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OBJECTIVE: Cardiovascular risk factors in middle-age are associated with cognitive impairment and dementia in older age. Less is known about the burden of calcified subclinical atherosclerosis and cognition, especially in midlife. We examined the association of coronary artery and abdominal aortic calcified plaque (CAC and AAC, respectively) with cognitive functioning in middle-aged adults. METHODS: This cross-sectional study included 2510 black and white adults (age: 43-55 years) without heart disease or stroke who completed a year 25 follow-up exam (2010-11) as part of the Coronary Artery Risk Development in Young Adults Study. CAC and AAC were measured with non-contrast computed tomography. Cognition was assessed with the Digit Symbol Substitution Test (DSST) (psychomotor speed), Stroop Test (executive function), and Rey Auditory Verbal Learning Test (RAVLT) (verbal memory). RESULTS: A greater amount of CAC and AAC was associated with worse performance on each test of cognitive function after adjustment for age, sex, race, education, and study center. Associations were attenuated, but remained significant for the DSST and RAVLT following additional adjustment for vascular risk factors, including adiposity, smoking, alcohol use, dyslipidemia, hypertension, and diabetes. Compared to participants without CAC or AAC, those with both CAC and AAC, but not CAC or AAC alone was associated with lower DSST scores (p < 0.05). CONCLUSIONS: In this community-based sample, greater subclinical atherosclerotic calcification was associated with worse psychomotor speed and memory in midlife. These findings underscore the importance of a life course approach to the study of cognitive impairment with aging.

Background: The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort., Methods and Results: Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p < 0.001), carotid plaque score (1.2 ms/unit change in score, p < 0.001), and log transformed CAC+1 (0.66 ms/unit log-CAC+1, p = 0.018). These findings were consistent with other parameter of LV dyssynchrony i.e. max-min., Conclusion: In the MESA cohort, measures of atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: We used magnetic resonance imaging (MRI) to study the prevalence and associated clinical characteristics of high-risk plaque (defined as presence of lipid-rich necrotic core [LRNC] and intraplaque hemorrhage) in the superficial femoral arteries (SFA) among people with peripheral artery disease (PAD)., Background: The prevalence and clinical characteristics associated with high-risk plaque in the SFA are unknown., Methods: Three-hundred-three participants with PAD underwent MRI of the proximal SFA using a 1.5 T S platform. Twelve contiguous 2.5 mm cross-sectional images were obtained., Results: LRNC was present in 68 (22.4%) participants. Only one had intra-plaque hemorrhage. After adjusting for age and sex, smoking prevalence was higher among adults with LRNC than among those without LRNC (35.9% vs. 21.4%, p = 0.02). Among participants with vs. without LRNC there were no differences in mean percent lumen area (31% vs. 33%, p = 0.42), normalized mean wall area (0.71 vs. 0.70, p = 0.67) or maximum wall area (0.96 vs. 0.92, p = 0.54) in the SFA. Among participants with LRNC, cross-sectional images containing LRNC had a smaller percent lumen area (33% ± 1% vs. 39% ± 1%, p < 0.001), greater normalized mean wall thickness (0.25 ± 0.01 vs. 0.22 ± 0.01, p < 0.001), and greater normalized maximum wall thickness (0.41 ± 0.01 vs. 0.31 ± 0.01, p < 0.001), compared to cross-sectional images without LRNC., Conclusions: Fewer than 25% of adults with PAD had high-risk plaque in the proximal SFA using MRI. Smoking was the only clinical characteristic associated with presence of LRNC. Further study is needed to determine the prognostic significance of LRNC in the SFA., Clinical Trial Registration-Url: http://www.clinicaltrials.gov. Unique identifier: NCT00520312., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: We evaluated family history as a predictor of incident and progressive coronary artery calcium (CAC) using data from the Multi-Ethnic Study of Atherosclerosis (MESA)., Background: MESA is a multi-center prospective study of 6814 asymptomatic individuals. The relationship between family history of coronary heart disease (CHD) and CAC incidence or progression has not been described previously., Methods: A total of 5099 participants had detailed information about family history of CHD (late versus premature and parental versus sibling history). The mean time between CAC scans was 3.1 ± 1.3 years. The association of late versus premature family history was assessed against CAC change using multivariate regression model adjusted for demographics and cardiac risk factors., Results: A family history of premature CHD was associated with an odds ratio (OR) of 1.55 (p < 0.01) for incident development of CAC after adjusting for risk factors and demographics. A premature family history was associated with 14.4 units (p < 0.01) greater volume scores compared to those with no family history in similarly adjusted models by median regression analysis. A combined parental and sibling family history was associated with the greatest incidence and progression in demographic-adjusted models. Caucasians demonstrated the most consistent predictive relationship between family history of premature CHD and incidence (p < 0.01) and progression (p < 0.05) of CAC, though no significant interaction with ethnicity was noted., Conclusions: Family history of premature CHD is associated with enhanced development and progression of subclinical disease, independent of other risk factors, in a multiethnic, population-based study., (Copyright © 2013. Published by Elsevier Ireland Ltd.)

Background: Calcified coronary plaque (CCP) is a complex trait influenced by both genes and environment, and plausibly an interaction between the two. Because the familial aggregation of CCP has been demonstrated and smoking is a significant, independent predictor of CCP, we assessed the evidence for genotype-by-smoking interaction and conducted linkage analysis of quantitative Agatston CCP scores in participants of the NHLBI Family Heart Study (FHS)., Methods: During standardized clinical exams smoking habits were ascertained and CCP was quantified with cardiac computed tomography (CT). Among 4387 relationship pairs from 2128 Caucasian examinees variance component analysis was implemented in SOLAR to examine: (1) additive genotype-by-smoking status interaction using a variance component approach; (2) linkage analysis in the full sample and among smoking subsets defined by individual smoking exposure; (3) QTL-specific genotype-by-smoking interaction in the regions that appeared to differentiate between smoking strata., Results: The prevalence of CCP (and median Agatston score) was 75% (184.6) in men and 48% (51.0) in women. We detected four genome-wide significant logarithm of odds (LOD) scores in samples stratified by individual smoking exposure: chromosome 4 at 122cM (nearest marker D4S2297; robust adjusted LOD=3.1; q=0.053), chromosome 6 at 99cM (nearest marker D6S1056; robust adjusted LOD=3.3; q=0.053), chromosome 11 at 19cM (nearest marker D11S199; robust adjusted LOD=4.0; q=0.02) and chromosome 13 at 77cM (nearest marker D13S892; robust adjusted LOD=3.1; q=0.053). Additive and QTL-specific genotype-by-smoking interaction was detected on chromosomes 4, 6, 11 and 13; all P<0.05. Three of the four QTLs identified in this report have been previously linked to atherosclerosis and harbor interesting candidate genes., Conclusions: These findings demonstrate the importance of considering complex interactions in the search for genes that influence the pathogenesis of CCP.