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Reis J.P.,U.S. National Institutes of Health | Loria C.M.,U.S. National Institutes of Health | Steffen L.M.,University of Minnesota | Zhou X.,University of Minnesota | And 5 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2010

Objective-: To determine the association of coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood with the presence and progression of coronary artery calcified (CAC) plaque and carotid intima-media thickness later in life. Methods and results-: The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a cohort of 5115 white and black adults who were aged 18 to 30 years when they completed a baseline clinic examination from 1985 to 1986. Subsequent examinations were conducted 2, 5, 7, 10, 15, and 20 years later. After multivariable adjustment, no association was observed between average coffee, decaffeinated coffee, or caffeine consumption (years 0 and 7) and presence of CAC (score, >0 Agatston units at year 15 or 20), CAC progression (incident CAC at year 20 or increase in CAC score by ≥20 Agatston units), or high carotid intima-media thickness (>80th percentile, year 20). However, tea consumption displayed a nonsignificant trend for an inverse association with CAC (P=0.08 for trend) and an inverse association with CAC progression (P=0.04 for trend) but no association with high carotid intima-media thickness (P>0.20 for trend). Stratification of the coffee analyses by sex, race, or smoking yielded similar nonsignificant patterns. Conclusion-: We observed no substantial association between coffee or caffeine intake and coronary and carotid atherosclerosis. However, our results suggested an inverse association between tea and CAC but not carotid atherosclerosis. © 2010 American Heart Association, Inc.

Mathew J.S.,959 NE Pacific St | Patton K.K.,959 NE Pacific St | Heckbert S.R.,Cardiovascular Health Research Unit | Hoofnagle A.N.,University of Washington | And 5 more authors.
Circulation | Year: 2014

BACKGROUND - : Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF-23 concentrations increase markedly in chronic kidney disease and are associated with increased risk of clinical cardiovascular events. FGF-23 may promote atrial fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left atrial dysfunction. METHODS AND RESULTS - : We tested the associations of circulating FGF-23 concentration with incident AF among 6398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over a median of 7.7 and 8.0 years of follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each 2-fold-higher FGF-23 concentration was associated with a 41% higher risk of incident AF in MESA (hazard ratio, 1.41; 95% confidence interval, 1.13-1.76; P=0.003) and a 30% higher risk of incident AF in CHS (hazard ratio, 1.30; 95% confidence interval, 1.05-1.61; P=0.016) after adjustment for potential confounding characteristics, including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (hazard ratio, 1.15 per 0.5 mg/dL; 95% confidence interval, 1.02-1.31; P=0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjustment for FGF-23. CONCLUSION - : Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF. © 2014 American Heart Association, Inc.

Thacker E.L.,Cardiovascular Health Research Unit | Thacker E.L.,University of Alabama at Birmingham | McKnight B.,Cardiovascular Health Research Unit | Psaty B.M.,Cardiovascular Health Research Unit | And 7 more authors.
Neurology | Year: 2013

Objective: We sought to determine whether in the absence of clinical stroke, people with atrial fibrillation experience faster cognitive decline than people without atrial fibrillation. Methods: Weconducted a longitudinal analysis in theCardiovascularHealth Study, a community-based study of 5,888 men and women aged 65 years and older, enrolled in 1989/1990 or 1992/1993. Participants did not have atrial fibrillation or a history of stroke at baseline. Participants were censored when they experienced incident clinical stroke. Incident atrial fibrillation was identified by hospital discharge diagnosis codes and annual study ECGs. The main outcome was rate of decline in mean scores on the 100-pointModifiedMini-Mental State Examination (3MSE), administered annually up to 9 times. Results: Analyses included 5,150 participants, of whom552 (10.7%) developed incident atrial fibrillation during a mean of 7 years of follow-up. Mean 3MSE scores declined faster after incident atrial fibrillation compared with no prior atrial fibrillation. For example, the predicted 5-year decline in mean 3MSE score from age 80 to age 85 was 26.4 points (95%confidence interval [CI]: 27.0, 25.9) for participants without a history of atrial fibrillation, but was 210.3 points (95% CI: 211.8, 28.9) for participants experiencing incident atrial fibrillation at age 80, a 5-year difference of 23.9 points (95% CI: 25.3, 22.5). Conclusions: In the absence of clinical stroke, people with incident atrial fibrillation are likely to reach thresholds of cognitive impairment or dementia at earlier ages than people with no history of atrial fibrillation. © 2013 American Academy of Neurology.

de Boer I.H.,Kidney Research Institute | Levin G.,Box | Robinson-Cohen C.,Kidney Research Institute | Biggs M.L.,Collaborative Health Studies Coordinating Center | And 2 more authors.
Annals of Internal Medicine | Year: 2012

Background: Circulating concentrations of 25-hydroxyvitamin D [25-(OH)D] are used to define vitamin D deficiency. Current clinical 25-(OH)D targets based on associations with intermediate markers of bone metabolism may not reflect optimal levels for other chronic diseases and do not account for known seasonal variation in 25-(OH)D concentration. Objective: To evaluate the relationship of 25-(OH)D concentration with the incidence of major clinical disease events that are patho-physiologically relevant to vitamin D. Design: Cohort study. Setting: The Cardiovascular Health Study conducted in 4 U.S. communities. Data from 1992 to 2006 were included in this analysis. Participants: 1621 white older adults. Measurements: Serum 25-(OH)D concentration (using a high-performance liquid chromatography-tandem mass spectrometry assay that conforms to National Institute of Standards and Technology reference standards) and associations with time to a composite outcome of incident hip fracture, myocardial infarction, cancer, or death. Results: Over a median 11-year follow-up, the composite outcome occurred in 1018 participants (63%). Defining events included 137 hip fractures, 186 myocardial infarctions, 335 incidences of cancer, and 360 deaths. The association of low 25-(OH)D concentration with risk for the composite outcome varied by season (P = 0.057). A concentration lower than a season-specific Z score of -0.54 best discriminated risk for the composite outcome and was associated with a 24% higher risk in adjusted analyses (95% CI, 9% to 42%). Corresponding season-specific 25-(OH)D concentrations were 43, 50, 61, and 55 nmol/L (17, 20, 24, and 22 ng/mL) in winter, spring, summer, and autumn, respectively. Limitation: The observational study was restricted to white participants. Conclusion: Threshold concentrations of 25-(OH)D associated with increased risk for relevant clinical disease events center near 50 nmol/L (20 ng/mL). Season-specific targets for 25-(OH)D concentration may be more appropriate than static targets when evaluating health risk. Primary Funding Source: National Institutes of Health. © 2012 American College of Physicians.

Psaty B.M.,Cardiovascular Health Research Unit | Psaty B.M.,University of Washington | Curtis L.H.,Duke University | Heckbert S.R.,University of Washington | And 3 more authors.
Circulation | Year: 2016

Background - Increasingly, the diagnostic codes from administrative claims data are being used as clinical outcomes. Methods and Results - Data from the Cardiovascular Health Study (CHS) were used to compare event rates and risk factor associations between adjudicated hospitalized cardiovascular events and claims-based methods of defining events. The outcomes of myocardial infarction (MI), stroke, and heart failure were defined in 3 ways: the CHS adjudicated event (CHS[adj]), selected International Classification of Diseases, Ninth Edition diagnostic codes only in the primary position for Medicare claims data from the Center for Medicare & Medicaid Services (CMS[1st]), and the same selected diagnostic codes in any position (CMS[any]). Conventional claims-based methods of defining events had high positive predictive values but low sensitivities. For instance, the positive predictive value of International Classification of Diseases, Ninth Edition code 410.x1 for a new acute MI in the first position was 90.6%, but this code identified only 53.8% of incident MIs. The observed event rates for CMS[1st] were low. For MI, the incidence was 14.9 events per 1000 person-years for CHS[adj] MI, 8.6 for CMS[1st] MI, and 12.2 for CMS[any] MI. In general, cardiovascular disease risk factor associations were similar across the 3 methods of defining events. Indeed, traditional cardiovascular disease risk factors were also associated with all first hospitalizations not resulting from an MI. Conclusions - The use of diagnostic codes from claims data as clinical events, especially when restricted to primary diagnoses, leads to an underestimation of event rates. Additionally, claims-based events data represent a composite end point that includes the outcome of interest and selected (misclassified) nonevent hospitalizations. © 2015 American Heart Association, Inc.

PubMed | U.S. National Institute on Aging, University of Washington, Cardiovascular Health Research Unit, Oregon State University and 3 more.
Type: Journal Article | Journal: The journals of gerontology. Series A, Biological sciences and medical sciences | Year: 2016

The present study aimed to (i) evaluate previous observations that the association of blood pressure (BP) with outcomes varies by gait speed and (ii) evaluate the association of subsequent changes in BP and cardiovascular risk.Participants included 2,669 adults aged 70-79 years in the Health, Aging, and Body Composition (Health ABC) study. Gait speed was dichotomized at 1.0 m/s over a 20-m test at baseline. BP was measured at baseline, and changes in BP over 5 years were evaluated using (i) population-based trajectory models and (ii) intraindividual mean and slope.Over a mean of 10 years, there were 1,366 deaths, 336 first myocardial infarctions, and 295 first strokes. There was a differential pattern of association between baseline systolic BP and diastolic BP and outcomes among brisk and moderate speed walkers. For example, the association between higher diastolic BP and mortality was in the protective direction for moderate speed walkers (hazard ratio = 0.75; 95% confidence interval: 0.63, 0.91) per 10 mmHg higher, whereas it was null in brisk walkers (hazard ratio = 1.05; 95% confidence interval: 0.98, 1.11), p value for interaction .01. The 5-year population-based trajectories did not add important information beyond baseline BP. Individual slopes in both systolic BP and diastolic BP did not appear to have important associations with the outcomes.In this study, we found that the overall level of BP was associated with myocardial infarction, stroke, and death, and this association differed by baseline gait speed, whereas changes in BP were not associated with these outcomes.

Polonsky T.S.,University of Chicago | Young R.,Cardiovascular Health Research Unit | McClelland R.L.,Cardiovascular Health Research Unit | Delaney J.C.,Cardiovascular Health Research Unit | And 9 more authors.
Circulation | Year: 2015

Background-In the general population, the majority of cardiovascular events occur in people at the low to moderate end of population risk distribution. The 2013 American College of Cardiology/American Heart Association guideline on the treatment of blood cholesterol recommends consideration of statin therapy for adults with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥7.5% based on traditional risk factors. Whether use of nontraditional risk markers can improve risk assessment in those below this threshold for statin therapy is unclear. Methods and Results-Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population sample free of clinical CVD at baseline, we calibrated the Pooled Cohort Equations (cPCE). ASCVD was defined as myocardial infarction, coronary heart disease death, or fatal or nonfatal stroke. Adults with an initial cPCE <7.5% and elevated levels of additional risk markers (abnormal test) whose new calculated risk was ≥7.5% were considered statin eligible: low-density lipoprotein cholesterol ≥160 mg/dL; family history of ASCVD; high-sensitivity C-reactive protein ≥2 mg/dL; coronary artery calcium score ≥300 Agatston units or ≥75th percentile for age, sex, and ethnicity; and ankle-brachial index <0.9. We compared the absolute and relative ASCVD risks among those with versus without elevated posttest estimated risk. We calculated the number needed to screen to identify 1 person with abnormal test for each risk marker, defined as the number of participants with baseline cPCE risk <7.5% divided by the number with an abnormal test reclassified as statin eligible. Of 5185 participants not taking statins with complete data (age, 45-84 years), 4185 had a cPCE risk <7.5%. During 10 years of follow-up, 57% of the ASCVD events (183 of 320) occurred among adults with a cPCE risk <7.5%. When people with diabetes mellitus were excluded, the coronary artery calcium criterion reclassified 6.8% upward, with an event rate of 13.3%, absolute risk of 10%, relative risk of 4.0 (95% confidence interval [CI], 2.8-5.7), and number needed to screen of 14.7. The corresponding numbers for family history of ASCVD were 4.6%, 15.1%, 12%, 4.3 (95% CI, 3.0-6.4), and 21.8; for high-sensitivity C-reactive protein criteria, 2.6%, 10%, 6%, 2.6 (95% CI, 1.4-4.8), and 39.2; for ankle-brachial index criteria, 0.6%, 9%, 5%, 2.3 (95% CI, 0.6-8.6), and 176.5; and for low-density lipoprotein cholesterol criteria, 0.5%, 5%, 1%, 1.2 (95% CI, 0.2-8.4), and 193.3, respectively. Of the 3882 with <7.5% cPCE risk, 431 (11.1%) were reclassified to ≥7.5% (statin eligible) by at least 1 of the additional risk marker criteria. Conclusions-In this generally low-risk population sample, a large proportion of ASCVD events occurred among adults with a 10-year cPCE risk <7.5%. We found that the coronary artery calcium score, high-sensitivity C-reactive protein, family history of ASCVD, and ankle-brachial index recommendations by the American College of Cardiology/American Heart Association cholesterol guidelines (Class IIB) identify small subgroups of asymptomatic population with a 10-year cPCE risk <7.5% but with observed ASCVD event rates >7.5% who may warrant statin therapy considerations. © 2015 American Heart Association, Inc.

Mozaffarian D.,Harvard University | Lemaitre R.N.,Cardiovascular Health Research Unit | King I.B.,University of New Mexico | Song X.,Fred Hutchinson Cancer Research Center | And 5 more authors.
Annals of Internal Medicine | Year: 2013

Background: Long-chain ω-3 polyunsaturated fatty acids (ω3-PUFAs), including eicosapentaenoic acid (EPA) (20:5ω-3), docosa-pentaenoic acid (DPA) (22:5ω-3), and docosahexaenoic acid (DHA) (22:6ω-3), have been shown to reduce cardiovascular risk, but effects on cause-specific and total mortality and potential dose-responses remain controversial. Most observational studies have assessed self-reported dietary intake and most randomized trials have tested effects of adding supplements to dietary intake and evaluated secondary prevention, thus limiting inference for dietary ω3-PUFAs or primary prevention. Objective: To investigate associations of plasma phospholipid EPA, DPA, DHA, and total ω3-PUFA levels with total and cause-specific mortality among healthy older adults not receiving supplements. Design: Prospective cohort study. Setting: 4 U.S. communities. Participants: 2692 U.S. adults aged 74 years (±5 years) without prevalent coronary heart disease (CHD), stroke, or heart failure at baseline. Measurements: Phospholipid fatty acid levels and cardiovascular risk factors were measured in 1992. Relationships with total and cause-specific mortality and incident fatal or nonfatal CHD and stroke through 2008 were assessed. Results: During 30 829 person-years, 1625 deaths (including 570 cardiovascular deaths), 359 fatal and 371 nonfatal CHD events, and 130 fatal and 276 nonfatal strokes occurred. After adjustment, higher plasma levels of ω3-PUFA biomarkers were associated with lower total mortality, with extreme-quintile hazard ratios of 0.83 for EPA (95% CI, 0.71 to 0.98; P for trend = 0.005), 0.77 for DPA (CI, 0.66 to 0.90; P for trend = 0.008), 0.80 for DHA (CI, 0.67 to 0.94; P for trend = 0.006), and 0.73 for total ω3-PUFAs (CI, 0.61 to 0.86; P for trend < 0.001). Lower risk was largely attributable to fewer cardiovascular than noncardiovascular deaths. Individuals in the highest quintile of phospholipid ω3-PUFA level lived an average of 2.22 more years (CI, 0.75 to 3.13 years) after age 65 years than did those in the lowest quintile. Limitation: Temporal changes in fatty acid levels and misclassifica-tion of causes of death may have resulted in underestimated asso-ciations, and unmeasured or imperfectly measured covariates may have caused residual confounding. Conclusion: Higher circulating individual and total ω3-PUFA levels are associated with lower total mortality, especially CHD death, in older adults. Primary Funding Source: National Institutes of Health. © 2013 American College of Physicians.

Mozaffarian D.,Harvard University | Cao H.,U.S. National Institutes of Health | King I.B.,University of New Mexico | Lemaitre R.N.,Cardiovascular Health Research Unit | And 3 more authors.
Annals of Internal Medicine | Year: 2010

Background: Palmitoleic acid (cis-16:1n-7), which is produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Transpalmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative. Objective: To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes. Design: Prospective cohort study from 1992 to 2006. Setting: Four U.S. communities. Patients: 3736 adults in the Cardiovascular Health Study. Measurements: Anthropometric characteristics and levels of plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose-insulin measured at baseline in 1992 and dietary habits measured 3 years earlier. Multivariate-adjusted models were used to investigate how demographic, clinical, and lifestyle factors independently related to plasma phospholipid trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). Findings were validated for metabolic risk factors in an independent cohort of 327 women. Results: In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9% across quintiles; P = 0.040), lower triglyceride levels (-19.0%; P < 0.001), a lower total cholesterol-HDL cholesterol ratio (-4.7%; P < 0.001), lower C-reactive protein levels (-13.8%; P = 0.05), and lower insulin resistance (-16.7%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort. Limitation: Results could be affected by measurement error or residual confounding. Conclusion: Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation. Primary Funding Source: National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. © 2010 American College of Physicians.

Jensen P.N.,Cardiovascular Health Research Unit | Jensen P.N.,University of Washington | Johnson K.,Group Health Research Institute | Floyd J.,Cardiovascular Health Research Unit | And 7 more authors.
Pharmacoepidemiology and Drug Safety | Year: 2012

Purpose: The objectives of this study were to characterize the validity of algorithms to identify AF from electronic health data through a systematic review of the literature and to identify gaps needing further research. Methods: Two reviewers examined publications during 1997-2008 that identified patients with atrial fibrillation (AF) from electronic health data and provided validation information. We abstracted information including algorithm sensitivity, specificity, and positive predictive value (PPV). Results: We reviewed 544 abstracts and 281 full-text articles, of which 18 provided validation information from 16 unique studies. Most used data from before 2000, and 10 of 16 used only inpatient data. Three studies incorporated electronic ECG data for case identification or validation. A large proportion of prevalent AF cases identified by ICD-9 code 427.31 were valid (PPV 70%-96%, median 89%). Seven studies reported algorithm sensitivity (range, 57%-95%, median 79%). One study validated an algorithm for incident AF and reported a PPV of 77%. Conclusions: The ICD-9 code 427.31 performed relatively well, but conclusions about algorithm validity are hindered by few recent data, use of nonrepresentative populations, and a disproportionate focus on inpatient data. An optimal contemporary algorithm would likely draw on inpatient and outpatient codes and electronic ECG data. Additional research is needed in representative, contemporary populations regarding algorithms that identify incident AF and incorporate electronic ECG data. © 2012 John Wiley & Sons, Ltd.

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