Modification of the Effect of Glycemic Status on Aortic Distensibility by Age in the Multi-Ethnic Study of Atherosclerosis

Abstract

Elevated serum glucose from diabetes mellitus (DM) or impaired fasting glucose (IFG) shares many mechanisms with aging that decrease aortic distensibility (AD), such as glycation of the extra-cellular matrix. However, little data compares the simultaneous effects of elevated serum glucose and aging on AD. To study this, we examined the relationship between fasting glucose status, age, and AD in the Multi-Ethnic Study of Atherosclerosis (MESA): a multi-ethnic cohort of individuals aged 45-84 years without clinical cardiovascular disease. In MESA, participants with normal fasting glucose (NFG; n = 2270), IFG (n = 870), and DM (n = 412) underwent MRI assessment of proximal thoracic aortic distensibility. This sample was 46% male, 42% white, 30% AA, 11% Asian, and 17% Hispanic. The relationship between glucose status, age, and AD was analyzed with general linear models by adjusting for factors influential on AD. An interaction term was used to determine if age modified the effect of glucose status on AD. AD was lowest among those with DM. The interaction term was significant (p = 0.024). Comparing participants less than 65 years of age, AD was different between NFG and DM (p < 0.01), and between NFG and IFG (p = 0.02). In those older than 65, fasting glucose group was no longer a significant predictor of AD. Our data indicate that there are overall differences in AD between DM, IFG, and NFG. However, age modified the effect of glucose status such that differences between the groups diminished with advancing age.

Introduction

The aging population will present difficult challenges for health care providers in the coming decades. By 2040 in the United States, individuals who are 65 years old or over will double from 40 million to over 80 million people.¹ This age group accounts for over 80% of deaths related to coronary artery disease in the United States, as well as 75% of the total population diagnosed with heart failure.²

One well-described change that occurs with aging is aortic stiffness. Aortic stiffness is a strong, independent predictor of cardiovascular mortality in elderly patients.³ Aging and diabetes mellitus affect the vasculature through glycation of the vascular wall.^4,5,6,7 Prior researchers have described an interaction between age and diabetes in which increasing age decreased the difference in pulse wave velocity between diabetics and non-diabetics.⁸ However, this has not been replicated. In addition, no major studies have addressed whether impaired fasting glucose also modifies this relationship.

With almost 3,500 MRI scans measuring aortic distensibility, the Multi-Ethnic Study of Atherosclerosis (MESA) provides an opportunity to revisit these relationships with more precise imaging techniques and a larger study population. The purpose of this study is to determine if age modifies the effect of diabetes mellitus on aortic distensibility. In addition, we also seek to determine if age modifies the effect of impaired fasting glucose on aortic distensibility.

Methods

Study Participants

The recruitment criteria of participants in MESA has been previously published.⁹ The MESA study is a population-based cohort of 6,814 men and women aged 45-84 from four ethnic groups (Caucasian, African-American, Hispanic, and Chinese) who were free of clinical cardiovascular disease when recruited from 2000-2002. Of these, we excluded 1,810 who did not have cardiac MRI. We further excluded 1,443 participants without aortic distensibility measures, and 9 participants with missing diabetes status.

As part of the baseline exam, participants submitted fasting blood samples. Samples were collected at each clinical site and sent to the central laboratory for analysis. Glucose was measured in serum at the University of Minnesota Central Laboratory using thin film adaptation of the glucose oxidase method on the Vitros analyzer (Johnson & Johnson Clinical Diagnostics, Inc., Rochester, NY 14650). Total cholesterol and HDL-C were measured in EDTA plasma on the Roche/Hitachi 911 Automatic Analyzer (Roche Diagnostics Corporation, Indianapolis, IN) using a cholesterol esterase, cholesterol oxidase reaction (Chol R1, Roche Diagnostics Corporation). Before measurement of HDL-C, the non-HDL-C fractions were precipitated with magnetic 50,000 MW dextran sulfate and magnesium chloride. Triglycerides were measured using a glycerol blanked enzymatic method (Trig/GB, Roche Diagnostics Corporation). LDL-C was calculated in specimens having a triglyceride value <400 mg/dL using the Friedewald equation.

Individuals in this study were classified into 1 of 3 groups using criteria based on fasting glucose level established by the American Diabetes Association.¹⁰ These groups included normal fasting glucose (NFG: fasting glucose level < 100 mg/dl), impaired fasting glucose (IFG: fasting glucose level 100-125 mg/dl), and diabetes mellitus (DM: fasting glucose level >126 mg/dl). Individuals with a history of diabetes were classified into the DM group without regard to their fasting glucose level.

Resting, seated systolic and diastolic blood pressure was measured 3 times using a Dinamap automated oscillometric sphygmomanometer (Model pro100l Critkon, Tampa Fl); the last 2 measures were averaged for analyses. Hypertension was defined on the basis of use of an antihypertensive medications or BP>= 140/90. Use of lipid-lowering medication was used as an indicator of being diagnosed wtih high cholesterol. Cigarette use was divided into 3 groups: never, former, and current, which was defined as having smoked within the past 30 days.

Magnetic Resonance Imaging Technique

MRI studies were acquired at 6 participating sites using 1.5 Tesla magnets (3 were Siemens Medical Solutions [Erlangen, Germany] Symphony or Sonata platforms, and 3 were General Electric Medical Systems [Waukesha, WI] CV/I or LX platforms). Participants were scanned in a supine position using a torso phased array coil placed anteriorly and posteriorly.

Images of the proximal thoracic aorta were acquired axially at the level of the main pulmonary artery identified on a sagittal scout image. Imaging parameters included a phase-contrast gradient-echo sequence. Imaging parameters were as follows: repetition time = 10 msec; echo time = 1.9 msec; field of view = 34 cm; slice thickness = 8 mm; matrix size = 256 × 224; 2 signal averages; temporal resolution = 20 ms; velocity encoding gradient = 150 cm/s in the superior to inferior direction; and receiver bandwidth ± 32 kHz. Blood pressure was measured in the supine position at the beginning and end of the 45 minute MRI session; the two results were averaged for the final blood pressure measurement.

Ascending Aortic Stiffness

To determine ascending thoracic aortic stiffness, aortic distensibility was calculated by using the following validated formula:^11,12,13

$$\text{Aortic Distensibility}=\frac{\left[(\text{max}.\text{aortic area}-\text{min}.\text{aortic area})/\text{minimum aortic area}\right]}{\text{Pulse Pressure}}$$

Pulse pressure was calculated by the following formula:

$$\text{Pulse Pressure}=\text{Systolic Blood Pressure}-\text{Diastolic Blood Pressure}$$

Statistical Analyses

Baseline characteristics were described for each fasting glucose group (NFG, IFG, and DM). T-tests and chi-square tests were performed to identify statistical differences in baseline characteristics between the groups with normal fasting glucose serving as our reference. Next, we compared aortic distensibility between the fasting glucose groups through ANCOVA. From this point, multiple linear regression lines of aortic distensibility for each fasting glucose group on age were generated by PROC GLM in SAS Enterprise Guide 4.1 (Copyright by SAS Institute, Inc.). We first included fasting glucose group and age as well as an interaction term between the two in the model to predict aortic distensibility (Model 1--see below). Next, additional covariates were adjusted for their influence on the relationship between fasting glucose level and age (Model 2-- see below). Graphs depicting these relationships were generated with GraphPad Prism version 4.00 for Windows (GraphPad Software: San Diego California USA; www.graphpad.com).

There were 2 models fit to describe aortic distensibility. These models included:

Model 1:	age, fasting glucose group, age*fasitng glucose group (interaction term)
Model 2:	Model 1 + adjustment for gender, race, body mass index (BMI), mean arterial pressure, use of anti-hypertensive medication, LDL, HDL, Triglycerides, use of lipid-lowering medications, smoking history, pack years, creatinine and C-reactive protein levels (CRP).

For these models, the interaction term was examined. If significant at level of 0.05, specific pairwise comparisons of the slopes of the regression lines on age were performed.

From this point, age was divided into 2 groups (45-64 years vs. 65-84 years) as a categorical variable to use for both a main effect as well as a part of an interaction term with fasting glucose group to interpret the interaction. First, the adjusted means of aortic distensibility were compared using model 1. Next, ANCOVA analyses were performed using model 2.

Results

After exclusions, our study population consisted of 3,552 participants. Their characteristics by glycemic status are shown in Table 1. Both the IFG and DM groups had higher BMI, higher systolic blood pressure, and higher C-reactive protein than the NFG group. In addition, both IFG and DM groups had lower HDL cholesterol than the NFG group. In comparing demographic features, the NFG group was younger and composed of more women and white participants. A box plot of aortic distensibility by 5-year age groups is presented in Figure 1.

Tabel1. Baseline Characteristics of Participants.

Variable	Normal (n=2270) Mean ± Std. Dev.	IFG (n=870) Mean ± Std. Dev.		DM (n=412) Mean ± Std. Dev.
Age (yrs)	59.4 ± 10.0	62.2 ± 9.9	*	63.5 ± 9.4	*
BMI (kg/m2)	27.1 ± 4.7	28.8 ± 5.1	*	29.8 ± 5.3	*
LDL (mmol/L)	3.0 ± 0.8	3.1 ± 0.8		3.0 ± 0.9
HDL (mmol/L)	1.4 ± 0.4	1.3 ± 0.4	*	1.2 ± 0.4	*
Trig (mmol/Ll)	1.3 ± 0.9	1.5 ± 0.9	*	1.7 ± 1.4	*
Glucose (mmol/L)	5.0 ± 0.3	5.9 ± 0.3	*	8.4 ± 2.8	*
SBP (mmHg)	122.1 ± 20.3	128.2 ±21.1	*	132.7 ± 22	*
DBP (mmHg)	71.3 ± 10.2	73.4 ± 10.4	*	72.8 ± 10.4	*
MAP (mmHg)	88.2 ± 12.3	91.7 ± 12.6	*	92.8 ± 12.6	*
GFR (ml/min)	80.8 ± 15.6	81.4 ± 16.7		87.4 ± 23.7	*
Creatinine (μmol/L)	83.1 ± 17.7	85.7 ± 17.7	*	85.7 ± 51.3
Smoking pack years	10.3 ± 22.8	12.1 ± 22.4		12.1 ± 22.4
C-Reactive Protein (mg/L)	3.3 ± 5.4	4.0 ± 6.4	*	4.5 ± 6.6	*
Aortic Distensibility (103 * mmHg−1)	2.1 ± 1.5	1.9 ± 1.3	*	1.6 ± 1.0	*
	Number (%)	Number (%)		Number (%)
Lipid medication use	278 (12%)	155 (18%)	*	116 (28%)	*
HTN medication use	623 (27%)	377 (43%)	*	258 (63%)	*
Race			*		*
Caucasian Hispanic Afro-American Chinese	1061 (47%) 233 (10%) 605 (27%) 372 (16%)	337 (39%) 111 (13%) 267 (31%) 156 (18%)		98 (24%) 49 (12%) 189 (46%) 77 (19%)
Gender			*		*
Male Female	939 (41%) 1332 (59%)	475 (55%) 396 (45%)		209 (51%) 204 (49%)
Smoking					*
Never Former Current	1188 (52%) 767 (34%) 308 (14%)	429 (49%) 326 (37%) 111 (13%)		202 (49%) 167 (40%) 43 (10%)

Asterisk by either IFG or DM variable indicates difference with NFG with a p < 0.05.

Figure 1.

Mean values of aortic distensibility for each 5 years of age.

In analyzing Model 1, the interaction term was statistically significant (p=0.04). Individually assessing the glucose status comparisons, the slope of age was different between the DM group and the NFG group (p= 0.031), but there was no difference in the slopes of age between the DM group and the IFG group (p = 0.39). There was a trend towards a difference in the slope of age between the IFG group and the NFG group (p = 0.088). These comparisons are shown in Table 2, and are presented graphically in Figure 2.

Table 2. Comparison of Regression Coefficients.

Fasting glucose group	Model 1 Standardized Regression β Coefficient for Age	Model 2 Standardized Regression β Coefficient for Age	Aortic Distensibility Comparisons	Model 1 p-value	Model 2 p-value
NFG	−0.43	−0.38	Age	<0.001	<0.001
IFG	−0.36	−0.30	Overall interaction term	0.0412	0.024
DM	−0.32	−0.26	NFG Age β vs. IFG Age β	0.088	0.057
			IFG Age β vs. DM Age β	0.39	0.38
			NFG Age β vs. DM Age β	0.031	0.022

NFG is reference group, except for IFG vs. DM, in which IFG serves as the reference group.

Figure 2.

Model 1: Unadjusted linear regression lines of AD on age stratified by fasting glucose group.

Adjusting for additional covariates in model 2, the overall interaction term continued to be statistically significant (p = 0.024). There continued to be a difference in the slope of age between the NFG group and the DM group (p = 0.022). In addition, the trend towards a difference between slope of age in the IFG group and slope of age in the NFG group was strengthened (p = 0.057). There was no difference between slopes of age in the IFG group and the DM group (p = 0.38). These comparisons are shown in Table 2, and they are represented graphically in Figure 3.

Figure 3.

Model 2: Linear regression lines of AD on age stratified by fasting glucose group. Adjusted for gender, race, body mass index, mean arterial pressure, use of anti-hypertensive medication, LDL, HDL, Triglycerides, use of lipid-lowering medications, smoking history, pack years, creatinine, and C-reactive protein levels (CRP).

To further interpret this interaction, age was divided into 2 groups (45-64 years vs. 65-84 years) to use as a categorical variable in an interaction term with fasting glucose group through two-way ANCOVA. The overall interaction term was significant (p = 0.04). In comparing aortic distensibility between the fasting glucose groups for the 2 age groups, it reflects the results obtained from our overall regression models (see table 3). In the younger group, NFG is different from IFG (Model 2 p-value: 0.024) and DM (Model 2 p-value: <0.0001). Analyzing the older group through model 2, NFG was no longer statistically different from IFG (Model 2 p-value: 0.5), nor was it significantly different from DM (Model 2 p-value: 0.2). For stratified comparisons, please refer to Table 3 and Figure 4.

Table 3. Model 1 and Model 2 Means for Aortic Distensibility by Age.

Age Group And Model	NFG AD (103*mmHg−1)	IFG AD (103*mmHg−1)	DM AD (103*mmHg−1)
Age < 65 years
Model 1	2.42 (2.35, 2.48)	2.22 (2.1, 2.33) *	1.91 (1.74, 2.08)*
Model 2	2.31 (2.22, 2.39)	2.16 (2.03,2.28)*	1.88 (1.71, 2.07)*
Age ≥65 years
Model 1	1.47 (1.38, 1.57)	1.47 (1.35, 1.6)	1.24 (1.05, 1.41) *
Model 2	1.52 (1.41, 1.63)	1.57 (1.43, 1.7)	1.38 (1.03,1.40)

Means and 95% confidence intervals between fasting glucose group stratified by age 65. For comparisons, NFG serves as the reference g. An asterisk (*) means statistically different at p-value < 0.05.

Figure 4.

Model 2 stratified by age. Adjusted for race, gender, body mass index, mean arterial pressure, use of anti-hypertensive medication, LDL, HDL, Triglycerides, use of lipid-lowering medications, smoking history, pack years, creatinine, and C-reactive protein levels (CRP). Black bars represent age < 65; Grey bars represent age > 65. Error bars represent 95% Confidence Interval.

To determine if these results differed by race or gender, three-way interaction terms were used. Using model 2, age, fasting glucose group, and race were used as the interaction term, but failed to reach statistical significance (p-value: 0.15). In a separate analysis using model 2, age, fasting glucose group, and gender were used as the interaction term, but likewise, the term failed to reach statistical significance (p-value: 0.2). Next, we stratified the cohort according to race and gender, separately. The absolute values in the differences between the fasting glucose groups in the 2 age categories for each ethnic group and gender paralleled those of the entire cohort.

To determine if the variables in the numerator (percent change in aortic area for proximal thoracic aorta) or the denominator (pulse pressure) of aortic distensibility were more influential in accounting for the results, additional analyses using Model 2 were performed. Overall, the interaction term continued to be signficant (p = 0.002). After adjusting for the cardiac cycle dependent percent change in aortic area, aortic distensibility before age 65 was 2.18 10⁻³ mmHg⁻¹ for NFG, 2.11 10⁻³ mmHg⁻¹ for IFG (p=0.01 from NFG), and 2.00 10⁻³ mmHg⁻¹ for DM (p < 0.001 from NFG), and after age 65, aortic distensibility was 1.75 10⁻³ mmHg⁻¹ for NFG, 1.78 10⁻³ mmHg⁻¹ for IFG (p=0.32 from NFG), and 1.75 10⁻³ mmHg⁻¹ for DM (p > 0.4 from NFG). In separate analyses adjusting for pulse pressure, the interaction term was less significant (p = 0.054). After adjustment for pulse pressure, aortic distensibility before age 65 was 2.18 10⁻³ mmHg⁻¹ for NFG, 2.06 10⁻³ mmHg⁻¹ for IFG (p=0.06 from NFG), and 1.86 10⁻³ mHg⁻¹ for DM (p < 0.001 from NFG), and after age 65, aortic distensibility was 1.71 10⁻³ mmHg⁻¹ for NFG, 1.76 10⁻³ mmHg⁻¹ for IFG (p = 0.5 from NFG), and 1.67 10⁻³ mmHg⁻¹ for DM (p=0.6 from NFG). Since many of the patterns noted between the groups in Model 2 remain, the results of these adjustments suggest that both values in the numerators and denominators are important for influencing the differences or similarities in aortic distensibility noted between the groups assessed in this study.

Finally, to determine the influence of aortic size on aortic distensibility, additional analyses using Model 2 adjusted for minimum aortic area were performed. The interaction term was no longer significant (p = 0.18). After adjusting for the minimum aortic area, aortic distensibility before age 65 was 2.27 10⁻³ mmHg⁻¹ for NFG, 2.14 10⁻³ mmHg⁻¹ for IFG (p=0.039 from NFG), and 1.85 10⁻³ mmHg⁻¹ for DM (p < 0.001 from NFG), and after age 65, aortic distensibility was 1.67 10⁻³ mmHg⁻¹ for NFG, 1.68 10⁻³ mmHg⁻¹ for IFG (p=0.8 from NFG), and 1.44 10⁻³ mmHg⁻¹ for DM (p=0.02 from NFG). While the pattern persists, after age 65 NFG and DM become statistically different. This suggests that the lack of difference seen previously may be related to aortic size.

Discussion

The relationship between aging and aortic stiffness has been described for many years.^14,15 In this study, we sought to determine if increasing age modified the effect of DM on aortic distensibility, and to determine if the effect of IFG on aortic distensibility would also be modified by increasing age. From this study, several relationships can be described. First, increasing age decreases the differences in aortic distensibility between fasting glucose groups. Second, at younger ages, IFG decreased aortic distensibility when compared to NFG, and as expected, it behaves as an intermediate between DM and NFG.

Multiple mechanisms describe how aging affects aortic distensibility. Glycation of the extra-cellular matrix, including both elastin and collagen, occurs even at normal levels of glucose as a consequence of aging.^{16,17,18,19,20,21} Glycation of collagen results in less flexibility, greater strength²², and an increased resistance to proteolysis.²³ Though not as well studied as collagen, glycation of elastin results in fragmentation²⁴ and loss of elasticity.^25,26,27 These same non-enzymatic glycation processes occur with increased frequency to both collagen and elastin in hyperglycemic states.^28,29 In addition to glycation, age and diabetes also affect the vasculature through formation of atherosclerosis, inflammation,^30,31 and decreased endothelial function.^32,33

Increased ascending aortic distensibility greatly reduces the energy cost of cardiac work.³⁴ As such, therapeutic options to improve aortic distensibility may be an attractive option, particularly in heart failure. One such option, collagen cross-link breakers, failed to improve aortic distensibility.³⁵ In the ascending aorta, elastin is at its highest concentration and organization, whereas collagen is uniformly-distributed throughout the vascular tree.³⁶ Hence, in describing aortic distensibility from MRI measurements of the ascending aorta, the effects of age and diabetes on elastin may account for the behaviors seen in our study, and as such, may serve as a target of future therapy.

The interaction seen in this study is due to a greater association between fasting glucose group and aortic distensibility at younger ages than at older ages. Aortic distensibility started at a lower level in the DM and IFG groups than the normal group. As such, both DM and IFG had lower slopes than the normal group with the differences between the 3 groups decreasing with increasing age. If this study were performed prospectively, one would expect a steep decline in aortic distensibility during the time of impaired fasting glucose and early diabetes that would be followed by the lower slopes observed in our analysis. In addition, studies in younger populations are needed to further describe the relationship between different measures of vascular stiffness and fasting glucose level. One issue that may have influenced our analysis is that many of our participants already had stiff vessels as a result of aging alone.

The shared mechanisms of action between diabetes and aging enable us to consider a previously published concept.³⁷ Diabetes may act by increasing the physiologic age of the cardiovascular system. From our study, this influence can be described quantitatively from the regression models (see table 4). This provides us with an additional perspective to consider how diabetes mellitus often leads to conditions at younger ages, such as diastolic dysfunction, that otherwise are not encountered until later in life. In addition, it provides us with a vehicle to explain to patients how diabetes affects their vasculature.

Table 4. Equivalent Age for Same Level of Aortic Distensibility Between Fasting Glucose Groups.

DM age (yrs)	Equivalent IFG Age (yrs)	Equivalent NFG Age (yrs)
45	50.2	53.6
50	54.4	57.2
55	58.6	60.8
60	62.8	64.4
65	66.9	67.9
70	71.1	71.5
75	75.3	75.1

Based on the adjusted regression equations, for the predicted AD in a diabetic at a given age, the equivalent age for that predicted AD is given for the NFG and IFG groups.

The MESA study provided us with the unique opportunity to pursue these questions. Due to a balanced recruiting of individuals from major ethnic groups, our results are more generalizable to diverse populations. In addition, the MESA study afforded us the opportunity to investigate aortic stiffness using area measurements derived from MRI scans, a technique validated by prior research studies. Likewise, with 3,500 MRI scans describing aortic distensibility, the MESA study provided us with enough statistical power to develop and test more directed hypotheses.

There are several implications of our study. First, increasing age is a powerful and often under-appreciated risk factor in the development of cardiovascular disease. To demonstrate its significance, increasing age reduced the difference between normal fasting glucose and diabetes mellitus, a powerful risk factor for morbidity and mortality from cardiac pathology.

Second, a growing body of literature supports the place of aortic stiffness in the pathway between traditional cardiac risk factors and heart failure. A stiffened aorta is associated with diastolic dysfunction,³⁸ which is one of the main features of diabetic cardiomyopathy.³⁹ These changes in diastolic function start to occur in individuals with impaired fasting glucose.⁴⁰ As age increases, the incidence ratios of congestive heart failure between diabetics and non-diabetics decrease from 11 before age 45 to 1.2 in the ninth decade of life.⁴¹ This parallels the relationship between age and fasting glucose status on aortic distensibility seen in our study.

Third, with 25% of the adult U.S. population having impaired fasting glucose, even a minor increase in risk can translate into a significant public health problem.⁴² Hence, the decrease in aortic distensibility at younger ages by even mild hyperglycemia may represent a major health care risk. Further studies are needed to determine if more aggressive lifestyle and/or pharmacological intervention in younger patients with IFG or DM prevents the premature morbidity and mortality that may result from aortic stiffness.^{43, 44}

There are several limitations of this study. First, non-invasive blood pressure measurements were used to calculate aortic distensibility. While not ideal, previous studies have indicated that noninvasive measures are adequate approximations and that that they do predict cardiac mortality.⁴⁵ In addition, our results are consistent with prior invasive studies that demonstrated that central pulse pressure is different between those with normal fasting glucose and those with impaired fasting glucose.⁴⁶ Second, a selection bias may be present in our study. The MESA study specifically recruited individuals without cardiovascular disease, and as such, our participants may have more resistance or fewer risk factors than the general population to cardiovascular disease. Likewise, this limits the generalizability of this study to individuals without cardiac disease. Third, our analysis is limited by the cross-sectional nature of our data. As such, temporality cannot be assessed. Another weakness of cross-sectional data is trying to determine if covariates are confounders or mediators. Fourth, one measurement of fasting glucose was used to identify participants’ glycemic status, which may have resulted in misclassification.

Conclusion

There are differences in aortic distensibility between fasting glucose groups. However, increasing age decreases the differences in aortic distensibility between the fasting glucose groups.

Perspectives

In many societies, the proportion of elderly individuals in the population is increasing. Parallel to this trend, there is a rapid expansion of individuals with impaired fasting glucose and diabetes mellitus. To help assess the potential burden of these trends, this study described the interaction between age and fasting glucose status on aortic distensibility. A growing body of literature recognizes the significant role that aortic stiffness and its associated measures have on the development and progression of cardiovascular disease. This study demonstrated that at younger ages, those individuals with impaired fasting glucose had significant less aortic distensibility than those with normal fasting glucose. With 25% of the adult population having impaired fasting glucose, even a small increase in cardiovascular risk can have significant public health ramifications. As such, further studies are needed to see if correction of mild hyperglycemia at younger ages can prevent premature morbidity and mortality from aortic stiffness. Diabetes mellitus has long been recognized as a significant risk factor for cardiovascular disease, and as a result, guidelines have been developed to help clinicians to manage their patients’ risk. More data needs to be collected to develop guidelines that can assist clinicians in managing the cardiovascular risk in patients with impaired fasting glucose.