Reproducibility of coronary artery calcified plaque with cardiac 64-MDCT: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: The Multi-Ethnic Study of Atherosclerosis is a longitudinal study evaluating determinants of future cardiac events and progression of atherosclerosis. Emerging data are showing that coronary artery calcification (CAC) is a robust independent predictor of future cardiac events and that measurement of progression depends on reproducibility of the measure. Reproducibility previously was reported on baseline scans obtained with both electron-beam tomography (EBT) and MDCT. The aim of this study was to compare the interscan variability for both Agatston and volume scores derived with newer (16- and 64-MDCT) scanners with that derived with older scanners in the Multi-Ethnic Study of Atherosclerosis. SUBJECTS AND METHODS: The participants in this study were 4,054 persons who underwent dual scanning with EBT (n = 1,716), 4-MDCT (n = 370), 16-MDCT (n = 1,245), or 64-MDCT (n = 723). Agreement on the presence or absence of CAC was assessed with logistic regression models adjusted for age, sex, body mass index, and scanner type. Among participants with CAC, the log-transformed interscan difference was regressed on log-transformed amount of CAC, age, sex, and body mass index. RESULTS: The percentage agreement for the presence or absence of CAC was high and similar across scanner groups (EBT, 16-MDCT, and 64-MDCT). The greatest adjusted average absolute CAC differences between scans were found with the Aquilion 64 (24%; 95% CI, 20.9-27.6) and LightSpeed Pro 16 (19%; 95% CI, 17.4-21.0) scanners, both differences being significantly greater than with the EBT scanner (16%; 95% CI, 15.4-17.5) (p < 0.05). No differences were found between the EBT, Sensation 16, and Sensation 64 scanners. For volume score, the Aquilion 64 was the only scanner with significantly greater average absolute interscan differences than the EBT scanner (p < 0.001). Volume scoring resulted in lower rescan differences for all scanners. CONCLUSION: For CAC scoring, interscan variability with newer-generation MDCT scanners was similar to but not superior to that with the EBT scanner.

The association between physical activity and subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis.

Prior reports regarding the association between physical activity and subclinical cardiovascular disease have not been consistent. The authors assessed physical activity and walking pace via questionnaire among 6,482 US adults aged 45-84 years without prior clinical cardiovascular disease participating in the Multi-Ethnic Study of Atherosclerosis from 2000 to 2002. Ankle-brachial index (ABI), coronary artery calcification, and internal and common carotid intima-media thickness (IMT) were measured. Metabolic equivalent-hours/week of physical activity were calculated. These data were analyzed by using multivariable linear or relative prevalence regression in gender-specific strata. After adjustment for age, race/ethnicity, clinic site, education, income, and smoking (model 1), increasing total, moderate + vigorous, and intentional-exercise physical activity were not associated with IMT or coronary artery calcification in either gender. These factors were associated with increased ABI (P<0.05) in women only. Walking pace was associated favorably with common carotid IMT, ABI, and coronary artery calcification in men and with common carotid IMT and ABI in women (all P<0.05) after adjustment for model 1 variables. These associations were attenuated and, for common carotid IMT, no longer significant when lipids, hypertension, diabetes, and body mass index were added to the model. These data suggest that walking pace is associated with less subclinical atherosclerosis; these associations may be mediated by cardiovascular disease risk factors.

Frequency and type of seafood consumed influence plasma (n-3) fatty acid concentrations.

Few studies have adequately considered the type of seafood and background dietary factors when evaluating diet-biomarker and diet-disease associations. The objective of this paper is to evaluate the relationship between different seafood meals and long-chain (n-3) fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] biomarkers in the Multi-Ethnic Study of Atherosclerosis (MESA) with white, Chinese-American, black, and Hispanic participants. Dietary intake from a FFQ and plasma phospholipid fatty acids were assessed in 900 MESA participants who were not taking fish oil supplements. When simultaneously adjusting for all seafood groups, concentrations of EPA and DHA in plasma phospholipids were positively correlated with nonfried fish consumption in all 4 ethnic groups (r = 0.24-0.46; P < 0.01) but not with nonfried shellfish, fried fish, or fish in mixed dishes. The magnitude of this correlation was attenuated by up to 67% when type of seafood was not taken into account. After further adjusting for demographic characteristics and other dietary characteristics in multivariate regression models, the association of nonfried fish consumption remained significant (P-trend < 0.001). Data were suggestive of a plateau effect at a nonfried fish intake of about twice weekly. The association of nonfried fish consumption was not modified by intake of (n-6) PUFA or alpha-linolenic acid. This study highlights the importance of cooking methods (nonfried vs. fried fish), types of seafood (fish vs. shellfish), and the overall seafood consumption when assessing health effects of long-chain (n-3) fatty acids of seafood consumption.

Graphical exploration of network meta-analysis data: the use of multidimensional scaling.

BACKGROUND: Evidence synthesis is increasingly being used to compare more than two treatments from multiple randomized trials. In a network of randomized comparisons, direct (head-to-head) evidence might be inconsistent with indirect evidence. However, the issue of potential incoherence of the network is not taken into account in statistical models with fixed treatment effects only, which are commonly employed in practice. PURPOSE: We present a graphical method to summarize a network of randomized comparisons and to examine the incoherence of the network, without making any distributional assumptions. METHODS: At each treatment-pair level, the inverse variance method is used to pool results from multiple studies. We consider the magnitude of pairwise treatment contrasts as a measure of pairwise dissimilarity. We summarize a network of randomized comparisons as a dissimilarity matrix, and then apply weighted multidimensional scaling to the dissimilarity matrix. The weights are chosen according to the inverse variance method. We show that, with this weighting scheme, 1D multidimensional scaling configuration is closely related to a fixed effect model. Therefore, our interest is to explore a departure from 1D constraint. RESULTS: Two-dimensional multidimensional scaling configuration is useful to explore the incoherence of the network. Our method is illustrated with two published datasets. LIMITATIONS: The weighting scheme in our multidimensional scaling setting is chosen to be optimal for independent treatment pairs. Pairwise differences within a multi-arm trial are correlated to one another and intrinsically coherent. Thus our weighting scheme may not apply to data with large numbers of multi-arm trials. CONCLUSIONS: Multidimensional scaling provides a useful tool for investigators to visualize the network of randomized comparisons and to assess incoherence of the network.

The impact of obesity on cardiovascular disease risk factors and subclinical vascular disease: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: To assess the importance of the obesity epidemic on cardiovascular disease (CVD) risk, we determined the prevalence of obesity and the relationship of obesity to CVD risk factors and subclinical vascular disease. METHODS: The Multi-Ethnic Study of Atherosclerosis is an observational cohort study involving 6814 persons aged 45 to 84 years who were free of clinical CVD at baseline (2000-2002). The study assessed the association between body size and CVD risk factors, medication use, and subclinical vascular disease (coronary artery calcium, carotid artery intimal medial thickness, and left ventricular mass). RESULTS: A large proportion of white, African American, and Hispanic participants were overweight (60% to 85%) and obese (30% to 50%), while fewer Chinese American participants were overweight (33%) or obese (5%). Hypertension and diabetes were more prevalent in obese participants despite a much higher use of antihypertensive and/or antidiabetic medications. Obesity was associated with a greater risk of coronary artery calcium (17%), internal carotid artery intimal medial thickness greater than 80th percentile (32%), common carotid artery intimal medial thickness greater than 80th percentile (45%), and left ventricular mass greater than 80th percentile (2.7-fold greater) compared with normal body size. These associations persisted after adjustment for traditional CVD risk factors. CONCLUSIONS: These data confirm the epidemic of obesity in most but not all racial and ethnic groups. The observed low prevalence of obesity in Chinese American participants indicates that high rates of obesity should not be considered inevitable. These findings may be viewed as indicators of potential future increases in vascular disease burden and health care costs associated with the obesity epidemic.

Antidepressant treatment and worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.

BACKGROUND AND PURPOSE: In some studies, late life depression is associated with white matter lesions on MRI. The effect of different classes of antidepressants on progression of white matter lesions is unknown. Selective serotonergic reuptake inhibitors (SSRIs) may decrease platelet aggregation. We hypothesized that Cardiovascular Health Study participants taking SSRIs would less often have worsening white matter on serial MRI than participants not on antidepressants. METHODS: Among 1826 participants who were not using an antidepressant at initial MRI scan, we examined the association of worsening in white matter grade from initial to follow-up MRI scans, 5 years apart on average, and antidepressant use between the scans. Logistic regression models were used, controlling for a variety of potential confounding variables. RESULTS: Use of any antidepressant during the period of study was associated with worsening white matter. In a multivariable model, risk was slightly increased, not reduced, with use of serotonergic agents (OR 1.36, 95% CI 0.87 to 2.12) and was significantly increased with the use of tricyclic antidepressants (OR 1.77, 95% CI 1.07 to 2.94). CONCLUSIONS: The association between worsening white matter and use of tricyclic antidepressants was an unexpected finding that may relate to indications for use other than depression or to side effects such as hypotension. Protection against worsening was not seen with use of serotonergic agents.

Repeatability limits for measurement of coronary artery calcified plaque with cardiac CT in the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: The purposes of this study were to examine the repeatability of the findings of coronary artery calcification (CAC) measured with CT on repeated scans, to estimate 95% repeatability limits for CAC, and to use these limits to quantify detectable change in CAC over time. SUBJECTS AND METHODS: The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study with 6,814 participants 45-84 years old and free of clinical cardiovascular disease at enrollment. Agreement for presence of CAC was assessed for 6,742 participants who had baseline replicate scans on which a CAC score of 0 indicated no coronary calcification. Among 3,380 participants with baseline CAC, the 95% repeatability limits were established with a quantile regression model. Detectable change in CAC during follow-up was defined by an increase or decrease beyond the baseline repeatability limit. RESULTS: At baseline, 274 (4.1%) of the rescan pairs were discordant (presence or absence of CAC). Greater body mass index was associated with a discordant pair (trend, p < 0.05). The upper 95% repeatability limits were (0.17 x Agatston score) + (4.89 x sq rt(Agatston score)) + (0.44 x body mass index) - 10.84 for Agatston score and (0.16 x volumetric calcium score) + (4.30 x sq rt(volumetric calcium score)) + (0.23 x body mass index) - 5.00 for volumetric calcium score. Rescan repeatability was comparable for electron beam and 4-MDCT scanners. At 2.5 years of average follow-up (range, 0.9-5.0 years), a detectable increase in Agatston and volumetric calcium scores was observed in 1,027 (36.3%) and 1,020 (36.0%), respectively, of 2,832 participants with baseline CAC. CONCLUSION: The repeatability limits derived can be used to evaluate whether an increase in CAC score exceeds that expected from measurement error alone.

Alcohol consumption and risk of coronary heart disease in older adults: the Cardiovascular Health Study.

OBJECTIVES: To evaluate several aspects of the relationship between alcohol use and coronary heart disease in older adults, including beverage type, mediating factors, and type of outcome. DESIGN: Prospective cohort study. SETTING: Four U.S. communities. PARTICIPANTS: Four thousand four hundred ten adults aged 65 and older free of cardiovascular disease at baseline. MEASUREMENTS: Risk of incident myocardial infarction or coronary death according to self-reported consumption of beer, wine, and spirits ascertained yearly. RESULTS: During an average follow-up period of 9.2 years, 675 cases of incident myocardial infarction or coronary death occurred. Compared with long-term abstainers, multivariate relative risks of 0.90 (95% confidence interval (CI)=0.71-1.14), 0.93 (95% CI=0.73-1.20), 0.76 (95% CI=0.53-1.10), and 0.58 (95% CI=0.39-0.86) were found in consumers of less than one, one to six, seven to 13, and 14 or more drinks per week, respectively (P for trend=.007). Associations were similar for secondary coronary outcomes, including nonfatal and fatal events. No strong mediators of the association were identified, although fibrinogen appeared to account for 9% to 10% of the relationship. The associations were statistically similar for intake of wine, beer, and liquor and generally similar in subgroups, including those with and without an apolipoprotein E4 allele. CONCLUSION: In this population, consumption of 14 or more drinks per week was associated with the lowest risk of coronary heart disease, although clinicians should not recommend moderate drinking to prevent coronary heart disease based on this evidence alone, because current National Institute on Alcohol Abuse and Alcoholism guidelines suggest that older adults limit alcohol intake to one drink per day.

Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Coronary artery calcium (CAC) has been demonstrated to be associated with the risk of coronary heart disease. The Multi-Ethnic Study of Atherosclerosis (MESA) provides a unique opportunity to examine the distribution of CAC on the basis of age, gender, and race/ethnicity in a cohort free of clinical cardiovascular disease and treated diabetes. METHODS AND RESULTS: MESA is a prospective cohort study designed to investigate subclinical cardiovascular disease in a multiethnic cohort free of clinical cardiovascular disease. The percentiles of the CAC distribution were estimated with nonparametric techniques. Treated diabetics were excluded from analysis. There were 6110 included in the analysis, with 53% female and an average age of 62 years. Men had greater calcium levels than women, and calcium amount and prevalence were steadily higher with increasing age. There were significant differences in calcium by race, and these associations differed across age and gender. For women, whites had the highest percentiles and Hispanics generally had the lowest; in the oldest age group, however, Chinese women had the lowest values. Overall, Chinese and black women were intermediate, with their order dependent on age. For men, whites consistently had the highest percentiles, and Hispanics had the second highest. Blacks were lowest at the younger ages, and Chinese were lowest at the older ages. At the MESA public website (http://www.mesa-nhlbi.org), an interactive form allows one to enter an age, gender, race/ethnicity, and CAC score to obtain a corresponding estimated percentile. CONCLUSIONS: The information provided here can be used to examine whether a patient has a high CAC score relative to others with the same age, gender, and race/ethnicity who do not have clinical cardiovascular disease or treated diabetes.

Alcohol use and risk of ischemic stroke among older adults: the cardiovascular health study.

BACKGROUND AND PURPOSE: The association of light to moderate alcohol consumption with risk of ischemic stroke remains uncertain, as are the roles of potentially mediating factors and modification by apolipoprotein E (apoE) genotype. METHODS: We studied the prospective association of alcohol consumption and risk of ischemic stroke among 4410 participants free of cardiovascular disease at baseline in the Cardiovascular Health Study, a population-based cohort study of older adults from 4 US communities. Participants reported their consumption of alcoholic beverages yearly. RESULTS: During an average follow-up period of 9.2 years, 434 cases of incident ischemic stroke occurred. Compared with long-term abstainers, the multivariate relative risks of ischemic stroke were 0.85 (95% CI, 0.63 to 1.13), 0.75 (95% CI, 0.53 to 1.06), 0.82 (95% CI, 0.51 to 1.30), and 1.03 (95% CI, 0.68 to 1.57) among consumers of <1, 1 to 6, 7 to 13, and > or =14 drinks per week (P quadratic trend 0.06). ApoE genotype appeared to modify the alcohol-ischemic stroke relationship (P interaction 0.08), with generally lower risks among drinkers than abstainers in apoE4-negative participants but higher risks among drinkers than abstainers among apoE4-positive participants. We could not identify candidate mediators among lipid, inflammatory, and prothrombotic factors. CONCLUSIONS: In this study of older adults, the association of alcohol use and risk of ischemic stroke was U-shaped, with modestly lower risk among consumers of 1 to 6 drinks per week. However, apoE genotype may modify this association, and even moderate alcohol intake may be associated with an increased risk of ischemic stroke among apoE4-positive older adults.

Subclinical brain magnetic resonance imaging abnormalities predict physical functional decline in high-functioning older adults.

OBJECTIVES: To determine whether severity of subclinical brain magnetic resonance imaging (MRI) abnormalities predicts incident self-reported physical impairment or rate of decline in motor performance. DESIGN: Longitudinal analysis, average follow-up time: 4.0 years. SETTING: Cardiovascular Health Study (CHS). PARTICIPANTS: CHS participants with modified Mini-Mental State Examination (3MS) score of 80 or greater, no self-reported disability, no history of stroke, and at least one assessment of mobility (n=2,450, mean age=74.4). MEASUREMENTS: Brain MRI abnormalities (ventricular enlargement, white matter hyperintensities, subcortical and basal ganglia small brain infarcts), self-reported physical impairment (difficulty walking half a mile or with one or more activities of daily living), and motor performance (gait speed, timed chair stand). RESULTS: After adjusting for demographics, cardiovascular risk factors, and diseases, risk of incident self-reported physical impairment was 35% greater for those with severe ventricular enlargement than for those with minimal ventricular enlargement, 22% greater for those with moderate white matter hyperintensities than for those with minimal white matter hyperintensities, and 26% greater for participants with at least one brain infarct than for those with no infarcts. Those with moderate to severe brain abnormalities experienced faster gait speed decline (0.02 m/s per year) than those with no MRI abnormalities (0.01 m/s per year). Further adjustment for incident stroke, incident dementia, and 3MS score did not substantially attenuate hazard ratios for incident self-reported physical impairment or coefficients for decline in gait speed. CONCLUSION: Subclinical structural brain abnormalities in high-functioning older adults can increase the risk of developing physical disabilities and declining in motor performance.