Obstructive sleep apnea, nocturnal hypoxemia, and retinal microvasculature: The Atherosclerosis Risk in Communities Study.

Study Objectives: Retinal microvascular pathology (RMP) and obstructive sleep apnea (OSA) are both cardiovascular disease risk factors. Limited data exists on their interrelationship. We tested the hypotheses that OSA and nocturnal hypoxemia would be associated with RMP and vessel calibers. Methods: We conducted a quasi-cross-sectional analysis of 1625 participants in the Atherosclerosis Risk in Communities Sleep Heart Health Study. Participants completed in-home polysomnography monitoring (1996-1998) and were categorized by OSA severity (apnea-hypopnea index: <5, 5-14.9, and ≥15) and proportion of total sleep time with oxygen saturation < 90% (T90). Retinal photography (1993-1995) was used to assess RMP and measure vascular diameters (central retinal arteriolar equivalent [CRAE] and central retinal venular equivalent [CRVE]). Logistic and linear models were adjusted for demographics, behaviors, and BMI. Results: Of the participants, 19% had OSA (AHI > 15) and 4% had RMP. Severe OSA was not associated with RMP [OR (95% CI): 1.08 (0.49 to 2.38)] or CRAE in adjusted models. OSA severity showed a positive linear relationship with CRVE; adjusted mean CRVE for those with OSA was 195.8 µm compared to 193.2 µm for those without OSA (Ptrend = 0.03). T90 was strongly associated with CRVE, but not with RMP or CRAE. Adjusted mean CRVE for T90 ≥ 5% was 199.0 and 192.9 for T90 < 1% (ptrend < 0.0001). Conclusions: OSA and T90 were not associated with RMP or CRAE. However, both OSA and T90 ≥ 5% were associated with wider venules, which may be early and indicative changes of increased inflammation and future risk of stroke and CHD.

Omega-3 Polyunsaturated Fatty Acids are not associated with Peripheral Artery Disease in a Meta-Analysis from the Multi-Ethnic Study of Atherosclerosis and Atherosclerosis Risk in Communities Study Cohorts.

BACKGROUND: Research suggests omega-3 polyunsaturated fatty acids (PUFAs) exert favorable effects on several biological processes involved in the development and progression of atherosclerotic cardiovascular disease (ASCVD). However, studies examining the relationship between omega-3 PUFAs and peripheral artery disease (PAD) are scarce. OBJECTIVES: We evaluated the associations between omega-3 PUFAs and incident PAD in a meta-analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerosis Risk in Communities (ARIC) study cohorts. METHODS: Omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured at baseline for all MESA (n = 6495) and Minnesota ARIC participants (n = 3612). Incident clinical PAD events (MESA n = 106; ARIC n = 149) identified primarily through ICD discharge codes were assessed through follow-up of each cohort. Associations between omega-3 PUFAs (EPA, DHA, and EPA+DHA) and incident PAD were modeled in MESA and ARIC as quartiles and continuously using Cox proportional hazards regression, respectively. A fixed-effects meta-analysis was conducted to evaluate associations in the 2 cohorts combined. RESULTS: In the fully adjusted model, in 10,107 participants, no significant associations were observed between EPA, DHA, or EPA+DHA, and incident PAD modeled as quartiles or continuously for either MESA or ARIC cohorts separately or in the meta-analysis after a follow-up of approximately 15 y. CONCLUSION: This study is consistent with previous literature indicating that the beneficial effects of omega-3 PUFAs on the markers of ASCVD may not translate to a clinically meaningful decrease in PAD risk.

Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation.

BACKGROUND: The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial. OBJECTIVES: This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF. METHODS: We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS: Among 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively. CONCLUSIONS: In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.

Sleep Architecture, Obstructive Sleep Apnea, and Cognitive Function in Adults.

Importance: Good sleep is essential for health, yet associations between sleep and dementia risk remain incompletely understood. The Sleep and Dementia Consortium was established to study associations between polysomnography (PSG)-derived sleep and the risk of dementia and related cognitive and brain magnetic resonance imaging endophenotypes. Objective: To investigate association of sleep architecture and obstructive sleep apnea (OSA) with cognitive function in the Sleep and Dementia Consortium. Design, Setting, and Participants: The Sleep and Dementia Consortium curated data from 5 population-based cohorts across the US with methodologically consistent, overnight, home-based type II PSG and neuropsychological assessments over 5 years of follow-up: the Atherosclerosis Risk in Communities study, Cardiovascular Health Study, Framingham Heart Study (FHS), Osteoporotic Fractures in Men Study, and Study of Osteoporotic Fractures. Sleep metrics were harmonized centrally and then distributed to participating cohorts for cohort-specific analysis using linear regression; study-level estimates were pooled in random effects meta-analyses. Results were adjusted for demographic variables, the time between PSG and neuropsychological assessment (0-5 years), body mass index, antidepressant use, and sedative use. There were 5946 participants included in the pooled analyses without stroke or dementia. Data were analyzed from March 2020 to June 2023. Exposures: Measures of sleep architecture and OSA derived from in-home PSG. Main Outcomes and Measures: The main outcomes were global cognitive composite z scores derived from principal component analysis, with cognitive domains investigated as secondary outcomes. Higher scores indicated better performance. Results: Across cohorts, 5946 adults (1875 females [31.5%]; mean age range, 58-89 years) were included. The median (IQR) wake after sleep onset time ranged from 44 (27-73) to 101 (66-147) minutes, and the prevalence of moderate to severe OSA ranged from 16.9% to 28.9%. Across cohorts, higher sleep maintenance efficiency (pooled ß per 1% increase, 0.08; 95% CI, 0.03 to 0.14; P < .01) and lower wake after sleep onset (pooled ß per 1-min increase, -0.07; 95% CI, -0.13 to -0.01 per 1-min increase; P = .02) were associated with better global cognition. Mild to severe OSA (apnea-hypopnea index [AHI] ≥5) was associated with poorer global cognition (pooled ß, -0.06; 95% CI, -0.11 to -0.01; P = .01) vs AHI less than 5; comparable results were found for moderate to severe OSA (pooled ß, -0.06; 95% CI, -0.11 to -0.01; P = .02) vs AHI less than 5. Differences in sleep stages were not associated with cognition. Conclusions and Relevance: This study found that better sleep consolidation and the absence of OSA were associated with better global cognition over 5 years of follow-up. These findings suggest that the role of interventions to improve sleep for maintaining cognitive function requires investigation.

Incidence of Dementia Following Hospitalization With Infection Among Adults in the Atherosclerosis Risk in Communities (ARIC) Study Cohort.

Importance: Factors associated with the risk of dementia remain to be fully understood. Systemic infections are hypothesized to be such factors and may be targets for prevention and screening. Objective: To investigate the association between hospitalization with infection and incident dementia. Design, Setting, and Participants: Data from the community-based Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, were used. Enrollment occurred at 4 research centers in the US, initiated in 1987 to 1989. The present study includes data up to 2019, for 32 years of follow-up. Data analysis was performed from April 2021 to June 2022. Exposures: Hospitalizations with infections were identified via medical record review for selected International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, from baseline until administrative censoring or dementia diagnosis. Participants were considered unexposed until first hospitalization with infection and exposed thereafter. Selected infection subtypes were also considered. Main Outcomes and Measures: Incident dementia and time-to-event data were identified through surveillance of ICD-9 and ICD-10 hospitalization and death certificate codes, in-person assessments, and telephone interviews. A sensitivity analysis was conducted excluding cases occurring within 3 years or beyond 20 years from exposure. Data were collected before study hypothesis formulation. Results: Of the 15 792 ARIC study participants, an analytical cohort of 15 688 participants who were dementia free at baseline and of Black or White race were selected (8658 female [55.2%]; 4210 Black [26.8%]; mean [SD] baseline age, 54.7 [5.8] years). Hospitalization with infection occurred among 5999 participants (38.2%). Dementia was ascertained in 2975 participants (19.0%), at a median (IQR) of 25.1 (22.2-29.1) years after baseline. Dementia rates were 23.6 events per 1000 person-years (95% CI, 22.3-25.0 events per 1000 person-years) among the exposed and 5.7 events per 1000 person-years (95% CI, 5.4-6.0 events per 1000 person-years) among the unexposed. Patients hospitalized with infection were 2.02 (95% CI, 1.88-2.18; P < .001) and 1.70 (95% CI, 1.55-1.86; P < .001) times more likely to experience incident dementia according to unadjusted and fully adjusted Cox proportional hazards models compared with individuals who were unexposed. When excluding individuals who developed dementia less than 3 years or more than 20 years from baseline or the infection event, the adjusted hazard ratio was 5.77 (95% CI, 4.92-6.76; P < .001). Rates of dementia were significantly higher among those hospitalized with respiratory, urinary tract, skin, blood and circulatory system, or hospital acquired infections. Multiplicative and additive interactions were observed by age and APOE-ε genotype. Conclusions and Relevance: Higher rates of dementia were observed among participants who experienced hospitalization with infection. These findings support the hypothesis that infections are factors associated with higher risk of dementias.

OSA and Subsequent Risk of Hospitalization With Pneumonia, Respiratory Infection, and Total Infection: The Atherosclerosis Risk in Communities Study.

BACKGROUND: OSA has been linked to microaspiration, systemic inflammation, and suboptimal immune function. RESEARCH QUESTION: Is OSA prospectively associated with risk of hospitalization for pneumonia, respiratory, and total infections? STUDY DESIGN AND METHODS: Prospective cohort. Participants in the Atherosclerosis Risk in Communities (ARIC) study (N = 1,586) underwent polysomnography in 1996-1998 and were followed up through 2018 for infection-related hospitalizations. The apnea-hypopnea index (AHI; events/h) was used to categorize participants as having severe OSA (≥ 30), moderate OSA (15-29), mild OSA (5-14), or a normal breathing pattern (< 5). Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. RESULTS: ARIC participants were on average 62.7 (SD = 5.5) years of age, and 52.8% were female. Severe OSA was present in 6.0%, moderate OSA in 12.7%, mild OSA in 30.0%, and normal breathing in 51.3%. A total of 253 hospitalizations with pneumonia occurred over a median 20.4 (max, 22.9) years' follow-up. Participants with severe OSA were at 1.87 times (95% CI, 1.19-2.95) higher risk of hospitalization with pneumonia compared with those with a normal breathing pattern after adjustment for demographics and lifestyle behaviors. Results were attenuated modestly after adjustment for BMI (1.62 [0.99-2.63]), and prevalent asthma and COPD (1.62 [0.99-2.63]). A similar pattern existed for hospitalization with respiratory infection and composite infection (demographic and behavior-adjusted HRs: 1.47 [0.96-2.25] and 1.48 [1.07-2.04], respectively). INTERPRETATION: Severe OSA was associated with increased risk of hospitalizations with pneumonia in this community-based cohort. OSA patients may benefit from more aggressive efforts to prevent pneumonia and other infectious conditions.

Proteomic profiling identifies novel proteins for genetic risk of severe COVID-19: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Genome-wide association studies have identified six genetic variants associated with severe COVID-19, yet the mechanisms through which they may affect disease remains unclear. We investigated proteomic signatures related to COVID-19 risk variants rs657152 (ABO), rs10735079 (OAS1/OAS2/OAS3), rs2109069 (DPP9), rs74956615 (TYK2), rs2236757 (IFNAR2) and rs11385942 (SLC6A20/LZTFL1/CCR9/FYCO1/CXCR6/XCR1) as well as their corresponding downstream pathways that may promote severe COVID-19 in risk allele carriers and their potential relevancies to other infection outcomes. METHODS: A DNA aptamer-based array measured 4870 plasma proteins among 11 471 participants. Linear regression estimated associations between the COVID-19 risk variants and proteins with correction for multiple comparisons, and canonical pathway analysis was conducted. Cox regression assessed associations between proteins identified in the main analysis and risk of incident hospitalized respiratory infections (2570 events) over a 20.7-year follow-up. RESULTS: The ABO variant rs657152 was associated with 84 proteins in 7241 white participants with 24 replicated in 1671 Black participants. The TYK2 variant rs74956615 was associated with ICAM-1 and -5 in white participants with ICAM-5 replicated in Black participants. Of the 84 proteins identified in the main analysis, seven were significantly associated with incident hospitalized respiratory infections including Ephrin type-A receptor 4 (hazard ratio (HR): 0.87; P = 2.3 × 10-11) and von Willebrand factor type A (HR: 1.17; P = 1.6x10-13). CONCLUSIONS: Novel proteomics signatures and pathways for COVID-19-related risk variants TYK2 and ABO were identified. A subset of these proteins predicted greater risk of incident hospitalized pneumonia and respiratory infections. Further studies to examine these proteins in COVID-19 patients are warranted.

Promoting Aspirin Use for Cardiovascular Disease Prevention Among an Adult Internet-Using Population: A Pilot Study.

Cardiovascular disease prevention strategies include aspirin use as a preventive measure. The internet can be used to raise public awareness, promote healthy lifestyles, and improve disease management. This pilot study describes the feasibility of an educational website to recruit and follow adult internet users to examine whether they talked to their physician about aspirin and initiated aspirin use. As part of a statewide intervention promoting an aspirin regimen to prevent heart attacks and strokes in Minnesota, visitors to the website were encouraged to complete an aspirin candidacy tool. Between October, 2015 and February, 2016, men 45-79 and women 55-79 who identified as aspirin candidates were invited to participate in a 6-month study involving four, 5 min online surveys to examine physician discussions about aspirin, aspirin use, and mobile technology use. During the 5-month recruitment period, 234 adults enrolled in the study. Of the 174 who completed the baseline survey and at least one follow-up survey, 74 (43.5%) did not use aspirin at baseline. During follow-up, 12 (16.2%) talked to their doctor about aspirin and 31 (41.8%) initiated aspirin use. Internet, social media, and mobile technology use were high among this population. An educational website may have provided a cue to action for aspirin discussions with physicians and aspirin initiation. More research is needed to evaluate the utility of on-line tools to increase appropriate aspirin use among internet-using populations.

Low-dose aspirin for primary prevention of cardiovascular disease: Trends in use patterns among African American adults in Minnesota, 2015-2019.

Cardiovascular disease (CVD) disproportionately affects African Americans. Aspirin has long been recommended to reduce cardiovascular events. However, national guideline changes in 2016 limited the aspirin recommended population and several clinical trials questioning the utility of primary prevention aspirin were published in 2018. In light of the recent guidelines and study findings, we investigated primary prevention aspirin use among urban African American adults. Using three cross-sectional surveys, we collected data from self-identified African Americans with no CVD in 2015, 2017 and 2019, querying information on CVD risk factors, health behaviors and beliefs, and aspirin use. Poisson regression modeling was used to estimate age- and risk-factor adjusted aspirin prevalence, trends and associations. A total of 1491 African Americans adults, ages 45-79, were included in this analysis; 61% were women. There was no change in age- and risk factor-adjusted aspirin use over the 3 surveys for women (37%, 34% and 35% respectively) or men (27%, 25%, 30% respectively). However, fewer participants believed aspirin was helpful in 2019 compared to 2015-75% versus 84% (p < 0.001). Aspirin discussions with a health care practitioner were highly associated with aspirin use (adjusted RR 2.97, 95% CI 2.49-3.54) and aspirin use was 2.56 times higher (adjusted RR 95% CI 2.17-3.03) in respondents who agreed that people close to them thought they should take aspirin compared with those who disagreed or did not know. Despite major changes in national guidelines, overall primary prevention aspirin use did not significantly change in these African American samples from 2015 to 2019.

Aspirin Use and Misuse for the Primary Prevention of Cardiovascular Diseases.

INTRODUCTION: Daily aspirin use for primary cardiovascular disease prevention is common among adults. Numerous clinical trials observe reduced cardiovascular disease with regular low-dose aspirin. The U.S. Preventive Services Task Force in 2016 published guidelines for aspirin use, but controversy exists about the side effects, and overuse or underuse may be common despite the guidelines. Using the Task Force recommendations, this paper describes the prevalence of appropriate aspirin use and physician advice in a population sample. METHODS: A random sample of men and women (aged 50-69 years) living in the Upper Midwest in 2017-2018 were surveyed, collecting demographic data, health history, and aspirin use. Appropriate primary prevention with aspirin was defined as having ≥10% cardiovascular disease risk (hypertension, hyperlipidemia, diabetes, smoking) with daily or every other day aspirin use. Those with prevalent cardiovascular disease were labeled as secondary prevention. RESULTS: A total of 1,352 adults were surveyed (697 women, 655 men). The criteria for secondary prevention were fulfilled in 188 participants, and these were eliminated from the analysis. In the remaining group, aspirin was indicated in 32.9% (383 of 1,164). Among those, 46.0% (176 of 383) were appropriate users, and 54.0% (207 of 383) were nonusers despite indications. Overuse, where aspirin is not indicated, was common at 26.9% (210 of 781). Discussion with a physician, although reported in 29% of subjects, was associated with some improvement in the appropriate use but also with overuse and underuse. CONCLUSIONS: Aspirin use for primary cardiovascular disease prevention is common. However, many adults are medicating without indication (overuse) or are not using aspirin despite guidelines (underuse).

Long-Term Association of Venous Thromboembolism With Frailty, Physical Functioning, and Quality of Life: The Atherosclerosis Risk in Communities Study.

Background Relatively little is known about the long-term consequences of venous thromboembolism (VTE) on physical functioning. We compared long-term frailty status, physical function, and quality of life among survivors of VTE with survivors of coronary heart disease (CHD) and stroke, and with those without these diseases. Methods and Results Cases of VTE, CHD, and stroke were continuously identified since ARIC (Atherosclerosis Risk in Communities Study) recruitment during 1987 to 1989. Functional measures were objectively captured at ARIC clinic visits 5 (2011-2013) and 6 (2016-2017); quality of life was self-reported. The 6161 participants at visit 5 were, on average, 75.7 (range, 66-90) years of age. By visit 5, 3.2% had had a VTE, 6.9% CHD, and 3.4% stroke. Compared with those without any of these conditions, VTE survivors were more likely to be frail (odds ratio [OR], 3.11; 95% CI, 1.80-5.36) and have low (<10) versus good scores on the Short Physical Performance Battery (OR, 3.59; 95% CI, 2.36-5.47). They also had slower gait speed, less endurance, and lower physical quality of life. VTE survivors were similar to coronary heart disease and stroke survivors on categorical frailty and outcomes on Short Physical Performance Battery assessment. When score on the Short Physical Performance Battery instrument was modeled continuously, VTE survivors performed better than stroke survivors but worse than CHD survivors. Conclusions VTE survivors had triple the odds of frailty and poorer physical function than those without the vascular diseases considered. Their function was somewhat worse than that of CHD survivors, but better than stroke survivors. These findings suggest that VTE patients may benefit from additional efforts to improve postevent physical functioning.

Plasma phospholipid very-long-chain SFAs in midlife and 20-year cognitive change in the Atherosclerosis Risk in Communities (ARIC): a cohort study.

BACKGROUND: Very-long-chain SFAs (VLSFAs) have recently gained considerable attention as having beneficial effects on health and aging. OBJECTIVES: The objective of this study was to assess the associations of plasma phospholipid VLSFAs [arachidic acid (20:0), behenic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0)] with 20-y cognitive decline in the Atherosclerosis Risk in Communities (ARIC) participants. Furthermore, this study compared the associations of plasma phospholipid VLSFAs with 5 common groups of fatty acids [i.e., total SFAs, total MUFAs, total ω-3 (n-3) PUFAs, total marine-derived ω-3 PUFAs, total ω-6 PUFAs]. METHODS: This study used a cohort study design of 3229 ARIC participants enrolled at the Minnesota field center. Fatty acids were measured at visit 1 (1987-1989); and cognition was assessed at visits 2 (1990-1992), 4 (1996-1998), and 5 (2011-2013) using 3 tests: the Delayed Word Recall Test (DWRT), the Digit-Symbol Substitution Test (DSST), and the Word Fluency Test (WFT). RESULTS: Higher proportions of plasma phospholipid total VLSFAs and each individual VLSFA were associated with less decline in WFT, a test of verbal fluency. For example, 1 SD higher in total VLSFAs at baseline was associated with 0.057 SD (95% CI: 0.018, 0.096, P = 0.004) less cognitive decline over 20 y as measured by WFT score. None of the 5 common fatty acid groups were associated with change in WFT, but a higher proportion of plasma phospholipid total MUFAs was associated with greater decline in DWRT; higher total ω-6 PUFAs with less decline in DWRT; and higher total ω-3 and total marine-derived ω-3 PUFAs with less decline in DSST. CONCLUSIONS: This study suggests that higher proportions of plasma phospholipid VLSFAs in midlife may be associated with less 20-y cognitive decline.

Aspirin Use and Awareness for Cardiovascular Disease Prevention Among Hispanics: Prevalence and Associations with Health Behavior Beliefs.

Cardiovascular disease (CVD) persists as the leading cause of death and disability in many Americans including Hispanics. Primary prevention for CVD may be achieved through regular aspirin use in high risk individuals. This study examined regular aspirin use and specific attitudes and social norms toward CVD and aspirin use within an urban Hispanic population in Minnesota. A sample of primary prevention Hispanics aged 45-79 years were surveyed about CVD history and risk factors, aspirin use, demographic characteristics, and health beliefs and social norms in relation to CVD and aspirin. Relative risk estimation using Poisson regression with robust error variance was used to examine associations with aspirin use. In this sample of 152 Hispanics (55% women), the mean age was 53 years, 70% had a regular healthcare provider, and 22% used aspirin. Aspirin discussions with a regular healthcare provider were strongly associated with aspirin use (adjusted risk ratio 3.02, 95% CI 1.20-7.60). There was a positive association between health beliefs and social norms that affirm preventive behaviors and aspirin use (adjusted linear risk ratio 1.23, 95% CI 1.04-1.45) while uncertainty about the role of aspirin for individual use and in the community was negatively associated with aspirin use (adjusted linear risk ratio 0.85, 95% CI 0.70-1.03). This growing population may benefit from health education about CVD risk and the role of aspirin in prevention.

Resting heart rate and incidence of venous thromboembolism.

BACKGROUND/OBJECTIVES: Higher resting heart rate is a risk factor for arterial cardiovascular diseases. We assessed whether higher heart rate is a risk factor for venous thromboembolism (VTE). METHODS: In a prospective epidemiologic cohort, the Atherosclerosis Risk in Communities (ARIC) Study, we associated resting heart rate by electrocardiogram with physician-validated incident hospitalized VTE through 2015. We also examined whether lower heart rate variability (HRV), a marker of cardiac autonomic imbalance, might be a risk factor for VTE. RESULTS: Resting heart rate at Visit 1 (1987-1989), when participants were 45 to 64 years old (mean, 54 years), was not associated with incidence of VTE (n = 882 cases). However, heart rate at Visit 4 (1996-1998; mean age, 63 years) was associated positively with VTE (n = 557 cases). The adjusted hazard ratios (95% confidence intervals) of VTE across Visit 4 heart rate categories of <60, 60 to 69, 70 to 79, and ≥80 bpm were 1 (reference), 1.22 (1.01-1.49), 1.39 (1.09-1.78), and 1.44 (1.01-2.06), respectively, and when evaluated continuously 1.11 (1.02-1.21) per 10 bpm greater heart rate. For the most part, HRV indices were not associated with VTE or associations were explained by inverse correlations of HRV indices with heart rate. CONCLUSION: We found a significant positive and independent association of resting heart rate at ARIC Visit 4 with incidence of VTE. The reason why high heart rate is a risk marker for VTE warrants further exploration.

Serum magnesium and the incidence of coronary artery disease over a median 27 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) Study and a meta-analysis.

BACKGROUND: Low serum magnesium (Mg) concentrations have been associated with higher coronary artery disease (CAD) risk. A previous Atherosclerosis Risk in Communities (ARIC) Study article that evaluated the Mg-CAD association, based on 319 events occurring over 4-7 y, identified a sex-interaction whereby the inverse Mg-CAD association was much stronger among women than men. More than 1700 additional ARIC CAD events have since accrued. OBJECTIVE: We aimed to test our hypothesis that serum Mg is inversely and independently associated with long-term CAD risk in ARIC and in a meta-analysis with other prospective studies. METHODS: A total of 14,446 ARIC study participants (baseline mean ± SD age: 54 ± 6 y, 57% women, 27% African American) were followed for incident CAD through 2017. CAD events were defined by myocardial infarction or CAD mortality. Serum Mg was modeled as quintiles based on mean visit 1 (1987-1989) and visit 2 (1990-1992) concentrations. Cox regression models were used. We also conducted a random-effects meta-analysis incorporating these contemporary ARIC findings. RESULTS: Over a median follow-up of 27 y, 2131 incident CAD cases accrued. Overall, low serum Mg was associated with higher CAD risk after adjustment for demographics, lifestyle factors, and other CAD risk factors than was higher serum Mg (HR Q1 compared with Q5: 1.28; 95% CI: 1.11, 1.47; P-linear trend <0.001). The association was stronger among women (HR Q1 compared with Q5: 1.53; 95% CI: 1.22, 1.92) than men (HR: 1.11; 95% CI: 0.92, 1.34) (P-interaction = 0.05). In the meta-analysis including 5 studies, the pooled RR (95% CI) for CAD in the lowest compared with the highest circulating Mg category was 1.18 (1.06, 1.31) (I2 = 22%, P-heterogeneity = 0.27). CONCLUSIONS: In this large community-based cohort and updated meta-analysis, low circulating Mg was associated with higher CAD risk than was higher Mg. Whether increasing Mg concentrations within healthy limits is a useful strategy for CAD prevention remains to be seen.

Prospective study of plasma high molecular weight kininogen and prekallikrein and incidence of coronary heart disease, ischemic stroke and heart failure.

INTRODUCTION: High molecular weight kininogen (HK) and prekallikrein (PK) are proteins in the kallikrein/kinin system of the coagulation cascade. They play an important role in the contact activation system of the intrinsic coagulation pathway, renin-angiotensin activation, and inflammation. Hence these proteins have been posited to affect the occurrence of cardiovascular events and thus to be potential therapeutic targets. Previous case-control studies have provided inconsistent evidence for an association of HK and PK with cardiovascular disease. METHODS: In the prospective population-based Atherosclerosis Risk in Communities(ARIC) Study, we used Cox proportional hazards regression models to investigate the association in 4195 middle-aged adults of plasma HK and PK concentrations in 1993-95 (linearly and in quartiles) with incident coronary heart disease, ischemic stroke, and heart failure through 2016. RESULTS: Over a mean of 18 years follow-up, we identified incident cardiovascular events (coronary heart disease and ischemic stroke) in 618 participants and heart failure in 667. We observed no significant relation between HK or PK and cardiovascular disease or heart failure, before and after adjusting for several potential confounding variables. CONCLUSIONS: We found no compelling evidence to support an association of plasma HK or PK concentrations with incident CHD, ischemic stroke, or heart failure.

A prospective study of migraine history and venous thromboembolism in older adults.

BACKGROUND: Limited evidence suggests that migraine might be a risk factor for venous thromboembolism (VTE). We conducted an epidemiologic study to assess whether migraine history is associated prospectively with VTE or cross sectionally with hemostatic risk markers for VTE. METHODS: In a population-based US cohort, 11 985 participants free of VTE reported headache symptoms in 1993-1995. We classified participants as having either migraines with or without aura, severe nonmigraine headaches, or no severe headaches. We followed them through 2015 for incident VTE verified by medical records. RESULTS: Participants' mean age at baseline was 60 years (SD: 6). Eleven percent were classified as having a migraine history (932 without aura and 396 with aura). Over a mean of 18 years and 211 913 person-years at risk, 688 participants developed VTE. Participants with a migraine history had no greater risk of VTE compared with those free of severe headache (adjusted hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 0.82-1.36). Those with migraine history with aura had an HR of 1.25 (95% CI: 0.85-1.85). Self-reported physician diagnosis of migraine carried an HR of 1.22 (0.96-1.55). At baseline, those with a history of migraine, furthermore, did not have a higher frequency of elevated hemostatic risk factors or a higher genetic risk score for VTE. CONCLUSION: This study does not support the hypothesis that migraine history is an important risk factor for VTE in older adults.

Plasma Metabolites Associated with Brain MRI Measures of Neurodegeneration in Older Adults in the Atherosclerosis Risk in Communities⁻Neurocognitive Study (ARIC-NCS).

BACKGROUND: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. METHODS: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. RESULTS: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm3] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm3 [5.5, 18.6], 11.8 cm3 [5.0, 18.6], and 7.3 cm3 [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). CONCLUSIONS: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

Aspirin Use for Cardiovascular Disease Prevention in an African American Population: Prevalence and Associations with Health Behavior Beliefs.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in the United States, disproportionately affecting African Americans. Aspirin is an effective, low cost option to reduce cardiovascular events. This study sought to describe the use of aspirin for CVD prevention in African Americans and evaluate associations with demographics, cardiovascular risk factors and health behaviors and beliefs. A total of 684 African Americans adults ages 45-79 years completed surveys and were included in this analysis. Proportions of aspirin use were stratified by primary and secondary prevention and by number of CVD risk factors in the primary prevention population. Logistic regression was used to evaluate associations with aspirin use. Secondary prevention aspirin use was 62%. Primary prevention aspirin use was 32% overall and increased to 54% in those with > 2 CVD risk factors. A history of diabetes [adjusted odds ratio (aOR) 3.42, 95% CI 2.18-5.35] and hypertension (aOR 2.25, 95% CI 1.39-3.65) were strongly associated with primary prevention aspirin use, but a conversation with a health care provider was even stronger (aOR 6.41, 95% CI 4.07-10.08). Participants who answered positively to statements about people similar to them taking aspirin or that close contacts think they should take aspirin, were much more likely to take aspirin (aOR 4.80; 95% CI 2.58-8.93 and aOR 7.45; 95% CI 4.70-11.79 respectively). These findings support a hypothesis that aspirin use may increase by encouraging conversations with health care providers and creating a supportive social environment for aspirin use. Further studies need to be done to test this hypothesis.

Plasma Concentrations of High Molecular Weight Kininogen and Prekallikrein and Venous Thromboembolism Incidence in the General Population.

The kallikrein/kinin system, an intravascular biochemical pathway that includes several proteins involved in the contact activation system of coagulation, renin-angiotensin activation and inflammation, may or may not play a role in venous thromboembolism (VTE) occurrence. Within a large prospective population-based study in the United States, we conducted a nested case-cohort study to test the hypothesis that higher plasma levels of high molecular weight kininogen (HK) or prekallikrein are associated with greater VTE incidence. We related baseline enzyme-linked immunosorbent assay measures of HK and prekallikrein in 1993 to 1995 to incidence VTE of the lower extremity (n = 612) through 2015 (mean follow-up = 18 years). We found no evidence that plasma HK or prekallikrein was associated positively with incident VTE. HK, in fact, was associated inversely and significantly with VTE in most proportional hazards regression models. For example, the hazard ratio of VTE per standard deviation higher HK concentration was 0.88 (95% confidence interval = 0.81, 0.97), after adjustment for several VTE risk factors. Our findings suggest that plasma levels of these factors do not determine the risk of VTE in the general population.