Cigarette smoking confers a higher risk for peripheral arterial disease, myocardial infarction, heart failure,1
as well as for lung, pancreatic, renal, cervical, and gastric cancers.3
Whereas efforts have been made to reduce cigarette smoking in public areas both in Europe and North America, 17.5%– 45% of adults in the European Union and United States continue to smoke.4
Because those in lower socioeconomic strata tend to smoke more, a study of adult men in Europe and the United States revealed that smoking accounted for almost half of the mortality in persons in the lowest socio-economic stratum.5,6
Additionally, a study of adolescents in ten European countries reported up to 20% of boys and 24.7% of girls smoke daily, implying that smoking-related health complications will persist in the next 20–30 years.7
The World Health Organization estimates that of the 1.1 billion smokers worldwide, 800 million (73%) are in developing nations,8
thereby placing a disproportionate burden on those health-care systems. Globally, cigarette smoking remains a major public health concern and a premier modifiable risk factor for cardiovascular disease.
We and others have noted that systemic markers of inflammation, such as C-reactive protein (CRP),9–14
soluble intercellular adhesion molecule-1 (ICAM-1),15
and monocyte chemoattractant protein-1 (MCP-1)16
are elevated in smokers but there is little data on other novel markers of inflammation in smokers such as, myeloperoxidase (MPO) and tumor necrosis factor receptor 2 (TNFR2). Whereas previous studies have examined inflammatory markers in smokers, they have been limited by small sample sizes,9,17
and examination of ≤3 markers.10,18
Additionally, most previous studies have not examined the relation of exposure acuity on markers.
We sought to study markers that would reflect critical phases in the inflammatory pathway of atherosclerotic plaque development. Up-regulation of serum and plasma CD40L, urinary isoprostanes, and P-selectin are thought to represent the initiation of the atherothrombotic cascade by stimulating cytokines (such as tumor necrosis factor-α, whose effects are mediated in part by TNFR2) in response to damage of the endothelium or vascular smooth muscle.19,20
P-selectin and ICAM-1 are involved in the rolling phase of leukocyte adhesion and early plaque development.15,19
MCP-1, a chemokine found in atherosclerotic plaque, attracts monocytes to developing plaque.21,22
MPO, a leukocyte enzyme, is elevated in culprit lesions of patients with acute coronary syndrome.20
Urinary isoprostanes indexed to urinary creatinine (isoprostanes) are measures of oxidative stress.23
The remainder of the markers in our panel (fibrinogen, CRP, and IL-6) are non-specific inflammatory markers found in multiple sites. The current investigation expands upon previous reports by examining a broad panel of circulating biomarkers that we hypothesized reflects the multiple inflammatory pathways activated by smoking. Further, we hypothesized that inflammatory markers would be elevated in a dose-response relation to smoking, and that acute exposure would result in higher inflammatory markers than less proximate exposure. We analyzed the relation of various aspects of smoking behavior to circulating CD40L, CRP, fibrinogen, ICAM-1, IL-6, urinary isoprostanes, MCP-1, MPO, P-selectin, and TNFR2 in the community-based Framingham Heart Study.