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Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies.

IL6R Genetics Consortium Emerging Risk Factors CollaborationSarwar N, Butterworth AS, Freitag DF, Gregson J, Willeit P, Gorman DN, Gao P, Saleheen D, Rendon A, Nelson CP, Braund PS, Hall AS, Chasman DI, Tybjærg-Hansen A, Chambers JC, Benjamin EJ, Franks PW, Clarke R, Wilde AA, Trip MD, Steri M, Witteman JC, Qi L, van der Schoot CE, de Faire U, Erdmann J, Stringham HM, Koenig W, Rader DJ, Melzer D, Reich D, Psaty BM, Kleber ME, Panagiotakos DB, Willeit J, Wennberg P, Woodward M, Adamovic S, Rimm EB, Meade TW, Gillum RF, Shaffer JA, Hofman A, Onat A, Sundström J, Wassertheil-Smoller S, Mellström D, Gallacher J, Cushman M, Tracy RP, Kauhanen J, Karlsson M, Salonen JT, Wilhelmsen L, Amouyel P, Cantin B, Best LG, Ben-Shlomo Y, Manson JE, Davey-Smith G, de Bakker PI, O'Donnell CJ, Wilson JF, Wilson AG, Assimes TL, Jansson JO, Ohlsson C, Tivesten Å, Ljunggren Ö, Reilly MP, Hamsten A, Ingelsson E, Cambien F, Hung J, Thomas GN, Boehnke M, Schunkert H, Asselbergs FW, Kastelein JJ, Gudnason V, Salomaa V, Harris TB, Kooner JS, Allin KH, Nordestgaard BG, Hopewell JC, Goodall AH, Ridker PM, Hólm H, Watkins H, Ouwehand WH, Samani NJ, Kaptoge S, Di Angelantonio E, Harari O, Danesh J - Lancet (2012)

Bottom Line: Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0·04 for each).By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34·3% (95% CI 30·4-38·2) and of interleukin 6 by 14·6% (10·7-18·4), and mean concentration of C-reactive protein was reduced by 7·5% (5·9-9·1) and of fibrinogen by 1·0% (0·7-1·3).Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes.

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(A) Cross-sectional associations between interleukin 6, C-reactive protein, and fibrinogen concentrations in the general population and (B) associations of interleukin 6, C-reactive protein, and fibrinogen concentrations with incident coronary heart diseaseAdjusted for age, sex, smoking, body-mass index, diabetes status, systolic blood pressure, and total cholesterol. Studies included in these analyses had information on at least two of the biomarkers studied and had recorded at least ten incident coronary heart disease events during follow-up. Error bars show 95% CI.
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fig3: (A) Cross-sectional associations between interleukin 6, C-reactive protein, and fibrinogen concentrations in the general population and (B) associations of interleukin 6, C-reactive protein, and fibrinogen concentrations with incident coronary heart diseaseAdjusted for age, sex, smoking, body-mass index, diabetes status, systolic blood pressure, and total cholesterol. Studies included in these analyses had information on at least two of the biomarkers studied and had recorded at least ten incident coronary heart disease events during follow-up. Error bars show 95% CI.

Mentions: Among people with no history of cardiovascular disease at the time of blood sampling, circulating concentrations of interleukin 6, C-reactive protein, and fibrinogen were each positively associated with one another (figure 3A). The age-adjusted and sex-adjusted partial correlation coefficient was 0·49 (95% CI 0·46–0·52) between loge interleukin 6 and loge C-reactive protein, 0·35 (0·31–0·39) between loge interleukin 6 and fibrinogen, and 0·48 (0·45–0·50) between loge C-reactive protein and fibrinogen. There were roughly log-linear associations between baseline concentrations of each of interleukin 6, C-reactive protein, and fibrinogen and subsequent risk of coronary heart disease (figure 3B).


Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies.

IL6R Genetics Consortium Emerging Risk Factors CollaborationSarwar N, Butterworth AS, Freitag DF, Gregson J, Willeit P, Gorman DN, Gao P, Saleheen D, Rendon A, Nelson CP, Braund PS, Hall AS, Chasman DI, Tybjærg-Hansen A, Chambers JC, Benjamin EJ, Franks PW, Clarke R, Wilde AA, Trip MD, Steri M, Witteman JC, Qi L, van der Schoot CE, de Faire U, Erdmann J, Stringham HM, Koenig W, Rader DJ, Melzer D, Reich D, Psaty BM, Kleber ME, Panagiotakos DB, Willeit J, Wennberg P, Woodward M, Adamovic S, Rimm EB, Meade TW, Gillum RF, Shaffer JA, Hofman A, Onat A, Sundström J, Wassertheil-Smoller S, Mellström D, Gallacher J, Cushman M, Tracy RP, Kauhanen J, Karlsson M, Salonen JT, Wilhelmsen L, Amouyel P, Cantin B, Best LG, Ben-Shlomo Y, Manson JE, Davey-Smith G, de Bakker PI, O'Donnell CJ, Wilson JF, Wilson AG, Assimes TL, Jansson JO, Ohlsson C, Tivesten Å, Ljunggren Ö, Reilly MP, Hamsten A, Ingelsson E, Cambien F, Hung J, Thomas GN, Boehnke M, Schunkert H, Asselbergs FW, Kastelein JJ, Gudnason V, Salomaa V, Harris TB, Kooner JS, Allin KH, Nordestgaard BG, Hopewell JC, Goodall AH, Ridker PM, Hólm H, Watkins H, Ouwehand WH, Samani NJ, Kaptoge S, Di Angelantonio E, Harari O, Danesh J - Lancet (2012)

(A) Cross-sectional associations between interleukin 6, C-reactive protein, and fibrinogen concentrations in the general population and (B) associations of interleukin 6, C-reactive protein, and fibrinogen concentrations with incident coronary heart diseaseAdjusted for age, sex, smoking, body-mass index, diabetes status, systolic blood pressure, and total cholesterol. Studies included in these analyses had information on at least two of the biomarkers studied and had recorded at least ten incident coronary heart disease events during follow-up. Error bars show 95% CI.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3316940&req=5

fig3: (A) Cross-sectional associations between interleukin 6, C-reactive protein, and fibrinogen concentrations in the general population and (B) associations of interleukin 6, C-reactive protein, and fibrinogen concentrations with incident coronary heart diseaseAdjusted for age, sex, smoking, body-mass index, diabetes status, systolic blood pressure, and total cholesterol. Studies included in these analyses had information on at least two of the biomarkers studied and had recorded at least ten incident coronary heart disease events during follow-up. Error bars show 95% CI.
Mentions: Among people with no history of cardiovascular disease at the time of blood sampling, circulating concentrations of interleukin 6, C-reactive protein, and fibrinogen were each positively associated with one another (figure 3A). The age-adjusted and sex-adjusted partial correlation coefficient was 0·49 (95% CI 0·46–0·52) between loge interleukin 6 and loge C-reactive protein, 0·35 (0·31–0·39) between loge interleukin 6 and fibrinogen, and 0·48 (0·45–0·50) between loge C-reactive protein and fibrinogen. There were roughly log-linear associations between baseline concentrations of each of interleukin 6, C-reactive protein, and fibrinogen and subsequent risk of coronary heart disease (figure 3B).

Bottom Line: Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0·04 for each).By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34·3% (95% CI 30·4-38·2) and of interleukin 6 by 14·6% (10·7-18·4), and mean concentration of C-reactive protein was reduced by 7·5% (5·9-9·1) and of fibrinogen by 1·0% (0·7-1·3).Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes.

View Article: PubMed Central - PubMed

Show MeSH
Related in: MedlinePlus