Association of obesity with arterial stiffness: The Multi-Ethnic Study of Atherosclerosis (MESA).

Arterial stiffness (AS) and obesity are recognized as important risk factors of cardiovascular disease (CVD). The purpose of this study was to investigate the relationship between AS and obesity. AS was defined as high augmentation index (AIx) and low elasticity (C1, large artery elasticity; C2, small artery elasticity) in participants enrolled in the Multi-Ethnic Study of Atherosclerosis at baseline. We compared AIx, C1, and C2 by body mass index (BMI) (< 25, 25-29.9, 30-39.9, ⩾ 40 kg/m2) and waist-hip ratio (WHR) (< 0.85, 0.85-0.99, ⩾ 1). The obesity-AS association was tested across 10-year age intervals. Among 6177 participants (62 ± 10 years old, 52% female), a significant inverse relationship was observed between obesity and AS. After adjustments for CVD risk factors, participants with a BMI > 40 kg/m2 had 5.4% lower AIx (mean difference [Δ] = -0.82%; 95% CI: -1.10, -0.53), 15.4% higher C1 (Δ = 1.66 mL/mmHg ×10; 95% CI: 1.00, 2.33), and 40.2% higher C2 (Δ = 1.49 mL/mmHg ×100; 95% CI: 1.15, 1.83) compared to those with a BMI < 25 kg/m2 (all p for trend < 0.001). Participants with a WHR ⩾ 1 had 5.6% higher C1 (∆ = 0.92 mL/mmHg ×10; 95% CI: 0.47, 1.37) compared to those with a WHR < 0.85. The WHR had a significant interaction with age on AIx and C2, but not with BMI; the inverse relationships of the WHR with AIx and C2 were observed only in participants < 55 years between the normal (WHR < 0.85) and the overweight (0.85 ⩽ WHR < 0.99) groups. Different associations of WHR and BMI with arterial stiffness among older adults should be further investigated.

Thoracic Aorta Calcification and Noncardiovascular Disease-Related Mortality.

Objective- Arterial calcification is highly correlated with underlying atherosclerosis. Arterial calcification of the thoracic aorta is evident in many older individuals at high susceptibility to aging-related diseases and non-cardiovascular disease (CVD)-related mortality. In this study, we evaluated the association of thoracic aorta calcification (TAC) with non-CVD morbidity and mortality. Approach and Results- We analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis, a prospective cohort study of subclinical atherosclerosis, in which participants underwent cardiac computed tomography at baseline and were followed longitudinally for incident CVD events and non-CVD events. Using modified proportional hazards models accounting for the competing risk of CVD death and controlling for demographics, CVD risk factors, coronary artery calcium, and CVD events, we evaluated whether TAC was independently associated with non-CVD morbidity and mortality. Among 6765 participants (mean age, 62 years), 704 non-CVD deaths occurred for a median follow-up of 12.2 years. Compared with no TAC, the highest tertile of TAC volume was associated with a higher risk of non-CVD mortality (hazard ratio, 1.56; 95% confidence interval, 1.23-1.97), as well as several non-CVD diagnoses, including hip fracture (2.14; 1.03-4.46), chronic obstructive pulmonary disease (2.06; 1.29-3.29), and pneumonia (1.79; 1.30-2.45), with magnitudes of association that were larger than for those of coronary artery calcium. Conclusions- TAC is associated with non-CVD morbidity and non-CVD mortality, potentially through a pathway that is unrelated to atherosclerosis. TAC may be a general marker of biological aging and an indicator of increased risk of non-CVD and death.

Ankle-brachial index predicts change over time in functional status in the San Diego Population Study.

BACKGROUND: Peripheral artery disease (PAD) affects millions of people, both in the U.S. and worldwide. Even when asymptomatic, PAD and the ankle-brachial index (ABI), the major clinical diagnostic criterion for PAD, are associated with decreased functional status and quality of life, as well as mobility impairment. Whether the ABI or change in the ABI predicts decline in functional status over time has not been previously assessed in a population-based setting. METHODS: Participants were 812 non-Hispanic white, African American, Hispanic, and Asian men and women from the San Diego Population Study (SDPS) who attended a baseline examination (1994-1998), and follow-up clinic examination approximately 11 years later. The Medical Outcomes Study 36-Item Short Form (SF-36) was obtained at both the baseline and follow-up examinations, and the summary performance score (SPS) at the follow-up examination. Associations of the baseline ABI and clinically relevant change in the ABI (<-0.15 vs ≥-0.15) with change in SF-36 scores over time were assessed using growth curve models, a type of mixed model that accounts for within participant correlation of measurements over time, and using linear regression for SPS. Models were adjusted for baseline age, sex, race/ethnicity, body mass index, ever smoking, physical activity, hypertension, diabetes, and dyslipidemia. RESULTS: Mean ± standard deviation (SD) for the baseline ABI was 1.11 ± 0.10, and 50.8 ± 9.0 for the baseline Physical Component Score (PCS), 50.1 ± 9.5 for the baseline Mental Component Score (MCS), and 11.2 ± 1.9 for the SPS at the follow-up examination. In fully adjusted models, each SD lower of the baseline ABI was significantly associated with an average decrease over time of 0.6 (95% confidence interval [CI], -1.1 to -0.1; P = .02) units on SF-36 PCS. Each SD lower of the baseline ABI was also significantly associated with an average decrease over time of 1.2 units (95% CI, -2.3 to -0.2; P = .02) on the SF-36 physical functioning subscale, and a decrease of 1.3 units (95% CI, -2.3 to -0.3; P = .01) on the SF-36 energy/vitality subscale in fully adjusted models. Baseline ABI was not significantly associated with change in the SF-36 MCS over time, or the SPS at the follow-up examination. Change in the ABI was not associated with SF-36 PCS, MCS, or the SPS. CONCLUSIONS: In this multiethnic population of healthy middle-aged community-living men and women, we showed that participants with a lower baseline ABI had declines in functional status over 11 years. Findings suggest that small differences in the ABI, even within the normal range, may identify subclinical lower extremity PAD, which in turn may help to identify individuals at risk for declining functional status with age.

Sex and ethnic differences in the associations between lipoprotein(a) and peripheral arterial disease in the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: Higher lipoprotein(a) [Lp(a)] has been linked with peripheral arterial disease (PAD). Also, elevated Lp(a) serum levels have been observed in women and African Americans (AAs). It remains uncertain if sex and ethnicity modify the association between Lp(a) and PAD. METHODS: Lp(a) mass concentration was measured with a latex-enhanced turbidimetric immunoassay, from blood collected at baseline clinic visits after a 12-hour fast, in a multiethnic cohort. Also at baseline, the ankle-brachial index was measured. PAD was defined as an ankle-brachial index <1.0. Multivariable logistic regression was used to determine sex and ethnic differences in associations of log-transformed Lp(a) and the presence of PAD. RESULTS: In 4618 participants, the mean age was 62 ± 10 years; Lp(a) mean was 30 ± 32 mg/dL and median (interquartile range) was 18 (8-40 mg/dL); 48% were male; 36% were European American, 29% were AA, 23% were Hispanic American (HA), and 12% were Chinese American; and 11% had PAD. Across all ethnic groups, serum Lp(a) was higher among women compared with men and highest among AAs compared with other ethnicities. After adjustments for traditional cardiovascular disease risk factors (age, sex, ethnicity, hypertension, diabetes, smoking, total cholesterol, and high-density lipoprotein cholesterol) as well as interleukin-6, fibrinogen, D-dimer, and homocysteine levels, one log unit increase in Lp(a) was associated with greater odds for PAD (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.01-1.25). In fully adjusted models, significant gender(∗)ln[Lp(a)] and ethnicity(∗)ln[Lp(a)] interactions were observed (P = .08 for both). The association between higher Lp(a) and PAD was strongest in HA men (OR, 1.73; 95% CI, 1.07-2.80) and HA women (OR, 1.49; 95% CI, 1.07-2.08). Nonsignificant associations were observed for European American, AA, and Chinese American men and women. CONCLUSIONS: We observed a significant and independent association between elevated Lp(a) and PAD only among HA women and men, despite higher serum Lp(a) levels among AAs. Future studies are needed to determine the role that lowering of Lp(a) may have on the burden of PAD in HAs.

In vivo breath-hold (1) H MRS simultaneous estimation of liver proton density fat fraction, and T1 and T2 of water and fat, with a multi-TR, multi-TE sequence.

PURPOSE: To examine the intra-examination repeatability of proton density fat fraction (PDFF) and T1 and T2 of liver water and fat as estimated by a novel multi-repetition time (TR)-echo time (TE) (1) H magnetic resonance spectroscopy (MRS)-stimulated echo acquisition mode (STEAM) sequence that acquires 32 spectra for a range of TRs and TEs in single breath-hold. MATERIALS AND METHODS: Sixty-seven subjects undergoing liver MRI examinations at 3T had three multi-TR-TE sequences acquired consecutively in a single session. This sequence was designed to allow accurate estimation of T1 and T2 of both water and fat, as well as PDFF, in a single breath-hold. A standard long-TR, multi-TE sequence was also acquired to allow comparison of estimated PDFF. Regression and interclass correlation (ICC) analyses were performed. RESULTS: There was strong agreement between PDFF estimated by the multi-TR-TE and long-TR, multi-TE sequences (slope 0.997; intercept -0.03; R = 0.997). The multi-TR-TE sequence had high repeatability for estimating PDFF (ICC = 0.999), water T2 (ICC = 0.920), water T1 (ICC = 0.845), and fat T2 (ICC = 0.760), and moderate repeatability for estimating fat T1 (ICC = 0.556). CONCLUSION: A novel multi-TR-TE sequence can estimate PDFF and water and fat T1 and T2 in a single breath-hold. Refinement may be needed to improve repeatability for fat T1 estimation.

Association of foot and ankle characteristics with progression of venous disease.

Although risk factors have been identified for the cross-sectional prevalence of venous disease, few studies have investigated risk factors for venous disease progression. Therefore, the aim of this study was to investigate the relationship between foot and ankle characteristics and the progression of venous disease. A total of 1025 participants from the San Diego Population Study were assessed at baseline and at follow-up 11 years later. Risk factors were assessed by questionnaire and physical measurements, while venous disease was determined by physical examination and Duplex ultrasound. Change in venous disease from baseline to 11-year follow-up was characterized as stable or progression. Those with venous disease progression were less likely to spend increased time lying per day, more likely to have a history of hypertension, lie supine for a surgical procedure greater than an hour, and report an occupation that was professional, technical, administrative, or management. Those with a normal arch reported the greatest degree of plantar flexion. In multivariable logistic regression, including adjustment for weight-bearing arch characteristics, greater dorsiflexion (per 5 degrees) was significantly associated with progression of venous disease (OR = 1.11, p = 0.01). A weight-bearing flat arch compared to a weight-bearing normal arch was of borderline significance as a protective factor against progression of venous disease with adjustment for dorsiflexion (OR = 0.56, p = 0.07). Our results indicate that the ability to have higher levels of dorsiflexion is a risk factor for the progression of venous disease, and suggest a role for connective tissue laxity in the pathogenesis of venous disease.

Ankle-brachial index, toe-brachial index, and cardiovascular mortality in persons with and without diabetes mellitus.

BACKGROUND: The prognostic utility of the ankle-brachial index (ABI) may be hampered in persons with diabetes due to peripheral arterial stiffening in the ankles. Stiffening of toe arteries occurs infrequently in diabetes. We aimed to determine the nature of the relationship of the toe-brachial index (TBI) and ABI with cardiovascular disease (CVD) mortality and to determine whether the associations are modified in individuals with diabetes. METHODS: Individuals with clinically suspected atherosclerotic peripheral arterial disease who underwent ABI and TBI measurements in a vascular laboratory were monitored longitudinally for CVD mortality. RESULTS: Among 469 participants (89% men), the mean age was 68 ± 9 years, and 36% had diabetes. The mean ABI was 0.83 ± 0.28 and the mean TBI was 0.60 ± 0.24. During median 7.0 years of follow-up, there were 158 CVD deaths. The association of the ABI categories with CVD deaths differed in diabetic vs nondiabetic participants (P = .002 for interaction). In contrast, the association of the TBI categories with CVD deaths was similar, irrespective of diabetes status (P = .17 for interaction). Among diabetic patients, a U-shaped relationship was observed between ABI categories and CVD death: those with low (<0.90) and high (>1.30) ABIs were both at higher risk than those with normal ABIs (range, 0.90-1.30). In nondiabetic patients, association of ABI categories with CVD death was linear, such that those with an ABI >1.30 were at the lowest risk, whereas those with an ABI <0.90 were at higher risk. In contrast, the association of TBI categories with CVD death was linear irrespective of diabetes status. High TBI categories consistently predicted low risk, whereas risk was higher with progressively lower TBI categories. CONCLUSIONS: Among diabetic individuals with clinically suspected peripheral arterial disease, those with low and high ABIs are both at higher risk of CVD death. In contrast, a linear relationship was observed between TBI categories and CVD death irrespective of diabetes status. These findings suggest that stiffened ankle arteries may limit the predictive value of the ABI in individuals with diabetes, a limitation that may be overcome by measurement of the TBI.

Associations of diabetes mellitus and other cardiovascular disease risk factors with decline in the ankle-brachial index.

We compared the associations of diabetes mellitus (DM) and other cardiovascular disease (CVD) risk factors with decline in the ankle-brachial index (ABI) over 4 years in participants with and without peripheral artery disease (PAD). A total of 566 participants, 300 with PAD, were followed prospectively for 4 years. Mean (SD) baseline ABI values were 0.70 (0.13) for participants with both PAD and DM, 0.67 (0.14) for participants with only PAD, 1.10 (0.13) for participants with only DM, and 1.10 (0.10) for participants with neither PAD nor DM. After adjusting for age, sex, and baseline ABI, the corresponding ABI change from baseline to 4-year follow-up were -0.02, -0.04, +0.05, and +0.05, respectively. Compared to participants with neither PAD nor DM, participants with only PAD showed significantly more ABI decline (p <0.01), while the decline in participants with both PAD and DM was borderline non-significant (p = 0.06). After adjustments for baseline ABI, age, sex, African American ethnicity, and other CVD risk factors, independent factors associated with ABI decline in participants with PAD in the lower ABI leg were older age and elevated D-dimer. DM was not related to ABI decline. Despite being an important risk factor for PAD, DM was not independently associated with ABI decline. This could reflect the effect of DM promoting both PAD and lower-extremity arterial stiffness, resulting in a small decline in the ABI over time. In conclusion, ABI change over time in persons with diabetes may not accurately reflect underlying atherosclerosis.

All-cause and cause-specific mortality rates after severe extremity injuries among previously deployed active duty service members.

BACKGROUND: Previous research has shown that active duty military personnel who sustain extremity injuries while in service are at elevated risk for serious physical and psychological health issues that could affect their long-term functioning and quality of life yet longer-term mortality has not been studied in this population. OBJECTIVE: To determine whether rates of all-cause and cause-specific mortality are elevated for active duty U.S. service members who sustained traumatic limb injuries in service, compared to the broader population of deploying service members. To assess differences in mortality rates between service members with traumatic limb injuries that did versus did not result in amputation. DESIGN: Retrospective cohort study; archival Department of Defense deployment, personnel, medical, and death records were combined and analyzed. Standardized mortality ratios (SMR) adjusted for age, sex, and ethnoracial group, along with associated 95% confidence intervals (CIs), were calculated to directly compare all-cause and cause-specific mortality rates in each of the two injury groups to rates in the total study population. SETTING: Not applicable. PARTICIPANTS: Service members who deployed in support of the global war on terror between 2001 and 2016 were eligible for inclusion; the final sample included 1,875,206 individuals surveilled through 2019. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: All-cause and cause-specific mortality rates. RESULTS: Overall, the number of deaths was over three times higher than expected among service members with amputations (SMR = 3.01; CI: 2.36-3.65), and nearly two times higher among those with serious limb injuries not resulting in amputation (SMR = 1.72; CI: 1.54-1.90) when compared to the larger study population. Rates for both internal and external causes of death were significantly elevated among those with limb injuries. CONCLUSIONS: Long-term mortality rates are elevated among service members with traumatic limb injuries, though mortality patterns may differ based on whether the injury results in amputation. Although further research into causal mechanisms is needed, these results may inform the development of interventions to improve long-term health outcomes among injured military personnel.

Associations of abdominal muscle area and density with coronary artery calcium volume and density: The multi-ethnic study of atherosclerosis.

BACKGROUND: Due to the opposing cardiovascular risk profiles of CAC volume and density, we tested the hypothesis that increased abdominal muscle area (AMA) and density (AMD) were significantly associated with lower coronary arterial calcium (CAC) volume and higher CAC density. METHODS: Using data from 787 participants from the Multi-Ethnic Study of Atherosclerosis, Ancillary Body Composition Study, we analyzed abdominal and chest computed tomography (CT) scans. Abdominal scans were scored for muscle area, muscle density (attenuation) and visceral and subcutaneous fat. Chest scans were scored for CAC volume and Agatston values, which were used to derive CAC density scores. RESULTS: The mean (SD) age and BMI of the participants was 67.8 (9.0) years and 27.9 (4.8) kg/m2, respectively. Forty-one percent were female, 46% were Caucasian, 60% had hypertension, 17% had diabetes, and 46% had dyslipidemia. AMA was positively associated with CAC volume (p < .001) and inversely associated with CAC density (p < .001). Conversely, AMD was inversely associated with CAC volume and positively associated with CAC density in minimally adjusted models (p < .001), but not significant in confounder adjusted models. CONCLUSION: AMA and AMD had differing associations with CAC volume and density, with AMA significantly associated with a higher risk CAC profile (high volume, low density) and AMD not significantly associated with CAC volume or density. Future research needs to account for the unique components of both muscle composition and CAC.

Associations of recreational and non-recreational physical activity with coronary artery calcium density vs. volume and cardiovascular disease events: the Multi-Ethnic Study of Atherosclerosis.

AIMS: The benefits of physical activity (PA) on cardiovascular disease (CVD) are well known. However, studies suggest PA is associated with coronary artery calcium (CAC), a subclinical marker of CVD. In this study, we evaluated the associations of self-reported recreational and non-recreational PA with CAC composition and incident CVD events. Prior studies suggest high CAC density may be protective for CVD events. METHODS AND RESULTS: We evaluated 3393 participants of the Multi-Ethnic Study of Atherosclerosis with prevalent CAC. After adjusting for demographics, the highest quintile of recreational PA was associated with 0.07 (95% confidence interval 0.01-0.13) units greater CAC density but was not associated with CAC volume. In contrast, the highest quintile of non-recreational PA was associated with 0.08 (0.02-0.14) units lower CAC density and a trend toward 0.13 (-0.01 to 0.27) log-units higher CAC volume. There were 520 CVD events over a 13.7-year median follow-up. Recreational PA was associated with lower CVD risk (hazard ratio 0.88, 0.79-0.98, per standard deviation), with an effect size that was not changed with adjustment for CAC composition or across levels of prevalent CAC. CONCLUSION: Recreational PA may be associated with a higher density but not a higher volume of CAC. Non-recreational PA may be associated with lower CAC density, suggesting these forms of PA may not have equivalent associations with this subclinical marker of CVD. While PA may affect the composition of CAC, the associations of PA with CVD risk appear to be independent of CAC.

The evolving view of coronary artery calcium and cardiovascular disease risk.

Calcification of the coronary artery is a complex pathophysiologic process that is intimately associated with atherosclerosis. Extensive investigation has demonstrated the value of identifying and quantifying coronary artery calcium (CAC) in atherosclerotic cardiovascular disease (CVD) prognostication. However, over the last several years, an increasing body of evidence has suggested that CAC has underappreciated aspects that modulate, and at times attenuate, future CVD risk. The most commonly used measure of CAC, the Agatston unit, effectively models both higher density and higher area of CAC as risk factors for future CVD events. Recent findings from the Multi-Ethnic Study of Atherosclerosis (MESA) have challenged this assumption, demonstrating that higher density of CAC is protective for coronary heart disease and CVD events. Statins may be associated with an increase in CAC, an unexpected finding given their clear benefits in the prevention and treatment of CVD. Studies utilizing intracoronary ultrasound and coronary computed tomography angiography have demonstrated that calcified atherosclerotic plaque-as compared with noncalcified or sparsely calcified plaque-is associated with fewer CVD events. These studies lend support to the often-asserted (but as yet unvalidated) view that calcification may play a role in plaque stabilization. Furthermore, vascular calcification, though a surrogate for atherosclerotic plaque burden, may also possess identifiable aspects that can refine CVD risk assessment.

Progression of calcium density in the ascending thoracic aorta is inversely associated with incident cardiovascular disease events.

Aims: Little is known regarding the risk of atherosclerotic cardiovascular disease (ASCVD) conferred by changes in the volume and density of ascending thoracic aorta calcium (ATAC) over time. We evaluated changes in ATAC volume and density scores and incident ASCVD events. Methods and results: The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of individuals without baseline clinical ASCVD. Ascending thoracic aorta calcium was measured from baseline and follow-up (mean interval 2.4 years) cardiac computed tomography (CT). Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) per standard deviation for events after the follow-up exam adjusted for ASCVD risk factors, baseline ATAC and coronary artery calcium (CAC) volume and density, and changes in CAC volume and density. Among 5887 participants, 296 (5.0%) had detectable ATAC at baseline, follow-up, or both exams. A total of 403 events occurred over 9.5 years. An increase in ATAC volume was associated with coronary heart disease (CHD) (HR 1.90, 95% CI 1.14-3.16), ASCVD (HR 1.93, 95% CI 1.26-2.94), and ischaemic stroke (HR 2.14, CI 1.21-3.78). An increase in ATAC density was inversely associated with CHD (HR 0.29, 95% CI 0.14-0.60) and ASCVD (HR 0.42, 95% CI 0.23-0.76), but not stroke (HR 0.61, CI 0.23-1.61). Conclusion: Ascending thoracic aorta calcium is uncommon on serial cardiac CT. However, changes in ATAC volume and density are both associated with incident ASCVD events, but in opposite directions. Serial assessments in those with baseline ATAC may provide insight into an individual's trajectory of ASCVD risk.

Association of cardiovascular disease risk factors with coronary artery calcium volume versus density.

OBJECTIVES: Recently, the density score of coronary artery calcium (CAC) has been shown to be associated with a lower risk of cardiovascular disease (CVD) events at any level of CAC volume. Whether risk factors for CAC volume and CAC density are similar or distinct is unknown. We sought to evaluate the associations of CVD risk factors with CAC volume and CAC density scores. METHODS: Baseline measurements from 6814 participants free of clinical CVD were collected for the Multi-Ethnic Study of Atherosclerosis. Participants with detectable CAC (n=3398) were evaluated for this study. Multivariable linear regression models were used to evaluate independent associations of CVD risk factors with CAC volume and CAC density scores. RESULTS: Whereas most CVD risk factors were associated with higher CAC volume scores, many risk factors were associated with lower CAC density scores. For example, diabetes was associated with a higher natural logarithm (ln) transformed CAC volume score (standardised ß=0.44 (95% CI 0.31 to 0.58) ln-units) but a lower CAC density score (ß=-0.07 (-0.12 to -0.02) density units). Chinese, African-American and Hispanic race/ethnicity were each associated with lower ln CAC volume scores (ß=-0.62 (-0.83to -0.41), -0.52 (-0.64 to -0.39) and -0.40 (-0.55 to -0.26) ln-units, respectively) and higher CAC density scores (ß= 0.41 (0.34 to 0.47), 0.18 (0.12 to 0.23) and 0.21 (0.15 to 0.26) density units, respectively) relative to non-Hispanic White. CONCLUSIONS: In a cohort free of clinical CVD, CVD risk factors are differentially associated with CAC volume and density scores, with many CVD risk factors inversely associated with the CAC density score after controlling for the CAC volume score. These findings suggest complex associations between CVD risk factors and these components of CAC.

Coronary Artery Calcium Volume and Density: Potential Interactions and Overall Predictive Value: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVES: This study sought to determine the possibility of interactions between coronary artery calcium (CAC) volume or CAC density with each other, and with age, sex, ethnicity, the new atherosclerotic cardiovascular disease (ASCVD) risk score, diabetes status, and renal function by estimated glomerular filtration rate, and, using differing CAC scores, to determine the improvement over the ASCVD risk score in risk prediction and reclassification. BACKGROUND: In MESA (Multi-Ethnic Study of Atherosclerosis), CAC volume was positively and CAC density inversely associated with cardiovascular disease (CVD) events. METHODS: A total of 3,398 MESA participants free of clinical CVD but with prevalent CAC at baseline were followed for incident CVD events. RESULTS: During a median 11.0 years of follow-up, there were 390 CVD events, 264 of which were coronary heart disease (CHD). With each SD increase of ln CAC volume (1.62), risk of CHD increased 73% (p < 0.001) and risk of CVD increased 61% (p < 0.001). Conversely, each SD increase of CAC density (0.69) was associated with 28% lower risk of CHD (p < 0.001) and 25% lower risk of CVD (p < 0.001). CAC density was inversely associated with risk at all levels of CAC volume (i.e., no interaction was present). In multivariable Cox models, significant interactions were present for CAC volume with age and ASCVD risk score for both CHD and CVD, and CAC density with ASCVD risk score for CVD. Hazard ratios were generally stronger in the lower risk groups. Receiver-operating characteristic area under the curve and Net Reclassification Index analyses showed better prediction by CAC volume than by Agatston, and the addition of CAC density to CAC volume further significantly improved prediction. CONCLUSIONS: The inverse association between CAC density and incident CHD and CVD events is robust across strata of other CVD risk factors. Added to the ASCVD risk score, CAC volume and density provided the strongest prediction for CHD and CVD events, and the highest correct reclassification.

Race/ethnic and sex disparities in the non-alcoholic fatty liver disease-abdominal aortic calcification association: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: This study investigated the associations of non-alcoholic fatty liver disease (NAFLD) and abdominal aortic calcification (AAC) volume and density, and whether these relationships vary by race/ethnicity and/or sex, information that are limited in current literature. METHODS: We studied 1004 adults from the Multi-Ethnic Study of Atherosclerosis to assess the relationship between NAFLD (liver-to-spleen ratio <1) and the following measures of AAC: presence (volume score >0, using Poisson regression); change in volume score (increasing vs. no change, using Poisson regression); and morphology (volume and density score, where volume score >0, using linear regression); and interaction by race/ethnicity and sex. RESULTS: Among Blacks, those with NAFLD had greater prevalence for AAC compared to Whites regardless of sex (Prevalence Ratio [PR] = 1.41, CI = 1.15-1.74, p-interaction = 0.02). Concurrent interaction by race/ethnicity and sex was found comparing Chinese and Blacks to Whites (p-interaction = 0.017 and 0.042, respectively) in the association between NAFLD and the prevalence of increasing AAC. Among women, this relationship was inverse among Chinese (PR = 0.59, CI = 0.28-1.27), and positive among Whites (PR = 1.34, CI = 1.02-1.76). This finding was reversed evaluating the men counterpart. Black men also had a positive association (PR = 1.86, CI = 1.29-2.70), which differed from the inverse relationship among White men, and was greater compared to Black women (PR = 1.45, CI = 1.09-1.94). NAFLD was unrelated to AAC morphology. CONCLUSIONS: NAFLD was related to the presence of AAC, however, limited to Blacks. Significant concurrent interaction by race/ethnicity (Chinese and Blacks vs. Whites) and sex was found in the relationship between NAFLD and increasing AAC. These findings suggest disparities in the pathophysiologic pathways in which atherosclerosis develops.

Density of calcium in the ascending thoracic aorta and risk of incident cardiovascular disease events.

BACKGROUND AND AIMS: The volume and density of coronary artery calcium (CAC) both independently predict cardiovascular disease (CVD) beyond standard risk factors, with CAC density inversely associated with incident CVD after accounting for CAC volume. We tested the hypothesis that ascending thoracic aorta calcium (ATAC) volume and density predict incident CVD events independently of CAC. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of participants without clinical CVD at baseline. ATAC and CAC were measured from baseline cardiac computed tomography (CT). Cox regression models were used to estimate the associations of ATAC volume and density with incident coronary heart disease (CHD) events and CVD events, after adjustment for standard CVD risk factors and CAC volume and density. RESULTS: Among 6811 participants, 234 (3.4%) had prevalent ATAC and 3395 (49.8%) had prevalent CAC. Over 10.3 years, 355 CHD and 562 CVD events occurred. One-standard deviation higher ATAC density was associated with a lower risk of CHD (HR 0.48 [95% CI 0.29-0.79], p<0.01) and CVD (HR 0.56 [0.37-0.84], p<0.01) after full adjustment. ATAC volume was not associated with outcomes after full adjustment. CONCLUSIONS: ATAC was uncommon in a cohort free of clinical CVD at baseline. However, ATAC density was inversely associated with incident CHD and CVD after adjustment for CVD risk factors and CAC volume and density.

Femoral Artery Atherosclerosis Is Associated With Physical Function Across the Spectrum of the Ankle-Brachial Index: The San Diego Population Study.

BACKGROUND: The ankle-brachial index (ABI) is inadequate to detect early-stage atherosclerotic disease, when interventions to prevent functional decline may be the most effective. We determined associations of femoral artery atherosclerosis with physical functioning, across the spectrum of the ABI, and within the normal ABI range. METHODS AND RESULTS: In 2007-2011, 1103 multiethnic men and women participated in the San Diego Population Study, and completed all components of the summary performance score. Using Doppler ultrasound, superficial and common femoral intima media thickness and plaques were ascertained. Logistic regression was used to assess associations of femoral atherosclerosis with the summary performance score and its individual components. Models were adjusted for demographics, lifestyle factors, comorbidities, lipids, and kidney function. In adjusted models, among participants with a normal-range ABI (1.00-1.30), the highest tertile of superficial intima media thickness was associated with lower odds of a perfect summary performance score of 12 (odds ratio=0.56 [0.36, 0.87], P=0.009), and lower odds of a 4-m walk score of 4 (0.34 [0.16, 0.73], P=0.006) and chair rise score of 4 (0.56 [0.34, 0.94], P=0.03). Plaque presence (0.53 [0.29, 0.99], P=0.04) and greater total plaque burden (0.61 [0.43, 0.87], P=0.006) were associated with worse 4-m walk performance in the normal-range ABI group. Higher superficial intima media thickness was associated with lower summary performance score in all individuals (P=0.02). CONCLUSIONS: Findings suggest that use of femoral artery atherosclerosis measures may be effective in individuals with a normal-range ABI, especially, for example, those with diabetes mellitus or a family history of peripheral artery disease, when detection can lead to earlier intervention to prevent functional declines and improve quality of life.

Lower Aorto-Iliac Bifurcation Position and Incident Cardiovascular Disease: A Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: With increasing age, a downward shift of the aorto-iliac bifurcation relative to the lumbar spine occurs. A lower bifurcation position is an independent marker for adverse vascular aging and is associated with increased burden of cardiovascular disease (CVD) risk factors; however, the associations between lower bifurcation position and CVD events remain unknown. METHODS: Abdominal computed tomography scans were used to measure the aorto-iliac bifurcation distance (AIBD, distance from the aorto-iliac bifurcation to the L5/S1 disc space). Cox proportional hazard analysis was used to determine the independent hazard of a lower bifurcation position (smaller AIBD) for incident coronary heart disease (CHD, defined as myocardial infarction, resuscitated cardiac arrest, or sudden cardiac death), CVD (CHD plus stroke or stroke death), and all-cause mortality (ACM). RESULTS: In the 1,711 study participants (51% male), the mean AIBD was 26 ± 15 mm. After a median follow-up of 10 years, 63 (3.7%) developed CHD, 100 (5.8%) developed CVD, and 129 (7.5%) were deceased. Compared to the 4th quartile of AIBD (highest bifurcation position), participants in the 1st quartile (lowest bifurcation position) had increased risk for CHD (hazard ratio (HR) = 1.5, 95% confidence interval (CI): 0.8-3.0, P = 0.2), CVD (HR = 1.8, 95% CI: 0.9-2.7, P = 0.1), and ACM (HR = 2.2, 95% CI: 1.3-3.6, P = 0.01). After adjustments for CVD risk factors, the HR for ACM was no longer significant. CONCLUSION: Despite being an independent marker for adverse vascular changes in the aorta, a lower aorto-iliac bifurcation position was not independently associated with future CVD events. The opposing effects of atherosclerosis and stiffness in the aorta may, in part, explain our null findings.

Peripheral Artery Disease and Aortic Disease.

We reviewed published MESA (Multi-Ethnic Study of Atherosclerosis) study articles concerning peripheral arterial disease, subclavian stenosis (SS), abdominal aortic calcium (AAC), and thoracic artery calcium (TAC). Important findings include, compared to non-Hispanic whites, lower ankle-brachial index (ABI) and more SS in African Americans, and higher ABI and less SS in Hispanic and Chinese Americans. Abnormal ABI and brachial pressure differences were associated with other subclinical cardiovascular disease (CVD) measures. Both very high and low ABI independently predicted increased CVD events. Looking at aortic measures, TAC and AAC were significantly associated with other subclinical CVD measures. Comparisons of AAC with coronary artery calcium (CAC) showed that both were less common in ethnic minority groups. However, although CAC was much more common in men than in women in multivariable analysis, this was not true of AAC. Also, when AAC and CAC were adjusted for each other in multivariable analysis, there was a stronger association for AAC than for CAC with CVD and total mortality.