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Importance: Familial hypercholesterolemia (FH) is a genetic disorder that often results in severely high low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). However, the impact of FH variants on CHD risk among individuals with moderately elevated LDL-C is not well quantified., Objective: To assess CHD risk associated with FH variants among individuals with moderately (130-189 mg/dL) and severely (≥190 mg/dL) elevated LDL-C and to quantify excess CHD deaths attributable to FH variants in US adults., Design, Setting, and Participants: A total of 21 426 individuals without preexisting CHD from 6 US cohort studies (Atherosclerosis Risk in Communities study, Coronary Artery Risk Development in Young Adults study, Cardiovascular Health Study, Framingham Heart Study Offspring cohort, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis) were included, 63 of whom had an FH variant. Data were collected from 1971 to 2018, and the median (IQR) follow-up was 18 (13-28) years. Data were analyzed from March to May 2023., Exposures: LDL-C, cumulative past LDL-C, FH variant status., Main Outcomes and Measures: Cox proportional hazards models estimated associations between FH variants and incident CHD. The Cardiovascular Disease Policy Model projected excess CHD deaths associated with FH variants in US adults., Results: Of the 21 426 individuals without preexisting CHD (mean [SD] age 52.1 [15.5] years; 12 041 [56.2%] female), an FH variant was found in 22 individuals with moderately elevated LDL-C (0.3%) and in 33 individuals with severely elevated LDL-C (2.5%). The adjusted hazard ratios for incident CHD comparing those with and without FH variants were 2.9 (95% CI, 1.4-6.0) and 2.6 (95% CI, 1.4-4.9) among individuals with moderately and severely elevated LDL-C, respectively. The association between FH variants and CHD was slightly attenuated when further adjusting for baseline LDL-C level, whereas the association was no longer statistically significant after adjusting for cumulative past LDL-C exposure. Among US adults 20 years and older with no history of CHD and LDL-C 130 mg/dL or higher, more than 417 000 carry an FH variant and were projected to experience more than 12 000 excess CHD deaths in those with moderately elevated LDL-C and 15 000 in those with severely elevated LDL-C compared with individuals without an FH variant., Conclusions and Relevance: In this pooled cohort study, the presence of FH variants was associated with a 2-fold higher CHD risk, even when LDL-C was only moderately elevated. The increased CHD risk appeared to be largely explained by the higher cumulative LDL-C exposure in individuals with an FH variant compared to those without. Further research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening.

Background: Cancer survivors may have elevated atherosclerotic cardiovascular disease (ASCVD) risk. Therefore, we tested how accurately the American College of Cardiology/American Heart Association 2013 pooled cohort equations (PCEs) predict 10-year ASCVD risk in cancer survivors., Objectives: To estimate the calibration and discrimination of the PCEs in cancer survivors compared to non-cancer participants in the Atherosclerosis Risk in Communities (ARIC) study., Methods: We evaluated the PCEs' performance among 1244 cancer survivors and 3849 cancer-free participants who were free of ASCVD at the start of follow-up. Each cancer survivor was incidence-density matched with up to five controls by age, race, sex, and study center. Follow-up began at the first study visit at least 1 year after the diagnosis date of the cancer survivor and finished at the ASCVD event, death, or end of follow-up. Calibration and discrimination were assessed and compared between cancer survivors and cancer-free participants., Results: Cancer survivors had higher PCE-predicted risk, at 26.1%, compared with 23.1% for cancer-free participants. There were 110 ASCVD events in cancer survivors and 332 ASCVD events in cancer-free participants. The PCEs overestimated ASCVD risk in cancer survivors and cancer-free participants by 45.6% and 47.4%, respectively, with poor discrimination in both groups (C-statistic for cancer survivors = 0.623; for cancer-free participants, C = 0.671)., Conclusions: The PCEs overestimated ASCVD risk in all participants. The performance of the PCEs was similar in cancer survivors and cancer-free participants., Implications for Cancer Survivors: Our findings suggest that ASCVD risk prediction tools tailored to survivors of adult cancers may not be needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Management of orthostatic hypotension (OH) prioritizes prevention of standing hypotension, sometimes at the expense of supine hypertension. It is unclear whether supine hypertension is associated with adverse outcomes relative to standing hypotension., Objectives: To compare the long-term clinical consequences of supine hypertension and standing hypotension among middle-aged adults with and without OH., Methods: The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure (BP) in adults aged 45 to 64 years, without neurogenic OH, between 1987 and 1989. We defined OH as a positional drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg, supine hypertension as supine BP≥140/≥90 mm Hg, and standing hypotension as standing BP≤105/≤65 mm Hg. Participants were followed for >30 years. We used Cox regression models to examine associations with cardiovascular disease events, all-cause mortality, falls, and syncope., Results: Of 12 489 participants (55% female, 26% Black, mean age 54 years, SD 6), 4.4% had OH. Among those without OH (N=11 943), 19% had supine hypertension and 21% had standing hypotension, while among those with OH (N=546), 58% had supine hypertension and 38% had standing hypotension. Associations with outcomes did not differ by OH status ( P -interactions >0.25). Supine hypertension was associated with heart failure (hazard ratio, 1.83 [95% CI, 1.68-1.99]), falls (hazard ratio, 1.12 [95% CI, 1.02-1.22]), and all-cause mortality (hazard ratio, 1.45 [95% CI, 1.37-1.54]), while standing hypotension was only significantly associated with mortality (hazard ratio, 1.06 [95% CI, 1.00-1.14])., Conclusions: Supine hypertension was associated with higher risk of adverse events than standing hypotension, regardless of OH status. This challenges conventional OH management, which prioritizes standing hypotension over supine hypertension., Competing Interests: Disclosures None.

Objective: To assess the association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and other second-line diabetes therapies with risk of cardiovascular disease (CVD), as well as conduct head-to-head comparisons between SGLT2 inhibitors., Patients and Methods: Using data from the MarketScan databases (January 1, 2013, through December 31, 2019), SGLT2 inhibitor users were matched with up to five other second-line therapy users by age, sex, date of enrollment, and date of second-line therapy initiation. The primary composite outcome included stroke, atrial fibrillation, myocardial infarction, and heart failure. Hazard ratios were estimated, adjusting for demographics and a propensity score reflecting comorbidities and medications., Results: In this study population of 313,396 patients (mean age 53±10 years; 47% female), 9787 incident CVD events occurred over a median follow-up of 1.36 years. After multivariable adjustments, SGLT2 inhibitor users had a lower risk of CVD than other second-line therapy users (HR, 0.66; 95% CI, 0.62 to 0.71). Significant associations were also observed when each CVD outcome was assessed separately. No differences were noted when comparing individual SGLT2 inhibitors., Conclusion: SGLT2 inhibitors were associated with a clinically meaningfully lower CVD risk in the real-world setting. In head-to-head comparisons, the different SGLT2 inhibitors were consistent in their protective associations with CVD. This suggests that as a class, SGLT2 inhibitors may have widespread benefit in preventing CVD among patients with type 2 diabetes., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Introduction: We evaluated whether better cardiovascular health at midlife and improvement of cardiovascular health within midlife were associated with dementia risk., Methods: Two longitudinal population-based studies were used: Atherosclerosis Risk in Communities (ARIC) (n = 11,460/visits at ages 54 and 60), and Age, Gene/Environment Susceptibility (AGES)-Reykjavik (n = 3907/visit at age 51). A cardiovascular health score (range 0-12/0-14, depending on diet availability) including six/seven items was calculated at each visit, with weight assigned to each item as poor (0), intermediate (1), or ideal (2). Cardiovascular health was defined as low (score 0-4/0-5), intermediate (5-7/6-9), or high (8-12/10-14). Incident dementia was ascertained through linkage to health records and with neuropsychological examinations., Results: Midlife high compared to low cardiovascular health (hazard ratios [HRs]: for ARIC: 0.60 [95% confidence interval: 0.52, 0.69]); for AGES-Reykjavik: 0.83 [0.66, 0.99] and improvement of cardiovascular health score within midlife (HR per one-point increase: ARIC: 0.94 [0.92, 0.96]) were associated with lower dementia risk., Discussion: Better cardiovascular health at midlife and improvement of cardiovascular health within midlife are associated with lower dementia risk., Highlights: Cardiovascular health and dementia were studied in two large cohort studies. Better cardiovascular health at midlife relates to lower dementia risk. Improvement of cardiovascular health within midlife relates to lower dementia risk. Promotion of cardiovascular health at midlife can help to reduce dementia risk., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background Sleep irregularity has been linked to incident cardiovascular disease. Less is known about associations of sleep regularity with atherosclerosis. We examined cross-sectional associations of actigraphy-assessed sleep duration and sleep timing regularity with subclinical atherosclerosis in the community-based MESA (Multi-Ethnic Study of Atherosclerosis). Methods and Results MESA Sleep Ancillary Study participants (N=2032; mean age, 68.6±9.2 years; 37.9% White) completed 7-day wrist actigraphy. Participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and the ankle-brachial index. Sleep regularity was quantified by the 7-day with-in person SD of sleep duration and sleep onset timing. Relative risk regression models were used to calculate prevalence ratios and 95% CIs. Models are adjusted for demographics, cardiovascular disease risk factors, and other objectively assessed sleep characteristics including obstructive sleep apnea, sleep duration, and sleep fragmentation. After adjustment, compared with participants with more regular sleep durations (SD ≤60 minutes), participants with greater sleep duration irregularity (SD >120 minutes) were more likely to have high coronary artery calcium burden (>300; prevalence ratio, 1.33 [95% CI, 1.03-1.71]) and abnormal ankle-brachial index (<0.9; prevalence ratio, 1.75 [95% CI, 1.03-2.95]). Compared with participants with more regular sleep timing (SD ≤30 minutes), participants with irregular sleep timing (SD >90 minutes) were more likely to have high coronary artery calcium burden (prevalence ratio, 1.39 [95% CI, 1.07-1.82]). Associations persisted after adjustment for cardiovascular disease risk factors and average sleep duration, obstructive sleep apnea, and sleep fragmentation. Conclusions Sleep irregularity, particularly sleep duration irregularity, was associated with several measures of subclinical atherosclerosis. Sleep regularity may be a modifiable target for reducing atherosclerosis risk. Future investigation into cardiovascular risk reduction interventions targeting sleep irregularity may be warranted.

Background: Statins are prescribed to reduce LDL-c and risk of CVD. Statins have pleiotropic effects, affecting pathophysiological functions beyond LDL-c reduction. We compared the proteome of statin users and nonusers (controls). We hypothesized that statin use is associated with proteins unrelated to lipid metabolism., Methods: Among 10,902 participants attending ARIC visit 3 (1993-95), plasma concentrations of 4955 proteins were determined using SOMAlogic's DNA aptamer-based capture array. 379 participants initiated statins within the 2 years prior. Propensity scores (PS) were calculated based on visit 2 (1990-92) LDL-c levels and visit 3 demographic/clinical characteristics. 360 statin users were PS matched to controls. Log2-transformed and standardized protein levels were compared using t-tests, with false discovery rate (FDR) adjustment for multiple comparisons. Analyses were replicated in visit 2., Results: Covariates were balanced after PS matching, except for higher visit 3 LDL-c levels among controls (125.70 vs 147.65 mg/dL; p < 0.0001). Statin users had 11 enriched and 11 depleted protein levels after FDR adjustment (q < 0.05). Proteins related and unrelated to lipid metabolism differed between groups. Results were largely replicated in visit 2., Conclusion: Proteins unrelated to lipid metabolism differed by statin use. Pending external validation, exploring their biological functions could elucidate pleiotropic effects of statins., Significance: Statins are the primary pharmacotherapy for lowering low-density lipoprotein (LDL) cholesterol and preventing cardiovascular disease. Their primary mechanism of action is through inhibiting the protein 3hydroxy-3-methylglutaryl CoA reductase (HMGCR) in the mevalonate pathway of LDL cholesterol synthesis. However, statins have pleiotropic effects and may affect other biological processes directly or indirectly, with hypothesized negative and positive effects. The present study contributes to identifying these pathways by comparing the proteome of stain users and nonusers with propensity score matching. Our findings highlight potential biological mechanisms underlying statin pleiotropy, informing future efforts to identify statin users at risk of rare nonatherosclerotic outcomes and identify health benefits of statin use independent of LDL-C reduction., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background Reduced physical function, a representative phenotype of aging, has been associated with cardiovascular disease (CVD). However, few studies have comprehensively investigated its association with composite and individual CVD outcomes in community-dwelling older adults and its predictive value for CVD beyond traditional risk factors. Methods and Results We studied 5570 participants (mean age 75 [SD 5] years, female 58%, Black 22%) at visit 5 (2011-2013) of the ARIC (Atherosclerosis Risk in Communities) study. Physical function was evaluated with the Short Physical Performance Battery (SPPB), which incorporates a walk test, chair stands, and balance tests. The SPPB score was modeled categorically (low [0-6], intermediate [7-9], and high [10-12]) and continuously. We assessed the associations of SPPB score with subsequent composite (coronary heart disease, stroke, or heart failure) and individual CVD outcomes (components within composite outcome) using multivariable Cox models adjusting for major CVD risk factors and history of CVD. We also evaluated improvement in C-statistics by adding SPPB to traditional CVD risk factors in the Pooled Cohort Equation. Among the study participants, 13% had low, 30% intermediate, and 57% high SPPB scores. During a median follow-up of 7.0 (interquartile interval 5.3-7.8) years, there were 930 composite CVD events (386 coronary heart disease, 251 stroke, and 529 heart failure cases). The hazard ratios of composite CVD in low and intermediate versus high SPPB score were 1.47 (95% CI, 1.20-1.79) and 1.25 (95% CI, 1.07-1.46), respectively, after adjusting for potential confounders. Continuous SPPB score demonstrated independent associations with each CVD outcome. The associations were largely consistent across subgroups (including participants with prevalent CVD at baseline). The addition of SPPB to traditional CVD risk factors significantly improved the C-statistics of CVD outcomes (eg, ΔC-statistic 0.019 [95% CI, 0.011-0.027] for composite CVD). Conclusions Reduced physical function was independently associated with the risk of composite and individual CVD outcomes and improved their risk prediction beyond traditional risk factors in community-dwelling older adults. Although confirmatory studies are needed, our results suggest the potential usefulness of SPPB for classifying CVD risk in older adults.

Elevated levels of testosterone and fibroblast growth factor 23 (FGF-23) are both independently associated with a higher risk of cardiovascular disease (CVD). However, the relationship between sex hormones and FGF-23 is not well established. We explored the association between sex hormones and FGF-23 among middle-aged to older men and women in MESA. We studied 3,052 men and 2,868 postmenopausal women free of CVD at the time of enrollment with baseline serum sex hormones [total testosterone (T), free T, estradiol (E2) and sex hormone binding globulin (SHBG)] and intact FGF-23. In sex-stratified analyses, we examined the cross-sectional associations between log-transformed sex hormones (per 1 SD) and log-transformed FGF-23 using multiple linear regression adjusted for socio-demographics, CVD risk factors, estimated glomerular filtration rate and mineral metabolites (25-hydroxyvitamin D, calcium, phosphorus and parathyroid hormone). The mean (SD) age of study participants was 64 (10) years. The median (IQR) of FGF-23 was similar in women and men [38 (30-46) vs 38 (31-47) pg/mL]. In adjusted analyses, among women, 1 SD increment in free T was associated with 3% higher FGF-23 while SHBG was associated with 2% lower FGF-23. In men, 1 SD increment in E2 was associated with 6% higher FGF-23 whereas total T/E2 ratio was associated with 7% lower FGF-23. In conclusion, this exploratory analysis found that a more androgenic sex hormone profile was directly associated with FGF-23 in women and inversely associated with FGF-23 in men. Longitudinal studies are required to determine whether FGF-23 mediates the relationship between sex hormones and CVD risk., Competing Interests: RM has interest in Abbot Laboratories, AbbVie, Inc. and Teva Pharmaceuticals Industries Ltd and consultant/honoraria fees from Akebia/Oksuba. EDM served on Medical Advisory Boards for Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Esperion, Novartis, Novo Nordisk, and Pfizer. The other authors do not report any disclosures. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Study Objectives: Evaluate the association between obstructive sleep apnea (OSA), coronary artery calcium (CAC) density, and cardiovascular events in the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: We analyzed 1,041 participants with nonzero CAC scores who had polysomnography and CAC density data from the fifth examination of the Multi-Ethnic Study of Atherosclerosis. OSA was defined as apnea-hypopnea index ≥ 15 events/h. Multivariable linear regression models were used to evaluate the independent association between OSA and CAC density. Additionally, we evaluated the impact of OSA on associations of CAC measures with incident cardiovascular disease events by testing for interaction in Cox proportional hazard regression models., Results: Our analytical sample was 45% female with a mean age of 70.6 +/- 9 years. Of this sample, 36.7% (n = 383/1041) had OSA (apnea-hypopnea index ≥ 15 events/h). OSA was inversely and weakly associated with CAC density ( β = -0.09; 95% CI, -0.17 to -0.02; P = .014 ) and remained significantly associated after controlling for traditional cardiovascular risk factors (β = -0.08; 95% CI, -0.16 to 0; P = .043). However, this inverse association was attenuated after controlling for body mass index (β = -0.05; 95% CI, -0.13 to 0.02; P = .174). The mean follow-up period for cardiovascular disease events was 13.3 +/- 2.8 years. Additionally, exploratory analysis demonstrated that CAC density was independently and inversely associated with cardiovascular disease events only in the non-OSA subgroup (apnea-hypopnea index ≤ 15 events/h) (hazard ratio, 0.509; 95% CI, 0.323-0.801); P = .0035)., Conclusions: OSA was associated with lower CAC density, but this association was attenuated by body mass index. Further, increased CAC density was associated with a reduced risk of cardiovascular disease events only in individuals within the non-OSA group in exploratory analysis., Citation: Newman SB, Kundel V, Matsuzaki M, et al. Sleep apnea, coronary artery calcium density, and cardiovascular events: results from the Multi-Ethnic Study of Atherosclerosis. J Clin Sleep Med . 2021;17(10):2075-2083., (© 2021 American Academy of Sleep Medicine.)

Goals: The goal of this study was to evaluate whether proton pump inhibitor (PPI) use is cross-sectionally associated with hypomagnesemia and whether hypomagnesemia mediates the prospective association between PPIs and cardiovascular disease (CVD) risk., Background: Use of PPIs has been associated with hypomagnesemia, primarily in case reports or within insurance databases. Both PPI use and low serum magnesium (Mg) have been associated with modestly higher CVD risk. Yet, the interrelation between PPI use and Mg in relation to CVD risk is unclear., Study: The 4436 Atherosclerosis Risk in Communities participants without prevalent CVD at visit 5 (baseline, 2011-2013) were included. Multivariable relative risk regression was used for cross-sectional analyses between PPI and hypomagnesemia prevalence (≤0.75 mmol/L). Incident CVD (defined by atrial fibrillation, coronary heart disease, CVD mortality, heart failure, stroke) was identified through 2017. Multivariable Cox regression was used to examine the PPI-CVD association., Results: Participants were mean±SD aged 75±5 years; 63% were women, 23% Black, and 24% were PPI users. PPI users had 1.24-fold (95% confidence interval: 1.08-1.44) higher prevalence of hypomagnesemia than nonusers. Over a median 5 years of follow-up, 684 incident CVD events occurred. PPI users had higher CVD risk [hazard ratio (95% confidence interval) 1.31 (1.10-1.57)] than nonusers. The effect estimate was largely unchanged when hypomagnesemia was added to the model as a potential mediator., Conclusions: In this elderly community-based study, PPI users had a higher prevalence of hypomagnesemia than in nonusers. PPI users also had higher CVD risk than nonusers; however, it appears unlikely that hypomagnesemia explains associations of PPIs with CVD risk., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Acute infections are known triggers of cardiovascular disease (CVD) but how this association varies across infection types is unknown. We hypothesized while acute infections increase CVD risk, the strength of this association varies across infection types., Method: Acute coronary heart disease (CHD) and ischemic stroke cases were identified in the Atherosclerosis Risk in Communities Study (ARIC). ICD-9 codes from Medicare claims were used to identify cellulitis, pneumonia, urinary tract infections (UTI), and bloodstream infections. A case-crossover design and conditional logistic regression were used to compare infection types among acute CHD and stroke cases 14, 30, 42, and 90 days before the event with two corresponding control periods (1 and 2 years prior)., Results: Of the 1312 acute CHD cases, 116 had a UTI, 102 had pneumonia, 43 had cellulitis, and 28 had a bloodstream infection 90 days before the CHD event. Pneumonia (OR = 25.53 (9.21,70.78)), UTI (OR = 3.32 (1.93, 5.71)), bloodstream infections (OR = 5.93 (2.07, 17.00)), and cellulitis (OR = 2.58 (1.09, 6.13)) were associated with higher acute CHD risk within 14 days of infection. Of the 727 ischemic stroke cases, 12 had cellulitis, 27 had pneumonia, 56 had a UTI, and 5 had a bloodstream infection within 90 days of the stroke. Pneumonia (OR = 5.59 (1.77, 17.67)) and UTI (OR = 3.16 (1.68, 5.94)) were associated with higher stroke risk within 14 days of infection., Conclusions: Patients with pneumonia, UTI, or bloodstream infection appear to be at a 2.5 to 25.5 fold elevated CVD risk following infection. Preventive therapies during this high-risk period should be considered., Competing Interests: Declaration of Competing Interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

(1) Background: Magnesium supplementation may be effective for the prevention of cardiometabolic diseases, but the mechanisms are unclear. Proteomic approaches can assist in identifying the underlying mechanisms. (2) Methods: We collected repeated blood samples from 52 individuals enrolled in a double-blind trial which randomized participants 1:1 to oral magnesium supplementation (400 mg magnesium/day in the form of magnesium oxide) or a matching placebo for 10 weeks. Plasma levels of 91 proteins were measured at baseline with follow-up samples using the Olink Cardiovascular Disease III proximity extension assay panel and were modeled as arbitrary units in a log 2 scale. We evaluated the effect of oral magnesium supplementation for changes in protein levels and the baseline association between serum magnesium and protein levels. The Holm procedure was used to adjust for multiple comparisons. (3) Results: Participants were 73% women, 94% white, and had a mean age of 62. Changes in proteins did not significantly differ between the two intervention groups after correction for multiple comparisons. The most statistically significant effects were on myoglobin [difference -0.319 log 2 units, 95% confidence interval (CI) (-0.550, -0.088), p = 0.008], tartrate-resistant acid phosphatase type 5 (-0.187, (-0.328, -0.045), p = 0.011), tumor necrosis factor ligand superfamily member 13B (-0.181, (-0.332, -0.031), p = 0.019), ST2 protein (-0.198, (-0.363, -0.032), p = 0.020), and interleukin-1 receptor type 1 (-0.144, (-0.273, -0.015), p = 0.029). Similarly, none of the associations of baseline serum magnesium with protein levels were significant after correction for multiple comparisons. (4) Conclusions: Although we did not identify statistically significant effects of oral magnesium supplementation in this relatively small study, this study demonstrates the value of proteomic approaches for the investigation of mechanisms underlying the beneficial effects of magnesium supplementation. Clinical Trials Registration: ClinicalTrials.gov NCT02837328.

Background: Cardiorenal syndrome is a well known concept, bolstered by extensive investigations of CKD as a risk factor of cardiovascular disease. However, data on whether cardiovascular disease increases long-term risk of ESKD are sparse., Methods: We assessed the association of incident hospitalization with major cardiovascular diseases (heart failure, atrial fibrillation, coronary heart disease, and stroke) with subsequent risk of ESKD among individuals enrolled in the Atherosclerosis Risk in Communities study; the analysis included 9047 individuals without prevalent cardiovascular disease at their fourth study visit. Each relevant incident cardiovascular disease event was entered into multivariable Cox proportional hazard models as a time-varying exposure to estimate hazard ratios., Results: During a median follow-up of 17.5 years, there were 2598 cases of hospitalization with cardiovascular disease (heart failure, n =1269; atrial fibrillation, n =1337; coronary heart disease, n =696; and stroke, n =559) and 210 cases of incident ESKD. The incidence of major cardiovascular disease was associated with increased risk of ESKD, with the highest risk for heart failure (hazard ratio, 11.40; 95% confidence interval, 8.38 to 15.50), followed by coronary heart disease, atrial fibrillation, and stroke. When we analyzed heart failure with preserved ejection fraction and heart failure with reduced ejection fraction separately, the risk was nominally higher for heart failure with preserved ejection fraction., Conclusions: Major incident cardiovascular disease events were associated with ESKD, independent of kidney risk factors. In particular, heart failure showed a very strong association with ESKD. Our findings highlight the importance of monitoring and managing kidney disease in patients with cardiovascular disease. The potentially distinct contribution to ESKD of heart failure with preserved versus reduced ejection fraction deserves future investigation., (Copyright © 2020 by the American Society of Nephrology.)

Objectives: Previous studies on a potential association between endodontic infection (EI) and cardiovascular disease (CVD) produced mixed results. Endodontic treatment (ET) may also be linked to cardiovascular risk, as a marker for prior chronic dental infection and subclinical EI in other teeth. We tested the hypothesis that ET is associated with elevated risk of coronary heart disease (CHD), ischemic stroke (IS), heart failure (HF), or venous thromboembolism (VTE)., Methods: ARIC participants who completed the dental ancillary study exam 4 (1996-1998; n = 6,638) were included in the analyses. Participants were followed through 2013 for CHD, stroke, and HF and 2011 for VTE. Cox-proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for CHD, IS, HF, and VTE across ET classifications adjusting for age, sex, race/center, education, income, smoking, alcohol consumption, BMI, statin use, family history of CHD, physical activity, diet quality, insurance status, last dental visit, dental visit frequency, having a current dentist, and tooth loss due to gum disease., Results: Among participants, 21.0% reported a single ET, while 28.5% reported multiple ETs. Over a median of 15.8 years of follow-up, there were 506 incident CHD events, 311 IS events, 739 HF events, and 219 VTE events. There were no significant associations between self-reported history of ET and any of our outcomes (HR (95%CI): CHD = 1.16 (0.87,1.44), IS = 0.77 (0.55,1.09), HF = 1.00 (0.81,1.24), VTE = 0.98 (0.67,1.43)) after adjustment., Conclusions: Our results do not support an independent association between ET and development of CHD, IS, HF, or VTE., (© 2020 American Association of Public Health Dentistry.)

Importance: Higher income is associated with lower incident cardiovascular disease (CVD). However, there is limited research on the association between changes in income and incident CVD., Objective: To examine the association between change in household income and subsequent risk of CVD., Design, Setting, and Participants: The Atherosclerosis Risk In Communities (ARIC) study is an ongoing, prospective cohort of 15 792 community-dwelling men and women, of mostly black or white race, from 4 centers in the United States (Jackson, Mississippi; Washington County, Maryland; suburbs of Minneapolis, Minnesota; and Forsyth County, North Carolina), beginning in 1987. For our analysis, participants were followed up until December 31, 2016., Exposures: Participants were categorized based on whether their household income dropped by more than 50% (income drop), remained unchanged/changed less than 50% (income unchanged), or increased by more than 50% (income rise) over a mean (SD) period of approximately 6 (0.3) years between ARIC visit 1 (1987-1989) and visit 3 (1993-1995)., Main Outcomes and Measures: Our primary outcome was incidence of CVD after ARIC visit 3, including myocardial infarction (MI), fatal coronary heart disease, heart failure (HF), or stroke during a mean (SD) of 17 (7) years. Analyses were adjusted for sociodemographic variables, health behaviors, and CVD biomarkers., Results: Of the 8989 included participants (mean [SD] age at enrollment was 53 [6] years, 1820 participants were black [20%], and 3835 participants were men [43%]), 900 participants (10%) experienced an income drop, 6284 participants (70%) had incomes that remained relatively unchanged, and 1805 participants (20%) experienced an income rise. After full adjustment, those with an income drop experienced significantly higher risk of incident CVD compared with those whose incomes remained relatively unchanged (hazard ratio, 1.17; 95% CI, 1.03-1.32). Those with an income rise experienced significantly lower risk of incident CVD compared with those whose incomes remained relatively unchanged (hazard ratio, 0.86; 95% CI, 0.77-0.96)., Conclusions and Relevance: Income drop over 6 years was associated with higher risk of subsequent incident CVD over 17 years, while income rise over 6 years was associated with lower risk of subsequent incident CVD over 17 years. Health professionals should have greater awareness of the influence of income change on the health of their patients.

The associations between dietary sodium intake and markers of subclinical cardiovascular disease (CVD), such as high-sensitivity cardiac troponin T (hs-cTnT) and amino terminal pro b-type natriuretic peptide (NT-proBNP), may provide mechanistic insight into the relation between dietary sodium and cardiovascular events. We studied 6,131 participants of the Multi-Ethnic Study of Atherosclerosis, who were free of clinical CVD at baseline. Food frequency questionnaires were used to assess estimated sodium intake (ESI) at baseline. We tested the associations between 5 quintiles of ESI (quintile 1: 0.2 to 1.3 grams/day, quintile 2: 1.3 to 1.8 grams/day, quintile 3: 1.8 to 2.4 grams/day, quintile 4: 2.4 to 3.2 grams/day, and quintile 5: 3.2 to 9.9 grams/day) with cross-sectional and 5-year longitudinal change in hs-cTnT and NT-proBNP concentrations. Restricted cubic spline plots were utilized to explore the shape of the associations between ESI and biomarker outcomes. A cross-sectional association between baseline sodium intake and hs-cTnT (but not NT-proBNP) was observed, driven predominantly by a strong positive relation at an intake range of 0.2 to 2.4 g/day. Conversely, a longitudinal association between baseline sodium intake and NT-proBNP (but not hs-cTnT) was observed, driven predominantly by a strong positive relation at intake levels ≥2.4 g/day. In conclusion, temporal shifts in the association between increased ESI and markers of subclinical CVD, hs-cTnT in the short term and NT-proBNP in the longer term, point to the complex pathobiology of the association between sodium intake and CVD. There was also no consistent evidence supporting a J-curve (i.e., excess biomarker values at very low ESI)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background The association of antidepressant medication type with the risk of cardiovascular disease ( CVD ) is unclear. We hypothesized that selective serotonin reuptake inhibitors ( SSRI s) are associated with lower risks of CVD events relative to tricyclics and other non- SSRI antidepressants. Methods and Results We studied 2027 participants from the ARIC (Atherosclerosis Risk in Communities) study (mean age 63±10 years; 29% men; 78% white) treated with antidepressants at some time between 1987 and 2013. Antidepressant usage was confirmed by participants bringing pill bottles to study visits. CVD events in the study sample were identified, including atrial fibrillation, heart failure, myocardial infarction, and ischemic stroke. Hazard ratios were used to compare CVD events adjusted for sociodemographic and clinical risk factors in SSRI s users (47%) versus non- SSRI users. Participants were followed from antidepressant initiation up to 2016 for a median of 13.5 years. We identified 332 atrial fibrillation, 365 heart failure, 174 myocardial infarction and 119 ischemic stroke events. CVD risk was similar for SSRI s and non- SSRI antidepressant users (hazard ratio, 1.10; 95% CI , 0.86-1.41 for atrial fibrillation; hazard ratio, 0.98; 95% CI, 0.77-1.25 for heart failure; hazard ratio, 0.91; 95% CI , 0.64-1.29 for myocardial infarction; and hazard ratio, 1.07; 95% CI , 0.70-1.63 for ischemic stroke). Conclusions SSRI use was not associated with reduced risk of incident CVD compared with non- SSRI antidepressant use. These results do not provide evidence supporting the use of SSRI s compared with tricyclics and other non- SSRI antidepressants in relation to CVD risk.

Objective: To test cross-sectional associations between urinary concentrations of 2,5-dichlorophenol (2,5-DCP) and 2,4-dichlorophenol (2,4-DCP) with the prevalence of cardiovascular disease (CVD), cancer, lung disease, thyroid problems and liver conditions., Methods: Logistic regression was used to evaluate associations of urinary concentrations of 2,5-DCP and 2,4-DCP with prevalence of various medical conditions among 3617 National Health and Nutrition Examination Survey participants from 2007-2008 and 2009-2010. ORs and 95% CIs for each disease were estimated. All regression models were adjusted for urinary creatinine., Results: We observed a monotonically increasing association between quartiles of 2,5-DCP and prevalence of CVD. After adjustment for sociodemographic and lifestyle characteristics, participants with the highest versus lowest quartile of urinary 2,5-DCP had an OR=1.84 (95% CI 1.26 to 2.70) (p linear trend=0.006). The association was similar with further adjustment for established clinical CVD risk factors. Higher 2,5-DCP was also associated with prevalence of all cancers combined (OR Q4 vs Q1 =1.50 (95% CI 1.00 to 2.26); p trend=0.05) and, in exploratory analyses, with gynaecological cancers (OR Q4 vs Q1 =4.15 (95% CI 1.51 to 11.40; p trend=0.01)). No associations were detected between 2,5-DCP and lung diseases, thyroid problems or liver conditions, nor between 2,4-DCP and prevalent disease., Conclusion: In this nationally representative study, higher urinary 2,5-DCP concentrations were associated with greater prevalence of CVD and all cancers combined. Further examination may be warranted to assess whether chronic exposure to 2,5-DCP is associated with incidence of adverse health outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Structural and functional properties of the proximal thoracic aorta have important implications in clinical and subclinical cardiovascular disease (CVD). We examined whether obstructive sleep apnea (OSA) is associated with proximal aortic size and aortic stiffness in a multi-ethnic community-based cohort., Methods: The sample included the Multi-Ethnic Study of Atherosclerosis (MESA) Sleep Ancillary study participants without known CVD who underwent cardiac magnetic resonance imaging. The main exposure variable was OSA severity based on the polysomnography-derived apnea hypopnea index (AHI; normal, AHI <5/h; mild, 5≤ AHI <15/h; moderate to severe, AHI ≥15/h). The study outcomes were ascending aortic diameter (AoD, cm), aortic pulse wave velocity (AoPWV, m/s), and ascending aortic distensibility (AAD, %/mm Hg). Analyses were performed in the overall sample and in sex-specific strata, adjusted for multiple potential confounders., Results: The 708 participants were 55.9% female and on average 68 years old (54-93 years). There was a significant trend (p < 0.0001) of greater mean (SD) AoD across the three OSA groups: normal (n = 87), 3.13 cm (0.35); mild (n = 215), 3.25 (0.34); moderate to severe (n = 406), 3.37 (0.36). In adjusted analysis, participants with moderate to severe OSA had a greater mean AoD compared with the normal group: adjusted mean difference (95% CI), 0.12 cm (0.05, 0.20), p = 0.002. This AoD gradient was observed in women but not in men (p for interaction = 0.02). No differences were found in AoPWV or AAD among the OSA groups., Conclusion: In a diverse community-based cohort, moderate to severe OSA (vs. no OSA) was associated with a larger ascending AoD in women., (© 2019 S. Karger AG, Basel.)

Background Acute infections are known cardiovascular disease ( CVD ) triggers, but little is known regarding how CVD risk varies following inpatient versus outpatient infections. We hypothesized that in- and outpatient infections are associated with CVD risk and that the association is stronger for inpatient infections. Methods and Results Coronary heart disease (CHD) and ischemic stroke cases were identified and adjudicated in the ARIC (Atherosclerosis Risk in Communities Study). Hospital discharge diagnosis codes and Medicare claims data were used to identify infections diagnosed in in- and outpatient settings. A case-crossover design and conditional logistic regression were used to compare in- and outpatient infections among CHD and ischemic stroke cases (14, 30, 42, and 90 days before the event) with corresponding control periods 1 and 2 years previously. A total of 1312 incident CHD cases and 727 incident stroke cases were analyzed. Inpatient infections (14-day odds ratio [ OR ]=12.83 [5.74, 28.68], 30-day OR =8.39 [4.92, 14.31], 42-day OR =6.24 [4.02, 9.67], and 90-day OR =4.48 [3.18, 6.33]) and outpatient infections (14-day OR =3.29 [2.50, 4.32], 30-day OR =2.69 [2.14, 3.37], 42-day OR =2.45 [1.97, 3.05], and 90-day OR =1.99 [1.64, 2.42]) were more common in all CHD case periods compared with control periods and inpatient infection was a stronger CHD trigger for all time periods ( P<0.05). Inpatient infection was also a stronger stroke trigger with the difference borderline statistically significant ( P<0.10) for the 42- and 90-day time periods. Conclusions In- and outpatient infections are associated with CVD risk. Patients with an inpatient infection may be at particularly elevated CVD risk and should be considered potential candidates for CVD prophylaxis.

Background: We examined associations of three markers of subclinical cardiovascular disease (intimal-medial thickening, coronary artery calcification , and ankle-brachial index) with changes in self-reported walking over time., Methods: Data were from 6,490 Multi-Ethnic Study of Atherosclerosis participants (aged 45-84 years), free of clinical cardiovascular disease at baseline. Outcomes, assessed four times over 11 years, included self-reported walking pace (none to striding pace; score, 0-4) and total walking time (minutes/week). Linear generalized estimating equation models estimated associations of baseline intimal-medial thickening (z-scored), coronary artery calcification (Agatston units), and ankle-brachial index (ratio of ankle-to-arm systolic blood pressure) with walking pace and walking time modeled continuously in separate analyses., Results: Median follow-up was 9.2 years (maximum, 11.4). Walking pace (estimate, -0.042 points [95% CI; -0.048, -0.036], p < 0.0001) and walking time (estimate, -4.71 minutes [95% CI: -8.54, -0.88], p = 0.016) decreased yearly. Greater baseline intimal-medial thickening related to faster decline in walking pace in multivariable analyses: walking pace score decreased 0.004 points (95% CI: -0.008, -0.001) more per year for each 1-SD higher intimal-medial thickening z-score, equivalent to an additional 10% slower yearly walking. Greater coronary artery calcification was associated with slower walking but inconsistently related to decline in walking pace. Higher ankle-brachial index was associated with faster baseline walking pace (estimate, 0.043 points [95% CI: 0.027, 0.059] per 1-SD) but unrelated to changes in walking pace. Cardiovascular disease measures were unrelated to total walking time., Conclusions: Greater subclinical cardiovascular disease is associated with prevalent slower self-reported walking pace in middle-aged and older adults but has limited impact on changes in walking over time., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Cardiovascular outcomes in mild thyroid dysfunction (treatment controversial) and moderate or severe dysfunction (treatment standard) remain uncertain., Objective: To examine cross-sectional and prospective associations of thyroid function with cardiovascular risk factors and events., Design: In the Atherosclerosis Risk in Communities Study, we measured concentrations of thyrotropin, free thyroxine, and total triiodothyronine (T3) in stored serum samples originally collected in 1990-1992. We used multivariable linear regression to assess cross-sectional associations of thyroid function with cardiovascular risk factors and Cox regression to assess prospective associations with cardiovascular events. Follow-up occurred through 31 December 2014., Setting: General community., Participants: Black and white men and women from the United States, without prior myocardial infarction (MI), stroke, or heart failure., Main Outcomes and Measures: Cross-sectional outcomes were blood pressure, glycemic markers, and blood lipids. Prospective outcomes were adjudicated fatal and nonfatal MI and stroke., Results: Among 11,359 participants (57 ± 6 years, 58% women), thyroid function was more strongly associated with blood lipids than blood pressure or glycemic measures. Mean adjusted differences in low-density lipoprotein cholesterol were +15.1 (95% confidence interval: 10.5 to 19.7) and +3.2 (0.0 to 6.4) mg/dL in those with moderate/severe and mild chemical hypothyroidism, relative to euthyroidism; an opposite pattern was seen in hyperthyroidism. Similar differences were seen in triglycerides and non-high-density lipoprotein cholesterol. With a 22.5-year median follow-up, 1102 MIs and 838 strokes occurred, with similar outcomes among baseline thyroid function groups and by T3 concentrations., Conclusions: Hypothyroidism is associated with hyperlipidemia, but the magnitude is small in mild chemical hypothyroidism, and cardiovascular outcomes are similar between thyroid function groups., (Copyright © 2017 Endocrine Society)

Objectives: To examine the association between midlife cardiovascular health and physical performance 25 years later., Design: Cohort study (Atherosclerosis Risk in Communities Study); multinomial logistic and logistic regression adjusted for demographic characteristics and clinical measures., Setting: Four U.S. communities: Forsyth County, North Carolina; Washington County, Maryland; Minneapolis, Minnesota; and Jackson, Mississippi., Participants: Individuals aged 54.2 ± 5.8 at baseline (N = 15,744; 55% female, 27% black)., Measurements: Cardiovascular health was measured at baseline using the American Heart Association's Life's Simple 7 (LS7) score (0-14) and LS7 component categories (poor, intermediate, ideal) for each risk factor. The Short Physical Performance Battery (SPPB) was used to quantify physical function as ordinal (0-12) and categorical (low (0-6), fair (7-9), good (10-12) outcomes., Results: Mean baseline LS7 score was 7.9 ± 2.4; 6,144 (39%) individuals returned 25 years later for the fifth ARIC examination, at which point the SPPB was administered. Of 5,916 individuals who completed the SPPB, 3,288 (50%) had good physical performance. Each 1-unit increase in LS7 score was associated with a 17% higher SPPB score (rate ratio (RR) = 1.17, 95% confidence interval (CI) = 1.15-1.19) and a 29% greater chance of having a late-life SPPB score of 10 or greater compared to SPPB score of less than 10 (RR = 1.29, 95% CI = 1.25-1.34). Ideal baseline glucose (RR = 2.53, 95% CI = 2.24-2.87), smoking (RR = 1.97, 95% CI = 1.81-2.15), blood pressure (RR = 1.70, 95% CI = 1.54-1.88), body mass index (RR = 1.51, 95% CI = 1.37-1.66), and physical activity (RR = 1.31, 95% CI = 1.20-1.43) had the strongest associations with late-life SPPB score, adjusting for other LS7 components., Conclusion: Better cardiovascular health during midlife may lead better physical functioning in older age., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Background: Few adults have ideal cardiovascular health (CVH). We studied associations of an overall CVH score with subclinical cardiovascular disease and events. We assessed whether associations varied by race/ethnicity., Methods and Results: Among 5961 participants in the Multi-Ethnic Study of Atherosclerosis, components of CVH were measured at baseline, 2000-2002: systolic blood pressure, total cholesterol, fasting glucose, smoking, physical activity, diet, and body mass index. Levels were classified as ideal (2 points), intermediate (1 point), and poor (0 points) according to American Heart Association definitions. Points were summed to produce a CVH score (0-7 low, 8-11 moderate, 12-14 high). Coronary artery calcium, carotid intima-media thickness, and left ventricular mass were measured at baseline. Cardiovascular disease was defined as myocardial infarction, coronary heart disease death, resuscitated cardiac arrest, stroke, heart failure, or peripheral artery disease. Follow-up was 10.3 years. Regression models were used to examine associations of the CVH score with subclinical disease and events, adjusting for age, sex, and education. Analyses were stratified by race/ethnicity. Adults with high or moderate CVH scores had significantly lower odds of coronary artery calcium and lower carotid intima-media thickness and left ventricular mass than adults with low CVH scores. Adults with high or moderate CVH scores were 67% (95%CI 41% to 82%) and 37% (95%CI 22% to 49%) less likely, respectively, to experience a cardiovascular disease event than adults with low scores. There was no interaction with race/ethnicity., Conclusions: There is a graded inverse association between CVH scores and measures of subclinical and overt cardiovascular disease that is similar across race/ethnic groups., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Hispanics/Latinos are purportedly at increased risk for neurocognitive decline and dementias. Without dementia cures, low-cost, well-tolerated public health means for mitigating neurocognitive decline are needed., Objective: We examined associations between neurocognition and cardiovascular health (CVH) metrics (Life's Simple 7; LS7) among diverse Hispanics/Latinos. We hypothesized that higher LS7 would be associated with healthier brain function (neurocognitive performance)., Methods: We used baseline (2008-2011) Hispanic Community Health Study/Study of Latinos (HCHS/SOL; N = 9,623; ages 45-74 years) to examine neurocognition in relation to CVH LS7 scores., Results: In age and sex adjusted models, a one unit LS7 score increase (range = 0-14) was associated with higher neurocognitive function on the B-SEVLT sum (0.23 [p < 0.01]; range = 3-42), B-SEVLT recall (0.12 [p < 0.01]; range = 0-15), Word Fluency (phonemic; 0.46 (p < 0.01); range = 0-49), and Digit Symbol Substitution (0.49 (p < 0.01); range = 0-83) tests, respectively. Stated differently, a change from the minimum LS7 (0) to maximum LS7 (14) score corresponded to higher scores on verbal learning (4.62) and memory (2.24), verbal fluency (7.0), and psychomotor processing speed (12). In fully adjusted models the associations were attenuated, but remained statistically significant. Incremental adjustments indicated that Latino background and, to a lesser extent, education were primary contributors to the evinced attenuations., Conclusions: We found that higher neurocognitive function was associated with better LS7 CVH metrics among middle-aged and older Hispanics/Latinos. Associations between neurocognitive function and LS7 were strongest among two at-risk groups for neurocognitive decline and dementia, women and Hispanics/Latinos with lower education. Public health efforts to reduce cardiovascular disease morbidity and mortality may have additional neurocognitive benefits among at-risk Hispanics/Latinos.

Background: Relative risks (RRs) for cardiovascular disease (CVD) by smoking rate exhibit a concave pattern, with RRs in low rate smokers exceeding a linear extrapolation from higher rate smokers. However, cigarettes/day does not by itself fully characterize smoking-related risks. A reexamination of the concave pattern using a comprehensive representation of smoking may enhance insights., Methods: Data were from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort enrolled in four areas of the US in 1987-1989. Follow-up was through 2008. Analyses included 14,233 participants, 245,915 person-years, and 3,411 CVD events., Results: The concave RRs with cigarettes/day were consistent with cigarettes/day modifying a linear RR association of pack-years with CVD (i.e., strength of the pack-years association depended on cigarettes/day, indicating that the manner of pack-years accrual impacted risk). Smoking fewer cigarettes/day for longer duration was more deleterious than smoking more cigarettes/day for shorter duration (P < 0.01). For 50 pack-years (365,000 cigarettes), estimated RRs of CVD were 2.1 for accrual at 20 cigarettes/day and 1.6 for accrual at 50 cigarettes/day. Years since smoking cessation did not alter the diminishing strength of association with increasing cigarettes/day. Analyses that accounted for competing risks did not affect findings., Conclusion: Pack-years remained the primary determinant of smoking-related CVD risk; however, accrual influenced RRs. For equal pack-years, smoking fewer cigarettes/day for longer duration was more deleterious than smoking more cigarettes/day for shorter duration. This observation provides clues to better understanding the biological mechanisms, and reinforces the importance of cessation rather than smoking less to reduce CVD risk.

Background: A higher American Heart Association cardiovascular health score (CVHS) predicts a lower incidence of cardiovascular disease (CVD). However, the relationship of CVHS attainment through midlife to late life with CVD prevalence and cardiovascular structure and function in late life is not well described., Methods and Results: The following 6 ideal cardiovascular health metrics were assessed in the Atherosclerosis Risk in Communities (ARIC) study participants at 5 examination visits between 1987 and 2013: nonsmoking, body mass index <25 kg/m(2), untreated total cholesterol <200 mg/dL, untreated blood pressure <120/<80 mm Hg, fasting blood glucose <100 mg/dL, and ideal physical activity. Attainment over time was assessed as the percentage of maximum possible CVHS metrics achieved at visits 1 through 5, the slope of change in CVHS per decade of follow-up, and CVHS trajectory through follow-up. At visit 5, participant groups were characterized with respect to CVD prevalence (n=6520) and echocardiographic measures of cardiac structure and function (n=5903 free of CVD). CVHS was low at baseline and declined with age. Both greater CVHS attainment and improvement in CVHS during follow-up were associated with a lower prevalence of CVD and better left ventricular structure and systolic and diastolic function at visit 5., Conclusions: Greater attainment of, and improvements in, ideal cardiovascular health through midlife to late life are associated with lower CVD prevalence and better cardiovascular structure and function when elderly. These findings highlight the importance of consistent primordial and primary prevention efforts throughout midlife to late life as a potential intervention to decrease the burden of CVD among the elderly., (© 2015 American Heart Association, Inc.)

Perceived discrimination is positively related to cardiovascular disease (CVD) risk factors; its relationship with incident CVD is unknown. Using data from the Multi-Ethnic Study of Atherosclerosis, a population-based multiethnic cohort study of 6,508 adults aged 45-84 years who were initially free of clinical CVD, we examined lifetime discrimination (experiences of unfair treatment in 6 life domains) and everyday discrimination (frequency of day-to-day occurrences of perceived unfair treatment) in relation to incident CVD. During a median 10.1 years of follow-up (2000-2011), 604 incident events occurred. Persons reporting lifetime discrimination in ≥2 domains (versus none) had increased CVD risk, after adjustment for race/ethnicity and sociodemographic factors, behaviors, and traditional CVD risk factors (hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.09, 1.70) and after control for chronic stress and depressive symptoms (HR = 1.28, 95% CI: 1.01, 1.60). Reported discrimination in 1 domain was unrelated to CVD (HR = 1.05, 95% CI: 0.86, 1.30). There were no differences by race/ethnicity, age, or sex. In contrast, everyday discrimination interacted with sex (P = 0.03). Stratified models showed increased risk only among men (for each 1-standard deviation increase in score, adjusted HR = 1.14, 95% CI: 1.03, 1.27); controlling for chronic stress and depressive symptoms slightly reduced this association (HR = 1.11, 95% CI: 0.99, 1.25). This study suggests that perceived discrimination is adversely related to CVD risk in middle-aged and older adults., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Single measurements of elevated high-sensitivity C-reactive protein (hs-CRP) are associated with increased risk of diabetes, cardiovascular disease, and mortality. Large increases or sustained elevations in hs-CRP may be associated with even greater risk of these outcomes. The objective of this study was to characterize the association of 6-year change in hs-CRP with incident diabetes, incident cardiovascular events (heart disease, stroke, and heart failure), and mortality., Methods: We included 10,160 ARIC participants with hs-CRP measured at visits 2 (1990-1992) and 4 (1996-1998). Change in hs-CRP was categorized as sustained low/moderate (<3 mg/L at both visits), decreased (≥3 mg/L at visit 2 and <3 mg/L at visit 4), increased (<3 mg/L at visit 2 and ≥3 mg/L at visit 4), and sustained elevated (≥3 mg/L at both visits). Cox proportional hazards models were used to assess the association of 6-year change in hs-CRP with incident diabetes, cardiovascular events, and death during ~15 years after visit 4., Results: Compared with persons with sustained low/moderate hs-CRP, those with increased or sustained elevated hs-CRP had an increased risk of incident diabetes (hazard ratios [95% CIs] 1.56 [1.38-1.76] and 1.39 [1.25-1.56], respectively), whereas those with deceased hs-CRP did not. Persons with sustained elevated hs-CRP had an increased risk of coronary heart disease, ischemic stroke, heart failure, and mortality (hazard ratios [95% CIs] 1.51 [1.23-1.85], 1.70 [1.32-2.20], 1.60 [1.35-1.89], and 1.52 [1.37-1.69], respectively) compared with those with sustained low/moderate hs-CRP. Associations for sustained elevated hs-CRP were greater than for those with increased hs-CRP over 6 years., Conclusions: Large increases or sustained elevations in hs-CRP over a 6-year period were associated with a subsequent increased risk of diabetes, and persons with sustained elevations in hs-CRP were at the highest risk for cardiovascular disease and mortality. Two measurements of hs-CRP are better than one for characterizing risk, and large increases are particularly prognostic., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: According to a recent meta-analysis, parathyroid hormone (PTH) excess is associated with increased cardiovascular disease (CVD) risk, but existing studies are limited. We examined in a prospective study the association of PTH with the incidence of CVD, taking into account vitamin D and other confounding variables., Methods: The ARIC study measured PTH using a second-generation assay (Roche, Indianapolis, IN) in stored serum samples from 1990 to 1992 and related levels in 10,392 adults to incident cardiovascular outcomes (coronary heart disease [n = 808], heart failure [n = 1,294], stroke [n = 586], peripheral artery disease [n = 873], atrial fibrillation [n = 1,190], and CVD mortality [n = 647]) through 2010 (median follow-up 19 years)., Results: Contrary to the hypothesis, PTH level was not associated positively with any CVD outcome. The associations of incident heart failure, peripheral artery disease, and CVD mortality with PTH actually were weakly inverse (P trend = .02-.04) in the most fully adjusted models. For example, the hazard ratios across PTH quartiles were 1.00, 1.07, 1.07, and 0.96 (P trend = .74) for coronary heart disease incidence and were 1.00, 0.69, 0.74, and 0.74 (P trend = .02) for CVD mortality. Patterns were similar when restricted to participants with normal baseline kidney function., Conclusions: This large prospective study failed to support the hypothesis that elevated PTH is an independent risk marker for incident CVD. When our data were added to the previous meta-analysis, the pooled hazard ratio remained statistically significant but weakened., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Fibroblast growth factor-23 (FGF-23) is a hormone involved in phosphorous regulation and vitamin D metabolism that may be associated with cardiovascular risk, and it is a potential target for intervention. We tested whether elevated FGF-23 is associated with incident coronary heart disease, heart failure, and cardiovascular mortality, even at normal kidney function., Methods and Results: A total of 11 638 Atherosclerosis Risk In Communities study participants, median age 57 at baseline (1990-1992), were followed through 2010. Cox regression was used to evaluate the independent association of baseline serum active FGF-23 with incident outcomes. Models were adjusted for traditional cardiovascular risk factors and estimated glomerular filtration rate. During a median follow-up of 18.6 years, 1125 participants developed coronary heart disease, 1515 developed heart failure, and 802 died of cardiovascular causes. For all 3 outcomes, there was a threshold, whereby FGF-23 was not associated with risk at <40 pg/mL but was positively associated with risk at >40 pg/mL. Compared with those with FGF-23 <40 pg/mL, those in the highest FGF-23 category (≥ 58.8 pg/mL) had a higher risk of incident coronary heart disease (adjusted hazard ratio, 95% CIs: 1.65, 1.40 to 1.94), heart failure (1.75, 1.52 to 2.01), and cardiovascular mortality (1.65, 1.36 to 2.01). Associations were modestly attenuated but remained statistically significant after further adjustment for estimated glomerular filtration rate. In stratified analyses, similar results were observed in African Americans and among persons with normal kidney function., Conclusions: High levels of serum FGF-23 were associated with increased risk of coronary heart disease, heart failure, and cardiovascular mortality in this large, biracial, population-based cohort. This association was independent of traditional cardiovascular risk factors and kidney function., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Purpose: Although there is substantial evidence that physical activity reduces a person's risk of cardiovascular disease (CVD), few of these studies have included African Americans. The studies that have included African Americans offer inconclusive evidence on the association, and none studied heart failure separately. We used data from the Atherosclerosis Risk in Communities study cohort to examine, in African Americans, the association of physical activity with the incidence of CVD and its major components-stroke, heart failure, and CHD., Methods: Participants age 45-64 yr (3707 African Americans and, for comparison, 10,018 Caucasians) had physical activity assessed via questionnaire in 1987 and were followed for incident CVD (n = 1039) through 2008., Results: After adjustment for potential confounders, physical activity was inversely related to CVD, heart failure, and CHD incidence in both races (P values for trend <0.0001), and with stroke in African Americans. Hazard ratios (95% confidence intervals) for CVD for each higher physical activity category were similar by race: 1.0, 0.65 (0.56-0.75), and 0.59 (0.49-0.71) for African Americans and 1.0, 0.74 (0.66-0.83), and 0.67 (0.59-0.75) for Caucasians (P value for interaction = 0.38)., Conclusions: Our findings reinforce recommendations that regular physical activity is important for CVD risk reduction in African Americans as well as Caucasians and support the idea that some physical activity is better than none.

Purpose: We sought to evaluate the associations of high-sensitivity troponin T (Hs-TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high sensitivity C-reactive protein (Hs-CRP) with mortality from any cause, cardiovascular disease (CVD), coronary heart disease (CHD), stroke, cancer, and respiratory disease in the Atherosclerosis Risk in Communities cohort., Methods: We included 11,193 participants aged 54 to 74 years, initially free of the conditions being studied, and who had biomarkers measured. Participants were followed for a mean of 9.9 years., Results: Hazard ratios (HR), adjusted for multiple risk factors, for mortality in participants in the highest Hs-TnT category compared with those with undetectable levels were: Total 3.42 (95% confidence interval [CI], 2.75-4.26); CVD, 7.34 (95% CI, 4.64-11.6); CHD, 6.06 (95% CI, 2.91-12.6); stroke, 3.31 (95% CI, 1.26-8.66); cancer, 1.60 (95% CI, 1.08-2.38); and respiratory, 3.85 (95% CI, 1.39-10.7). Comparing the highest NT-proBNP quintile with those in the lowest quintile, the adjusted HRs for mortality were: Total, 3.05 (95% CI, 2.46-3.77); CVD, 7.48 (95% CI, 4.67-12.0); CHD, 4.07 (95% CI, 2.07-7.98); and stroke, 10.4 (95% CI, 2.26-47.7). Comparing extreme Hs-CRP quintiles, the adjusted HRs for mortality were: Total, 1.61 (95% CI, 1.32-1.97); CVD, 1.76 (95% CI, 1.19-2.62); and respiratory, 3.36 (95% CI, 1.34-8.45). Having multiple markers elevated simultaneously greatly increased cause-specific mortality risks., Conclusions: Greater levels of Hs-TnT, NT-proBNP and Hs-CRP are associated with increased risk of death, not just from CVD, but also from some noncardiovascular causes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Apart from obesity, it remains controversial whether atherosclerosis and its cardiovascular risk disease (CVD) factors are associated with risk of venous thromboembolism (VTE). Using data from the Atherosclerosis Risk in Communities study (ARIC), we evaluated associations between CVD risk factors and incident VTE in a cohort of 15,340 participants who were free a history of VTE and/or anticoagulant use on enrolment. The CVD risk factors were updated during the follow-up period. Over a mean follow-up time of 15.5 years (237,375 person-years), 468 participants had VTE events. Adjusting for demographic variables and body mass index (BMI), current smokers were at greater risk [HR of 1.44 (95% CI: 1.12-1.86)] compared to non-smokers. There was a positive monotonic association between BMI and VTE risk. Individuals with a BMI ≥35 kg/m² had a HR for VTE of 3.09 (95%CI: 2.26-4.23) compared to those with normal BMI (<25 kg/m²). Greater physical activity was associated with lower VTE risk in a demographic adjusted model; however, this association became non-significant following adjustment for BMI. Alcohol intake, diabetes, hypertension, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides were not associated with VTE risk. In conclusion, among the well-established CVD risk factors, only current smoking and obesity were independently associated with VTE risk in this large cohort where risk factors were updated serially during follow-up. This finding corroborates that the pathogenesis of venous disease differs from that of atherosclerotic disease.

Despite reportedly having less tobacco exposure compared with whites, African Americans account for a disproportionate number of smoking-related deaths. The purpose of this study was to compare the prospective associations between smoking and cardiovascular risk in whites and African Americans. Smoking status was obtained on 14,200 participants from the Atherosclerosis Risk in Communities Study. Incidence of cardiovascular disease (CVD) was ascertained from 1987 through 2007. Adjusted Cox proportional hazard models were used to estimate the CVD incidence associated with smoking behavior. Over 17 years' follow-up, there were 2,777 cardiovascular events. In men, compared with never smoking, current smoking was independently associated with 67% (95% confidence interval (CI): 43, 95) and 72% (95% CI: 30, 126) greater risk of CVD in whites and African Americans, respectively. In women, the smoking-related cardiovascular risk was higher: 136% (95% CI: 88, 196) and 169% (95% CI: 126, 219) in African-American and white women, respectively. Early age at smoking initiation was independently associated with increased risk among all participants irrespective of race. Smoking cessation during follow-up was equally beneficial in both whites and African Americans. African Americans who smoke incur a similar level of cardiovascular risk as white smokers and would derive the same benefits from quitting as whites.

Functional biomarkers like large artery elasticity (LAE) and small artery elasticity (SAE) may predict cardiovascular disease (CVD) events beyond blood pressure. The authors examined the prognostic value of LAE and SAE for clinical CVD events among 6,235 Multi-Ethnic Study of Atherosclerosis participants who were initially aged 45-84 years and without symptomatic CVD. LAE and SAE were derived from diastolic pulse contour analysis. During a median 5.8 years of follow-up between 2000 and 2008, 454 adjudicated CVD events occurred, including 256 cases of coronary heart disease (CHD), 93 strokes, and 126 heart failures (multiple diagnoses were possible). After adjustment for age, race/ethnicity, sex, clinic, height, heart rate, body mass index, systolic and diastolic blood pressure, use of antihypertensive and cholesterol-lowering medications, smoking, total cholesterol, high density lipoprotein cholesterol, triglycerides, diabetes, and high-sensitivity C-reactive protein, the hazard ratio for any CVD per standard-deviation increase in SAE was 0.71 (95% confidence interval: 0.61, 0.83; P < 0.0001). The lowest (stiffest) SAE quartile had a hazard ratio of 2.28 (95% confidence interval: 1.55, 3.36) versus the highest (most elastic) quartile. The net reclassification index, conditional on base risk, was 0.11. SAE was significantly associated with future CHD, stroke, and heart failure. After adjustment, LAE was not significantly related to CVD. In asymptomatic participants free of overt CVD, lower SAE added prognostic information for CVD, CHD, stroke, and heart failure events.

Objectives: The purpose of this study is to estimate the prevalence of ideal cardiovascular health and its relationship with incident cardiovascular disease (CVD)., Background: An American Heart Association committee recently set a goal to improve the cardiovascular health of Americans by 20% by 2020. The committee developed definitions of "ideal," "intermediate," and "poor" cardiovascular health for adults and children based on 7 CVD risk factors or health behaviors., Methods: We used data from the Atherosclerosis Risk in Communities Study cohort, age 45 to 64 years, to estimate the prevalence of ideal cardiovascular health in 1987 to 1989 and the corresponding incidence rates of CVD. Incident CVD comprised stroke, heart failure, myocardial infarction, and fatal coronary disease., Results: Among 12,744 participants initially free of CVD, only 0.1% had ideal cardiovascular health, 17.4% had intermediate cardiovascular health, and 82.5% had poor cardiovascular health. CVD incidence rates through 2007 showed a graded relationship with the ideal, intermediate, and poor categories and with the number of ideal health metrics present: rates were one-tenth as high in those with 6 ideal health metrics (3.9 per 1,000 person-years) compared with zero ideal health metrics (37.1 per 1,000 person-years)., Conclusions: In this community-based sample, few adults in 1987 to 1989 had ideal cardiovascular health by the new American Heart Association definition. Those who had the best levels of cardiovascular health nevertheless experienced relatively few events. Clearly, to achieve the American Heart Association goal of improving cardiovascular health by 20% by 2020, we will need to redouble nationwide primordial prevention efforts at the population and individual levels., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

To examine the associations of three understudied hemostatic factors--D-dimer, factor VIII(c), and plasmin-antiplasmin (PAP) complex--with incident cardiovascular disease (CVD) and all cause mortality in the Multiethnic Study of Atherosclerosis cohort. Hemostatic factors were measured at baseline in 45-84-year-old patients (n = 6,391) who were free of clinically recognized CVD. Over 4.6 years of follow-up, we identified 307 CVD events, 207 hard coronary heart disease events, and 210 deaths. D-dimer, factor VIII(c), and PAP were not associated with CVD incidence after adjustment for other risk factors. In contrast, each factor was associated positively with total mortality, and D-dimer and factor VIII(c) were associated positively with cancer mortality. When modeled as ordinal variables and adjusted for risk factors, total mortality was greater by 33% (95% CI 15-54) for each quartile increment of D-dimer, 26% (11-44) for factor VIIIc, and 20% (4-38) for PAP. This prospective cohort study did not find D-dimer, factor VIII(c), or PAP to be risk factors for CVD. Instead, elevated levels of these three hemostatic factors were associated independently with increased risk of death. Elevated D-dimer and factor VIII(c) were associated with increased cancer death.

We examined the relationship between whole grain intake and obesity, insulin resistance, inflammation, diabetes and subclinical CVD using baseline data from the Multi-Ethnic Study of Atherosclerosis. Whole grain intake was measured by a 127-item FFQ in 5496 men and women free of CHD and previously known diabetes. Mean whole grain intake was 0.5 (sd 0.5) servings per d; biochemical measures reflect fasting levels. After adjustment for demographic and health behaviour variables, mean differences for the highest quintile of whole grain intake minus the lowest quintile of intake were 0.6 kg/m2 for BMI, 0.36 mg/l for C-reactive protein, 0.82 micromol/l for homocysteine, 0.15 mU/l*mmol/l for homeostasis model assessment (HOMA), 0.48 mU/l for serum insulin, 2.0 mg/dl for glucose and 5.7 % for prevalence of newly diagnosed impaired fasting glucose (glucose >or= 100 mg/dl or diabetes medication). These differences represent 11-13 % of a standard deviation of BMI, HOMA, glucose and impaired fasting glucose, but 23 %, 52 % and 80 % of a standard deviation of homocysteine, C-reactive protein and insulin, respectively. An inverse association between whole grains and urine albumin excretion was suggested but retained statistical significance after adjustment only in Chinese and Hispanic participants. No associations were observed between whole grain intake and two subclinical disease measures: carotid intima-media thickness and coronary artery calcification. Concordant with previous research, whole grain intake was inversely associated with obesity, insulin resistance, inflammation and elevated fasting glucose or newly diagnosed diabetes. Counter to hypothesis, however, whole grain intake was unrelated to subclinical CVD.

Background: An understanding of the relation in adolescents between serum homocysteine and foods rich in vitamin B-6, vitamin B-12, and folate is important because high homocysteine concentrations in childhood and adolescence may be a risk factor for later cardiovascular disease. However, little is known about the relation between food intake and homocysteine in adolescents., Objective: Five years after national folic acid fortification of enriched grain products, cross-sectional relations between food intake and serum homocysteine concentrations were examined in 2695 adolescents [x age: 18.3 (range: 15-20) y] enrolled in the Child and Adolescent Trial for Cardiovascular Health., Design: A nonfasting blood specimen was analyzed for serum homocysteine, folate, and vitamins B-6 and B-12. Dietary intake was assessed by using a food-frequency questionnaire. Multiple regression analyses were used to evaluate the relation of intakes of whole grains, refined grains, fruit, vegetables, dairy products, red and processed meats, and poultry with serum homocysteine concentrations after adjustment for demographic characteristics, lifestyle factors, and food intake., Results: Serum homocysteine concentrations were lower with greater intakes of whole grains (P for trend = 0.002), refined grains (P for trend = 0.02), and dairy foods (P for trend <0.001); were higher with greater intake of poultry (P for trend = 0.004); and were not related to intakes of fruit, vegetables, or red or processed meat. After additional adjustment for serum B vitamins, the relations of serum homocysteine with most food groups were attenuated., Conclusion: These observational findings suggest a beneficial effect of whole-grain, refined-grain, and dairy products on serum homocysteine concentrations in an adolescent population.

BACKGROUND: Management of orthostatic hypotension (OH) prioritizes prevention of standing hypotension, sometimes at the expense of supine hypertension. It is unclear whether supine hypertension is associated with adverse outcomes relative to standing hypotension. OBJECTIVES: To compare the long-term clinical consequences of supine hypertension and standing hypotension among middle-aged adults with and without OH. METHODS: The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure (BP) in adults aged 45 to 64 years, without neurogenic OH, between 1987 and 1989. We defined OH as a positional drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg, supine hypertension as supine BP≥140/≥90 mm Hg, and standing hypotension as standing BP≤105/≤65 mm Hg. Participants were followed for >30 years. We used Cox regression models to examine associations with cardiovascular disease events, all-cause mortality, falls, and syncope. RESULTS: Of 12 489 participants (55% female, 26% Black, mean age 54 years, SD 6), 4.4% had OH. Among those without OH (N=11 943), 19% had supine hypertension and 21% had standing hypotension, while among those with OH (N=546), 58% had supine hypertension and 38% had standing hypotension. Associations with outcomes did not differ by OH status (P-interactions >0.25). Supine hypertension was associated with heart failure (hazard ratio, 1.83 [95% CI, 1.68-1.99]), falls (hazard ratio, 1.12 [95% CI, 1.02-1.22]), and all-cause mortality (hazard ratio, 1.45 [95% CI, 1.37-1.54]), while standing hypotension was only significantly associated with mortality (hazard ratio, 1.06 [95% CI, 1.00-1.14]). CONCLUSIONS: Supine hypertension was associated with higher risk of adverse events than standing hypotension, regardless of OH status. This challenges conventional OH management, which prioritizes standing hypotension over supine hypertension. [ABSTRACT FROM AUTHOR]

BACKGROUND ACC/AHA guidelines caution against the use of antihypertensive therapy in the setting of low standing systolic BP (SBP) < 110 mm Hg due to unclear benefits. METHODS The Atherosclerosis Risk in Communities (ARIC) Study measured supine and standing SBP in adults aged 45–64 years between 1987 and 1989. We used Cox regression to evaluate the associations of low standing SBP (<110 mm Hg) with risk of falls, syncope, coronary heart disease (CHD), and mortality through December 31, 2019. Falls and syncope were ascertained by hospitalization and outpatient claims; CHD events were adjudicated. Associations were examined overall and in strata of hypertension stage, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and sex. RESULTS Among 12,467 adults followed a median of 24 years (mean age at enrollment 54.1 ± 5.8 years, 55% women, 26% Black adults), 3,000 (24%) had a standing SBP < 110 mm Hg. A standing SBP < 110 mm Hg compared to standing SBP ≥ 110 mm Hg was not significantly associated with falls or syncope, and was associated with a lower risk of CHD events and mortality with HRs of 1.02 (95% CI 0.94, 1.11), 1.02 (0.93, 1.11), 0.88 (0.80, 0.97), and 0.91 (0.86, 0.97), respectively. There were no clinically meaningful differences when stratified by hypertension stage, 10-year ASCVD risk, age, and sex. CONCLUSIONS In this community-based population, low standing SBP was common and not significantly associated with falls or syncope, but was associated with a lower risk of CHD and mortality. These findings do not support screening for low standing BP as a risk factor for adverse events. [ABSTRACT FROM AUTHOR]

Background: Social determinants of health are relevant to cardiovascular outcomes but have had limited examination in atrial fibrillation (AF).Objectives: The purpose of this study was to examine the association of annual household income and cardiovascular outcomes in individuals with AF.Methods: We analysed administrative claims for individuals with AF from 2009 to 2015 captured by a health claims database. We categorised estimates of annual household income as <$40 000; $40-$59 999; $60-$74 999; $75-$99 999; and ≥$100 000. Covariates included demographics, education, cardiovascular disease risk factors, comorbid conditions and anticoagulation. We examined event rates by income category and in multivariable-adjusted models in reference to the highest income category (≥$100 000).Results: Our analysis included 336 736 individuals (age 72.7±11.9 years; 44.5% women; 82.6% white, 8.4% black, 7.0% Hispanic and 2.1% Asian) with AF followed for median (25th and 75th percentile) of 1.5 (95% CI 0.6 to 3.0) years. We observed an inverse association between income and heart failure and myocardial infarction (MI) with evidence of progressive risk across decreased income categories. Individuals with household income <$40 000 had the greatest risk for heart failure (HR 1.17; 95% CI 1.05 to 1.30) and MI (HR 1.18; 95% CI 0.98 to 1.41) compared with those with income ≥$100 000.Conclusions: We identified an association between lower household income and adverse outcomes in a large cohort of individuals with AF. Our findings support consideration of income in the evaluation of cardiovascular risk in individuals with AF. [ABSTRACT FROM AUTHOR]