Article Text

Download PDFPDF

Original research
Sex-specific distributions and determinants of thoracic aortic diameters in the elderly
  1. Lidia R Bons1,2,
  2. Oscar L Rueda-Ochoa3,4,
  3. Khalid El Ghoul1,
  4. Sofie Rohde1,
  5. Ricardo PJ Budde2,
  6. Maarten JG Leening1,3,5,
  7. Meike W Vernooij2,3,
  8. Oscar H Franco3,6,
  9. Aad van der Lugt2,
  10. Jolien W Roos-Hesselink1,
  11. Maryam Kavousi3,
  12. Daniel Bos2,3,5
  1. 1 Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
  2. 2 Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
  3. 3 Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
  4. 4 Electrocardiography Research Group, School of Medicine, Universidad Industrial de Santander, Bucaramanga, Santander, Colombia
  5. 5 Department of Clinical Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  6. 6 Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
  1. Correspondence to Dr Jolien W Roos-Hesselink, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3015CN, The Netherlands; j.roos{at}erasmusmc.nl

Abstract

Objective To provide population-based distributions of thoracic aortic diameters in men and women aged 55 years or older and to identify determinants of thoracic aortic diameters.

Methods From 2003 to 2006, 2505 participants (1208 men, mean age 69.1±6.8 years) from the prospective population-based Rotterdam Study underwent non-enhanced cardiac CT. The diameter of the ascending (AA) and descending aorta (DA) was measured at the level of the pulmonary bifurcation.

Results The mean diameter of the ascending and descending aorta was substantially larger in men (38±4 mm and 30±2 mm) than in women (35±3 mm and 27±2 mm). An ascending aortic diameter of larger than 40 mm was found in 228 (18.9%) men and 76 (5.9%) women and a descending aortic diameter larger than 40 mm was found in two men and no women. Male sex was found to be independently associated with larger DA diameter (standardised β 0.24, 95% CI 0.19 to 0.30), while a statistically non-significant trend was found for the AA diameter (standardised β 0.06, 95% CI 0.00 to 0.12). Age, height, weight and traditional cardiovascular risk factors were also associated with larger AA and/or DA diameters. Diabetes was associated with smaller AA and DA diameters. We found no evidence for effect modification by sex.

Conclusions In persons aged 55 years or older, an ascending aortic diameter of 40 mm or larger was found in 18.9% of men and 5.9% of women. Given the importance of sex, sex-specific distribution values may prove useful in clinical practice, even when correcting for body surface area or height.

  • aortic aneurysm
  • epidemiology
  • cardiac computer tomographic (CT) imaging
  • cardiac risk factors and prevention

Statistics from Altmetric.com

Introduction

Individuals with a thoracic aorta dilatation of larger than 60 mm are at high risk for severe complications, such as aortic dissection and rupture,1 which are related to mortality rates of up to 50% in the acute phase. These serious consequences have led to the development of the current guidelines stating that patients with an absolute thoracic aortic diameter of 55 mm or larger qualify for preventive aortic surgery.2 3 Yet, the definition of the threshold for aortic dilatation remains a topic of debate. Some argue that the absolute diameter provides a better risk estimate than diameters corrected for height and weight, while others propose to correct for body measurements such as body surface area (BSA),4 especially when it concerns women with short height. The current guidelines from the European Society of Cardiology2 define aortic dilatation as an absolute aortic diameter of larger than 40 mm. When aortic dilatation is found, follow-up visits are recommended to identify patients who will reach the threshold for preventive surgery due to further aortic growth. An important note regarding this definition of aortic dilatation is that this threshold is derived from cohort data of relatively young individuals with an age range from 9 to 59 years.5 Hence, this threshold of 40 mm6 may not be directly applicable to older individuals, especially given increasing evidence suggesting that aortic diameters change with age.7–9 Together with the finding that aortic complications mostly occur at older age,10 this emphasizes the need for data on the distribution of aortic diameters among older persons.11

In addition, more insight is required into the existence of sex-specific thoracic aortic diameters, as well as into which determinants influence thoracic aortic diameters. These topics are crucial for further research into the clinical relevance of aortic diameters in the elderly and may even contribute to the development of sex-specific recommendations. Against this background, we investigated (1) sex-specific distributions of absolute and BSA-corrected thoracic aortic diameters in a large sample of middle-aged and elderly persons from the general population, and (2) examined determinants of thoracic aortic diameters.

Methods

Study population

The Rotterdam Study is a prospective population-based cohort study that started in 1990, initially including participants aged 55 years or older from the Ommoord district in Rotterdam.12 Between 2003 and 2006, a random sample of 2524 participants underwent non-enhanced multidetector CT as part of a large project on arterial calcification. We excluded 17 CT examinations due to image artefacts because of the presence of pacemakers or coronary stent implantations (n=5), poor image acquisition quality (n=4) or absence of the pulmonary artery bifurcation level in the images (n=8). From two participants with complete data of aortic measurements, cardiovascular risk factor assessment at baseline was lacking. The remaining 2505 persons form the basis of the current analyses. In these 2505 participants, the ascending aortic diameter could be measured in 2500 (99.8%) and the descending aorta in 2462 (98.3%) participants. The Rotterdam Study complies with the Declaration of Helsinki and has been approved by the medical ethics committee, according to the Population Screening Act: Rotterdam Study, executed by the Ministry of Health, Welfare and Sports of the Netherlands. Participants were not involved in the design and conduct of the current research.

Assessment of aortic diameters

Non-contrast CT images were obtained using 16-slice (n=775) or 64-slice (n=1730) multidetector CT scanners (Somatom Sensation 16 or 64; Siemens, Forchheim, Germany). Two scans were obtained: a prospective ECG-triggered cardiac scan started at the apex of the heart and ended at the tracheal bifurcation and an extracardiac scan that reached from the aortic arch to the intracranial vasculature. Aortic diameters were measured primarily on the cardiac scan at an R–R interval of 50%. When the ascending or descending aorta was not visible in the heart scan, the extracardiac scan was used (ascending aorta n=162 and descending aorta n=173). Detailed information on the scan protocol has been provided previously.13 Both the ascending and descending aortic diameters were measured in millimetres in two directions at the bifurcation level of the pulmonary artery using the double-oblique method in a reconstruction perpendicular to the vessel axis. The largest diameter of the two measurements was used for further analysis. Given the lack of contrast material, we measured the aortic diameter with the outer edge-to-outer edge method. Assuming that calcified plaques are located in the intimal layer of the aorta, they were included in the measurement. The aortic diameters were measured by three observers. To assess interobserver variability, each observer measured the aortic diameters of the first 100 participants. The intraclass correlation coefficient was 0.985 for the ascending aorta and 0.989 for the descending aorta. Mean differences between the three observers were determined by Bland-Altman plots (online eFigure 1).14 Since body size area (BSA)–adjusted values are introduced by others,4 we also presented the diameter adjusted for BSA. BSA was calculated using the Dubois and Dubois formula: BSA (m2)=0.007184×height (m)0.725×weight (kg)0.425.

Assessment of determinants

We gathered information on the following determinants: age, body measurements, systolic and diastolic blood pressure, smoking, alcohol consumption, coronary and aortic arch calcification volume, cholesterol levels, diabetes, history of cardiovascular disease (CVD) and medication use. Detailed information on the assessment strategy for each determinant is provided in online appendix A.

Supplemental material

Mortality due to aortic events during follow-up

For all Rotterdam Study participants, municipal records were checked for information on vital status. Mortality due to an aortic event (aortic aneurysm or dissection) is collected according to WHO including ICD-10 code I71 and was available until 1 January 2014.

Statistical analysis

Continuous variable are expressed as mean±SD or as median±IQR. Data distribution was checked using histograms and the Shapiro-Wilk test. Categorical variables are presented as frequencies with percentages. We calculated the sex-specific distributions with mean and 95th percentile of absolute and BSA-adjusted thoracic aortic diameters for the total group and for different age groups (55–64 years, 65–74 years and ≥75 years). As sensitivity analysis, we excluded the participants with a history of CVD.

Associations between the determinants and absolute ascending or descending aortic diameters were quantified with univariable and multivariable linear regression models. We certified that the following assumptions underlying linear regression were met: linearity and homoscedasticity with a plot of *ZRESID against *ZPRED, normal distribution of residuals with histograms and normal P–P plots, multicollinearity with the variance inflation factor (VIF) and independent errors with the Durbin-Watson test. In multivariable linear regression analyses, all determinants (ie, age, anthropometrics, sex, smoking, alcohol consumption, diabetes, blood pressure, medication use, lipids, calcification volumes and history of CVD) were included in the model. For the analyses of calcification volumes, we used natural log-transformed values and added 1.0 mm3 to the non-transformed calcification values (ln(calcification volume+1)) to deal with calcium volumes of zero. In order to reduce the effect of multicollinearity, we removed a variable when a VIF of more than 10 was found. All models were adjusted for cohort and scanner type. We investigated statistical interaction of sex on all associations of determinants with the aortic diameters by adding interaction terms (sex×determinant) to the models. In addition, we determined to what extent only age and sex and age, sex and anthropometrics explained the variance in ascending and descending aortic diameters.

In 12.7% of the participants, ≥1 of the covariates were missing and they were handled by multiple imputation with five iterations.15 IBM SPSS statistics software V.21.0 was used to analyse the data and a p value of <0.05 was considered statistically significant.

Results

Study population

The median age of the 2505 participants was 67 (IQR 64–73) years, and 51.8% were women (table 1). CVD was prevalent in 303 participants (12%).

Table 1

Baseline characteristics of study participants

Sex-specific distributions of thoracic aortic diameters

Sex-specific distributions of absolute and BSA-adjusted aortic diameters are given for the total group and for different age groups in table 2. For the ascending and descending thoracic aorta, the mean diameters in men were 38±4 mm and 30±2 mm, and 35±3 mm and 27±2 mm in women. The full distribution of the absolute diameters, including the 90th and 95th percentiles, are shown in figure 1. After exclusion of participants with a history of CVD, the results did not substantially change. An ascending aortic diameter larger than 40 mm was found in 228/1208 men (18.9%) and in 76/1292 women (5.9%). An aortic diameter larger than 45 mm was found in 26/1208 men (2.2%) and 7/1292 women (0.5%), among whom 4 (0.2%, 3 men) had a diameter larger than 50 mm. A descending aortic diameter of larger than 35 mm was found in 20/1169 (1.7%) men and 4/1293 women (0.3%), and larger than 40 mm in 2 (0.2%) men and no women. None of the participants had a descending diameter of 45 mm or larger. From the 304 participants (12.2%) with an aortic diameter of more than 40 mm, only 4 (1.3%, 3 men and 1 woman) participants died of an aortic event (online eTable 1).

Figure 1

Distribution of the ascending and descending aortic diameters for both men (blue) and women (red), marking mean values, the 90th and 95th percentiles.

Table 2

Distribution of absolute aortic diameter and adjusted for BSA

Determinants of ascending and descending aortic diameters

The results for invariable analyses are presented in online eTable 2 and the univariable associations of height, weight and BSA with aortic diameters are visualised in online eFigure 2. Multivariable linear regression analysis showed that higher age, taller height and larger weight, higher diastolic blood pressure, lower systolic blood pressure, larger volume of calcifications in coronary arteries and aortic arch, and the use of blood pressure–lowering medication were associated with larger absolute ascending and descending aortic diameters (figures 2 and 3). Conversely, the presence of diabetes and the use of lipid-modifying agents were associated with smaller ascending and descending aortic diameters. A smaller hip circumference was specifically associated with a smaller ascending aortic diameter. Male sex, current smoking, alcohol consumption and lower high-density lipoprotein (HDL) cholesterol were specifically associated with larger descending aortic diameters. None of the interaction terms between the potential determinants and sex was significant. Age, sex and anthropometrics explained 15% of the variance in ascending aortic diameters while age and sex explained 34% of the variance in descending thoracic aortic diameters. Addition of anthropometrics and conventional cardiovascular risk factors increased this to 21% for the ascending aorta and to 39% for the descending aorta.

Figure 2

Determinants of ascending aortic diameters in multivariable analysis. Models were further adjusted for cohort and scanner type. The variance of the ascending aortic diameter was explained by conventional cardiovascular risk factors for 21%. *p<0.05. †Values represent transformed calcification volumes in mm3: ln(calcification volume+1 mm3). CVD, cardiovascular disease; HDL, high-density lipoprotein.

Figure 3

Determinants of descending aortic diameters in multivariable analysis. Models were further adjusted for cohort and scanner type. The variance of the descending aortic diameter was explained by conventional cardiovascular risk factors for 39%. *p<0.05. †Values represent transformed calcification volumes in mm3: ln(calcification volume+1 mm3). CVD, cardiovascular disease; HDL, high-density lipoprotein.

Discussion

Using data from a large population-based cohort, we provide new sex-specific distributions of absolute and BSA-corrected thoracic aortic diameters in middle-aged and elderly persons. For the ascending and descending aorta, the mean diameters in men were 38 mm and 30 mm, and 35 mm and 27 mm in women. An ascending aortic diameter larger than 40 mm was found in 304 participants (12.2%, 228 men) and a descending aortic diameter larger than 40 mm was found in two participants. Although we found a thoracic aortic diameter of more than 40 in a considerable amount of persons aged 55 years or older, only 4 (1.3%) of them died as a result of an aortic event. This number seems rather low and raises the question whether a cut-off of 40 mm is an appropriate one. Yet, given the low number of events, this should be confirmed by larger studies.

Although the difference in mean aortic diameter between the age group of 55–65 years and ≥75 years was only 1 mm for both the ascending and descending aorta, the aortic diameter above 55 years still increased. Our results show the 95th percentile for persons above the age of 75 years old to be 43 mm for ascending and 35 mm for descending aorta for men and 41 mm and 33 for women, an age group for whom distribution data are currently scarce.11 Our data further establish the range of thoracic aortic diameters, which is similar to data found in a study performed in Germany.16 Absolute aortic diameters measured in the Rotterdam Study are larger than previous studies performed in the USA,9 17 which also used non-enhanced CT imaging. They reported older participants (≥55 years) as subanalysis of the entire population studied and therefore contained smaller samples. The larger aortic diameters measured in our study may partly be explained by the larger average height of the study population. Native Dutch people are relatively tall.18 BSA of our cohort (1.9±0.2 m2) was comparable with the aforementioned two studies (both 1.9±0.3 m2), but height was not reported by others and therefore could not be compared. BSA describes height and also weight, and since American individuals are more likely to be obese than Dutch individuals,19 this might suggest a taller height in our group. Nevertheless, both our cohorts as previously smaller cohorts show that an aortic diameter of >40 mm is not uncommon in middle-aged and elderly persons.

In our cohort, both weight and height were found to be important determinants of the aortic diameters, which supports previous findings on this matter.7 8 Whether the aortic diameter should be corrected for height, weight or BSA in defining aortic dilatation is an ongoing discussion. While some authors suggest to use only height,20 others advocate the use of BSA, which takes into account both height and weight.4 However, longitudinal data are needed to establish the abilities of indexed aortic diameters compared with the abilities of absolute aortic diameters in the prediction of aortic events. Interestingly, from our data, it appeared that absolute values are substantially larger for men than for women, yet BSA-corrected values are statistically larger for women than for men. This suggest that differences in body measures partly explain sex differences in aortic diameters, but that there is still a remaining sex difference which results in larger BSA-indexed values for women. Therefore, we conclude that distribution values should be provided for men and women separately, even when correcting for weight, height or BSA.

In line with previous literature,9 17 21 smoking was associated with the diameter of the descending but not the ascending aorta. In addition, HDL cholesterol had a significant inverse relation with only the descending aorta. Based on figures 2 and 3, 39% of the variance in descending aortic diameter but only 21% of the variance in ascending aortic diameter was explained by age, sex, anthropometrics and traditional cardiovascular risk factors. Probably, other factors such as genetic predisposition are more important in the ascending aorta. Already 34% of the variation in descending aortic diameter and 15% of the variation in ascending aortic diameter was explained by age, sex and anthropometrics. Therefore, there is only a small increase in explained variance caused by the addition of traditional cardiovascular risk factors to the model. Since this small increase in explained variance was shown in both the ascending and descending aorta, we provide no clear evidence that the descending aorta is more susceptible to cardiovascular risk factors than the ascending aorta. Both the ascending and descending aortic diameter were associated with calcifications of the coronary arteries or aortic arch and use of lipid-modifying agents. This is in contrast to recent literature showing a significant relation of aortic plaques and calcium with only the descending aorta.21 22 In conclusion, although we found differences between the ascending and descending aorta in the association between smoking, alcohol consumption and HDL cholesterol, the effect of these cardiovascular risk factors seems of limited importance in explaining the overall variation in aortic diameter.

In addition, we found that blood pressure was associated with thoracic aortic diameters. We found a positive association of the diastolic blood pressure but a negative association of the systolic blood pressure with aortic diameters. Whether hypertension is indeed a risk factor for aortic dilatation is still unknown,23 but our results suggest that high diastolic blood pressure might be more important in the development of aortic dilatation than high systolic blood pressure. Current guidelines2 advise to reduce blood pressure (both systolic and diastolic). The importance of high diastolic blood pressure on aortic diameters should be stressed and deserves more attention, also in research.

We found diabetes to be negatively associated with both the ascending and descending aortic diameters. This phenomenon has already been shown in the abdominal aorta, where it is described that diabetes is associated with less aortic dilatation of the abdominal aorta.24 25 This might be caused by advanced glycation associated with diabetes which inhibits through intermediate steps secretion of the matrix metalloproteinases.25 Also, the fibrinolytic pathway, more specifically the plasminogen activator inhibitor-1, is mentioned as a candidate mechanism for hyperglycaemic inhibition of abdominal aortic disease.26 More research is warranted to elucidate the role of these pathways in the development of both thoracic and abdominal aortic aneurysms.

Strengths of our study include the population-based setting and the relatively large sample size. By including participants with hypertension or a history of CVD, we measure the aortic diameter in the general population and not only in healthy people. Therefore, the results can be generalised to a larger proportion of the older population.

Limitations

The use of ECG-gated CT scans allowed highly accurate measurements of the aorta. The use of contrast-enhanced CT would have made the measurements even more accurate. However, the use of contrast in predominantly healthy people from the general population is unethical and can cause unnecessary complications, such as an allergic reaction to contrast fluid.

Conclusion

We provide novel sex-specific distributions of thoracic aortic diameter for the middle-aged and elderly general population. Our distribution show high prevalence (12.2%) of an ascending aortic diameter more than 40 mm, which is typically considered dilated. However, mortality due to aortic aneurysm or dissection in these participants seems rather low, and raises the question whether a cut-off of 40 mm is an appropriate one. Yet, given the low number of events, this should be confirmed by larger studies.

Sex was independently associated with descending aortic diameters and tended to be associated with ascending aortic diameters. This indicates that distribution values should be provided for men and women separately, even when correcting for BSA or height. Traditional cardiovascular risk factors are responsible for only a limited part of the variance in aortic diameters. We found no evidence for effect modification of these associations by sex.

Key messages

What is already known on this subject?

  • While aortic diameters change with age and most aortic complications due to aneurysmatic aortic diameters occur at older age, data about the distribution of aortic diameters among older persons are scarce.

What might this study add?

  • In our population-based cohort, the mean ascending and descending aortic diameters were 38 mm and 30 mm in men, and 35 mm and 27 mm in women. In 18.9% of the male participants and 5.9% of the female participants, the ascending aortic diameter was larger than 40 mm. Most important determinants of thoracic aortic diameters were age, sex, body measures and traditional cardiovascular risk factors.

How might this impact on clinical practice?

  • In middle-aged and elderly persons, the prevalence of an ascending aortic diameter of more than 40 mm is relatively high. Further research is needed to assess whether a higher cut-off value for aortic dilatation should be applied for the elderly.

Acknowledgments

The dedication, commitment and contribution of participants, general practitioners and pharmacists of the Rotterdam Study are gratefully acknowledged.

References

Footnotes

  • LRB and OLR-O are joint first authors.

  • JWR-H, MK and DB shared last authorship.

  • Contributors LRB, OLR-O, DB, MK, OHF, AvdL and JWR-H contributed to the concept/design, data analysis/interpretation and drafting of the article. KE and SR contributed to data collection and writing. MV, MJGL and RB contributed to the concept/design, critical revision of the article and approval of the article. JWR-H, MK and DB shared last authorship.

  • Funding The Rotterdam Study is funded by Erasmus MC and Erasmus University, Rotterdam, the Netherlands; the Netherlands Organisation for Scientific Research (NWO); the Netherlands Organisation for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. MK is supported by a VENI grant (91616079) from ZonMw. JWR-H and LRB are supported by the Dutch Heart Foundation (2013T093) and ZonMW (849200014). OLR-O is supported by COLCIENCIAS and Universidad Industrial de Santander, Colombia.

  • Disclaimer The funding organisations had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; or decision to submit the manuscript for publication.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles