@article {1053, title = {Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The Cardiovascular Health study.}, journal = {J Am Coll Cardiol}, volume = {52}, year = {2008}, month = {2008 Sep 30}, pages = {1152-9}, abstract = {

OBJECTIVES: The goal of this study was to determine whether subclinical thyroid dysfunction was associated with incident heart failure (HF) and echocardiogram abnormalities.

BACKGROUND: Subclinical hypothyroidism and hyperthyroidism have been associated with cardiac dysfunction. However, long-term data on the risk of HF are limited.

METHODS: We studied 3,044 adults>or=65 years of age who initially were free of HF in the Cardiovascular Health Study. We compared adjudicated HF events over a mean 12-year follow-up and changes in cardiac function over the course of 5 years among euthyroid participants, those with subclinical hypothyroidism (subdivided by thyroid-stimulating hormone [TSH] levels: 4.5 to 9.9, >or=10.0 mU/l), and those with subclinical hyperthyroidism.

RESULTS: Over the course of 12 years, 736 participants developed HF events. Participants with TSH>or=10.0 mU/l had a greater incidence of HF compared with euthyroid participants (41.7 vs. 22.9 per 1,000 person years, p=0.01; adjusted hazard ratio: 1.88; 95\% confidence interval: 1.05 to 3.34). Baseline peak E velocity, which is an echocardiographic measurement of diastolic function associated with incident HF in the CHS cohort, was greater in those patients with TSH>or=10.0 mU/l compared with euthyroid participants (0.80 m/s vs. 0.72 m/s, p=0.002). Over the course of 5 years, left ventricular mass increased among those with TSH>or=10.0 mU/l, but other echocardiographic measurements were unchanged. Those patients with TSH 4.5 to 9.9 mU/l or with subclinical hyperthyroidism had no increase in risk of HF.

CONCLUSIONS: Compared with euthyroid older adults, those adults with TSH>or=10.0 mU/l have a moderately increased risk of HF and alterations in cardiac function but not older adults with TSH<10.0 mU/l. Clinical trials should assess whether the risk of HF might be ameliorated by thyroxine replacement in individuals with TSH>or=10.0 mU/l.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Echocardiography, Female, Heart, Heart Failure, Heart Function Tests, Humans, Hyperthyroidism, Hypertrophy, Left Ventricular, Hypothyroidism, Male, Risk Factors, Time Factors}, issn = {1558-3597}, doi = {10.1016/j.jacc.2008.07.009}, author = {Rodondi, Nicolas and Bauer, Douglas C and Cappola, Anne R and Cornuz, Jacques and Robbins, John and Fried, Linda P and Ladenson, Paul W and Vittinghoff, Eric and Gottdiener, John S and Newman, Anne B} } @article {1545, title = {Subclinical hyperthyroidism and the risk of coronary heart disease and mortality.}, journal = {Arch Intern Med}, volume = {172}, year = {2012}, month = {2012 May 28}, pages = {799-809}, abstract = {

BACKGROUND: Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting.We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts.

METHODS: Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications.

RESULTS: Of 52 674 participants, 2188 (4.2\%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio[HR], 1.24, 95\% CI, 1.06-1.46), CHD mortality (HR,1.29; 95\% CI, 1.02-1.62), CHD events (HR, 1.21; 95\%CI, 0.99-1.46), and AF (HR, 1.68; 95\% CI, 1.16-2.43).Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5\% for total mortality to 41.5\% forAF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L(for both, P value for trend, .03).

CONCLUSION: Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.

}, keywords = {Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Atrial Fibrillation, Cause of Death, Cohort Studies, Coronary Artery Disease, Female, Humans, Hyperthyroidism, Male, Middle Aged, Prognosis, Prospective Studies, Risk Assessment, Severity of Illness Index, Sex Distribution, Survival Analysis, Switzerland, Thyroid Function Tests, Thyrotropin, Young Adult}, issn = {1538-3679}, doi = {10.1001/archinternmed.2012.402}, author = {Collet, Tinh-Hai and Gussekloo, Jacobijn and Bauer, Douglas C and den Elzen, Wendy P J and Cappola, Anne R and Balmer, Philippe and Iervasi, Giorgio and Asvold, Bj{\o}rn O and Sgarbi, Jos{\'e} A and V{\"o}lzke, Henry and Gencer, Bari{\c s} and Maciel, Rui M B and Molinaro, Sabrina and Bremner, Alexandra and Luben, Robert N and Maisonneuve, Patrick and Cornuz, Jacques and Newman, Anne B and Khaw, Kay-Tee and Westendorp, Rudi G J and Franklyn, Jayne A and Vittinghoff, Eric and Walsh, John P and Rodondi, Nicolas} } @article {6077, title = {Long-term outcomes of left anterior fascicular block in the absence of overt cardiovascular disease.}, journal = {JAMA}, volume = {309}, year = {2013}, month = {2013 Apr 17}, pages = {1587-8}, keywords = {Aged, Atrial Fibrillation, Biomarkers, Bundle-Branch Block, Cohort Studies, Electrocardiography, Endomyocardial Fibrosis, Female, Heart Failure, Humans, Kaplan-Meier Estimate, Male, Prognosis, Risk}, issn = {1538-3598}, doi = {10.1001/jama.2013.2729}, author = {Mandyam, Mala C and Soliman, Elsayed Z and Heckbert, Susan R and Vittinghoff, Eric and Marcus, Gregory M} } @article {5998, title = {The QT interval and risk of incident atrial fibrillation.}, journal = {Heart Rhythm}, volume = {10}, year = {2013}, month = {2013 Oct}, pages = {1562-8}, abstract = {

BACKGROUND: Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine.

OBJECTIVE: To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF.

METHODS: We examined a prolonged QT interval corrected by using the Framingham formula (QT(Fram)) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by using other formulas.

RESULTS: Among 14,538 ARIC study participants, a prolonged QT(Fram) predicted a roughly 2-fold increased risk of AF (hazard ratio [HR] 2.05; 95\% confidence interval [CI] 1.42-2.96; P < .001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in Cardiovascular Health Study and Health, Aging, and Body Composition study and were similar across various QT correction methods. Also in the ARIC study, each 10-ms increase in QT(Fram) was associated with an increased unadjusted (HR 1.14; 95\% CI 1.10-1.17; P < .001) and adjusted (HR 1.11; 95\% CI 1.07-1.14; P < .001) risk of AF. Findings regarding a short QT interval were inconsistent across cohorts.

CONCLUSIONS: A prolonged QT interval is associated with an increased risk of incident AF.

}, keywords = {Aged, Atrial Fibrillation, Cohort Studies, Electrocardiography, Female, Humans, Incidence, Long QT Syndrome, Male, Middle Aged, Risk Factors}, issn = {1556-3871}, doi = {10.1016/j.hrthm.2013.07.023}, author = {Mandyam, Mala C and Soliman, Elsayed Z and Alonso, Alvaro and Dewland, Thomas A and Heckbert, Susan R and Vittinghoff, Eric and Cummings, Steven R and Ellinor, Patrick T and Chaitman, Bernard R and Stocke, Karen and Applegate, William B and Arking, Dan E and Butler, Javed and Loehr, Laura R and Magnani, Jared W and Murphy, Rachel A and Satterfield, Suzanne and Newman, Anne B and Marcus, Gregory M} } @article {8792, title = {Cardiovascular Risk Factors Across the Life Course and Cognitive Decline: A Pooled Cohort Study.}, journal = {Neurology}, volume = {96}, year = {2021}, month = {2021 04 27}, pages = {e2212-e2219}, abstract = {

OBJECTIVE: Cardiovascular risk factors (CVRFs) are associated with increased risk of cognitive decline, but little is known about how early adult CVRFs and those across the life course might influence late-life cognition. To test the hypothesis that CVRFs across the adult life course are associated with late-life cognitive changes, we pooled data from 4 prospective cohorts (n = 15,001, ages 18-95).

METHODS: We imputed trajectories of body mass index (BMI), fasting glucose (FG), systolic blood pressure (SBP), and total cholesterol (TC) for older adults. We used linear mixed models to determine the association of early adult, midlife, and late-life CVRFs with late-life decline on global cognition (Modified Mini-Mental State Examination [3MS]) and processing speed (Digit Symbol Substitution Test [DSST]), adjusting for demographics, education, and cohort.

RESULTS: Elevated BMI, FG, and SBP (but not TC) at each time period were associated with greater late-life decline. Early life CVRFs were associated with the greatest change, an approximate doubling of mean 10-year decline (an additional 3-4 points for 3MS or DSST). Late-life CVRFs were associated with declines in early late life (<80 years) but with gains in very late life (>=80 years). After adjusting for CVRF exposures at all time periods, the associations for early adult and late-life CVRFs persisted.

CONCLUSIONS: We found that imputed CVRFs across the life course, especially in early adulthood, were associated with greater late-life cognitive decline. Our results suggest that CVRF treatment in early adulthood could benefit late-life cognition, but that treatment in very late life may not be as helpful for these outcomes.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Aging, Blood Pressure, Cardiovascular Diseases, Cognition, Cognitive Dysfunction, Cohort Studies, Female, Heart Disease Risk Factors, Humans, Hypertension, Male, Middle Aged, Risk Factors, Young Adult}, issn = {1526-632X}, doi = {10.1212/WNL.0000000000011747}, author = {Yaffe, Kristine and Vittinghoff, Eric and Hoang, Tina and Matthews, Karen and Golden, Sherita H and Zeki Al Hazzouri, Adina} } @article {8987, title = {Depressive Symptoms Imputed Across the Life Course Are Associated with Cognitive Impairment and Cognitive Decline.}, journal = {J Alzheimers Dis}, volume = {83}, year = {2021}, month = {2021}, pages = {1379-1389}, abstract = {

BACKGROUND: Depressive symptoms may increase risk for dementia, but findings are controversial because late-life depression may be a prodromal dementia symptom. Life course data on depression and dementia risk may clarify this association; however, data is limited.

OBJECTIVE: To impute adult depressive symptoms trajectories across adult life stages and estimate the association with cognitive impairment and decline.

METHODS: Using a pooled study of 4 prospective cohorts (ages 20-89), we imputed adult life course depressive symptoms trajectories based on Center for Epidemiologic Studies Depression Scale-10 (CESD-10) and calculated time-weighted averages for early adulthood (ages 20-49), mid-life (ages 50-69), and late-life (ages 70-89) for 6,122 older participants. Adjusted pooled logistic and mixed-effects models estimated associations of imputed depressive symptoms with two cognitive outcomes: cognitive impairment defined by established criteria and a composite cognitive score.

RESULTS: In separate models, elevated depressive symptoms in each life stage were associated with cognitive outcomes: early adulthood OR for cognitive impairment = 1.59 (95\%CI: 1.35,1.87); mid-life OR = 1.94 (95\%CI:1.16, 3.26); and late-life OR = 1.77 (95\%CI:1.42, 2.21). When adjusted for depressive symptoms in the other life-stages, elevated depressive symptoms in early adulthood (OR = 1.73; 95\%CI: 1.42,2.11) and late-life (OR = 1.43; 95\%CI: 1.08,1.89) remained associated with cognitive impairment and were also associated with faster rates of cognitive decline (p < 0.05).

CONCLUSION: Imputing depressive symptom trajectories from pooled cohorts may help expand data across the life course. Our findings suggest early adulthood depressive symptoms may be a risk factor for cognitive impairment independent of mid- or late-life depressive symptoms.

}, keywords = {Adult, Aged, Aged, 80 and over, Aging, Cognitive Dysfunction, Cohort Studies, Dementia, Depression, Female, Humans, Male, Middle Aged, Prodromal Symptoms, Risk Factors}, issn = {1875-8908}, doi = {10.3233/JAD-210588}, author = {Brenowitz, Willa D and Zeki Al Hazzouri, Adina and Vittinghoff, Eric and Golden, Sherita H and Fitzpatrick, Annette L and Yaffe, Kristine} }