Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2167-2176
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© 1997 American Heart Association, Inc.
Articles |
Lifetime Smoking Exposure Affects the Association of C-Reactive Protein with Cardiovascular Disease Risk Factors and Subclinical Disease in Healthy Elderly Subjects
From the Departments of Pathology and Biochemistry (R.P.T.), Pathology (E.M., E.G.B., E.S.C.), Medicine and Pathology (M.C.), University of Vermont, Colchester, the Departments of Epidemiology and Health Services and Medicine (B.M.P.), University of Washington, Seattle, and the Departments of Epidemiology and Medicine (L.H.K.), University of Pittsburgh, Penn.
Correspondence and reprint requests to Russell P. Tracy, University of Vermont, Aquatec Bldg, T205, 55A S. Park Drive, Colchester, VT 05446. Email: rtracy{at}salus.uvm.edu
Abstract Blood levels of C-reactive protein (CRP), a marker
of inflammation, are related to cardiovascular disease
risk. To determine cross-sectional correlates in the elderly, we
measured CRP in 400 men and women older than 65 years and free of
clinical cardiovascular disease at baseline as part of
the Cardiovascular Health Study. Only 2% of the values
were greater than 10 mg/L, the cut-point usually used to identify
inflammation. CRP levels appeared tightly regulated, since there were
strong bivariate correlations between CRP and the following:
inflammation-sensitive proteins such as fibrinogen (r=.52);
measures of fibrinolysis such as plasmin-antiplasmin
complex (r=.23); pack-years of smoking (r=.30);
and body mass index (r=.24; all P values
.001).
The association with pack-years was independent of the length of time
since cessation of smoking. CRP levels were also associated with
coagulation factors VIIc, IXc, and Xc; HDL cholesterol
(negative) and triglyceride; diabetes status;
diuretic use; ECG abnormalities; and level of exercise. Because
of effect modification, two multiple linear regression prediction
models were developed for CRP, one each for never smokers and ever
smokers. An a priori physiologic model was used to guide these
analyses, which disallowed the use of other
inflammation-sensitive variables such as fibrinogen. In never
smokers, the independent predictors were body mass index (+), diabetes
status (+), plasmin-antiplasmin complex (+), and the presence of ECG
abnormalities (+); this model predicted 15% of the CRP population
variance. In ever smokers, the predictors were body mass index (+),
plasmin-antiplasmin complex (+), pack-years of smoking (+), HDL
cholesterol (-), and ankle-arm blood pressure index (-);
this model predicted 42% of the population variance. We conclude that
levels of CRP in the healthy elderly are tightly regulated and reflect
lifetime exposure to smoking as well as level of obesity, ongoing level
of fibrinolysis, diabetes status, and level of
subclinical atherothrombotic disease. Moreover, exposure to smoking
affects the relation of CRP to these other factors.
Key Words: atherosclerosis • thrombosis • fibrinolysis • inflammation • acute-phase proteins
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