Glycaemia (haemoglobin A1c) and incident ischaemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study

BACKGROUND: Individuals with diabetes have a raised risk of stroke, but it is unclear whether sustained hyperglycaemia contributes to the development of cerebrovascular disease. Haemoglobin A1c (HbA(1c)), a measure of long-term glycaemia, is strongly related to retinopathy, nephropathy, and neuropathy in diabetes. We sought to assess the association between HbA(1c) and stroke in people with and without diabetes. METHODS: 10,886 participants without diabetes and 1635 participants with diabetes in the ARIC study, who did not have cardiovascular disease, were followed up for incident ischaemic stroke over 8-10 years. We assayed HbA(1c) for all 167 stroke cases and a sample of 680 non-cases in the adults without diabetes and for the full cohort of 1635 adults with diabetes (including 89 stroke cases). We assessed the relation between HbA(1c) concentrations (in tertiles specific for individuals with and without diabetes) and incident ischaemic stroke during follow-up using Cox proportional hazards models, controlling for risk factors for stroke. FINDINGS: The adjusted relative risks of stroke increased with increasing tertile of HbA1c in both adults without diabetes (p=0.02) and with diabetes (p<0.0001). Compared with adults without diabetes in the lowest tertile of HbA1c, the adjusted relative risks of stroke by HbA(1c) tertile were 1.18 (0.70-2.00) and 1.58 (0.94-2.66) in adults without diabetes and 1.75 (0.90-3.42), 2.29 (1.24-4.21), and 4.71 (2.69-8.25) in adults with diabetes. INTERPRETATION: Raised HbA(1c) could be an independent risk factor for stroke in people with and without diabetes, with relative risks similar to those previously reported for coronary heart disease.     

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.     

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.     

Association of lung function with cognitive decline and dementia: the Atherosclerosis Risk in Communities (ARIC) Study

Background: Previous studies reported a higher risk of cognitive decline and dementia amongst individuals with impaired lung function. However, many did not adjust for important confounders or did not include women and non‐whites. Methods: We studied 10 975 men and women aged 47–70 years (23% African‐Americans) enrolled in the Atherosclerosis Risk in Communities Study. Pulmonary function tests and a cognitive assessment, including the Delayed Word Recall, the Digit Symbol Substitution, and the World Fluency Tests, were carried out in 1990–1992. Repeated cognitive assessments were performed in 1996–1998 for the entire cohort, and in 1993–1995, and 2004–2006 in 904 eligible individuals. Dementia hospitalization was ascertained through 2005. Results: In analysis adjusted for lifestyles, APOE genotype, and cardiovascular risk factors, impaired lung function was associated with worse cognitive function at baseline. No association was found between lung function and cognitive decline over time. Impaired lung function at baseline was associated with higher risk of dementia hospitalization during follow‐up, particularly amongst younger individuals. The hazard ratios (95% confidence intervals) of dementia hospitalization were 1.6 (0.9, 2.8) and 2.1 (1.2, 3.7) comparing the lowest with the highest quartile of forced expiratory volume in 1 s and forced vital capacity, respectively. Presence of a restrictive ventilatory pattern, but not of an obstructive pattern, was associated with reduced cognitive scores and higher dementia risk. Conclusion: Reduced lung function was associated with worse performance in cognitive assessments and with an increased risk of dementia hospitalization. Future research should determine whether maintaining optimal pulmonary health might prevent cognitive impairment and dementia.     

Stroke incidence and survival among middle-aged adults: 9-year follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort

BACKGROUND AND PURPOSE: Although stroke mortality rates in the United States are well documented, assessment of incidence rates and case fatality are less well studied. METHODS: A cohort of 15 792 men and women aged 45 to 64 years from a population sample of households in 4 US communities was followed from 1987 to 1995, an average of 7. 2 years. Incident strokes were identified through annual phone contacts and hospital record searching and were then validated. RESULTS: Of the 267 incident definite or probable strokes, 83% (n=221) were categorized as ischemic strokes, 10% (n=27) were intracerebral hemorrhages, and 7% (n=19) were subarachnoid hemorrhages. The age-adjusted incidence rate (per 1000 person-years) of total strokes was highest among black men (4.44), followed by black women (3.10), white men (1.78), and white women (1.24). The black versus white age-adjusted rate ratio (RR) for ischemic stroke was 2.41 (95% CI, 1.85 to 3.15), which was attenuated to 1.38 (95% CI, 1.01 to 1.89) after adjustment for baseline hypertension, diabetes, education level, smoking status, and prevalent coronary heart disease. There was a tendency for the adjusted case fatality rates to be higher among blacks and men, although none of the case fatality comparisons across sex or race was statistically significant. CONCLUSIONS: After accounting for established baseline risk factors, blacks still had a 38% greater risk of incident ischemic stroke compared with whites. Identification of new individual and community-level risk factors accounting for the elevated incidence of stroke requires further investigation and incorporation into intervention planning.     

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 Young's 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) x (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 greater than female, p = 0.0006) only in the 45-49-year-old age group. Significant (p less than 0.0001) sex differences were found, with men having a greater lumen diameter calculated as 2 x (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.