***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: Sub clinical hypothyroidism ( sHT ) affects 5 - 15 % of the general population ; however , the need of lifelong L-T(4 ) therapy is still controversial . As myocardium is a main target of thyroid hormone action , we investigated whether sHT induces cardiovascular alterations .  Twenty sHT patients were r and omly assigned to receive placebo or L-T(4 ) therapy  and were followed for 1 yr . Twenty sex- and age-matched normal subjects served as controls .  Doppler echocardiography and videodensitometric analysis  were performed in all subjects . Myocardium textural parameters were obtained as mean gray levels , which were then used to calculate the cyclic variation index ( CVI ; percent systolic/diastolic change in mean gray levels ) . Patients had a significantly higher isovolumic relaxation time ( 3.1 + /- 0.5 vs. 2.6 + /- 0.6 ; P < 0.03 ) , peak A ( 0.77 + /- 0.16 vs. 0.56 + /- 0.13 m/s ; P < 0.01 ) , and preejection/ejection time ( PEP/ET ) ratio ( 0.72 + /- 0.05 vs. 0.57 + /- 0.06 ; P < 0.03 ) and a lower CVI ( P < 0.0001 ) than controls . CVI was inversely related to TSH level ( P < 0.0001 ) and PEP/ET ratio ( P < 0.01 ) . L-T(4)-treated patients showed a significant reduction of the PEP/ET ratio ( P < 0.05 ) , peak A ( P < 0.05 ) , and isovolumic relaxation time ( P < 0.05 ) along with a normalization of CVI . Conversely , no changes were observed in the placebo-treated group . In conclusion , sHT affects both myocardial structure and contractility . These alterations may be reversed by L-T(4 ) therapy Sub clinical hypothyroidism ( sHT ) is associated with dyslipidemia and enhanced cardiovascular risk . We assessed carotid artery intima-media thickness ( IMT , high-resolution ultrasonography ) and lipoprotein profile in 45 sHT patients ( aged 37 + /- 11 yr ) at baseline and after 6 months of r and omized , placebo-controlled L-T(4 ) replacement .  In comparison with 32 age- and sex-matched controls , sHT patients had elevated total and low-density lipoprotein ( LDL ) cholesterol and ApoB levels ( P = 0.002 , P = 0.0007 , and P = 0.01 , respectively ) and higher mean-IMT values ( P < 0.0001 ) . In stepwise regression analysis , mean-IMT was positively related ( r(2 ) = 0.71 , P < 0.0001 ) to age , TSH , and LDL cholesterol . L-T(4 ) replacement significantly reduced both total and LDL cholesterol ( P < 0.0001 for both ) and mean-IMT ( by 11 % , P < 0.0001 ) . The decrement in IMT was directly related to the decrements of both total cholesterol and TSH ( P = 0.02 and P = 0.0001 , respectively ) . We conclude that early carotid artery wall alterations are present in sHT patients . Whether such IMT increase is related to an early atherosclerotic involvement of the arterial wall can not be clearly decided on the basis of the present results . However , the fact that L-T(4 ) replacement therapy was able to improve both the atherogenic lipoprotein profile and intima-media thickening suggests that lipid infiltration of arterial wall may represent a major mechanism underlying IMT increase in sub clinical hypothyroidism BACKGROUND Sub clinical hypothyroidism ( SCH ) is postulated to increase stroke risk via atherogenic changes associated with abnormal thyroid function . However , the direct relationship of SCH with subsequent stroke is poorly studied . METHODS In this nested case-cohort study , we prospect ively evaluated the association between any SCH and severity of SCH in relation to incident ischemic stroke risk among postmenopausal women in the Women 's Health Initiative Observational Study . Trained Women 's Health Initiative staff , masked to thyroid status , adjudicated stroke cases . We assessed thyroid function  using baseline blood specimens .  Women with normal free thyroxine levels and thyrotropin ( TSH ) levels ≥4.69 mU/L were considered to have SCH . Primary analysis included 639 ischemic stroke cases and 2927 r and omly selected subcohort members with an average of seven years of follow-up . RESULTS The multivariable adjusted hazard ratios ( HR ) from weighted Cox models were 1.06 ( 95 % confidence interval [ CI ] : 0.77 , 1.46 ) and 0.99 ( 95 % CI : 0.67 , 1.47 ) for women with any SCH and with mild SCH ( TSH 4.69 to 6.99 mU/L ) , when compared with women with normal thyroid function . The HR for moderate/severe SCH ( TSH ≥7.00 mU/L ) was modestly elevated ( HR : 1.22 ; 95 % CI : 0.73 , 2.05 ) . CONCLUSIONS We found no evidence to suggest an association between SCH and ischemic stroke among healthy postmenopausal women Background Health technology assessment s of surgical interventions frequently require the inclusion of non-r and omised evidence . Literature search strategies employed to identify this evidence often exclude a method ological component because of uncertainty surrounding the use of appropriate search terms . This can result in the retrieval of a large number of irrelevant records . Method ological filters would help to minimise this , making literature search ing more efficient . Methods An objective approach was employed to develop MEDLINE and EMBASE filters , using a reference st and ard derived from screening the results of an electronic literature search that contained only subject-related terms . C and i date terms for MEDLINE ( N = 37 ) and EMBASE ( N = 35 ) were derived from examination of the records of the reference st and ard . The filters were vali date d on two sets of studies that had been included in previous health technology assessment s. Results The final filters were highly sensitive ( MEDLINE 99.5 % , EMBASE 100 % , MEDLINE / EMBASE combined 100 % ) with precision ranging between 16.7 % – 21.1 % , specificity 35.3 % – 43.5 % , and a reduction in retrievals of over 30 % . Against the validation st and ards , the individual filters retrieved 85.2 % – 100 % of records . In combination , however , the MEDLINE and EMBASE filters retrieved 100 % against both validation st and ards with a reduction in retrieved records of 28.4 % and 30.1 % Conclusion The MEDLINE and EMBASE filters were highly sensitive and substantially reduced the number of records retrieved , indicating that they are useful tools for efficient literature search ing CONTEXT Data regarding the association between sub clinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospect i ve cohort studies . This might reflect differences in participants ' age , sex , thyroid-stimulating hormone ( TSH ) levels , or preexisting cardiovascular disease . OBJECTIVE To assess the risks of coronary heart disease ( CHD ) and total mortality  for adults with sub clinical hypothyroidism . DATA SOURCES AND STUDY SELECTION The data bases of MEDLINE and EMBASE ( 1950 to May 31 , 2010 ) were search ed without language restrictions for prospect i ve cohort studies with baseline thyroid function and subsequent CHD events , CHD mortality , and total mortality . The reference lists of retrieved articles also were search ed . DATA EXTRACTION Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospect i ve cohorts in the United States , Europe , Australia , Brazil , and Japan . The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data . Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Sub clinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations . RESULTS Among 55,287 adults , 3450 had sub clinical hypothyroidism ( 6.2 % ) and 51,837 had euthyroidism . During follow-up , 9664 participants died ( 2168 of CHD ) , and 4470 participants had CHD events ( among 7 studies ) . The risk of CHD events and CHD mortality increased with higher TSH concentrations . In age- and sex-adjusted analyses , the hazard ratio ( HR ) for CHD events was 1.00 ( 95 % confidence interval [ CI ] , 0.86 - 1.18 ) for a TSH level of 4.5 to 6.9 mIU/L ( 20.3 vs 20.3/1000 person-years for participants with euthyroidism ) , 1.17 ( 95 % CI , 0.96 - 1.43 ) for a TSH level of 7.0 to 9.9 mIU/L ( 23.8/1000 person-years ) , and 1.89 ( 95 % CI , 1.28 - 2.80 ) for a TSH level of 10 to 19.9 mIU/L ( n = 70 events/235 ; 38.4/1000 person-years ; P < .001 for trend ) . The corresponding HRs for CHD mortality were 1.09 ( 95 % CI , 0.91 - 1.30 ; 5.3 vs 4.9/1000 person-years for participants with euthyroidism ) , 1.42 ( 95 % CI , 1.03 - 1.95 ; 6.9/1000 person-years ) , and 1.58 ( 95 % CI , 1.10 - 2.27 , n = 28 deaths/333 ; 7.7/1000 person-years ; P = .005 for trend ) . Total mortality was not increased among participants with sub clinical hypothyroidism . Results were similar after further adjustment for traditional cardiovascular risk factors . Risks did not significantly differ by age , sex , or preexisting cardiovascular disease . CONCLUSIONS Sub clinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels , particularly in those with a TSH concentration of 10 mIU/L or greater Sub clinical hypothyroidism ( sHT ) is associated with enhanced cardiovascular risk . To test the hypothesis that patients with sHT are characterized by endothelial dysfunction and impaired nitric oxide ( NO ) availability , in 14 patients [ serum cholesterol , 218 + /- 41 mg/dl ( 5.6 + /- 0.9 mM ) ] and 28 euthyroid subjects , subdivided into groups A and B [ serum cholesterol , 170 + /- 19 mg/dl ( 4.4 + /- 0.5 mM ) and 217 + /- 21 mg/dl ( 5.6 + /- 0.5 mM ) , respectively ] , we studied the forearm blood flow ( strain-gauge plethysmography ) response to intrabrachial acetylcholine , an endothelium-dependent vasodilator , at baseline and during infusion of N(G)-monomethyl-L-arginine ( L-NMMA ) , a NO synthase inhibitor . Response to  sodium nitroprusside and minimal forearm vascular resistances were also evaluated . In sHT patients , vasodilation to acetylcholine was reduced , compared with group B ( + 358 + /- 29 % vs. + 503 + /- 19 % , P = 0.0003 ) and group A ( 663 + /- 65 % , P = 0.02 vs. group B and P = 0.0002 vs. sHT ) . L-NMMA blunted the vasodilation to acetylcholine in groups A and B ( 49.1 + /- 6.3 % and 42.7 + /- 5.5 % maximal forearm blood flow reduction , respectively , P < 0.0001 vs. acetylcholine ) , whereas it was ineffective in sHT patients ( 12.8 + /- 2.5 % ) . Response to sodium nitroprusside and minimal vascular resistances were similar . In sHT ( n = 9 ) patients , 6 months of euthyroidism by levothyroxine replacement increased acetylcholine-vasodilation and restored L-NMMA inhibition .  Patients with sHT are characterized by endothelial dysfunction result ing from a reduction in NO availability , an alteration partially independent of dyslipidemia and reversed by levothyroxine supplementation CONTEXT Sub clinical hypothyroidism ( SCH ) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range . It is uncertain whether treatment of SCH with L-thyroxine improves cardiovasc 
    Output:
    
Our systematic review provides no evidence supporting an increased risk for stroke associated with sub clinical thyroid dysfunction .