Effects Of Simvastatin On Aging Of Artery And Sex Hormone In Patients With CHD

BackgroundHealth in our country is seriously threatened by cancers and cardiovascular diseases which take up the first and second place in proportional mortality.the world health organization predicts that cardiovascular and cerebrovascular diseases will become the biggest cause of death. How to prevent and control cardiovascular and cerebrovascular diseases will be the chief mission of epidemiology. As the basical pathological change of cardiovascular and cerebrovascular diseases,atherosclerosis (AS) becomes the major factor of death and cripple, its morbidity grows quickly in recent years.study shows that both inflammatory factors and free radicals induce free fatty acids to lipid peroxidatio(LPO),which can injure endothelial cells and smooth muscle cell,then macrophagocytes swallow low densith lipoprotein (LDL) with scavenger receptor, lipids congregate into subendocardial, smooth muscle cell apoptosis, migrate, proliferate,finally AS forms.In the progress of AS formation, free radicals and ox-LDL are the important initiation factors.The second Risk factors cross-sectional study of Chinese MONICA plan shows that total cholesterol(TC) has a positive correlation(male:r=0.830,P<0.001;femal:r=0.880,P<0.001) with Acute coronary events after standardization age in each place and partly correlation(male: r=0.830, P<0.001;femal:r=0.880,P<0.001) with stroke.The study of correlation between Dyslipidemia and Sub-clinical atherosclerosis shows that following the density of serum TC the tendency of carotid atherosclerotic plaque and carotid artery intima-media thickness(IMT) increased in ten years.With serum TC>=6.24mmol/L, the incidence of carotid atherosclerosis was 46.80%,which was thrice more than the incidence of carotid atherosclerosis with TC<3.64mmol/L.statins named as hydroxylmethylglutaryl-coenzyme A(HMG-CoA) reductase inhibitor(HMG-CoA) competitively inhibit HMG-CoA reductase,then inhibit biosynthesis of cholesterol and decrease serum lipid density.Compounds from oxidizing reactions are oxidative and harmful to our tissue and cell in vivo, and they could lead chronic diseases and artery aging. Malondialdehyde (MDA) which springs from LPO is the most poisonous one among those compounds. superoxide dismutase(SOD) is an important and specialized enzyme which can scavenger excess free radicals and anti-oxidation. Determination of MDA and SOD is often complement each other, the level of SOD activity indirect responses the ability to clear oxygen free radicals, while the level of MDA also indirectly reflects the severity of body's cells by free radicals attack.When free radicals attack arachidonic acid on cell membrane,they produce a toxic substance,that is 8-iso-prostaglandin F2 a (8-iso-PGF2 a) which is stable in blood and body fluid. Epidemiology proved that uric acid(UA) participate in inflammatory reactions of blood vessel,and hyperuricosuria predict high risk of coronary heart disease. Statins not only decrease the level of serum lipids,also could stabilize plaques and play a role in anti-inflammatory.From this study we try to know the effects of simvastatin on plasma SOD,MDA,8-iso-PGF2a,UA and Serum lipids in patients with stable angina,deeply discuss the anti-atherosclerosis effect.The difference of morbidity in coronary heart disease between man and woman is remarkable. Morbidity of CHD in women before menopause is lower than in men, but is equalized after menopause, even more higher than that in man.these show that levels of sex hormone may play a role in that difference.along with aging,sex hormones have tremendous changes in vivo, even few changes may cause a complicated and hardly estimated influences on cardiovascular and other systems.as known to all,LDL in circulation is an important original material of composing steroid hormones in adrenal gland and gonad.As an important anti-atherosclerosis drug, statins could reduce the level of LDL, we pay more attention to the influsiong if it break up the balance of the metabolism or secretion of steroid hormones,studies show that these effect of statin exist disputation.more studie tend to show that statin dosen't have influence on sex hormone,but partly animal trials show that statins could decrease the level of sex hormone. In our study,we try to find out if short-term treatment of simvastatin influence the level of sex hormone in old men with CHD.PurposeTo observe the influence of serum lipids on the activity of SOD,the level of MDA,UA and 8-iso-PGF2αin vivo.To evaluate the effects of short-term treatment of simvastatin on serum SOD, MDA,8-iso-PGF2α,UA and Serum lipids in patients with stable angina.To observe the relationships of ageing,serum sex hormones and lipids in men with coronary heart diseases and effect of simvastatins on serum sex hormones.MethodAll the cases come from the Cardiology Department in Nanfang Hospital affiliated to Southern Medical University during 2009.6 to 2010.5. Inclusion criteria: one got sick of CHD whose stenosis of coronary artery is low to middle-grade (stenosis<70%)proved by coronary arteriography and 64 contrast enhancement CT scan,recording the number of culprit coronary artery. Exclusion criteria:the one that suffer elder than 80 year, heart failure with heart function is worse thanⅡ-grade (New york heart function assessment,NYHA), acute coronary syndrome(ACS), cancer, severe infection, endocrine desease, liver or kidney desease, Surgical Documentation,infectious diseases,treatment of anticoagulation or thrombolysis in seven days,treatment of contraceptive drugs or hormone replacement therapy are Excluded.Part 1:According to the standard of hyperlipidaemia(TC>6.22mmol/L or LDL>4.14mmol/L),the 85 cases fall into two groups:hyperlipid group(51) and ortholiposis group(34);According to treatment with simvastatin or not, the 85 cases fall into two groups:treatment group(53) and control group(32);Male(46),femal(39). each patient keep to treatment according to the AHA/ACC guideline of chronic stable angina in 2007,including platelet aggregation, anti-anginal drugs,controlling Bp, Glu and other risk factors. Simvastatin 40mg qn is given to treatment group,and placebo is given to control group.drawing venous blood with an empty stomach before and after treatment,measuring levels of serum LDL,HDL,TG,TC,UA,SOD, MDA and 8-iso-PGF2α.Comparison in two groups'general conditions using Crosstabs; Comparison between two groups using Independent-Sample T test;comparison between before treatment and after treatment using Paired-Sample T test. P<0.05 shows significant difference on statistics.Enzyme-linked immunosorbent assay(ELISA) is taken to measure 8-iso-PGF2α;Colorimetric method is taken to measure MDA and SOD.Part 2:According to the standard of hyperlipidaemia(TC>6.22mmol/L or LDL>4.14mmol/L),the 46 cases fall into two groups:hyperlipid group(28) and ortholiposis group(18);According to treatment with simvastatin or not, the cases fall into two groups:treatment group(28) and control group(18);each patient keep to treatment according to the AHA/ACC guideline of chronic stable angina published in 2007,including platelet aggregations, anti-anginal drugs,control Bp, Glu and other risk factors. Simvastatin 40mg qn is given to treatment group,and placebo is given to control group,then drawing venous blood with an empty stomach before and after treatment,measuring levels of serum LDL, HDL,TG,TC, luteinizing hormone (LH), total testosterone(TT), estradiol(E2), prolactin (PRL), progesterone (P) and follicule-stimulating hormone (FSH). Comparison in two groups'general conditions using Crosstabs;Comparison between two groups using Independent-Sample T test;comparison between before treatment and after treatment using Paired-Sample T test.Correlation among serum lipids,aging,numbers of coronary lesions and sex hormone use pearson Bivariate. P<0.05 shows significant difference on statistics.ResultCompared with the level of SOD(66.59±3.77 U/ml) in ortholiposis group. The level of SOD in hyperlipid group is lower to 64.28±2.59 U/ml(P=0.001); Compared with the level of MDA(4.12±0.26 nmol/ml) in ortholiposis group. The level of MDA in hyperlipid group is significant higher to 4.31±0.47 nmol/ml(P=0.039); Compared with the level of 8-iso-PGF2 a (440.08±187.82 pg/ml) in ortholiposis group, The level of 8-iso-PGF2 a in hyperlipid group is higher to 539.80±195.52 pg/ml (P=0.022);there isn't significant difference between the level of UA(431.12±88.78 umol/1) in ortholiposis group(431.12±88.78 umol/1) and hyperlipid group(426. 12±92.60 umol/1)(P=0.805).After treated three months,levels of serum LDL,TC,TG and HDL decreased significantly(P<0.05),the activity of SOD increased by 3.75±5.72 U/ml after treatment with simvastatin(P=0.000); the activity of SOD increased by 1.33±3.11 U/ml after treatment with placebo(P=0.022); the level of MDA decreased by 0.62±0.56 nmol/ml after treatment with simvastatin(P=0.000),but the control group didn't have a significant change;the level of 8-iso-PGF2 a decreased by 155.27±290.65 pg/ml after treatment with simvastatin(P=0.000),but the control group didn't have a significant change; the level of UA decreased by 40.42±129.25 umol/1 after treatment with simvastatin(P=0.027), the control group didn't have a significant change either.Cpmpared with ortholiposis group,the level of serum TT,FSH,P and PRL have non-significant differences in hyperlipid group.the level of E2 is 35.14±4.23pg/ml in hyperlipid group,but 31.67±3.75pg/ml in ortholiposis group,this difference have a statistical significance(P<0.05).Correlate study shows that There is positive correlation between aging and E2 but negative correlation between aging and TT,it means that ratio of E2/TT extend with aging in male with CHD.Numbers of coronary lesions has a negative correlation with TT(r=-0.500,P=0.000) but a positive correlation with E2(r=0.679,P=0.000),it means that low level of TT and high level of E2 may the risk factor of CHD. E2 has a positive correlate with LDL(r=0.417,P=0.000), TT have no correlation with lipids,LDL is the risk factor of AS,it means E2 may act on AS by increasing the serum level of LDL.P have noting with aging, lipids and numbers of coronary lesions.Paired-Sample T-test shows that the level of lipid suffer a significant decreasing after treatment,TT,E2,PRL,LH have non-significant decreaseing or increasing,but FSH increase about 0.08+/-0.09Miu/ml after treatment(P<0.05).Conclusion1. Compared with ortholiposis group, the activities of oxidative stress are more severe and the capability of clearing free radical is a decline in patient with CHD.2. Simvastins not only decrease the level of lipid,but also inhibit producing free radicals, suppress inflammatory reaction and improve the abilities of scavenger in patient with chronic stable angina.3. The change of sex hormone always goes with the aging,The level of E2 increased TT decreased year by year,those may have relationships with the ranul of AS.we also could see that there is a positive correlation between E2 and high Cholesterol in male,E2 may influence AS by increasing the level of serum LDL.4. Routine dose treatment of simvastatin cause lipid density to decrease significantly but don't influence the composing and secreting of sex hormone,but mayHave an effect on the reactivity of hypothalamic-pituitary-testicular axis in male with CHD.