Context Coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear. Objective To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk. Design, Setting and Participants CACS was measured by computed tomography on 6,814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded for the primary analysis. Five-year risk estimates for incident CHD were categorized as 0-<3%, 3-<10%, and ≥10% using Cox proportional hazards models. Model 1 used age, gender, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement (NRI) and compared the distribution of risk using Model 2 versus Model 1. Main Outcome Measures Incident CHD events Results Over 5.8 years median follow-up, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared to Model 1 (NRI=0.25, 95% confidence interval 0.16-0.34, P<0.001). With Model 1, 69% of the cohort was classified in the highest or lowest risk categories, compared to 77% with Model 2. An additional 23% of those who experienced events were reclassified to high risk, and an additional 13% without events were reclassified to low risk using Model 2. Conclusions In the MESA cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories.

In 2001, we followed up all patients from the 1991 Olmsted County Multiple Sclerosis (MS) prevalence cohort. We found that the longer the duration of MS and the lower the disability, the more likely a patient is to remain stable and not progress. This is particularly powerful for patients with benign MS with Expanded Disability Status Scale score of 2 or lower for 10 years or longer who have a greater than 90% chance of remaining stable. This is important because these patients represent 17% of the entire prevalence cohort. These data should assist in the shared therapeutic decision-making process of whether to start immunomodulatory medications.

Background Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk prediction. However, to date no risk score incorporating CAC has been developed. Objectives Our goal was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors. Methods Algorithm development was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective community-based cohort study of 6814 participants aged 45–84, free of clinical heart disease at baseline and followed for 10 years. MESA is gender balanced and included 39% Non-Hispanic whites, 12% Chinese American, 28% African American, and 22% Hispanic Americans. External validation was conducted in the Heinz Nixdorf Recall Study (HNR) and the Dallas Heart Study (DHS). Results Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 versus 0.75, p<0.0001). External validation in both HNR and DHS provided evidence of very good discrimination and calibration. Harrell’s C-statistic was 0.779 in HNR, and 0.816 in DHS. Additionally the difference in estimated 10-year risk between events and non-events was approximately 8–9%, indicating excellent discrimination. Mean calibration, or calibration-in-the-large, was excellent for both studies, with average predicted 10-year risk within half a percent of the observed event rate. Conclusions An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians in the communication of risk to patients and when determining risk-based treatment strategies.

After age and sex adjustment to a common population, these prevalence and incidence rates of MS appear to have been stable rather than increasing over the past 20 years.

Though MS can cause significant disability, most patients with MS in the Olmsted County prevalence cohort continue to report a good QOL.

Although survival was reduced and 30% of patients progressed to needing a cane or wheelchair or worse over the 10-year follow-up period, most remained stable or minimally progressed. Patients within the EDSS 3.0 through 5.0 range are at moderate risk of developing important gait limitations over the 10-year period. The authors did not identify factors strongly predictive of worsening disability in this study.

Background Air pollution is associated with cardiovascular disease, and systemic inflammation may mediate this effect. We assessed associations between long- and short-term concentrations of air pollution and markers of inflammation, coagulation, and endothelial activation. Methods We studied participants from the Multi-Ethnic Study of Atherosclerosis from 2000 to 2012 with repeat measures of serum C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, D-dimer, soluble E-selectin, and soluble Intercellular Adhesion Molecule-1. Annual average concentrations of ambient fine particulate matter (PM2.5), individual-level ambient PM2.5 (integrating indoor concentrations and time–location data), oxides of nitrogen (NOx), nitrogen dioxide (NO2), and black carbon were evaluated. Short-term concentrations of PM2.5 reflected the day of blood draw, day prior, and averages of prior 2-, 3-, 4-, and 5-day periods. Random-effects models were used for long-term exposures and fixed effects for short-term exposures. The sample size was between 9,000 and 10,000 observations for CRP, IL-6, fibrinogen, and D-dimer; approximately 2,100 for E-selectin; and 3,300 for soluble Intercellular Adhesion Molecule-1. Results After controlling for confounders, 5 µg/m3 increase in long-term ambient PM2.5 was associated with 6% higher IL-6 (95% confidence interval = 2%, 9%), and 40 parts per billion increase in long-term NOx was associated with 7% (95% confidence interval = 2%, 13%) higher level of D-dimer. PM2.5 measured at day of blood draw was associated with CRP, fibrinogen, and E-selectin. There were no other positive associations between blood markers and short- or long-term air pollution. Conclusions These data are consistent with the hypothesis that long-term exposure to air pollution is related to some markers of inflammation and fibrinolysis.

Background and Purpose-Internal carotid artery (ICA) occlusion is an important cause of transient ischemic attack (TIA) and cerebral infarction. There are no previous population-based natural history studies evaluating outcome after symptomatic ICA occlusion (SICAO). Methods-We performed a retrospective, population-based study of SICAO. All Olmsted County (Minnesota) residents with possible SICAO from 1986 to 2000 were identified by cross-referencing appropriate clinical and imaging codes. Inclusion criteria were cerebral infarction or TIA in a carotid distribution and imaging documentation of ipsilateral ICA occlusion Ͻ3 months after the index event. Kaplan-Meier estimates were used to calculate the risk of cerebral infarction, myocardial infarction, and death after SICAO. Results-Seventy-five patients qualified. Annual SICAO incidence was 6 per 100 000 persons (age and gender adjusted to the 2000 US white population). Risk of cerebral infarction during follow-up was 8% at 30 days, 10% at 1 year, and 14% at 5 years. Five of 11 cerebral infarctions occurred within the first week after diagnosis of occlusion. Risk of myocardial infarction was 0% at 30 days, 8% at 1 year, and 24% at 5 years. Risk of death was 7%, 13%, and 29%, respectively. Conclusions-There may be 15 000 to 20 000 incident cases of SICAO in the United States annually. Risk of cerebral infarction after SICAO is initially high and then stabilizes, whereas risk of myocardial infarction is initially low but gradually increases. Better strategies are needed to reduce early stroke recurrence in this setting. Key Words: carotid arteries Ⅲ occlusion Ⅲ cerebral infarction Ⅲ cerebral ischemia, transient S ymptomatic internal carotid artery occlusion (SICAO) is a relatively uncommon but still important cause of transient ischemic attack (TIA) and cerebral infarction. Although SICAO has been the subject of previous studies, most have been limited by referral and selection bias. 1,2 Furthermore, little data have been provided about the very early (Ͻ1 month) risk of adverse events after SICAO. We undertook the first population-based study of SICAO to (1) calculate SI-CAO incidence rates and (2) determine its natural history in a defined population. Subjects and MethodsThis study was performed under the auspices of the Rochester Epidemiology Project (REP). 3 Most inpatient and outpatient medical care for Olmsted County, Minnesota, residents is provided at either Mayo Medical Center or a non-Mayo-affiliated community hospital and clinic, and virtually all patients in the community have care provided at one of these medical centers during any 3-year period. 3 The medical care data for the few Olmsted County residents receiving some of their medical care at the Veterans Administration Hospital in Minneapolis are also included in the REP database. The comprehensive medical record availability increases the likelihood of essentially complete ascertainment of a specified diagnosis for Olmsted County residents.We retrospectively identified patients with potential SI...