Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men
Open accessAbstract
BACKGROUND: Inflammation may be important in the pathogenesis of atherothrombosis. We studied whether inflammation increases the risk of a first thrombotic event and whether treatment with aspirin decreases the risk. METHODS: We measured plasma C-reactive protein, a marker for systemic inflammation, in 543 apparently healthy men participating in the Physicians' Health Study in whom myocardial infarction, stroke, or venous thrombosis subsequently developed, and in 543 study participants who did not report vascular disease during a follow-up period exceeding eight years. Subjects were randomly assigned to receive aspirin or placebo at the beginning of the trial. RESULTS: Base-line plasma C-reactive protein concentrations were higher among men who went on to have myocardial infarction (1.51 vs. 1.13 mg per liter, P<0.001) or ischemic stroke (1.38 vs. 1.13 mg per liter, P=0.02), but not venous thrombosis (1.26 vs. 1.13 mg per liter, P=0.34), than among men without vascular events. The men in the quartile with the highest levels of C-reactive protein values had three times the risk of myocardial infarction (relative risk, 2.9; P<0.001) and two times the risk of ischemic stroke (relative risk, 1.9; P=0.02) of the men in the lowest quartile. Risks were stable over long periods, were not modified by smoking, and were independent of other lipid-related and non-lipid-related risk factors. The use of aspirin was associated with significant reductions in the risk of myocardial infarction (55.7 percent reduction, P=0.02) among men in the highest quartile but with only small, nonsignificant reductions among those in the lowest quartile (13.9 percent, P=0.77). CONCLUSIONS: The base-line plasma concentration of C-reactive protein predicts the risk of future myocardial infarction and stroke. Moreover, the reduction associated with the use of aspirin in the risk of a first myocardial infarction appears to be directly related to the level of C-reactive protein, raising the possibility that antiinflammatory agents may have clinical benefits in preventing cardiovascular disease.
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High concentrations of CRP predicted the risk of future cardiovascular disease in apparently healthy men.
“high concentrations of CRP predicted the risk of future cardiovascular disease in apparently healthy men (12).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [12]
Inflammation may be an important mechanism mediating the adverse effect of early life stress on adult health.
“Inflammation may be an important developmental mediator linking adverse experiences in early life to poor adult health.”
From Childhood maltreatment predicts adult inflammation in a life-course study (2007) · cites this paper as [22]
High hsCRP is known to predict future disease in midlife and old age.
“Instead, we focused on intermediate risk factors, such as high hsCRP, that are known to predict future disease in midlife and old age (22–24).”
From Childhood maltreatment predicts adult inflammation in a life-course study (2007) · cites this paper as [22]
Immunosuppressive drug regimens can adversely affect lipid metabolism, raising total cholesterol, VLDL, triglycerides, and LDL particle size and density.
“Immunosuppressive drug regimens may have adverse effects on lipid metabolism leading to increases in TC, VLDL, and TGs, and in the size and density of LDL particles.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [506]
The adverse lipid effects of immunosuppressive drugs differ between drugs.
“These effects vary with different immunosuppressive drugs [497,498,502-506].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [506]
High blood levels of high-sensitivity CRP and IL-6 predict cardiovascular disease risk in middle-aged and older adults, independent of other CVD risk factors.
“longitudinal studies demonstrate that high blood levels of pro-inflammatory markers, including high-sensitivity CRP assay and IL-6, predict the risk of cardiovascular disease in both middle-aged and older adults, independent of other CVD risk factors”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [157]
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- Authors
- Ridker, P. M., Cushman, M., Stampfer, M. J., Tracy, R. P., & Hennekens, C. H.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Vermont (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1997-04-03
- Volume
- 336
- Issue
- 14
- Pages
- 973-979
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2316376271
- Cited by
- 5,504
- References
- 36
- Citations by year
- 2026: 67 · 2025: 81 · 2024: 77 · 2023: 92 · 2022: 95 · 2021: 103 · 2020: 100 · 2019: 115 · 2018: 107 · 2017: 98 · 2016: 114 · 2015: 135 · 2014: 141 · 2013: 171 · 2012: 164
- FWCI
- 148.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (CA 34944, CA 40360, HL-26490)
- National Heart, Lung, and Blood Institute (HL-34595, R01HL046690, HL 26490, HL-46690, R01HL034595)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Keywords
- C-reactive protein, inflammation, aspirin, cardiovascular disease, myocardial infarction, ischemic stroke, venous thrombosis, atherothrombosis, anti-inflammatory therapy, cardiovascular risk prediction, Physicians' Health Study
- MeSH terms
- Adult, Aged, Aged, 80 and over, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, C-Reactive Protein, Brain Ischemia, Humans, Inflammation, Male, Middle Aged, Myocardial Infarction, Risk, Thrombophlebitis
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