Lori L. Boland

Cardiovascular risk factors and cognitive decline in middle-aged adults

Objective: To perform serial neuropsychological assessments to detect vascular risk factors for cognitive decline in the Atherosclerosis Risk in Communities cohort, a large biracial, multisite, longitudinal investigation of initially middle-aged individuals. Methods: The authors administered cognitive assessments to 10,963 individuals (8,729 white individuals and 2,234 black individuals) on two occasions separated by 6 years. Subjects ranged in age at the first assessment from 47 to 70 years. The cognitive assessments included the delayed word recall (DWR) test, a 10-word delayed free recall task in which the learning phase included sentence generation with the study words, the digit symbol subtest (DSS) of the Wechsler Adult Intelligence Scale–Revised and the first-letter word fluency (WF) test using letters F, A, and S. Results: In multivariate analyses (controlling for demographic factors), the presence of diabetes at baseline was associated with greater decline in scores on both the DSS and WF (p < 0.05), and the presence of hypertension at baseline was associated with greater decline on the DSS alone (p < 0.05). The association of diabetes with cognitive decline persisted when analysis was restricted to the 47- to 57-year-old subgroup. Smoking status, carotid intima–media wall thickness, and hyperlipidemia at baseline were not associated with change in cognitive test scores. Conclusions: Hypertension and diabetes mellitus were positively associated with cognitive decline over 6 years in this late middle-aged population. Interventions aimed at hypertension or diabetes that begin before age 60 might lessen the burden of cognitive impairment in later life.

Plasma Lipid Profile and Incident Ischemic Stroke The Atherosclerosis Risk in Communities (ARIC) Study

Background and Purpose— The role of circulating lipids and lipoproteins in the pathogenesis of ischemic stroke remains uncertain despite 3 decades of research. We examined this issue in a large population-based cohort. Methods— Between 1987 and 1989, 14 175 middle-aged men and women, free of clinical cardiovascular disease, took part in the first examination of the Atherosclerosis Risk in Communities (ARIC) study cohort. Baseline measurements included plasma levels of LDL cholesterol, HDL cholesterol, apolipoprotein B, apolipoprotein A-1, and triglycerides and myriad risk factors for cardiovascular disease. The cohort was followed for cardiovascular disease end points. Results— Over an average follow-up of 10 years (142 704 person-years at risk), we documented clinical ischemic stroke in 305 participants (161 men and 144 women). After multivariable adjustment for stroke risk factors, categorical and spline regression analyses of the entire sample, as well as the sample of men alone, revealed weak and inconsistent associations between ischemic stroke and each of the 5 lipid factors. Among women, the most consistent findings were decreasing risk of ischemic stroke within the top half of the distribution of HDL cholesterol and increasing risk within the lower range of the triglyceride distribution. Conclusions— The relation of circulating cholesterol to ischemic stroke does not resemble its well-known relation to coronary heart disease. Either the pathogenesis of a substantial proportion of ischemic strokes does not involve classic atherosclerotic mechanisms, or the effect of plasma lipids on atherogenesis is substantially different in the intracranial vascular bed.

Retinal Microvascular Abnormalities and Cognitive Impairment in Middle-Aged Persons The Atherosclerosis Risk in Communities Study

Background and Purpose— Cerebral microvascular disease has been hypothesized to contribute to cognitive impairment, but few clinical data are available. Here, we examine the relation of retinal microvascular abnormalities with cognitive function in middle-aged persons free of stroke. Methods— The Atherosclerosis Risk in Communities Study is a population-based study with examinations every 3 years from 1987 through 1998. At visit 3, when participants were 51 to 70 years of age, retinal photographs were obtained and evaluated for retinal microvascular abnormalities according to standardized protocols. Cognitive function was assessed with standardized tests (Delayed Word Recall Test, Digit Symbol Subtest, and Word Fluency Test) at visits 2 and 4 and averaged for analysis. Persons with stroke or taking central nervous system–relevant medications were excluded, leaving 8734 with data for this study. Results— After education, diabetes mellitus, blood pressure, carotid intima-media thickness, and other risk factors were controlled for, retinopathy was associated with lower cognitive test scores. The adjusted odds ratios for persons with Delayed Word Recall scores 2 SD or lower than the mean were 2.60 [95% confidence interval (CI), 1.30 to 2.91] for any retinopathy, 3.00 (95% CI, 1.81 to 4.98) for microaneurysms, 3.39 (95% CI, 1.99 to 5.78) for retinal hemorrhage, and 3.07 (95% CI, 1.53 to 6.17) for soft exudates. Results were similar for the other 2 cognitive tests and in people with and without diabetes and hypertension. Conclusions— Retinopathy is independently associated with poorer cognitive function in middle-aged persons without stroke, suggesting that cerebral microvascular disease may contribute to the development of cognitive impairment.

Therapeutic Hypothermia After Out-of-Hospital Cardiac Arrest Evaluation of a Regional System to Increase Access to Cooling

Background— Therapeutic hypothermia (TH) improves survival and confers neuroprotection in out-of-hospital cardiac arrest (OHCA), but TH is underutilized, and regional systems of care for OHCA that include TH are needed. Methods and Results— The Cool It protocol has established TH as the standard of care for OHCA across a regional network of hospitals transferring patients to a central TH-capable hospital. Between February 2006 and August 2009, 140 OHCA patients who remained unresponsive after return of spontaneous circulation were cooled and rewarmed with the use of an automated, noninvasive cooling device. Three quarters of the patients (n=107) were transferred to the TH-capable hospital from referring network hospitals. Positive neurological outcome was defined as Cerebral Performance Category 1 or 2 at discharge. Patients with non–ventricular fibrillation arrest or cardiogenic shock were included, and patients with concurrent ST-segment elevation myocardial infarction (n=68) received cardiac intervention and cooling simultaneously. Overall survival to hospital discharge was 56%, and 92% of survivors were discharged with a positive neurological outcome. Survival was similar in transferred and nontransferred patients. Non–ventricular fibrillation arrest and presence of cardiogenic shock were associated strongly with mortality, but survivors with these event characteristics had high rates of positive neurological recovery (100% and 89%, respectively). A 20% increase in the risk of death (95% confidence interval, 4% to 39%) was observed for every hour of delay to initiation of cooling. Conclusions— A comprehensive TH protocol can be integrated into a regional ST-segment elevation myocardial infarction network and achieves broad dispersion of this essential therapy for OHCA.Background— Therapeutic hypothermia (TH) improves survival and confers neuroprotection in out-of-hospital cardiac arrest (OHCA), but TH is underutilized, and regional systems of care for OHCA that include TH are needed. Methods and Results— The Cool It protocol has established TH as the standard of care for OHCA across a regional network of hospitals transferring patients to a central TH-capable hospital. Between February 2006 and August 2009, 140 OHCA patients who remained unresponsive after return of spontaneous circulation were cooled and rewarmed with the use of an automated, noninvasive cooling device. Three quarters of the patients (n=107) were transferred to the TH-capable hospital from referring network hospitals. Positive neurological outcome was defined as Cerebral Performance Category 1 or 2 at discharge. Patients with non–ventricular fibrillation arrest or cardiogenic shock were included, and patients with concurrent ST-segment elevation myocardial infarction (n=68) received cardiac intervention and cooling simultaneously. Overall survival to hospital discharge was 56%, and 92% of survivors were discharged with a positive neurological outcome. Survival was similar in transferred and nontransferred patients. Non–ventricular fibrillation arrest and presence of cardiogenic shock were associated strongly with mortality, but survivors with these event characteristics had high rates of positive neurological recovery (100% and 89%, respectively). A 20% increase in the risk of death (95% confidence interval, 4% to 39%) was observed for every hour of delay to initiation of cooling. Conclusions— A comprehensive TH protocol can be integrated into a regional ST-segment elevation myocardial infarction network and achieves broad dispersion of this essential therapy for OHCA. # Clinical Perspective {#article-title-40}

Prospective study of subclinical atherosclerosis as a risk factor for venous thromboembolism

Summary.  Background: Whether atherosclerotic disease predisposes to venous thrombosis is uncertain. Objective: To determine whether subclinical atherosclerosis, manifested as increased carotid intima‐media thickness (IMT) or presence of carotid plaque, is associated with increased incidence of venous thromboembolism (VTE). Patients and methods: The Atherosclerosis Risk in Communities study is a prospective cohort of adults aged 45–64 years, examined at baseline (1987–89) and followed for cardiovascular events. Bilateral carotid ultrasound for IMT measurements was done at baseline for portions of the common and internal carotid arteries, and carotid bifurcation and also to detect the presence of carotid plaque. Exclusion criteria included baseline anticoagulant use, history of coronary heart disease, stroke, or VTE, and incomplete data. First VTE during follow‐up was validated using abstracted medical records. Results: Among 13 081 individuals followed for a mean of 12.5 years, 225 first VTE events were identified. Unadjusted hazard ratios (HR) (95% CI) of VTE across quartiles of baseline IMT were 1.0, 1.16 (0.77–1.75), 1.64 (1.12–2.40), and 1.52 (1.03–2.25). However, this association disappeared after adjustment for age, sex, and ethnicity (HRs: 1.0, 1.06, 1.40, and 1.18). Further adjustment for body mass index and diabetes weakened the relative risks even further. Presence of carotid plaque at baseline also was not associated with VTE occurrence; adjusted HR = 0.97, 95% CI = 0.72–1.29. Conclusion: Increased carotid IMT or presence of carotid plaque was not associated with an increased incidence of VTE in this middle‐aged cohort, suggesting subclinical atherosclerosis itself is not a VTE risk factor.

Hypertension and arterial stiffness: the atherosclerosis risk in communities study☆

Our objective was to describe the relationship of arterial stiffness and hypertension in a large, population-based sample of men and women. Hypertension-related increases in arterial stiffness may reflect the distending pressure and/or structural alterations in the artery. Included were 10,712 participants, ages 45 to 64 years, of the Atherosclerosis Risk in Communities Study, free of prevalent cardiovascular disease. Hypertension was classified as systolic or diastolic blood pressure (BP) > or =140/90 mm Hg, respectively, or the current use of antihypertensive medications. Common carotid arterial diameter change was measured using B-mode ultrasound and an electronic device that utilized radio frequency signals to track the motion of the arterial walls. Using statistical models to control for diastolic BP and pulse pressure, arterial diameter change was calculated separately in normotensive/ nonmedicated and medicated hypertensives. Hypertension was associated with a smaller adjusted diameter change (ie, greater stiffness) in comparison to optimal blood pressure (BP < 120/80 mm Hg): normotensive/nonmedicated men, 0.33 versus 0.43 mm (P < 0.001); medicated men, 0.34 versus 0.42 mm (P < 0.001); normotensive/ nonmedicated women, 0.34 versus 0.40 mm (P < 0.001), and medicated women, 0.33 versus 0.40 mm (P < 0.001). The relationship between pulse pressure and diameter change (ie, the slope of pulse pressure and diameter change) did not differ between hypertensives and normotensives. These cross-sectional data suggest that hypertension is associated with carotid arterial stiffness; however, these differences in the calculated stiffness appear to be the effect of distending pressure rather than structural changes in the carotid artery.

Occurrence of unrecognized myocardial infarction in subjects aged 45 to 65 years (the ARIC study).

Previous observational studies conducted predominantly in white men before 1988 estimated that 20% to 40% of myocardial infarctions (MIs) are unrecognized. Recent data on the proportion of MIs that are unrecognized, especially in women and African-Americans, are largely unavailable. Participants in the Atherosclerosis Risk in Communities (ARIC) study were men and women, aged 45 to 65 years, who were free of clinically recognized coronary heart disease and electrocardiographic evidence of MI at baseline (n = 12,843). Three follow-up clinic examinations were conducted approximately 3, 6, and 9 years after baseline, and included a 12-lead electrocardiogram at rest. Electrocardiographic evidence of infarction was defined as the appearance between the baseline and subsequent examinations of a major Q wave or a minor Q wave with ischemic ST-T changes. Clinically recognized (hospitalized) MI events were also identified and validated. Incident unrecognized MI was defined as electrocardiographic evidence of MI before, or in the absence of, a clinically recognized MI during the follow-up period. Of 508 MIs, 20% were unrecognized (95% confidence interval 16% to 23%), with African-Americans having a slightly higher percentage (23%) than whites (19%). The percentage of unrecognized MIs in men and women was similar. The percentage of unrecognized MIs in the ARIC sample between 1987 and 1998 was slightly lower than previous estimates from other populations.

Measures of cognitive function in persons with varying degrees of sleep-disordered breathing: the Sleep Heart Health Study

Epidemiologic literature suggests that persons with clinically diagnosed sleep apnoea frequently have impaired cognitive function, but whether milder degrees of sleep‐disordered breathing (SDB) are associated with cognitive dysfunction in the general population is largely unknown. Approximately 1700 subjects free of clinically diagnosed SDB underwent at‐home polysomnography (PSG) as part of the Sleep Heart Health Study (SHHS) and completed three cognitive function tests within 1–2 years of their PSG: the Delayed Word Recall Test (DWR), the WAIS‐R Digit Symbol Subtest (DSS), and the Word Fluency test (WF). A respiratory disturbance index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour of sleep. After adjustment for age, education, occupation, field centre, diabetes, hypertension, body‐mass index, use of CNS medications, and alcohol drinking status, there was no consistent association between the RDI and any of the three cognitive function measures. There was no evidence of a dose–response relation between the RDI and cognitive function scores and the adjusted mean scores by quartiles of RDI never differed from one another by more than 5% for any of the tests. In this sample of free‐living individuals with mostly mild to moderate levels of SDB, the degree of SDB appeared to be unrelated to three measures of cognitive performance.

Multidisciplinary Standardized Care for Acute Aortic Dissection Design and Initial Outcomes of a Regional Care Model

> “No physician can diagnose a condition he never thinks about.” > > — Michael DeBakey Patients with acute aortic dissection (AAD) have an in-hospital mortality of 26%, and for those patients with type A AAD, the mortality risk is 1% to 2% per hour until emergency surgical repair is performed.1,2 It is therefore critical that AAD be recognized promptly and that surgical care be provided expeditiously. Data from the International Registry of Acute Aortic Dissection (IRAD) indicate that the median time from emergency department (ED) presentation to definitive diagnosis of AAD is 4.3 hours, with an additional 4 hours between diagnosis and surgical intervention for type A patients.2,3 A portion of the delay to surgery is often the result of the patients presenting to smaller community hospitals underequipped to manage emergent AAD. Transfer to high-volume aortic care centers with highly specialized facilities and expertise is routine, but even at such centers, current surgical mortality is 25%.4 In an effort to address factors that delay AAD recognition and optimal management, a standardized, quality-improvement protocol for the regional treatment of AAD was developed and implemented with the goal of providing consistent, integrated, and coordinated care for patients with AAD throughout all phases of care. Modeled, in part, after a successful regional program for ST-segment elevation myocardial infarction,5, the specific aims of the program were to decrease the time from hospital arrival to diagnosis and treatment and to improve clinical outcomes for patients with AAD. A collaborative team designed program elements directed at (1) increasing awareness and knowledge of AAD among emergency care providers, (2) standardizing optimal care for AAD through the use of a formal protocol, (3) improving care coordination and communication across disciplines, and (4) providing …

Is early age-related maculopathy related to cognitive function? The atherosclerosis risk in communities study

PURPOSE Age-related maculopathy (ARM) and cognitive impairment are both neurodegenerative disorders associated with aging and have been hypothesized to share common pathogenic pathways. We describe the association between cognitive function and ARM in middle-aged persons. DESIGN Population-based, cross-sectional study involving participants of the Atherosclerosis Risk in Communities Study, an ongoing cardiovascular investigation of persons 51 to 70 years of age, examined every 3 years between 1987 to 1998. METHODS At visit three (1993-1995), retinal photographs were obtained and evaluated for ARM using a modification of the Wisconsin ARM Grading System. Cognitive function was assessed using standardized tests (Delayed Word Recall, Digit Symbol, and Word Fluency) at visits two (1990-1992) and four (1996-1998) and averaged for analysis. Severe cognitive impairment was defined as scores falling in the lowest 10th percentile of the population. RESULTS Data were available in 9286 persons after exclusion of persons with stroke or using antipsychotic medication. After adjusting for age, gender, race, education, diabetes, hypertension, cigarette smoking, and alcohol consumption, persons with severe cognitive impairment based on Word Fluency Test scores were more likely to have early ARM (odds ratio [OR]: 1.6, 95% confidence interval [CI]: 1.1-2.2) and its components, soft drusen (OR: 1.6; 95% CI: 1.1-2.3) and pigmentary abnormality (OR: 1.5; 95% CI: 0.9-2.5) than those without severe impairment. However, severe cognitive impairment in scores of the other two cognitive function tests was not associated with ARM. CONCLUSION These population-based data suggest a weak association between cognitive function and early ARM in middle-aged persons.