Alonso, Álvaro

Background: Although associations between hypertension in mid-life and the development of dementia and cognitive decline have been established, the impact of the new 2017 ACC/AHA guidelines on dementia risk at the population level has not been evaluated. Objectives: To assess the association of hypertension categories with the risk of incident dementia and to calculate the population attributable fraction (PAF) for dementia from hypertension categories according to the 2017 ACC/AHA guidelines, and compare these associations with hypertension defined according to JNC7. Methods: We studied dementia-free participants recruited to the Atherosclerosis Risk in Communities (ARIC) cohort in 1987-89. Hypertension was defined by 2003 JNC7 and 2017 ACC/AHA guidelines using blood pressure measured at baseline; participants using antihypertensive medication were included in hypertension stage 2 for both sets of guidelines. Dementia was defined using adjudicated consensus diagnoses at visit 5 (2011-13), informant telephone interviews, and ICD-9 codes from hospitalizations and death certificates through 2013. Cox proportional hazards regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) by hypertension categories, adjusting for potential confounders, including sociodemographic, lifestyle and clinical variables. PAF of dementia by hypertension category was calculated using rate ratios from Poisson regression and the prevalence of the risk factor in the population. Results: Among 13,971 participants followed for a median of 23.0 years, 1381 cases of dementia were identified. Prevalence of elevated BP (systolic BP [SBP] 120-129 and diastolic BP [DBP] <80), hypertension stage 1 (SBP 130-139 or DBP 80-89) and hypertension stage 2 (SBP ≥140 or DPB ≥90) according to 2017 ACC/AHA categories was 13%, 15% and 44%, respectively. Corresponding HR (95%CI) compared to normal BP were 1.35 (95%CI 1.12, 1.61), 1.28 (1.07, 1.52) and 1.36 (1.18, 1.57), respectively. PAF (95%CI) of dementia from hypertension categories were 3% (1%, 5%), 3% (1%, 5%) and 9% (4%, 14%). PAF using JNC7 categories were similar to 2017 ACC/AHA: 6% (3%, 9%) for prehypertension (SBP 120-129 or DBP 80-89), 0% (-2%, 2%) for hypertension stage 1 (SBP 140-159 or DBP 90-99), and 9% (5%, 13%) for hypertension stage 2 (SBP ≥160 or DBP ≥100). Conclusions: Risk of dementia was increased across categories defined by the new ACC/AHA hypertension guidelines. However, the population impact on dementia incidence using 2017 ACC/AHA was similar to the impact of JNC7. These results suggest that the new criteria for diagnosis of hypertension will not increase the number of persons in whom hypertension could be reasonably labeled as a risk for dementia.

Introduction: The prevalence of atrial fibrillation (AF) and multimorbidity increase with age; however, the burden imposed by concurrent conditions on outcomes is unknown. Therefore, we aimed to determine the effect of the number and type of comorbid conditions on outcomes in elderly individuals with incident AF. Methods: Patients with non-valvular AF 75 years and older were identified in the MarketScan Medicare Supplemental database from 2007-2015. Fourteen chronic conditions, defined by two occurrences of a diagnostic code from inpatient and outpatient claims prior to or at the time of AF diagnosis, were obtained and classified into two categories: cardiovascular (CV) or non-CV (listed in Table footnote). We used Cox regression to estimate the associations of the number and type of conditions with stroke, severe bleeding, and heart failure hospitalizations (HF). Results: Among 275,617 patients with AF (mean age 83 years, 51% women), 90% had at least one or more additional chronic conditions. The mean (SD) number of conditions per participant was 1.8 (0.9) for CV conditions and 2.1 (1.2) for non-CV conditions. Over a mean follow-up of 23 months, 7,814 strokes, 13,622 severe bleeds, and 19,252 HF events occurred. After adjustment for age, sex, the number of conditions in the other comorbidity group, an increase of one CV condition was associated with greater risk of stroke, severe bleeding, and HF (Table). In contrast, an increase in one non-CV condition was associated with a lower risk of stroke, and a small increase in bleeding and HF risk (Table). After further adjustments for frailty and medications, the strength of the associations within each group decreased across outcomes. Conclusion: CV conditions in AF patients 75 years and older are more strongly associated with stroke, HF, and bleeding than non-CV conditions. This underscores the effect of CV conditions on CV outcomes in a population in which multimorbidity is most common and health care management and delivery is complex.

Background: Multimorbidity is common in atrial fibrillation (AF); however, the impact of the number and type of comorbid conditions on death and hospitalizations is uncertain. Methods: The prevalence of 17 chronic conditions was obtained in 1430 patients with incident AF from 2000-2010 from Olmsted County, MN. Chronic conditions were ascertained electronically prior to AF and were classified into 3 groups: cardiovascular (CV), other physical, and mental. All hospitalizations and deaths were obtained through 12/31/2014. Associations of the number and type of condition and each individual condition with hospitalizations and death were determined using Andersen-Gill and Cox regression, respectively. Results: Among the 1430 patients with AF (median age 76 years, 48.6% men), the mean (SD) number of chronic conditions was 4.7 (2.7). A total of 4496 hospitalizations and 812 deaths occurred over a mean (SD) follow-up of 5.4 (4.1) years. An increase in the number of conditions of each type was associated with increased risks of death and hospitalizations (Table). Mental conditions (which included depression, anxiety, dementia, schizophrenia, and substance abuse) exhibited the strongest association with death, whereas other physical conditions exhibited the strongest association with hospitalizations. Individual predictors of death included heart failure (HF), hypertension, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), depression, dementia, and substance abuse. Predictors of hospitalizations included HF, coronary artery disease, diabetes, COPD, CKD, arthritis, osteoporosis, and substance abuse. Conclusions: Patients with AF have many comorbid conditions which are associated with death and hospitalizations. Although conditions of each type were associated with outcomes, mental conditions exhibited strongest association with death. These data highlight the importance of management of not only CV comorbidities but other physical and mental comorbidities in patients with AF.

Background and Purpose— Despite modest predictive ability for ischemic stroke (IS), the CHA 2 DS 2 -VASc score is widely used for stroke prediction in atrial fibrillation. Among patients with atrial fibrillation, we aimed to (1) compare the IS or transient ischemic attack (TIA) incidence by CHA 2 DS 2 -VASc in blacks and Hispanics versus whites; (2) compare predictive ability of CHA 2 DS 2 -VASc score for IS or TIA in blacks and Hispanics versus whites; and (3) determine improvement in predictive ability of CHA 2 DS 2 -VASc score from addition of race/ethnicity. Methods— Using data from Optum Clinformatics, a large administrative claims database, we analyzed patients with atrial fibrillation enrolled in commercial and Medicare Advantage health plans from 2009 to 2015. We computed IS or TIA incidence rates, improvement in C statistic, continuous and categorical net reclassification improvement, and relative integrated discrimination improvement from addition of race/ethnicity to CHA 2 DS 2 -VASc. Results— A total of 267 419 patients (mean age, 73.1 [SD, 12.3] years; 46.6% women; 84.2% white, 8.5% black, 7.3% Hispanic) were studied. After a mean follow-up of 22 months, there were 6202 IS or TIA events. IS or TIA incidence rates were higher in blacks than Hispanics or whites (1.65, 1.40, and 1.22 cases per 100 person-years, respectively) and increased with higher CHA 2 DS 2 -VASc, with no race/ethnicity-based differences ( P for interaction=0.17). The CHA 2 DS 2 -VASc and CHA 2 DS 2 -VASc+race/ethnicity C statistic (95% CI) were 0.679 (0.670–0.686) and 0.679 (0.671–0.688). The CHA 2 DS 2 -VASc C statistic in the 3 groups were comparable. With addition of race/ethnicity, the categorical net reclassification improvement, continuous net reclassification improvement, and relative integrated discrimination improvement were −0.045 (95% CI, −0.067 to −0.025), 0.045 (95% CI, 0.025–0.068), and 0.016 (95% CI, 0.014–0.018). Conclusions— The predictive ability of CHA 2 DS 2 -VASc for IS or TIA in atrial fibrillation is comparable among whites, blacks, and Hispanics; hence, it can be used in the latter 2 groups. Addition of race/ethnicity to the CHA 2 DS 2 -VASc does not improve its predictive ability.

Background Oral anticoagulants ( OACs ) in patients with atrial fibrillation ( AF ), in addition to reducing stroke risk, could also prevent adverse cognitive outcomes. The purpose of this study was to compare the risk of dementia incidence across patients with AF initiating different OAC s. Methods and Results We identified patients with nonvalvular AF initiating OAC s in 2 US healthcare claim databases, MarketScan (2007–2015) and Optum Clinformatics (2009–2015). Dementia, comorbidities, and use of medications were defined on the basis of inpatient and outpatient claims. We performed head‐to‐head comparisons of warfarin, dabigatran, rivaroxaban, and apixaban in propensity score–matched cohorts. We calculated hazard ratios ( HR s) and 95% confidence intervals ( CI s) of incident dementia for each propensity score–matched cohort and meta‐analyzed database‐specific results. We analyzed 307 099 patients with AF from the MarketScan database and 161 346 from the Optum database, of which 6572 and 4391, respectively, had a diagnosis of incident dementia. The mean follow‐up of each cohort ranged between 0.7 and 2.2 years. Patients initiating direct OACs experienced lower rates of dementia than those initiating warfarin (dabigatran: HR , 0.85; 95% CI , 0.71–1.01; rivaroxaban: HR , 0.85; 95% CI , 0.76–0.94; apixaban: HR , 0.80; 95% CI , 0.65–0.97). There were no differences in rates of dementia comparing direct OAC user groups (dabigatran versus rivaroxaban: HR , 1.02; 95% CI , 0.79–1.32; dabigatran versus apixaban: HR , 0.92; 95% CI , 0.63–1.36; apixaban versus rivaroxaban: HR , 1.01; 95% CI , 0.86–1.19). Conclusions Patients with AF initiating direct OACs experienced lower rates of incident dementia than warfarin users. No obvious benefit was observed for any particular direct OAC in relation to dementia rates.

Abstract Rationale Growing evidence suggests that compromised lung health may be linked to dementia and worsening cognitive ability. Objectives To test the hypothesis that impaired lung function or lung disease in midlife is associated with greater risk of incident dementia and mild cognitive impairment (MCI) later in life. Methods A total of 14,184 Atherosclerosis Risk in Communities study participants who underwent spirometry and were asked about lung health (1987–1989) were followed. Dementia and MCI were defined by hospitalization diagnosis codes (1987–2013) in the whole cohort and with adjudication among 42% who attended a comprehensive neurocognitive examination (2011–2013). Measurements and Main Results In analysis using adjudicated outcomes, odds of dementia or MCI were higher among participants with restrictive (multivariable-adjusted odds ratio, 1.58; 95% confidence interval, 1.14–2.19) and obstructive lung disease (multivariable-adjusted odds ratio, 1.33; 95% confidence interval, 1.07–1.64), compared with those without disease or respiratory symptoms. Associations were similar in analyses restricted to nonsmokers, and present for both Alzheimer’s disease–related dementia and cerebrovascular etiologies. Low FEV1% predicted and FVC% predicted were also associated with increased dementia risk. Conclusions Midlife lung disease and reduced lung function were associated with modestly increased odds of dementia and MCI later in life. Magnitudes of association were more pronounced for restrictive impairment than for obstructive lung disease. These associations were present in smokers and nonsmokers. If the observed associations are causal, policy and public health efforts to reduce smoking and improve air quality may have the added benefit of preventing the development of dementia and MCI.

Objectives To examine the association between hospitalization, critical illness, and infection occurring during middle‐ and late‐life and structural brain abnormalities in older adults. Design Prospective cohort study. Setting Atherosclerosis Risk in Communities (ARIC) Study. Participants A community sample of adults who were 44 to 66 years of age at study baseline. Measurements Active surveillance of local hospitals and annual participant contact were used to gather hospitalization information (including International Classification of Diseases, Ninth Revision , codes) on all participants over a 24‐year surveillance period. Subsequently, a subset of participants underwent 3‐Tesla brain magnetic resonance imaging (MRI) to quantify total and regional brain volumes, white matter hyperintensity (WMH) volume, and white matter microstructural integrity (fractional anisotropy (FA) and mean diffusivity (MD) as measured using diffusion tensor imaging (DTI)). Results Of the 1,689 participants included (mean age at MRI 76±5), 72% were hospitalized, 14% had a major infection, and 4% had a critical illness during the surveillance period. Using covariate‐adjusted regression, hospitalization was associated with 0.12–standard deviation (SD) greater WMH volume (95% confidence interval (CI)=0.00–0.24) and poorer white matter microstructural integrity (0.17‐SD lower FA, 95% CI=–0.27 to –0.06; 0.16‐SD greater MD, 95% CI=0.07–0.25) than no hospitalization. There was a dose‐dependent relationship between number of hospitalizations, smaller brain volumes, and lower white matter integrity ( p ‐trends ≤.048). In hospitalized participants, critical illness was associated with smaller Alzheimer's disease (AD) signature region (–1.64 cm 3 , 95% CI=–3.16 to –0.12); major infection was associated with smaller AD signature region (–1.28 cm 3 , 95% CI=–2.21 to –0.35) and larger ventricular volume (3.79 cm 3 , 95% CI= 0.81–6.77). Conclusions Whereas all‐cause hospitalization was primarily associated with lower white matter integrity, critical illness and major infection were associated with smaller brain volume, particularly within regions implicated in AD.

Abstract Introduction The interplay between midlife vascular risk factors and midlife cognitive function with later life mild cognitive impairment (MCI) and dementia (DEM) is not well understood. Methods In the Atherosclerosis Risk in Communities Study, cardiovascular risk factors and cognition were assessed in midlife, ages 45–64 years. In 2011–2013, 20–25 years later, all consenting Atherosclerosis Risk in Communities participants underwent a cognitive and neurological evaluation and were given adjudicated diagnoses of cognitively normal, MCI, or DEM. Results In 5995 participants with complete covariate data, midlife diabetes, hypertension, obesity, and hypercholesterolemia were associated with late‐life MCI and DEM. Low midlife cognition function was also associated with greater likelihood of late‐life MCI or DEM. Both midlife vascular risk factors and midlife cognitive function remained associated with later life MCI or DEM when both were in the model. Discussion Later life MCI and DEM were independently associated with midlife vascular risk factors and midlife cognition.

Background Differences in anticoagulation rates and direct oral anticoagulant use by provider specialty may identify an area of practice improvement to reduce future stroke events in patients with atrial fibrillation ( AF ). Methods and Results We examined anticoagulant prescription fills in 388 045 (mean age, 68±15 years; 59% male) patients with incident AF from the MarketScan databases between 2009 and 2014. Provider specialty and filled anticoagulant prescriptions around the time of AF diagnosis (3 months before through 6 months after) were obtained from outpatient services and pharmacy claims. We estimated the association of provider specialty (cardiology versus primary care) with filling oral anticoagulant prescriptions, adjusting for patient characteristics. The risk of stroke and bleeding events also was explored. A total of 235 739 patients (61%) had a cardiology provider claim, whereas 152 306 (39%) were exclusively managed by primary care. Patients seen by cardiology providers were more likely to fill anticoagulant prescriptions than those seen by primary care (39% versus 27%; relative risk, 1.39; 95% confidence interval [ CI ], 1.37–1.40). Differences were observed for direct oral anticoagulants (relative risk, 1.74; 95% CI , 1.71–1.78) and warfarin (relative risk, 1.24; 95% CI , 1.22–1.26). A reduced risk of stroke events was observed among those seen by cardiology providers (hazard ratio, 0.90; 95% CI , 0.86–0.94) compared with primary care, without an increased bleeding risk (hazard ratio, 1.03; 95% CI , 0.98–1.07). Conclusions Patients seen by an outpatient cardiology provider shortly after AF diagnosis were more likely to initiate oral anticoagulation and were at lower risk of future stroke events without a higher rate of bleeding. Early referral to cardiology specialists may increase initiation of anticoagulant therapies and improve outcomes in AF .

AbstractIntroductionThe aim was to examine associations between midlife cardiovascular health (CVH) and 20‐year cognitive decline among blacks and whites.MethodsMidlife CVH metrics (American Heart Association's Life's Simple 7) were calculated and examined in relation to midlife and 20‐year change in cognitive function among 13,270 whites and blacks from the Atherosclerosis Risk in Communities Cohort Study. We used linear mixed models to estimate adjusted associations of midlife CVH with midlife cognitive status and change.ResultsHigher midlife (Life's Simple 7) scores and individual metrics, particularly blood pressure and glucose, were associated with better midlife cognition and reduced 20‐year decline. Midlife CVH 20‐year neuroprotection was more pronounced among whites than blacks.DiscussionBetter midlife CVH was associated with higher midlife and reduced decline in cognitive function 20 years later. However, the benefits of midlife CVH on cognition were stronger for whites than for blacks. Our findings suggest that improved midlife CVH may promote enduring cognitive health.