Infertility and Risk of Cardiovascular Disease: A Prospective Cohort Study

Farland, Leslie V.; Wang, Yi‐Xin; Gaskins, Audrey J.; Rich‐Edwards, Janet W.; Wang, Siwen; Magnus, Maria C; Chavarro, Jorge E.; Missmer, Stacey A.

doi:10.1161/jaha.122.027755

Cited by 23 publications

(25 citation statements)

References 55 publications

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“…In an analysis of the Nurses’ Health Study II, Wang et al reported that infertility was unrelated to premature CVD mortality in the overall sample, although individuals with infertility and no subsequent pregnancies had a 49% higher risk of CVD mortality (hazard ratio, 1.49; 95% CI, 1.06 to 2.10). Also in the Nurses’ Health Study II, Farland et al observed a 13% higher CHD risk with infertility history, but only with overweight or obesity; this association was preserved only with infertility occurring before age 25 years in age-stratified models. Compared with our analyses, this latter Nurses’ Health Study II study specifically examined associations of infertility with incident CHD and stroke at ages 53 to 70 years, whereas our investigation assessed associations with components of CVH.…”

Section: Discussionmentioning

confidence: 98%

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History of Infertility and Midlife Cardiovascular Health in Female Individuals

Nichols,

Rifas-Shiman,

Switkowski

et al. 2024

JAMA Netw Open

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ImportanceFertility status is a marker for future health, and infertility has been associated with risk for later cancer and diabetes, but associations with midlife cardiovascular health (CVH) in female individuals remain understudied.ObjectiveTo evaluate the association of infertility history with CVH at midlife (approximately age 50 years) among parous individuals.Design, Setting, and ParticipantsProject Viva is a prospective cohort study of pregnant participants enrolled between 1999 and 2002 who delivered a singleton live birth in the greater Boston, Massachusetts, area. Infertility history was collected at a midlife visit between 2017 and 2021, approximately 18 years after enrollment. Data analysis was performed from January to June 2023.ExposuresThe primary exposure was any lifetime history of infertility identified by self-report, medical record, diagnosis, or claims for infertility treatment.Main Outcomes and MeasuresThe American Heart Association’s Life’s Essential 8 (LE8) is a construct for ranking CVH that includes scores from 0 to 100 (higher scores denote better health status) in 4 behavioral (diet, physical activity, sleep, and smoking status) and 4 biomedical (body mass index, blood pressure, blood lipids, and glycemia) domains to form an overall assessment of CVH. Associations of a history of infertility (yes or no) with mean LE8 total, behavioral, biomedical, and blood biomarker (lipids and glycemia) scores were examined, adjusting for age at outcome (midlife visit), race and ethnicity, education, household income, age at menarche, and perceived body size at age 10 years.ResultsOf 468 included participants (mean [SD] age at the midlife visit, 50.6 [5.3] years) with exposure and outcome data, 160 (34.2%) experienced any infertility. Mean (SD) LE8 scores were 76.3 (12.2) overall, 76.5 (13.4) for the behavioral domain, 76.0 (17.5) for the biomedical domain, and 78.9 (19.2) for the blood biomarkers subdomain. In adjusted models, the estimated overall LE8 score at midlife was 2.94 points lower (95% CI, −5.13 to −0.74 points), the biomedical score was 4.07 points lower (95% CI, −7.33 to −0.78 points), and the blood subdomain score was 5.98 points lower (95% CI, −9.71 to −2.26 points) among those with vs without history of infertility. The point estimate also was lower for the behavioral domain score (β = −1.81; 95% CI, −4.28 to 0.66), although the result was not statistically significant.Conclusions and RelevanceThis cohort study of parous individuals found evidence for an association between a history of infertility and lower overall and biomedical CVH scores. Future study of enhanced cardiovascular preventive strategies among those who experience infertility is warranted.

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Section: Discussionmentioning

confidence: 98%

“…with increased risk among female individuals for any type of CVD, 41 CVD events, 36 CVD mortality, 42 coronary heart disease (CHD), [43][44][45] stroke, 43,44,46 and heart failure. 43,47 Several distinctions should be noted, however.…”

Section: Discussionmentioning

confidence: 99%

History of Infertility and Midlife Cardiovascular Health in Female Individuals

Nichols,

Rifas-Shiman,

Switkowski

et al. 2024

JAMA Netw Open

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“…Cardiovascular disease is more incident among individuals reporting fertility problems (1)(2)(3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Parental infertility and offspring cardiometabolic trajectories up to 25 years: a pooled analysis of three European cohorts

Hernáez,

Elhakeem,

Barros

et al. 2023

Preprint

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ObjectiveTo assess whether parental infertility is associated with differences in cardiometabolic trajectories in offspring from childhood to 25 years of age.DesignPooled analysis of three European pregnancy cohort studies.SubjectsUp to 14,609 singletons from three pregnancy cohorts (the UK Avon Longitudinal Study of Parents and Children, the Portuguese Geraçao 21, and the Amsterdam Born Children and their Development study).ExposureParental infertility defined as time-to-pregnancy ≥12 months.Main Outcome MeasuresTrajectories of body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose from childhood to 25 years of age were compared in offspring of couples with and without infertility. Trajectories were modelled using mixed-effects models with natural cubic splines adjusting for cohort, sex of the offspring, and maternal factors (age, body mass index, smoking, educational level, parity, and ethnicity). Predicted levels of cardiometabolic traits up to 25 years of age were compared by parental infertility.ResultsOffspring of couples with infertility had increasingly higher BMI (difference in mean predicted levels by age 25: +1.09 kg/m2, 95% confidence interval [0.68 to 1.50]) and suggestively higher DBP at age 25 (+1.21 mmHg [0.00 to 2.43]). Their LDL-C tended to be higher, and their HDL-C values tended to be lower over time (age 25, LDL-C: +4.07% [-0.79 to 8.93]; HDL-C: −2.78% [-6.99 to 1.43]). At middle-late adolescence, offspring of couples with infertility had higher waist circumference (age 17: +1.05 cm [0.11 to 1.99]) and SBP (age 17: +0.93 mmHg [0.044 to 1.81]), but these differences attenuated at later ages. No clear inter-group differences in triglyceride and glucose trajectories were observed. Further adjustment for paternal age, body mass index, smoking, and educational level, and both parent’s history of diabetes and hypertension in the cohort with this information available (Avon Longitudinal Study of Parents and Children) did not attenuate inter-group differences.ConclusionOffspring of couples with infertility have increasingly higher BMI over the years, suggestively higher blood pressure levels, and tend to have greater values of LDL-C and lower values of HDL-C with age.

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“…Infertility causes such as ovulatory disorders and endometriosis not captured with these large datasets have been associated with cardiovascular diseases and may partially account for associations that were seen in the US study. 8 The fact that haemorrhagic stroke seemed to be consistently more common than ischaemic stroke does raise the possibility that any minimal risk that may exist is mediated by severe peripartum or postpartum hypertension. Preeclampsia-related stroke syndromes are common causes of preeclampsia-related mortality, can occur postpartum and are largely the haemorrhagic stroke type.…”

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confidence: 99%