炎癥和CHD的流行病學(xué)：hsCRP的證據(jù)講座

1、Castelli WP. Atherosclerosis. 1996;124(suppl):S1-S9.1996 Reprinted with permission from Elsevier Science.150200Total Cholesterol (mg/dL)250300No CHDCHDFramingham Heart Study26-Year Follow-upn Inflammation may determine plaque stability - Unstable plaques have increased leukocytic infiltrates - T cel

2、ls, macrophages predominate rupture sites - Cytokines and metalloproteinases influence both stability and degradation of the fibrous capn Lipid lowering may reduce plaque inflammation - Decreased macrophage number - Decreased expression of collagenolytic enzymes (MMP-1) - Increased interstitial coll

3、agen - Decreased expression of E-selectin - Reduced calcium depositionLibby P. Circulation 1995;91:2844-2850. Ross R. N Engl J Med 1999;340:115-126.0123Ridker PM et al. N Engl J Med 1997;336:973-979.10.211P 0.001P 0.0010.00.51.01.52.02.53.0Ridker PM et al. N Engl J Med 1997;336:973-979.1Relative Ris

4、k of Future MIQuartile of CRP234All PatientsNonsmokers0.01.02.0Ridker PM et al. N Engl J Med 1997;336:973-979.1997 Massachusetts Medical Society. All rights reserved.0 2Relative Risk(per Quartile)Years of Study Follow-up2 44 66+012Ridker PM et al. N Engl J Med 1997;336:973-979.10.211P =0.02P =0.020.

5、01.02.0Ridker PM et al. Circulation 1998;97:425-428.1998 Lippincott Williams & Wilkins.Nonehs-CRP (mg/dL)IntermittentClaudicationPeripheral ArterySurgeryn9、 人的價(jià)值，在招收誘惑的一瞬間被決定。2022-5-162022-5-16Monday, May 16, 2022n10、低頭要有勇氣，抬頭要有低氣。2022-5-162022-5-162022-5-165/16/2022 10:11:21 PMn11、人總是珍惜為得到。2022-5-1

6、62022-5-162022-5-16May-2216-May-22n12、人亂于心，不寬余請(qǐng)。2022-5-162022-5-162022-5-16Monday, May 16, 2022n13、生氣是拿別人做錯(cuò)的事來(lái)懲罰自己。2022-5-162022-5-162022-5-162022-5-165/16/2022n14、抱最大的希望，作最大的努力。2022年5月16日星期一2022-5-162022-5-162022-5-16n15、一個(gè)人炫耀什么，說(shuō)明他內(nèi)心缺少什么。2022年5月2022-5-162022-5-162022-5-165/16/2022n16、業(yè)余生活要有意義，不要越軌

7、。2022-5-162022-5-16May 16, 2022n17、一個(gè)人即使已登上頂峰，也仍要自強(qiáng)不息。2022-5-162022-5-162022-5-162022-5-1601234567Ridker PM et al. Circulation 1998;98:731-733.10.73Any EventMI or Stroke01234567Ridker PM et al. Circulation 1998;98:731-733.10.73No hypertensionNo hyperlipidemiaNo current smokingNo diabetesNo family hi

8、story01234Koenig W et al. Circulation 1999;99:237-242.14.51.02.03.04.05.06.0Relative Risk (upper vs lower quartile)CHD DeathMIStrokeCHDPVDCVDCHDCHDCHDCHD0MRFIT (Kuller 1996)PHS (Ridker 1997)PHS (Ridker 1997)CHS/RHPP (Tracy 1997)PHS (Ridker 1998)WHS (Ridker 1998, 2000)MONICA (Koenig 1999)Helsinki (Ro

9、ivainen 2000)Caerphilly(Mendall 2000)Britain (Danesh 2000)0123456Ridker PM et al. Circulation 1998;97:2007-2011.1998 Lippincott Williams & Wilkins.Adjusted Relative RiskCRP 75thpercentileTC 75thpercentile+P = 0.02P = 0.001P = 0.0020.01.02.03.04.05.0HighMediumLowLowMediumHighRidker PM et al. Circulat

10、ion 1998;97:2007-2011.1998 Lippincott Williams & Wilkins.Total Cholesterol:HDL Ratiohs-CRP432112349876543210Ridker PM et al. N Engl J Med 2000;342:836-843.Ridker PM et al. Lancet 1998;351:88-92.1998 Reprinted with permission from Elsevier Science.Years of Study Follow-up013210122448Relative RiskRidk

11、er PM et al. N Engl J Med 2000;342:836-843.2000 Massachusetts Medical Society. All rights reserved.43210HighMediumLowHighMediumLowRidker PM et al. Circulation 2000;101:2149-2153.2000 Lippincott Williams & Wilkins.2.52.01.51.002.47(1st50th)Relative RiskTNF- Concentration, pg/mL (percentile of control

12、 distribution)2.483.05(51st75th)3.064.17(76th95th)4.18+(95th)Relative Risk of Future Cardiovascular Events0Ridker PM et al. N Engl J Med 2000;342:836-843.Lipoprotein(a)HomocysteineIL-6TCLDL-CsICAM-1SAAApo BTC:HDL-Chs-CRPhs-CRP + TC:HDL-C1.02.04.06.0Ridker PM et al. N Engl J Med 2000;342:836-843.4321

13、1Relative Risk of FutureCoronary EventsQuartile of Inflammatory Markerhs-CRP234SAAIL-6sICAM-1nConfounding by cigarette consumptionnInnocent bystander- Acute phase responsenCytokine surrogate- IL-6, TNF-, IL-1nDirect effects of CRP- Innate immunity- Complement activation- CAM inductionnPrior infectio

14、n- Chlamydia, H pylori, CMVnMarker for subclinical atherosclerosis- EBCT / IMT / ABInMarker for insulin resistance/ obesitynMarker for endothelial dysfunctionnMarker for dysmetabolic syndromenMarker for plaque vulnerabilitynConsistency of prospective datanStrength of associationnIndependence of asso

15、ciationnImprove predictive valuenStandardized measurenLow variabilitynHigh reproducibilitynBiologic plausibilitynLow costnModifiablenCRP is an acute-phase protein produced by the liver in response to cytokine production (IL-6, IL-1, tumor necrosis factor) during tissue injury, inflammation, or infec

16、tion. tests determine levels which are increased up to 1,000-fold in response to infection or tissue destruction, but cannot adequately assess the normal range (hs-CRP) assays (i.e. Dade Behring) detect levels of CRP within the normal range, levels proven to predict future cardiovascular events.5432

17、10-1-2-3Dadehs-CRP (Latex, Inmg/L)hs-CRP (ELISA, Inmg/L) (In-house)-3-2-1012354Rifai N et al. Clin Chem 1999;45:2136-2141.r = 0.93P 0.001ParameterrPhs-CRP0.600.001Total Cholesterol0.370.001LDL-C0.320.001HDL-C0.740.001Triglycerides0.490.001Ridker PM et al. Circulation 1999;100:230-235.QuintileRange (

18、mg/dL)Risk Estimate10.010.069Low20.070.11Mild30.120.19Moderate40.200.38High50.391.50HighestRidker PM et al. Circulation. In press.ParameterVenousArterialFibrinogen+Factor VII+vWF: ag+tPA: ag+PAI-1: ag+Platelet function+Lp(a)+hs-CRP / SAA / IL-6 / TNF+ParameterVenousArterialFactor V Leiden+Prothrombin mutation+Prothrombin+Factor VIII+Anti-thrombin III+Protein C+Protein S+Homocysteine+D-dimer+Lp(a)+/+/Homocysteine+/+/tPA and PAI-1+/+