Myocardial Infarction in Systemic Lupus Erythematosus - the Sex-Specific Risk Profile.

BACKGROUND: Accelerated atherosclerosis is widely present in patients with systemic lupus erythematosus. OBJECTIVE: The aim of this review was to analyze the relationship between systemic lupus erythematosus and cardiovascular diseases, with the emphasis on acute myocardial infarction. METHODS: We conducted a literature review through PubMed and Cochrane, using keywords: SLE, atherosclerosis, atherothrombosis, coronary artery disease, myocardial infarction, prognosis, sex specifics. RESULTS: Various molecular mechanisms triggered by infection/inflammation are responsible for endothelial dysfunction and the development of atherosclerosis at an earlier age. A contributing factor is the cumulative effect of traditional cardiovascular risk factors interaction with disease-related characteristics. Myocardial infarction rates are 2- to 10-fold higher compared to the general population. Young women have the highest relative risk, however, men carry at least 3-fold higher risk than women. Coronary involvement varies from normal coronary artery with thrombosis, coronary microartery vasculitis, coronary arteritis, and coronary atherosclerosis. Typical clinical presentation is observed in men and older women, while atypical is more frequent in young women. Treatment is guided by the underlying mechanism, engaging invasive procedures alone, or accompanied with immunosuppressive and/or anti-inflammatory therapy. There are significant gender differences in pathophysiology and clinical presentation. However, they receive the same therapeutic treatments. CONCLUSION: Systemic lupus erythematosus is a major contributor to atherosclerotic and non-atherosclerotic mechanisms involved in the development of myocardial infarction, which should be taken into account during therapeutic treatment. Although systemic lupus erythematosus per se is a "female" disease, males are at increased cardiovascular risk and worse outcomes.

Myocardial Perfusion Abnormalities in Young and Premenopausal Women with Systemic Lupus Erythematosus, Detected with 99MTC MIBI Myocardial Perfusion Scintigraphy - Prevalence and Correlation with Proatherogenic Factors.

INTRODUCTION: Atherosclerosis in young and premenopausal women with systemic lupus erythematosus (SLE) is frequent, premature and progressive. Although asymptomatic or with atypical clinical presentation, the patients are at high risk of cardiac events. Aim of this study is to estimate the risk profile for atherogenesis and the prevalence of myocardial perfusion abnormalities with 99mTc myocardial perfusion scintigraphy (MPS) in young and premenopausal women. MATERIAL AND METHODS: Sixty female patients, aged 30-72 years (divided into two subgroups - patients under 45 years of age and patients over 45 years), diagnosed with SLE for over of 5 years, in active phase of the disease were analyzed for disease activity scores (SLEDAI), the immunologic status of the disease (ANA and a-DNA antibodies in the serum), procoagulant tendency (antiphospholipid antibodies-APhL and lupus-anticoagulant-LAC), the activity of the inflammatory process (hsCRP), the anti-SLE therapeutic approach and the presence of traditional risk factors for atherosclerosis (BMI, smoking, hypertension, hyperlipidemia, diabetes, and familial history for the CAD). Using one-day Dipyridamol - Rest 99mTc SPECT Gated MPS SPECT the extent, severity and reversibility of myocardial perfusion abnormalities were estimated, along with summed scores at stress, rest and summed difference scores and left ventricle volumes and ejection fraction. RESULTS: Abnormal MPS SPECT were detected in 27/60 or in 45% of patients, with one vessel affection of 66.7% (18/27pts) of LAD and 14.8% (4/27pts) o RCA and with two vessel disease of LAD/RCA in 2/27 pts (7.4%) and LAD/Cx in 3/27pts (11.1%). Myocardial perfusion abnormalities were equally prevalent in subgroups of patients younger than 45 years (44,4%) and in patients older than 45 years (45.5%) (ns). The subgroups did not differ significantly concerning the extent of perfusion abnormalities (9,8±3.2% of LV myocardial mass vs. 9,8±7.1%,ns), their severity (with predominance of mild perfusion defects, 48,6% vs. 51,3%,ns) and reversibility (reversible in 41.3% and 58.6%, ns). The differences between the summed scores of severity and the extent of ischemia in the two subgroups were statistically nonsignificant. Younger patients had significantly higher end-diastolic, end-systolic and stroke volumes during stress and rest conditions, compared to older patients (p<0,01) although there were no differences in systolic function, which was not affected in either of the groups as expressed threw ejection fraction. Although nonsignificant, younger patients had higher values of hsCRP and higher procoagulant activity (positive aPhL, LAC) while they were with more active disease activity, with higher SLEDAI score compared to older patients (p=0.028). Higher SLEDAI score and LV volumes, especially EDV at stress were identified as predictor of abnormal MPS in younger groups and more aggressive multidrug anti SLE treatment as predictor of normal MPS. CONCLUSION: The prevalence and characteristics of myocardial perfusion abnormalities in young SLE are equal as the same in older SLE patients, which indicates the presence of premature, accelerated atherosclerosis in young cohort of patients with SLE. Younger SLE patients with pure disease control (higher SLEDAI score, less aggressive treatment, high hsCRP values and pronounced procoagulant tendency) should undergo screening for myocardial perfusion abnormalities s using 99mTc MIBI MPS).

Diagnostic value of brush border enzymes of the proximal renal tubules in rheumatoid arthritis.

BACKGROUND: Proximal tubules of the kidney have a dominant function in the excretion of different enzymes in the urine. These enzymes can be used as markers for secondary renal damage under the action of different diseases, medicines, and toxins. The aim of this study was to evaluate the values of alanine aminopeptidase (AAP), gamma-glutamyl transferase (gamma-GT), and beta2 microglobulin (beta2m) in urine of patients with untreated rheumatoid arthritis (RA) and to define the possible association between untreated rheumatoid arthritis and tubular function at the brush border region. METHODS: We used a kinetic assay for AAP, standard methods by the International Federation for Clinical Chemistry (IFCC) for gamma-GT and Microparticle Enzyme Immunoassay (MEIA), (Abbott A(x)SYM System) for the determination of beta2m in urine of 70 participants (35 untreated RA patients and 35 healthy volunteers (HC)). RESULTS: From the total of 35 RA patients, AAP enzymuria was found in 24 patients with test sensitivity (68.57%), gamma-GT in 16 patients with test sensitivity (45.71%), while the presence of urinary beta2m was found in a very low percentage of cases. Out of 18 rheumatoid factor (RF) negative patients, 14 patients were AAP and 10 patients were gamma-GT positive, while the presence of beta2m in urine was not detected. Among 17 RF positive RA patients, the presence of AAP and gamma-GT was noticed in 10 and 6 patients, respectively, while the presence of beta2m in urine was not detected. CONCLUSIONS: In conclusion, AAP had a higher sensitivity than gamma-GT and beta2m in detection of asymptomatic renal lesions in untreated RA.

Association of cytokine gene polymorphisms with chronic obstructive pulmonary disease in Macedonians.

The aim of this study was to examine the association of 22 cytokine gene polymorphism in Macedonians with chronic obstructive pulmonary disease (COPD). The sample of the population comprised of 301 normal respondents and 62 patients with COPD. Cytokine genotyping was performed by polymerase chain reaction with sequence-specific priming (PCR-SSP). Positive (susceptible) association was found between patient with COPD and IL-1alpha -889/C allele; where as negative (protective) association among was found for the following alleles IL-1beta +3962/C; IL-12B -1188/A; IFNgamma +874/T; IL-2 -330/G; IL-4 -1098/G and IL-4-33/C. We found positive (susceptible) association between patients with COPD and following genotypes: IL4 -33/T:T; IFNgamma +874/A:A; IL-4 -1098/T:T ; IL-1alpha -889/C:C; IL-1beta +3962/C:T; IL-12B -1188/C:C; IL-4Ralpha +1902/G:G; IL-10 -1082/G:G; IL-2 -330/T:T; IL-4 -590/C:C; and IL-1alpha -889/C:T. Negative (protective) association between patients with COPD and following genotypes was found: IFNgamma +874/A:T; IL-4 -33/C:T; IL-4 -1098/G:T; IL-2 -330/G:T; IL-1beta +3962/C:T; IL-4 -590/C:T; IL-10 -1082/A:G; and IL-4 -33/C:C. Positive (susceptible) association between patients with COPD and following haplotypes was found: IL-4/TCT; IL-10/ATC; and IL-2/TG, and negative (protective) association was found between the patients with COPD and haplotypes for: IL-4/TTC; and IL-4/GCC. It could be concluded that several cytokine polymorphisms are positively (susceptible), or negatively (protective) associated with COPD in Macedonians.

Association of cytokine gene polymorphisms with bronchial asthma in Macedonians.

Bronchial asthma is a multifactorial disease whereby both environmental and genetic factors contribute to its aetiology and/or clinical severity. The aim of this study was to examine the association of 22 cytokine gene polymorphism in the Macedonian population with bronchial asthma (BA). The sample of the population comprised of 301 normal unrelated individuals and 74 patients with BA. Cytokine genotyping was performed by PCR. Susceptible cytokine polymorphisms for BA for ten genotypes (IL-4 -1098/T:T, TNF-alpha -238/A:G, IL-4 -590/C:C, IL-2 +166/T:T, IL-2 -330/T:T, IL-10 -1082/G:G, IFNgamma utr5644/T:T, IL-10 -1082/A:A, IL-1beta +3962/T:T, IL-6 -174/G:G), six diplotypes, four haplotypes, and two alleles were found. Protective cytokine polymorphisms for BA for seven cytokine genotypes (IL-4 -1098/G:T, TNF- alpha -238/G:G, IL-2 -330/G:T, IL-4 -590/C:T, IFNgamma utr5644/A:T, IL-1beta +3962/C:T, IL-10 -1082/A:G), six cytokine diplotypes, four cytokine haplotypes, and four cytokine alleles were found. We concluded that several cytokine polymorphisms are protective, or susceptible associated with BA in population of Macedonians.