Cigarette smoking and cardiovascular events: role of inflammation and subclinical atherosclerosis from the MultiEthnic Study of Atherosclerosis

Abstract

Objectives: To examine the contemporary effect of smoking in a multiethnic sample, and to explore the respective contributions of inflammation and subclinical atherosclerosis to the cardiovascular consequences of smoking.

Approach and results: We studied 6814 participants free of cardiovascular disease and coronary heart disease (CHD) from the Multiethnic Study of Atherosclerosis. Smoking status and cumulative exposure were determined by self-report and confirmed by urinary cotinine. Multivariable Cox regression was used to estimate the association between smoking parameters and all-cause cardiovascular disease, all-cause CHD, and hard CHD events. We further adjusted for high-sensitivity C-reactive protein and coronary artery calcium (CAC) in hierarchical Cox models. We identified 3218 never smokers, 2607 former smokers, and 971 current smokers. Median follow-up was 10.2 years. Compared with never smokers, adjusted hazard ratios in current smokers were 1.7 (95% confidence interval, 1.3-2.2) for all-cause cardiovascular disease, 1.6 (1.1-2.1) for all-cause CHD, and 1.7 (1.2-2.4) for hard CHD. Similarly, among current smokers, hazard ratios were higher in the 4th versus 1st quartile of pack-years (eg, all-cause CHD hazard ratio=2.7 [1.1-6.6]). Both CAC>100 and high-sensitivity C-reactive protein ≥3 mg/L identified higher relative risk among current smokers (eg, all-cause CHD hazard ratio of 3.0 [1.5-6.0, compared with CAC=0] and 2.6 [1.4-4.8, compared with high-sensitivity C-reactive protein <2 mg/L], respectively). However, CAC was a stronger mediator of events and adversely modified the effect of smoking on events (eg, P-interaction=0.02 for hard CHD). Compared with never smokers, former smokers (median cessation interval=22 years) had similar adjusted hazard for events.

Conclusions: In this multiethnic cohort, current smoking and cumulative exposure remain important modifiable determinants of cardiovascular disease. Both high-sensitivity C-reactive protein ≥3 mg/L and, particularly, CAC>100 identified high-risk smokers who may benefit from more intensive smoking-cessation efforts.

Keywords: coronary artery disease; inflammation; smoking.

Figure 1. Kaplan-Meier Survival by Smoking Status

A= All-cause CVD events according to smoking status group B= All-cause CHD events according to smoking status group C= Hard CHD events according to smoking status group CHD=Coronary heart disease events, CVD=Cardiovascular disease events.

Figure 1. Kaplan-Meier Survival by Smoking Status

A= All-cause CVD events according to smoking status group B= All-cause CHD events according to smoking status group C= Hard CHD events according to smoking status group CHD=Coronary heart disease events, CVD=Cardiovascular disease events.

Figure 1. Kaplan-Meier Survival by Smoking Status

A= All-cause CVD events according to smoking status group B= All-cause CHD events according to smoking status group C= Hard CHD events according to smoking status group CHD=Coronary heart disease events, CVD=Cardiovascular disease events.

Figure 2. All-cause CVD Incidence Rates (per 1000 person-years) by Smoking Status and Exposure: Stratified by CAC and hsCRP

A= All-cause CVD by smoking group, stratified by CAC B= All-cause CVD by quartiles of smoking exposure in pack-years, stratified by CAC C= All-cause CVD by smoking group, stratified by hsCRP D= All-cause CVD by quartiles of smoking exposure in pack-years, stratified by hsCRP CVD=Cardiovascular disease events, CAC=Coronary artery calcium in Agatston Units, hsCRP=high-sensitivity C-Reactive Protein (in milligrams per deciliter), PYH=Pack-year history in Ever-smokers