Introduction Previous reports have noted associations between subfertility in women and increased risk of cardiovascular disease (CVD) events in later life. However, reports conflict regarding the associations between subfertility and CVD risk factors. Using data from a population-based cohort of Black and White women, we examined the association between longitudinal assessments of CVD risk factors and subfertility. Methods The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective cohort of Black and White women who have undergone repeated assessment of CVD risk factors beginning at study baseline (1985-1986). Risk factors included cigarette smoking, body mass index (BMI), blood pressure, lipid levels, glucose, and C-reactive protein. At approximately 40 years of age, an ancillary study assessed histories of subfertility. We used generalized estimating equations with a logit link model to examine associations between subfertility (dependent variable) and repeated CVD risk factors (independent variables), with adjustment for age, race, center, and education level in 1107 women. Results Cigarette use and higher levels of BMI, glucose, and triglycerides and lower levels of high-density lipoprotein cholesterol (HDL) were associated with subfertility after adjustment for age, race, and education. In multivariable models which included all of these risk factors, cigarette use (odds ratio [OR] 1.004, 95% confidence interval [CI] 1.002, 1.006, p<0.0001) and HDL (OR 0.99, 95% CI 0.99, 0.995, p=0.046) were still associated with subfertility, but associations with BMI, glucose, and triglycerides were no longer significant. Conclusions Women with subfertility histories have adverse CVD risk factors across the reproductive lifespan. Cigarette use is a strong risk factor for infertility.

The authors have declared no competing interest.

Yes

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRBs of CARDIA Field Centers (University of Alabama, Northwestern University, Kaiser Permanente Northern California, University of Minnesota)

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data are available from the CARDIA study, dopm.uab.edu by reasonable reqeust