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Abstract Aims Heart failure (HF) has shared genetic architecture with its risk factors: atrial fibrillation (AF), body mass index (BMI), coronary heart disease (CHD), systolic blood pressure (SBP), and type 2 diabetes (T2D). We aim to assess the association and risk prediction performance of risk‐factor polygenic risk scores (PRSs) for incident HF and its subtypes in bi‐racial populations. Methods and results Five PRSs were constructed for AF, BMI, CHD, SBP, and T2D in White participants of the Atherosclerosis Risk in Communities (ARIC) study. The associations between PRSs and incident HF and its subtypes were assessed using Cox models, and the risk prediction performance of PRSs was assessed using C statistics. Replication was performed in the ARIC study Black and Cardiovascular Health Study (CHS) White participants. In 8624 ARIC study Whites, 1922 (31% cumulative incidence) HF cases developed over 30 years of follow‐up. PRSs of AF, BMI, and CHD were associated with incident HF (P

Abstract Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome‐wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow‐up following heart failure diagnosis ranged from 2 to 116 months. Forty‐nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low‐frequency variants (allele frequency 0.01–0.05) at P

Abstract Objectives Most acute stroke research is conducted at academic and larger hospitals, which may differ from many non‐academic (ie, community) and smaller hospitals with respect to resources and consultant availability. We describe current emergency department (ED) and hospital‐level stroke‐related capabilities among a sample of community EDs participating in the Emergency Quality Network (E‐QUAL) stroke collaborative. Methods Among E‐QUAL‐participating EDs, we conducted a survey to collect data on ED and hospital stroke‐related structural and process capabilities associated with quality of stroke care delivery and patient outcomes. EDs submitted data using a web‐based submission portal. We present descriptive statistics of self‐reported capabilities. Results Of 154 participating EDs in 30 states, 97 (63%) completed the survey. Many were rural (33%); most (82%) were not certified stroke centers. Although most reported having stroke protocols (67%), many did not include hemorrhagic stroke or transient ischemic attack (45% and 57%, respectively). Capability to perform emergent head computed tomography and to administer thrombolysis were not universal (absent in 4% and 5%, respectively). Access to neurologic consultants varied; 18% reported no 24/7 availability onsite or remotely. Of those with access, 48% reported access through telemedicine only. Admission capabilities also varied with patient transfer commonly performed (79%). Conclusion Stroke‐related capabilities vary substantially between community EDs and are different from capabilities typically found in larger stroke centers. These data may be valuable for identifying areas for future investment. Additionally, the design of stroke quality improvement interventions and metrics to evaluate emergency stroke care delivery should account for these key structural differences.

Background High blood pressure (BP) is a well‐known risk factor for atrial fibrillation (AF), but a single BP measurement may provide limited information about AF risk in older adults. Methods and Results This study included 1256 MESA (Multi‐Ethnic Study of Atherosclerosis) and 1948 ARIC (Atherosclerosis Risk in Communities) study participants who underwent extended ambulatory electrocardiographic monitoring and who were free of clinically detected cardiovascular disease, including AF. Using BP measurements from 6 examinations (2000–2018 in MESA and 1987–2017 in ARIC study), we calculated individual long‐term mean, trend, and detrended visit‐to‐visit variability in systolic BP and pulse pressure for each participant. Outcomes, assessed at examination 6, included subclinical AF and supraventricular ectopy. Results from each study were combined with inverse variance‐weighted meta‐analysis. At examination 6, the mean age was 73 years in MESA and 79 years in ARIC study, and 4% had subclinical AF. Higher visit‐to‐visit detrended variability in systolic BP was associated with a greater prevalence of subclinical AF (odds ratio [OR], 1.20; 95% CI, 1.02–1.38) and with more premature atrial contractions/hour (geometric mean ratio, 1.08; 95% CI, 1.01–1.15). For pulse pressure as well, higher visit‐to‐visit detrended variability was associated with a greater prevalence of AF (OR, 1.18; 95% CI, 1.00–1.37). In addition, higher long‐term mean pulse pressure was associated with a greater prevalence of subclinical AF (OR, 1.36; 95% CI, 1.08–1.70). Conclusions Antecedent visit‐to‐visit variability in systolic BP and pulse pressure, but not current BP, is associated with a higher prevalence of subclinical atrial arrhythmias. Prior longitudinal BP assessment, rather than current BP, may be more helpful in identifying older adults who are at higher risk of atrial arrhythmias.

Abstract Solar energy development is a significant driver of land‐use change worldwide, and desert ecosystems are particularly well suited to energy production because of their high insolation rates. Deserts are also characterized by uncertain rainfall, high species endemism, and distinct landforms that vary in geophysical properties. Weather and physical features that differ across landforms interact with shade and water runoff regimes imposed by solar panels, creating novel microhabitats that influence biotic communities. Endemic species may be particularly affected because they often have limited distributions, narrow climatic envelopes, or specialized life histories. We used experimental panels to simulate the effects of solar development on microhabitats and annual plant communities present on gravelly bajada and caliche pan habitat, two common habitat types in California's Mojave Desert. We evaluated soils and microclimatic conditions and measured community response under panels and in the open for seven years (2012–2018). We found that differences in site characteristics and weather affected the ecological impact of panels on the annual plant community. Panel shade tended to increase species richness on the more stressful caliche pan habitat, and this effect was strongest in dry years. Shade effects on diversity and abundance also tended to be positive or neutral on caliche pan habitat. On gravelly bajada habitat, panel shade did not significantly affect richness or diversity and tended to decrease plant abundance. Panel runoff rarely affected richness or diversity on either habitat type, but effects on abundance tended to be negative—suggesting that panel rain shadows were more important than runoff from low‐volume rain events. These results demonstrate that the ecological consequences of solar development can vary over space and time, and suggest that a nuanced approach will be needed to predict impacts across desert landforms differing in physical characteristics.

Background Ceramides exhibit multiple biological activities that may influence the pathophysiological characteristics of atrial fibrillation (AF). Whether the length of the saturated fatty acid carried by the ceramide or their sphingomyelin precursors are associated with AF risk is not known. Methods and Results Among 4206 CHS (Cardiovascular Health Study) participants (mean age, 76 years; 40% men) who were free of prevalent AF at baseline, we identified 1198 incident AF cases over a median 8.7 years of follow‐up. We examined 8 sphingolipid species: ceramide and sphingomyelin species with palmitic acid and species with very‐long‐chain saturated fatty acids: arachidic; behenic; and lignoceric. In adjusted Cox regression analyses, ceramides and sphingomyelins with very‐long‐chain saturated fatty acids were associated with reduced AF risk (ie, per 2‐fold higher ceramide with behenic acid hazard ratio, 0.71; 95% CI, 0.59–0.86; sphingomyelin with behenic acid hazard ratio, 0.60; 95% CI, 0.46–0.77). In contrast, ceramides and sphingomyelins with palmitic acid were associated with increased AF risk (ceramide with palmitic acid hazard ratio, 1.31; 95% CI, 1.03–1.66; sphingomyelin with palmitic acid hazard ratio, 1.73; 95% CI, 1.18–2.55). Associations were attenuated with adjustment for NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), but did not differ significantly by age, sex, race, body mass index, or history of coronary heart disease. Conclusions Our findings suggest that several ceramide and sphingomyelin species are associated with incident AF, and that these associations differ on the basis of the fatty acid. Ceramides and sphingomyelins with palmitic acid were associated with increased AF risk, whereas ceramides and sphingomyelins with very‐long‐chain saturated fatty acids were associated with reduced AF risk.

Background Genetic variation in catechol‐O‐methyltransferase (COMT), a key enzyme in estrogen and catecholamine metabolism, has plausible physiological links to cardiovascular disease (CVD) and its risk factors. In WHS (Women's Health Study), COMT variants rs4818 and rs4680 were associated with a lower risk of CVD among women receiving placebo but not aspirin, suggesting a possible role of COMT in thrombosis. Methods and Results To evaluate potential pathways linking COMT with CVD, and COMT effect modification of aspirin in prevention, we examined COMT association with CVD risk and subclinical measures, coronary artery calcium, and carotid intima‐media thickness in MESA (Multi‐Ethnic Study of Atherosclerosis). In 65 957 person‐years of follow‐up, during which 498 events occurred, COMT rs4818 was associated with lower CVD risk (hazard ratio, 0.85; 95% CI, 0.74–0.97 [P=0.02]). This association remained virtually unchanged after adjusting for common CVD risk factors. Fibrinogen was the only risk factor associated with rs4818 (β, −3.65; SE, 1.35 mg/dL [P=0.007]). Results were directionally similar but not significant for rs4680. Adjusted hazard ratios for COMT rs4818 CVD association were 0.79 (95% CI, 0.65–0.95; P=0.02) among individuals who used aspirin

Background Synthesized fatty acids (FAs) from de novo lipogenesis may affect cardiometabolic health, but longitudinal associations between serially measured de novo lipogenesis–related fatty acid biomarkers and mortality or cardiovascular disease (CVD) are not well established. Methods and Results We investigated longitudinal associations between de novo lipogenesis–related fatty acids with all‐cause mortality, cause‐specific mortality, and incident CVD among 3869 older US adults, mean (SD) age 75 (5) years and free of prevalent CVD at baseline. Levels of plasma phospholipid palmitic (16:0), palmitoleic (16:1n‐7), stearic (18:0), oleic acid (18:1n‐9), and other risk factors were serially measured at baseline, 6 years, and 13 years. All‐cause mortality, cause‐specific mortality, and incident fatal and nonfatal CVD were centrally adjudicated. Risk was assessed in multivariable‐adjusted Cox models with time‐varying FAs and covariates. During 13 years, median follow‐up (maximum 22.4 years), participants experienced 3227 deaths (1131 CVD, 2096 non‐CVD) and 1753 incident CVD events. After multivariable adjustment, higher cumulative levels of 16:0, 16:1n‐7, and 18:1n‐9 were associated with higher all‐cause mortality, with extreme‐quintile hazard ratios (95% CIs) of 1.35 (1.17–1.56), 1.40 (1.21–1.62), and 1.56 (1.35–1.80), respectively, whereas higher levels of 18:0 were associated with lower mortality (hazard ratio=0.76; 95% CI=0.66–0.88). Associations were generally similar for CVD mortality versus non‐CVD mortality, as well as total incident CVD. Changes in levels of 16:0 were positively, and 18:0 inversely, associated with all‐cause mortality (hazard ratio=1.23, 95% CI=1.08–1.41; and hazard ratio=0.78, 95% CI=0.68–0.90). Conclusions Higher long‐term levels of 16:0, 16:1n‐7, and 18:1n‐9 and changes in 16:0 were positively, whereas long‐term levels and changes in 18:0 were inversely, associated with all‐cause mortality in older adults.

Abstract Background Left ventricular (LV) hypertrophy affects up to 43% of African Americans (AAs). Antihypertensive treatment reduces LV mass (LVM). However, interindividual variation in LV traits in response to antihypertensive treatments exists. We hypothesized that genetic variants may modify the association of antihypertensive treatment class with LV traits measured by echocardiography. Methods We evaluated the main effects of the three most common antihypertensive treatments for AAs as well as the single nucleotide polymorphism (SNP)‐by‐drug interaction on LVM and relative wall thickness (RWT) in 2,068 participants across five community‐based cohorts. Treatments included thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACE‐Is), and dihydropyridine calcium channel blockers (dCCBs) and were compared in a pairwise manner. We performed fixed effects inverse variance weighted meta‐analyses of main effects of drugs and 2.5 million SNP‐by‐drug interaction estimates. Results We observed that dCCBs versus TDs were associated with higher LVM after adjusting for covariates (p = 0.001). We report three SNPs at a single locus on chromosome 20 that modified the association between RWT and treatment when comparing dCCBs to ACE‐Is with consistent effects across cohorts (smallest p = 4.7 × 10−8, minor allele frequency range 0.09–0.12). This locus has been linked to LV hypertrophy in a previous study. A marginally significant locus in BICD1 (rs326641) was validated in an external population. Conclusions Our study identified one locus having genome‐wide significant SNP‐by‐drug interaction effect on RWT among dCCB users in comparison to ACE‐I users. Upon additional validation in future studies, our findings can enhance the precision of medical approaches in hypertension treatment.

Background Blacks harbor more cardiovascular risk factors than whites, but experience less atrial fibrillation (AF). Conversely, whites may have a lower risk of heart failure (CHF). N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) levels are higher in whites, predict incident AF, and have diuretic effects in the setting of increased ventricular diastolic pressures, potentially providing a unifying explanation for these racial differences. Methods and Results We used data from the CHS (Cardiovascular Health Study) to determine the degree to which baseline NT‐proBNP levels mediate the relationships between race and incident AF and CHF by comparing beta estimates between models with and without NT‐proBNP. The ARIC (Atherosclerosis Risk in Communities) study was used to assess reproducibility. Among 4731 CHS (770 black) and 12 418 ARIC (3091 black) participants, there were 1277 and 1253 incident AF events, respectively. Whites had higher baseline NT‐proBNP (CHS: 40% higher than blacks; 95% CI, 29–53; ARIC: 39% higher; 95% CI, 33–46) and had a greater risk of incident AF compared with blacks (CHS: adjusted hazard ratio, 1.60; 95% CI, 1.31–1.93; ARIC: hazard ratio, 1.93; 95% CI, 1.57–2.27). NT‐proBNP levels explained a significant proportion of the racial difference in AF risk (CHS: 36.2%; 95% CI, 23.2–69.2%; ARIC: 24.6%; 95% CI, 14.8–39.6%). Contrary to our hypothesis, given an increased risk of CHF among whites in CHS (adjusted hazard ratio, 1.20; 95% CI, 1.05–1.47) and the absence of a significant association between race and CHF in ARIC (adjusted hazard ratio, 1.07; 95% CI, 0.94–1.23), CHF‐related mediation analyses were not performed. Conclusions A substantial portion of the relationship between race and AF was statistically explained by baseline NT‐proBNP levels. No consistent relationship between race and CHF was observed.

Background Circulating very‐long‐chain saturated fatty acids (VLSFAs) are integrated biomarkers of diet and metabolism that may point to new risk pathways and potential targets for heart failure (HF) prevention. The associations of VLSFA to HF in humans are not known. Methods and Results Using a cohort study design, we studied the associations of serially measured plasma phospholipid VLSFA with incident HF in the Cardiovascular Health Study. We investigated the associations of time‐varying levels of the 3 major circulating VLSFAs, lignoceric acid (24:0), behenic acid (22:0), and arachidic acid (20:0), with the risk of incident HF using Cox regression. During 45030 person‐years among 4249 participants, we identified 1304 cases of incident HF, including 489 with preserved and 310 with reduced ejection fraction. Adjusting for major HF risk factors and other circulating fatty acids, higher levels of each VLSFAs were associated with lower risk of incident HF (P trend≤0.0007 each). The hazard ratio comparing the highest quintile to the lowest quintile was 0.67 (95% confidence interval, 0.55–0.81) for 24:0, 0.72 (95% confidence interval, 0.60–0.87) for 22:0 and 0.72 (95% confidence interval, 0.59–0.88) for 20:0. The associations were similar in subgroups defined by sex, age, body mass index, coronary heart disease, and diabetes mellitus. Among those with ejection fraction data, the associations appeared similar for those with preserved and with reduced ejection fraction. Conclusions Higher levels of circulating VLSFAs are associated with lower risk of incident HF in older adults. These novel associations should prompt further research on the role of VLSFA in HF, including relevant new risk pathways. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005133.

BackgroundAtrial fibrillation and heart failure are 2 of the most common diseases, yet ready means to identify individuals at risk are lacking. The 12‐lead ECG is one of the most accessible tests in medicine. Our objective was to determine whether a premature atrial contraction observed on a standard 12‐lead ECG would predict atrial fibrillation and mortality and whether a premature ventricular contraction would predict heart failure and mortality. Methods and ResultsWe utilized the CHS (Cardiovascular Health) Study, which followed 5577 participants for a median of 12 years, as the primary cohort. The ARIC (Atherosclerosis Risk in Communities Study), the replication cohort, captured data from 15 792 participants over a median of 22 years. In the CHS, multivariable analyses revealed that a baseline 12‐lead ECG premature atrial contraction predicted a 60% increased risk of atrial fibrillation (hazard ratio, 1.6; 95% CI, 1.3–2.0; P