The Correlation Between Plasma Homocysteine, Dyslipoproteinemia And The Intima-media Thickness Of Carotid Artery In Female Patients With Systemic Lupus Erythematosus

It is well known that female patients with systemic lupus erythematosus (SLE),especially in the later course of the disease, have a high prevalence of cardiovasculardisease, which is the major cause of morbidity and mortality. Atherosclerosis(AS) is themost frequent pathological foundation. In recent decades, as the developmenteffectiveness of the diagnosis and treatment, the prognosis and life span of SLE havebeen improved, but the mortality still remains high among SLE patients, and most of thedeath involves atherosclerosis, which is the number one killer among SLE patients.Pre-menopaysal women with SLE aged 35-44 years take 52 times greater risk ofmyocardial infarction than healthy women of a similar age. A postmortem study byBulkley et al. showed that the overall prevalence of myocardial infarction in a group ofpre-menopaysal women with SLE aged 35-44 years is more than 90%, and a large part ofSLE patients have no final diagnosis until they present with typical angina pectoris,serious arhythmia and myocardial infarction, mainly because these lesions could beclinically mild or even silent, so, in recent years, researchers concentrate on the study onhow to diagnose and find out the risk of early AS to prophylaxis it. Although, more andmore studies show that dyslipoproteinemia is a common feature in adult SLE premenopausal patients and a significant correlation has been found betweendyslipoproteinemia and pathogenesis of AS, a lot of western researchers mainlyconcentrate on TC and HDL, LDL, ignoring that TG and VLDL may also participate inthe onset of AS. Especially, when multiple factor analysis is used to confirm what areimportant factors inducing AS, TG and VLDL are always excluded. But recently,epidemiologic study confirms that not only TG is an independent risk of AS, but alsoVLDL and all of lipoproteins contribute to AS. Up to now, we still apply TC and LDL-Clevels to control lipid and to predict cardiovascular and cerebrovascular disease of SLE,however, these two indexes are not sufficient so that we may sometimes make mistakesin diagnosis. For these reasons, it is necessary to identify the risk factors and predictindexes of early AS of SLE. In 2001, NECP mentioned a new opinion "Non-HDL-C",which includes all of lipidproteins except HDL-C. Non-HDL-C is more efficient todiagnose early AS and can be conveniently applied to clinic practice. Hcy is asulfur-containing amino acid forming during the metabolism of methionine. Substantiveinvestigations have confirmed that mortality of myocardial infarction and stroke inpatients with elevating plasma Hcy concentration greatly exceeds that in those withnormal plasma Hcy concentration. It has recently become dear thathyperhomocysteinemia is an independent risk factor for cardiovascular andcerebrovascular disease induced by AS. Because people with SLE, compared with thegeneral population, are at substantially increased mortality and morbidity, especially inthe later course of disease, the relationship between hyperhomocysteinemia andcardiovascular and cerebrovascular diseases have drawn our great attention. Carotidartery IMT is confirmed by academic circles as an index to estimate the early AS, and ithave been applied to observe regression of AS. The thickening of carotid arterial IMT isclosely associated with increase in the risk of cardiovascular and cerebrovascular diseaseand myocardial infarction. On the other hand, the simplicity and the reduplication of IMT facilitate us in reflection of early AS. There are large numbers of SLE patients in ourcountry, and there are many differences in the dominant and in races between China andthe western countries. There are little studies about dyslipoproteinemia in SLE patientsand little knowledge about the plasma Hcy concentration in Chinese SLE patients and itsrole in the pathogenesis of early AS. Therefore, investigation of lipid profiles in the SLEpatients and probe into the relationship between dyslipoproteinemia, Hcy and early AScome into our consideration so as to find out predict index of early AS.Objective:1. To observe the lipid profiles in female SLE patients and to analysis the riskfactors of dyslipoproteinemia in female SLE patients.2. To investigate the plasma Hcy levels and non-HDL-C levels in female SLEpatients, and analysis the correlation between plasma Hcy levels, non-HDL-C levels andCarotid artery IMT. So as to find out clinical predict index of early AS.MethodsSubjects: In this study involved 52 female SLE patients aged 27.79+7.71 years.Among them, there were 35 SLE patients treated with glucocorticoid (GC), and 17 SLEpatients treated without GC. 30 control subjects (30 women) were chosen without anyfamilial or personal history of connective tissue disease, cardiovascular andcerebrovascular disease, hypertensive disease, diabetes and endocrinopathy.Methods: The height, weight, and the calculated BMI in all subjects were measured.Fasting blood samples taken from 52 SLE patients and 30 healthy controls were preparedfor the detection and assessment of total cholesterol (TC), teiglyceride(TG), high-densitylipoprotein (HDL), low-density lipoprotein (LDL)-cholesterol and plasma homocysteine(hcy) levels. All of lipid levels were determined by standard laboratory techniques andHcy levels by HPLD-FD. Carotid artery intima-media thickness of carotid artery IMTwas measured by HP5500 color doplarapparatus, using a linear array transducer (7.5～10MHz). The mean of the measured values represented the carotid artery IMT ofeach subject.Results1. The lipid profiles of SLE patients and the influential factors1.1. Both TG level and VLDL-C level were higher in SLE patients than in controlsubjects (P＜0.01).1.2. TG levels were higher in SLE patients on GC therapy than in non-GC-treatedpatients.1.3. A significant correlation was found between TG levels and 24h proteinuria(P=0.011). TG (P=0.001) and LDL-C (P=0.012) levels were dramatically correlated withBMI. Moreover, in SLE patients on GC therapy, a significant correlation was foundbetween TG levels (P=0.010) and 24h proteinuria and TG (P=0.035), TC(P=0.006) levelswere also significantly correlated with the dose of GC. But any lipid level was found tobe correlated with SLEDAI in the patient on GC therapy. In the non-GC-treated patients,a negative correlation was found between SLEDAI scores and HDL-C levels (P=0.026).HDL-C level was also negatively correlated with 24h proteinuria(P=0.018). The levels ofHcy and the value of IMT in the SLE patients were observed significantly higher thanthose in controls (p＜0.010). Moreover, a significant correlation was found betweenplasma homocysteine and the intima-media thickness of carotid artery (r=0.853,P=0.000).2. Non-HDL-C levels, plasma Hcy, the value of carotid artery IMT in SLE patients2.1. The value of carotid artery IMT, levels of Hcy, and non-HDL-C levels in theSLE patients were observed significantly higher than those in controls (p＜0.01).2.2. There were no differences in carotid artery IMT, levels of Hcy, and non-HDL-Clevels between SLE patients on GC therapy and non-GC-treated patients.3. Comparisons in the indexes of the SLE patients with early AS and those without early ASAccording to 2004 HBP prevention and cure guidance, SLE patients are classifiedinto two groups: One is AS group and the other NAS. Our findings indicated age, TGlevels, TC levels, Non-HDL-C levels, Hcy levels were found larger and higher in ASgroup than those in NAS group, while HDL-C levels were lower in AS group than thosein NAS group.4. The correlations between carotid artery IMT and age, BMI,non-HDL-C levels,plasma Hcy, plasma Hcy were significantly correlated with the value of carotid arteryIMT, and HDL-C levels was negatively correlated with carotid artery IMT. Multiplefactors stepwise regression showed that non-HDL-C levels, plasma Hcy and TC levelswere independent risk factors of SLE early AS, non-HDL-C levels were the mostsignificant risk factor of SLE early AS. Stepwise Regression equation was:Y=0.430+0.015X1 (Hcy)+0.227X2 (non-HDL-C) -0.151X3 (TC) (R2=0.547, P＜0.010) andtypical regression equation was: Y=0.430+0.352X1 (Hcy) +1.221 X2 (non-HDL-C)-0.827X3 (TC). Fisher discriminatory analysis showed that non-HDL-C levels andplasma Hcy were able to be diagnostic indexes of SLE early AS. Fisher stepwisediscriminatory function was: early AS (+)=-46.460+11.499 X11 (non-HDL-C) +2.013X12 (Hcy), early AS(-)=-26.236+8.646 X11 (non-HDL-C) +1.524 X12 (Hcy), witha coincidence of 90.4％, sensibility of 77.8％, and specificity of 97.1％.Conclusions1.The results of this study show that dyslipoproteinemia is a frequent disorder infemale SLE patients, with a pattern that is characterized by an increase in TC and andegrade HDL-C. 24h proteinuria, GC, BMI are the main factors related todyslipoproteinemia in these patients. In non-GC-treated patients, HDL-C levels werenegatively correlated with 24h proteinuria. Therefore, HDL-C levels may be regarded asa indicator in the estimation of atherosclerosis in SLE patients, especially in the patients with renal infraction.2. SLE patients have greater risk of early AS than common peoples.3. Plasma Hcy and Non-HDL-C levels are observed significantly higher in SLEpatients than those in controls. Non-HDL-C levels, plasma Hcy and TC levels areindependent risk factors of SLE early AS. Among them, Non-HDL-C levels are the mostsignificant risk factor. Non-HDL-C levels and plasma hyperhomocysteine may be the twoimportant factors of the obesity-induced atherosclerosis in SLE patients.4. In order to prevent early AS, control disease activity, reduce morbidity andmortality and improve survival quality, it is necessary to apply GC rationally, reduceproteinuria, rectificate dyslipoproteinemia, and slow down plasma Hcy in clinicalpractice.