Bilateral common carotid artery ultrasound for prediction of incident strokes using intima-media thickness and external diameter: an observational study.

BACKGROUND: External common carotid artery (CCA) diameter and intima-media thickness (IMT) are independently associated with incident stroke and other cardiovascular events. Arterial geometry such as large IMT and large diameter may reflect vulnerable plaques and so impact stroke risk. Finally, arterial changes that exist bilaterally may increase stroke risk. METHOD: We studied middle-aged men and women (n=7276) from a prospective observational study who had right (R) and left (L) CCA IMT and external diameters measured via B-mode ultrasound (1987-89) in order to categorize CCA geometry. Using side- and gender-specific IMT and diameter medians, we categorized each measurement as large (≥ median) vs. not large (< median) and defined four geometries: both IMT and diameter were large, only one parameter was large, or neither was large (reference group). Participants were followed for first time stroke through December 31, 1999. We used proportional hazards models to assess associations between right and left CCA geometries with new stroke. We also calculated positive and negative likelihood ratios (+LR and -LR) for CCA bilateral phenotypes as a measure of diagnostic accuracy. RESULTS: Presence of both large CCA IMT and large diameter on one side was associated with strong stroke risk even after risk factor adjustment (men: RCCA hazard ratio [HR]=3.7 95% confidence interval [CI]=1.9-7.4; LCCA HR=2.4 95% CI=1.4-4.4; women: RCCA HR=4.0 95% CI=1.5-10.5; LCCA HR=5.7 95% CI=1.7-19.0). Presence of both large IMT and large diameter bilaterally was the strongest predictor of stroke identifying 64% of women and 44% of men who developed strokes. This phenotype showed potential for predicting stroke among individuals (women: +LR=3.1, 95% CI=2.6-3.8; men: +LR=2.3, 95% CI=1.8-2.8). CONCLUSION: Bilateral carotid artery geometries may be useful for stroke risk prediction.

Association of catalytic iron with cardiovascular disease.

The ability of iron to cycle reversibly between its ferrous and ferric oxidation states is essential for the biological functions of iron but may contribute to vascular injury through the generation of powerful oxidant species. We examined the association between chemical forms of iron that can participate in redox cycling, often referred to as "catalytic" or "labile" iron, and cardiovascular disease (CVD). In our cross-sectional study of 496 participants, 85 had CVD. Serum catalytic iron was measured using the bleomycin-detectable iron assay that detects biologically active iron. The odds of existing CVD for subjects in the upper third of catalytic iron were 10 times that of subjects with lower catalytic iron in unadjusted analyses. The association was decreased by 1/2 by age adjustment, but little additional attenuation occurred after adjusting for age, Framingham Risk Score, estimated glomerular filtration rate, hypertension status, high-density lipoprotein cholesterol, and systolic blood pressure, with the association remaining strong and significant (odds ratio 3.8, 95% confidence interval 1.4 to 10.1). In conclusion, we provide preliminary evidence for a strong detrimental association between high serum catalytic iron and CVD even after adjusting for several co-morbid conditions; however, broader prospective studies are needed to confirm these findings, which would support therapeutic trials to assess the beneficial effects of iron chelators on CVD.

Orthostatic hypotension and cognitive function: the Atherosclerosis Risk in Communities Study.

BACKGROUND: To examine the association between orthostatic hypotension (OH) and cognitive function in middle-aged adults. METHODS: Participants were 12,702 men and women from the Atherosclerosis Risk in Communities Study. OH was defined as decrease in systolic blood pressure (BP) by > or =20 mm Hg or diastolic BP by > or =10 mm Hg upon standing. At the 2nd and the 4th follow-up examinations, cognitive function was assessed using the Delayed Word Recall Test, Digit Symbol Substitution Test (DSST) and Word Fluency Test (WFT). RESULTS: After age adjustment, those with OH were more likely to be in the lowest quintile of the DSST (OR = 1.34, 95% CI = 1.12-1.62) and WFT (OR = 1.25, 95% CI = 1.03-1.51) than were those without OH. After adjustment for sociodemographic and cardiovascular risk factors, associations were no longer significant. In age-adjusted models only, OH was associated with increased odds of being in the greatest quintile of decline in DSST score between visits 2 and 4 (OR = 1.28, 95% CI = 1.04-1.58). CONCLUSIONS: OH was associated with less favorable cognitive function, but this association was largely attributable to demographic and cardiovascular risk factors. Episodic asymptomatic hypotension in middle age may not be an independent cause of cognitive decline. Further study, including emphasis on neuroimaging, is needed.

Coronary artery circumferential stress: departure from Laplace expectations with aging.

Normal, youthful arteries generally maintain constant radius/wall thickness ratios, with the relationship being described by the Laplace Law. Whether this relationship is maintained during aging is unclear. This study first examines the Laplace relationships in postmortem coronary arteries using a novel method to correct measurements for postmortem artifacts, uses data from the literature to provide preliminary validation, and then describes histology associated with low circumferential stress. Measurements of radius and wall thickness, taken at sites free from atheromas, were used with national population estimates of age-, gender-, and race-specific blood pressure data to calculate average circumferential stress within demographic groups. The estimated circumferential stress at ages 55-74 years was about half that at ages 18-24 years because of a disproportionate increase of wall thickness relative to artery radius at older ages, violating the expected relationships described by the Laplace Law. Arteries with low circumferential stress (estimated at sites distant from atherosclerosis) had more necrotic atheromas than arteries with high stress. At sites with low stress and intimal thickening, smooth muscle cells (SMCs) were spread apart, thereby diminishing their density within both the intima and media. Thus, older arteries displayed both low circumferential stress and abundant matrix of low cellularity microscopically. Such changes might alter SMC-matrix interactions.

B-mode ultrasound common carotid artery intima-media thickness and external diameter: cross-sectional and longitudinal associations with carotid atherosclerosis in a large population sample.

BACKGROUND: Arterial diameter and intima-media thickness (IMT) enlargement may each be related to the atherosclerotic process. Their separate or combined enlargement may indicate different arterial phenotypes with different atherosclerosis risk. METHODS: We investigated cross-sectional (baseline 1987-89: n = 7956) and prospective (median follow-up = 5.9 years: n = 4845) associations between baseline right common carotid artery (RCCA) external diameter and IMT with existing and incident carotid atherosclerotic lesions detected by B-mode ultrasound in any right or left carotid segments. Logistic regression models (unadjusted, adjusted for IMT, or adjusted for IMT and risk factors) were used to relate baseline diameter to existing carotid lesions while comparably adjusted parametric survival models assessed baseline diameter associations with carotid atherosclerosis progression (incident carotid lesions). Four baseline arterial phenotypes were categorized as having 1) neither IMT nor diameter enlarged (reference), 2) isolated IMT thickening, 3) isolated diameter enlargement, and 4) enlargement of both IMT and diameter. The association between these phenotypes and progression to definitive carotid atherosclerotic lesions was assessed over the follow-up period. RESULTS: Each standard deviation increment of baseline RCCA diameter was associated with increasing carotid lesion prevalence (unadjusted odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.47-1.62) and with progression of carotid atherosclerosis (unadjusted hazards ratio (HR) = 1.37, 95% CI = 1.28-1.46); and the associations remained significant even after adjustment for IMT and risk factors (prevalence OR = 1.11, 95% CI = 1.04-1.18; progression HR = 1.11, 95% CI = 1.03-1.19). Controlling for gender, age and race, persons with both RCCA IMT and diameter in the upper 50th percentiles had the greatest risk of progressing to clearly defined carotid atherosclerotic lesions (all HR = 1.71, 95% CI = 1.47-2.0; men HR = 1.88, 95% CI = 1.48-2.39; women HR = 1.59, 95% CI = 1.31-1.95) while RCCA IMT or diameter alone in the upper 50th percentile produced significantly lower estimated risks. CONCLUSION: RCCA IMT and external diameter provide partially overlapping information relating to carotid atherosclerotic lesions. More importantly, the RCCA phenotype of coexistent wall thickening with external diameter enlargement indicates higher atherosclerotic risk than isolated wall thickening or diameter enlargement.

Pancreatitis: prevalence and risk factors among male veterans in a detoxification program.

OBJECTIVES: To determine the prevalence of pancreatitis and associated risk factors among heavy-drinking veterans. METHODS: At a large Veterans Administration Outpatient Detoxification Program (ODP) that systematically collects risk information, 1409 black and white male veterans with International Classification of Diseases, Ninth Revision codes for alcohol abuse enrolling in the ODP from January 2002 to December 2003 were identified. Among these patients, pancreatitis at any time (before the ODP admission or occurring through June 2005) was identified using International Classification of Diseases, Ninth Revision codes. Cases were verified by chart review. Logistic regression analyses were used for multivariable analyses. RESULTS: Overall, history of smoking (89.6%) and current or past drug use (90.1%) were very common, whereas intravenous drug use (22.3%) was less so. Although 87 (6.2%) subjects had pancreatitis codes (acute, 50; chronic, 15; both, 22), chart review verified only 42 cases (acute, 29; chronic, 5; both, 8) for a 3% prevalence. Alcohol appeared to be the definite etiology in 39 of these 42 patients. In bivariate analyses, patients with pancreatitis were older, had more substance abuse admissions, reported a significantly heavier current alcohol use, and lower drug dependence (each P < 0.05). In multivariable models, alcoholic pancreatitis was associated positively with age (odds ratio, 1.08; 95% confidence interval, 1.04-1.12) and number of substance abuse admissions (odds ratio, 1.08; 95% confidence interval, 0.995-1.18; P = 0.06). CONCLUSIONS: In this high-risk population of heavy drinkers, the prevalence of pancreatitis is at least 3%. Our study provides preliminary data regarding potential cofactors for pancreatitis in heavy drinkers.

Common carotid artery wall thickness and external diameter as predictors of prevalent and incident cardiac events in a large population study.

BACKGROUND: Arterial diameters enlarge in response to wall thickening, plaques, and many atherosclerotic risk factors. We hypothesized that right common carotid artery (RCCA) diameter would be independently associated with cardiac disease and improve risk discrimination. METHODS: In a middle-aged, biracial population (baseline n = 11225), we examined associations between 1 standard deviation increments of baseline RCCA diameter with prevalent myocardial infarction (MI) and incident cardiac events (MI or cardiac death) using logistic regression and Cox proportional hazards models, respectively. Areas under the receiver operator characteristic curve (AUC) were used to estimate model discrimination. RESULTS: MI was present in 451 (4%) participants at baseline (1987-89), and incident cardiac events occurred among 646 (6%) others through 1999. Adjusting for IMT, RCCA diameter was associated with prevalent MI (female OR = 2.0, 95%CI = 1.61-2.49; male OR = 1.16, 95% CI = 1.04-1.30) and incident cardiac events (female HR = 1.75, 95% CI = 1.51-2.02; male HR = 1.27, 95% CI = 1.15-1.40). Associations were attenuated but persisted after adjustment for risk factors (not including IMT) (prevalent MI: female OR = 1.73, 95% CI = 1.40-2.14; male OR = 1.14, 95% CI = 1.02-1.28, and incident cardiac events: female HR = 1.26, 95% CI = 1.08-1.48; male HR = 1.19, 95% CI = 1.08-1.32). After additional adjustment for IMT, diameter was associated with incident cardiac events in women (HR = 1.18, 95% CI = 1.00-1.40) and men (HR = 1.17, 95% CI = 1.06-1.29), and with prevalent MI only in women (OR = 1.73; 95% CI = 1.37-2.17). In women, when adjustment was limited, diameter models had larger AUC than other models. CONCLUSION: RCCA diameter is an important correlate of cardiac events, independent of IMT, but adds little to overall risk discrimination after risk factor adjustment.

Orthostatic hypotension predicts mortality in middle-aged adults: the Atherosclerosis Risk In Communities (ARIC) Study.

BACKGROUND: An association between orthostatic hypotension (OH) and mortality has been reported, but studies are limited to older adults or high-risk populations. METHODS AND RESULTS: We investigated the association between OH (a decrease of 20 mm Hg in systolic blood pressure or a decrease of 10 mm Hg in diastolic blood pressure on standing) and 13-year mortality among middle-aged black and white men and women from the Atherosclerosis Risk in Communities Study (1987-1989). At baseline, 674 participants (5%) had OH. All-cause mortality was higher among those with (13.7%) than without (4.2%) OH. After we controlled for ethnicity, gender, and age, the hazard ratio (HR) for OH for all-cause mortality was 2.4 (95% confidence interval [CI], 2.1 to 2.8). Adjustment for risk factors for cardiovascular disease and mortality and selected health conditions at baseline attenuated but did not completely explain this association (HR = 1.7; 95% CI, 1.4 to 2.0). This association persisted among subsets that (1) excluded those who died within the first 2 years of follow-up and (2) were limited to those without coronary heart disease, cancer, stroke, diabetes, hypertension, or fair/poor perceived health status at baseline. In analyses by causes of death, a significant increased hazard of death among those with versus without OH persisted after adjustment for risk factors for cardiovascular disease (HR = 2.0; 95% CI, 1.6 to 2.7) and other deaths (HR = 2.1; 95% CI, 1.6 to 2.8) but not for cancer (odds ratio = 1.1; 95% CI, 0.8 to 1.6). CONCLUSIONS: OH predicts mortality in middle-aged adults. This association is only partly explained by traditional risk factors for cardiovascular disease and overall mortality.

Changing drinking pattern does not influence health perception: a longitudinal study of the atherosclerosis risk in communities study.

OBJECTIVE: To investigate if dynamic changes in the pattern of alcoholic beverages consumption are associated with modifications in health perception. DESIGN, SETTING, AND PARTICIPANTS: This study investigated 12 332 middle aged men and women from the atherosclerosis risk in communities study who reported drinking status and perceived health triennially from 1987 to 1995. Crude and adjusted risks for change in health perception between visits two and three by change in drinking status between visits one and two were computed. In the multivariate analysis the sample was restricted to participants with stable drinking status between visit two and three and stable health perception between visits one and two, to assure that exposure and outcome were not temporary. Covariates included age, sex, race, income, smoking status, educational level, and obesity. RESULTS: Health for persons who stopped or started drinking, or continued to abstain was more likely to decline than was health for persons who continued to drink even after adjustment and restrictions (drinking cessation: OR = 1.6, 95% CI = 1.1, 2.3; started drinking; OR = 1.4, 95% CI = 0.9, 2.2; continued abstaining from alcohol: OR = 1.5, 95% CI = 1.3, 1.9). Among participants with poor perceived health, starting, stopping, or continuing to abstain from alcohol did not improve health in relation to participants that continued to drink. CONCLUSION: Increasing and decreasing drinking patterns and continuous abstinence were associated with declining health perception in comparison with continuous drinking, while starting or stopping drinking did not improve health perception of persons with poor perceived health. These findings suggest that change in health perception was not biologically related to alcohol consumption.

Common carotid arterial interadventitial distance (diameter) as an indicator of the damaging effects of age and atherosclerosis, a cross-sectional study of the Atherosclerosis Risk in Community Cohort Limited Access Data (ARICLAD), 1987-89.

BACKGROUND: The effect of age on common carotid artery diameter is unclear for varying atherosclerosis risk levels. METHODS: Cross-sectional data from the Atherosclerosis Risk in Communities Limited Access Data set were used to estimate the association of age with B-mode ultrasound common carotid artery diameter for three atherosclerosis risk levels. Based on information from clinical examinations, B-mode ultrasounds, questionnaires, blood and other tests, participants were categorized into three groups: pre-existing disease (prevalent stroke and/or coronary heart disease), high risk group (no pre-existing disease, but prevalent diabetes, hypertension, plaques/shadowing, body mass index > or = 30, current smoking, or hyperlipidemia), and a low risk group (no pre-existing disease, no plaques/shadowing, and no major elevated risk factors). Multivariable linear regression analyses modeled the common carotid artery diameter relationship with age. RESULTS: Age was positively and significantly associated with common carotid artery diameter after risk factor adjustment in the overall sample, but age had a larger effect among persons with evidence of atherosclerosis (interaction p < 0.05). Each year of older age was associated with 0.03 mm larger diameter/year among persons with pre-existing disease, with 0.027 mm larger diameter/year in the high risk group, but only 0.017 mm/year among the low risk group. Results were qualitatively similar using plaques/shadowing status to indicate atherosclerosis severity. CONCLUSION: The significant impact of age on common carotid artery diameter among low risk, middle-aged, black and white men and women suggests arterial remodelling may occur in the absence of identified risk factors. The significantly larger impact of age among persons with, compared to persons without identified atherosclerosis or its risk factors, suggests that arterial remodelling may be an indicator of exposure duration.

Association between alcoholic beverage consumption and incidence of coronary heart disease in whites and blacks: the Atherosclerosis Risk in Communities Study.

The authors evaluated the relation between consumption of alcoholic beverages and incidence of coronary heart disease in White and African-American participants in the Atherosclerosis Risk in Communities Study. The average duration of follow-up was 9.8 years between 1987 and 1998. The association was analyzed by means of Cox proportional hazards regression models. The authors found a positive association between ethanol consumption and incident coronary heart disease for Black men (for a 13-g/day increment in ethanol consumption, adjusted hazard ratio (HR) = 1.13, 95% confidence interval (CI): 1.01, 1.28) and an inverse association for White men (HR = 0.88, 95% CI: 0.79, 0.99). There was an inverse association of coronary heart disease with rare drinking (HR = 0.47, 95% CI: 0.28, 0.80) and with consumption of > or =70 g of ethanol per week (HR = 0.49, 95% CI: 0.24, 0.98) in White women and with consumption of > or =210 g/week (HR = 0.56, 95% CI: 0.33, 0.95) in White men. In Black men, the association was positive for consumption of 140-<210 g/week (HR = 2.61, 95% CI: 1.11, 6.17). The contrasting findings in Whites and Black men in this cohort raise the question of whether the cardioprotective effect of alcohol is real or may be confounded by lifestyle characteristics of drinkers.

Alcohol intake and cerebral abnormalities on magnetic resonance imaging in a community-based population of middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: Although the risks associated with heavy drinking for increased stroke and neurodegenerative changes are well established, the effects on the brain of low to moderate alcohol intake are unclear. Subclinical cerebral abnormalities identified on MRI have been associated with neurocognitive decline and incident stroke. We examined the associations of alcohol intake with MRI-defined cerebral abnormalities in a middle-aged, population-based cohort. METHODS: During 1993-1994, a total of 1909 middle-aged adults (40% men and 49% blacks) from 2 communities in the Atherosclerosis Risk in Communities (ARIC) Study (Forsyth County, North Carolina, and Jackson, Miss) underwent a cerebral MRI examination. Trained neuroradiologists coded the images for the presence of infarction and the extent (10-point scale) of white matter lesions, ventricular size, and sulcal size. RESULTS: In logistic regression analyses, there was no association between alcohol intake and the presence of MRI infarction. In linear regression analyses, alcohol intake was not associated with white matter grade. However, intake of each additional alcoholic drink per week was associated with a 0.01 grade greater ventricular size (P=0.03) and a 0.009 grade greater sulcal size (P=0.02) after adjustment for age, sex, race, body mass index, smoking, income, sports index, and diabetes. The positive associations of alcohol intake with ventricular and sulcal size were consistent across sex and race subgroups. CONCLUSIONS: A protective effect of low to moderate alcohol intake on cerebral infarction was not found; moreover, increased alcohol intake was associated with brain atrophy.