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Introduction: Medication non-adherence increases the risk of hospitalization and mortality in older adults. Evidence from previous studies was not conclusive due to small sample size or lack of adjustment for potential confounders. This study aims to investigate the prevalence and predictors of medication non-adherence in older adults, considering both individual-level and neighborhood-level factors. Methods: We studied participants (aged 66-90 years) who were on at least one medication at visit 5 (2011-2013) of the ARIC Study. Potential predictors included demographic factors, individual-level and neighborhood-level socioeconomic factors, behavioral factors, depressive symptoms, and cognitive function. We estimated the prevalence of self-reported medication adherence using the Morisky Green Levine medication adherence questionnaire and considered intermediate and low as medication non-adherence. We used multivariable logistic regression to identify independent predictors of medication non-adherence, further adjusting for race-center, insurance types, comorbidities, and number of medications. Results: Among 5304 participants (mean age of 75.5 [SD 5.1] years, 21.6% Black, and 58.2% female), 2.3% and 37.1% reported low and intermediate medication adherence, respectively. After adjustment, age 66-74 (odds ratio [OR]= 1.23 [95% CI, 1.10-1.38]), current drinker (1.31 [1.10-1.55]), lack of physical activity (PA) (1.18 [1.01-1.37] for intermediate PA; 1.38 [1.21-1.58] for low PA), and depressive symptoms (2.30 [1.82-2.91]) were significant predictors of medication non-adherence ( Table ). Education and ADI were not associated with medication non-adherence. Conclusions: We found that almost 40% of older adults have medication non-adherence. Unhealthy lifestyle factors and depressive symptoms were associated with medication non-adherence. Education and neighborhood-level SES were not. Depression is an important modifiable factor to improve medication adherence in older adults.

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.

Background: In 2007, the American Heart Association published updated evidence-based guidelines on the recommended use of antibiotic prophylaxis to prevent viridans group streptococcal (VGS) infective endocarditis (IE) in cardiac patients undergoing invasive procedures. The 2007 guidelines significantly scaled back the underlying conditions for which antibiotic prophylaxis was recommended, leaving only 4 categories thought to confer the highest risk of adverse outcome. The purpose of this update is to examine interval evidence of the acceptance and impact of the 2007 recommendations on VGS IE and, if needed, to make revisions based on this evidence. Methods and Results: A writing group was formed consisting of experts in prevention and treatment of infective endocarditis including members of the American Dental Association, the Infectious Diseases Society of America, and the American Academy of Pediatrics, in addition to the American Heart Association. MEDLINE database searches were done for English language articles on compliance with the recommendations in the 2007 guidelines and the frequency of and morbidity or mortality from VGS IE after publication of the 2007 guidelines. Overall, there was good general awareness of the 2007 guidelines but variable compliance with recommendations. There was no convincing evidence that VGS IE frequency, morbidity, or mortality has increased since 2007. Conclusions: On the basis of a review of the available evidence, there are no recommended changes to the 2007 VGS IE prevention guidelines. We continue to recommend VGS IE prophylaxis only for categories of patients at highest risk for adverse outcome while emphasizing the critical role of good oral health and regular access to dental care for all. Randomized controlled studies to determine whether antibiotic prophylaxis is effective against VGS IE are needed to further refine recommendations.

Introduction: Intensive systolic blood pressure (SBP) treatment ( Methods: We projected life expectancy after SPRINT using six US cohort studies in the National Heart, Lung, and Blood Institute Pooled Cohorts Study (NHLBI-PCS). We included SPRINT-eligible NHLBI-PCS participants as those aged >=50 years with SBP 130-180 mm Hg and increased cardiovascular disease (CVD) risk without diabetes or history of stroke. We used propensity scores to weight NHLBI-PCS participants to resemble SPRINT participants. In SPRINT participants, we estimated in-trial survival (=4 years) using an age-based FPSM and applied the formula to SPRINT participants to predict post-trial survival. We combined in- and post-trial survival to project overall life expectancy for each SPRINT participant and compared it to commonly used Gompertz methods. Results: We included 8,584 SPRINT and 10,610 SPRINT-eligible NHLBI-PCS participants. After propensity weighting, mean (SD) age was 67.9 (9.4) and 68.7 (8.8) years, 35.5% and 38.3% were female in SPRINT and NHLBI-PCS, respectively. Predicted in-trial survival was similar to that observed in SPRINT with both FPSM and Gompertz models (Figure). Assuming constant treatment effects, projected mean life expectancy using the NHLBI-PCS method was 21.1 (7.4) years with intensive and 19.3 (7.2) years with standard treatment; compared to 11.2 (2.3) and 10.5 (2.2) years, respectively, using the Gompertz method. Conclusions: Combining SPRINT and NHLBI-PCS observed data may offer a more realistic estimate of life expectancy than by parametrically extrapolating SPRINT data.

Background: Smoking is a risk factor for vascular diseases and likely associated with cognitive decline. However, observed associations may be impacted by higher cohort attrition, particularly mortality, among smokers. We incorporated surveillance data between visits using multiple imputation by chained equations (MICE) and assumed the Missing At Random mechanism in missing cognitive function. We assessed the impact of addressing the influence of differential visit attendance driven by mortality on the association of smoking with cognitive decline. Methods: We studied 4,960 participants in Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, who were free from dementia at baseline (2011-2013) with cognitive batteries at baseline and follow-up (2016-2017, N = 3,078). Cognitive decline was measured as change in standardized global cognitive factor scores. Self-reported smoking was collected at previous visits (1987-1998) and annual follow-up interviews (1998 to 2011) of the ARIC study, and pack years were estimated. We used baseline factor scores, dementia risk factors, and cognitive function screening at annual follow-ups and dementia surveillance information after baseline to impute missing factor scores. Cognitive decline was analyzed using linear regression on both complete data and using MICE. Results: Participants had a mean age of 75.7 (SD: 5.1) at the index visit. 59.6% (2956 of 4960) were female and 18.6% (921 of 4960) were African American. Smoking ≥25 pack-years prior to baseline was associated with moderately lower visit attendance and higher mortality at older age. The association of smoking with cognitive decline was stronger after addressing differential attrition driven by mortality using MICE for smoking ≥25 pack-years, with two-fold increase in the effect size (Table 1). Conclusions: Smoking, particularly of longer duration and intensity, is a risk factor for cognitive decline, with larger effect size when dealing with the differentially higher mortality among heavier smokers.

Background— Race and sex differences in silent myocardial infarction (SMI) are not well established. Methods and Results— The analysis included 9498 participants from the Atherosclerosis Risk in Communities (ARIC) study who were free of cardiovascular disease at baseline (visit 1, 1987–1989). Incident SMI was defined as ECG evidence of MI without clinically documented MI (CMI) after the baseline until ARIC visit 4 (1996–1998). Coronary heart disease and all-cause deaths were ascertained starting from ARIC visit 4 until 2010. During a median follow-up of 8.9 years, 317 participants (3.3%) developed SMI and 386 (4.1%) developed CMI. The incidence rates of both SMI and CMI were higher in men (5.08 and 7.96 per 1000-person years, respectively) than in women (2.93 and 2.25 per 1000-person years, respectively; P P =0.217), but whites had higher rate of CMI than blacks (5.04 versus 3.24 per 1000-person years; P =0.002). SMI and CMI (compared with no MI) were associated with increased risk of coronary heart disease death (hazard ratio, 3.06 [95% confidence interval, 1.88–4.99] and 4.74 [95% confidence interval, 3.26–6.90], respectively) and all-cause mortality (hazard ratio, 1.34 [95% confidence interval, 1.09–1.65] and 1.55 [95% confidence interval, 1.30–1.85], respectively). However, SMI and CMI were associated with increased mortality among both men and women, with potentially greater increased risk among women (interaction P =0.089 and 0.051, respectively). No significant interactions by race were detected. Conclusions— SMI represents >45% of incident MIs and is associated with poor prognosis. Race and sex differences in the incidence and prognostic significance of SMI exist that may warrant considering SMI in personalized assessments of coronary heart disease risk.

Introduction: Abdominal aortic aneurysms (AAA) are an important manifestation of vascular disease in older age and rupture of an AAA is associated with high mortality. Traditional atherosclerotic disease risk factors contribute to the etiology of AAA. Biomarkers for novel etiopathogenic mechanisms, including extracellular matrix remodeling and inflammation, have been assessed primarily in cross-sectional studies of AAA. The objective of this study was to prospectively assess the association between biomarkers for these novel mechanisms and clinical AAA during 24 years of follow-up in the ARIC study, a large, community-based cohort. Methods: Clinical AAAs were ascertained from baseline in 1987-1989 (45-64 years of age) to 2011 through hospital discharge codes, death codes, and Medicare outpatient claims. Over a maximum 24 years of follow-up, a total of 554 AAAs (85.3% whites) were identified. Using a nested case-cohort design, novel biomarkers, including MMP3, MMP9, IL6, IL1-beta, N-terminal propeptide of Type III procollagen (PIIINP), and osteopontin, were measured at baseline (90% of sample) or Visit 2 (1990-1992, 10% of sample) in all AAAs and a random sample of 747 participants who were selected from baseline and matched with AAAs by age (≤55 and >55), race, and gender. The association of the biomarkers with the risk of future AAA was estimated using multivariable Cox proportional hazard models with weighting to adjust for the varying sampling fractions of cases and controls across strata. Results: MMP9, IL6, PIIINP, and osteopontin were significantly associated with future risk of AAA after adjusting for age, gender, race and field center (Table). The associations for PIIINP and osteopontin were no longer significant after further adjusting for other traditional risk factors for AAA. Conclusions: Blood concentrations of MMP9, IL6, and osteopontin measured in middle-age were risk markers for incident AAA. These results highlight the role of inflammation and extracellular remodeling in the development of AAA.

Background: Animal models and large population studies have related habitual milk intake to impaired cognitive performance via oxidative stress, but results are inconclusive. We report on the association of milk intake at midlife with 20-year cognitive decline in ARIC-NCS cohort. Methods: Average daily milk intake was assessed in 15,766 ARIC study participants with a standardized FFQ administered at cohort inception in 1987-1989. Reported milk intake was categorized as almost never, 1 glass/day. Domain-specific and global cognitive decline was assessed on three occasions from 1990 through 2013, testing Delayed Word Recall (memory), Digit Symbol Substitution (executive function), and Word Fluency (language). A mixed effects model adjusted for age, race, sex, education, smoking, physical activity and ApoE4 was used to evaluate the association of milk intake with change in cognitive performance over 20 years. The MICE method was used to account for attrition. Results: Among 13,821 participants in the analytic set, the distribution of milk intake across the above four categories was 18.7%, 35.8%, 27.3%, and 18.1%, respectively. In race-combined fully adjusted models greater milk intake was associated with greater cognitive decline (Figure) as indicated by a significant trend (p=0.018). The average difference in the 20-year rate of change in global z between those who reported almost never drinking milk and those who consumed >1glass/day was -0.053 [95%CI: -0.092, -0.014], approximately equivalent to 1 year of additional cognitive aging. The trend met nominal statistical significance in Whites, but not African Americans. Conclusions: Results of this study add to reports indicating that greater milk intake may be associated with greater rate of cognitive decline. Replication of these results and insights into interactions with the intestinal microbiota and other putative modifying factors of the reported association is warranted considering the widely prevalent intake of milk in US adults.

Background: Carotid-femoral pulse wave velocity (cfPWV) is a reference measure of central (elastic) artery stiffness and a risk factor for cardiovascular disease. Femoral-ankle pulse wave velocity (faPWV) is a measure of peripheral (musculo-elastic) arterial stiffness. The ratio of fasting triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) is a novel and practical marker of insulin resistance (IR), a dysregulation that often precedes diabetes. While diabetes is a known risk factor for arterial stiffening, associations of IR with segment-specific measures of PWV, in those without diabetes, have not been well characterized. Objective: To characterize the cross-sectional association of IR, as indexed by TG/HDL-C, with central and peripheral arterial stiffness by race and gender in older adults without diagnosed diabetes. We hypothesized that TG/HDL-C is positively associated with cfPWV and inversely associated with faPWV. Methods: Our study population included 2477 white and 564 African American adults without diagnosed diabetes examined in 2011-2013 by the ARIC study. cfPWV (cm/s) and faPWV (cm/s) were measured using the Omron VP-1000 Plus system. TG (mg/dL)/HDL-C (mg/dL) was evaluated continuously and categorically. For TG/HDL-C categories, race and gender specific receiver operator characteristic curves were used to determine cut points corresponding to the 75th percentile of fasting insulin, optimized using the Youden index. Elevated TG/HDL-C was dichotomously defined by cut points. Multivariable linear regression was used to model associations, adjusted for age, heart rate, gender, current smoking, and race-center; analyses were stratified by race and gender. Results: The study population was 19% African American and 62% women; mean age was 75 years (SD: 5). TG/HDL-C was positively and monotonically associated with cfPWV, and inversely associated with faPWV. Overall, compared to those without elevated TG/HDL, those with elevated TG/HDL-C had higher cfPWV (β=56 cm/s, 95% CI 35, 78) and, although not significant, lower faPWV (β=-9 cm/s, 95% CI -22, 5). cfPWV was higher in those with elevated TG/HDL-C: 59 cm/s (95% CI 32, 87) in white women, 40 cm/s (95% CI 3, 78) in white men, 50 cm/s (95% CI -20, 120) in African American women, and 101 cm/s (95% CI -10, 212) in African American men. faPWV was lower in white women (β=-23 cm/s, 95% CI -42, -4), but not statistically different in other subgroups. The association of elevated TG/HDL-C with cfPWV and faPWV did not differ by race or gender (p-values >0.1 for all tests for interaction). Conclusions: Higher levels of IR, as indexed by TG/HDL-C, were associated with higher central arterial stiffness and lower peripheral arterial stiffness. These results suggest a role of IR in arterial stiffening in older adults without diabetes.

Background: Differences in the incidence and prognostic significance of silent myocardial infarction (SMI) vs. MI with clinical manifestations (CMI) are not well-established in racially diverse populations. Methods: We compared the incidence of SMI and CMI and their associations with coronary heart disease (CHD) death and death from all causes in 9,498 participants (mean age 54 years, 56.9% women, 20.3% African-American) from the Atherosclerosis Risk in Communities (ARIC) study who were free of cardiovascular disease at baseline visit (1987-89). Incident SMI was defined as ECG evidence of MI without documented CMI occurring after the baseline visit until visit 4 (1996-98). CHD and all-cause deaths were ascertained starting from ARIC visit 4 until 2010 (median follow up 12 years). Results: There were 386 (4.1%) incident CMIs and 317 (3.3%) SMIs. Both CMI and SMI were more common in men (6.8% and 4.3%, respectively) than in women (2.0% and 2.6%, respectively) pTable ). A significant interaction by sex was observed; SMI and CMI were associated with higher risk of CHD and all-cause deaths in women compared to men (interaction p-value= 0.014). No significant interactions by age or race were detected. Conclusions: SMI is as common as CMI, and both are associated with increased risk of CHD and all-cause mortality. Racial and sex differences in the distribution of SMI and CMI, as well as sex differences in the prognostic significance of SMI and CMI exist. These findings suggest that an ECG finding of MI in persons without a history of MI may warrant consideration in personalized CHD prevention risk management efforts particularly in women.

Background: The 2013 ACC/AHA Guidelines on the Treatment of Blood Cholesterol recommended initiating statin therapy when an individual’s 10-year estimated ASCVD risk ≥7.5% We sought to determine whether adults who eventually experienced ASCVD events were more likely to be identified as having ≥7.5% risk using the ACC/AHA’s Pooled Cohort Equations (PCE) compared to the ATP III-Framingham (FRS) and Reynolds risk scores (RRS). Methods: We used data from the biracial Atherosclerosis Risk in Communities Study (ARIC) visit 4 (1996-1998) because hsCRP was measured at this exam. We excluded participants with an ASCVD event prior to visit 4, diabetes, statin use at visit 4, age>74, LDL-C >190 mg/dl, or missing data. Published models for the PCE, ATP III-FRS, and RRS estimated risk. We defined statin eligibility as an estimated 10-year risk ≥7.5% for the PCE and RRS, and ≥10% for the ATP III-FRS. The primary outcome for each score was based on the outcomes originally used to derive the scores: ATP III-FRS (MI or CHD death), PCE (MI, CHD death, stroke) and RRS (MI, CHD death, stroke and revascularization). Results: Using the PCE, 2592 participants had an estimated risk ≥7.5% and 2760 80% of men who experienced events had an estimated risk ≥7.5% (see Table). In contrast, a much smaller proportion of women who experienced events had an estimated risk ≥7.5%, although the PCE yielded the highest proportion (52%). Conclusions: A cutoff of ≥7.5% 10-year ASCVD risk identified the majority of male participants in ARIC who experienced subsequent ASCVD events regardless of the risk score used. Substantially fewer women who experienced events were identified. Lower risk cutoffs or additional markers of ASCVD risk may be required when making decisions about statin therapy for women.

Introduction: Arterial stiffness is an indicator of subclinical cardiovascular disease (CVD) and is associated with increased CVD risk. The determinants of arterial stiffness may be explained in part by a clustering of metabolic abnormalities (as defined by the metabolic syndrome). Our goal was to examine the association of central and peripheral arterial stiffness (as measured by carotid-femoral, brachial-ankle, and femoral-ankle pulse wave velocity) with the metabolic syndrome in older adults. We predicted higher arterial stiffness (i.e. higher pulse wave velocity measurements) in persons with compared to persons without the metabolic syndrome. Methods: We analyzed 3542 persons without diabetes at the ARIC Visit 5 examination in 2011-13 (61% female; 18% African American; median age 75 yrs). The metabolic syndrome was defined as ≥3 of the following: (1) abdominal obesity (waist circumference ≥102 cm in males and ≥88 cm in females); (2) hypertriglyceridemia (≥150 mg/dL), (3) low HDL-cholesterol ( Results: The prevalence of metabolic syndrome was 49% (SE 2); the three metabolic abnormalities with the highest prevalence were abdominal obesity (63% (SE 1)), elevated fasting glucose (60% (SE 1)), and high blood pressure (76% (SE 1)). A majority of participants had two (29% (SE 3)) or three (28% (SE 3)) metabolic abnormalities. Persons with the metabolic syndrome had a higher mean cfPWV (54 cm/s; 95% CI: 35, 73 cm/s), higher mean baPWV (22; 95% CI: 2, 42 cm/s, respectively), and lower mean faPWV (-18 cm/s; 95% CI: -31, -6 cm/s) compared to persons without the metabolic syndrome. Each additional metabolic abnormality was associated with a 28 cm/s (95% CI: 20, 36 cm/s) higher cfPWV, 19 cm/s (95% CI: 11, 27 cm/s) higher baPWV, and 6 cm/s (95% CI: -11, -1 cm/s) lower faPWV. Conclusion: Metabolic syndrome and each additional metabolic abnormality was positively associated with cfPWV and baPWV, and inversely associated with faPWV in older adults. Abdominal obesity, elevated fasting glucose, and high blood pressure were the most common metabolic abnormalities in this cohort of older men and women. Having the metabolic syndrome and its abnormalities may contribute to arterial stiffness that is predictive of CVD events and mortality.

Background: Despite the growing use of pulse wave velocity (PWV), a measure of arterial stiffness that is predictive of cardiovascular disease and all-cause mortality, the repeatability of central, lower-extremity, and composite measures of PWV has not been examined. Objectives: Characterize the repeatability of PWV in a multi-center, population-based study of older adults. Methods: We included a subset of the ARIC visit 5 (2011-2013) participants (n=79; mean age 75.7 years; 46 females) from the following four United States communities: Forsyth County, NC; Jackson, MS; Minneapolis, MN; and Washington County, MD who underwent two standardized exams 4-8 weeks apart. At each exam, trained and certified technicians obtained two PWV measurements following a standardized protocol using the VP-1000 Plus system (Omron Co., Ltd., Kyoto, Japan). Measurements included carotid-femoral PWV (cfPWV), right brachial-ankle PWV (baPWV) and right femoral-ankle PWV (faPWV). We excluded participants with evidence of a major arrhythmia on a 12-lead electrocardiogram, aortic stenosis, body mass index >40 kg/m 2 , and excluded PWV values >3 standard deviations away from the mean. We used random-effects mixed models to parse the variance of the measures into their between-participant, between-visit, and within-visit components, then calculated the intra-class correlation coefficient (ICC) and estimated the number of replicates needed to achieve an ICC of 0.9 using the Spearman-Brown formula and the lower bound of the ICC 95% confidence interval (95% CI). We also calculated the minimal detectable change (MDC; 95% confidence) and minimal detectable difference (MDD). Results: Between-participant variation accounted for 69% to 84% of the total variation in cfPWV, baPWV and faPWV. The ICCs (95% CIs) were 0.70 (0.59, 0.81) for cfPWV, 0.84 (0.78, 0.90) for baPWV, and 0.69 (0.59, 0.79) for faPWV. The number of replicates to achieve an ICC of 0.90 was 6 for cfPWV and faPWV and 3 for baPWV. The overall means and standard deviations (SD) were 1,198.9 ± 269.6 cm/s for cfPWV, 1,742.0 ± 328.3 cm/s for baPWV, and 1,063.4 ± 189.4 cm/s for faPWV. The MDC between repeat measures within an individual was 411.0 cm/s for cfPWV, 370.6 cm/s for baPWV, and 301.4 cm/s for faPWV. The MDD for two independent samples of 100 per group was 139.3 cm/s for cfPWV, 172.3 cm/s for baPWV, and 100.4 cm/s for faPWV. Conclusion: The repeatability is excellent for baPWV and fair for cfPWV and faPWV. The MDC was approximately 1 SD for baPWV and 1.5 SDs for cfPWV and faPWV and the MDD for 100 per group was approximately 0.5 SD for cfPWV, baPWV and faPWV. Averaging replicates would reduce the effects of measurement variability. These results support the use of PWV in clinical and epidemiologic studies; however, to minimize potential bias, studies need to consider measurement variability in design development and in the analysis and interpretation of results.

Introduction: Understanding the role of risk factors associated with accelerated cognitive decline has important public health relevance for the aging US population. To test hypotheses that mid-life cardiovascular (CV) risk factors increase risk of dementia in old age, the Atherosclerosis Risk in Communities (ARIC) cohort was evaluated for dementia in 2011-2013. Anticipating challenges of complete dementia ascertainment in an elderly population, supplementary data sources were collected to aid analysis accounting for potentially informative attrition. Methods: ARIC enrolled 15,792 participants 45-64 years old at baseline (1987-1989) from four US communities and collected baseline CV exposure data. A complete neurocognitive battery including informant interview was completed 2011-2013, yielding an algorithmic diagnosis of dementia, mild cognitive impairment (MCI) or normal cognition. Cognitively impaired and a random sample of cognitively normal were selected for further clinical evaluation. Syndromic diagnoses (dementia/MCI/normal) and etiologic diagnoses were made by a panel of experts using standardized criteria. Standardized protocols, timely reports of reviewer reliability, ongoing training of reviewers and a web-based data management system were developed to ensure reliability, consistency and efficiency of data collection and review. Living participants not attending the visit were asked to complete the Telephone Interview for Cognitive Status (TICS). Based on dementia discharge codes and death codes identified during cohort surveillance, interviewer impression of hearing loss or cognitive impairment or need for a proxy during semi-annual calls, or random sampling, participants refusing the TICS are eligible for proxy dementia interview. Medicare claims are being examined to identify missed dementia discharge codes. Results: Of 11,017 participants alive as of 2011, 6495 (59%) completed the neurocognitive battery; 2937 of these (45%) were selected for, and completed, additional clinical assessments and classification by committee (algorithmic or reviewer diagnosis: dementia 5%, MCI 21%). Of the 4522 participants who did not undergo the neurocognitive battery, 1463 (32%) completed the TICS (dementia 7%), while 1627 of the remaining participants were eligible for proxy calls (903 completed to date, dementia 58%). Conclusions: Participants who were not examined were more likely to be cognitively impaired, highlighting the importance of collecting supplementary data to support analyses of midlife CV risk factors accounting for informative attrition. Collection of exam data in an elderly cohort is difficult and requires a multi-pronged approach, especially for an outcome highly correlated with attrition. The strategy described here could be applied in other settings.

Background— An association between orthostatic hypotension (OH) and mortality has been reported, but studies are limited to older adults or high-risk populations. Methods and Results— We investigated the association between OH (a decrease of 20 mm Hg in systolic blood pressure or a decrease of 10 mm Hg in diastolic blood pressure on standing) and 13-year mortality among middle-aged black and white men and women from the Atherosclerosis Risk in Communities Study (1987–1989). At baseline, 674 participants (5%) had OH. All-cause mortality was higher among those with (13.7%) than without (4.2%) OH. After we controlled for ethnicity, gender, and age, the hazard ratio (HR) for OH for all-cause mortality was 2.4 (95% confidence interval [CI], 2.1 to 2.8). Adjustment for risk factors for cardiovascular disease and mortality and selected health conditions at baseline attenuated but did not completely explain this association (HR=1.7; 95% CI, 1.4 to 2.0). This association persisted among subsets that (1) excluded those who died within the first 2 years of follow-up and (2) were limited to those without coronary heart disease, cancer, stroke, diabetes, hypertension, or fair/poor perceived health status at baseline. In analyses by causes of death, a significant increased hazard of death among those with versus without OH persisted after adjustment for risk factors for cardiovascular disease (HR=2.0; 95% CI, 1.6 to 2.7) and other deaths (HR=2.1; 95% CI, 1.6 to 2.8) but not for cancer (odds ratio=1.1; 95% CI, 0.8 to 1.6). Conclusions— OH predicts mortality in middle-aged adults. This association is only partly explained by traditional risk factors for cardiovascular disease and overall mortality.

Background— Results from studies relating periodontal disease to cardiovascular disease have been mixed. Residual confounding by smoking and use of clinical measures of periodontal disease rather than measures of infection have been 2 major criticisms. The aims of this study were to investigate relationships between prevalent coronary heart disease (CHD) and 2 exposures, (1) clinical periodontal disease and (2) IgG antibodies to 17 oral organisms, and to evaluate the role of smoking in these relationships. Methods and Results— Our study is based on a subset of participants in the Atherosclerosis Risk in Communities (ARIC) Study, who received a complete periodontal examination during visit 4 (1996–1998). The exposures were periodontal status and serum IgG antibody levels against 17 periodontal organisms, and the outcome was prevalent CHD at visit 4. Multivariable analyses indicate that periodontal status is not significantly associated with CHD in either ever smokers or never smokers. Similar analyses evaluating antibodies indicate that high antibodies (above the median) to Treponema denticola (odds ratio [OR]=1.7; 95% CI, 1.2 to 2.3), Prevotella intermedia (OR=1.5; 95% CI, 1.1 to 2.0), Capnocytophaga ochracea (OR=1.5; 95% CI, 1.1 to 2.1), and Veillonella parvula (OR=1.7; 95% CI, 1.2 to 2.3) are significantly associated with CHD among ever smokers, whereas Prevotella nigrescens (OR=1.7; 95% CI, 1.1 to 2.6), Actinobacillus actinomycetemcomitans (OR=1.7; 95% CI, 1.2 to 2.7), and Capnocytophaga ochracea (OR=2.0; 95% CI, 1.3 to 3.0) were associated with CHD among never smokers. Conclusions— Clinical signs of periodontal disease were not associated with CHD, whereas systemic antibody response was associated with CHD in ever smokers and never smokers. These findings indicate that the quality and quantity of the host response to oral bacteria may be an exposure more relevant to systemic atherothrombotic coronary events than clinical measures.

Background: Comparability of laboratory measures over time is important for studies of disease prevalence and progression. While a small amount of bias may seem negligible on an individual level, it can result in substantial misclassification of disease in the population. We conducted a calibration study of important biomarkers across five study visits (25 years) in ARIC. Methods: We re-measured 15 analytes in 200 blood samples to calibrate original measurements at each time point using Bland-Altman plots and Deming regression. We also assessed the impact of calibration on the prevalence of chronic kidney disease (CKD), defined by estimated glomerular filtration rate using creatinine (eGFRcr), and on trends over time. Results: Assays in samples frozen 12-27 years were highly correlated with original values (median r=0.95) after removing outliers (median 4% of values). The range of bias (% difference in means) across visits for each original analyte compared to its reference were: creatinine: 13-49%; uric acid: 3-24%; C-reactive protein: 3-9%; total cholesterol: 1-6%; high density lipoprotein cholesterol: 4-8% (but new methods differed); low density lipoprotein cholesterol: 1-5%; triglycerides: 2-4%; glucose: 1-4%; N-terminal prohormone of brain natriuretic peptide: 2-12%; high sensitivity cardiac troponin T: 1-9%; alanine transaminase (ALT): 21%; aspartate transaminase (AST): 17%; gamma glutamyl transpeptidase: 0.2%; ß2-microglobulin: 1%; beta-trace protein: 13%. Four analytes met calibration criteria: creatinine, uric acid, ALT and AST. The impact on CKD prevalence was substantial and similar to previous statistical calibration (22% uncalibrated, 1.9% previously and 1.3% current laboratory calibration). Trends in eGFRcr over time were better aligned after calibration ( Figure ). Conclusions: Repeat assay of samples shows high correlation with original values. Calibration enables application of absolute cutoffs (required for defining CKD and other conditions) and improves longitudinal analyses.

Introduction: Since the 1980’s, length of stay (LOS) for acute MI (AMI) has declined in the US. However, little is known about trends in LOS for non-white racial groups and whether change in LOS is related to insurance type or hospital complications. Methods: We determined 22 year trends in LOS for nonfatal (definite or probable) AMI among black and white residents age 35–74 in 4 US communities (N=396,514 in 2008 population) under surveillance in the ARIC Study. Events were randomly sampled and independently validated using a standardized algorithm. All analyses accounted for sampling scheme. We excluded MI events which started after admission (n=1,677), events within 28 days for the same person (n=3,817), hospital transfers (n=571), and those with LOS=0 or LOS >66 (top 0.5% of distribution, N= 144) leaving 22,258 weighted events for analysis. The average annual change in log LOS was modeled using weighted linear regression with year as a quadratic term. All models adjusted for age and secondary models adjusted for insurance type (Medicare, Medicaid, private, or other), and complications during admission (cardiac arrest, cardiogenic shock, or heart failure). Results: The average age-adjusted LOS from 1987 to 2008 was reduced by 5 days in black men (9.5 to 4.5 days); 4.6 days in white women (9.4 to 4.8 days); 4 days in white men (8.3 to 4.3 days) and 3.6 days in black women (9.0 to 5.4 days). Between 1987 and 2008, the age-adjusted average annual percent change (with 95% CI) in LOS was largest for white men at −4.40 percent per year (−4.91, −3.89) followed by −3.89 percent (−4.52, −3.26) for white women, −3.72 percent (−4.46, −2.89) for black men, and −2.94 percent (−3.92, −1.96) for black women (see Figure). Adjustment for insurance type, and complications did not change the pattern by race and gender. Conclusions: Between 1987 and 2008, LOS for AMI declined significantly and similarly in men and women, blacks and whites. These changes appear independent of differences in insurance type and hospital complications among race-gender groups.