs inhibits the endogenous synthesis of cholesterol by means of inhibiting the HMG-CoA reductase. The sample consisted of 30 men aged 28-68 years: in 17 of them heterozygotic familial hypercholesterolemia (FH) was diagnosed and in 13--primary non familial hypercholesterolemia (NFH). After 12 weeks of treatment in both groups a significant reduction of total serum cholesterol concentration was observed--(-28%) and--(-32%) as well as LDL-cholesterol concentration (in both groups about -37%) and apo B concentration--(-32%) and -34%. Only in one patients with NFH a significant reduction of VLDL-cholesterol (-29%) and or triglycerides (-15%) concentrations was observed. In this group also a 9% increase of HLD-cholesterol, mainly HDL-2 concentration, was found. Side effects were observed in 6 patients--in 4 of them a minor increase of ALAT, AsPAT or CPK activities (less than 3 times above norm were observed) without any symptoms and with a spontaneous normalization with no need to stop treatment, and in 2 of them abdominal pains not causing drug treatment cessation.
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