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BackgroundThere are multiple predictive factors for cardiovascular (CV) mortality measured at, or after heart failure (HF) diagnosis. However, the predictive role of long-term exposure to these predictors prior to HF diagnosis is unknown.ObjectivesWe aim to identify predictive factors of CV mortality in participants with HF, using cumulative exposure to risk factors before HF development.MethodsParticipants of Multi-Ethnic Study of Atherosclerosis (MESA) with incident HF were included. We used stepwise Akaike Information Criterion to select CV mortality predictors among clinical, biochemical, and imaging markers collected prior to HF. Using the AUC of B-spline-corrected curves, we estimated cumulative exposure to predictive factors from baseline to the last exam before HF. The prognostic performance for CV mortality after HF was evaluated using competing risk regression with non-CV mortality as the competing risk.ResultsOverall, 375 participants had new HF events (42.9% female, mean age: 74). Over an average follow-up of 4.7 years, there was no difference in the hazard of CV death for HF with reduced versus preserved ejection fraction (HR = 1.27, p = 0.23). The selected predictors of CV mortality in models with the least prediction error were age, cardiac arrest, myocardial infarction, and diabetes, QRS duration, HDL, cumulative exposure to total cholesterol and glucose, NT-proBNP, left ventricular mass, and statin use. The AUC of the models were 0.72 when including the latest exposure to predictive factors and 0.79 when including cumulative prior exposure to predictive factors (p = 0.20).ConclusionIn HF patients, besides age and diagnosed diabetes or CVD, prior lipid profile, NT-proBNP, LV mass, and QRS duration available at the diagnosis time strongly predict CV mortality. Implementing cumulative exposure to cholesterol and glucose, instead of latest measures, improves predictive accuracy for HF mortality, though not reaching statistical significance.

ABSTRACT Studies on associations between biomarkers of vitamin D metabolism and fracture risk have focused predominantly on White or elderly populations and may not be generalizable to relatively healthy multiethnic populations. We tested associations of total 25‐hydroxyvitamin D (25[OH]D), the ratio of 24,25‐dihydroxyvitamin D3 to 25‐hydroxyvitamin D3 (vitamin D metabolite ratio, VDMR), parathyroid hormone (PTH), and fibroblast growth factor‐23 (FGF‐23) concentrations measured in serum with risk of hip and vertebral fractures in the Multi‐Ethnic Study of Atherosclerosis (MESA). Serum 25‐hydroxyvitamin D2 and D3 and 24,25‐dihydroxyvitamin D3 were measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The study cohort of 6466 participants was without clinically apparent cardiovascular disease and was 39% White, 27% Black, 22% Hispanic, and 12% Chinese. The mean age was 62 years, and 53% were female. There were 128 hip and vertebral fractures over a mean follow‐up of 14.2 years. 25(OH)D, the VDMR, PTH, and FGF‐23 were not significantly associated with fracture risk after adjustment for demographics, diabetes, smoking, systolic blood pressure, body mass index, medication use, albuminuria, and estimated glomerular filtration rate. Principal component analysis did not suggest differences in linear combinations of 25(OH)D, the VDMR, PTH, and FGF‐23 between participants who experienced fractures and those who did not. We did not observe significant interaction between race and ethnicity and any biomarker of vitamin D metabolism on fracture risk. In conclusion, none of the four serum biomarkers of vitamin D metabolism investigated showed a significant association with fracture risk in relatively healthy multiethnic populations. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Background Atrial fibrillation (AF) is associated with increased stroke risk and accelerated cognitive decline, but the association of early manifestations of left atrial (LA) impairment with subclinical changes in brain structure is unclear. We investigated whether abnormal LA structure and function, greater supraventricular ectopy, and intermittent AF are associated with small vessel disease on magnetic resonance imaging of the brain. Methods and Results In the Multi‐Ethnic Study of Atherosclerosis, 967 participants completed 14‐day ambulatory electrocardiographic monitoring, speckle tracking echocardiography and, a median 17 months later, magnetic resonance imaging of the brain. We assessed associations of LA volume index and reservoir strain, supraventricular ectopy, and prevalent AF with brain magnetic resonance imaging measures of small vessel disease and atrophy. The mean age of participants was 72 years; 53% were women. In multivariable models, LA enlargement was associated with lower white matter fractional anisotropy and greater prevalence of microbleeds; reduced LA strain, indicating worse LA function, was associated with more microbleeds. More premature atrial contractions were associated with lower total gray matter volume. Compared with no AF, intermittent AF (prevalent AF with

Background Cardiovascular risk factors are associated with cognitive decline and dementia. Magnetic resonance imaging provides sensitive measurement of brain morphology and vascular brain injury. However, associations of risk factors with brain magnetic resonance imaging findings have largely been studied in White participants. We investigated associations of race, ethnicity, and cardiovascular risk factors with brain morphology and white matter (WM) injury in a diverse population. Methods and Results In the Multi‐Ethnic Study of Atherosclerosis, measures were made in 2018 to 2019 of total brain volume, gray matter and WM volume, and WM injury, including WM hyperintensity volume and WM fractional anisotropy. We assessed cross‐sectional associations of race and ethnicity and of cardiovascular risk factors with magnetic resonance imaging measures. Magnetic resonance imaging data were complete in 1036 participants; 25% Black, 15% Chinese‐American, 19% Hispanic, and 41% White. Mean (SD) age was 72 (8) years and 53% were women. Although WM injury was greater in Black than in White participants in a minimally adjusted model, additional adjustment for cardiovascular risk factors and socioeconomic status each attenuated this association, rendering it nonsignificant. Overall, greater average WM hyperintensity volume was associated with older age and current smoking (69% greater vs never smoking); lower fractional anisotropy was additionally associated with higher diastolic blood pressure, use of antihypertensive medication, and diabetes. Conclusions We found no statistically significant difference in measures of WM injury by race and ethnicity after adjustment for cardiovascular risk factors and socioeconomic status. In all racial and ethnic groups, older age, current smoking, hypertension, and diabetes were strongly associated with WM injury.