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1.
Eur J Prev Cardiol ; : 2047487319865378, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362534

RESUMO

AIMS: The aim of this study was to evaluate the associations of blood pressure categorization based on the 2017 American College of Cardiology and American Heart Association guideline with the risk of peripheral artery disease (PAD). METHODS: Among 13,113 middle-aged participants, we investigated the associations of 2017 blood pressure categories (systolic <120 and diastolic <80 mmHg (normal if no anti-hypertensive medications; reference), 120-129 and <80 (elevated), 130-139 and/or 80-89 (stage 1 hypertension), and ≥140 and/or ≥90 (stage 2 hypertension)) with incident PAD (hospitalizations with a diagnosis or leg revascularization) using Cox regression models. Analyses were separately conducted in individuals with and without anti-hypertensive medications. RESULTS: During a median follow-up of 25.4 years, 466 incident PAD occurred (271 cases in 9858 participants without anti-hypertensive medications). In participants without anti-hypertensive medications, we observed significant hazard ratios of PAD in elevated blood pressure (1.80 (1.28-2.51)) and stage 2 hypertension (2.40 (1.72-3.34)), but not in stage 1 hypertension. Analyzing systolic and diastolic blood pressure separately, higher systolic blood pressure categories showed significant associations with incident PAD in a graded fashion whereas, for diastolic blood pressure, only ≥90 mmHg did. Generally similar patterns were seen among participants on anti-hypertensive medication, while they had higher risk of PAD than those without at each blood pressure category. CONCLUSIONS: Systolic blood pressure, including the category of 130-139 mmHg, showed stronger associations with incident PAD than did diastolic blood pressure. Consequently, elevated blood pressure conferred similar or even greater risk of PAD than stage 1 hypertension, with implications on how to interpret new blood pressure categories in terms of leg vascular health.

2.
Am J Hematol ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31429114

RESUMO

Sickle cell trait (SCT) has been associated with hypercoagulability, chronic kidney disease (CKD), and ischemic stroke. Whether concomitant CKD modifies long-term ischemic stroke risk in individuals with SCT is uncertain. We analyzed data from 3,602 genotyped black adults (female=62%, mean baseline age = 54 years) who were followed for a median 26 years by the Atherosclerosis Risk in Communities Study. Ischemic stroke was verified by physician review. Associations between SCT and ischemic stroke were analyzed using repeat-events Cox regression, adjusted for potential confounders. SCT was identified in 236 (7%) participants, who more often had CKD at baseline than noncarriers (18% vs. 13%, P=0.02). Among those with CKD, elevated factor VII activity was more prevalent with SCT genotype (36% vs. 22%; P=0.05). From 1987-2017, 555 ischemic strokes occurred in 436 individuals. The overall hazard ratio of ischemic stroke associated with SCT was 1.31 (95% CI: 0.95 - 1.80) and was stronger in participants with concomitant CKD (HR = 2.18; 95% CI: 1.16 - 4.12) than those without CKD (HR = 1.09; 95% CI: 0.74 - 1.61); P for interaction = 0.04. The hazard ratio of composite ischemic stroke and / or death associated with SCT was 1.20 (95% CI: 1.01 - 1.42) overall, 1.44 (95% CI: 1.002 - 2.07) among those with CKD, and 1.15 (95% CI: 0.94 - 1.39) among those without CKD; P for interaction = 0.18. The long-term risk of ischemic stroke associated with SCT relative to noncarrier genotype appears to be modified by concomitant CKD. This article is protected by copyright. All rights reserved.

3.
J Am Coll Cardiol ; 74(4): 498-507, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31345423

RESUMO

BACKGROUND: Public statements about the effect of smoking on cardiovascular disease are predominantly based on investigations of coronary heart disease (CHD) and stroke, although smoking is recognized as a strong risk factor for peripheral artery disease (PAD). No study has comprehensively compared the long-term association of cigarette smoking and its cessation with the incidence of 3 major atherosclerotic diseases (PAD, CHD, and stroke). OBJECTIVES: The aim of this study was to quantify the long-term association of cigarette smoking and its cessation with the incidence of the 3 outcomes. METHODS: A total of 13,355 participants aged 45 to 64 years in the ARIC (Atherosclerosis Risk In Communities) study without PAD, CHD, or stroke at baseline (1987 to 1989) were included. The associations of smoking parameters (pack-years, duration, intensity, and cessation) with incident PAD were quantified and contrasted with CHD and stroke using Cox models. RESULTS: Over a median follow-up of 26 years, there were 492 PAD cases, 1,798 CHD cases, and 1,106 stroke cases. A dose-response relationship was identified between pack-years of smoking and 3 outcomes, with the strongest results for PAD. The pattern was consistent when investigating duration and intensity separately. A longer period of smoking cessation was consistently related to lower risk of PAD, CHD, and stroke, but a significantly elevated risk persisted up to 30 years following smoking cessation for PAD and up to 20 years for CHD. CONCLUSIONS: All smoking measures showed significant associations with 3 major atherosclerotic diseases, with the strongest effect size for incident PAD. The risk due to smoking lasted up to 30 years for PAD and 20 years for CHD. Our results further highlight the importance of smoking prevention and early smoking cessation, and indicate the need for public statements to take PAD into account when acknowledging the impact of smoking on overall cardiovascular health.

4.
Am Heart J ; 216: 1-8, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31352135

RESUMO

BACKGROUND: A lower prevalence of atrial fibrillation (AF), but paradoxically higher burden of cardiovascular disease risk factors, has been observed among African Americans compared to Whites in studies of AF identified by mostly 12-lead electrocardiograms (ECGs) and clinically. METHODS: We performed 48-hour ambulatory electrocardiography (aECG) in a biracial sample of 1,193 participants in the Atherosclerosis Risk in Communities (ARIC) (mean age = 78 years, 62% African Americans, 64% female). Atrial fibrillation was identified from aECG, study visit ECGs, and discharge codes from cohort hospitalizations. We used covariate-adjusted logistic regression to estimate prevalence odds ratios (ORs) for AF in African Americans versus Whites, with adjustment for sampling and nonresponse. RESULTS: African Americans were more likely than Whites to have hypertension and diabetes but less likely to have coronary heart disease. The prevalence of AF detected by aECG or ARIC study ECG (adjusted for age and coronary heart disease) was lower in African Americans than Whites (2.7% vs 5.0%). White men had a higher (although not significant) AF prevalence of 7.8% compared to the other race and gender groups at 2.3%-2.8%. The adjusted OR for AF was 0.49 (0.24-0.99) comparing African Americans to Whites. Findings were similar when AF was defined to include prior AF hospitalizations (OR = 0.42, 0.25-0.72). There were no significant differences by race for asymptomatic or paroxysmal AF. CONCLUSIONS: Atrial fibrillation was less prevalent in African American than white older adults, regardless of detection method. Although overall detection of new AF cases with aECG was low, future studies should consider longer-term monitoring to characterize AF by race.

5.
J Am Geriatr Soc ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31359423

RESUMO

OBJECTIVES: Cardiac troponin T, measured using a high-sensitive assay (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased stroke risk and perhaps with cognitive decline. However, few well-designed prospective studies with extended follow-up have been conducted. We aimed to estimate the association of hs-cTnT and NT-proBNP with 15-year cognitive change in the Atherosclerosis Risk in Communities (ARIC) study. DESIGN: Prospective cohort study. SETTING: Four US communities. PARTICIPANTS: A total of 9114 and 9108 participants from the Atherosclerosis Risk in Communities study for analyses of hs-cTnT and NT-proBNP, respectively. MEASUREMENTS: We examined association of hs-cTnT and NT-proBNP with 15-year change (1996-1998 to 2011-2013) in three cognitive tests of executive function (Digit Symbol Substitution Test), verbal learning memory (Delayed Word Recall Test), and semantic fluency (Word Fluency Test), and an overall score combining the three tests using multivariable linear mixed effect models. We conducted several sensitivity analyses including multiple imputations to address bias due to missing data and attrition, and we compared associations within groups combining hs-cTnT and NT-proBNP into a three-level categorical variable. RESULTS: At baseline (1996-1998), mean age was 63.4 (standard deviation [SD] = 5.7) years; 56.4% were women, and 17.5% were black. The hs-cTnT at baseline was not associated with cognitive change in any measure. Some evidence indicated accelerated decline in verbal learning and memory when comparing those in the highest with the lowest NT-proBNP quintiles; however, this association was not replicated when considering clinically relevant cutoffs or deciles of exposure in survivors. Sensitivity analyses were consistent with our primary analyses. There was little evidence to support effect modification by any considered factors. People with highest levels of both biomarkers had excessive decline in global z scores vs people with lowest levels (-.34; 95% confidence interval = -.63 to -.04). CONCLUSION: Markers of myocardial injury and stretch were not associated with cognitive decline following 15 years among survivors, but when combined together they were suggestive in post hoc analysis. Whether this represents targets of intervention should be examined in the future.

6.
Neurology ; 92(22): e2580-e2593, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31043469

RESUMO

OBJECTIVE: To examine the association of specific lipoproteins/inflammatory enzyme with cognitive change. METHODS: We examined the association of apolipoprotein B (ApoB), small-dense low-density lipoprotein cholesterol (sdLDL-C), lipoprotein (a) (Lp[a]), and lipoprotein-associated phospholipase A2 (LpPLA2) activity with 15-year change in Delayed Word Recall Test, Digit Symbol Substitution Test (DSST), Word Fluency Test (WFT), and overall summary score in 9,350 participants in the Atherosclerosis Risk in Communities study. We assessed interaction by race, sex, education, APOE ε4 status, and statin use. We also addressed questions of informative missingness, the role of stroke, and the influence of fasting status. RESULTS: The mean (SD) age was 63.4 (5.7) years; 56.4% were women and 17.4% were black. We observed faster cognitive decline on DSST and global z scores with every 10-mg/dL higher sdLDL-C level (Δ DSST z score, -0.010; 95% confidence interval [CI] -0.017, -0.002 and Δ global z score, -0.011; -0.021, -0.001) and the highest vs the lowest ApoB quintiles (Δ DSST z score, -0.092; -0.0164, -0.019 and Δ global z score, -0.101; -0.200, -0.002). Association for the ApoB quintiles with Δ global z score (-0.10) was comparable with that of having 1 APOE ε4 allele (-0.11). Higher Lp(a) was associated with slower decline in DSST, WFT, and global z scores. LpPLA2 activity was not associated with cognitive change. Results were similar in sensitivity analyses. The associations of sdLDL-C or Lp(a) on cognitive change were more pronounced in statin users. CONCLUSIONS: Optimal control of atherogenic lipoproteins such as ApoB and sdLDL-C in midlife for cardiovascular health may also benefit late-life cognitive health.

7.
Circulation ; 139(23): 2642-2653, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31030544

RESUMO

BACKGROUND: We assessed whether plasma troponin I measured by a high-sensitivity assay (hs-TnI) is associated with incident cardiovascular disease (CVD) and mortality in a community-based sample without prior CVD. METHODS: ARIC study (Atherosclerosis Risk in Communities) participants aged 54 to 74 years without baseline CVD were included in this study (n=8121). Cox proportional hazards models were constructed to determine associations between hs-TnI and incident coronary heart disease (CHD; myocardial infarction and fatal CHD), ischemic stroke, atherosclerotic CVD (CHD and stroke), heart failure hospitalization, global CVD (atherosclerotic CVD and heart failure), and all-cause mortality. The comparative association of hs-TnI and high-sensitivity troponin T with incident CVD events was also evaluated. Risk prediction models were constructed to assess prediction improvement when hs-TnI was added to traditional risk factors used in the Pooled Cohort Equation. RESULTS: The median follow-up period was ≈15 years. Detectable hs-TnI levels were observed in 85% of the study population. In adjusted models, in comparison to low hs-TnI (lowest quintile, hs-TnI ≤1.3 ng/L), elevated hs-TnI (highest quintile, hs-TnI ≥3.8 ng/L) was associated with greater incident CHD (hazard ratio [HR], 2.20; 95% CI, 1.64-2.95), ischemic stroke (HR, 2.99; 95% CI, 2.01-4.46), atherosclerotic CVD (HR, 2.36; 95% CI, 1.86-3.00), heart failure hospitalization (HR, 4.20; 95% CI, 3.28-5.37), global CVD (HR, 3.01; 95% CI, 2.50-3.63), and all-cause mortality (HR, 1.83; 95% CI, 1.56-2.14). hs-TnI was observed to have a stronger association with incident global CVD events in white than in black individuals and a stronger association with incident CHD in women than in men. hs-TnI and high-sensitivity troponin T were only modestly correlated ( r=0.47) and were complementary in prediction of incident CVD events, with elevation of both troponins conferring the highest risk in comparison with elevation in either one alone. The addition of hs-TnI to the Pooled Cohort Equation model improved risk prediction for atherosclerotic CVD, heart failure, and global CVD. CONCLUSIONS: Elevated hs-TnI is strongly associated with increased global CVD incidence in the general population independent of traditional risk factors. hs-TnI and high-sensitivity troponin T provide complementary rather than redundant information.

8.
PLoS One ; 14(2): e0212892, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30811490

RESUMO

BACKGROUND: Arterial stiffness independently predicts cardiovascular disease. However, few studies have evaluated the associations of central and peripheral pulse wave velocity (PWV) with biomarkers of both myocardial stress (natriuretic peptide [NT-proBNP]) and damage (high-sensitivity cardiac troponin-T [hs-cTnT]) among persons without cardiac disease. METHODS: We examined 3,348 participants (67-90 years) without prevalent cardiac disease in the Atherosclerosis Risk in Communities (ARIC) Study (2011-13). The cross-sectional associations of PWV quartiles for central arterial segments (carotid-femoral, heart-carotid, heart-femoral) and peripheral artery (femoral-ankle) with NT-proBNP and hs-cTnT were evaluated accounting for potential confounders. RESULTS: Most PWV measures demonstrated J- or U-shaped associations with the two cardiac biomarkers. The highest (Q4) vs. second lowest (Q2) quartile of central PWV measures (carotid-femoral, heart-carotid, heart-femoral PWV) were associated with higher levels of NT-proBNP independently of demographic characteristics. The associations were less evident for hs-cTnT. These associations were attenuated after adjusting for traditional cardiovascular risk factors, but the heart-carotid PWV-NT-proBNP relationship remained borderline significant (difference in log-NT-proBNP = 0.08 [-0.01, 0.17] in Q4 vs. Q2, p = 0.07). Peripheral PWV demonstrated inverse associations. Higher values of NT-proBNP were seen in the lowest vs. second lowest quartile of all PWV measures. CONCLUSIONS: Central stiffness measures showed stronger associations with cardiac biomarkers (particularly NT-proBNP) than peripheral measures among older adults without cardiac disease. Our findings are consistent with the concept of ventricular-vascular coupling and suggest that central rather than peripheral arterial hemodynamics are more closely related to myocardial stress rather than damage.

9.
Am J Epidemiol ; 188(5): 917-927, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30698634

RESUMO

Exposure to total hydrocarbons (THC) and volatile organic compounds from air pollution is associated with risk of coronary heart disease. THC exposure from oil spills might be similarly associated, but no research has examined this. We assessed the relationship between THC exposure during the response and cleanup of the Deepwater Horizon oil spill (Gulf of Mexico) and heart attack risk among 24,375 oil spill workers enrolled in the Gulf Long-Term Follow-up Study. There were 312 first heart attacks (self-reported physician-diagnosed myocardial infarction, or fatal coronary heart disease) ascertained during the study period (2010-2016). THC exposures were estimated using a job-exposure matrix incorporating self-reported activities and personal air measurements. We used Cox proportional hazards regression to estimate hazard ratios, with inverse-probability weights to account for confounding and censoring. Maximum THC levels of ≥0.30 parts per million (ppm) were associated with heart attack risk, with a 1.8-fold risk for exposure of ≥3.00 ppm versus <0.30 ppm (hazard ratio = 1.81, 95% confidence interval: 1.11, 2.95). The risk difference for highest versus lowest THC level was 10 excess cases per 1,000 workers. This is the first study of the persistent health impacts of THC exposure during oil spill work, and results support increased protection against oil exposure during cleanup of future spills.

10.
J Am Heart Assoc ; 8(2): e011045, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30646799

RESUMO

Background Central arterial stiffening and increased pulsatility, with consequent cerebral hypoperfusion, may result in structural brain damage and cognitive impairment. Methods and Results We analyzed a cross-sectional sample of ARIC - NCS (Atherosclerosis Risk in Communities-Neurocognitive Study) participants (aged 67-90 years, 60% women) with measures of cognition (n=3703) and brain magnetic resonance imaging (n=1255). Central arterial hemodynamics were assessed as carotid-femoral pulse wave velocity and pressure pulsatility (central pulse pressure). We derived factor scores for cognitive domains. Brain magnetic resonance imaging using 3-Tesla scanners quantified lacunar infarcts; cerebral microbleeds; and volumes of white matter hyperintensities, total brain, and the Alzheimer disease signature region. We used logistic regression, adjusted for demographics, apolipoprotein E ɛ4, heart rate, mean arterial pressure, and select cardiovascular risk factors, to estimate the odds of lacunar infarcts or cerebral microbleeds. Linear regression, additionally adjusted for intracranial volume, estimated the difference in log-transformed volumes of white matter hyperintensities , total brain, and the Alzheimer disease signature region. We estimated the mean difference in cognitive factor scores across quartiles of carotid-femoral pulse wave velocity or central pulse pressure using linear regression. Compared with participants in the lowest carotid-femoral pulse wave velocity quartile, participants in the highest quartile of carotid-femoral pulse wave velocity had a greater burden of white matter hyperintensities ( P=0.007 for trend), smaller total brain volumes (-18.30 cm3; 95% CI , -27.54 to -9.07 cm3), and smaller Alzheimer disease signature region volumes (-1.48 cm3; 95% CI , -2.27 to -0.68 cm3). These participants also had lower scores in executive function/processing speed (ß=-0.04 z score; 95% CI , -0.07 to -0.01 z score) and general cognition (ß=-0.09 z score; 95% CI , -0.15 to -0.03 z score). Similar results were observed for central pulse pressure . Conclusions Central arterial hemodynamics were associated with structural brain damage and poorer cognitive performance among older adults.

11.
Environ Res ; 168: 70-79, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30278364

RESUMO

BACKGROUND: Chemical, physical and psychological stressors due to the 2010 Deepwater Horizon oil spill may impact coronary heart disease (CHD) among exposed populations. Using longitudinal information from two interviews in the Gulf Long Term Follow-up (GuLF) STUDY, we assessed CHD among oil spill workers and community members. OBJECTIVE: To assess the associations between duration of oil spill clean-up work, residential proximity to the oil spill, and incidence of self-reported myocardial infarction or fatal CHD. METHODS: Among respondents with two GuLF STUDY interviews (n = 21,256), there were 395 first incident heart disease events (self-reported myocardial infarction or fatal CHD) across 5 years. We estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for associations with duration of oil spill clean-up work and residential proximity to the oil spill. To assess potential impacts of non-response, we compared covariate distributions for those who did (n = 21,256) and did not (n = 10,353) complete the second interview and used inverse probability (IP) of censoring weights to correct for potential non-response bias. RESULTS: Living in proximity to the oil spill (vs. living further away) was associated with heart disease, with [HR(95%CI) = 1.30(1.01-1.67)] and without [1.29(1.00-1.65)] censoring weights. For work duration, hazard of heart disease appeared to be higher for those who worked > 180 days (vs. 1-30 days), with and without censoring weights [1.43(0.91-2.25) and 1.36(0.88-2.11), respectively]. Associations persisted throughout the 5-year follow-up. CONCLUSIONS: Residential proximity to the spill and duration of clean-up work were associated with a suggested 29-43% higher hazard of heart disease events. Associations were robust to censoring.

12.
Kidney Int Rep ; 3(6): 1276-1284, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30450454

RESUMO

Introduction: Although sleep-disordered breathing has been found to be associated with higher urine albumin excretion, this association has not been evaluated in Hispanic/Latino populations, which experience a high burden of end-stage renal disease compared with non-Hispanics. We evaluated the association of sleep-disordered breathing with prevalent albuminuria among US Hispanics/Latinos. Methods: This was a cross-sectional study of baseline data from participants in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a population-based study that enrolled 16,415 adults in 4 US communities. Sleep-disordered breathing was assessed using a home sleep apnea monitor for overnight recording and was defined using 3 thresholds of the apnea-hypopnea index (AHI; 3% desaturation): ≥5, ≥15, and ≥30. Albuminuria was defined as a urine albumin-to-creatinine ratio of ≥30 mg/g. Results: There were 12,572 participants with complete data available for analysis. The age- and sex-adjusted prevalence of albuminuria was 9.1%. Mean age was 41 years, and 48% were men. Age- and sex-adjusted prevalence of sleep-disordered breathing was higher among individuals with albuminuria compared with those without albuminuria (36% vs. 25% had AHI ≥5, 18% vs. 9% had AHI ≥15, and 9% vs. 4% had AHI ≥30). In multivariable logistic regression analyses, AHIs ≥5, ≥15, and ≥30 were associated with greater odds of albuminuria compared with those with AHIs <5, <15, and <30 (odds ratio [OR] 1.42, 95% confidence interval [CI]: 1.14-1.76; OR: 1.71, 95% CI: 1.33-2.20; and OR 1.93, 95% CI 1.34-2.79), respectively. This association varied by Hispanic/Latino background group. Conclusion: In US Hispanic/Latinos, sleep-disordered breathing was independently associated with higher odds of prevalent albuminuria.

13.
Am J Prev Med ; 55(5): 642-649, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30342629

RESUMO

INTRODUCTION: The American Heart Association's Life's Simple 7 includes seven metrics of ideal cardiovascular health to target for cardiovascular disease prevention. This study determined the relationship between Life's Simple 7 and incident peripheral artery disease in a biracial cohort of middle- and older-aged adults. METHODS: This analysis included 12,865 participants from the Atherosclerosis Risk in Communities study recruited between 1987 and 1989 (mean age=54years, 55% women, 25% black) and free of peripheral artery disease or other cardiovascular disease at baseline. Overall, Life's Simple 7 score was calculated as the sum of the Life's Simple 7 component scores (two points if ideal, one point if intermediate, and zero if poor) and classified as inadequate (zero to four), average (five to nine), or optimal (ten to 14) cardiovascular health and linked to incident peripheral artery disease identified by hospital discharge diagnosis and leg revascularization. Analysis was conducted in 2017. RESULTS: A total of 434 incident peripheral artery disease cases occurred over a median follow-up of 24.4years. Compared with the inadequate category (n=1,008), participants in the average (n=8,395) and optimal (n=3,462) categories each had a substantially lower risk of developing peripheral artery disease in a Cox proportional hazards model adjusted for potential confounders (hazard ratio=0.36, 95% CI=0.28, 0.46 for average, and hazard ratio=0.09, 95% CI=0.06, 0.15 for optimal). In a similar model, a one-point higher Life's Simple 7 score was associated with a 25% lower risk of incident peripheral artery disease (hazard ratio=0.75, 95% CI=0.72, 0.79). CONCLUSIONS: Better cardiovascular health, as defined by higher Life's Simple 7 score, is associated with a substantially lower risk of peripheral artery disease.

14.
Alzheimers Dement ; 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30321503

RESUMO

INTRODUCTION: We tested the hypotheses that higher levels of and persistence of midlife leisure-time physical activity (LTPA) are associated long-term with lower cognitive decline and less incident dementia. METHODS: A total of 10,705 participants (mean age: 60 years) had LTPA (no, low, middle, or high) measured in 1987-1989 and 1993-1995. LTPA was assessed in relation to incident dementia and 14-year change in general cognitive performance. RESULTS: Over a median follow-up of 17.4 years, 1063 dementia cases were observed. Compared with no LTPA, high LTPA in midlife was associated with lower incidence of dementia (hazard ratio [95% confidence interval], 0.71 [0.61, 0.86]) and lower declines in general cognitive performance (-0.07 standard deviation difference [-0.12 to -0.04]). These associations were stronger when measured against persistence of midlife LTPA over 6 years. DISCUSSION: LTPA is a readily modifiable factor associated inversely with long-term dementia incidence and cognitive decline.

15.
J Am Heart Assoc ; 7(16): e008644, 2018 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-30369315

RESUMO

Background We conducted an analysis of data from the ARIC (Atherosclerosis Risk in Communities) study to assess the independent association of obesity with peripheral artery disease ( PAD ) and critical limb ischemia ( CLI ). Methods and Results All black and white ARIC participants without prevalent PAD at baseline (1987-1989) were included. We used Cox proportional hazards models adjusting for potential confounders and then potential mediators to quantify the association between body mass index ( BMI ) and incident hospitalizations related to PAD without CLI and with CLI through 2013. Our analysis included 13 988 men and women followed for a median of 24 years. Incident PAD without CLI and PAD with CLI occurred in 373 and 201 participants, respectively. After adjusting for potential confounders, higher BMI at baseline was associated with increased risk of PAD without CLI when BMI was modeled continuously (hazard ratio per 1- SD increment in BMI: 1.23; 95% confidence interval, 1.11-1.37) and with PAD with CLI regardless of whether BMI was modeled categorically ( P<0.05) or continuously (hazard ratio per 1- SD increment in BMI: 1.51; 95% confidence interval, 1.34-1.69). The associations of BMI with PAD without CLI and with CLI were attenuated after further accounting for potential mediators but remained significant for PAD with CLI when BMI was linearly modeled (hazard ratio per 1- SD increment in BMI: 1.19; 95% confidence interval, 1.04-1.36). The positive association between BMI and PAD with CLI was stronger than the association between BMI and PAD without CLI for all models ( P<0.001). Conclusions In the general population, BMI is positively associated with incident hospitalized PAD after adjusting for potential confounders, particularly its most severe form of CLI . Maintaining an optimal weight, in addition to controlling other cardiovascular risk factors, may play a role in reducing risk of PAD with CLI .

16.
J Am Heart Assoc ; 7(15): e009578, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-30371241

RESUMO

Background To understand how blood pressure ( BP ) from midlife and beyond is related to cognition in older age, a lifespan approach is needed. We assessed the associations of BP levels and variability from midlife on with subsequent cognitive change. Methods and Results The ARIC (Atherosclerosis Risk in Communities) Study participants underwent 4 clinic BP measurements (visit 1, 2, 3, and 4 BP s) between 1987 and 1998, and their mean levels and average real variability ( ARV ) were assessed as exposures. A global cognitive z score, estimated from the Delayed Word Recall Test, Digit Symbol Substitution Test, and Word Fluency Test scores, was calculated at 1996 to 1998 (visit 4) and 2011 to 2013 (visit 5). Among 11 408 participants (mean age, 54 years; 56% women; 21% black race), mean systolic BP ( SBP )/diastolic BP ( DBP ) level was 123/72 mm Hg, and ARVSBP / ARVDBP was 11/7 mm Hg. With linear mixed models, 1- SD increases of ARVSBP (standardized regression coefficient [95% confidence interval], -0.03 [-0.04 to -0.01] points) and ARVDBP (standardized regression coefficient [95% confidence interval], -0.02 [-0.03 to -0.002] points; both P<0.05), but not mean SBP or DBP levels, were associated with lower global cognitive z scores at visit 4. In contrast, mean SBP (standardized regression coefficient [95% confidence interval], -0.04 [-0.06 to -0.02] points) or DBP (standardized regression coefficient [95% confidence interval], 0.04 [0.02-0.06] points; both P<0.001) level, but not ARVSBP or ARVDBP , was associated with change in global cognitive z scores from visits 4 to 5. Conclusions Greater visit-to-visit SBP or DBP variability from midlife on is modestly associated with lower cognitive function, whereas higher mean SBP and lower DBP levels from midlife to later life are modestly associated with cognitive decline in later life.

17.
PLoS One ; 13(7): e0200486, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30044860

RESUMO

Current knowledge of the genetic architecture of key reproductive events across the female life course is largely based on association studies of European descent women. The relevance of known loci for age at menarche (AAM) and age at natural menopause (ANM) in diverse populations remains unclear. We investigated 32 AAM and 14 ANM previously-identified loci and sought to identify novel loci in a trans-ethnic array-wide study of 196,483 SNPs on the MetaboChip (Illumina, Inc.). A total of 45,364 women of diverse ancestries (African, Hispanic/Latina, Asian American and American Indian/Alaskan Native) in the Population Architecture using Genomics and Epidemiology (PAGE) Study were included in cross-sectional analyses of AAM and ANM. Within each study we conducted a linear regression of SNP associations with self-reported or medical record-derived AAM or ANM (in years), adjusting for birth year, population stratification, and center/region, as appropriate, and meta-analyzed results across studies using multiple meta-analytic techniques. For both AAM and ANM, we observed more directionally consistent associations with the previously reported risk alleles than expected by chance (p-valuesbinomial≤0.01). Eight densely genotyped reproductive loci generalized significantly to at least one non-European population. We identified one trans-ethnic array-wide SNP association with AAM and two significant associations with ANM, which have not been described previously. Additionally, we observed evidence of independent secondary signals at three of six AAM trans-ethnic loci. Our findings support the transferability of reproductive trait loci discovered in European women to women of other race/ethnicities and indicate the presence of additional trans-ethnic associations both at both novel and established loci. These findings suggest the benefit of including diverse populations in future studies of the genetic architecture of female growth and development.

18.
Neurology ; 91(8): e759-e768, 2018 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-30045960

RESUMO

OBJECTIVE: To examine associations of orthostatic hypotension (OH) with dementia and long-term cognitive decline and to update previously published results in the same cohort for stroke with an additional 16 years of follow-up. METHODS: We analyzed data from 11,709 participants without a history of coronary heart disease or stroke who attended the baseline examination (1987-1989) of the prospective Atherosclerosis Risk in Communities (ARIC) study. OH was defined as a drop in systolic blood pressure (BP) of at least 20 mm Hg or a drop in diastolic BP of at least 10 mm Hg on standing. Dementia was ascertained via examination, contact with participants or their proxy, or medical record surveillance. Ischemic stroke was ascertained via cohort surveillance of hospitalizations, cohort follow-up, and linkage with registries. Both outcomes were adjudicated. Cognitive function was ascertained via 3 neuropsychological tests administered in 1990 to 1992 and 1996 to 1998 and a full battery of tests in 2011 to 2013. Scores were summarized and reported as SDs. We used adjusted Cox regression and linear mixed models. RESULTS: Over ≈25 years, 1,068 participants developed dementia and 842 had an ischemic stroke. Compared to persons without OH at baseline, those with OH had a higher risk of dementia (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.20-1.97) and ischemic stroke (HR 2.08, 95% CI 1.65-2.62). Persons with OH had greater, although nonsignificant, cognitive decline over 20 years (SD 0.09, 95% CI -0.02 to 0.21). CONCLUSIONS: OH assessed in midlife was independently associated with incident dementia and ischemic stroke. Additional studies are needed to elucidate potential mechanisms for these associations and possible applications for prevention.

19.
Am J Kidney Dis ; 72(5): 682-690, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30007506

RESUMO

RATIONALE & OBJECTIVE: Arterial stiffness is suggested as a mediator of cardiorenal interaction. However, previous studies reported inconsistent associations between chronic kidney disease (CKD) and arterial stiffness and were limited by using either estimated glomerular filtration rate (eGFR) or albumin-creatinine ratio (ACR) and examining arterial stiffness at limited segments. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 3,424 Atherosclerosis in Communities (ARIC) Study participants aged 66 to 90 years during 2011 to 2013. PREDICTORS: eGFR and ACR. OUTCOME: Pulse wave velocity (PWV) at 6 segments: carotid-femoral (cfPWV), heart-carotid (hcPWV), and heart-femoral (hfPWV), reflecting central stiffness; heart-ankle (haPWV) and brachial-ankle (baPWV), representing both central and peripheral stiffness; and femoral-ankle (faPWV), indicating peripheral stiffness. ANALYTICAL APPROACH: Multiple linear and logistic regression models to quantify the associations of eGFR and ACR with continuous PWV and elevated PWV (in the highest quartile), respectively. RESULTS: After adjusting for age, sex, and race, higher cfPWV and hfPWV were consistently associated with lower eGFR and higher ACR. Higher haPWV and baPWV were also observed with higher ACR. The independent association of both CKD measures with elevated cfPWV remained consistent after adjusting for additional confounders (ORs of elevated cfPWV were 1.09 [95% CI, 1.01-1.18] per 15-mL/min/1.73m2 lower eGFR and 1.20 [95% CI, 1.07-1.33] per 4-fold higher ACR). Higher ACR was also associated with elevated hfPWV and haPWV (ORs per 4-fold higher ACR were 1.25 [95% CI, 1.12-1.39] for elevated hfPWV and 1.19 [95% CI, 1.06-1.33] for elevated haPWV). Lower eGFR was associated with lower odds of elevated baPWV and faPWV (ORs per 15-mL/min/1.73m2 lower eGFR were 0.92 [95% CI, 0.84-0.99] and 0.91 [95% CI, 0.85-0.99], respectively). LIMITATION: Unable to address temporality between CKD measures and arterial stiffness. CONCLUSIONS: Both lower eGFR and higher ACR are independently associated with measures of central arterial stiffness, with stronger associations for ACR over eGFR. Our findings suggest that central arterial stiffness may be an important pathophysiologic phenotype of vascular disease in CKD.

20.
Hum Mol Genet ; 27(16): 2940-2953, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29878111

RESUMO

C-reactive protein (CRP) is a circulating biomarker indicative of systemic inflammation. We aimed to evaluate genetic associations with CRP levels among non-European-ancestry populations through discovery, fine-mapping and conditional analyses. A total of 30 503 non-European-ancestry participants from 6 studies participating in the Population Architecture using Genomics and Epidemiology study had serum high-sensitivity CRP measurements and ∼200 000 single nucleotide polymorphisms (SNPs) genotyped on the Metabochip. We evaluated the association between each SNP and log-transformed CRP levels using multivariate linear regression, with additive genetic models adjusted for age, sex, the first four principal components of genetic ancestry, and study-specific factors. Differential linkage disequilibrium patterns between race/ethnicity groups were used to fine-map regions associated with CRP levels. Conditional analyses evaluated for multiple independent signals within genetic regions. One hundred and sixty-three unique variants in 12 loci in overall or race/ethnicity-stratified Metabochip-wide scans reached a Bonferroni-corrected P-value <2.5E-7. Three loci have no (HACL1, OLFML2B) or only limited (PLA2G6) previous associations with CRP levels. Six loci had different top hits in race/ethnicity-specific versus overall analyses. Fine-mapping refined the signal in six loci, particularly in HNF1A. Conditional analyses provided evidence for secondary signals in LEPR, IL1RN and HNF1A, and for multiple independent signals in CRP and APOE. We identified novel variants and loci associated with CRP levels, generalized known CRP associations to a multiethnic study population, refined association signals at several loci and found evidence for multiple independent signals at several well-known loci. This study demonstrates the benefit of conducting inclusive genetic association studies in large multiethnic populations.

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