Abstract
Background
Aortic root remodeling in adulthood is known to be associated with cardiovascular outcomes. However, there is a lack of longitudinal data defining the clinical correlates of aortic root remodeling over the adult life course.
Methods and Results
We used serial routine echocardiograms in participants of the Framingham Heart Study to track aortic root diameter over 16 years in mid-to-late adulthood, and to determine its short-term (4 years, n=6099 observations in 3506 individuals) and long-term (16 years, n=14628 observations in 4542 individuals) clinical correlates by multilevel modeling. Age, sex, body size and blood pressure were principal correlates of aortic remodeling in both short- and long-term analyses (all P≤0.01). Aortic root diameter increased with age in both men and women, but was larger in men at any given age. Each 10-year increase in age was associated with a larger aortic root (by 0.89mm in men; 0.68mm in women) adjusting for body size and blood pressure. A 5-kg/m2 increase in body mass index was associated with a larger aortic root (by 0.78mm in men; 0.51mm in women), adjusting for age and blood pressure. Each 10-mmHg increase in pulse pressure was related to a smaller aortic root (by 0.19mm in men; 0.08mm in women), adjusting for age and body size.
Conclusions
These longitudinal community-based data show that aortic root remodeling occurs over mid-to-late adulthood and is principally associated with age, sex, body size and blood pressure. The underlying basis for these differences and implications for the development of cardiovascular events deserve further study.
Keywords: Aorta, Epidemiology, Echocardiography, Remodeling, Risk factors
Arterial remodeling with aging is widely recognized to play a key role in the pathogenesis of cardiovascular disease.1 Numerous cross-sectional2–5 and postmortem studies6 have demonstrated an association between increasing age and dilatation of the proximal (central) aorta, with underlying age-related changes in the aortic media such as reduced elastin content, elastin fractures, collagen deposition and calcification. An enlarged aortic root has been shown to be a marker of cardiac and extra-cardiac target organ damage,7 which is associated with cardiovascular events and mortality.8 The cross-sectional correlates of aortic root size include age, anthropometric factors (sex, body size), as well as cardiovascular risk factors (mainly hypertension).2–5 These factors have been postulated to interact in a complex fashion over the life course to affect vascular structure and function.1
In contrast to the wealth of cross-sectional data on aortic root size, surprisingly little longitudinal data exists regarding evolution of aortic root size over the adult life course, and the clinical correlates of tracking of aortic size. Such longitudinal data are needed to define the natural history of aortic remodeling in adulthood and to understand factors influencing aging-associated aortic root dilatation. Accordingly, we evaluated the clinical correlates of long-term longitudinal tracking of aortic root size, as well as short-term changes in aortic root size, in a large sample from the community. For this purpose, we assessed factors influencing both short-term change (4 years) and long-term tracking (16 years) of aortic root size using multi-level modeling and aortic root measurements obtained over mid-to-late adulthood in the Framingham Offspring Study. We hypothesized that age, sex, body size and blood pressure would also be the key correlates of longitudinal tracking and short-term changes in aortic root size. We further hypothesized that age and sex would interact with other clinical covariates to influence aortic remodeling over the adult life course.
METHODS
Study design
The design, sampling strategy and recruitment of the Framingham Offspring Study have been previously detailed.9 Briefly, since initiation of the study in 1971, participants have been examined at the Framingham Heart Study clinic approximately every four to eight years. At each visit, participants undergo a comprehensive review of their cardiovascular risk profiles and anthropometric data, as well as a targeted physical examination. Blood pressure was measured in the left arm of the seated subject using a mercury column sphygmomanometer. All procedures are performed according to standardized study protocols. All participants provided written informed consent and protocols were approved by the Boston University Medical Center Institutional Review Board.
Echocardiographic measurement
Transthoracic echocardiograms were performed at Offspring examination cycles 2 (1979–82), 4 (1987–90), 5 (1991–95) and 6 (1996–98). All echocardiograms were performed by trained technicians using standardized protocols. M-mode images of the aortic root were obtained with two-dimensional echocardiographic guidance. Aortic root diameter was measured from the M-mode tracings using the leading-edge to leading-edge technique, as recommended by the American Society of Echocardiography.10 Aortic root measurements obtained in this fashion were highly reproducible, as systematically assessed at the sixth examination cycle.11
To evaluate the progression of aortic root size in mid-to-late adulthood, observations were included if participants were within limits of the age group of interest (25 to 74 years) at the time of echocardiography. Significant valve disease (244 observations), defined as greater than mild valve disease at examination cycle 6, was excluded. Short-term (4-year) change in aortic root diameter was evaluated in participants who had at least 2 consecutive echocardiograms (Figure 1). Data regarding the change in aortic root diameter over any 4-year period (examination 4 to 5 or examination 5 to 6) were pooled to maximize statistical power (n=6099 observations in 3506 participants). Long-term (over the course of 16 years) tracking of aortic root size was evaluated in a total of 4542 participants who attended any of the examinations of interest, giving a total of 14628 observations. The number of data points from each examination cycle that contributed to the analyses are available online (Supplemental Table).
Figure 1. Study design.
Routine echocardiograms were used to track aortic root diameter in participants of the Framingham Heart Study. Short-term (4 years) change in aortic root diameter was evaluated in 3506 individuals with at least 2 consecutive echocardiograms (6099 observations). Long-term (16 years) tracking of aortic root size was performed in 4542 individuals who attended up to 4 serial echocardiograms (14628 observations).
Statistical analyses
Correlates of short-term change in aortic root diameter
Generalized estimating equations were used to model the change in aortic root diameter over 4 years, where the dependent variable was change in diameter between examination cycles 4 and 5, and between cycles 5 and 6 (approximately 4 year intervals) (Figure 1), while predictor variables were obtained at the earlier of two consecutive examination cycles. Clinical covariates were selected based on reported cross-sectional associations with aortic root size2–5 and included: age, sex, body mass index (BMI), systolic blood pressure, diastolic blood pressure, antihypertensive therapy, smoking status and diabetes mellitus (Model 1). Since peak (systolic blood pressure) and trough (diastolic blood pressure) blood pressure provide only a limited view of vascular hemodynamics, mean arterial pressure (MAP) and pulse pressure (PP) were also derived as indices of steady-flow (MAP) and pulsatile (PP) components of blood pressure.12 Thus, MAP and PP were included in place of systolic blood pressure and diastolic blood pressure in a second multivariable model (Model 2), along with the other clinical covariates. Both models also were adjusted for examination cycle and baseline aortic root size. Main effects were investigated, as well as biologically plausible interactions between age, sex and other clinical covariates, by including appropriate terms in the multivariable models.
Correlates of long-term tracking of aortic root diameter
Multilevel modeling was used to model individual growth curves for aortic root diameter over the long-term (up to 16 years). This analytical method is applicable to hierarchical data structures and is therefore well-suited for analysis of data that vary on both the patient-level and over time. Further, the method allows maximization of the number of observations that can be analyzed as the analytic approach accommodates missing data at some of the serial examinations. Multilevel modeling of aortic root diameter was performed incorporating the same set of covariates and interaction terms as used in the short-term analysis. Models were fit by direct entry of candidate variables and using the maximum likelihood approach. Non-linear effects of age were tested but they were not statistically significant. Random intercepts and random effects of age were used to account for variation in initial aortic root sizes and slopes for age respectively in different participants. Regression coefficients, their corresponding standard errors and P values were reported. In addition, the change in aortic root diameter for a clinically meaningful increment of each significant predictor variable was calculated and presented to aid in the interpretation of the data.
Finally, to illustrate the expected changes in aortic root diameter over the life course according to risk factor profile,13, 14 we modeled separate growth curves for four hypothetical groups:
Participants without hypertension and without obesity (blood pressure 125/75 mmHg, BMI 25 kg/m2)
Participants with hypertension, but without obesity (blood pressure 160/100 mmHg, BMI 25 kg/m2)
Participants with obesity, but without hypertension (blood pressure 125/75 mmHg, BMI 35 kg/m2)
Participants with both hypertension and obesity (blood pressure 160/100 mmHg, BMI 35 kg/m2)
All analyses were performed using SAS software. Statistical significance was determined at a P value of <0.05. All authors had full access to the data and take responsibility for the integrity of the data.
RESULTS
Baseline characteristics
The study sample consisted of middle-aged men and women (Table 1). Participant characteristics are described at the first examination of any 4-year period between consecutive examinations in the pooled short-term sample, and at the first available examination of the 16-year period for the long-term sample (Figure 1).
Table 1.
Baseline Characteristics of Study Sample Used in Short-Term (4 years) and Long-Term (16 years) Longitudinal Analyses of Aortic Root Diameter
| Variable | Sample for Short-Term Analyses (n=3506) | Sample for Long-Term Analyses (n=4542) | ||
|---|---|---|---|---|
| Men (n=1671) | Women (n=1835) | Men (n=2187) | Women (n=2355) | |
| Age, years | 52±10 | 51±10 | 46±10 | 45±10 |
| Weight, kg | 85.3±13.5 | 68.3±14.5 | 83.0±12.9 | 65.5±13.8 |
| Height, m | 175.3±6.7 | 161.9±6.1 | 175.6±6.9 | 161.9±6.2 |
| Body mass index, kg/m2 | 27.7±3.9 | 26.0±5.4 | 26.9±3.8 | 25.0±5.1 |
| Systolic blood pressure, mm Hg | 129±17 | 124±20 | 127±16 | 120±17 |
| Diastolic blood pressure, mm Hg | 81±10 | 76±10 | 81±9 | 76±9 |
| Mean arterial pressure, mmHg | 97±11 | 92±12 | 96±11 | 90±11 |
| Pulse pressure, mmHg | 48±13 | 47±14 | 46±12 | 44±12 |
| Hypertension, % | 40.6% | 29.2% | 31.2% | 20.4% |
| Antihypertensive treatment, % | 20.1% | 14.4% | 13.0% | 10.6% |
| Diabetes, % | 7.3% | 4.2% | 4.8% | 2.5% |
| Smoking, % | 23.3% | 22.7% | 34.6% | 36.2% |
| Baseline aortic root size, crude, mm | 34.0±3.7 | 29.5±3.1 | 32.8±3.2 | 28.4±2.9 |
Values are mean±SD or percentages.
Characteristics shown are from the first of two consecutive examinations for the short-term sample and the first eligible examination for the long-term sample.
Correlates of short-term change in aortic root diameter
Adjusting for baseline aortic root size, examination cycle and antihypertensive therapy, short-term (4 years) increases in aortic root diameter were associated with older age, male sex and larger body size (increasing BMI) (Table 2). Interestingly, divergent effects of blood pressure were observed, even after adjusting for the effect of antihypertensive medications: lower systolic blood pressure and higher diastolic blood pressure were associated with short-term increases in aortic root diameter (Table 2 Model 1). Accordingly, aortic root dilation over 4 years was related to lower pulsatile component (PP) but higher steady-flow component (MAP) of blood pressure at baseline (Table 2, Model 2).
Table 2.
Correlates of Short-Term (4-year) Change in Aortic Root Diameter (in mm)
| Model 1 (modeling BP as SBP & DBP) | Model 2 (modeling BP as PP & MAP) | |||||
|---|---|---|---|---|---|---|
| Regression Coefficient | Standard Error | P value | Regression Coefficient | Standard Error | P value | |
| Age, 52 years | 0.030 | 0.004 | <0.0001 | 0.030 | 0.004 | <0.0001 |
| Male sex | 1.796 | 0.082 | <0.0001 | 1.796 | 0.082 | <0.0001 |
| BMI, kg/m2 | 0.051 | 0.007 | <0.0001 | 0.051 | 0.007 | <0.0001 |
| SBP, mmHg | −0.134 | 0.053 | 0.01 | - | - | - |
| DBP, mmHg | 0.209 | 0.051 | <0.0001 | - | - | - |
| PP, mmHg | - | - | - | −0.162 | 0.045 | 0.0004 |
| MAP, mmHg | - | - | - | 0.157 | 0.043 | 0.0002 |
| Antihypertensive treatment, % | 0.193 | 0.095 | 0.04 | 0.193 | 0.095 | 0.04 |
BP, blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; PP, pulse pressure; MAP, mean arterial pressure; BMI, body mass index.
Age, 52 years: age was centered at the mean of all participants at all exams (52 years) to reduce multi-co-linearity between regression coefficients.
Regression coefficients represent the change in mean difference in aortic root diameter (in mm) between 4-yearly examination cycles per 1 SD difference in each continuous predictor variable (1 unit difference in age and BMI) or presence vs. absence of each categorical predictor variable. Models were also adjusted for examination cycle and baseline aortic root size.
Correlates of long-term tracking of aortic root diameter
Consistent with the analysis of short-term change in aortic root diameter, significant correlates of mean aortic root diameter over 16 years (Table 3) were older age, male sex, higher BMI, higher diastolic blood pressure (Table 3 Model 1) or lower PP and higher MAP (Table 3 Model 2), adjusting for antihypertensive therapy and examination cycle. Similar results were observed among hypertensive participants alone (not shown).
Table 3.
Correlates of Long-Term (16-year) Longitudinal Tracking of Mean Aortic Root Diameter
| Model 1 (modeling BP as SBP & DBP) | Model 2 (modeling BP as PP & MAP) | |||||
|---|---|---|---|---|---|---|
| Regression Coefficient | Standard Error | P value | Regression Coefficient | Standard Error | P value | |
| Age52 | 0.1175 | 0.01426 | <0.0001 | 0.1172 | 0.01426 | <0.0001 |
| Male sex | 2.654 | 0.4063 | <0.0001 | 2.490 | 0.3962 | <0.0001 |
| BMI, kg/m2 | 0.1011 | 0.00890 | <0.0001 | 0.09860 | 0.00880 | <0.0001 |
| SBP, mmHg | −0.0071 | 0.05388 | 0.9 | - | - | - |
| DBP, mmHg | 0.1879 | 0.04995 | 0.0002 | - | - | - |
| PP, mmHg | - | - | - | −0.1174 | 0.04396 | 0.008 |
| MAP, mmHg | - | - | - | 0.2699 | 0.03259 | <0.0001 |
| Antihypertensive treatment | 0.2224 | 0.07477 | 0.003 | 0.2184 | 0.07475 | 0.004 |
| Age52*Men | 0.02066 | 0.00611 | 0.0007 | 0.01957 | 0.00608 | 0.001 |
| Age52*BMI | −0.0020 | 0.00053 | 0.0002 | −0.0019 | 0.00053 | 0.0002 |
| BMI*Men | 0.05433 | 0.01469 | 0.0002 | 0.06041 | 0.01430 | <0.0001 |
| SBP*Men | −0.1928 | 0.07978 | 0.02 | - | - | - |
| DBP*Men | 0.2040 | 0.07086 | 0.004 | - | - | - |
| PP*Men | - | - | - | −0.1442 | 0.06127 | 0.02 |
BP, blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; PP, pulse pressure; MAP, mean arterial pressure; BMI, body mass index.
Age, 52 years: age was centered at the mean of all participants at all exams (52 years) to reduce multi-co-linearity between regression coefficients.
Regression coefficients represent the change in mean aortic root diameter (in mm) per 1 SD difference in each continuous predictor variable (1 unit difference in age and BMI) or presence vs. absence of each categorical predictor variable.
Models were also adjusted for examination cycle.
Interactions between age, sex and other clinical covariates
Interactions were observed between age and sex, age and BMI, BMI and sex, and blood pressure and sex. To facilitate the interpretation of the interaction terms, we calculated the expected effect of each variable of interest on tracking of aortic root diameter over 16 years (Table 4) in men and women, accounting for its main effect as well as its interactions. Each 10-year increase in age was associated with a larger predicted aortic root diameter of 0.89 mm in men and 0.68 mm in women (both of average BMI of 25 kg/m2), adjusting for blood pressure and antihypertensive therapy. A 5-kg/m2 increase in BMI was associated with a larger predicted aortic root diameter in men (0.78 mm) than in women (0.51 mm), adjusting for age and blood pressure. Each 10-mmHg increase in diastolic blood pressure was associated with a larger predicted aortic root diameter in men (0.39 mm) than in women (0.19 mmHg) adjusting for all other clinical covariates. The predicted effect of systolic blood pressure was small in both sexes. Of note, each 10-mmHg increase in PP was related to a smaller predicted aortic root diameter in men (0.19 mm) and women (0.08 mm), adjusting for age, BMI and antihypertensive therapy.
Table 4.
Interaction of Clinical Correlates of Longitudinal Aortic Root Tracking Over a 16-Year Period
| Tracking of Aortic Root Diameter Mean (95% CI) in mm | ||
|---|---|---|
| Model 1 (modeling BP as SBP & DBP) | Model 2 (modeling BP as PP & MAP) | |
| Men vs women with: | ||
| age 52 years, BMI 25 kg/m2, SBP 125 mmHg, DBP 75 mmHg, PP 49 mmHg | 3.9780 (3.8180 to 4.1380) | 3.9970 (3.8378 to 4.1562) |
| Effect of age (per 10-year increase) in: | ||
| Men, BMI 25 kg/m2 | 0.8888 (0.79 to 0.9876) | 0.8815 (0.7830 to 0.9800) |
| Women, BMI 25 kg/m2 | 0.6822 (0.5844 to 0.7800) | 0.6858 (0.5880 to 0.7836) |
| Effect of BMI (per 5-kg/m2 increase) in: | ||
| Men, age 52 years | 0.7772 (0.6596 to 0.8947) | 0.7951 (0.6790 to 0.9111) |
| Women, age 52 years | 0.5055 (0.4183 to 0.5927) | 0.4930 (0.4068 to 0.5792) |
| Effect of SBP (per 10-mmHg increase) in: | ||
| Men | −0.1090 (−0.1722 to −0.0458) | - |
| Women | −0.0040 (−0.0616 to 0.0536) | - |
| Effect of DBP (per 10-mmHg increase) in: | ||
| Men | 0.3925 (0.2910 to 0.4940) | - |
| Women | 0.1882 (0.0902 to 0.2862) | - |
| Effect of PP (per 10-mmHg increase) in: | ||
| Men | - | −0.1860 (−0.2524 to −0.1196) |
| Women | - | −0.0830 (−0.1443 to −0.0217) |
| Effect of MAP (per 10-mmHg increase) | 0.2329 (0.1778 to 0.288) | |
| Antihypertensive treatment | 0.2224 (0.0759 to 0.3689) | 0.2184 (0.0719 to 0.3649) |
BP, blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; PP, pulse pressure; MAP, mean arterial pressure; BMI, body mass index.
Table shows the effect of each variable on long-term (16 years) tracking of mean aortic root diameter in indicated subgroups, adjusting for all other clinical covariates.
Impact of hypertension and obesity on tracking of aortic root diameter
Figure 2 illustrates the expected mean aortic root diameter over the life course in modeled growth curves according to different clinical risk factor profiles. As shown, mean aortic root diameter enlarged over the mid-to-late adulthood period in both men and women, but at any given age, men had larger mean aortic roots compared to women. Further, greater aortic dilatation was expected in the presence of hypertension or obesity, and the presence of both factors had a greater impact (steeper slope) on aortic root dilatation in men than women.
Figure 2. Predicted mean aortic root growth curves in men and women with and without obesity or hypertension.
Sex-specific growth curves were modeled in men (A) and women (B), tracking mean aortic root diameter over 16 years in (1) participants without hypertension (HTN) and without obesity (blood pressure 125/75 mmHg, body mass index 25 kg/m2); (2) participants with HTN, but without obesity (blood pressure 160/100 mmHg, body mass index 25 kg/m2); (3) participants with obesity, but without HTN (blood pressure 125/75 mmHg, body mass index 35 kg/m2); (4) participants with both HTN and obesity (blood pressure 160/100 mmHg, body mass index 35 kg/m2).
DISCUSSION
Our study provides longitudinal community-based data regarding tracking of aortic root size over mid to late adulthood. Age, sex, body size and blood pressure were principal correlates of aortic remodeling in both the short- (4 year) and long- (16 year) term analyses. Separate components of hemodynamic load differed in their relation with aortic root size: steady flow load (mean arterial pressure) was associated positively with aortic root diameter whereas pulsatile load (pulse pressure) was associated negatively with aortic root diameter over the adult life course. Given the discordant effects of mean and pulse pressure on aortic root diameter but their concordant contributions to systolic blood pressure, systolic blood pressure alone had a limited relationship to aortic root diameter. Further, sex emerged as an important modifier of the associations of age, body size and blood pressure with aortic root remodeling.
The importance of aortic remodeling over the adult life course and its role in the pathogenesis of cardiovascular disease have been the focus of considerable interest.1, 15–18 A modest increase in diameter of the proximal aorta with advancing age has been well-established in cross-sectional2–5 and postmortem studies.6 Associated structural changes in the arterial wall have also been described.19, 20 Age-related increases in collagen synthesis within the aortic wall result in increasing proximal aortic stiffness, since mechanical stresses, no longer buffered by elastin, are transferred to the less extensible collagen fibres.16 Pulse pressure, generally regarded as an index of arterial stiffening, is well-known to increase with age and to be associated with adverse cardiovascular events including heart failure.21 Similarly, an enlarged aortic root has been associated with cardiac disease, adverse cardiovascular outcomes and mortality.7, 8
Despite widespread recognition of the significance of aortic remodeling and the wealth of cross-sectional data describing its clinical correlates, longitudinal data are scarce. Our current study in a large community-based cohort establishes that the aortic root size gradually increases in mid-to-late adulthood by 0.9 mm in men and 0.7 mm in women for each decade of life, assuming a normal BMI and adjusting for blood pressure. In modeled growth curves, the presence of hypertension or obesity was associated with greater mean aortic root size over time, with the greatest effect predicted when both risk factors were present. These results are consistent with previous cross-sectional studies in which age, sex, body size and blood pressure were identified as key factors influencing aortic root size in adulthood.2–5 The current longitudinal data extend previous studies by characterizing the contributions of these key factors to aortic dilatation over time and provides insight into interactions between various clinical factors that affect aortic root size over the life course, thus defining the natural history of aortic remodeling in adulthood.
Blood pressure can be viewed as separate components of steady flow (mean arterial pressure) and pulsatile (pulse pressure) hemodynamic load. This separation is clinically meaningful since each component relates physiologically to different regions of the arterial tree (mean arterial pressure relates predominantly to small artery function and pulse pressure to large artery stiffness), and has differential effects on other physiological variables such as left ventricular mass.12, 22 Considerable debate surrounds the relation between blood pressure components and aortic root size.18, 23–26 Cross-sectional studies have shown both direct2, 7, 8 and indirect3, 4 associations but in general suggest that aortic root diameter increases with increasing diastolic blood pressure but decreases with increasing pulse pressure. This is counterintuitive to the classic notion that age-related elastic fragmentation, passive aortic dilatation, wall stiffening and premature wave reflection lead directly to increasing pulse pressure with age. On the contrary, these observations have led to the hypothesis that a smaller aortic root may play a key role in the pathogenesis of systolic hypertension, by introducing a mismatch between aortic root diameter and blood flow, such that forward wave amplitude is increased.23 Indeed, direct measurements of pulsatile hemodynamics in patients with systolic hypertension showed that while aortic root dilatation and stiffening occurred with increasing age, higher pulse pressure was associated with increased characteristic impedance and reduced rather than increased aortic root diameter.23 However, in the only prospective study testing this hypothesis,26 a smaller aortic root was not found to be associated with the incidence of hypertension in middle-aged adults from the community.
Thus, instead of being an antecedent cause of hypertension, it is conceivable that dynamic aortic remodeling occurs as an active, compensatory response to changing hemodynamic load. Outward remodeling of the aortic root may serve to limit the increase in pulse pressure as the aortic wall stiffens with age. “Blunted remodeling” may therefore explain the association between smaller aortic root size and increasing pulse pressure, as observed in this study and others.3–5, 18 Our results further suggest that sex is an important correlate and effect modifier of the extent of aortic remodeling in adulthood, with men displaying a greater propensity to outward remodeling of the aortic root compared to women. This is consistent with the detailed impedance analyses performed in the large Asklepios study,27 where cross-sectional hemodynamic study of adults 35 to 55 years of age showed that total arterial compliance decreased with age in women but not in men, leading to age-associated increases in arterial input impedance in women but not in men. Further, characteristic impedance even decreased in men in this age range, while it was unchanged in women. While authors did not specifically relate these findings to measured sex-related differences in aortic root size, they derived a theoretical “effective cross sectional aortic area” and suggested that the increase in effective cross sectional area in men outweighed the increase in aortic wall stiffness and may therefore explain the decrease in characteristic impedance with age in men. While our study cannot conclusively prove that blunted aortic remodeling causes increased pulse pressure, we provide convincing longitudinal evidence of sex-associated differences in aortic remodeling over time, whether with aging alone or with superimposed risk factors of obesity or hypertension. Further research is warranted to elucidate the underlying mechanisms for such differences. An understanding of the consequences of these differences on central pulse pressure, cardiac afterload and ventricular remodeling may also provide insight into the predisposition of elderly hypertensive women to heart failure with preserved ejection fraction.
Limitations
We recognize that there is heterogeneity in remodeling characteristics across the arterial tree and our observations are limited to aortic root diameter measured at the level of the sinuses of Valsalva. While geometric complexities at this level may limit the precision of measurements, our measurements were highly reproducible.11 Invasive hemodynamic measurements were not possible in this large community-based sample, and brachial blood pressure may be a suboptimal surrogate for central pulse pressure. Nonetheless, these longitudinal data add to our understanding of aortic remodeling over the adult life course, by harnessing the unique availability of systematic routine measurements in the large community-based cohort of the Framingham Heart Study.
Conclusions
Aortic root remodeling occurs over mid-to-late adulthood and is principally related to age, sex, body size and blood pressure. These factors interact in a complex fashion in their associations with aortic root remodeling over the life course. In particular, obese, hypertensive individuals show the greatest dilatation, while women display less aortic root dilatation than men. The underlying basis for these differences and implications for the development of hypertensive heart disease and its sequelae, such as heart failure with preserved ejection fraction, deserve further study.
CLINICAL SUMMARY.
Our study provides longitudinal community-based data regarding tracking of aortic root size over 16 years in mid-to-late adulthood. The aortic root gradually enlarges over the life course and is principally related to age, sex, body size and blood pressure. These factors interact in a complex fashion in their associations with aortic root remodeling. In particular, obese individuals with hypertension show the greatest dilatation, while women display less aortic root dilatation than men. Further, separate components of hemodynamic load differed in their relation with aortic root size: steady flow load (mean arterial pressure) was associated positively with aortic root diameter whereas pulsatile load (pulse pressure) was associated inversely with aortic root diameter. The underlying basis for these differences and implications for the development of cardiovascular events deserve further study
Supplementary Material
Acknowledgments
Funding Sources
This work was supported by the National Heart, Lung and Blood Institute’s Framingham Heart Study (Contract No. NO1-HC-25195) and the following grants: 6RO1-NS 17950, RO1HL080124 (RSV).
Footnotes
Conflict of Interest Disclosures
None
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