Stroke disparities and selection bias in an American Indian cohort: the Strong Heart and Strong Heart Stroke Studies

University of Minnesota Ph.D. dissertation. December 2015. Major: Epidemiology. Advisor: Richard MacLehose. 1 computer file (PDF); xi, 91 pages.Abstract Background. American Indians experience higher stroke morbidity and mortality compared to US general population, but are underrepresented in public health research. Data on incident stroke in American Indians derive mainly from the Strong Heart Study (SHS), a population-based cohort study of cardiovascular disease in 4549 American Indians who were 45-74 years old when baseline exams were conducted from 1988-1990. The SHS had higher stroke rates than reported for Whites and African Americans in external comparisons to other cohorts. These findings suggested similar disparities in covert vascular brain injury (VBI), an often asymptomatic form of cerebrovascular disease that precedes clinical events. Accordingly, from 2010-2013 the Strong Heart Stroke Study (SHSS) used structural cranial magnetic resonance imaging to assess covert VBI in 1033 surviving members of the SHS. Goals. In this dissertation we addressed three limitations to using SHS and SHSS data for analysis of stroke and covert VBI in American Indians: Manuscript 1) lack of research that directly compares stroke incidence and mortality in American Indians vs. other racial groups, and which limits current knowledge to external comparisons that do not account for differences in stroke risk factors; Manuscript 2) potential selection bias in SHSS data when survival and participation of cohort members depends on both the exposures and outcomes of interest; and Manuscript 3) an inherent limitation in effect measures estimates that condition on categories defined by progressively older age or longer time since exposure, and which leads to observed point estimates that are potentially biased estimates of the true effects. Manuscript 1. Methods: We pooled data from the SHS and the Atherosclerosis Risk in Communities Study (ARIC) to compare stroke risk and post-stroke mortality in American Indians vs. Blacks and Whites. We used Cox regression to estimate hazard ratios (HR) with attained age as the time scale to account for differences in baseline age at enrollment, and adjusted estimates for baseline factors that included prevalent hypertension and diabetes. Due to effect modification, analyses were stratified by birth year tertile (1914-1930, 1931-1937, and 1938-1947). We used logistic regression to compare 30-day and 1-year post-stroke mortality among participants from both studies who experienced stroke during follow-up. Results: Stroke risk among American Indians in the SHS was lower than among Blacks for all birth year tertiles (1914-1930: HR = 0.9 (95% CI = 0.7, 1.1); 1931-1937: HR = 0.9 (95% CI = 0.7, 1.2); 1938-1947: HR = 0.9 (95% CI = 0.7, 1.2)), but higher than among Whites (1914-1930: HR = 1.6 (95% CI = 1.3, 2.0); 1931-1937: HR = 2.2 (95% CI = 1.7, 2.8); 1938-1947: HR = 2.7 (95% CI = 2.0, 3.6)) in ARIC. Adjusting for risk factors including prevalent diabetes at baseline resulted in strengthening of associations compared to Blacks (oldest to youngest tertile HR = 0.8 (95% CI = 0.6-1.0); 0.7 (95% CI = 0.5-1.0); and 0.6 (95% CI = 0.4-0.8)), and attenuation of associations compared to Whites (oldest to youngest tertile HR = 1.1 (95% CI = 0.9-1.5); 1.2 (95% CI = 0.9-1.6); and 1.1 (95% CI = 0.8-1.5)). American Indians had higher risk of 30-day and 1-year mortality compared to Blacks (relative risk = 2.2 (95% CI = 1.4-3.0) and 1.4 (95% CI = 1.1-1.8), respectively) and Whites (relative risk = 1.8 (95% CI = 1.2-2.3) and 1.5 (95% CI = 1.1-1.8), respectively). These comparisons persisted after adjusting for risk factors. Manuscript 2. Methods: We used marginal structural models with inverse probability weighting to adjust for selection bias in the SHSS, applied to the analysis of prevalent hypertension and covert VBI as measured by white matter hyperintensities. Predicted probabilities of survival from 1988-2010 and participation of survivors were estimated and inverted to create weights, and stabilized using conventional methods to reflect the distribution of hypertension in cohort participants. In addition, we computed novel stabilized weights that account for each person’s probability of meeting the inclusion criterion of remaining stroke-free up to their SHSS exam. These weights allowed us to avoid over-correcting for attrition of individuals who would have subsequently gone on to experience clinical stroke. We applied these weights to estimate the prevalence difference (PD) for the association of hypertension with a binary indicator of abnormal VBI, as well as the mean difference (MD) for a continuous variable reflecting the ratio of white matter/total intracranial volume; the ratio estimates were multiplied by 1000 to simplify presentation of results. Hypertension was evaluated as both a cross-sectional risk factor and accounting for longitudinal trends in prevalence since baseline. Results: In the cross-sectional analysis, hypertension was associated with higher prevalence of abnormal VBI in unweighted models (PD = 7.9% (95% CI = -2, 17)). The point estimate increased 13% after selection weighting (PD = 8.9% (95% CI = 0, 18)). Prevalent hypertension was likewise associated with a higher proportion of white matter volume compared to the total intracranial volume in unweighted models (MD = 0.8 (95% CI = -0.4, 2.0)) and after selection weighting (MD = 0.9 (95% CI = -0.3, 2.1)). Adjusting weights to account for the stroke-free inclusion criterion did not change results compared to the conventional stabilized estimates. In the analysis treating hypertension as a longitudinal exposure, prevalent hypertension at all three study exams was associated with higher prevalence of abnormal VBI (PD = 8.0% (95% CI = -6, 22)) and higher ratio of white matter/total intracranial volume (MD = 1.7 (95% CI = 0.0, 3.4)) compared to not having hypertension at any exam. Selection weighting had no appreciable impact on point estimates in the longitudinal analysis. Manuscript 3. Methods: We used Mathematica software with constrained optimization to identify bounds for the risk difference (RD) when conditioning on event-free survival to some minimum age or time since exposure. Bounds were identified assuming only causative exposure effects in the target population, and allowing for exposure to prevent disease in some individuals so long as the causative effects were proportionally greater in the overall population. We applied these bounds to the analysis of post-stroke survival from Manuscript 1, with follow-up time divided into 0-30 days, 31-180 days, and 181-365 days after the stroke event. Results: The RD attenuated across follow-up periods for American Indians vs. Blacks (0-30 days: RD = 14% (95% CI = 6, 23); 31-180 days: RD = -1% (95% CI = -7, 4); 181-365 days: RD = -3% (95% CI = -7, 2)) and Whites (0-30 days: RD = 12% (95% CI = 3, 21); 31-180 days: RD = 1% (95% CI = -5, 6); 181-365 days: RD = -2% (95% CI = -6, 3)). With assumptions of only causative exposure effects, bounds on the the conditional risk difference for American Indians vs. Blacks were 0-16% for 0-30 days post-stroke event, and 1-13% for 181-365 days post-stroke. For American Indians vs. Whites the bounds were 0-14% for 0-30 days post stroke, and 0-13% for 31-180 days post-stroke. Allowing for preventive effects that were equal to or less than causative effects yielded bounds that were too wide for meaningful interpretation (all lower bounds = 0; all upper bounds ≥ 30). Conclusions. We found that American Indians in the SHS had lower stroke risk than Blacks, but not than Whites, in ARIC after adjusting for risk factors that included prevalent diabetes. These findings suggest that diabetes may be a factor behind stroke disparities in some American Indian communities. American Indians had higher post-stroke mortality than Blacks and Whites especially in the first 30 days after stroke onset, but cumulative risk comparisons and analyses using bounds for conditional effects were consistent with elevated risk persisting for at least 1 year. Among long-term survivors of the SHS who participated in the SHSS assessment of covert VBI, selection bias may be of concern for some analyses. Although adjusting selection weights for the stroke-free inclusion criterion did not change results in this example, other studies with inclusion criteria that result in excluding larger proportions of the study population may wish to include sensitivity analyses with similar adjustments

Heart Rate Variability and Incident Stroke

BACKGROUND AND PURPOSE: Low heart rate variability (HRV), a marker of cardiac autonomic dysfunction, has been associated with increased all-cause and cardiovascular mortality. We examined the association between reduced HRV and incident stroke in a community-based cohort. METHODS: The Atherosclerosis Risk in Communities (ARIC) study measured HRV using 2-minute ECG readings in 12 550 middle-aged adults at baseline (1987-1989). HRV indices were calculated using the SD of RR intervals (SDNN), the mean of all normal RR intervals (meanNN), the root mean square of successive differences of successive RR intervals (RMSSD), low (LF) and high (HF) frequency power, and the LF/HF ratio. All HRV measures were categorized into quintiles. Incident stroke was adjudicated through 2011. Cox regression was used to estimate hazard ratios (HRs) with the lowest HRV quintile as the reference, with and without stratification by prevalent diabetes mellitus. RESULTS: Over a median follow-up of 22 years, 816 (6.5%) participants experienced incident stroke. After covariate adjustment, there was no strong evidence of association between HRV and stroke risk. In stratified analyses, the lowest HRV quintile was associated with higher stroke risk compared with the highest quintile for SDNN (HR, 2.0, 95% confidence interval, 1.1-4.0), RMSSD (HR, 1.7; 95% confidence interval, 0.9-3.2), LF (HR, 1.5; 95% confidence interval, 0.8-3.0), and HF (HR, 1.7; 95% confidence interval, 0.9-3.0) only among people with diabetes mellitus. CONCLUSIONS: Lower HRV was associated with higher risk of incident stroke among middle-aged adults with prevalent diabetes mellitus but not among people without diabetes mellitus

Cost effectiveness of a cultural physical activity intervention to reduce blood pressure among Native Hawaiians with hypertension

Objective: The aim of this study was to calculate the costs and assess whether a culturally grounded physical activity intervention offered through community-based organizations is cost effective in reducing blood pressure among Native Hawaiian adults with hypertension. Methods: Six community-based organizations in Hawai'i completed a randomized controlled trial between 2015 and 2019. Overall, 263 Native Hawaiian adults with uncontrolled hypertension (≥ 140 mmHg systolic, ≥ 90 mmHg diastolic) were randomized to either a 12-month intervention group of hula (traditional Hawaiian dance) lessons and self-regulation classes, or to an education-only waitlist control group. The primary outcome was change in systolic blood pressure collected at baseline and 3, 6, and 12 months for the intervention compared with the control group. Incremental cost-effectiveness ratios (ICERs) were calculated for primary and secondary outcomes. Non-parametric bootstrapping and sensitivity analyses evaluated uncertainty in parameters and outcomes. Results: The mean intervention cost was US$361/person, and the 6-month ICER was US$103/mmHg reduction in systolic blood pressure and US$95/mmHg in diastolic blood pressure. At 12 months, the intervention group maintained reductions in blood pressure, which exceeded reductions for usual care based on blood pressure outcomes. The change in blood pressure at 12 months resulted in ICERs of US$100/mmHg reduction in systolic blood pressure and US$93/mmHg in diastolic blood pressure. Sensitivity analyses suggested that at the estimated intervention cost, the probability that the program would lower systolic blood pressure by 5 mmHg was 67 and 2.5% at 6 and 12 months, respectively. Conclusion: The 6-month Ola Hou program may be cost effective for low-resource community-based organizations. Maintenance of blood pressure reductions at 6 and 12 months in the intervention group contributed to potential cost effectiveness. Future studies should further evaluate the cost effectiveness of indigenous physical activity programs in similar settings and by modeling lifetime costs and quality-adjusted life-years. Trial registration number: NCT02620709.Sociolog

The Impact of Patient and Provider Factors on Depression Screening of American Indian and Alaska Native People in Primary Care

Introduction : The US Preventive Services Task Force recommends routine depression screening in primary care, yet regular screening does not occur in most health systems serving Alaska Native and American Indian people. The authors examined factors associated with administration of depression screening among Alaska Native and American Indian people in a large urban clinic. Methods : Medical records of 18 625 Alaska Native and American Indian adults were examined 1 year after implementation of a depression screening initiative. Multilevel logistic regression models examined associations between patient and provider factors and administration of the Patient Health Questionnaire–9. Results : Forty-seven percent of patients were screened. Women were more likely than men to be screened (50% vs 43%, P < .001). Increased screening odds were associated with older age, increased service use, and chronic disease ( P < .001) but not with substance abuse disorders or prior antidepressant dispensation. Women previously diagnosed with depression had higher odds of screening ( P = .002). Men seen by male providers had higher odds of screening than did men seen by female providers ( P = .040). Screening rates peaked among providers with 2 to 5 years of employment with the clinic. Limitations : Cross-sectional analysis of medical record data was of unknown reliability; there were limited sociodemographic data. Conclusions : Even with significant organizational support for annual depression screening, primary care providers systematically missed men and patients with infrequent primary care visits. Outreach to male patients and additional supports for primary care providers, especially in the first years of practice, may improve screening and treatment for depression among Alaska Native and American Indian people

Communication about Alzheimer's disease and research among American Indians and Alaska Natives

Abstract Introduction American Indian and Alaska Native (AI/AN) people infrequently participate in Alzheimer's disease (AD) research, despite the rapidly increasing population of AI/AN people aged 65 and older. Methods We surveyed 320 adults who identified as AI/AN at two Native‐focused events and used ordinary least squares regression and logistic regression models to test associations between demographic factors and perceived risk of AD, knowledge about AD, and willingness to participate in research, along with preferred source of AD information. Results Willingness to participate in research was highest among those living in a city versus reservation and associated with perceived personal risk for AD. Health professionals and the internet were preferred sources of information about AD. Discussion These hypothesis‐generating results provide insight into perceptions of AD and willingness to participate in research. Conclusions could inform development of AD recruitment strategies for AI/ANs and influence participation in AD research

Social Media Use among American Indian and Alaska Native People: Implications for Health Communication Strategies

Patients, health professionals, and communities use social media to communicate information about health determinants and associated risk factors. Studies have highlighted the potential for social media to reach underserved populations, suggesting these platforms can be used to disseminate health information tailored for diverse and hard-to-reach populations. Little is known, however, about the use of social media among American Indian and Alaska Native populations. The objective of this cross-sectional study is to better understand the use of social media platforms to disseminate health information in this population. We surveyed 429 American Indian and Alaska Native adults attending cultural events in Washington State on their use of various types of social media. We used logistic regressions to assess participant use of Twitter, Snapchat, Facebook, and Instagram as related to participant demographics, including age, gender, education, and residence (either reservation, rural area but not a reservation, or large metropolitan area). Facebook was used by more participants (79%) than other platforms, followed by Instagram (31%); Nearly half of participants used only one social media platform (48%). Age was negatively associated with using Instagram (0.8 OR, 95% CI: 0.7, 0.9) and Snapchat (0.6 OR, 95% CI: 0.5, 0.7). College education was associated with a higher odds of using an additional social media platform compared to those without any college education (2.0 OR, 95% CI: 1.1, 3.6). Most participants used social media platforms, suggesting that they may be a useful tool in disseminating health and health risk information to American Indian and Alaska Native people. Further research should document how social media can be used to effectively disseminate risk and health information across the life course and assess whether it can influence health knowledge and behaviors among this populations

Patterns of Healthcare Use and Mortality After Alzheimer's Disease or Related Dementia Diagnosis Among Alaska Native Patients: Results of a Cluster Analysis in a Tribal Healthcare Setting

Background: Alaska Native and American Indian (AN/AI) people represent a rapidly aging population with disproportionate burdens of Alzheimer's disease and related dementias (ADRD) risk factors. Objective: To characterize healthcare service use patterns and mortality in the years following ADRD diagnosis for patients in an Alaska Native Tribal health system. Methods: The study sample included all AN/AI patients aged 55 or older with an ADRD diagnosis who were seen between 2012-2018 (n = 407). We used cluster analysis to identify distinct patterns of healthcare use for primary care, emergency and urgent care, inpatient hospital stays, and selected specialty care. We compared demographic and clinical factors between clusters and used regression to compare mortality. Results: We identified five clusters of healthcare service use patterns after ADRD diagnosis: 1) people who use a low amount of all services (n = 107), 2) people who use a high amount of all services (n = 60), 3) people who use a high amount of primary and specialty care (n = 105), 4) people who use a high amount of specialty care (n = 65), and 5) people who use a high amount of emergency and urgent care (n = 70). The cluster with the highest use had the greatest proportion of comorbidities and had a 2.3-fold increased risk of mortality compared to the cluster with the lowest healthcare service use. Conclusion: Results indicate that those receiving the most services had the greatest healthcare-related needs and increased mortality. Future research could isolate factors that predict service use following ADRD diagnosis and identify other differential health risks

Psychological Trauma Symptoms and Type 2 Diabetes Prevalence, Glucose Control, and Treatment Modality Among American Indians in the Strong Heart Family Study

Aims The aims of this paper are to examine the relationship between psychological trauma symptoms and Type 2 diabetes prevalence, glucose control, and treatment modality among 3776 American Indians in Phase V of the Strong Heart Family Study. Methods This cross-sectional analysis measured psychological trauma symptoms using the National Anxiety Disorder Screening Day instrument, diabetes by American Diabetes Association criteria, and treatment modality by four categories: no medication, oral medication only, insulin only, or both oral medication and insulin. We used binary logistic regression to evaluate the association between psychological trauma symptoms and diabetes prevalence. We used ordinary least squares regression to evaluate the association between psychological trauma symptoms and glucose control. We used binary logistic regression to model the association of psychological trauma symptoms with treatment modality. Results Neither diabetes prevalence (22%–31%; p = 0.19) nor control (8.0–8.6; p = 0.25) varied significantly by psychological trauma symptoms categories. However, diabetes treatment modality was associated with psychological trauma symptoms categories, as people with greater burden used either no medication, or both oral and insulin medications (odds ratio = 3.1, p \u3c 0.001). Conclusions The positive relationship between treatment modality and psychological trauma symptoms suggests future research investigate patient and provider treatment decision making