Abstract
Background and Aims: Growing data suggest that antibiotic use, which may alter the gut microbiome, is related to risk of cardiovascular disease (CVD) and mortality. However, evidence from prospective cohort studies is still scarce; and no large prospective study has investigated associations between cumulative antibiotic use during adulthood and risk of CVD. We aimed to examine duration of antibiotic use and risk of CVD among apparently healthy women from the Nurses’ Health Study (NHS). Methods: This study included 36,922 women without history of myocardial infarction (MI), angina pectoris, stroke, or cancer in the NHS and with available data on total days of antibiotics use per year (0 to <15 days, 15 days to <2 months, or 2 months or more) during ages 20-39, 40-59 and after age 60, as reported on the 2004 questionnaire. Incidence of CVD (MI or stroke) over 8 years was assessed. Hazard ratios (HRs) were estimated as categories of duration of use compared with the none to <15 days per year group, using multivariate-adjusted Cox proportional hazards model including traditional risk factors (such as demographic variables, hypertension, diabetes, hypercholesterolemia, smoking, physical activity, Alternative Healthy Eating Index score, body mass index, aspirin, and anti-inflammatory medication), and reasons for antibiotics use (respiratory infection, urinary tract infections, acne or rosacea, chronic bronchitis, or dental), as well as other medications (such as H2 blockers, proton pump inhibitors), and other diseases (such as lung or kidney disease). Results: As compared to women with “none to <15 days per year of use” during age 40-59 y, those with a history of antibiotics use “15 days to < 2 months” or “2 months or more” had a significantly increased risk of CVD with an adjusted hazard ratio (HR [95%CI])_ of 1.19 (1.03, 1.38) and 1.34 (1.08, 1.66), respectively. Reported use of antibiotics for 2 months or more per year after age 60 was also associated with a HR of 1.24 (1.02, 1.51) for CVD. A longer exposure of antibiotics use was more strongly associated with increased risk of stroke than MI Antibiotic use during young adulthood (age 20-39) was not significantly associated with elevated risk of CVD. Conclusions: Our results suggest greater duration of exposure to antibiotics in middle- and older adulthood may be related to an increased risk of future CVD, independent of traditional risk factors.
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