Genome-Wide Interaction Analyses of Serum Calcium on Ventricular Repolarization Time in 125 393 Participants.

BACKGROUND: Ventricular repolarization time (ECG QT and JT intervals) is associated with malignant arrhythmia. Genome-wide association studies have identified 230 independent loci for QT and JT; however, 50% of their heritability remains unexplained. Previous work supports a causal effect of lower serum calcium concentrations on longer ventricular repolarization time. We hypothesized calcium interactions with QT and JT variant associations could explain a proportion of the missing heritability. METHODS AND RESULTS: We performed genome-wide calcium interaction analyses for QT and JT intervals. Participants were stratified by their calcium level relative to the study distribution (top or bottom 20%). We performed a 2-stage analysis (genome-wide discovery [N=62 532] and replication [N=59 861] of lead variants) and a single-stage genome-wide meta-analysis (N=122 393, [European ancestry N=117 581, African ancestry N=4812]). We also calculated 2-degrees of freedom joint main and interaction and 1-degree of freedom interaction P values. In 2-stage and single-stage analyses, 50 and 98 independent loci, respectively, were associated with either QT or JT intervals (2-degrees of freedom joint main and interaction P value <5×10-8). No lead variant had a significant interaction result after correcting for multiple testing and sensitivity analyses provided similar findings. Two loci in the single-stage meta-analysis were not reported previously (SPPL2B and RFX6). CONCLUSIONS: We have found limited support for an interaction effect of serum calcium on QT and JT variant associations despite sample sizes with suitable power to detect relevant effects. Therefore, such effects are unlikely to explain a meaningful proportion of the heritability of QT and JT, and factors including rare variation and other environmental interactions need to be considered.

Atrial cardiopathy biomarkers and atrial fibrillation in the ARCADIA trial.

BACKGROUND: ARCADIA compared apixaban to aspirin for secondary stroke prevention in patients with cryptogenic stroke and atrial cardiopathy. One possible explanation for the neutral result is that biomarkers used did not optimally identify atrial cardiopathy. We examined the relationship between biomarker levels and subsequent detection of AF, the hallmark of atrial cardiopathy. METHODS: Patients were randomized if they met criteria for atrial cardiopathy, defined as P-wave terminal force >5000 µV*ms in ECG lead V1 (PTFV1), NT-proBNP >250 pg/mL, or left atrial diameter index (LADI) ⩾3 cm/m2. For this analysis, the outcome was AF detected per routine care. RESULTS: Of 3745 patients who consented to screening for atrial cardiopathy, 254 were subsequently diagnosed with AF; 96 before they could be randomized and 158 after randomization. In unadjusted analyses, ln(NT-proBNP) (RR per SD, 1.99; 95% CI, 1.85-2.13), PTFV1 (RR per SD, 1.15; 95% CI, 1.03-1.28) and LADI (RR per SD, 1.34; 95% CI, 1.20-1.50) were associated with AF. In a model containing all 3 biomarkers, demographics, and AF risk factors, age (RR per 10 years, 1.24; 95% CI, 1.09-1.41), ln(NT-proBNP) (RR per SD, 1.88; 95% CI, 1.67-2.11) and LADI (RR per SD, 1.25; 95% CI, 1.14-1.37) were associated with AF. These three variables together had a c-statistic of 0.82 (95% CI, 0.79-0.85) but only modest calibration. Discrimination was attenuated in sensitivity analyses of patients eligible for randomization who may have been more closely followed for AF. CONCLUSIONS: Biomarkers used to identify atrial cardiopathy in ARCADIA were moderately predictive of subsequent AF.

Association between Atherogenic Dyslipidemia and Subclinical Myocardial Injury in the General Population.

Background: Subclinical myocardial injury (SCMI) is associated with an increased risk of poor cardiovascular disease (CVD) outcomes. Understanding the underlying risk factors for SCMI is crucial for the prevention and management of CVD. We hypothesized that atherogenic dyslipidemia, a combination of high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C), is associated with an increased risk of SCMI. Methods: This analysis from the third National Health and Nutrition Examination Survey (NHANES-III) included 7093 participants (age 59.3 ± 13.4 years, 52.8% women, and 49.4% White) free of CVD. Atherogenic dyslipidemia was defined as TG ≥ 150 mg/dL and HDL-C < 40 mg/dL in men or <50 mg/dL in women. A validated electrocardiographic-based cardiac infarction injury score (CIIS) ≥ 10 was considered positive for SCMI. Multivariable logistic regression analysis was used to examine the association of different combinations of TG and HDL-C groups, including atherogenic dyslipidemia with SCMI. Results: About 22.5% (n = 1594) of participants had atherogenic dyslipidemia, and 26.3% (n = 1862) had SCMI. Compared to participants with normal TG and normal HDL-C, those with atherogenic dyslipidemia had a higher prevalence of SCMI (31.2% vs. 23.9%, p-value < 0.001). In a multivariable logistic regression model, atherogenic dyslipidemia was associated with the highest odds of SCMI followed by high TG/normal HDL-C, then low HDL-C/normal TG [OR (95% CI): 131 (1.14, 1.52), 1.13 (0.97, 1.33), and 1.01 (0.86, 1.20), respectively). Conclusions: Atherogenic dyslipidemia is associated with a higher risk of SCMI, which highlights the role of nontraditional risk factors in the development of subclinical CVD.

Self-rated health and risk of incident cardiovascular events among individuals with hypertension.

BACKGROUND: The relationship between self-rated health (SRH) and cardiovascular events in individuals with hypertension, but without diabetes mellitus, is understudied. METHODS: We performed a post hoc analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). SRH was categorized into excellent, very good, good and fair/poor. Using multivariable Cox regression, we estimated hazard ratios and 95% confidence intervals (CIs) for the association of SRH with both all-cause mortality and a composite of cardiovascular events (the primary outcome), which was defined to include myocardial infarction (MI), other acute coronary syndromes, stroke, acute decompensated heart failure, and cardiovascular death. RESULTS: We included 9319 SPRINT participants (aged 67.9 ±â€Š9 years, 35.6% women) with a median follow-up of 3.8 years. Compared with SRH of excellent, the risk [hazard ratio (95% CI)] of the primary outcome associated with very good, good, and fair/poor SRH was 1.11(0.78-1.56), 1.45 (1.03-2.05), and 1.87(1.28-2.75), respectively. Similarly, compared with SRH of excellent, the risk of all-cause mortality [hazard ratio (95% CI)] associated with very good, good, and fair/poor SRH was 1.13 (0.73-1.76), 1.72 (1.12-2.64), and 2.11 (1.32-3.38), respectively. Less favorable SRH (LF-SRH) was also associated with a higher risk of each component of the primary outcome and serious adverse events (SAE). CONCLUSION: Among individuals with hypertension, SRH is independently associated with the risk of incident cardiovascular events, all-cause mortality, and SAE. Our study suggest that guidelines should consider the potential significance of including SRH in the clinical history of patients with hypertension.

High-Sensitivity Troponin T, NT-proBNP, and Cognitive Outcomes in SPRINT.

BACKGROUND: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets. METHODS: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories. RESULTS: Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; Pinteraction=0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively. CONCLUSIONS: In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar.

Malignant left ventricular hypertrophy and risk of cognitive impairment in SPRINT MIND trial.

BACKGROUND: The association of malignant left ventricular hypertrophy (LVH), a specific subphenotype of LVH characterized by elevated levels of high-sensitivity cardiac troponin (hs-cTnT) or N-terminal pro-B-type natriuretic peptide (NT-proBNP), with cognitive decline remains understudied. METHODS: This post-hoc analysis included a total of 8,027 (67.9 ± 9.3 years) SPRINT MIND trial participants who had with at least 1 follow-up cognitive assessment. Participants were classified into 6 groups on the basis of LVH status on electrocardiogram (ECG), and elevations in levels of hs-cTnT ≥14 ng/L or NT-proBNP ≥125 pg/mL at baseline visit. Multivariate Cox proportional hazard models were used to examine the association of LVH/biomarker groups with incident probable dementia, mild cognitive impairment (MCI) and a composite of MCI/probable dementia. RESULTS: Over a median follow-up period of 5 years, there were 306, 597, and 818 incidents of MCI, probable dementia and a composite of MCI/probable dementia, respectively. Compared with participants without LVH and normal biomarker levels, those with concomitant LVH and elevated levels of both biomarkers were associated with a higher risk of probable dementia (HR, 2.50; 95% CI (1.26-4.95), MCI (HR, 1.78; 95% CI (0.99-3.23) and the composite of MCI/ probable dementia (HR, 1.89; 95% CI, 1.16-3.10). CONCLUSIONS: Among SPRINT participants, malignant LVH is associated with incident probable dementia and mild cognitive impairment. These findings underscore the potential utility of measuring hs-cTnT and NT-proBNP levels when LVH is detected on ECG, aiding in the differentiation of individuals with a favorable risk for cognitive impairment from those with a higher risk.

Safety and efficacy of L-Glutamine in reducing the frequency of acute complications among patients with sickle cell disease: A randomized controlled study.

To evaluate the safety and efficacy of L-glutamine in reducing vaso-occlusive crisis (VOC) and improving cerebral arterial blood flow in children with sickle cell disease (SCD). This is an interventional randomized controlled trial that recruited sixty SCD patients, aged 9.2 ± 3.7 years, who had at least two VOCs during the last 12 months and on a stable dose of hydroxyurea. They were randomly assigned in a 1:1 ratio to receive glutamine (0.3 gm/kg/dose/12h) orally for 24 weeks or the standard of care (SOC). All patients had VOCs in the last year > 3, those on glutamine had a higher number of VOCs and hospitalization for VOC in the last year. There was a decreasing trend in the number, severity, and hospitalization of VOC and a significantly lower cumulative number of VOCs and hospitalizations in the glutamine group than in SOC (p = 0.008, p < 0.001 respectively). Time-averaged mean maximum velocity for the glutamine group had a marginal increase in both middle cerebral arteries, all values remained normal within a normal range, and in both internal carotid arteries, values increased from abnormally low to normal ranges at week 24. Glutamine reduced the number of VOCs and severity and may have a potentially favorable impact on the cerebral arterial flow velocities.

Cardiac Mechanics and the Risk of Atrial Fibrillation in a Community-Based Cohort of Older Adults.

BACKGROUND: Assessment of cardiac structure and function improves risk prediction of new-onset atrial fibrillation (AF) in different populations. We aimed to comprehensively compare standard and newer measures of cardiac structure and function in improving prediction of AF in a cohort of older adults without history of AF and stroke. METHODS: We included 5050 participants without prevalent AF and stroke (mean age 75 ± 5 years, 59% women and 22% Black) from the Atherosclerosis Risk in Communities (ARIC) study who underwent complete 2-dimensional echocardiography, including speckle-tracking analysis of the left ventricle (LV) and left atrium (LA). We assessed the association of cardiac measures with incident AF (including atrial flutter) and quantified the extent to which these measures improved model discrimination and risk classification of AF compared with the CHARGE-AF score. RESULTS: Over a median follow-up time of 7 years, 676 participants developed AF (incidence rate, 2.13 per 100 person-years). LV mass index and wall thickness, E/e' and measures of LA structure and function, but not LV systolic function, were associated with incident AF, after accounting for confounders. Above all, LA reservoir strain, contraction strain, and LA minimal volume index (C-statistics [95%Confidence interval]: 0.73 [0.70,0.75], 0.72 [0.70,0.75] and 0.72 [0.69,0.75], respectively) significantly improved the risk discrimination of the CHARGE-AF score (baseline C-statistic: 0.68 [0.65,0.70]) and achieved the highest category-based net reclassification improvement (29%, 24% and 20%, respectively). CONCLUSIONS: In a large cohort of older adults without prevalent AF and stroke, measures of LA function improved the prediction of AF more than other conventional cardiac measures.

Associations of Physical Activity and Heart Rate Variability from a Two-Week ECG Monitor with Cognitive Function and Dementia: The ARIC Neurocognitive Study.

Low physical activity (PA) measured by accelerometers and low heart rate variability (HRV) measured from short-term ECG recordings are associated with worse cognitive function. Wearable long-term ECG monitors are now widely used, and some devices also include an accelerometer. The objective of this study was to evaluate whether PA or HRV measured from long-term ECG monitors was associated with cognitive function among older adults. A total of 1590 ARIC participants had free-living PA and HRV measured over 14 days using the Zio® XT Patch [aged 72-94 years, 58% female, 32% Black]. Cognitive function was measured by cognitive factor scores and adjudicated dementia or mild cognitive impairment (MCI) status. Adjusted linear or multinomial regression models examined whether higher PA or higher HRV was cross-sectionally associated with higher factor scores or lower odds of MCI/dementia. Each 1-unit increase in the total amount of PA was associated with higher global cognition (ß = 0.30, 95% CI: 0.16-0.44) and executive function scores (ß = 0.38, 95% CI: 0.22-0.53) and lower odds of MCI (OR = 0.38, 95% CI: 0.22-0.67) or dementia (OR = 0.25, 95% CI: 0.08-0.74). HRV (i.e., SDNN and rMSSD) was not associated with cognitive function. More research is needed to define the role of wearable ECG monitors as a tool for digital phenotyping of dementia.

Association between blood pressure levels and premature atrial contractions in patients with hypertension.

BACKGROUND: High blood pressure (BP) induces left atrial structural and functional remodeling that increases susceptibility to atrial arrhythmia. We hypothesized that lower systolic BP (SBP) levels are associated with a lower prevalence of premature atrial contractions (PACs) in patients with hypertension. METHODS: This analysis included 4,697 participants (mean age 62±13.1 years, 50% women, 25.6% blacks) with hypertension from the Third National Health and Nutrition Examination Survey who did not have a prior history of cardiovascular disease (CVD). Multivariable logistic regression was used to examine the cross-sectional association between SBP and prevalence of PACs ascertained from 12-lead resting electrocardiograms. Multivariable Cox proportional hazard analysis was used to examine the association between baseline PACs and CVD mortality. RESULTS: Approximately 1.6% (n=74) of participants had baseline PACs. Patients with SBP ≤140 mmHg had a lower prevalence of PACs than those with SBP ≥140 mmHg (1.1% vs. 1.9%, p-value=0.01). In a multivariable logistic regression model, each 10 mmHg decrease in SBP was associated with a 12% lower odds of PACs (OR (95%CI): 0.88 (0.77-0.99)). During 14 years of follow-up, 645 CVD deaths occurred. In a multivariable-adjusted Cox model, presence of PACs was associated with a 78% increased risk of CVD mortality (HR (95%CI): 1.78 (1.23-2.60)). CONCLUSIONS: In patients with hypertension, lower SBP levels are associated with a lower prevalence of PACs, and presence of PACs is associated with a higher risk of CVD mortality risk. These findings highlight the potential role of BP lowering in the management of cardiac arrhythmias.

Association of Cumulative Systolic Blood Pressure With Left Atrial Function in the Setting of Normal Left Atrial Size: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Lower left atrial (LA) function is associated with increased risk for cardiovascular disease events; data on risk factors for impaired LA function are limited. We evaluated the effect of cumulative systolic blood pressure (cSBP) from midlife to older age on LA strain in adults with normal LA size. METHODS: We included participants in the Atherosclerosis Risk in Communities study with LA strain measured on the visit 5 echocardiogram (2011-13), excluding those with atrial fibrillation and LA volume index >34 mL/m2. The cSBP was calculated from visit 1 (1987-89) through visit 5. Linear regression models were used to evaluate associations between cSBP and LA strain measures. RESULTS: A total of 3,859 participants with a mean (SD) age of 75.2 (5.0) years were included in the analysis; 725 (18.8%) were Black and 2,342 (60.7%) were women. After adjusting for demographics, cardiovascular disease risk factors, heart failure, and coronary heart disease, each 10 mm Hg increase in cSBP was associated with 0.32% (95% CI, -0.52%, -0.13%) and 0.37% (95% CI, -0.51%, -0.22%) absolute reduction in LA reservoir and conduit strain, respectively. Associations were attenuated after adjustment for left ventricular (LV) systolic and diastolic function and mass (-0.12%: 95% CI, -0.31, 0.06 for reservoir strain; and -0.24%: 95% CI -0.38%, -0.10% for conduit strain). In subgroup analyses, the association of cSBP with conduit strain was statistically significant among those with normal LV systolic and diastolic function. CONCLUSIONS: Cumulative exposure to elevated blood pressure from midlife to late life was modestly associated with lower LA reservoir and conduit strain in older adults with normal LA size, mostly related to the effect of blood pressure on LV function and mass. However, the association of cSBP and LA conduit strain in subgroups with normal LV function suggests that LA remodeling in response to hypertension occurs before LV dysfunction is detected on echocardiography.

Exploring the Link between Anticoagulation, Cognitive Impairment and Dementia in Atrial Fibrillation: A Systematic Review.

Background: The impact of oral anticoagulants (OACs) on cognitive impairment and dementia in patients with atrial fibrillation (AF) is not well characterized. This systematic review aims to address this knowledge gap. Methods: SCOPUS and PubMed searches were conducted to identify articles in the English language investigating the association between the use of OACs and cognitive impairment and dementia. We excluded non-original research studies and studies that did not report data on cognitive impairment or included patients who underwent open heart surgery or had psychiatric illnesses or cancer. Results: Out of 22 studies (n = 606,404 patients), 13 studies (n = 597,744 patients) reported a reduction in cognitive impairment/dementia in those undergoing thromboprophylaxis. Using direct oral anticoagulants (DOACs) was associated with a lower incidence of cognitive impairment in 10 studies (n = 284,636 patients). One study found that patients undergoing dual therapy (n = 6794 patients) had a greater incidence of cognitive impairment compared to those undergoing monotherapy (n = 9994 patients). Three studies (n = 61,991 patients) showed that AF patients on DOACs had a lower likelihood of dementia diagnosis than those on vitamin K antagonists (VKAs). Dementia incidence was lower when VKAs were under good control. Conclusions: The use of oral anticoagulants has the potential to prevent cognitive impairment and dementia in patients with AF. Since most of the published research on this subject is observational in nature, more randomized controlled trials are needed to fully understand the effect of anticoagulants on cognitive function.

Deep terminal negative of the P wave in V1 and incidence of ischemic stroke: The atherosclerosis risk in communities (ARIC) study.

BACKGROUND: Deep terminal negative of the P wave in V1 (DTNPV1) is a marker of left atrial remodeling. We aimed to evaluate the association of DTNPV1 with incident ischemic stroke. METHODS: The Atherosclerosis Risk in Communities study is a prospective community-based cohort study. All participants at visit 4 (1996-1998) except those with prevalent stroke, missing covariates, and missing or uninterpretable ECG were included. DTNPV1 was defined as the absolute value of the depth of the terminal negative phase >100 µV in the presence of biphasic P wave in V1. Association between DTNPV1 as a time-dependent exposure variable and incident ischemic stroke was evaluated. The accuracy of the prediction model consisting of DTNPV1 and CHA2DS2-VASc variables in predicting ischemic stroke was analyzed. RESULTS: Among 10,605 participants (63 ± 6 years, 56% women, 20% Black), 803 cases of ischemic stroke occurred over a median follow-up of 20.19 years. After adjusting for demographics, DTNPV1 was associated with an increased risk of stroke (HR 1.96, [95% CI 1.39-2.77]). After further adjusting for stroke risk factors, use of aspirin and anticoagulants, and time-dependent atrial fibrillation, DTNPV1 was associated with a 1.50-fold (95% CI 1.06-2.13) increased risk of stroke. When added to the CHA2DS2-VASc variables, DTNPV1 did not significantly improve stroke prediction as assessed by C-statistic. However, there was improvement in risk classification for participants who did not develop stroke. CONCLUSION: DTNPV1 is significantly associated with higher risk of ischemic stroke. Since DTNPV1 is a simplified electrocardiographic parameter, it may help stroke prediction, a subject for further research.

Associations of Physical Activity and Heart Rate Variability from a Two-Week ECG Monitor with Cognitive Function and Dementia: the ARIC Neurocognitive Study.

BACKGROUND: Low physical activity (PA) measured from accelerometers and low heart rate variability (HRV) measured from short-term ECG recordings are associated with worse cognitive function. Wearable long-term ECG monitors are now widely used. These monitors can provide long-term HRV data and, if embedded with an accelerometer, they can also provide PA data. Whether PA or HRV measured from long-term ECG monitors is associated with cognitive function among older adults is unknown. METHODS: Free-living PA and HRV were measured simultaneously over 14-days using the Zio ® XT Patch among 1590 participants in the Atherosclerosis Risk in Communities Study [aged 72-94 years, 58% female, 32% Black]. Total amount of PA was estimated by total mean amplitude deviation (TMAD) from the 14-day accelerometry raw data. HRV indices (SDNN and rMSSD) were measured from the 14-day ECG raw data. Cognitive factor scores for global cognition, executive function, language, and memory were derived using latent variable methods. Dementia or mild cognitive impairment (MCI) status was adjudicated. Linear or multinomial regression models examined whether higher PA or higher HRV was cross-sectionally associated with higher factor scores or lower odds of MCI/dementia. Models were adjusted for demographic and medical comorbidities. RESULTS: Each 1-unit higher in total amount of PA was significantly associated with 0.30 higher global cognition factor scores (95% CI: 0.16-0.44), 0.38 higher executive function factor scores (95% CI: 0.22-0.53), and 62% lower odds of MCI (OR: 0.38, 95% CI: 0.22-0.67) or 75% lower odds of dementia (OR: 0.25, 95% CI: 0.08-0.74) versus unimpaired cognition. Neither HRV measure was significantly associated with cognitive function or dementia. CONCLUSIONS: PA derived from a 2-week ECG monitor with an embedded accelerometer was significantly associated with higher cognitive test performance and lower odds of MCI/dementia among older adults. By contrast, HRV indices measured over 2 weeks were not significantly associated with cognitive outcomes. More research is needed to define the role of wearable ECG monitors as a tool for digital phenotyping of dementia. CLINICAL PERSPECTIVE: What Is New?: This cross-sectional study evaluated associations between physical activity (PA) and heart rate variability (HRV) measured over 14 days from a wearable ECG monitor with cognitive function.Higher total amount of PA was associated with higher global cognition and executive function, as well as lower odds of mild cognitive impairment or dementia.HRV indices measured over 2 weeks were not significantly associated with cognitive outcomes.What Are the Clinical Implications?: These findings replicate positive associations between PA and cognitive function using accelerometer data from a wearable ECG monitor with an embedded accelerometer.These findings raise the possibility of using wearable ECG monitors (with embedded accelerometers) as a promising tool for digital phenotyping of dementia.

Association between Blood Lead Levels and Silent Myocardial Infarction in the General Population.

Background: Although the link between lead exposure and patterns of cardiovascular disease (CVD) has been reported, its association with silent myocardial infarction (SMI) remains unexplored. We aimed to assess the association between blood lead levels (BLLs) and SMI risk. Methods: We included 7283 (mean age 56.1 ± 2.52 years, 52.5% women) participants free of CVD from the Third National Health and Nutrition Examination Survey. BLL was measured using graphite-furnace atomic absorption spectrophotometry. SMI was defined as ECG evidence of myocardial infarction (MI) without history of MI. The association between SMI and BLLs was examined using multivariable logistic regression. Results: SMI was detected in 120 participants with an unweighted prevalence of 1.65%. Higher BLL correlated with higher SMI prevalence across BLL tertiles. In multivariable-adjusted models, participants in the third BLL tertile had more than double the odds of SMI (OR: 3.42, 95%CI: 1.76-6.63) compared to the first tertile. Each 1 µg/dL increase in BLL was linked to a 9% increase in SMI risk. This association was consistent across age, sex, and race subgroups. Conclusions: Higher BLLs are associated with higher odds of SMI in the general population. These results underscore the significance of the ongoing efforts to mitigate lead exposure and implement screening strategies for SMI in high-risk populations.

Validation of a Zio XT Patch Accelerometer for the Objective Assessment of Physical Activity in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Combination devices to monitor heart rate/rhythms and physical activity are becoming increasingly popular in research and clinical settings. The Zio XT Patch (iRhythm Technologies, San Francisco, CA, USA) is US Food and Drug Administration (FDA)-approved for monitoring heart rhythms, but the validity of its accelerometer for assessing physical activity is unknown. OBJECTIVE: To validate the accelerometer in the Zio XT Patch for measuring physical activity against the widely-used ActiGraph GT3X. METHODS: The Zio XT and ActiGraph wGT3X-BT (Actigraph, Pensacola, FL, USA) were worn simultaneously in two separately-funded ancillary studies to Visit 6 of the Atherosclerosis Risk in Communities (ARIC) Study (2016-2017). Zio XT was worn on the chest and ActiGraph was worn on the hip. Raw accelerometer data were summarized using mean absolute deviation (MAD) for six different epoch lengths (1-min, 5-min, 10-min, 30-min, 1-h, and 2-h). Participants who had ≥3 days of at least 10 h of valid data between 7 a.m-11 p.m were included. Agreement of epoch-level MAD between the two devices was evaluated using correlation and mean squared error (MSE). RESULTS: Among 257 participants (average age: 78.5 ± 4.7 years; 59.1% female), there were strong correlations between MAD values from Zio XT and ActiGraph (average r: 1-min: 0.66, 5-min: 0.90, 10-min: 0.93, 30-min: 0.93, 1-h: 0.89, 2-h: 0.82), with relatively low error values (Average MSE × 106: 1-min: 349.37 g, 5-min: 86.25 g, 10-min: 56.80 g, 30-min: 45.46 g, 1-h: 52.56 g, 2-h: 54.58 g). CONCLUSIONS: These findings suggest that Zio XT accelerometry is valid for measuring duration, frequency, and intensity of physical activity within time epochs of 5-min to 2-h.

Racial differences in prevalence and impact of electrocardiographic subclinical myocardial injury risk factors.

BACKGROUND: We explored whether the reported racial differences in subclinical myocardial injury (SCMI) are due to variations in the prevalence or differential impact of the SCMI risk factors. METHODS: This analysis included 3074 Whites, 1337 Blacks, and 1441 Mexican Americans from the Third National Health and Nutrition Examination Survey who were free of cardiovascular disease. SCMI was defined from standard electrocardiograms as a cardiac infarction/injury score ≥ 10 points. Multivariable logistic regression analysis was used to assess the association of SCMI with its risk factors stratified by race. Multiplicative interaction between each risk factor and race was also examined. RESULTS: Overall prevalence of SCMI was 20.3%, with Mexican Americans exhibiting a lower prevalence than Whites and Blacks (16.5%, 20.4%, and 20.7%, respectively). Whites had more prevalence of dyslipidemia and smoking. Mexican Americans had more diabetes, while Blacks had more hypertension, obesity, and left ventricular hypertrophy. Significant risk factors for SCMI were older age, lower income (<20 K), smoking, diabetes, and no regular exercise. The association of SCMI with age was more pronounced in Mexican Americans (p-value for interaction 0.03), whereas the associations of SCMI with smoking, no-regular exercise, and diabetes were stronger in Whites (p-value for interaction 0.04, 0.001, 0.007, respectively). CONCLUSIONS: Heterogeneity in the racial differences in the prevalence of SCMI risk factors exists, but they do not explain racial differences in SCMI. The stronger associations of smoking, diabetes, and no regular exercise with SCMI partially explain the higher prevalence of SCMI in Whites.

Prevalence of frequent premature ventricular contractions and nonsustained ventricular tachycardia in older women screened for atrial fibrillation in the Women's Health Initiative.

BACKGROUND: Frequent premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) have been associated with cardiovascular disease and mortality. Their prevalence, especially in ambulatory populations, is understudied and limited by few female participants and the use of short-duration (24- to 48-hour) monitoring. OBJECTIVE: The objective of this study was to report the prevalence of frequent PVCs and NSVT in a community-based population of women likely to undergo electrocardiogram (ECG) screening by sequential patch monitoring. METHODS: Participants from the Women's Health Initiative Strong and Healthy (WHISH) trial with no history of atrial fibrillation (AF) but 5-year predicted risk of incident AF ≥5% by CHARGE-AF score were randomly selected to undergo screening with 7-day ECG patch monitors at baseline, 6 months, and 12 months. Recordings were reviewed for PVCs and NSVT (>5 beats); data were analyzed with multivariate regression models. RESULTS: There were 1067 participants who underwent ECG screening at baseline, 866 at 6 months, and 777 at 12 months. Frequent PVCs were found on at least 1 patch from 4.3% of participants, and 1 or more episodes of NSVT were found in 12 (1.1%) women. PVC frequency directly correlated with CHARGE-AF score and NSVT on any patch. Detection of frequent PVCs increased with sequential monitoring. CONCLUSION: In postmenopausal women at high risk for AF, frequent PVCs were relatively common (4.3%) and correlated with higher CHARGE-AF score. As strategies for AF screening continue to evolve, particularly in those individuals at high risk of AF, the prevalence of incidental ventricular arrhythmias is an important benchmark to guide clinical decision-making.