Matthew Jay Budoff

OBJECTIVES: To assess coronary plaque burden in Los Angeles Fire Department firefighters compared to matched control subjects. METHODS: 302 LAFD subjects matched 1:1 with control subjects. Coronary artery calcium imaging, coronary computed tomography angiography, and AI-assisted quantitative plaque analysis compared coronary plaque burden between groups. 62 underwent follow-up CCTA. RESULTS: The LAFD cohort had significantly higher total plaque volume (138 vs 84 mm³), non-calcified plaque volume (108 vs 73 mm³), percent atheroma volume (3.5% vs 2.3%), and prevalence of low-density plaque (31% vs 19%), all p ≤ 0.01. In the serial-CCTA subset, annualized progression of total plaque volume, calcified plaque, and percent atheroma volume was significantly higher than NATURE-CT. CONCLUSIONS: These findings reveal an elevated burden and accelerated progression of coronary plaque in LAFD firefighters, emphasizing the need for comprehensive cardiovascular risk assessment and prevention strategies.

BACKGROUND: Coronary artery calcium (CAC) scoring is a useful tool for coronary heart disease (CHD) risk prediction. The current standard method, the Agatston score, weights plaque area upward by density. However, higher density is inversely associated with CHD. We aimed to develop and validate a CAC score accounting for the inverse association of density with CHD, and the nonlinear association between CAC volume and density in a prospective cohort study. METHODS: A CAC volume and density score was developed, which adjusts CAC volume for density based on whether the volume level was 0 and follow-up for CHD events. Score performance for CHD risk prediction was compared with the pooled cohort equations and the Agatston score using Cox proportional hazards models and Harrell C -index and continuous and categorical net reclassification improvement. Analyses were also stratified by Agatston score, age, sex, race/ethnicity, and statin use. Finally, performance was evaluated in 4 longitudinal cohorts for external validation. RESULTS: The MESA cohort included 3360 individuals. CAC volume and density score improved the C -index for CHD to a greater degree over the pooled cohort equation (0.699 [95% CI, 0.675–0.723]) compared with the Agatston score (0.687 [95% CI, 0.663–0.711]) and resulted in greater continuous net reclassification improvement (0.54 [95% CI, 0.43–0.64]) compared with the Agatston score (0.45 [95% CI, 0.34–0.56]) when added to the pooled cohort equation. The greatest improvement in risk prediction was in those with lower burden of CAC (Agatston <300). Consistent results were seen in stratified analyses and external validation cohorts. CONCLUSIONS: The CAC volume and density score, which adjusts CAC volume downward for higher density, and can be calculated from existing CAC reports, significantly improves risk discrimination and reclassification compared with the Agatston score.

Background: Aortic valve calcification (AVC) and mitral annual calcification (MAC) may progress to aortic and mitral stenosis in older adults. The role of major mineralization regulators MGP (matrix Gla protein), FGF‐23 (fibroblast growth factor‐23), and fetuin‐A in long‐term progression of AVC and MAC remains unexamined. Methods: We measured blood levels of dp‐ucMGP (n=2663) at study baseline and evaluated these concurrently with prior baseline measures of FGF‐23 (n=6547) and fetuin‐A (n=2550) in relation to AVC and MAC quantified on ≤3 serial computed tomography scans over 9.4 (interquartile range, 9.0–9.8) years in MESA (Multi‐Ethnic Study of Atherosclerosis). We used linear mixed‐effects models to simultaneously assess the incidence and progression of AVC and MAC. Results: Our objective was to investigate the association of circulating dephosphorylated–uncarboxylated (dp‐uc) MGP, reflecting vitamin K deficiency/diminished MGP anticalcific capacity; FGF‐23, a phosphaturic hormone; and fetuin‐A, a calcium‐phosphate solubilizer, with long‐term incidence and progression of AVC and MAC. After adjustment for demographic and clinical characteristics, dp‐ucMGP was associated with higher annual incidence/progression of AVC (0.94 [95% CI, 0.42, 1.46] Agatston units/y) and MAC (3.90 [95% CI, 1.06, 6.74] Agatston units/y); FGF‐23 with higher annual incidence/progression of MAC (2.61 [95% CI, 0.50, 4.72] Agatston units/y); and fetuin‐A with lower annual incidence/progression of AVC (−0.89 [95% CI, −1.55, −0.23] Agatston units/y (all per SD increment in regulator). Conclusions: In this multiethnic sample, dp‐ucMGP and FGF‐23 were associated with higher, and fetuin‐A with lower, long‐term incidence/progression of valvular or annular calcification. This has implications for therapeutic trials of calcific valvular disease, particularly targeting vitamin K supplementation to individuals with higher dp‐ucMGP levels.

Objective: To investigate whether coronary artery calcium (CAC) modifies the association between hormone therapy (HT) use and cardiovascular disease (CVD) events. Methods: A total of 3,235 female participants free of clinical CVD at baseline were included from the Multi-Ethnic Study of Atherosclerosis and monitored for incident CVD. HT status was self-reported and categorized as never, former, and current users. Cox proportional hazards regression models were fit to examine the relationships between HT and CVD outcomes, with and without CAC (as categories), including standard risk factors as covariates. Results: Participants were 63.4 ± 9.8 years of age, and 90% were postmenopausal. There were 1,024 (32%) current, 1,618 (50%) never, and 593 (18%) former HT users. Current HT users were significantly younger, more likely to be White, had lower prevalence of diabetes mellitus, and higher education and income levels. During the 14.4-year follow-up period, 734 deaths (14.8 per 1000 person-years) and 454 CVD events (10.1 per 1000 person-years) were identified. In multivariable Cox regression analysis including CAC, current HT use versus never use was associated with lower risk for all-cause death (hazard ratio [HR]: 0.70, 95% CI: 0.58-0.86) and in current versus former users (HR: 0.77, 95% CI: 0.61-0.98). Former users did not differ significantly from never users in risk of death or cardiovascular outcomes. Addition of CAC to adjusted models did not meaningfully modify the association between HT status and all-cause death (HR: without CAC: 0.69 [0.57-0.85]; HR with CAC: 0.70 [0.58-0.86]). Conclusions: Women who received HT have a significantly lower risk of all-cause death compared with never and former users, with CVD and coronary heart disease outcomes trending lower but not reaching statistical significance after adjustment. CAC did not modify the observed association between HT and mortality.

Lower vertebral bone mineral density from chest CT was associated with modestly accelerated white matter injury and cognitive decline, particularly among participants with diabetes, suggesting utility for detecting accelerated brain aging.

Paraspinal muscle attenuation at opportunistic noncontrast chest CT helps predict longitudinal thoracic vertebral bone mineral density loss beyond clinical risk factors in the Multi-Ethnic Study of Atherosclerosis.