***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective To examine the role of the variants of the PTPN22 and HLA – DRB1 genes as predictors of mortality in inflammatory polyarthritis ( IP ) and rheumatoid arthritis ( RA ) . Methods Patients were recruited from a primary care – based inception cohort of patients with IP and were followed up prospect ively . For patients who died , the cause and date of death was obtained . Cox proportional hazards regression models were used to assess the association of the HLA – DRB1 ( including the shared epitope [ SE ] ) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease ( CVD ) and to assess the interactions between SE , smoking  , and  anti – cyclic citrullinated peptide ( anti-CCP ) status  , adjusted by age at symptom onset and sex . Results DNA sample s were available from 1,022 IP patients . During followup , 751 of them ( 74 % ) satisfied the American College of Rheumatology 1987 criteria for RA , and 242 of them ( 24 % ) died . Carriage of 2 copies of SE alleles predicted death from all causes ( hazard ratio [ HR ] 1.57 [ 95 % confidence interval ( 95 % CI ) 1.1–2.2 ] ) and from CVD ( HR 1.68 [ 95 % CI 1.1–2.7 ] ) . This effect was most marked for individuals with the HLA – DRB1 * 01/*04 combination . An interaction of smoking , SE alleles , and anti-CCP antibodies was observed and was associated with the greatest risk of death from CVD ( HR 7.81 [ 95 % CI 2.6–23.2 ] ) . No association of the PTPN22 gene with mortality was detected . Conclusion SE alleles , particularly compound heterozygotes , are associated with death from all causes and from CVD , independently of autoantibody status . However , the combination of SE , smoking , and anti-CCP antibodies is associated with a high risk of premature death in patients with IP and RA , which raises the possibility of a targeted strategy to prevent CVD in these patients OBJECTIVE Heart failure is an important cause of death in patients with rheumatoid arthritis ( RA ) . Evidence suggests that immune mechanisms contribute to myocardial injury and fibrosis , leading to left ventricular diastolic dysfunction ( LVDD ) . The purpose of this study was to identify a signature of LVDD in patients with RA by analyzing the responsiveness of the innate and adaptive immune systems to stimulation ex vivo . METHODS RA patients ( n=212 ) enrolled prospect ively in a population -based cohort underwent echocardiography , and LV function was classified as normal , mild LVDD , or moderate-to-severe LVDD . The release of 17 cytokines by blood mononuclear cells in response to stimulation with a panel of 7 stimuli or in media alone was analyzed using multiplex immunoassays . Logistic regression models were used to test for associations between a multicytokine immune response score and LVDD , after adjusting for clinical covariates . RESULTS An 11-cytokine profile effectively differentiated patients with moderate-to-severe LVDD from those with normal LV function . An immune response score ( range 0 - 100 ) was strongly associated with moderate-to-severe LVDD ( odds ratio per 10 units 1.5 [ 95 % confidence interval 1.2 - 2.1 ] ) after adjusting for serum interleukin-6 levels , brain natriuretic peptide values , and glucocorticoid use , as well as other RA characteristics and LVDD risk factors . CONCLUSION The major finding of this study was that aberrant systemic immune responsiveness is associated with advanced myocardial dysfunction in patients with RA . The unique information added by the immune response score concerning the likelihood of LVDD warrants future longitudinal studies of its value in predicting future deterioration in myocardial function BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed  CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P<.001 ) . Sex-specific prediction equations were formulated to predict CHD risk according to age , diabetes , smoking , JNC-V blood pressure categories , and NCEP total cholesterol and LDL cholesterol categories . The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD Objective : Rheumatoid arthritis ( RA ) patients have an increased risk of developing cardiovascular diseases ( CVD ) . Other autoimmune diseases such as hypothyroidism are also associated with an enhanced risk for CVD . Our objective was to determine first , the prevalence of hypothyroid disorders in RA patients , and second , the risk of CVD in RA patients with hypothyroid abnormalities . Methods : Subjects were RA patients who participated in an ongoing prospect i ve cohort study of cardiovascular mortality and morbidity ( n = 358 ) in which hypothyroid abnormalities were assessed .  CVD was defined as a verified medical history of coronary , cerebral or peripheral arterial disease . Results : Clinical hypothyroidism was observed in 16 of 236 female RA patients ( 6.8 % ) , which is significantly higher than in the general population of The Netherl and s. Sub clinical hypothyroidism was detected in 6 out of 236 RA women ( 2.5 % ) . In female RA patients , CVD was present in 6 out of 16 ( 37.5 % ) of all hypothyroid women . The odds ratio for CVD comparing female hypothyroid RA patients with female euthyroid RA patients was 4.1 ( 95 % CI 1.2–14.3 ) after adjustment for sex , age , diabetes , smoking ( ever ) , hypertension and statin use . Conclusions : Clinical hypothyroidism was observed three times more often in female RA patients than females in the general population . In female RA patients , clinical hypothyroidism was associated with a fourfold higher risk of CVD in comparison with euthyroid female RA patients independently of the traditional risk factors Introduction In this study , we aim ed to determine the relationship between flow-mediated endothelium-dependent vasodilatation ( FMD ) and carotid artery intima-media wall thickness ( IMT ) , two surrogate markers of atherosclerosis , in a series of Spanish patients with rheumatoid arthritis ( RA ) without clinical ly evident cardiovascular ( CV ) disease . Methods One hundred eighteen patients who fulfilled the 1987 American College of Rheumatology classification criteria for RA , had no history of CV disease and had at least one year of follow-up after disease diagnosis were r and omly selected .  Brachial and carotid ultrasonography were performed to  determine FMD  and  carotid IMT  , respectively . Results Carotid IMT values were higher and FMD percentages derived by performing ultrasonography were lower in individuals with a long duration from the time of disease diagnosis . Patients with a disease duration ≤ 7 years had significantly lower carotid IMT ( mean ± SD ) 0.69 ± 0.17 mm than those with long disease duration ( 0.81 ± 0.12 mm in patients with ≥ 20 years of follow-up ) . Also , patients with a long disease duration had severe endothelial dysfunction ( FMD 4.0 ± 4.0 % in patients with disease duration from 14.5 to 19.7 years ) compared with those with shorter disease duration ( FMD 7.4 ± 3.8 % in patients with disease duration ≤ 7 years ) . Linear regression analysis revealed that carotid IMT was unrelated to FMD in the whole sample of 118 patients . However , carotid IMT was negatively associated with FMD when the time from disease diagnosis ranged from 7.5 to 19.7 years ( P = 0.02 ) . Conclusions In patients with RA without CV disease  , endothelial dysfunction and carotid IMT increased with the duration of RA . The association between FMD and carotid IMT values was observed only in patients with long disease duration OBJECTIVE To investigate the prospect i ve effect of hemostatic factors and inflammatory variables on the progression of cardiovascular disease in rheumatoid arthritis ( RA ) . METHODS Von Willebr and factor ( vWF ) and the fibrinolytic factors tissue plasminogen activator ( tPA ) , measured as tPA capacity , and plasminogen activator inhibitor 1 ( PAI-1 ) , platelets , fibrinogen , and inflammatory markers  were measured in 74 patients with active seropositive RA .  Lipid levels , lipoprotein(a ) , and cardiolipin antibodies  were also analyzed . Cardiovascular disease , measured by past cardiovascular events including thrombotic events , was registered in an 8 year followup . RESULTS Patients with a cardiovascular event during the followup period ( n = 26 ) had significantly higher levels of vWF , PAI-1 , erythrocyte sedimentation rate ( ESR ) , and haptoglobin at entry to the study . In a multiple logistic regression model controlling for several conventional cardiovascular risk factors and pharmacological treatment at sampling , PAI-1 and tPA were significantly associated with cardiovascular disease progression . CONCLUSION The altered levels of vWF , PAI-1 , and , in logistic regression , tPA in RA patients with cardiovascular disease progression indicates a status of hypofibrinolysis in these patients . Higher levels of ESR and haptoglobin may reflect the importance of the inflammatory process for the development of cardiovascular disease in RA OBJECTIVE To assess the risk of  acute myocardial infa rct ion ( AMI ) associated with the use of disease-modifying antirheumatic drugs ( DMARDs ) and other medications commonly used in rheumatoid arthritis ( RA ) . METHODS We conducted a nested case-control analysis within a cohort of subjects with RA , observed between 1999 and 2003 , identified from the PharMetrics cl aims data base . For each first AMI hospitalization identified during followup , 10 controls matched on sex , age , and time of study entry were r and omly selected from the cohort . Conditional logistic regression was used to estimate the rate ratio ( RR ) of AMI associated with the current use of anti-RA therapy , as measured from dispensed prescriptions , after adjustment for AMI risk factors . RESULTS The cohort included 107,908 subjects ( average age 54 years at cohort entry ) . During followup , 558 AMI cases occurred ( 3.4 per 1,000 per year ) . AMI rate was significantly decreased with the current use of any DMARD ( adjusted RR 0.80 , 95 % confidence interval [ 95 % CI ] 0.65 - 0.98 ) . This effect was consistent across all DMARDs , including methotrexate ( RR 0.81 , 95 % CI 0.60 - 1.08 ) , leflunomide ( RR 0.28 , 95 % CI 0.12 - 0.65 ) , and other traditional DMARDs ( RR 0.67 , 95 % CI 0.46 - 0.97 ) , but not biologic agents ( RR 1.30 , 95 % CI 0.92 - 1.83 ) . AMI rate increased with the use of glucocorticoids ( RR 1.32 , 95 % CI 1.02 - 1.72 ) but not with nonselective nonsteroidal antiinflammatory drugs ( RR 1.05 , 95 % CI 0.81 - 1.36 ) or cyclooxygenase 2 ( COX-2 ) inhibitors ( RR 1.11 , 95 % CI 0.87 - 1.43 ) . CONCLUSION DMARD use is associated with a reduction in AMI risk in patients with RA . No risk increase was found with the COX-2 inhibitors in this population OBJECTIVE The risk of cardiovascular disease ( CVD ) is increased in patients with rheumatoid arthritis ( RA ) . The objective of this study was to examine the distribution of known CVD risk factors and 
    Output:
    
Hypercholesterolemia , type 2 diabetes mellitus , abnormal body mass index , abdominal obesity , and current smoking were all traditional risk factors significantly associated with CVD in Colombians .