Determinants of Incident Atherosclerotic Cardiovascular Disease Events Among Those With Absent Coronary Artery Calcium: Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The 2018 American Heart Association/American College of Cardiology/Multisociety cholesterol guideline states that statin therapy may be withheld or delayed among intermediate-risk individuals in the absence of coronary artery calcium (CAC=0). We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) events among individuals with CAC=0 over long-term follow-up. METHODS: We included participants with CAC=0 at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of clinical ASCVD at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors (cigarette smoking, diabetes, hypertension, preventive medication use [aspirin and statin], family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers) and adjudicated incident ASCVD outcomes. RESULTS: We studied 3416 individuals (mean [SD] age 58 [9] years; 63% were female, 33% White, 31% Black, 12% Chinese American, and 24% Hispanic). Over a median follow-up of 16 years, there were 189 ASCVD events (composite of coronary heart disease and stroke) of which 91 were coronary heart disease, 88 were stroke, and 10 were both coronary heart disease and stroke events. The unadjusted event rates of ASCVD were ≤5 per 1000 person-years among individuals with CAC=0 for most risk factors with the exception of current cigarette smoking (7.3), diabetes (8.9), hypertension (5.4), and chronic kidney disease (6.8). After multivariable adjustment, risk factors that were significantly associated with ASCVD included current cigarette smoking: hazard ratio, 2.12 (95% CI, 1.32-3.42); diabetes: hazard ratio, 1.68 (95% CI, 1.01-2.80); and hypertension: hazard ratio, 1.57 (95% CI, 1.06-2.33). CONCLUSIONS: Current cigarette smoking, diabetes, and hypertension are independently associated with incident ASCVD over a 16-year follow-up among those with CAC=0.

Associations of Vitamin D-Binding Globulin and Bioavailable Vitamin D Concentrations With Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA).

Context: Low 25-hydroxyvitamin D [25(OH)D] is associated with coronary heart disease (CHD) in people who are white and Chinese but not black or Hispanic. Vitamin D binding globulin (VDBG) avidly binds 25(OH)D, reducing its bioavailability, and differs in isoform and concentration by race. Objective: Evaluate associations of VDBG with CHD and whether accounting for VDBG or estimating bioavailable 25(OH)D explains the heterogeneity of the association of 25(OH)D with CHD. Design and Setting: We conducted a case-cohort study within the Multi-Ethnic Study of Atherosclerosis. Participants with an incident CHD event over 12 years of follow-up (n = 538) and a randomly assigned subcohort (n = 999) were included. We measured baseline 25(OH)D, VDBG, and isoforms using mass spectrometry and estimated bioavailable 25(OH)D from published equations. Results: VDBG was associated with an increased risk of CHD [hazard ratio, 1.77 (95% confidence interval, 1.46 to 2.14) per standard deviation increment, P < 0.0001], without evidence of heterogeneity by race or isoform (each P for interaction > 0.1). Low total 25(OH)D was differentially associated with CHD events, by race, with or without adjustment for VDBG (P for interaction = 0.04 or 0.05, respectively). Associations of 25(OH)D with CHD were strengthened with adjustment for VDBG among participants who were white or Chinese, and bioavailable 25(OH)D was associated with CHD events only among white participants. Conclusions: High VDBG concentration was associated with CHD events in all racial and ethnic groups. Incorporation of VDBG strengthened existing associations of 25(OH)D with CHD but did not explain racial heterogeneity in associations of 25(OH)D with CHD.

Sleep Disturbances and Depression in the Multi-Ethnic Study of Atherosclerosis.

STUDY OBJECTIVES: We examined the association of objectively and subjectively measured sleep disturbances with depression, and explored if race/ethnicity, socioeconomic status, and sex modified these associations. METHODS: We used data from the cross-sectional Multi-Ethnic Study of Atherosclerosis Sleep Study. Participants included 1,784 adults (ages 54-93 y), 36.8% non-Hispanic Whites, 28.0% African Americans, 23.7% Hispanics, 11.5% Chinese, and 46.0% males. Sleep was assessed with actigraphy, polysomnography, and self-report. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. We used relative risk regression to evaluate the association of sleep measures and depression (CES-D score ≥ 16) adjusting for site, sociodemographics, and behavioral and medical risk factors. RESULTS: Overall, 14.5% had depression, 29.3% had insomnia symptoms, 14.1% had excessive daytime sleepiness (EDS), 15.1% had apnea-hypopnea index (AHI) ≥ 30, and 30.4% experienced short sleep (< 6 h). Depression was associated with short sleep duration (adjusted prevalence ratio [PR] = 1.47, 95% confidence interval [CI] = 1.11, 1.94), < 10% rapid eye movement [REM] sleep (PR = 1.57, 95% CI = 1.08, 2.27), ≥ 25% REM sleep (PR = 1.42, 95% CI = 1.03, 1.95), insomnia (PR = 1.83, 95% CI = 1.39, 2.40), excessive daytime sleepiness (EDS) (PR = 1.61, 95% CI = 1.19, 2.18), and AHI > 15 + EDS (PR = 1.55, 95% CI = 1.01, 2.39). Short sleep duration was associated with depression among those with high school education or beyond, but not among those with less education. Insomnia was more strongly associated with depression among men than women. CONCLUSIONS: Sleep disturbances are associated with depression among middle-aged and older adults; these associations may be modified by education and sex. Future research should further test these hypotheses, evaluate whether early detection or treatment of sleep disturbances ameliorate depression, and explore subpopulation differences.