04398nas a2200577 4500008004100000022001400041245008500055210006900140260001600209300001200225490000800237520282500245653001503070653001003085653000903095653002203104653002103126653001103147653001103158653001903169653000903188653001603197653001403213653002403227653000903251653001603260653001603276100002103292700002603313700002203339700002103361700001803382700001903400700002203419700002103441700001903462700002103481700002303502700002503525700002103550700001803571700002603589700002003615700002003635700002303655700002603678700002203704700002403726710003403750856003603784 2010 eng d a1538-359800aSubclinical hypothyroidism and the risk of coronary heart disease and mortality.0 aSubclinical hypothyroidism and the risk of coronary heart diseas c2010 Sep 22 a1365-740 v3043 a
CONTEXT: Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective 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 subclinical hypothyroidism.
DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched.
DATA EXTRACTION: Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective 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. Subclinical 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 subclinical 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 subclinical 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: Subclinical 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.
10aAdolescent10aAdult10aAged10aAged, 80 and over10aCoronary Disease10aFemale10aHumans10aHypothyroidism10aMale10aMiddle Aged10aMortality10aProspective Studies10aRisk10aThyrotropin10aYoung Adult1 aRodondi, Nicolas1 aElzen, Wendy, P J den1 aBauer, Douglas, C1 aCappola, Anne, R1 aRazvi, Salman1 aWalsh, John, P1 aAsvold, Bjørn, O1 aIervasi, Giorgio1 aImaizumi, Misa1 aCollet, Tinh-Hai1 aBremner, Alexandra1 aMaisonneuve, Patrick1 aSgarbi, José, A1 aKhaw, Kay-Tee1 aVanderpump, Mark, P J1 aNewman, Anne, B1 aCornuz, Jacques1 aFranklyn, Jayne, A1 aWestendorp, Rudi, G J1 aVittinghoff, Eric1 aGussekloo, Jacobijn1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/123104117nas a2200721 4500008004100000022001400041245008600055210006900141260001600210300001200226490000800238520212100246653001502367653001002382653002102392653000902413653002202422653002402444653001902468653001902487653002802506653001102534653001102545653002002556653000902576653001602585653001402601653002402615653002002639653003002659653002102689653002202710653001602732653002702748653001602775653001602791100002102807700002402828700002202852700002602874700002102900700002102921700002102942700002202963700002102985700001903006700001903025700002103044700002203065700002303087700002103110700002503131700002003156700002003176700001803196700002603214700002303240700002203263700001903285700002103304710003403325856003603359 2012 eng d a1538-367900aSubclinical hyperthyroidism and the risk of coronary heart disease and mortality.0 aSubclinical hyperthyroidism and the risk of coronary heart disea c2012 May 28 a799-8090 v1723 aBACKGROUND: Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting.We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts.
METHODS: Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications.
RESULTS: Of 52 674 participants, 2188 (4.2%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio[HR], 1.24, 95% CI, 1.06-1.46), CHD mortality (HR,1.29; 95% CI, 1.02-1.62), CHD events (HR, 1.21; 95%CI, 0.99-1.46), and AF (HR, 1.68; 95% CI, 1.16-2.43).Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% forAF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L(for both, P value for trend, .03).
CONCLUSION: Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.
10aAdolescent10aAdult10aAge Distribution10aAged10aAged, 80 and over10aAtrial Fibrillation10aCause of Death10aCohort Studies10aCoronary Artery Disease10aFemale10aHumans10aHyperthyroidism10aMale10aMiddle Aged10aPrognosis10aProspective Studies10aRisk Assessment10aSeverity of Illness Index10aSex Distribution10aSurvival Analysis10aSwitzerland10aThyroid Function Tests10aThyrotropin10aYoung Adult1 aCollet, Tinh-Hai1 aGussekloo, Jacobijn1 aBauer, Douglas, C1 aElzen, Wendy, P J den1 aCappola, Anne, R1 aBalmer, Philippe1 aIervasi, Giorgio1 aAsvold, Bjørn, O1 aSgarbi, José, A1 aVölzke, Henry1 aGencer, Bariş1 aMaciel, Rui, M B1 aMolinaro, Sabrina1 aBremner, Alexandra1 aLuben, Robert, N1 aMaisonneuve, Patrick1 aCornuz, Jacques1 aNewman, Anne, B1 aKhaw, Kay-Tee1 aWestendorp, Rudi, G J1 aFranklyn, Jayne, A1 aVittinghoff, Eric1 aWalsh, John, P1 aRodondi, Nicolas1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/154503588nas a2200589 4500008004100000022001400041245014200055210006900197260001600266300001100282490000800293520192100301653001002222653000902232653002202241653001602263653001102279653002202290653001802312653001102330653001902341653000902360653001602369653002402385653000902409653001702418653003202435653001602467653001402483100001902497700002102516700002102537700002202558700002402580700002102604700001902625700002602644700002102670700002102691700002402712700002402736700002002760700002002780700001802800700001902818700002602837700002202863700002202885700002102907710003402928856003602962 2012 eng d a1524-453900aSubclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts.0 aSubclinical thyroid dysfunction and the risk of heart failure ev c2012 Aug 28 a1040-90 v1263 aBACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events.
METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors.
CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L.
10aAdult10aAged10aAged, 80 and over10aComorbidity10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aHypothyroidism10aMale10aMiddle Aged10aProspective Studies10aRisk10aRisk Factors10aSensitivity and Specificity10aThyrotropin10aThyroxine1 aGencer, Bariş1 aCollet, Tinh-Hai1 aVirgini, Vanessa1 aBauer, Douglas, C1 aGussekloo, Jacobijn1 aCappola, Anne, R1 aNanchen, David1 aElzen, Wendy, P J den1 aBalmer, Philippe1 aLuben, Robert, N1 aIacoviello, Massimo1 aTriggiani, Vincenzo1 aCornuz, Jacques1 aNewman, Anne, B1 aKhaw, Kay-Tee1 aJukema, Wouter1 aWestendorp, Rudi, G J1 aVittinghoff, Eric1 aAujesky, Drahomir1 aRodondi, Nicolas1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/608703608nas a2200601 4500008004100000022001400041245013800055210006900193260001300262300001200275490000700287520190900294653001002203653000902213653002202222653001902244653002102263653001102284653001102295653001902306653001402325653000902339653001602348653001502364653001402379653001702393653003002410653003002440653001602470100002102486700002202507700002102529700002202550700001902572700002202591700002402613700002302637700002602660700002102686700002602707700002002733700001802753700002502771700002002796700002102816700001802837700001902855700001902874700002202893700002102915710003402936856003602970 2014 eng d a1945-719700aThyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: an individual participant data analysis.0 aThyroid antibody status subclinical hypothyroidism and the risk c2014 Sep a3353-620 v993 aCONTEXT: Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk.
OBJECTIVE: The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs).
DATA SOURCES AND STUDY SELECTION: A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes.
DATA EXTRACTION: Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events.
DATA SYNTHESIS: Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87-1.53 vs HR 1.26, CI 1.01-1.58, P for interaction = .62], as were risks of CHD events (HR 1.16, CI 0.87-1.56 vs HR 1.26, CI 1.02-1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status.
CONCLUSIONS: CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes.
10aAdult10aAged10aAged, 80 and over10aAutoantibodies10aCoronary Disease10aFemale10aHumans10aHypothyroidism10aIncidence10aMale10aMiddle Aged10aPrevalence10aPrognosis10aRisk Factors10aSeroepidemiologic Studies10aSeverity of Illness Index10aYoung Adult1 aCollet, Tinh-Hai1 aBauer, Douglas, C1 aCappola, Anne, R1 aAsvold, Bjørn, O1 aWeiler, Stefan1 aVittinghoff, Eric1 aGussekloo, Jacobijn1 aBremner, Alexandra1 aElzen, Wendy, P J den1 aMaciel, Rui, M B1 aVanderpump, Mark, P J1 aCornuz, Jacques1 aDörr, Marcus1 aWallaschofski, Henri1 aNewman, Anne, B1 aSgarbi, José, A1 aRazvi, Salman1 aVölzke, Henry1 aWalsh, John, P1 aAujesky, Drahomir1 aRodondi, Nicolas1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/655303870nas a2200721 4500008004100000022001400041245012000055210006900175260001300244300001200257490000800269520185000277653001002127653002602137653001102163653001102174653001902185653001402204653000902218653001702227653001102244653001602255100001802271700002702289700002602316700002002342700002002362700002102382700002502403700001902428700002602447700002102473700001902494700002902513700001802542700002102560700002002581700001402601700002302615700002202638700002002660700002002680700002302700700002102723700002302744700002102767700002402788700001902812700001902831700002302850700002202873700001902895700001802914700001802932700002102950700001902971700002102990700002403011700002103035700002203056710003403078856003603112 2015 eng d a1945-719700aSubclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis.0 aSubclinical Hypothyroidism and the Risk of Stroke Events and Fat c2015 Jun a2181-910 v1003 aOBJECTIVE: The objective was to determine the risk of stroke associated with subclinical hypothyroidism.
DATA SOURCES AND STUDY SELECTION: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels.
DATA EXTRACTION AND SYNTHESIS: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or ≥ 80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations.
CONCLUSIONS: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.
10aAdult10aAsymptomatic Diseases10aFemale10aHumans10aHypothyroidism10aIncidence10aMale10aRisk Factors10aStroke10aThyrotropin1 aChaker, Layal1 aBaumgartner, Christine1 aElzen, Wendy, P J den1 aIkram, Arfan, M1 aBlum, Manuel, R1 aCollet, Tinh-Hai1 aBakker, Stephan, J L1 aDehghan, Abbas1 aDrechsler, Christiane1 aLuben, Robert, N1 aHofman, Albert1 aPortegies, Marileen, L P1 aMedici, Marco1 aIervasi, Giorgio1 aStott, David, J1 aFord, Ian1 aBremner, Alexandra1 aWanner, Christoph1 aFerrucci, Luigi1 aNewman, Anne, B1 aDullaart, Robin, P1 aSgarbi, José, A1 aCeresini, Graziano1 aMaciel, Rui, M B1 aWestendorp, Rudi, G1 aJukema, Wouter1 aImaizumi, Misa1 aFranklyn, Jayne, A1 aBauer, Douglas, C1 aWalsh, John, P1 aRazvi, Salman1 aKhaw, Kay-Tee1 aCappola, Anne, R1 aVölzke, Henry1 aFranco, Oscar, H1 aGussekloo, Jacobijn1 aRodondi, Nicolas1 aPeeters, Robin, P1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/680005194nas a2200733 4500008004100000022001400041245007200055210006900127260001600196300001200212490000800224520318200232653001503414653001003429653000903439653002203448653001103470653002003481653001803501653001103519653002003530653001903550653000903569653001603578653001703594653002103611653001603632653001603648100002003664700002203684700002103706700002003727700002103747700002303768700002403791700002203815700002203837700002603859700002103885700001903906700002603925700002303951700002103974700002503995700002404020700002104044700001504065700002304080700002604103700002804129700002004157700002604177700001804203700002204221700002004243700002404263700002404287700001904311700001704330700002204347700002104369710003404390856003604424 2015 eng d a1538-359800aSubclinical thyroid dysfunction and fracture risk: a meta-analysis.0 aSubclinical thyroid dysfunction and fracture risk a metaanalysis c2015 May 26 a2055-650 v3133 aIMPORTANCE: Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking.
OBJECTIVE: To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures.
DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures.
DATA EXTRACTION: Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations.
MAIN OUTCOME AND MEASURES: The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes.
RESULTS: Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk.
CONCLUSIONS AND RELEVANCE: Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.
10aAdolescent10aAdult10aAged10aAged, 80 and over10aFemale10aFractures, Bone10aHip Fractures10aHumans10aHyperthyroidism10aHypothyroidism10aMale10aMiddle Aged10aRisk Factors10aSpinal Fractures10aThyrotropin10aYoung Adult1 aBlum, Manuel, R1 aBauer, Douglas, C1 aCollet, Tinh-Hai1 aFink, Howard, A1 aCappola, Anne, R1 ada Costa, Bruno, R1 aWirth, Christina, D1 aPeeters, Robin, P1 aAsvold, Bjørn, O1 aElzen, Wendy, P J den1 aLuben, Robert, N1 aImaizumi, Misa1 aBremner, Alexandra, P1 aGogakos, Apostolos1 aEastell, Richard1 aKearney, Patricia, M1 aStrotmeyer, Elsa, S1 aWallace, Erin, R1 aHoff, Mari1 aCeresini, Graziano1 aRivadeneira, Fernando1 aUitterlinden, André, G1 aStott, David, J1 aWestendorp, Rudi, G J1 aKhaw, Kay-Tee1 aLanghammer, Arnuf1 aFerrucci, Luigi1 aGussekloo, Jacobijn1 aWilliams, Graham, R1 aWalsh, John, P1 aJüni, Peter1 aAujesky, Drahomir1 aRodondi, Nicolas1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/679504076nas a2200553 4500008004100000022001400041245013600055210006900191260001300260300001200273490000800285520245400293653001902747653002102766653001102787653001902798653001602817100002202833700002002855700001802875700002202893700002302915700002102938700002302959700002602982700002003008700002103028700002303049700002403072700002103096700001903117700002503136700001803161700002103179700002003200700002203220700002003242700001803262700002103280700002003301700002003321700002603341700001903367700001903386700002603405700002103431710003403452856003603486 2015 eng d a2168-611400aThyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts.0 aThyroid function within the normal range and risk of coronary he c2015 Jun a1037-470 v1753 aIMPORTANCE: Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD).
OBJECTIVE: To assess the association between differences in thyroid function within the reference range and CHD risk.
DESIGN, SETTING, AND PARTICIPANTS: Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55,412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline.
EXPOSURES: Thyroid function as expressed by serum thyrotropin levels at baseline.
MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status.
RESULTS: Among 55,412 individuals, 1813 people (3.3%) died of CHD during 643,183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48,875 individuals (9.5%) experienced a first-time CHD event during 533,408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results.
CONCLUSIONS AND RELEVANCE: Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.
10aCohort Studies10aCoronary Disease10aHumans10aHypothyroidism10aThyrotropin1 aAsvold, Bjørn, O1 aVatten, Lars, J1 aBjøro, Trine1 aBauer, Douglas, C1 aBremner, Alexandra1 aCappola, Anne, R1 aCeresini, Graziano1 aElzen, Wendy, P J den1 aFerrucci, Luigi1 aFranco, Oscar, H1 aFranklyn, Jayne, A1 aGussekloo, Jacobijn1 aIervasi, Giorgio1 aImaizumi, Misa1 aKearney, Patricia, M1 aKhaw, Kay-Tee1 aMaciel, Rui, M B1 aNewman, Anne, B1 aPeeters, Robin, P1 aPsaty, Bruce, M1 aRazvi, Salman1 aSgarbi, José, A1 aStott, David, J1 aTrompet, Stella1 aVanderpump, Mark, P J1 aVölzke, Henry1 aWalsh, John, P1 aWestendorp, Rudi, G J1 aRodondi, Nicolas1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/679803627nas a2200637 4500008004100000022001400041245011300055210006900168260001300237300001400250490000800264520178200272100001802054700002702072700002602099700002102125700002002146700002002166700001902186700002602205700002102231700002902252700002102281700001802302700002002320700002302340700001402363700002302377700002002400700002202420700002102442700001802463700002002481700002002501700002002521700002102541700002402562700001902586700002302605700001902628700001902647700002502666700002302691700001802714700002202732700001902754700001802773700002402791700001902815700002102834700002102855700002102876700002202897710003402919856003602953 2016 eng d a1945-719700aThyroid Function Within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis.0 aThyroid Function Within the Reference Range and the Risk of Stro c2016 Nov a4270-42820 v1013 aCONTEXT: The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously.
DESIGN AND SETTING: We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T4, and stroke outcomes were included, and we collected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L.
RESULTS: We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449 908 person-years. Age- and sex-adjusted pooled hazard ratio for TSH was 0.78 (95% confidence interval [CI] 0.65-0.95 across the reference range of TSH) for all stroke and 0.83 (95% CI 0.62-1.09) for fatal stroke. For the free T4 analyses, the hazard ratio was 1.08 (95% CI 0.99-1.15 per SD increase) for all stroke and 1.10 (95% CI 1.04-1.19) for fatal stroke. This was independent of cardiovascular risk factors including systolic blood pressure, total cholesterol, smoking, and prevalent diabetes.
CONCLUSION: Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within the reference range of thyroid function.
1 aChaker, Layal1 aBaumgartner, Christine1 aElzen, Wendy, P J den1 aCollet, Tinh-Hai1 aIkram, Arfan, M1 aBlum, Manuel, R1 aDehghan, Abbas1 aDrechsler, Christiane1 aLuben, Robert, N1 aPortegies, Marileen, L P1 aIervasi, Giorgio1 aMedici, Marco1 aStott, David, J1 aDullaart, Robin, P1 aFord, Ian1 aBremner, Alexandra1 aNewman, Anne, B1 aWanner, Christoph1 aSgarbi, José, A1 aDörr, Marcus1 aLongstreth, W T1 aPsaty, Bruce, M1 aFerrucci, Luigi1 aMaciel, Rui, M B1 aWestendorp, Rudi, G1 aJukema, Wouter1 aCeresini, Graziano1 aImaizumi, Misa1 aHofman, Albert1 aBakker, Stephan, J L1 aFranklyn, Jayne, A1 aKhaw, Kay-Tee1 aBauer, Douglas, C1 aWalsh, John, P1 aRazvi, Salman1 aGussekloo, Jacobijn1 aVölzke, Henry1 aFranco, Oscar, H1 aCappola, Anne, R1 aRodondi, Nicolas1 aPeeters, Robin, P1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/723804137nas a2200745 4500008004100000022001400041245011100055210006900166260001600235300001400251490000800265520205100273653001002324653000902334653002202343653002602365653002402391653001502415653002802430653001102458653001102469653001902480653001402499653000902513653001602522653003002538653001402568653003202582653002002614653001702634653002702651653001802678653001602696653001402712653001702726653001602743100002702759700002302786700002102809700001902830700002102849700002202870700002102892700002302913700002302936700002402959700002602983700002203009700001803031700001903049700001803068700001903086700002303105700002403128700002203152700001803174700002003192700002603212700001803238700002203256700002203278700002103300710003403321856003603355 2017 eng d a1524-453900aThyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation.0 aThyroid Function Within the Normal Range Subclinical Hypothyroid c2017 Nov 28 a2100-21160 v1363 aBACKGROUND: Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF.
METHODS: We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF.
RESULTS: Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease.
CONCLUSIONS: In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.
10aAdult10aAged10aAged, 80 and over10aAsymptomatic Diseases10aAtrial Fibrillation10aBiomarkers10aChi-Square Distribution10aFemale10aHumans10aHypothyroidism10aIncidence10aMale10aMiddle Aged10aPredictive Value of Tests10aPrognosis10aProportional Hazards Models10aRisk Assessment10aRisk Factors10aThyroid Function Tests10aThyroid Gland10aThyrotropin10aThyroxine10aTime Factors10aYoung Adult1 aBaumgartner, Christine1 ada Costa, Bruno, R1 aCollet, Tinh-Hai1 aFeller, Martin1 aFloriani, Carmen1 aBauer, Douglas, C1 aCappola, Anne, R1 aHeckbert, Susan, R1 aCeresini, Graziano1 aGussekloo, Jacobijn1 aElzen, Wendy, P J den1 aPeeters, Robin, P1 aLuben, Robert1 aVölzke, Henry1 aDörr, Marcus1 aWalsh, John, P1 aBremner, Alexandra1 aIacoviello, Massimo1 aMacfarlane, Peter1 aHeeringa, Jan1 aStott, David, J1 aWestendorp, Rudi, G J1 aKhaw, Kay-Tee1 aMagnani, Jared, W1 aAujesky, Drahomir1 aRodondi, Nicolas1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/755003623nas a2200589 4500008004100000022001400041245009600055210006900151260001600220520189500236100002702131700002202158700002102180700002002201700002402221700002202245700002002267700002402287700001502311700001802326700001802344700002102362700002202383700001802405700002002423700002502443700002002468700002102488700002202509700002302531700002002554700002502574700002502599700001902624700002502643700002002668700002202688700002102710700001902731700001902750700002302769700002102792700002102813700001902834700001702853700002202870700002102892700002402913700002602937710003402963856003602997 2018 eng d a1460-238500aLow thyroid function is not associated with an accelerated deterioration in renal function.0 aLow thyroid function is not associated with an accelerated deter c2018 Apr 183 aBackground: Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups.
Methods: Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models.
Results: A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function.
Conclusions: Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.
1 aMeuwese, Christiaan, L1 avan Diepen, Merel1 aCappola, Anne, R1 aSarnak, Mark, J1 aShlipak, Michael, G1 aBauer, Douglas, C1 aFried, Linda, P1 aIacoviello, Massimo1 aVaes, Bert1 aDegryse, Jean1 aKhaw, Kay-Tee1 aLuben, Robert, N1 aAsvold, Bjørn, O1 aBjøro, Trine1 aVatten, Lars, J1 ade Craen, Anton, J M1 aTrompet, Stella1 aIervasi, Giorgio1 aMolinaro, Sabrina1 aCeresini, Graziano1 aFerrucci, Luigi1 aDullaart, Robin, P F1 aBakker, Stephan, J L1 aJukema, Wouter1 aKearney, Patricia, M1 aStott, David, J1 aPeeters, Robin, P1 aFranco, Oscar, H1 aVölzke, Henry1 aWalsh, John, P1 aBremner, Alexandra1 aSgarbi, José, A1 aMaciel, Rui, M B1 aImaizumi, Misa1 aOhishi, Waka1 aDekker, Friedo, W1 aRodondi, Nicolas1 aGussekloo, Jacobijn1 aElzen, Wendy, P J den1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/780503682nas a2200577 4500008004100000022001400041245010400055210006900159260001600228520196600244100002302210700002202233700002202255700001902277700002302296700002502319700002202344700002102366700002302387700001802410700002502428700001902453700002002472700002102492700002102513700002402534700002102558700001902579700001902598700001802617700002102635700002202656700002002678700002202698700002202720700002002742700001802762700002502780700002702805700002002832700001502852700002602867700001902893700002602912700002102938700002502959700002402984700002603008710003403034856003603068 2018 eng d a1945-719700aThe relation between thyroid function and anemia: a pooled analysis of individual participant data.0 arelation between thyroid function and anemia a pooled analysis o c2018 Aug 023 aContext: Anemia and thyroid dysfunction often co-occur and both increase with age. Human data on the relationship between thyroid disease and anemia are scarce.
Objective: To investigate the cross-sectional and longitudinal associations between clinical thyroid status and anemia.
Design: Individual participant data meta-analysis.
Setting: Sixteen cohorts participating in the Thyroid Studies Collaboration (n=42 162).
Main outcome measures: Primary outcome measure was anemia (hemoglobin <130 g/L in men and <120 g/L in women).
Results: Cross-sectionally, participants with abnormal thyroid status had an increased risk of having anemia compared with euthyroid participants (overt hypothyroidism, pooled odds ratio 1.84 [95% CI: 1.35-2.50], subclinical hypothyroidism 1.21 [1.02-1.43], subclinical hyperthyroidism 1.27 [1.03-1.57], overt hyperthyroidism 1.69 [1.00-2.87]). Hemoglobin levels were lower in all groups compared to participants with euthyroidism. In the longitudinal analyses (n=25,466 from 14 cohorts), the pooled hazard ratio for the risk of development of anemia was 1.38 [95% CI: 0.86-2.20] for overt hypothyroidism, 1.18 [1.00-1.38] for subclinical hypothyroidism, 1.15 [0.94-1.42] for subclinical hyperthyroidism and 1.47 [0.91-2.38] for overt hyperthyroidism. Sensitivity analyses excluding thyroid medication or high levels of C-reactive protein yielded similar results. No differences in mean annual change in hemoglobin levels were observed between the thyroid hormone status groups.
Conclusion: Higher odds of having anemia were observed in both participants with hypothyroid function and hyperthyroid function. In addition, reduced thyroid function at baseline showed a trend of increased risk of developing anemia during follow-up. It remains to be assessed in a randomized controlled trial whether treatment is effective in reducing anemia.
1 aWopereis, Daisy, M1 aPuy, Robert, S Du1 avan Heemst, Diana1 aWalsh, John, P1 aBremner, Alexandra1 aBakker, Stephan, J L1 aBauer, Douglas, C1 aCappola, Anne, R1 aCeresini, Graziano1 aDegryse, Jean1 aDullaart, Robin, P F1 aFeller, Martin1 aFerrucci, Luigi1 aFloriani, Carmen1 aFranco, Oscar, H1 aIacoviello, Massimo1 aIervasi, Georgio1 aImaizumi, Misa1 aJukema, Wouter1 aKhaw, Kay-Tee1 aLuben, Robert, N1 aMolinaro, Sabrina1 aNauck, Matthias1 aPatel, Kushang, V1 aPeeters, Robin, P1 aPsaty, Bruce, M1 aRazvi, Salman1 aSchindhelm, Roger, K1 avan Schoor, Natasja, M1 aStott, David, J1 aVaes, Bert1 aVanderpump, Mark, P J1 aVölzke, Henry1 aWestendorp, Rudi, G J1 aRodondi, Nicolas1 aCobbaert, Christa, M1 aGussekloo, Jacobijn1 aElzen, Wendy, P J den1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/7817