Childhood Smoking Initiation, Genetic Susceptibility, and Incident Cardiovascular Diseases in Adulthood

PURPOSE: We aimed to assess the associations of age of smoking initiation and polygenic risk scores (PRSs), individually and jointly, with the incidence of overall cardiovascular diseases (CVDs), coronary artery disease (CAD), atrial fibrillation (AF), and stroke in adulthood. METHODS: Multivariable-adjusted accelerated failure time models were used to assess the impacts of age of smoking initiation and PRSs on incident overall CVDs, CAD, AF, and stroke in adulthood and to examine their joint effect on these outcomes. RESULTS: Compared with never smokers, the time ratio (TR) with a 95% confidence interval (CI) for incident overall CVDs was 0.80 (0.78-0.82) among participants who initiated smoking at age 5-14 years, and 0.85 (0.84-0.86) at age 15-17 years. The corresponding TRs (95% CIs) for CAD were 0.74 (0.72-0.76) and 0.81 (0.79-0.83), respectively; for AF were 0.89 (0.86-0.91) and 0.91 (0.89-0.93), respectively; and for stroke were 0.84 (0.80-0.87) and 0.87 (0.85-0.90), respectively. Notably, participants with high PRSs who initiated smoking at age 5-14 years (vs. never smokers with low PRSs) were the fastest ones to develop overall CVDs (TR = 0.63, 95% CI = 0.61-0.65), CAD (TR = 0.48, 95% CI = 0.46-0.51), AF (TR = 0.55, 95% CI = 0.53-0.57), and stroke (TR = 0.70, 95% CI = 0.66-0.75). DISCUSSION: Smoking initiation in childhood significantly accelerated the incidence of overall CVDs, CAD, AF, and stroke in adulthood. Of note, participants with high genetic susceptibility who initiated smoking in childhood had the earliest onset time of CVDs later in life.