202 results on '"Lutsey, Pamela L."'
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2. Association of diabetes and glycemic control with left atrial function: The Atherosclerosis Risk in Communities (ARIC) study.
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Garg, Parveen K., Ji, Yuekai, Wang, Wendy, Hof, Jeremy Van't, Decker, Joseph, Inciardi, Riccardo M., Lutsey, Pamela L., Alonso, Alvaro, Shah, Amil M., Solomon, Scott, Selvin, Elizabeth, and Chen, Lin Yee
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Although glycemic status is associated with impaired cardiac structure and function, less is known on left atrial (LA) function across the glycemic spectrum. We evaluated the association of diabetes and glycemic control with LA function in a community-based cohort of older adults. This cross-sectional analysis included 5075 participants from the Atherosclerosis Risk in Communities Study (mean age 75.5 years, 58 % women, and 20 % Black adults) with echocardiographic strain data for LA reservoir, conduit, and contractile function. Multivariable linear regression was used to assess associations of diabetes status and glycemic control with LA function. In participants without diabetes, we used ordinal linear regression to evaluate associations of fasting glucose and HbA1c with LA function. Compared to individuals with a normal fasting glucose, prevalent diabetes was associated with 0.68 % lower LA conduit function (95 % confidence interval (CI): 1.11 to −0.25) and prediabetes a 0.47 % reduction (95 % CI: 0.85 to −0.09) in fully adjusted analyses. Persons with diabetes and high HbA1c (HgbA1c ≥ 7 % vs <7 %) had 1.05 % lower LA conduit function (95 % CI: 1.63, −0.48). Among individuals without diagnosed diabetes, higher fasting glucose, but not HbA1c, was significantly associated with worse LA conduit function. No significant associations were observed for LA reservoir and contractile function. A history of diabetes, prediabetes, and higher fasting glucose levels in persons without diabetes were associated with worse LA conduit function. Corroborative research is needed in prospective cohorts as well as studies that explore underlying mechanisms. • We evaluated differences in LA function according to diabetes status and glycemic control. • Diabetes and prediabetes were associated with worse LA function compared to those with normal fasting glucose levels. • Poorer diabetes control was associated with worse LA function. • Higher fasting glucose amongst those without diabetes was associated with worse LA function. • Findings suggest impaired glucose may adversely affect LA function. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Impact of Sleep Disorders and Disturbed Sleep on Brain Health: A Scientific Statement From the American Heart Association.
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Gottesman, Rebecca F., Lutsey, Pamela L., Benveniste, Helene, Brown, Devin L., Full, Kelsie M., Jin-Moo Lee, Osorio, Ricardo S., Pase, Matthew P., Redeker, Nancy S., Redline, Susan, and Spira, Adam P.
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- 2024
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4. Plasma Ferritin Levels, Incident Heart Failure, and Cardiac Structure and Function
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Aboelsaad, Iman A.F., Claggett, Brian L., Arthur, Victoria, Dorbala, Pranav, Matsushita, Kunihiro, Lennep, Brandon W., Yu, Bing, Lutsey, Pamela L., Ndumele, Chiadi E., Farag, Youssef M.K., Shah, Amil M., and Buckley, Leo F.
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Whether iron deficiency contributes to incident heart failure (HF) and cardiac dysfunction has important implications given the prevalence of iron deficiency and the availability of several therapeutics for iron repletion.
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- 2024
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5. Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol
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Zhang, Yiyi, Dron, Jacqueline S., Bellows, Brandon K., Khera, Amit V., Liu, Junxiu, Balte, Pallavi P., Oelsner, Elizabeth C., Amr, Sami Samir, Lebo, Matthew S., Nagy, Anna, Peloso, Gina M., Natarajan, Pradeep, Rotter, Jerome I., Willer, Cristen, Boerwinkle, Eric, Ballantyne, Christie M., Lutsey, Pamela L., Fornage, Myriam, Lloyd-Jones, Donald M., Hou, Lifang, Psaty, Bruce M., Bis, Joshua C., Floyd, James S., Vasan, Ramachandran S., Heard-Costa, Nancy L., Carson, April P., Hall, Michael E., Rich, Stephen S., Guo, Xiuqing, Kazi, Dhruv S., de Ferranti, Sarah D., and Moran, Andrew E.
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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.
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- 2024
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6. Impact of Sleep Disorders and Disturbed Sleep on Brain Health: A Scientific Statement From the American Heart Association
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Gottesman, Rebecca F., Lutsey, Pamela L., Benveniste, Helene, Brown, Devin L., Full, Kelsie M., Lee, Jin-Moo, Osorio, Ricardo S., Pase, Matthew P., Redeker, Nancy S., Redline, Susan, and Spira, Adam P.
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Accumulating evidence supports a link between sleep disorders, disturbed sleep, and adverse brain health, ranging from stroke to subclinical cerebrovascular disease to cognitive outcomes, including the development of Alzheimer disease and Alzheimer disease–related dementias. Sleep disorders such as sleep-disordered breathing (eg, obstructive sleep apnea), and other sleep disturbances, as well, some of which are also considered sleep disorders (eg, insomnia, sleep fragmentation, circadian rhythm disorders, and extreme sleep duration), have been associated with adverse brain health. Understanding the causal role of sleep disorders and disturbances in the development of adverse brain health is complicated by the common development of sleep disorders among individuals with neurodegenerative disease. In addition to the role of sleep disorders in stroke and cerebrovascular injury, mechanistic hypotheses linking sleep with brain health and biomarker data (blood-based, cerebrospinal fluid-based, and imaging) suggest direct links to Alzheimer disease–specific pathology. These potential mechanisms and the increasing understanding of the “glymphatic system,” and the recognition of the importance of sleep in poststroke recovery, as well, support a biological basis for the indirect (through the worsening of vascular disease) and direct (through specific effects on neuropathology) connections between sleep disorders and brain health. Given promising evidence for the benefits of treatment and prevention, sleep disorders and disturbances represent potential targets for early treatment that may improve brain health more broadly. In this scientific statement, we discuss the evidence supporting an association between sleep disorders and disturbances and poor brain health ranging from stroke to dementia and opportunities for prevention and early treatment.
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- 2024
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7. Association of Supine Hypertension Versus Standing Hypotension Wi Among Middle-Aged Adults.
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Earle, William B., Kondo, Jordan K., Kendrick, Karla N., Turkson-Ocran, Ruth-Alma, Long Ngo, Cluett, Jennifer L., Mukamal, Kenneth J., Malek, Natalie Daya, Selvin, Elizabeth, Lutsey, Pamela L., Coresh, Josef, and Juraschek, Stephen P.
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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]
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- 2023
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8. Non-cigarette tobacco products, aryl-hydrocarbon receptor repressor gene methylation and smoking-related health outcomes
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Eckhardt, Christina M, Balte, Pallavi, Morris, Jack E, Bhatt, Surya P, Couper, David, Fetterman, Jessica, Freedman, Neal, Jacobs, David R, Hou, Lifang, Kalhan, Ravi, Liu, Yongmei, Loehr, Laura, Lutsey, Pamela L, Schwartz, Joseph E, White, Wendy, Yende, Sachin, London, Stephanie J, Sanchez, Tiffany R, and Oelsner, Elizabeth C
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IntroductionCigarette smoking leads to altered DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) gene. However, it remains unknown whether pipe or cigar smoking is associated with AHRR methylation. We evaluated associations of non-cigarette tobacco use with AHRR methylation and determined if AHRR methylation was associated with smoking-related health outcomes.MethodsData were pooled across four population-based cohorts that enrolled participants from 1985 to 2002. Tobacco exposures were evaluated using smoking questionnaires. AHRR cg05575921 methylation was measured in peripheral blood leucocyte DNA. Spirometry and respiratory symptoms were evaluated at the time of methylation measurements and in subsequent visits. Vital status was monitored using the National Death Index.ResultsAmong 8252 adults (mean age 56.7±10.3 years, 58.1% women, 40.6% black), 4857 (58.9%) participants used cigarettes and 634 (7.7%) used non-cigarette tobacco products. Exclusive use of non-cigarette tobacco products was independently associated with lower AHRR methylation (−2.44 units, 95% CI −4.42 to −0.45), though to a lesser extent than exclusive use of cigarettes (−6.01 units, 95% CI −6.01 to −4.10). Among participants who exclusively used non-cigarette tobacco products, reduced AHRR methylation was associated with increased respiratory symptom burden (OR 1.60, 95% CI 1.03 to 2.68) and higher all-cause mortality (log-rank p=0.02).ConclusionPipe and cigar smoking were independently associated with lower AHRR methylation in a multiethnic cohort of US adults. Among users of non-cigarette tobacco products, lower AHRR methylation was associated with poor respiratory health outcomes and increased mortality. AHRR methylation may identify non-cigarette tobacco users with an increased risk of adverse smoking-related health outcomes.
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- 2024
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9. Multi-dimensional sleep and mortality: The Multi-Ethnic Study of Atherosclerosis.
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Chung, Joon, Goodman, Matthew, Huang, Tianyi, Wallace, Meredith L, Lutsey, Pamela L, Chen, Jarvis T, Castro-Diehl, Cecilia, Bertisch, Suzanne, and Redline, Susan
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- 2023
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10. Dementia occurring over a 32‐year follow‐up attributable to hypertension observed at different ages: Implications for dementia prevention.
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Smith, Jason R., Sharrett, A. Richey, Pike, James Russel, Gottesman, Rebecca F., Knopman, David S., Lee, Mark, Lutsey, Pamela L., Palta, Priya, Windham, B. Gwen, Coresh, Josef, and Deal, Jennifer A.
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INTRODUCTION: The fraction of dementia attributable to hypertension might vary depending on the age of the population considered and the age through which dementia occurs. METHODS: In the Atherosclerosis Risk in Communities study, we quantified population attributable fractions (PAF) of dementia by age 80 and 90 from hypertension assessed at ages of 45–54 (n = 7572), 55–64 (n = 12,033), 65–74 (n = 6561), and 75–84 (n = 2086). RESULTS: The PAF for dementia by age 80 from all non‐normal blood pressure at ages 45–54 was 15.3% (95% confidence interval [CI] = 6.9%–22.3%), 19.1% (95% CI = 9.9%–26.9%) at ages 55–64, and 19.9% (95% CI = −4.4%–38.5%) at ages 65–74. The strongest PAFs were from stage 2 hypertension (11.9%–21.3%). For dementia by age 90, PAFs from non‐normal blood pressure up through age 75 were smaller (10.9%–13.8%), and non‐significant by age 75–84. DISCUSSION: Interventions targeting hypertension even in early late life might reduce a sizeable proportion of dementia. Highlights: We estimated prospective population attributable risks of dementia for hypertension.15%–20% of dementia cases by age 80 are from non‐normal blood pressure (BP).Associations between hypertension and dementia persisted through age 75.Midlife to early late‐life BP control might reduce a large proportion of dementia. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Social engagement and the risk of incident dementia: the Atherosclerosis Risk in Communities study.
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Groechel, Renée C., Liu, Albert C., Lutsey, Pamela L., Palta, Priya, Kucharska‐Newton, Anna M., Koton, Silvia, Sharrett, A. Richey, Gross, Alden L., Walker, Keenan A., and Gottesman, Rebecca F.
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Background: Strong psychosocial health has been linked to preserved cognition and functional independence in older adults. Associations between late‐life psychosocial health and dementia risk have been established in older adults, but it remains less clear how one's social interactions in mid‐life may relate to dementia risk in late life. We hypothesized that social engagement in mid‐life will be negatively associated with the risk of dementia in late‐life. Method: We included data from 13,216 dementia‐free participants at midlife (mean age: 57.0 years, SD: 5.7 years, 54.9% female, 23.8% Black) from the Atherosclerosis Risk in Communities (ARIC) cohort study. Social support and isolation were assessed via interviewer‐administered questionnaires (visit 2: 1990‐1992). Based upon categorization of both factors, participants were classified as having high, intermediate, or low mid‐life social engagement. Incident dementia cases were identified from visit 2 through December 31, 2019 with ongoing surveillance (e.g., in‐person neurocognitive testing, informant interviews, and hospitalization codes). Primary analyses used Cox proportional hazards regression models and were adjusted for demographics, APOE ε4, occupational/marital status, depressive symptoms, and vascular risk factors measured at visit 2. Secondary analyses examined whether sex and/or race modified the association between mid‐life social engagement and dementia risk with formal tests for interaction. Result: Among 13,261 participants, 2,555 developed dementia (median follow‐up: 23.7 years). Participants with high (hazard ratio (HR): 0.77, 95% CI: 0.68 ‐ 0.86) or intermediate social engagement (HR: 0.84, 95% CI: 0.74 – 0.95) in mid‐life had a lower risk for developing dementia, compared to participants with low social engagement in mid‐life (Figure 1, Table 1). Sex modified this effect (p‐value for interaction = 0.042) whereas race did not. In males, only those with high social engagement in mid‐life had a lower risk of dementia; the association between males with intermediate social engagement in mid‐life and dementia risk was not significant (Table 2). Conclusion: Greater social engagement in mid‐life is associated with a lower risk of dementia. This finding provides further evidence that mid‐life may be a critical time window for dementia prevention. Longitudinal studies evaluating the mechanisms by which psychosocial factors modify the likelihood of incident dementia are needed. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Polysomnography derived sleep metrics and cognition in the Sleep and Dementia Consortium (SDC): a study of 5 population‐based cohorts.
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Pase, Matthew P., Harrison, Stephanie, Misialek, Jeffrey, Kline, Christopher, Cavuoto, Marina G., Baril, Andree‐Ann, Yiallourou, Stephanie, Bisson, Alycia, Himali, Dibya, Leng, Yue, Yang, Qiong, Seshadri, Sudha, Beiser, Alexa S., Gottesman, Rebecca F., Redline, Susan, Lopez, Oscar L., Lutsey, Pamela L., Yaffe, Kristine, Stone, Katie L, and Purcell, Shaun
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Background: Good sleep is essential for health, yet the role of sleep in dementia risk is incompletely understood. The Sleep and Dementia Consortium (SDC) was established to study associations between polysomnography (PSG)‐derived sleep metrics and the risk of dementia and related cognitive and brain MRI endophenotypes. This study presents the associations of sleep architecture and obstructive sleep apnea (OSA) with cognitive function across participating cohorts. Method: The SDC curates data from five population‐based cohorts with methodologically consistent, overnight, home‐based PSG and neuropsychological assessments over 5 years of follow‐up. Cohorts include the Atherosclerosis Risk in Communities (ARIC) study, Cardiovascular Health Study (CHS), Framingham Heart Study (FHS), Osteoporotic Fractures in Men Study (MrOS), and Study of Osteoporotic Fractures (SOF). Global cognitive composite scores were derived from principal component analysis as the primary outcome. All sleep metrics were harmonized centrally and then distributed to the participating cohorts for cohort‐specific analysis using linear regression; study‐level estimates were pooled in random effects meta‐analyses. Results are adjusted for demographic variables, the time interval between the PSG and neuropsychological assessment (0‐5 years), body mass index, antidepressant use, and sedative medication use. Result: The mean age of the cohorts ranged from 58 to 89 years (Figure 1) with a pooled sample of 5,946 participants. As shown in Figure 2, across cohorts, higher REM sleep percentage (pooled β±SE = 0.49±0.18 per % increase; p = 0.008) and Sleep Maintenance Efficiency (pooled β±SE = 0.08±0.03 per % increase; p = 0.01) were associated with better global cognition whereas OSA (Apnea‐hypopnea index [AHI] ≥ 5) was associated with worse global cognition (pooled β±SE = ‐0.06±0.02 vs. AHI<5; p = 0.03). Differences in N3 sleep were not associated with cognition. Conclusion: Better sleep consolidation and higher REM sleep percentage were associated with better cognition whereas OSA was associated with worse cognition over 5‐years follow‐up. The role of interventions to improve sleep for maintaining cognitive function and potentially reduce dementia risk requires investigation. [ABSTRACT FROM AUTHOR]
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- 2023
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13. Social engagement, amyloid burden, and dementia: the Atherosclerosis Risk in Communities (ARIC)‐PET study.
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Groechel, Renée C., Liu, Chelsea, Knopman, David S., Koton, Silvia, Kucharska‐Newton, Anna M., Liu, Albert C., Lutsey, Pamela L., Mosley, Thomas H., Palta, Priya, Sharrett, Richey, Walker, Keenan A., Wong, Dean F., and Gottesman, Rebecca F.
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Background: Although amyloid deposition in the brain is often associated with subsequent dementia risk, not everyone with brain amyloid will develop dementia. This discrepancy illustrates the potential importance that risk factors and lived experiences may have in modifying this association. Compared to participants with low social engagement (SE) in mid‐life, we hypothesized that participants with high mid‐life SE will show a weaker association between amyloid burden and incident dementia. Method: We included data from 310 non‐demented participants of the Atherosclerosis Risk in Communities (ARIC)‐PET study. Social support and isolation were assessed via interviewer‐administered questionnaires (Visit 2; 1990 – 1992). Based upon categorization of both factors, participants were classified as having high, intermediate, or low mid‐life SE (Table 1). Brain amyloid was evaluated with florbetapir PET (Visit 5; 2011‐2014). Elevated amyloid burden was defined as standardized uptake value ratio (SUVR) >1.2 in the global cortex. Incident dementia cases were identified from visit 5 through 2019 through ongoing surveillance utilizing in‐person neurocognitive testing, informant interviews, and hospitalization codes. Relative contributions of mid‐life SE and elevated florbetapir SUVR to incident dementia, independently and with multiplicative interaction terms, were evaluated with Cox regression models, adjusted for demographics, APOEε4 and vascular risk factors Result: Among 310 participants, 48 developed dementia (median follow‐up: 4.7 years). Mid‐life SE and elevated SUVR each independently predicted dementia risk but did not interact on a multiplicative scale. Participants with high or intermediate mid‐life SE, relative to low mid‐life SE, were less likely to develop dementia (Table 2). Although the interaction between mid‐life SE and elevated SUVR was not significant, stratified models suggested a stronger association between amyloid burden and dementia in participants with high mid‐life SE (Table 3). Conclusion: Greater mid‐life SE was associated with lower odds of developing dementia, independent of elevated SUVR. Although protective, there was no strong evidence for effect modification of mid‐life SE on the association between amyloid and dementia risk. Future longitudinal studies evaluating the potential influence of social factors measured throughout the life course are needed to inform our understanding as to what factors may preserve cognition in the presence of elevated brain pathology. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Social engagement, amyloid burden, and dementia: the Atherosclerosis Risk in Communities (ARIC)‐PET study.
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Groechel, Renée C., Liu, Chelsea, Knopman, David S., Koton, Silvia, Kucharska‐Newton, Anna M., Liu, Albert C., Lutsey, Pamela L., Mosley, Thomas H., Palta, Priya, Sharrett, Richey, Walker, Keenan A., Wong, Dean F., and Gottesman, Rebecca F.
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Background: Although amyloid deposition in the brain is often associated with subsequent dementia risk, not everyone with brain amyloid will develop dementia. This discrepancy illustrates the potential importance that risk factors and lived experiences may have in modifying this association. Compared to participants with low social engagement (SE) in mid‐life, we hypothesized that participants with high mid‐life SE will show a weaker association between amyloid burden and incident dementia. Method: We included data from 310 non‐demented participants of the Atherosclerosis Risk in Communities (ARIC)‐PET study. Social support and isolation were assessed via interviewer‐administered questionnaires (Visit 2; 1990 – 1992). Based upon categorization of both factors, participants were classified as having high, intermediate, or low mid‐life SE (Table 1). Brain amyloid was evaluated with florbetapir PET (Visit 5; 2011‐2014). Elevated amyloid burden was defined as standardized uptake value ratio (SUVR) >1.2 in the global cortex. Incident dementia cases were identified from visit 5 through 2019 through ongoing surveillance utilizing in‐person neurocognitive testing, informant interviews, and hospitalization codes. Relative contributions of mid‐life SE and elevated florbetapir SUVR to incident dementia, independently and with multiplicative interaction terms, were evaluated with Cox regression models, adjusted for demographics, APOEe4 and vascular risk factors Result: Among 310 participants, 48 developed dementia (median follow‐up: 4.7 years). Mid‐life SE and elevated SUVR each independently predicted dementia risk but did not interact on a multiplicative scale. Participants with high or intermediate mid‐life SE, relative to low mid‐life SE, were less likely to develop dementia (Table 2). Although the interaction between mid‐life SE and elevated SUVR was not significant, stratified models suggested a stronger association between amyloid burden and dementia in participants with high mid‐life SE (Table 3). Conclusion: Greater mid‐life SE was associated with lower odds of developing dementia, independent of elevated SUVR. Although protective, there was no strong evidence for effect modification of mid‐life SE on the association between amyloid and dementia risk. Future longitudinal studies evaluating the potential influence of social factors measured throughout the life course are needed to inform our understanding as to what factors may preserve cognition in the presence of elevated brain pathology. [ABSTRACT FROM AUTHOR]
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- 2023
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15. Changes in Cardiovascular Health Across Midlife and Late-Life and Magnetic Resonance Imaging Markers of Cerebral Vascular Disease in Late-Life.
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Sedaghat, Sanaz, Ji, Yuekai, Empana, Jean-Philippe, Hughes, Timothy M., Mosley, Thomas H., Gottesman, Rebecca F., Griswold, Michael, Jack Jr, Clifford R., Lutsey, Pamela L., and van Sloten, Thomas T.
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- 2023
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16. Association of change in cardiovascular risk factors with incident dementia.
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Sedaghat, Sanaz, Lutsey, Pamela L., Ji, Yuekai, Empana, Jean‐Philippe, Sorond, Farzaneh, Hughes, Timothy M., Mosley, Thomas H., Gottesman, Rebecca F., Knopman, David S., Walker, Keenan A., Gudnason, Vilmundur, Launer, Lenore J., and van Sloten, Thomas T.
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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. [ABSTRACT FROM AUTHOR]
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- 2023
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17. Associations of sleep characteristics in late midlife with late-life hearing loss in the Atherosclerosis Risk in Communities-Sleep Heart Health Study (ARIC-SHHS)
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Jiang, Kening, Spira, Adam P., Gottesman, Rebecca F., Full, Kelsie M., Lin, Frank R., Lutsey, Pamela L., Garcia Morales, Emmanuel E., Punjabi, Naresh M., Reed, Nicholas S., Sharrett, A. Richey, and Deal, Jennifer A.
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This study investigated associations of late midlife sleep characteristics with late-life hearing, which adds to the existing cross-sectional evidence and is novel in examining polysomnographic sleep measures and central auditory processing.
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- 2023
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18. Association of Severe Hypercholesterolemia and Familial Hypercholesterolemia Genotype With Risk of Coronary Heart Disease
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Zhang, Yiyi, Dron, Jacqueline S., Bellows, Brandon K., Khera, Amit V., Liu, Junxiu, Balte, Pallavi P., Oelsner, Elizabeth C., Amr, Sami Samir, Lebo, Matthew S., Nagy, Anna, Peloso, Gina M., Natarajan, Pradeep, Rotter, Jerome I., Willer, Cristen, Boerwinkle, Eric, Ballantyne, Christie M., Lutsey, Pamela L., Fornage, Myriam, Lloyd-Jones, Donald M., Hou, Lifang, Psaty, Bruce M., Bis, Joshua C., Floyd, James S., Vasan, Ramachandran S., Heard-Costa, Nancy L., Carson, April P., Hall, Michael E., Rich, Stephen S., Guo, Xiuqing, Kazi, Dhruv S., de Ferranti, Sarah D., and Moran, Andrew E.
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- 2023
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19. Changes in Cardiovascular Health Across Midlife and Late-Life and Magnetic Resonance Imaging Markers of Cerebral Vascular Disease in Late-Life
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Sedaghat, Sanaz, Ji, Yuekai, Empana, Jean-Philippe, Hughes, Timothy M., Mosley, Thomas H., Gottesman, Rebecca F., Griswold, Michael, Jack, Clifford R., Lutsey, Pamela L., and van Sloten, Thomas T.
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- 2023
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20. OSA and Subsequent Risk of Hospitalization With Pneumonia, Respiratory Infection, and Total Infection
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Lutsey, Pamela L., Zineldin, Islam, Misialek, Jeffrey R., Full, Kelsie M., Lakshminarayan, Kamakshi, Ishigami, Junichi, Cowan, Logan T., Matsushita, Kunihiro, and Demmer, Ryan T.
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OSA has been linked to microaspiration, systemic inflammation, and suboptimal immune function.
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- 2023
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21. Epidemiology and prevention of venous thromboembolism
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Lutsey, Pamela L. and Zakai, Neil A.
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Venous thromboembolism, that consists of the interrelated conditions deep-vein thrombosis and pulmonary embolism, is an under-appreciated vascular disease. In Western regions, approximately 1 in 12 individuals will be diagnosed with venous thromboembolism in their lifetime. Rates of venous thromboembolism are lower in Asia, but data from other regions are sparse. Numerous risk factors for venous thromboembolism have been identified, which can be classified as acute or subacute triggers (provoking factors that increase the risk of venous thromboembolism) and basal or acquired risk factors (which can be modifiable or static). Approximately 20% of individuals who have a venous thromboembolism event die within 1 year (although often from the provoking condition), and complications are common among survivors. Fortunately, opportunities exist for primordial prevention (prevention of the development of underlying risk factors), primary prevention (management of risk factors among individuals at high risk of the condition) and secondary prevention (prevention of recurrent events) of venous thromboembolism. In this Review, we describe the epidemiology of venous thromboembolism, including the incidence, risk factors, outcomes and opportunities for prevention. Meaningful health disparities exist in both the incidence and outcomes of venous thromboembolism. We also discuss these disparities as well as opportunities to reduce them.
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- 2023
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22. Proteomics Analysis of Genetic Liability of Abdominal Aortic Aneurysm Identifies Plasma Neogenin and Kit Ligand: The ARIC Study
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Steffen, Brian T., Pankow, James S., Norby, Faye L., Lutsey, Pamela L., Demmer, Ryan T., Guan, Weihua, Pankratz, Nathan, Li, Aixin, Liu, Guning, Matsushita, Kunihiro, Tin, Adrienne, and Tang, Weihong
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- 2023
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23. Adipokines and incident venous thromboembolism: The Multi-Ethnic Study of Atherosclerosis
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Broni, Eric K., Ogunmoroti, Oluseye, Quispe, Renato, Sweeney, Ty, Varma, Bhavya, Fashanu, Oluwaseun E., Lutsey, Pamela L., Allison, Matthew, Szklo, Moyses, Ndumele, Chiadi E., and Michos, Erin D.
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Obesity leads to adipocyte hypertrophy and adipokine dysregulation and is an independent risk factor for venous thromboembolism (VTE). However, the association between adipokines and VTE is not well established.
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- 2023
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24. Cross-Ancestry Investigation of Venous Thromboembolism Genomic Predictors
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Thibord, Florian, Klarin, Derek, Brody, Jennifer A., Chen, Ming-Huei, Levin, Michael G., Chasman, Daniel I., Goode, Ellen L., Hveem, Kristian, Teder-Laving, Maris, Martinez-Perez, Angel, Aïssi, Dylan, Daian-Bacq, Delphine, Ito, Kaoru, Natarajan, Pradeep, Lutsey, Pamela L., Nadkarni, Girish N., de Vries, Paul S., Cuellar-Partida, Gabriel, Wolford, Brooke N., Pattee, Jack W., Kooperberg, Charles, Braekkan, Sigrid K., Li-Gao, Ruifang, Saut, Noemie, Sept, Corriene, Germain, Marine, Judy, Renae L., Wiggins, Kerri L., Ko, Darae, O’Donnell, Christopher J., Taylor, Kent D., Giulianini, Franco, De Andrade, Mariza, Nøst, Therese H., Boland, Anne, Empana, Jean-Philippe, Koyama, Satoshi, Gilliland, Thomas, Do, Ron, Huffman, Jennifer E., Wang, Xin, Zhou, Wei, Manuel Soria, Jose, Carlos Souto, Juan, Pankratz, Nathan, Haessler, Jeffery, Hindberg, Kristian, Rosendaal, Frits R., Turman, Constance, Olaso, Robert, Kember, Rachel L., Bartz, Traci M., Lynch, Julie A., Heckbert, Susan R., Armasu, Sebastian M., Brumpton, Ben, Smadja, David M., Jouven, Xavier, Komuro, Issei, Clapham, Katharine R., Loos, Ruth J.F., Willer, Cristen J., Sabater-Lleal, Maria, Pankow, James S., Reiner, Alexander P., Morelli, Vania M., Ridker, Paul M, Vlieg, Astrid van Hylckama, Deleuze, Jean-François, Kraft, Peter, Rader, Daniel J., Min Lee, Kyung, Psaty, Bruce M., Heidi Skogholt, Anne, Emmerich, Joseph, Suchon, Pierre, Rich, Stephen S., Vy, Ha My T., Tang, Weihong, Jackson, Rebecca D., Hansen, John-Bjarne, Morange, Pierre-Emmanuel, Kabrhel, Christopher, Trégouët, David-Alexandre, Damrauer, Scott M., Johnson, Andrew D., and Smith, Nicholas L.
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- 2022
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25. Periodontal Status, C-Reactive Protein, NT-proBNP, and Incident Heart Failure
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Molinsky, Rebecca L., Yuzefpolskaya, Melana, Norby, Faye L., Yu, Bing, Shah, Amil M., Pankow, James S., Ndumele, Chiadi E., Lutsey, Pamela L., Papapanou, Panos N., Beck, James D., Colombo, Paolo C., and Demmer, Ryan T.
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Periodontal disease (PD), resulting from inflammatory host response to dysbiotic subgingival microbiota, has been linked to cardiovascular disease; however, its relationship to heart failure (HF) and its subtypes (heart failure with reduced ejection fraction [HFrEF] and heart failure with preserved ejection fraction [HFpEF]) is unexplored.
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- 2022
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26. Venous thrombosis risk during and after medical and surgical hospitalizations: The medical inpatient thrombosis and hemostasis (MITH) study
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Jordan Bruno, Ximena, Koh, Insu, Lutsey, Pamela L., Walker, Robert F., Roetker, Nicholas S., Wilkinson, Katherine, Smith, Nicolas L., Plante, Timothy B., Repp, Allen B., Holmes, Chris E., Cushman, Mary, and Zakai, Neil A.
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Thirty to seventy percent of all venous thromboembolism (VTE) events are associated with hospitalization. The absolute and relative risks during and after hospitalization are poorly characterized.
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- 2022
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27. Venous thrombosis risk during and after medical and surgical hospitalizations: The medical inpatient thrombosis and hemostasis (MITH) study
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Jordan Bruno, Ximena, Koh, Insu, Lutsey, Pamela L., Walker, Robert F., Roetker, Nicholas S., Wilkinson, Katherine, Smith, Nicolas L., Plante, Timothy B., Repp, Allen B., Holmes, Chris E., Cushman, Mary, and Zakai, Neil A.
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Thirty to seventy percent of all venous thromboembolism (VTE) events are associated with hospitalization. The absolute and relative risks during and after hospitalization are poorly characterized. Quantify the absolute rate and relative risk of VTE during and up to 3 months after medical and surgical hospitalizations. We conducted an observational cohort study between 2010 and 2016 of patients cared for by the University of Vermont (UVM) Health Network's primary care population. Cox proportional hazard models with hospitalization modeled as a time‐varying covariate were used to estimate VTE risk. Over 4.3 years of follow‐up, 55 220 hospitalizations (156 per 1000 person‐years) and 713 first venous thromboembolism events (2.0 per 1000 person‐years) occurred. Among individuals not recently hospitalized, the rate of venous thromboembolism was 1.4 per 1000 person‐years and 71.8 per 1000 person‐years during hospitalization. During the first, second, and third months after discharge, the rates of venous thromboembolism were 35.1, 11.3, and 5.2 per 1000 person‐years, respectively. Relative to those not recently hospitalized, the age‐ and sex‐adjusted HRs of venous thromboembolism were 38.0 (95% CI 28.0, 51.5) during hospitalization, and 18.4 (95% CI 15.0, 22.6), 6.3 (95% CI 4.3, 9.0), and 3.0 (95% CI 1.7, 5.4) during the first, second, and third months after discharge, respectively. Stratified by medical versus surgical services the rates were similar. Hospitalization and up to 3 months after discharge were strongly associated with increased venous thromboembolism risk. These data quantify this risk for use in future studies.
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- 2022
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28. Association of birth weight with incident dementia: The Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study.
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Emanuel, Olivia M, Lee, Mark, Lutsey, Pamela L., Sullivan, Kevin J, Groechel, Renee C., Mosley, Thomas H., Schneider, Andrea LC, Wong, Dean F., and Gottesman, Rebecca F.
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Background: Early life factors, such as birth weight (BW), may have long‐term health consequences, but the importance of these factors in dementia risk is poorly understood. Our objective was to prospectively examine the association of BW with dementia incidence over mid‐ to late‐adulthood in the ARIC study. We hypothesized that participants who report lower BW experience more incident dementia than participants who report normal BW, and this association may differ by race. Method: 10,789 participants who were dementia‐free at ARIC baseline (Visit 1: 1987‐1989; ages 45‐64) and followed through 2019 were included. Participants were asked their BW through standard interviews at Visit 4 (1996‐1998), but if unable to recall, they selected their BW category: low (<5.5 lbs.), medium (normal) (5.5‐9.0 lbs.), or high (>9.0 lbs.), and to identify if they were premature (yes/no). Adjudicated dementia cases from baseline through 2019 were classified using in‐person cognitive evaluations, informant interviews, and phone assessments as well as hospitalization codes and death certificate codes. The associations between having high or low (vs medium) BW and dementia, or premature birth status and dementia were investigated using Cox proportional hazards models, with testing for interaction by race. Result: Our overall population was 54 yo at baseline, 56% female, and 20% Black; 2,255 dementia cases were identified over a median of 28.2 years. Participants who reported a low BW had 1.2 times (95% CI 1.02, 1.41) increased risk of incident dementia compared to those with medium BW in demographic‐ and APOE‐adjusted models (Table 1). This association was no longer significant when the model additionally adjusted for vascular risk factors. The risk for dementia was not increased among participants who reported having been born premature (vs not premature). When stratified by race, the risk of incident dementia was elevated in Black participants reporting high (vs medium) BW, but not in White participants reporting high BW (p‐interaction = 0.006) (Table 2). Conclusion: In this cohort, low BW was associated with risk of dementia in minimally adjusted models. The association was attenuated after accounting for vascular risk factors. High BW was associated with risk of dementia in Black participants only. [ABSTRACT FROM AUTHOR]
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- 2023
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29. Sleep Patterns and Prospective Diffusion Weighted Imaging Biomarkers: the Sleep and Dementia Consortium (SDC).
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Baril, Andree‐Ann, Misialek, Jeffrey, Cavuoto, Marina G., Yiallourou, Stephanie, Himali, Dibya, Sanchez, Erlan, Kline, Christopher, Redline, Susan, Purcell, Shaun, Beiser, Alexa S., Seshadri, Sudha, Gottesman, Rebecca F, Lutsey, Pamela L., Pase, Matthew P., and Himali, Jayandra Jung
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Background: Adequate sleep is necessary to maintain brain health, with sleep disturbances associated with higher Alzheimer's disease (AD) risk. Diffusion‐weighted imaging (DWI) metrics are increasingly recognized as useful neuroimaging biomarkers to detect AD‐related white matter degeneration. We assessed the relationship between sleep patterns and prospective DWI metrics in the Sleep and Dementia Consortium (SDC). The SDC studies associations between polysomnography (PSG)‐derived sleep with dementia risk and cognitive and MRI endophenotypes. Method: The SDC includes five community‐based cohorts, two of which have DWI acquisitions: The Framingham Heart Study (FHS) and the Atherosclerosis Risk in Communities study (ARIC). Dementia‐free participants who underwent both PSG and DWI‐MRI were selected, including 354 FHS participants (56.6±7.1y, 57%W), and 184 ARIC participants (61.6±5.0y, 52%W). The MRI session was approximately 15 years after the PSG on average (FHS:17.0±1.3y; ARIC:15.8±0.8y). Fractional anisotropy (FA) and mean diffusivity (MD) were considered for both cohorts, in addition to free‐water (FW) in the FHS. Sleep metrics were harmonized centrally, distributed for cohort‐specific linear regressions, and study‐level estimates were pooled in random effects meta‐analyses. Analyses were adjusted for demographics, obesity, time between PSG and MRI, antidepressants and sedative medication usage. An interaction term by APOE4 allele carrier status in regression models was used to test its moderating effect. Result: In the FHS, sleep fragmentation was associated with DWI measures in the expected direction: Higher Wake After Sleep Onset and lower Sleep Maintenance Efficiency were associated with lower FA (β±SE = ‐0.17±0.09,p = 0.04; β±SE = 0.23±0.10,p = 0.03), higher MD (β±SE = 0.15±0.07,p = 0.04; β±SE = ‐0.20±0.09,p = 0.03), and higher FW (β±SE = 0.17±0.07,p = 0.02; β±SE = ‐0.22±0.08,p = 0.008). Meta‐analysis of FHS and ARIC revealed significant pooled effects between lower Sleep Maintenance Efficiency and lower FA (β±SE = 0.17±0.08,p = 0.04). In the FHS, APOE4 allele significantly moderated the association between REM sleep proportion with FA and MD, where lower REM sleep percentage was associated with higher MD (β±SE = ‐4.89±1.95,p = 0.02) and lower FA (β±SE = 4.93±2.26,p = 0.03) in APOE4 carriers only. Conclusion: In the SDC, sleep fragmentation was associated with MRI markers of poorer white matter integrity 15 years later. Less REM sleep was associated with poorer white matter integrity in APOE4 allele carriers only, suggesting that disrupted sleep architecture may contribute and interact with neurodegenerative processes to affect brain integrity. [ABSTRACT FROM AUTHOR]
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- 2023
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30. Proteomic‐based Biological Aging Clock and MRI Markers of Cerebrovascular Disease: Atherosclerosis Risk in Community Study.
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Sedaghat, Sanaz, Wang, Shuo, Liu, Jialing, Hughes, Tim M., Sabayan, Behnam, Tang, Weihong, Coresh, Josef, Pankow, James, Walker, Keenan A., Lutsey, Pamela L., Guan, Weihua, and Prizment, Anna
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Background: Biological aging state can be quantified by composite metrics called aging clocks using proteomics. Proteomic aging clocks (PACs) are accurate, easily measured, and are associated with age‐related diseases including Alzheimer's Disease and Related Dementias. We aim to investigate whether an accelerated biological aging (a discrepancy between chronological age and PAC) is associated with subclinical cerebrovascular structural changes. Method: 1494 participants from the Atherosclerosis Risk in Communities (ARIC) Study with proteomics and 3T brain MRI data at ARIC visit 5 in 2011‐13 (mean age 76, 59% female, 25% Black) were included. Nearly 5000 plasma proteins were measured using the SomaScan assay. PAC was developed using elastic net regression model and was internally validated. Age acceleration was calculated as residuals after regressing PAC on chronological age (positive value indicates biological age is higher than the person's chronological age). Linear and logistic regression models were used to assess the associations of age acceleration with white matter hyperintensity volume (in cm3, log2 transformed, median [IQR]: 11[6‐20]) and the presence of: subcortical (n = 281), lacunar (n = 263), and cortical infarcts (n = 150), and microbleeds (n = 355). Result: Accelerated age (median [IQR]:‐0.04[‐1.4,1.3]; correlation with chronological age = 0) was associated with MRI markers of cerebrovascular disease after adjusting for demographic, cardiovascular risk factors, education, and kidney function. Every five years higher age acceleration was associated with larger white matter hyperintensity volume (Difference:0.34[95%CI 0.19,0.49]), higher odds of lacunar (OR:1.61[1.13,2.30]), subcortical (OR:1.63[1.15, 2.32]), and cortical infarcts (OR:1.72[1.11,2.67]). There was no association with presence of microbleeds (OR:1.25[0.91,1.73]) (Figure). Findings were consistent after excluding participants with clinical stroke and there was no difference between APOEe4+ and APOEe4‐ participants. Conclusion: Higher accelerated age is cross‐sectionally associated with a greater prevalence of MRI markers of cerebrovascular disease. Understanding this relation has potential to help with risk stratification and personalized prevention and treatment strategies to promote brain health. [ABSTRACT FROM AUTHOR]
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- 2023
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31. Gender differences in the association of insomnia symptoms and coronary artery calcification in the multi-ethnic study of atherosclerosis.
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Bertisch, Suzanne M, Reid, Michelle, Lutsey, Pamela L, Kaufman, Joel D, McClelland, Robyn, Patel, Sanjay R, and Redline, Susan
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- 2021
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32. Sleep apnea, hypoxia, and late-onset epilepsy: the Atherosclerosis Risk in Communities study
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Carosella, Christopher M, Gottesman, Rebecca F, Kucharska-Newton, Anna, Lutsey, Pamela L, Spira, Adam P, Punjabi, Naresh M, Schneider, Andrea L C, Full, Kelsie M, and Johnson, Emily L
- Abstract
Graphical Abstract
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- 2024
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33. Body mass index prediction rule for mid-upper arm circumference: the atherosclerosis risk in communities study
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Northuis, Carin A., Murray, Thomas A., Lutsey, Pamela L., Butler, Kenneth R., Nguyen, Steve, Palta, Priya, and Lakshminarayan, Kamakshi
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Supplemental Digital Content is available in the text.
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- 2022
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34. Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study.
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Northuis, Carin A., Bell, Elizabeth J., and Lutsey, Pamela L.
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- 2023
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35. CKD and Risk of Incident Hospitalization With Clostridioides difficileInfection: Findings From the Atherosclerosis Risk in Communities (ARIC) Study
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Ishigami, Junichi, Sumida, Keiichi, Grams, Morgan E., Chang, Alexander R., Lutsey, Pamela L., Levey, Andrew S., Coresh, Josef, Dowdy, David W., and Matsushita, Kunihiro
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- 2022
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36. Cognition and 20-year subsequent sleep disturbances
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West, Nancy A., Johnson, Dayna A., Lutsey, Pamela L., Mosley, Thomas H., and Redline, Susan
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There is a paucity of data exploring the extent that preclinical cognitive changes are predictive of subsequent sleep outcomes.
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- 2021
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37. Proteins Associated with Risk of Kidney Function Decline in the General Population
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Grams, Morgan E., Surapaneni, Aditya, Chen, Jingsha, Zhou, Linda, Yu, Zhi, Dutta, Diptavo, Welling, Paul A., Chatterjee, Nilanjan, Zhang, Jingning, Arking, Dan E., Chen, Teresa K., Rebholz, Casey M., Yu, Bing, Schlosser, Pascal, Rhee, Eugene P., Ballantyne, Christie M., Boerwinkle, Eric, Lutsey, Pamela L., Mosley, Thomas, Feldman, Harold I., Dubin, Ruth F., Ganz, Peter, Lee, Hongzhe, Zheng, Zihe, and Coresh, Josef
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- 2021
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38. Association of Type of Antidepressant Initiation with Bleeding Risk in Atrial Fibrillation Patients Taking Oral Anticoagulants
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Shao, Iris Yuefan, Claxton, J’Neka S., Lutsey, Pamela L., Chen, Lin Yee, MacLehose, Richard F., and Alonso, Alvaro
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Background: Inconsistent evidence suggests that use of certain antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), in patients using oral anticoagulants (OACs) might be associated with an elevated risk of bleeding. Objective: This study aims to investigate the risk of bleeding associated with initiation of different types of antidepressants among atrial fibrillation (AF) patients on OAC therapy. Patients and methods: A total of 30,336 AF patients (mean age 72.2 years; 54% female) on OAC therapy that started antidepressant treatment were identified from the Truven Health Analytics MarketScan Commercial and Medicare Databases for the period 2007–2015. Exposure was defined as filling a prescription for antidepressant, and categorized as SSRI, serotonin/norepinephrine reuptake inhibitors (SNRIs), serotonin reuptake inhibitors (SRIs), tricyclic antidepressants (TCAs), or other antidepressants. The primary outcome was incident hospitalized bleeding. Associations of antidepressant type with bleeding were assessed calculating hazard ratios (HRs) and 95% confidence intervals (CIs) with adjusted Cox models in pairwise propensity score-matched cohorts. Results: During a mean follow-up of 21 months, we identified 1612 bleeding episodes. In pairwise comparisons, SSRI use was associated with an increased risk of bleeding when compared to most other antidepressants (HR 1.22, 95% CI 0.96–1.54 vs SNRI; HR 1.10, 95% CI 0.90–1.35 vs SRI; HR 1.03, 95% CI 0.82–1.30 vs TCA). SNRI use was associated with the lowest bleeding risk. Results did not differ by OAC type, age, and sex. Conclusions: Among AF patients on OAC initiating antidepressants, risk of bleeding varied across antidepressant type. This information can inform treatment choices among patients receiving OAC.
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- 2021
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39. Proton Pump Inhibitor Use, Hypomagnesemia and Risk of Cardiovascular Diseases
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Rooney, Mary R., Bell, Elizabeth J., Alonso, Alvaro, Pankow, James S., Demmer, Ryan T., Rudser, Kyle D., Chen, Lin Y., and Lutsey, Pamela L.
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Supplemental Digital Content is available in the text.
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- 2021
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40. Association of Differential Leukocyte Count With Incident Abdominal Aortic Aneurysm Over 22.5 Years: The ARIC Study
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Parikh, Romil R., Folsom, Aaron R., Poudel, Kripa, Lutsey, Pamela L., Demmer, Ryan T., Pankow, James S., Chen, Lin Y., and Tang, Weihong
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Supplemental Digital Content is available in the text.
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- 2021
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41. Diurnal circadian variations in paroxysmal atrial fibrillation: The atherosclerosis risk in communities (ARIC) study.
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Kim, Jonathan, Wang, Wendy, Norby, Faye L., Zhang, Michael, Alonso, Alvaro, Lutsey, Pamela L., Soliman, Elsayed Z., Wolfson, Julian, and Chen, Lin Y.
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Background: Paroxysmal atrial fibrillation (AF) is challenging to diagnose due to its intermittent nature. Circadian rhythmicity has been reported for cardiovascular events such as myocardial infarction; whether diurnal variation exists for paroxysmal AF is less known. We characterized the temporal pattern of AF initiation in the Atherosclerosis Risk in Communities (ARIC) study, a prospective community-based cohort study.Methods: We included 74 ARIC study participants with paroxysmal AF detected by the Zio XT Patch at ARIC Visit 6 in 2016-17. We divided each participant's 2-week continuous monitoring data into 3-h intervals and summed the number of AF episodes in each interval. We performed Poisson regression using generalized estimating equations to estimate the effect of time of day on the number of AF episodes.Results: Compared to the reference interval of time 00:00-02:59, the time intervals 12:00-14:59, 15:00-17:59, and 18:00-20:59 had significantly higher frequency of AF initiation. Rate ratios (95% CI) for mean number of episodes in these three intervals were 1.91 (1.11, 2.92), 2.54 (1.42, 4.53), and 1.99 (1.19, 3.25) respectively. Furthermore, we found no significant association between duration of episode and time of day.Conclusion: There is diurnal variation in the initiation of AF episodes, with a peak in frequency in the late afternoon. Our finding is consistent with sympathetically driven AF. Pulse palpation or obtaining an electrocardiogram in the late afternoon may produce the highest diagnostic yield for AF. [ABSTRACT FROM AUTHOR]- Published
- 2020
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42. Hemostatic factors, inflammatory markers, and risk of incident venous thromboembolism: The Multi‐Ethnic Study of Atherosclerosis
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Evensen, Line H., Folsom, Aaron R., Pankow, James S., Hansen, John‐Bjarne, Allison, Matthew A., Cushman, Mary, and Lutsey, Pamela L.
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Several hemostatic factors and inflammatory markers are associated with the risk of incident venous thromboembolism (VTE), however, most existing data are from case‐control studies in Caucasian populations.
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- 2021
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43. Hemostatic factors, inflammatory markers, and risk of incident venous thromboembolism: The Multi‐Ethnic Study of Atherosclerosis
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Evensen, Line H., Folsom, Aaron R., Pankow, James S., Hansen, John‐Bjarne, Allison, Matthew A., Cushman, Mary, and Lutsey, Pamela L.
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Several hemostatic factors and inflammatory markers are associated with the risk of incident venous thromboembolism (VTE), however, most existing data are from case‐control studies in Caucasian populations. We aimed to prospectively confirm previous findings and explore less studied biomarkers in relation to VTE risk in a multi‐racial/multi‐ethnic cohort. Circulating levels of factor VIII, fibrinogen, D‐dimer, plasmin‐antiplasmin complex (PAP), C‐reactive protein (CRP), and interleukin‐6 (IL‐6) were measured at baseline (2000–2002) in 6706 participants of the Multi‐Ethnic Study of Atherosclerosis. Incident VTE was identified using hospitalization discharge codes from baseline to December 31, 2015. Hazard ratios (HRs) of VTE were estimated in Cox regression models. There were 227 events during a median of 14 years of follow‐up. Compared with participants in the lowest quartile, the HRs for those above the 95th percentile and pfor trend across categories were 3.50 (95% confidence interval [CI] 1.98–6.19; p< .001) for D‐dimer, 1.49 (95% CI 0.84–2.63; p= .02) for factor VIII, 1.32 (95% CI 0.76–2.28; p= .99) for fibrinogen, 1.92 (95% CI 1.08–3.42; p= .15) for PAP, 1.68 (95% CI 0.81–3.48; p= .08) for CRP, and 2.55 (95% CI 1.15–5.66; p= .07) for IL‐6, after adjustment for demographics and body mass index. For CRP and IL‐6, follow‐up was restricted to 10 years because of violations of the proportional hazards assumption. No significant interactions by age/ethnicity were observed. We demonstrated a fairly novel association between PAP and risk of incident VTE, and contributed further prospective confirmation regarding the associations of D‐dimer, factor VIII, and IL‐6 with VTE.
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- 2021
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44. Periodontal disease and incident dementia: The Atherosclerosis Risk in Communities Study (ARIC).
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Demmer, Ryan T., Norby, Faye L., Lakshminarayan, Kamakshi, Walker, Keenan A., Pankow, James S., Folsom, Aaron R., Mosley, Thomas, Beck, Jim, and Lutsey, Pamela L.
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- 2020
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45. Serum magnesium and burden of atrial and ventricular arrhythmias: The Atherosclerosis Risk in Communities (ARIC) Study.
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Rooney, Mary R., Lutsey, Pamela L., Alonso, Alvaro, Selvin, Elizabeth, Pankow, James S., Rudser, Kyle D., Dudley, Samuel C., Chen, Lin Yee, and Dudley, Samuel C Jr
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Introduction: Low serum magnesium (Mg) is associated with an increased incidence of atrial and ventricular arrhythmias. A richer phenotyping of arrhythmia indices, such as burden or frequency, may provide etiologic insights.Objectives: To evaluate cross-sectional associations of serum Mg with burden of atrial arrhythmias [atrial fibrillation (AF), premature atrial contractions (PAC), supraventricular tachycardia (SVT)], and ventricular arrhythmias [premature ventricular contractions (PVC), non-sustained ventricular tachycardia (NSVT)] over 2-weeks of ECG monitoring.Methods: We included 2513 ARIC Study visit 6 (2016-2017) participants who wore the Zio XT Patch-a leadless, ambulatory ECG-monitor-for up to 2-weeks. Serum Mg was modeled categorically and continuously. AF burden was categorized as intermittent or continuous based on the percent of analyzable time spent in AF. Other arrhythmia burdens were defined by the average number of abnormal beats per day. Linear regression was used for continuous outcomes; logistic and multinomial regression were used for categorical outcomes.Results: Participants were mean ± SD age 79 ± 5 years, 58% were women and 25% black. Mean serum Mg was 0.82 ± 0.08 mmol/L and 19% had hypomagnesemia (<0.75 mmol/L). Serum Mg was inversely associated with PVC burden and continuous AF. The AF association was no longer statistically significant with further adjustment for traditional lifestyle risk factors, only the association with PVC burden remained significant. There were no associations between serum Mg and other arrhythmias examined.Conclusions: In this community-based cohort of older adults, we found little evidence of independent cross-sectional associations between serum Mg and arrhythmia burden. [ABSTRACT FROM AUTHOR]- Published
- 2020
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46. Circulating electrolytes and the prevalence of atrial fibrillation and supraventricular ectopy: The Atherosclerosis Risk in Communities (ARIC) study.
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Alonso, Alvaro, Rooney, Mary R., Chen, Lin Y., Norby, Faye L., Saenger, Amy K., Soliman, Elsayed Z., O'Neal, Wesley T., Hootman, Katie C., Selvin, Elizabeth, and Lutsey, Pamela L.
- Abstract
Background and Aims: Evaluating associations of circulating electrolytes with atrial fibrillation (AF) and burden of supraventricular arrhythmias can give insights into arrhythmia pathogenesis.Methods and Results: We conducted a cross-sectional analysis of 6398 participants of the Atherosclerosis Risk in Communities (ARIC) study, ages 71-90, with data on serum electrolytes (magnesium, calcium, potassium, phosphorus, chloride, sodium). Prevalence of AF was determined from electrocardiograms and history of AF hospitalizations. A subset of 317 participants also underwent electrocardiographic recordings for up to 14 days using the Zio® patch. Burden of other supraventricular arrhythmias [premature atrial contractions (PACs), supraventricular tachycardia] was determined with the Zio® patch. We used logistic and linear regression adjusting for potential confounders to determine associations of electrolytes with arrhythmia prevalence and burden. Among 6394 eligible participants, 614 (10%) had AF. Participants in the top quintiles of magnesium [odds ratio (OR) 0.82, 95% confidence interval (CI) 0.62, 1.08], potassium (OR 0.82, 95%CI 0.68, 1.00), and phosphorus (OR 0.73, 95%CI 0.59, 0.89) had lower AF prevalence compared to those in the bottom quintiles. No clear association was found for circulating chloride, calcium or sodium. Higher concentrations of circulating calcium were associated with lower prevalence of PACs in the 12-lead electrocardiogram, while higher concentrations of potassium, chloride and sodium were associated with higher PAC prevalence. Circulating electrolytes were not significantly associated with burden of PACs or supraventricular tachycardia among 317 participants with extended electrocardiographic monitoring.Conclusion: Concentrations of circulating electrolytes present complex associations with selected supraventricular arrhythmias. Future studies should evaluate underlying mechanisms. [ABSTRACT FROM AUTHOR]- Published
- 2020
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47. Association of serum calcium and phosphorus with measures of left ventricular structure and function: The ARIC study.
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Poudel, Kripa, Shah, Amil M., Michos, Erin D., Folsom, Aaron R., Konety, Suma, and Lutsey, Pamela L.
- Abstract
Background and Aims: Elevated serum calcium and phosphorus have been associated with increased risk of cardiovascular disorders. We evaluated whether abnormal calcium and high serum phosphorus are associated cross-sectionally with echocardiographic measures of left ventricular (LV) structure and function, as doing so may provide insight into the etiology of cardiac disorders.Methods and Results: Included in the analysis were 5213 Atherosclerosis Risk in Communities Study (ARIC) participants who in 2011-2013 had echocardiography and serum calcium and phosphorus measurements. We evaluated the association of serum calcium (corrected for albumin) and phosphorus quintiles with measures of LV structure and function, after adjusting for other cardiovascular risk factors. Participants were on average 75.3 years old; 59.1% were female and 19.8% were African American. Mean (±SD) concentrations of calcium and phosphorus were 9.33 ± 0.38 and 3.46 ± 0.45 mg/dL, respectively. Higher calcium was associated with lower LV end-diastolic diameter (LVEDD) but greater prevalence of concentric remodeling (p-trend: 0.005 and 0.004 respectively). We observed association between high phosphorus and high septal E/e' (p-trend: 0.02). Likewise, higher serum phosphorus was associated with higher left atrial volume index (p-trend: 0.001) and LV hypertrophy prevalence (p-trend: 0.04).Conclusions: In conclusion, higher calcium was associated with more concentric remodeling but lower LVEDD, suggesting complex associations between calcium and cardiac function. Serum phosphorus was related to worse indices of LV diastolic function and LV hypertrophy, but not to LV systolic function. However, the magnitudes of association were modest, so clinical implications of these findings may be limited. [ABSTRACT FROM AUTHOR]- Published
- 2020
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48. Replication of Newly Identified Genetic Associations Between Abdominal Aortic Aneurysm and SMYD2, LINC00540, PCIF1/MMP9/ZNF335, and ERG.
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Tang, Weihong, Saratzis, Athanasios, Pattee, Jack, Smith, Jacqueline, Pankratz, Nathan, Leavy, Olivia C., Guan, Weihua, Dudbridge, Frank, Pankow, James S., Kitas, George D., Lutsey, Pamela L., and Bown, Matthew J.
- Abstract
A recently published genome wide association study of abdominal aortic aneurysms (AAA), based on pooled case control data of European ancestry, identified four new loci for AAA: SMYD2 (top single nucleotide polymorphism [SNP] rs1795061), LINC00540 (rs9316871), PCIF1/MMP9/ZNF335 (rs3827066), and ERG (rs2836411). Of the four, rs1795061 and rs2836411 showed significant heterogeneity across studies and the p value for rs9316871 did not reach the genome wide significance threshold until discovery and replication data were pooled together in that study. The objective of this study was to replicate these newly identified genetic associations for AAA in a US based prospective cohort study, the Atherosclerosis Risk in Communities (ARIC) Study, and a Greece based case control study. ARIC identified 408 clinically diagnosed AAAs among 8 962 individuals of European ancestry during a median of 22 years of follow up. The Greek case control study included 341 AAAs of European ancestry recruited in a tertiary referral centre and 292 geographically and ethnically matched controls recruited from the same institution. A Cox proportional hazards model was used to analyse the ARIC data and logistic regression to analyse the Greek data. In ARIC, rs9316871 and rs3827066 were significantly associated with AAA risk (HR [p] was 0.77 [.004] and 1.22 [.03], respectively), rs2836411 was associated at borderline significance (1.13 [.08]), whereas rs1795061 was not associated (p =.55). In the Greek case control study, rs1795061 and rs2836411 were significantly associated with AAA (OR [p] was 1.66 [<.001] and 1.29 [.04], respectively), whereas rs9316871 was not (p =.81). Genotyping of rs3827066 did not succeed. In the meta-analysis of the two studies, the association for rs9316871and rs2836411 was statistically significant and consistent between the two studies: p =.02 and.007, respectively. Associations between rs9316871and rs2836411 and AAA risk were replicated in the meta-analysis of the two independent cohorts, providing further support for the importance of these loci in the aetiology of AAA. [ABSTRACT FROM AUTHOR]
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- 2020
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49. Metabolic Syndrome and Risk of Ischemic Stroke in Atrial Fibrillation: ARIC Study.
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Decker, Joseph J., Norby, Faye L., Rooney, Mary R., Soliman, Elsayed Z., Lutsey, Pamela L., Pankow, James S., Alonso, Alvaro, and Chen, Lin Y.
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- 2019
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50. Diagnosed Sleep Apnea and Cardiovascular Disease in Atrial Fibrillation Patients: The Role of Measurement Error from Administrative Data.
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Ogilvie, Rachel P., MacLehose, Richard F., Alonso, Alvaro, Norby, Faye L., Lakshminarayan, Kamakshi, Iber, Conrad, Chen, Lin Y., and Lutsey, Pamela L.
- Abstract
Background: Atrial fibrillation and obstructive sleep apnea are common conditions, but little is known about obstructive sleep apnea and cardiovascular risk among atrial fibrillation patients.Methods: Using the Truven Health MarketScan databases, we constructed a prospective cohort of atrial fibrillation patients from 2007 to 2014. Atrial fibrillation, obstructive sleep apnea, stroke, myocardial infarction, and confounders were defined using the International Classification of Disease-9-CM codes. We matched individuals with an obstructive sleep apnea diagnosis with up to five individuals without a diagnosis by age, sex, and enrollment date. Cox proportional hazards models adjusted for confounders and high-dimensional propensity scores. We included migraines as a control outcome. Bias analysis used published sensitivities and specificities to generate rate ratios adjusted for obstructive sleep apnea misclassification.Results: We matched 56,969 individuals with an obstructive sleep apnea diagnosis to 323,246 without. During a mean follow-up of 16 months, 3234 incident strokes and 4639 incident myocardial infarctions occurred. After adjustment, obstructive sleep apnea diagnosis was strongly associated with reduced risk of incident stroke (hazard ratio = 0.48, 95% confidence interval = 0.43, 0.53) and myocardial infarction (0.40, [0.37, 0.44]) and a smaller reduced risk of migraines (0.82, [0.68, 0.99]). Bias analysis produced wide-ranging or inestimable rate ratios adjusted for misclassification of obstructive sleep apnea.Conclusions: Obstructive sleep apnea diagnosis in atrial fibrillation patients was strongly associated with reduced risk of incident cardiovascular disease. We discuss misclassification, selection bias, and residual confounding as potential explanations. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
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