Jill M. Killian

Coronary atherosclerosis in diabetes mellitus: A population-based autopsy study

OBJECTIVES The study was conducted to test the hypothesis that the prevalence of coronary atherosclerosis is greater among diabetic than among nondiabetic individuals and is similar for diabetic individuals without clinical coronary artery disease (CAD) and nondiabetics with clinical CAD. BACKGROUND Persons with diabetes but without clinical CAD encounter cardiovascular mortality similar to nondiabetic individuals with clinical CAD. This excess mortality is not fully explained. We examined the association between diabetes and coronary atherosclerosis in a geographically defined autopsied population, while capitalizing on the autopsy rate and medical record linkage system available via the Rochester Epidemiology Project, which allows rigorous ascertainment of coronary atherosclerosis, clinical CAD, and diabetes. METHODS Using two measures, namely a global coronary score and high-grade stenoses, the prevalence of atherosclerosis was analyzed in a cohort of autopsied residents of Rochester, Minnesota, age 30 years or older at death, while stratifying on diabetes, clinical CAD diagnosis, age, and gender. RESULTS In this cohort, diabetes was associated with a higher prevalence of atherosclerosis. Among diabetic decedents without clinical CAD, almost three-fourths had high-grade coronary atherosclerosis and more than half had multivessel disease. Without diabetes, women had less atherosclerosis than men, but this female advantage was lost with diabetes. Among those without clinical CAD, diabetes was associated with a global coronary disease burden and a prevalence of high-grade atherosclerosis similar to that observed among nondiabetic subjects with clinical CAD. CONCLUSIONS These findings provide mechanistic insights into the excess risk of clinical CAD among diabetic individuals, thereby supporting the need for aggressive prevention of atherosclerosis in all diabetic individuals, irrespective of clinical CAD symptoms.

Trends in Incidence, Severity, and Outcome of Hospitalized Myocardial Infarction

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.

Trends in the incidence and survival of patients with hospitalized myocardial infarction, Olmsted County, Minnesota, 1979 to 1994.

Context Mortality from coronary disease and the number of people hospitalized for myocardial infarction have decreased in recent years. Medical care or reduced incidence of disease could be responsible. Contribution Between 1979 and 1994, age-adjusted incidence of myocardial infarction in Olmsted County, Minnesota, changed little overall, although it decreased 8% in men, increased 36% in women, and increased in older compared with younger persons. Mortality rates from myocardial infarction decreased in younger but not older persons. Implications Secular trends in myocardial infarction reflect changes in both incidence and survival and vary significantly with sex and age. The Editors Although age-adjusted mortality due to coronary disease had decreased in recent decades, the continuing burden of coronary disease should not be underestimated, and the determinants of this decrease have not been fully elucidated. Recent data from the United States indicate that the incidence of hospitalized myocardial infarction decreased modestly in recent years (1, 2), suggesting that medical care has contributed greatly to the decrease in mortality. Conversely, the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease study conversely found that changes in incidence were the major reason for the decrease in deaths from coronary disease (3). These divergent findings warrant further analyses in different populations. Moreover, because neither of these studies included persons older than 74 years of age, trends among elderly persons, the fastest growing segment of the population, could not be measured (1, 3-5). The Worcester Heart Attack Study showed that survival after myocardial infarction improved over time, but advancing age had a markedly adverse effect on survival (6). Although the explanations for these adverse findings are probably multifactorial and include more comorbid conditions and less use of efficacious therapies in elderly persons, these results emphasize the importance of monitoring coronary disease trends in this group. Data from Olmsted County, Minnesota, for persons of all ages indicated that the decrease in coronary mortality affected primarily middle-aged men; this finding suggests that the burden of coronary deaths has been shifted toward women and elderly persons (7). These data further highlight the importance of including older age groups in studies and the need to elucidate age- and sex-specific mortality trends. We sought to examine the trends in incidence and survival of patients with hospitalized myocardial infarction in Olmsted County, Minnesota. We tested two hypotheses: 1) that the incidence of myocardial infarction has not decreased overall over time, but that trends differ by sex and age, and 2) that survival after incident myocardial infarction has improved over time but that the magnitude of improvement differs by sex and age. Methods Setting Epidemiologic research in Olmsted County, Minnesota, is possible because the county is relatively isolated from other centers, and a few providers deliver nearly all medical care to local residents. The Mayo Clinic provides approximately half of the primary care and nearly all specialty care to the region, and Olmsted Medical Center and its affiliate Olmsted Community Hospital provide care for the region in every medical field. The characteristics of the Olmsted County population are similar to those of white persons in the United States overall, except that a higher proportion of Olmsted County residents are employed in the health care sector (8). Each medical care provider uses a medical record system in which the details of every encounter are entered and can be easily retrieved; the Mayo Clinic has maintained extensive indices of clinical and histologic diagnoses and surgical procedures since the 1900s (9, 10). Since 1966, similar indices have been developed for non-Mayo Clinic providers through the Rochester Epidemiology Project, resulting in the linkage of medical records from all sources of care used by the population. This system provides a unique infrastructure for analyzing disease determinants and outcomes. Enumeration of Hospitalized Patients with Acute Myocardial Infarction Case Finding and Investigation Lists of patients discharged from hospitals in Olmsted County who had diagnoses compatible with myocardial infarction were obtained from the Rochester Epidemiology Project index of diagnoses and the Hospital Utilization Review Database, an administrative database of hospitalizations maintained by the Mayo Clinic. The target International Classification of Diseases, Ninth Revision, codes were 410 (acute myocardial infarction), 411 (other acute and subacute forms of ischemic heart disease), 412 (old myocardial infarction), 413 (angina pectoris), and 414 (other forms of ischemic heart disease). All events coded as 410, a 50% random sample of code 411, and a 10% random sample of codes 412, 413, and 414 were reviewed. The sampling fractions were similar to those used in other studies (11). Trained abstracters reviewed the medical records of Olmsted County residents and collected information on cardiac pain (defined as pain occurring in the anterior chest, arms or jaw, back, shoulder, or abdomen) and timing of its onset. Pain was categorized as present if it met these criteria and no other cause of pain could be determined (11). Creatinine phosphokinase values were transcribed for up to three measurements on each of the first 3 days after admission. Information on a potential history of trauma or surgery, which might invalidate enzyme values, was recorded. Copies of up to three electrocardiograms (from the first day of the event or hospital admission, the last day of hospitalization, and the third day) were printed and sent to the Electrocardiogram Reading Center at the University of Minnesota to assign a Minnesota code (12). Determination of Incident Status of Myocardial Infarction The full medical record of each candidate case was searched for any episode compatible with previous infarction. Abstracters were asked to first examine the history surrounding the index event. If no previous cardiac history was specifically mentioned, the search for antecedent infarction was terminated. If a previous infarction was mentioned or if nothing was specified, all records before the index event were examined. If data were available, the possible antecedent event was validated by using the classification rule described below. If data were unavailable, the event was described qualitatively on the basis of the available documentation (confirmed by attending physician, history of heart attack according to the patient, mention of silent infarction without further descriptor, or mention of old infarction on physicians review of a routine electrocardiogram). Classification of the Index Hospitalized Myocardial Infarction Once the data for a hospitalized myocardial infarction were collected, a standardized classification rule was applied to assign an epidemiologic diagnosis (5, 11, 13). Cardiac pain was categorized as present or absent, and enzyme values were classified as abnormal, equivocal, or normal. When review by a physician-author confirmed a potential nonischemic cause of elevated enzyme levels, the classification was downgraded to equivocal. According to the Minnesota system, one of five codes was assigned to the electrocardiograms (evolving diagnostic, diagnostic, evolving ST-T changes, equivocal, or absent). According to the classification rule, myocardial infarctions were classified as definite, probable, suspect, or no myocardial infarction on the basis of cardiac pain, enzyme, and electrocardiographic data. According to published criteria (13), fatal myocardial infarction can be definitively diagnosed if the patient had a definite hospitalized infarction within 4 weeks of death or an acute infarction was found at autopsy. Of hospitalized persons with discharge codes 410 to 414, those who died in the emergency department, those who were dead on arrival, and those with in-hospital events with a rapid fatal course for whom no or little data were available were categorized as having infarction if they had an autopsy diagnosis of myocardial infarction. Follow-up In hospitalized patients, vital status was determined at discharge. Thereafter, it was determined by verification of death certificates, performed by the Rochester Epidemiology Project. Reliability of the Myocardial Infarction Ascertainment Process The abstracters were trained in methods for case finding and residency ascertainment through the Rochester Epidemiology Project. Quality control involved reabstraction of a random sample of 19 cases. The coefficient was used to evaluate interobserver variability for categorical variables. By convention, arbitrary categories were used to define poor ( 0.4), fair to good (0.4 < 0.7), and excellent ( > 0.7) agreement beyond chance. Categorical variables were history of myocardial infarction and cardiac pain. Agreement was excellent for history of infarction ( = 0.92 [(95% CI, 0.79 to 1.0)], presence of cardiac pain ( = 0.93 [CI, 0.84 to 1.0]), and presence of prolonged cardiac pain ( = 0.96 [CI, 0.88 to 1.0]). Statistical Analysis Age-, sex-, and year-specific incidences of hospitalized myocardial infarction were calculated. The numerators were the number of all definite and probable incident infarctions, and the denominators were the Olmsted County population as determined from census data for the years 1970, 1980, and 1990, with linear interpolation for the intercensus years and extrapolation after 1990 (14). Rates were directly adjusted to the age distribution of the 2000 U.S. population. Standard errors and 95% CIs were calculated on the basis of the Poisson error distribution. Age- and sex-specific trends in the incidence of hospitalized myocardial infarction were assessed by using weighted Poisson regression. The analyse

Clinical study: obesity, diabetes, and heart diseaseCoronary atherosclerosis in diabetes mellitus: A population-based autopsy study☆

OBJECTIVES The study was conducted to test the hypothesis that the prevalence of coronary atherosclerosis is greater among diabetic than among nondiabetic individuals and is similar for diabetic individuals without clinical coronary artery disease (CAD) and nondiabetics with clinical CAD. BACKGROUND Persons with diabetes but without clinical CAD encounter cardiovascular mortality similar to nondiabetic individuals with clinical CAD. This excess mortality is not fully explained. We examined the association between diabetes and coronary atherosclerosis in a geographically defined autopsied population, while capitalizing on the autopsy rate and medical record linkage system available via the Rochester Epidemiology Project, which allows rigorous ascertainment of coronary atherosclerosis, clinical CAD, and diabetes. METHODS Using two measures, namely a global coronary score and high-grade stenoses, the prevalence of atherosclerosis was analyzed in a cohort of autopsied residents of Rochester, Minnesota, age 30 years or older at death, while stratifying on diabetes, clinical CAD diagnosis, age, and gender. RESULTS In this cohort, diabetes was associated with a higher prevalence of atherosclerosis. Among diabetic decedents without clinical CAD, almost three-fourths had high-grade coronary atherosclerosis and more than half had multivessel disease. Without diabetes, women had less atherosclerosis than men, but this female advantage was lost with diabetes. Among those without clinical CAD, diabetes was associated with a global coronary disease burden and a prevalence of high-grade atherosclerosis similar to that observed among nondiabetic subjects with clinical CAD. CONCLUSIONS These findings provide mechanistic insights into the excess risk of clinical CAD among diabetic individuals, thereby supporting the need for aggressive prevention of atherosclerosis in all diabetic individuals, irrespective of clinical CAD symptoms.

Mortality, ADHD, and Psychosocial Adversity in Adults With Childhood ADHD: A Prospective Study

OBJECTIVE: We examined long-term outcomes of attention-deficit/hyperactivity disorder (ADHD) in a population-based sample of childhood ADHD cases and controls, prospectively assessed as adults. METHODS: Adults with childhood ADHD and non-ADHD controls from the same birth cohort (N = 5718) were invited to participate in a prospective outcome study. Vital status was determined for birth cohort members. Standardized mortality ratios (SMRs) were constructed to compare overall and cause-specific mortality between childhood ADHD cases and controls. Incarceration status was determined for childhood ADHD cases. A standardized neuropsychiatric interview was administered. RESULTS: Vital status for 367 childhood ADHD cases was determined: 7 (1.9%) were deceased, and 10 (2.7%) were currently incarcerated. The SMR for overall survival of childhood ADHD cases versus controls was 1.88 (95% confidence interval [CI], 0.83–4.26; P = .13) and for accidents only was 1.70 (95% CI, 0.49–5.97; P = .41). However, the cause-specific mortality for suicide only was significantly higher among ADHD cases (SMR, 4.83; 95% CI, 1.14–20.46; P = .032). Among the childhood ADHD cases participating in the prospective assessment (N = 232; mean age, 27.0 years), ADHD persisted into adulthood for 29.3% (95% CI, 23.5–35.2). Participating childhood ADHD cases were more likely than controls (N = 335; mean age, 28.6 years) to have ≥1 other psychiatric disorder (56.9% vs 34.9%; odds ratio, 2.6; 95% CI, 1.8–3.8; P < .01). CONCLUSIONS: Childhood ADHD is a chronic health problem, with significant risk for mortality, persistence of ADHD, and long-term morbidity in adulthood.

Redefinition of Myocardial Infarction Prospective Evaluation in the Community

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.

A Contemporary Appraisal of the Heart Failure Epidemic in Olmsted County, Minnesota, 2000 to 2010

IMPORTANCE Heart failure (HF) is commonly referred to as an epidemic, posing major clinical and public health challenges. Yet, contemporary data on its magnitude and implications are scarce. OBJECTIVE To evaluate recent trends in HF incidence and outcomes overall and by preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF). DESIGN, SETTING, AND PARTICIPANTS Incidence rates of HF in Olmsted County, Minnesota (population, approximately 144,248), between January 1, 2000, and December 31, 2010, were assessed. MAIN OUTCOMES AND MEASURES Patients identified with incident HF (n = 2762) (mean age, 76.4 years; 43.1% male) were followed up for all-cause and cause-specific hospitalizations (through December 2012) and death (through March 2014). RESULTS The age- and sex-adjusted incidence of HF declined substantially from 315.8 per 100,000 in 2000 to 219.3 per 100,000 in 2010 (annual percentage change, -4.6), equating to a rate reduction of 37.5% (95% CI, -29.6% to -44.4%) over the last decade. The incidence declined for both HF types but was greater (interaction P = .08) for HFrEF (-45.1%; 95% CI, -33.0% to -55.0%) than for HFpEF (-27.9%; 95% CI, -12.9% to -40.3%). Mortality was high (24.4% for age 60 years and 54.4% for age 80 years at 5 years of follow-up), frequently ascribed to noncardiovascular causes (54.3%), and did not decline over time. The risk of cardiovascular death was lower for HFpEF than for HFrEF (multivariable-adjusted hazard ratio, 0.79; 95% CI, 0.67-0.93), whereas the risk of noncardiovascular death was similar (1.07; 95% CI, 0.89-1.29). Hospitalizations were common (mean, 1.34; 95% CI, 1.25-1.44 per person-year), particularly among men, and did not differ between HFpEF and HFrEF. Most hospitalizations (63.0%) were due to noncardiovascular causes. Hospitalization rates for cardiovascular causes did not change over time, whereas those for noncardiovascular causes increased. CONCLUSIONS AND RELEVANCE Over the last decade, the incidence of HF declined substantially, particularly for HFrEF, contrasting with no apparent change in mortality. Noncardiovascular conditions have an increasing role in hospitalizations and remain the most frequent cause of death. These results underscore the need to augment disease-centric management approaches with holistic strategies to reduce the population burden of HF.

Childhood ADHD is Strongly Associated with a Broad Range of Psychiatric Disorders during Adolescence: a Population-Based Birth Cohort Study

BACKGROUND To evaluate associations between attention-deficit/hyperactivity disorder (ADHD) and comorbid psychiatric disorders using research-identified incident cases of ADHD and population-based controls. METHODS Subjects included a birth cohort of all children born 1976-1982 remaining in Rochester, MN after age five (n = 5,718). Among them we identified 379 ADHD incident cases and 758 age-gender matched non-ADHD controls, passively followed to age 19 years. All psychiatric diagnoses were identified and abstracted, but only those confirmed by qualified medical professionals were included in the analysis. For each psychiatric disorder, cumulative incidence rates for subjects with and without ADHD were estimated using the Kaplan-Meier method. Corresponding hazard ratios (HR) were estimated using Cox models adjusted for gender and mothers age and education at the subjects birth. The association between ADHD and the likelihood of having an internalizing or externalizing disorder was summarized by estimating odds ratios (OR). RESULTS Attention-deficit/hyperactivity disorder was associated with a significantly increased risk of adjustment disorders (HR = 3.88), conduct/oppositional defiant disorder (HR = 9.54), mood disorders (HR = 3.67), anxiety disorders (HR = 2.94), tic disorders (HR = 6.53), eating disorders (HR = 5.68), personality disorders (HR = 5.80), and substance-related disorders (HR = 4.03). When psychiatric comorbidities were classified on the internalization-externalization dimension, ADHD was strongly associated with coexisting internalizing/externalizing (OR = 10.6), or externalizing-only (OR = 10.0) disorders. CONCLUSION This population-based study confirms that children with ADHD are at significantly increased risk for a wide range of psychiatric disorders. Besides treating the ADHD, clinicians should identify and provide appropriate treatment for psychiatric comorbidities.

Secular trends in deaths from cardiovascular diseases: A 25-year community study

Background— Although age-adjusted cardiovascular disease (CVD) mortality has declined over the past decades, controversies remain about whether this trend was similar across locations of death and disease categories and about the existence of age and sex disparities. Methods and Results— We examined CVD mortality trends in Olmsted County, Minnesota, between 1979 and 2003 using the categories defined by the American Heart Association, including coronary heart disease (CHD), non-CHD diseases of the heart, and noncardiac circulatory diseases. Data on demographics, cause, and location of death of all 6378 residents who died of CVD were analyzed. Although decreases in the age-adjusted rates occurred in all groups, the magnitude of the decline varied widely. Lesser annual declines were noted in out-of-hospital than in-hospital deaths (1.8% versus 4.8%; P<0.001), in older than in younger persons (1.5% at age ≥85 years versus 3.9% for those ≤74 years of age; P<0.001), and in women relative to men (2.5% versus 3.3%; P=0.007). Furthermore, although CHD showed a marked annual decrease (3.3%), more modest decrements were found for non-CHD diseases of the heart (2.1%) and noncardiac circulatory diseases (2.4%) (P=0.02 and P=0.04 for the comparison with CHD decline, respectively). Conclusions— Over the past 25 years, CVD mortality declined markedly in the community, but there were large disparities in the magnitude of the decline, resulting in a shift in the distribution toward out-of-hospital and non-CHD deaths. Further reduction in CVD mortality will require strategies directed at elderly persons and women, in whom out-of-hospital rates have improved only minimally.

Scores for Post–Myocardial Infarction Risk Stratification in the Community

Background—Several scores, most of which were derived from clinical trials, have been proposed for stratifying risk after myocardial infarctions (MIs). Little is known about their generalizability to the community, their respective advantages, and whether the ejection fraction (EF) adds prognostic information to the scores. The purpose of this study is to evaluate the Thrombolysis in Myocardial Infarction (TIMI) and Predicting Risk of Death in Cardiac Disease Tool (PREDICT) scores in a geographically defined MI cohort and determine the incremental value of EF for risk stratification. Methods and Results—MIs occurring in Olmsted County were validated with the use of standardized criteria and stratified with the ECG into ST-segment elevation (STEMI) and non–ST-segment elevation (NSTEMI) MI. Logistic regression examined the discriminant accuracy of the TIMI and PREDICT scores to predict death and recurrent MI and assessed the incremental value of the EF. After 6.3±4.7 years, survival was similar for the 562 STEMIs and 717 NSTEMIs. The discriminant accuracy of the TIMI score was good in STEMI but only fair in NSTEMI. Across time and end points, irrespective of reperfusion therapy, the discriminant accuracy of the PREDICT score was consistently superior to that of the TIMI scores, largely because PREDICT includes comorbidity; EF provided incremental information over that provided by the scores and comorbidity. Conclusion—In the community, comorbidity and EF convey important prognostic information and should be included in approaches for stratifying risk after MI.