Ralph W. Barnes

Arterial Wall Thickness Is Associated With Prevalent Cardiovascular Disease in Middle-Aged Adults: The Atherosclerosis Risk in Communities (ARIC) Study

BACKGROUND AND PURPOSE This study was done to assess the relationship between prevalent cardiovascular disease and arterial wall thickness in middle-aged US adults. METHODS The association of preexisting coronary heart disease, cerebrovascular disease, and peripheral vascular disease with carotid and popliteal intimal-medial thickness (IMT) (measured by B-mode ultrasound) was assessed in 13,870 black and white men and women, aged 45 to 64, during the Atherosclerosis Risk in Communities (ARIC) Study baseline examination (1987 through 1989). Prevalent disease was determined according to both participant self-report and measurements at the baseline examination (including electrocardiogram, fasting blood glucose, and medication use). RESULTS Across four race and gender strata, mean carotid far wall IMT was consistently greater in participants with prevalent clinical cardiovascular disease than in disease-free subjects. Similarly, the prevalence of cardiovascular disease was consistently greater in participants with progressively thicker IMT. The greatest differences in carotid IMT associated with prevalent disease were observed for reported symptomatic peripheral vascular disease (0.09 to 0.22 mm greater IMT in the four race-gender groups). CONCLUSIONS These data document the substantially greater arterial wall thickness observed in middle-aged adults with prevalent cardiovascular disease. Both carotid and popliteal arterial IMT were related to clinically manifest cardiovascular disease affecting distant vascular beds, such as the cerebral, peripheral, and coronary artery vascular beds.

Relation of carotid artery wall thickness to diabetes mellitus, fasting glucose and insulin, body size, and physical activity. Atherosclerosis Risk in Communities (ARIC) Study Investigators.

Background and Purpose We tested the hypothesis that body mass, waist-to-hip circumference ratio, physical inactivity, diabetes, hyperglycemia, and fasting insulin are each positively associated with asymptomatic carotid artery wall thickness. Methods Average intimal-medial carotid wall thickness (an indicator of atherosclerosis) was measured noninvasively by B-mode ultrasonography in cross-sectional samples of 45- to 64-year-old adults, both blacks and whites, free of symptomatic cardiovascular disease, in four US communities. Results Sample mean carotid wall thickness was approximately 0.7 mm in women (n=7956) and 0.8 mm in men (n=6474). Body mass, waist-to-hip ratio, work physical activity, diabetes, and fasting insulin were associated (P < .05) with carotid wall thickness in the hypothesized direction. Adjusted for age, race, smoking, body mass index, artery depth, and Atherosclerosis Risk in Communities field center, mean wall thickness was greater by 0.02 mm in women and 0.03 mm in men for a 0.07-unit (one SD) larger waist-to-hip ratio. Adjusted mean wall thickness was about 0.07 mm thicker in participants with diabetes mellitus and 0.02 mm thicker in participants with hyperglycemia (fasting glucose 6.4 to 7.7 mmol/L) than in subjects with fasting glucose <6.4 mmol/L. Adjusted mean wall thickness increased by about 0.02 mm with an increase of 100 mmol/L in fasting serum insulin. Conclusions Abdominal adiposity, physical inactivity, and abnormal glucose metabolism are associated positively with carotid intimal-medial wall thickness, suggesting these factors contribute to atherogenesis.

Age, race, and sex differences in autonomic cardiac function measured by spectral analysis of heart rate variability—The ARIC study

To investigate the distribution of heart rate variability (HRV) spectral power in an unselected sample of the population, and to ascertain the population correlates of HRV, we examined 1,984 healthy persons, aged 45 to 64 years, randomly selected from the Atherosclerosis Risk in Communities (ARIC) study cohort. Resting, supine, 2-minute, beat-to-beat heart rate data were collected between 7 A.M. and 12 noon. The race- and sex-adjusted geometric means of low-frequency component (LF, 0.025 to 0.15 Hz) were 4.00 and 3.13 (beats/min)2; of high-frequency component (HF, 0.16 to 0.35 Hz), 1.65 and 1.21 (beats/min)2; and of the HF/LF ratio, 0.41 and 0.39, for 45-to-54 and 55-to-64 years age groups, respectively (test of mean difference by age, p < 0.01, p < 0.01, and p = 0.11 for LF, HF, and HF/LF ratio, respectively). Comparing black with white examinees, the age- and sex-adjusted geometric means of LF were 3.06 and 3.70 (beats/min)2; of HF, 1.66 and 1.36 (beats/min)2; of HF/LF, 0.54 and 0.37, respectively (test of mean difference by race, p < 0.01, p < 0.01, and p < 0.01). The age- and race-adjusted geometric means of LF for women and men were 3.12 and 4.10 (beats/min)2; of HF, 1.46 and 1.38 (beats/min)2; and of HF/LF, 0.47 and 0.34, respectively (test of mean difference, p < 0.01, p = 0.34, and p < 0.01). We conclude that HRV spectral indexes are associated with age, race, and sex. With increasing age, the parasympathetic and sympathetic spectral power components decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

High-resolution B-Mode Ultrasound Scanning Methods in the Atherosclerosis Risk in Communities Study (ARIC)

The Atherosclerosis Risk in Communities study examined popliteal and extracranial carotid arteries in approximately 16,000 randomly selected participants, aged 45 to 64 years. Vessels were studied noninvasively using high‐resolution B‐mode ultrasound imaging at baseline, to be repeated again after 3 years. The ultrasound examinations were performed according to a detailed standardized protocol by trained, certified sonographers subject to semiannual evaluation. Data on intrasonographer reliability from May 15, 1987, to June 30, 1989, showed that sonographers were able to visualize consistently a similar number of points along each of four arterial interfaces. Furthermore, the variability of measured combined intima‐medial thicknesses was low, with 80% or more of duplicate scans differing by less than 0.267 mm. The validity of B‐mode ultrasound imaging to detect asymptomatic carotid and popliteal artery atherosclerosis combined with high measurement reproducibility provides a powerful noninvasive scientific tool to test cross‐sectional and prospective hypotheses related to disease epidemiology.

Reproducibility of noninvasive ultrasonic measurement of carotid atherosclerosis. The Asymptomatic Carotid Artery Plaque Study.

Background and Purpose To determine the effect of a lipid-lowering agent and/or a low-dose antithrombotic agent on the progression of early-stage carotid atherosclerosis, noninvasive B-mode ultrasound was used to measure intimal-medial thickness in asymptomatic individuals with moderately elevated lipids as part of the ongoing multicenter Asymptomatic Carotid Artery Plaque Study. Methods Uniform ultrasonic scanning and reading protocols were implemented to obtain maximum intimal-medial thickness measurements in 12 standard segments in patients having a small to moderate wall thickness (1.5-3.5 mm) in at least one of the carotid arteries. Paired B-mode image recordings on 858 patients, performed 1 month apart and read at a core laboratory (each pair by the same reader), determined both within-sonographer (W, n=405) and between-sonographer (B, n=453) reproducibility. Results The primary end point (mean±SD), denned in each individual as the mean value of the 12 maximum intimal-medial thickness measurements, was 1.31±0.21 mm (W) and 1.32±0.22 (B) at the time of the second examination. The mean difference in the primary end point (exam 2-exam 1) was −0.01±0.13 mm (W) and 0.00±0.15 mm (B). The Pearson correlation coefficients were 0.79 (W) and 0.75 (B). In 90% of the patients, the absolute difference in the primary end point was <0.22 mm (W) and <0.24 mm (B). Variability of the secondary end point, denned as the single largest intimal-medial thickness measurement in a patient, was between three and four times larger than the variability for the primary end point. Differences in sonographer performance between clinical centers were very small. Conclusions The results demonstrate that standardized noninvasive ultrasonic techniques yield highly reproducible measures of carotid intimal-medial thickness, which can serve as a measure of carotid atherosclerosis in clinical trials that monitor small rates of lesion progression.

High-Resolution B-Mode Ultrasound Reading Methods in the Atherosclerosis Risk in Communities (ARIC) Cohort

To measure the association of cardiovascular disease risk factors with carotid artery diameter and thickness of the intima and media in the general population, standardized ultrasound scanning and reading protocols were performed on 15,800 individuals in the multicenter Atherosclerosis Risk in Communities (ARIC) Study. In a randomly selected subset of 855 participants, the mean artery diameter, minimum lumen diameter, and maximum near‐and far‐wall thicknesses were measured at a core laboratory from B‐mode image recordings of the common carotid, bifurcation, and internal carotid arteries to determine both within‐reader and between‐reader variability. Measurements associated with the wall thickness are sensitive indicators of reader reproducibility, with between‐reader reliability coefficients ranging from 0. 78 to 0.93 and coefficients of variation ranging from 13.1 to 18.3%. The percent of paired readings in the three carotid segments for which the absolute difference of the far‐wall thickness measured by different readers was no greater than one image pixel (0.067 mm) was 58% (common carotid), 53% (internal carotid), and 42% (bifurcation). Highly reproducible measurements of carotid artery dimensions can be achieved with standardized training and performance of ultrasound scanning and reading protocols.

B-mode-detected carotid artery plaque in a general population. Atherosclerosis Risk in Communities (ARIC) Study Investigators.

There is little information on the distribution of atherosclerotic lesions of the extracranial carotid artery wall in free-living populations. The purpose of the present study was to describe the prevalence from 1987 through 1989 of extracranial carotid artery plaque and plaque with acoustic attenuation (shadowing) lesions in a general population of white and black adults from four US communities. Methods B-mode ultrasound was used to characterize wall lesions in the common and internal carotid arteries and at the carotid artery bifurcation in 14 046 men and women 45 to 64 years old who participated in the Atherosclerosis Risk in Communities Study baseline survey. Results Thirty-four percent of participants had plaque and 6.4% had plaque with acoustic shadowing. The prevalence of plaque with acoustic shadowing increased steadily with age from 2.5% at ages 45 to 49 to 12.4% at ages 60 to 64. Overall, whites had more plaque with acoustic shadowing lesions than blacks (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.02 to 1.46), and men had more than women (OR, 1.42; 95% CI, 1.22 to 1.63). However, plaque lesions in the common carotid artery were less common among whites than among blacks, and no racial difference was observed in the prevalence of plaque with acoustic shadowing at this segment. Conclusions Although these prevalence rates are likely to be underestimated because of the emphasis on arterial boundary visualization of the scanning protocol, they show a large, mostly asymptomatic burden of atherosclerosis in these populations, especially among older individuals. Site-specific frequency rates of plaque varied between blacks and whites. Among those with plaque, however, whites had more lesions with acoustic shadowing attenuation.

Association of cardiac autonomic function and the development of hypertension : The ARIC study

To relate cardiac autonomic function measured by heart rate variability (HRV) with prevalent and incident hypertension at the population level, the authors examined a stratified random sample of 2,061 examinees from the biracial Atherosclerosis Risk in Communities (ARIC) cohort. Baseline, supine, resting beat-to-beat heart rate data were collected. High frequency (HF, 0.15 to 0.35 Hz), low frequency (LF, 0.025 to 0.15 Hz) spectral powers, and LF/HF ratio, estimated from spectral analysis, and standard deviation of all normal RR intervals (SDNN), calculated from time domain analysis, were used as the conventional indices of cardiac autonomic function. From this sample, 650 prevalent hypertensives were identified. Of those normotensive at baseline (n = 1,338), 64 participants developed hypertension during 3 years of follow-up. In the cross-sectional analysis, the adjusted geometric means of HF were 1.26, 1.20, and 1.00 (beat/min)2 for normotensives, untreated hypertensives, and treated hypertensives, respectively; means of LF were 3.24, 3.26, and 2.58; means of LF/HF ratio were 2.57, 2.70, and 2.56; and means of SDNN were 39, 34, and 35 (ms) respectively. In the prospective analysis, a statistically significant, graded inverse association between baseline HF and the risk of incident hypertension was observed: the adjusted incident odds ratios (95% CI) were 1.00, 1.46 (0.61, 3.46), 1.50 (0.65, 3.50) and 2.44 (1.15, 5.20) from the highest to the lowest quartile of HF. No clear pattern of association was observed for LF. Significant trends of association for LF/HF and SDNN and incident hypertension were also found. These results suggest that cardiac autonomic function is associated with prevalent hypertension, and that reduced vagal function and the imbalance of sympatho-vagal function are associated with the risk of developing hypertension.

Ultrasonic measurement of the elastic modulus of the common carotid artery. The Atherosclerosis Risk in Communities (ARIC) Study.

Background and Purpose The Atherosclerosis Risk in Communities Study is a prospective investigation of the etiology and natural history of atherosclerosis and the etiology of clinical disease in four US communities. Methods Noninvasive ultrasonic methods were used to determine mean wall thickness (WT), radius (R), and circumferential arterial strain (CAS) in the left common carotid artery of 3,321 white male and female study participants between the ages of 45 and 64 years. The mean and standard deviation of Youngs elastic modulus (Y) in 5-year age groups were determined for each sex by combining the ultrasonic data with concurrent noninvasive measurements of pulse pressure (PP) in the right brachial artery using the equation Y=(R/WT)×(PP/CAS). Results Significant (p=0.0001) age group differences in Y were observed in both sexes, with the mean value increasing from 701 kPa in women and 771 kPa in men in the 45–49-year-old age group to 965 and 983 kPa, respectively, in the 60–64-year-old age group. Significant (p=0.0001) age group differences were also observed for WT, the WT/R ratio, PP, CAS, and the PP/CAS ratio in both sexes. A sex difference in Y was detected (male > female, p=0.0006) only in the 45–49-year-old age group. Significant (p< 0.0001) sex differences were found, with men having a greater lumen diameter calculated as 2×(R−WT), a greater WT, and a greater 2R in all age groups. The WT/R ratio did not differ in both sexes in all age groups. Conclusions Knowledge of the arterial wall elastic modulus and the parameters required for its determination can provide important insight into structural changes occurring within the arterial wall with age and sex, and possibly with the onset of very early arterial disease.

Association of vagal tone with serum insulin, glucose, and diabetes mellitus — The ARIC Study

Reduced vagal activity assessed by heart rate variability (HRV) has been observed in studies of diabetics, but this association has not been reported at the population level. To investigate the association of HRV with diabetes mellitus, as well as fasting serum insulin, and glucose, we examined a stratified random sample of 1933 individuals (154 diabetics and 1779 non-diabetics), aged 45-65 years from the Atherosclerosis Risk in Communities (ARIC) study cohort. Two-minute, resting, supine beat-to-beat heart rate records were collected. Power spectral density estimation was used to derive HRV high frequency power (HF, 0.15-0.35 Hz) as the conventional marker of vagal function. Age, race, and gender-adjusted geometric means of HF were 0.78 and 1.27 (beat/min)(2) for diabetics and non-diabetics respectively (P for mean difference <0.01), reflecting a reduced vagal activity in diabetics. In individuals not diagnosed as diabetics, a graded, inverse association was observed between fasting serum insulin and HF (P for trend <0.01): the age, race, and gender-adjusted geometric mean values of HF in the lowest and highest quartiles of serum insulin were 1.34 and 1.14 (beat/minute)(2), respectively. A similar association was observed between glucose and HF in a univariate model, but not in the adjusted model. This first population-based study on this subject confirmed that diabetics have significantly lower vagal activity than non-diabetics. In individuals not diagnosed as diabetics, serum insulin, and, to a lesser degree, serum glucose were inversely associated with vagal function, suggesting a role in the pathogenesis of diabetic neuropathy.