Comparison of Intima-Media Thickness of the Carotid Artery and Cardiovascular Disease Risk Factors in Adults With Versus Without the Down Syndrome




Adults with Down syndrome (DS) residing in large institutional settings possess low levels of atherosclerosis. The purpose of this study was to determine whether community-residing adults with DS possess less atherosclerosis than adults without DS. The second purpose was to examine the relation between cardiovascular disease risk factors and intima-media thickness (IMT), a measure of atherosclerosis, in patients with DS. B-mode images of the left common carotid artery were collected to assess IMT in 52 adults with DS and age-, gender-, and race-matched adults without DS (27 women, 25 men; mean age 42 ± 5 years). Total body fat, blood pressure, fasting lipid profiles, insulin, glucose, C-reactive protein, homocysteine, physical activity, and dietary intake were also assessed. Adults with DS possessed lower IMT (0.43 ± 0.07 vs 0.48 ± 0.09 mm, p <0.001), systolic blood pressure (116 ± 15 vs 125 ± 17 mm Hg, p <0.011), and diastolic blood pressure (59 ± 10 vs 73 ± 9 mm Hg, p <0.001) and higher C-reactive protein (0.58 ± 0.55 vs 0.30 ± 0.42 mg/dl, p <0.003), triglycerides (126.5 ± 55.2 vs 103.8 ± 53.2 mg/dl, p <0.048), and total body fat (37.8 ± 10.2% vs 32.4 ± 11.2%, p <0.002) than controls. Male gender (p <0.001) and physical activity (p = 0.020) were identified as predictors of IMT for adults with DS and fasting insulin (p <0.001), age (p <0.001), gender (p <0.001), fruit and vegetable intake (p = 0.001), low-density lipoprotein cholesterol (p = 0.004), and smoking (p = 0.023) for controls. In conclusion, community residing adults with DS may be protected against atherosclerosis despite elevated total body fat and elevated cardiovascular disease risk factors. Predictors of IMT differed for patients with DS compared to controls, which indicates that patients with DS possess a unique model of atherogenesis.


Patients with Down syndrome (DS) residing in large institutional settings (long-term care facilities) have previously been reported to have less atherosclerotic plague formation (atherosclerotic burden) than other age-matched subjects with and without mental retardation (MR). All these previous studies, however, were performed on cadavers of subjects who previously had resided in large congregate institutional settings, where the behavioral risk factors for cardiovascular disease (CVD), such as dietary intake and physical activity levels, were under the direct supervision of health care professionals, and the subjects’ CVD risk profiles were not elevated. In addition, to date, research on the atherosclerotic burden of adults with DS has been limited by small sample sizes, the inability to include appropriate controls, and the inability to identify potential factors responsible for the reduced atherosclerotic burden. Presently, adults with DS are living longer than in the past and have a more elevated CVD risk profile than in the past, which supports the possibility that adults with DS may no longer be protected against atherosclerosis. Therefore, the purpose of this research was to determine whether community-residing adults with DS possess reduced atherosclerotic burden (estimated by a noninvasive intima-media thickness [IMT] assessment of the carotid artery) compared with an appropriate control group of age-, gender-, and race-matched adults without DS. The second purpose was to examine the relation between IMT and known CVD risk factors, including cholesterol profiles, fasting plasma insulin and glucose, C-reactive protein (CRP), homocysteine, blood pressure, body composition, and health behaviors, in community-residing adults with DS.


Methods


We used a cross-sectional, descriptive, comparative study design to determine whether the IMT of adults with DS differed from that of adults without DS and to determine the relation between IMT and known CVD risk factors in adults with DS. Fifty-two adults with DS with mild to moderate MR aged 35 to 60 years participated in the study. Participants were recruited through each county’s office of developmental disabilities services and area Arc offices of 1 midwestern state. Because of the confidentiality policies of the service agencies, the researchers were not allowed to recruit participants directly until the service agencies had performed an initial screening of interested participants. Care providers were asked to use participants’ medical records to identify those previously diagnosed with DS and to identify eligible participants on the basis of each of the following inclusion criteria: (1) diagnosis of DS and MR ; (2) the need for intermittent to limited support for independence or interdependence, productivity, community integration, and satisfaction ; (3) residence in a community setting; (4) interest in volunteering for study participation; and (5) independent ambulation. Unfortunately, because of the confidentiality policies of the service agencies, specific screening information about the subjects who did not meet the screening criteria was not available. Fifty-two age-, gender-, and race-matched subject without DS or MR were recruited from similar geographic areas. All participants were Caucasian. Descriptive characteristics of participants with and without DS are listed in Table 1 . The university’s institutional review board approved all procedures and consent forms for the protection of human subjects. All participants (and parents or guardians when needed) signed informed consent forms. Participants and direct care staff members were compensated for their time, effort, and contributions to the study with $20.00 gift cards.



Table 1

Comparison of mean ± SE carotid artery intima-media thickness and cardiovascular disease risk factors



























































































































































Variable Adults With DS Adults Without DS p Value
Descriptive variables
Age (years) 42.0 ± 5 42.0 ± 5 0.727
Height (cm) 152.0 ± 8 172.0 ± 8 <0.0001
Weight (kg) 73.0 ± 17 84.0 ± 20 0.005
Body mass index (kg/m 2 ) 31.0 ± 6 28.0 ± 7 0.015
Men/women 25/27 25/27 1.000
Carotid artery measures
Intima-media thickness (mm) 0.43 ± 0.07 0.48 ± 0.09 0.000
Luminal diameter (mm) 5.38 ± 0.78 5.63 ± 0.61 0.137
Wall cross-sectional area (mm 2 ) 23.80 ± 6.30 26.40 ± 5.60 0.069
Fasting plasma levels
Total cholesterol (mg/dl) 185.40 ± 34.20 185.60 ± 31.00 0.974
High-density lipoprotein cholesterol (mg/dl) 45.00 ± 10.20 49.00 ± 13.10 0.072
Low-density lipoprotein cholesterol (mg/dl) 115.00 ± 29.60 115.80 ± 29.10 0.895
Triglycerides (mg/dl) 126.50 ± 55.20 103.80 ± 53.20 0.021
Insulin (μU/ml) 10.90 ± 9.60 9.90 ± 7.30 0.531
Glucose (mg/dl) 88.00 ± 15.10 88.80 ± 10.10 0.738
C-reactive protein (mg/dl) 0.58 ± 0.55 0.30 ± 0.42 0.003
Homocysteine (μmol/L) 8.80 ± 1.80 9.00 ± 2.00 0.629
Systolic blood pressure (mm Hg) 115.90 ± 14.60 124.70 ± 16.80 0.011
Diastolic blood pressure (mm Hg) 59.40 ± 10.20 72.80 ± 8.90 0.000
Body composition
Total body fat (%) 37.80 ± 10.20 32.40 ± 11.40 0.002
Waist circumference (cm) 94.60 ± 14.00 90.30 ± 14.30 0.081
Questionnaires
Dietary fat score 25.00 ± 6.50 20.80 ± 8.00 0.004
Dietary fruit and vegetable score § 21.50 ± 4.60 19.60 ± 5.80 0.045
Moderate to vigorous physical activity (minutes/week) 188.20 ± 326.50 317.90 ± 349.70 0.019
Smoking status 1 (1.9%) 5 (9.6%) 0.060

Data are expressed as mean ± SE or as number (percentage).

Significant at p <0.05.


Variables were logarithmically transformed before analysis; nontransformed values are presented.


Score from the Block Screening Questionnaire for Fat Intake.


§ Score from the Behavioral Risk Factor Surveillance System, Fruit and Vegetable Module.


Chi-square = 3.54 (1 degree of freedom).



A standard ultrasound machine (Image Point Hx; Philips Medical Systems, Bothell, Washington) with a 7.5-MHz linear-array transducer was used to collect B-mode images of the left common carotid artery to assess IMT. Participants were measured in the supine position with the head positioned at 45°. End-diastolic images (gated off the R wave on electrocardiography) were collected and transmitted to a personal computer for off-line analysis. Electronic wall-tracking software (CVI; Information Integrity, Boston, Massachusetts) was used to measure IMT on the far wall. Measurements were taken from the leading edge of the intima to the beginning of the adventitial layer. Luminal diameter was measured, and wall cross-sectional area was calculated. The same technician analyzed all data in a blinded fashion.


All blood draws were made in the morning after an overnight fast (12 hours). Participants and care providers were phoned the night before testing and again in the morning before the testing session to remind them of the 12 hour fast. Assays were conducted at Fairview Diagnostic Laboratories, Fairview University Medical Center (Minneapolis, Minnesota). Cholesterol profiles, triglycerides, and glucose levels were determined by colorimetric reflectance spectrophotometry. CRP was analyzed with an ultrasensitive assay using rate nephelometry. Insulin was determined by chemiluminescent immunoassay. Homocysteine was determined through a fluorescence polarization immunoassay. Seated auscultatory blood pressure was measured with a mercury sphygmomanometer according to the guidelines established by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.


With participants dressed in lightweight clothing, weight was measured to the nearest 0.5 kg. Height was measured to the nearest 0.5 cm. Body mass index was calculated by dividing the weight in kilograms by the height in meters squared. Total body fat was assessed by dual-energy x-ray absorptiometry (Prodigy, software version 6.7; GE Medical Systems, Madison, Wisconsin). Waist circumference was measured to the nearest 0.1 cm with a cloth measuring tape, as previously described. The mean of 2 measurements was used for anthropometric measurements.


Because of reduced comprehension and shortened attention spans of subjects with MR, the questionnaires were chosen for use because of their brevity and their short directions. The questionnaires have previously been shown to be reliable and associated with CVD risk factors in subjects with MR. The Physical Activity Questionnaire section of the National Health and Nutrition Examination Survey (NHANES) III was used to assess the participants’ regular physical activity habits. The duration of reported activities was also determined. The physical activity questionnaire was administered by research staff members through interviews with the participants and the participants’ direct care providers (who assisted with the questions as needed). The intensity of each specific activity was estimated using the Ainsworth Compendium for Physical Activities. Moderate to vigorous physical activity (MVPA) was defined as any physical activity ≥3.5 METs.


The Block Screening Questionnaire for Fat Intake was used to calculate a dietary fat score and to estimate the percentage of dietary fat intake of the total dietary intake. The Behavioral Risk Factor Surveillance System, Fruit and Vegetable Module, was used to calculate the fruit and vegetable score and estimate the mean number of fruits and vegetables eaten per day. Questionnaire scoring procedures used were those recommended in the “Dietary Assessment Resource Manual.” The food frequency questionnaires were administered as an interview with the participant and the participant’s direct care provider present to assist with the questions as needed. Participants’ current smoking status was recorded.


Each variable was screened for missing data, outliers, and normal distribution. The distributions of fasting triglycerides, insulin, CRP, and weekly MVPA were each positively skewed. The values of triglycerides, insulin, CRP, and weekly MVPA were logarithmically transformed. The transformed values were used in the statistical analysis. For simplicity in presenting the findings, the original means and SDs of the transformed variables are presented throughout this report. Means and SDs of all variables were calculated for each group. Separate dependent Student’s t tests were used to determine mean differences in carotid artery measures, plasma CVD risk factors, blood pressure, body composition measures, and health behaviors between the age-, gender-, and race-matched groups with and without DS. Separate analyses of covariance were used to determine mean differences in carotid artery measures between the groups with and without DS with adjustment for smoking status. Because similar differences in the carotid artery measures were identified within the t tests and after adjusting for smoking status in the analysis of covariance, only the results of the t tests are included. A separate chi-square test was used to determine whether the prevalence of participants who smoked differed between the 2 groups. Separate stepwise linear regression analyses were used to determine significant predictors of IMT for participants with and without DS. Variables included in the regression analyses were cholesterol profiles, fasting plasma insulin and glucose, CRP, homocysteine, blood pressure, body composition, and health behaviors.

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Dec 22, 2016 | Posted by in CARDIOLOGY | Comments Off on Comparison of Intima-Media Thickness of the Carotid Artery and Cardiovascular Disease Risk Factors in Adults With Versus Without the Down Syndrome

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