How Does a Patient’s Sex Affect Aortic Valve Calcification Progression?

Aortic valve, computer illustration.
Researchers sought to determine the natural progression of aortic valve calcification in the general population and to identify how sex may affect it.

The magnitude of computed tomography (CT)-assessed aortic valve calcification (AVC) score, one of the most important risk markers for AVC progression (ΔAVC), is affected by the sex of the patient, according to a study published in Circulation: Cardiovascular Imaging.

Reseachers used data from the Danish Cardiovascular Screening (DANCAVAS) pilot study, in which 1298 participants who had initial screening in 2014 to 2015 were invited for a reexamination in 2019. Each screening examination involved a cardiac CT and a truncal CT.

The AVC score was measured during the CT, and ΔAVC was defined as the numerical difference between the AVC score measured at follow-up and baseline.

A total of 823 individuals (383 women and 440 men) participated in the follow-up examination. The mean time interval was 4.7 years (SD, 0.1; range, 3.8-5.4 years) between the baseline and follow-up examinations. The participants had a mean age of 73 years at follow-up, and men had significantly higher AVC scores at baseline and follow-up compared with women.

At baseline, 362 participants (44%) did not have AVC, and 461 (56%) had some degree of AVC. After 4.7 years, 581 (71%) had AVC. Overall, AVC increased by 11 Agatston units (AU) (IQR, 0-64 AU).

Men had a greater progression rate (26 AU [IQR, 0-101 AU] compared with women (4 AU [IQR, 0-37 AU], P<.001) and were more likely than women to have an increase in AVC (73% vs 58%, respectively) and less likely to have an unchanged AVC (21% vs 33%, respectively; P<.001).

After adjustment for baseline AVC, hypertension was associated with ΔAVC in women (incidence rate ratio [IRR], 1.43 [95% CI, 1.01-2.04], P=.047) but not in men. Dyslipidemia was associated with ΔAVC in men (IRR, 1.59 [95% CI, 1.14-2.21], P=.006) but not in women.

Baseline AVC (IRR, 3.03 [95% CI, 2.72-3.37], P<.001) had the strongest association with ΔAVC in the univariate zero-inflated negative binomial model.

C-reactive protein was the only biomarker associated with ΔAVC when adjusting for baseline AVC, but the effect was blunted in the multivariable analysis and remained significant only in men (IRR, 1.02 [95% CI, 1.00-1.03], P=.008).

The rate of AVC progression increased with the number of risk factors, including male sex, age older than 69 years, smoking status, hypertension, dyslipidemia, and diabetes.

The multivariable model also showed that only baseline AVC remained significantly associated with AVC progression in both men and women, and age was associated with AVC progression only in women. The area under the curve was 0.8418 and 0.9097 for women and men, respectively.

The study authors noted that selection bias is unavoidable, as only about two-thirds of the invited participants were included in the follow-up examination. Further, nonparticipants were older and had a higher level of comorbidity and AVC and coronary artery calcification scores than participants, which may have led to an underestimation of the findings.

“Our study further adds to the theory of a sex-dependent relationship between AVC and aortic stenosis and suggests that the development of aortic stenosis and potential therapies to prevent AVC progression may demonstrate sex-dependent differences,” the researchers noted.


Diederichsen A, Lindholt JS, Møller JE, Gerke O, Rasmussen LM, Dahl JS. Sex differences in factors associated with progression of aortic valve calcification in the general population. Circ Cardiovasc Imaging. Published online January 5, 2022. doi:10.1161/CIRCIMAGING.121.013165