Elsevier

Fertility and Sterility

Volume 118, Issue 3, September 2022, Pages 537-547
Fertility and Sterility

Original article
Risk of cardiovascular disease in women and men with subfertility: the Trøndelag Health Study

https://doi.org/10.1016/j.fertnstert.2022.05.038Get rights and content
Under a Creative Commons license
open access

Objective

To investigate the association between subfertility and risk of cardiovascular disease (CVD) outcomes.

Design

Prospective study.

Setting

Population-based cohort.

Patient(s)

We studied 31,629 women and 17,630 men participating in the Trøndelag Health Study.

Intervention(s)

Self-reported subfertility. As men were not directly asked about fertility, male partners of female participants were identified through linkage to the Medical Birth Registry of Norway and assigned the fertility information obtained from their partners.

Main Outcome Measure(s)

The primary outcomes were stroke and coronary heart disease in women and men with and without a history of subfertility. The secondary outcomes were myocardial infarction and angina (subgroups of coronary heart disease) and any CVD (stroke or coronary heart disease). Information on CVD was available by linkage to hospital records. We used Cox proportional hazards models adjusted for age at participation in the Trøndelag Health Study (linear + squared), birth year, smoking history, cohabitation, and education. Cardiometabolic factors were assessed in separate models.

Result(s)

A total of 17% of women and 15% of men reported subfertility. In women, subfertility was modestly associated with an increased risk of stroke (age-adjusted hazard ratio [aaHR], 1.19; 95% confidence interval [CI], 1.02–1.39; adjusted hazard ratio [aHR]; 1.18; 95% CI, 1.01–1.37) and coronary heart disease (aaHR, 1.19; 95% CI, 1.06–1.33; aHR, 1.16; 95% CI, 1.03–1.30) compared with fertile women. In men, we observed a weak positive association for stroke (aaHR, 1.11; 95% CI, 0.91–1.34; aHR, 1.10; 95% CI, 0.91–1.33) and a weak inverse association for coronary heart disease (aaHR, 0.92; 95% CI, 0.81–1.05; aHR, 0.93; 95% CI, 0.81–1.06).

Conclusion(s)

We observed modestly increased risks of CVD outcomes in women and some weak associations in men, although with no strong statistical evidence on sex differences. We acknowledge that we were only able to include men linked to pregnancies ending at 12 completed gestational weeks or later, potentially resulting in selection bias and misclassification of history of subfertility in analyses of male partners. Despite the large sample size, our results indicate the need for larger studies to obtain precise results in both sexes and determine whether there are true sex differences.

Riesgo de enfermedad cardiovascular en mujeres y hombres con subfertilidad: Trøndelag Health Study.

Objetivo

Investigar la asociación entre subfertilidad y el riesgo en los resultados de enfermedades cardiovasculares (CVD).

Diseño

Estudio prospectivo.

Entorno

Estudio de cohortes poblacional.

Paciente(s)

Estudiamos 31,629 mujeres y 17,630 varones que participaron en el Trøndelag Health Study.

Intervención(es)

Subfertilidad informada por ellos mismos. Puesto que a los varones no se les preguntó directamente sobre la fertilidad, se identificó a las parejas masculinas de las mujeres participantes a través del enlace con el Registro de Nacimientos de Noruega y se les asignó la información sobre fertilidad obtenida de sus parejas.

Medida(s) del resultado principal

Los resultados principales fueron accidente cerebrovascular y patología coronaria en mujeres y hombres con y sin historia de subfertilidad. Los resultados secundarios fueron infarto de miocardio y angina (subgrupos de enfermedad coronaria cardiaca) y cualquier enfermedad cardiovascular (accidente cerebrovascular o enfermedad coronaria cardiaca). La información sobre CVD estaba disponible a través de enlace con los registros hospitalarios. Se utilizaron los modelos de riesgos proporcionales de Cox ajustados por edad y participación en el Trøndelag Health Study (lineal + cuadrado), año de nacimiento, historia de tabaquismo, convivencia y nivel de estudios. Los factores cardiometabólicos se evaluaron en modelos separados.

Resultado(s)

Un total de 17% de mujeres y un 15% de hombres reportaron subfertilidad. En mujeres, la subfertilildad se asoció de manera modesta con aumento de riesgo de accidente cerebrovascular (ratio de riesgo ajustado por edad [aaHR], 1.19; 95% intervalo de confianza [CI], 1.02–1.39; ratio de riesgo ajustado [aHR]; 1.18; 95% CI, 1.01–1.37) y enfermedad coronaria cardiaca (aaHR, 1.19; 95% CI, 1.06–1.33; aHR, 1.16; 95% CI, 1.03–1.30) en comparación con mujeres fértiles. En varones, se observó una débil asociación con ictus (aaHR, 1.11; 95% CI, 0.91–1.34; aHR, 1.10; 95% CI, 0.91– 1.33) y una asociación inversa débil con enfermedad coronaria cardiaca (aaHR, 0.92; 95% CI, 0.81–1.05; aHR, 0.93; 95% CI, 0.81–1.06).

Conclusión(es)

Se observó un modesto incremento del riesgo de resultados de CVD en mujeres y alguna asociación débil en hombres, aunque no hubo evidencias estadísticas fuertes en las diferencias de sexo. Reconocemos que solamente fuimos capaces de incluir hombres relacionados con embarazos finalizados a las 12 semanas completas o más de gestación, lo cual puede resultar en un sesgo de selección y clasificación errónea de la historia de subfertilidad en el análisis de las parejas masculinas. A pesar del amplio tamaño muestral, nuestros resultados indican la necesidad de estudios más grandes para obtener resultados precisos en ambos sexos y determinar si existen diferencias reales entre los dos sexos.

Key Words

Subfertility
infertility
cardiovascular disease
the HUNT Study

Cited by (0)

K.H.S. has nothing to disclose. B.O.A. has nothing to disclose. A.H. has nothing to disclose. A.F. has nothing to disclose. J.W.R.-E. has nothing to disclose. L.V.F. has nothing to disclose. O.N. has nothing to disclose. D.A.L. reports grants from the European Research Council, UK Medical Research Council, and British Heart Foundation outside the submitted work and grants from Medtronic Ltd and Roche Diagnostics outside the submitted work. B.B. has nothing to disclose. M.C.M. reports grants from the Research Council of Norway and the European Research Council for the submitted work.

Supported by grants from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreements No 947684 and 101021566). This research was also supported by the Research Council of Norway through its Centres of Excellence funding scheme (project No 262700), and partly funded by the Research Council of Norway, project: Women’s fertility – an essential component of health and well-being (project No 320656). D.A.L., A.F., and M.C.M. work in or are affiliated with a unit that is supported by the University of Bristol and the UK Medical Research Council (MC_UU_00011/6). D.A.L.’s contribution to the article is further supported by the British Heart Foundation (CH/F/20/90003 and AA/18/7/34219). None of the funding organizations influenced the study design, reporting, or interpretation of results. The views expressed in the present article are those of the authors and not necessarily any acknowledged funding organization.

Consent given by the participants does not open for storage of data on an individual level, in repositories or journals. Researchers who want access to HUNT material for replication should apply to HUNT’s Data Access Committee. Access to data sets requires approval from the Regional Committee for Medical and Health Research Ethics in Norway and an agreement with HUNT.