Killian, Jill M.

OBJECTIVE: We determined the incidence of written-language disorder (WLD) among children with and without attention-deficit/hyperactivity disorder (ADHD) in a population-based birth cohort. METHODS: Subjects included a birth cohort of all children born in 1976–1982 who remained in Rochester, Minnesota, after 5 years of age (N = 5718). Information from medical, school, and private tutorial records was abstracted. Cumulative incidences of WLD with or without reading disability (RD), identified with any of 3 formulas, among children with and without ADHD and hazard ratios (HRs) were calculated. RESULTS: For both genders, the cumulative incidence of WLD by 19 years of age was significantly higher for children with ADHD than for children without ADHD (boys: 64.5% vs 16.5%; girls: 57.0% vs 9.4%). The magnitude of association between ADHD and WLD with RD was significantly higher for girls than for boys (adjusted HR: girls: 9.8; boys: 4.2; P < .001). However, this was not true for WLD without RD (adjusted HR: girls: 7.4; boys: 6.6; P = .64). CONCLUSIONS: ADHD is strongly associated with an increased risk of WLD (with or without RD) for both boys and girls. Girls with ADHD are at higher risk of having WLD with RD compared with boys with ADHD, whereas boys and girls are at the same risk of having WLD without RD.

Background and Purpose— Coronary artery disease is the leading cause of death after TIA. Reliable estimates of the risk of MI after TIA, however, are lacking. Methods— Our purpose was to determine the incidence of and risk factors for MI after TIA. We cross-referenced preexisting incidence cohorts from the Rochester Epidemiology Project for TIA (1985–1994) and MI (1979–2006) to identify all community residents with incident MI after incident TIA. Incidence of MI after TIA was determined using Kaplan–Meier life-table methods. This was compared to the age-, sex-, and period-specific MI incidences in the general population. Proportional hazards regression analysis was used to examine associations between clinical variables and the occurrence of MI after TIA. Results— Average annual incidence of MI after TIA was 0.95%. Relative risk for incident MI in the TIA cohort compared to the general population was 2.09 (95% CI, 1.52–2.81). This was highest in patients younger than 60 years old (relative risk, 15.1; 95% CI, 4.11–38.6). Increasing age (hazard ratio, 1.51 per 10 years; 95% CI, 1.14–2.01), male sex (hazard ratio, 2.19; 95% CI, 1.18–4.06), and the use of lipid-lowering therapy at the time of TIA (hazard ratio, 3.10; 95% CI, 1.20–8.00) were independent risk factors for MI after TIA. Conclusions— Average annual incidence of MI after TIA is ≈1%, approximately double that of the general population. The relative risk increase is especially high in patients younger than 60 years old. These data are useful for identifying subgroups of patients with TIA at highest risk for subsequent MI.

OBJECTIVE: To determine the incidence of reading disability (RD) among children with and without research-identified attention-deficit/hyperactivity disorder (ADHD), separately according to gender, in a population-based birth cohort. METHOD: Subjects included all children born in 1976–1982 remaining in Rochester, Minnesota, after 5 years of age (n = 5718). Information from medical, school, and private tutorial records was abstracted. Cumulative incidence of RD, by any of 3 RD formulas, in children with and without ADHD and corresponding hazard ratios (HRs) were calculated separately according to gender. RESULTS: Cumulative incidence of RD by the age of 19 years was significantly higher in children with ADHD (51% in boys, 46.7% in girls) compared with those without ADHD (14.5% in boys, 7.7% in girls). Among children with ADHD, the risk for RD was similar in boys versus girls (HR: 1.0). However, among children without ADHD, boys were 2.0 times more likely than girls to meet RD criteria. Among girls, the HR for the risk for RD associated with ADHD (versus those without ADHD) was 8.1 (95% confidence interval: 5.7–11.5), which was significantly higher than the corresponding HR among boys (3.9 [95% confidence interval: 3.2–4.9]). CONCLUSIONS: The risk for RD is significantly greater among children with ADHD compared with those without ADHD. Among children with ADHD, the risk for RD is the same for boys and girls. However, among children without ADHD, boys are more at risk for RD than girls. Among girls, the magnitude of increased risk for RD associated with ADHD is nearly twice that among boys, because girls without ADHD are less likely to have RD than boys without ADHD.

Background— In 2000, the definition of myocardial infarction (MI) changed to rely on troponin rather than creatine kinase (CK) and its MB fraction (CK-MB). The implications of this change on trends in MI incidence and outcome are not defined. Methods and Results— This was a community study of 2816 patients hospitalized with incident MI from 1987 to 2006 in Olmsted County, Minnesota, with prospective measurements of troponin and CK-MB from August 2000 forward. Outcomes were MI incidence, severity, and survival. After troponin was introduced, 278 (25%) of 1127 incident MIs met only troponin-based criteria. When cases meeting only troponin criteria were included, incidence did not change between 1987 and 2006. When restricted to cases defined by CK/CK-MB, the incidence of MI declined by 20%. The incidence of non–ST-segment elevation MI increased markedly by relying on troponin, whereas that of ST-segment elevation MI declined regardless of troponin. The age- and sex-adjusted hazard ratio of death within 30 days for an infarction occurring in 2006 (compared with 1987) was 0.44 (95% confidence interval, 0.30 to 0.64). Among 30-day survivors, survival did not improve, but causes of death shifted from cardiovascular to noncardiovascular ( P =0.001). Trends in long-term survival among 30-day survivors were similar regardless of troponin. Conclusions— Over the last 2 decades, a substantial change in the epidemiology of MI occurred that was only partially mediated by the introduction of troponin. Non–ST-segment elevation MIs now constitute the majority of MIs. Although the 30-day case fatality improved markedly, long-term survival did not change, and the cause of death shifted from cardiovascular to noncardiovascular.

Background— Mortality among patients with heart failure is high. Though individual biomarkers have been investigated to determine their value in mortality risk prediction, the role of a multimarker strategy requires further evaluation. Methods and Results— Olmsted County residents presenting with heart failure from July 2004 to September 2007 were recruited to undergo biomarker measurement. We investigated whether addition of C-reactive protein, B-type natriuretic peptide, and troponin T to a model including established risk indicators improved 1-year mortality risk prediction using the c statistic, integrated discrimination improvement, and net reclassification improvement. Among 593 participants, the mean age was 76.4 years, and 48% were men. After 1 year of follow-up, 122 (20.6%) participants had died. Patients with C-reactive protein (<11.8 mg/L), B-type natriuretic peptide (<350 pg/mL), and troponin T (≤0.01 ng/mL) less than the median had low 1-year mortality (3.3%), whereas those with 2 or 3 biomarkers greater than the median had markedly increased mortality (30.8% and 35.5%, respectively). The addition of 2 or more biomarkers to the model offered greater improvement in 1-year mortality risk prediction than use of a single biomarker. The combination of C-reactive protein and B-type natriuretic peptide resulted in an increase in the c statistic from 0.757 to 0.810 ( P <0.001), an integrated discrimination improvement gain of 7.1% ( P <0.001), and a net reclassification improvement of 22.1% ( P <0.001). Use of all 3 biomarkers offered no incremental gain (integrated discrimination improvement gain 0.7% versus C-reactive protein+B-type natriuretic peptide, P =0.065). Conclusions— Biomarkers improved 1-year mortality risk prediction beyond established indicators. The use of a 2-biomarker combination was superior to a single biomarker in risk prediction, though addition of a third biomarker conferred no added benefit.

Background— Tumor necrosis factor-α (TNFα), an inflammatory cytokine, was reported to be elevated in trials of heart failure (HF) with reduced ejection fraction (EF) and associated with mortality. Whether this is true for HF with preserved EF is unknown, and community data are lacking. We evaluated the distribution of TNFα, its association with baseline characteristics and mortality, and its benefit in assessing risk in community HF patients. Methods and Results— Olmsted County residents with active HF from July 2004 to March 2007 (n=486; mean age, 76.7 years; EF ≥50%, 55%) were prospectively recruited. Clinical characteristics and TNFα were measured. Elevated TNFα (more than the assay limit of normal of 2.8 pg/mL) was present in 143 (29%). Higher TNFα was associated with decreased creatinine clearance, nonsmoking status, anemia, and greater comorbidity ( P trend <0.05 for all). Mortality increased with increasing TNFα ( P =0.016), with 1-year mortality estimates of 16%, 18%, 23%, and 32% from the lowest to highest quartile, respectively. After adjustment for age, sex, and EF, the hazard ratios for death were 1.24, 1.37, and 1.90 from the second to the highest TNFα quartile, respectively ( P trend =0.007). TNFα contributed to risk assessment as indicated by increases in the area under the receiver operating characteristic curves in all models examined ( P <0.05 for all). Results did not differ by EF ( P =0.60 interaction term of TNFα and EF). Conclusions— TNFα was elevated in a large portion of community HF patients, was associated with a large decrease in survival, and provided a significant incremental increase in risk assessment above established indicators. TNFα is useful for risk assessment in HF patients with preserved and reduced EF.

OBJECTIVE—To determine whether women with diabetes undergo fewer screening mammograms than matched control subjects.RESEARCH DESIGN AND METHODS—A total of 424 women with diabetes aged 50–75 years who received their primary care from general internists at a large Midwestern multispecialty group practice were retrospectively studied for frequency of mammography from August 1997 to January 2000. Two control subjects without diabetes (n = 845) were matched to each case by age, sex, provider, and date of visit. The main outcome measure was the percentage of subjects undergoing mammography 1 year before and 30 days after an index date, defined as the most recent health care visit after August 1997 and before January 2000.RESULTS—Analysis by conditional logistic regression demonstrated that women with diabetes had significantly lower rates of mammograms than control subjects (78.1 vs. 84.9%, respectively; odds ratio 0.63, P = 0.002). After adjusting for insurance status and race, women with diabetes continued to have significantly lower rates of mammography (odds ratio 0.70, P = 0.027).CONCLUSIONS—Women with diabetes were significantly less likely to undergo screening mammography than control subjects. Considering the increasing incidence of diabetes and the equal incidence of malignancy in women with and without diabetes, it would be beneficial to improve breast cancer screening in this population.

Background— The 2000 European Society of Cardiology/American College of Cardiology definition for myocardial infarction (MI) combines ischemic symptoms, electrocardiographic changes, and troponin rather than creatine kinase levels. The use of troponins will increase the detection of MI by a magnitude to be quantified, and the clinical acceptance of the new definition is unknown. Method and Results— Subjects presenting to an Olmsted County facility with a troponin T value ≥0.03 ng/mL between November 2002 and March 2005 were prospectively classified through the use of standardized MI criteria, relying on cardiac pain, Minnesota coding of the ECG, and troponin, creatine kinase, and its MB fraction measured simultaneously. Through the use of dynamic changes in troponin, 538 MIs were identified versus 327 with creatine kinase and 427 with only the MB fraction of creatine kinase. This represents a 74% (95% confidence interval [CI], 69% to 79%) increase above the number of MIs identified with creatine kinase and a 41% (95% CI, 37% to 46%) increase above the number identified with criteria including only its MB fraction. When relying on single values of troponin, increases in the number of MIs were always large but varied widely according to the threshold used for troponin. Cases meeting only troponin-based criteria were less likely to have electrocardiographic ST-segment elevation and had better survival than those identified with previous criteria. Clinician diagnoses mentioned MI in 42% (95% CI, 34% to 49%) of cases meeting only troponin-based criteria versus 74% (95% CI, 69% to 78%) for MIs meeting the previous criteria ( P <0.001). Conclusions— The prospective application of the new criteria in the community results in a large increase in the number of MIs and a change in case mix. The clinical acceptance of the new criteria is incomplete, and studies that rely exclusively on dismissal diagnoses to assess MI rates may underestimate the burden of disease as presently defined.

Objective— We evaluated the role of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), an inflammatory biomarker, in defining risk after myocardial infarction (MI). Methods and Results— Olmsted County, Minn, residents who experienced an MI meeting standardized criteria between 2003 and 2005 (n=271) were prospectively identified and followed. Lp-PLA 2 levels were measured at baseline and evaluated along with traditional risk indicators. Lp-PLA 2 was modestly associated with total and low-density lipoprotein cholesterol, smoking, and age (inversely) but not with MI characteristics or severity, comorbidities, C-reactive protein, or the time from symptom onset to blood sampling. During the first year of follow-up, 42 deaths occurred. The survival estimates (95% confidence intervals [CI]) at 1 year were 92% (86% to 98%), 85% (78% to 93%), and 74% (65% to 84%) in the lowest, middle, and upper Lp-PLA 2 tertiles, respectively ( P =0.007). After adjustment for age and sex, the hazard ratios for death in the middle and upper Lp-PLA 2 tertiles were 2.20 (95% CI: 0.88 to 5.54) and 4.93 (95% CI: 2.10 to 11.60), compared with the lowest tertile, respectively ( P trend <0.001). Further adjustment for other risk indicators resulted in even stronger associations. Lp-PLA 2 also contributed to risk discrimination as indicated by the increases in the area under the receiver operating characteristic curves obtained in each of the models examined (all P ≤0.05). Conclusions— Among community subjects presenting with MI, increased Lp-PLA 2 levels measured early after MI are strongly and independently associated with mortality and provide incremental value in risk discrimination over traditional predictors.