The relationship between smoking intensity and subclinical cardiovascular injury: The Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Background and aims: Modern tobacco regulatory science requires an understanding of which biomarkers of cardiovascular injury are most sensitive to cigarette smoking exposure.

Methods: We studied self-reported current smokers from the Multi-Ethnic Study of Atherosclerosis. Smoking intensity was defined by number of cigarettes/day and urinary cotinine levels. Subclinical cardiovascular injury was assessed using markers of inflammation [high-sensitivity C-reactive protein (hsCRP), interleukin 6 & 2 (IL-2 & IL-6), tumor necrosis factor alpha (TNF-α)], thrombosis (fibrinogen, D-dimer, homocysteine), myocardial injury (troponin T; TnT), endothelial damage (albumin: creatinine ratio), and vascular function [aortic & carotid distensibility, flow-mediated dilation (FMD)]. Biomarkers were modeled as absolute and percent change using multivariable-adjusted linear regression models adjusted for cardiovascular risk factors and smoking duration.

Results: Among 843 current smokers, mean age was 58 (9) years, 53% were men, 39% were African American, mean number of cigarettes per day was 13 (10), and median smoking duration was 39 (15) years. Cigarette count was significantly associated with higher hsCRP, IL-6 and fibrinogen (β coefficients: 0.013, 0.011, 0.60 respectively), while ln-transformed cotinine was associated with the same biomarkers (β coefficients: 0.12, 0.04, 5.3 respectively) and inversely associated with aortic distensibility (β coefficient: -0.13). There was a limited association between smoking intensity and homocysteine, D-dimer, and albumin:creatinine ratio in partially adjusted models only, while there was no association with IL-2, TNF-α, carotid distensibility, FMD, or TnT in any model. In percent change analyses, relationships were strongest with hsCRP.

Conclusions: Smoking intensity was associated with early biomarkers of CVD, particularly, markers of systemic inflammation. Of these, hsCRP may be the most sensitive.

Keywords: Cigarette smoking; Endothelial damage; Inflammation; Myocardial injury; Smoking intensity; Thrombosis; Tobacco regulatory science; Vascular dysfunction.

Fig. 1. Multi-variable adjusted percent change in biomarkers as a function of cigarettes per day

(A) For the entire range of cigarette count. Restricted cubic splines were used with 3 knots placed at 2, 10 and 25 cigarettes per day. Splines were adjusted for age, sex, race, education, body mass index, systolic blood pressure, anti-hypertensive medication use, statin use, diabetes mellitus, heart rate, physical activity, alcohol use, and duration of smoking. (B) In the typical range of smoking intensity. Restricted cubic splines were used with 2 knots placed at 2 and 10 cigarettes per day. Splines were adjusted for age, sex, race, education, body mass index, systolic blood pressure, anti-hypertensive medication use, statin use, diabetes mellitus, heart rate, physical activity, alcohol use, and duration of smoking.

Fig. 1. Multi-variable adjusted percent change in biomarkers as a function of cigarettes per day

(A) For the entire range of cigarette count. Restricted cubic splines were used with 3 knots placed at 2, 10 and 25 cigarettes per day. Splines were adjusted for age, sex, race, education, body mass index, systolic blood pressure, anti-hypertensive medication use, statin use, diabetes mellitus, heart rate, physical activity, alcohol use, and duration of smoking. (B) In the typical range of smoking intensity. Restricted cubic splines were used with 2 knots placed at 2 and 10 cigarettes per day. Splines were adjusted for age, sex, race, education, body mass index, systolic blood pressure, anti-hypertensive medication use, statin use, diabetes mellitus, heart rate, physical activity, alcohol use, and duration of smoking.

Fig. 2. Multi-variable adjusted percent change in biomarkers as a function of log_e -transformed urinary cotinine

(A) For the entire range of cotinine. Restricted cubic splines were used with 3 knots placed at 5.60, 8.37 and 9.44 ng/mL cotinine. Splines were adjusted for age, sex, race, education, body mass index, systolic blood pressure, anti-hypertensive medication use, statin use, diabetes mellitus, heart rate, physical activity, alcohol use, and duration of smoking. (B) In the typical range of smoking intensity. Restricted cubic splines were used with 3 knots placed at 5.60, 8.37 and 9.44 ng/mL cotinine. Splines were adjusted for age, sex, race, education, body mass index, systolic blood pressure, anti-hypertensive medication use, statin use, diabetes mellitus, heart rate, physical activity, alcohol use, and duration of smoking.

Fig. 2. Multi-variable adjusted percent change in biomarkers as a function of log_e -transformed urinary cotinine

(A) For the entire range of cotinine. Restricted cubic splines were used with 3 knots placed at 5.60, 8.37 and 9.44 ng/mL cotinine. Splines were adjusted for age, sex, race, education, body mass index, systolic blood pressure, anti-hypertensive medication use, statin use, diabetes mellitus, heart rate, physical activity, alcohol use, and duration of smoking. (B) In the typical range of smoking intensity. Restricted cubic splines were used with 3 knots placed at 5.60, 8.37 and 9.44 ng/mL cotinine. Splines were adjusted for age, sex, race, education, body mass index, systolic blood pressure, anti-hypertensive medication use, statin use, diabetes mellitus, heart rate, physical activity, alcohol use, and duration of smoking.