Lifetime Smoking Exposure Affects the Association of C-Reactive Protein with Cardiovascular Disease Risk Factors and Subclinical Disease in Healthy Elderly Subjects

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 < or = .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.

Genetic and environmental contributions to plasma C-reactive protein and interleukin-6 levels – a study in twins

“…However, after adjustment for all confounding covariates, estimated heritability for CRP was substantially lower (Vogel-Motulsky heritability coefficient 0.22, 95% confidence interval [À0.16-0.61]), pointing to a moderate genetic influence on the observed variability (Table 4). Similar to previous studies, 6,10,15,19,[21][22][23][24]31,44 CRP levels were strongly influenced by factors such as female gender (Po0.0005), older age (Po0.0005) or the BMI (Po0.0001). Particularly, the BMI, which has a large degree of heritability, 55,56 was significantly associated with higher plasma CRP levels in a linear multiple regression analysis.…”

“…[16][17][18] In addition, it is known that (environmental) factors such as obesity, older age, female gender, smoking, diabetes mellitus, chronic infections, lower socio-economic status, greater alcohol consumption and medications such as oral contraceptives are involved in a low-grade inflammatory response with elevated plasma CRP levels. 6,[19][20][21][22][23][24][25][26] An aim of determining plasma CRP levels could be related to polymorphisms in upstream cytokines such as interleukin (IL)-6. 13,27 IL-6 induces CRP production in hepatocytes and it is the only cytokine that can stimulate the synthesis of all other acute-phase proteins.…”

Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases

“…35 The basis for this association is unclear, but it is postulated to relate to increased rates of smoking and obesity in deprived patients. 36 The association of socioeconomic deprivation with systemic inflammation and prognosis in the context of CLM has yet to be explored.…”

Relation of smoking status to a panel of inflammatory markers: The Framingham offspring

“…Whereas previous studies have examined inflammatory markers in smokers, they have been limited by small sample sizes, 9,17 hospital-based samples, 17 and examination of ≤3 markers. 10,18 Additionally, most previous studies have not examined the relation of exposure acuity on markers.…”