Should regression calibration or multiple imputation be used when calibrating different devices in a longitudinal study?

In longitudinal studies, the devices used to measure exposures can change from visit to visit. Calibration studies, wherein a subset of participants is measured using both devices at follow-up, may be used to assess between-device differences (i.e., errors). Then, statistical methods are needed to adjust for between-device differences and the missing measurement data that often appear in calibration studies. Regression calibration and multiple imputation are two possible methods. We compared both methods in linear regression with a simulation study, considering various real-world scenarios for a longitudinal study of pulse wave velocity. Regression calibration and multiple imputation were both essentially unbiased, but correctly estimating the standard errors posed challenges. Multiple imputation with predicted mean matching produced close agreement with the empirical standard error. Fully stochastic multiple imputation underestimated the standard error by up to 50%, and regression calibration with bootstrapped standard errors performed slightly better than fully stochastic multiple imputation. Regression calibration was slightly more efficient than either multiple imputation method. The results suggest use of multiple imputation with predictive mean matching over fully stochastic imputation or regression calibration in longitudinal studies where a new device at follow-up might be error-prone compared to the device used at baseline.

Relationship Between Central Artery Stiffness, Brain Arterial Dilation, and White Matter Hyperintensities in Older Adults: The ARIC Study-Brief Report.

[Figure: see text].

Association of Carotid Intima-Media Thickness with Brain MRI Markers in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

OBJECTIVE: Elevated carotid intima-media thickness (cIMT) and carotid plaque are markers of arterial injury and may be linked to structural brain injury. We hypothesized cIMT or presence of carotid plaque at midlife are associated with presence of infarcts and cerebral microbleeds, greater white matter hyperintensity (WMH) volume, and smaller regional brain volumes in late-life. METHODS: We included 1,795 Atherosclerosis Risk in Communities (ARIC) Study participants (aged 57±6 years, 57% female, 23% Black) with carotid ultrasounds in 1990-1992 and brain MRI scans in 2011-2013. Weighted linear regression was used for brain volume outcomes, while logistic regression was used for infarcts and cerebral microbleeds. RESULTS: After multivariable adjustments, the highest cIMT quintile was associated with smaller deep gray matter (ß [95% CI]: -0.11 [-0.22, -0.01]) and cortical volume in a temporal-parietal meta region of interest (ROI) (ß [95% CI]: -0.10 [-0.20, -0.01]) in late-life. Similarly, those with carotid plaque had smaller regional brain volumes than those without (ßs [95% CIs]: -0.05 [-0.12, 0.03] and -0.06 [-0.13, 0.01] for deep gray matter and temporal-parietal meta ROI). No significant relations were observed with WMH volume, infarcts, or cerebral microbleeds. CONCLUSION: Over a median follow-up of 21 years, greater midlife cIMT and presence of carotid plaque were associated with smaller deep gray matter volume and cortical volume in a meta ROI involving temporal and parietal lobe regions typically involved in neurodegeneration, including Alzheimer's disease, in later life. Contrary to our hypothesis, associations between measures of arterial injury and markers of vascular brain injury were null.

Short-term repeatability of the peguero-lo presti electrocardiographic left ventricular hypertrophy criteria.

BACKGROUND: Electrocardiographic left ventricular hypertrophy (ECG-LVH) represents preclinical cardiovascular disease and predicts cardiovascular disease morbidity and mortality. While the newly developed Peguero-Lo Presti ECG-LVH criteria have greater sensitivity for LVH than the Cornell voltage and Sokolow-Lyon criteria, its short-term repeatability is unknown. Therefore, we characterized the short-term repeatability of Peguero-Lo Presti ECG-LVH criteria and evaluate its agreement with Cornell voltage and Sokolow-Lyon ECG-LVH criteria. METHODS: Participants underwent two resting, standard, 12-lead ECGs at each of two visits one week apart (n = 63). We defined a Peguero-Lo Presti index as a sum of the deepest S wave amplitude in any single lead and lead V4 (i.e., SD  + SV4 ) and defined Peguero-Lo Presti LVH index as ≥ 2,300 µV among women and ≥ 2,800 µV among men. We estimated repeatability as an intraclass correlation coefficient (ICC), agreement as a prevalence-adjusted bias-adjusted kappa coefficient (κ), and precision using 95% confidence intervals (CIs). RESULTS: The Peguero-Lo Presti index was repeatable: ICC (95% CI) = 0.94 (0.91-0.97). Within-visit agreement of Peguero-Lo Presti LVH was high at the first and second visits: κ (95% CI) = 0.97 (0.91-1.00) and 1.00 (1.00-1.00). Between-visit agreement of the first and second measurements at each visit was comparable: κ (95% CI) = 0.90 (0.80-1.00) and 0.93 (0.85-1.00). Agreement of Peguero-Lo Presti and Cornell or Sokolow-Lyon LVH on any one of the four ECGs was slightly lower: κ (95% CI) = 0.71 (0.54-0.89). CONCLUSION: The Peguero-Lo Presti index and LVH have excellent repeatability and agreement, which support their use in clinical and epidemiological studies.

Cardiometabolic Health and Carotid-Femoral Pulse Wave Velocity in Children: A Systematic Review and Meta-Regression.

OBJECTIVE: To identify, in children the normal rate of carotid-femoral pulse wave velocity (cfPWV) progression, and whether presence of cardiometabolic risk factors is associated with cfPWV. STUDY DESIGN: Electronic databases (PubMed, Google Scholar) were searched from inception to May 2018, for all studies which reported cfPWV in children (<19 years of age). Random effects meta-regression quantified the association between time (years) and cfPWV, and a systematic review was performed to determine whether cardiometabolic risk factors are associated with cfPWV. RESULTS: Data from 28 articles were eligible for inclusion, including 9 reference value (n = 13 100), 5 cardiovascular risk (n = 5257), 10 metabolic risk (n = 2999), and 8 obesity-focused (n = 8760) studies. Meta-regression findings (9 studies) showed that the increase in cfPWV per year (age) was 0.12 m/second (95% CI, 0.07-0.16 m/second) per year, and when stratified by sex the CIs overlapped. Systematic review findings showed that cardiometabolic risk factors were positively associated with cfPWV, including positive associations with blood pressure, impaired glucose metabolism, and metabolic syndrome. However, obesity was not consistently associated with cfPWV. CONCLUSIONS: Arterial stiffness in children progresses with age and is associated with cardiometabolic risk factors. Although further longitudinal studies are warranted, the presented reference data will be valuable to epidemiologists tracking children, and to scientists and clinicians prescribing therapies to mitigate risk in a population that is increasingly more vulnerable to cardiovascular disease.

Association of insulin resistance, from mid-life to late-life, with aortic stiffness in late-life: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Insulin resistance may contribute to aortic stiffening that leads to end-organ damage. We examined the cross-sectional association and prospective association of insulin resistance and aortic stiffness in older adults without diabetes. METHODS: We analyzed 2571 men and women at Visit 5 (in 2011-2013), and 2350 men and women at repeat examinations from baseline at Visit 1 (in 1987-1989) to Visit 5 (in 2011-2013). Linear regression was used to estimate the difference in aortic stiffness per standard unit of HOMA-IR, TG/HDL-C, and TyG at Visit 5. Linear mixed effects were used to assess if high, as opposed to non-high, aortic stiffness (> 75th percentile) was preceded by a faster annual rate of change in log-HOMA-IR, log-TG/HDL-C, and log-TyG from Visit 1 to Visit 5. RESULTS: The mean age of participants was 75 years, 37% (n = 957) were men, and 17% (n = 433) were African American. At Visit 5, higher HOMA-IR, higher TG/HDL-C, and higher TyG were associated with higher aortic stiffness (16 cm/s per SD (95% CI 6, 27), 29 cm/s per SD (95% CI 18, 40), and 32 cm/s per SD (95% CI 22, 42), respectively). From Visit 1 to Visit 5, high aortic stiffness, compared to non-high aortic stiffness, was not preceded by a faster annual rate of change in log-HOMA-IR from baseline to 9 years (0.030 (95% CI 0.024, 0.035) vs. 0.025 (95% CI 0.021, 0.028); p = 0.15) or 9 years onward (0.011 (95% CI 0.007, 0.015) vs. 0.011 (95% CI 0.009, 0.013); p = 0.31); in log-TG/HDL-C from baseline to 9 years (0.019 (95% CI 0.015, 0.024) vs. 0.024 (95% CI 0.022, 0.026); p = 0.06) or 9 years onward (- 0.007 (95% CI - 0.010, - 0.005) vs. - 0.009 (95% CI - 0.010, - 0.007); p = 0.08); or in log-TyG from baseline to 9 years (0.002 (95% CI 0.002, 0.003) vs. 0.003 (95% CI 0.003, 0.003); p = 0.03) or 9 years onward (0 (95% CI 0, 0) vs. 0 (95% CI 0, 0); p = 0.08). CONCLUSIONS: Among older adults without diabetes, insulin resistance was associated with aortic stiffness, but the putative role of insulin resistance in aortic stiffness over the life course requires further study.

Long-term trajectories of anxiety and depression in patients with stable coronary heart disease and risk of subsequent cardiovascular events.

BACKGROUND: Anxiety and depression seem to be under-recognized in their importance and are often not incorporated in subsequent prevention strategies in routine clinical care of coronary heart disease. METHODS: The KAROLA cohort included coronary heart disease patients participating in an in-patient rehabilitation program (years 1999/2000) and followed after 1, 3, 6, 8, 10, 13, and 15 years. We identified anxiety and depression trajectories based on the hospital anxiety and depression scale subdomains using joint latent class mixture time-to-event models. We included cardiovascular (CV) events and non-CV mortality as competing endpoints. RESULTS: We included 1,109 patients (15.4% female; mean age, 59.4 (standard deviation [SD] = 8.0) years) with baseline covariate data. Over a median follow-up of 14.8 years, participants experienced 324 subsequent CV events. We identified four anxiety and depression trajectory classes, a low-stable class (52.2% and 69.6% of patients for anxiety and depression, respectively), moderate-stable class (37.6% and 23.8%), increasing class (2.3% and 3.3%), and high-stable/high-decreasing class (7.9% and 3.3%). The hazard ratio (HR) for subsequent CV events for the increasing anxiety class was 2.13 (95% confidence interval [CI], 0.61; 7.45) compared with the low-stable class after covariate adjustment. Patients following the high-decreasing anxiety trajectory showed an HR of 1.72 (95% CI, 1.11; 2.68) and patients following the high-stable depression trajectory an HR of 2.47 (95% CI, 1.35; 4.54). CONCLUSIONS: Chronic high anxiety and depression trajectory classes were associated with increased risk of subsequent CV events. Assessments of both symptoms of anxiety and depression during long-term routine medical care are recommended to identify patients who would benefit from appropriate interventions.

Short-term repeatability of electrocardiographic criteria of left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is a marker of cardiac end-organ damage and a risk factor for cardiovascular morbidity and mortality. Although clinical trials and cohort studies commonly use the electrocardiogram (ECG) for LVH assessment, the repeatability of ECG-LVH criteria has not been sufficiently examined. Therefore, we evaluated the repeatability of ECG-LVH criteria. METHODS: Participants (n = 63) underwent two standard ECGs at each of two visits, two weeks apart. The ECGs were processed centrally to calculate Cornell voltage (CV) LVH, Cornell voltage product (CVP) LVH, Sokolow-Lyon (SL) LVH, and Sokolow-Lyon product (SLP) LVH. We also used the waveforms measurements contributing to these LVH criteria as continuous variables, referred to here as CV-index, CVP-index, and SL-index. We calculated the intraclass correlation coefficient (ICC), minimal detectable change (95% confidence), and the prevalence-adjusted bias-adjusted kappa (PABAK). RESULTS: ICCs (95% confidence intervals (CI)) were 0.97 (0.96, 0.98) for CV-index, 0.97 (0.95, 0.98) for CVP-index, and 0.93 (0.90, 0.96) for log of SL-index. Minimal detectable change between repeat measures of CV-index, CVP-index, and log of SL-index were ≥236.7 mV, ≥26.7 mV, and ≥0.09 mV, respectively. The within-visit PABAK was 1 for all ECG-LVH criteria, except for the first visit SLP-LVH (PABAK = 0.93). Between-visit PABAK ranged from 0.83 to 0.97 across LVH criteria. CONCLUSIONS: CV, CVP, and SL ECG-LVH as continuous variables have excellent repeatability, and as binary variables have excellent within-visit agreement and good between-visit agreement. These results alleviate concerns about the repeatability the ECG-LVH use in clinical trials and epidemiologic studies.

Determinants of Vascular Age: An Epidemiological Perspective.

BACKGROUND: Vascular age is an emerging health indicator and predictor of end-organ damage to the heart, brain, and kidney. Although there have been many review publications concerning risk factors for vascular aging, most include cross-sectional epidemiological studies, limiting inferences about temporality. There is a need for a review of longitudinal epidemiological studies with repeated measures of vascular structure and function to allow for a systematic examination of determinants of vascular age and the association of vascular aging with outcomes. CONTENT: Arterial stiffness is the most frequently used measure of vascular aging. We report here results of an extensive literature review of longitudinal cohort studies with repeated measures of arterial stiffness to characterize determinants of vascular age. Additionally, we summarize population-based studies that have focused on the association of arterial stiffness with end-organ damage and adverse cardiovascular outcomes. SUMMARY: Changes in arterial stiffness are evident in early childhood. In adults, arterial stiffness has been observed to progress at the average rate of 0.2 to 0.7 m/s for every 5 years of life. The state of the science is limited by the small number of studies with repeated measures of arterial stiffness and determinants of arterial stiffness progression, as well as limited studies in children and diverse race/ethnic groups. Several extant studies suggest that beyond age, cardiometabolic risk factors and adverse lifestyle behaviors contribute to arterial stiffening. Therefore, arterial stiffness is important in the assessment of healthy vascular aging and a possible target for the prevention of subclinical and clinical disease.

Repeatability of ectopic beats from 48-hr ambulatory electrocardiography: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: The purpose of this study was to characterize the repeatability of ectopic beats, defined by premature atrial contractions (PACs) and premature ventricular contractions (PVCs), on ambulatory electrocardiogram (aECG) monitoring and evaluate the effect of length of aECG monitoring on the repeatability estimates. METHODS: This analysis includes 95 randomly selected participants from the Atherosclerosis Risk in Communities Study (ARIC; 2011-2013). The participants wore a Holter monitor for two, 48-hr periods separated by a mean of 38 days following an identical, standardized protocol. We divided each 48-hr recording into 3-, 6-, 12-, and 24-hr recording periods and calculated intraclass correlation coefficients (ICCs) for PACs and PVCs and also as a percentage of the corresponding total of recorded beats per hour among these periods. RESULTS: All participants had ≥1 PAC during the 48-hr recordings, and only two participants had no PVCs. ICCs were >0.83 for all indices and recording lengths ≥12 hrs. ICCs were intermediate for 6-hr recordings (range 0.80-0.83) and lower for 3-hr recordings (range 0.74-0.80). The ratio of the between- to within-participant variation increased with recording length. CONCLUSION: Repeatability of PACs and PVCs was excellent for recording lengths of 6-24 hr and fair for 3 hr. Repeatability varies over shorter duration recordings within the 48-hr recording period, and thus the present results have implications for detection algorithms for ectopic beats and can facilitate epidemiologic and clinical applications in which knowledge of measurement variability and misclassification are needed.

Racial Differences in the Association between Parity and Incident Stroke: Results from the REasons for Geographic and Racial Differences in Stroke Study.

BACKGROUND: Circulatory and vascular changes across consecutive pregnancies may increase the risk of later-life cerebrovascular health outcomes. METHODS: The association between parity and incident stroke was assessed among 7674 white and 6280 black women, aged 45 years and older, and enrolled in the REasons for Geographic and Racial Differences in Stroke Study from 2003 to 2007. Parity was assessed at baseline, and incident stroke was ascertained from physician-adjudicated medical records through September 2014. Cox proportional hazards models were used to estimate hazard ratios (HR) for the association between parity and stroke, adjusting for baseline measures. RESULTS: At baseline, 12.7% of white women and 16.2% of black women reported 1 live birth, while 8.2% and 19.0%, respectively, reported 5 or more live births. Mean follow-up time was 7.5 years (standard deviation = 2.8); there were 447 incident strokes. A significant interaction between race and parity was detected (P = .05). Among white women, those with 5 or more live births had a higher stroke risk than those with 1 live birth (HR = 1.57; 95% confidence interval [CI] .93-2.65). However, the association was eliminated after adjustment for baseline characteristics (HR = 1.00, 95% CI .59-1.71). For black women, those with 5 or more live births had the highest stroke risk compared with those with 1 live birth (HR = 1.91, 95% CI 1.25-2.93), but the association was attenuated and no longer statistically significant after adjustment for confounders (HR = 1.40, 95% CI .89-2.18). CONCLUSIONS: In adjusted models, no statistically significantassociations were observed between parity and stroke risk in a diverse cohort of U.S. women. Further studies are needed to elucidate the role of lifestyle and psychosocial factors in the race-specific associations that were observed.

Association of glucose homeostasis measures with heart rate variability among Hispanic/Latino adults without diabetes: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: Reduced heart rate variability (HRV), a measure of cardiac autonomic function, is associated with an increased risk of cardiovascular disease (CVD) and mortality. Glucose homeostasis measures are associated with reduced cardiac autonomic function among those with diabetes, but inconsistent associations have been reported among those without diabetes. This study aimed to examine the association of glucose homeostasis measures with cardiac autonomic function among diverse Hispanic/Latino adults without diabetes. METHODS: The Hispanic community Health Study/Study of Latinos (HCHS/SOL; 2008-2011) used two-stage area probability sampling of households to enroll 16,415 self-identified Hispanics/Latinos aged 18-74 years from four USA communities. Resting, standard 12-lead electrocardiogram recordings were used to estimate the following ultrashort-term measures of HRV: RR interval (RR), standard deviation of all normal to normal RR (SDNN) and root mean square of successive differences in RR intervals (RMSSD). Multivariable regression analysis was used to estimate associations between glucose homeostasis measures with HRV using data from 11,994 adults without diabetes (mean age 39 years; 52 % women). RESULTS: Higher fasting glucose was associated with lower RR, SDNN, and RMSSD. Fasting insulin and the homeostasis model assessment of insulin resistance was negatively associated with RR, SDNN, and RMSSD, and the association was stronger among men compared with women. RMSSD was, on average, 26 % lower in men with higher fasting insulin and 29 % lower in men with lower insulin resistance; for women, the corresponding estimates were smaller at 4 and 9 %, respectively. Higher glycated hemoglobin was associated with lower RR, SDNN, and RMSSD in those with abdominal adiposity, defined by sex-specific cut-points for waist circumference, after adjusting for demographics and medication use. There were no associations between glycated hemoglobin and HRV measures among those without abdominal adiposity. CONCLUSIONS: Impairment in glucose homeostasis was associated with lower HRV in Hispanic/Latino adults without diabetes, most prominently in men and individuals with abdominal adiposity. These results suggest that reduced cardiac autonomic function is associated with metabolic impairments before onset of overt diabetes in certain subgroups, offering clues for the pathophysiologic processes involved as well as opportunity for identification of those at high risk before autonomic control is manifestly impaired.

Social support and cognition in a community-based cohort: the Atherosclerosis Risk in Communities (ARIC) study.

OBJECTIVE: social support has demonstrated cross-sectional associations with greater cognitive function and a protective effect against cognitive decline in older adults, but exploration of its temporal role in cognitive ageing from mid-life to older adulthood has been limited. We aimed to quantify the associations of social support, assessed at mid-life, with cognitive function in mid-life and with cognitive decline into late life among African Americans and Caucasians. METHODS: data from the community-based, prospective Atherosclerosis Risk in Communities (ARIC) cohort of 15,792 biracial participants were examined for baseline and longitudinal associations of mid-life social support with global cognition at mid-life and with 20-year change in global cognition, respectively, stratified by race. Interactions with sociodemographic and cardiometabolic covariates were additionally explored within each race group. Social support was ascertained using two metrics: interpersonal support and social network. RESULTS: interpersonal support was directly associated with greater global cognition at baseline in both race groups. Social network was directly associated with greater global cognition at baseline among Caucasians and African American females, but it was not significantly associated with global cognition in African American males. Neither mid-life social support measure was associated with 20-year change in global cognition. CONCLUSIONS: higher levels of social support were moderately associated with greater multi-dimensional cognitive function at mid-life, but mid-life social support was not associated with temporal change in global cognitive function over 20 years into late life. Prospective studies with time-dependent measures of social support and cognition are needed to better understand the role of social engagement in ageing-related cognitive functioning.

Varying patterns of brachial artery flow-mediated dilatation in women with polycystic ovary syndrome and controls: An application of the group-based trajectory modeling.

PURPOSE: To identify changing patterns of absolute change in brachial artery lumen diameter (LD) after reactive hyperemia in women with polycystic ovary syndrome (PCOS) and controls and to quantify the association of PCOS status and participants' factors with these patterns. METHODS: Brachial flow-mediated dilation was measured in 128 women with PCOS and 148 controls aged 30-60 years. Group-based trajectory modeling was used to investigate absolute change in LD every 30 seconds for 2 minutes after occluding cuff deflation. Multinomial logistic regression was used to identify factors associated with trajectories. RESULTS: Three patterns emerged, namely nondilators (42.2%), dilators (44.6%), and enhanced dilators (13.0%). The proportion of women with PCOS did not differ across groups. Independently of age and PCOS status, larger baseline LD (odds ratio; 95% confidence interval: 2.51; 1.29, 4.89) and lower insulin levels (0.70; 0.52, 0.93) were associated with nondilators rather than with dilators. Higher total cholesterol was associated with dilators in women with PCOS but with nondilators in controls. CONCLUSIONS: Trajectory modeling identified distinct patterns of change in LD and factors associated with the endothelial response. This method may be a useful tool to understand the brachial flow-mediated vasodilator response.

Contralateral differences in ankle SBP and pulse wave velocity: associations with incident heart failure and mortality.

BACKGROUND: Contralateral differences in brachial SBP are indicative of underlaying cardiovascular issues. OBJECTIVES: To examine the association of contralateral differences in ankle SBP, brachial-ankle pulse wave velocity (baPWV), and heart-ankle pulse wave velocity (haPWV) with incident heart failure and all-cause and cardiovascular mortality. METHODS: Cox proportional-hazards models were used to calculate hazard ratios and 95% confidence intervals (95% CIs) in 5077 participants (75 ±â€Š5 years) of the Atherosclerosis Risk in Communities study. RESULTS: Over a mean follow-up of 7.5 ±â€Š2.2 years, there were 457 heart failure events, 1275 all-cause and 363 cardiovascular deaths. Interankle SBP difference of at least 10 mmHg [hazard ratio = 1.12; confidence interval (CI) 1.00-1.28], at least 15 mmHg (hazard ratio = 1.21; CI 1.03-1.43), contralateral difference in baPWV more than 240 cm/s (hazard ratio = 1.22; CI 1.02-1.46), and haPWV more than 80 cm/s (hazard ratio = 1.24; CI 1.04-1.48) were each independently associated with all-cause mortality after adjustment for confounders. Contralateral differences in ankle SBP of at least 15 mmHg (hazard ratio = 1.56; CI 1.17-2.09), and haPWV more than 80 cm/s (hazard ratio = 1.42; CI 1.03-1.96) were both independently associated with cardiovascular mortality. Unadjusted analysis revealed that those with contralateral differences in ankle SBP of at least 10 and at least 15 mmHg, baPWV more than 240, and haPWV more than 80 cm/s had higher risks of heart failure (all P < 0.05). CONCLUSION: These results underscore the significance of evaluating contralateral differences in ankle SBP and PWV as potential markers of increased mortality risk among older adults.

Sex and Age Differences in Atypical Chief Complaints for Acute Decompensated Heart Failure in Emergency Department Visits.

Objectives: Around one million United States emergency department (ED) visits annually are due to acute decompensated heart failure (ADHF) symptoms. Characterizing ED symptom presentation of ADHF patients may improve clinical care, yet sex and age differences in ED chief complaints have not been thoroughly investigated. This paper aims to describe differences in chief complaints and comorbid conditions for ED patients with a ADHF diagnosis, stratified by sex and age. Methods: Retrospective analysis of adults presenting to North Carolina EDs in NC DETECT, a statewide syndromic surveillance system, between 2010 and 2016 with a diagnosis of ADHF. Frequencies of chief complaint categories for ED visits and comorbid conditions, stratified by sex and age, were evaluated and standardized differences computed. Results: Top chief complaints were dyspnea (19.1%), chest pain (13.5%), and other respiratory complaints (13.4%). In the 18-44 age group, females when compared to males reported more nausea/vomiting (6.7% versus 4.1%) and headache (4.2% versus 2.0%). In those 45-64 and 65+ years old, complaints were similar by sex. When stratified by age group alone, the 18-44 and 45-64 age groups had more complaints of chest pain, whereas balance issues, weakness, and confusion were more common in the 65+ age group. Conclusion: Sex and age differences in atypical ADHF symptoms were seen in in ED patients with ADHF. Characterizing variation of ADHF symptoms in ED patients can inform the identification of ED patients with ADHF and the management of ADHF-related symptoms.

Protocol for a Study Investigating Context-Specific Sedentary Behaviors and Cardiometabolic Health in College-Based Young Adults (CONTEXT-SB).

Background: Sedentary behavior (SB) is detrimental to cardiometabolic disease (CMD) risk, which can begin in young adulthood. To devise effective SB-CMD interventions in young adults, it is important to understand which context-specific sedentary behaviors (CS-SB) are most detrimental for CMD risk, the lifestyle behaviors that co-exist with CS-SBs, and the socioecological predictors of CS-SB. Methods: This longitudinal observational study will recruit 500 college-aged (18-24 years) individuals. Two laboratory visits will occur, spaced 12 months apart, where a composite CMD risk score (e.g., arterial stiffness, metabolic and inflammatory biomarkers, heart rate variability, and body composition) will be calculated, and questionnaires to measure lifestyle behaviors and different levels of the socioecological model will be administered. After each visit, total SB (activPAL) and CS-SB (television, transportation, academic/ occupational, leisure computer, "other"; ecological momentary assessment) will be measured across seven days. Discussion: It is hypothesized that certain CS-SB will show stronger associations with CMD risk, compared to T-SB, even after accounting for coexisting lifestyle behaviors. It is expected that a range of intra-individual, inter-individual, and physical environment socioecological factors will predict CS-SB. The findings from this study will support the development of an evidence-based, multi-level intervention to target SB reduction and mitigate CMD risk in CBYA.

Polycystic Ovary Syndrome, Metabolic Syndrome, and Inflammation in the Hispanic Community Health Study/Study of Latinos.

CONTEXT: Polycystic Ovary Syndrome (PCOS) is a multifaceted endocrine disorder with reproductive and metabolic dysregulation. PCOS has been associated with inflammation and Metabolic Syndrome (MetS); however, the moderating effects of inflammation as measured by C-reactive protein (CRP) and menopause on the PCOS-MetS association have not been studied in Hispanic/Latinas with PCOS who have a higher metabolic burden. OBJECTIVE: We studied the cross-sectional association between PCOS and (i) MetS in 7316 females of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), (ii) subcomponents of MetS including impaired fasting glucose (IFG) and elevated triglycerides (TGL), and (iii) effect modification by menopausal status and CRP. DESIGN: HCHS/SOL is a multicenter, longitudinal, and observational study of US Hispanic/Latinos. Our study sample included females from Visit 2 with self-reported PCOS and MetS (ages 23-82 years). RESULTS: PCOS (prevalence=18.8%) was significantly associated with MetS prevalence (OR=1.41[95% confidence interval: 1.13-1.76]), IFG and TGL (OR=1.42[1.18-1.72], OR=1.48[1.20-1.83] respectively). We observed effect modification by menopausal status (ORpre=1.46, pint=0.02; ORpost=1.34, pint=0.06) and CRP (ORelevated=1.41, pint=0.04; ORnormal=1.26, pint=0.16) on the PCOS-MetS association. We also observed a super-additive interaction between CRP and PCOS, adjusting for which resulted in an attenuated effect of PCOS on MetS (OR=1.29[0.93-1.78]). CONCLUSIONS: Hispanic/Latino females with PCOS had higher odds of MetS, IFG, and elevated TGL, than their peers without PCOS. Interaction analyses revealed that the odds of MetS are higher among PCOS females who have pre-menopausal status or high inflammation. Interventions in Hispanic/Latinas should target these outcomes for effective management of the disease.

Association of Segment-Specific Pulse Wave Velocity With Vascular Calcification: The ARIC (Atherosclerosis Risk in Communities) Study.

BACKGROUND: Pulse wave velocity (PWV) is a noninvasive measure of arterial stiffness and predictor of cardiovascular disease. However, the association between PWV and vascular calcification across different vascular beds has not been fully investigated. This study aimed to quantify the association between PWV and multiterritory calcification and to explore whether PWV can identify individuals with vascular calcification beyond traditional risk factors. METHODS AND RESULTS: Among 1351 older adults (mean age, 79.2 years [SD, 4.1]) from the ARIC (Atherosclerosis Risk in Communities) study, we measured segment-specific PWVs: heart-carotid, heart-femoral, carotid-femoral, heart-ankle, brachial-ankle, and femoral-ankle. Dependent variables were high calcium score (≥75th percentile of Agatston score) across different vascular beds: coronary arteries, aortic valve ring, aortic valve, mitral valve, ascending aorta, and descending aorta. Quartiles of carotid-femoral, heart-femoral, heart-ankle, and brachial-ankle PWV were significantly associated with coronary artery calcium (eg, adjusted odds ratio [OR] for the highest versus lowest quartile of carotid-femoral PWV, 1.84 [95% CI, 1.24-2.74]). Overall, PWVs were most strongly associated with descending aorta calcification, with significant results for carotid-femoral, heart-femoral, heart-ankle, and brachial-ankle PWV (eg, adjusted OR for the highest versus lowest quartile of carotid-femoral PWV, 3.99 [95% CI, 2.61-6.17]). In contrast, femoral-ankle PWV was inversely associated with descending aorta calcification. Some PWVs improved the discrimination of coronary artery calcium and descending aorta calcification beyond traditional risk factors. CONCLUSIONS: The associations of PWV with vascular calcification varied substantially across segments, with descending aorta calcification most closely linked to PWVs. Our study suggests that some PWVs, especially carotid-femoral PWV, are helpful to identify individuals with coronary artery calcium and descending aorta calcification.

Coronary artery calcium as a marker of healthy and unhealthy aging in adults aged 75 and older: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND AIMS: Coronary artery calcium (CAC) is validated for risk prediction among middle-aged adults, but there is limited research exploring implications of CAC among older adults. We used data from the Atherosclerosis Risk in Communities (ARIC) study to evaluate the association of CAC with domains of healthy and unhealthy aging in adults aged ≥75 years. METHODS: We included 2,290 participants aged ≥75 years free of known coronary heart disease who underwent CAC scoring at study visit 7. We examined the cross-sectional association of CAC = 0, 1-999 (reference), and ≥1000 with seven domains of aging: cognitive function, hearing, ankle-brachial index (ABI), pulse-wave velocity (PWV), forced vital capacity (FVC), physical functioning, and grip strength. RESULTS: The mean age was 80.5 ± 4.3 years, 38.6% male, and 77.7% White. 10.3% had CAC = 0 and 19.2% had CAC≥1000. Individuals with CAC = 0 had the lowest while those with CAC≥1000 had the highest proportion with dementia (2% vs 8%), hearing impairment (46% vs 67%), low ABI (3% vs 18%), high PWV (27% vs 41%), reduced FVC (34% vs 42%), impaired grip strength (66% vs 74%), and mean composite abnormal aging score (2.6 vs 3.7). Participants with CAC = 0 were less likely to have abnormal ABI (aOR:0.15, 95%CI:0.07-0.34), high PWV (aOR:0.57, 95%CI:0.41-0.80), and reduced FVC (aOR:0.69, 95%CI:0.50-0.96). Conversely, participants with CAC≥1000 were more likely to have low ABI (aOR:1.74, 95%CI:1.27-2.39), high PWV (aOR:1.52, 95%CI:1.15-2.00), impaired physical functioning (aOR:1.35, 95%CI:1.05-1.73), and impaired grip strength (aOR:1.46, 95%CI:1.08-1.99). CONCLUSIONS: Our findings highlight CAC as a simple measure broadly associated with biological aging, with clinical and research implications for estimating the physical and physiological aging trajectory of older individuals.