Background: Overweight and obesity are increasing globally, as are life expectancy and disorders associated with aging, including calcific aortic stenosis (AS). Studies investigating the correlation between high body mass index (BMI) and AS are contradictory and inconclusive. This study examines a potential association between BMI and early AS in women. Methods: By linking the Swedish Medical Birth Register (MBR) and the Swedish National Patient Register (NPR), we included women between 18 and 55 years with a first childbirth from 1982 to 2020. Diagnosis of subsequent AS and comorbidities were defined according to the International Classification of Diseases (ICD) 8, 9, and 10 codes. The women were divided into eight groups based on their BMI, with BMI 20 kg/m2-<22.5 kg/m2 as reference. Cox proportional hazards regression models were used to investigate the difference in the risk of being diagnosed with AS. Results: The mean age at inclusion among 1,722,798 women was 28 years, and the mean BMI was 24 kg/m2. Some 21% were overweight (BMI 30 kg/m2-<35 kg/m2) and 10.7% were obese (BMI≥35 kg/m2). During a median follow-up of 19.5 years, 2,513 women (0.15%) were diagnosed with AS. The age-adjusted risk of being diagnosed with AS, compared to a reference group with BMI 20 -<22.5 kg/m2, increased with higher BMI to 2.8 (95%CI 2.43-3.24) times higher in women with BMI 30 -<35 kg/m2, and to 3.67 (95%CI 2.91-4.64) times higher in those with severe obesity (BMI ≥35 kg/m2). Similar results were found after excluding AS of rheumatic and congenital etiology. Conclusions: Higher BMI correlated with a higher risk of developing AS in women, regardless of etiology, beginning with increased risk even within the upper normal range, reaching a three times higher risk in women with severe obesity.

The authors have declared no competing interest.

This work was supported by grants from the Swedish state under an agreement between the Swedish government and the county councils concerning economic support of research and education of doctors [ALFGBG-966211]; [ALFGBG-971608], the Swedish Heart and Lung Foundation [2021-0345], and the Swedish Research Council [2018-02527; VRREG 2019-00193].

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:

The study was approved by the Regional Ethics Review Board in Gothenburg.

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.

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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).

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

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The data that support the findings of this study are available on request from the corresponding author, SK.