Introduction: Although several potential respiratory and cardiovascular health effects of e-cigarettes have been reported, their association with incident cardiometabolic conditions remains unclear.

Methods: We used longitudinal data from the All of Us research program to investigate the association between current exclusive e-cigarette use (EE), exclusive combustible cigarette use (ECC), and dual use (DU) with incident cardiometabolic conditions, including hypertension, type 2 diabetes mellitus (T2DM), chronic obstructive pulmonary disease (COPD), heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD), using Cox regression analyses adjusted for age, sex, race and ethnicity, and body mass index (BMI). ECC use was used as a positive control to validate our methodology/findings.

Results: Among 249,190 individuals (67.2% female, 52.0% non-Hispanic White, 21.5% non-Hispanic Black) followed for 3.7-3.9 years, EE, compared with nonuse, was not significantly associated with hypertension (aHR 1.01[95%CI 0.83-1.23]), T2DM (0.88[0.66-1.16]), ASCVD (1.05[0.59-1.86]), or HF (0.82[0.47-1.41]), but was significantly associated with COPD (2.29[1.42-3.71]). Among individuals aged 30-70 years, EE was significantly associated with hypertension (1.39[1.09-1.77]). ECC and DU were strongly associated with all outcomes with DU having higher point estimates but overlapping confidence intervals for all outcomes except ASCVD (2.18[1.82-2.62]).

Conclusion: We demonstrated significant longitudinal association between exclusive e-cigarette use and COPD, and hypertension only among individuals aged 30-70 years. ECC and DU were strongly associated with all conditions, with dual use potentially associated with higher ASCVD risk. These findings highlight some potential risks of e-cigarette use and provide context to inform advisories and regulatory policies on novel products on their health risks.

Implication: These findings help to clarify the potential risks associated with e-cigarette use. Understanding these risks can aid the FDA in developing regulatory frameworks for tobacco products.