Kathryn M. Rose

Orthostatic Hypotension as a Risk Factor for Stroke The Atherosclerosis Risk in Communities (ARIC) Study, 1987–1996

Background and Purpose The association between orthostatic hypotension (OH) and stroke has rarely been investigated in longitudinal studies. The purpose of the present study was to determine whether OH predicts ischemic stroke in a middle-aged, biethnic population after adjustment for known stroke risk factors. Diastolic, systolic, and consensus OH were evaluated for baseline associations and for the ability to predict stroke. Methods In 11 707 persons from the Atherosclerosis Risk in Communities (ARIC) cohort who were free of stroke and overt heart disease at baseline, Cox proportional hazards analyses modeled the association between OH at baseline and incident ischemic stroke over 7.9 years of follow-up. OH was defined as a systolic blood pressure drop ≥20 mm Hg (systolic OH), a diastolic blood pressure drop ≥10 mm Hg (diastolic OH), or a drop in either (consensus OH) when a person changed from a supine to standing position. Results OH was predictive of ischemic stroke, even after adjustment for numerous stroke risk factors (consensus OH: hazard ratio, 2.0; 95% CI, 1.2 to 3.2). While the baseline characteristics associated with OH varied depending on the type of OH, all types of OH had a similar risk of stroke. Conclusions OH is an easily obtained measurement that may help to identify middle-aged persons at risk for stroke.

Headache, cerebrovascular symptoms, and stroke. The Atherosclerosis Risk in Communities Study

Objective: To evaluate the occurrence of stroke/TIA symptoms and ischemic stroke events among those with a lifetime history of migraine or other headaches with some migraine features in a biracial cohort of older adults. Methods: Participants were 12,750 African-American and white men and women from the Atherosclerosis Risk in Communities Study (1993 to 1995). The participants were queried about their lifetime headache history and characterized using modified International Headache Society diagnostic criteria. Stroke/TIA symptoms were classified using a computerized diagnostic algorithm, and ischemic stroke events were identified and validated using medical records. Multivariate logistic regression was used to assess the relationship between headache types and stroke/TIA symptoms and ischemic stroke events. Results: Migraine with aura was strongly associated with stroke symptoms (odds ratio [OR] 5.46, 95% CI: 3.64 to 8.18), TIA symptoms (OR 4.28, 95% CI: 3.02 to 6.08), and verified ischemic stroke events (OR 2.81, 95% CI: 1.60 to 4.92). Similarly, other headaches with aura were significantly associated with stroke symptoms (OR 3.68, 95% CI: 2.26 to 5.99) and TIA symptoms (OR 4.53, 95% CI: 3.08 to 6.67). In contrast, the associations for migraine without aura and other headaches without aura were not as consistent or robust. Conclusions: Migraines and other headaches, particularly those accompanied by aura, were associated with an increased occurrence of stroke/TIA symptoms and ischemic stroke events.

Orthostatic hypotension and the incidence of coronary heart disease: The Atherosclerosis Risk in Communities study

We examined the association between orthostatic hypotension (OH) at baseline examination (1987-1989) and the incidence of coronary heart disease (CHD) over an average of 6 years, among 12,433 black and white middle-aged men and women participating in the Atherosclerosis Risk in Communities (ARIC) study. OH was defined as a SBP decrease > or = 20 mm Hg or a DBP decrease > or = 10 mm Hg after changing from supine to standing. CHD events included definite or probable myocardial infarctions (MI), silent MI, and fatal CHD. Five percent of participants had OH. Prevalence increased with advancing age and was more common among those with cardiovascular disease (CVD)-related comorbidities and risk factors. Those with OH had an increased risk of CHD (hazard ratio [HR] = 3.49, 95% confidence interval [CI] = 2.58, 4.73). This association was attenuated after controlling for age, ethnicity, gender, comorbid conditions, and CVD risk factors (HR = 1.85, 95% CI = 1.31, 2.63).

Early-life and adult socioeconomic status and inflammatory risk markers in adulthood

Background: Associations between childhood and adult socioeconomic status (SES) and adult levels of inflammatory markers (C-reactive protein [CRP], fibrinogen, white blood cell count [WBC], and von Willebrand factor [vWF]) were examined in the Atherosclerosis Risk in Communities (ARIC) Study cohort. Methods: A total of 12,681 white and African-American participants provided information on SES (via education and social class) and place of residence in childhood and adulthood. Residences were linked to census data for neighborhood SES information. Multiple imputation was used to impute missing data. Hierarchical and linear regression were used to estimate the effects of SES and possible mediation by adult cardiovascular disease (CVD) risk factors. Findings: Low childhood social class and education were associated with elevated levels of CRP, fibrinogen, WBC, and vWF (increments of 17%, 2%, 4% and 3% for lowest versus highest education in childhood, respectively) among whites. Findings were less consistent among African-Americans. Adult SES was more strongly associated with inflammation than childhood SES. Individual-level SES measures were more consistently associated with inflammation than neighborhood-level measures. Fibrinogen and WBC showed the most consistent associations with SES; the largest changes in inflammation by SES were observed for CRP. Covariate adjustment strongly attenuated these associations. Mediation of the SES-inflammation associations by BMI, smoking and HDL cholesterol (HDL-C) are suggested by these data. Conclusion: Low individual- and neighborhood-level SES in childhood and adulthood are associated with modest increments in adult inflammatory burden. These associations may operate through the influence of low SES on traditional CVD risk factors, especially BMI, smoking and HDL-C.

Prevalence and sociodemographic correlates of antinuclear antibodies in the United States

OBJECTIVE To estimate the prevalence, types, and sociodemographic and biobehavioral correlates of antinuclear antibodies (ANAs) in the US. METHODS We conducted a cross-sectional analysis of 4,754 individuals from the National Health and Nutrition Examination Survey 1999-2004. ANAs were assessed by indirect immunofluorescence. In ANA-positive individuals, cellular staining patterns were determined, and specific autoantibody reactivities were assessed by immunoprecipitation. RESULTS The ANA prevalence in the US population of individuals ages 12 years and older was 13.8% (95% confidence interval [95% CI] 12.2-15.5%). ANA prevalence increased with age (P=0.01), and ANAs were more prevalent among females than males (17.8% versus 9.6%; P<0.001), with the female-to-male ratio peaking at 40-49 years of age. ANA prevalence was modestly higher in African Americans compared with whites (age-adjusted prevalence odds ratio [POR] 1.30, 95% CI 1.00-1.70). Remarkably, ANAs were less common in overweight and obese individuals (age-adjusted POR 0.74) than in persons of normal weight. No significant associations of ANA with education, family income, alcohol use, smoking history, serum levels of cotinine, or C-reactive protein were observed. In ANA-positive individuals, nuclear patterns were seen in 84.6%, cytoplasmic patterns were seen in 21.8%, and nucleolar patterns were seen in 6.1%; the most common specific autoantibodies were anti-Ro (3.9%) and anti-Su (2.4%). CONCLUSION These findings suggest that more than 32 million persons in the US have ANAs, and that the prevalence is higher among females, older individuals, African Americans, and those with a normal body weight. These data will serve as a useful baseline for future investigations of predictors and changes in ANA prevalence over time.

Migraine and other headaches Associations with Rose angina and coronary heart disease

Objective: To examine the association between a lifetime history of migraines and other headaches with and without aura and Rose angina and coronary heart disease (CHD). Methods: Participants were 12,409 African American and white men and women from the Atherosclerosis Risk in Communities Study, categorized by their lifetime history of headaches lasting ≥4 hours (migraine with aura, migraine without aura, other headaches with aura, other headaches without aura, no headaches). Gender-specific associations of headaches with Rose angina and CHD, adjusted for sociodemographic and cardiovascular disease risk factors, were evaluated using Poisson regression. Results: Participants with a history of migraines and other headaches were more likely to have a history of Rose angina than those without headaches. The associations were stronger for migraine and other headaches with aura (prevalence ratio [PR] = 3.0, 95% CI = 2.4, 3.7 and PR = 2.0, 95% CI = 1.5, 2.7 for women; PR = 2.2, 95% CI = 1.2, 3.9 and PR = 2.4, 95% CI = 1.4, 3.9 for men) than for migraine and other headaches without aura (PR = 1.5, 95% CI = 1.2, 1.9 and PR = 1.3, 95% CI = 1.1, 1.6 for women; PR = 1.9, 95% CI = 1.2, 2.9 and OR = 1.4, 95% CI = 1.0, 1.8 for men). In contrast, migraine and other headaches were not associated with CHD, regardless of the presence of aura. Conclusions: The lack of association of migraines with coronary heart disease suggests that the association of migraine with Rose angina is not related to coronary artery disease. Future research assessing other common underlying pathologic mechanisms is warranted.

Prospective Analysis of Traffic Exposure as a Risk Factor for Incident Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Background For people living close to busy roads, traffic is a major source of air pollution. Few prospective data have been published on the effects of long-term exposure to traffic on the incidence of coronary heart disease (CHD). Objectives In this article, we examined the association between long-term traffic exposure and incidence of fatal and nonfatal CHD in a population-based prospective cohort study. Methods We studied 13,309 middle-age men and women in the Atherosclerosis Risk in Communities study, without previous CHD at enrollment, from 1987 to 1989 in four U.S. communities. Geographic information system–mapped traffic density and distance to major roads served as measures of traffic exposure. We examined the association between traffic exposure and incident CHD using proportional hazards regression models, with adjustment for background air pollution and a wide range of individual cardiovascular risk factors. Results Over an average of 13 years of follow-up, 976 subjects developed CHD. Relative to those in the lowest quartile of traffic density, the adjusted hazard ratio (HR) in the highest quartile was 1.32 [95% confidence interval (CI), 1.06–1.65; p-value for trend across quartiles = 0.042]. When we treated traffic density as a continuous variable, the adjusted HR per one unit increase of log-transformed density was 1.03 (95% CI, 1.01–1.05; p = 0.006). For residents living within 300 m of major roads compared with those living farther away, the adjusted HR was 1.12 (95% CI, 0.95–1.32; p = 0.189). We found little evidence of effect modification for sex, smoking status, obesity, low-density lipoprotein cholesterol level, hypertension, age, or education. Conclusion Higher long-term exposure to traffic is associated with incidence of CHD, independent of other risk factors. These prospective data support an effect of traffic-related air pollution on the development of CHD in middle-age persons.

Possible Locus on Chromosome 18q Influencing Postural Systolic Blood Pressure Changes

We conducted a genome-wide scan for quantitative trait loci influencing the systolic blood pressure, diastolic blood pressure, and pulse responses to a postural challenge in 498 white sibling-pairs from the Hypertension Genetic Epidemiology Network, a multicenter study of the genetic susceptibility to hypertension. All participants were hypertensive (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or on antihypertensive medications) with diagnosis before age 60. Blood pressure and pulse were measured by an oscillometric method after a 5-minute rest in a supine position and again immediately on standing. The genome scan included a total of 387 autosomal short-tandem-repeat polymorphisms typed by the National Heart, Lung, and Blood Institute Mammalian Genotyping Service at Marshfield. We used multipoint variance-components linkage analysis to identify possible quantitative trait loci influencing postural change phenotypes after adjusting for sex, age, and use of antihypertensive medications. There was suggestive evidence for linkage on chromosome 18q for the postural systolic blood pressure response (maximum logarithm of the odds score=2.6 at 80 centiMorgans). We also observed a maximum logarithm of the odds score of 1.9 for the systolic blood pressure response and 1.7 for the diastolic blood pressure response on chromosome 6p. The marker that demonstrated the strongest evidence for linkage for the systolic blood pressure response (D18S858) lies within 20 centiMorgans of a marker previously linked to rare familial orthostatic hypotensive syndrome. Our findings indicate that there may be 1 or more genes on chromosome 18q that regulate systolic blood pressure during the physiological recovery period after a postural stressor.

Blood Pressure and White-Matter Disease Progression in a Biethnic Cohort Atherosclerosis Risk in Communities (ARIC) Study

Background and Purpose— Blood pressure (BP) is a predictor of concurrent and subsequently measured white-matter hyperintensity (WMH), but longitudinal studies of WMH changes and data in black participants are lacking. We hypothesized that WMH progression would be (1) strongly related to BP in blacks and whites and (2) predicted more strongly by earlier (midlife) or cumulative BP measurements than by measures at older ages. Methods— Participants were 983 individuals (49% black) from the Atherosclerosis Risk in Communities (ARIC) Study who underwent cerebral magnetic resonance imaging in 1993–1995 and 2004–2006. Associations between BP (measured at each of 5 visits, in addition to a time-averaged cumulative BP) and progression of WMHs were analyzed and compared. Results— Cumulative systolic BP (SBP) was the strongest BP predictor of WMH progression in adjusted models. Higher cumulative SBP (by 20 mm Hg) was associated with greater progression of WMHs and was similar in blacks (2.5 cm3, P<0.0001) and whites (2.6 cm3, P<0.0001). Higher cumulative SBP (per 20 mm Hg) was also associated with being in the top quintile of WMH progression (adjusted odds ratio=2.0; 95% CI, 1.6 to 2.6). Earlier SBP measurements were stronger predictors of WMH progression than were later SBP measurements, but in blacks only. Conclusions— In this population-based cohort, cumulative SBP was a stronger predictor of WMH progression than SBP from individual visits, in both blacks and whites. Earlier BPs were stronger predictors than BPs measured at later time points in blacks only.

Cumulative life course and adult socioeconomic status and markers of inflammation in adulthood

Objective: To examine the association between cumulative life course and adult socioeconomic status (SES) and adult levels of inflammatory risk markers (fibrinogen, white blood cell count (WBC), C-reactive protein (CRP), von Willebrand factor (vWF) and an overall inflammatory score). Design: Retrospective cohort study. Setting: 12 681 white and African-American participants in the Atherosclerosis Risk in Communities (ARIC) study and two ancillary studies. Methods: Participants provided information on SES and place of residence in childhood and young (30–40 years) and mature (45+) adulthood. Residences were linked to census data for neighbourhood SES information. Multiple imputation (MI) was used for missing data. Linear regression and adjusted geometric means were used to estimate the effects of SES on inflammatory risk marker levels. Results: Graded, statistically significant associations were observed between greater cumulative life-course exposure to low education and social class and elevated levels of fibrinogen and WBC among white participants. Stronger graded, statistically significant associations were observed between low adult education, social class and neighbourhood SES and elevated inflammatory levels. Associations were weaker and less consistent in African-Americans. Covariate adjustment attenuated results but many associations remained strong. Conclusions: Our results suggest that cumulative exposure to adverse SES conditions across the life course and low adult SES are associated with an elevated systemic inflammatory burden in adulthood. Chronic systemic inflammation may be one pathway linking low life-course SES and elevated cardiovascular disease risk.