Chronic disease what comes after risk factor epidemiology
- 1. Chronic Disease : What comes after risk factor epidemiology? William McClellan, MD, MPH Professor of Medicine and Epidemiology Emory University
- 2. www.smj.org.uk/0803/CHD%20figure_1.htm . Trends in coronary heart disease mortality among men aged 35-64 in selected countries/areas
- 4. Remaining lifetime risks for atherosclerotic CVD in men and women at 50 years of age. Optimal risk factors (RFs) are defined as untreated total cholesterol <4.65 mmol/L (<180 mg/dL), untreated blood pressure <120/<80 mm Hg, nonsmoker, and nondiabetic. Circulation. 2010; 121: 1768-1777
- 5. Lipoprotein-associated Apolipoprotein B Lipoprotein (a) LDL particle size LDL particle number Triglycerides Cholesterol ester transfer protein level Lipoprotein-associated phospholipase A2 Small-dense LDL Oxidized LDL Apolipoprotein A1 Paraxonase-1 Inflammatory C-reactive protein Interleukin-18 Interleukin-6 Interleukin-10 Tumour necrosis factor-a Serum amyloid A Serum inter-cellular adhesion molecule-1 Myeloperoxidase sCD40 Vascular cell adhesion molecule Interleukin-1 receptor antagonist Thrombosis-related Fibrinogen Fibrin D-dimer Plasminogen activator inhibitor-1 von Willebrand factor Soluble CD40 ligand Homocysteine Factor VIII Others Matrix metalloproteases-9 Tissue inhibitor of metalloproteinases-1 Natriuretic peptides Insulin E-selectin Adiponectin Leptin Ferritin Fasting glucose Hemoglobin A1c Urinary albumin Non-Framingham Risk Factors
- 6. Nature. 2011 Apr 7;472(7341):57-63. doi: [PubMed - in S Intestinal microbial metabolism of phosphatidylcholine an Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, F N Engl J Med. 2013 Apr 25;368(17):1575-84. doi: 10.10 Systems biology: Detailed, integrated, orthogonally linked networks at each level of biological organization Biological organization • Genes • Transcript • Protein • Metabolite • Organelle • Cell • Organ • Organism • Social System • Ecological systems Recent applications •Geospatial variations and hierarchical models • Complex biomarkers – Genome – Proteome – Metabolome – Microbiome • Non-linear causal networks •Chronic disease surveillance and T2 translation •Evidence-based public health practice
- 8. Heart disease death rates are spatially smoothed to enhance the stability of rates in counties with small populations. Deaths are defined according to the following International Classification of Diseases (ICD) codes: ICD-9: 390–398, 402, 404–429; ICD-10: 100–109, I11, I13, 120–151. Data Sources: National Vital Statistics System, CDC, and the U.S. Census Bureau. Orthogonally linked
- 10. J Am Coll Cardiol. 2012;60:1715-21 Complex (interacting) biomarkers
- 11. Features of CAD Genetic Risk Variants • Risk variants associated with – Lipids (8) – Hypertension (2) – Independent of known risk factors (23) • RR of each varies (6% to 92%); mean 18%. • Population frequency varies (2% to 91%); mean 47%. • Alleles/individual varies from 0 to 46; mean 17, and range 7-37. • Variants generally associated with risk of early CAD • Most genetic risk variants for CAD are located in non-coding DNA sequences
- 12. Cellular proteins belong to large, connected systems
- 14. Tests of the reno- and cardio-protection by erythropoietin in CKD hypotheses: No benefit Large biological systems generate unexpected (emergent) behavior when perturbed
- 15. J Biomed Biotechnol. 2011;2011:790132 Lewis GD et al. Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury. J Clin Invest. 2008 Oct;118(10):3503-12.
- 16. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease: Linking biological systems Nature 2011; 472:57-63.
- 17. Social Contagion in non-linear causal networks N Engl J Med. 2007;357:370-9 Stat Med. 2013; 32:556-77
- 18. Evidence-based public health practice • Social Networks and Childhood Obesity • The Role of the Built Environment • Interventions – Targeting Existing Social Networks – Purposeful Development of Social Networks – Social Media: E-Mail and Texting Interventions • Randomized Trials of Internet-Based Obesity Interventions Circulation. 2013;127:260-7
- 19. Disease surveillance systems and T2 translation Diabetes Care. 2000; 23:1794-8 Am. J. Epidemiol. 2010; 172: 517-524
- 20. Healthy People 2020: Reduce the proportion of adults with high total blood cholesterol levels Reduce the proportion of adults with high total blood cholesterol levels Baseline: 15.0 percent of adults aged 20 years and older had total blood cholesterol levels of 240 mg/dL or greater in 2005– 08 (age adjusted to the year 2000 standard population) Target: 13.5 percent Target-Setting Method: 10 percent improvement Data Source: National Health and Nutrition Examination Survey (NHANES), CDC/NCHS More Information: Data for this objective The HP2010 objective with the same definition was 12-14. View on DATA2010
- 21. † A serum total cholesterol level greater than or equal to 240 mg/dL *Significant decreasing trend (p<0.005). NOTE: HP 2010 = Healthy People 2010 Objective (17%). Source: CDC/NCHS NHANES
- 23. Summary • Successes and limitations of single risk factor epidemiology • Emerging interest in complex systems to account for residual CHD risk • New tools to study these relationships (GIS, large biological and social databases, network analysis, and surveillance systems) • Comprehensive synthesis and application remain a challenge for the future
Editor's Notes
- #17: 7Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, Didonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Nat Med. 2013 May;19(5):576-85. doi: 10.1038/nm.3145. Epub 2013 Apr 7. PMID: 23563705 [PubMed - in process] Related citations Select item 214751952. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922. PMID: 21475195 [PubMed - indexed for MEDLINE] Free PMC Article Related citations Select item 236145843. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. N Engl J Med. 2013 Apr 25;368(17):1575-84. doi: 10.1056/NEJMoa1109400.