Lipidomic Markers of Tobacco Use and Cessation Associated With Cardiovascular Risk Factors: A Longitudinal Study in...

Research is warranted to identify lipidomic markers longitudinally associated with tobacco smoking and cessation and examine their associations with cardiovascular risk metrics.

Using untargeted liquid chromatography-mass spectrometry, we measured 1542 lipids among 1845 American Indian individuals at 2 visits (~5.5 years apart). Information on smoking and cessation was collected using questionnaires at both visits. Using mixed-effects linear regression, we first identified lipids associated with current smoking between current and never smokers and past smoking between former and never smokers. Random effects were used to account for family relatedness and within-individual correlations across visits. We then investigated whether longitudinal changes in smoking-related lipids were associated with smoking cessation that occurred between baseline and follow-up. We examined the longitudinal associations of a lipidomic score and each lipid with various cardiovascular risk metrics.

Concentrations of 126 named lipids differed between current and never smokers (false discovery rate<0.05), whereas none differed between former and never smokers. Smoking cessation during the study period was associated with a decrease in phosphatidylcholine(p-16:0/2:0)/phosphatidylcholine(o-16:1/2:0) at false discovery rate <0.05, an upregulated lipid in current smokers. At P<0.05, cessation was linked to decreases in 8 of 50 upregulated lipids (eg, lysoglycerophospholipids) and increases in 11 of 76 downregulated lipids (eg, sphingomyelins). The lipidomic score and multiple individual lipids were associated with blood pressure, waist circumference, C-reactive protein, fasting glucose, insulin resistance, and insulin sensitivity.

Current smoking, but not past smoking, is associated with a broad range of lipidomic markers in American Indian individuals. Longitudinal profiling reveals suggestive evidence of lipidomic markers recovering after cessation. Once validated, these findings may elucidate key lipid pathways underlying the effects of smoking and cessation.