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C-Reactive Protein, the Metabolic Syndrome, and Prediction of Cardiovascular Events in the Framingham Offspring Study
Abstract
Background— Inflammation (assessed by C-reactive protein [CRP]) and the metabolic syndrome (MetS) are associated with cardiovascular disease (CVD), but population-based data are limited. Methods and Results— We assessed the cross-sectional relations of CRP to the MetS (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III definition) in 3037 subjects (1681 women; mean age, 54 years) and the utility of CRP and the MetS to predict new CVD events (n=189) over 7 years. MetS (≥3 of 5 traits) was present in 24% of subjects; mean age-adjusted CRP levels for those with 0, 1, 2, 3, 4, or 5 MetS traits were 2.2, 3.5, 4.2, 6.0, or 6.6 mg/L, respectively ( P trend <0.0001). In persons with MetS, age-adjusted CRP levels were higher in women than men (7.8 versus 4.6 mg/L; P <0.0001). MetS and baseline CRP were individually related to CVD events (for MetS: age-sex-adjusted hazard ratio [HR], 2.1; 95% CI, 1.5 to 2.8; for highest versus lowest CRP quartile: HR, 2.2; 95% CI, 1.4 to 3.5). Greater risk of CVD persisted for MetS and CRP even after adjustment in a model including age, sex, MetS (HR, 1.8; 95% CI, 1.4 to 2.5), and CRP (HR, 1.9; 95% CI, 1.2 to 2.9). The c-statistic associated with the age- and sex-adjusted model including CRP was 0.72; including MetS, 0.74; and including CRP and MetS, 0.74. Conclusions— Elevated CRP levels are related to insulin resistance and the presence of the MetS, especially in women. Although discrimination of subjects at risk of CVD events using both MetS and CRP is not better than using either phenotype alone, both CRP and MetS are independent predictors of new CVD events.
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“The MS has been associated with incident CHD and CHD mortality, [5][6][7][8][9][10][11]”
From Diabetes, the Metabolic Syndrome, and Angiographic Progression of Coronary Arterial Disease in Postmenopausal Women (2006) · cites this paper as [10]
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“CRP C-reactive protein GM-CSF Granulocyte/macrophage colony stimulating factor LPS Lipopolysaccharide MFI Mean fluorescence intensity ND Non-diabetic ODN Oligodeoxynucleotide Pam3 Pam3CSK4 PD Periodontal disease rLPS Rhodobacter sphaeroides lipopolysaccharide TLR Toll-like receptor M. Jagannathan Department of Patholo…”
BackgroundInfluentialHigh prevalence of metabolic syndrome after allogeneic hematopoietic cell transplantation
Majhail, N. S., Flowers, M. E. D., Ness, K. K., Jagasia, M., Carpenter, P. A., Arora, M., Arai, S., Johnston, L., Martin, P. J., Baker, K. S., et al. (2008) · Bone Marrow Transplantation · doi:10.1038/bmt.2008.263 · Cited by 149
Impaired Lung Function Is Associated with Obesity and Metabolic Syndrome in Adults
Lin, W., Yao, C., Wang, H., & Huang, K. (2006) · Obesity · doi:10.1038/oby.2006.190 · Cited by 150
“(46) have found, for example, that elevated CRP levels are related to metabolic syndrome.”
BackgroundMutungi, G., Ratliff, J. C., Puglisi, M. J., Torres‐Gonzalez, M., Vaishnav, U., Leite, J. O. M., Quann, E. E., Volek, J. S., & Fernández, M. L. (2008) · Journal of Nutrition · doi:10.1093/jn/138.2.272 · Cited by 151
Eberly, L. E., Prineas, R., Cohen, J. D., Vazquez, G., Zhi, X., Neaton, J. D., & Kuller, L. H. (2006) · Diabetes Care · doi:10.2337/diacare.29.1.123 · Cited by 164
Al‐Rasheed, N. M., Al-Rasheed, N. M., Hasan, I. H., Alamin, M. A., Al‐Ajmi, H. N., Mohamad, R. A., & Mahmoud, A. M. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/1092015 · Cited by 144
“Elevated CRP in STZ-induced diabetic rats in the present investigation was in agreement with the findings of previous studies showing increased serum CRP levels in diabetic patients [62] and STZ-induced type 1 diabetic animals [63].”
ResultMalik, S., Wong, N. D., Franklin, S. S., Pio, J. R., Fairchild, C., & Chen, R. K. (2005) · Diabetes Care · doi:10.2337/diacare.28.3.690 · Cited by 144
“(16), who recently demonstrated in the Framingham Heart Study that both CRP and metabolic syndrome (inclusive of diabetes) are independent predictors of new CVD events.”
BackgroundMetabolic Syndrome: Definition and Therapeutic Implications
Prasad, H., Ryan, D. A., Celzo, M. F., & Stapleton, D. D. (2012) · Postgraduate Medicine · doi:10.3810/pgm.2012.01.2514 · Cited by 142
Rizvi, A. A. (2009) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e3181a4158c · Cited by 138
Metabolic syndrome and risk for heart failure in middle-aged men
Ingelsson, E., Ärnlöv, J., Lind, L., & Sundström, J. (2006) · Heart · doi:10.1136/hrt.2006.089011 · Cited by 139
Oeffinger, K. C., ADAMS-HUET, B. A., Victor, R. G., Church, T. S., Snell, P. G., Dunn, A. L., Eshelman‐Kent, D. A., Ross, R., Janiszewski, P. M., Turoff, A. J., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.19.7251 · Cited by 130
“among women in the general population is associated with insulin resistance and metabolic syndrome.(36) Notably, a CRP of 3 mg/L or higher in women has an additive effect when combined with metabolic syndrome in predicting future cardiovascular events.”
BackgroundHeresi, G. A., Aytekin, M., Newman, J. E., DiDonato, J. A., & Dweik, R. A. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201001-0007oc · Cited by 128
Inflammation, the metabolic syndrome, and risk of coronary heart disease in women and men
Pischon, T., Hu, F. B., Rexrode, K. M., Girman, C. J., Manson, J. E., & Rimm, E. B. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.06.022 · Cited by 122
The Metabolic Syndrome as a Concept of Adipose Tissue Disease
Oda, E. (2008) · Hypertension Research · doi:10.1291/hypres.31.1283 · Cited by 120
Glycoprotein Acetyls: A Novel Inflammatory Biomarker of Early Cardiovascular Risk in the Young
Chiesa, S. T., Charakida, M., Georgiopoulos, G., Roberts, J. D., Stafford, S. J., Park, C. M., Mykkänen, J., Kähönen, M. A. P., Lehtimäki, T. J., Ala‐Korpela, M., et al. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.121.024380 · Cited by 118
“Our findings show that (1) GlycA is a stable marker of chronic inflammation which potentially lies downstream of different immune- related pathways to that underlying CRP, (2) that GlycA is associated with a wide- range of well- established lifestylerelated CVD risk factors for cardiovascular disease even at this earl…”
Jacobs, M., van Greevenbroek, M. M. J., Kallen, C., Ferreira, I., Blaak, E. E., Feskens, E. J. M., Jansen, E. H. J. M., Schalkwijk, C., & Stehouwer, C. D. A. (2009) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2009.02129.x · Cited by 114
Epidemiology of the Metabolic Syndrome
Reynolds, K., & He, J. (2005) · The American Journal of the Medical Sciences · doi:10.1097/00000441-200512000-00004 · Cited by 111
Serum antibodies to periodontal pathogens and markers of systemic inflammation
Dye, B. A., Choudhary, K., Shea, S., & Papapanou, P. N. (2005) · Journal Of Clinical Periodontology · doi:10.1111/j.1600-051x.2005.00856.x · Cited by 113
High prevalence of metabolic syndrome in patients with ankylosing spondylitis
Malesci, D., Niglio, A., Mennillo, G., Buono, R., Valentini, G., & MONTAGNA, G. L. (2006) · Clinical Rheumatology · doi:10.1007/s10067-006-0380-5 · Cited by 109
“Moreover, some studies have pointed out a relationship among some CV risk factors or MetS and inflammation [ 10 , 11].”
BackgroundPhysical activity, exercise and low-grade systemic inflammation
Wärnberǵ, J., Cunningham, K., Romeo, J., & Marcos, A. (2010) · Proceedings of The Nutrition Society · doi:10.1017/s0029665110001928 · Cited by 111
“Furthermore, CRP levels are more strongly related to insulin resistance and the individual components of the metabolic syndrome in women than in men((78)).”
Gupta, S. K., Dongare, S., Mathur, R., Mohanty, I. R., Srivastava, S., Mathur, S. R., & Nag, T. C. (2015) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-015-2483-2 · Cited by 107
Metabolic Consequences of Sleep-Disordered Breathing
Jun, J. C., & Polotsky, V. Y. (2009) · ILAR Journal · doi:10.1093/ilar.50.3.289 · Cited by 107
Serum C-reactive protein as a marker for wellness assessment.
Kao, P. C., Shiesh, S. C., & Wu, T. J. (2006) · PubMed · Cited by 101
Kressel, G., Trunz, B., Bub, A., Hülsmann, O., Wolters, M., Lichtinghagen, R., Stichtenoth, D. O., & Hahn, A. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.04.012 · Cited by 101
Time-Restricted Eating and Metabolic Syndrome: Current Status and Future Perspectives
Świątkiewicz, I., Woźniak, A., & Taub, P. R. (2021) · Nutrients · doi:10.3390/nu13010221 · Cited by 106
You, T., Nicklas, B. J., Ding, J., Penninx, B. W. J. H., Goodpaster, B. H., Bauer, D. C., Tylavsky, F. A., Harris, T. B., Kritchevsky, S. B., & for the Health, A. A. B. C. S. (2008) · The Journals of Gerontology Series A · doi:10.1093/gerona/63.4.414 · Cited by 101
Dietary Epicatechin Promotes Survival of Obese Diabetic Mice and Drosophila melanogaster
Si, H., Fu, Z., Babu, P. V. A., Wei, Z. C., LeRoith, T., Meaney, M. P., Voelker, K. A., Jia, Z., Grange, R. W., & Liu, D. (2011) · Journal of Nutrition · doi:10.3945/jn.110.134270 · Cited by 101
Predictors of cardiovascular events after liver transplantation
Coss, E., Watt, K. D. S., Pedersen, R. A., Dierkhising, R., Heimbach, J. K., & Charlton, M. (2010) · Liver Transplantation · doi:10.1002/lt.22140 · Cited by 100
Obstructive sleep apnea syndrome is a systemic disease. Current evidence
Zamarrón, C., García-Paz, V., & Riveiro, A. (2008) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2007.12.006 · Cited by 100
“inflammation with major implications for cardiovascular morbidity and atherogenesis [126,127] is increased in OSAS in accordance with disease severity [128–130].”
BackgroundAcute Phase Reactants as Novel Predictors of Cardiovascular Disease
Ahmed, M. S., Jadhav, A. B., Hassan, A. J., & Meng, Q. H. (2012) · ISRN Inflammation · doi:10.5402/2012/953461 · Cited by 104
“As well, it adds a prognostic information on vascular risk at all levels of the metabolic syndrome [44].”
BackgroundExtraintestinal manifestations ofHelicobacter pylori: A concise review
Wong, F. T. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i34.11950 · Cited by 104
Metadata
- Authors
- Rutter, M. K., Meigs, J. B., Sullivan, L. M., D’Agostino, R. B., & Wilson, P. W. F.
- Affiliations
- Boston University (US)
- Venue
- Circulation
- Published
- 2004-07-27
- Volume
- 110
- Issue
- 4
- Pages
- 380-385
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1983997573
- Cited by
- 664
- References
- 36
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 9 · 2023: 15 · 2022: 19 · 2021: 9 · 2020: 8 · 2019: 11 · 2018: 15 · 2017: 13 · 2016: 19 · 2015: 20 · 2014: 36 · 2013: 36 · 2012: 26
- FWCI
- 48.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- National Institutes of Health (n01hc25195-41-0-1)
- National Heart, Lung, and Blood Institute (R01HL073272, N01‐HC25195, R01-HL 073272-01)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- C-reactive protein, metabolic syndrome, cardiovascular risk prediction, inflammation, insulin resistance, sex differences, Framingham Offspring Study, cardiovascular events, risk discrimination, cardiovascular risk in women, NCEP ATP III criteria, Framingham risk score, Framingham risk equation
- MeSH terms
- Adult, Aged, Aged, 80 and over, C-Reactive Protein, Cardiovascular Diseases, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Inflammation, Insulin Resistance, Male, Middle Aged, Predictive Value of Tests, Risk, Sex Factors, Cohort Studies, Metabolic Syndrome
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